Sample records for elucidating key factors

  1. Elucidation of Factors Effecting Enzymatic Saccharification using Transgenic Hardwoods

    NASA Astrophysics Data System (ADS)

    Min, Douyong

    Three groups of transgenic wood samples were used as starting materials to elucidate the recalcitrance of enzymatic saccharification with/without pretreatments. The first group of transgenic wood samples is low lignin P. trichocarpa. The second group is low xylan P. trichocarpa. The third one is 12 hybrid poplars which have different levels of S/V ratio and lignin content. Four pretreatments were carried out in this research including dilute sulfuric acid, green liquor, auto hydrolysis and ozone delignification. The behavior among pretreatments as a function of removal of lignin appears to be different. Lignin is the major factor of recalcitrance of the lignocellulosic material to ethanol conversion process. Xylan also plays key role in this process. In addition, the crude milled wood lignin was isolated from these three groups of transgenic samples. Lignin carbohydrate complexes was characterized by 1H-13C HMQC and 13C NMR. Thus the effect of LCCs on enzymatic saccharification was elucidated. High S/V ratio propels the lignin removal during pretreatments however; high S/V ratio retards the enzymatic saccharification on the lignocellulosic material without pretreatments. The level of LCCs linkages accounts for additional recalcitrance of the lignocellulosic material to ethanol conversion process. The amount of LCCs linkages is affected by xylan content, lignin content and S/V ratio.

  2. [Elucidation of key genes in sex determination in genetics teaching].

    PubMed

    Li, Meng; He, Zhumei

    2014-06-01

    Sex is an important and complex feature of organisms, which is controlled by the genetic and environmental factors. The genetic factors, i.e., genes, are vital in sex determination. However, not all the related genes play the same roles, and some key genes play a vital role in the sex determination and differentiation. With the development of the modern genetics, a great progress on the key genes has been made in sex determination. In this review, we summarize the mechanism of sex determination and the strategy of how to study the key genes in sex determination. It will help us to understand the mechanism of sex determination better in the teaching of genetics.

  3. Identification of Key Transcription Factors Associated with Lung Squamous Cell Carcinoma

    PubMed Central

    Zhang, Feng; Chen, Xia; Wei, Ke; Liu, Daoming; Xu, Xiaodong; Zhang, Xing; Shi, Hong

    2017-01-01

    Background Lung squamous cell carcinoma (lung SCC) is a common type of lung cancer, but its mechanism of pathogenesis is unclear. The aim of this study was to identify key transcription factors in lung SCC and elucidate its mechanism. Material/Methods Six published microarray datasets of lung SCC were downloaded from Gene Expression Omnibus (GEO) for integrated bioinformatics analysis. Significance analysis of microarrays was used to identify differentially expressed genes (DEGs) between lung SCC and normal controls. The biological functions and signaling pathways of DEGs were mapped in the Gene Otology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, respectively. A transcription factor gene regulatory network was used to obtain insights into the functions of DEGs. Results A total of 1,011 genes, including 539 upregulated genes and 462 downregulated genes, were filtered as DEGs between lung SCC and normal controls. DEGs were significantly enriched in cell cycle, DNA replication, p53 signaling pathway, pathways in cancer, adherens junction, and cell adhesion molecules signaling pathways. There were 57 transcription factors identified, which were used to construct a regulatory network. The network consisted of 736 interactions between 49 transcription factors and 486 DEGs. NFIC, BRCA1, and NFATC2 were the top 3 transcription factors that had the highest connectivity with DEGs and that regulated 83, 82, and 75 DEGs in the network, respectively. Conclusions NFIC, BRCA1, and NFATC2 might be the key transcription factors in the development of lung SCC by regulating the genes involved in cell cycle and DNA replication pathways. PMID:28081052

  4. Key Impact Factors on Dam Break Fatalities

    NASA Astrophysics Data System (ADS)

    Huang, D.; Yu, Z.; Song, Y.; Han, D.; Li, Y.

    2016-12-01

    Dam failures can lead to catastrophes on human society. However, there is a lack of research about dam break fatalities, especially on the key factors that affect fatalities. Based on the analysis of historical dam break cases, most studies have used the regression analysis to explore the correlation between those factors and fatalities, but without implementing optimization to find the dominating factors. In order to understand and reduce the risk of fatalities, this study has proposed a new method to select the impact factors on the fatality. It employs an improved ANN (Artificial Neural Network) combined with LOOCV (Leave-one-out cross-validation) and SFS (Stepwise Forward Selection) approach to explore the nonlinear relationship between impact factors and life losses. It not only considers the factors that have been widely used in the literature but also introduces new factors closely involved with fatalities. Dam break cases occurred in China from 1954 to 2013 are summarized, within which twenty-five cases are selected with a comprehensive coverage of geographic position and temporal variation. Twelve impact factors are taken into account as the inputs, i.e., severity of dam break flood (SF), population at risk (PR), public understanding of dam break (UB), warning time (TW), evacuation condition (EC), weather condition during dam break (WB), dam break mode (MB), water storage (SW), building vulnerability (VB), dam break time (TB), average distance from the affected area to the dam (DD) and preventive measures by government (PG).From those, three key factors of SF, MB and TB are chosen. The proposed method is able to extract the key factors, and the derived fatality model performs well in various types of dam break conditions.

  5. Key Factors in Development of Man-Made and Natural Ecosystems

    NASA Astrophysics Data System (ADS)

    Pechurkin, N. S.

    1999-01-01

    Key factors of ecosystem functioning are of the same nature for artificial and natural types. An hierarchical approach gives the opportunity for estimation of the quantitative behavior of both individual links and the system as a whole. At the organismic level we can use interactions of studied macroorganisms (man, animal, higher plant) with selected microorganisms as key indicating factors of the organisms immune status. The most informative factor for the population/community level is an age structure of populations and relationships of domination/elimination. The integrated key factors of the ecosystems level are productivity and rates of cycling of the limiting substances. The key factors approach is of great value for growth regulations and monitoring the state of any ecosystem, including the life support system (LSS)-type.

  6. WRKY Transcription Factors: Key Components in Abscisic Acid Signaling

    DTIC Science & Technology

    2011-01-01

    Review article WRKY transcription factors : key components in abscisic acid signalling Deena L. Rushton1, Prateek Tripathi1, Roel C. Rabara1, Jun Lin1...May 2011. *Correspondence (Tel +605 688 5749; fax +605 688 5624; email paul.rushton@sdstate.edu) Keywords: abscisic acid, WRKY transcription factor ...seed germination, drought, abiotic stress. Summary WRKY transcription factors (TFs) are key regulators of many plant processes, including the responses

  7. Identification of key factors regulating self-renewal and differentiation in EML hematopoietic precursor cells by RNA-sequencing analysis.

    PubMed

    Zong, Shan; Deng, Shuyun; Chen, Kenian; Wu, Jia Qian

    2014-11-11

    Hematopoietic stem cells (HSCs) are used clinically for transplantation treatment to rebuild a patient's hematopoietic system in many diseases such as leukemia and lymphoma. Elucidating the mechanisms controlling HSCs self-renewal and differentiation is important for application of HSCs for research and clinical uses. However, it is not possible to obtain large quantity of HSCs due to their inability to proliferate in vitro. To overcome this hurdle, we used a mouse bone marrow derived cell line, the EML (Erythroid, Myeloid, and Lymphocytic) cell line, as a model system for this study. RNA-sequencing (RNA-Seq) has been increasingly used to replace microarray for gene expression studies. We report here a detailed method of using RNA-Seq technology to investigate the potential key factors in regulation of EML cell self-renewal and differentiation. The protocol provided in this paper is divided into three parts. The first part explains how to culture EML cells and separate Lin-CD34+ and Lin-CD34- cells. The second part of the protocol offers detailed procedures for total RNA preparation and the subsequent library construction for high-throughput sequencing. The last part describes the method for RNA-Seq data analysis and explains how to use the data to identify differentially expressed transcription factors between Lin-CD34+ and Lin-CD34- cells. The most significantly differentially expressed transcription factors were identified to be the potential key regulators controlling EML cell self-renewal and differentiation. In the discussion section of this paper, we highlight the key steps for successful performance of this experiment. In summary, this paper offers a method of using RNA-Seq technology to identify potential regulators of self-renewal and differentiation in EML cells. The key factors identified are subjected to downstream functional analysis in vitro and in vivo.

  8. Identification of Key Factors Regulating Self-renewal and Differentiation in EML Hematopoietic Precursor Cells by RNA-sequencing Analysis

    PubMed Central

    Chen, Kenian; Wu, Jia Qian

    2014-01-01

    Hematopoietic stem cells (HSCs) are used clinically for transplantation treatment to rebuild a patient's hematopoietic system in many diseases such as leukemia and lymphoma. Elucidating the mechanisms controlling HSCs self-renewal and differentiation is important for application of HSCs for research and clinical uses. However, it is not possible to obtain large quantity of HSCs due to their inability to proliferate in vitro. To overcome this hurdle, we used a mouse bone marrow derived cell line, the EML (Erythroid, Myeloid, and Lymphocytic) cell line, as a model system for this study. RNA-sequencing (RNA-Seq) has been increasingly used to replace microarray for gene expression studies. We report here a detailed method of using RNA-Seq technology to investigate the potential key factors in regulation of EML cell self-renewal and differentiation. The protocol provided in this paper is divided into three parts. The first part explains how to culture EML cells and separate Lin-CD34+ and Lin-CD34- cells. The second part of the protocol offers detailed procedures for total RNA preparation and the subsequent library construction for high-throughput sequencing. The last part describes the method for RNA-Seq data analysis and explains how to use the data to identify differentially expressed transcription factors between Lin-CD34+ and Lin-CD34- cells. The most significantly differentially expressed transcription factors were identified to be the potential key regulators controlling EML cell self-renewal and differentiation. In the discussion section of this paper, we highlight the key steps for successful performance of this experiment. In summary, this paper offers a method of using RNA-Seq technology to identify potential regulators of self-renewal and differentiation in EML cells. The key factors identified are subjected to downstream functional analysis in vitro and in vivo. PMID:25407807

  9. Elucidating the triggers, progression, and effects of Alzheimer's disease.

    PubMed

    Medeiros, Rodrigo; Chabrier, Meredith A; LaFerla, Frank M

    2013-01-01

    As the number of patients with Alzheimer's disease (AD) continues to rise, the need for efficacious therapeutics is becoming more and more urgent. Understanding the molecular relationship and interactions between Aβ and tau and their contribution to cognitive decline remain one of the most fundamental and unresolved questions in the AD field. Likewise, elucidating the initial triggers of disease pathology, as well as the impact of various factors such as stress and inflammation on disease progression, are equally important to fully understand this devastating disorder. Here we discuss recent studies that have illuminated the importance of key facilitators of disease progression using the 3xTg-AD and CaM/Tet-DTA mouse models, and suggest viable targets for ameliorating both molecular pathology and cognitive decline.

  10. SARS: Key factors in crisis management.

    PubMed

    Tseng, Hsin-Chao; Chen, Thai-Form; Chou, Shieu-Ming

    2005-03-01

    This study was conducted at a single hospital selected in Taipei during the SARS (Severe Acute Respiratory Syndrome) outbreak from March to July, 2003 in Taiwan. During this period of time, 104 SARS patients were admitted to the hospital. There were no negative reports related to the selected hospital despite its being located right in the center of an area struck by the epidemic. The purpose of this study was to identify the key factors enabling the hospital to survive SARS unscathed. Data were collected from in-depth interviews with the nursing directors and nursing managers of the SARS units, along with a review of relevant hospital documents. The five key elements identified as survival factors during this SARS crisis are as follows: 1. good control of timing for crisis management, 2. careful decision-making, 3. thorough implementation, 4. effective communication, and 5. trust between management and employees. The results of this study reconfirmed the selected hospital as a model for good crisis management during the SARS epidemic.

  11. Key factors affecting dying children and their families.

    PubMed

    Hinds, Pamela S; Schum, Lisa; Baker, Justin N; Wolfe, Joanne

    2005-01-01

    The death of a child alters the life and health of others immediately and for the rest of their lives. How a child dies influences parents' abilities to continue their role functions as well as siblings' abilities to make and maintain friendships, and may be the basis for health care providers' decisions to exit direct care roles. Thus, facilitating a "good death"-an obvious care priority for all involved with the dying child-ought also to be a priority for the health of bereaved families and affected health care providers. Making this a care priority is complicated by a serious lack of data, as details of the last hours or weeks of a dying child or adolescent's life are largely unknown. The purpose of this paper is to identify key factors that affect the course of dying children and adolescents and that of their bereaved survivors, and to link those key factors to needed research that could produce clinically relevant findings to improve the care of these patients. Key factors described here include suffering (physical, psychological, and spiritual), communication, decision making, prognostic ambiguities, ability of the seriously ill child to give assent to research participation, and educational preparation of health care providers to give competent end-of-life care.

  12. Organization of Anti-Phase Synchronization Pattern in Neural Networks: What are the Key Factors?

    PubMed Central

    Li, Dong; Zhou, Changsong

    2011-01-01

    Anti-phase oscillation has been widely observed in cortical neural network. Elucidating the mechanism underlying the organization of anti-phase pattern is of significance for better understanding more complicated pattern formations in brain networks. In dynamical systems theory, the organization of anti-phase oscillation pattern has usually been considered to relate to time delay in coupling. This is consistent to conduction delays in real neural networks in the brain due to finite propagation velocity of action potentials. However, other structural factors in cortical neural network, such as modular organization (connection density) and the coupling types (excitatory or inhibitory), could also play an important role. In this work, we investigate the anti-phase oscillation pattern organized on a two-module network of either neuronal cell model or neural mass model, and analyze the impact of the conduction delay times, the connection densities, and coupling types. Our results show that delay times and coupling types can play key roles in this organization. The connection densities may have an influence on the stability if an anti-phase pattern exists due to the other factors. Furthermore, we show that anti-phase synchronization of slow oscillations can be achieved with small delay times if there is interaction between slow and fast oscillations. These results are significant for further understanding more realistic spatiotemporal dynamics of cortico-cortical communications. PMID:22232576

  13. From shared care to disease management: key-influencing factors

    PubMed Central

    Eijkelberg, Irmgard M.J.G.; Spreeuwenberg, Cor; Mur-Veeman, Ingrid M.; Wolffenbuttel, Bruce H.R.

    2001-01-01

    Abstract Background In order to improve the quality of care of chronically ill patients the traditional boundaries between primary and secondary care are questioned. To demolish these boundaries so-called ‘shared care’ projects have been initiated in which different ways of substitution of care are applied. When these projects end, disease management may offer a solution to expand the achieved co-operation between primary and secondary care. Objective Answering the question: What key factors influence the development and implementation of shared care projects from a management perspective and how are they linked? Theory The theoretical framework is based on the concept of the learning organisation. Design Reference point is a multiple case study that finally becomes a single case study. Data are collected by means of triangulation. The studied cases concern two interrelated Dutch shared care projects for type 2 diabetic patients, that in the end proceed as one disease management project. Results In these cases the predominant key-influencing factors appear to be the project management, commitment and local context, respectively. The factor project management directly links the latter two, albeit managing both appear prerequisites to its success. In practice this implies managing the factors' interdependency by the application of change strategies and tactics in a committed and skilful way. Conclusion Project management, as the most important and active key factor, is advised to cope with the interrelationships of the influencing factors in a gradually more fundamental way by using strategies and tactics that enable learning processes. Then small-scale shared care projects may change into a disease management network at a large scale, which may yield the future blueprint to proceed. PMID:16896415

  14. From shared care to disease management: key-influencing factors.

    PubMed

    Eijkelberg, I M; Spreeuwenberg, C; Mur-Veeman, I M; Wolffenbuttel, B H

    2001-01-01

    In order to improve the quality of care of chronically ill patients the traditional boundaries between primary and secondary care are questioned. To demolish these boundaries so-called 'shared care' projects have been initiated in which different ways of substitution of care are applied. When these projects end, disease management may offer a solution to expand the achieved co-operation between primary and secondary care. Answering the question: What key factors influence the development and implementation of shared care projects from a management perspective and how are they linked? The theoretical framework is based on the concept of the learning organisation. Reference point is a multiple case study that finally becomes a single case study. Data are collected by means of triangulation. The studied cases concern two interrelated Dutch shared care projects for type 2 diabetic patients, that in the end proceed as one disease management project. In these cases the predominant key-influencing factors appear to be the project management, commitment and local context, respectively. The factor project management directly links the latter two, albeit managing both appear prerequisites to its success. In practice this implies managing the factors' interdependency by the application of change strategies and tactics in a committed and skillful way. Project management, as the most important and active key factor, is advised to cope with the interrelationships of the influencing factors in a gradually more fundamental way by using strategies and tactics that enable learning processes. Then small-scale shared care projects may change into a disease management network at a large scale, which may yield the future blueprint to proceed.

  15. Elucidating Key Motifs Required for Arp2/3-Dependent and Independent Actin Nucleation by Las17/WASP

    PubMed Central

    Urbanek, Agnieszka N.; Smaczynska-de Rooij, Iwona I.

    2016-01-01

    Actin nucleation is the key rate limiting step in the process of actin polymerization, and tight regulation of this process is critical to ensure actin filaments form only at specific times and at defined regions of the cell. Arp2/3 is a well-characterised protein complex that can promote nucleation of new filaments, though its activity requires additional nucleation promotion factors (NPFs). The best recognized of these factors are the WASP family of proteins that contain binding motifs for both monomeric actin and for Arp2/3. Previously we demonstrated that the yeast WASP homologue, Las17, in addition to activating Arp2/3 can also nucleate actin filaments de novo, independently of Arp2/3. This activity is dependent on its polyproline rich region. Through biochemical and in vivo analysis we have now identified key motifs within the polyproline region that are required for nucleation and elongation of actin filaments, and have addressed the role of the WH2 domain in the context of actin nucleation without Arp2/3. We have also demonstrated that full length Las17 is able to bind liposomes giving rise to the possibility of direct linkage of nascent actin filaments to specific membrane sites to which Las17 has been recruited. Overall, we propose that Las17 functions as the key initiator of de novo actin filament formation at endocytic sites by nucleating, elongating and tethering nascent filaments which then serve as a platform for Arp2/3 recruitment and function. PMID:27637067

  16. The Future of Government Funding for Persons with Disabilities: Some Key Factors.

    ERIC Educational Resources Information Center

    Ross, E. Clarke

    1980-01-01

    The paper identifies and discusses key factors associated with government funding for disabled individuals. An introductory section traces the growth of public expenditures in recent years. Five key factors affecting government funding are examined (sample subtopics in parentheses): state government tax and spending limits (Proposition 13 and the…

  17. A systems biology approach for elucidating the interaction of curcumin with Fanconi anemia FANC G protein and the key disease targets of leukemia.

    PubMed

    Mahato, David; Samanta, Dipayan; Mukhopadhyay, Sudit S; Krishnaraj, R Navanietha

    2017-06-01

    Fanconi anemia (FA) is an autosomal recessive disorder with a high risk of malignancies including acute myeloid leukemia and squamous cell carcinoma. There is a constant search out of new potential therapeutic molecule to combat this disorder. In most cases, patients with FA develop haematological malignancies with acute myeloid leukemia and acute lymphoblastic leukemia. Identifying drugs which can efficiently block the pathways of both these disorders can be an ideal and novel strategy to treat FA. The curcumin, a natural compound obtained from turmeric is an interesting therapeutic molecule as it has been reported in the literature to combat both FA as well as leukemia. However, its complete mechanism is not elucidated. Herein, a systems biology approach for elucidating the therapeutic potential of curcumin against FA and leukemia is investigated by analyzing the computational molecular interactions of curcumin ligand with FANC G of FA and seven other key disease targets of leukemia. The proteins namely DOT1L, farnesyl transferase (FDPS), histone decetylase (EP3000), Polo-like kinase (PLK-2), aurora-like kinase (AUKRB), tyrosine kinase (ABL1), and retinoic acid receptor alpha (RARA) were chosen as disease targets for leukemia and modeled structure of FANC G protein as the disease target for FA. The docking investigations showed that curcumin had a very high binding affinity of -8.1 kcal/mol with FANC G protein. The key disease targets of leukemia namely tyrosine kinase (ABL1), aurora-like kinase (AUKRB), and polo-like kinase (PLK-2) showed that they had the comparable binding affinities of -9.7 k cal/mol, -8.7 k cal/mol, and -8.6 k cal/mol, respectively with curcumin. Further, the percentage similarity scores obtained from PAM50 using EMBOSS MATCHER was shown to provide a clue to understand the structural relationships to an extent and to predict the binding affinity. This investigation shows that curcumin effectively interacts with the disease targets of both

  18. Key Factors that Influence Recruiting Young Chinese Students

    ERIC Educational Resources Information Center

    Wang, Zhenmin

    2007-01-01

    The discussion in this paper is based on the assumption that international education is equated to recruiting and educating international students, even though its true concept goes far beyond this narrow understanding. The purpose of this research is to look at the key factors that influence recruiting young Chinese students, and make sure all…

  19. Experimental Infections with Mycoplasma agalactiae Identify Key Factors Involved in Host-Colonization

    PubMed Central

    Baranowski, Eric; Bergonier, Dominique; Sagné, Eveline; Hygonenq, Marie-Claude; Ronsin, Patricia; Berthelot, Xavier; Citti, Christine

    2014-01-01

    Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i) the development of a specific antibody response and (ii) dynamic changes in expression of M. agalactiae surface variable proteins (Vpma), with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs. PMID:24699671

  20. Elucidating determinants of aerosol composition through particle-type-based receptor modeling

    NASA Astrophysics Data System (ADS)

    McGuire, M. L.; Jeong, C.-H.; Slowik, J. G.; Chang, R. Y.-W.; Corbin, J. C.; Lu, G.; Mihele, C.; Rehbein, P. J. G.; Sills, D. M. L.; Abbatt, J. P. D.; Brook, J. R.; Evans, G. J.

    2011-08-01

    An aerosol time-of-flight mass spectrometer (ATOFMS) was deployed at a semi-rural site in southern Ontario to characterize the size and chemical composition of individual particles. Particle-type-based receptor modelling of these data was used to investigate the determinants of aerosol chemical composition in this region. Individual particles were classified into particle-types and positive matrix factorization (PMF) was applied to their temporal trends to separate and cross-apportion particle-types to factors. The extent of chemical processing for each factor was assessed by evaluating the internal and external mixing state of the characteristic particle-types. The nine factors identified helped to elucidate the coupled interactions of these determinants. Nitrate-laden dust was found to be the dominant type of locally emitted particles measured by ATOFMS. Several factors associated with aerosol transported to the site from intermediate local-to-regional distances were identified: the Organic factor was associated with a combustion source to the north-west; the ECOC Day factor was characterized by nearby local-to-regional carbonaceous emissions transported from the south-west during the daytime; and the Fireworks factor consisted of pyrotechnic particles from the Detroit region following holiday fireworks displays. Regional aerosol from farther emissions sources was reflected through three factors: two Biomass Burning factors and a highly chemically processed Long Range Transport factor. The Biomass Burning factors were separated by PMF due to differences in chemical processing which were in part elucidated by the passage of two thunderstorm gust fronts with different air mass histories. The remaining two factors, ECOC Night and Nitrate Background, represented the night-time partitioning of nitrate to pre-existing particles of different origins. The distinct meteorological conditions observed during this month-long study in the summer of 2007 provided a unique

  1. Exploring key factors in online shopping with a hybrid model.

    PubMed

    Chen, Hsiao-Ming; Wu, Chia-Huei; Tsai, Sang-Bing; Yu, Jian; Wang, Jiangtao; Zheng, Yuxiang

    2016-01-01

    Nowadays, the web increasingly influences retail sales. An in-depth analysis of consumer decision-making in the context of e-business has become an important issue for internet vendors. However, factors affecting e-business are complicated and intertwined. To stimulate online sales, understanding key influential factors and causal relationships among the factors is important. To gain more insights into this issue, this paper introduces a hybrid method, which combines the Decision Making Trial and Evaluation Laboratory (DEMATEL) with the analytic network process, called DANP method, to find out the driving factors that influence the online business mostly. By DEMATEL approach the causal graph showed that "online service" dimension has the highest degree of direct impact on other dimensions; thus, the internet vendor is suggested to made strong efforts on service quality throughout the online shopping process. In addition, the study adopted DANP to measure the importance of key factors, among which "transaction security" proves to be the most important criterion. Hence, transaction security should be treated with top priority to boost the online businesses. From our study with DANP approach, the comprehensive information can be visually detected so that the decision makers can spotlight on the root causes to develop effectual actions.

  2. Identifying Key Hospital Service Quality Factors in Online Health Communities

    PubMed Central

    Jung, Yuchul; Hur, Cinyoung; Jung, Dain

    2015-01-01

    Background The volume of health-related user-created content, especially hospital-related questions and answers in online health communities, has rapidly increased. Patients and caregivers participate in online community activities to share their experiences, exchange information, and ask about recommended or discredited hospitals. However, there is little research on how to identify hospital service quality automatically from the online communities. In the past, in-depth analysis of hospitals has used random sampling surveys. However, such surveys are becoming impractical owing to the rapidly increasing volume of online data and the diverse analysis requirements of related stakeholders. Objective As a solution for utilizing large-scale health-related information, we propose a novel approach to identify hospital service quality factors and overtime trends automatically from online health communities, especially hospital-related questions and answers. Methods We defined social media–based key quality factors for hospitals. In addition, we developed text mining techniques to detect such factors that frequently occur in online health communities. After detecting these factors that represent qualitative aspects of hospitals, we applied a sentiment analysis to recognize the types of recommendations in messages posted within online health communities. Korea’s two biggest online portals were used to test the effectiveness of detection of social media–based key quality factors for hospitals. Results To evaluate the proposed text mining techniques, we performed manual evaluations on the extraction and classification results, such as hospital name, service quality factors, and recommendation types using a random sample of messages (ie, 5.44% (9450/173,748) of the total messages). Service quality factor detection and hospital name extraction achieved average F1 scores of 91% and 78%, respectively. In terms of recommendation classification, performance (ie, precision) is

  3. Identifying key hospital service quality factors in online health communities.

    PubMed

    Jung, Yuchul; Hur, Cinyoung; Jung, Dain; Kim, Minki

    2015-04-07

    The volume of health-related user-created content, especially hospital-related questions and answers in online health communities, has rapidly increased. Patients and caregivers participate in online community activities to share their experiences, exchange information, and ask about recommended or discredited hospitals. However, there is little research on how to identify hospital service quality automatically from the online communities. In the past, in-depth analysis of hospitals has used random sampling surveys. However, such surveys are becoming impractical owing to the rapidly increasing volume of online data and the diverse analysis requirements of related stakeholders. As a solution for utilizing large-scale health-related information, we propose a novel approach to identify hospital service quality factors and overtime trends automatically from online health communities, especially hospital-related questions and answers. We defined social media-based key quality factors for hospitals. In addition, we developed text mining techniques to detect such factors that frequently occur in online health communities. After detecting these factors that represent qualitative aspects of hospitals, we applied a sentiment analysis to recognize the types of recommendations in messages posted within online health communities. Korea's two biggest online portals were used to test the effectiveness of detection of social media-based key quality factors for hospitals. To evaluate the proposed text mining techniques, we performed manual evaluations on the extraction and classification results, such as hospital name, service quality factors, and recommendation types using a random sample of messages (ie, 5.44% (9450/173,748) of the total messages). Service quality factor detection and hospital name extraction achieved average F1 scores of 91% and 78%, respectively. In terms of recommendation classification, performance (ie, precision) is 78% on average. Extraction and

  4. Enhanced Two-Factor Authentication and Key Agreement Using Dynamic Identities in Wireless Sensor Networks.

    PubMed

    Chang, I-Pin; Lee, Tian-Fu; Lin, Tsung-Hung; Liu, Chuan-Ming

    2015-11-30

    Key agreements that use only password authentication are convenient in communication networks, but these key agreement schemes often fail to resist possible attacks, and therefore provide poor security compared with some other authentication schemes. To increase security, many authentication and key agreement schemes use smartcard authentication in addition to passwords. Thus, two-factor authentication and key agreement schemes using smartcards and passwords are widely adopted in many applications. Vaidya et al. recently presented a two-factor authentication and key agreement scheme for wireless sensor networks (WSNs). Kim et al. observed that the Vaidya et al. scheme fails to resist gateway node bypassing and user impersonation attacks, and then proposed an improved scheme for WSNs. This study analyzes the weaknesses of the two-factor authentication and key agreement scheme of Kim et al., which include vulnerability to impersonation attacks, lost smartcard attacks and man-in-the-middle attacks, violation of session key security, and failure to protect user privacy. An efficient and secure authentication and key agreement scheme for WSNs based on the scheme of Kim et al. is then proposed. The proposed scheme not only solves the weaknesses of previous approaches, but also increases security requirements while maintaining low computational cost.

  5. Enhanced Two-Factor Authentication and Key Agreement Using Dynamic Identities in Wireless Sensor Networks

    PubMed Central

    Chang, I-Pin; Lee, Tian-Fu; Lin, Tsung-Hung; Liu, Chuan-Ming

    2015-01-01

    Key agreements that use only password authentication are convenient in communication networks, but these key agreement schemes often fail to resist possible attacks, and therefore provide poor security compared with some other authentication schemes. To increase security, many authentication and key agreement schemes use smartcard authentication in addition to passwords. Thus, two-factor authentication and key agreement schemes using smartcards and passwords are widely adopted in many applications. Vaidya et al. recently presented a two-factor authentication and key agreement scheme for wireless sensor networks (WSNs). Kim et al. observed that the Vaidya et al. scheme fails to resist gateway node bypassing and user impersonation attacks, and then proposed an improved scheme for WSNs. This study analyzes the weaknesses of the two-factor authentication and key agreement scheme of Kim et al., which include vulnerability to impersonation attacks, lost smartcard attacks and man-in-the-middle attacks, violation of session key security, and failure to protect user privacy. An efficient and secure authentication and key agreement scheme for WSNs based on the scheme of Kim et al. is then proposed. The proposed scheme not only solves the weaknesses of previous approaches, but also increases security requirements while maintaining low computational cost. PMID:26633396

  6. Identification of the key ecological factors influencing vegetation degradation in semi-arid agro-pastoral ecotone considering spatial scales

    NASA Astrophysics Data System (ADS)

    Peng, Yu; Wang, Qinghui; Fan, Min

    2017-11-01

    When assessing re-vegetation project performance and optimizing land management, identification of the key ecological factors inducing vegetation degradation has crucial implications. Rainfall, temperature, elevation, slope, aspect, land use type, and human disturbance are ecological factors affecting the status of vegetation index. However, at different spatial scales, the key factors may vary. Using Helin County, Inner-Mongolia, China as the study site and combining remote sensing image interpretation, field surveying, and mathematical methods, this study assesses key ecological factors affecting vegetation degradation under different spatial scales in a semi-arid agro-pastoral ecotone. It indicates that the key factors are different at various spatial scales. Elevation, rainfall, and temperature are identified as crucial for all spatial extents. Elevation, rainfall and human disturbance are key factors for small-scale quadrats of 300 m × 300 m and 600 m × 600 m, temperature and land use type are key factors for a medium-scale quadrat of 1 km × 1 km, and rainfall, temperature, and land use are key factors for large-scale quadrats of 2 km × 2 km and 5 km × 5 km. For this region, human disturbance is not the key factor for vegetation degradation across spatial scales. It is necessary to consider spatial scale for the identification of key factors determining vegetation characteristics. The eco-restoration programs at various spatial scales should identify key influencing factors according their scales so as to take effective measurements. The new understanding obtained in this study may help to explore the forces which driving vegetation degradation in the degraded regions in the world.

  7. SCOR based key success factors in cooking oil supply chain buyers perspective in Padang City

    NASA Astrophysics Data System (ADS)

    Zahara, Fatimah; Hadiguna, Rika Ampuh

    2017-11-01

    Supply chain of cooking oil is a network of companies from palm oil as raw material to retailers which work to create the value and deliver products into the end consumers. This paper is aimed to study key success factors based on consumer's perspective as the last stage in the supply chain. Consumers who are examined in this study are restaurants management or owners. Restaurant is the biggest consumption of cooking oil. The factors is studied based on Supply Chain Operation Reference (SCOR) version 10.0. Factors used are formulated based on the third-level metrics of SCOR Model. Factors are analyzed using factors analysis. This study found factors which become key success factors in managing supply chain of cooking oil encompass reliability, responsiveness and agility. Key success factors can be applied by governments as policy making and cooking oil companies as formulation of the distribution strategies.

  8. Teachers' Professional Development: What Are the Key Change Factors for Mathematics Teachers?

    ERIC Educational Resources Information Center

    Pehkonen, Erkki; Torner, Gunter

    1999-01-01

    Surveyed and interviewed 13 experienced German middle school mathematics teachers to examine key factors causing discontinuity in their professional development. Results included 49 statements about change that fell into four categories. Researchers extracted three change factors not reported in earlier literature: experiences and observations…

  9. Graduate Entrepreneurship Incubation Environments: A Framework of Key Success Factors

    ERIC Educational Resources Information Center

    Al-Dajani, Haya; Dedoussis, Evangelos; Watson, Erika; Tzokas, Nikalaos

    2014-01-01

    The benchmarking framework developed in this study is specifically designed for higher education institutions to consider when developing environments to encourage entrepreneurship among their students, graduates and staff. The objective of the study was to identify key success factors of Graduate Entrepreneurship Incubator Environments (GEIEs)…

  10. Identifying Key Drivers of Return Reversal with Dynamical Bayesian Factor Graph

    PubMed Central

    Zhao, Shuai; Tong, Yunhai; Wang, Zitian; Tan, Shaohua

    2016-01-01

    In the stock market, return reversal occurs when investors sell overbought stocks and buy oversold stocks, reversing the stocks’ price trends. In this paper, we develop a new method to identify key drivers of return reversal by incorporating a comprehensive set of factors derived from different economic theories into one unified dynamical Bayesian factor graph. We then use the model to depict factor relationships and their dynamics, from which we make some interesting discoveries about the mechanism behind return reversals. Through extensive experiments on the US stock market, we conclude that among the various factors, the liquidity factors consistently emerge as key drivers of return reversal, which is in support of the theory of liquidity effect. Specifically, we find that stocks with high turnover rates or high Amihud illiquidity measures have a greater probability of experiencing return reversals. Apart from the consistent drivers, we find other drivers of return reversal that generally change from year to year, and they serve as important characteristics for evaluating the trends of stock returns. Besides, we also identify some seldom discussed yet enlightening inter-factor relationships, one of which shows that stocks in Finance and Insurance industry are more likely to have high Amihud illiquidity measures in comparison with those in other industries. These conclusions are robust for return reversals under different thresholds. PMID:27893780

  11. Identifying Key Drivers of Return Reversal with Dynamical Bayesian Factor Graph.

    PubMed

    Zhao, Shuai; Tong, Yunhai; Wang, Zitian; Tan, Shaohua

    2016-01-01

    In the stock market, return reversal occurs when investors sell overbought stocks and buy oversold stocks, reversing the stocks' price trends. In this paper, we develop a new method to identify key drivers of return reversal by incorporating a comprehensive set of factors derived from different economic theories into one unified dynamical Bayesian factor graph. We then use the model to depict factor relationships and their dynamics, from which we make some interesting discoveries about the mechanism behind return reversals. Through extensive experiments on the US stock market, we conclude that among the various factors, the liquidity factors consistently emerge as key drivers of return reversal, which is in support of the theory of liquidity effect. Specifically, we find that stocks with high turnover rates or high Amihud illiquidity measures have a greater probability of experiencing return reversals. Apart from the consistent drivers, we find other drivers of return reversal that generally change from year to year, and they serve as important characteristics for evaluating the trends of stock returns. Besides, we also identify some seldom discussed yet enlightening inter-factor relationships, one of which shows that stocks in Finance and Insurance industry are more likely to have high Amihud illiquidity measures in comparison with those in other industries. These conclusions are robust for return reversals under different thresholds.

  12. Part II--Factors Associated with School Nurse Ratios: Key State Informants' Perceptions

    ERIC Educational Resources Information Center

    Maughan, Erin

    2009-01-01

    This paper is the second of a two-part series examining factors influencing school nurse to pupil staffing ratios. The paper reports data from a qualitative study exploring the social and political factors that potentially influence ratios. Interviews were conducted with 30 key state informants from these states. Content analysis of the data…

  13. Key success factors of health research centers: A mixed method study.

    PubMed

    Tofighi, Shahram; Teymourzadeh, Ehsan; Heydari, Majid

    2017-08-01

    In order to achieve success in future goals and activities, health research centers are required to identify their key success factors. This study aimed to extract and rank the factors affecting the success of research centers at one of the medical universities in Iran. This study is a mixed method (qualitative-quantitative) study, which was conducted between May to October in 2016. The study setting was 22 health research centers. In qualitative phase, we extracted the factors affecting the success in research centers through purposeful interviews with 10 experts of centers, and classified them into themes and sub-themes. In the quantitative phase, we prepared a questionnaire and scored and ranked the factors recognized by 54 of the study samples by Friedman test. Nine themes and 42 sub-themes were identified. Themes included: strategic orientation, management, human capital, support, projects, infrastructure, communications and collaboration, paradigm and innovation and they were rated respectively as components of success in research centers. Among the 42 identified factors, 10 factors were ranked respectively as the key factors of success, and included: science and technology road map, strategic plan, evaluation indexes, committed human resources, scientific evaluation of members and centers, innovation in research and implementation, financial support, capable researchers, equipment infrastructure and teamwork. According to the results, the strategic orientation was the most important component in the success of research centers. Therefore, managers and authorities of research centers should pay more attention to strategic areas in future planning, including the science and technology road map and strategic plan.

  14. Key success factors of health research centers: A mixed method study

    PubMed Central

    Tofighi, Shahram; Teymourzadeh, Ehsan; Heydari, Majid

    2017-01-01

    Background In order to achieve success in future goals and activities, health research centers are required to identify their key success factors. Objective This study aimed to extract and rank the factors affecting the success of research centers at one of the medical universities in Iran. Methods This study is a mixed method (qualitative-quantitative) study, which was conducted between May to October in 2016. The study setting was 22 health research centers. In qualitative phase, we extracted the factors affecting the success in research centers through purposeful interviews with 10 experts of centers, and classified them into themes and sub-themes. In the quantitative phase, we prepared a questionnaire and scored and ranked the factors recognized by 54 of the study samples by Friedman test. Results Nine themes and 42 sub-themes were identified. Themes included: strategic orientation, management, human capital, support, projects, infrastructure, communications and collaboration, paradigm and innovation and they were rated respectively as components of success in research centers. Among the 42 identified factors, 10 factors were ranked respectively as the key factors of success, and included: science and technology road map, strategic plan, evaluation indexes, committed human resources, scientific evaluation of members and centers, innovation in research and implementation, financial support, capable researchers, equipment infrastructure and teamwork. Conclusion According to the results, the strategic orientation was the most important component in the success of research centers. Therefore, managers and authorities of research centers should pay more attention to strategic areas in future planning, including the science and technology road map and strategic plan. PMID:28979733

  15. EG-VEGF: a key endocrine factor in placental development.

    PubMed

    Brouillet, Sophie; Hoffmann, Pascale; Feige, Jean-Jacques; Alfaidy, Nadia

    2012-10-01

    Endocrine gland-derived vascular endothelial growth factor (EG-VEGF), also named prokineticin 1, is the canonical member of the prokineticin family. Numerous reports suggest a direct involvement of this peptide in normal and pathological reproductive processes. Recent advances propose EG-VEGF as a key endocrine factor that controls many aspects of placental development and suggest its involvement in the development of preeclampsia (PE), the most threatening pathology of human pregnancy. This review describes the finely tuned action and regulation of EG-VEGF throughout human pregnancy, argues for its clinical relevance as a potential diagnostic marker of the onset of PE, and discusses future research directions for therapeutic targeting of EG-VEGF. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Integrating Genetic and Functional Genomic Data to Elucidate Common Disease Tra

    NASA Astrophysics Data System (ADS)

    Schadt, Eric

    2005-03-01

    The reconstruction of genetic networks in mammalian systems is one of the primary goals in biological research, especially as such reconstructions relate to elucidating not only common, polygenic human diseases, but living systems more generally. Here I present a statistical procedure for inferring causal relationships between gene expression traits and more classic clinical traits, including complex disease traits. This procedure has been generalized to the gene network reconstruction problem, where naturally occurring genetic variations in segregating mouse populations are used as a source of perturbations to elucidate tissue-specific gene networks. Differences in the extent of genetic control between genders and among four different tissues are highlighted. I also demonstrate that the networks derived from expression data in segregating mouse populations using the novel network reconstruction algorithm are able to capture causal associations between genes that result in increased predictive power, compared to more classically reconstructed networks derived from the same data. This approach to causal inference in large segregating mouse populations over multiple tissues not only elucidates fundamental aspects of transcriptional control, it also allows for the objective identification of key drivers of common human diseases.

  17. Key factors of clinical research network capacity building.

    PubMed

    Li, Guowei; Wu, Qianyu; Jin, Yanling; Vanniyasingam, Thuva; Thabane, Lehana

    2018-01-01

    In general, clinical research network capacity building refers to programs aimed at enhancing networks of researchers to conduct clinical research. Although in the literature there is a large body of research on how to develop and build capacity in clinical research networks, the conceptualizations and implementations remain controversial and challenging. Moreover, the experiences learnt from the past accomplishments and failures can assist in the future capacity building efforts to be more practical, effective and efficient. In this paper, we aim to provide an overview of capacity building in clinical research network by (1) identifying the key barriers to clinical research network capacity building, (2) providing insights into how to overcome those obstacles, and (3) sharing our experiences in collaborating with national and international partners to build capacity in clinical research networks. In conclusion, we have provided some insight into how to address the key factors of clinical research network capacity building and shared some empirical experiences. A successful capacity building practice requires a joint endeavor to procure sufficient resources and support from the relevant stakeholders, to ensure its efficiency, cost-effectiveness, and sustainability.

  18. Identification of key transcription factors in caerulein-induced pancreatitis through expression profiling data

    PubMed Central

    QI, DACHUAN; WU, BO; TONG, DANIAN; PAN, YE; CHEN, WEI

    2015-01-01

    The current study aimed to isolate key transcription factors (TFs) in caerulein-induced pancreatitis, and to identify the difference between wild type and Mist1 knockout (KO) mice, in order to elucidate the contribution of Mist1 to pancreatitis. The gene profile of GSE3644 was downloaded from the Gene Expression Omnibus database then analyzed using the t-test. The isolated differentially expressed genes (DEGs) were mapped into a transcriptional regulatory network derived from the Integrated Transcription Factor Platform database and in the network, the interaction pairs involving at least one DEG were screened. Fisher’s exact test was used to analyze the functional enrichment of the target genes. A total of 1,555 and 3,057 DEGs were identified in the wild type and Mist1KO mice treated with caerulein, respectively. DEGs screened in Mist1KO mice were predominantly enriched in apoptosis, mitogen-activated protein kinase signaling and other cancer-associated pathways. A total of 188 and 51 TFs associated with pathopoiesis were isolated in Mist1KO and wild type mice, respectively. Out of the top 10 TFs (ranked by P-value), 7 TFs, including S-phase kinase-associated protein 2 (Skp2); minichromosome maintenance complex component 3 (Mcm3); cell division cycle 6 (Cdc6); cyclin B1 (Ccnb1); mutS homolog 6 (Msh6); cyclin A2 (Ccna2); and cyclin B2 (Ccnb2), were expressed in the two types of mouse. These TFs were predominantly involved in phosphorylation, DNA replication, cell division and DNA mismatch repair. In addition, specific TFs, including minichromosome maintenance complex component 7 (Mcm7); lymphoid-specific helicase (Hells); and minichromosome maintenance complex component 6 (Mcm6), that function in the unwinding of DNA were identified to participate in Mist1KO pancreatitis. The DEGs, including Cdc6, Mcm6, Msh6 and Wdr1 are closely associated with the regulation of caerulein-induced pancreatitis. Furthermore, other identified TFs were also involved in this type of

  19. Elucidation of Sigma Factor-Associated Networks in Pseudomonas aeruginosa Reveals a Modular Architecture with Limited and Function-Specific Crosstalk

    PubMed Central

    Schulz, Sebastian; Eckweiler, Denitsa; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Dötsch, Andreas; Hornischer, Klaus; Bruchmann, Sebastian; Düvel, Juliane; Häussler, Susanne

    2015-01-01

    Sigma factors are essential global regulators of transcription initiation in bacteria which confer promoter recognition specificity to the RNA polymerase core enzyme. They provide effective mechanisms for simultaneously regulating expression of large numbers of genes in response to challenging conditions, and their presence has been linked to bacterial virulence and pathogenicity. In this study, we constructed nine his-tagged sigma factor expressing and/or deletion mutant strains in the opportunistic pathogen Pseudomonas aeruginosa. To uncover the direct and indirect sigma factor regulons, we performed mRNA profiling, as well as chromatin immunoprecipitation coupled to high-throughput sequencing. We furthermore elucidated the de novo binding motif of each sigma factor, and validated the RNA- and ChIP-seq results by global motif searches in the proximity of transcriptional start sites (TSS). Our integrated approach revealed a highly modular network architecture which is composed of insulated functional sigma factor modules. Analysis of the interconnectivity of the various sigma factor networks uncovered a limited, but highly function-specific, crosstalk which orchestrates complex cellular processes. Our data indicate that the modular structure of sigma factor networks enables P. aeruginosa to function adequately in its environment and at the same time is exploited to build up higher-level functions by specific interconnections that are dominated by a participation of RpoN. PMID:25780925

  20. RM-DEMATEL: a new methodology to identify the key factors in PM2.5.

    PubMed

    Chen, Yafeng; Liu, Jie; Li, Yunpeng; Sadiq, Rehan; Deng, Yong

    2015-04-01

    Weather system is a relative complex dynamic system, the factors of the system are mutually influenced PM2.5 concentration. In this paper, a new method is proposed to quantify the influence on PM2.5 by other factors in the weather system and identify the most important factors for PM2.5 with limited resources. The relation map (RM) is used to figure out the direct relation matrix of 14 factors in PM2.5. The decision making trial and evaluation laboratory(DEMATEL) is applied to calculate the causal relationship and extent to a mutual influence of 14 factors in PM2.5. According to the ranking results of our proposed method, the most important key factors is sulfur dioxide (SO2) and nitrogen oxides (NO(X)). In addition, the other factors, the ambient maximum temperature (T(max)), concentration of PM10, and wind direction (W(dir)), are important factors for PM2.5. The proposed method can also be applied to other environment management systems to identify key factors.

  1. Myopic Loss Aversion: Demystifying the Key Factors Influencing Decision Problem Framing

    ERIC Educational Resources Information Center

    Hardin, Andrew M.; Looney, Clayton Arlen

    2012-01-01

    Advancement of myopic loss aversion theory has been hamstrung by conflicting results, methodological inconsistencies, and a piecemeal approach toward understanding the key factors influencing decision problem framing. A series of controlled experiments provides a more holistic view of the variables promoting myopia. Extending the information…

  2. Six Key Factors for Changing Preservice Teachers' Attitudes/Beliefs about Diversity

    ERIC Educational Resources Information Center

    Garmon, M. Arthur

    2005-01-01

    In this article the author postulates there are six key factors associated with changing preservice teachers' attitudes toward and beliefs about diversity-their dispositions, which include openness, self-awarenesss/self-reflectiveness, and commitment to social justice; and their experiences, which include intercultural, educational, and support…

  3. Protein analysis: key to the future.

    PubMed

    Boodhun, Nawsheen

    2018-05-01

    Protein analysis is crucial to elucidating the function of proteins and understanding the impact of their presence, absence and alteration. This is key to advancing knowledge about diseases, providing the opportunity for biomarker discovery and development of therapeutics. In this issue of Tech News, Nawsheen Boodhun explores the various means of protein analysis.

  4. Structural modeling of the AhR:ARNT complex in the bHLH-PASA-PASB region elucidates the key determinants of dimerization.

    PubMed

    Corrada, Dario; Denison, Michael S; Bonati, Laura

    2017-05-02

    Elucidation of the dimerization process of the aryl hydrocarbon receptor (AhR) with the AhR nuclear translocator (ARNT) is crucial for understanding the mechanisms underlying the functional activity of AhR, including mediation of the toxicity of environmental contaminants. In this work, for the first time a structural model of the AhR:ARNT dimer encompassing the entire bHLH-PASA-PASB domain region is proposed. It is developed by using a template-based modeling approach, relying on the recently available crystallographic structures of two dimers of homologous systems in the bHLH-PAS family of proteins: the CLOCK:BMAL1 and the HIF2α:ARNT heterodimers. The structural and energetic characteristics of the modeled AhR:ARNT protein-protein interface are determined by evaluating the variations in solvent accessible surface area, the total binding free energy and the per-residue free energy contributions obtained by the MM-GBSA method and the Energy Decomposition Analysis. The analyses of the intricate network of inter-domain interactions at the dimerization interfaces provide insights into the key determinants of dimerization. These are confirmed by comparison of the computational findings with the available experimental mutagenesis and functional analysis data. The results presented here on the AhR:ARNT dimer structure and interactions provide a framework to start analyzing the mechanism of AhR transformation into its functional DNA binding form.

  5. Three-factor anonymous authentication and key agreement scheme for Telecare Medicine Information Systems.

    PubMed

    Arshad, Hamed; Nikooghadam, Morteza

    2014-12-01

    Nowadays, with comprehensive employment of the internet, healthcare delivery services is provided remotely by telecare medicine information systems (TMISs). A secure mechanism for authentication and key agreement is one of the most important security requirements for TMISs. Recently, Tan proposed a user anonymity preserving three-factor authentication scheme for TMIS. The present paper shows that Tan's scheme is vulnerable to replay attacks and Denial-of-Service attacks. In order to overcome these security flaws, a new and efficient three-factor anonymous authentication and key agreement scheme for TMIS is proposed. Security and performance analysis shows superiority of the proposed scheme in comparison with previously proposed schemes that are related to security of TMISs.

  6. Psychological factors mediate key symptoms of fibromyalgia through their influence on stress.

    PubMed

    Malin, Katrina; Littlejohn, Geoffrey Owen

    2016-09-01

    The clinical features of fibromyalgia are associated with various psychological factors, including stress. We examined the hypothesis that the path that psychological factors follow in influencing fibromyalgia symptoms is through their direct effect on stress. Ninety-eight females with ACR 1990 classified fibromyalgia completed the following questionnaires: The Big 5 Personality Inventory, Fibromyalgia Impact Questionnaire, Perceived Stress Scale, Profile of Mood States, Mastery Scale, and Perceived Control of Internal States Scale. SPSS (PASW version 22) was used to perform basic t tests, means, and standard deviations to show difference between symptom characteristics. Pathway analysis using structural equation modelling (Laavan) examined the effect of stress on the relationships between psychological factors and the elements that define the fibromyalgia phenotype. The preferred model showed that the identified path clearly linked the psychological variables of anxiety, neuroticism and mastery, but not internal control, to the three key elements of fibromyalgia, namely pain, fatigue and sleep (p < 0.001), via the person's perceived stress. Confusion, however, did not fit the preferred model. This study confirms that stress is a necessary link in the pathway between certain identified, established and significant psychological factors and key fibromyalgia symptoms. This has implications for the understanding of contributing mechanisms and the clinical care of patients with fibromyalgia.

  7. Key factors influencing the intention of telecare adoption: an institutional perspective.

    PubMed

    Liu, Chung-Feng

    2011-05-01

    The objective of this study was to explore key factors of influence on the adoption of telecare by care institutions. This investigation was based on an extensive Technology-Organization-Environment framework comprising the four constructs of technology, organization, environment, and the project planning as well as corresponding variables. This study utilized a self-administered questionnaire for data collection, focusing on the managers of all 339 nursing homes in Taiwan for the census survey. A total of 70 valid questionnaires yielded a response rate of 20.65%. After analyzing the responses through the Partial Least Squares approach, government support, technological knowledge, supplier support, team skills, and compatibility were found to be the five key factors that positively impact intention to adopt telecare from an institutional perspective. The results of this study indicated that care institutions, for the most part, are willing to develop telecare and are already incorporating preliminary applications of telecare, such as distance learning and resident positioning. Solutions to potential issues related to implementing telecare in practice are also proposed in this study.

  8. Fibroblast growth factors: key players in regeneration and tissue repair.

    PubMed

    Maddaluno, Luigi; Urwyler, Corinne; Werner, Sabine

    2017-11-15

    Tissue injury initiates a complex repair process, which in some organisms can lead to the complete regeneration of a tissue. In mammals, however, the repair of most organs is imperfect and results in scar formation. Both regeneration and repair are orchestrated by a highly coordinated interplay of different growth factors and cytokines. Among the key players are the fibroblast growth factors (FGFs), which control the migration, proliferation, differentiation and survival of different cell types. In addition, FGFs influence the expression of other factors involved in the regenerative response. Here, we summarize current knowledge on the roles of endogenous FGFs in regeneration and repair in different organisms and in different tissues and organs. Gaining a better understanding of these FGF activities is important for appropriate modulation of FGF signaling after injury to prevent impaired healing and to promote organ regeneration in humans. © 2017. Published by The Company of Biologists Ltd.

  9. Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

    PubMed

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

  10. Key factors of low carbon development strategy for sustainable transport

    NASA Astrophysics Data System (ADS)

    Thaveewatanaseth, K.; Limjirakan, S.

    2018-02-01

    Cities become more vulnerable to climate change impacts causing by urbanization, economic growth, increasing of energy consumption and carbon dioxide (CO2) emissions. People who live in the cities have already been affected from the impacts in terms of socioeconomic and environmental aspects. Sustainable transport plays the key role in CO2 mitigation and contributes positive impacts on sustainable development for the cities. Several studies in megacities both in developed and developing countries support that mass transit system is an important transportation mode in CO2 mitigation and sustainable transport development. This paper aims to study key factors of low carbon development strategy for sustainable transport. The Bangkok Mass Rapid Transit System (MRT) located in Bangkok was the study area. Data collection was using semi-structured in-depth interview protocol with thirty respondents consisting of six groups i.e. governmental agencies, the MRT operators, consulting companies, international organizations, non-profit organizations, and experts. The research findings highlighted the major factors and supplemental elements composing of institution and technical capacity, institutional framework, policy setting and process, and plan of implementation that would support more effective strategic process for low carbon development strategy (LCDS) for sustainable transport. The study would highly recommend on readiness of institution and technical capacities, stakeholder mapping, high-level decision- makers participation, and a clear direction of the governmental policies that are strongly needed in achieving the sustainable transport.

  11. Association, intrinsic shape, and molecular recognition: Elucidating DNA biophysics through coarse-grained simulation

    NASA Astrophysics Data System (ADS)

    Freeman, Gordon Samuel

    DNA is of central importance in biology as it is responsible for carrying, copying, and translating the genetic code into the building blocks that comprise life. In order to accomplish these tasks, the DNA molecule must be versatile and robust. Indeed, the underlying molecular interactions that allow DNA to execute these tasks are complex and their origins are only beginning to be understood. While experiments are able to elucidate many key biophysical phenomena, there remain many unanswered questions. Molecular simulation is able to shed light on phenomena at the molecular scale and provide information that is missing from experimental views of DNA behavior. In this dissertation I use state-of-the-art coarse-grained DNA models to address two key problems. In the first, metadynamics calculations are employed to uncover the free energy surface of two complimentary DNA strands. This free energy surface takes on the appearance of a hybridization funnel and reveals candidates for intermediate states in the hybridization of short DNA oligomers. Such short oligomers are important building blocks for DNA-driven self-assembly and the mechanism of hybridization in this regime is not well understood. The second problem is that of nucleosome formation. Nucleosomes are the fundamental subunit of genome compaction in the nucleus of a cell. As such, nucleosomes are a key epigenetic factor and affect gene expression and the ability of DNA-binding proteins to locate and bind to the appropriate position in the genome. However, the factors that drive nucleosome positioning are not well understood. While DNA sequence is known to affect nucleosome formation, the mechanism by which it does so has not been established and a number of hypotheses explaining this sequence-dependence exist in the literature. I demonstrate that DNA shape dominates this process with contributions arising from both intrinsic DNA curvature as well as DNA-protein interactions driven by sequence

  12. Key factors controlling ozone production in wildfire plumes

    NASA Astrophysics Data System (ADS)

    Jaffe, D. A.

    2017-12-01

    Production of ozone in wildfire plumes is complex and highly variable. As a wildfire plume mixes into an urban area, ozone is often, but not always, produced. We have examined multiple factors that can help explain some of this variability. This includes CO/NOy enhancement ratios, photolysis rates, PAN/NOy fraction and degree of NOx oxidation. While fast ozone production is well known, on average, ozone production increases downwind in a plume for several days. Peroxyacetyl nitrate (PAN) is likely a key cause for delayed ozone formation. Recent observations at the Mt. Bachelor Observatory a mountain top observatory relatively remote from nearby anthropogenic influence and in Boise Idaho, an urban setting, show the importance of PAN in wildfire plumes. From these observations we can devise a conceptual model that considers four factors in ozone production: NOx/VOC emission ratio; degree of NOx oxidation; transport time and pathway; and mixing with urban pollutants. Using this conceptual model, we can then devise a lagrangian modeling strategy that can be used to improve our understanding of ozone production in wildfire plumes, both in remote and urban settings.

  13. That's why I take my ONS. Means-end chain as a novel approach to elucidate the personally relevant factors driving ONS consumption in nutritionally frail elderly users.

    PubMed

    den Uijl, Louise C; Kremer, Stefanie; Jager, Gerry; van der Stelt, Annelies J; de Graaf, Cees; Gibson, Peter; Godfrey, James; Lawlor, J Ben

    2015-06-01

    Oral nutritional supplements (ONS) are a recommended form of nutritional intervention for older malnourished persons when a 'food first' approach and/or food fortification prove ineffective. The efficacy of ONS will depend on, amongst other factors, whether persons do, or do not, consume their prescribed amount. Factors influencing ONS consumption can be product, context, or person related. Whereas product and context have received some attention, little is known about the person factors driving ONS consumption. In addition, the relative importance of the product, context, and person factors to ONS consumption is not known. Using the means-end chain (MEC) method, the current study elucidated personally relevant factors (product, context, and person factors) related to ONS consumption in two groups of older nutritionally frail ONS users: community-dwelling persons and care home residents with mainly somatic disorders. To our knowledge, the current work is the first to apply the MEC method to study older nutritionally frail ONS users. Forty ONS users (n = 20 per group) were recruited via healthcare professionals. The level of frailty was assessed using the FRAIL scale. Both groups were interviewed for 30 to 45 minutes using the soft laddering technique. The laddering data were analysed using LadderUX software™. The MEC method appeared to work well in both groups. The majority of the participants took ONS on their doctor's or dietician's prescription as they trusted their advice. The community-dwelling group took ONS to prolong their independence, whereas the care home group reported values that related more to small improvements in quality of life. In addition, care home residents perceived themselves as dependent on their caregiver for their ONS arrangements, whereas this dependence was not reported by community-dwelling persons. Key insights from this work will enable doctors and dieticians to customize their nutritional interventions to ONS users' personal

  14. Key Educational Factors in the Education of Students with a Medical Condition

    ERIC Educational Resources Information Center

    Capurso, Michele; Dennis, John L.

    2017-01-01

    The education of children with a medical condition represents a unique educational context. The key educational factors that can help these children continue their education despite the burdens associated with their illness were discussed and analysed by a pool of experts for an EU funded project. In this context, "relationships,"…

  15. Part II--Factors associated with school nurse ratios: key state informants' perceptions.

    PubMed

    Maughan, Erin

    2009-08-01

    This paper is the second of a two-part series examining factors influencing school nurse to pupil staffing ratios. The paper reports data from a qualitative study exploring the social and political factors that potentially influence ratios. Interviews were conducted with 30 key state informants from these states. Content analysis of the data identified common themes. Positive factors reported to influence ratios included: the approach taken to effect change, value placed upon school nurses, local support (from both educators and parents) and community buy-in, fear of litigation, and dynamic leadership. Barriers to improving ratios included: lack of funding and misunderstanding of the role of the school nurse. Philosophical beliefs and state geography were "swing" factors that influenced staffing positively or negatively. This study adds to our knowledge of the factors influencing staffing and highlights important social and political factors that school nurses can target to improve nurse to pupil ratios.

  16. Pharmacokinetics of Exosomes-An Important Factor for Elucidating the Biological Roles of Exosomes and for the Development of Exosome-Based Therapeutics.

    PubMed

    Morishita, Masaki; Takahashi, Yuki; Nishikawa, Makiya; Takakura, Yoshinobu

    2017-09-01

    Exosomes are small membrane vesicles containing lipids, proteins, and nucleic acids. Recently, researchers have uncovered that exosomes are involved in various biological events, such as tumor growth, metastasis, and the immune response, by delivering their cargos to exosome-receiving cells. Moreover, exosomes are expected to be used in therapeutic treatments, such as tissue regeneration therapy and antitumor immunotherapy, because exosomes are effective delivery vehicles for proteins, nucleic acids, and other bioactive compounds. To elucidate the biological functions of exosomes, and for the development of exosome-based therapeutics, the pharmacokinetics of exosomes is important. In this review, we aim to summarize current knowledge about the pharmacokinetics and biodistribution of exosomes. The pharmacokinetics of exogenously administered exosomes is discussed based on the tissue distribution, types of cells taking up exosomes, and key molecules in the pharmacokinetics of exosomes. In addition, recent progress in the methods to control the pharmacokinetics of exosomes is reviewed. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  17. Key Factors Influencing Rapid Development of Potentially Dune-Stabilizing Moss-Dominated Crusts

    PubMed Central

    Bu, Chongfeng; Zhang, Kankan; Zhang, Chunyun; Wu, Shufang

    2015-01-01

    Biological soil crusts (BSCs) are a widespread photosynthetic ground cover in arid and semiarid areas. They have many positive ecological functions, such as increasing soil stability, and reducing water and wind erosion. Using artificial technology to achieve the rapid development of BSCs is expected to become a low-cost and highly beneficial ecological restoration measure. In the present study, typical moss-dominated crusts in a region characterized by mobile dunes (Mu Us Sandland, China) were collected, and a 40-day cultivation experiment was performed to investigate key factors, including watering frequency, light intensity and a nutrient addition, which affect the rapid development of moss crusts and their optimal combination. The results demonstrated that watering frequency and illumination had a significant positive effect (P=0.049, three-factor ANOVA) and a highly significant, complicated effect (P=0.000, three-factor ANOVA), respectively, on the plant density of bryophytes, and a highly significant positive effect on the chlorophyll a and exopolysaccharide contents (P=0.000, P=0.000; P=0.000, P=0.000; one-way ANOVA). Knop nutrient solution did not have a significant positive but rather negative effect on the promotion of moss-dominated crust development (P=0.270, three-factor ANOVA). Moss-dominated crusts treated with the combination of moderate-intensity light (6,000 lx) + high watering frequency (1 watering/2 days) - Knop had the highest moss plant densities, while the treatment with high-intensity light (12,000 lx) + high watering frequency (1 watering/2 days) + Knop nutrient solution had higher chlorophyll a contents than that under other treatments. It is entirely feasible to achieve the rapid development of moss crusts under laboratory conditions by regulating key factors and creating the right environment. Future applications may seek to use cultured bryophytes to control erosion in vulnerable areas with urgent needs. PMID:26230324

  18. Targeted intervention: Computational approaches to elucidate and predict relapse in alcoholism.

    PubMed

    Heinz, Andreas; Deserno, Lorenz; Zimmermann, Ulrich S; Smolka, Michael N; Beck, Anne; Schlagenhauf, Florian

    2017-05-01

    Alcohol use disorder (AUD) and addiction in general is characterized by failures of choice resulting in repeated drug intake despite severe negative consequences. Behavioral change is hard to accomplish and relapse after detoxification is common and can be promoted by consumption of small amounts of alcohol as well as exposure to alcohol-associated cues or stress. While those environmental factors contributing to relapse have long been identified, the underlying psychological and neurobiological mechanism on which those factors act are to date incompletely understood. Based on the reinforcing effects of drugs of abuse, animal experiments showed that drug, cue and stress exposure affect Pavlovian and instrumental learning processes, which can increase salience of drug cues and promote habitual drug intake. In humans, computational approaches can help to quantify changes in key learning mechanisms during the development and maintenance of alcohol dependence, e.g. by using sequential decision making in combination with computational modeling to elucidate individual differences in model-free versus more complex, model-based learning strategies and their neurobiological correlates such as prediction error signaling in fronto-striatal circuits. Computational models can also help to explain how alcohol-associated cues trigger relapse: mechanisms such as Pavlovian-to-Instrumental Transfer can quantify to which degree Pavlovian conditioned stimuli can facilitate approach behavior including alcohol seeking and intake. By using generative models of behavioral and neural data, computational approaches can help to quantify individual differences in psychophysiological mechanisms that underlie the development and maintenance of AUD and thus promote targeted intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Agri-Environmental Resource Management by Large-Scale Collective Action: Determining KEY Success Factors

    ERIC Educational Resources Information Center

    Uetake, Tetsuya

    2015-01-01

    Purpose: Large-scale collective action is necessary when managing agricultural natural resources such as biodiversity and water quality. This paper determines the key factors to the success of such action. Design/Methodology/Approach: This paper analyses four large-scale collective actions used to manage agri-environmental resources in Canada and…

  20. KF-finder: identification of key factors from host-microbial networks in cervical cancer.

    PubMed

    Hu, Jialu; Gao, Yiqun; Zheng, Yan; Shang, Xuequn

    2018-04-24

    The human body is colonized by a vast number of microbes. Microbiota can benefit many normal life processes, but can also cause many diseases by interfering the regular metabolism and immune system. Recent studies have demonstrated that the microbial community is closely associated with various types of cell carcinoma. The search for key factors, which also refer to cancer causing agents, can provide an important clue in understanding the regulatory mechanism of microbiota in uterine cervix cancer. In this paper, we investigated microbiota composition and gene expression data for 58 squamous and adenosquamous cell carcinoma. A host-microbial covariance network was constructed based on the 16s rRNA and gene expression data of the samples, which consists of 259 abundant microbes and 738 differentially expressed genes (DEGs). To search for risk factors from host-microbial networks, the method of bi-partite betweenness centrality (BpBC) was used to measure the risk of a given node to a certain biological process in hosts. A web-based tool KF-finder was developed, which can efficiently query and visualize the knowledge of microbiota and differentially expressed genes (DEGs) in the network. Our results suggest that prevotellaceade, tissierellaceae and fusobacteriaceae are the most abundant microbes in cervical carcinoma, and the microbial community in cervical cancer is less diverse than that of any other boy sites in health. A set of key risk factors anaerococcus, hydrogenophilaceae, eubacterium, PSMB10, KCNIP1 and KRT13 have been identified, which are thought to be involved in the regulation of viral response, cell cycle and epithelial cell differentiation in cervical cancer. It can be concluded that permanent changes of microbiota composition could be a major force for chromosomal instability, which subsequently enables the effect of key risk factors in cancer. All our results described in this paper can be freely accessed from our website at http://www.nwpu-bioinformatics.com/KF-finder/ .

  1. ION COMPOSITION ELUCIDATION (ICE)

    EPA Science Inventory



    Ion Composition Elucidation (ICE) utilizes selected ion recording with a double focusing mass spectrometer to simultaneously determine exact masses and relative isotopic abundances from mass peak profiles. These can be determined more accurately and at higher sensitivity ...

  2. Elucidating determinants of aerosol composition through particle-type-based receptor modeling

    NASA Astrophysics Data System (ADS)

    McGuire, M. L.; Jeong, C.-H.; Slowik, J. G.; Chang, R. Y.-W.; Corbin, J. C.; Lu, G.; Mihele, C.; Rehbein, P. J. G.; Sills, D. M. L.; Abbatt, J. P. D.; Brook, J. R.; Evans, G. J.

    2011-03-01

    An aerosol time-of-flight mass spectrometer (ATOFMS) was deployed at a semi-rural site in Southern Ontario to characterize the size and chemical composition of individual particles. Particle-type-based receptor modelling of these data was used to investigate the determinants of aerosol chemical composition in this region. Individual particles were classified into particle-types and positive matrix factorization (PMF) was applied to their temporal trends to separate and cross-apportion particle-types to factors. The extent of chemical processing for each factor was assessed by evaluating the internal and external mixing state of the characteristic particle-types. The nine factors identified helped to elucidate the coupled interactions of these determinants. Nitrate-laden dust was found to be the dominant type of locally emitted particles measured by ATOFMS. Several factors associated with aerosol transported to the site from intermediate local-to-regional distances were identified: the Organic factor was associated with a combustion source to the north-west; the ECOC Day factor was characterized by nearby local-to-regional carbonaceous emissions transported from the south-west during the daytime; and the Fireworks factor consisted of pyrotechnic particles from the Detroit region following holiday fireworks displays. Regional aerosol from farther emissions sources were reflected through three factors: two biomass burning factors and a highly chemically processed long range transport factor. The biomass burning factors were separated by PMF due to differences in chemical processing which were caused in part by the passage of two thunderstorm gust fronts with different air mass histories. The remaining two factors, ECOC Night and Nitrate Background, represented the night-time partitioning of nitrate to pre-existing particles of different origins. The distinct meteorological conditions observed during this month-long study in the summer of 2007 provided a unique range

  3. Key factors of successful JIT integration with IBS - An overview

    NASA Astrophysics Data System (ADS)

    Asri, Mohammad Azwanie Naim Mohammad; Nawi, Mohd Nasrun Mohd; Nadarajan, Santhirasegaran

    2016-08-01

    The Just-In-Time (JIT) philosophy has been used for many decades to increase productivity through waste elimination process. The purpose of this paper is to contribute to the knowledge by addressing the transportation and material delivery activities in Industrialized Building System (IBS) and integrating JIT to improve the performance of those activities. The literature review has been conducted through relevant database. It was found that there is a need for more holistic approach to be adopted to integrate JIT in IBS project. This paper discusses the key success factors for effective integration between JIT and IBS in the context of transportation and material delivery activities.

  4. Key factors influencing allied health research capacity in a large Australian metropolitan health district

    PubMed Central

    Alison, Jennifer A; Zafiropoulos, Bill; Heard, Robert

    2017-01-01

    Objective The aim of this study was to identify key factors affecting research capacity and engagement of allied health professionals working in a large metropolitan health service. Identifying such factors will assist in determining strategies for building research capacity in allied health. Materials and methods A total of 276 allied health professionals working within the Sydney Local Health District (SLHD) completed the Research Capacity in Context Tool (RCCT) that measures research capacity and culture across three domains: organization, team, and individual. An exploratory factor analysis was undertaken to identify common themes within each of these domains. Correlations were performed between demographic variables and the identified factors to determine possible relationships. Results Research capacity and culture success/skill levels were reported to be higher within the organization and team domains compared to the individual domain (median [interquartile range, IQR] 6 [5–8], 6 [5–8], 5 [3–7], respectively; Friedman χ2(2)=42.04, p<0.001). Exploratory factor analyses were performed to identify factors that were perceived by allied health respondents to affect research capacity. Factors identified within the organization domain were infrastructure for research (eg, funds and equipment) and research culture (eg, senior manager’s support for research); within the team domain the factors were research orientation (eg, dissemination of results at research seminars) and research support (eg, providing staff research training). Within the individual domain, only one factor was identified which was the research skill of the individual (eg, literature evaluation, submitting ethics applications and data analysis, and writing for publication). Conclusion The reported skill/success levels in research were lower for the individual domain compared to the organization or team domains. Key factors were identified in each domain that impacted on allied health

  5. Social Work Practice with Latinos: Key Issues for Social Workers

    ERIC Educational Resources Information Center

    Furman, Rich; Negi, Nalini Junko; Iwamoto, Derek Kenji; Rowan, Diana; Shukraft, Allison; Gragg, Jennifer

    2009-01-01

    The Latino population is the fastest growing group in the United States; thus, it is imperative that social workers and other mental health practitioners be knowledgeable about the current literature on how to effectively serve this population. This article elucidates key issues and knowledge, such as immigration and migration concerns; discusses…

  6. Key factors of case management interventions for frequent users of healthcare services: a thematic analysis review.

    PubMed

    Hudon, Catherine; Chouinard, Maud-Christine; Lambert, Mireille; Diadiou, Fatoumata; Bouliane, Danielle; Beaudin, Jérémie

    2017-10-22

    The aim of this paper was to identify the key factors of case management (CM) interventions among frequent users of healthcare services found in empirical studies of effectiveness. Thematic analysis review of CM studies. We built on a previously published review that aimed to report the effectiveness of CM interventions for frequent users of healthcare services, using the Medline, Scopus and CINAHL databases covering the January 2004-December 2015 period, then updated to July 2017, with the keywords 'CM' and 'frequent use'. We extracted factors of successful (n=7) and unsuccessful (n=6) CM interventions and conducted a mixed thematic analysis to synthesise findings. Chaudoir's implementation of health innovations framework was used to organise results into four broad levels of factors: (1) ,environmental/organisational level, (2) practitioner level, (3) patient level and (4) programme level. Access to, and close partnerships with, healthcare providers and community services resources were key factors of successful CM interventions that should target patients with the greatest needs and promote frequent contacts with the healthcare team. The selection and training of the case manager was also an important factor to foster patient engagement in CM. Coordination of care, self-management support and assistance with care navigation were key CM activities. The main issues reported by unsuccessful CM interventions were problems with case finding or lack of care integration. CM interventions for frequent users of healthcare services should ensure adequate case finding processes, rigorous selection and training of the case manager, sufficient intensity of the intervention, as well as good care integration among all partners. Other studies could further evaluate the influence of contextual factors on intervention impacts. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted

  7. Key factors of case management interventions for frequent users of healthcare services: a thematic analysis review

    PubMed Central

    Hudon, Catherine; Chouinard, Maud-Christine; Lambert, Mireille; Diadiou, Fatoumata; Bouliane, Danielle; Beaudin, Jérémie

    2017-01-01

    Objective The aim of this paper was to identify the key factors of case management (CM) interventions among frequent users of healthcare services found in empirical studies of effectiveness. Design Thematic analysis review of CM studies. Methods We built on a previously published review that aimed to report the effectiveness of CM interventions for frequent users of healthcare services, using the Medline, Scopus and CINAHL databases covering the January 2004–December 2015 period, then updated to July 2017, with the keywords ‘CM’ and ‘frequent use’. We extracted factors of successful (n=7) and unsuccessful (n=6) CM interventions and conducted a mixed thematic analysis to synthesise findings. Chaudoir’s implementation of health innovations framework was used to organise results into four broad levels of factors: (1) environmental/organisational level, (2) practitioner level, (3) patient level and (4) programme level. Results Access to, and close partnerships with, healthcare providers and community services resources were key factors of successful CM interventions that should target patients with the greatest needs and promote frequent contacts with the healthcare team. The selection and training of the case manager was also an important factor to foster patient engagement in CM. Coordination of care, self-management support and assistance with care navigation were key CM activities. The main issues reported by unsuccessful CM interventions were problems with case finding or lack of care integration. Conclusions CM interventions for frequent users of healthcare services should ensure adequate case finding processes, rigorous selection and training of the case manager, sufficient intensity of the intervention, as well as good care integration among all partners. Other studies could further evaluate the influence of contextual factors on intervention impacts. PMID:29061623

  8. The Key Factors Analysis of Palisades Temperature in Deep Open-pit Mine

    NASA Astrophysics Data System (ADS)

    Wang, Yuan; Du, Cuifeng; Jin, Wenbo; Wang, Puyu

    2018-01-01

    In order to study the key factors of palisades temperature field in a deep open-pit mine in the natural environment, the influence of natural factors on the palisades temperature in a deep open-pit mine were analysed based on the principle of heat transfer. Four typical places with different ways of solar radiation were selected to carry out the field test. The results show that solar radiation, atmospheric temperature, and wind speed are three main factors affecting the temperature of palisades and that the direct sunlight plays a leading role. The time period of the sun shining directly on the shady slope of the palisades is short because of blocking effect, whose temperature changes in a smaller scale. At the same time, the sun slope of the palisades suffers from the solar radiation for a long time, whose temperature changes in a larger scale, and the variation is similar to the air temperature.

  9. Isolation and structure elucidation of the nucleoside antibiotic strepturidin from Streptomyces albus DSM 40763.

    PubMed

    Pesic, Alexander; Steinhaus, Britta; Kemper, Sebastian; Nachtigall, Jonny; Kutzner, Hans Jürgen; Höfle, Gerhard; Süssmuth, Roderich D

    2014-06-01

    The antibiotic strepturidin (1) was isolated from the microorganism Streptomyces albus DSM 40763, and its structure elucidated by spectroscopic methods and chemical degradation studies. The determination of the relative and absolute stereocenters was partially achieved using chiral GC/EI-MS analysis and microderivatization by acetal ring formation and subsequent 2D-NMR analysis of key (1)H,(1)H-NOESY NMR correlations and extraction of (1)H,(13)C coupling constants from (1)H,(13)C-HMBC NMR spectra. Based on these results, a biosynthesis model was proposed.

  10. Applying iPSCs for Preserving Endangered Species and Elucidating the Evolution of Mammalian Sex Determination.

    PubMed

    Honda, Arata

    2018-06-01

    The endangered species Tokudaia osimensis has the unique chromosome constitution of 2n = 25, with an XO/XO sex chromosome configuration (2n = 25; XO). There is urgency to preserve this species and to elucidate the regulator(s) that can discriminate the males and females arising from the indistinguishable sex chromosome constitution. However, it is not realistic to examine this rare animal species by sacrificing individuals. Recently, true naïve induced pluripotent stem cells were successfully generated from a female T. osimensis, and the sexual plasticity of its germ cells was elucidated. This achievement constitutes the basis of an attractive research area, including embryonic fate determination, sex determination, and factor(s) that can replace the Y chromosome. In this essay, concrete strategies to conserve rare animal species and to reveal their specific characteristics using other compatible and abundant animals are proposed. © 2018 WILEY Periodicals, Inc.

  11. Teaching Experiment to Elucidate a Cation-Pi Effect in an Alkyne Cycloaddition Reaction and Illustrate Hypothesis-Driven Design of Experiments

    ERIC Educational Resources Information Center

    St.Germain, Elijah J.; Horowitz, Andrew S.; Rucco, Dominic; Rezler, Evonne M.; Lepore, Salvatore D.

    2017-01-01

    An organic chemistry experiment is described that is based on recent research to elucidate a novel cation-pi interaction between tetraalkammonium cations and propargyl hydrazines. This nonbonded interaction is a key component of the mechanism of ammonium-catalyzed intramolecular cycloaddition of nitrogen to the terminal carbon of a C-C triple bond…

  12. Key factors influencing lung cancer survival in northern Italy.

    PubMed

    Mangone, Lucia; Minicozzi, Pamela; Vicentini, Massimo; Giacomin, Adriano; Caldarella, Adele; Cirilli, Claudia; Falcini, Fabio; Giorgi Rossi, Paolo; Sant, Milena

    2013-06-01

    Lung cancer is a major cause of cancer death worldwide. The aims of this study were to analyze presentation, treatment and survival for lung cancer in northern Italy, and identify factors influencing survival. A total of 1180 lung cancer cases diagnosed in four north Italian cancer registries (Biella, Modena, Reggio Emilia, Romagna) in 2003-2005 were analyzed. Information on morphology, stage, diagnostic examinations, chemotherapy, radiotherapy, and surgical treatment was collected from clinical records. Three-year relative survival and relative excess risks of death were estimated. Overall, 10% of cases were stage I, 50% stage IV, and 12% stage unknown. Romagna - where sophisticated diagnostic examinations were performed more often - had proportionately more microscopically verified cases and resected cases than Biella. Romagna had also high proportions of cases given chemotherapy and radiotherapy. Three-year survival was 14%, range 10% (Biella) to 19% (Romagna); 69% for stage I, 3% for stage IV. Stage I survival was higher in Romagna (82%) than Reggio Emilia and Biella (60-61%) but for operated stage I cases, survival was similar (88%) in Romagna and Biella. The fully adjusted model showed a higher risk of death in Biella (1.23, 95%CI 1.02-1.48) than Modena (reference). Stage and surgery are key factors influencing survival. Centralizing lung cancer treatment to improve diagnostic work-up may improve outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Do the key prognostic factors for non-specific neck pain have moderation effects? - A study protocol.

    PubMed

    Balasundaram, Arun Prasad; Robinson, Hilde Stendal; Vøllestad, Nina Køpke

    2018-05-01

    Neck pain is one of the common musculoskeletal conditions prevalent in the general population in Norway. Patients with neck pain, seek treatment from different health professionals such as general practitioners, physiotherapists, chiropractors and alternative medicine practitioners. The interventions for neck pain are typically provided in a primary care or specialised healthcare setting depending on the general practitioners' referral patterns. Clinicians are interested to know the various prognostic factors that can explain the recovery from neck pain. In order to know this, studies have explored and reported on a range of prognostic factors that contribute to the outcomes in patients with neck pain. This information is currently available only for neck pain following whiplash injury that has a traumatic origin. There is limited information on the role of prognostic factors specifically for non-specific neck pain without a traumatic episode. Moreover, there is a lack of data on whether there are interactions (moderation effects) between the prognostic factors. Therefore, we propose a hypothesis to elucidate whether the same set of prognostic factors found in neck pain associated with whiplash injuries are also identified in patients with neck pain without trauma. Additionally, we hypothesize that the association between a prognostic factor and the outcome variable (s) would be dependent on the third variable, thereby confirming the moderation effects. Clinicians could make informed decisions in the clinical management of neck pain with the knowledge of prognostic factors that explain the outcomes. It could also be used for the development of new interventions or for modifying the existing ones. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Elucidation and functional characterization of CsPSY and CsUGT promoters in Crocus sativus L.

    PubMed Central

    Bhat, Archana; Mishra, Sonal; Kaul, Sanjana

    2018-01-01

    The dried stigmas of Crocus sativus constitute the saffron, which is considered to be the costliest spice of the world. Saffron is valuable for its constituents, which are mainly apocarotenoids. In order to enhance the production of apocarotenoids, it is imperative to understand the regulation of apocarotenoid biosynthetic pathway. In C. sativus, although the pathway has been elucidated, the information regarding the regulation of the pathwaygenes is scanty. During the present investigation, the characterization of promoters regulating the expression of two important genes i.e. CsPSY and CsUGT was performed. We successfully cloned the promoters of both the genes, which were functionally characterized in Crocus sativus and Nicotiana tabaccum. In silico analysis of the promoters demonstrated the presence of several important cis regulatory elements responding tolight, hormonesand interaction with transcription factors (TFs). Further analysis suggested the regulation of CsPSY promoter by Abscisic acid (ABA) and that of CsUGT by Gibberellic acid (GA). In addition, we also observed ABA and GA mediated modulation in the expression of significant TFs and CsPSY and CsUGT transcripts. Overall, the study addresses issues related to regulation of key genes of apocarotenoid pathway in C.sativus. PMID:29634744

  15. Elucidation and functional characterization of CsPSY and CsUGT promoters in Crocus sativus L.

    PubMed

    Bhat, Archana; Mishra, Sonal; Kaul, Sanjana; Dhar, Manoj K

    2018-01-01

    The dried stigmas of Crocus sativus constitute the saffron, which is considered to be the costliest spice of the world. Saffron is valuable for its constituents, which are mainly apocarotenoids. In order to enhance the production of apocarotenoids, it is imperative to understand the regulation of apocarotenoid biosynthetic pathway. In C. sativus, although the pathway has been elucidated, the information regarding the regulation of the pathwaygenes is scanty. During the present investigation, the characterization of promoters regulating the expression of two important genes i.e. CsPSY and CsUGT was performed. We successfully cloned the promoters of both the genes, which were functionally characterized in Crocus sativus and Nicotiana tabaccum. In silico analysis of the promoters demonstrated the presence of several important cis regulatory elements responding tolight, hormonesand interaction with transcription factors (TFs). Further analysis suggested the regulation of CsPSY promoter by Abscisic acid (ABA) and that of CsUGT by Gibberellic acid (GA). In addition, we also observed ABA and GA mediated modulation in the expression of significant TFs and CsPSY and CsUGT transcripts. Overall, the study addresses issues related to regulation of key genes of apocarotenoid pathway in C.sativus.

  16. Key Factors in the Success of an Organization's Information Security Culture: A Quantitative Study and Analysis

    ERIC Educational Resources Information Center

    Pierce, Robert E.

    2012-01-01

    This research study reviewed relative literature on information security and information security culture within organizations to determine what factors potentially assist an organization in implementing, integrating, and maintaining a successful organizational information security culture. Based on this review of literature, five key factors were…

  17. Key Motivational Factors in the Retention of Three Generations of Public High School Mathematics Teachers

    ERIC Educational Resources Information Center

    Pospichal, Wendy

    2011-01-01

    Purpose: The purpose of this study was to describe and compare the similarities and differences between five key motivational factors: (a) new teacher induction, (b) noninduction mentor support in the early years of teaching, (c) salary and benefits, (d) working conditions, and (e) administrative support influential in retention of employment in…

  18. WRKY transcription factors: key components in abscisic acid signalling.

    PubMed

    Rushton, Deena L; Tripathi, Prateek; Rabara, Roel C; Lin, Jun; Ringler, Patricia; Boken, Ashley K; Langum, Tanner J; Smidt, Lucas; Boomsma, Darius D; Emme, Nicholas J; Chen, Xianfeng; Finer, John J; Shen, Qingxi J; Rushton, Paul J

    2012-01-01

    WRKY transcription factors (TFs) are key regulators of many plant processes, including the responses to biotic and abiotic stresses, senescence, seed dormancy and seed germination. For over 15 years, limited evidence has been available suggesting that WRKY TFs may play roles in regulating plant responses to the phytohormone abscisic acid (ABA), notably some WRKY TFs are ABA-inducible repressors of seed germination. However, the roles of WRKY TFs in other aspects of ABA signalling, and the mechanisms involved, have remained unclear. Recent significant progress in ABA research has now placed specific WRKY TFs firmly in ABA-responsive signalling pathways, where they act at multiple levels. In Arabidopsis, WRKY TFs appear to act downstream of at least two ABA receptors: the cytoplasmic PYR/PYL/RCAR-protein phosphatase 2C-ABA complex and the chloroplast envelope-located ABAR-ABA complex. In vivo and in vitro promoter-binding studies show that the target genes for WRKY TFs that are involved in ABA signalling include well-known ABA-responsive genes such as ABF2, ABF4, ABI4, ABI5, MYB2, DREB1a, DREB2a and RAB18. Additional well-characterized stress-inducible genes such as RD29A and COR47 are also found in signalling pathways downstream of WRKY TFs. These new insights also reveal that some WRKY TFs are positive regulators of ABA-mediated stomatal closure and hence drought responses. Conversely, many WRKY TFs are negative regulators of seed germination, and controlling seed germination appears a common function of a subset of WRKY TFs in flowering plants. Taken together, these new data demonstrate that WRKY TFs are key nodes in ABA-responsive signalling networks. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  19. Population attributable risk of key modifiable risk factors associated with non-exclusive breastfeeding in Nigeria.

    PubMed

    Ogbo, Felix Akpojene; Page, Andrew; Idoko, John; Agho, Kingsley E

    2018-02-13

    Non-exclusive breastfeeding (non-EBF) is a risk factor for many of the 2300 under-five deaths occurring daily in Nigeria - a developing country with approximately 40 million children. This study aimed to quantify and compare the attributable burden of key modifiable risk factors associated with non-EBF in Nigeria to inform strategic policy responses and initiatives. Relative risk and exposure prevalence for selected modifiable risk factors were used to calculate population attributable fractions based on Nigeria Demographic and Health Surveys data for the period (1999-2013). Scenarios based on feasible impact of community-based interventions in reducing exposure prevalence were also considered to calculate comparative potential impact fractions. In Nigeria, an estimated 22.8% (95% Confidence Interval, CI: 9.2-37.0%) of non-EBF was attributable to primary and no maternal education; 24.7% (95% CI: 9.5-39.5%) to middle and poor household wealth, 9.7% (1.7-18.1%) to lower number (1-3) and no antenatal care visits; 18.8% (95% CI: 6.9-30.8%) to home delivery and 16.6% (95% CI: 3.0-31.3%) to delivery assisted by a non-health professional. In combination, more than half of all cases of non-EBF (64.5%; 95% CI: 50.0-76.4%) could be attributed to those modifiable risk factors. Scenarios based on feasible impacts of community-based approaches to improve health service access and human capacity suggest that an avoidable burden of non-EBF practice of approximately 11% (95% CI: -5.4; 24.7) is achievable. Key modifiable risk factors contribute significantly to non-EBF in Nigerian women. Community-based initiatives and appropriate socio-economic government policies that specifically consider those modifiable risk factors could substantially reduce non-EBF practice in Nigeria.

  20. A genetic approach to elucidate the genotoxic pathway of monomethylarsonousacid (MMAIII) suggests a key role for catalase

    EPA Science Inventory

    Arsenic-contaminated drinking water causes cancer, neuropathy, respiratory effects, diabetes, and cardiovascular disease. Its exact mode of action (MOA) is not fully understood. Oxidative stress has been proposed as a key event in the toxic MOA of arsenic. Our studies are centere...

  1. A genetic approach to elucidate the genotoxic pathway of monomethylarsonous acid suggests a key role for catalase

    EPA Science Inventory

    Although it is widely known that arsenic-contaminated drinking water causes many diseases, arsenic's exact mode of action (MOA) is not fully understood. Induction of oxidative stress has been proposed as an important key event in the toxic MOA of arsenic. Our studies are centered...

  2. Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal

    PubMed Central

    Munger, Steven C.; Aylor, David L.; Syed, Haider Ali; Magwene, Paul M.; Threadgill, David W.; Capel, Blanche

    2009-01-01

    Despite the identification of some key genes that regulate sex determination, most cases of disorders of sexual development remain unexplained. Evidence suggests that the sexual fate decision in the developing gonad depends on a complex network of interacting factors that converge on a critical threshold. To elucidate the transcriptional network underlying sex determination, we took the first expression quantitative trait loci (eQTL) approach in a developing organ. We identified reproducible differences in the transcriptome of the embryonic day 11.5 (E11.5) XY gonad between C57BL/6J (B6) and 129S1/SvImJ (129S1), indicating that the reported sensitivity of B6 to sex reversal is consistent with a higher expression of a female-like transcriptome in B6. Gene expression is highly variable in F2 XY gonads from B6 and 129S1 intercrosses, yet strong correlations emerged. We estimated the F2 coexpression network and predicted roles for genes of unknown function based on their connectivity and position within the network. A genetic analysis of the F2 population detected autosomal regions that control the expression of many sex-related genes, including Sry (sex-determining region of the Y chromosome) and Sox9 (Sry-box containing gene 9), the key regulators of male sex determination. Our results reveal the complex transcription architecture underlying sex determination, and provide a mechanism by which individuals may be sensitized for sex reversal. PMID:19884258

  3. On the Security of a Two-Factor Authentication and Key Agreement Scheme for Telecare Medicine Information Systems.

    PubMed

    Arshad, Hamed; Teymoori, Vahid; Nikooghadam, Morteza; Abbassi, Hassan

    2015-08-01

    Telecare medicine information systems (TMISs) aim to deliver appropriate healthcare services in an efficient and secure manner to patients. A secure mechanism for authentication and key agreement is required to provide proper security in these systems. Recently, Bin Muhaya demonstrated some security weaknesses of Zhu's authentication and key agreement scheme and proposed a security enhanced authentication and key agreement scheme for TMISs. However, we show that Bin Muhaya's scheme is vulnerable to off-line password guessing attacks and does not provide perfect forward secrecy. Furthermore, in order to overcome the mentioned weaknesses, we propose a new two-factor anonymous authentication and key agreement scheme using the elliptic curve cryptosystem. Security and performance analyses demonstrate that the proposed scheme not only overcomes the weaknesses of Bin Muhaya's scheme, but also is about 2.73 times faster than Bin Muhaya's scheme.

  4. "Disease entity" as the key theoretical concept of medicine.

    PubMed

    Hucklenbroich, Peter

    2014-12-01

    Philosophical debates about the concept of disease, particularly of mental disease, might benefit from reconsideration and a closer look at the established terminology and conceptual structure of contemporary medical pathology and clinical nosology. The concepts and principles of medicine differ, to a considerable extent, from the ideas and notions of philosophical theories of disease. In medical theory, the concepts of disease entity and pathologicity are, besides the concept of disease itself, of fundamental importance, and they are essentially connected to the concepts cause of disease or etiological factor, natural course or natural history of disease, and pathological disposition. It is the concept of disease entity that is of key importance for understanding medical pathology and theory of disease. Its central role is shown by a short reconstruction of its main features and its intrinsic connection to the concept of pathologicity. The meaning of pathologicity is elucidated by explicating the underlying criteria. © The Author 2014. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. ION COMPOSITION ELUCIDATION (ICE): AN INVESTIGATIVE ...

    EPA Pesticide Factsheets

    Ion Composition Elucidation (ICE) often leads to identification of compounds and provides high quality evidence for tracking compounds to their sources. Mass spectra for most organic compounds are not found in mass spectral libraries used to tentatively identify analytes. In addition, multiple matches are common. Ion Composition Elucidation provides the numbers of atoms of each element in the ions in the mass spectrum, greatly limiting the number of possible compounds that could produce the mass spectrum. Review of chemical and commercial literature then limits the number of possible compounds to one or a few that can be purchased to confirm tentative compound identifications by comparison of mass spectra and chromatographic retention times. Ion Composition Elucidation is conceptually simple relative to other analytical techniques and more easily explained to a judge or jury. It is based on sums of the exact masses of atoms and their isotopic abundances. Several applications of ICE are demonstrated for ultra-trace-level compounds in an extract of the effluent from a tertiary sewage treatment plant including: (i) measurement of five values to determine an ion's composition and to generate evidence for the compound's identity, (ii) rejection of incorrect library matches, (iii) rapid screening for a target compound in an extract, and (iv) a strategy for tracking unidentified compounds to their sources. The research focused on in the subtasks is the development and

  6. Hypoxia inducible factor 1 (HIF-1) and cardioprotection

    PubMed Central

    Tekin, Demet; Dursun, Ali D; Xi, Lei

    2010-01-01

    Since its discovery in early 1990s, hypoxia inducible factor 1 (HIF-1) has been increasingly recognized for its key role in transcriptional control of more than a hundred genes that regulate a wide-spectrum of cellular functional events, including angiogenesis, vasomotor control, glucose and energy metabolism, erythropoiesis, iron homeostasis, pH regulation, cell proliferation and viability. Evidence accumulated during the past 7 years suggests a critical role for HIF-1α in mediating cardioprotection. The purpose of our present article is to provide an updated overview on this important regulator of gene expression in the cellular stress-responsive and adaptive process. We have particularly emphasized the involvement of HIF-1 in the induction of cardioprotective molecules, such as inducible nitric oxide synthase (iNOS), hemeoxygenase 1 (HO-1), and erythropoietin (EPO), which in turn alleviate myocardial damages caused by harmful events such as ischemia-reperfusion injury. Despite these advances, further in-depth studies are needed to elucidate the possible coordination or interaction between HIF-1α and other key transcription factors in regulating protein expression that leads to cardioprotection. PMID:20711226

  7. Identification of key factors affecting the water pollutant concentration in the sluice-controlled river reaches of the Shaying River in China via statistical analysis methods.

    PubMed

    Dou, Ming; Zhang, Yan; Zuo, Qiting; Mi, Qingbin

    2015-08-01

    The construction of sluices creates a strong disturbance in water environmental factors within a river. The change in water pollutant concentrations of sluice-controlled river reaches (SCRRs) is more complex than that of natural river segments. To determine the key factors affecting water pollutant concentration changes in SCRRs, river reaches near the Huaidian Sluice in the Shaying River of China were selected as a case study, and water quality monitoring experiments based on different regulating modes were implemented in 2009 and 2010. To identify the key factors affecting the change rates for the chemical oxygen demand of permanganate (CODMn) and ammonia nitrogen (NH3-N) concentrations in the SCRRs of the Huaidian Sluice, partial correlation analysis, principal component analysis and principal factor analysis were used. The results indicate four factors, i.e., the inflow quantity from upper reaches, opening size of sluice gates, water pollutant concentration from upper reaches, and turbidity before the sluice, which are the common key factors for the CODMn and NH3-N concentration change rates. Moreover, the dissolved oxygen before a sluice is a key factor for the permanganate concentration from CODMn change rate, and the water depth before a sluice is a key factor for the NH3-N concentration change rate. Multiple linear regressions between the water pollutant concentration change rate and key factors were established via multiple linear regression analyses, and the quantitative relationship between the CODMn and NH3-N concentration change rates and key affecting factors was analyzed. Finally, the mechanism of action for the key factors affecting the water pollutant concentration changes was analyzed. The results reveal that the inflow quantity from upper reaches, opening size of sluice gates, permanganate concentration from CODMn from upper reaches and dissolved oxygen before the sluice have a negative influence and the turbidity before the sluice has a positive

  8. TSLP: A Key Regulator of Asthma Pathogenesis.

    PubMed

    West, Erin E; Kashyap, Mohit; Leonard, Warren J

    2012-12-01

    Asthma is a complex disorder of the airways that is characterized by T helper type 2 (Th2) inflammation. The pleiotrophic cytokine TSLP has emerged as an important player involved in orchestrating the inflammation seen in asthma and other atopic diseases. Early research elucidated the role of TSLP on CD4 + T cells, and recent work has revealed the impact of TSLP on multiple cell types. Furthermore, TSLP plays an important role in the sequential progression of atopic dermatitis to asthma, clarifying the key role of TSLP in the pathogenesis of asthma, a finding with therapeutic implications.

  9. Three-Factor User Authentication and Key Agreement Using Elliptic Curve Cryptosystem in Wireless Sensor Networks.

    PubMed

    Park, YoHan; Park, YoungHo

    2016-12-14

    Secure communication is a significant issue in wireless sensor networks. User authentication and key agreement are essential for providing a secure system, especially in user-oriented mobile services. It is also necessary to protect the identity of each individual in wireless environments to avoid personal privacy concerns. Many authentication and key agreement schemes utilize a smart card in addition to a password to support security functionalities. However, these schemes often fail to provide security along with privacy. In 2015, Chang et al. analyzed the security vulnerabilities of previous schemes and presented the two-factor authentication scheme that provided user privacy by using dynamic identities. However, when we cryptanalyzed Chang et al.'s scheme, we found that it does not provide sufficient security for wireless sensor networks and fails to provide accurate password updates. This paper proposes a security-enhanced authentication and key agreement scheme to overcome these security weaknesses using biometric information and an elliptic curve cryptosystem. We analyze the security of the proposed scheme against various attacks and check its viability in the mobile environment.

  10. Three-Factor User Authentication and Key Agreement Using Elliptic Curve Cryptosystem in Wireless Sensor Networks

    PubMed Central

    Park, YoHan; Park, YoungHo

    2016-01-01

    Secure communication is a significant issue in wireless sensor networks. User authentication and key agreement are essential for providing a secure system, especially in user-oriented mobile services. It is also necessary to protect the identity of each individual in wireless environments to avoid personal privacy concerns. Many authentication and key agreement schemes utilize a smart card in addition to a password to support security functionalities. However, these schemes often fail to provide security along with privacy. In 2015, Chang et al. analyzed the security vulnerabilities of previous schemes and presented the two-factor authentication scheme that provided user privacy by using dynamic identities. However, when we cryptanalyzed Chang et al.’s scheme, we found that it does not provide sufficient security for wireless sensor networks and fails to provide accurate password updates. This paper proposes a security-enhanced authentication and key agreement scheme to overcome these security weaknesses using biometric information and an elliptic curve cryptosystem. We analyze the security of the proposed scheme against various attacks and check its viability in the mobile environment. PMID:27983616

  11. Elucidating the Pathogenesis of Pre-eclampsia Using In Vitro Models of Spiral Uterine Artery Remodelling.

    PubMed

    McNally, Ross; Alqudah, Abdelrahim; Obradovic, Danilo; McClements, Lana

    2017-10-23

    The aim of the study is to perform a critical assessment of in vitro models of pre-eclampsia using complementary human and cell line-based studies. Molecular mechanisms involved in spiral uterine artery (SUA) remodelling and trophoblast functionality will also be discussed. A number of proteins and microRNAs have been implicated as key in SUA remodelling, which could be explored as early biomarkers or therapeutic targets for prevention of pre-eclampsia. Various 2D and 3D in vitro models involving trophoblast cells, endothelial cells, immune cells and placental tissue were discussed to elucidate the pathogenesis of pre-eclampsia. Nevertheless, pre-eclampsia is a multifactorial disease, and the mechanisms involved in its pathogenesis are complex and still largely unknown. Further studies are required to provide better understanding of the key processes leading to inappropriate placental development which is the root cause of pre-eclampsia. This new knowledge could identify novel biomarkers and treatment strategies.

  12. Petunia as model for elucidating adventitious root formation and mycorrhizal symbiosis: at the nexus of physiology, genetics, microbiology and horticulture.

    PubMed

    Druege, Uwe; Franken, Philipp

    2018-05-17

    Adventitious root formation in cuttings and establishment of arbuscular mycorrhizal symbiosis reflect the enormous plasticity of plants and are key factors in the efficient and sustainable clonal propagation and production of ornamental crops. Based on the high importance of Petunia hybrida for the European and US annual bedding plant markets and its suitability as a model for basic plant sciences, petunia has been established as an experimental system for elucidating the molecular and physiological processes underlying adventitious root formation and mycorrhizal symbiosis. In the present review, we introduce the tools of the Petunia model system. Then, we discuss findings regarding the hormonal and metabolic control of adventitious rooting in the context of diverse environmental factors as well as findings on the function of arbuscular mycorrhiza related to nutrient uptake and resistance to root pathogens. Considering the recent publication of the genomes of the parental species of P. hybrida and other tools available in the petunia scientific community, we will outline the quality of petunia as a model for future system-oriented analysis of root development and function in the context of environmental and genetic control, which are at the heart of modern horticulture. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. Why do children and adolescents bully their peers? A critical review of key theoretical frameworks.

    PubMed

    Thomas, Hannah J; Connor, Jason P; Scott, James G

    2018-05-01

    Bullying is a significant public health problem for children and adolescents worldwide. Evidence suggests that both being bullied (bullying victimisation) and bullying others (bullying perpetration) are associated with concurrent and future mental health problems. The onset and course of bullying perpetration are influenced by individual as well as systemic factors. Identifying effective solutions to address bullying requires a fundamental understanding of why it occurs. Drawing from multi-disciplinary domains, this review provides a summary and synthesis of the key theoretical frameworks applied to understanding and intervening on the issue of bullying. A number of explanatory models have been used to elucidate the dynamics of bullying, and broadly these correspond with either system (e.g., social-ecological, family systems, peer-group socialisation) or individual-level (e.g., developmental psychopathology, genetic, resource control, social-cognitive) frameworks. Each theory adds a unique perspective; however, no single framework comprehensively explains why bullying occurs. This review demonstrates that the integration of theoretical perspectives achieves a more nuanced understanding of bullying which is necessary for strengthening evidence-based interventions. Future progress requires researchers to integrate both the systems and individual-level theoretical frameworks to further improve current interventions. More effective intervention across different systems as well as tailoring interventions to the specific needs of the individuals directly involved in bullying will reduce exposure to a key risk factor for mental health problems.

  14. Structure Elucidation of a Natural Product.

    ERIC Educational Resources Information Center

    Letcher, Roy M.

    1983-01-01

    Describes an experiment simulating a real-life structure elucidation problem through isolation, characterization, and chemical transformation of an "unknown," naturally occurring monoterpene, with extensive use being made of spectroscopy and aided by biogenetic considerations. Information given to students, procedures, results, and discussion of…

  15. ELUCID. V. Lighting Dark Matter Halos with Galaxies

    NASA Astrophysics Data System (ADS)

    Yang, Xiaohu; Zhang, Youcai; Wang, Huiyuan; Liu, Chengze; Lu, Tianhuan; Li, Shijie; Shi, Feng; Jing, Y. P.; Mo, H. J.; van den Bosch, Frank C.; Kang, Xi; Cui, Weiguang; Guo, Hong; Li, Guoliang; Lim, S. H.; Lu, Yi; Luo, Wentao; Wei, Chengliang; Yang, Lei

    2018-06-01

    In a recent study, using the distribution of galaxies in the north galactic pole of the SDSS DR7 region enclosed in a 500 {h}-1 {Mpc} box, we carried out our ELUCID simulation (ELUCID III). Here, we light the dark matter halos and subhalos in the reconstructed region in the simulation with galaxies in the SDSS observations using a novel neighborhood abundance matching method. Before we make use of the galaxy–subhalo connections established in the ELUCID simulation to evaluate galaxy formation models, we set out to explore the reliability of such a link. For this purpose, we focus on the following few aspects of galaxies: (1) the central–subhalo luminosity and mass relations, (2) the satellite fraction of galaxies, (3) the conditional luminosity function (CLF) and conditional stellar mass function (CSMF) of galaxies, and (4) the cross-correlation functions between galaxies and dark matter particles, most of which are measured separately for all, red, and blue galaxy populations. We find that our neighborhood abundance matching method accurately reproduces the central–subhalo relations, satellite fraction, and the CLFs, CSMFs, and biases of galaxies. These features ensure that galaxy–subhalo connections thus established will be very useful in constraining galaxy formation processes. We provide some suggestions for the three levels of using the galaxy–subhalo pairs for galaxy formation constraints. The galaxy–subhalo links and the subhalo merger trees in the SDSS DR7 region extracted from our ELUCID simulation are available upon request.

  16. Periods of Child Growth up to age 8 Years in Ethiopia, India, Peru and Vietnam: Key Distal Household and Community Factors

    PubMed Central

    Schott, Whitney B.; Crookston, Benjamin T.; Lundeen, Elizabeth A.; Stein, Aryeh D.; Behrman, Jere R.

    2013-01-01

    Recent research has demonstrated some growth recovery among children stunted in infancy. Less is known about key age ranges for such growth recovery, and what factors are correlates with this growth. This study characterized child growth up to age 1 year, and from ages 1 to 5 and 5 to 8 years controlling for initial height-for-age z-score (HAZ), and identified key distal household and community factors associated with these growth measures using longitudinal data on 7,266 children in the Young Lives (YL) study in Ethiopia, India, Peru and Vietnam. HAZ at about age 1 year and age in months predicted much of the variation in HAZ at age 5 years, but 40 to 71% was not predicted. Similarly, HAZ at age 5 years and age in months did not predict 26 to 47% of variation in HAZ at 8 years. Multiple regression analysis suggests that parental schooling, consumption, and mothers’ height are key correlates of HAZ at about age 1 and also are associated with unpredicted change in HAZ from ages 1 to 5 and 5 to 8 years, given initial HAZ. These results underline the importance of a child’s starting point in infancy in determining his or her growth, point to key distal household and community factors that may determine early growth in early life and subsequent growth recovery and growth failure, and indicate that these factors vary some by country, urban/rural designation, and child sex. PMID:23769211

  17. Periods of child growth up to age 8 years in Ethiopia, India, Peru and Vietnam: key distal household and community factors.

    PubMed

    Schott, Whitney B; Crookston, Benjamin T; Lundeen, Elizabeth A; Stein, Aryeh D; Behrman, Jere R

    2013-11-01

    Recent research has demonstrated some growth recovery among children stunted in infancy. Less is known about key age ranges for such growth recovery, and what factors are correlates with this growth. This study characterized child growth up to age 1 year, and from ages 1 to 5 and 5 to 8 years controlling for initial height-for-age z-score (HAZ), and identified key distal household and community factors associated with these growth measures using longitudinal data on 7266 children in the Young Lives (YL) study in Ethiopia, India, Peru and Vietnam. HAZ at about age 1 year and age in months predicted much of the variation in HAZ at age 5 years, but 40-71% was not predicted. Similarly, HAZ at age 5 years and age in months did not predict 26-47% of variation in HAZ at 8 years. Multiple regression analysis suggests that parental schooling, consumption, and mothers' height are key correlates of HAZ at about age 1 and also are associated with unpredicted change in HAZ from ages 1 to 5 and 5 to 8 years, given initial HAZ. These results underline the importance of a child's starting point in infancy in determining his or her growth, point to key distal household and community factors that may determine early growth in early life and subsequent growth recovery and growth failure, and indicate that these factors vary some by country, urban/rural designation, and child sex. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. A platform for actively loading cargo RNA to elucidate limiting steps in EV-mediated delivery.

    PubMed

    Hung, Michelle E; Leonard, Joshua N

    2016-01-01

    Extracellular vesicles (EVs) mediate intercellular communication through transfer of RNA and protein between cells. Thus, understanding how cargo molecules are loaded and delivered by EVs is of central importance for elucidating the biological roles of EVs and developing EV-based therapeutics. While some motifs modulating the loading of biomolecular cargo into EVs have been elucidated, the general rules governing cargo loading and delivery remain poorly understood. To investigate how general biophysical properties impact loading and delivery of RNA by EVs, we developed a platform for actively loading engineered cargo RNAs into EVs. In our system, the MS2 bacteriophage coat protein was fused to EV-associated proteins, and the cognate MS2 stem loop was engineered into cargo RNAs. Using this Targeted and Modular EV Loading (TAMEL) approach, we identified a configuration that substantially enhanced cargo RNA loading (up to 6-fold) into EVs. When applied to vesicles expressing the vesicular stomatitis virus glycoprotein (VSVG) - gesicles - we observed a 40-fold enrichment in cargo RNA loading. While active loading of mRNA-length (>1.5 kb) cargo molecules was possible, active loading was much more efficient for smaller (~0.5 kb) RNA molecules. We next leveraged the TAMEL platform to elucidate the limiting steps in EV-mediated delivery of mRNA and protein to prostate cancer cells, as a model system. Overall, most cargo was rapidly degraded in recipient cells, despite high EV-loading efficiencies and substantial EV uptake by recipient cells. While gesicles were efficiently internalized via a VSVG-mediated mechanism, most cargo molecules were rapidly degraded. Thus, in this model system, inefficient endosomal fusion or escape likely represents a limiting barrier to EV-mediated transfer. Altogether, the TAMEL platform enabled a comparative analysis elucidating a key opportunity for enhancing EV-mediated delivery to prostate cancer cells, and this technology should be of

  19. Key Response Planning Factors for the Aftermath of Nuclear Terrorism

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

    Buddemeier, B R; Dillon, M B

    Despite hundreds of above-ground nuclear tests and data gathered from Hiroshima and Nagasaki, the effects of a ground-level, low-yield nuclear detonation in a modern urban environment are still the subject of considerable scientific debate. Extensive review of nuclear weapon effects studies and discussions with nuclear weapon effects experts from various federal agencies, national laboratories, and technical organizations have identified key issues and bounded some of the unknowns required to support response planning for a low-yield, ground-level nuclear detonation in a modern U.S. city. This study, which is focused primarily upon the hazards posed by radioactive fallout, used detailed fallout predictionsmore » from the advanced suite of three-dimensional (3-D) meteorology and plume/fallout models developed at Lawrence Livermore National Laboratory (LLNL), including extensive global Key Response Planning Factors for the Aftermath of Nuclear Terrorism geographical and real-time meteorological databases to support model calculations. This 3-D modeling system provides detailed simulations that account for complex meteorology and terrain effects. The results of initial modeling and analysis were presented to federal, state, and local working groups to obtain critical, broad-based review and feedback on strategy and messaging. This effort involved a diverse set of communities, including New York City, National Capitol Regions, Charlotte, Houston, Portland, and Los Angeles. The largest potential for reducing casualties during the post-detonation response phase comes from reducing exposure to fallout radiation. This can be accomplished through early, adequate sheltering followed by informed, delayed evacuation.B The response challenges to a nuclear detonation must be solved through multiple approaches of public education, planning, and rapid response actions. Because the successful response will require extensive coordination of a large number of organizations

  20. Mental workload as a key factor in clinical decision making.

    PubMed

    Byrne, Aidan

    2013-08-01

    The decision making process is central to the practice of a clinician and has traditionally been described in terms of the hypothetico-deductive model. More recently, models adapted from cognitive psychology, such as the dual process and script theories have proved useful in explaining patterns of practice not consistent with purely cognitive based practice. The purpose of this paper is to introduce the concept of mental workload as a key determinant of the type of cognitive processing used by clinicians. Published research appears to be consistent with 'schemata' based cognition as the principle mode of working for those engaged in complex tasks under time pressure. Although conscious processing of factual data is also used, it may be the primary mode of cognition only in situations where time pressure is not a factor. Further research on the decision making process should be based on outcomes which are not dependant on conscious recall of past actions or events and include a measure of mental workload. This further appears to support the concept of the patient, within the clinical environment, as the most effective learning resource.

  1. Thermal control of virulence factors in bacteria: A hot topic

    PubMed Central

    Lam, Oliver; Wheeler, Jun; Tang, Christoph M

    2014-01-01

    Pathogenic bacteria sense environmental cues, including the local temperature, to control the production of key virulence factors. Thermal regulation can be achieved at the level of DNA, RNA or protein and although many virulence factors are subject to thermal regulation, the exact mechanisms of control are yet to be elucidated in many instances. Understanding how virulence factors are regulated by temperature presents a significant challenge, as gene expression and protein production are often influenced by complex regulatory networks involving multiple transcription factors in bacteria. Here we highlight some recent insights into thermal regulation of virulence in pathogenic bacteria. We focus on bacteria which cause disease in mammalian hosts, which are at a significantly higher temperature than the outside environment. We outline the mechanisms of thermal regulation and how understanding this fundamental aspect of the biology of bacteria has implications for pathogenesis and human health. PMID:25494856

  2. Prognosis in advanced lung cancer--A prospective study examining key clinicopathological factors.

    PubMed

    Simmons, Claribel P; Koinis, Filippos; Fallon, Marie T; Fearon, Kenneth C; Bowden, Jo; Solheim, Tora S; Gronberg, Bjorn Henning; McMillan, Donald C; Gioulbasanis, Ioannis; Laird, Barry J

    2015-06-01

    In patients with advanced incurable lung cancer deciding as to the most appropriate treatment (e.g., chemotherapy or supportive care only) is challenging. In such patients the TNM classification system has reached its ceiling therefore other factors are used to assess prognosis and as such, guide treatment. Performance status (PS), weight loss and inflammatory biomarkers (Glasgow Prognostic Score (mGPS)) predict survival in advanced lung cancer however these have not been compared. This study compares key prognostic factors in advanced lung cancer. Patients with newly diagnosed advanced lung cancer were recruited and demographics, weight loss, other prognostic factors (mGPS, PS) were collected. Kaplan-Meier and Cox regression methods were used to compare these prognostic factors. 390 patients with advanced incurable lung cancer were recruited; 341 were male, median age was 66 years (IQR 59-73) and patients had stage IV non-small cell (n=288) (73.8%) or extensive stage small cell lung cancer (n=102) (26.2%). The median survival was 7.8 months. On multivariate analysis only performance status (HR 1.74 CI 1.50-2.02) and mGPS (HR 1.67, CI 1.40-2.00) predicted survival (p<0.001). Survival at 3 months ranged from 99% (ECOG 0-1) to 74% (ECOG 2) and using mGPS, from 99% (mGPS0) to 71% (mGPS2). In combination, survival ranged from 99% (mGPS 0, ECOG 0-1) to 33% (mGPS2, ECOG 3). Performance status and the mGPS are superior prognostic factors in advanced lung cancer. In combination, these improved survival prediction compared with either alone. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  3. P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non-small-cell lung cancer.

    PubMed

    Kato, Shinichiro; Yokoyama, Satoru; Hayakawa, Yoshihiro; Li, Luhui; Iwakami, Yusuke; Sakurai, Hiroaki; Saiki, Ikuo

    2016-10-01

    Although the secretory matricellular protein connective tissue growth factor (CTGF) has been reported to be related to lung cancer metastasis, the precise mechanism by which CTGF regulates lung cancer metastasis has not been elucidated. In the present study, we show the molecular link between CTGF secretion and the p38 pathway in the invasive and metastatic potential of non-small-cell lung cancer (NSCLC). Among three different human NSCLC cell lines (PC-14, A549, and PC-9), their in vitro invasiveness was inversely correlated with the level of CTGF secretion. By supplementing or reducing CTGF secretion in NSCLC culture, dysregulation of the invasive and metastatic potential of NSCLC cell lines was largely compensated. By focusing on the protein kinases that are known to be regulated by CTGF, we found that the p38 pathway is a key downstream signal of CTGF to regulate the metastatic potential of NSCLC. Importantly, a negative correlation between CTGF and phosphorylation status of p38 was identified in The Cancer Genome Atlas lung adenocarcinoma dataset. In the context of the clinical importance of our findings, we showed that p38 inhibitor, SB203580, reduced the metastatic potential of NSCLC secreting low levels of CTGF. Collectively, our present findings indicate that the CTGF/p38 axis is a novel therapeutic target of NSCLC metastasis, particularly NSCLC secreting low levels of CTGF. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  4. Problem-Based Learning Environment in Basic Computer Course: Pre-Service Teachers' Achievement and Key Factors for Learning

    ERIC Educational Resources Information Center

    Efendioglu, Akin

    2015-01-01

    This experimental study aims to determine pre-service teachers' achievements and key factors that affect the learning process with regard to problem-based learning (PBL) and lecture-based computer course (LBCC) conditions. The research results showed that the pre-service teachers in the PBL group had significantly higher achievement scores than…

  5. Factor Analysis of Key Success Indicators in Curriculum Quality Assurance Operation for Bachelor's Degree in Physical Education

    ERIC Educational Resources Information Center

    Sukdee, Thitipong; Tornee, Songpol; Kraipetch, Chanita

    2017-01-01

    The purpose of this study was to analyze the factors of key success indicators in curriculum quality assurance operation for bachelor's degree in Physical Education. The 576 subjects were selected using cluster sampling from curriculum lecturers, staffs, and lecturers at the Academy of Physical Education Curriculum. The instrument was a related…

  6. Elucidating the genetic architecture of reproductive ageing in the Japanese population.

    PubMed

    Horikoshi, Momoko; Day, Felix R; Akiyama, Masato; Hirata, Makoto; Kamatani, Yoichiro; Matsuda, Koichi; Ishigaki, Kazuyoshi; Kanai, Masahiro; Wright, Hollis; Toro, Carlos A; Ojeda, Sergio R; Lomniczi, Alejandro; Kubo, Michiaki; Ong, Ken K; Perry, John R B

    2018-05-17

    Population studies elucidating the genetic architecture of reproductive ageing have been largely limited to European ancestries, restricting the generalizability of the findings and overlooking possible key genes poorly captured by common European genetic variation. Here, we report 26 loci (all P < 5 × 10 -8 ) for reproductive ageing, i.e. puberty timing or age at menopause, in a non-European population (up to 67,029 women of Japanese ancestry). Highlighted genes for menopause include GNRH1, which supports a primary, rather than passive, role for hypothalamic-pituitary GnRH signalling in the timing of menopause. For puberty timing, we demonstrate an aetiological role for receptor-like protein tyrosine phosphatases by combining evidence across population genetics and pre- and peri-pubertal changes in hypothalamic gene expression in rodent and primate models. Furthermore, our findings demonstrate widespread differences in allele frequencies and effect estimates between Japanese and European associated variants, highlighting the benefits and challenges of large-scale trans-ethnic approaches.

  7. Successful collaboration between occupational health service providers and client companies: Key factors.

    PubMed

    Schmidt, Lisa; Sjöström, John; Antonsson, Ann-Beth

    2015-06-05

    Occupational health services (OHS) are often described as an important resource to reduce work-related diseases and improve the workplace. This paper identifies key factors for successful collaboration between Swedish OHS providers and their client companies. Interviews were carried out with representatives of 15 companies and their OHS providers. The interviews were transcribed and their content analyzed. The results revealed that successful collaboration was highly correlated with six factors. First, the collaboration depends on both parties; ``it takes two to tango''. Second, the company and the OHS provider have a joint commitment to a long-term collaboration. Third, the collaboration is built on frequent contact at different organizational levels. Fourth, the company has a well-structured work environment for occupational health and safety management. Fifth, the OHS provider uses a consultative approach in its prevention and promotion activities. Finally, OHS providers seek to treat the company, not the individual. Our research indicates that a successful collaboration requires both occupational health and safety management (OHSM) within the company and the assistance of a competent OHS provider. A change toward more promotion and prevention services benefits the company, since the occupational health services are better tailored to the company's needs.

  8. Available nitrogen is the key factor influencing soil microbial functional gene diversity in tropical rainforest.

    PubMed

    Cong, Jing; Liu, Xueduan; Lu, Hui; Xu, Han; Li, Yide; Deng, Ye; Li, Diqiang; Zhang, Yuguang

    2015-08-20

    Tropical rainforests cover over 50% of all known plant and animal species and provide a variety of key resources and ecosystem services to humans, largely mediated by metabolic activities of soil microbial communities. A deep analysis of soil microbial communities and their roles in ecological processes would improve our understanding on biogeochemical elemental cycles. However, soil microbial functional gene diversity in tropical rainforests and causative factors remain unclear. GeoChip, contained almost all of the key functional genes related to biogeochemical cycles, could be used as a specific and sensitive tool for studying microbial gene diversity and metabolic potential. In this study, soil microbial functional gene diversity in tropical rainforest was analyzed by using GeoChip technology. Gene categories detected in the tropical rainforest soils were related to different biogeochemical processes, such as carbon (C), nitrogen (N) and phosphorus (P) cycling. The relative abundance of genes related to C and P cycling detected mostly derived from the cultured bacteria. C degradation gene categories for substrates ranging from labile C to recalcitrant C were all detected, and gene abundances involved in many recalcitrant C degradation gene categories were significantly (P < 0.05) different among three sampling sites. The relative abundance of genes related to N cycling detected was significantly (P < 0.05) different, mostly derived from the uncultured bacteria. The gene categories related to ammonification had a high relative abundance. Both canonical correspondence analysis and multivariate regression tree analysis showed that soil available N was the most correlated with soil microbial functional gene structure. Overall high microbial functional gene diversity and different soil microbial metabolic potential for different biogeochemical processes were considered to exist in tropical rainforest. Soil available N could be the key factor in shaping the

  9. [Construction of automatic elucidation platform for mechanism of traditional Chinese medicine].

    PubMed

    Zhang, Bai-xia; Luo, Si-jun; Yan, Jing; Gu, Hao; Luo, Ji; Zhang, Yan-ling; Tao, Ou; Wang, Yun

    2015-10-01

    Aim at the two problems in the field of traditional Chinese medicine (TCM) mechanism elucidation, one is the lack of detailed biological processes information, next is the low efficient in constructing network models, we constructed an auxiliary elucidation system for the TCM mechanism and realize the automatic establishment of biological network model. This study used the Entity Grammar Systems (EGS) as the theoretical framework, integrated the data of formulae, herbs, chemical components, targets of component, biological reactions, signaling pathways and disease related proteins, established the formal models, wrote the reasoning engine, constructed the auxiliary elucidation system for the TCM mechanism elucidation. The platform provides an automatic modeling method for biological network model of TCM mechanism. It would be benefit to perform the in-depth research on TCM theory of natures and combination and provides the scientific references for R&D of TCM.

  10. Is equol the key to the efficacy of soy foods?

    PubMed

    Lampe, Johanna W

    2009-05-01

    Gut bacterial modification of soy isoflavones produces metabolites that differ in biological activity from the parent compounds. Hydrolysis of glycosides results in more active compounds. In contrast, further degradation and transformation of aglycones produce more or less active compounds, depending on the substrate metabolized and the product formed. Bacterial metabolism of soy isoflavones varies among individuals. The predominant daidzein metabolites produced by human intestinal bacteria are equol and O-desmethylangolensin. Among humans, 30-50% have the bacteria capable of producing equol and 80-90% harbor O-desmethylangolensin-producing bacteria. Factors that influence the capacity to produce equol and O-desmethylangolensin are not clearly established; however, gut physiology, host genetics, and diet are reported to contribute to interindividual differences in conversion of daidzein to equol. Effects of these phenotypes on human health are poorly characterized. Some studies in high soy-consuming populations reported an inverse association between urinary and serum equol concentrations and breast and prostate cancer risk. Furthermore, several studies of soy supplementation and bone density suggest that soy products may be more effective in maintaining bone density in equol-producing individuals. Factors that contribute to the phenotypes and the relation of these specific phenotypes to human health need to be further elucidated. The extent to which isoflavone metabolism is key to the efficacy of soy foods remains to be established.

  11. A data mining paradigm for identifying key factors in biological processes using gene expression data.

    PubMed

    Li, Jin; Zheng, Le; Uchiyama, Akihiko; Bin, Lianghua; Mauro, Theodora M; Elias, Peter M; Pawelczyk, Tadeusz; Sakowicz-Burkiewicz, Monika; Trzeciak, Magdalena; Leung, Donald Y M; Morasso, Maria I; Yu, Peng

    2018-06-13

    A large volume of biological data is being generated for studying mechanisms of various biological processes. These precious data enable large-scale computational analyses to gain biological insights. However, it remains a challenge to mine the data efficiently for knowledge discovery. The heterogeneity of these data makes it difficult to consistently integrate them, slowing down the process of biological discovery. We introduce a data processing paradigm to identify key factors in biological processes via systematic collection of gene expression datasets, primary analysis of data, and evaluation of consistent signals. To demonstrate its effectiveness, our paradigm was applied to epidermal development and identified many genes that play a potential role in this process. Besides the known epidermal development genes, a substantial proportion of the identified genes are still not supported by gain- or loss-of-function studies, yielding many novel genes for future studies. Among them, we selected a top gene for loss-of-function experimental validation and confirmed its function in epidermal differentiation, proving the ability of this paradigm to identify new factors in biological processes. In addition, this paradigm revealed many key genes in cold-induced thermogenesis using data from cold-challenged tissues, demonstrating its generalizability. This paradigm can lead to fruitful results for studying molecular mechanisms in an era of explosive accumulation of publicly available biological data.

  12. Determining the key drivers and mitigating factors that influence the role of the Nurse and/or Midwife Consultant: a cross-sectional survey.

    PubMed

    Fernandez, Ritin S; Sheppard-Law, Suzanne; Manning, Vicki

    2017-06-01

    Globally, many nurses and midwives are working at an advanced practice level. The role of a Nurse and/or Midwife Consultant encompasses a diverse and complex interaction between five specified domains namely Clinical Service and Consultancy, Clinical Leadership, Research, Education, and Clinical Services Planning and Management. The objective of this replication study was to identify the key drivers and mitigating factors that impact the role of Australian Nurse and/or Midwife Consultants. Cross-sectional survey. The study was conducted in a large metropolitan health district in Sydney, Australia. Participants for this study consisted of all Nurse and/or Midwife Consultants working within a health district in New South Wales (NSW). Data were collected by an anonymous online survey. Key drivers and mitigating factors perceived to influence their role were identified using previously implemented instruments. Data were analysed using SPSS version 21. Responses were obtained from 122 Nurse and/or Midwife Consultants. The number of years of experience as a Nurse and/or Midwife Consultant ranged from 6 months to 25.5 years. Personal attributes which included personal motivation and own communication skills were identified as key drivers to role performance with a mean score of 7.7±0.6. Other key drivers included peer support, organisational culture, personal attributes, professional learning, Nurse and/or Midwife Consultant experience, and collaborative relationships. Of the 14 mitigating factors to the role, the most common factors were lack of resources to set up and develop the role (2.6 ± 0.9), lack of secretarial support (2.6 ± 1.1), lack of managerial support (2.45 ± 1.1), and lack of understanding of the role by other health professionals (2.40 ± 0.8). Understanding the key drivers and mitigating factors that influence the role of the Nurse and/or Midwife Consultant is important for healthcare managers. Given the changing landscape of nursing

  13. Intervertebral disc degeneration-induced expression of pain-related molecules: glial cell-derived neurotropic factor as a key factor.

    PubMed

    Jung, Woon-Won; Kim, Hyun-Sook; Shon, Jong-Ryeul; Lee, Min; Lee, Sang-Heon; Sul, Donggeun; Na, Heung Sik; Kim, Joo Han; Kim, Byung-Jo

    2011-10-01

    Discogenic low back pain has been shown to develop into chronic intractable pain due to an unknown pathogenesis. To study the mechanism of discogenic pain, we analyzed the serial expression of pain-related molecules in the dorsal root ganglia (DRG) and thalamus using a newly developed rat model of disc degeneration. Ten microliters of complete Freund's adjuvant was injected into the L5-6 disc of male Sprague-Dawley rats for 10 minutes using a 26-gauge needle. Using a behavioral test, rats with significant pain were selected and subsequently serial gene expression of pain-related molecules in the DRG and the thalamus was analyzed by reverse transcriptase polymerase chain reaction. The expression of tumor necrosis factor-α and interleukin-1β significantly increased at 4 and 8 weeks in the DRG of rats with pain. Furthermore, interleukin-6 was significantly increased at 4 weeks in the DRG; however, these cytokines did not show a significant change in the thalamus. Calcitonin gene-related peptide and substance P were significantly increased in DRG at 4 and 8 weeks and in the thalamus at 2 and 4 weeks. The level of nerve growth factor-β did not significantly increase in the DRG or thalamus, whereas glial cell line-derived neurotropic factor (GDNF) was significantly increased at 2 weeks and was sustained through 8 weeks in both the DRG and thalamus. The disc degeneration rat model described herein led to significant pain of a chronic nature. The gradual and persistent increase of GDNF in both the thalamus and DRG suggests that GDNF might be a key factor in the development of intractable, chronic discogenic pain.

  14. Museum specimens reveal loss of pollen host plants as key factor driving wild bee decline in The Netherlands.

    PubMed

    Scheper, Jeroen; Reemer, Menno; van Kats, Ruud; Ozinga, Wim A; van der Linden, Giel T J; Schaminée, Joop H J; Siepel, Henk; Kleijn, David

    2014-12-09

    Evidence for declining populations of both wild and managed bees has raised concern about a potential global pollination crisis. Strategies to mitigate bee loss generally aim to enhance floral resources. However, we do not really know whether loss of preferred floral resources is the key driver of bee decline because accurate assessment of host plant preferences is difficult, particularly for species that have become rare. Here we examine whether population trends of wild bees in The Netherlands can be explained by trends in host plants, and how this relates to other factors such as climate change. We determined host plant preference of bee species using pollen loads on specimens in entomological collections that were collected before the onset of their decline, and used atlas data to quantify population trends of bee species and their host plants. We show that decline of preferred host plant species was one of two main factors associated with bee decline. Bee body size, the other main factor, was negatively related to population trend, which, because larger bee species have larger pollen requirements than smaller species, may also point toward food limitation as a key factor driving wild bee loss. Diet breadth and other potential factors such as length of flight period or climate change sensitivity were not important in explaining twentieth century bee population trends. These results highlight the species-specific nature of wild bee decline and indicate that mitigation strategies will only be effective if they target the specific host plants of declining species.

  15. Museum specimens reveal loss of pollen host plants as key factor driving wild bee decline in The Netherlands

    PubMed Central

    Scheper, Jeroen; Reemer, Menno; van Kats, Ruud; Ozinga, Wim A.; van der Linden, Giel T. J.; Schaminée, Joop H. J.; Siepel, Henk; Kleijn, David

    2014-01-01

    Evidence for declining populations of both wild and managed bees has raised concern about a potential global pollination crisis. Strategies to mitigate bee loss generally aim to enhance floral resources. However, we do not really know whether loss of preferred floral resources is the key driver of bee decline because accurate assessment of host plant preferences is difficult, particularly for species that have become rare. Here we examine whether population trends of wild bees in The Netherlands can be explained by trends in host plants, and how this relates to other factors such as climate change. We determined host plant preference of bee species using pollen loads on specimens in entomological collections that were collected before the onset of their decline, and used atlas data to quantify population trends of bee species and their host plants. We show that decline of preferred host plant species was one of two main factors associated with bee decline. Bee body size, the other main factor, was negatively related to population trend, which, because larger bee species have larger pollen requirements than smaller species, may also point toward food limitation as a key factor driving wild bee loss. Diet breadth and other potential factors such as length of flight period or climate change sensitivity were not important in explaining twentieth century bee population trends. These results highlight the species-specific nature of wild bee decline and indicate that mitigation strategies will only be effective if they target the specific host plants of declining species. PMID:25422416

  16. G.A.M.E.: GPU-accelerated mixture elucidator.

    PubMed

    Schurz, Alioune; Su, Bo-Han; Tu, Yi-Shu; Lu, Tony Tsung-Yu; Lin, Olivia A; Tseng, Yufeng J

    2017-09-15

    GPU acceleration is useful in solving complex chemical information problems. Identifying unknown structures from the mass spectra of natural product mixtures has been a desirable yet unresolved issue in metabolomics. However, this elucidation process has been hampered by complex experimental data and the inability of instruments to completely separate different compounds. Fortunately, with current high-resolution mass spectrometry, one feasible strategy is to define this problem as extending a scaffold database with sidechains of different probabilities to match the high-resolution mass obtained from a high-resolution mass spectrum. By introducing a dynamic programming (DP) algorithm, it is possible to solve this NP-complete problem in pseudo-polynomial time. However, the running time of the DP algorithm grows by orders of magnitude as the number of mass decimal digits increases, thus limiting the boost in structural prediction capabilities. By harnessing the heavily parallel architecture of modern GPUs, we designed a "compute unified device architecture" (CUDA)-based GPU-accelerated mixture elucidator (G.A.M.E.) that considerably improves the performance of the DP, allowing up to five decimal digits for input mass data. As exemplified by four testing datasets with verified constitutions from natural products, G.A.M.E. allows for efficient and automatic structural elucidation of unknown mixtures for practical procedures. Graphical abstract .

  17. New Insights from Elucidating the Role of LMP1 in Nasopharyngeal Carcinoma

    PubMed Central

    Shair, Kathy H. Y.; Reddy, Akhil

    2018-01-01

    Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV) oncogenic protein that has no intrinsic enzymatic activity or sequence homology to cellular or viral proteins. The oncogenic potential of LMP1 has been ascribed to pleiotropic signaling properties initiated through protein-protein interactions in cytosolic membrane compartments, but the effects of LMP1 extend to nuclear and extracellular processes. Although LMP1 is one of the latent genes required for EBV-immortalization of B cells, the biology of LMP1 in the pathogenesis of the epithelial cancer nasopharyngeal carcinoma (NPC) is more complex. NPC is prevalent in specific regions of the world with high incidence in southeast China. The epidemiology and time interval from seroconversion to NPC onset in adults would suggest the involvement of multiple risk factors that complement the establishment of a latent and persistent EBV infection. The contribution of LMP1 to EBV pathogenesis in polarized epithelia has only recently begun to be elucidated. Furthermore, the LMP1 gene has emerged as one of the most divergent sequences in the EBV genome. This review will discuss the significance of recent advances in NPC research from elucidating LMP1 function in epithelial cells and lessons that could be learned from mining LMP1 sequence diversity. PMID:29561768

  18. Optimizing Requirements Decisions with KEYS

    NASA Technical Reports Server (NTRS)

    Jalali, Omid; Menzies, Tim; Feather, Martin

    2008-01-01

    Recent work with NASA's Jet Propulsion Laboratory has allowed for external access to five of JPL's real-world requirements models, anonymized to conceal proprietary information, but retaining their computational nature. Experimentation with these models, reported herein, demonstrates a dramatic speedup in the computations performed on them. These models have a well defined goal: select mitigations that retire risks which, in turn, increases the number of attainable requirements. Such a non-linear optimization is a well-studied problem. However identification of not only (a) the optimal solution(s) but also (b) the key factors leading to them is less well studied. Our technique, called KEYS, shows a rapid way of simultaneously identifying the solutions and their key factors. KEYS improves on prior work by several orders of magnitude. Prior experiments with simulated annealing or treatment learning took tens of minutes to hours to terminate. KEYS runs much faster than that; e.g for one model, KEYS ran 13,000 times faster than treatment learning (40 minutes versus 0.18 seconds). Processing these JPL models is a non-linear optimization problem: the fewest mitigations must be selected while achieving the most requirements. Non-linear optimization is a well studied problem. With this paper, we challenge other members of the PROMISE community to improve on our results with other techniques.

  19. Research Trend of Physical Skill Science --Towards Elucidation of Physical Skill--

    NASA Astrophysics Data System (ADS)

    Furukawa, Koichi; Ueno, Ken; Ozaki, Tomonobu; Kamisato, Shihoko; Kawamoto, Ryuji; Shibuya, Koji; Shiratori, Naruhiko; Suwa, Masaki; Soga, Masato; Taki, Hirokazu; Fujinami, Tsutomu; Hori, Satoshi; Motomura, Yoichi; Morita, Souhei

    Physical skills and language skills are both fundamental intelligent abilities of human being. In this paper, we focus our attention to such sophisticated physical skills as playing sports and playing instruments and introduce research activities aiming at elucidating and verbalizing them. This research area has been launched recently. We introduce approaches from physical modeling, measurements and data analysis, cognitive science and human interface. We also discuss such issues as skill acquisition and its support systems. Furthermore, we consider a fundamental issue of individual differences occurring in every application of skill elucidation. Finally we introduce several attempts of skill elucidation in the fields of dancing, manufacturing, playing string instruments, sports science and medical care.

  20. Predicting Arrest in a Sample of Youth Perinatally Exposed to HIV: The Intersection of HIV and Key Contextual Factors.

    PubMed

    Elkington, Katherine S; Peters, Zachary; Choi, C Jean; Bucek, Amelia; Leu, Cheng-Shiun; Abrams, Elaine J; Mellins, Claude A

    2017-11-22

    We examined the role of youth HIV status and other key factors on past-year arrest in perinatally HIV-exposed but uninfected (PHIV-) and perinatally HIV-infected (PHIV+) youth using data from a multi-site study of psychosocial behaviors in PHIV-exposed urban youth (N = 340; 61% PHIV+; 51% female; ages 9-16 at baseline). Youth and caregivers were administered 5 interviews, spanning approximately 7.5 years. Using longitudinal logistic mixed-effect models, we explored the association between past year arrest, internal [e.g., substance use disorder (SUD)] and external (e.g., neighborhood arrest rates) contextual factors, and social-regulation processes (e.g., in-school/work). Arrest rates increased from 2.6 to 19.7% across follow-ups; there were no differences in arrest over time by HIV status. In the final model, odds of arrest were greater for youth who were male, with SUD, ≥ 18 years old, with high levels of city stress, and neither in school nor employed. PHIV-exposed, urban youth have much higher rates of arrest than national samples. Lack of differences in arrest by HIV status suggests key contextual factors are more important in promoting arrest.

  1. Identification of a key structural element for protein folding within beta-hairpin turns.

    PubMed

    Kim, Jaewon; Brych, Stephen R; Lee, Jihun; Logan, Timothy M; Blaber, Michael

    2003-05-09

    Specific residues in a polypeptide may be key contributors to the stability and foldability of the unique native structure. Identification and prediction of such residues is, therefore, an important area of investigation in solving the protein folding problem. Atypical main-chain conformations can help identify strains within a folded protein, and by inference, positions where unique amino acids may have a naturally high frequency of occurrence due to favorable contributions to stability and folding. Non-Gly residues located near the left-handed alpha-helical region (L-alpha) of the Ramachandran plot are a potential indicator of structural strain. Although many investigators have studied mutations at such positions, no consistent energetic or kinetic contributions to stability or folding have been elucidated. Here we report a study of the effects of Gly, Ala and Asn substitutions found within the L-alpha region at a characteristic position in defined beta-hairpin turns within human acidic fibroblast growth factor, and demonstrate consistent effects upon stability and folding kinetics. The thermodynamic and kinetic data are compared to available data for similar mutations in other proteins, with excellent agreement. The results have identified that Gly at the i+3 position within a subset of beta-hairpin turns is a key contributor towards increasing the rate of folding to the native state of the polypeptide while leaving the rate of unfolding largely unchanged.

  2. The routine utilization of dental care during pregnancy in eastern China and the key underlying factors: a Hangzhou City study.

    PubMed

    Sun, Wei; Guo, Jing; Li, Xiuyang; Zhao, Yongqi; Chen, Hui; Wu, Gang

    2014-01-01

    Oral diseases are associated with adverse pregnancy outcomes. The routine utilization of dental care (RUDC) during pregnancy is an effective way to improve pregnant women's oral health, and thus safeguard the health of their babies. As China has one fifth of the world's population, it is especially meaningful to encourage RUDC there. However, the status of RUDC in China and the key underlying factors are largely unknown. This cross-sectional survey investigated the current status of RUDC during pregnancy and the key underlying factors in Hangzhou City, Zhejiang Province, eastern China. We collected participants' demographics, individual oral-hygiene behaviors, individual lifestyle, oral-health conditions and attitudes, and also their RUDC during pregnancy. Binary Logistic Regression Analysis was used to analyze the key underlying factors. Only 16.70% of the participants reported RUDC during pregnancy. The percentage of RUDC was significantly lower among pregnant women with the following characteristics: aged 30 or less, an annual household income under $8,000, brushing once a day or less, never flossing or rinsing the mouth, paying no attention to pregnancy-related oral-health knowledge, and being dissatisfied with one's individual dental hygiene behavior. RUDC during pregnancy is very low in eastern China and is greatly influenced not only by a woman's age, annual income, individual hygiene behavior, but also by her attention and attitudes to oral health. To improve this population's access to and use of dental care during pregnancy, appropriate programs and policies are urgently needed.

  3. An SSH key management system: easing the pain of managing key/user/account associations

    NASA Astrophysics Data System (ADS)

    Arkhipkin, D.; Betts, W.; Lauret, J.; Shiryaev, A.

    2008-07-01

    Cyber security requirements for secure access to computing facilities often call for access controls via gatekeepers and the use of two-factor authentication. Using SSH keys to satisfy the two factor authentication requirement has introduced a potentially challenging task of managing the keys and their associations with individual users and user accounts. Approaches for a facility with the simple model of one remote user corresponding to one local user would not work at facilities that require a many-to-many mapping between users and accounts on multiple systems. We will present an SSH key management system we developed, tested and deployed to address the many-to-many dilemma in the environment of the STAR experiment. We will explain its use in an online computing context and explain how it makes possible the management and tracing of group account access spread over many sub-system components (data acquisition, slow controls, trigger, detector instrumentation, etc.) without the use of shared passwords for remote logins.

  4. A Comprehensive Test of General Strain Theory: Key Strains, Situational- and Trait-Based Negative Emotions, Conditioning Factors, and Delinquency

    ERIC Educational Resources Information Center

    Moon, Byongook; Morash, Merry; McCluskey, Cynthia Perez; Hwang, Hye-Won

    2009-01-01

    Using longitudinal data on South Korean youth, the authors addressed limitations of previous tests of general strain theory (GST), focusing on the relationships among key strains, situational- and trait-based negative emotions, conditioning factors, and delinquency. Eight types of strain previously shown most likely to result in delinquency,…

  5. Clinical and physiological assessments for elucidating falls risk in Parkinson's disease.

    PubMed

    Latt, Mark D; Lord, Stephen R; Morris, John G L; Fung, Victor S C

    2009-07-15

    The study aims were to devise (1) a fall risk screen for people with PD using routine clinical measures and (2) an explanatory (physiological) fall risk assessment for guiding fall prevention interventions. One hundred thirteen people with PD (age 66 +/- 95% CI 1.6 years) underwent clinical assessments and quantitative tests of sway, gait, strength, reaction time, and lower limb sensation. Participants were then followed up for 12 months to determine fall incidence. In the follow-up year, 51 participants (45%) fell one or more times whereas 62 participants (55%) did not fall. Multivariate analyses of routine clinical measures revealed that a fall in the past year, abnormal axial posture, cognitive impairment, and freezing of gait were independent risk factors for falls and predicted 38/51 fallers (75%) and 45/62 non-fallers (73%). A multivariate model combining clinical and physiological measures that elucidate the pathophysiology of falls identified abnormal posture, freezing of gait, frontal impairment, poor leaning balance, and leg weakness as independent risk factors. This model correctly classified 39/51 fallers (77%) and 51/62 non-fallers (82%). Patients with PD at risk of falls can be identified accurately with routine clinical assessments and quantitative physiological tests. Many of the risk factors identified are amenable to targeted intervention. 2009 Movement Disorder Society.

  6. The Angiocrine Factor Rspondin3 Is a Key Determinant of Liver Zonation.

    PubMed

    Rocha, Ana Sofia; Vidal, Valerie; Mertz, Marjolijn; Kendall, Timothy J; Charlet, Aurelie; Okamoto, Hitoshi; Schedl, Andreas

    2015-12-01

    Liver zonation, the spatial separation of different metabolic pathways along the liver sinusoids, is fundamental for proper functioning of this organ, and its disruption can lead to the development of metabolic disorders such as hyperammonemia. Metabolic zonation involves the induction of β-catenin signaling around the central veins, but how this patterned activity is established and maintained is unclear. Here, we show that the signaling molecule Rspondin3 is specifically expressed within the endothelial compartment of the central vein. Conditional deletion of Rspo3 in mice disrupts activation of central fate, demonstrating its crucial role in determining and maintaining β-catenin-dependent zonation. Moreover, ectopic expression of Rspo1, a close family member of Rspo3, induces the expression of pericentral markers, demonstrating Rspondins to be sufficient to imprint a more central fate. Thus, Rspo3 is a key angiocrine factor that controls metabolic zonation of liver hepatocytes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Elucidation of Thermally Induced Changes in Key Odorants of White Mustard Seeds (Sinapis alba L.) and Rapeseeds (Brassica napus L.) Using Molecular Sensory Science.

    PubMed

    Ortner, Eva; Granvogl, Michael; Schieberle, Peter

    2016-11-02

    Heat-processing of Brassica seeds led to the formation of a characteristic pleasant popcorn-like and coffee-like aroma impression compared to the mainly pea-like aroma of the corresponding raw seeds. To analyze this phenomenon on a molecular basis, raw and roasted white mustard seeds and rapeseeds were analyzed using the sensomics approach. Application of comparative aroma extract dilution analysis (cAEDA) and identification experiments to raw and roasted (140 °C, 30 min) mustard seeds revealed 36 odorants (all identified for the first time) and 47 odorants (41 newly identified), respectively. Twenty-seven odorants in raw and 43 odorants in roasted (140 °C, 60 min) rapeseeds were found, which were all described for the first time. Among the set of volatiles, 2-isopropyl-3-methoxypyrazine (earthy, pea-like) and 4-ethenyl-2-methoxyphenol (clove-like, smoky) showed high FD factors in both raw seeds. 4-Hydroxy-2,5-dimethylfuran-3(2H)-one (caramel-like), 2,3-diethyl-5-methylpyrazine (earthy), dimethyl trisulfide (cabbage-like), and 2-acetyl-1-pyrroline (popcorn-like) were present at high flavor dilution (FD) factors in both roasted Brassica seeds. Odorants, differing in cAEDA or showing high FD factors in at least one of the seeds, were quantitated by stable isotope dilution analysis (SIDA), followed by the calculation of odor activity values (OAVs) using odor thresholds determined in refined sunflower oil. Eighteen aroma compounds in raw and 28 in roasted mustard seeds as well as 14 in raw and 25 in roasted rapeseeds revealed OAVs ≥1. All four aroma recombinates, prepared by mixing the odorants showing OAVs ≥1 in their naturally occurring concentrations, showed a very good similarity with the original seeds and, thus, proved the successful characterization of the respective key odorants.

  8. Security analysis and improvements of two-factor mutual authentication with key agreement in wireless sensor networks.

    PubMed

    Kim, Jiye; Lee, Donghoon; Jeon, Woongryul; Lee, Youngsook; Won, Dongho

    2014-04-09

    User authentication and key management are two important security issues in WSNs (Wireless Sensor Networks). In WSNs, for some applications, the user needs to obtain real-time data directly from sensors and several user authentication schemes have been recently proposed for this case. We found that a two-factor mutual authentication scheme with key agreement in WSNs is vulnerable to gateway node bypassing attacks and user impersonation attacks using secret data stored in sensor nodes or an attacker's own smart card. In this paper, we propose an improved scheme to overcome these security weaknesses by storing secret data in unique ciphertext form in each node. In addition, our proposed scheme should provide not only security, but also efficiency since sensors in a WSN operate with resource constraints such as limited power, computation, and storage space. Therefore, we also analyze the performance of the proposed scheme by comparing its computation and communication costs with those of other schemes.

  9. Security Analysis and Improvements of Two-Factor Mutual Authentication with Key Agreement in Wireless Sensor Networks

    PubMed Central

    Kim, Jiye; Lee, Donghoon; Jeon, Woongryul; Lee, Youngsook; Won, Dongho

    2014-01-01

    User authentication and key management are two important security issues in WSNs (Wireless Sensor Networks). In WSNs, for some applications, the user needs to obtain real-time data directly from sensors and several user authentication schemes have been recently proposed for this case. We found that a two-factor mutual authentication scheme with key agreement in WSNs is vulnerable to gateway node bypassing attacks and user impersonation attacks using secret data stored in sensor nodes or an attacker's own smart card. In this paper, we propose an improved scheme to overcome these security weaknesses by storing secret data in unique ciphertext form in each node. In addition, our proposed scheme should provide not only security, but also efficiency since sensors in a WSN operate with resource constraints such as limited power, computation, and storage space. Therefore, we also analyze the performance of the proposed scheme by comparing its computation and communication costs with those of other schemes. PMID:24721764

  10. Distributed Factorization Computation on Multiple Volunteered Mobile Resource to Break RSA Key

    NASA Astrophysics Data System (ADS)

    Jaya, I.; Hardi, S. M.; Tarigan, J. T.; Zamzami, E. M.; Sihombing, P.

    2017-01-01

    Similar to common asymmeric encryption, RSA can be cracked by usmg a series mathematical calculation. The private key used to decrypt the massage can be computed using the public key. However, finding the private key may require a massive amount of calculation. In this paper, we propose a method to perform a distributed computing to calculate RSA’s private key. The proposed method uses multiple volunteered mobile devices to contribute during the calculation process. Our objective is to demonstrate how the use of volunteered computing on mobile devices may be a feasible option to reduce the time required to break a weak RSA encryption and observe the behavior and running time of the application on mobile devices.

  11. Does Pictorial Elucidation Foster Recollection of Idioms?

    ERIC Educational Resources Information Center

    Boers, Frank; Piquer Piriz, Ana Maria; Stengers, Helene; Eyckmans, June

    2009-01-01

    Experimental evidence suggests that pictorial elucidation helps learners comprehend and remember the meaning of second language (L2) idioms. In this article we address the question whether it also helps retention of the form of idioms, i.e. their precise lexical composition. In a small-scale experiment, the meaning of English idioms was clarified…

  12. Mycobacterium biofilms: factors involved in development, dispersal, and therapeutic strategies against biofilm-relevant pathogens.

    PubMed

    Xiang, Xiaohong; Deng, Wanyan; Liu, Minqiang; Xie, Jianping

    2014-01-01

    Many bacteria can develop biofilm (BF), a multicellular structure largely combining bacteria and their extracellular polymeric substances (EPS). The formation of biofilm results in an alternative existence in which microbes ensure their survival in adverse environments. Biofilm-relevant infections are more persistent, resistant to most antibiotics, and more recalcitrant to host immunity. Mycobacterium tuberculosis, the causative agent of tuberculosis, can develop biofilm, though whether M. tuberculosis can form biofilm within tuberculosis patients has yet to be determined. Here, we summarize the factors involved in the development and dispersal of mycobacterial biofilms, as well as underlying regulatory factors and inhibitors against biofilm to deepen our understanding of their development and to elucidate potential novel modes of action for future antibiotics. Key factors in biofilm formation identified as drug targets represent a novel and promising avenue for developing better antibiotics.

  13. Key factors of eddy current separation for recovering aluminum from crushed e-waste.

    PubMed

    Ruan, Jujun; Dong, Lipeng; Zheng, Jie; Zhang, Tao; Huang, Mingzhi; Xu, Zhenming

    2017-02-01

    Recovery of e-waste in China had caused serious pollutions. Eddy current separation is an environment-friendly technology of separating nonferrous metallic particles from crushed e-waste. However, due to complex particle characters, separation efficiency of traditional eddy current separator was low. In production, controllable operation factors of eddy current separation are feeding speed, (ωR-v), and S p . There is little special information about influencing mechanism and critical parameters of these factors in eddy current separation. This paper provided the special information of these key factors in eddy current separation of recovering aluminum particles from crushed waste refrigerator cabinets. Detachment angles increased as the increase of (ωR-v). Separation efficiency increased with the growing of detachment angles. Aluminum particles were completely separated from plastic particles in critical parameters of feeding speed 0.5m/s and detachment angles greater than 6.61deg. S p /S m of aluminum particles in crushed waste refrigerators ranged from 0.08 to 0.51. Separation efficiency increased as the increase of S p /S m . This enlightened us to develop new separator to separate smaller nonferrous metallic particles in e-waste recovery. High feeding speed destroyed separation efficiency. However, greater S p of aluminum particles brought positive impact on separation efficiency. Greater S p could increase critical feeding speed to offer greater throughput of eddy current separation. This paper will guide eddy current separation in production of recovering nonferrous metals from crushed e-waste. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Elucidating the transcriptome of Fasciola hepatica - a key to fundamental and biotechnological discoveries for a neglected parasite.

    PubMed

    Young, Neil D; Hall, Ross S; Jex, Aaron R; Cantacessi, Cinzia; Gasser, Robin B

    2010-01-01

    Liver flukes of animals are parasitic flatworms (Platyhelminthes: Digenea) of major socioeconomic importance in many countries. Key representatives, such as Fasciola hepatica and F. gigantica, cause "liver fluke disease" (= fascioliasis), which is of major animal health significance worldwide. In particular, F. hepatica is a leading cause of production losses to the livestock (mainly sheep and cattle) and meat industries due to clinical disease, reduced weight gain and milk production, and deaths. This parasite is also a major food-borne pathogen of humans throughout parts of the Middle East, Asia and South America. Currently, there is a significant focus on the development of new approaches for the prevention and control of fascioliasis in livestock. Recent technological advances in genomics and bioinformatics provide unique opportunities for the identification and prevalidation of drug targets and vaccines through a better understanding of the biology of F. hepatica and related species as well as their relationship with their hosts at the molecular level. Surprisingly, despite the widespread socioeconomic impact of fascioliasis, genomic datasets for F. hepatica are scant, limiting the molecular biological research of this parasite. The present article explores specifically the transcriptome of the adult stage of F. hepatica using an integrated genomic-bioinformatic platform. The analysis of the current data reveals numerous molecules of biological relevance, some of which are inferred to be involved in key biological processes or pathways that could serve as targets for new trematocidal drugs or vaccines. Improved insights into the transcriptome of F. hepatica should pave the way for future, comparative analysis of the transcriptomes of other developmental stages of this and related parasites, such as F. gigantica, cancer-causing flatworms (Clonorchis sinensis and Opisthorchis viverrini) and blood flukes (Schistosoma mansoni and S. japonicum). Prediction of the

  15. A Service evaluation of a hospital child death review process to elucidate understanding of contributory factors to child mortality and inform practice in the English National Health Service.

    PubMed

    Magnus, Daniel S; Schindler, Margrid B; Marlow, Robin D; Fraser, James I

    2018-03-16

    To describe a novel approach to hospital mortality meetings to elucidate understanding of contributory factors to child death and inform practice in the National Health Service. All child deaths were separately reviewed at a meeting attended by professionals across the healthcare pathway, and an assessment was made of contributory factors to death across domains intrinsic to the child, family and environment, parenting capacity and service delivery. Data were analysed from a centrally held database of records. All child deaths in a tertiary children's hospital between 1 April 2010 and 1 April 2013. Descriptive data summarising contributory factors to child deaths. 95 deaths were reviewed. In 85% cases, factors intrinsic to the child provided complete explanation for death. In 11% cases, factors in the family and environment and, in 5% cases, factors in parenting capacity, contributed to patient vulnerability. In 33% cases, factors in service provision contributed to patient vulnerability and in two patients provided complete explanation for death. 26% deaths were classified as potentially preventable and in those cases factors in service provision were more commonly identified than factors across other domains (OR: 4.89; 95% CI 1.26 to 18.9). Hospital child death review meetings attended by professionals involved in patient management across the healthcare pathway inform understanding of events leading to a child's death. Using a bioecological approach to scrutinise contributory factors the multidisciplinary team concluded most deaths occurred as a consequence of underlying illness. Although factors relating to service provision were commonly identified, they rarely provided a complete explanation for death. Efforts to reduce child mortality should be driven by an understanding of modifiable risk factors. Systematic data collection arising from a standardised approach to hospital reviews should be the basis for national mortality review processes and database

  16. Partition of some key regulating services in terrestrial ecosystems: Meta-analysis and review.

    PubMed

    Viglizzo, E F; Jobbágy, E G; Ricard, M F; Paruelo, J M

    2016-08-15

    Our knowledge about the functional foundations of ecosystem service (ES) provision is still limited and more research is needed to elucidate key functional mechanisms. Using a simplified eco-hydrological scheme, in this work we analyzed how land-use decisions modify the partition of some essential regulatory ES by altering basic relationships between biomass stocks and water flows. A comprehensive meta-analysis and review was conducted based on global, regional and local data from peer-reviewed publications. We analyzed five datasets comprising 1348 studies and 3948 records on precipitation (PPT), aboveground biomass (AGB), AGB change, evapotranspiration (ET), water yield (WY), WY change, runoff (R) and infiltration (I). The conceptual framework was focused on ES that are associated with the ecological functions (e.g., intermediate ES) of ET, WY, R and I. ES included soil protection, carbon sequestration, local climate regulation, water-flow regulation and water recharge. To address the problem of data normality, the analysis included both parametric and non-parametric regression analysis. Results demonstrate that PPT is a first-order biophysical factor that controls ES release at the broader scales. At decreasing scales, ES are partitioned as result of PPT interactions with other biophysical and anthropogenic factors. At intermediate scales, land-use change interacts with PPT modifying ES partition as it the case of afforestation in dry regions, where ET and climate regulation may be enhanced at the expense of R and water-flow regulation. At smaller scales, site-specific conditions such as topography interact with PPT and AGB displaying different ES partition formats. The probable implications of future land-use and climate change on some key ES production and partition are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Elucidation of wear mechanisms by ferrographic analysis

    NASA Technical Reports Server (NTRS)

    Jones, W. R., Jr.

    1981-01-01

    The use of ferrographic analysis in conjunction with light and scanning electron microscopy is described for the elucidation of wear mechanisms taking place in operating equipment. Example of adhesive wear, abrasive wear, corrosive wear, rolling element fatigue, lubricant breakdown, and other wear modes are illustrated. In addition, the use of magnetic solutions to precipitate nonmagnetic debris from aqueous and nonaqueous fluids is described.

  18. A Study of the Relationship between Key Factors of Academic Innovation and Faculties' Teaching Goals--The Mediatory Role of Knowledge

    ERIC Educational Resources Information Center

    Mohammadi, Mehdi; Marzooghi, Rahmatullah; Dehghani, Fatemeh

    2017-01-01

    The following research tries to study the Relationship between key factors of academic innovations and faculties' teaching goals with the mediatory role of their pedagogical, technological and content knowledge. The statistical population in this research included faculty members of Shiraz University. By simple random sampling, 127 faculty members…

  19. Chilling Stress—The Key Predisposing Factor for Causing Alternaria alternata Infection and Leading to Cotton (Gossypium hirsutum L.) Leaf Senescence

    PubMed Central

    Zhao, Jingqing; Li, Sha; Jiang, Tengfei; Liu, Zhi; Zhang, Wenwei; Jian, Guiliang; Qi, Fangjun

    2012-01-01

    Leaf senescence plays a vital role in nutrient recycling and overall capacity to assimilate carbon dioxide. Cotton premature leaf senescence, often accompanied with unexpected short-term low temperature, has been occurring with an increasing frequency in many cotton-growing areas and causes serious reduction in yield and quality of cotton. The key factors for causing and promoting cotton premature leaf senescence are still unclear. In this case, the relationship between the pre-chilling stress and Alternaria alternata infection for causing cotton leaf senescence was investigated under precisely controlled laboratory conditions with four to five leaves stage cotton plants. The results showed short-term chilling stress could cause a certain degree of physiological impairment to cotton leaves, which could be recovered to normal levels in 2–4 days when the chilling stresses were removed. When these chilling stress injured leaves were further inoculated with A. alternata, the pronounced appearance and development of leaf spot disease, and eventually the pronounced symptoms of leaf senescence, occurred on these cotton leaves. The onset of cotton leaf senescence at this condition was also reflected in various physiological indexes such as irreversible increase in malondialdehyde (MDA) content and electrolyte leakage, irreversible decrease in soluble protein content and chlorophyll content, and irreversible damage in leaves' photosynthesis ability. The presented results demonstrated that chilling stress acted as the key predisposing factor for causing A. alternata infection and leading to cotton leaf senescence. It could be expected that the understanding of the key factors causing and promoting cotton leaf senescence would be helpful for taking appropriate management steps to prevent cotton premature leaf senescence. PMID:22558354

  20. Key factors for the implementation of successful, stand-alone village electrification schemes in Peru

    NASA Astrophysics Data System (ADS)

    Sanchez-Campos, Teodoro

    The hypothesis of this work is that there are social, financial, technical, managerial institutional and political key factors that may either support or prevent the success of small stand alone energy systems in rural areas. This research work aims at contributing to the identification of such factors and study their relevance to the performance and sustainability of stand alone energy systems in rural areas; to meet its purpose, a wide range of literature was reviewed including rural electrification programmes and projects, research and development projects on access to electricity in rural areas, impact studies and others, and a field research survey was done the Andes and Upper Jungle regions in Peru. Nineteen possible critical factors were identified, thirteen with relevance at the local context (the community or village), and six with relevance at the national (or wider) context. From literature review it was found that the possible local critical factors were relevant only to four categories of factors instead of the six considered initially (i.e. social, financial, technological and managerial): the other two categories, political and institutional were found to be more relevant to the national context, therefore those were included in the group of possible critical factors of wider context. A series of questionnaires were designed to collect field data information, which was later used to analyse and establish the relation of each identified factor with the success of the systems studied. The survey research was implemented in 14 villages, 7 with small diesel sets and 7 with small hydropower schemes, all spread in the Andes and Upper Jungle of Peru, which were carefully selected to be representative of regions with isolated stand alone systems and with different socioeconomic background. Out of the 13 possible critical factors of local context, it was found that only 3 are really critical, the others are important but not critical; one of them (technical

  1. CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A assembly

    PubMed Central

    Shono, Nobuaki; Ohzeki, Jun-ichirou; Otake, Koichiro; Martins, Nuno M. C.; Nagase, Takahiro; Kimura, Hiroshi; Larionov, Vladimir; Earnshaw, William C.; Masumoto, Hiroshi

    2015-01-01

    ABSTRACT Although it is generally accepted that chromatin containing the histone H3 variant CENP-A is an epigenetic mark maintaining centromere identity, the pathways leading to the formation and maintenance of centromere chromatin remain unclear. We previously generated human artificial chromosomes (HACs) whose centromeres contain a synthetic alpha-satellite (alphoid) DNA array containing the tetracycline operator (alphoidtetO). We also obtained cell lines bearing the alphoidtetO array at ectopic integration sites on chromosomal arms. Here, we have examined the regulation of CENP-A assembly at centromeres as well as de novo assembly on the ectopic arrays by tethering tetracycline repressor (tetR) fusions of substantial centromeric factors and chromatin modifiers. This analysis revealed four classes of factors that influence CENP-A assembly. Interestingly, many kinetochore structural components induced de novo CENP-A assembly at the ectopic site. We showed that these components work by recruiting CENP-C and subsequently recruiting M18BP1. Furthermore, we found that CENP-I can also recruit M18BP1 and, as a consequence, enhances M18BP1 assembly on centromeres in the downstream of CENP-C. Thus, we suggest that CENP-C and CENP-I are key factors connecting kinetochore to CENP-A assembly. PMID:26527398

  2. Succesful Lean Manufacturing Implementation: Internal Key Influencing Factors

    NASA Astrophysics Data System (ADS)

    Virginia, Iuga; Claudiu, Kifor

    2015-09-01

    Manufacturing sectors and companies all over the world are successfully implementing lean principles within their processes. Nowadays, lean has become an indispensable part of global players. Companies worldwide need to be aware of multiple factors which weigh heavily on the success or failure of lean implementation. This paper focuses on giving a brief and structured overview over the fundamental organizational factors which play a substantial role for the lean manufacturing (LM) implementation process. The study below focuses on internal factors which are indispensable for a successful LM implementation within organizations. It is imperative that these internal factors are known, recognized and taken into consideration during the whole LM implementation process. Ignoring their influence on the process's implementation may lead to endangering the expected results or to making the process more difficult which could result in much higher human resource consumption.

  3. Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

    PubMed Central

    Hwang, Jiwon; Kim, Jungyeon; Lee, You Sun; Koh, Eun-Mi; Kim, Kyoung Heon; Cha, Hoon-Suk

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3), which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS)-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF)-α-stimulated and curcumin-treated FLS was performed using GC/TOF-MS in conjunction with univariate and multivariate statistical analyses. A total of 119 metabolites were identified. Metabolomic analysis revealed that metabolite profiles were clearly distinct between TNF-α-stimulated vs. the control group (not stimulated by TNF-α or curcumin). Treatment of FLS with curcumin showed that the metabolic perturbation by TNF-α could be reversed to that of the control group to a considerable extent. Curcumin-treated FLS had higher restoration of amino acid and fatty acid metabolism, as indicated by the prominent metabolic restoration of intermediates of amino acid and fatty acid metabolism, compared with that observed in TNF-α-stimulated FLS. In particular, the abundance of glycine, citrulline, arachidonic acid, and saturated fatty acids in TNF-α-stimulated FLS was restored to the control level after treatment with curcumin, suggesting that the effect of curcumin on preventing joint inflammation may be elucidated with the levels of these metabolites. Our results suggest that GC/TOF-MS-based metabolomic investigation using FLS has the potential for discovering the mechanism of action of curcumin and new targets for therapeutic drugs in RA. PMID:26716989

  4. Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.

    PubMed

    Ahn, Joong Kyong; Kim, Sooah; Hwang, Jiwon; Kim, Jungyeon; Lee, You Sun; Koh, Eun-Mi; Kim, Kyoung Heon; Cha, Hoon-Suk

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3), which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS)-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF)-α-stimulated and curcumin-treated FLS was performed using GC/TOF-MS in conjunction with univariate and multivariate statistical analyses. A total of 119 metabolites were identified. Metabolomic analysis revealed that metabolite profiles were clearly distinct between TNF-α-stimulated vs. the control group (not stimulated by TNF-α or curcumin). Treatment of FLS with curcumin showed that the metabolic perturbation by TNF-α could be reversed to that of the control group to a considerable extent. Curcumin-treated FLS had higher restoration of amino acid and fatty acid metabolism, as indicated by the prominent metabolic restoration of intermediates of amino acid and fatty acid metabolism, compared with that observed in TNF-α-stimulated FLS. In particular, the abundance of glycine, citrulline, arachidonic acid, and saturated fatty acids in TNF-α-stimulated FLS was restored to the control level after treatment with curcumin, suggesting that the effect of curcumin on preventing joint inflammation may be elucidated with the levels of these metabolites. Our results suggest that GC/TOF-MS-based metabolomic investigation using FLS has the potential for discovering the mechanism of action of curcumin and new targets for therapeutic drugs in RA.

  5. Public/private partners. Key factors in creating a strategic alliance for community health.

    PubMed

    Nelson, J C; Rashid, H; Galvin, V G; Essien, J D; Levine, L M

    1999-04-01

    The rapidly evolving American health system creates economic and societal incentives for public and private health organizations to collaborate. Despite the apparent benefits of collaboration, there is a paucity of information available to help local agencies develop partnerships. This study, itself a collaboration between a school of public health (SPH) and a Georgia health district, was undertaken to identify critical factors necessary to successfully initiate and sustain a public/private community health collaboration. Professional staff at the SPH conducted 26 standardized interviews involving participants from Cobb and Douglas counties Boards of Health; Promina Northwest (now known as Wellstar), a not-for-profit health system; and community stakeholders. Content analysis of each interview question was performed and comparisons were made both within each group and across groups. Trends were identified in the following key areas: vision of health care for Cobb and Douglas counties, forces driving collaboration, strengths of each organization, critical negotiating issues, and potential community gain resulting from the partnership. A shared vision between potential collaborators facilitates communication regarding strategies to achieve common goals. A previous history of working together in limited capacities allowed the partners to develop trust and respect for one another prior to entering negotiations. These factors, when taken in conjunction with each organization's strong leadership and knowledge of the community, build a strong foundation for a successful partnership.

  6. Key Factors Controlling the Applicability and Efficiency of Bioremediation of Chlorinated Ethenes In Situ

    NASA Astrophysics Data System (ADS)

    Zhang, M.; Yoshikawa, M.; Takeuchi, M.; Komai, T.

    2012-12-01

    Bioremediation has been considered as one of environmentally friendly and cost effective approaches for cleaning up the sites polluted by organic contaminants, such as chlorinated ethenes. Although bioremediation, in its widest sense, is not new, and many researches have been performed on bioremediation of different kinds of pollutants, an effective design and implication of in situ bioremediation still remains a challenging problem because of the complexity. Many factors may affect the applicability and efficiency of bioremediation of chlorinated ethenes in situ, which include the type and concentration of contaminants, biological, geological and hydro-geological conditions of the site, physical and chemical characteristics of groundwater and soils to be treated, as well as the constraints in engineering. In this presentation, an overview together with a detailed discussion on each factor will be provided. The influences of individual factors are discussed using the data obtained or cited from different sites and experiments, and thus under different environmental conditions. The results of this study illustrated that 1) the establishment of microbial consortium is of crucial importance for a complete degradation of chlorinated ethenes, 2) in situ control of favorable conditions for increasing microbial activities for bio-degradation through a designed pathway is the key to success, 3) the focus of a successful remediation system is to design an effective delivery process that is capable of producing adequate amendment mixing of contaminant-degrading bacteria, appropriate concentrations of electron acceptors, electron donors, and microbial nutrients in the subsurface treatment area.

  7. Use the predictive models to explore the key factors affecting phytoplankton succession in Lake Erhai, China.

    PubMed

    Zhu, Rong; Wang, Huan; Chen, Jun; Shen, Hong; Deng, Xuwei

    2018-01-01

    Increasing algae in Lake Erhai has resulted in frequent blooms that have not only led to water ecosystem degeneration but also seriously influenced the quality of the water supply and caused extensive damage to the local people, as the lake is a water resource for Dali City. Exploring the key factors affecting phytoplankton succession and developing predictive models with easily detectable parameters for phytoplankton have been proven to be practical ways to improve water quality. To this end, a systematic survey focused on phytoplankton succession was conducted over 2 years in Lake Erhai. The data from the first study year were used to develop predictive models, and the data from the second year were used for model verification. The seasonal succession of phytoplankton in Lake Erhai was obvious. The dominant groups were Cyanobacteria in the summer, Chlorophyta in the autumn and Bacillariophyta in the winter. The developments and verification of predictive models indicated that compared to phytoplankton biomass, phytoplankton density is more effective for estimating phytoplankton variation in Lake Erhai. CCA (canonical correlation analysis) indicated that TN (total nitrogen), TP (total phosphorus), DO (dissolved oxygen), SD (Secchi depth), Cond (conductivity), T (water temperature), and ORP (oxidation reduction potential) had significant influences (p < 0.05) on the phytoplankton community. The CCA of the dominant species found that Microcystis was significantly influenced by T. The dominant Chlorophyta, Psephonema aenigmaticum and Mougeotia, were significantly influenced by TN. All results indicated that TN and T were the two key factors driving phytoplankton succession in Lake Erhai.

  8. The physical and mental health of lesbian, gay male, and bisexual (LGB) older adults: the role of key health indicators and risk and protective factors.

    PubMed

    Fredriksen-Goldsen, Karen I; Emlet, Charles A; Kim, Hyun-Jun; Muraco, Anna; Erosheva, Elena A; Goldsen, Jayn; Hoy-Ellis, Charles P

    2013-08-01

    Based on resilience theory, this paper investigates the influence of key health indicators and risk and protective factors on health outcomes (including general health, disability, and depression) among lesbian, gay male, and bisexual (LGB) older adults. A cross-sectional survey was conducted with LGB older adults, aged 50 and older (N = 2,439). Logistic regressions were conducted to examine the contributions of key health indicators (access to health care and health behaviors), risk factors (lifetime victimization, internalized stigma, and sexual identity concealment), and protective factors (social support and social network size) to health outcomes, when controlling for background characteristics. The findings revealed that lifetime victimization, financial barriers to health care, obesity, and limited physical activity independently and significantly accounted for poor general health, disability, and depression among LGB older adults. Internalized stigma was also a significant predictor of disability and depression. Social support and social network size served as protective factors, decreasing the odds of poor general health, disability, and depression. Some distinct differences by gender and sexual orientation were also observed. High levels of poor general health, disability, and depression among LGB older adults are of major concern. These findings highlight the important role of key risk and protective factors, which significantly influences health outcomes among LGB older adults. Tailored interventions must be developed to address the distinct health issues facing this historically disadvantaged population.

  9. Perceived key injury risk factors in World Cup alpine ski racing—an explorative qualitative study with expert stakeholders

    PubMed Central

    Spörri, Jörg; Kröll, Josef; Amesberger, Günter; Blake, Ollie M; Müller, Erich

    2012-01-01

    Background There is limited knowledge about key injury risk factors in alpine ski racing, particularly for World Cup (WC) athletes. Objective This study was undertaken to compile and explore perceived intrinsic and extrinsic risk factors for severe injuries in WC alpine ski racing. Methods Qualitative study. Interviews were conducted with 61 expert stakeholders of the WC ski racing community. Experts’ statements were collected, paraphrased and loaded into a database with inductively derived risk factor categories (Risk Factor Analysis). At the end of the interviews, experts were asked to name those risk factors they believed to have a high potential impact on injury risk and to rank them according to their priority of impact (Risk Factor Rating). Results In total, 32 perceived risk factors categories were derived from the interviews within the basic categories Athlete, Course, Equipment and Snow. Regarding their perceived impact on injury risk, the experts’ top five categories were: system ski, binding, plate and boot; changing snow conditions; physical aspects of the athletes; speed and course setting aspects and speed in general. Conclusions Severe injuries in WC alpine ski racing can have various causes. This study compiled a list of perceived intrinsic and extrinsic risk factors and explored those factors with the highest believed impact on injury risk. Hence, by using more detailed hypotheses derived from this explorative study, further studies should verify the plausibility of these factors as true risk factors for severe injuries in WC alpine ski racing. PMID:22872684

  10. Helicopter training simulators: Key market factors

    NASA Technical Reports Server (NTRS)

    Mcintosh, John

    1992-01-01

    Simulators will gain an increasingly important role in training helicopter pilots only if the simulators are of sufficient fidelity to provide positive transfer of skills to the aircraft. This must be done within an economic model of return on investment. Although rotor pilot demand is still only a small percentage of overall pilot requirements, it will grow in significance. This presentation described the salient factors influencing the use of helicopter training simulators.

  11. Social Work Practice with Latinos: Key Issues for Social Workers

    PubMed Central

    Furman, Rich; Negi, Nalini Junko; Iwamoto, Derek Kenji; Rowan, Diana; Shukraft, Allison; Gragg, Jennifer

    2010-01-01

    The Latino population is the fastest growing group in the United States; thus, it is imperative that social workers and other mental health practitioners be knowledgeable about the current literature on how to effectively serve this population. This article elucidates key issues and knowledge, such as immigration and migration concerns; discusses how to assess for levels of acculturation; examines cultural values; and highlights salient work issues and health disparities that Latinos experience. Recommendations on how agencies and universities can recruit and promote bilingual practitioners are introduced. Finally, culturally responsive strategies for professional use of self and fostering the therapeutic alliance are discussed. PMID:19366165

  12. A Secure Three-Factor User Authentication and Key Agreement Protocol for TMIS With User Anonymity.

    PubMed

    Amin, Ruhul; Biswas, G P

    2015-08-01

    Telecare medical information system (TMIS) makes an efficient and convenient connection between patient(s)/user(s) and doctor(s) over the insecure internet. Therefore, data security, privacy and user authentication are enormously important for accessing important medical data over insecure communication. Recently, many user authentication protocols for TMIS have been proposed in the literature and it has been observed that most of the protocols cannot achieve complete security requirements. In this paper, we have scrutinized two (Mishra et al., Xu et al.) remote user authentication protocols using smart card and explained that both the protocols are suffering against several security weaknesses. We have then presented three-factor user authentication and key agreement protocol usable for TMIS, which fix the security pitfalls of the above mentioned schemes. The informal cryptanalysis makes certain that the proposed protocol provides well security protection on the relevant security attacks. Furthermore, the simulator AVISPA tool confirms that the protocol is secure against active and passive attacks including replay and man-in-the-middle attacks. The security functionalities and performance comparison analysis confirm that our protocol not only provide strong protection on security attacks, but it also achieves better complexities along with efficient login and password change phase as well as session key verification property.

  13. Key factors associated with oral health-related quality of life (OHRQOL) in Hong Kong Chinese adults with orofacial pain.

    PubMed

    Zheng, Jun; Wong, May C M; Lam, Cindy L K

    2011-08-01

    To investigate key factors associated with oral health-related quality of life (OHRQOL) of Hong Kong Chinese adults with orofacial pain (OFP) symptoms. A cross-sectional study was conducted amongst a random sample of registered patients at a primary medical care teaching clinic in Hong Kong. Patients who were aged 35-70 years and had experienced OFP symptoms in the past 1 month were included. The OHRQOL was assessed by the Chinese version of the Oral Health Impact Profile (OHIP-14). A structured questionnaire on OFP symptoms and characteristics in the past 1 month, the depression and non-specific physical symptoms (NPS) scale in the research diagnostic criteria for temporomandibular disorders (RDC/TMD) questionnaire, and questions about professional treatment and dental attendance were administered before a standard clinical assessment. Negative binomial regression with forward stepwise selection was used to investigate key factors associated with the OHIP-14 additive score. The mean OHIP-14 additive score of the 200 participants was 10.1 (SD 9.4). Regression analysis revealed that five independent factors were significantly associated with higher OHIP-14 additive scores (indicating a poorer OHRQOL): a higher pain scale rating in the past 1 month (p=0.001), OFP clinical classification as musculoligamentous/soft tissue (MST) or dentoalveolar (DA) instead of neurological/vascular (NV) (p<0.001), more frequent dental attendance (p=0.008), moderate/severe RDC/TMD depression (p=0.005) and moderate/severe RDC/TMD NPS with pain (p=0.003). Various factors were associated with OHRQOL and could have implications for the improvement of OHRQOL in people in the community who have OFP symptoms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Secondary Analysis and Integration of Existing Data to Elucidate the Genetic Architecture of Cancer Risk and Related Outcomes, R21 | Informatics Technology for Cancer Research (ITCR)

    Cancer.gov

    This funding opportunity announcement (FOA) encourages applications that propose to conduct secondary data analysis and integration of existing datasets and database resources, with the ultimate aim to elucidate the genetic architecture of cancer risk and related outcomes. The goal of this initiative is to address key scientific questions relevant to cancer epidemiology by supporting the analysis of existing genetic or genomic datasets, possibly in combination with environmental, outcomes, behavioral, lifestyle, and molecular profiles data.

  15. Secondary Analysis and Integration of Existing Data to Elucidate the Genetic Architecture of Cancer Risk and Related Outcomes, R01 | Informatics Technology for Cancer Research (ITCR)

    Cancer.gov

    This funding opportunity announcement (FOA) encourages applications that propose to conduct secondary data analysis and integration of existing datasets and database resources, with the ultimate aim to elucidate the genetic architecture of cancer risk and related outcomes. The goal of this initiative is to address key scientific questions relevant to cancer epidemiology by supporting the analysis of existing genetic or genomic datasets, possibly in combination with environmental, outcomes, behavioral, lifestyle, and molecular profiles data.

  16. Flavonoid glycosides from Olax mannii: Structure elucidation and effect on the nuclear factor kappa B pathway.

    PubMed

    Okoye, Festus B C; Sawadogo, Wamtinga Richard; Sendker, Jandirk; Aly, Amal H; Quandt, Bettina; Wray, Victor; Hensel, Andreas; Esimone, Charles O; Debbab, Abdessamad; Diederich, Marc; Proksch, Peter

    2015-12-24

    Olax mannii Oliv. (Olacaceae) is among the many medicinal plants used in Nigeria for the ethnomedicinal management of both cancer and inflammation. Such plants represent potential sources of innovative therapeutic agents for the treatment of cancer and other malignant disorders. While the majority of medicinal plants exert their anticancer effects by direct cytotoxicity on tumor cells, it is important that other mechanisms through which these plants can exhibit anticancer effects are investigated. Preliminary studies indicated that Olax mannii leaves are rich sources of novel flavonoid glycosides. The detailed chemistry as well the mechanisms through which these flavonoid constituents may exert their cancer chemo-preventive and therapeutic effects are, however, not yet investigated. The aim of this study is to carry out a detailed chemical investigation of Olax mannii leaves and the effects of the isolated constituents on the nuclear factor kappa B (NF-κB) pathway. A methanol leaf extract was subjected to various chromatographic separations to achieve isolation of flavonoid glycosides and the structures of the isolated compounds were elucidated by a combination of 1D and 2D NMR and high resolution mass spectrometry. Biological activities were assessed by measurement of cellular viability and proliferation using quantitative IncuCyte videomicroscopy, trypan blue staining and by quantification of the number of metabolically active K562 cells based on quantitation of ATP. The effect of the compounds on the inhibition of the NF-κB pathway as well as toxicity towards peripheral blood mononuclear cells to evaluate differential toxicity was also assayed. Chemical investigation of the methanol leaf extract of the plant material led to the isolation of three new flavonoid triglycosides, kaempferol 3-O-[α-D-apiofuranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O-α-L-rhamnopyranoside (1), kaempferol 3-O-[β-D-glucopyranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O

  17. A key factor to the spin parameter of uniformly rotating compact stars: crust structure

    NASA Astrophysics Data System (ADS)

    Qi, Bin; Zhang, Nai-Bo; Sun, Bao-Yuan; Wang, Shou-Yu; Gao, Jian-Hua

    2016-04-01

    We study the dimensionless spin parameter j ≡ cJ/(GM2) of different kinds of uniformly rotating compact stars, including traditional neutron stars, hyperonic neutron stars and hybrid stars, based on relativistic mean field theory and the MIT bag model. It is found that jmax ˜ 0.7, which had been suggested in traditional neutron stars, is sustained for hyperonic neutron stars and hybrid stars with M > 0.5 M⊙. Not the interior but rather the crust structure of the stars is a key factor to determine jmax for three kinds of selected compact stars. Furthermore, a universal formula j = 0.63(f/fK) - 0.42(f/fK)2 + 0.48(f/fK)3 is suggested to determine the spin parameter at any rotational frequency f smaller than the Keplerian frequency fK.

  18. Elucidating dominant pathways of the nano-particle self-assembly process.

    PubMed

    Zeng, Xiangze; Li, Bin; Qiao, Qin; Zhu, Lizhe; Lu, Zhong-Yuan; Huang, Xuhui

    2016-09-14

    Self-assembly processes play a key role in the fabrication of functional nano-structures with widespread application in drug delivery and micro-reactors. In addition to the thermodynamics, the kinetics of the self-assembled nano-structures also play an important role in determining the formed structures. However, as the self-assembly process is often highly heterogeneous, systematic elucidation of the dominant kinetic pathways of self-assembly is challenging. Here, based on mass flow, we developed a new method for the construction of kinetic network models and applied it to identify the dominant kinetic pathways for the self-assembly of star-like block copolymers. We found that the dominant pathways are controlled by two competing kinetic parameters: the encounter time Te, characterizing the frequency of collision and the transition time Tt for the aggregate morphology change from rod to sphere. Interestingly, two distinct self-assembly mechanisms, diffusion of an individual copolymer into the aggregate core and membrane closure, both appear at different stages (with different values of Tt) of a single self-assembly process. In particular, the diffusion mechanism dominates the middle-sized semi-vesicle formation stage (with large Tt), while the membrane closure mechanism dominates the large-sized vesicle formation stage (with small Tt). Through the rational design of the hydrophibicity of the copolymer, we successfully tuned the transition time Tt and altered the dominant self-assembly pathways.

  19. Key handling in wireless sensor networks

    NASA Astrophysics Data System (ADS)

    Li, Y.; Newe, T.

    2007-07-01

    With the rapid growth of Wireless Sensor Networks (WSNs), many advanced application areas have received significant attention. However, security will be an important factor for their full adoption. Wireless sensor nodes pose unique challenges and as such traditional security protocols, used in traditional networks cannot be applied directly. Some new protocols have been published recently with the goal of providing both privacy of data and authentication of sensor nodes for WSNs. Such protocols can employ private-key and/or public key cryptographic algorithms. Public key algorithms hold the promise of simplifying the network infrastructure required to provide security services such as: privacy, authentication and non-repudiation, while symmetric algorithms require less processing power on the lower power wireless node. In this paper a selection of key establishment/agreement protocols are reviewed and they are broadly divided into two categories: group key agreement protocols and pair-wise key establishment protocols. A summary of the capabilities and security related services provided by each protocol is provided.

  20. A Peptidomics Strategy to Elucidate the Proteolytic Pathways that Inactivate Peptide Hormones

    PubMed Central

    Tinoco, Arthur D.; Kim, Yun-Gon; Tagore, Debarati M.; Wiwczar, Jessica; Lane, William S.; Danial, Nika N.; Saghatelian, Alan

    2011-01-01

    Proteolysis plays a key role in regulating the levels and activity of peptide hormones. Characterization of the proteolytic pathways that cleave peptide hormones is of basic interest and can, in some cases, spur the development of novel therapeutics. The lack, however, of an efficient approach to identify endogenous fragments of peptide hormones has hindered the elucidation of these proteolytic pathways. Here, we apply a mass spectrometry (MS)-based peptidomics approach to characterize the intestinal fragments of peptide histidine isoleucine (PHI), a hormone that promotes glucose-stimulated insulin secretion (GSIS). Our approach reveals a proteolytic pathway in the intestine that truncates PHI at its C-terminus to produce a PHI fragment that is inactive in a GSIS assay—a result that provides a potential mechanism of PHI regulation in vivo. Differences between these in vivo peptidomics studies and in vitro lysate experiments, which showed N- and C-terminal processing of PHI, underscore the effectiveness of this approach to discover physiologically relevant proteolytic pathways. Moreover, integrating this peptidomics approach with bioassays (i.e. GSIS) provides a general strategy to reveal proteolytic pathways that may regulate the activity of peptide hormones. PMID:21299233

  1. Monte Carlo Study Elucidates the Type 1/Type 2 Choice in Apoptotic Death Signaling in Healthy and Cancer Cells

    PubMed Central

    Raychaudhuri, Subhadip; Raychaudhuri, Somkanya C

    2013-01-01

    Apoptotic cell death is coordinated through two distinct (type 1 and type 2) intracellular signaling pathways. How the type 1/type 2 choice is made remains a central problem in the biology of apoptosis and has implications for apoptosis related diseases and therapy. We study the problem of type 1/type 2 choice in silico utilizing a kinetic Monte Carlo model of cell death signaling. Our results show that the type 1/type 2 choice is linked to deterministic versus stochastic cell death activation, elucidating a unique regulatory control of the apoptotic pathways. Consistent with previous findings, our results indicate that caspase 8 activation level is a key regulator of the choice between deterministic type 1 and stochastic type 2 pathways, irrespective of cell types. Expression levels of signaling molecules downstream also regulate the type 1/type 2 choice. A simplified model of DISC clustering elucidates the mechanism of increased active caspase 8 generation and type 1 activation in cancer cells having increased sensitivity to death receptor activation. We demonstrate that rapid deterministic activation of the type 1 pathway can selectively target such cancer cells, especially if XIAP is also inhibited; while inherent cell-to-cell variability would allow normal cells stay protected. PMID:24709706

  2. Unravelling Some of the Key Transformations in the Hydrothermal Liquefaction of Lignin.

    PubMed

    Lui, Matthew Y; Chan, Bun; Yuen, Alexander K L; Masters, Anthony F; Montoya, Alejandro; Maschmeyer, Thomas

    2017-05-22

    Using both experimental and computational methods, focusing on intermediates and model compounds, some of the main features of the reaction mechanisms that operate during the hydrothermal processing of lignin were elucidated. Key reaction pathways and their connection to different structural features of lignin were proposed. Under neutral conditions, subcritical water was demonstrated to act as a bifunctional acid/base catalyst for the dissection of lignin structures. In a complex web of mutually dependent interactions, guaiacyl units within lignin were shown to significantly affect overall lignin reactivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Neuromuscular Risk Factors for Knee and Ankle Ligament Injuries in Male Youth Soccer Players

    PubMed Central

    Read, Paul J.; Oliver, Jon L.; De Ste Croix, Mark B. A.; Myer, Gregory D.; Lloyd, Rhodri S.

    2017-01-01

    Injuries reported in male youth soccer players most commonly occur in the lower extremities, and include a high proportion of ligament sprains at the ankle and knee with a lower proportion of overuse injuries. There is currently a paucity of available literature that examines age- and sex-specific injury risk factors for such injuries within youth soccer players. Epidemiological data have reported movements that lead to non-contact ligament injury include running, twisting and turning, over-reaching and landing. Altered neuromuscular control during these actions has been suggested as a key mechanism in females and adult populations; however, data available in male soccer players is sparse. The focus of this article is to review the available literature and elucidate prevalent risk factors pertaining to male youth soccer players which may contribute to their relative risk of injury. PMID:26856339

  4. Neuromuscular Risk Factors for Knee and Ankle Ligament Injuries in Male Youth Soccer Players.

    PubMed

    Read, Paul J; Oliver, Jon L; De Ste Croix, Mark B A; Myer, Gregory D; Lloyd, Rhodri S

    2016-08-01

    Injuries reported in male youth soccer players most commonly occur in the lower extremities, and include a high proportion of ligament sprains at the ankle and knee with a lower proportion of overuse injuries. There is currently a paucity of available literature that examines age- and sex-specific injury risk factors for such injuries within youth soccer players. Epidemiological data have reported movements that lead to non-contact ligament injury include running, twisting and turning, over-reaching and landing. Altered neuromuscular control during these actions has been suggested as a key mechanism in females and adult populations; however, data available in male soccer players is sparse. The focus of this article is to review the available literature and elucidate prevalent risk factors pertaining to male youth soccer players which may contribute to their relative risk of injury.

  5. How the Adoption of the Big-Data Paradigm Affects the Key Factors That Influence the Effectiveness of an Information Assurance (IA) Framework: A Multiple-Case Study

    ERIC Educational Resources Information Center

    Apple, Benjamin G.

    2017-01-01

    This qualitative study identified those factors that influence the perceived effectiveness of traditional IA control frameworks. The key factors examined in this study are risk management, governance, access control, privacy protection, integrity, availability, reliability, and usability. The researcher endeavored to determine how the…

  6. Phosphate homeostasis in the yeast Saccharomyces cerevisiae, the key role of the SPX domain-containing proteins.

    PubMed

    Secco, David; Wang, Chuang; Shou, Huixia; Whelan, James

    2012-02-17

    In the yeast Saccharomyces cerevisiae, a working model for nutrient homeostasis in eukaryotes, inorganic phosphate (Pi) homeostasis is regulated by the PHO pathway, a set of phosphate starvation induced genes, acting to optimize Pi uptake and utilization. Among these, a subset of proteins containing the SPX domain has been shown to be key regulators of Pi homeostasis. In this review, we summarize the recent progresses in elucidating the mechanisms controlling Pi homeostasis in yeast, focusing on the key roles of the SPX domain-containing proteins in these processes, as well as describing the future challenges and opportunities in this fast-moving field. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  7. Streamlined structure elucidation of an unknown compound in a pigment formulation.

    PubMed

    Yüce, Imanuel; Morlock, Gertrud E

    2016-10-21

    A fast and reliable quality control is important for ink manufacturers to ensure a constant production grade of mixtures and chemical formulations, and unknown components attract their attention. Structure elucidating techniques seem time-consuming in combination with column-based methods, but especially the low solubility of pigment formulations is challenging the analysis. In contrast, layer chromatography is more tolerant with regard to pigment particles. One PLC plate for NMR and FTIR analyses and one HPTLC plate for recording of high resolution mass spectra, MS/MS spectra and for gathering information on polarity and spectral properties were needed to characterize a structure, exemplarily shown for an unknown component in pigment Red 57:1 to be 3-hydroxy-2-naphtoic acid. A preparative layer chromatography (PLC) workflow was developed that used an Automated Multiple Development 2 (AMD 2) system. The 0.5-mm PLC plate could still be operated in the AMD 2 system and allowed a smooth switch from the analytical to the preparative gradient separation. Through automated gradient development and the resulting focusing of bands, the sharpness of the PLC bands was improved. For NMR, the necessary high load of the target compound on the PLC plate was achieved via a selective solvent extraction that discriminated the polar sample matrix and thus increased the application volume of the extract that could maximally be applied without overloading. By doing so, the yield for NMR analysis was improved by a factor of 9. The effectivity gain through a simple, but thoroughly chosen extraction solvent is often overlooked, and for educational purpose, it was clearly illustrated and demonstrated by an extended solvent screening. Thus, PLC using an automated gradient development after a selective extraction was proven to be a new powerful combination for structural elucidation by NMR. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Behaviour, the key factor for sports injury prevention.

    PubMed

    Verhagen, Evert A L M; van Stralen, Maartje M; van Mechelen, Willem

    2010-11-01

    Safety in sports and physical activity is an important prerequisite for continuing participation in sports, as well as for maintenance of a healthy physically active lifestyle. For this reason, prevention, reduction and control of sports injuries are important goals for society as a whole. Recent advances in sports medicine discuss the need for research on real-life injury prevention. Such views call for a more behavioural approach when it comes to actual sports injury prevention. Nevertheless, the role of behaviour in sports injury prevention remains under-researched. In order to push the field of sports injury prevention forward, this article provides an overview of the relationship between behaviour and sports injury risk. Different types of behaviour relate to injury risk factors and injury mechanisms. Behaviour that influences risk factors and injury mechanisms is not confined only to the athlete. Various types of behaviour by, for example, the coach, referee, physical therapist or sports associations, also influence risk factors and injury mechanisms. In addition, multiple behaviours often act together. Some types of behaviour may directly affect injury risk and are by definition a risk factor. Other behaviours may only affect risk factors and injury mechanisms, and influence injury risk indirectly. Recent ideas on injury prevention that call for studies on real-life injury prevention still rely heavily on preventive measures that are established through efficacy research. A serious limitation in such an approach is that one expects that proven preventive measures will be adopted if the determinants and influences of sports safety behaviours are understood. Therefore, if one truly wants to prevent sports injuries in a real-life situation, a broader research focus is needed. In trying to do so, we need to look at lessons learned from other fields of injury prevention research.

  9. Elucidating the Key Role of a Lewis Base Solvent in the Formation of Perovskite Films Fabricated from the Lewis Adduct Approach.

    PubMed

    Cao, Xiaobing; Zhi, Lili; Li, Yahui; Fang, Fei; Cui, Xian; Yao, Youwei; Ci, Lijie; Ding, Kongxian; Wei, Jinquan

    2017-09-27

    High-quality perovskite films can be fabricated from Lewis acid-base adducts through molecule exchange. Substantial work is needed to fully understand the formation mechanism of the perovskite films, which helps to further improve their quality. Here, we study the formation of CH 3 NH 3 PbI 3 perovskite films by introducing some dimethylacetamide into the PbI 2 /N,N-dimethylformamide solution. We reveal that there are three key processes during the formation of perovskite films through the Lewis acid-base adduct approach: molecule intercalation of solvent into the PbI 2 lattice, molecule exchange between the solvent and CH 3 NH 3 I, and dissolution-recrystallization of the perovskite grains during annealing. The Lewis base solvents play multiple functions in the above processes. The properties of the solvent, including Lewis basicity and boiling point, play key roles in forming smooth perovskite films with large grains. We also provide some rules for choosing Lewis base additives to prepare high-quality perovskite films through the Lewis adduct approach.

  10. Computer-aided study of key factors determining high mechanical properties of nanostructured surface layers in metal-ceramic composites

    NASA Astrophysics Data System (ADS)

    Konovalenko, Igor S.; Shilko, Evgeny V.; Ovcharenko, Vladimir E.; Psakhie, Sergey G.

    2017-12-01

    The paper presents the movable cellular automaton method. It is based on numerical models of surface layers of the metal-ceramic composite NiCr-TiC modified under electron beam irradiation in inert gas plasmas. The models take into account different geometric, concentration and mechanical parameters of ceramic and metallic components. The authors study the contributions of key structural factors in mechanical properties of surface layers and determine the ranges of their variations by providing the optimum balance of strength, strain hardening and fracture toughness.

  11. Microtubule actin crosslinking factor 1 promotes osteoblast differentiation by promoting β-catenin/TCF1/Runx2 signaling axis.

    PubMed

    Hu, Lifang; Su, Peihong; Yin, Chong; Zhang, Yan; Li, Runzhi; Yan, Kun; Chen, Zhihao; Li, Dijie; Zhang, Ge; Wang, Liping; Miao, Zhiping; Qian, Airong; Xian, Cory J

    2018-02-01

    Osteoblast differentiation is a multistep process delicately regulated by many factors, including cytoskeletal dynamics and signaling pathways. Microtubule actin crosslinking factor 1 (MACF1), a key cytoskeletal linker, has been shown to play key roles in signal transduction and in diverse cellular processes; however, its role in regulating osteoblast differentiation is still needed to be elucidated. To further uncover the functions and mechanisms of action of MACF1 in osteoblast differentiation, we examined effects of MACF1 knockdown (MACF1-KD) in MC3T3-E1 osteoblastic cells on their osteoblast differentiation and associated molecular mechanisms. The results showed that knockdown of MACF1 significantly suppressed mineralization of MC3T3-E1 cells, down-regulated the expression of key osteogenic genes alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and type I collagen α1 (Col Iα1). Knockdown of MACF1 dramatically reduced the nuclear translocation of β-catenin, decreased the transcriptional activation of T cell factor 1 (TCF1), and down-regulated the expression of TCF1, lymphoid enhancer-binding factor 1 (LEF1), and Runx2, a target gene of β-catenin/TCF1. In addition, MACF1-KD increased the active level of glycogen synthase kinase-3β (GSK-3β), which is a key regulator for β-catenin signal transduction. Moreover, the reduction of nuclear β-catenin amount and decreased expression of TCF1 and Runx2 were significantly reversed in MACF1-KD cells when treated with lithium chloride, an agonist for β-catenin by inhibiting GSK-3β activity. Taken together, these findings suggest that knockdown of MACF1 in osteoblastic cells inhibits osteoblast differentiation through suppressing the β-catenin/TCF1-Runx2 axis. Thus, a novel role of MACF1 in and a new mechanistic insight of osteoblast differentiation are uncovered. © 2017 Wiley Periodicals, Inc.

  12. Integrated Proteomic and Transcriptomic-Based Approaches to Identifying Signature Biomarkers and Pathways for Elucidation of Daoy and UW228 Subtypes.

    PubMed

    Higdon, Roger; Kala, Jessie; Wilkins, Devan; Yan, Julia Fangfei; Sethi, Manveen K; Lin, Liang; Liu, Siqi; Montague, Elizabeth; Janko, Imre; Choiniere, John; Kolker, Natali; Hancock, William S; Kolker, Eugene; Fanayan, Susan

    2017-02-03

    Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Patient survival has remained largely the same for the past 20 years, with therapies causing significant health, cognitive, behavioral and developmental complications for those who survive the tumor. In this study, we profiled the total transcriptome and proteome of two established MB cell lines, Daoy and UW228, using high-throughput RNA sequencing (RNA-Seq) and label-free nano-LC-MS/MS-based quantitative proteomics, coupled with advanced pathway analysis. While Daoy has been suggested to belong to the sonic hedgehog (SHH) subtype, the exact UW228 subtype is not yet clearly established. Thus, a goal of this study was to identify protein markers and pathways that would help elucidate their subtype classification. A number of differentially expressed genes and proteins, including a number of adhesion, cytoskeletal and signaling molecules, were observed between the two cell lines. While several cancer-associated genes/proteins exhibited similar expression across the two cell lines, upregulation of a number of signature proteins and enrichment of key components of SHH and WNT signaling pathways were uniquely observed in Daoy and UW228, respectively. The novel information on differentially expressed genes/proteins and enriched pathways provide insights into the biology of MB, which could help elucidate their subtype classification.

  13. HnRNPL as a key factor in spermatogenesis: Lesson from functional proteomic studies of azoospermia patients with sertoli cell only syndrome.

    PubMed

    Li, Jingping; Guo, Wenbin; Li, Fei; He, Jincan; Yu, Qingfeng; Wu, Xiaoqiang; Li, Jianming; Mao, Xiangming

    2012-06-06

    Sertoli cell only syndrome (SCOS) is one of the main causes leading to the abnormal spermatogenesis. However, the mechanisms for abnormal spermatogenesis in SCOS are still unclear. Here, we analyzed the clinical testis samples of SCOS patients by two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOF MS) to find the key factors contributing to SCOS. Thirteen differential proteins were identified in clinical testis samples between normal spermatogenesis group and SCOS group. Interestingly, in these differential proteins, Heterogeneous nuclear ribonucleoprotein L(HnRNPL) was suggested as a key regulator involved in apoptosis, death and growth of spermatogenic cells by String and Pubgene bioinformatic programs. Down-regulated HnRNPL in testis samples of SCOS patients was further confirmed by immunohistochemical staining and western blotting. Moreover, in vitro and in vivo experiments demonstrated that knockdown of HnRNPL led to inhibited proliferation, increased apoptosis of spermatogenic cell but decreased apoptosis of sertoli cells. Expression of carcinoembryonic antigen-related cell adhesion molecule 1 in GC-1 cells or expression of inducible nitric oxide synthases in TM4 sertoli cells, was found to be regulated by HnRNPL. Our study first shows HnRNPL as a key factor involved in the spermatogenesis by functional proteomic studies of azoospermia patients with sertoli cell only syndrome. This article is part of a Special Issue entitled: Proteomics: The clinical link. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Elucidating Article 45.6 of the International Code of Zoological Nomenclature: A dichotomous key for the determination of subspecific or infrasubspecific rank

    USDA-ARS?s Scientific Manuscript database

    We present an overview of the difficulties sometimes encountered when determining whether a published name following a binomen is available or infrasubspecific and unavailable, following Article 45.6 of the International Code of Zoological Nomenclature (ICZN, 1999). We propose a dichotomous key that...

  15. Factors affecting construction performance: exploratory factor analysis

    NASA Astrophysics Data System (ADS)

    Soewin, E.; Chinda, T.

    2018-04-01

    The present work attempts to develop a multidimensional performance evaluation framework for a construction company by considering all relevant measures of performance. Based on the previous studies, this study hypothesizes nine key factors, with a total of 57 associated items. The hypothesized factors, with their associated items, are then used to develop questionnaire survey to gather data. The exploratory factor analysis (EFA) was applied to the collected data which gave rise 10 factors with 57 items affecting construction performance. The findings further reveal that the items constituting ten key performance factors (KPIs) namely; 1) Time, 2) Cost, 3) Quality, 4) Safety & Health, 5) Internal Stakeholder, 6) External Stakeholder, 7) Client Satisfaction, 8) Financial Performance, 9) Environment, and 10) Information, Technology & Innovation. The analysis helps to develop multi-dimensional performance evaluation framework for an effective measurement of the construction performance. The 10 key performance factors can be broadly categorized into economic aspect, social aspect, environmental aspect, and technology aspects. It is important to understand a multi-dimension performance evaluation framework by including all key factors affecting the construction performance of a company, so that the management level can effectively plan to implement an effective performance development plan to match with the mission and vision of the company.

  16. Privacy Protection for Telecare Medicine Information Systems Using a Chaotic Map-Based Three-Factor Authenticated Key Agreement Scheme.

    PubMed

    Zhang, Liping; Zhu, Shaohui; Tang, Shanyu

    2017-03-01

    Telecare medicine information systems (TMIS) provide flexible and convenient e-health care. However, the medical records transmitted in TMIS are exposed to unsecured public networks, so TMIS are more vulnerable to various types of security threats and attacks. To provide privacy protection for TMIS, a secure and efficient authenticated key agreement scheme is urgently needed to protect the sensitive medical data. Recently, Mishra et al. proposed a biometrics-based authenticated key agreement scheme for TMIS by using hash function and nonce, they claimed that their scheme could eliminate the security weaknesses of Yan et al.'s scheme and provide dynamic identity protection and user anonymity. In this paper, however, we demonstrate that Mishra et al.'s scheme suffers from replay attacks, man-in-the-middle attacks and fails to provide perfect forward secrecy. To overcome the weaknesses of Mishra et al.'s scheme, we then propose a three-factor authenticated key agreement scheme to enable the patient to enjoy the remote healthcare services via TMIS with privacy protection. The chaotic map-based cryptography is employed in the proposed scheme to achieve a delicate balance of security and performance. Security analysis demonstrates that the proposed scheme resists various attacks and provides several attractive security properties. Performance evaluation shows that the proposed scheme increases efficiency in comparison with other related schemes.

  17. Elucidation and Optimization of Resistive Random Access Memory Switching Behavior for Advanced Computing Applications

    NASA Astrophysics Data System (ADS)

    Alamgir, Zahiruddin

    RRAM has recently emerged as a strong candidate for non-volatile memory (NVM). Beyond memory applications, RRAM holds promise for use in performing logic functions, mimicking neuromorphic activities, enabling multi-level switching, and as one of the key elements of hardware based encryption or signal processing systems. It has been shown previously that RRAM resistance levels can be changed by adjusting compliance current or voltage level. This characteristic makes RRAM suitable for use in setting the synaptic weight in neuromorphic computing circuits. RRAM is also considered as a key element in hardware encryption systems, to produce unique and reproducible signals. However, a key challenge to implement RRAM in these applications is significant cycle to cycle performance variability. We sought to develop RRAM that can be tuned to different resistance levels gradually, with high reliability, and low variability. To achieve this goal, we focused on elucidating the conduction mechanisms underlying the resistive switching behavior for these devices. Electrical conduction mechanisms were determined by curve fitting I-V data using different current conduction equations. Temperature studies were also performed to corroborate these data. It was found that Schottky barrier height and width modulation was one of the key parameters that could be tuned to achieve different resistance levels, and for switching resistance states, primarily via oxygen vacancy movement. Oxygen exchange layers with different electronegativity were placed between top electrode and the oxide layer of TaOx devices to determine the effect of oxygen vacancy concentrations and gradients in these devices. It was found that devices with OELs with lower electronegativity tend to yield greater separation in the OFF vs. ON state resistance levels. As an extension of this work, TaOx based RRAM with Hf as the OEL was fabricated and could be tuned to different resistance level using pulse width and height

  18. The Arabidopsis transcription factor AtTCP15 regulates endoreduplication by modulating expression of key cell-cycle genes.

    PubMed

    Li, Zi-Yu; Li, Bin; Dong, Ai-Wu

    2012-01-01

    Plant cells frequently undergo endoreduplication, a modified cell cycle in which genome is repeatedly replicated without cytokinesis. As the key step to achieve final size and function for cells, endoreduplication is prevalent during plant development. However, mechanisms to control the balance between endoreduplication and mitotic cell division are still poorly understood. Here, we show that the Arabidopsis TCP (CINCINNATA-like TEOSINTE BRANCHED1-CYCLOIDEA-PCF)-family transcription factor gene AtTCP15 is expressed in trichomes, as well as in rapidly dividing and vascular tissues. Expression of AtTCP15SRDX, AtTCP15 fused with a SRDX repressor domain, induces extra endoreduplication in trichomes and cotyledon cells in transgenic Arabidopsis. On the contrary, overexpression of AtTCP15 suppresses endoreduplication in trichomes and other examined cells. Misregulation of AtTCP15 affects the expression of several important genes involved in cell-cycle regulation. AtTCP15 protein binds directly to the promoter regions of CYCA2;3 and RETINOBLASTOMA-RELATED (RBR) genes, which play key roles in endoreduplication. Taken together, AtTCP15 plays an important role in regulating endoreduplication during Arabidopsis development.

  19. Building blocks for automated elucidation of metabolites: natural product-likeness for candidate ranking.

    PubMed

    Jayaseelan, Kalai Vanii; Steinbeck, Christoph

    2014-07-05

    In metabolomics experiments, spectral fingerprints of metabolites with no known structural identity are detected routinely. Computer-assisted structure elucidation (CASE) has been used to determine the structural identities of unknown compounds. It is generally accepted that a single 1D NMR spectrum or mass spectrum is usually not sufficient to establish the identity of a hitherto unknown compound. When a suite of spectra from 1D and 2D NMR experiments supplemented with a molecular formula are available, the successful elucidation of the chemical structure for candidates with up to 30 heavy atoms has been reported previously by one of the authors. In high-throughput metabolomics, usually 1D NMR or mass spectrometry experiments alone are conducted for rapid analysis of samples. This method subsequently requires that the spectral patterns are analyzed automatically to quickly identify known and unknown structures. In this study, we investigated whether additional existing knowledge, such as the fact that the unknown compound is a natural product, can be used to improve the ranking of the correct structure in the result list after the structure elucidation process. To identify unknowns using as little spectroscopic information as possible, we implemented an evolutionary algorithm-based CASE mechanism to elucidate candidates in a fully automated fashion, with input of the molecular formula and 13C NMR spectrum of the isolated compound. We also tested how filters like natural product-likeness, a measure that calculates the similarity of the compounds to known natural product space, might enhance the performance and quality of the structure elucidation. The evolutionary algorithm is implemented within the SENECA package for CASE reported previously, and is available for free download under artistic license at http://sourceforge.net/projects/seneca/. The natural product-likeness calculator is incorporated as a plugin within SENECA and is available as a GUI client and

  20. Elucidating Reaction Mechanisms on Quantum Computers

    NASA Astrophysics Data System (ADS)

    Wiebe, Nathan; Reiher, Markus; Svore, Krysta; Wecker, Dave; Troyer, Matthias

    We show how a quantum computer can be employed to elucidate reaction mechanisms in complex chemical systems, using the open problem of biological nitrogen fixation in nitrogenase as an example. We discuss how quantum computers can augment classical-computer simulations for such problems, to significantly increase their accuracy and enable hitherto intractable simulations. Detailed resource estimates show that, even when taking into account the substantial overhead of quantum error correction, and the need to compile into discrete gate sets, the necessary computations can be performed in reasonable time on small quantum computers. This demonstrates that quantum computers will realistically be able to tackle important problems in chemistry that are both scientifically and economically significant.

  1. Regulation and Function of Cdt1; A Key Factor in Cell Proliferation and Genome Stability

    PubMed Central

    Pozo, Pedro N.; Cook, Jeanette Gowen

    2016-01-01

    Successful cell proliferation requires efficient and precise genome duplication followed by accurate chromosome segregation. The Cdc10-dependent transcript 1 protein (Cdt1) is required for the first step in DNA replication, and in human cells Cdt1 is also required during mitosis. Tight cell cycle controls over Cdt1 abundance and activity are critical to normal development and genome stability. We review here recent advances in elucidating Cdt1 molecular functions in both origin licensing and kinetochore–microtubule attachment, and we describe the current understanding of human Cdt1 regulation. PMID:28025526

  2. Innate factors causing differences in gene flow frequency from transgenic rice to different weedy rice biotypes.

    PubMed

    Zuo, Jiao; Zhang, Lianju; Song, Xiaoling; Dai, Weimin; Qiang, Sheng

    2011-06-01

    The compatibility and outcrossing rates between transgenic rice and weedy rice biotypes have been studied in some previous cases. However, few studies have addressed the reasons for these differences. The present study compared the compatibility and outcrossing rates between transgenic rice and selected weedy rice biotypes using manual and natural crossing experiments to elucidate the key innate factors causing the different outcrossing rates. Hybrid seed sets from manual crossing between transgenic rice and weedy rice varied from 31.8 to 82.7%, which correlated directly with genetic compatibility. Moreover, the significant differences in the quantity of germinated donor pollens and pollen tubes entering the weedy rice ovule directly contributed to the different seed sets. The natural outcrossing rates varied from 0 to 6.66‰. The duration of flowering overlap was the key factor influencing natural outcrossing. Plant and panicle height also affected outcrossing success. From this study, it is concluded that the likelihood of gene flow between transgenic rice and weedy rice biotypes is primarily determined by floral synchronisation and secondarily influenced by genetic compatibility and some morphological characteristics. Copyright © 2011 Society of Chemical Industry.

  3. Key Planning Factors for Recovery from a Biological Terrorism Incident

    DTIC Science & Technology

    2012-08-30

    Goals, this document identifies key technical planning areas that may be used to inform subsequent FEMA response and recovery guidance documents. The...expressed herein do not necessarily state or reflect those of their respective organizations or the US Government. The modeling and analysis provided by...responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would

  4. A Drought-Inducible Transcription Factor Delays Reproductive Timing in Rice.

    PubMed

    Zhang, Chunyu; Liu, Jun; Zhao, Tao; Gomez, Adam; Li, Cong; Yu, Chunsheng; Li, Hongyu; Lin, Jianzhong; Yang, Yuanzhu; Liu, Bin; Lin, Chentao

    2016-05-01

    The molecular mechanisms underlying photoperiod or temperature control of flowering time have been recently elucidated, but how plants regulate flowering time in response to other external factors, such as water availability, remains poorly understood. Using a large-scale Hybrid Transcription Factor approach, we identified a bZIP transcriptional factor, O. sativa ABA responsive element binding factor 1 (OsABF1), which acts as a suppressor of floral transition in a photoperiod-independent manner. Simultaneous knockdown of both OsABF1 and its closest homologous gene, OsbZIP40, in rice (Oryza sativa) by RNA interference results in a significantly earlier flowering phenotype. Molecular and genetic analyses demonstrate that a drought regime enhances expression of the OsABF1 gene, which indirectly suppresses expression of the Early heading date 1 (Ehd1) gene that encodes a key activator of rice flowering. Furthermore, we identified a drought-inducible gene named OsWRKY104 that is under the direct regulation of OsABF1 Overexpression of OsWRKY104 can suppress Ehd1 expression and confers a later flowering phenotype in rice. Together, these findings reveal a novel pathway by which rice modulates heading date in response to the change of ambient water availability. © 2016 American Society of Plant Biologists. All Rights Reserved.

  5. Detector-device-independent quantum key distribution: Security analysis and fast implementation

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

    Boaron, Alberto; Korzh, Boris; Houlmann, Raphael

    One of the most pressing issues in quantum key distribution (QKD) is the problem of detector side-channel attacks. To overcome this problem, researchers proposed an elegant “time-reversal” QKD protocol called measurement-device-independent QKD (MDI-QKD), which is based on time-reversed entanglement swapping. But, MDI-QKD is more challenging to implement than standard point-to-point QKD. Recently, we proposed an intermediary QKD protocol called detector-device-independent QKD (DDI-QKD) in order to overcome the drawbacks of MDI-QKD, with the hope that it would eventually lead to a more efficient detector side-channel-free QKD system. We analyze the security of DDI-QKD and elucidate its security assumptions. We find thatmore » DDI-QKD is not equivalent to MDI-QKD, but its security can be demonstrated with reasonable assumptions. On the more practical side, we consider the feasibility of DDI-QKD and present a fast experimental demonstration (clocked at 625 MHz), capable of secret key exchange up to more than 90 km.« less

  6. Detector-device-independent quantum key distribution: Security analysis and fast implementation

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

    Boaron, Alberto; Korzh, Boris; Boso, Gianluca

    One of the most pressing issues in quantum key distribution (QKD) is the problem of detector side-channel attacks. To overcome this problem, researchers proposed an elegant “time-reversal” QKD protocol called measurement-device-independent QKD (MDI-QKD), which is based on time-reversed entanglement swapping. However, MDI-QKD is more challenging to implement than standard point-to-point QKD. Recently, an intermediary QKD protocol called detector-device-independent QKD (DDI-QKD) has been proposed to overcome the drawbacks of MDI-QKD, with the hope that it would eventually lead to a more efficient detector side-channel-free QKD system. Here, we analyze the security of DDI-QKD and elucidate its security assumptions. We find thatmore » DDI-QKD is not equivalent to MDI-QKD, but its security can be demonstrated with reasonable assumptions. On the more practical side, we consider the feasibility of DDI-QKD and present a fast experimental demonstration (clocked at 625 MHz), capable of secret key exchange up to more than 90 km.« less

  7. Detector-device-independent quantum key distribution: Security analysis and fast implementation

    DOE PAGES

    Boaron, Alberto; Korzh, Boris; Houlmann, Raphael; ...

    2016-08-09

    One of the most pressing issues in quantum key distribution (QKD) is the problem of detector side-channel attacks. To overcome this problem, researchers proposed an elegant “time-reversal” QKD protocol called measurement-device-independent QKD (MDI-QKD), which is based on time-reversed entanglement swapping. But, MDI-QKD is more challenging to implement than standard point-to-point QKD. Recently, we proposed an intermediary QKD protocol called detector-device-independent QKD (DDI-QKD) in order to overcome the drawbacks of MDI-QKD, with the hope that it would eventually lead to a more efficient detector side-channel-free QKD system. We analyze the security of DDI-QKD and elucidate its security assumptions. We find thatmore » DDI-QKD is not equivalent to MDI-QKD, but its security can be demonstrated with reasonable assumptions. On the more practical side, we consider the feasibility of DDI-QKD and present a fast experimental demonstration (clocked at 625 MHz), capable of secret key exchange up to more than 90 km.« less

  8. Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme

    PubMed Central

    Bailey, Lucas J; Tan, Yong Zi; Wei, Hui; Wang, Andrew; Farcasanu, Mara; Woods, Virgil A; McCord, Lauren A; Lee, David; Shang, Weifeng; Deprez-Poulain, Rebecca; Deprez, Benoit; Liu, David R; Koide, Akiko; Koide, Shohei; Kossiakoff, Anthony A

    2018-01-01

    Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity. We also used cryoEM, X-ray crystallography, SAXS, and HDX-MS to elucidate the molecular basis of how amyloidogenic peptides stabilize the disordered IDE catalytic cleft, thereby inducing selective degradation by substrate-assisted catalysis. Furthermore, our insulin-bound IDE structures explain how IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds. Together, our studies provide a mechanism for how IDE selectively degrades amyloidogenic peptides and offers structural insights for developing IDE-based therapies. PMID:29596046

  9. HIF-1 α as a Key Factor in Bile Duct Ligation-Induced Liver Fibrosis in Rats.

    PubMed

    Moczydlowska, Joanna; Miltyk, Wojciech; Hermanowicz, Adam; Lebensztejn, Dariusz M; Palka, Jerzy A; Debek, Wojciech

    2017-02-01

    Although several studies suggested hypoxia as an important microenvironmental factor contributing to inflammation and fibrosis in chronic liver diseases, the mechanism of this process is not fully understood. We considered hypoxia inducible factor (HIF-1α) as a key transcription factor in liver fibrosis. The aim of the study was to evaluate the mechanisms of signaling pathway during bile duct ligation (BDL)-induced liver fibrosis in rats. BDL animal model of liver fibrosis was used in the study. Male Wistar rats were divided randomly into two experimental groups: sham group (n = 15), BDL group (n = 30). Hydroxyproline (Hyp) content as a marker of collagen accumulation in liver of rats subjected to BDL was evaluated according to the method described by Gerling B et al. Expression of signaling proteins [integrin β 1 receptor, HIF-1α, nuclear factor kappa B (NF-κB), and transforming growth factor (TGF-β)] was evaluated applying Western-immunoblot analysis. In all experiments, the mean values for six assays ± standard deviations (SD) were calculated. The results were submitted to the statistical analysis using the Student's "t" test, accepting p < 0.05 as significant. Ligation of bile ducts was found to increase Hyp content in rat liver, accompanied by increase of HIF-1α expression during 10 weeks after BDL. The Hyp level was time dependent. There was not such a difference in control group (p < 0.001). Simultaneously expression of NF-κB, TGF-β, β 1 -integrin receptor was significantly elevated starting from sixth week after ligation. Activity of metalloproteinases 2 and 9 in the livers were increased 1 week after surgery and remained increased until the end of the experiment. The mechanism of development of liver fibrosis involves activation of Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9), upregulation of HIF-1α transcriptional activity and its related factors, NF-κB and TGF-β. It suggests that they may represent targets for

  10. Key Factors for a High-Quality Peritoneal Dialysis Program — The Role of the PD Team and Continuous Quality Improvement

    PubMed Central

    Fang, Wei; Ni, Zhaohui; Qian, Jiaqi

    2014-01-01

    The proportion of end-stage renal disease (ESRD) patients on peritoneal dialysis (PD) has increased very fast in China over the last decade. Renji Hospital, affiliated with Shanghai Jiaotong University School of Medicine, is a recognized high-quality PD unit with a high PD utilization rate, excellent patient and technique survival (1-year and 5-year patient survival rate of 93% and 71%, and 1-year and 5-year technique survival of 96% and 82%, respectively), low peritonitis rate and a well-documented good quality of life of the treated patients. We believe that a dedicated and experienced PD team, a structured patient training program, continuous patient support, establishing and utilizing standardized protocols, starting PD with low dialysis dose, monitoring key performance indicators (KPIs), and continuous quality improvement (CQI) are the key factors underlying this successful PD program. PMID:24962961

  11. Interferon regulatory factors: A key to tumour immunity.

    PubMed

    Chen, Yan-Jie; Li, Jing; Lu, Nan; Shen, Xi-Zhong

    2017-08-01

    Interferon regulatory factors (IRFs), which have 10 members, belong to the transcription factor family and were named because of the regulation of interferon expression. They play important roles in the immune regulation, cell differentiation, cell apoptosis, and cell cycle regulation. This article will review the functional characteristics and immune activity of the family members, especially in the role of cell differentiation and autoimmune diseases. Intensive studies will help uncover the pathogenesis of the disease in a more comprehensive view, and provide novel targets for disease treatment. But the most important problems yet to solve is IRFs function in the development processes of tumour, and whether IRFs can be an important regulator in tumour immune treatment. Copyright © 2017. Published by Elsevier B.V.

  12. The adenoid as a key factor in upper airway infections.

    PubMed

    van Cauwenberge, P B; Bellussi, L; Maw, A R; Paradise, J L; Solow, B

    1995-06-01

    The adenoids (and the nasopharynx) play a key role in the normal functioning and in various pathologies of the upper respiratory tract. In this paper the role of adenoidal pathology and the beneficial effect of adenoidectomy in some upper respiratory tract and facial anomalies and diseases are discussed; otitis media with effusion, recurrent acute otitis media, sinusitis, snoring and sleep apnea and abnormal patterns in the midface growth and development.

  13. Study of the key factors affecting the triple grid lifetime of the LIPS-300 ion thruster

    NASA Astrophysics Data System (ADS)

    Mingming, SUN; Liang, WANG; Juntai, YANG; Xiaodong, WEN; Yongjie, HUANG; Meng, WANG

    2018-04-01

    In order to ascertain the key factors affecting the lifetime of the triple grids in the LIPS-300 ion thruster, the thermal deformation, upstream ion density and component lifetime of the grids are simulated with finite element analysis, fluid simulation and charged-particle tracing simulation methods on the basis of a 1500 h short lifetime test. The key factor affecting the lifetime of the triple grids in the LIPS-300 ion thruster is obtained and analyzed through the test results. The results show that ion sputtering erosion of the grids in 5 kW operation mode is greater than in the case of 3 kW. In 5 kW mode, the decelerator grid shows the most serious corrosion, the accelerator grid shows moderate corrosion, and the screen grid shows the least amount of corrosion. With the serious corrosion of the grids in 5 kW operation mode, the intercept current of the acceleration and deceleration grids increases substantially. Meanwhile, the cold gap between the accelerator grid and the screen grid decreases from 1 mm to 0.7 mm, while the cold gap between the accelerator grid and the decelerator grid increases from 1 mm to 1.25 mm after 1500 h of thruster operation. At equilibrium temperature with 5 kW power, the finite element method (FEM) simulation results show that the hot gap between the screen grid and the accelerator grid reduces to 0.2 mm. Accordingly, the hot gap between the accelerator grid and the decelerator grid increases to 1.5 mm. According to the fluid method, the plasma density simulated in most regions of the discharge chamber is 1 × 1018‑8 × 1018 m‑3. The upstream plasma density of the screen grid is in the range 6 × 1017‑6 × 1018 m‑3 and displays a parabolic characteristic. The charged particle tracing simulation method results show that the ion beam current without the thermal deformation of triple grids has optimal perveance status. The ion sputtering rates of the accelerator grid hole and the decelerator hole are 5.5 × 10‑14 kg s‑1 and

  14. Uncertainty about effects is a key factor influencing institutional review boards' approval of clinical studies.

    PubMed

    Wao, Hesborn; Mhaskar, Rahul; Kumar, Ambuj; Miladinovic, Branko; Guterbock, Thomas; Hozo, Iztok; Djulbegovic, Benjamin

    2014-10-01

    To investigate factors, which influence institutional review boards' (IRBs') decision to approve or not approve clinical studies, a nationwide vignette-based online survey of IRB members was conducted. A factorial design was used, whereby seven aspects of each hypothetical study were randomly varied in 15 phrases in each vignette to produce unique vignettes. Participants indicated the degree of study approval and described factors influencing approval decision. Qualitative responses were thematically content analyzed. Sixteen themes were obtained from 208 participants from 42 institutions. Uncertainty, adherence, study design, and harms were frequently and intensely cited to influence study approval. Analysis of two extreme subgroups (approvers vs. nonapprovers) showed that uncertainty influenced approval decisions, odds ratios (OR) = 3.5 (95% confidence interval [CI], 1.3-9.8) and OR = 3.2 (95% CI, 1.1-8.9), respectively, based on theme frequency and theme intensity, ignoring multiple observations per person. Taking into consideration multiple observations per person, similar results were obtained for uncertainty: OR = 8.9 (95% CI, 0.93-85.4). Perceived uncertainty about benefits and harms of a proposed intervention is a key driver in IRB members' approval of clinical trials. This, in turn, calls for improved standardization in the communications of information on benefits and harms in the research protocols considered by the IRBs. Published by Elsevier Inc.

  15. A key role for Pre-B cell colony-enhancing factor in experimental hepatitis.

    PubMed

    Moschen, Alexander R; Gerner, Romana; Schroll, Andrea; Fritz, Teresa; Kaser, Arthur; Tilg, Herbert

    2011-08-01

    Pre-B cell colony-enhancing factor (PBEF), also known as nicotinamide phosphoribosyltransferase or visfatin, plays an important role in metabolic, inflammatory, and malignant diseases. Recent evidence suggests that blocking its enzymatic activity using a specific small-molecule inhibitor (FK866) might be beneficial in acute experimental inflammation. We investigated the role of PBEF in human liver disease and experimental hepatitis. PBEF serum levels and hepatic expression were determined in patients with chronic liver diseases. These studies were followed by in vivo experiments using concanavalin A (ConA) and D-galactosamine/lipopolysaccharide (LPS) models of experimental hepatitis. PBEF was either overexpressed by hydrodynamic perfusion or inhibited by FK866. In vivo findings were corroborated studying inflammatory responses of lentivirally PBEF-silenced or control FL83B mouse hepatocytes. Here, we demonstrate that PBEF serum levels were increased in patients with chronic liver diseases irrespective of disease stage and etiology. In particular, we observed enhanced PBEF expression in hepatocytes. Liver-targeted overexpression of PBEF rendered mice more susceptible to ConA- and D-galactosamine/LPS-induced hepatitis compared with control animals. In contrast, inhibition of PBEF using FK866 protected mice from ConA-induced liver damage and apoptosis. Administration of FK866 resulted in depletion of liver nicotinamide adenine dinucleotide+ levels and reduced proinflammatory cytokine expression. Additionally, FK866 protected mice in the D-galactosamine/LPS model of acute hepatitis. In vitro, PBEF-silenced mouse hepatocytes showed decreased responses after stimulation with LPS, lipoteichoic acid, and tumor necrosis factor α. In primary murine Kupffer cells, FK866 suppressed LPS-induced interleukin (IL)-6 production, whereas incubation with recombinant PBEF resulted in increased IL-6 release. Our data suggest that PBEF is of key importance in experimental hepatitis

  16. Structure elucidation of a novel oligosaccharide (Medalose) from camel milk

    NASA Astrophysics Data System (ADS)

    Gangwar, Lata; Singh, Rinku; Deepak, Desh

    2018-02-01

    Free oligosaccharides are the third most abundant solid component in milk after lactose and lipids. The study of milk oligosaccharides indicate that nutrients are not only benefits the infant's gut but also perform a number of other functions which include stimulation of growth, receptor analogues to inhibit binding of pathogens and substances that promote postnatal brain development. Surveys reveal that camel milk oligosaccharides possess varied biological activities that help in the treatment of diabetes, asthma, anaemia, piles and also a food supplement to milking mothers. In this research, camel milk was selected for its oligosaccharide contents, which was then processed by Kobata and Ginsburg method followed by the HPLC and CC techniques. Structure elucidation of isolated compound was done by the chemical degradation, chemical transformation and comparison of chemical shift of NMR data of natural and acetylated oligosaccharide structure reporter group theory, the 1H, 13C NMR, 2D-NMR (COSY, TOCSY and HSQC) techniques, and mass spectrometry. The structure was elucidated as under: MEDALOSE

  17. Soil physical properties: Key factors for successful reclamation of disturbed landscapes

    NASA Astrophysics Data System (ADS)

    Krümmelbein, Julia; Raab, Thomas

    2013-04-01

    The practice of open cast mining, e.g. for lignite, results in major landscape disturbances and especially affects soils because relocation and subsequent mixing of naturally developed soil horizons leads to areas with extremely altered soil properties compared to the undisturbed conditions. Various reclamation measures are applied to recover the reconstructed landscape for different land use options. Major parts of the post mining landscapes are used for agriculture, agroforestry or silviculture, the remaining voids of the coal mines fill successively with groundwater after mine closure and are or will be used mainly for touristic and leisure purposes. Small proportions of the post mining areas are left for natural succession, or habitats for endangered flora and fauna are initiated. In reclamation research, many studies have focused on soil chemical and biological constraints of post mining substrates and investigated factors such as unsuitable pH, in many cases very low pH, (poor) nutrient contents and (poor) biological activity. But the initial and developing soil physical parameters and functions are also key factors for the success of reclamation practices. The soil water and gas balance influence strongly the suitability of a site for the intended future land use. The mechanical stability of the soil determines the rigidity of the pore system against deforming forces and thereby the persistence of soil functions, such as water and air permeability over time. The amendment of unfavourable (initial) soil physical properties is in most cases more complex and time-consuming than e.g. optimization of pH or fertilization with nutrients. Moreover, regarding the suitability of a site e.g. as a habitat for plants or microorganisms, poor physical pre-conditions can turn substrates with perfect nutrient contents and composition and pH into infertile locations of very low productivity. We show results of an on-going field study where the effects of different

  18. Key factors that influence government policies and decision making about healthcare priorities: Lessons for the field of eating disorders.

    PubMed

    Whiteford, Harvey; Weissman, Ruth Striegel

    2017-03-01

    Worldwide, the demand for healthcare exceeds what individuals and governments are able to afford. Priority setting is therefore inevitable, and mental health services have often been given low priority in the decision-making process. Drawing on established economic criteria, and specifically the work of Philip Musgrove, key factors which influence government decision-making about health priorities are reviewed. These factors include the size of the health burden, the availability of cost-effective interventions to reduce the burden, whether private markets can provide the necessary treatment efficiently, whether there are "catastrophic costs" incurred in accessing treatment, whether negative externalities arise from not providing care, and if the "rule of rescue" applies. Beyond setting priorities for resource allocation, governments also become involved where there is a need for regulation to maintain quality in the delivery of healthcare. By providing field-specific examples for each factor, we illustrate how advocates in the eating disorder field may use evidence to inform government policy about resource allocation and regulation in support of individuals with an eating disorder. © 2017 Wiley Periodicals, Inc.

  19. Transcription initiation complex structures elucidate DNA opening.

    PubMed

    Plaschka, C; Hantsche, M; Dienemann, C; Burzinski, C; Plitzko, J; Cramer, P

    2016-05-19

    Transcription of eukaryotic protein-coding genes begins with assembly of the RNA polymerase (Pol) II initiation complex and promoter DNA opening. Here we report cryo-electron microscopy (cryo-EM) structures of yeast initiation complexes containing closed and open DNA at resolutions of 8.8 Å and 3.6 Å, respectively. DNA is positioned and retained over the Pol II cleft by a network of interactions between the TATA-box-binding protein TBP and transcription factors TFIIA, TFIIB, TFIIE, and TFIIF. DNA opening occurs around the tip of the Pol II clamp and the TFIIE 'extended winged helix' domain, and can occur in the absence of TFIIH. Loading of the DNA template strand into the active centre may be facilitated by movements of obstructing protein elements triggered by allosteric binding of the TFIIE 'E-ribbon' domain. The results suggest a unified model for transcription initiation with a key event, the trapping of open promoter DNA by extended protein-protein and protein-DNA contacts.

  20. [Discussion on developing a data management plan and its key factors in clinical study based on electronic data capture system].

    PubMed

    Li, Qing-na; Huang, Xiu-ling; Gao, Rui; Lu, Fang

    2012-08-01

    Data management has significant impact on the quality control of clinical studies. Every clinical study should have a data management plan to provide overall work instructions and ensure that all of these tasks are completed according to the Good Clinical Data Management Practice (GCDMP). Meanwhile, the data management plan (DMP) is an auditable document requested by regulatory inspectors and must be written in a manner that is realistic and of high quality. The significance of DMP, the minimum standards and the best practices provided by GCDMP, the main contents of DMP based on electronic data capture (EDC) and some key factors of DMP influencing the quality of clinical study were elaborated in this paper. Specifically, DMP generally consists of 15 parts, namely, the approval page, the protocol summary, role and training, timelines, database design, creation, maintenance and security, data entry, data validation, quality control and quality assurance, the management of external data, serious adverse event data reconciliation, coding, database lock, data management reports, the communication plan and the abbreviated terms. Among them, the following three parts are regarded as the key factors: designing a standardized database of the clinical study, entering data in time and cleansing data efficiently. In the last part of this article, the authors also analyzed the problems in clinical research of traditional Chinese medicine using the EDC system and put forward some suggestions for improvement.

  1. [Strategies of elucidation of biosynthetic pathways of natural products].

    PubMed

    Zou, Li-Qiu; Kuang, Xue-Jun; Sun, Chao; Chen, Shi-Lin

    2016-11-01

    Elucidation of the biosynthetic pathways of natural products is not only the major goal of herb genomics, but also the solid foundation of synthetic biology of natural products. Here, this paper reviewed recent advance in this field and put forward strategies to elucidate the biosynthetic pathway of natural products. Firstly, a proposed biosynthetic pathway should be set up based on well-known knowledge about chemical reactions and information on the identified compounds, as well as studies with isotope tracer. Secondly, candidate genes possibly involved in the biosynthetic pathway were screened out by co-expression analysis and/or gene cluster mining. Lastly, all the candidate genes were heterologously expressed in the host and then the enzyme involved in the biosynthetic pathway was characterized by activity assay. Sometimes, the function of the enzyme in the original plant could be further studied by RNAi or VIGS technology. Understanding the biosynthetic pathways of natural products will contribute to supply of new leading compounds by synthetic biology and provide "functional marker" for herbal molecular breeding, thus but boosting the development of traditional Chinese medicine agriculture. Copyright© by the Chinese Pharmaceutical Association.

  2. Identifying Key Factors Relevant for Base Camp Siting

    DTIC Science & Technology

    2017-12-01

    designated by other authorized documents. DESTROY THIS REPORT WHEN NO LONGER NEEDED. DO NOT RETURN IT TO THE ORIGINATOR. ERDC TR-17-17 iii Contents...Criteria Framework .......................................................................................... 6 3.1 Design templates...18 Tables Table 1. Design choice factors. Each

  3. Key volatile compounds in red koji-shochu, a Monascus-fermented product, and their formation steps during fermentation.

    PubMed

    Rahayu, Yen Yen Sally; Yoshizaki, Yumiko; Yamaguchi, Keiko; Okutsu, Kayu; Futagami, Taiki; Tamaki, Hisanori; Sameshima, Yoshihiro; Takamine, Kazunori

    2017-06-01

    Red koji, which refers the solid culture grown koji mold on the steamed rice, is one of the ingredients of Asian fermented foods including the Japanese spirit shochu. This study was aimed at elucidating the characteristic flavor and key volatile compounds of red koji-shochu as well as the mechanism of their formation. Sensory evaluation showed that red koji-shochu has the distinctive flavors cheese, sour, milky, and oily. Fifteen key volatile compounds of red koji-shochu were identified by gas chromatography-mass spectrometry and high-performance liquid chromatography, and by comparison between red koji-shochu and white koji-shochu, as another typical shochu. The mash analysis revealed that ketone compounds and short-chain acids derive from red koji. Furthermore, although other key compounds were produced by yeast, it is highly likely that their concentrations were affected directly or indirectly by the high activities of protease and lipase in red koji. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Developing culturally adapted lifestyle interventions for South Asian migrant populations: a qualitative study of the key success factors and main challenges.

    PubMed

    Terragni, L; Beune, E; Stronks, K; Davidson, E; Qureshi, S; Kumar, B; Diaz, E

    2018-06-11

    South Asian migrant populations have a high risk of non-communicable diseases, such as type 2 diabetes (T2D). The aim of this study is to provide in-depth insight into key success factors and challenges in developing culturally adapted lifestyle interventions to prevent T2D within South Asian migrant populations. The study has a qualitative research design. In-depth interviews, using a semi-structured interview guide, were conducted with eight researchers and project leaders from five studies of culturally adapted lifestyle interventions for South Asian migrant populations. Data were analysed using a grounded theory approach. Four main themes emerged as key factors for success: 'approaching the community in the right way', 'the intervention as a space for social relations', 'support from public authorities' and 'being reflexive and flexible'. Two themes emerged as challenges: 'struggling with time' and 'overemphasising cultural differences'. Our findings augment existing research by establishing the importance of cooperation at the organisational and institutional levels, of fostering the creation of social networks through interventions and of acknowledging the multiplicity of identities and resources among individuals of the same ethnic origin. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  5. Analysis of transcription factors key for mouse pancreatic development establishes NKX2-2 and MNX1 mutations as causes of neonatal diabetes in man.

    PubMed

    Flanagan, Sarah E; De Franco, Elisa; Lango Allen, Hana; Zerah, Michele; Abdul-Rasoul, Majedah M; Edge, Julie A; Stewart, Helen; Alamiri, Elham; Hussain, Khalid; Wallis, Sam; de Vries, Liat; Rubio-Cabezas, Oscar; Houghton, Jayne A L; Edghill, Emma L; Patch, Ann-Marie; Ellard, Sian; Hattersley, Andrew T

    2014-01-07

    Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Analysis of Transcription Factors Key for Mouse Pancreatic Development Establishes NKX2-2 and MNX1 Mutations as Causes of Neonatal Diabetes in Man

    PubMed Central

    Flanagan, Sarah E.; De Franco, Elisa; Lango Allen, Hana; Zerah, Michele; Abdul-Rasoul, Majedah M.; Edge, Julie A.; Stewart, Helen; Alamiri, Elham; Hussain, Khalid; Wallis, Sam; de Vries, Liat; Rubio-Cabezas, Oscar; Houghton, Jayne A.L.; Edghill, Emma L.; Patch, Ann-Marie; Ellard, Sian; Hattersley, Andrew T.

    2014-01-01

    Summary Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development. PMID:24411943

  7. Genomic approaches for the elucidation of genes and gene networks underlying cardiovascular traits.

    PubMed

    Adriaens, M E; Bezzina, C R

    2018-06-22

    Genome-wide association studies have shed light on the association between natural genetic variation and cardiovascular traits. However, linking a cardiovascular trait associated locus to a candidate gene or set of candidate genes for prioritization for follow-up mechanistic studies is all but straightforward. Genomic technologies based on next-generation sequencing technology nowadays offer multiple opportunities to dissect gene regulatory networks underlying genetic cardiovascular trait associations, thereby aiding in the identification of candidate genes at unprecedented scale. RNA sequencing in particular becomes a powerful tool when combined with genotyping to identify loci that modulate transcript abundance, known as expression quantitative trait loci (eQTL), or loci modulating transcript splicing known as splicing quantitative trait loci (sQTL). Additionally, the allele-specific resolution of RNA-sequencing technology enables estimation of allelic imbalance, a state where the two alleles of a gene are expressed at a ratio differing from the expected 1:1 ratio. When multiple high-throughput approaches are combined with deep phenotyping in a single study, a comprehensive elucidation of the relationship between genotype and phenotype comes into view, an approach known as systems genetics. In this review, we cover key applications of systems genetics in the broad cardiovascular field.

  8. Studying work practices: a key factor in understanding accidents on the level triggered by a balance disturbance.

    PubMed

    Derosier, C; Leclercq, S; Rabardel, P; Langa, P

    2008-12-01

    Accidents on the level (AOL) rank second amongst the most numerous and serious occupational accidents with days lost in France and are a major health and safety problem in every sector of activity. The case study described in this paper was conducted at a metallurgical company with 300 employees. The aims of this work were dual: 1) to extend the general knowledge required for preventing these accidents; 2) to propose prevention measures to this company. Existing data on company occupational accidents were gathered and analysed to identify a work situation that appeared likely to cause AOL. This work situation was analysed in detail. Several risk factors were identified within this work situation, by way of interviews with 12 operators. These risk factors concerned various dimensions of the work situation, particularly its physical dimension (e.g. templates structure) and organisational dimension (e.g. parts availability). Interviews were conducted, focusing on risk factors perceived by operators and involving allo-confrontations based on accounts of four AOL occurring in this situation. Allo-confrontations were interviews confronting operators with a risk occupational situation that was accidental for one of their colleagues, the latter being absent from the interview. Results highlighted the fact that the work practices implemented are key factors in understanding these accidents. This study underlines the role of work practices in AOL causality and prevention. It also provides explanations associated with various work situation dimensions involving adoption of more or less safe work practices. AOL are serious and frequent in occupational situations. Injury claims analysis and interviews in an industrial company emphasise the specific characteristics of an occupational situation and of prevention actions forming the basis of an intervention. The need for a better understanding of factors affecting work practice is highlighted in relation to research.

  9. A key for the Forest Service hardwood tree grades

    Treesearch

    Gary W. Miller; Leland F. Hanks; Harry V., Jr. Wiant

    1986-01-01

    A dichotomous key organizes the USDA Forest Service hardwood tree grade specifications into a stepwise procedure for those learning to grade hardwood sawtimber. The key addresses the major grade factors, tree size, surface characteristics, and allowable cull deductions in a series of paried choices that lead the user to a decision regarding tree grade.

  10. Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

    PubMed

    Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

    2017-01-29

    Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The Brassinosteroid Signaling Pathway—New Key Players and Interconnections with Other Signaling Networks Crucial for Plant Development and Stress Tolerance

    PubMed Central

    Gruszka, Damian

    2013-01-01

    Brassinosteroids (BRs) are a class of steroid hormones regulating a wide range of physiological processes during the plant life cycle from seed development to the modulation of flowering and senescence. The last decades, and recent years in particular, have witnessed a significant advance in the elucidation of the molecular mechanisms of BR signaling from perception by the transmembrane receptor complex to the regulation of transcription factors influencing expression of the target genes. Application of the new approaches shed light on the molecular functions of the key players regulating the BR signaling cascade and allowed identification of new factors. Recent studies clearly indicated that some of the components of BR signaling pathway act as multifunctional proteins involved in other signaling networks regulating diverse physiological processes, such as photomorphogenesis, cell death control, stomatal development, flowering, plant immunity to pathogens and metabolic responses to stress conditions, including salinity. Regulation of some of these processes is mediated through a crosstalk between BR signalosome and the signaling cascades of other hormones, including auxin, abscisic acid, ethylene and salicylic acid. Unravelling the complicated mechanisms of BR signaling and its interconnections with other molecular networks may be of great importance for future practical applications in agriculture. PMID:23615468

  12. Iris recognition based on key image feature extraction.

    PubMed

    Ren, X; Tian, Q; Zhang, J; Wu, S; Zeng, Y

    2008-01-01

    In iris recognition, feature extraction can be influenced by factors such as illumination and contrast, and thus the features extracted may be unreliable, which can cause a high rate of false results in iris pattern recognition. In order to obtain stable features, an algorithm was proposed in this paper to extract key features of a pattern from multiple images. The proposed algorithm built an iris feature template by extracting key features and performed iris identity enrolment. Simulation results showed that the selected key features have high recognition accuracy on the CASIA Iris Set, where both contrast and illumination variance exist.

  13. Elucidating the neurophysiological underpinnings of autism spectrum disorder: new developments.

    PubMed

    Luckhardt, C; Jarczok, T A; Bender, S

    2014-09-01

    The study of neurophysiological approaches together with rare and common risk factors for Autism Spectrum Disorder (ASD) allows elucidating the specific underlying neurobiology of ASD. Whereas most neurophysiologically based research in ASD to date has focussed on case-control differences based on the DSM- or ICD-based categorical ASD diagnosis, more recent studies have aimed at studying genetically and/or neurophysiologically defined homogeneous ASD subgroups for specific neuronal biomarkers. This review addresses the neurophysiological investigation of ASD by evoked and event-related potentials, by EEG/MEG connectivity measures such as coherence, and transcranial magnetic stimulation. As an example of classical neurophysiological studies in ASD, we report event-related potential studies which have illustrated which brain areas and processing stages are affected in the visual perception of socially relevant stimuli. However, a paradigm shift has taken place in recent years focussing on how these findings can be tracked down to basic neuronal functions such as deficits in cortico-cortical connectivity and the interaction between brain areas. Disconnectivity, for example, can again be related to genetically induced shifts in the excitation/inhibition balance. Genetic causes of ASD may be grouped by their effects on the brain's system level to identify ASD subgroups which respond differentially to therapeutic interventions.

  14. VfrB Is a Key Activator of the Staphylococcus aureus SaeRS Two-Component System.

    PubMed

    Krute, Christina N; Rice, Kelly C; Bose, Jeffrey L

    2017-03-01

    In previous studies, we identified the fatty acid kinase virulence factor regulator B (VfrB) as a potent regulator of α-hemolysin and other virulence factors in Staphylococcus aureus In this study, we demonstrated that VfrB is a positive activator of the SaeRS two-component regulatory system. Analysis of vfrB , saeR , and saeS mutant strains revealed that VfrB functions in the same pathway as SaeRS. At the transcriptional level, the promoter activities of SaeRS class I ( coa ) and class II ( hla ) target genes were downregulated during the exponential growth phase in the vfrB mutant, compared to the wild-type strain. In addition, saePQRS expression was decreased in the vfrB mutant strain, demonstrating a need for this protein in the autoregulation of SaeRS. The requirement for VfrB-mediated activation was circumvented when SaeS was constitutively active due to an SaeS (L18P) substitution. Furthermore, activation of SaeS via human neutrophil peptide 1 (HNP-1) overcame the dependence on VfrB for transcription from class I Sae promoters. Consistent with the role of VfrB in fatty acid metabolism, hla expression was decreased in the vfrB mutant with the addition of exogenous myristic acid. Lastly, we determined that aspartic acid residues D38 and D40, which are predicted to be key to VfrB enzymatic activity, were required for VfrB-mediated α-hemolysin production. Collectively, this study implicates VfrB as a novel accessory protein needed for the activation of SaeRS in S. aureus IMPORTANCE The SaeRS two-component system is a key regulator of virulence determinant production in Staphylococcus aureus Although the regulon of this two-component system is well characterized, the activation mechanisms, including the specific signaling molecules, remain elusive. Elucidating the complex regulatory circuit of SaeRS regulation is important for understanding how the system contributes to disease causation by this pathogen. To this end, we have identified the fatty acid kinase

  15. Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

    PubMed

    Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

    2017-05-01

    Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

  16. Key-value store with internal key-value storage interface

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

    Bent, John M.; Faibish, Sorin; Ting, Dennis P. J.

    A key-value store is provided having one or more key-value storage interfaces. A key-value store on at least one compute node comprises a memory for storing a plurality of key-value pairs; and an abstract storage interface comprising a software interface module that communicates with at least one persistent storage device providing a key-value interface for persistent storage of one or more of the plurality of key-value pairs, wherein the software interface module provides the one or more key-value pairs to the at least one persistent storage device in a key-value format. The abstract storage interface optionally processes one or moremore » batch operations on the plurality of key-value pairs. A distributed embodiment for a partitioned key-value store is also provided.« less

  17. OBJECTIVE METEOROLOGICAL CLASSIFICATION SCHEME DESIGNED TO ELUCIDATE OZONE'S DEPENDENCE ON METEOROLOGY

    EPA Science Inventory

    This paper utilizes a two-stage clustering approach as part of an objective classification scheme designed to elucidate 03's dependence on meteorology. hen applied to ten years (1981-1990) of meteorological data for Birmingham, Alabama, the classification scheme identified seven ...

  18. Elucidation of Small RNAs that Activate Transcription in Bacteria

    DTIC Science & Technology

    2012-03-01

    bacterial sRNAs that activate transcription of a target gene in E. coli to varying degrees. Mutation of the strongest activator modified its...identified RNA- based transcriptional activators in yeast (Buskirk et al., 2003) although the underlying mechanism was not elucidated. We show that the...previous yeast two-hybrid (Buskirk et al., 2003) and three-hybrid studies (Bernstein et al., 2002). Colonies were observed from co-transformations of pBT

  19. Effect of the Key Mixture Parameters on Shrinkage of Reactive Powder Concrete

    PubMed Central

    Zubair, Ahmed

    2014-01-01

    Reactive powder concrete (RPC) mixtures are reported to have excellent mechanical and durability characteristics. However, such concrete mixtures having high amount of cementitious materials may have high early shrinkage causing cracking of concrete. In the present work, an attempt has been made to study the simultaneous effects of three key mixture parameters on shrinkage of the RPC mixtures. Considering three different levels of the three key mixture factors, a total of 27 mixtures of RPC were prepared according to 33 factorial experiment design. The specimens belonging to all 27 mixtures were monitored for shrinkage at different ages over a total period of 90 days. The test results were plotted to observe the variation of shrinkage with time and to see the effects of the key mixture factors. The experimental data pertaining to 90-day shrinkage were used to conduct analysis of variance to identify significance of each factor and to obtain an empirical equation correlating the shrinkage of RPC with the three key mixture factors. The rate of development of shrinkage at early ages was higher. The water to binder ratio was found to be the most prominent factor followed by cement content with the least effect of silica fume content. PMID:25050395

  20. Effect of the key mixture parameters on shrinkage of reactive powder concrete.

    PubMed

    Ahmad, Shamsad; Zubair, Ahmed; Maslehuddin, Mohammed

    2014-01-01

    Reactive powder concrete (RPC) mixtures are reported to have excellent mechanical and durability characteristics. However, such concrete mixtures having high amount of cementitious materials may have high early shrinkage causing cracking of concrete. In the present work, an attempt has been made to study the simultaneous effects of three key mixture parameters on shrinkage of the RPC mixtures. Considering three different levels of the three key mixture factors, a total of 27 mixtures of RPC were prepared according to 3(3) factorial experiment design. The specimens belonging to all 27 mixtures were monitored for shrinkage at different ages over a total period of 90 days. The test results were plotted to observe the variation of shrinkage with time and to see the effects of the key mixture factors. The experimental data pertaining to 90-day shrinkage were used to conduct analysis of variance to identify significance of each factor and to obtain an empirical equation correlating the shrinkage of RPC with the three key mixture factors. The rate of development of shrinkage at early ages was higher. The water to binder ratio was found to be the most prominent factor followed by cement content with the least effect of silica fume content.

  1. Key Success Factors for Statistical Literacy Poster Competitions

    ERIC Educational Resources Information Center

    MacFeely, Steve; Campos, Pedro; Helenius, Reija

    2017-01-01

    Statistical literacy is complex and multifaceted. In every country, education and numeracy are a function of a multitude of factors including culture, history, and societal norms. Nevertheless, since the launch of the International Statistical Poster Competition (ISLP) in 1994, a number of patterns have emerged to suggest there are some common or…

  2. Multi-factor authentication

    DOEpatents

    Hamlet, Jason R; Pierson, Lyndon G

    2014-10-21

    Detection and deterrence of spoofing of user authentication may be achieved by including a cryptographic fingerprint unit within a hardware device for authenticating a user of the hardware device. The cryptographic fingerprint unit includes an internal physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a PUF value. Combining logic is coupled to receive the PUF value, combines the PUF value with one or more other authentication factors to generate a multi-factor authentication value. A key generator is coupled to generate a private key and a public key based on the multi-factor authentication value while a decryptor is coupled to receive an authentication challenge posed to the hardware device and encrypted with the public key and coupled to output a response to the authentication challenge decrypted with the private key.

  3. Elucidating reaction mechanisms on quantum computers.

    PubMed

    Reiher, Markus; Wiebe, Nathan; Svore, Krysta M; Wecker, Dave; Troyer, Matthias

    2017-07-18

    With rapid recent advances in quantum technology, we are close to the threshold of quantum devices whose computational powers can exceed those of classical supercomputers. Here, we show that a quantum computer can be used to elucidate reaction mechanisms in complex chemical systems, using the open problem of biological nitrogen fixation in nitrogenase as an example. We discuss how quantum computers can augment classical computer simulations used to probe these reaction mechanisms, to significantly increase their accuracy and enable hitherto intractable simulations. Our resource estimates show that, even when taking into account the substantial overhead of quantum error correction, and the need to compile into discrete gate sets, the necessary computations can be performed in reasonable time on small quantum computers. Our results demonstrate that quantum computers will be able to tackle important problems in chemistry without requiring exorbitant resources.

  4. Elucidating reaction mechanisms on quantum computers

    PubMed Central

    Reiher, Markus; Wiebe, Nathan; Svore, Krysta M.; Wecker, Dave; Troyer, Matthias

    2017-01-01

    With rapid recent advances in quantum technology, we are close to the threshold of quantum devices whose computational powers can exceed those of classical supercomputers. Here, we show that a quantum computer can be used to elucidate reaction mechanisms in complex chemical systems, using the open problem of biological nitrogen fixation in nitrogenase as an example. We discuss how quantum computers can augment classical computer simulations used to probe these reaction mechanisms, to significantly increase their accuracy and enable hitherto intractable simulations. Our resource estimates show that, even when taking into account the substantial overhead of quantum error correction, and the need to compile into discrete gate sets, the necessary computations can be performed in reasonable time on small quantum computers. Our results demonstrate that quantum computers will be able to tackle important problems in chemistry without requiring exorbitant resources. PMID:28674011

  5. Elucidating reaction mechanisms on quantum computers

    NASA Astrophysics Data System (ADS)

    Reiher, Markus; Wiebe, Nathan; Svore, Krysta M.; Wecker, Dave; Troyer, Matthias

    2017-07-01

    With rapid recent advances in quantum technology, we are close to the threshold of quantum devices whose computational powers can exceed those of classical supercomputers. Here, we show that a quantum computer can be used to elucidate reaction mechanisms in complex chemical systems, using the open problem of biological nitrogen fixation in nitrogenase as an example. We discuss how quantum computers can augment classical computer simulations used to probe these reaction mechanisms, to significantly increase their accuracy and enable hitherto intractable simulations. Our resource estimates show that, even when taking into account the substantial overhead of quantum error correction, and the need to compile into discrete gate sets, the necessary computations can be performed in reasonable time on small quantum computers. Our results demonstrate that quantum computers will be able to tackle important problems in chemistry without requiring exorbitant resources.

  6. Hypoxia and the Edema Syndrome: Elucidation of a Mechanism of Teratogenesis

    EPA Science Inventory

    The elucidation of mechanisms and pathogenesis of birth defects is exceedingly complex. Consequently, there are few examples where the etiology of birth defects caused by a specific agent has been well described. One such example is the "Edema Syndrome" first described by Casimer...

  7. Glucose and Insulin Stimulate Lipogenesis in Porcine Adipocytes: Dissimilar and Identical Regulation Pathway for Key Transcription Factors.

    PubMed

    Hua, Zhang Guo; Xiong, Lu Jian; Yan, Chen; Wei, Dai Hong; YingPai, ZhaXi; Qing, Zhao Yong; Lin, Qiao Zi; Fei, Feng Ruo; Ling, Wang Ya; Ren, Ma Zhong

    2016-11-30

    Lipogenesis is under the concerted action of ChREBP, SREBP-1c and other transcription factors in response to glucose and insulin. The isolated porcine preadipocytes were differentiated into mature adipocytes to investigate the roles and interrelation of these transcription factors in the context of glucose- and insulin-induced lipogenesis in pigs. In ChREBP-silenced adipocytes, glucose-induced lipogenesis decreased by ~70%, however insulin-induced lipogenesis was unaffected. Moreover, insulin had no effect on ChREBP expression of unperturbed adipocytes irrespective of glucose concentration, suggesting ChREBP mediate glucose-induced lipogenesis. Insulin stimulated SREBP-1c expression and when SREBP-1c activation was blocked, and the insulin-induced lipogenesis decreased by ~55%, suggesting SREBP-1c is a key transcription factor mediating insulin-induced lipogenesis. LXRα activation promoted lipogenesis and lipogenic genes expression. In ChREBP-silenced or SREBP-1c activation blocked adipocytes, LXRα activation facilitated lipogenesis and SREBP-1c expression, but had no effect on ChREBP expression. Therefore, LXRα might mediate lipogenesis via SREBP-1c rather than ChREBP. When ChREBP expression was silenced and SREBP-1c activation blocked simultaneously, glucose and insulin were still able to stimulated lipogenesis and lipogenic genes expression, and LXRα activation enhanced these effects, suggesting LXRα mediated directly glucose- and insulin-induced lipogenesis. In summary, glucose and insulin stimulated lipogenesis through both dissimilar and identical regulation pathway in porcine adipocytes.

  8. Traumatic Brain Injury as a Risk Factor for Alzheimer's Disease: Is Inflammatory Signaling a Key Player?

    PubMed

    Djordjevic, Jelena; Sabbir, Mohammad Golam; Albensi, Benedict C

    2016-01-01

    Traumatic brain injury (TBI) has become a significant medical and social concern within the last 30 years. TBI has acute devastating effects, and in many cases, seems to initiate long-term neurodegeneration. With advances in medical technology, many people are now surviving severe brain injuries and their long term consequences. Post trauma effects include communication problems, sensory deficits, emotional and behavioral problems, physical complications and pain, increased suicide risk, dementia, and an increased risk for chronic CNS diseases, such as Alzheimer's disease (AD). In this review, we provide an introduction to TBI and hypothesize how it may lead to neurodegenerative disease in general and AD in particular. In addition, we discuss the evidence that supports the hypothesis that TBI may lead to AD. In particular, we focus on inflammatory responses as key processes in TBI-induced secondary injury, with emphasis on nuclear factor kappa B (NF-κB) signaling.

  9. Engaging fathers in child protection services: A review of factors and strategies across ecological systems

    PubMed Central

    Gordon, Derrick M.; Oliveros, Arazais; Hawes, Samuel W.; Iwamoto, Derek K.; Rayford, Brett S.

    2014-01-01

    Current policy regarding child protection services places increasing demands for providers to engage fathers whose children are involved in the child protection process. This requisite brings to the fore the ongoing challenges that fathers have historically faced in working within these systems. Despite this need, there is little empirical evidence regarding the factors and strategies that impact the engagement of fathers in interventions relevant to child protection services. This comprehensive and systemic review synthesizes the available literature regarding factors and strategies that may foster paternal involvement in the child protection system and their services. We organize the literature concerning paternal engagement in child and family services around an ecological model that examines paternal engagement from individual, family, service provider, program, community, and policy levels. We consider factors and strategies along a continuum of engagement through intent to enroll, enrollment, and retention. This review advances theory by elucidating key factors that foster father engagement. The review also highlights the gaps in the literature and provides strategies for how researchers can address these areas. Future directions in the arenas of practice and policy are discussed. PMID:25232202

  10. Florida Keys

    NASA Image and Video Library

    2002-12-13

    The Florida Keys are a chain of islands, islets and reefs extending from Virginia Key to the Dry Tortugas for about 309 kilometers (192 miles). The keys are chiefly limestone and coral formations. The larger islands of the group are Key West (with its airport), Key Largo, Sugarloaf Key, and Boca Chica Key. A causeway extends from the mainland to Key West. This image was acquired on October 28, 2001, by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER images Earth to map and monitor the changing surface of our planet. http://photojournal.jpl.nasa.gov/catalog/PIA03890

  11. Key Transcription Factors in the Differentiation of Mesenchymal Stem Cells

    PubMed Central

    Almalki, Sami G.; Agrawal, Devendra K.

    2016-01-01

    Mesenchymal stem cells (MSCs) are multipotent cells that represent a promising source for regenerative medicine. MSCs are capable of osteogenic, chondrogenic, adipogenic and myogenic differentiation. Efficacy of differentiated MSCs to regenerate cells in the injured tissues requires the ability to maintain the differentiation toward the desired cell fate. Since MSCs represent an attractive source for autologous transplantation, cellular and molecular signaling pathways and micro-environmental changes have been studied in order to understand the role of cytokines, chemokines, and transcription factors on the differentiation of MSCs. The differentiation of MSC into a mesenchymal lineage is genetically manipulated and promoted by specific transcription factors associated with a particular cell lineage. Recent studies have explored the integration of transcription factors, including Runx2, Sox9, PPARγ, MyoD, GATA4, and GATA6 in the differentiation of MSCs. Therefore, the overexpression of a single transcription factor in MSCs may promote trans-differentiation into specific cell lineage, which can be used for treatment of some diseases. In this review, we critically discussed and evaluated the role of transcription factors and related signaling pathways that affect the differentiation of MSCs toward adipocytes, chondrocytes, osteocytes, skeletal muscle cells, cardiomyocytes, and smooth muscle cells. PMID:27012163

  12. Salinity is a key factor driving the nitrogen cycling in the mangrove sediment.

    PubMed

    Wang, Haitao; Gilbert, Jack A; Zhu, Yongguan; Yang, Xiaoru

    2018-08-01

    Coastal ecosystems are hotspots for nitrogen cycling, and specifically for nitrogen removal from water and sediment through the coupled nitrification-denitrification process. Salinity is globally important in structuring bacterial and archaeal communities, but the association between salinity and microbially-mediated nitrification and denitrification remains unclear. The denitrification activity and composition and structure of microbial nitrifiers and denitrifiers were characterized across a gradient of manipulated salinity (0, 10, 20 and 30ppt) in a mangrove sediment. Salinity negatively correlated with both denitrifying activity and the abundance of nirK and nosZ denitrifying genes. Ammonia-oxidizing bacteria (AOB), which dominated nitrification, had significantly greater abundance at intermediate salinity (10 and 20ppt). However, a positive correlation between ammonia concentration and salinity suggested that nitrifying activity might also be inhibited at higher salinity. The community structure of ammonia-oxidizing archaea (AOA) and bacteria (AOB), as well as nirK, nirS and nosZ denitrifying communities, were all significantly correlated with salinity. These changes were also associated with structural shifts in phylogeny. These findings provide a strong evidence that salinity is a key factor that influences the nitrogen transformations in coastal wetlands, indicating that salinity intrusion caused by climate change might have a broader impact on the coastal biospheres. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Factors affecting implementation of an evidence-based practice in the Veterans Health Administration: Illness management and recovery.

    PubMed

    McGuire, Alan B; Salyers, Michelle P; White, Dominique A; Gilbride, Daniel J; White, Laura M; Kean, Jacob; Kukla, Marina

    2015-12-01

    Illness management and recovery (IMR) is an evidence-based practice that assists consumers in managing their illnesses and pursuing personal recovery goals. Although research has examined factors affecting IMR implementation facilitated by multifaceted, active roll-outs, the current study attempted to elucidate factors affecting IMR implementation outside the context of a research-driven implementation. Semi-structured interviews with 20 local recovery coordinators and 18 local IMR experts were conducted at 23 VA medical centers. Interviews examined perceived and experienced barriers and facilitators to IMR implementation. Data were analyzed via thematic inductive/deductive analysis in the form of crystallization/immersion. Six factors differed between sites implementing IMR from those not providing IMR: awareness of IMR, importer-champions, autonomy-supporting leadership, veteran-centered care, presence of a sensitive period, and presence of a psychosocial rehabilitation and recovery center. Four factors were common in both groups: recovery orientation, evidence-based practices orientation, perceived IMR fit within program structure, and availability of staff time. IMR can be adopted in lieu of active implementation support; however, knowledge dissemination appears to be key. Future research should examine factors affecting the quality of implementation. (c) 2015 APA, all rights reserved).

  14. R2R3 MYB transcription factors: key regulators of the flavonoid biosynthetic pathway in grapevine.

    PubMed

    Czemmel, Stefan; Heppel, Simon C; Bogs, Jochen

    2012-06-01

    Flavonoids compose one of the most abundant and important subgroups of secondary metabolites with more than 6,000 compounds detected so far in higher plants. They are found in various compositions and concentrations in nearly all plant tissues. Besides the attraction of pollinators and dispersers to fruits and flowers, flavonoids also protect against a plethora of stresses including pathogen attack, wounding and UV irradiation. Flavonoid content and composition of fruits such as grapes, bilberries, strawberries and apples as well as food extracts such as green tea, wine and chocolate have been associated with fruit quality including taste, colour and health-promoting effects. To unravel the beneficial potentials of flavonoids on fruit quality, research has been focused recently on the molecular basis of flavonoid biosynthesis and regulation in economically important fruit-producing plants such as grapevine (Vitis vinifera L.). Transcription factors and genes encoding biosynthetic enzymes have been characterized, studies that set a benchmark for future research on the regulatory networks controlling flavonoid biosynthesis and diversity. This review summarizes recent advances in the knowledge of regulatory cascades involved in flavonoid biosynthesis in grapevine. Transcriptional regulation of flavonoid biosynthesis during berry development is highlighted, with a particular focus on MYB transcription factors as molecular clocks, key regulators and powerful biotechnological tools to identify novel pathway enzymes to optimize flavonoid content and composition in grapes.

  15. Identification of key climatic factors regulating the transport of pesticides in leaching and to tile drains.

    PubMed

    Nolan, Bernard T; Dubus, Igor G; Surdyk, Nicolas; Fowler, Hayley J; Burton, Aidan; Hollis, John M; Reichenberger, Stefan; Jarvis, Nicholas J

    2008-09-01

    Key climatic factors influencing the transport of pesticides to drains and to depth were identified. Climatic characteristics such as the timing of rainfall in relation to pesticide application may be more critical than average annual temperature and rainfall. The fate of three pesticides was simulated in nine contrasting soil types for two seasons, five application dates and six synthetic weather data series using the MACRO model, and predicted cumulative pesticide loads were analysed using statistical methods. Classification trees and Pearson correlations indicated that simulated losses in excess of 75th percentile values (0.046 mg m(-2) for leaching, 0.042 mg m(-2) for drainage) generally occurred with large rainfall events following autumn application on clay soils, for both leaching and drainage scenarios. The amount and timing of winter rainfall were important factors, whatever the application period, and these interacted strongly with soil texture and pesticide mobility and persistence. Winter rainfall primarily influenced losses of less mobile and more persistent compounds, while short-term rainfall and temperature controlled leaching of the more mobile pesticides. Numerous climatic characteristics influenced pesticide loss, including the amount of precipitation as well as the timing of rainfall and extreme events in relation to application date. Information regarding the relative influence of the climatic characteristics evaluated here can support the development of a climatic zonation for European-scale risk assessment for pesticide fate.

  16. Review of Railgun Modeling Techniques: The Computation of Railgun Force and Other Key Factors

    NASA Astrophysics Data System (ADS)

    Eckert, Nathan James

    Currently, railgun force modeling either uses the simple "railgun force equation" or finite element methods. It is proposed here that a middle ground exists that does not require the solution of partial differential equations, is more readily implemented than finite element methods, and is more accurate than the traditional force equation. To develop this method, it is necessary to examine the core railgun factors: power supply mechanisms, the distribution of current in the rails and in the projectile which slides between them (called the armature), the magnetic field created by the current flowing through these rails, the inductance gradient (a key factor in simplifying railgun analysis, referred to as L'), the resultant Lorentz force, and the heating which accompanies this action. Common power supply technologies are investigated, and the shape of their current pulses are modeled. The main causes of current concentration are described, and a rudimentary method for computing current distribution in solid rails and a rectangular armature is shown to have promising accuracy with respect to outside finite element results. The magnetic field is modeled with two methods using the Biot-Savart law, and generally good agreement is obtained with respect to finite element methods (5.8% error on average). To get this agreement, a factor of 2 is added to the original formulation after seeing a reliable offset with FEM results. Three inductance gradient calculations are assessed, and though all agree with FEM results, the Kerrisk method and a regression analysis method developed by Murugan et al. (referred to as the LRM here) perform the best. Six railgun force computation methods are investigated, including the traditional railgun force equation, an equation produced by Waindok and Piekielny, and four methods inspired by the work of Xu et al. Overall, good agreement between the models and outside data is found, but each model's accuracy varies significantly between

  17. Design and efficient synthesis of novel GM2 analogues with respect to the elucidation of the function of GM2 activator.

    PubMed

    Komori, Tatsuya; Ando, Takayuki; Imamura, Akihiro; Li, Yu-Teh; Ishida, Hideharu; Kiso, Makoto

    2008-10-01

    To elucidate the mechanism underlying the hydrolysis of the GalNAcbeta1-->4Gal linkage in ganglioside GM2 [GalNAcbeta1-->4(NeuAcalpha2-->3)Galbeta1-->4Glcbeta1-->1' Cer] by beta-hexosaminidase A (Hex A) with GM2 activator protein, we designed and synthesized two kinds of GM2 linkage analogues-6'-NeuAc-GM2 and alpha-GalNAc-GM2. In this paper, the efficient and systematic synthesis of these GM2 analogues was described. The highlight of our synthesis process is that the key intermediates, newly developed sialyllactose derivatives, were efficiently prepared in sufficient quantities; these derivatives directly served as highly reactive glycosyl acceptors and coupled with GalNTroc donors to furnish the assembly of GM2 tetrasaccharides in large quantities.

  18. Elucidating Proteoform Families from Proteoform Intact-Mass and Lysine-Count Measurements

    PubMed Central

    2016-01-01

    Proteomics is presently dominated by the “bottom-up” strategy, in which proteins are enzymatically digested into peptides for mass spectrometric identification. Although this approach is highly effective at identifying large numbers of proteins present in complex samples, the digestion into peptides renders it impossible to identify the proteoforms from which they were derived. We present here a powerful new strategy for the identification of proteoforms and the elucidation of proteoform families (groups of related proteoforms) from the experimental determination of the accurate proteoform mass and number of lysine residues contained. Accurate proteoform masses are determined by standard LC–MS analysis of undigested protein mixtures in an Orbitrap mass spectrometer, and the lysine count is determined using the NeuCode isotopic tagging method. We demonstrate the approach in analysis of the yeast proteome, revealing 8637 unique proteoforms and 1178 proteoform families. The elucidation of proteoforms and proteoform families afforded here provides an unprecedented new perspective upon proteome complexity and dynamics. PMID:26941048

  19. Epistemological controversies in the analytic field elucidated by the theological realm.

    PubMed

    Squverer, Amos

    2015-08-01

    This article proposes to address certain epistemological controversies in psychoanalysis by elucidating them through the religious field. The theological field serves the author as the repressed, which indicates the latent stakes that continue to do work at the heart of these debates. The goal is to show how debates that take place on the epistemological level bring into confrontation different anthropological concepts and discursive traditions that have their roots in religious discourses. The principal hypothesis of the author is that the dissident theories of psychoanalysis can be understood as a return to a pre-monotheistic theological conception or to an idolatrous practice that aims, primarily, to undo castration. This hypothesis will be used to elucidate the debates with two authors: Adler and Rank. The author shows how these theorists, by leaving analytical ground, connect their theories to pre-monotheistic conceptions and highlight conceptual tools that are characteristic to them. Copyright © 2015 Institute of Psychoanalysis.

  20. Regulation of sucrose metabolism in higher plants: localization and regulation of activity of key enzymes

    NASA Technical Reports Server (NTRS)

    Winter, H.; Huber, S. C.; Brown, C. S. (Principal Investigator)

    2000-01-01

    Sucrose (Suc) plays a central role in plant growth and development. It is a major end product of photosynthesis and functions as a primary transport sugar and in some cases as a direct or indirect regulator of gene expression. Research during the last 2 decades has identified the pathways involved and which enzymes contribute to the control of flux. Availability of metabolites for Suc synthesis and 'demand' for products of sucrose degradation are important factors, but this review specifically focuses on the biosynthetic enzyme sucrose-phosphate synthase (SPS), and the degradative enzymes, sucrose synthase (SuSy), and the invertases. Recent progress has included the cloning of genes encoding these enzymes and the elucidation of posttranslational regulatory mechanisms. Protein phosphorylation is emerging as an important mechanism controlling SPS activity in response to various environmental and endogenous signals. In terms of Suc degradation, invertase-catalyzed hydrolysis generally has been associated with cell expansion, whereas SuSy-catalyzed metabolism has been linked with biosynthetic processes (e.g., cell wall or storage products). Recent results indicate that SuSy may be localized in multiple cellular compartments: (1) as a soluble enzyme in the cytosol (as traditionally assumed); (2) associated with the plasma membrane; and (3) associated with the actin cytoskeleton. Phosphorylation of SuSy has been shown to occur and may be one of the factors controlling localization of the enzyme. The purpose of this review is to summarize some of the recent developments relating to regulation of activity and localization of key enzymes involved in sucrose metabolism in plants.

  1. Function key and shortcut key use in airway facilities.

    DOT National Transportation Integrated Search

    2003-02-01

    This document provides information on the function keys and shortcut keys used by systems in the Federal Aviation Administration : Airway Facilities (AF) work environment. It includes a catalog of the function keys and shortcut keys used by each syst...

  2. Elucidation and visualization of solid-state transformation and mixing in a pharmaceutical mini hot melt extrusion process using in-line Raman spectroscopy.

    PubMed

    Van Renterghem, Jeroen; Kumar, Ashish; Vervaet, Chris; Remon, Jean Paul; Nopens, Ingmar; Vander Heyden, Yvan; De Beer, Thomas

    2017-01-30

    Mixing of raw materials (drug+polymer) in the investigated mini pharma melt extruder is achieved by using co-rotating conical twin screws and an internal recirculation channel. In-line Raman spectroscopy was implemented in the barrels, allowing monitoring of the melt during processing. The aim of this study was twofold: to investigate (I) the influence of key process parameters (screw speed - barrel temperature) upon the product solid-state transformation during processing of a sustained release formulation in recirculation mode; (II) the influence of process parameters (screw speed - barrel temperature - recirculation time) upon mixing of a crystalline drug (tracer) in an amorphous polymer carrier by means of residence time distribution (RTD) measurements. The results indicated a faster mixing endpoint with increasing screw speed. Processing a high drug load formulation above the drug melting temperature resulted in the production of amorphous drug whereas processing below the drug melting point produced solid dispersions with partially amorphous/crystalline drug. Furthermore, increasing the screw speed resulted in lower drug crystallinity of the solid dispersion. RTD measurements elucidated the improved mixing capacity when using the recirculation channel. In-line Raman spectroscopy has shown to be an adequate PAT-tool for product solid-state monitoring and elucidation of the mixing behavior during processing in a mini extruder. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Toward a Method for Exposing and Elucidating Ethical Issues with Human Cognitive Enhancement Technologies.

    PubMed

    Hofmann, Bjørn

    2017-04-01

    To develop a method for exposing and elucidating ethical issues with human cognitive enhancement (HCE). The intended use of the method is to support and facilitate open and transparent deliberation and decision making with respect to this emerging technology with great potential formative implications for individuals and society. Literature search to identify relevant approaches. Conventional content analysis of the identified papers and methods in order to assess their suitability for assessing HCE according to four selection criteria. Method development. Amendment after pilot testing on smart-glasses. Based on three existing approaches in health technology assessment a method for exposing and elucidating ethical issues in the assessment of HCE technologies was developed. Based on a pilot test for smart-glasses, the method was amended. The method consists of six steps and a guiding list of 43 questions. A method for exposing and elucidating ethical issues in the assessment of HCE was developed. The method provides the ground work for context specific ethical assessment and analysis. Widespread use, amendments, and further developments of the method are encouraged.

  4. Tendencies and Key Factors in the Health of School Students

    ERIC Educational Resources Information Center

    Rimashevskaia, N. M.; Shabunova, A. A.

    2013-01-01

    According to research data, in today's Russia 70 percent of children are born with various health risk factors, and this leads to a rapid deterioration of their health during their school years. The health of school students is getting worse as a consequence of the effect of a whole set of social and economic and psychological factors, and the…

  5. Iterative key-residues interrogation of a phytase with thermostability increasing substitutions identified in directed evolution.

    PubMed

    Shivange, Amol V; Roccatano, Danilo; Schwaneberg, Ulrich

    2016-01-01

    Bacterial phytases have attracted industrial interest as animal feed supplement due to their high activity and sufficient thermostability (required for feed pelleting). We devised an approach named KeySIDE,  an iterative Key-residues interrogation of the wild type with Substitutions Identified in Directed Evolution for improving Yersinia mollaretii phytase (Ymphytase) thermostability by combining key beneficial substitutions and elucidating their individual roles. Directed evolution yielded in a discovery of nine positions in Ymphytase and combined iteratively to identify key positions. The "best" combination (M6: T77K, Q154H, G187S, and K289Q) resulted in significantly improved thermal resistance; the residual activity improved from 35 % (wild type) to 89 % (M6) at 58 °C and 20-min incubation. Melting temperature increased by 3 °C in M6 without a loss of specific activity. Molecular dynamics simulation studies revealed reduced flexibility in the loops located next to helices (B, F, and K) which possess substitutions (Helix-B: T77K, Helix-F: G187S, and Helix-K: K289E/Q). Reduced flexibility in the loops might be caused by strengthened hydrogen bonding network (e.g., G187S and K289E/K289Q) and a salt bridge (T77K). Our results demonstrate a promising approach to design phytases in food research, and we hope that the KeySIDE might become an attractive approach for understanding of structure-function relationships of enzymes.

  6. DIANA-microT web server: elucidating microRNA functions through target prediction.

    PubMed

    Maragkakis, M; Reczko, M; Simossis, V A; Alexiou, P; Papadopoulos, G L; Dalamagas, T; Giannopoulos, G; Goumas, G; Koukis, E; Kourtis, K; Vergoulis, T; Koziris, N; Sellis, T; Tsanakas, P; Hatzigeorgiou, A G

    2009-07-01

    Computational microRNA (miRNA) target prediction is one of the key means for deciphering the role of miRNAs in development and disease. Here, we present the DIANA-microT web server as the user interface to the DIANA-microT 3.0 miRNA target prediction algorithm. The web server provides extensive information for predicted miRNA:target gene interactions with a user-friendly interface, providing extensive connectivity to online biological resources. Target gene and miRNA functions may be elucidated through automated bibliographic searches and functional information is accessible through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The web server offers links to nomenclature, sequence and protein databases, and users are facilitated by being able to search for targeted genes using different nomenclatures or functional features, such as the genes possible involvement in biological pathways. The target prediction algorithm supports parameters calculated individually for each miRNA:target gene interaction and provides a signal-to-noise ratio and a precision score that helps in the evaluation of the significance of the predicted results. Using a set of miRNA targets recently identified through the pSILAC method, the performance of several computational target prediction programs was assessed. DIANA-microT 3.0 achieved there with 66% the highest ratio of correctly predicted targets over all predicted targets. The DIANA-microT web server is freely available at www.microrna.gr/microT.

  7. Spectrin-ankyrin interaction mechanics: A key force balance factor in the red blood cell membrane skeleton.

    PubMed

    Saito, Masakazu; Watanabe-Nakayama, Takahiro; Machida, Shinichi; Osada, Toshiya; Afrin, Rehana; Ikai, Atsushi

    2015-01-01

    As major components of red blood cell (RBC) cytoskeleton, spectrin and F-actin form a network that covers the entire cytoplasmic surface of the plasma membrane. The cross-linked two layered structure, called the membrane skeleton, keeps the structural integrity of RBC under drastically changing mechanical environment during circulation. We performed force spectroscopy experiments on the atomic force microscope (AFM) as a means to clarify the mechanical characteristics of spectrin-ankyrin interaction, a key factor in the force balance of the RBC cytoskeletal structure. An AFM tip was functionalized with ANK1-62k and used to probe spectrin crosslinked to mica surface. A force spectroscopy study gave a mean unbinding force of ~30 pN under our experimental conditions. Two energy barriers were identified in the unbinding process. The result was related to the well-known flexibility of spectrin tetramer and participation of ankyrin 1-spectrin interaction in the overall balance of membrane skeleton dynamics. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Citizen science participation in research in the environmental sciences: key factors related to projects' success and longevity.

    PubMed

    Cunha, Davi G F; Marques, Jonatas F; Resende, Juliana C DE; Falco, Patrícia B DE; Souza, Chrislaine M DE; Loiselle, Steven A

    2017-01-01

    The potential impacts of citizen science initiatives are increasing across the globe, albeit in an imbalanced manner. In general, there is a strong element of trial and error in most projects, and the comparison of best practices and project structure between different initiatives remains difficult. In Brazil, the participation of volunteers in environmental research is limited. Identifying the factors related to citizen science projects' success and longevity within a global perspective can contribute for consolidating such practices in the country. In this study, we explore past and present projects, including a case study in Brazil, to identify the spatial and temporal trends of citizen science programs as well as their best practices and challenges. We performed a bibliographic search using Google Scholar and considered results from 2005-2014. Although these results are subjective due to the Google Scholar's algorithm and ranking criteria, we highlighted factors to compare projects across geographical and disciplinary areas and identified key matches between project proponents and participants, project goals and local priorities, participant profiles and engagement, scientific methods and funding. This approach is a useful starting point for future citizen science projects, allowing for a systematic analysis of potential inconsistencies and shortcomings in this emerging field.

  9. Methods developed to elucidate nursing related adverse events in Japan.

    PubMed

    Yamagishi, Manaho; Kanda, Katsuya; Takemura, Yukie

    2003-05-01

    Financial resources for quality assurance in Japanese hospitals are limited and few hospitals have quality monitoring systems of nursing service systems. However, recently its necessity has been recognized. This study has cost effectively used adverse event occurrence rates as indicators of the quality of nursing service, and audited methods of collecting data on adverse events to elucidate their approximate true numbers. Data collection was conducted in July, August and November 2000 at a hospital in Tokyo that administered both primary and secondary health care services (281 beds, six wards, average length of stay 23 days). We collected adverse events through incident reports, logs, check-lists, nurse interviews, medication error questionnaires, urine leucocyte tests, patient interviews and medical records. Adverse events included the unplanned removals of invasive lines, medication errors, falls, pressure sores, skin deficiencies, physical restraints, and nosocomial infections. After evaluating the time and useful outcomes of each source, it soon became clear that we could elucidate adverse events most consistently and cost-effectively through incident reports, check lists, nurse interviews, urine leucocyte tests and medication error questionnaires. This study suggests that many hospitals in Japan could monitor the quality of the nursing service using these sources.

  10. Key Factors to Instructors' Satisfaction of Learning Management Systems in Blended Learning

    ERIC Educational Resources Information Center

    Al-Busaidi, Kamla Ali; Al-Shihi, Hafedh

    2012-01-01

    Learning Management System (LMS) enables institutions to administer their educational resources, and support their traditional classroom education and distance education. LMS survives through instructors' continuous use, which may be to a great extent associated with their satisfaction of the LMS. Consequently, this study examined the key factors…

  11. Proteomic profiling of isogenic primary and metastatic medulloblastoma cell lines reveals differential expression of key metastatic factors.

    PubMed

    Gu, Shuo; Chen, Kai; Yin, Minzhi; Wu, Zhixiang; Wu, Yeming

    2017-05-08

    Medulloblastoma is the most common malignant brain tumor in children. Around 30% of medulloblastoma patients are diagnosed with metastasis, which often results in a poor prognosis. Unfortunately, molecular mechanisms of medulloblastoma metastasis remain largely unknown. In this study, we employed the recently developed deep proteome analysis approach to quantitatively profile the expression of >10,000 proteins from CHLA-01-MED and CHLA-01R-MED isogenic cell lines derived from the primary and metastatic tumor of the same patient diagnosed with a group IV medulloblastoma. Using statistical analysis, we identified ~1400 significantly altered proteins between the primary and metastatic cell lines including known factors such as placental growth factor (PLGF), LIM homeobox 1 (LHX1) and prominim 1 (PROM1), as well as the negative regulator secreted protein acidic and cysteine rich (SPARC). Additional transwell experiments and immunohistochemical analysis of clinical medulloblastoma samples implicated yes-associated protein 1 (YAP1) as a potential key factor contributing to metastasis. Taken together, our data broadly defines the metastasis-relevant regulated proteome and provides a precious resource for further investigating potential mechanisms of medulloblastoma metastasis. This study represented the first deep proteome analysis of metastatic medulloblastomas and provided a valuable candidate list of altered proteins in metastatic medulloblastomas. The primary data suggested YAP1 as a potential driver for the metastasis of medulloblastoma. These results open up numerous avenues for further investigating the underlying mechanisms of medulloblastoma metastasis and improving the prognosis of medulloblastoma patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Elucidating Article 45.6 of the International Code of Zoological Nomenclature: a dichotomous key for the determination of subspecific or infrasubspecific rank.

    PubMed

    Lingafelter, Steven W; Nearns, Eugenio H

    2013-01-01

    We present an overview of the difficulties sometimes encountered when determining whether a published name following a binomen is available or infrasubspecific and unavailable, following Article 45.6 of the International Code of Zoological Nomenclature (ICZN, 1999). We propose a dichotomous key that facilitates this determination and as a preferable method, given the convoluted and subordinate discussion, exceptions, and qualifications laid out in ICZN (1999: 49-50). Examples and citations are provided for each case one can encounter while making this assessment of availability status of names following the binomen.

  13. Erythropoietin and Nrf2: key factors in the neuroprotection provided by apo-lactoferrin.

    PubMed

    Zakharova, E T; Sokolov, A V; Pavlichenko, N N; Kostevich, V A; Abdurasulova, I N; Chechushkov, A V; Voynova, I V; Elizarova, A Yu; Kolmakov, N N; Bass, M G; Semak, I V; Budevich, A I; Kozhin, P M; Zenkov, N K; Klimenko, V M; Kirik, O V; Korzhevskii, D E; Menshchikova, E B; Vasilyev, V B

    2018-05-10

    Among the properties of lactoferrin (LF) are bactericidal, antianemic, immunomodulatory, antitumour, antiphlogistic effects. Previously we demonstrated its capacity to stabilize in vivo HIF-1-alpha and HIF-2-alpha, which are redox-sensitive multiaimed transcription factors. Various tissues of animals receiving recombinant human LF (rhLF) responded by expressing the HIF-1-alpha target genes, hence such proteins as erythropoietin (EPO), ceruloplasmin, etc. were synthesized in noticeable amounts. Among organs in which EPO synthesis occurred were brain, heart, spleen, liver, kidneys and lungs. Other researchers showed that EPO can act as a protectant against severe brain injury and status epilepticus in rats. Therefore, we tried rhLF as a protector against the severe neurologic disorders developed in rats, such as the rotenone-induced model of Parkinson's disease and experimental autoimmune encephalomyelitis as a model of multiple sclerosis, and observed its capacity to mitigate the grave symptoms. Moreover, an intraperitoneal injection of rhLF into mice 1 h after occlusion of the medial cerebral artery significantly diminished the necrosis area measured on the third day in the ischaemic brain. During this period EPO was synthesized in various murine tissues. It was known that EPO induces nuclear translocation of Nrf2, which, like HIF-1-alpha, is a transcription factor. In view that under conditions of hypoxia both factors demonstrate a synergistic protective effect, we suggested that LF activates the Keap1/Nrf2 signaling pathway, an important link in proliferation and differentiation of normal and malignant cells. J774 macrophages were cultured for 3 days without or in the presence of ferric and ferrous ions (RPMI-1640 and DMEM/F12, respectively). Then cells were incubated with rhLF or Deferiprone. Confocal microscopy revealed nuclear translocation of Nrf2 (the key event in Keap1/Nrf2 signaling) induced by apo-rhLF (iron-free, RPMI-1640). The reference compound

  14. Environmental impact and risk assessments and key factors contributing to the overall uncertainties.

    PubMed

    Salbu, Brit

    2016-01-01

    , ignoring sensitive history life stages of organisms and transgenerational effects. To link sources, ecosystem transfer and biological effects to future impact and risks, a series of models are usually interfaced, while uncertainty estimates are seldom given. The model predictions are, however, only valid within the boundaries of the overall uncertainties. Furthermore, the model predictions are only useful and relevant when uncertainties are estimated, communicated and understood. Among key factors contributing most to uncertainties, the present paper focuses especially on structure uncertainties (model bias or discrepancies) as aspects such as particle releases, ecosystem dynamics, mixed exposure, sensitive life history stages and transgenerational effects, are usually ignored in assessment models. Research focus on these aspects should significantly reduce the overall uncertainties in the impact and risk assessment of radioactive contaminated ecosystems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Screening Active Components from Yu-Ping-Feng-San for Regulating Initiative Key Factors in Allergic Sensitization

    PubMed Central

    Zhu, Zhijie; Yu, Xi; Liu, Hailiang; Wang, Huizhu; Fan, Hongwei; Wang, Dawei; Jiang, Guorong; Hong, Min

    2014-01-01

    Yu-ping-feng-san (YPFS) is a Chinese medical formula that is used clinically for allergic diseases and characterized by reducing allergy relapse. Our previous studies demonstrated that YPFS efficiently inhibited T helper 2 cytokines in allergic inflammation. The underlying mechanisms of action of YPFS and its effective components remain unclear. In this study, it was shown that YPFS significantly inhibited production of thymic stromal lymphopoietin (TSLP), an epithelial cell-derived initiative factor in allergic inflammation, in vitro and in vivo. A method of human bronchial epithelial cell (16HBE) binding combined with HPLC-MS (named 16HBE-HPLC-MS) was established to explore potential active components of YPFS. The following five components bound to 16HBE cells: calycosin-7-glucoside, ononin, claycosin, sec-o-glucosylhamaudol and formononetin. Serum from YPFS-treated mice was analyzed and three major components were detected claycosin, formononetin and cimifugin. Among these, claycosin and formononetin were detected by 16HBE-HPLC-MS and in the serum of YPFS-treated mice. Claycosin and formononetin decreased the level of TSLP markedly at the initial stage of allergic inflammation in vivo. Nuclear factor (NF)-κB, a key transcription factor in TSLP production, was also inhibited by claycosin and formononetin, either in terms of transcriptional activation or its nuclear translocation in vitro. Allergic inflammation was reduced by claycosin and formononetin when they are administered only at the initial stage in a murine model of atopic contact dermatitis. Thus, epithelial cell binding combined with HPLC-MS is a valid method for screening active components from complex mixtures of Chinese medicine. It was demonstrated that the compounds screened from YPFS significantly attenuated allergic inflammation probably by reducing TSLP production via regulating NF-κB activation. PMID:25198676

  16. Sources and Sinks: Elucidating Mechanisms, Documenting Patterns, and Forecasting Impacts

    DTIC Science & Technology

    2017-01-18

    Molecular Ecology 17: 3628-3639. Fazio III, V. W., Miles, D. B., & White, M. M. 2004. Genetic differentiation in the endangered Black-capped Vireo...exploration of accuracy and power. Molecular Ecology 13: 55–65. Raymond, M., & Rousset, F. 1995. GENEPOP (version 1.2): population genetics software for...SUPPLEMENTAL GENETICS MEMO Sources and Sinks: Elucidating Mechanisms, Documenting Patterns, and Forecasting Impacts SERDP Project RC-2120

  17. Components of breeding productivity in a marine bird community: key factors and concordance

    USGS Publications Warehouse

    Hatch, Scott A.; Hatch, Martha A.

    1990-01-01

    We estimated components of annual breeding productivity for eight species of marine birds on the Semidi Islands in the western Gulf of Alaska. Mortality of eggs and young, caused primarily by avian predators, accounted for most of the annual variation in productivity. Failure to produce eggs, clutch size variation, and the hatchability of eggs were generally less important. The stage of breeding at which annual productivity was most strongly regulated differed among species. In murres, chick-rearing success accounted for the largest share of annual variation in overall productivity, whereas incubation success was the key factor in fulmars, kittiwakes, and puffins. Although avian predators were the dominant proximate cause of egg and chick losses in some species, food supply seemed ultimately responsible for variation in all the major components of productivity. Concordance of productivity among species was low for the marine bird community as a whole, but selected pairs of species exhibited a greater tendency for high and low productivities to occur in the same years. Compared with the same or similar species outside Alaska, Semidi Islands birds were in one of three categories: (i) species whose productivity was about the same as reported from other areas (fulmars and gulls), (ii) species with comparatively low productivity (murres, puffins, kittiwakes), and (iii) species with similar mean productivity but greater annual variation (cormorants). These patterns suggest that specialized consumers of forage fish experienced food shortages at the Semidi Islands and that surface feeders were more severely affected than divers.

  18. Simple Web-based interactive key development software (WEBiKEY) and an example key for Kuruna (Poaceae: Bambusoideae).

    PubMed

    Attigala, Lakshmi; De Silva, Nuwan I; Clark, Lynn G

    2016-04-01

    Programs that are user-friendly and freely available for developing Web-based interactive keys are scarce and most of the well-structured applications are relatively expensive. WEBiKEY was developed to enable researchers to easily develop their own Web-based interactive keys with fewer resources. A Web-based multiaccess identification tool (WEBiKEY) was developed that uses freely available Microsoft ASP.NET technologies and an SQL Server database for Windows-based hosting environments. WEBiKEY was tested for its usability with a sample data set, the temperate woody bamboo genus Kuruna (Poaceae). WEBiKEY is freely available to the public and can be used to develop Web-based interactive keys for any group of species. The interactive key we developed for Kuruna using WEBiKEY enables users to visually inspect characteristics of Kuruna and identify an unknown specimen as one of seven possible species in the genus.

  19. Final report of the APMP water flow key comparison: APMP.M.FF-K1

    NASA Astrophysics Data System (ADS)

    Lee, Kwang-Bock; Chun, Sejong; Terao, Yoshiya; Thai, Nguyen Hong; Tsair Yang, Cheng; Tao, Meng; Gutkin, Mikhail B.

    2011-01-01

    The key comparison, APMP.M.FF-K1, was undertaken by APMP/TCFF, the Technical Committee for Fluid Flow (TCFF) under the Asia Pacific Metrology Program (APMP). One objective of the key comparison was to demonstrate the degree of equivalence among six participating laboratories (KRISS, NMIJ, VMI, CMS, NIM and VNIIM) in water flow rate metrology by comparing the results with the key comparison reference value (KCRV) determined from the CCM.FF-K1 key comparison. The other objective of this key comparison was to provide supporting evidence for the calibration and measurement capabilities (CMCs), which had been declared by the participating laboratories during this key comparison. The Transfer Standard Package (TSP) was a Coriolis mass flowmeter, which had been used in the CCM.FF-K1 key comparison. Because the K-factors in the APMP.M.FF-K1 key comparison were slightly lower than the K-factors of the CCM.FF-K1 key comparison due to long-term drifts of the TSP, a correction value D was introduced. The value of D was given by a weighted sum between two link laboratories (NMIJ and KRISS), which participated in both the CCM.FF-K1 and the APMP.M.FF-K1 key comparisons. By this correction, the K-factors were laid between 12.004 and 12.017 at either low (Re = 254 000) or high (Re = 561 000) flow rates. Most of the calibration data were within expected uncertainty bounds. However, some data showed undulations, which gave large fluctuations of the metering factor at Re = 561 000. Calculation of degrees of equivalence showed that all the participating laboratories had deviations between -0.009 and 0.007 pulses/kg from the CCM.FF-K1 KCRV at either the low or the high flow rates. In case of En calculation, all the participating laboratories showed values less than 1, indicating that the corrected K-factors of all the laboratories were equivalent with the KCRV at both Re = 254 000 and 561 000. When the corrected K-factors from two participating laboratories were compared, all the

  20. The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals.

    PubMed

    Nautiyal, Jaya; Steel, Jennifer H; Mane, Meritxell Rosell; Oduwole, Olayiwola; Poliandri, Ariel; Alexi, Xanthippi; Wood, Nicholas; Poutanen, Matti; Zwart, Wilbert; Stingl, John; Parker, Malcolm G

    2013-03-01

    Nuclear receptor interacting protein (Nrip1), also known as RIP140, is a co-regulator for nuclear receptors that plays an essential role in ovulation by regulating the expression of the epidermal growth factor-like family of growth factors. Although several studies indicate a role for RIP140 in breast cancer, its role in the development of the mammary gland is unclear. By using RIP140-null and RIP140 transgenic mice, we demonstrate that RIP140 is an essential factor for normal mammary gland development and that it functions by mediating oestrogen signalling. RIP140-null mice exhibit minimal ductal elongation with no side-branching, whereas RIP140-overexpressing mice show increased cell proliferation and ductal branching with age. Tissue recombination experiments demonstrate that RIP140 expression is required in both the mammary epithelial and stromal compartments for ductal elongation during puberty and that loss of RIP140 leads to a catastrophic loss of the mammary epithelium, whereas RIP140 overexpression augments the mammary basal cell population and shifts the progenitor/differentiated cell balance within the luminal cell compartment towards the progenitors. For the first time, we present a genome-wide global view of oestrogen receptor-α (ERα) binding events in the developing mammary gland, which unravels 881 ERα binding sites. Unbiased evaluation of several ERα binding sites for RIP140 co-occupancy reveals selectivity and demonstrates that RIP140 acts as a co-regulator with ERα to regulate directly the expression of amphiregulin (Areg), the progesterone receptor (Pgr) and signal transducer and activator of transcription 5a (Stat5a), factors that influence key mitogenic pathways that regulate normal mammary gland development.

  1. Toward structural elucidation of the gamma-secretase complex

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

    Li, H.; Wolfe, M. S.; Selkoe, D. J.

    2009-03-11

    {gamma}-Secretase is an intramembrane protease complex that mediates the Notch signaling pathway and the production of amyloid {beta}-proteins. As such, this enzyme has emerged as an important target for development of novel therapeutics for Alzheimer disease and cancer. Great progress has been made in the identification and characterization of the membrane complex and its biological functions. One major challenge now is to illuminate the structure of this fascinating and important protease at atomic resolution. Here, we review recent progress on biochemical and biophysical probing of the structure of the four-component complex and discuss obstacles and potential pathways toward elucidating itsmore » detailed structure.« less

  2. Polypyrimidine Tract Binding Protein Homologs from Arabidopsis Are Key Regulators of Alternative Splicing with Implications in Fundamental Developmental Processes[W

    PubMed Central

    Rühl, Christina; Stauffer, Eva; Kahles, André; Wagner, Gabriele; Drechsel, Gabriele; Rätsch, Gunnar; Wachter, Andreas

    2012-01-01

    Alternative splicing (AS) generates transcript variants by variable exon/intron definition and massively expands transcriptome diversity. Changes in AS patterns have been found to be linked to manifold biological processes, yet fundamental aspects, such as the regulation of AS and its functional implications, largely remain to be addressed. In this work, widespread AS regulation by Arabidopsis thaliana Polypyrimidine tract binding protein homologs (PTBs) was revealed. In total, 452 AS events derived from 307 distinct genes were found to be responsive to the levels of the splicing factors PTB1 and PTB2, which predominantly triggered splicing of regulated introns, inclusion of cassette exons, and usage of upstream 5′ splice sites. By contrast, no major AS regulatory function of the distantly related PTB3 was found. Dependent on their position within the mRNA, PTB-regulated events can both modify the untranslated regions and give rise to alternative protein products. We find that PTB-mediated AS events are connected to diverse biological processes, and the functional implications of selected instances were further elucidated. Specifically, PTB misexpression changes AS of PHYTOCHROME INTERACTING FACTOR6, coinciding with altered rates of abscisic acid–dependent seed germination. Furthermore, AS patterns as well as the expression of key flowering regulators were massively changed in a PTB1/2 level-dependent manner. PMID:23192226

  3. Bombyx mori P-element Somatic Inhibitor (BmPSI) Is a Key Auxiliary Factor for Silkworm Male Sex Determination

    PubMed Central

    Chen, Shuqing; Zeng, Baosheng; James, Anthony A.; Tan, Anjiang; Huang, Yongping

    2017-01-01

    Manipulation of sex determination pathways in insects provides the basis for a wide spectrum of strategies to benefit agriculture and public health. Furthermore, insects display a remarkable diversity in the genetic pathways that lead to sex differentiation. The silkworm, Bombyx mori, has been cultivated by humans as a beneficial insect for over two millennia, and more recently as a model system for studying lepidopteran genetics and development. Previous studies have identified the B. mori Fem piRNA as the primary female determining factor and BmMasc as its downstream target, while the genetic scenario for male sex determination was still unclear. In the current study, we exploite the transgenic CRISPR/Cas9 system to generate a comprehensive set of knockout mutations in genes BmSxl, Bmtra2, BmImp, BmImpM, BmPSI and BmMasc, to investigate their roles in silkworm sex determination. Absence of Bmtra2 results in the complete depletion of Bmdsx transcripts, which is the conserved downstream factor in the sex determination pathway, and induces embryonic lethality. Loss of BmImp or BmImpM function does not affect the sexual differentiation. Mutations in BmPSI and BmMasc genes affect the splicing of Bmdsx and the female reproductive apparatus appeared in the male external genital. Intriguingly, we identify that BmPSI regulates expression of BmMasc, BmImpM and Bmdsx, supporting the conclusion that it acts as a key auxiliary factor in silkworm male sex determination. PMID:28103247

  4. Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

    PubMed

    van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

    2012-10-01

    The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

  5. Key role of heat shock protein 90 in leptin‐induced STAT3 activation and feeding regulation

    PubMed Central

    Kohda, Toshiko; Matsuzaki, Syu; Ishiguchi, Mizuho; Kuwamura, Ayaka; Akita, Tomoyuki; Tanaka, Junko

    2016-01-01

    Abstract Background and Purpose Leptin, an important regulator of the energy balance, acts on the brain to inhibit feeding. However, the mechanisms involved in leptin signalling have not yet been fully elucidated. Heat shock protein 90 (HSP90) is a molecular chaperone that is involved in regulating cellular homeostasis. In the present study, we investigated the possible involvement of HSP90 in leptin signal transduction. Experimental Approach HEK293 and SH‐SY5Y cell lines stably transfected with the Ob‐Rb leptin receptor (HEK293 Ob‐Rb, SH‐SY5Y Ob‐Rb) were used in the present study. Phosphorylation of JAK2 and STAT3 was analysed by western blotting. An HSP90 inhibitor was administered i.c.v. into rats and their food intake was analysed. Key Results The knock‐down of HSP90 in the HEK293 Ob‐Rb cell line attenuated leptin‐induced JAK2 and STAT3 signalling. Moreover, leptin‐induced JAK2/STAT3 phosphorylation was markedly attenuated by the HSP90 inhibitors geldanamycin, radicicol and novobiocin. However, these effects were not mediated through previously known factors, which are known to be involved in the development of leptin resistance, such as suppressor of cytokine signalling 3 or endoplasmic reticulum stress. The infusion of an HSP90 inhibitor into the CNS blunted the anorexigenic actions of leptin in rats (male Wister rat). Conclusions and Implications HSP90 may be a novel factor involved in leptin‐mediated signalling that is linked to anorexia. PMID:27205876

  6. Identification of the Key Genes and Pathways in Esophageal Carcinoma.

    PubMed

    Su, Peng; Wen, Shiwang; Zhang, Yuefeng; Li, Yong; Xu, Yanzhao; Zhu, Yonggang; Lv, Huilai; Zhang, Fan; Wang, Mingbo; Tian, Ziqiang

    2016-01-01

    Objective . Esophageal carcinoma (EC) is a frequently common malignancy of gastrointestinal cancer in the world. This study aims to screen key genes and pathways in EC and elucidate the mechanism of it. Methods . 5 microarray datasets of EC were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were screened by bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction were performed to obtain the biological roles of DEGs in EC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression level of DEGs in EC. Results . A total of 1955 genes were filtered as DEGs in EC. The upregulated genes were significantly enriched in cell cycle and the downregulated genes significantly enriched in Endocytosis. PPI network displayed CDK4 and CCT3 were hub proteins in the network. The expression level of 8 dysregulated DEGs including CDK4, CCT3, THSD4, SIM2, MYBL2, CENPF, CDCA3, and CDKN3 was validated in EC compared to adjacent nontumor tissues and the results were matched with the microarray analysis. Conclusion . The significantly DEGs including CDK4, CCT3, THSD4, and SIM2 may play key roles in tumorigenesis and development of EC involved in cell cycle and Endocytosis.

  7. Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma

    PubMed Central

    Herrero-Martin, David; Fourtouna, Argyro; Niedan, Stephan; Riedmann, Lucia T.; Schwentner, Raphaela; Aryee, Dave N. T.

    2011-01-01

    Ewing's sarcoma family tumors (ESFT) are characterized by specific chromosomal translocations, which give rise to EWS-ETS chimeric proteins. These aberrant transcription factors are the main pathogenic drivers of ESFT. Elucidation of the factors influencing EWS-ETS expression and/or activity will guide the development of novel therapeutic agents against this fatal disease. PMID:22135504

  8. Elucidating the role of the FoxO3a transcription factor in the IGF-1-induced migration and invasion of uveal melanoma cancer cells.

    PubMed

    Yan, Fengxia; Liao, Rifang; Farhan, Mohd; Wang, Tinghuai; Chen, Jiashu; Wang, Zhong; Little, Peter J; Zheng, Wenhua

    2016-12-01

    Uveal melanoma (UM) is the most common primary intraocular malignant tumor of adults. It has high mortality rate due to liver metastasis. However, the epidemiology and pathogenesis of liver metastasis in UM are not elucidated and there is no effective therapy available for preventing the development of this disease. IGF-1 is a growth factor involved in cell proliferation, malignant transformation and inhibition of apoptosis. In previous report, IGF-1 receptor was found to be highly expressed in UM and this was related to tumor prognosis. FoxO3a is a Forkhead box O (FOXO) transcription factor and a downstream target of the IGF-1R/PI3K/Akt pathway involved in a number of physiological and pathological processes including cancer. However, the role of FoxO3a in UM is unknown. In the present study, we investigated fundamental mechanisms in the growth, migration and invasion of UM and the involvement of FoxO3a. IGF-1 increased the cell viability, invasion, migration and S-G2/M cell cycle phase accumulation of UM cells. Western blot analysis showed that IGF-1 led to activation of Akt and concomitant phosphorylation of FoxO3a. FoxO3a phosphorylation was associated with its translocation into the cytoplasm from the nucleus and its functional inhibition led to the inhibition of expression of Bim and p27, but an increase in the expression of Cyclin D1. The effects of IGF-1 on UM cells were reversed by LY294002 (a PI3K inhibitor) or Akt siRNA, and the overexpression of FoxO3a also attenuated basal invasion and migration of UM. Taken all together, these results suggest that inhibition of FoxO3a by IGF-1 via the PI3K/Akt pathway has an important role in IGF-1 induced proliferation and invasion of UM cells. These findings also support FoxO3a and IGF signaling may represent a valid target for investigating the development of new strategies for the treatment and prevention of the pathology of UM. Copyright © 2016. Published by Elsevier Masson SAS.

  9. Migration towards fibre to the home: key cost factors

    NASA Astrophysics Data System (ADS)

    Zhou, L. W.; Mas Machuca, C.; Zhao, R.; Grunert, K.

    2010-12-01

    This paper presents a comprehensive cost model for migration towards FTTH, some case study results from different network area scenarios, as well as the identification of the most important cost factors to be considered by operators aiming at increasing the profitability of their networks.

  10. Elucidation of the genome organization of tobacco mosaic virus.

    PubMed Central

    Zaitlin, M

    1999-01-01

    Proteins unique to tobacco mosaic virus (TMV)-infected plants were detected in the 1970s by electrophoretic analyses of extracts of virus-infected tissues, comparing their proteins to those generated in extracts of uninfected tissues. The genome organization of TMV was deduced principally from studies involving in vitro translation of proteins from the genomic and subgenomic messenger RNAs. The ultimate analysis of the TMV genome came in 1982 when P. Goelet and colleagues sequenced the entire genome. Studies leading to the elucidation of the TMV genome organization are described below. PMID:10212938

  11. An adipoinductive role of inflammation in adipose tissue engineering: key factors in the early development of engineered soft tissues.

    PubMed

    Lilja, Heidi E; Morrison, Wayne A; Han, Xiao-Lian; Palmer, Jason; Taylor, Caroline; Tee, Richard; Möller, Andreas; Thompson, Erik W; Abberton, Keren M

    2013-05-15

    Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

  12. Elucidating the reaction pathways in the synthesis of organolead trihalide perovskite for high-performance solar cells.

    PubMed

    Wang, Baohua; Young Wong, King; Xiao, Xudong; Chen, Tao

    2015-05-28

    The past two years have witnessed unprecedentedly rapid development of organic-inorganic halide perovskite-based solar cells. The solution-processability and high efficiency make this technology extraordinarily attractive. The intensive investigations have accumulated rich experiences in the perovskite fabrication; while the mechanism of the chemical synthesis still remains unresolved. Here, we set up the chemical equation of the synthesis and elucidate the reactions from both thermodynamic and kinetic perspectives. Our study shows that gaseous products thermodynamically favour the reaction, while the activation energy and "collision" probability synergistically determine the reaction rate. These understandings enable us to finely tune the crystal size for high-quality perovskite film, leading to a record fill factor among similar device structures in the literature. This investigation provides a general strategy to explore the mechanism of perovskite synthesis and benefits the fabrication of high-efficiency perovskite photoactive layer.

  13. A Genome-wide Regulatory Network Identifies Key Transcription Factors for Memory CD8+ T Cell Development

    PubMed Central

    Hu, Guangan; Chen, Jianzhu

    2014-01-01

    Memory CD8+ T cell development is defined by the expression of a specific set of memory signature genes (MSGs). Despite recent progress, many components of the transcriptional control of memory CD8+ T cell development are still unknown. To identify transcription factors (TFs) and their interactions in memory CD8+ T cell development, we construct a genome-wide regulatory network and apply it to identify key TFs that regulate MSGs. Most of the known TFs in memory CD8+ T cell development are rediscovered and about a dozen new TFs are also identified. Sox4, Bhlhe40, Bach2 and Runx2 are experimentally verified and Bach2 is further shown to promote both development and recall proliferation of memory CD8+ T cells through Prdm1 and Id3. Gene perturbation study identifies the mode of interactions among the TFs with Sox4 as a hub. The identified TFs and insights into their interactions should facilitate further dissection of molecular mechanisms underlying memory CD8+ T cell development. PMID:24335726

  14. Key factors for a high-quality VR experience

    NASA Astrophysics Data System (ADS)

    Champel, Mary-Luc; Doré, Renaud; Mollet, Nicolas

    2017-09-01

    For many years, Virtual Reality has been presented as a promising technology that could deliver a truly new experience to users. The media and entertainment industry is now investigating the possibility to offer a video-based VR 360 experience. Nevertheless, there is a substantial risk that VR 360 could have the same fate as 3DTV if it cannot offer more than just being the next fad. The present paper aims at presenting the various quality factors required for a high-quality VR experience. More specifically, this paper will focus on the main three VR quality pillars: visual, audio and immersion.

  15. Simple Web-based interactive key development software (WEBiKEY) and an example key for Kuruna (Poaceae: Bambusoideae)1

    PubMed Central

    Attigala, Lakshmi; De Silva, Nuwan I.; Clark, Lynn G.

    2016-01-01

    Premise of the study: Programs that are user-friendly and freely available for developing Web-based interactive keys are scarce and most of the well-structured applications are relatively expensive. WEBiKEY was developed to enable researchers to easily develop their own Web-based interactive keys with fewer resources. Methods and Results: A Web-based multiaccess identification tool (WEBiKEY) was developed that uses freely available Microsoft ASP.NET technologies and an SQL Server database for Windows-based hosting environments. WEBiKEY was tested for its usability with a sample data set, the temperate woody bamboo genus Kuruna (Poaceae). Conclusions: WEBiKEY is freely available to the public and can be used to develop Web-based interactive keys for any group of species. The interactive key we developed for Kuruna using WEBiKEY enables users to visually inspect characteristics of Kuruna and identify an unknown specimen as one of seven possible species in the genus. PMID:27144109

  16. Key factors associated with postoperative complications in patients undergoing colorectal surgery.

    PubMed

    Manilich, E; Vogel, J D; Kiran, R P; Church, J M; Seyidova-Khoshknabi, Dilara; Remzi, F H

    2013-01-01

    Surgical outcomes are determined by complex interactions among a variety of factors including patient characteristics, diagnosis, and type of procedure. The aim of this study was to prioritize the effect and relative importance of the surgeon (in terms of identity of a surgeon and surgeon volume), patient characteristics, and the intraoperative details on complications of colorectal surgery including readmission, reoperation, sepsis, anastomotic leak, small-bowel obstruction, surgical site infection, abscess, need for transfusion, and portal and deep vein thrombosis. This study uses a novel classification methodology to measure the influence of various risk factors on postoperative complications in a large outcomes database. Using prospectively collected information from the departmental outcomes database from 2010 to 2011, we examined the records of 3552 patients who underwent colorectal surgery. Instead of traditional statistical methods, we used a family of 7000 bootstrap classification models to examine and quantify the impact of various factors on the most common serious surgical complications. For each complication, an ensemble of multivariate classification models was designed to determine the relative importance of potential factors that may influence outcomes of surgery. This is a new technique for analyzing outcomes data that produces more accurate results and a more reliable ranking of study variables in order of their importance in producing complications. Patients who underwent colorectal surgery in 2010 and 2011 were included. This study was conducted at a tertiary referral department at a major medical center. Postoperative complications were the primary outcomes measured. Factors sorted themselves into 2 groups: a highly important group (operative time, BMI, age, identity of the surgeon, type of surgery) and a group of low importance (sex, comorbidity, laparoscopy, and emergency). ASA score and diagnosis were of intermediate importance. The outcomes

  17. Balance of antiangiogenic and angiogenic factors in the context of the etiology of preeclampsia.

    PubMed

    Seki, Hiroyuki

    2014-10-01

    The "two-stage disorder" theory that is assumed for the etiology of preeclampsia hypothesizes that antiangiogenic and angiogenic factors and/or placental debris play an important role in this disorder. The physiological actions of placental debris occur via the balance between antiangiogenic and angiogenic factors. Accordingly, this balance between antiangiogenic and angiogenic factors should be investigated to elucidate the various pathological features of preeclampsia. Their accurate evaluation is needed to investigate not only antiangiogenic factors (such as sFlt-1 and sEng) and angiogenic factors (such as vascular endothelial growth factor, placental growth factor and transforming growth factor-β) but also the expression level of their receptors such as Flt-1 and Eng. However, it is ethically and technically difficult to investigate the above-mentioned factors at antepartum in human patients. The examination of the ratios of sFlt-1/vascular endothelial growth factor receptor ligands and sEng/transforming vascular endothelial growth factor-β and the use of experimental animal models may help in elucidating various unresolved issues in preeclampsia. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  18. Dome effect of black carbon and its key influencing factors: a one-dimensional modelling study

    NASA Astrophysics Data System (ADS)

    Wang, Zilin; Huang, Xin; Ding, Aijun

    2018-02-01

    Black carbon (BC) has been identified to play a critical role in aerosol-planetary boundary layer (PBL) interaction and further deterioration of near-surface air pollution in megacities, which has been referred to as the dome effect. However, the impacts of key factors that influence this effect, such as the vertical distribution and aging processes of BC, as well as the underlying land surface, have not been quantitatively explored yet. Here, based on available in situ measurements of meteorology and atmospheric aerosols together with the meteorology-chemistry online coupled model WRF-Chem, we conduct a set of parallel simulations to quantify the roles of these factors in influencing the BC dome effect and surface haze pollution. Furthermore, we discuss the main implications of the results to air pollution mitigation in China. We found that the impact of BC on the PBL is very sensitive to the altitude of aerosol layer. The upper-level BC, especially that near the capping inversion, is more essential in suppressing the PBL height and weakening the turbulent mixing. The dome effect of BC tends to be significantly intensified as BC mixed with scattering aerosols during winter haze events, resulting in a decrease in PBL height by more than 15 %. In addition, the dome effect is more substantial (up to 15 %) in rural areas than that in the urban areas with the same BC loading, indicating an unexpected regional impact of such an effect to air quality in countryside. This study indicates that China's regional air pollution would greatly benefit from BC emission reductions, especially those from elevated sources from chimneys and also domestic combustion in rural areas, through weakening the aerosol-boundary layer interactions that are triggered by BC.

  19. Particle size distribution: A key factor in estimating powder dustiness.

    PubMed

    López Lilao, Ana; Sanfélix Forner, Vicenta; Mallol Gasch, Gustavo; Monfort Gimeno, Eliseo

    2017-12-01

    A wide variety of raw materials, involving more than 20 samples of quartzes, feldspars, nephelines, carbonates, dolomites, sands, zircons, and alumina, were selected and characterised. Dustiness, i.e., a materials' tendency to generate dust on handling, was determined using the continuous drop method. These raw materials were selected to encompass a wide range of particle sizes (1.6-294 µm) and true densities (2650-4680 kg/m 3 ). The dustiness of the raw materials, i.e., their tendency to generate dust on handling, was determined using the continuous drop method. The influence of some key material parameters (particle size distribution, flowability, and specific surface area) on dustiness was assessed. In this regard, dustiness was found to be significantly affected by particle size distribution. Data analysis enabled development of a model for predicting the dustiness of the studied materials, assuming that dustiness depended on the particle fraction susceptible to emission and on the bulk material's susceptibility to release these particles. On the one hand, the developed model allows the dustiness mechanisms to be better understood. In this regard, it may be noted that relative emission increased with mean particle size. However, this did not necessarily imply that dustiness did, because dustiness also depended on the fraction of particles susceptible to be emitted. On the other hand, the developed model enables dustiness to be estimated using just the particle size distribution data. The quality of the fits was quite good and the fact that only particle size distribution data are needed facilitates industrial application, since these data are usually known by raw materials managers, thus making additional tests unnecessary. This model may therefore be deemed a key tool in drawing up efficient preventive and/or corrective measures to reduce dust emissions during bulk powder processing, both inside and outside industrial facilities. It is recommended, however

  20. The IP vs. VDE competition as a key factor determining the stability of the MgBX 5 (X = F, Cl) compounds

    NASA Astrophysics Data System (ADS)

    Sikorska, Celina; Skurski, Piotr

    2010-11-01

    The explanation of the MgBX 5 (X = F, Cl) systems existence and stability is provided on the basis of theoretical considerations supported by ab initio calculations. The equilibrium structures and most probable fragmentation processes of 26 (including isomers) MgBX 5 molecules and six OBX 5 compounds (for comparison) were examined and discussed. The competition between the ionization potential (IP) of the MgX subunit and the electron binding energy (VDE) of the BX 4 fragment was found to be the key factor determining the ability to form a stable compound of MgBX 5 type.

  1. Nature's Migraine Treatment: Isolation and Structure Elucidation of Parthenolide from "Tanacetum parthenium"

    ERIC Educational Resources Information Center

    Walsh, Emma L.; Ashe, Siobhan; Walsh, John J.

    2012-01-01

    The purpose of this experiment is to provide students with the essential skills and knowledge required to perform the extraction, isolation, and structural elucidation of parthenolide from "Tanacetum parthenium" or feverfew. Students are introduced to a background of the traditional medicinal uses of parthenolide, while more modern applications of…

  2. Quantum key management

    DOEpatents

    Hughes, Richard John; Thrasher, James Thomas; Nordholt, Jane Elizabeth

    2016-11-29

    Innovations for quantum key management harness quantum communications to form a cryptography system within a public key infrastructure framework. In example implementations, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a Merkle signature scheme (using Winternitz one-time digital signatures or other one-time digital signatures, and Merkle hash trees) to constitute a cryptography system. More generally, the quantum key management innovations combine quantum key distribution and a quantum identification protocol with a hash-based signature scheme. This provides a secure way to identify, authenticate, verify, and exchange secret cryptographic keys. Features of the quantum key management innovations further include secure enrollment of users with a registration authority, as well as credential checking and revocation with a certificate authority, where the registration authority and/or certificate authority can be part of the same system as a trusted authority for quantum key distribution.

  3. Beyond Collinear Factorization

    NASA Astrophysics Data System (ADS)

    Neill, Duff

    2017-01-01

    Collinear factorization is the basis of many collider observables, and is one of the most highly tested bedrocks of QCD. And yet, it reveals a very limited picture of the nucleon, and the internal dynamics of the partons bound within. I will attempt to elucidate what observables do not fall into a naive collinear factorization framework, what sorts of pictures that have been proposed to replace it in these observables, and what one can learn about the nucleon. Time permitting, I will cover new developments in Soft Collinear Effective Field Theory that allow one to discuss and calculate both collinear factorization and spectator interactions on a first principles basis, hopefully paving the way to investigate the whole coherent structure of the nucleon, not just a single lucky parton involved in the hard interaction.

  4. Key drivers of airline loyalty.

    PubMed

    Dolnicar, Sara; Grabler, Klaus; Grün, Bettina; Kulnig, Anna

    2011-10-01

    This study investigates drivers of airline loyalty. It contributes to the body of knowledge in the area by investigating loyalty for a number of a priori market segments identified by airline management and by using a method which accounts for the multi-step nature of the airline choice process. The study is based on responses from 687 passengers. Results indicate that, at aggregate level, frequent flyer membership, price, the status of being a national carrier and the reputation of the airline as perceived by friends are the variables which best discriminate between travellers loyal to the airline and those who are not. Differences in drivers of airline loyalty for a number of segments were identified. For example, loyalty programs play a key role for business travellers whereas airline loyalty of leisure travellers is difficult to trace back to single factors. For none of the calculated models satisfaction emerged as a key driver of airline loyalty.

  5. Key drivers of airline loyalty

    PubMed Central

    Dolnicar, Sara; Grabler, Klaus; Grün, Bettina; Kulnig, Anna

    2011-01-01

    This study investigates drivers of airline loyalty. It contributes to the body of knowledge in the area by investigating loyalty for a number of a priori market segments identified by airline management and by using a method which accounts for the multi-step nature of the airline choice process. The study is based on responses from 687 passengers. Results indicate that, at aggregate level, frequent flyer membership, price, the status of being a national carrier and the reputation of the airline as perceived by friends are the variables which best discriminate between travellers loyal to the airline and those who are not. Differences in drivers of airline loyalty for a number of segments were identified. For example, loyalty programs play a key role for business travellers whereas airline loyalty of leisure travellers is difficult to trace back to single factors. For none of the calculated models satisfaction emerged as a key driver of airline loyalty. PMID:27064618

  6. Factors Influencing the Choice of Anesthesia as a Career by Undergraduates of the University of Rwanda.

    PubMed

    Chan, Denise M; Wong, Rex; Runnels, Sean; Muhizi, Epaphrodite; McClain, Craig D

    2016-08-01

    Rwanda currently faces a severe shortage of trained medical personnel, including physician anesthesiologists. The recruitment of residents into the anesthesia program has been consistently low. This study aimed at determining the factors that influence undergraduates' decision to pursue anesthesia as a career choice. A questionnaire was created and administered to final year undergraduate medical students at the University of Rwanda. The questionnaire was created based on factors identified from literature review and key informant interviews. The questionnaire was translated, field-tested, and refined. The final survey questionnaire contains 27 4-point Likert scale items and 4 free-text questions. Seventy-nine final year undergraduate medical students responded to the survey. Only 2 students (2.5%) chose anesthesia as their top choice for postgraduate training. The most frequently named factors for not choosing anesthesiology were long work hours and high stress level, insufficient mentorship, and low job opportunity. The issues identified by our survey must be considered when making efforts toward increasing anesthesia recruitment in Rwanda. Factors such as lack of material resources and high workload will not be easily addressed. Others can be addressed through changes in medical student anesthesiology rotations and better mentorship by anesthesiologists during formative years. Focusing on factors that can be changed now may increase enrollment into anesthesiology. Future studies will include broadening the survey population and further investigating the influencing factors elucidated by this study.

  7. A comparison study on detection of key geochemical variables and factors through three different types of factor analysis

    NASA Astrophysics Data System (ADS)

    Hoseinzade, Zohre; Mokhtari, Ahmad Reza

    2017-10-01

    Large numbers of variables have been measured to explain different phenomena. Factor analysis has widely been used in order to reduce the dimension of datasets. Additionally, the technique has been employed to highlight underlying factors hidden in a complex system. As geochemical studies benefit from multivariate assays, application of this method is widespread in geochemistry. However, the conventional protocols in implementing factor analysis have some drawbacks in spite of their advantages. In the present study, a geochemical dataset including 804 soil samples collected from a mining area in central Iran in order to search for MVT type Pb-Zn deposits was considered to outline geochemical analysis through various fractal methods. Routine factor analysis, sequential factor analysis, and staged factor analysis were applied to the dataset after opening the data with (additive logratio) alr-transformation to extract mineralization factor in the dataset. A comparison between these methods indicated that sequential factor analysis has more clearly revealed MVT paragenesis elements in surface samples with nearly 50% variation in F1. In addition, staged factor analysis has given acceptable results while it is easy to practice. It could detect mineralization related elements while larger factor loadings are given to these elements resulting in better pronunciation of mineralization.

  8. Community perceptions of risk factors for interpersonal violence in townships in Cape Town, South Africa: A focus group study.

    PubMed

    Makanga, Prestige Tatenda; Schuurman, Nadine; Randall, Ellen

    2017-10-01

    Interpersonal violence is a major contributor to the burden of disease globally, and in South Africa, it is the leading cause of injury. There is an emerging consensus that the development of actionable policy and effective prevention strategies for interpersonal violence requires an understanding of the contextual matters that elevate risk for interpersonal violence. The objective of this study was to explore community perceptions of risks for interpersonal violence in five townships in Cape Town, South Africa, with high rates of violence. Focus group discussions were conducted with community members to identify key factors in that contributed to being either a perpetrator or victim of interpersonal violence. The ecological framework was used to classify the risk factors as occurring at individual, relationship, community or society levels. Some of the risk factors identified included alcohol abuse, poverty, informality of settlements and cultural norms. Differences in how each of these risk factors are expressed and experienced in the five communities are also elucidated. This approach enabled the collection of contextual community-based data that can complement conventional surveillance data in the development of relevant community-level strategies for interpersonal violence prevention.

  9. Key factors in children's competence to consent to clinical research.

    PubMed

    Hein, Irma M; Troost, Pieter W; Lindeboom, Robert; Benninga, Marc A; Zwaan, C Michel; van Goudoever, Johannes B; Lindauer, Ramón J L

    2015-10-24

    Although law is established on a strong presumption that persons younger than a certain age are not competent to consent, statutory age limits for asking children's consent to clinical research differ widely internationally. From a clinical perspective, competence is assumed to involve many factors including the developmental stage, the influence of parents and peers, and life experience. We examined potential determining factors for children's competence to consent to clinical research and to what extent they explain the variation in competence judgments. From January 1, 2012 through January 1, 2014, pediatric patients aged 6 to 18 years, eligible for clinical research studies were enrolled prospectively at various in- and outpatient pediatric departments. Children's competence to consent was assessed by MacArthur Competence Assessment Tool for Clinical Research. Potential determining child variables included age, gender, intelligence, disease experience, ethnicity and socio-economic status (SES). We used logistic regression analysis and change in explained variance in competence judgments to quantify the contribution of a child variable to the total explained variance. Contextual factors included risk and complexity of the decision to participate, parental competence judgment and the child's or parents decision to participate. Out of 209 eligible patients, 161 were included (mean age, 10.6 years, 47.2 % male). Age, SES, intelligence, ethnicity, complexity, parental competence judgment and trial participation were univariately associated with competence (P < 0.05). Total explained variance in competence judgments was 71.5 %. Only age and intelligence significantly and independently explained the variance in competence judgments, explaining 56.6 % and 12.7 % of the total variance respectively. SES, male gender, disease experience and ethnicity each explained less than 1 % of the variance in competence judgments. Contextual factors together explained an extra 2

  10. Starting a hospital-based home health agency: Part II--Key success factors.

    PubMed

    Montgomery, P

    1993-09-01

    In Part II of a three-part series, the financial, technological and legislative issues of a hospital-based home health-agency are discussed. Beginning a home healthcare service requires intensive research to answer key environmental and operational questions--need, competition, financial projections, initial start-up costs and the impact of delayed depreciation. Assessments involving technology, staffing, legislative and regulatory issues can help project service volume, productivity and cost-control.

  11. Human Factors Engineering Program Review Model (NUREG-0711)Revision 3: Update Methodology and Key Revisions

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

    OHara J. M.; Higgins, J.; Fleger, S.

    The U.S. Nuclear Regulatory Commission (NRC) reviews the human factors engineering (HFE) programs of applicants for nuclear power plant construction permits, operating licenses, standard design certifications, and combined operating licenses. The purpose of these safety reviews is to help ensure that personnel performance and reliability are appropriately supported. Detailed design review procedures and guidance for the evaluations is provided in three key documents: the Standard Review Plan (NUREG-0800), the HFE Program Review Model (NUREG-0711), and the Human-System Interface Design Review Guidelines (NUREG-0700). These documents were last revised in 2007, 2004 and 2002, respectively. The NRC is committed to the periodicmore » update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool. To this end, the NRC is updating its guidance to stay current with recent research on human performance, advances in HFE methods and tools, and new technology being employed in plant and control room design. NUREG-0711 is the first document to be addressed. We present the methodology used to update NUREG-0711 and summarize the main changes made. Finally, we discuss the current status of the update program and the future plans.« less

  12. Whole Body Plethysmography Reveals Differential Ventilatory Responses to Ozone in Rat Models of Cardiovascular Disease

    EPA Science Inventory

    Increasingly, urban air pollution is recognized as an important determinant of cardiovascular disease. Host susceptibility to air pollution can vary due to genetic predisposition and underlying disease. To elucidate key factors of host ...

  13. Elucidating Dimensions of Posttraumatic Stress Symptoms and their Functional Correlates in Disaster-Exposed Adolescents

    PubMed Central

    Sumner, Jennifer A.; Pietrzak, Robert H.; Danielson, Carla Kmett; Adams, Zachary W.; Ruggiero, Kenneth J.

    2014-01-01

    The aim of this study was to elucidate the dimensional structure of posttraumatic stress disorder (PTSD) and potential moderators and functional correlates of this structure in disaster-affected adolescents. A population-based sample of 2,000 adolescents aged 12–17 years (M=14.5 years; 51% female) completed interviews on post-tornado PTSD symptoms, substance use, and parent-adolescent conflict between 4 and 13 months (M=8.8, SD=2.6) after tornado exposure. Confirmatory factor analyses revealed that all models fit well but a 5-factor dysphoric arousal model provided a statistically significantly better representation of adolescent PTSD symptoms compared to 4-factor dysphoria and emotional numbing models. There was evidence of measurement invariance of the dysphoric arousal model across gender and age, although girls and older adolescents aged 15–17 years had higher mean scores than boys and younger adolescents aged 12–14 years, respectively, on some PTSD dimensions. Differential magnitudes of association between PTSD symptom dimensions and functional correlates were observed, with emotional numbing symptoms most strongly positively associated with problematic substance use since the tornado, and dysphoric arousal symptoms most strongly positively associated with parent-adolescent conflict; both correlations were significantly larger than the corresponding correlations with anxious arousal. Taken together, these results suggest that the dimensional structure of tornado-related PTSD symptomatology in adolescents is optimally characterized by five separate clusters of re-experiencing, avoidance, numbing, dysphoric arousal, and anxious arousal symptoms, which showed unique associations with functional correlates. Findings emphasize that PTSD in disaster-exposed adolescents is not best conceptualized as a homogeneous construct and highlight potential differential targets for post-disaster assessment and intervention. PMID:25248557

  14. Elucidating dimensions of posttraumatic stress symptoms and their functional correlates in disaster-exposed adolescents.

    PubMed

    Sumner, Jennifer A; Pietrzak, Robert H; Danielson, Carla Kmett; Adams, Zachary W; Ruggiero, Kenneth J

    2014-12-01

    The aim of this study was to elucidate the dimensional structure of posttraumatic stress disorder (PTSD) and potential moderators and functional correlates of this structure in disaster-affected adolescents. A population-based sample of 2000 adolescents aged 12-17 years (M = 14.5 years; 51% female) completed interviews on post-tornado PTSD symptoms, substance use, and parent-adolescent conflict between 4 and 13 months (M = 8.8, SD = 2.6) after tornado exposure. Confirmatory factor analyses revealed that all models fit well but a 5-factor dysphoric arousal model provided a statistically significantly better representation of adolescent PTSD symptoms compared to 4-factor dysphoria and emotional numbing models. There was evidence of measurement invariance of the dysphoric arousal model across gender and age, although girls and older adolescents aged 15-17 years had higher mean scores than boys and younger adolescents aged 12-14 years, respectively, on some PTSD dimensions. Differential magnitudes of association between PTSD symptom dimensions and functional correlates were observed, with emotional numbing symptoms most strongly positively associated with problematic substance use since the tornado, and dysphoric arousal symptoms most strongly positively associated with parent-adolescent conflict; both correlations were significantly larger than the corresponding correlations with anxious arousal. Taken together, these results suggest that the dimensional structure of tornado-related PTSD symptomatology in adolescents is optimally characterized by five separate clusters of re-experiencing, avoidance, numbing, dysphoric arousal, and anxious arousal symptoms, which showed unique associations with functional correlates. Findings emphasize that PTSD in disaster-exposed adolescents is not best conceptualized as a homogenous construct and highlight potential differential targets for post-disaster assessment and intervention. Copyright © 2014 Elsevier Ltd. All rights

  15. Identification of Key Factors Involved in the Biosorption of Patulin by Inactivated Lactic Acid Bacteria (LAB) Cells.

    PubMed

    Wang, Ling; Wang, Zhouli; Yuan, Yahong; Cai, Rui; Niu, Chen; Yue, Tianli

    2015-01-01

    The purpose of this study was to identify the key factors involved in patulin adsorption by heat-inactivated lactic acid bacteria (LAB) cells. For preventing bacterial contamination, a sterilization process was involved in the adsorption process. The effects of various physical, chemical, and enzymatic pre-treatments, simultaneous treatments, and post-treatments on the patulin adsorption performances of six LAB strains were evaluated. The pre-treated cells were characterized by scanning electron microscopy (SEM). Results showed that the removal of patulin by viable cells was mainly based on adsorption or degradation, depending on the specific strain. The adsorption abilities were widely increased by NaOH and esterification pre-treatments, and reduced by trypsin, lipase, iodate, and periodate pre-treatments. Additionally, the adsorption abilities were almost maintained at pH 2.2-4.0, and enhanced significantly at pH 4.0-6.0. The effects of sodium and magnesium ions on the adsorption abilities at pH 4 were slight and strain-specific. A lower proportion of patulin was released from the strain with higher adsorption ability. Analyses revealed that the physical structure of peptidoglycan was not a principal factor. Vicinal OH and carboxyl groups were not involved in patulin adsorption, while alkaline amino acids, thiol and ester compounds were important for patulin adsorption. Additionally, besides hydrophobic interaction, electrostatic interaction also participated in patulin adsorption, which was enhanced with the increase in pH (4.0-6.0).

  16. Optimizing human factors in dentistry

    PubMed Central

    Gupta, Arpit; Ankola, Anil V.; Hebbal, Mamata

    2013-01-01

    Occupational health hazards among dental professionals are on a continuous rise and they have a significant negative overall impact on daily life. This review is intended to provide the information regarding risk factors and to highlight the prevention strategies for optimizing human factors in dentistry. Risk factors among dentists are multifactorial, which can be categorized into biomechanical and psychosocial. To achieve a realistic target of safety and health at work, prevention is clearly the best approach; therefore, musculoskeletal disorders can be reduced through proper positioning of dental worker and patient, regular rest breaks, general good health, using ergonomic equipment, and exercises designed to counteract the particular risk factors for the dental occupation. However, substantial evidences are still required to elucidate the potential risk factors and to formulate effective prevention programs. PMID:23946745

  17. Optimizing human factors in dentistry.

    PubMed

    Gupta, Arpit; Ankola, Anil V; Hebbal, Mamata

    2013-03-01

    Occupational health hazards among dental professionals are on a continuous rise and they have a significant negative overall impact on daily life. This review is intended to provide the information regarding risk factors and to highlight the prevention strategies for optimizing human factors in dentistry. Risk factors among dentists are multifactorial, which can be categorized into biomechanical and psychosocial. To achieve a realistic target of safety and health at work, prevention is clearly the best approach; therefore, musculoskeletal disorders can be reduced through proper positioning of dental worker and patient, regular rest breaks, general good health, using ergonomic equipment, and exercises designed to counteract the particular risk factors for the dental occupation. However, substantial evidences are still required to elucidate the potential risk factors and to formulate effective prevention programs.

  18. The key factors affecting students' individual interest in school science lessons

    NASA Astrophysics Data System (ADS)

    Cheung, Derek

    2018-01-01

    Individual interest in school science lessons can be defined as a relatively stable and enduring personal emotion comprising affective and behavioural reactions to events in the regular science lessons at school. Little research has compared the importance of different factors affecting students' individual interest in school science lessons. The present study aimed to address this gap, using a mixed methods design. Qualitative interview data were collected from 60 Hong Kong junior secondary school students, who were asked to describe the nature of their interest in science lessons and the factors to which they attribute this. Teacher interviews, parent interviews, and classroom observations were conducted to triangulate student interview data. Five factors affecting students' individual interest in school science lessons were identified: situational influences in science lessons, individual interest in science, science self-concept, grade level, and gender. Quantitative data were then collected from 591 students using a questionnaire. Structural equation modelling was applied to test a hypothesised model, which provided an acceptable fit to the student data. The strongest factor affecting students' individual interest in school science lessons was science self-concept, followed by individual interest in science and situational influences in science lessons. Grade level and gender were found to be nonsignificant factors. These findings suggest that teachers should pay special attention to the association between academic self-concept and interest if they want to motivate students to learn science at school.

  19. From stock bottle to vaccine: Elucidating the particle size distributions of aluminum adjuvants using dynamic light scattering.

    NASA Astrophysics Data System (ADS)

    Shardlow, Emma; Mold, Matthew; Exley, Christopher

    2016-12-01

    The physicochemical properties of aluminum salts are key determinants of their resultant adjuvanticity in vivo when administered as part of a vaccine. While there are links between particle size and the efficacy of the immune response, the limited literature directly characterizing the PSD of aluminum adjuvants has stymied the elucidation of such a relationship for these materials. Hence, this comparative study was undertaken to monitor the PSD of aluminum adjuvants throughout the process of vaccine formulation using DLS. A significant proportion of the stock suspensions was highly agglomerated (>6.5µm), although a large degree of disaggregation was observed upon the dilution of all materials into saline. Adju-Phos® yielded the largest particles in this diluent (4251±137nm); however, the higher affinity of BSA for the surface of Alhydrogel® resulted in a comparable size being observed for both commercial adjuvants when this protein was included in the formulation. These results suggest that the PSD of aluminum adjuvants is greatly influenced by dilution and the degree of protein adsorption experienced within the vaccine itself. The size of the resultant antigen-adjuvant complex may be important for its immunological recognition and subsequent clearance from the injection site.

  20. Key paediatric messages from Amsterdam

    PubMed Central

    Barben, Jürg; Bohlin, Kajsa; Everard, Mark L.; Hall, Graham; Pijnenburg, Mariëlle; Priftis, Kostas N.; Rusconi, Franca; Midulla, Fabio

    2016-01-01

    The Paediatric Assembly of the European Respiratory Society (ERS) maintained its high profile at the 2015 ERS International Congress in Amsterdam. There were symposia on preschool wheeze, respiratory sounds and cystic fibrosis; an educational skills workshop on paediatric respiratory resuscitation; a hot topic session on risk factors and early origins of respiratory diseases; a meet the expert session on paediatric lung function test reference values; and the annual paediatric grand round. In this report the Chairs of the Paediatric Assembly's Groups highlight the key messages from the abstracts presented at the Congress. PMID:27730186

  1. Pain-related work interference is a key factor in a worker/workplace model of work absence duration due to musculoskeletal conditions in Canadian nurses.

    PubMed

    Murray, Eleanor; Franche, Renée-Louise; Ibrahim, Selahadin; Smith, Peter; Carnide, Nancy; Côté, Pierre; Gibson, Jane; Guzman, Jaime; Koehoorn, Mieke; Mustard, Cameron

    2013-12-01

    To examine the role of pain experiences in relation to work absence, within the context of other worker health factors and workplace factors among Canadian nurses with work-related musculoskeletal (MSK) injury. Structural equation modeling was used on a sample of 941 employed, female, direct care nurses with at least one day of work absence due to a work-related MSK injury, from the cross-sectional 2005 National Survey of the Work and Health of Nurses. The final model suggests that pain severity and pain-related work interference mediate the impact of the following worker health and workplace factors on work absence duration: depression, back problems, age, unionization, workplace physical demands and low job control. The model accounted for 14 % of the variance in work absence duration and 46.6 % of the variance in pain-related work interference. Our findings support a key role for pain severity and pain-related work interference in mediating the effects of workplace factors and worker health factors on work absence duration. Future interventions should explore reducing pain-related work interference through addressing workplace issues, such as providing modified work, reducing physical demands, and increasing job control.

  2. Polyacrylamide grafted cellulose as an eco-friendly flocculant: Key factors optimization of flocculation to surfactant effluent.

    PubMed

    Zhu, Hangcheng; Zhang, Yong; Yang, Xiaogang; Shao, Lan; Zhang, Xiumei; Yao, Juming

    2016-01-01

    The discharge of effluents from surfactant manufacturers is giving rise to increasingly serious environmental problems. In order to develop the eco-friendly flocculation materials to achieve effective removal of pollutants from the surfactant effluents, the bamboo pulp cellulose from Phyllostachys heterocycla is employed as the skeleton material to synthesize an eco-friendly bamboo pulp cellulose-g-polyacrylamide (BPC-g-PAM) for flocculation. The BPC-g-PAM is used with the metal ions as the coagulant to treat the effluent from a surfactant manufacturer. The response surface methodology coupled with Box-behnken design is employed to optimize the key factors of coagulation-flocculation. The results show that the combination of Fe(3+) with BPC-g-PAM achieves the best coagulation-flocculation performance like, the fast treatment time, minimum coagulant and BPC-g-PAM dosages compared with the other two combinations of Al(3+) with BPC-g-PAM and Ca(2+) with BPC-g-PAM. Therefore, the combination of Fe(3+) with BPC-g-PAM is expected to promote its application for the pollution control in the surfactant manufacturers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Elucidating carbon sources driving microbial metabolism during oil sands reclamation.

    PubMed

    Bradford, Lauren M; Ziolkowski, Lori A; Goad, Corey; Warren, Lesley A; Slater, Gregory F

    2017-03-01

    Microbial communities play key roles in remediation and reclamation of contaminated environments via biogeochemical cycling of organic and inorganic components. Understanding the trends in in situ microbial community abundance, metabolism and carbon sources is therefore a crucial component of effective site management. The focus of this study was to use radiocarbon analysis to elucidate the carbon sources driving microbial metabolism within the first pilot wetland reclamation project in the Alberta oil sands region where the observation of H 2 S had indicated the occurrence of microbial sulphate reduction. The reclamation project involved construction of a three compartment system consisting of a freshwater wetland on top of a sand cap overlying a composite tailings (CT) deposit. Radiocarbon analysis demonstrated that both dissolved and sediment associated organic carbon associated with the deepest compartments (the CT and sand cap) was primarily fossil (Δ 14 C = -769 to -955‰) while organic carbon in the overlying peat was hundreds to thousands of years old (Δ 14 C = -250 to -350‰). Radiocarbon contents of sediment associated microbial phospholipid fatty acids (PLFA) were consistent with the sediment bulk organic carbon pools (Peat: Δ 14 C PLFA  = -257‰; Sand cap Δ 14 C PLFA  = -805‰) indicating that these microbes were using sediment associated carbon. In contrast, microbial PLFA grown on biofilm units installed in wells within the deepest compartments contained much more modern carbon that the associated bulk carbon pools. This implied that the transfer of relatively more modern carbon was stimulating the microbial community at depth within the system. Correlation between cellular abundance estimates based on PLFA concentrations and the Δ 14 C PLFA indicated that the utilization of this more modern carbon was stimulating the microbial community at depth. These results highlight the importance of understanding the occurrence and potential

  4. X-ray elemental mapping techniques for elucidating the ecophysiology of hyperaccumulator plants.

    PubMed

    van der Ent, Antony; Przybyłowicz, Wojciech J; de Jonge, Martin D; Harris, Hugh H; Ryan, Chris G; Tylko, Grzegorz; Paterson, David J; Barnabas, Alban D; Kopittke, Peter M; Mesjasz-Przybyłowicz, Jolanta

    2018-04-01

    Contents Summary 432 I. Introduction 433 II. Preparation of plant samples for X-ray micro-analysis 433 III. X-ray elemental mapping techniques 438 IV. X-ray data analysis 442 V. Case studies 443 VI. Conclusions 446 Acknowledgements 449 Author contributions 449 References 449 SUMMARY: Hyperaccumulators are attractive models for studying metal(loid) homeostasis, and probing the spatial distribution and coordination chemistry of metal(loid)s in their tissues is important for advancing our understanding of their ecophysiology. X-ray elemental mapping techniques are unique in providing in situ information, and with appropriate sample preparation offer results true to biological conditions of the living plant. The common platform of these techniques is a reliance on characteristic X-rays of elements present in a sample, excited either by electrons (scanning/transmission electron microscopy), protons (proton-induced X-ray emission) or X-rays (X-ray fluorescence microscopy). Elucidating the cellular and tissue-level distribution of metal(loid)s is inherently challenging and accurate X-ray analysis places strict demands on sample collection, preparation and analytical conditions, to avoid elemental redistribution, chemical modification or ultrastructural alterations. We compare the merits and limitations of the individual techniques, and focus on the optimal field of applications for inferring ecophysiological processes in hyperaccumulator plants. X-ray elemental mapping techniques can play a key role in answering questions at every level of metal(loid) homeostasis in plants, from the rhizosphere interface, to uptake pathways in the roots and shoots. Further improvements in technological capabilities offer exciting perspectives for the study of hyperaccumulator plants into the future. © 2017 University of Queensland. New Phytologist © 2017 New Phytologist Trust.

  5. Replication and extension of a hierarchical model of social anxiety and depression: fear of positive evaluation as a key unique factor in social anxiety.

    PubMed

    Weeks, Justin W

    2015-01-01

    Wang, Hsu, Chiu, and Liang (2012, Journal of Anxiety Disorders, 26, 215-224) recently proposed a hierarchical model of social interaction anxiety and depression to account for both the commonalities and distinctions between these conditions. In the present paper, this model was extended to more broadly encompass the symptoms of social anxiety disorder, and replicated in a large unselected, undergraduate sample (n = 585). Structural equation modeling (SEM) and hierarchical regression analyses were employed. Negative affect and positive affect were conceptualized as general factors shared by social anxiety and depression; fear of negative evaluation (FNE) and disqualification of positive social outcomes were operationalized as specific factors, and fear of positive evaluation (FPE) was operationalized as a factor unique to social anxiety. This extended hierarchical model explicates structural relationships among these factors, in which the higher-level, general factors (i.e., high negative affect and low positive affect) represent vulnerability markers of both social anxiety and depression, and the lower-level factors (i.e., FNE, disqualification of positive social outcomes, and FPE) are the dimensions of specific cognitive features. Results from SEM and hierarchical regression analyses converged in support of the extended model. FPE is further supported as a key symptom that differentiates social anxiety from depression.

  6. Towards the elucidation of the cytoplasmic diversity of North American Grape Breeding Programs

    USDA-ARS?s Scientific Manuscript database

    Plants have an intriguing tripartite genetic system: Nuclear genome × Mitochondria × Plastids, and their interactions may impact germplasm breeding. In grapevine, the study of cytoplasmic genomes has been limited, and their role with respect to grapevine germplasm diversity has not been elucidated y...

  7. Interactions between environmental factors and maternal-fetal genetic variations: strategies to elucidate risks of preterm birth.

    PubMed

    Pereyra, Silvana; Bertoni, Bernardo; Sapiro, Rossana

    2016-07-01

    Preterm birth (PTB) is a complex disease in which medical, social, cultural, and hereditary factors contribute to the pathogenesis of this adverse event. Interactions between genes and environmental factors may complicate our understanding of the relative influence of both effects on PTB. To overcome this, we combined data obtained from a cohort of newborns and their mothers with multiplex analysis of inflammatory-related genes and several environmental risk factors of PTB to describe the environmental-genetic influence on PTB. The study aimed to investigate the association between maternal and fetal genetic variations in genes related to the inflammation pathway with PTB and to assess the interaction between environmental factors with these variations. We conducted a case-control study at the Pereira Rossell Hospital Center, Montevideo, Uruguay. The study included 143 mother-offspring dyads who delivered at preterm (gestational age<37 weeks) and 108 mother-offspring dyads who delivered at term. We used real-time PCR followed by a high-resolution melting analysis to simultaneously identify gene variations involved in inflammatory pathways in the context of environmental variables. The genes analyzed were: Toll-like receptor 4 (TLR4), Interleukin 6 (IL6), Interleukin 1 beta (IL1B) and Interleukin 12 receptor beta (IL12RB). We detected a significant interaction between IL1B rs16944 polymorphism in maternal samples and IL6 rs1800795 polymorphism in newborns, emphasizing the role of the interaction of maternal and fetal genomes in PTB. In addition, smoke exposure and premature rupture of membranes (PROM) were significantly different between the premature group and controls. IL1B and IL6 polymorphisms in mothers were significantly associated with PTB when controlling for smoke exposure. TLR4 polymorphism and PROM were significantly associated with PTB when controlling for PROM, but only in the case of severe PTB. Interactions between maternal and fetal genomes may

  8. A Contextual Factors Framework to Inform Implementation and Evaluation of Public Health Initiatives

    ERIC Educational Resources Information Center

    Vanderkruik, Rachel; McPherson, Marianne E.

    2017-01-01

    Evaluating initiatives implemented across multiple settings can elucidate how various contextual factors may influence both implementation and outcomes. Understanding context is especially critical when the same program has varying levels of success across settings. We present a framework for evaluating contextual factors affecting an initiative…

  9. Elucidation of peptide-directed palladium surface structure for biologically tunable nanocatalysts.

    PubMed

    Bedford, Nicholas M; Ramezani-Dakhel, Hadi; Slocik, Joseph M; Briggs, Beverly D; Ren, Yang; Frenkel, Anatoly I; Petkov, Valeri; Heinz, Hendrik; Naik, Rajesh R; Knecht, Marc R

    2015-05-26

    Peptide-enabled synthesis of inorganic nanostructures represents an avenue to access catalytic materials with tunable and optimized properties. This is achieved via peptide complexity and programmability that is missing in traditional ligands for catalytic nanomaterials. Unfortunately, there is limited information available to correlate peptide sequence to particle structure and catalytic activity to date. As such, the application of peptide-enabled nanocatalysts remains limited to trial and error approaches. In this paper, a hybrid experimental and computational approach is introduced to systematically elucidate biomolecule-dependent structure/function relationships for peptide-capped Pd nanocatalysts. Synchrotron X-ray techniques were used to uncover substantial particle surface structural disorder, which was dependent upon the amino acid sequence of the peptide capping ligand. Nanocatalyst configurations were then determined directly from experimental data using reverse Monte Carlo methods and further refined using molecular dynamics simulation, obtaining thermodynamically stable peptide-Pd nanoparticle configurations. Sequence-dependent catalytic property differences for C-C coupling and olefin hydrogenation were then elucidated by identification of the catalytic active sites at the atomic level and quantitative prediction of relative reaction rates. This hybrid methodology provides a clear route to determine peptide-dependent structure/function relationships, enabling the generation of guidelines for catalyst design through rational tailoring of peptide sequences.

  10. Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A Key Role for Pregnancy- Associated Plasma Protein-A.

    PubMed

    Beattie, James; Al-Khafaji, Hasanain; Noer, Pernille R; Alkharobi, Hanaa Esa; Alhodhodi, Aishah; Meade, Josephine; El-Gendy, Reem; Oxvig, Claus

    2018-01-01

    The insulin-like growth factor (IGF) axis is required for the differentiation, development, and maintenance of bone tissue. Accordingly, dysregulation of this axis is associated with various skeletal pathologies including growth abnormalities and compromised bone structure. It is becoming increasingly apparent that the action of the IGF axis must be viewed holistically taking into account not just the actions of the growth factors and receptors, but also the influence of soluble high affinity IGF binding proteins (IGFBPs).There is a recognition that IGFBPs exert IGF-dependent and IGF-independent effects in bone and other tissues and that an understanding of the mechanisms of action of IGFBPs and their regulation in the pericellular environment impact critically on tissue physiology. In this respect, a group of IGFBP proteinases (which may be considered as ancillary members of the IGF axis) play a crucial role in regulating IGFBP function. In this model, cleavage of IGFBPs by specific proteinases into fragments with lower affinity for growth factor(s) regulates the partition of IGFs between IGFBPs and cell surface IGF receptors. In this review, we examine the importance of IGFBP function in bone tissue with special emphasis on the role of pregnancy associated plasma protein-A (PAPP-A). We examine the function of PAPP-A primarily as an IGFBP-4 proteinase and present evidence that PAPP-A induced cleavage of IGFBP-4 is potentially a key regulatory step in bone metabolism. We also highlight some recent findings with regard to IGFBP-2 and IGFBP-5 (also PAPP-A substrates) function in bone tissue and briefly discuss the actions of the other three IGFBPs (-1, -3, and -6) in this tissue. Although our main focus will be in bone we will allude to IGFBP activity in other cells and tissues where appropriate.

  11. Identifying a key physical factor sensitive to the performance of Madden-Julian oscillation simulation in climate models

    NASA Astrophysics Data System (ADS)

    Kim, Go-Un; Seo, Kyong-Hwan

    2018-01-01

    A key physical factor in regulating the performance of Madden-Julian oscillation (MJO) simulation is examined by using 26 climate model simulations from the World Meteorological Organization's Working Group for Numerical Experimentation/Global Energy and Water Cycle Experiment Atmospheric System Study (WGNE and MJO-Task Force/GASS) global model comparison project. For this, intraseasonal moisture budget equation is analyzed and a simple, efficient physical quantity is developed. The result shows that MJO skill is most sensitive to vertically integrated intraseasonal zonal wind convergence (ZC). In particular, a specific threshold value of the strength of the ZC can be used as distinguishing between good and poor models. An additional finding is that good models exhibit the correct simultaneous convection and large-scale circulation phase relationship. In poor models, however, the peak circulation response appears 3 days after peak rainfall, suggesting unfavorable coupling between convection and circulation. For an improving simulation of the MJO in climate models, we propose that this delay of circulation in response to convection needs to be corrected in the cumulus parameterization scheme.

  12. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria.

    PubMed

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-07-29

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens.

  13. Elucidation of the glucose transport pathway in glucose transporter 4 via steered molecular dynamics simulations.

    PubMed

    Sheena, Aswathy; Mohan, Suma S; Haridas, Nidhina Pachakkil A; Anilkumar, Gopalakrishnapillai

    2011-01-01

    GLUT4 is a predominant insulin regulated glucose transporter expressed in major glucose disposal tissues such as adipocytes and muscles. Under the unstimulated state, GLUT4 resides within intracellular vesicles. Various stimuli such as insulin translocate this protein to the plasma membrane for glucose transport. In the absence of a crystal structure for GLUT4, very little is known about the mechanism of glucose transport by this protein. Earlier we proposed a homology model for GLUT4 and performed a conventional molecular dynamics study revealing the conformational rearrangements during glucose and ATP binding. However, this study could not explain the transport of glucose through the permeation tunnel. To elucidate the molecular mechanism of glucose transport and its energetic, a steered molecular dynamics study (SMD) was used. Glucose was pulled from the extracellular end of GLUT4 to the cytoplasm along the pathway using constant velocity pulling method. We identified several key residues within the tunnel that interact directly with either the backbone ring or the hydroxyl groups of glucose. A rotation of glucose molecule was seen near the sugar binding site facilitating the sugar recognition process at the QLS binding site. This study proposes a possible glucose transport pathway and aids the identification of several residues that make direct interactions with glucose during glucose transport. Mutational studies are required to further validate the observation made in this study.

  14. Differential Effects of Oral and Intravenous Lipid Administration on Key Molecules Related to Energy Homeostasis

    PubMed Central

    Vamvini, Maria T.; Hamnvik, Ole-Petter; Sahin-Efe, Ayse; Gavrieli, Anna; Dincer, Fadime; Farr, Olivia M.

    2016-01-01

    Context: The spectrum of lipid-induced changes in the secretion of hormones important in energy homeostasis has not yet been fully elucidated. Objective: To identify potential incretin-like effects in response to lipid administration, we examined the short-term effect of iv vs oral lipids on key molecules regulating energy homeostasis. Design, Intervention, and Participants: After a 10-hour overnight fast, 26 subjects were randomized to receive an oral lipid load, a 10% iv lipid emulsion, a 20% iv lipid emulsion, or an iv saline infusion. We obtained blood samples at 30-minute intervals for the first 2 hours and hourly thereafter for a total of 6 hours. Main Outcome Measures: Circulating levels of insulin, glucose, c-peptide, free fatty acids, incretins (glucagon-like peptide-1, gastric inhibitory polypeptide), glucagon, peptide YY, ghrelin, fibroblast growth factor 21, fetuin A, irisin, omentin, and adiponectin were measured. Results: Oral lipid ingestion resulted in higher glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon, and peptide YY levels, compared with the other three groups (incremental area under the curve P = .003, P < .001, P < .001, P < .001, respectively). The 20% lipid emulsion, leading to higher free fatty acid levels, resulted in greater insulin, c-peptide, and fibroblast growth factor 21 responses compared with placebo and the other two groups (incremental area under the curve P = .002, P = .005, P < .001, P < .001, respectively). Omentin, adiponectin, fetuin A, and irisin levels were not affected by either mode of lipid administration. Conclusions: Metabolic responses to lipids depend on the route of administration. Only iv lipids trigger a dose-dependent fibroblast growth factor 21 secretion, which is nonglucagon mediated. Intravenous lipids also induce hyperinsulinemia without concurrent decreases in glucose, a phenomenon observed in insulin-resistant states. Orally administered lipids mostly affect gastrointestinal tract

  15. Bridging the Gap between Aetiological and Maintaining Factors in Social Anxiety Disorder: The Impact of Socially Traumatic Experiences on Beliefs, Imagery and Symptomatology.

    PubMed

    Norton, Alice R; Abbott, Maree J

    2017-05-01

    A number of key environmental factors during childhood have been implicated in the aetiology of social anxiety disorder (SAD), including aversive social experiences, traumatic life events and parent-child interaction. However, understanding the nature, interactions and relative contributions of these factors remains unclear. Furthermore, the relation of aversive social experiences to the development of key maintaining factors in SAD requires elucidation. The current study aimed to extend previous research regarding the aetiology of SAD by investigating the relationship between key environmental factors in childhood, negative beliefs and self-imagery, and the development of SAD. Social anxiety disorder individuals (n = 40, 87.5% female, M age  = 20.25 years) completed self-report measures of social anxiety symptomatology, traumatic experiences and parenting style. In addition, participants were administered interviews assessing various domains of childhood trauma, as well as negative self-imagery and associated socially traumatic memories. Participants reported a high frequency of early traumatic experiences across all domains (physical, emotional, sexual, social and non-relational), as well as a high degree of parental overcontrol. However, social anxiety symptomatology was most strongly correlated with socially traumatic experiences, and mediation analyses suggest that appraisal of aversive social/peer experiences accounts for the relationship of SAD symptomatology with negative self-beliefs and imagery. These outcomes suggest that social trauma may be a key proximal cause of SAD development, leading to the development of negative beliefs and imagery that subsequently maintain the disorder. These findings have implications for understanding SAD aetiology, and improving treatment outcomes for the disorder. Copyright © 2016 John Wiley & Sons, Ltd. Negative social experiences have been implicated in the development of social anxiety disorder (SAD), but the

  16. Active Interaction Mapping as a tool to elucidate hierarchical functions of biological processes.

    PubMed

    Farré, Jean-Claude; Kramer, Michael; Ideker, Trey; Subramani, Suresh

    2017-07-03

    Increasingly, various 'omics data are contributing significantly to our understanding of novel biological processes, but it has not been possible to iteratively elucidate hierarchical functions in complex phenomena. We describe a general systems biology approach called Active Interaction Mapping (AI-MAP), which elucidates the hierarchy of functions for any biological process. Existing and new 'omics data sets can be iteratively added to create and improve hierarchical models which enhance our understanding of particular biological processes. The best datatypes to further improve an AI-MAP model are predicted computationally. We applied this approach to our understanding of general and selective autophagy, which are conserved in most eukaryotes, setting the stage for the broader application to other cellular processes of interest. In the particular application to autophagy-related processes, we uncovered and validated new autophagy and autophagy-related processes, expanded known autophagy processes with new components, integrated known non-autophagic processes with autophagy and predict other unexplored connections.

  17. What Contributes to Self-Control and Grit?: The Key Factors in College Students

    ERIC Educational Resources Information Center

    Sriram, Rishi; Glanzer, Perry L.; Allen, Cara Cliburn

    2018-01-01

    Although scholars know an increasing amount about the benefits of self-control and grit for college students, they know less about what influences self-control and grit in students. In this study we examined influences on self-control and a key element of grit in a national sample of college students. Results indicated that 5 of the 13 predictor…

  18. Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes

    PubMed Central

    Kuang, Zheng; Ji, Zhicheng

    2018-01-01

    Abstract Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. PMID:29325176

  19. Study of key factors influencing dust emission: An assessment of GEOS-Chem and DEAD simulations with observations

    NASA Astrophysics Data System (ADS)

    Bartlett, Kevin S.

    Mineral dust aerosols can impact air quality, climate change, biological cycles, tropical cyclone development and flight operations due to reduced visibility. Dust emissions are primarily limited to the extensive arid regions of the world, yet can negatively impact local to global scales, and are extremely complex to model accurately. Within this dissertation, the Dust Entrainment And Deposition (DEAD) model was adapted to run, for the first known time, using high temporal (hourly) and spatial (0.3°x0.3°) resolution data to methodically interrogate the key parameters and factors influencing global dust emissions. The dependence of dust emissions on key parameters under various conditions has been quantified and it has been shown that dust emissions within DEAD are largely determined by wind speeds, vegetation extent, soil moisture and topographic depressions. Important findings were that grid degradation from 0.3ºx0.3º to 1ºx1º, 2ºx2.5º, and 4°x5° of key meteorological, soil, and surface input parameters greatly reduced emissions approximately 13% and 29% and 64% respectively, as a result of the loss of sub grid detail within these key parameters at coarse grids. After running high resolution DEAD emissions globally for 2 years, two severe dust emission cases were chosen for an in-depth investigation of the root causes of the events and evaluation of the 2°x2.5° Goddard Earth Observing System (GEOS)-Chem and 0.3°x0.3° DEAD model capabilities to simulate the events: one over South West Asia (SWA) in June 2008 and the other over the Middle East in July 2009. The 2 year lack of rain over SWA preceding June 2008 with a 43% decrease in mean rainfall, yielded less than normal plant growth, a 28% increase in Aerosol Optical Depth (AOD), and a 24% decrease in Meteorological Aerodrome Report (METAR) observed visibility (VSBY) compared to average years. GEOS-Chem captured the observed higher AOD over SWA in June 2008. More detailed comparisons of GEOS

  20. Cloning of a cancer cell-producing hepatocyte growth factor, vascular endothelial growth factor, and interleukin-8 from gastric cancer cells.

    PubMed

    Iwai, Mineko; Matsuda, Masahiko; Iwai, Yoshiaki

    2003-01-01

    A cell colony (IM95m) that produces hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) was cloned from gastric cancer cells (IM95 cell line). In culture medium, the highest levels of HGF, VEGF, and IL-8 were about 1.1, 0.9, and 0.17 ng/ml culture medium at 3 d from 10(5) cells. IM95m may be useful in elucidating the role of tumor cells in angiogenesis.

  1. Elucidating the Chemical Complexity of Organic Aerosol Constituents Measured During the Southeastern Oxidant and Aerosol Study (SOAS)

    NASA Astrophysics Data System (ADS)

    Yee, L.; Isaacman, G. A.; Spielman, S. R.; Worton, D. R.; Zhang, H.; Kreisberg, N. M.; Wilson, K. R.; Hering, S. V.; Goldstein, A. H.

    2013-12-01

    Thousands of volatile organic compounds are uniquely created in the atmosphere, many of which undergo chemical transformations that result in more highly-oxidized and often lower vapor pressure species. These species can contribute to secondary organic aerosol, a complex mixture of organic compounds that is still not chemically well-resolved. Organic aerosol collected on filters taken during the Southeastern Oxidant and Aerosol Study (SOAS) constitute hundreds of unique chemical compounds. Some of these include known anthropogenic and biogenic tracers characterized using standardized analytical techniques (e.g. GC-MS, UPLC, LC-MS), but the majority of the chemical diversity has yet to be explored. By employing analytical techniques involving sample derivatization and comprehensive two-dimensional gas chromatography (GC x GC) with high-resolution-time-of-flight mass spectrometry (HR-ToF-MS), we elucidate the chemical complexity of the organic aerosol matrix along the volatility and polarity grids. Further, by utilizing both electron impact (EI) and novel soft vacuum ultraviolet (VUV) ionization mass spectrometry, a greater fraction of the organic mass is fully speciated. The GC x GC-HR-ToF-MS with EI/VUV technique efficiently provides an unprecedented level of speciation for complex ambient samples. We present an extensive chemical characterization and quantification of organic species that goes beyond typical atmospheric tracers in the SOAS samples. We further demonstrate that complex organic mixtures can be chemically deconvoluted by elucidation of chemical formulae, volatility, functionality, and polarity. These parameters provide insight into the sources (anthropogenic vs. biogenic), chemical processes (oxidation pathways), and environmental factors (temperature, humidity), controlling organic aerosol growth in the Southeastern United States.

  2. Orphan nuclear receptor ERRγ is a key regulator of human fibrinogen gene expression

    PubMed Central

    Zhang, Yaochen; Kim, Don-Kyu; Lu, Yan; Jung, Yoon Seok; Lee, Ji-min; Kim, Young-Hoon; Lee, Yong Soo; Kim, Jina; Dewidar, Bedair; Jeong, Won-IL; Lee, In-Kyu; Cho, Sung Jin; Dooley, Steven; Lee, Chul-Ho; Li, Xiaoying

    2017-01-01

    Fibrinogen, 1 of 13 coagulation factors responsible for normal blood clotting, is synthesized by hepatocytes. Detailed roles of the orphan nuclear receptors regulating fibrinogen gene expression have not yet been fully elucidated. Here, we identified estrogen-related receptor gamma (ERRγ) as a novel transcriptional regulator of human fibrinogen gene expression. Overexpression of ERRγ specially increased fibrinogen expression in human hepatoma cell line. Cannabinoid receptor types 1(CB1R) agonist arachidonyl-2'-chloroethylamide (ACEA) up-regulated transcription of fibrinogen via induction of ERRγ, whereas knockdown of ERRγ attenuated fibrinogen expression. Deletion analyses of the fibrinogen γ (FGG) gene promoter and ChIP assays revealed binding sites of ERRγ on human fibrinogen γ gene promoter. Moreover, overexpression of ERRγ was sufficient to increase fibrinogen gene expression, whereas treatment with GSK5182, a selective inverse agonist of ERRγ led to its attenuation in cell culture. Finally, fibrinogen and ERRγ gene expression were elevated in liver tissue of obese patients suggesting a conservation of this mechanism. Overall, this study elucidates a molecular mechanism linking CB1R signaling, ERRγ expression and fibrinogen gene transcription. GSK5182 may have therapeutic potential to treat hyperfibrinogenemia. PMID:28750085

  3. How to identify the key factors that affect driver perception of accident risk. A comparison between Italian and Spanish driver behavior.

    PubMed

    de Oña, Juan; de Oña, Rocio; Eboli, Laura; Forciniti, Carmen; Mazzulla, Gabriella

    2014-12-01

    Road crashes can be caused by different factors, including infrastructure, vehicles, and human variables. Many research studies have focused solely on identifying the key factors that cause road crashes. From these studies, it emerged that human factors have the most relevant impact on accident severity. More specifically, accident severity depends on several factors related directly to the driver, i.e., driving experience, driver's socio-economic characteristics, and driving behavior and attitudes. In this paper, we investigate driver behaviors and attitudes while driving and specifically focus on different methods for identifying the factors that most affect the driver's perception of accident risk. To this end, we designed and conducted a survey in two different European contexts: the city of Cosenza, which is located in the south of Italy, and the city of Granada, which is located in the south of Spain. Samples of drivers were contacted for their opinions on certain aspects of driving rules and attitudes while driving, and different types of questions were addressed to the drivers to assess their judgments of these aspects. Consequently, different methods of data analysis were applied to determine the aspects that heavily influence driver perception of accident risk. An experiment based on the stated preferences (SP) was carried out with the drivers, and the SP data were analyzed using an ordered probit (OP) model. Interesting findings emerged from different analyses of the data and from the comparisons among the data collected in the two different territorial contexts. We found that both Italian and Spanish drivers consider driving in an altered psychophysical state and violating the overtaking rules to be the most risky behaviors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Exploring the key predictors of retention in emergency nurses.

    PubMed

    Sawatzky, Jo-Ann V; Enns, Carol L

    2012-07-01

    To explore the factors that predict the retention of nurses working in emergency departments. The escalating shortage of nurses is one of the most critical issues facing specialty areas, such as the emergency department. Therefore, it is important to identify the key influencing and intermediary factors that affect emergency department nurses' intention to leave. As part of a larger study, a cross-sectional survey was completed by 261 registered nurses working in the 12 designated emergency departments within rural, urban community and tertiary hospitals in Manitoba, Canada. Twenty-six per cent of the respondents will probably/definitely leave their current emergency department jobs within the next year. Engagement was the key predictor of intention to leave (P < 0.001). Engagement was also associated with job satisfaction, compassion satisfaction, compassion fatigue, and burnout (P < 0.05). In an ordinal least-squares model (R(2) = 0.44), nursing management, professional practice, collaboration with physicians, staffing resources and shift work emerged as significant influencing factors for engagement. Engagement plays a central role in emergency department nurses intention to leave. Addressing the factors that influence engagement may reduce emergency department nurses' intention to leave. This study highlights the value of research-based evidence as the foundation for developing innovative strategies for the retention of emergency department nurses. © 2012 Blackwell Publishing Ltd.

  5. Nature's Anti-Alzheimer's Drug: Isolation and Structure Elucidation of Galantamine from "Leucojum Aestivum"

    ERIC Educational Resources Information Center

    Halpin, Catherine M.; Reilly, Ciara; Walsh, John J.

    2010-01-01

    The discovery that galantamine penetrates the blood-brain barrier has led to its clinical use in the treatment of choline-deficiency conditions in the brain, such as Alzheimer's disease. This experiment involves the isolation and structure elucidation of galantamine from "Leucojum aestivum". Isolation of the alkaloid constituents in "L. aestivum"…

  6. Public perceptions of key performance indicators of healthcare in Alberta, Canada.

    PubMed

    Northcott, Herbert C; Harvey, Michael D

    2012-06-01

    To examine the relationship between public perceptions of key performance indicators assessing various aspects of the health-care system. Cross-sequential survey research. Annual telephone surveys of random samples of adult Albertans selected by random digit dialing and stratified according to age, sex and region (n = 4000 for each survey year). The survey questionnaires included single-item measures of key performance indicators to assess public perceptions of availability, accessibility, quality, outcome and satisfaction with healthcare. Cronbach's α and factor analysis were used to assess the relationship between key performance indicators focusing on the health-care system overall and on a recent interaction with the health-care system. The province of Alberta, Canada during the years 1996-2004. Four thousand adults randomly selected each survey year. Survey questions measuring public perceptions of healthcare availability, accessibility, quality, outcome and satisfaction with healthcare. Factor analysis identified two principal components with key performance indicators focusing on the health system overall loading most strongly on the first component and key performance indicators focusing on the most recent health-care encounter loading most strongly on the second component. Assessments of the quality of care most recently received, accessibility of that care and perceived outcome of care tended to be higher than the more general assessments of overall health system quality and accessibility. Assessments of specific health-care encounters and more general assessments of the overall health-care system, while related, nevertheless comprise separate dimensions for health-care evaluation.

  7. Mass Spectra-Based Framework for Automated Structural Elucidation of Metabolome Data to Explore Phytochemical Diversity

    PubMed Central

    Matsuda, Fumio; Nakabayashi, Ryo; Sawada, Yuji; Suzuki, Makoto; Hirai, Masami Y.; Kanaya, Shigehiko; Saito, Kazuki

    2011-01-01

    A novel framework for automated elucidation of metabolite structures in liquid chromatography–mass spectrometer metabolome data was constructed by integrating databases. High-resolution tandem mass spectra data automatically acquired from each metabolite signal were used for database searches. Three distinct databases, KNApSAcK, ReSpect, and the PRIMe standard compound database, were employed for the structural elucidation. The outputs were retrieved using the CAS metabolite identifier for identification and putative annotation. A simple metabolite ontology system was also introduced to attain putative characterization of the metabolite signals. The automated method was applied for the metabolome data sets obtained from the rosette leaves of 20 Arabidopsis accessions. Phenotypic variations in novel Arabidopsis metabolites among these accessions could be investigated using this method. PMID:22645535

  8. Elucidating Neuronal Mechanisms Using Intracellular Recordings during Behavior.

    PubMed

    Lee, Albert K; Brecht, Michael

    2018-06-01

    Intracellular recording allows measurement and perturbation of the membrane potential of identified neurons with sub-millisecond and sub-millivolt precision. This gives intracellular recordings a unique capacity to provide rich information about individual cells (e.g., high-resolution characterization of inputs, outputs, excitability, and structure). Hence, such recordings can elucidate the mechanisms that underlie fundamental phenomena, such as brain state, sparse coding, gating, gain modulation, and learning. Technical developments have increased the range of behaviors during which intracellular recording methods can be employed, such as in freely moving animals and head-fixed animals actively performing tasks, including in virtual environments. Such advances, and the combination of intracellular recordings with genetic and imaging techniques, have enabled investigation of the mechanisms that underlie neural computations during natural and trained behaviors. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Structural basis of gene regulation by the Grainyhead/CP2 transcription factor family

    PubMed Central

    Ming, Qianqian; Roske, Yvette; Schuetz, Anja; Walentin, Katharina; Ibraimi, Ibraim; Schmidt-Ott, Kai M

    2018-01-01

    Abstract Grainyhead (Grh)/CP2 transcription factors are highly conserved in multicellular organisms as key regulators of epithelial differentiation, organ development and skin barrier formation. In addition, they have been implicated as being tumor suppressors in a variety of human cancers. Despite their physiological importance, little is known about their structure and DNA binding mode. Here, we report the first structural study of mammalian Grh/CP2 factors. Crystal structures of the DNA-binding domains of grainyhead-like (Grhl) 1 and Grhl2 reveal a closely similar conformation with immunoglobulin-like core. Both share a common fold with the tumor suppressor p53, but differ in important structural features. The Grhl1 DNA-binding domain binds duplex DNA containing the consensus recognition element in a dimeric arrangement, supporting parsimonious target-sequence selection through two conserved arginine residues. We elucidate the molecular basis of a cancer-related mutation in Grhl1 involving one of these arginines, which completely abrogates DNA binding in biochemical assays and transcriptional activation of a reporter gene in a human cell line. Thus, our studies establish the structural basis of DNA target-site recognition by Grh transcription factors and reveal how tumor-associated mutations inactivate Grhl proteins. They may serve as points of departure for the structure-based development of Grh/CP2 inhibitors for therapeutic applications. PMID:29309642

  10. Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.

    PubMed

    Pietz, Grzegorz; De, Rituparna; Hedberg, Maria; Sjöberg, Veronika; Sandström, Olof; Hernell, Olle; Hammarström, Sten; Hammarström, Marie-Louise

    2017-01-01

    Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria. Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels. Two in vitro models for human intestinal epithelium, small intestinal enteroids and polarized tight monolayers, were utilized to assess how interferon-γ, interleukin-17A, celiac disease-associated bacteria and gluten influence intestinal epithelial cells. More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were significantly upregulated in intestinal epithelial cells at active celiac disease. Of these genes, 70% were upregulated by interferon-γ via the IRF1 pathway. Most interestingly, IRF1 was also upregulated by celiac disease-associated bacteria. The NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin-18, which induces interferon-γ in intraepithelial lymphocytes, was expressed in intestinal epithelial cells. A key factor in the epithelial reaction in celiac disease appears to be over-expression of IRF1 that could be inherent and/or due to presence of undesirable microbes that act directly on IRF1. Dual activation of IRF1 and IRF1-regulated genes, both directly and via the interleukin-18 dependent inflammasome would drastically enhance the inflammatory response and lead to the pathological situation seen in active celiac disease.

  11. Immunopathology of childhood celiac disease—Key role of intestinal epithelial cells

    PubMed Central

    Hedberg, Maria; Sjöberg, Veronika; Sandström, Olof; Hernell, Olle; Hammarström, Sten

    2017-01-01

    Background & Aims Celiac disease is a chronic inflammatory disease of the small intestine mucosa due to permanent intolerance to dietary gluten. The aim was to elucidate the role of small intestinal epithelial cells in the immunopathology of celiac disease in particular the influence of celiac disease-associated bacteria. Methods Duodenal biopsies were collected from children with active celiac disease, treated celiac disease, and clinical controls. Intestinal epithelial cells were purified and analyzed for gene expression changes at the mRNA and protein levels. Two in vitro models for human intestinal epithelium, small intestinal enteroids and polarized tight monolayers, were utilized to assess how interferon-γ, interleukin-17A, celiac disease-associated bacteria and gluten influence intestinal epithelial cells. Results More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were significantly upregulated in intestinal epithelial cells at active celiac disease. Of these genes, 70% were upregulated by interferon-γ via the IRF1 pathway. Most interestingly, IRF1 was also upregulated by celiac disease-associated bacteria. The NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin-18, which induces interferon-γ in intraepithelial lymphocytes, was expressed in intestinal epithelial cells. Conclusion A key factor in the epithelial reaction in celiac disease appears to be over-expression of IRF1 that could be inherent and/or due to presence of undesirable microbes that act directly on IRF1. Dual activation of IRF1 and IRF1-regulated genes, both directly and via the interleukin-18 dependent inflammasome would drastically enhance the inflammatory response and lead to the pathological situation seen in active celiac disease. PMID:28934294

  12. Key management of the double random-phase-encoding method using public-key encryption

    NASA Astrophysics Data System (ADS)

    Saini, Nirmala; Sinha, Aloka

    2010-03-01

    Public-key encryption has been used to encode the key of the encryption process. In the proposed technique, an input image has been encrypted by using the double random-phase-encoding method using extended fractional Fourier transform. The key of the encryption process have been encoded by using the Rivest-Shamir-Adelman (RSA) public-key encryption algorithm. The encoded key has then been transmitted to the receiver side along with the encrypted image. In the decryption process, first the encoded key has been decrypted using the secret key and then the encrypted image has been decrypted by using the retrieved key parameters. The proposed technique has advantage over double random-phase-encoding method because the problem associated with the transmission of the key has been eliminated by using public-key encryption. Computer simulation has been carried out to validate the proposed technique.

  13. Optical key system

    DOEpatents

    Hagans, Karla G.; Clough, Robert E.

    2000-01-01

    An optical key system comprises a battery-operated optical key and an isolated lock that derives both its operating power and unlock signals from the correct optical key. A light emitting diode or laser diode is included within the optical key and is connected to transmit a bit-serial password. The key user physically enters either the code-to-transmit directly, or an index to a pseudorandom number code, in the key. Such person identification numbers can be retained permanently, or ephemeral. When a send button is pressed, the key transmits a beam of light modulated with the password information. The modulated beam of light is received by a corresponding optical lock with a photovoltaic cell that produces enough power from the beam of light to operate a password-screen digital logic. In one application, an acceptable password allows a two watt power laser diode to pump ignition and timing information over a fiberoptic cable into a sealed engine compartment. The receipt of a good password allows the fuel pump, spark, and starter systems to each operate. Therefore, bypassing the lock mechanism as is now routine with automobile thieves is pointless because the engine is so thoroughly disabled.

  14. Research on key factors and their interaction effects of electromagnetic force of high-speed solenoid valve.

    PubMed

    Liu, Peng; Fan, Liyun; Hayat, Qaisar; Xu, De; Ma, Xiuzhen; Song, Enzhe

    2014-01-01

    Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined.

  15. Research on Key Factors and Their Interaction Effects of Electromagnetic Force of High-Speed Solenoid Valve

    PubMed Central

    Fan, Liyun; Xu, De; Ma, Xiuzhen; Song, Enzhe

    2014-01-01

    Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined. PMID:25243217

  16. Elucidating compound mechanism of action by network perturbation analysis | Office of Cancer Genomics

    Cancer.gov

    Genome-wide identification of the mechanism of action (MoA) of small-molecule compounds characterizing their targets, effectors, and activity modulators represents a highly relevant yet elusive goal, with critical implications for assessment of compound efficacy and toxicity. Current approaches are labor intensive and mostly limited to elucidating high-affinity binding target proteins.

  17. Public-key quantum digital signature scheme with one-time pad private-key

    NASA Astrophysics Data System (ADS)

    Chen, Feng-Lin; Liu, Wan-Fang; Chen, Su-Gen; Wang, Zhi-Hua

    2018-01-01

    A quantum digital signature scheme is firstly proposed based on public-key quantum cryptosystem. In the scheme, the verification public-key is derived from the signer's identity information (such as e-mail) on the foundation of identity-based encryption, and the signature private-key is generated by one-time pad (OTP) protocol. The public-key and private-key pair belongs to classical bits, but the signature cipher belongs to quantum qubits. After the signer announces the public-key and generates the final quantum signature, each verifier can verify publicly whether the signature is valid or not with the public-key and quantum digital digest. Analysis results show that the proposed scheme satisfies non-repudiation and unforgeability. Information-theoretic security of the scheme is ensured by quantum indistinguishability mechanics and OTP protocol. Based on the public-key cryptosystem, the proposed scheme is easier to be realized compared with other quantum signature schemes under current technical conditions.

  18. Multi-omics approach to elucidate the gut microbiota activity: Metaproteomics and metagenomics connection.

    PubMed

    Guirro, Maria; Costa, Andrea; Gual-Grau, Andreu; Mayneris-Perxachs, Jordi; Torrell, Helena; Herrero, Pol; Canela, Núria; Arola, Lluís

    2018-02-10

    Over the last few years, the application of high-throughput meta-omics methods has provided great progress in improving the knowledge of the gut ecosystem and linking its biodiversity to host health conditions, offering complementary support to classical microbiology. Gut microbiota plays a crucial role in relevant diseases such as obesity or cardiovascular disease (CVD), and its regulation is closely influenced by several factors, such as dietary composition. In fact, polyphenol-rich diets are the most palatable treatment to prevent hypertension associated with CVD, although the polyphenol-microbiota interactions have not been completely elucidated. For this reason, the aim of this study was to evaluate microbiota effect in obese rats supplemented by hesperidin, after being fed with cafeteria or standard diet, using a multi meta-omics approaches combining strategy of metagenomics and metaproteomics analysis. We reported that cafeteria diet induces obesity, resulting in changes in the microbiota composition, which are related to functional alterations at proteome level. In addition, hesperidin supplementation alters microbiota diversity and also proteins involved in important metabolic pathways. Overall, going deeper into strategies to integrate omics sciences is necessary to understand the complex relationships between the host, gut microbiota, and diet. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Critical Role of Transforming Growth Factor Beta in Different Phases of Wound Healing

    PubMed Central

    Pakyari, Mohammadreza; Farrokhi, Ali; Maharlooei, Mohsen Khosravi; Ghahary, Aziz

    2013-01-01

    Significance This review highlights the critical role of transforming growth factor beta (TGF-β)1–3 within different phases of wound healing, in particular, late-stage wound healing. It is also very important to identify the TGF-β1–controlling factors involved in slowing down the healing process upon wound epithelialization. Recent Advances TGF-β1, as a growth factor, is a known proponent of dermal fibrosis. Several strategies to modulate or regulate TGF's actions have been thoroughly investigated in an effort to create successful therapies. This study reviews current discourse regarding the many roles of TGF-β1 in wound healing by modulating infiltrated immune cells and the extracellular matrix. Critical Issues It is well established that TGF-β1 functions as a wound-healing promoting factor, and thereby if in excess it may lead to overhealing outcomes, such as hypertrophic scarring and keloid. Thus, the regulation of TGF-β1 in the later stages of the healing process remains as critical issue of which to better understand. Future Directions One hypothesis is that cell communication is the key to regulate later stages of wound healing. To elucidate the role of keratinocyte/fibroblast cross talk in controlling the later stages of wound healing we need to: (1) identify those keratinocyte-released factors which would function as wound-healing stop signals, (2) evaluate the functionality of these factors in controlling the outcome of the healing process, and (3) formulate topical vehicles for these antifibrogenic factors to improve or even prevent the development of hypertrophic scarring and keloids as a result of deep trauma, burn injuries, and any type of surgical incision. PMID:24527344

  20. Keys to Success in Raising Funds: An Exchange Classic.

    ERIC Educational Resources Information Center

    Neugebauer, Roger

    2001-01-01

    Details survey of over 100 child care centers about successful and unsuccessful fundraising projects. Highlights ten key factors contributing to success: defining the purpose for fundraising, setting a goal, knowing the audience, making it fun, building on strengths, looking for repeated fundraisers, being cost effective, publicizing aggressively,…

  1. Youth-Adult Connectedness:: A Key Protective Factor for Adolescent Health.

    PubMed

    Sieving, Renee E; McRee, Annie-Laurie; McMorris, Barbara J; Shlafer, Rebecca J; Gower, Amy L; Kapa, Hillary M; Beckman, Kara J; Doty, Jennifer L; Plowman, Shari L; Resnick, Michael D

    2017-03-01

    Over the past 30 years, prevention science in the adolescent health field has moved from interventions focused on preventing single problem behaviors to efforts employing a dual approach, addressing risk factors that predict problems while simultaneously nurturing protective factors and promoting positive development. Through an examination of previous research and empirical case examples with vulnerable youth, this article considers the hypothesis that adolescents' sense of connectedness to caring adults acts as a protective factor against a range of risk behaviors. Multivariate analyses with existing data examined indicators of youth-adult connectedness among two groups at high risk for poor health outcomes: (1) mentor-youth relationship quality in an urban, ethnically diverse sample of students in a school-based mentoring program (2014 survey, N=239); and (2) parent-youth connectedness in a statewide sample of high school students who reported homelessness in the past year (2013 survey, N=3,627). For youth in the mentoring program, a high-quality youth-mentor relationship was significantly associated with positive social, academic, and health-related behaviors. Among students who experienced homelessness, all measures of parent connectedness were significantly associated with lower sexual risk levels. Collectively, findings from these analyses and previously published studies by this research group provide evidence that strong, positive relationships with parents and other caring adults protect adolescents from a range of poor health-related outcomes and promote positive development. Youth-adult connectedness appears to be foundational for adolescent health and well-being. Program, practice, and policy decisions should consider what strengthens or hinders caring, connected youth-adult relationships. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Elucidating electrolyte decomposition under electron-rich environments at the lithium-metal anode.

    PubMed

    Camacho-Forero, Luis E; Balbuena, Perla B

    2017-11-22

    The lithium metal anode is one of the key components of the lithium-sulfur (Li-S) batteries, which are considered one of the most promising candidates for the next generation of battery systems. However, one of the main challenges that have prevented Li-metal anodes from becoming feasible to be used in commercial batteries is the continuous decomposition of the electrolyte due to its high reactivity, which leads to the formation of solid-electrolyte interphase (SEI) layers. The properties of the SEI can dramatically affect the performance of the batteries. Thus, a rigorous understanding of the electrolyte decomposition is crucial to elucidate improvements in performance of the Li-S technology. In this work, using density functional theory (DFT) and ab initio molecular dynamics simulations (AIMD), we investigate the effect of electron-rich environments on the decomposition mechanism of electrolyte species in pure 1,2-dimethoxyethane (DME) solvent and 1 M lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and lithium bis(fluorosulfonyl)imide (LiFSI) salt solutions. It is found that systems with pure DME require an average environment of at least ∼0.9 |e| per molecule for a DME to decompose into CH 3 O - and C 2 H 4 2- via a 4-electron transfer. In the case of mixtures, the salts are very prone to react with any excess of electrons. In addition, DME dehydrogenation due to reactions with fragments coming from the salt decompositions was detected. Formation of oligomer anionic species from DME and salt fragments were also identified from the AIMD simulations. Finally, the thermodynamics and kinetics of the most relevant electrolyte decomposition reactions were characterized. DME decomposition reactions predicted from the AIMD simulations were found to be thermodynamically favorable under exposure to Li atoms and/or by reactions with salt fragments. In most cases, these reactions were shown to have low to moderate activation barriers.

  3. Key recovery factors for the August 24, 2014, South Napa Earthquake

    USGS Publications Warehouse

    Hudnut, Kenneth W.; Brocher, Thomas M.; Prentice, Carol S.; Boatwright, John; Brooks, Benjamin A.; Aagaard, Brad T.; Blair, James Luke; Fletcher, Jon Peter B.; Erdem, Jemile; Wicks, Chuck; Murray, Jessica R.; Pollitz, Fred F.; Langbein, John O.; Svarc, Jerry L.; Schwartz, David P.; Ponti, Daniel J.; Hecker, Suzanne; DeLong, Stephen B.; Rosa, Carla M.; Jones, Brenda; Lamb, Rynn M.; Rosinski, Anne M.; McCrink, Timothy P.; Dawson, Timothy E.; Seitz, Gordon G.; Glennie, Craig; Hauser, Darren; Ericksen, Todd; Mardock, Dan; Hoirup, Don F.; Bray, Jonathan D.; Rubin, Ron S.

    2014-01-01

    Through discussions between the Federal Emergency Management Agency (FEMA) and the U.S. Geological Survey (USGS) following the South Napa earthquake, it was determined that several key decision points would be faced by FEMA for which additional information should be sought and provided by USGS and its partners. This report addresses the four tasks that were agreed to. These tasks are (1) assessment of ongoing fault movement (called afterslip) especially in the Browns Valley residential neighborhood, (2) assessment of the shaking pattern in the downtown area of the City of Napa, (3) improvement of information on the fault hazards posed by the West Napa Fault System (record of past earthquakes and slip rate, for example), and (4) imagery acquisition and data processing to provide overall geospatial information support to FEMA.

  4. Finite-key analysis for measurement-device-independent quantum key distribution.

    PubMed

    Curty, Marcos; Xu, Feihu; Cui, Wei; Lim, Charles Ci Wen; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2014-04-29

    Quantum key distribution promises unconditionally secure communications. However, as practical devices tend to deviate from their specifications, the security of some practical systems is no longer valid. In particular, an adversary can exploit imperfect detectors to learn a large part of the secret key, even though the security proof claims otherwise. Recently, a practical approach--measurement-device-independent quantum key distribution--has been proposed to solve this problem. However, so far its security has only been fully proven under the assumption that the legitimate users of the system have unlimited resources. Here we fill this gap and provide a rigorous security proof against general attacks in the finite-key regime. This is obtained by applying large deviation theory, specifically the Chernoff bound, to perform parameter estimation. For the first time we demonstrate the feasibility of long-distance implementations of measurement-device-independent quantum key distribution within a reasonable time frame of signal transmission.

  5. The Promise of Virtual Teams: Identifying Key Factors in Effectiveness and Failure

    ERIC Educational Resources Information Center

    Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik

    2006-01-01

    Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…

  6. Tutorial for the structure elucidation of small molecules by means of the LSD software.

    PubMed

    Nuzillard, Jean-Marc; Plainchont, Bertrand

    2018-06-01

    Automatic structure elucidation of small molecules by means of the "logic for structure elucidation" (LSD) software is introduced in the context of the automatic exploitation of chemical shift correlation data and with minimal input from chemical shift values. The first step in solving a structural problem by means of LSD is the extraction of pertinent data from the 1D and 2D spectra. This operation requires the labeling of the resonances and of their correlations; its reliability highly depends on the quality of the spectra. The combination of COSY, HSQC, and HMBC spectra results in proximity relationships between nonhydrogen atoms that are associated in order to build the possible solutions of a problem. A simple molecule, camphor, serves as an example for the writing of an LSD input file and to show how solution structures are obtained. An input file for LSD must contain a nonambiguous description of each atom, or atom status, which includes the chemical element symbol, the hybridization state, the number of bound hydrogen atoms and the formal electric charge. In case of atom status ambiguity, the pyLSD program performs clarification by systematically generating the status of the atoms. PyLSD also proposes the use of the nmrshiftdb algorithm in order to rank the solutions of a problem according to the quality of the fit between the experimental carbon-13 chemical shifts, and the ones predicted from the proposed structures. To conclude, some hints toward future uses and developments of computer-assisted structure elucidation by LSD are proposed. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Optical key system

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

    Hagans, K.G.; Clough, R.E.

    2000-04-25

    An optical key system comprises a battery-operated optical key and an isolated lock that derives both its operating power and unlock signals from the correct optical key. A light emitting diode or laser diode is included within the optical key and is connected to transmit a bit-serial password. The key user physically enters either the code-to-transmit directly, or an index to a pseudorandom number code, in the key. Such person identification numbers can be retained permanently, or ephemeral. When a send button is pressed, the key transmits a beam of light modulated with the password information. The modulated beam ofmore » light is received by a corresponding optical lock with a photovoltaic cell that produces enough power from the beam of light to operate a password-screen digital logic. In one application, an acceptable password allows a two watt power laser diode to pump ignition and timing information over a fiberoptic cable into a sealed engine compartment. The receipt of a good password allows the fuel pump, spark, and starter systems to each operate. Therefore, bypassing the lock mechanism as is now routine with automobile thieves is pointless because the engine is so thoroughly disabled.« less

  8. Career Development Factors for Minority Disability and Health Research Leaders: A Key Informant Study

    ERIC Educational Resources Information Center

    Manyibe, Edward O.; Moore, Corey L.; Wang, Ningning; Davis, Dytisha; Aref, Fariborz; Washington, Andre L.; Johnson, Jean; Eugene-Cross, Kenyotta; Muhammad, Atashia; Lewis, Allen

    2017-01-01

    Purpose: This study examined and documented minority disability and health research leaders' experiences and perspectives on career development challenges and success strategies. Methods: A sample of 15 African American, American Indian or Alaskan Native, Latino, and Asian research leaders as key informants participated in the inquiry. Research…

  9. The use of mode of action information in risk assessment: quantitative key events/dose-response framework for modeling the dose-response for key events.

    PubMed

    Simon, Ted W; Simons, S Stoney; Preston, R Julian; Boobis, Alan R; Cohen, Samuel M; Doerrer, Nancy G; Fenner-Crisp, Penelope A; McMullin, Tami S; McQueen, Charlene A; Rowlands, J Craig

    2014-08-01

    The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative dose-response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the dose-response and timing of KEs resulting from a dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action-Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantitative dose-response information when assessing the effect of a Modulating Factor, that is, enzyme polymorphisms in humans, and 2) estrogen-induced uterotrophic responses in rodents, which demonstrate how quantitative dose-response modeling for KE, the understanding of temporal relationships between KEs and a counterfactual examination of hypothesized KEs can determine whether they are Associative Events or true KEs.

  10. Rice phytochrome-interacting factor-like protein OsPIL1 functions as a key regulator of internode elongation and induces a morphological response to drought stress

    PubMed Central

    Todaka, Daisuke; Nakashima, Kazuo; Maruyama, Kyonoshin; Kidokoro, Satoshi; Osakabe, Yuriko; Ito, Yusuke; Matsukura, Satoko; Fujita, Yasunari; Yoshiwara, Kyouko; Ohme-Takagi, Masaru; Kojima, Mikiko; Sakakibara, Hitoshi; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2012-01-01

    The mechanisms for plant growth restriction during stress conditions remains unclear. Here, we demonstrate that a phytochrome-interacting factor-like protein, OsPIL1/OsPIL13, acts as a key regulator of reduced internode elongation in rice under drought conditions. The level of OsPIL1 mRNA in rice seedlings grown under nonstressed conditions with light/dark cycles oscillated in a circadian manner with peaks in the middle of the light period. Under drought stress conditions, OsPIL1 expression was inhibited during the light period. We found that OsPIL1 was highly expressed in the node portions of the stem using promoter-glucuronidase analysis. Overexpression of OsPIL1 in transgenic rice plants promoted internode elongation. In contrast, transgenic rice plants with a chimeric repressor resulted in short internode sections. Alteration of internode cell size was observed in OsPIL1 transgenic plants, indicating that differences in cell size cause the change in internode length. Oligoarray analysis revealed OsPIL1 downstream genes, which were enriched for cell wall-related genes responsible for cell elongation. These data suggest that OsPIL1 functions as a key regulatory factor of reduced plant height via cell wall-related genes in response to drought stress. This regulatory system may be important for morphological stress adaptation in rice under drought conditions. PMID:22984180

  11. Risk factors in autism: Thinking outside the brain

    PubMed Central

    Matelski, Lauren; Van de Water, Judy

    2017-01-01

    Autism spectrum disorders (ASD) are complex neurodevelopmental conditions that have been rising markedly in prevalence for the past 30 years, now thought to affect 1 in 68 in the United States. This has prompted the search for possible explanations, and has even resulted in some controversy regarding the “true” prevalence of autism. ASD are influenced by a variety of genetic, environmental, and possibly immunological factors that act during critical periods to alter key developmental processes. This can affect multiple systems and manifests as the social and behavioral deficits that define these disorders. The interaction of environmental exposures in the context of an individual’s genetic susceptibilities manifests differently in each case, leading to heterogeneous phenotypes and varied comorbid symptoms within the disorder. This has also made it very difficult to elucidate underlying genes and exposure profiles, but progress is being made in this area. Some pharmaceutical drugs, toxicants, and metabolic and nutritional factors have been identified in epidemiological studies as increasing autism risk, especially during the prenatal period. Immunologic risk factors, including maternal infection during pregnancy, autoantibodies to fetal brain proteins, and familial autoimmune disease, have consistently been observed across multiple studies, as have immune abnormalities in individuals with ASD. Mechanistic research using animal models and patient-derived stem cells will help researchers to understand the complex etiology of these neurodevelopmental disorders, which will lead to more effective therapies and preventative strategies. Proposed therapies that need more investigation include special diets, probiotics, immune modulation, oxytocin, and personalized pharmacogenomic targets. The ongoing search for biomarkers and better treatments will result in earlier identification of ASD and provide much needed help and relief for afflicted families. PMID:26725748

  12. Elucidating genetic identities of cacao germplam in an international cacao collection using molecular markers

    USDA-ARS?s Scientific Manuscript database

    The conservation of cacao (Theobroma cacao L.) germplasm requires maintaining living trees in field genebanks in tropical regions. The International Cocoa Genebank, Trinidad is one of the largest cacao germplasm collections in the world. The objective of the present study was to elucidate the extent...

  13. Work Keys USA.

    ERIC Educational Resources Information Center

    Work Keys USA, 1998

    1998-01-01

    "Work Keys" is a comprehensive program for assessing and teaching workplace skills. This serial "special issue" features 18 first-hand reports on Work Keys projects in action in states across North America. They show how the Work Keys is helping businesses and educators solve the challenge of building a world-class work force.…

  14. A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria

    PubMed Central

    Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

    2016-01-01

    Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens. DOI: http://dx.doi.org/10.7554/eLife.19605.001 PMID:27472897

  15. Drug packaging. A key factor to be taken into account when choosing a treatment.

    PubMed

    2011-10-01

    A drug's packaging contributes to its harm-benefit balance. Highlighting the key practical information and identifying potential sources of error or mix-ups is part and parcel of the correct use of medicines. Select labelling that clearly and prominently displays the important information, including the international nonproprietary name (INN).

  16. Quadrature-quadrature phase-shift keying

    NASA Astrophysics Data System (ADS)

    Saha, Debabrata; Birdsall, Theodore G.

    1989-05-01

    Quadrature-quadrature phase-shift keying (Q2PSK) is a spectrally efficient modulation scheme which utilizes available signal space dimensions in a more efficient way than two-dimensional schemes such as QPSK and MSK (minimum-shift keying). It uses two data shaping pulses and two carriers, which are pairwise quadrature in phase, to create a four-dimensional signal space and increases the transmission rate by a factor of two over QPSK and MSK. However, the bit error rate performance depends on the choice of pulse pair. With simple sinusoidal and cosinusoidal data pulses, the Eb/N0 requirement for Pb(E) = 10 to the -5 is approximately 1.6 dB higher than that of MSK. Without additional constraints, Q2PSK does not maintain constant envelope. However, a simple block coding provides a constant envelope. This coded signal substantially outperforms MSKS and TFM (time-frequency multiplexing) in bandwidth efficiency. Like MSK, Q2PSK also has self-clocking and self-synchronizing ability. An optimum class of pulse shapes for use in Q2PSK-format is presented. One suboptimum realization achieves the Nyquist rate of 2 bits/s/Hz using binary detection.

  17. Systematic Review: Predisposing, Precipitating, Perpetuating, and Present Factors Predicting Anticipatory Distress to Painful Medical Procedures in Children

    PubMed Central

    Pillai Riddell, Rebecca R.; Khan, Maria; Calic, Masa; Taddio, Anna; Tablon, Paula

    2016-01-01

    Objective To conduct a systematic review of the factors predicting anticipatory distress to painful medical procedures in children. Methods A systematic search was conducted to identify studies with factors related to anticipatory distress to painful medical procedures in children aged 0–18 years. The search retrieved 7,088 articles to review against inclusion criteria. A total of 77 studies were included in the review. Results 31 factors were found to predict anticipatory distress to painful medical procedures in children. A narrative synthesis of the evidence was conducted, and a summary figure is presented. Conclusions Many factors were elucidated that contribute to the occurrence of anticipatory distress to painful medical procedures. The factors that appear to increase anticipatory distress are child psychopathology, difficult child temperament, parent distress promoting behaviors, parent situational distress, previous pain events, parent anticipation of distress, and parent anxious predisposition. Longitudinal and experimental research is needed to further elucidate these factors. PMID:26338981

  18. Elucidation of Enzymatic Mechanism of Phenazine Biosynthetic Protein PhzF Using QM/MM and MD Simulations

    PubMed Central

    Liu, Fei; Zhao, Yi-Lei; Wang, Xiaolei; Hu, Hongbo; Peng, Huasong; Wang, Wei; Wang, Jing-Fang; Zhang, Xuehong

    2015-01-01

    The phenazine biosynthetic pathway is of considerable importance for the pharmaceutical industry. The pathway produces two products: phenazine-1,6-dicarboxylic acid and phenazine-1-carboxylic acid. PhzF is an isomerase that catalyzes trans-2,3-dihydro-3-hydroxyanthranilic acid isomerization and plays an essential role in the phenazine biosynthetic pathway. Although the PhzF crystal structure has been determined recently, an understanding of the detailed catalytic mechanism and the roles of key catalytic residues are still lacking. In this study, a computational strategy using a combination of molecular modeling, molecular dynamics simulations, and quantum mechanics/molecular mechanics simulations was used to elucidate these important issues. The Apo enzyme, enzyme–substrate complexes with negatively charged Glu45, enzyme–transition state analog inhibitor complexes with neutral Glu45, and enzyme–product complexes with negatively charged Glu45 structures were optimized and modeled using a 200 ns molecular dynamics simulation. Residues such as Gly73, His74, Asp208, Gly212, Ser213, and water, which play important roles in ligand binding and the isomerization reaction, were comprehensively investigated. Our results suggest that the Glu45 residue at the active site of PhzF acts as a general base/acid catalyst during proton transfer. This study provides new insights into the detailed catalytic mechanism of PhzF and the results have important implications for PhzF modification. PMID:26414009

  19. The Key Pieces of the Career Survival and Success Puzzle.

    ERIC Educational Resources Information Center

    Simonetti, Jack L.

    1999-01-01

    Analysis of career-success factors identified by 5,000 managers yielded 10 key pieces: excellent performance record, communication skills, interpersonal skills, personality, skill currency, significant work experiences, power, ability to withstand pressure, ability to make difficult decisions, and having a mentor. (SK)

  20. Finite key analysis for symmetric attacks in quantum key distribution

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

    Meyer, Tim; Kampermann, Hermann; Kleinmann, Matthias

    2006-10-15

    We introduce a constructive method to calculate the achievable secret key rate for a generic class of quantum key distribution protocols, when only a finite number n of signals is given. Our approach is applicable to all scenarios in which the quantum state shared by Alice and Bob is known. In particular, we consider the six state protocol with symmetric eavesdropping attacks, and show that for a small number of signals, i.e., below n{approx}10{sup 4}, the finite key rate differs significantly from the asymptotic value for n{yields}{infinity}. However, for larger n, a good approximation of the asymptotic value is found.more » We also study secret key rates for protocols using higher-dimensional quantum systems.« less

  1. Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility

    DOE PAGES

    Dogan, Nergiz; Wu, Weisheng; Morrissey, Christapher S.; ...

    2015-04-23

    Regulated gene expression controls organismal development, and variation in regulatory patterns has been implicated in complex traits. Thus accurate prediction of enhancers is important for further understanding of these processes. Genome-wide measurement of epigenetic features, such as histone modifications and occupancy by transcription factors, is improving enhancer predictions, but the contribution of these features to prediction accuracy is not known. Given the importance of the hematopoietic transcription factor TAL1 for erythroid gene activation, we predicted candidate enhancers based on genomic occupancy by TAL1 and measured their activity. Contributions of multiple features to enhancer prediction were evaluated based on the resultsmore » of these and other studies. Results: TAL1-bound DNA segments were active enhancers at a high rate both in transient transfections of cultured cells (39 of 79, or 56%) and transgenic mice (43 of 66, or 65%). The level of binding signal for TAL1 or GATA1 did not help distinguish TAL1-bound DNA segments as active versus inactive enhancers, nor did the density of regulation-related histone modifications. A meta-analysis of results from this and other studies (273 tested predicted enhancers) showed that the presence of TAL1, GATA1, EP300, SMAD1, H3K4 methylation, H3K27ac, and CAGE tags at DNase hypersensitive sites gave the most accurate predictors of enhancer activity, with a success rate over 80% and a median threefold increase in activity. Chromatin accessibility assays and the histone modifications H3K4me1 and H3K27ac were sensitive for finding enhancers, but they have high false positive rates unless transcription factor occupancy is also included. Conclusions: Occupancy by key transcription factors such as TAL1, GATA1, SMAD1, and EP300, along with evidence of transcription, improves the accuracy of enhancer predictions based on epigenetic features.« less

  2. Partially Key Distribution with Public Key Cryptosystem Based on Error Control Codes

    NASA Astrophysics Data System (ADS)

    Tavallaei, Saeed Ebadi; Falahati, Abolfazl

    Due to the low level of security in public key cryptosystems based on number theory, fundamental difficulties such as "key escrow" in Public Key Infrastructure (PKI) and a secure channel in ID-based cryptography, a new key distribution cryptosystem based on Error Control Codes (ECC) is proposed . This idea is done by some modification on McEliece cryptosystem. The security of ECC cryptosystem obtains from the NP-Completeness of block codes decoding. The capability of generating public keys with variable lengths which is suitable for different applications will be provided by using ECC. It seems that usage of these cryptosystems because of decreasing in the security of cryptosystems based on number theory and increasing the lengths of their keys would be unavoidable in future.

  3. Homo-trimerization is essential for the transcription factor function of Myrf for oligodendrocyte differentiation.

    PubMed

    Kim, Dongkyeong; Choi, Jin-Ok; Fan, Chuandong; Shearer, Randall S; Sharif, Mohamed; Busch, Patrick; Park, Yungki

    2017-05-19

    Myrf is a key transcription factor for oligodendrocyte differentiation and central nervous system myelination. We and others have previously shown that Myrf is generated as a membrane protein in the endoplasmic reticulum (ER), and that it undergoes auto-processing to release its N-terminal fragment from the ER, which enters the nucleus to work as a transcription factor. These previous studies allow a glimpse into the unusual complexity behind the biogenesis and function of the transcription factor domain of Myrf. Here, we report that Myrf N-terminal fragments assemble into stable homo-trimers before ER release. Consequently, Myrf N-terminal fragments are released from the ER only as homo-trimers. Our re-analysis of a previous genetic screening result in Caenorhabditis elegans shows that homo-trimerization is essential for the biological functions of Myrf N-terminal fragment, and that the region adjacent to the DNA-binding domain is pivotal to its homo-trimerization. Further, our computational analysis uncovered a novel homo-trimeric DNA motif that mediates the homo-trimeric DNA binding of Myrf N-terminal fragments. Importantly, we found that homo-trimerization defines the DNA binding specificity of Myrf N-terminal fragments. In sum, our study elucidates the molecular mechanism governing the biogenesis and function of Myrf N-terminal fragments and its physiological significance. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Key Generation for Fast Inversion of the Paillier Encryption Function

    NASA Astrophysics Data System (ADS)

    Hirano, Takato; Tanaka, Keisuke

    We study fast inversion of the Paillier encryption function. Especially, we focus only on key generation, and do not modify the Paillier encryption function. We propose three key generation algorithms based on the speeding-up techniques for the RSA encryption function. By using our algorithms, the size of the private CRT exponent is half of that of Paillier-CRT. The first algorithm employs the extended Euclidean algorithm. The second algorithm employs factoring algorithms, and can construct the private CRT exponent with low Hamming weight. The third algorithm is a variant of the second one, and has some advantage such as compression of the private CRT exponent and no requirement for factoring algorithms. We also propose the settings of the parameters for these algorithms and analyze the security of the Paillier encryption function by these algorithms against known attacks. Finally, we give experimental results of our algorithms.

  5. Novel selective TOCSY method enables NMR spectral elucidation of metabolomic mixtures

    NASA Astrophysics Data System (ADS)

    MacKinnon, Neil; While, Peter T.; Korvink, Jan G.

    2016-11-01

    Complex mixture analysis is routinely encountered in NMR-based investigations. With the aim of component identification, spectral complexity may be addressed chromatographically or spectroscopically, the latter being favored to reduce sample handling requirements. An attractive experiment is selective total correlation spectroscopy (sel-TOCSY), which is capable of providing tremendous spectral simplification and thereby enhancing assignment capability. Unfortunately, isolating a well resolved resonance is increasingly difficult as the complexity of the mixture increases and the assumption of single spin system excitation is no longer robust. We present TOCSY optimized mixture elucidation (TOOMIXED), a technique capable of performing spectral assignment particularly in the case where the assumption of single spin system excitation is relaxed. Key to the technique is the collection of a series of 1D sel-TOCSY experiments as a function of the isotropic mixing time (τm), resulting in a series of resonance intensities indicative of the underlying molecular structure. By comparing these τm -dependent intensity patterns with a library of pre-determined component spectra, one is able to regain assignment capability. After consideration of the technique's robustness, we tested TOOMIXED firstly on a model mixture. As a benchmark we were able to assign a molecule with high confidence in the case of selectively exciting an isolated resonance. Assignment confidence was not compromised when performing TOOMIXED on a resonance known to contain multiple overlapping signals, and in the worst case the method suggested a follow-up sel-TOCSY experiment to confirm an ambiguous assignment. TOOMIXED was then demonstrated on two realistic samples (whisky and urine), where under our conditions an approximate limit of detection of 0.6 mM was determined. Taking into account literature reports for the sel-TOCSY limit of detection, the technique should reach on the order of 10 μ M

  6. Context or Key? Language in Four Adult Learning Programmes

    ERIC Educational Resources Information Center

    Robinson, Clinton

    2007-01-01

    Context is a key factor in designing and delivering adult learning programmes, and in multilingual environments the choice of language plays a decisive role. Four programmes, two in Asia (Bhutan Myanmar) and two in Africa (Ghana and Uganda), which focus on learning for development, integrate language considerations in different ways, related both…

  7. Alcohol-related aggression during the college years: theories, risk factors and policy implications.

    PubMed

    Giancola, Peter R

    2002-03-01

    The purpose of this article is to present an overview of the research literature on alcohol-related aggression with a focus on college students. Data from both survey studies and experimental laboratory investigations conducted on college students are reviewed. Various methodological approaches to studying the alcohol-aggression relation, and their associated limitations, are then presented and discussed. The literature indicates that alcohol consumption facilitates aggressive behavior and increases the risk of being the victim of a violent act, particularly in heavy drinkers. Results from these studies are then placed into a context by reviewing 12 influential theories of aggression and alcohol-related aggression. On the basis of these theories and empirical data, a preliminary risk profile is presented to help identify which factors are likely to be important in predicting who will and who will not become aggressive after drinking alcohol. Although much research is still needed to elucidate the intricate causes of alcohol-related aggression, current prevention efforts might focus on modifying key risk factors such as poor cognitive functioning and inaccurate expectations about the effects of alcohol. Other prevention efforts directed specifically at college students might focus on helping them to identify risky situations that might facilitate the expression of intoxicated aggression.

  8. Free acetic acid as the key factor for the inhibition of hydrogenotrophic methanogenesis in mesophilic mixed culture fermentation.

    PubMed

    Zhang, Wei; Dai, Kun; Xia, Xiu-Yang; Wang, Hua-Jie; Chen, Yun; Lu, Yong-Ze; Zhang, Fang; Zeng, Raymond Jianxiong

    2018-05-18

    The inhibition of acetate under acidic pH is an ideal way to reduce methanogenesis in mesophilic mixed culture fermentation (MCF). However, the effects of acetate concentration and acidic pH on methanogenesis remain unclear. Besides, although hydrogenotrophic methanogens can be suitable targets in MCF, they are generally ignored. Therefore, we intentionally enriched hydrogenotrophic methanogens and found that free acetic acid (FAA, x) concentration and specific methanogenic activity (SMA, y) were correlated according to the equation: y = 0.86 × 0.31/(0.31 + x) (R 2  = 0.909). The SMA was decreased by 50% and 90% at the FAA concentrations of 0.31 and 2.36 g/L, respectively. The coenzyme M concentration and relative electron transport activity agreed well with the FAA concentration. Moreover, the methanogenic activity could not be recovered when the FAA concentration exceeded 0.81 g/L. These findings indicated that neither acetate nor acidic pH, but FAA was the key factor to inhibit methanogenesis in MCF. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Keys to Scholarship

    ERIC Educational Resources Information Center

    Hebert, Terri

    2011-01-01

    Up ahead, a foreboding wooden door showing wear from passage of earlier travelers is spotted. As the old porch light emits a pale yellow glow, a key ring emerges from deep inside the coat pocket. Searching for just the right key, the voyager settles on one that also shows age. As the key enters its receptacle and begins to turn, a clicking noise…

  10. Elucidating Mechanisms of Molecular Recognition Between Human Argonaute and miRNA Using Computational Approaches.

    PubMed

    Jiang, Hanlun; Zhu, Lizhe; Héliou, Amélie; Gao, Xin; Bernauer, Julie; Huang, Xuhui

    2017-01-01

    MicroRNA (miRNA) and Argonaute (AGO) protein together form the RNA-induced silencing complex (RISC) that plays an essential role in the regulation of gene expression. Elucidating the underlying mechanism of AGO-miRNA recognition is thus of great importance not only for the in-depth understanding of miRNA function but also for inspiring new drugs targeting miRNAs. In this chapter we introduce a combined computational approach of molecular dynamics (MD) simulations, Markov state models (MSMs), and protein-RNA docking to investigate AGO-miRNA recognition. Constructed from MD simulations, MSMs can elucidate the conformational dynamics of AGO at biologically relevant timescales. Protein-RNA docking can then efficiently identify the AGO conformations that are geometrically accessible to miRNA. Using our recent work on human AGO2 as an example, we explain the rationale and the workflow of our method in details. This combined approach holds great promise to complement experiments in unraveling the mechanisms of molecular recognition between large, flexible, and complex biomolecules.

  11. Structure elucidation of organic compounds aided by the computer program system SCANNET

    NASA Astrophysics Data System (ADS)

    Guzowska-Swider, B.; Hippe, Z. S.

    1992-12-01

    Recognition of chemical structure is a very important problem currently solved by molecular spectroscopy, particularly IR, UV, NMR and Raman spectroscopy, and mass spectrometry. Nowadays, solution of the problem is frequently aided by the computer. SCANNET is a computer program system for structure elucidation of organic compounds, developed by our group. The structure recognition of an unknown substance is made by comparing its spectrum with successive reference spectra of standard compounds, i.e. chemical compounds of known chemical structure, stored in a spectral database. The computer program system SCANNET consists of six different spectral databases for following the analytical methods: IR, UV, 13C-NMR, 1H-NMR and Raman spectroscopy, and mass spectrometry. A chemist, to elucidate a structure, can use one of these spectral methods or a combination of them and search the appropriate databases. As the result of searching each spectral database, the user obtains a list of chemical substances whose spectra are identical and/or similar to the spectrum input into the computer. The final information obtained from searching the spectral databases is in the form of a list of chemical substances having all the examined spectra, for each type of spectroscopy, identical or simlar to those of the unknown compound.

  12. Advances in structure elucidation of small molecules using mass spectrometry

    PubMed Central

    Fiehn, Oliver

    2010-01-01

    The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules. Electronic supplementary material The online version of this article (doi:10.1007/s12566-010-0015-9) contains supplementary material, which is available to authorized users. PMID:21289855

  13. Integrin-Mediated Transforming Growth Factor-β Activation Regulates Homeostasis of the Pulmonary Epithelial-Mesenchymal Trophic Unit

    PubMed Central

    Araya, Jun; Cambier, Stephanie; Morris, Alanna; Finkbeiner, Walter; Nishimura, Stephen L.

    2006-01-01

    Trophic interactions between pulmonary epithelial and mesenchymal cell types, known as the epithelial-mesenchymal trophic unit (EMTU), are crucial in lung development and lung disease. Transforming growth factor (TGF)-β is a key factor in mediating these interactions, but it is expressed in a latent form that requires activation to be functional. Using intact fetal tracheal tissue and primary cultures of fetal tracheal epithelial cells and fibroblasts, we demonstrate that a subset of integrins, αvβ6 and αvβ8, are responsible for almost all of the TGF-β activation in the EMTU. Both αvβ8 and αvβ6 contribute to fetal tracheal epithelial activation of TGF-β, whereas only αvβ8 contributes to fetal tracheal fibroblast activation of TGF-β. Interestingly, fetal tracheal epithelial αvβ8-mediated TGF-β activation can be enhanced by phorbol esters, likely because of the increased activity of MT1-MMP, an essential co-factor in αvβ8-mediated activation of TGF-β. Autocrine αvβ8-mediated TGF-β activation by fetal tracheal fibroblasts results in suppression of both transcription and secretion of hepatocyte growth factor, which is sufficient to affect phosphorylation of the airway epithelial hepatocyte growth factor receptor, c-Met, as well as airway epithelial proliferation in a co-culture model of the EMTU. These findings elucidate the function and complex regulation of integrin-mediated activation of TGF-β within the EMTU. PMID:16877343

  14. Integrin-mediated transforming growth factor-beta activation regulates homeostasis of the pulmonary epithelial-mesenchymal trophic unit.

    PubMed

    Araya, Jun; Cambier, Stephanie; Morris, Alanna; Finkbeiner, Walter; Nishimura, Stephen L

    2006-08-01

    Trophic interactions between pulmonary epithelial and mesenchymal cell types, known as the epithelial-mesenchymal trophic unit (EMTU), are crucial in lung development and lung disease. Transforming growth factor (TGF)-beta is a key factor in mediating these interactions, but it is expressed in a latent form that requires activation to be functional. Using intact fetal tracheal tissue and primary cultures of fetal tracheal epithelial cells and fibroblasts, we demonstrate that a subset of integrins, alpha(v)beta(6) and alpha(v)beta(8), are responsible for almost all of the TGF-beta activation in the EMTU. Both alpha(v)beta(8) and alpha(v)beta(6) contribute to fetal tracheal epithelial activation of TGF-beta, whereas only alpha(v)beta(8) contributes to fetal tracheal fibroblast activation of TGF-beta. Interestingly, fetal tracheal epithelial alpha(v)beta(8)-mediated TGF-beta activation can be enhanced by phorbol esters, likely because of the increased activity of MT1-MMP, an essential co-factor in alpha(v)beta(8)-mediated activation of TGF-beta. Autocrine alpha(v)beta(8)-mediated TGF-beta activation by fetal tracheal fibroblasts results in suppression of both transcription and secretion of hepatocyte growth factor, which is sufficient to affect phosphorylation of the airway epithelial hepatocyte growth factor receptor, c-Met, as well as airway epithelial proliferation in a co-culture model of the EMTU. These findings elucidate the function and complex regulation of integrin-mediated activation of TGF-beta within the EMTU.

  15. Toward elucidating the heat activation mechanism of the TRPV1 channel gating by molecular dynamics simulation.

    PubMed

    Wen, Han; Qin, Feng; Zheng, Wenjun

    2016-12-01

    As a key cellular sensor, the TRPV1 cation channel undergoes a gating transition from a closed state to an open state in response to various physical and chemical stimuli including noxious heat. Despite years of study, the heat activation mechanism of TRPV1 gating remains enigmatic at the molecular level. Toward elucidating the structural and energetic basis of TRPV1 gating, we have performed molecular dynamics (MD) simulations (with cumulative simulation time of 3 μs), starting from the high-resolution closed and open structures of TRPV1 solved by cryo-electron microscopy. In the closed-state simulations at 30°C, we observed a stably closed channel constricted at the lower gate (near residue I679), while the upper gate (near residues G643 and M644) is dynamic and undergoes flickery opening/closing. In the open-state simulations at 60°C, we found higher conformational variation consistent with a large entropy increase required for the heat activation, and both the lower and upper gates are dynamic with transient opening/closing. Through ensemble-based structural analyses of the closed state versus the open state, we revealed pronounced closed-to-open conformational changes involving the membrane proximal domain (MPD) linker, the outer pore, and the TRP helix, which are accompanied by breaking/forming of a network of closed/open-state specific hydrogen bonds. By comparing the closed-state simulations at 30°C and 60°C, we observed heat-activated conformational changes in the MPD linker, the outer pore, and the TRP helix that resemble the closed-to-open conformational changes, along with partial formation of the open-state specific hydrogen bonds. Some of the residues involved in the above key hydrogen bonds were validated by previous mutational studies. Taken together, our MD simulations have offered rich structural and dynamic details beyond the static structures of TRPV1, and promising targets for future mutagenesis and functional studies of the TRPV1 channel

  16. Toward elucidating the heat activation mechanism of the TRPV1 channel gating by molecular dynamics simulation

    PubMed Central

    Wen, Han; Qin, Feng; Zheng, Wenjun

    2016-01-01

    As a key cellular sensor, the TRPV1 cation channel undergoes a gating transition from a closed state to an open state in response to various physical and chemical stimuli including noxious heat. Despite years of study, the heat activation mechanism of TRPV1 gating remains enigmatic at the molecular level. Toward elucidating the structural and energetic basis of TRPV1 gating, we have performed molecular dynamics (MD) simulations (with cumulative simulation time of 3 μs), starting from the high-resolution closed and open structures of TRPV1 solved by cryo-electron microscopy. In the closed-state simulations at 30°C, we observed a stably closed channel constricted at the lower gate (near residue I679), while the upper gate (near residues G643 and M644) is dynamic and undergoes flickery opening/closing. In the open-state simulations at 60°C, we found higher conformational variation consistent with a large entropy increase required for the heat activation, and both the lower and upper gates are dynamic with transient opening/closing. Through ensemble-based structural analyses of the closed state vs. the open state, we revealed pronounced closed-to-open conformational changes involving the membrane proximal domain (MPD) linker, the outer pore, and the TRP helix, which are accompanied by breaking/forming of a network of closed/open-state specific hydrogen bonds. By comparing the closed-state simulations at 30°C and 60°C, we observed heat-activated conformational changes in the MPD linker, the outer pore, and the TRP helix that resemble the closed-to-open conformational changes, along with partial formation of the open-state specific hydrogen bonds. Some of the residues involved in the above key hydrogen bonds were validated by previous mutational studies. Taken together, our MD simulations have offered rich structural and dynamic details beyond the static structures of TRPV1, and promising targets for future mutagenesis and functional studies of the TRPV1 channel

  17. Factors Influencing Teacher Appropriation of Professional Learning Focused on the Use of Technology in Science Classrooms

    ERIC Educational Resources Information Center

    Longhurst, Max L.; Jones, Suzanne H.; Campbell, Todd

    2017-01-01

    Understanding factors that impact teacher implementation of learning from professional development is critical in order to maximize the educational and financial investment in teacher professional learning. This multi-case qualitative investigation elucidates factors that influence the appropriation of instructional tools associated with…

  18. Turbidity in oil-in-water-emulsions - Key factors and visual perception.

    PubMed

    Linke, C; Drusch, S

    2016-11-01

    The aim of the present study is to systematically describe the factors affecting turbidity in beverage emulsions and to get a better understanding of visual perception of turbidity. The sensory evaluation of the human visual perception of turbidity showed that humans are most sensitive to turbidity differences between two samples in the range between 1000 and 1500 NTU (ratio) (nephelometric turbidity units). At very high turbidity values >2000 TU in NTU (ratio) were needed to distinguish between samples that they were perceived significantly different. Particle size was the most important factor affecting turbidity. It was shown that a maximum turbidity occurs at a mean volume - surface diameter of 0.2μm for the oil droplet size. Additional parameters were the refractive index, the composition of the aqueous phase and the presence of excess emulsifier. In a concentration typical for a beverage emulsion a change in the refractive index of the oil phase may allow the alteration of turbidity by up to 30%. With the knowledge on visual perception of turbidity and the determining factors, turbidity can be tailored in product development according to the customer requirements and in quality control to define acceptable variations in optical appearance. Copyright © 2016. Published by Elsevier Ltd.

  19. A large-scale, in vivo transcription factor screen defines bivalent chromatin as a key property of regulatory factors mediating Drosophila wing development

    PubMed Central

    Schertel, Claus; Albarca, Monica; Rockel-Bauer, Claudia; Kelley, Nicholas W.; Bischof, Johannes; Hens, Korneel

    2015-01-01

    Transcription factors (TFs) are key regulators of cell fate. The estimated 755 genes that encode DNA binding domain-containing proteins comprise ∼5% of all Drosophila genes. However, the majority has remained uncharacterized so far due to the lack of proper genetic tools. We generated 594 site-directed transgenic Drosophila lines that contain integrations of individual UAS-TF constructs to facilitate spatiotemporally controlled misexpression in vivo. All transgenes were expressed in the developing wing, and two-thirds induced specific phenotypic defects. In vivo knockdown of the same genes yielded a phenotype for 50%, with both methods indicating a great potential for misexpression to characterize novel functions in wing growth, patterning, and development. Thus, our UAS-TF library provides an important addition to the genetic toolbox of Drosophila research, enabling the identification of several novel wing development-related TFs. In parallel, we established the chromatin landscape of wing imaginal discs by ChIP-seq analyses of five chromatin marks and RNA Pol II. Subsequent clustering revealed six distinct chromatin states, with two clusters showing enrichment for both active and repressive marks. TFs that carry such “bivalent” chromatin are highly enriched for causing misexpression phenotypes in the wing, and analysis of existing expression data shows that these TFs tend to be differentially expressed across the wing disc. Thus, bivalently marked chromatin can be used as a marker for spatially regulated TFs that are functionally relevant in a developing tissue. PMID:25568052

  20. Exercise-induced neuroprotective effects on neurodegenerative diseases: the key role of trophic factors.

    PubMed

    Campos, Carlos; Rocha, Nuno Barbosa F; Lattari, Eduardo; Paes, Flávia; Nardi, António E; Machado, Sérgio

    2016-06-01

    Age-related neurodegenerative disorders, like Alzheimer's or Parkinson's disease, are becoming a major issue to public health care. Currently, there is no effective pharmacological treatment to address cognitive impairment in these patients. Here, we aim to explore the role of exercise-induced trophic factor enhancement in the prevention or delay of cognitive decline in patients with neurodegenerative diseases. There is a significant amount of evidence from animal and human studies that links neurodegenerative related cognitive deficits with changes on brain and peripheral trophic factor levels. Several trials with elderly individuals and patients with neurodegenerative diseases report exercise induced cognitive improvements and changes on trophic factor levels including BDNF, IGF-I, among others. Further studies with healthy aging and clinical populations are needed to understand how diverse exercise interventions produce different variations in trophic factor signaling. Genetic profiles and potential confounders regarding trophic factors should also be addressed in future trials.

  1. Automated secured cost effective key refreshing technique to enhance WiMAX privacy key management

    NASA Astrophysics Data System (ADS)

    Sridevi, B.; Sivaranjani, S.; Rajaram, S.

    2013-01-01

    In all walks of life the way of communication is transformed by the rapid growth of wireless communication and its pervasive use. A wireless network which is fixed and richer in bandwidth is specified as IEEE 802.16, promoted and launched by an industrial forum is termed as Worldwide Interoperability for Microwave Access (WiMAX). This technology enables seamless delivery of wireless broadband service for fixed and/or mobile users. The obscurity is the long delay which occurs during the handoff management in every network. Mobile WiMAX employs an authenticated key management protocol as a part of handoff management in which the Base Station (BS) controls the distribution of keying material to the Mobile Station (MS). The protocol employed is Privacy Key Management Version 2- Extensible Authentication Protocol (PKMV2-EAP) which is responsible for the normal and periodical authorization of MSs, reauthorization as well as key refreshing. Authorization key (AK) and Traffic Encryption key (TEK) plays a vital role in key exchange. When the lifetime of key expires, MS has to request for a new key to BS which in turn leads to repetition of authorization, authentication as well as key exchange. To avoid service interruption during reauthorization , two active keys are transmitted at the same time by BS to MS. The consequences of existing work are hefty amount of bandwidth utilization, time consumption and large storage. It is also endured by Man in the Middle attack and Impersonation due to lack of security in key exchange. This paper designs an automatic mutual refreshing of keys to minimize bandwidth utilization, key storage and time consumption by proposing Previous key and Iteration based Key Refreshing Function (PKIBKRF). By integrating PKIBKRF in key generation, the simulation results indicate that 21.8% of the bandwidth and storage of keys are reduced and PKMV2 mutual authentication time is reduced by 66.67%. The proposed work is simulated with Qualnet model and

  2. Transcriptional regulation of NADPH oxidase isoforms, Nox1 and Nox4, by nuclear factor-{kappa}B in human aortic smooth muscle cells

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

    Manea, Adrian, E-mail: adrian.manea@icbp.ro; Tanase, Laurentia I.; Raicu, Monica

    Inflammation-induced changes in the activity and expression of NADPH oxidases (Nox) play a key role in atherogenesis. The molecular mechanisms of Nox regulation are scantily elucidated. Since nuclear factor-{kappa}B (NF-{kappa}B) controls the expression of many genes associated to inflammation-related diseases, in this study we have investigated the role of NF-{kappa}B signaling in the regulation of Nox1 and Nox4 transcription in human aortic smooth muscle cells (SMCs). Cultured cells were exposed to tumor necrosis factor-{alpha} (TNF{alpha}), a potent inducer of both Nox and NF-{kappa}B, up to 24 h. Lucigenin-enhanced chemiluminescence and dichlorofluorescein assays, real-time polymerase chain reaction, and Western blot analysismore » showed that inhibition of NF-{kappa}B pathway reduced significantly the TNF{alpha}-dependent up-regulation of Nox-derived reactive oxygen species production, Nox1 and Nox4 expression. In silico analysis indicated the existence of typical NF-{kappa}B elements in the promoters of Nox1 and Nox4. Transient overexpression of p65/NF-{kappa}B significantly increased the promoter activities of both isoforms. Physical interaction of p65/NF-{kappa}B proteins with the predicted sites was demonstrated by chromatin immunoprecipitation assay. These findings demonstrate that NF-{kappa}B is an essential regulator of Nox1- and Nox4-containing NADPH oxidase in SMCs. Elucidation of the complex relationships between NF-{kappa}B and Nox enzymes may lead to a novel pharmacological strategy to reduce both inflammation and oxidative stress in atherosclerosis and its associated complications.« less

  3. Real-time elucidation of catalytic pathways in CO hydrogenation on Ru

    DOE PAGES

    LaRue, Jerry; Krejci, Ondrej; Yu, Liang; ...

    2017-07-31

    Here, the direct elucidation of the reaction pathways in heterogeneous catalysis has been challenging due the short-lived nature of reaction intermediates. Here, we directly measured on ultrafast timescales the initial hydrogenation steps of adsorbed CO on a Ru catalyst surface, which is known as the bottleneck reaction in syngas and CO 2 reforming processes. We initiated the hydrogenation of CO with an ultrafast laser temperature jump and probed transient changes in the electronic structure using real-time x-ray spectroscopy. In combination with theoretical simulations, we verified the formation of CHO during CO hydrogenation.

  4. Treatment concept of chronic subdural haematoma according to an algorithm using evidence-based medicine-derived key factors: A prospective controlled study.

    PubMed

    Weigel, Ralf; Schlickum, Linda; Weisser, Gerald; Krauss, Joachim K

    2015-01-01

    Surgical treatment for chronic subdural haematoma (CSH) has been analysed by applying evidence-based medicine (EBM) criteria earlier. Whether implementation of EBM-derived key factors into an optimised treatment algorithm would improve outcome, however, needs to be clarified. Symptomatic patients with CSH who fulfilled the inclusion criteria were either assigned to an optimised treatment algorithm (OA-EBM group) or to a control group treated by the standard departmental surgical technique (SDST group) in a prospective design. For the OA-EBM algorithm only one burr hole, extensive intraoperative irrigation and a closed system drainage with meticulous avoidance of entry of air was mandatory. A two-catheter technique was used to reduce intracavital air. Final endpoints were neurological outcome (Markwalder Score), recurrence and the amount of intracranial air. A total of 93 out of 117 patients were evaluated accounting for 113 cases because 20 patients had bilateral haematomas. Demographic data of 68 cases in the SDST group did not differ from 45 cases in the OA-EBM group. The Markwalder Score showed greater improvement in the OA-EBM group (0.5 ± 0.6 vs. 1.0 ± 1.0, p = 0.003). The recurrence rate was 18% (12 patients) in the SDST group versus 2% (1 patient) in the OA-EBM group (p < 0.05). The amount of intracranial air was significantly lower in the OA-EBM group (3.3 ± 5.0 cm(3) vs. 5.2 ± 7.7 cm(3)) with p = 0.04. In the standard group computerised tomography scanning was performed slightly earlier (3 ± 1.7 days vs. 3.6 ± 1.4 days). When comparing only non-recurrent cases in both groups no significant difference was apparent. Implementation of EBM key factors into a treatment algorithm for CSH can improve neurological outcome in a typical neurosurgical department, reduce recurrence and minimise the amount of postoperative air within the haematoma cavity.

  5. Profiling conserved biological pathways in Autosomal Dominant Polycystic Kidney Disorder (ADPKD) to elucidate key transcriptomic alterations regulating cystogenesis: A cross-species meta-analysis approach.

    PubMed

    Chatterjee, Shatakshee; Verma, Srikant Prasad; Pandey, Priyanka

    2017-09-05

    Initiation and progression of fluid filled cysts mark Autosomal Dominant Polycystic Kidney Disease (ADPKD). Thus, improved therapeutics targeting cystogenesis remains a constant challenge. Microarray studies in single ADPKD animal models species with limited sample sizes tend to provide scattered views on underlying ADPKD pathogenesis. Thus we aim to perform a cross species meta-analysis to profile conserved biological pathways that might be key targets for therapy. Nine ADPKD microarray datasets on rat, mice and human fulfilled our study criteria and were chosen. Intra-species combined analysis was performed after considering removal of batch effect. Significantly enriched GO biological processes and KEGG pathways were computed and their overlap was observed. For the conserved pathways, biological modules and gene regulatory networks were observed. Additionally, Gene Set Enrichment Analysis (GSEA) using Molecular Signature Database (MSigDB) was performed for genes found in conserved pathways. We obtained 28 modules of significantly enriched GO processes and 5 major functional categories from significantly enriched KEGG pathways conserved in human, mice and rats that in turn suggest a global transcriptomic perturbation affecting cyst - formation, growth and progression. Significantly enriched pathways obtained from up-regulated genes such as Genomic instability, Protein localization in ER and Insulin Resistance were found to regulate cyst formation and growth whereas cyst progression due to increased cell adhesion and inflammation was suggested by perturbations in Angiogenesis, TGF-beta, CAMs, and Infection related pathways. Additionally, networks revealed shared genes among pathways e.g. SMAD2 and SMAD7 in Endocytosis and TGF-beta. Our study suggests cyst formation and progression to be an outcome of interplay between a set of several key deregulated pathways. Thus, further translational research is warranted focusing on developing a combinatorial therapeutic

  6. Clustering of modifiable biobehavioral risk factors for chronic disease in US adults: a latent class analysis.

    PubMed

    Leventhal, Adam M; Huh, Jimi; Dunton, Genevieve F

    2014-11-01

    Examining the co-occurrence patterns of modifiable biobehavioral risk factors for deadly chronic diseases (e.g. cancer, cardiovascular disease, diabetes) can elucidate the etiology of risk factors and guide disease-prevention programming. The aims of this study were to (1) identify latent classes based on the clustering of five key biobehavioral risk factors among US adults who reported at least one risk factor and (2) explore the demographic correlates of the identified latent classes. Participants were respondents of the National Epidemiologic Survey of Alcohol and Related Conditions (2004-2005) with at least one of the following disease risk factors in the past year (N = 22,789), which were also the latent class indicators: (1) alcohol abuse/dependence, (2) drug abuse/dependence, (3) nicotine dependence, (4) obesity, and (5) physical inactivity. Housing sample units were selected to match the US National Census in location and demographic characteristics, with young adults oversampled. Participants were administered surveys by trained interviewers. Five latent classes were yielded: 'obese, active non-substance abusers' (23%); 'nicotine-dependent, active, and non-obese' (19%); 'active, non-obese alcohol abusers' (6%); 'inactive, non-substance abusers' (50%); and 'active, polysubstance abusers' (3.7%). Four classes were characterized by a 100% likelihood of having one risk factor coupled with a low or moderate likelihood of having the other four risk factors. The five classes exhibited unique demographic profiles. Risk factors may cluster together in a non-monotonic fashion, with the majority of the at-risk population of US adults expected to have a high likelihood of endorsing only one of these five risk factors. © Royal Society for Public Health 2013.

  7. DNA-mediated association of two histone-bound complexes of yeast Chromatin Assembly Factor-1 (CAF-1) drives tetrasome assembly in the wake of DNA replication.

    PubMed

    Mattiroli, Francesca; Gu, Yajie; Yadav, Tejas; Balsbaugh, Jeremy L; Harris, Michael R; Findlay, Eileen S; Liu, Yang; Radebaugh, Catherine A; Stargell, Laurie A; Ahn, Natalie G; Whitehouse, Iestyn; Luger, Karolin

    2017-03-18

    Nucleosome assembly in the wake of DNA replication is a key process that regulates cell identity and survival. Chromatin assembly factor 1 (CAF-1) is a H3-H4 histone chaperone that associates with the replisome and orchestrates chromatin assembly following DNA synthesis. Little is known about the mechanism and structure of this key complex. Here we investigate the CAF-1•H3-H4 binding mode and the mechanism of nucleosome assembly. We show that yeast CAF-1 binding to a H3-H4 dimer activates the Cac1 winged helix domain interaction with DNA. This drives the formation of a transient CAF-1•histone•DNA intermediate containing two CAF-1 complexes, each associated with one H3-H4 dimer. Here, the (H3-H4) 2 tetramer is formed and deposited onto DNA. Our work elucidates the molecular mechanism for histone deposition by CAF-1, a reaction that has remained elusive for other histone chaperones, and it advances our understanding of how nucleosomes and their epigenetic information are maintained through DNA replication.

  8. Harmonized patient-reported data elements in the electronic health record: supporting meaningful use by primary care action on health behaviors and key psychosocial factors

    PubMed Central

    Boyle, Maureen; Emmons, Karen M; Glasgow, Russell E; Hesse, Bradford W; Kaplan, Robert M; Krist, Alexander H; Moser, Richard P; Taylor, Martina V

    2012-01-01

    Background Electronic health records (EHR) have the potential to improve patient care through efficient access to complete patient health information. This potential may not be reached because many of the most important determinants of health outcome are rarely included. Successful health promotion and disease prevention requires patient-reported data reflecting health behaviors and psychosocial issues. Furthermore, there is a need to harmonize this information across different EHR systems. Methods To fill this gap a three-phased process was used to conceptualize, identify and recommend patient-reported data elements on health behaviors and psychosocial factors for the EHR. Expert panels (n=13) identified candidate measures (phase 1) that were reviewed and rated by a wide range of health professionals (n=93) using the grid-enabled measures wiki social media platform (phase 2). Recommendations were finalized through a town hall meeting with key stakeholders including patients, providers, researchers, policy makers, and representatives from healthcare settings (phase 3). Results Nine key elements from three areas emerged as the initial critical patient-reported elements to incorporate systematically into EHR—health behaviors (eg, exercise), psychosocial issues (eg, distress), and patient-centered factors (eg, demographics). Recommendations were also made regarding the frequency of collection ranging from a single assessment (eg, demographic characteristics), to annual assessment (eg, health behaviors), or more frequent (eg, patient goals). Conclusions There was strong stakeholder support for this initiative reflecting the perceived value of incorporating patient-reported elements into EHR. The next steps will include testing the feasibility of incorporating these elements into the EHR across diverse primary care settings. PMID:22511015

  9. Building blocks for automated elucidation of metabolites: machine learning methods for NMR prediction.

    PubMed

    Kuhn, Stefan; Egert, Björn; Neumann, Steffen; Steinbeck, Christoph

    2008-09-25

    Current efforts in Metabolomics, such as the Human Metabolome Project, collect structures of biological metabolites as well as data for their characterisation, such as spectra for identification of substances and measurements of their concentration. Still, only a fraction of existing metabolites and their spectral fingerprints are known. Computer-Assisted Structure Elucidation (CASE) of biological metabolites will be an important tool to leverage this lack of knowledge. Indispensable for CASE are modules to predict spectra for hypothetical structures. This paper evaluates different statistical and machine learning methods to perform predictions of proton NMR spectra based on data from our open database NMRShiftDB. A mean absolute error of 0.18 ppm was achieved for the prediction of proton NMR shifts ranging from 0 to 11 ppm. Random forest, J48 decision tree and support vector machines achieved similar overall errors. HOSE codes being a notably simple method achieved a comparatively good result of 0.17 ppm mean absolute error. NMR prediction methods applied in the course of this work delivered precise predictions which can serve as a building block for Computer-Assisted Structure Elucidation for biological metabolites.

  10. Elucidating the Performance Limitations of Lithium-ion Batteries due to Species and Charge Transport through Five Characteristic Parameters

    PubMed Central

    Jiang, Fangming; Peng, Peng

    2016-01-01

    Underutilization due to performance limitations imposed by species and charge transports is one of the key issues that persist with various lithium-ion batteries. To elucidate the relevant mechanisms, two groups of characteristic parameters were proposed. The first group contains three characteristic time parameters, namely: (1) te, which characterizes the Li-ion transport rate in the electrolyte phase, (2) ts, characterizing the lithium diffusion rate in the solid active materials, and (3) tc, describing the local Li-ion depletion rate in electrolyte phase at the electrolyte/electrode interface due to electrochemical reactions. The second group contains two electric resistance parameters: Re and Rs, which represent respectively, the equivalent ionic transport resistance and the effective electronic transport resistance in the electrode. Electrochemical modeling and simulations to the discharge process of LiCoO2 cells reveal that: (1) if te, ts and tc are on the same order of magnitude, the species transports may not cause any performance limitations to the battery; (2) the underlying mechanisms of performance limitations due to thick electrode, high-rate operation, and large-sized active material particles as well as effects of charge transports are revealed. The findings may be used as quantitative guidelines in the development and design of more advanced Li-ion batteries. PMID:27599870

  11. Healthcare public key infrastructure (HPKI) and non-profit organization (NPO): essentials for healthcare data exchange.

    PubMed

    Takeda, Hiroshi; Matsumura, Yasushi; Nakagawa, Katsuhiko; Teratani, Tadamasa; Qiyan, Zhang; Kusuoka, Hideo; Matsuoka, Masami

    2004-01-01

    To share healthcare information and to promote cooperation among healthcare providers and customers (patients) under computerized network environment, a non-profit organization (NPO), named as OCHIS, was established at Osaka, Japan in 2003. Since security and confidentiality issues on the Internet have been major concerns in the OCHIS, the system has been based on healthcare public key infrastructure (HPKI), and found that there remained problems to be solved technically and operationally. An experimental study was conducted to elucidate the central and the local function in terms of a registration authority and a time stamp authority by contracting with the Ministry of Economics and Trading Industries in 2003. This paper describes the experimental design with NPO and the results of the study concerning message security and HPKI. The developed system has been operated practically in Osaka urban area.

  12. Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes.

    PubMed

    Kuang, Zheng; Ji, Zhicheng; Boeke, Jef D; Ji, Hongkai

    2018-01-09

    Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Improved key-rate bounds for practical decoy-state quantum-key-distribution systems

    NASA Astrophysics Data System (ADS)

    Zhang, Zhen; Zhao, Qi; Razavi, Mohsen; Ma, Xiongfeng

    2017-01-01

    The decoy-state scheme is the most widely implemented quantum-key-distribution protocol in practice. In order to account for the finite-size key effects on the achievable secret key generation rate, a rigorous statistical fluctuation analysis is required. Originally, a heuristic Gaussian-approximation technique was used for this purpose, which, despite its analytical convenience, was not sufficiently rigorous. The fluctuation analysis has recently been made rigorous by using the Chernoff bound. There is a considerable gap, however, between the key-rate bounds obtained from these techniques and that obtained from the Gaussian assumption. Here we develop a tighter bound for the decoy-state method, which yields a smaller failure probability. This improvement results in a higher key rate and increases the maximum distance over which secure key exchange is possible. By optimizing the system parameters, our simulation results show that our method almost closes the gap between the two previously proposed techniques and achieves a performance similar to that of conventional Gaussian approximations.

  14. Toxicogenomics and cancer risk assessment: a framework for key event analysis and dose-response assessment for nongenotoxic carcinogens.

    PubMed

    Bercu, Joel P; Jolly, Robert A; Flagella, Kelly M; Baker, Thomas K; Romero, Pedro; Stevens, James L

    2010-12-01

    In order to determine a threshold for nongenotoxic carcinogens, the traditional risk assessment approach has been to identify a mode of action (MOA) with a nonlinear dose-response. The dose-response for one or more key event(s) linked to the MOA for carcinogenicity allows a point of departure (POD) to be selected from the most sensitive effect dose or no-effect dose. However, this can be challenging because multiple MOAs and key events may exist for carcinogenicity and oftentimes extensive research is required to elucidate the MOA. In the present study, a microarray analysis was conducted to determine if a POD could be identified following short-term oral rat exposure with two nongenotoxic rodent carcinogens, fenofibrate and methapyrilene, using a benchmark dose analysis of genes aggregated in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) biological processes, which likely encompass key event(s) for carcinogenicity. The gene expression response for fenofibrate given to rats for 2days was consistent with its MOA and known key events linked to PPARα activation. The temporal response from daily dosing with methapyrilene demonstrated biological complexity with waves of pathways/biological processes occurring over 1, 3, and 7days; nonetheless, the benchmark dose values were consistent over time. When comparing the dose-response of toxicogenomic data to tumorigenesis or precursor events, the toxicogenomics POD was slightly below any effect level. Our results suggest that toxicogenomic analysis using short-term studies can be used to identify a threshold for nongenotoxic carcinogens based on evaluation of potential key event(s) which then can be used within a risk assessment framework. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Catharanthus alkaloids XXXII: isolation of alkaloids from Catharanthus trichophyllus roots and structure elucidation of cathaphylline.

    PubMed

    Cordell, G A; Farnsworth, N R

    1976-03-01

    Further examination of the cytotoxic alkaloid fractions of Catharanthus trichophyllus roots afforded nine alkaloids. Two of these alkaloids, lochnericine and horhammericine, are responsible for part of the cytotoxic activity. The structure elucidation of cathaphylline, a new beta-anilino acrylate derivative, is described.

  16. Key factors for the bicycle use of visually impaired people: a Delphi study.

    PubMed

    Jelijs, Bart; Heutink, Joost; de Waard, Dick; Brookhuis, Karel A; Melis-Dankers, Bart J M

    2018-06-12

    This study aims to identify the most important factors that influence the independent bicycle use of visually impaired people in the Netherlands. Both visually impaired people and professionals participated in a two-round online Delphi study (n = 42). In Round 1 the participants identified the factors which they ranked by relevance in Round 2. The participants prioritised environmental factors related to the traffic situation, the characteristics of the infrastructure, and weather and light conditions (Kendall's W = 0.66). They indicated that the most influencing personal factors are related to personality, traffic experience, and personal background (W = 0.58). Glaucoma was ranked as the most relevant ophthalmic condition (W = 0.74), while glare was regarded as the most important factor with respect to the visual functions (W = 0.78). The factors provided by this study can be used to optimise the independent cycling mobility of visually impaired people. More research is needed to investigate, both, how and to what extent the mentioned factors influence the cycling behaviour. Implications for rehabilitation The results of this study can be used to set priorities during the rehabilitation and training of visually impaired people who wish to cycle independently. Visually impaired cyclists may compensate for the consequences of their visual impairments by taking alternative routes that suit their individual abilities and limitations. Since gaining and maintaining self-confidence is important for independent cycling with a visual impairment, practitioners such as mobility trainers should not only focus on cycling-related skills and abilities, but also aim to improve the self-confidence of visually impaired people who wish to cycle.

  17. Site-specific climate analysis elucidates revegetation challenges for post-mining landscapes in eastern Australia

    NASA Astrophysics Data System (ADS)

    Audet, P.; Arnold, S.; Lechner, A. M.; Baumgartl, T.

    2013-10-01

    In eastern Australia, the availability of water is critical for the successful rehabilitation of post-mining landscapes and climatic characteristics of this diverse geographical region are closely defined by factors such as erratic rainfall and periods of drought and flooding. Despite this, specific metrics of climate patterning are seldom incorporated into the initial design of current post-mining land rehabilitation strategies. Our study proposes that a few common rainfall parameters can be combined and rated using arbitrary rainfall thresholds to characterise bioregional climate sensitivity relevant to the rehabilitation these landscapes. This approach included assessments of annual rainfall depth, average recurrence interval of prolonged low intensity rainfall, average recurrence intervals of short or prolonged high intensity events, median period without rain (or water-deficit) and standard deviation for this period in order to address climatic factors such as total water availability, seasonality and intensity - which were selected as potential proxies of both short- and long-term biological sensitivity to climate within the context of post-disturbance ecological development and recovery. Following our survey of available climate data, we derived site "climate sensitivity" indexes and compared the performance of 9 ongoing mine sites: Weipa, Mt. Isa and Cloncurry, Eromanga, Kidston, the Bowen Basin (Curragh), Tarong, North Stradbroke Island, and the Newnes Plateau. The sites were then ranked from most-to-least sensitive and compared with natural bioregional patterns of vegetation density using mean NDVI. It was determined that regular rainfall and relatively short periods of water-deficit were key characteristics of sites having less sensitivity to climate - as found among the relatively more temperate inland mining locations. Whereas, high rainfall variability, frequently occurring high intensity events, and (or) prolonged seasonal drought were primary

  18. Academic mobility as a key factor of quality assurance in tertiary education

    NASA Astrophysics Data System (ADS)

    Voroshilova, Anna A.

    2015-01-01

    Academic mobility of both faculty and students forms a critical element of the international dimension of higher education and is one of the most important factors of quality assurance of higher education institutions worldwide. Internationalization and globalization of Russian higher education system is having one of the major impacts on the quality management and assurance. Faculty and student mobility figures are now one of the core factors for obtaining state accreditation for Russian universities as well as an important indicator showing the university success and prestige. The aim of the paper is a closer look at the perspectives and results of the academic mobility, the factors stimulating and discouraging mobility, and the outcomes of the mobility influencing the education in Russian universities. Siberian State Aerospace University has had more than 10 years experience in organizing student mobility. Most of the problems in carrying out international activities are common for the whole Russia but still there are some peculiarities featuring technical universities situated in the centre of Russia.

  19. Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia.

    PubMed

    Duncombe, Jessica; Kitamura, Akihiro; Hase, Yoshiki; Ihara, Masafumi; Kalaria, Raj N; Horsburgh, Karen

    2017-10-01

    Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia. While there is considerable overlap between features of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD), it appears that cerebral hypoperfusion is the common underlying pathophysiological mechanism which is a major contributor to cognitive decline and degenerative processes leading to dementia. Sustained cerebral hypoperfusion is suggested to be the cause of white matter attenuation, a key feature common to both AD and dementia associated with cerebral small vessel disease (SVD). White matter changes increase the risk for stroke, dementia and disability. A major gap has been the lack of mechanistic insights into the evolution and progress of VCID. However, this gap is closing with the recent refinement of rodent models which replicate chronic cerebral hypoperfusion. In this review, we discuss the relevance and advantages of these models in elucidating the pathogenesis of VCID and explore the interplay between hypoperfusion and the deposition of amyloid β (Aβ) protein, as it relates to AD. We use examples of our recent investigations to illustrate the utility of the model in preclinical testing of candidate drugs and lifestyle factors. We propose that the use of such models is necessary for tackling the urgently needed translational gap from preclinical models to clinical treatments. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  20. Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA-splicing factors during adipogenesis.

    PubMed

    Mugabo, Yves; Sadeghi, Mina; Fang, Nancy N; Mayor, Thibault; Lim, Gareth E

    2018-05-04

    Adipogenesis involves a complex signaling network requiring strict temporal and spatial organization of effector molecules. Molecular scaffolds, such as 14-3-3 proteins, facilitate such organization, and we have previously identified 14-3-3ζ as an essential scaffold in adipocyte differentiation. The interactome of 14-3-3ζ is large and diverse, and it is possible that novel adipogenic factors may be present within it, but this possibility has not yet been tested. Herein, we generated mouse embryonic fibroblasts from mice overexpressing a tandem affinity purification (TAP) epitope-tagged 14-3-3ζ molecule. After inducing adipogenesis, TAP-14-3-3ζ complexes were purified, followed by MS analysis to determine the 14-3-3ζ interactome. We observed more than 100 proteins that were unique to adipocyte differentiation, 56 of which were novel interacting partners. Among these, we were able to identify previously established regulators of adipogenesis ( i.e. Ptrf/Cavin1) within the 14-3-3ζ interactome, confirming the utility of this approach to detect adipogenic factors. We found that proteins related to RNA metabolism, processing, and splicing were enriched in the interactome. Analysis of transcriptomic data revealed that 14-3-3ζ depletion in 3T3-L1 cells affected alternative splicing of mRNA during adipocyte differentiation. siRNA-mediated depletion of RNA-splicing factors within the 14-3-3ζ interactome, that is, of Hnrpf, Hnrpk, Ddx6, and Sfpq, revealed that they have essential roles in adipogenesis and in the alternative splicing of Pparg and the adipogenesis-associated gene Lpin1 In summary, we have identified novel adipogenic factors within the 14-3-3ζ interactome. Further characterization of additional proteins within the 14-3-3ζ interactome may help identify novel targets to block obesity-associated expansion of adipose tissues. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Identification of the transcription factor ZEB1 as a central component of the adipogenic gene regulatory network

    PubMed Central

    Gubelmann, Carine; Schwalie, Petra C; Raghav, Sunil K; Röder, Eva; Delessa, Tenagne; Kiehlmann, Elke; Waszak, Sebastian M; Corsinotti, Andrea; Udin, Gilles; Holcombe, Wiebke; Rudofsky, Gottfried; Trono, Didier; Wolfrum, Christian; Deplancke, Bart

    2014-01-01

    Adipose tissue is a key determinant of whole body metabolism and energy homeostasis. Unraveling the regulatory mechanisms underlying adipogenesis is therefore highly relevant from a biomedical perspective. Our current understanding of fat cell differentiation is centered on the transcriptional cascades driven by the C/EBP protein family and the master regulator PPARγ. To elucidate further components of the adipogenic gene regulatory network, we performed a large-scale transcription factor (TF) screen overexpressing 734 TFs in mouse pre-adipocytes and probed their effect on differentiation. We identified 22 novel pro-adipogenic TFs and characterized the top ranking TF, ZEB1, as being essential for adipogenesis both in vitro and in vivo. Moreover, its expression levels correlate with fat cell differentiation potential in humans. Genomic profiling further revealed that this TF directly targets and controls the expression of most early and late adipogenic regulators, identifying ZEB1 as a central transcriptional component of fat cell differentiation. DOI: http://dx.doi.org/10.7554/eLife.03346.001 PMID:25163748

  2. Elucidating the alkaline oxygen evolution reaction mechanism on platinum

    DOE PAGES

    Favaro, M.; Valero-Vidal, C.; Eichhorn, J.; ...

    2017-03-07

    Understanding the interplay between surface chemistry, electronic structure, and reaction mechanism of the catalyst at the electrified solid/liquid interface will enable the design of more efficient materials systems for sustainable energy production. The substantial progress in operando characterization, particularly using synchrotron based X-ray spectroscopies, provides the unprecedented opportunity to uncover surface chemical and structural transformations under various (electro)chemical reaction environments. In this work, we study a polycrystalline platinum surface under oxygen evolution conditions in an alkaline electrolyte by means of ambient pressure X-ray photoelectron spectroscopy performed at the electrified solid/liquid interface. We elucidate previously inaccessible aspects of the surface chemistrymore » and structure as a function of the applied potential, allowing us to propose a reaction mechanism for oxygen evolution on a platinum electrode in alkaline solutions.« less

  3. Systematic Review: Predisposing, Precipitating, Perpetuating, and Present Factors Predicting Anticipatory Distress to Painful Medical Procedures in Children.

    PubMed

    Racine, Nicole M; Riddell, Rebecca R Pillai; Khan, Maria; Calic, Masa; Taddio, Anna; Tablon, Paula

    2016-03-01

    To conduct a systematic review of the factors predicting anticipatory distress to painful medical procedures in children. A systematic search was conducted to identify studies with factors related to anticipatory distress to painful medical procedures in children aged 0-18 years. The search retrieved 7,088 articles to review against inclusion criteria. A total of 77 studies were included in the review. 31 factors were found to predict anticipatory distress to painful medical procedures in children. A narrative synthesis of the evidence was conducted, and a summary figure is presented. Many factors were elucidated that contribute to the occurrence of anticipatory distress to painful medical procedures. The factors that appear to increase anticipatory distress are child psychopathology, difficult child temperament, parent distress promoting behaviors, parent situational distress, previous pain events, parent anticipation of distress, and parent anxious predisposition. Longitudinal and experimental research is needed to further elucidate these factors. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Maximizing the benefits of antiretroviral therapy for key affected populations.

    PubMed

    Grubb, Ian R; Beckham, Sarah W; Kazatchkine, Michel; Thomas, Ruth M; Albers, Eliot R; Cabral, Mauro; Lange, Joep; Vella, Stefano; Kurian, Manoj; Beyrer, Chris

    2014-01-01

    Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART), and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including comprehensive harm reduction and other prevention

  5. Public Key Cryptography.

    ERIC Educational Resources Information Center

    Tapson, Frank

    1996-01-01

    Describes public key cryptography, also known as RSA, which is a system using two keys, one used to put a message into cipher and another used to decipher the message. Presents examples using small prime numbers. (MKR)

  6. Three-dimensional bright-field scanning transmission electron microscopy elucidate novel nanostructure in microbial biofilms.

    PubMed

    Hickey, William J; Shetty, Ameesha R; Massey, Randall J; Toso, Daniel B; Austin, Jotham

    2017-01-01

    Bacterial biofilms play key roles in environmental and biomedical processes, and understanding their activities requires comprehension of their nanoarchitectural characteristics. Electron microscopy (EM) is an essential tool for nanostructural analysis, but conventional EM methods are limited in that they either provide topographical information alone, or are suitable for imaging only relatively thin (<300 nm) sample volumes. For biofilm investigations, these are significant restrictions. Understanding structural relations between cells requires imaging of a sample volume sufficiently large to encompass multiple cells and the capture of both external and internal details of cell structure. An emerging EM technique with such capabilities is bright-field scanning transmission electron microscopy (BF-STEM) and in the present report BF-STEM was coupled with tomography to elucidate nanostructure in biofilms formed by the polycyclic aromatic hydrocarbon-degrading soil bacterium, Delftia acidovorans Cs1-4. Dual-axis BF-STEM enabled high-resolution 3-D tomographic recontructions (6-10 nm) visualization of thick (1250 and 1500 nm) sections. The 3-D data revealed that novel extracellular structures, termed nanopods, were polymorphic and formed complex networks within cell clusters. BF-STEM tomography enabled visualization of conduits formed by nanopods that could enable intercellular movement of outer membrane vesicles, and thereby enable direct communication between cells. This report is the first to document application of dual-axis BF-STEM tomography to obtain high-resolution 3-D images of novel nanostructures in bacterial biofilms. Future work with dual-axis BF-STEM tomography combined with correlative light electron microscopy may provide deeper insights into physiological functions associated with nanopods as well as other nanostructures. © 2016 The Authors Journal of Microscopy © 2016 Royal Microscopical Society.

  7. Identification of Neurodegenerative Factors Using Translatome-Regulatory Network Analysis

    PubMed Central

    Brichta, Lars; Shin, William; Jackson-Lewis, Vernice; Blesa, Javier; Yap, Ee-Lynn; Walker, Zachary; Zhang, Jack; Roussarie, Jean-Pierre; Alvarez, Mariano J.; Califano, Andrea; Przedborski, Serge; Greengard, Paul

    2016-01-01

    For degenerative disorders of the central nervous system, the major obstacle to therapeutic advancement has been the challenge of identifying the key molecular mechanisms underlying neuronal loss. We developed a combinatorial approach including translational profiling and brain regulatory network analysis to search for key determinants of neuronal survival or death. Following the generation of transgenic mice for cell type-specific profiling of midbrain dopaminergic neurons, we established and compared translatome libraries reflecting the molecular signature of these cells at baseline or under degenerative stress. Analysis of these libraries by interrogating a context-specific brain regulatory network led to the identification of a repertoire of intrinsic upstream regulators that drive the dopaminergic stress response. The altered activity of these regulators was not associated with changes in their expression levels. This strategy can be generalized for the elucidation of novel molecular determinants involved in the degeneration of other classes of neurons. PMID:26214373

  8. Paenibacillus larvae Chitin-Degrading Protein PlCBP49 Is a Key Virulence Factor in American Foulbrood of Honey Bees

    PubMed Central

    Garcia-Gonzalez, Eva; Poppinga, Lena; Fünfhaus, Anne; Hertlein, Gillian; Hedtke, Kati; Jakubowska, Agata; Genersch, Elke

    2014-01-01

    Paenibacillus larvae, the etiological agent of the globally occurring epizootic American Foulbrood (AFB) of honey bees, causes intestinal infections in honey bee larvae which develop into systemic infections inevitably leading to larval death. Massive brood mortality might eventually lead to collapse of the entire colony. Molecular mechanisms of host-microbe interactions in this system and of differences in virulence between P. larvae genotypes are poorly understood. Recently, it was demonstrated that the degradation of the peritrophic matrix lining the midgut epithelium is a key step in pathogenesis of P. larvae infections. Here, we present the isolation and identification of PlCBP49, a modular, chitin-degrading protein of P. larvae and demonstrate that this enzyme is crucial for the degradation of the larval peritrophic matrix during infection. PlCBP49 contains a module belonging to the auxiliary activity 10 (AA10, formerly CBM33) family of lytic polysaccharide monooxygenases (LPMOs) which are able to degrade recalcitrant polysaccharides. Using chitin-affinity purified PlCBP49, we provide evidence that PlCBP49 degrades chitin via a metal ion-dependent, oxidative mechanism, as already described for members of the AA10 family. Using P. larvae mutants lacking PlCBP49 expression, we analyzed in vivo biological functions of PlCBP49. In the absence of PlCBP49 expression, peritrophic matrix degradation was markedly reduced and P. larvae virulence was nearly abolished. This indicated that PlCBP49 is a key virulence factor for the species P. larvae. The identification of the functional role of PlCBP49 in AFB pathogenesis broadens our understanding of this important family of chitin-binding and -degrading proteins, especially in those bacteria that can also act as entomopathogens. PMID:25080221

  9. Elucidation of the surface characteristics and electrochemistry of high-performance LiNiO 2

    DOE PAGES

    Xu, Jing; Lin, Feng; Nordlund, Dennis; ...

    2016-02-25

    Phase pure LiNiO 2 was prepared using a solid-state method and the optimal synthesis conditions led to a remarkably high capacity of 200 mA h g $-$1 with excellent retention. The combination of bulk and surface characterization elucidated an essential role of the excess Li in phase formation during synthesis and the subsequent electrochemical performance.

  10. Community Advisory Boards Guiding Engaged Research Efforts within a Clinical Translational Sciences Award: Key Contextual Factors Explored.

    PubMed

    Halladay, Jacqueline R; Donahue, Katrina E; Sleath, Betsy; Reuland, Dan; Black, Adina; Mitchell, C Madeline; Breland, Carol E; Coyne-Beasley, Tamera; Mottus, Kathleen; Watson, Sable Noelle; Lewis, Virginia; Wynn, Mysha; Corbie-Smith, Giselle

    2017-01-01

    Engaging stakeholders in research carries the promise of enhancing the research relevance, transparency, and speed of getting findings into practice. By describing the context and functional aspects of stakeholder groups, like those working as community advisory boards (CABs), others can learn from these experiences and operationalize their own CABs. Our objective is to describe our experiences with diverse CABs affiliated with our community engagement group within our institution's Clinical Translational Sciences Award (CTSA). We identify key contextual elements that are important to administering CABs. A group of investigators, staff, and community members engaged in a 6-month collaboration to describe their experiences of working with six research CABs. We identified the key contextual domains that illustrate how CABS are developed and sustained. Two lead authors, with experience with CABs and identifying contextual domains in other work, led a team of 13 through the process. Additionally, we devised a list of key tips to consider when devising CABs. The final domains include (1) aligned missions among stakeholders (2) resources/support, (3) defined operational processes/shared power, (4) well-described member roles, and (5) understanding and mitigating challenges. The tips are a set of actions that support the domains. Identifying key contextual domains was relatively easy, despite differences in the respective CAB's condition of focus, overall mission, or patient demographics represented. By contextualizing these five domains, other research and community partners can take an informed approach to move forward with CAB planning and engaged research.

  11. Information and professional support: key factors in the provision of family-centred early childhood intervention services.

    PubMed

    Fordham, L; Gibson, F; Bowes, J

    2012-09-01

    Much has been written on the principles of family-centred practice and on the service delivery methods and skills required of its practitioners. Far less has been written from the perspective of families whose children have a disability. The aims of this study were twofold: firstly to understand families' experiences of family-centred early childhood intervention services and secondly to explore other factors that might impact on these experiences. One hundred and thirty families attending two established early childhood intervention services in New South Wales, Australia completed a survey incorporating the Measure of Processes of Care-56, the Family Empowerment Scale, the Family Support Scale and the Parenting Daily Hassles Scale. Consistent with previous research using the Measure of Processes of Care-56, 'respectful and supportive care' was the domain of care families rated to occur most and 'provision of general information' was the domain they rated to occur least. Significant positive relationships existed between families' ratings of family-centred care and feelings of empowerment. Being provided with general information was strongly correlated with family empowerment. Families' social support networks played an important role but support from professionals was most strongly correlated with families' experiences of family-centred care. Finally, families whose children's early intervention services were co-ordinated by a professional experienced significantly better care. The provision of general information and professional support are key components of family-centred early childhood intervention services. © 2011 Blackwell Publishing Ltd.

  12. Suppression of savanna ants alters invertebrate composition and influences key ecosystem processes.

    PubMed

    Parr, C L; Eggleton, P; Davies, A B; Evans, T A; Holdsworth, S

    2016-06-01

    In almost every ecosystem, ants (Hymenoptera: Formicidae) are the dominant terrestrial invertebrate group. Their functional value was highlighted by Wilson (1987) who famously declared that invertebrates are the "little things that run the world." However, while it is generally accepted that ants fulfil important functions, few studies have tested these assumptions and demonstrated what happens in their absence. We report on a novel large-scale field experiment in undisturbed savanna habitat where we examined how ants influence the abundance of other invertebrate taxa in the system, and affect the key processes of decomposition and herbivory. Our experiment demonstrated that ants suppressed the abundance and activity of beetles, millipedes, and termites, and also influenced decomposition rates and levels of herbivory. Our study is the first to show that top-down control of termites by ants can have important ecosystem consequences. Further studies are needed to elucidate the effects ant communities have on other aspects of the ecosystem (e.g., soils, nutrient cycling, the microbial community) and how their relative importance for ecosystem function varies among ecosystem types (e.g., savanna vs. forest).

  13. Elucidation of the Molecular Mechanisms for Aberrant Expression of Breast Cancer Specific Gene 1 in Invasive and Metastatic Breast Carcinomas

    DTIC Science & Technology

    2004-06-01

    cells in mitosis. Mutations in any of these genes result in failure to arrest Keywords: BCSG I: BubRl; mitotic checkpoint; yeast the cell cycle at G2...AD Award Number: DAMD17-02-1-0534 TITLE: Elucidation of the Molecular Mechanisms for Aberrant Expression of Breast Cancer Specific Gene 1 in Invasive...SUBTITLE 5. FUNDING NUMBERS Elucidation of the Molecular Mechanisms for Aberrant DAMD17-02-1-0534 Expression of Breast Cancer Specific Gene 1 in Invasive

  14. Identification of Key Odorants in Withering-Flavored Green Tea by Aroma Extract Dilution Analysis

    NASA Astrophysics Data System (ADS)

    Mizukami, Yuzo; Yamaguchi, Yuichi

    This research aims to identify key odorants in withering-flavored green tea. Application of the aroma extract dilution analysis using the volatile fraction of green tea and withering-flavored green tea revealed 25 and 35 odor-active peaks with the flavor dilution factors of≥4, respectively. 4-mercapto-4-methylpentan-2-one, (E)-2-nonenal, linalool, (E,Z)-2,6-nonadienal and 3-methylnonane-2,4-dione were key odorants in green tea with the flavor dilution factor of≥16. As well as these 5 odorants, 1-octen-3-one, β-damascenone, geraniol, β-ionone, (Z)-methyljasmonate, indole and coumarine contributed to the withering flavor of green tea.

  15. Product ion isotopologue pattern: A tool to improve the reliability of elemental composition elucidations of unknown compounds in complex matrices.

    PubMed

    Kaufmann, A; Walker, S; Mol, G

    2016-04-15

    Elucidation of the elemental compositions of unknown compounds (e.g., in metabolomics) generally relies on the availability of accurate masses and isotopic ratios. This study focuses on the information provided by the abundance ratio within a product ion pair (monoisotopic versus the first isotopic peak) when isolating and fragmenting the first isotopic ion (first isotopic mass spectrum) of the precursor. This process relies on the capability of the quadrupole within the Q Orbitrap instrument to isolate a very narrow mass window. Selecting only the first isotopic peak (first isotopic mass spectrum) leads to the observation of a unique product ion pair. The lighter ion within such an isotopologue pair is monoisotopic, while the heavier ion contains a single carbon isotope. The observed abundance ratio is governed by the percentage of carbon atoms lost during the fragmentation and can be described by a hypergeometric distribution. The observed carbon isotopologue abundance ratio (product ion isotopologue pattern) gives reliable information regarding the percentage of carbon atoms lost in the fragmentation process. It therefore facilitates the elucidation of the involved precursor and product ions. Unlike conventional isotopic abundances, the product ion isotopologue pattern is hardly affected by isobaric interferences. Furthermore, the appearance of these pairs greatly aids in cleaning up a 'matrix-contaminated' product ion spectrum. The product ion isotopologue pattern is a valuable tool for structural elucidation. It increases confidence in results and permits structural elucidations for heavier ions. This tool is also very useful in elucidating the elemental composition of product ions. Such information is highly valued in the field of multi-residue analysis, where the accurate mass of product ions is required for the confirmation process. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. 75 FR 17463 - Key West Bank, Key West, Florida; Notice of Appointment of Receiver

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-06

    ... DEPARTMENT OF THE TREASURY Office of Thrift Supervision Key West Bank, Key West, Florida; Notice of Appointment of Receiver Notice is hereby given that, pursuant to the authority contained in... Federal Deposit Insurance Corporation as sole Receiver for Key West Bank, Key West, Florida, (OTS No...

  17. Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi.

    PubMed

    Cordes, Frank S; Kraiczy, Peter; Roversi, Pietro; Simon, Markus M; Brade, Volker; Jahraus, Oliver; Wallis, Russell; Goodstadt, Leo; Ponting, Chris P; Skerka, Christine; Zipfel, Peter F; Wallich, Reinhard; Lea, Susan M

    2006-05-01

    Borrelia burgdorferi, a spirochaete transmitted to human hosts during feeding of infected Ixodes ticks, is the causative agent of Lyme disease, the most frequent vector-borne disease in Eurasia and North America. Sporadically Lyme disease develops into a chronic, multisystemic disorder. Serum-resistant B. burgdorferi strains bind complement factor H (FH) and FH-like protein 1 (FHL-1) on the spirochaete surface. This binding is dependent on the expression of proteins termed complement-regulator acquiring surface proteins (CRASPs). The atomic structure of BbCRASP-1, the key FHL-1/FH-binding protein of B. burgdorferi, has recently been determined. Our analysis indicates that its protein topology apparently evolved to provide a high affinity interaction site for FH/FHL-1 and leads to an atomic-level hypothesis for the functioning of BbCRASP-1. This work demonstrates that pathogens interact with complement regulators in ways that are distinct from the mechanisms used by the host and are thus obvious targets for drug design.

  18. Key Objectives Bank: Year 9. Key Stage 3: National Strategy.

    ERIC Educational Resources Information Center

    Department for Education and Skills, London (England).

    In each sub-section of the "Framework for Teaching English: Years 7, 8 and 9," certain key objectives are identified in boldface print. These objectives are key because they signify skills or understanding which are crucial to pupils' language development. They are challenging for the age group and are important markers of progress. This…

  19. Experimental quantum key distribution with finite-key security analysis for noisy channels.

    PubMed

    Bacco, Davide; Canale, Matteo; Laurenti, Nicola; Vallone, Giuseppe; Villoresi, Paolo

    2013-01-01

    In quantum key distribution implementations, each session is typically chosen long enough so that the secret key rate approaches its asymptotic limit. However, this choice may be constrained by the physical scenario, as in the perspective use with satellites, where the passage of one terminal over the other is restricted to a few minutes. Here we demonstrate experimentally the extraction of secure keys leveraging an optimal design of the prepare-and-measure scheme, according to recent finite-key theoretical tight bounds. The experiment is performed in different channel conditions, and assuming two distinct attack models: individual attacks or general quantum attacks. The request on the number of exchanged qubits is then obtained as a function of the key size and of the ambient quantum bit error rate. The results indicate that viable conditions for effective symmetric, and even one-time-pad, cryptography are achievable.

  20. Elucidating electrolyte decomposition under electron-rich environments at the lithium-metal anode

    DOE PAGES

    Camacho-Forero, Luis E.; Balbuena, Perla B.

    2017-11-07

    The lithium metal anode is one of the key components of the lithium–sulfur (Li–S) batteries, which are considered one of the most promising candidates for the next generation of battery systems. However, one of the main challenges that have prevented Li-metal anodes from becoming feasible to be used in commercial batteries is the continuous decomposition of the electrolyte due to its high reactivity, which leads to the formation of solid–electrolyte interphase (SEI) layers. The properties of the SEI can dramatically affect the performance of the batteries. Thus, a rigorous understanding of the electrolyte decomposition is crucial to elucidate improvements inmore » performance of the Li–S technology. Here, in this work, using density functional theory (DFT) and ab initio molecular dynamics simulations (AIMD), we investigate the effect of electron-rich environments on the decomposition mechanism of electrolyte species in pure 1,2-dimethoxyethane (DME) solvent and 1 M lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and lithium bis(fluorosulfonyl)imide (LiFSI) salt solutions. It is found that systems with pure DME require an average environment of at least ~0.9 |e| per molecule for a DME to decompose into CH 3O - and C 2H 4 2-via a 4-electron transfer. In the case of mixtures, the salts are very prone to react with any excess of electrons. In addition, DME dehydrogenation due to reactions with fragments coming from the salt decompositions was detected. Formation of oligomer anionic species from DME and salt fragments were also identified from the AIMD simulations. Finally, the thermodynamics and kinetics of the most relevant electrolyte decomposition reactions were characterized. DME decomposition reactions predicted from the AIMD simulations were found to be thermodynamically favorable under exposure to Li atoms and/or by reactions with salt fragments. Lastly, in most cases, these reactions were shown to have low to moderate activation barriers.« less

  1. Elucidating electrolyte decomposition under electron-rich environments at the lithium-metal anode

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

    Camacho-Forero, Luis E.; Balbuena, Perla B.

    The lithium metal anode is one of the key components of the lithium–sulfur (Li–S) batteries, which are considered one of the most promising candidates for the next generation of battery systems. However, one of the main challenges that have prevented Li-metal anodes from becoming feasible to be used in commercial batteries is the continuous decomposition of the electrolyte due to its high reactivity, which leads to the formation of solid–electrolyte interphase (SEI) layers. The properties of the SEI can dramatically affect the performance of the batteries. Thus, a rigorous understanding of the electrolyte decomposition is crucial to elucidate improvements inmore » performance of the Li–S technology. Here, in this work, using density functional theory (DFT) and ab initio molecular dynamics simulations (AIMD), we investigate the effect of electron-rich environments on the decomposition mechanism of electrolyte species in pure 1,2-dimethoxyethane (DME) solvent and 1 M lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and lithium bis(fluorosulfonyl)imide (LiFSI) salt solutions. It is found that systems with pure DME require an average environment of at least ~0.9 |e| per molecule for a DME to decompose into CH 3O - and C 2H 4 2-via a 4-electron transfer. In the case of mixtures, the salts are very prone to react with any excess of electrons. In addition, DME dehydrogenation due to reactions with fragments coming from the salt decompositions was detected. Formation of oligomer anionic species from DME and salt fragments were also identified from the AIMD simulations. Finally, the thermodynamics and kinetics of the most relevant electrolyte decomposition reactions were characterized. DME decomposition reactions predicted from the AIMD simulations were found to be thermodynamically favorable under exposure to Li atoms and/or by reactions with salt fragments. Lastly, in most cases, these reactions were shown to have low to moderate activation barriers.« less

  2. Elucidation of spin echo small angle neutron scattering correlation functions through model studies.

    PubMed

    Shew, Chwen-Yang; Chen, Wei-Ren

    2012-02-14

    Several single-modal Debye correlation functions to approximate part of the overall Debey correlation function of liquids are closely examined for elucidating their behavior in the corresponding spin echo small angle neutron scattering (SESANS) correlation functions. We find that the maximum length scale of a Debye correlation function is identical to that of its SESANS correlation function. For discrete Debye correlation functions, the peak of SESANS correlation function emerges at their first discrete point, whereas for continuous Debye correlation functions with greater width, the peak position shifts to a greater value. In both cases, the intensity and shape of the peak of the SESANS correlation function are determined by the width of the Debye correlation functions. Furthermore, we mimic the intramolecular and intermolecular Debye correlation functions of liquids composed of interacting particles based on a simple model to elucidate their competition in the SESANS correlation function. Our calculations show that the first local minimum of a SESANS correlation function can be negative and positive. By adjusting the spatial distribution of the intermolecular Debye function in the model, the calculated SESANS spectra exhibit the profile consistent with that of hard-sphere and sticky-hard-sphere liquids predicted by more sophisticated liquid state theory and computer simulation. © 2012 American Institute of Physics

  3. Nonmarket economic user values of the Florida Keys/Key West

    Treesearch

    Vernon R. Leeworthy; J. Michael Bowker

    1997-01-01

    This report provides estimates of the nonmarket economic user values for recreating visitors to the Florida Keys/Key West that participated in natural resource-based activities. Results from estimated travel cost models are presented, including visitor’s responses to prices and estimated per person-trip user values. Annual user values are also calculated and presented...

  4. The physical size of transcription factors is key to transcriptional regulation in chromatin domains

    NASA Astrophysics Data System (ADS)

    Maeshima, Kazuhiro; Kaizu, Kazunari; Tamura, Sachiko; Nozaki, Tadasu; Kokubo, Tetsuro; Takahashi, Koichi

    2015-02-01

    Genetic information, which is stored in the long strand of genomic DNA as chromatin, must be scanned and read out by various transcription factors. First, gene-specific transcription factors, which are relatively small (˜50 kDa), scan the genome and bind regulatory elements. Such factors then recruit general transcription factors, Mediators, RNA polymerases, nucleosome remodellers, and histone modifiers, most of which are large protein complexes of 1-3 MDa in size. Here, we propose a new model for the functional significance of the size of transcription factors (or complexes) for gene regulation of chromatin domains. Recent findings suggest that chromatin consists of irregularly folded nucleosome fibres (10 nm fibres) and forms numerous condensed domains (e.g., topologically associating domains). Although the flexibility and dynamics of chromatin allow repositioning of genes within the condensed domains, the size exclusion effect of the domain may limit accessibility of DNA sequences by transcription factors. We used Monte Carlo computer simulations to determine the physical size limit of transcription factors that can enter condensed chromatin domains. Small gene-specific transcription factors can penetrate into the chromatin domains and search their target sequences, whereas large transcription complexes cannot enter the domain. Due to this property, once a large complex binds its target site via gene-specific factors it can act as a ‘buoy’ to keep the target region on the surface of the condensed domain and maintain transcriptional competency. This size-dependent specialization of target-scanning and surface-tethering functions could provide novel insight into the mechanisms of various DNA transactions, such as DNA replication and repair/recombination.

  5. Shining light on neurons--elucidation of neuronal functions by photostimulation.

    PubMed

    Eder, Matthias; Zieglgänsberger, Walter; Dodt, Hans-Ulrich

    2004-01-01

    Many neuronal functions can be elucidated by techniques that allow for a precise stimulation of defined regions of a neuron and its afferents. Photolytic release of neurotransmitters from 'caged' derivates in the vicinity of visualized neurons in living brain slices meets this request. This technique allows the study of the subcellular distribution and properties of functional native neurotransmitter receptors. These are prerequisites for a detailed analysis of the expression and spatial specificity of synaptic plasticity. Photostimulation can further be used to fast map the synaptic connectivity between nearby and, more importantly, distant cells in a neuronal network. Here we give a personal review of some of the technical aspects of photostimulation and recent findings, which illustrate the advantages of this technique.

  6. Correlation of cellular factors and differential scrapie prion permissiveness in ovine microglia

    USDA-ARS?s Scientific Manuscript database

    Prion diseases are fatal neurodegenerative disorders by which the native cellular prion protein (PrP-C) is misfolded into an accumulating, disease-associated isoform (PrP-D). To improve the understanding of prion pathogenesis and develop effective treatments, it is essential to elucidate factors con...

  7. Computational Models of HIV-1 Resistance to Gene Therapy Elucidate Therapy Design Principles

    PubMed Central

    Aviran, Sharon; Shah, Priya S.; Schaffer, David V.; Arkin, Adam P.

    2010-01-01

    Gene therapy is an emerging alternative to conventional anti-HIV-1 drugs, and can potentially control the virus while alleviating major limitations of current approaches. Yet, HIV-1's ability to rapidly acquire mutations and escape therapy presents a critical challenge to any novel treatment paradigm. Viral escape is thus a key consideration in the design of any gene-based technique. We develop a computational model of HIV's evolutionary dynamics in vivo in the presence of a genetic therapy to explore the impact of therapy parameters and strategies on the development of resistance. Our model is generic and captures the properties of a broad class of gene-based agents that inhibit early stages of the viral life cycle. We highlight the differences in viral resistance dynamics between gene and standard antiretroviral therapies, and identify key factors that impact long-term viral suppression. In particular, we underscore the importance of mutationally-induced viral fitness losses in cells that are not genetically modified, as these can severely constrain the replication of resistant virus. We also propose and investigate a novel treatment strategy that leverages upon gene therapy's unique capacity to deliver different genes to distinct cell populations, and we find that such a strategy can dramatically improve efficacy when used judiciously within a certain parametric regime. Finally, we revisit a previously-suggested idea of improving clinical outcomes by boosting the proliferation of the genetically-modified cells, but we find that such an approach has mixed effects on resistance dynamics. Our results provide insights into the short- and long-term effects of gene therapy and the role of its key properties in the evolution of resistance, which can serve as guidelines for the choice and optimization of effective therapeutic agents. PMID:20711350

  8. An analysis of the structure of the compound biological effectiveness factor.

    PubMed

    Ono, Koji

    2016-08-01

    This report is an analysis of the structure of the compound biological effectiveness (CBE) factor. The value of the CBE factor previously reported was revalued for the central nervous system, skin and lung. To describe the structure, the following terms are introduced: the vascular CBE (v-CBE), intraluminal CBE (il-CBE), extraluminal CBE (el-CBE) and non-vascular CBE (nv-CBE) factors and the geometric biological factor (GBF), i.e. the contributions that are derived from the total dose to the vasculature, each dose to vasculature from the intraluminal side and the extraluminal side, the dose to the non-vascular tissue and the factor to calculate el-CBE from il-CBE, respectively. The el-CBE factor element was also introduced to relate il-CBE to el-CBE factors. A CBE factor of 0.36 for disodium mercaptoundecahydrododecaborate (BSH) for the CNS was independent of the (10)B level in the blood; however, that for p-Boron-L-phenylalanine (BPA) increased with the (10)B level ratio of the normal tissue to the blood (N/B). The CBE factor was expressed as follows: factor = 0.32 + N/B × 1.65. The factor of 0.32 at 0 of N/B was close to the CBE factor for BSH. GBFs had similar values, between BSH and BPA, 1.39 and 1.52, respectively. The structure of the CBE factor for BPA to the lung was also elucidated based on this idea. The factor is described as follows: CBE factor = 0.32 + N/B × 1.80. By this elucidation of the structure of the CBE factor, it is expected that basic and clinical research into boron neutron capture therapy will progress. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  9. Demographic, genetic, and environmental factors that modify disease course.

    PubMed

    Marrie, Ruth Ann

    2011-05-01

    As with susceptibility to disease, it is likely that multiple factors interact to influence the phenotype of multiple sclerosis and long-term disease outcomes. Such factors may include genetic factors, socioeconomic status, comorbid diseases, and health behaviors, as well as environmental exposures. An improved understanding of the influence of these factors on disease course may reap several benefits, such as improved prognostication, allowing us to tailor disease management with respect to intensity of disease-modifying therapies and changes in specific health behaviors, in the broad context of coexisting health issues. Such information can facilitate appropriately adjusted comparisons within and between populations. Elucidation of these factors will require careful study of well-characterized populations in which the roles of multiple factors are considered simultaneously. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Elucidating anionic oxygen activity in lithium-rich layered oxides

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

    Xu, Jing; Sun, Meiling; Qiao, Ruimin

    Recent research has explored combining conventional transition metal redox with anionic lattice oxygen redox as a new and exciting direction to search for high-capacity lithium-ion cathodes. For this study, we probe the poorly understood electrochemical activity of anionic oxygen from a material perspective by elucidating the effect of the transition metal on oxygen redox activity. We study two lithium-rich layered oxides, specifically lithium nickel metal oxides where metal is either manganese or ruthenium, which possess similar structure and discharge characteristics, but exhibit distinctly different charge profiles. By combining X-ray spectroscopy with operando differential electrochemical mass spectrometry, we reveal completely differentmore » oxygen redox activity in each material, likely resulting from the different interaction between the lattice oxygen and transition metals. This work provides additional insights into the complex mechanism of oxygen redox and development of advanced high-capacity lithium-ion cathodes.« less

  11. Elucidating anionic oxygen activity in lithium-rich layered oxides

    DOE PAGES

    Xu, Jing; Sun, Meiling; Qiao, Ruimin; ...

    2018-03-05

    Recent research has explored combining conventional transition metal redox with anionic lattice oxygen redox as a new and exciting direction to search for high-capacity lithium-ion cathodes. For this study, we probe the poorly understood electrochemical activity of anionic oxygen from a material perspective by elucidating the effect of the transition metal on oxygen redox activity. We study two lithium-rich layered oxides, specifically lithium nickel metal oxides where metal is either manganese or ruthenium, which possess similar structure and discharge characteristics, but exhibit distinctly different charge profiles. By combining X-ray spectroscopy with operando differential electrochemical mass spectrometry, we reveal completely differentmore » oxygen redox activity in each material, likely resulting from the different interaction between the lattice oxygen and transition metals. This work provides additional insights into the complex mechanism of oxygen redox and development of advanced high-capacity lithium-ion cathodes.« less

  12. Cortistatin Is a Key Factor Regulating the Sex-Dependent Response of the GH and Stress Axes to Fasting in Mice.

    PubMed

    Cordoba-Chacón, José; Gahete, Manuel D; Pozo-Salas, Ana I; de Lecea, Luis; Castaño, Justo P; Luque, Raúl M

    2016-07-01

    Cortistatin (CORT) shares high structural and functional similarities with somatostatin (SST) but displays unique sex-dependent pituitary actions. Indeed, although female CORT-knockout (CORT-KO) mice exhibit enhanced GH expression/secretion, Proopiomelanocortin expression, and circulating ACTH/corticosterone/ghrelin levels, male CORT-KO mice only display increased plasma GH/corticosterone levels. Changes in peripheral ghrelin and SST (rather than hypothalamic levels) seem to regulate GH/ACTH axes in CORT-KOs under fed conditions. Because changes in GH/ACTH axes during fasting provide important adaptive mechanisms, we sought to determine whether CORT absence influences GH/ACTH axes during fasting. Accordingly, fed and fasted male/female CORT-KO were compared with littermate controls. Fasting increased circulating GH levels in male/female controls but not in CORT-KO, suggesting that CORT can be a relevant regulator of GH secretion during fasting. However, GH levels were already higher in CORT-KO than in controls in fed state, which might preclude a further elevation in GH levels. Interestingly, although fasting-induced pituitary GH expression was elevated in both male/female controls, GH expression only increased in fasted female CORT-KOs, likely owing to specific changes observed in key factors controlling somatotrope responsiveness (ie, circulating ghrelin and IGF-1, and pituitary GHRH and ghrelin receptor expression). Fasting increased corticosterone levels in control and, most prominently, in CORT-KO mice, which might be associated with a desensitization to SST signaling and to an augmentation in CRH and ghrelin-signaling regulating corticotrope function. Altogether, these results provide compelling evidence that CORT plays a key, sex-dependent role in the regulation of the GH/ACTH axes in response to fasting.

  13. Maturity-onset diabetes of the young as a model for elucidating the multifactorial origin of type 2 diabetes mellitus.

    PubMed

    Horikawa, Yukio

    2018-02-06

    Maturity-onset diabetes of the young (MODY) is a form of diabetes classically characterized as having autosomal dominant inheritance, onset before the age of 25 years in at least one family member and partly preserved pancreatic β-cell function. The 14 responsible genes are reported to be MODY type 1~14, of which MODY 2 and 3 might be the most common forms. Although MODY is currently classified as diabetes of a single gene defect, it has become clear that mutations in rare MODYs, such as MODY 5 and MODY 6, have small mutagenic effects and low penetrance. In addition, as there are differences in the clinical phenotypes caused by the same mutation even in the same family, other phenotypic modifying factors are thought to exist; MODY could well have characteristics of type 2 diabetes mellitus, which is of multifactorial origin. Here, we outline the effects of genetic and environmental factors on the known phenotypes of MODY, focusing mainly on the examples of MODY 5 and 6, which have low penetrance, as suggestive models for elucidating the multifactorial origin of type 2 diabetes mellitus. © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  14. ION COMPOSITION ELUCIDATION (ICE): AN INVESTIGATIVE TOOL FOR CHARACTERIZATION AND IDENTIFICATION OF COMPOUNDS OF REGULATORY IMPORTANCE

    EPA Science Inventory

    Ion Composition Elucidation (ICE) often leads to identification of compounds and provides high quality evidence for tracking compounds to their sources. Mass spectra for most organic compounds are not found in mass spectral libraries used to tentatively identify analytes. In addi...

  15. Secure key storage and distribution

    DOEpatents

    Agrawal, Punit

    2015-06-02

    This disclosure describes a distributed, fault-tolerant security system that enables the secure storage and distribution of private keys. In one implementation, the security system includes a plurality of computing resources that independently store private keys provided by publishers and encrypted using a single security system public key. To protect against malicious activity, the security system private key necessary to decrypt the publication private keys is not stored at any of the computing resources. Rather portions, or shares of the security system private key are stored at each of the computing resources within the security system and multiple security systems must communicate and share partial decryptions in order to decrypt the stored private key.

  16. Fundamental finite key limits for one-way information reconciliation in quantum key distribution

    NASA Astrophysics Data System (ADS)

    Tomamichel, Marco; Martinez-Mateo, Jesus; Pacher, Christoph; Elkouss, David

    2017-11-01

    The security of quantum key distribution protocols is guaranteed by the laws of quantum mechanics. However, a precise analysis of the security properties requires tools from both classical cryptography and information theory. Here, we employ recent results in non-asymptotic classical information theory to show that one-way information reconciliation imposes fundamental limitations on the amount of secret key that can be extracted in the finite key regime. In particular, we find that an often used approximation for the information leakage during information reconciliation is not generally valid. We propose an improved approximation that takes into account finite key effects and numerically test it against codes for two probability distributions, that we call binary-binary and binary-Gaussian, that typically appear in quantum key distribution protocols.

  17. Environmental factors affecting contaminant toxicity in aquatic and terrestrial vertebrates

    USGS Publications Warehouse

    Rattner, Barnett A.; Heath, Alan G.; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

    2003-01-01

    Physical and natural factors have long been known to influence the toxicity of environmental contaminants to vertebrates. The majority of data that address this topic have been derived from studies on fish, highly inbred laboratory rodents, and man.' The degree to which these factors modify toxicity has principally been elucidated by controlled laboratory experiments. Until recently, the significance of such effects to free-ranging vertebrates Figure 23.1 was frequently overlooked in ecological risk assessments.' Drawing upon controlled experiments and observational science, we overview environmental factors that influence pollutant toxicity in fish and wildlife, and present some perspective on their ecotoxicological significance.

  18. Fire fatality and alcohol intake: analysis of key risk factors.

    PubMed

    Bruck, Dorothy; Ball, Michelle; Thomas, Ian R

    2011-09-01

    After a brief review of the literature on the role of alcohol in residential fire deaths, a comparison of different risk factors for residential fire fatality was undertaken by closely analyzing the circumstances of fire victims as a function of alcohol intake. Analyses were based on Australian coroners' fire fatality records for the state of Victoria (1998-2006) and considered demographic, behavioral, and environmental factors for the 95 adult fire victims who were tested for alcohol (64 male, 31 female). Most (58%) had a positive blood alcohol concentration (BAC) test, with 31% of the total sample having a BAC of more than 0.20 gm per 100 ml. Odds ratio analyses showed that four variables were significantly more associated with victims who had consumed alcohol compared with sober victims. In descending odds ratio order, these variables were as follows: (a) being aged 18-60 years, (b) involving smoking materials (e.g. cigarettes, pipes), (c) having no conditions preventing escape, and (d) being male. An important new finding is that fire fatalities with positive BAC levels were more than three times less likely to have their clothing alight or exits blocked than sober fire victims. The risk of dying in a fire for alcohol-affected people who are capable of being alerted and escaping may be reduced if they can be alerted more quickly and effectively. Suitable measures for improving smoke alarms via interlinking and the use of an alarm signal demonstrated to be more effective at waking sleepers, including those who are alcohol affected, are discussed.

  19. Key Factors in Smoking Cessation Intervention among 15-16-Year-Olds

    ERIC Educational Resources Information Center

    Heikkinen, Anna Maria; Broms, Ulla; Pitkaniemi, Janne; Koskenvuo, Markku; Meurman, Jukka

    2009-01-01

    The authors aimed to investigate factors associated with smoking cessation among adolescents after tobacco intervention. They examined smokers (n = 127) from one birth cohort (n = 545) in the city of Kotka in Finland. These smokers were randomized in 3 intervention groups the dentist (n = 44) and the school nurse (n = 42 groups), and a control…

  20. Structure elucidation of two triterpenoid saponins from rhizome of Anemone raddeana Regel.

    PubMed

    Lu, Jincai; Xu, Beibei; Gao, Song; Fan, Li; Zhang, Hongfen; Liu, Runxiang; Kodama, Hiroyuki

    2009-09-01

    Two new 27-hydroxy-oleanolic acid type triterpenoid saponins, raddeanoside 20 (1) and raddeanoside 21(2) were isolated from the rhizome of Anemone raddeana Regel. The structures of the two compounds were elucidated as 27-hydroxy-oleanolic acid 3-O-alpha-L-rhamnopyranosyl(1-->2) [beta-D-glucopyranosyl (1-->4)]-alpha-L-arabinopyranoside (1) and 3-O-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranosyl-27-hydroxy-oleanolic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (2) on the basis of chemical and spectral evidence.

  1. Proteomics approach combined with biochemical attributes to elucidate compatible and incompatible plant-virus interactions between Vigna mungo and Mungbean Yellow Mosaic India Virus.

    PubMed

    Kundu, Subrata; Chakraborty, Dipjyoti; Kundu, Anirban; Pal, Amita

    2013-01-01

    transferase are the three major hubs with high connectivity. These nodal proteins play the crucial role of key regulators in bringing about a coordinated defense response in highly orchestrated manner. Biochemical and proteomic analyses revealed early accumulation of the defense/stress related proteins involved in ROS metabolism during incompatible interaction. The robustness in induction of defense/stress and signal transduction related proteins is the key factor in inducing resistance. The mechanism of MYMIV-resistance in V. mungo involves redirection of carbohydrate flux towards pentose phosphate pathway. Some of these identified, differentially regulated proteins are also conferring abiotic stress responses illustrating harmony amongst different stress responses. To the best of our knowledge, this is the lone study deciphering differential regulations of V. mungo leaf proteome upon MYMIV infection elucidating the mode of resistance response at the biochemical level.

  2. Physical Unclonable Function Hardware Keys Utilizing Kirchhoff-Law Secure Key Exchange and Noise-Based Logic

    NASA Astrophysics Data System (ADS)

    Kish, Laszlo B.; Kwan, Chiman

    Weak unclonable function (PUF) encryption key means that the manufacturer of the hardware can clone the key but not anybody else. Strong unclonable function (PUF) encryption key means that even the manufacturer of the hardware is unable to clone the key. In this paper, first we introduce an "ultra" strong PUF with intrinsic dynamical randomness, which is not only unclonable but also gets renewed to an independent key (with fresh randomness) during each use via the unconditionally secure key exchange. The solution utilizes the Kirchhoff-law-Johnson-noise (KLJN) method for dynamical key renewal and a one-time-pad secure key for the challenge/response process. The secure key is stored in a flash memory on the chip to provide tamper-resistance and nonvolatile storage with zero power requirements in standby mode. Simplified PUF keys are shown: a strong PUF utilizing KLJN protocol during the first run and noise-based logic (NBL) hyperspace vector string verification method for the challenge/response during the rest of its life or until it is re-initialized. Finally, the simplest PUF utilizes NBL without KLJN thus it can be cloned by the manufacturer but not by anybody else.

  3. Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens

    PubMed Central

    Meliopoulos, Victoria A.; Andersen, Lauren E.; Birrer, Katherine F.; Simpson, Kaylene J.; Lowenthal, John W.; Bean, Andrew G. D.; Stambas, John; Stewart, Cameron R.; Tompkins, S. Mark; van Beusechem, Victor W.; Fraser, Iain; Mhlanga, Musa; Barichievy, Samantha; Smith, Queta; Leake, Devin; Karpilow, Jon; Buck, Amy; Jona, Ghil; Tripp, Ralph A.

    2012-01-01

    Influenza virus encodes only 11 viral proteins but replicates in a broad range of avian and mammalian species by exploiting host cell functions. Genome-wide RNA interference (RNAi) has proven to be a powerful tool for identifying the host molecules that participate in each step of virus replication. Meta-analysis of findings from genome-wide RNAi screens has shown influenza virus to be dependent on functional nodes in host cell pathways, requiring a wide variety of molecules and cellular proteins for replication. Because rapid evolution of the influenza A viruses persistently complicates the effectiveness of vaccines and therapeutics, a further understanding of the complex host cell pathways coopted by influenza virus for replication may provide new targets and strategies for antiviral therapy. RNAi genome screening technologies together with bioinformatics can provide the ability to rapidly identify specific host factors involved in resistance and susceptibility to influenza virus, allowing for novel disease intervention strategies.—Meliopoulos, V. A., Andersen, L. E., Birrer, K. F., Simpson, K. J., Lowenthal, J. W., Bean, A. G. D., Stambas, J., Stewart, C. R., Tompkins, S. M., van Beusechem, V. W., Fraser, I., Mhlanga, M., Barichievy, S., Smith, Q., Leake, D., Karpilow, J., Buck, A., Jona, G., Tripp, R. A. Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens. PMID:22247330

  4. Comparative transcriptome analysis of different chemotypes elucidates withanolide biosynthesis pathway from medicinal plant Withania somnifera

    PubMed Central

    Gupta, Parul; Goel, Ridhi; Agarwal, Aditya Vikram; Asif, Mehar Hasan; Sangwan, Neelam Singh; Sangwan, Rajender Singh; Trivedi, Prabodh Kumar

    2015-01-01

    Withania somnifera is one of the most valuable medicinal plants synthesizing secondary metabolites known as withanolides. Despite pharmaceutical importance, limited information is available about the biosynthesis of withanolides. Chemo-profiling of leaf and root tissues of Withania suggest differences in the content and/or nature of withanolides in different chemotypes. To identify genes involved in chemotype and/or tissue-specific withanolide biosynthesis, we established transcriptomes of leaf and root tissues of distinct chemotypes. Genes encoding enzymes for intermediate steps of terpenoid backbone biosynthesis with their alternatively spliced forms and paralogous have been identified. Analysis suggests differential expression of large number genes among leaf and root tissues of different chemotypes. Study also identified differentially expressing transcripts encoding cytochrome P450s, glycosyltransferases, methyltransferases and transcription factors which might be involved in chemodiversity in Withania. Virus induced gene silencing of the sterol ∆7-reductase (WsDWF5) involved in the synthesis of 24-methylene cholesterol, withanolide backbone, suggests role of this enzyme in biosynthesis of withanolides. Information generated, in this study, provides a rich resource for functional analysis of withanolide-specific genes to elucidate chemotype- as well as tissue-specific withanolide biosynthesis. This genomic resource will also help in development of new tools for functional genomics and breeding in Withania. PMID:26688389

  5. Rapid high-resolution four-dimensional NMR spectroscopy using the filter diagonalization method and its advantages for detailed structural elucidation of oligosaccharides.

    PubMed

    Armstrong, Geoffrey S; Mandelshtam, Vladimir A; Shaka, A J; Bendiak, Brad

    2005-03-01

    Four-dimensional nuclear magnetic resonance spectroscopy with high resolution of signals in the indirect dimensions is reported as an implementation of the filter diagonalization method (FDM). Using an oligosaccharide derivatized with 13C-labeled acetyl isotags, a four-dimensional constant-time pulse sequence was tailored for conjoint use with the FDM. Results demonstrate that high resolution in all dimensions can be achieved using a relatively short experimental time period (19 h), even though the spectrum is highly congested in the direct and all three indirect dimensions. The combined use of isotags, constant-time pulse sequences, and FDM permits rapid isolation of sugar ring proton spin systems in multiple dimensions and enables all endocyclic J-couplings to be simply measured, the key goal to assigning sugar stereochemistry and anomeric configuration. A general method for rapid, unambiguous elucidation of spin systems in oligosaccharides has been a long-sought goal of carbohydrate NMR, and isotags combined with the FDM now enable this to be easily performed. Additional general advantages of the FDM program for generating high-resolution 2D slices in any dimension from a 4D spectrum are emphasized.

  6. Maximizing the benefits of antiretroviral therapy for key affected populations

    PubMed Central

    Grubb, Ian R; Beckham, Sarah W; Kazatchkine, Michel; Thomas, Ruth M; Albers, Eliot R; Cabral, Mauro; Lange, Joep; Vella, Stefano; Kurian, Manoj; Beyrer, Chris

    2014-01-01

    Introduction Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART), and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Discussion Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Conclusions Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including comprehensive harm

  7. Key enzymes of the retinoid (visual) cycle in vertebrate retina

    PubMed Central

    Kiser, Philip D.; Golczak, Marcin; Maeda, Akiko; Palczewski, Krzysztof

    2011-01-01

    A major goal in vision research over the past few decades has been to understand the molecular details of retinoid processing within the retinoid (visual) cycle. This includes the consequences of side reactions that result from delayed all-trans-retinal clearance and condensation with phospholipids that characterize a variety of serious retinal diseases. Knowledge of the basic retinoid biochemistry involved in these diseases is essential for development of effective therapeutics. Photoisomerization of the 11-cis-retinal chromophore of rhodopsin triggers a complex set of metabolic transformations collectively termed phototransduction that ultimately lead to light perception. Continuity of vision depends on continuous conversion of all-trans-retinal back to the 11-cis-retinal isomer. This process takes place in a series of reactions known as the retinoid cycle, which occur in photoreceptor and RPE cells. All-trans-retinal, the initial substrate of this cycle, is a chemically reactive aldehyde that can form toxic conjugates with proteins and lipids. Therefore, much experimental effort has been devoted to elucidate molecular mechanisms of the retinoid cycle and all-trans-retinal-mediated retinal degeneration, resulting in delineation of many key steps involved in regenerating 11-cis-retinal. Three particularly important reactions are catalyzed by enzymes broadly classified as acyltransferases, short-chain dehydrogenases/reductases and carotenoid/retinoid isomerases/oxygenases. PMID:21447403

  8. Quantum key distribution with finite resources: Secret key rates via Renyi entropies

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

    Abruzzo, Silvestre; Kampermann, Hermann; Mertz, Markus

    A realistic quantum key distribution (QKD) protocol necessarily deals with finite resources, such as the number of signals exchanged by the two parties. We derive a bound on the secret key rate which is expressed as an optimization problem over Renyi entropies. Under the assumption of collective attacks by an eavesdropper, a computable estimate of our bound for the six-state protocol is provided. This bound leads to improved key rates in comparison to previous results.

  9. Elucidating the Activation Mechanism of the Insulin-Family Proteins with Molecular Dynamics Simulations.

    PubMed

    Papaioannou, Anastasios; Kuyucak, Serdar; Kuncic, Zdenka

    2016-01-01

    The insulin-family proteins bind to their own receptors, but insulin-like growth factor II (IGF-II) can also bind to the A isoform of the insulin receptor (IR-A), activating unique and alternative signaling pathways from those of insulin. Although extensive studies of insulin have revealed that its activation is associated with the opening of the B chain-C terminal (BC-CT), the activation mechanism of the insulin-like growth factors (IGFs) still remains unknown. Here, we present the first comprehensive study of the insulin-family proteins comparing their activation process and mechanism using molecular dynamics simulations to reveal new insights into their specificity to the insulin receptor. We have found that all the proteins appear to exhibit similar stochastic dynamics in their conformational change to an active state. For the IGFs, our simulations show that activation involves two opening locations: the opening of the BC-CT section away from the core, similar to insulin; and the additional opening of the BC-CT section away from the C domain. Furthermore, we have found that these two openings occur simultaneously in IGF-I, but not in IGF-II, where they can occur independently. This suggests that the BC-CT section and the C domain behave as a unified domain in IGF-I, but as two independent domains in IGF-II during the activation process, implying that the IGFs undergo different activation mechanisms for receptor binding. The probabilities of the active and inactive states of the proteins suggest that IGF-II is hyperactive compared to IGF-I. The hinge residue and the hydrophobic interactions in the core are found to play a critical role in the stability and activity of IGFs. Overall, our simulations have elucidated the crucial differences and similarities in the activation mechanisms of the insulin-family proteins, providing new insights into the molecular mechanisms responsible for the observed differences between IGF-I and IGF-II in receptor binding.

  10. A compact free space quantum key distribution system capable of daylight operation

    NASA Astrophysics Data System (ADS)

    Benton, David M.; Gorman, Phillip M.; Tapster, Paul R.; Taylor, David M.

    2010-06-01

    A free space quantum key distribution system has been demonstrated. Consideration has been given to factors such as field of view and spectral width, to cut down the deleterious effect from background light levels. Suitable optical sources such as lasers and RCLEDs have been investigated as well as optimal wavelength choices, always with a view to building a compact and robust system. The implementation of background reduction measures resulted in a system capable of operating in daylight conditions. An autonomous system was left running and generating shared key material continuously for over 7 days.

  11. Liquid chromatography with mass spectrometry method based two-step precursor ion scanning for the structural elucidation of flavonoids.

    PubMed

    Li, Yong; Pang, Tao; Shi, Junli; Lu, Xiuping; Deng, Jianhua; Lin, Qian

    2014-11-01

    Plant flavonoids are very important secondary metabolites for insect and virus control of their host plant and are potent nutrients for humans. To be able to understand the bioavailability and functions of plant flavonoids, it is necessary to reveal their exact chemical structures. Liquid chromatography with tandem mass spectrometry is a powerful approach for structural elucidation of metabolites. In this report, a two-step precursor ion scanning based liquid chromatography with tandem mass spectrometry method was developed for the structural elucidation of plant flavonoids. The established method consists of the two-step precursor ions scanning for possible flavonoids extraction, MS(2) fragment spectra acquisition and comparison with an online database, liquid chromatography retention rules correction, and commercial standards verification. The developed method was used for the structure elucidation of flavonoids in flowers and leaves of tobacco (Nicotiana tabacum), and 17 flavonoids were identified in the tobacco variety Yunyan 97. Nine of the 17 identified flavonoids were considered to be found in tobacco flowers or/and leaves for the first time based on the available references. This method was proved to be very effective and can be used for the identification of flavonoids in other plants. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. The Drosophila Duox maturation factor is a key component of a positive feedback loop that sustains regeneration signaling.

    PubMed

    Khan, Sumbul Jawed; Abidi, Syeda Nayab Fatima; Skinner, Andrea; Tian, Yuan; Smith-Bolton, Rachel K

    2017-07-01

    Regenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed whole-genome mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescently labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulates mol expression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by whole-genome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth.

  13. The Drosophila Duox maturation factor is a key component of a positive feedback loop that sustains regeneration signaling

    PubMed Central

    Skinner, Andrea; Tian, Yuan

    2017-01-01

    Regenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed whole-genome mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescently labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulates mol expression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by whole-genome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth. PMID:28753614

  14. Key Aroma Compounds in Smoked Cooked Loin.

    PubMed

    Kosowska, Monika; Majcher, Małgorzata A; Jeleń, Henryk H; Fortuna, Teresa

    2018-04-11

    Smoked cooked loin is one of the most popular meat products in Poland. In this study, key volatile compounds in this traditional Polish meat product were determined using gas chromatography-olfactometry and aroma extract dilution analysis (AEDA). In total, 27 odor-active volatile compounds were identified, with flavor dilution (FD) factors ranging from 4 to 1024, with the highest FD factors noted for 2-methoxyphenol, 2-methoxy-4-(prop-2-enyl)phenol, and 2-methoxy-4-( E)-(prop-1-en-1-yl)phenol. Results of the quantitative analyses based on determinations with stable isotope dilution assays (SIDAs) and standard addition (SA), followed by calculations of the odor activity value (OAV), enabled identifying 24 of the volatile compounds responsible for flavor development in the analyzed smoked cooked loin. The highest OAVs were obtained for 2-methoxyphenol, 2-methyl-3-furanthiol, 1-octen-3-one, and 2-methyl-3-(methyldithio)furan.

  15. Morphological elucidation of basal ganglia circuits contributing reward prediction

    PubMed Central

    Fujiyama, Fumino; Takahashi, Susumu; Karube, Fuyuki

    2015-01-01

    Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor–critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. PMID:25698913

  16. Metabolic analyses elucidate non-trivial gene targets for amplifying dihydroartemisinic acid production in yeast

    PubMed Central

    Misra, Ashish; Conway, Matthew F.; Johnnie, Joseph; Qureshi, Tabish M.; Lige, Bao; Derrick, Anne M.; Agbo, Eddy C.; Sriram, Ganesh

    2013-01-01

    Synthetic biology enables metabolic engineering of industrial microbes to synthesize value-added molecules. In this, a major challenge is the efficient redirection of carbon to the desired metabolic pathways. Pinpointing strategies toward this goal requires an in-depth investigation of the metabolic landscape of the organism, particularly primary metabolism, to identify precursor and cofactor availability for the target compound. The potent antimalarial therapeutic artemisinin and its precursors are promising candidate molecules for production in microbial hosts. Recent advances have demonstrated the production of artemisinin precursors in engineered yeast strains as an alternative to extraction from plants. We report the application of in silico and in vivo metabolic pathway analyses to identify metabolic engineering targets to improve the yield of the direct artemisinin precursor dihydroartemisinic acid (DHA) in yeast. First, in silico extreme pathway (ExPa) analysis identified NADPH-malic enzyme and the oxidative pentose phosphate pathway (PPP) as mechanisms to meet NADPH demand for DHA synthesis. Next, we compared key DHA-synthesizing ExPas to the metabolic flux distributions obtained from in vivo 13C metabolic flux analysis of a DHA-synthesizing strain. This comparison revealed that knocking out ethanol synthesis and overexpressing glucose-6-phosphate dehydrogenase in the oxidative PPP (gene YNL241C) or the NADPH-malic enzyme ME2 (YKL029C) are vital steps toward overproducing DHA. Finally, we employed in silico flux balance analysis and minimization of metabolic adjustment on a yeast genome-scale model to identify gene knockouts for improving DHA yields. The best strategy involved knockout of an oxaloacetate transporter (YKL120W) and an aspartate aminotransferase (YKL106W), and was predicted to improve DHA yields by 70-fold. Collectively, our work elucidates multiple non-trivial metabolic engineering strategies for improving DHA yield in yeast. PMID:23898325

  17. Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

    PubMed

    Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

    2013-07-01

    Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

  18. Thioredoxin plays a key role in retinal neuropathy prior to endothelial damage in diabetic mice

    PubMed Central

    Ren, Xiang; Li, Chen; Liu, Junli; Zhang, Chenghong; Fu, Yuzhen; Wang, Nina; Ma, Haiying; Lu, Heyuan; Kong, Hui; Kong, Li

    2017-01-01

    Diabetes is a chronic metabolic syndrome that results in changes in carbohydrate, lipid and protein metabolism. With diabetes for a long time, it increases the risk of diabetic retinopathy (DR) and long-term morbidity and mortality. Moreover, emerging evidence suggests that neuron damage occurs earlier than microvascular complications in DR patients, but the underlying mechanism is unclear. We investigated diabetes-induced retinal neuropathy and elucidated key molecular events to identify new therapeutic targets for the clinical treatment and prevention of DR. For in vivo studies, a high-fat diet and streptozotocin (STZ) injection were used to generate the diabetes model. Hematoxylin-eosin staining was used for morphological observations and measurements of the outer nuclear layer thickness. Electroretinography (ERG) was used to assess retinal function. For in vitro studies, Neuro2a cells were incubated in normal (5.5 mM) and high-glucose (30 mM) conditions. Flow cytometry assays were performed to analyze apoptosis. Additionally, real-time PCR and Western blotting analyses were carried out to determine gene and protein expression in vitro and in vivo. Taken together, the results indicated that retinal neuropathy occurred prior to endothelial damage induced by diabetes, and thioredoxin (Trx) plays a key role in this process. This underlying mechanism may be related to activation of the Trx/ASK1/p-p38/Trx-interacting protein pathway. PMID:28977868

  19. Quantum dense key distribution

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

    Degiovanni, I.P.; Ruo Berchera, I.; Castelletto, S.

    2004-03-01

    This paper proposes a protocol for quantum dense key distribution. This protocol embeds the benefits of a quantum dense coding and a quantum key distribution and is able to generate shared secret keys four times more efficiently than the Bennet-Brassard 1984 protocol. We hereinafter prove the security of this scheme against individual eavesdropping attacks, and we present preliminary experimental results, showing its feasibility.

  20. Secretome analysis to elucidate metalloprotease-dependent ectodomain shedding of glycoproteins during neuronal differentiation.

    PubMed

    Tsumagari, Kazuya; Shirakabe, Kyoko; Ogura, Mayu; Sato, Fuminori; Ishihama, Yasushi; Sehara-Fujisawa, Atsuko

    2017-02-01

    Many membrane proteins are subjected to limited proteolyses at their juxtamembrane regions, processes referred to as ectodomain shedding. Shedding ectodomains of membrane-bound ligands results in activation of downstream signaling pathways, whereas shedding those of cell adhesion molecules causes loss of cell-cell contacts. Secreted proteomics (secretomics) using high-resolution mass spectrometry would be strong tools for both comprehensive identification and quantitative measurement of membrane proteins that undergo ectodomain shedding. In this study, to elucidate the ectodomain shedding events that occur during neuronal differentiation, we establish a strategy for quantitative secretomics of glycoproteins released from differentiating neuroblastoma cells into culture medium with or without GM6001, a broad-spectrum metalloprotease inhibitor. Considering that most of transmembrane and secreted proteins are N-glycosylated, we include a process of N-glycosylated peptides enrichment as well as isotope tagging in our secretomics workflow. Our results show that differentiating N1E-115 neurons secrete numerous glycosylated polypeptides in metalloprotease-dependent manners. They are derived from cell adhesion molecules such as NCAM1, CADM1, L1CAM, various transporters and receptor proteins. These results show the landscape of ectodomain shedding and other secretory events in differentiating neurons and/or during axon elongation, which should help elucidate the mechanism of neurogenesis and the pathogenesis of neurological disorders. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  1. Transcription factor profiling reveals molecular choreography and key regulators of human retrotransposon expression

    PubMed Central

    Sun, Xiaoji; Wang, Xuya; Tang, Zuojian; Grivainis, Mark; Kahler, David; Yun, Chi; Mita, Paolo; Fenyö, David

    2018-01-01

    Transposable elements (TEs) represent a substantial fraction of many eukaryotic genomes, and transcriptional regulation of these factors is important to determine TE activities in human cells. However, due to the repetitive nature of TEs, identifying transcription factor (TF)-binding sites from ChIP-sequencing (ChIP-seq) datasets is challenging. Current algorithms are focused on subtle differences between TE copies and thus bias the analysis to relatively old and inactive TEs. Here we describe an approach termed “MapRRCon” (mapping repeat reads to a consensus) which allows us to identify proteins binding to TE DNA sequences by mapping ChIP-seq reads to the TE consensus sequence after whole-genome alignment. Although this method does not assign binding sites to individual insertions in the genome, it provides a landscape of interacting TFs by capturing factors that bind to TEs under various conditions. We applied this method to screen TFs’ interaction with L1 in human cells/tissues using ENCODE ChIP-seq datasets and identified 178 of the 512 TFs tested as bound to L1 in at least one biological condition with most of them (138) localized to the promoter. Among these L1-binding factors, we focused on Myc and CTCF, as they play important roles in cancer progression and 3D chromatin structure formation. Furthermore, we explored the transcriptomes of The Cancer Genome Atlas breast and ovarian tumor samples in which a consistent anti-/correlation between L1 and Myc/CTCF expression was observed, suggesting that these two factors may play roles in regulating L1 transcription during the development of such tumors. PMID:29802231

  2. [Neuropsychological approach to elucidating delusion and psychotic symptoms].

    PubMed

    Kato, Motoichiro

    2012-01-01

    Neuropsychological symptom-oriented approach is a critical method to elucidate delusion and psychotic symptoms in patients with focal brain damages and schizophrenia. In Capgras delusion (CD), the delusional misidentification of familiar people disguised as others, the patients with right amygdala damage and bilateral ventromedial prefrontal lesions have a deficient or reduced emotional valence of the person with intact configurational processes of the face. Reduplicative paramnesia (RP) is a specific phenomenon characterized by subjective certainty that a familiar place or person has been duplicated. Clinical evidences indicated that the patient with RP following right prefrontal damages showed the lack of emotional valence for the present hospital. This abnormal sense of familiarity triggered the deficits of the orientation of self to the outside world, that is, double orientation, resulting in the development of geographical reduplicative paramnesia. In line with the pathogenesis of CD and RP after brain damages, the delusion in schizophrenia may have a germ as developmental origins, which include the aberrant or salient perceptual experiences and abnormal sense of agency, and might be further aggravated by the impairment of causal reasoning process such as the jumping-to-conclusions bias.

  3. 33 CFR 110.189a - Key West Harbor, Key West, Fla., naval explosives anchorage area.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Key West Harbor, Key West, Fla..., DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.189a Key West Harbor, Key West, Fla., naval explosives anchorage area. (a) The anchorage ground. A circular area with its...

  4. 33 CFR 110.189a - Key West Harbor, Key West, Fla., naval explosives anchorage area.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Key West Harbor, Key West, Fla..., DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.189a Key West Harbor, Key West, Fla., naval explosives anchorage area. (a) The anchorage ground. A circular area with its...

  5. 33 CFR 110.189a - Key West Harbor, Key West, Fla., naval explosives anchorage area.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Key West Harbor, Key West, Fla..., DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.189a Key West Harbor, Key West, Fla., naval explosives anchorage area. (a) The anchorage ground. A circular area with its...

  6. 33 CFR 110.189a - Key West Harbor, Key West, Fla., naval explosives anchorage area.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Key West Harbor, Key West, Fla..., DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.189a Key West Harbor, Key West, Fla., naval explosives anchorage area. (a) The anchorage ground. A circular area with its...

  7. 33 CFR 110.189a - Key West Harbor, Key West, Fla., naval explosives anchorage area.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Key West Harbor, Key West, Fla..., DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.189a Key West Harbor, Key West, Fla., naval explosives anchorage area. (a) The anchorage ground. A circular area with its...

  8. PDZ binding to the BAR domain of PICK1 is elucidated by coarse-grained molecular dynamics.

    PubMed

    He, Yi; Liwo, Adam; Weinstein, Harel; Scheraga, Harold A

    2011-01-07

    A key regulator of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor traffic, PICK1 is known to interact with over 40 other proteins, including receptors, transporters and ionic channels, and to be active mostly as a homodimer. The current lack of a complete PICK1 structure determined at atomic resolution hinders the elucidation of its functional mechanisms. Here, we identify interactions between the component PDZ and BAR domains of PICK1 by calculating possible binding sites for the PDZ domain of PICK1 (PICK1-PDZ) to the homology-modeled, crescent-shaped dimer of the PICK1-BAR domain using multiplexed replica-exchange molecular dynamics (MREMD) and canonical molecular dynamics simulations with the coarse-grained UNRES force field. The MREMD results show that the preferred binding site for the single PDZ domain is the concave cavity of the BAR dimer. A second possible binding site is near the N-terminus of the BAR domain that is linked directly to the PDZ domain. Subsequent short canonical molecular dynamics simulations used to determine how the PICK1-PDZ domain moves to the preferred binding site on the BAR domain of PICK1 revealed that initial hydrophobic interactions drive the progress of the simulated binding. Thus, the concave face of the BAR dimer accommodates the PDZ domain first by weak hydrophobic interactions and then the PDZ domain slides to the center of the concave face, where more favorable hydrophobic interactions take over. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Susceptibility to Phytophthora ramorum in a key infectious host: landscape variation in host genotype, host phenotype, and environmental factors.

    PubMed

    Anacker, Brian L; Rank, Nathan E; Hüberli, Daniel; Garbelotto, Matteo; Gordon, Sarah; Harnik, Tami; Whitkus, Richard; Meentemeyer, Ross

    2008-01-01

    Sudden oak death is an emerging forest disease caused by the invasive pathogen Phytophthora ramorum. Genetic and environmental factors affecting susceptibility to P. ramorum in the key inoculum-producing host tree Umbellularia californica (bay laurel) were examined across a heterogeneous landscape in California, USA. Laboratory susceptibility trials were conducted on detached leaves and assessed field disease levels for 97 host trees from 12 225-m(2) plots. Genotype and phenotype characteristics were assessed for each tree. Effects of plot-level environmental conditions (understory microclimate, amount of solar radiation and topographic moisture potential) on disease expression were also evaluated. Susceptibility varied significantly among U. californica trees, with a fivefold difference in leaf lesion size. Lesion size was positively related to leaf area, but not to other phenotypic traits or to field disease level. Genetic diversity was structured at three spatial scales, but primarily among individuals within plots. Lesion size was significantly related to amplified fragment length polymorphism (AFLP) markers, but local environment explained most variation in field disease level. Thus, substantial genetic variation in susceptibility to P. ramorum occurs in its principal foliar host U. californica, but local environment mediates expression of susceptibility in nature.

  10. Proton Gradients as a Key Physical Factor in the Evolution of the Forced Transport Mechanism Across the Lipid Membrane.

    PubMed

    Strbak, Oliver; Kanuchova, Zuzana; Krafcik, Andrej

    2016-11-01

    A critical phase in the transition from prebiotic chemistry to biological evolution was apparently an asymmetric ion flow across the lipid membrane. Due to imbalance in the ion flow, the early lipid vesicles could selectively take the necessary molecules from the environment, and release the side-products from the vesicle. Natural proton gradients played a definitively crucial role in this process, since they remain the basis of energy transfer in the present-day cells. On the basis of this supposition, and the premise of the early vesicle membrane's impermeability to protons, we have shown that the emergence of the proton gradient in the lipid vesicle could be a key physical factor in the evolution of the forced transport mechanism (pore formation and active transport) across the lipid bilayer. This driven flow of protons across the membrane is the result of the electrochemical proton gradient and osmotic pressures on the integrity of the lipid vesicle. At a critical number of new lipid molecules incorporated into the vesicle, the energies associated with the creation of the proton gradient exceed the bending stiffness of the lipid membrane, and overlap the free energy of the lipid bilayer pore formation.

  11. Approaches to a global quantum key distribution network

    NASA Astrophysics Data System (ADS)

    Islam, Tanvirul; Bedington, Robert; Ling, Alexander

    2017-10-01

    Progress in realising quantum computers threatens to weaken existing public key encryption infrastructure. A global quantum key distribution (QKD) network can play a role in computational attack-resistant encryption. Such a network could use a constellation of high altitude platforms such as airships and satellites as trusted nodes to facilitate QKD between any two points on the globe on demand. This requires both space-to-ground and inter-platform links. However, the prohibitive cost of traditional satellite based development limits the experimental work demonstrating relevant technologies. To accelerate progress towards a global network, we use an emerging class of shoe-box sized spacecraft known as CubeSats. We have designed a polarization entangled photon pair source that can operate on board CubeSats. The robustness and miniature form factor of our entanglement source makes it especially suitable for performing pathfinder missions that studies QKD between two high altitude platforms. The technological outcomes of such mission would be the essential building blocks for a global QKD network.

  12. Image encryption using fingerprint as key based on phase retrieval algorithm and public key cryptography

    NASA Astrophysics Data System (ADS)

    Zhao, Tieyu; Ran, Qiwen; Yuan, Lin; Chi, Yingying; Ma, Jing

    2015-09-01

    In this paper, a novel image encryption system with fingerprint used as a secret key is proposed based on the phase retrieval algorithm and RSA public key algorithm. In the system, the encryption keys include the fingerprint and the public key of RSA algorithm, while the decryption keys are the fingerprint and the private key of RSA algorithm. If the users share the fingerprint, then the system will meet the basic agreement of asymmetric cryptography. The system is also applicable for the information authentication. The fingerprint as secret key is used in both the encryption and decryption processes so that the receiver can identify the authenticity of the ciphertext by using the fingerprint in decryption process. Finally, the simulation results show the validity of the encryption scheme and the high robustness against attacks based on the phase retrieval technique.

  13. Decoding the non-coding genome: elucidating genetic risk outside the coding genome.

    PubMed

    Barr, C L; Misener, V L

    2016-01-01

    Current evidence emerging from genome-wide association studies indicates that the genetic underpinnings of complex traits are likely attributable to genetic variation that changes gene expression, rather than (or in combination with) variation that changes protein-coding sequences. This is particularly compelling with respect to psychiatric disorders, as genetic changes in regulatory regions may result in differential transcriptional responses to developmental cues and environmental/psychosocial stressors. Until recently, however, the link between transcriptional regulation and psychiatric genetic risk has been understudied. Multiple obstacles have contributed to the paucity of research in this area, including challenges in identifying the positions of remote (distal from the promoter) regulatory elements (e.g. enhancers) and their target genes and the underrepresentation of neural cell types and brain tissues in epigenome projects - the availability of high-quality brain tissues for epigenetic and transcriptome profiling, particularly for the adolescent and developing brain, has been limited. Further challenges have arisen in the prediction and testing of the functional impact of DNA variation with respect to multiple aspects of transcriptional control, including regulatory-element interaction (e.g. between enhancers and promoters), transcription factor binding and DNA methylation. Further, the brain has uncommon DNA-methylation marks with unique genomic distributions not found in other tissues - current evidence suggests the involvement of non-CG methylation and 5-hydroxymethylation in neurodevelopmental processes but much remains unknown. We review here knowledge gaps as well as both technological and resource obstacles that will need to be overcome in order to elucidate the involvement of brain-relevant gene-regulatory variants in genetic risk for psychiatric disorders. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  14. Assessment of Human Factors

    NASA Technical Reports Server (NTRS)

    Mount, Frances; Foley, Tico

    1999-01-01

    Human Factors Engineering, often referred to as Ergonomics, is a science that applies a detailed understanding of human characteristics, capabilities, and limitations to the design, evaluation, and operation of environments, tools, and systems for work and daily living. Human Factors is the investigation, design, and evaluation of equipment, techniques, procedures, facilities, and human interfaces, and encompasses all aspects of human activity from manual labor to mental processing and leisure time enjoyments. In spaceflight applications, human factors engineering seeks to: (1) ensure that a task can be accomplished, (2) maintain productivity during spaceflight, and (3) ensure the habitability of the pressurized living areas. DSO 904 served as a vehicle for the verification and elucidation of human factors principles and tools in the microgravity environment. Over six flights, twelve topics were investigated. This study documented the strengths and limitations of human operators in a complex, multifaceted, and unique environment. By focusing on the man-machine interface in space flight activities, it was determined which designs allow astronauts to be optimally productive during valuable and costly space flights. Among the most promising areas of inquiry were procedures, tools, habitat, environmental conditions, tasking, work load, flexibility, and individual control over work.

  15. The fundamentals behind solving for unknown molecular structures using computer-assisted structure elucidation: a free software package at the undergraduate and graduate levels.

    PubMed

    Moser, Arvin; Pautler, Brent G

    2016-05-15

    The successful elucidation of an unknown compound's molecular structure often requires an analyst with profound knowledge and experience of advanced spectroscopic techniques, such as Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. The implementation of Computer-Assisted Structure Elucidation (CASE) software in solving for unknown structures, such as isolated natural products and/or reaction impurities, can serve both as elucidation and teaching tools. As such, the introduction of CASE software with 112 exercises to train students in conjunction with the traditional pen and paper approach will strengthen their overall understanding of solving unknowns and explore of various structural end points to determine the validity of the results quickly. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Limitations on quantum key repeaters.

    PubMed

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  17. Direction-dependent force-induced dissociation dynamics of an entropic-driven lock-and-key assembly.

    PubMed

    Chen, Yen-Fu; Chen, Hsuan-Yi; Sheng, Yu-Jane; Tsao, Heng-Kwong

    2017-09-01

    The unbinding dynamics of a nanosized sphere-and-cavity assembly under the pulling of constant force and constant loading rate is explored by dissipative particle dynamics simulations. The formation of this matched lock-and-key pair in a polymer solution is driven by the depletion attraction. The two-dimensional free energy landscape U(x,z) associated with this assembly is constructed. Our results indicate that the unbinding pathway along the orientation of the assembly is unfavorable due to the relatively high energy barrier compared to that along the tortuous minimum path whose energy barrier is not high. It is also found that the dissociation rate depends on the direction of the external force (θ) with respect to the assembly orientation. The presence of the force component perpendicular to the assembly orientation can reduce the bond lifetime significantly by driving the key particle to approach the minimum path. Moreover, the dissociation dynamics can be facilitated even by a pushing force compared to the spontaneous dissociation (without forces). To elucidate the effective pathway under pulling, the escaping position is analyzed and its mean direction with respect to the assembly orientation rises generally with increasing θ, revealing that the presence of the force component along the minimum pathway is helpful. The importance of the direction of the external pulling has been demonstrated in our simple system. Therefore, this effect should be considered in more complicated unbinding experiments.

  18. Direction-dependent force-induced dissociation dynamics of an entropic-driven lock-and-key assembly

    NASA Astrophysics Data System (ADS)

    Chen, Yen-Fu; Chen, Hsuan-Yi; Sheng, Yu-Jane; Tsao, Heng-Kwong

    2017-09-01

    The unbinding dynamics of a nanosized sphere-and-cavity assembly under the pulling of constant force and constant loading rate is explored by dissipative particle dynamics simulations. The formation of this matched lock-and-key pair in a polymer solution is driven by the depletion attraction. The two-dimensional free energy landscape U (x ,z ) associated with this assembly is constructed. Our results indicate that the unbinding pathway along the orientation of the assembly is unfavorable due to the relatively high energy barrier compared to that along the tortuous minimum path whose energy barrier is not high. It is also found that the dissociation rate depends on the direction of the external force (θ ) with respect to the assembly orientation. The presence of the force component perpendicular to the assembly orientation can reduce the bond lifetime significantly by driving the key particle to approach the minimum path. Moreover, the dissociation dynamics can be facilitated even by a pushing force compared to the spontaneous dissociation (without forces). To elucidate the effective pathway under pulling, the escaping position is analyzed and its mean direction with respect to the assembly orientation rises generally with increasing θ , revealing that the presence of the force component along the minimum pathway is helpful. The importance of the direction of the external pulling has been demonstrated in our simple system. Therefore, this effect should be considered in more complicated unbinding experiments.

  19. Extending key sharing: how to generate a key tightly coupled to a network security policy

    NASA Astrophysics Data System (ADS)

    Kazantzidis, Matheos

    2006-04-01

    Current state of the art security policy technologies, besides the small scale limitation and largely manual nature of accompanied management methods, are lacking a) in real-timeliness of policy implementation and b) vulnerabilities and inflexibility stemming from the centralized policy decision making; even if, for example, a policy description or access control database is distributed, the actual decision is often a centralized action and forms a system single point of failure. In this paper we are presenting a new fundamental concept that allows implement a security policy by a systematic and efficient key distribution procedure. Specifically, we extend the polynomial Shamir key splitting. According to this, a global key is split into n parts, any k of which can re-construct the original key. In this paper we present a method that instead of having "any k parts" be able to re-construct the original key, the latter can only be reconstructed if keys are combined as any access control policy describes. This leads into an easily deployable key generation procedure that results a single key per entity that "knows" its role in the specific access control policy from which it was derived. The system is considered efficient as it may be used to avoid expensive PKI operations or pairwise key distributions as well as provides superior security due to its distributed nature, the fact that the key is tightly coupled to the policy, and that policy change may be implemented easier and faster.

  20. Logic programming reveals alteration of key transcription factors in multiple myeloma.

    PubMed

    Miannay, Bertrand; Minvielle, Stéphane; Roux, Olivier; Drouin, Pierre; Avet-Loiseau, Hervé; Guérin-Charbonnel, Catherine; Gouraud, Wilfried; Attal, Michel; Facon, Thierry; Munshi, Nikhil C; Moreau, Philippe; Campion, Loïc; Magrangeas, Florence; Guziolowski, Carito

    2017-08-23

    Innovative approaches combining regulatory networks (RN) and genomic data are needed to extract biological information for a better understanding of diseases, such as cancer, by improving the identification of entities and thereby leading to potential new therapeutic avenues. In this study, we confronted an automatically generated RN with gene expression profiles (GEP) from a cohort of multiple myeloma (MM) patients and normal individuals using global reasoning on the RN causality to identify key-nodes. We modeled each patient by his or her GEP, the RN and the possible automatically detected repairs needed to establish a coherent flow of the information that explains the logic of the GEP. These repairs could represent cancer mutations leading to GEP variability. With this reasoning, unmeasured protein states can be inferred, and we can simulate the impact of a protein perturbation on the RN behavior to identify therapeutic targets. We showed that JUN/FOS and FOXM1 activities are altered in almost all MM patients and identified two survival markers for MM patients. Our results suggest that JUN/FOS-activation has a strong impact on the RN in view of the whole GEP, whereas FOXM1-activation could be an interesting way to perturb an MM subgroup identified by our method.

  1. Identifying key factors associated with aggression on acute inpatient psychiatric wards.

    PubMed

    Bowers, Len; Allan, Teresa; Simpson, Alan; Jones, Julia; Van Der Merwe, Marie; Jeffery, Debra

    2009-04-01

    Aggressive behaviour is a critical issue for modern acute psychiatric services, not just because of the adverse impact it has on patients and staff, but also because it puts a financial strain on service providers. The aim of this study was to assess the relationship of patient violence to other variables: patient characteristics, features of the service and physical environment, patient routines, staff factors, the use of containment methods, and other patient behaviours. A multivariate cross sectional design was utilised. Data were collected for a six month period on 136 acute psychiatric wards in 26 NHS Trusts in England. Multilevel modelling was conducted to ascertain those factors most strongly associated with verbal aggression, aggression toward objects, and physical aggression against others. High levels of aggression were associated with a high proportion of patients formally detained under mental health legislation, high patient turnover, alcohol use by patients, ward doors being locked, and higher staffing numbers (especially qualified nurses). The findings suggest that the imposition of restrictions on patients exacerbates the problem of violence, and that alcohol management strategies may be a productive intervention. Insufficient evidence is available to draw conclusions about the nature of the link between staffing numbers and violence.

  2. 46 CFR 7.100 - Florida Reefs and Keys from Miami, FL to Marquesas Keys, FL.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... latitude 24°27.7′ N. longitude 81°48.1′ W. (Key West Entrance Lighted Whistle Buoy); thence to Cosgrove... 46 Shipping 1 2014-10-01 2014-10-01 false Florida Reefs and Keys from Miami, FL to Marquesas Keys... TO THE PUBLIC BOUNDARY LINES Atlantic Coast § 7.100 Florida Reefs and Keys from Miami, FL to...

  3. 46 CFR 7.100 - Florida Reefs and Keys from Miami, FL to Marquesas Keys, FL.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... latitude 24°27.7′ N. longitude 81°48.1′ W. (Key West Entrance Lighted Whistle Buoy); thence to Cosgrove... 46 Shipping 1 2012-10-01 2012-10-01 false Florida Reefs and Keys from Miami, FL to Marquesas Keys... TO THE PUBLIC BOUNDARY LINES Atlantic Coast § 7.100 Florida Reefs and Keys from Miami, FL to...

  4. 46 CFR 7.100 - Florida Reefs and Keys from Miami, FL to Marquesas Keys, FL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... latitude 24°27.7′ N. longitude 81°48.1′ W. (Key West Entrance Lighted Whistle Buoy); thence to Cosgrove... 46 Shipping 1 2010-10-01 2010-10-01 false Florida Reefs and Keys from Miami, FL to Marquesas Keys... TO THE PUBLIC BOUNDARY LINES Atlantic Coast § 7.100 Florida Reefs and Keys from Miami, FL to...

  5. 46 CFR 7.100 - Florida Reefs and Keys from Miami, FL to Marquesas Keys, FL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... latitude 24°27.7′ N. longitude 81°48.1′ W. (Key West Entrance Lighted Whistle Buoy); thence to Cosgrove... 46 Shipping 1 2011-10-01 2011-10-01 false Florida Reefs and Keys from Miami, FL to Marquesas Keys... TO THE PUBLIC BOUNDARY LINES Atlantic Coast § 7.100 Florida Reefs and Keys from Miami, FL to...

  6. 46 CFR 7.100 - Florida Reefs and Keys from Miami, FL to Marquesas Keys, FL.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... latitude 24°27.7′ N. longitude 81°48.1′ W. (Key West Entrance Lighted Whistle Buoy); thence to Cosgrove... 46 Shipping 1 2013-10-01 2013-10-01 false Florida Reefs and Keys from Miami, FL to Marquesas Keys... TO THE PUBLIC BOUNDARY LINES Atlantic Coast § 7.100 Florida Reefs and Keys from Miami, FL to...

  7. Ravynic acid, an antibiotic polyeneyne tetramic acid from Penicillium sp. elucidated through synthesis.

    PubMed

    Myrtle, J D; Beekman, A M; Barrow, R A

    2016-09-21

    A new antibiotic natural product, ravynic acid, has been isolated from a Penicillium sp. of fungus, collected from Ravensbourne National Park. The 3-acylpolyenyne tetramic acid structure was definitively elucidated via synthesis. Highlights of the synthetic method include the heat induced formation of the 3-acylphosphorane tetramic acid and a selective Wittig cross-coupling to efficiently prepare the natural compounds carbon skeleton. The natural compound was shown to inhibit the growth of Staphylococcus aureus down to concentrations of 2.5 µg mL(-1).

  8. Effects of Psychological and Social Factors in Shiftwork on Symptoms of Anxiety and Depression in Nurses: A 1-Year Follow-Up.

    PubMed

    Berthelsen, Mona; Pallesen, Ståle; Magerøy, Nils; Tyssen, Reidar; Bjorvatn, Bjørn; Moen, Bente Elisabeth; Knardahl, Stein

    2015-10-01

    The aim of the current study was to elucidate prospective effects of both shift schedules and work environment on mental distress. A total of 2059 nurses participated at baseline (38.1%), and 1582 nurses completed wave 2 of the survey (76.8%). Psychosocial work factors were measured by the General Nordic Questionnaire for Psychological and Social factors at work and the Swedish Demand-Control-Support Questionnaire. Mental distress was measured by Hospital Anxiety and Depression Scale. Shiftwork was not associated with "caseness" anxiety or depression. Effects of shiftwork on mental distress were not moderated by psychosocial work factors. Mental distress predicted role clarity, role conflict, fair leadership, and social support. Job demands predicted symptoms of depression. Whether psychosocial working conditions buffer mental health effects of shiftwork remains undecided. Prospective studies with multiple measurement points are needed to elucidate potential mutual relationships between work factors and mental distress.

  9. Stress in hospital medicine: a problem for key hospital staff.

    PubMed

    Allen, I

    2001-08-01

    Many factors which contribute to stress in the workplace apply to both consultants and ward sisters. Both groups find that their roles have become more complex while they have increasingly lost control of their own clinical and professional territory in a managerial culture. The erosion of the key relationship between consultants and ward sisters is of concern and the need for teamworking is insufficiently recognized.

  10. Identification of the Key Fields and Their Key Technical Points of Oncology by Patent Analysis.

    PubMed

    Zhang, Ting; Chen, Juan; Jia, Xiaofeng

    2015-01-01

    This paper aims to identify the key fields and their key technical points of oncology by patent analysis. Patents of oncology applied from 2006 to 2012 were searched in the Thomson Innovation database. The key fields and their key technical points were determined by analyzing the Derwent Classification (DC) and the International Patent Classification (IPC), respectively. Patent applications in the top ten DC occupied 80% of all the patent applications of oncology, which were the ten fields of oncology to be analyzed. The number of patent applications in these ten fields of oncology was standardized based on patent applications of oncology from 2006 to 2012. For each field, standardization was conducted separately for each of the seven years (2006-2012) and the mean of the seven standardized values was calculated to reflect the relative amount of patent applications in that field; meanwhile, regression analysis using time (year) and the standardized values of patent applications in seven years (2006-2012) was conducted so as to evaluate the trend of patent applications in each field. Two-dimensional quadrant analysis, together with the professional knowledge of oncology, was taken into consideration in determining the key fields of oncology. The fields located in the quadrant with high relative amount or increasing trend of patent applications are identified as key ones. By using the same method, the key technical points in each key field were identified. Altogether 116,820 patents of oncology applied from 2006 to 2012 were retrieved, and four key fields with twenty-nine key technical points were identified, including "natural products and polymers" with nine key technical points, "fermentation industry" with twelve ones, "electrical medical equipment" with four ones, and "diagnosis, surgery" with four ones. The results of this study could provide guidance on the development direction of oncology, and also help researchers broaden innovative ideas and discover new

  11. Resilience in homeless youth: the key role of self-esteem.

    PubMed

    Kidd, Sean; Shahar, Golan

    2008-04-01

    This study examined the protective role of self-esteem, social involvement, and secure attachment among homeless youths. These protective factors were examined as they ameliorate risks among 208 homeless youths surveyed in New York City and Toronto. Both mental and physical health indicators were employed in this study, including loneliness, feeling trapped, suicidal ideation, subjective health status, and substance use. Self-esteem emerged as a key protective factor, predicting levels of loneliness, feeling trapped, and suicide ideation, and buffering against the deleterious effect of fearful attachment on loneliness. Findings highlight the role of the self-concept in risk and resilience among homeless youth. Copyright 2008 APA, all rights reserved.

  12. A qualitative investigation into key cultural factors that support abstinence or responsible drinking amongst some Pacific youth living in New Zealand

    PubMed Central

    2012-01-01

    Background Abstinence and responsible drinking are not typically associated with youth drinking culture. Amongst Pacific youth in New Zealand there are high numbers, compared to the general New Zealand population, who choose not to consume alcohol. The Pacific youth population is made up of several ethnic groups; their ethno-cultural values are largely Polynesian and heavily influenced by the socio-economic realities of living in New Zealand. This paper explores factors that support abstinence or responsible drinking amongst Pacific youth living in Auckland. Methods A qualitative study comprised of a series of ethnically-, age-, and gender-matched semi-structured focus group discussions with 69 Pacific youth, aged 15-25 years from a university and selected high-schools. Participants were purposively sampled. Results Key cultural factors that contributed to whether Pacific youth participants were abstinent or responsible drinkers were: significant experiences within Pacific family environments (e.g. young person directly links their decision about alcohol consumption to a positive or negative role model); awareness of the belief that their actions as children of Pacific parents affects the reputation and standing of their Pacific family and community (e.g. church); awareness of traditional Pacific values of respect, reciprocity and cultural taboos (e.g. male–female socialising); commitment to no-alcohol teachings of church or religious faith; having peer support and experiences that force them to consider negative effects of excessive alcohol consumption; and personal awareness that being part of an (excessive) drinking culture may seriously affect health or impede career aspirations. Conclusions The narratives offered by Pacific young people highlighted three key communities of influence: family (immediate and extended, but especially siblings), peers and church. Young people negotiated through these communities of influence their decisions whether to drink

  13. Gene-Environment Interplay in Internalizing Disorders: Consistent Findings across Six Environmental Risk Factors

    ERIC Educational Resources Information Center

    Hicks, Brian M.; Dirago, Ana C.; Iacono, William G.; McGue, Matt

    2009-01-01

    Background: Behavior genetic methods can help to elucidate gene-environment (G-E) interplay in the development of internalizing (INT) disorders (i.e., major depression and anxiety disorders). To date, however, no study has conducted a comprehensive analysis examining multiple environmental risk factors with the purpose of delineating general…

  14. Integrated RNA-Seq and sRNA-Seq Analysis Identifies Chilling and Freezing Responsive Key Molecular Players and Pathways in Tea Plant (Camellia sinensis).

    PubMed

    Zheng, Chao; Zhao, Lei; Wang, Yu; Shen, Jiazhi; Zhang, Yinfei; Jia, Sisi; Li, Yusheng; Ding, Zhaotang

    2015-01-01

    Tea [Camellia sinensis (L) O. Kuntze, Theaceae] is one of the most popular non-alcoholic beverages worldwide. Cold stress is one of the most severe abiotic stresses that limit tea plants' growth, survival and geographical distribution. However, the genetic regulatory network and signaling pathways involved in cold stress responses in tea plants remain unearthed. Using RNA-Seq, DGE and sRNA-Seq technologies, we performed an integrative analysis of miRNA and mRNA expression profiling and their regulatory network of tea plants under chilling (4℃) and freezing (-5℃) stress. Differentially expressed (DE) miRNA and mRNA profiles were obtained based on fold change analysis, miRNAs and target mRNAs were found to show both coherent and incoherent relationships in the regulatory network. Furthermore, we compared several key pathways (e.g., 'Photosynthesis'), GO terms (e.g., 'response to karrikin') and transcriptional factors (TFs, e.g., DREB1b/CBF1) which were identified as involved in the early chilling and/or freezing response of tea plants. Intriguingly, we found that karrikins, a new group of plant growth regulators, and β-primeverosidase (BPR), a key enzyme functionally relevant with the formation of tea aroma might play an important role in both early chilling and freezing response of tea plants. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis further confirmed the results from RNA-Seq and sRNA-Seq analysis. This is the first study to simultaneously profile the expression patterns of both miRNAs and mRNAs on a genome-wide scale to elucidate the molecular mechanisms of early responses of tea plants to cold stress. In addition to gaining a deeper insight into the cold resistant characteristics of tea plants, we provide a good case study to analyse mRNA/miRNA expression and profiling of non-model plant species using next-generation sequencing technology.

  15. Key factors affecting urban runoff pollution under cold climatic conditions

    NASA Astrophysics Data System (ADS)

    Valtanen, Marjo; Sillanpää, Nora; Setälä, Heikki

    2015-10-01

    Urban runoff contains various pollutants and has the potential of deteriorating the quality of aquatic ecosystems. In this study our objective is to shed light on the factors that control the runoff water quality in urbanized catchments. The effects of runoff event characteristics, land use type and catchment imperviousness on event mass loads (EML) and event mean concentrations (EMC) were studied during warm and cold periods in three study catchments (6.1, 6.5 and 12.6 ha in size) in the city of Lahti, Finland. Runoff and rainfall were measured continuously for two years at each catchment. Runoff samples were taken for total nutrients (tot-P and tot-N), total suspended solids (TSS), heavy metals (Zn, Cr, Al, Co, Ni, Cu, Pb, Mn) and total organic carbon (TOC). Stepwise multiple linear regression analysis (SMLR) was used to identify general relationships between the following variables: event water quality, runoff event characteristics and catchment characteristics. In general, the studied variables explained 50-90% of the EMLs but only 30-60% of the EMCs, with runoff duration having an important role in most of the SMLR models. Mean runoff intensity or peak flow was also often included in the runoff quality models. Yet, the importance (being the first, second or third best) and role (negative or positive impact) of the explanatory variables varied between the cold and warm period. Land use type often explained cold period concentrations, but imperviousness alone explained EMCs weakly. As for EMLs, the influence of imperviousness and/or land use was season and pollutant dependent. The study suggests that pollutant loads can be - throughout the year - adequately predicted by runoff characteristics given that seasonal differences are taken into account. Although pollutant concentrations were sensitive to variation in seasonal and catchment conditions as well, the accurate estimation of EMCs would require a more complete set of explanatory factors than used in this

  16. Molecular characterization and mRNA expression of two key enzymes of hypoxia-sensing pathways in eastern oysters Crassostrea virginica (Gmelin): Hypoxia-inducible factor α (HIF-α) and HIF-prolyl hydroxylase (PHD)

    PubMed Central

    Piontkivska, Helen; Chung, J. Sook; Ivanina, Anna V.; Sokolov, Eugene P.; Techa, Sirinart; Sokolova, Inna M.

    2010-01-01

    Oxygen homeostasis is crucial for development, survival and normal function of all metazoans. A family of transcription factors called hypoxia-inducible factors (HIF) is critical in mediating the adaptive responses to reduced oxygen availability. The HIF transcription factor consists of a constitutively expressed β subunit and an oxygen-dependent α subunit; the abundance of the latter determines the activity of HIF and is regulated by a family of O2- and Fe2+-dependent enzymes prolyl hydroxylases (PHDs). Currently very little is known about the function of this important pathway and the molecular structure of its key players in hypoxia-tolerant intertidal mollusks including oysters, which are among the animal champions of anoxic and hypoxic tolerance and thus can serve as excellent models to study the role of HIF cascade in adaptations to oxygen deficiency. We have isolated transcripts of two key components of the oxygen sensing pathway - the oxygen-regulated HIF-α subunit and PHD - from an intertidal mollusk, the eastern oyster Crassostrea virginica, and determined the transcriptional responses of these two genes to anoxia, hypoxia and cadmium (Cd) stress. HIF-α and PHD homologs from eastern oysters C. virginica show significant sequence similarity and share key functional domains with the earlier described isoforms from vertebrates and invertebrates. Phylogenetic analysis shows that genetic diversification of HIF and PHD isoforms occurred within the vertebrate lineage indicating functional diversification and specialization of the oxygen-sensing pathways in this group, which parallels situation observed for many other important genes. HIF-α and PHD homologs are broadly expressed at the mRNA level in different oyster tissues and show transcriptional responses to prolonged hypoxia in the gills consistent with their putative role in oxygen sensing and the adaptive response to hypoxia. Similarity in amino acid sequence, domain structure and transcriptional

  17. Coloring attributes of betalains: a key emphasis on stability and future applications.

    PubMed

    Martins, Natália; Roriz, Custódio Lobo; Morales, Patricia; Barros, Lillian; Ferreira, Isabel C F R

    2017-04-19

    Organoleptic characteristics largely determine food acceptance, selection, and subsequent consumption. Therefore, food colorants are extremely important in the food industry. However, based on the latest findings related to the side effects and toxicity issues of some synthetic colorants, consumers worldwide have shown increasing interest in natural alternatives. Betalains are good examples of natural colorants and therefore the present study reviews the main sources of these pigments, their structural elucidation and biosynthetic pathways, their chemical instability to different environmental factors, as well as their potential uses at the industrial level and also for pharmaceutical and cosmetic purposes, due to their ability to act as functional ingredients and health enhancers/promoters. Betalain natural pigments represent a promising and safe alternative to synthetic dyes, but their chemical instability has limited their widespread use. Temperature, pH, water activity, oxygen, light, chelating agents, the presence of other compounds, pigment concentration, storage, and processing conditions are the most important factors affecting their stability. It is, therefore, very important to establish optimum processing conditions to maximize the stability of betalains and their extraction yields, focusing on their effective use as natural food colorants, functional ingredients and value-added food products.

  18. Elucidating the role of surface chemistry on cationic phosphorus dendrimer-siRNA complexation.

    PubMed

    Deriu, Marco A; Tsapis, Nicolas; Noiray, Magali; Grasso, Gianvito; El Brahmi, Nabil; Mignani, Serge; Majoral, Jean-Pierre; Fattal, Elias; Danani, Andrea

    2018-06-14

    In the field of dendrimers targeting small interfering RNA (siRNA) delivery, dendrimer structural properties, such as the flexibility/rigidity ratio, play a crucial role in the efficiency of complexation. However, advances in organic chemistry have enabled the development of dendrimers that differ only by a single atom on their surface terminals. This is the case for cationic phosphorus dendrimers functionalized with either pyrrolidinium (DP) or morpholinium (DM) terminal groups. This small change was shown to strongly affect the dendrimer-siRNA complexation, leading to more efficient anti-inflammatory effects in the case of DP. Reasons for this different behavior can hardly be inferred only by biological in vitro and in vivo experiments due to the high number of variables and complexity of the investigated biological system. However, an understanding of how small chemical surface changes may completely modify the overall dendrimer-siRNA complexation is a significant breakthrough towards the design of efficient dendrimers for nucleic acid delivery. Herein, we present experimental and computational approaches based on isothermal titration calorimetry and molecular dynamics simulations to elucidate the molecular reasons behind different efficiencies and activities of DP and DM. Results of the present research highlight how chemical surface modifications may drive the overall dendrimer-siRNA affinity by influencing enthalpic and entropic contributions of binding free energy. Moreover, this study elucidates molecular reasons related to complexation stoichiometry that may be crucial in determining the dendrimer complexation efficiency.

  19. Social Cognition and Executive Functions As Key Factors for Effective Pedagogy in Higher Education.

    PubMed

    Correia, Rut; Navarrete, Gorka

    2017-01-01

    Higher education (HE) faces the challenge of responding to an increasing diversity. In this context, more attention is being paid to teachers and teaching skills positively related to students learning. Beyond the knowledges identified as key components of an effective teacher, teachers also need to be capable of unraveling what their students think and believe, and how they accommodate the new information. More importantly, teachers need to be able to adapt their own teaching to their audience's needs. In learners, social cognition (SC) has been related to a better receptivity to the different teacher-student interactions. Since these interactions are bidirectional, SC could also help to explain teachers' receptiveness to the information available in feedback situations. However, little is known about how SC is related to teacher development, and therefore teaching effectiveness, in HE. In addition, executive functions (EFs), closely related to SC, could play a key role in the ability to self-regulate their own teaching to better answering their students emerging needs. Although there is wide evidence regarding the association of EFs to performance in high demanding settings, as far as we know, there are no studies exploring the relationship between teachers' EFs and teaching effectiveness in HE. Establishing a positive association between teaching effectiveness and these socio-cognitive functions could be a promising first step in designing professional development programs that promote HE academics' ability to understand and care about students thoughts and emotions, to eventually adapt their teaching to their students needs for a better learning.

  20. Oxidation and cyclization of casbene in the biosynthesis of Euphorbia factors from mature seeds of Euphorbia lathyris L.

    DOE PAGES

    Luo, Dan; Callari, Roberta; Hamberger, Britta; ...

    2016-08-09

    The seed oil of Euphorbia lathyris L. contains a series of macrocyclic diterpenoids known as Euphorbia factors. They are the current industrial source of ingenol mebutate, which is approved for the treatment of actinic keratosis, a precancerous skin condition. Here, we report an alcohol dehydrogenase-mediated cyclization step in the biosynthetic pathway of Euphorbia factors, illustrating the origin of the intramolecular carbon–carbon bonds present in lathyrane and ingenane diterpenoids. This unconventional cyclization describes the ring closure of the macrocyclic diterpene casbene. Through transcriptomic analysis of E. lathyris L. mature seeds and in planta functional characterization, we identified three enzymes involved inmore » the cyclization route from casbene to jolkinol C, a lathyrane diterpene. These enzymes include two cytochromes P450 from the CYP71 clan and an alcohol dehydrogenase (ADH). CYP71D445 and CYP726A27 catalyze regio-specific 9-oxidation and 5-oxidation of casbene, respectively. When coupled with these P450-catalyzed monooxygenations, E. lathyris ADH1 catalyzes dehydrogenation of the hydroxyl groups, leading to the subsequent rearrangement and cyclization. The discovery of this nonconventional cyclization may provide the key link to complete elucidation of the biosynthetic pathways of ingenol mebutate and other bioactive macrocyclic diterpenoids.« less