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Sample records for address multiple factors

  1. Adaptation of a Counseling Intervention to Address Multiple Cancer Risk Factors among Overweight/Obese Latino Smokers

    ERIC Educational Resources Information Center

    Castro, Yessenia; Fernández, Maria E.; Strong, Larkin L.; Stewart, Diana W.; Krasny, Sarah; Hernandez Robles, Eden; Heredia, Natalia; Spears, Claire A.; Correa-Fernández, Virmarie; Eakin, Elizabeth; Resnicow, Ken; Basen-Engquist, Karen; Wetter, David W.

    2015-01-01

    More than 60% of cancer-related deaths in the United States are attributable to tobacco use, poor nutrition, and physical inactivity, and these risk factors tend to cluster together. Thus, strategies for cancer risk reduction would benefit from addressing multiple health risk behaviors. We adapted an evidence-based intervention grounded in social…

  2. Adaptation of a counseling intervention to address multiple cancer risk factors among overweight/obese Latino smokers.

    PubMed

    Castro, Yessenia; Fernández, Maria E; Strong, Larkin L; Stewart, Diana W; Krasny, Sarah; Hernandez Robles, Eden; Heredia, Natalia; Spears, Claire A; Correa-Fernández, Virmarie; Eakin, Elizabeth; Resnicow, Ken; Basen-Engquist, Karen; Wetter, David W

    2015-02-01

    More than 60% of cancer-related deaths in the United States are attributable to tobacco use, poor nutrition, and physical inactivity, and these risk factors tend to cluster together. Thus, strategies for cancer risk reduction would benefit from addressing multiple health risk behaviors. We adapted an evidence-based intervention grounded in social cognitive theory and principles of motivational interviewing originally developed for smoking cessation to also address physical activity and fruit/vegetable consumption among Latinos exhibiting multiple health risk behaviors. Literature reviews, focus groups, expert consultation, pretesting, and pilot testing were used to inform adaptation decisions. We identified common mechanisms underlying change in smoking, physical activity, and diet used as treatment targets; identified practical models of patient-centered cross-cultural service provision; and identified that family preferences and support as particularly strong concerns among the priority population. Adaptations made to the original intervention are described. The current study is a practical example of how an intervention can be adapted to maximize relevance and acceptability and also maintain the core elements of the original evidence-based intervention. The intervention has significant potential to influence cancer prevention efforts among Latinos in the United States and is being evaluated in a sample of 400 Latino overweight/obese smokers. PMID:25527143

  3. Adaptation of a Counseling Intervention to Address Multiple Cancer Risk Factors Among Overweight/Obese Latino Smokers

    PubMed Central

    Castro, Yessenia; Fernández, Maria E.; Strong, Larkin L.; Stewart, Diana W.; Krasny, Sarah; Robles, Eden Hernandez; Heredia, Natalia; Spears, Claire A.; Correa-Fernández, Virmarie; Eakin, Elizabeth; Resnicow, Ken; Basen-Engquist, Karen; Wetter, David W.

    2015-01-01

    More than 60% of cancer-related deaths in the United States are attributable to tobacco use, poor nutrition, and physical inactivity, and these risk factors tend to cluster together. Thus, strategies for cancer risk reduction would benefit from addressing multiple health risk behaviors. We adapted an evidence-based intervention grounded in social cognitive theory and principles of motivational interviewing originally developed for smoking cessation to also address physical activity and fruit/vegetable consumption among Latinos exhibiting multiple health risk behaviors. Literature reviews, focus groups, expert consultation, pretesting, and pilot testing were used to inform adaptation decisions. We identified common mechanisms underlying change in smoking, physical activity, and diet used as treatment targets; identified practical models of patient-centered cross-cultural service provision; and identified that family preferences and support as particularly strong concerns among the priority population. Adaptations made to the original intervention are described. The current study is a practical example of how an intervention can be adapted to maximize relevance and acceptability and also maintain the core elements of the original evidence-based intervention. The intervention has significant potential to influence cancer prevention efforts among Latinos in the United States and is being evaluated in a sample of 400 Latino overweight/obese smokers. PMID:25527143

  4. The design, implementation and acceptability of an integrated intervention to address multiple behavioral and psychosocial risk factors among pregnant African American women

    PubMed Central

    Katz, Kathy S; Blake, Susan M; Milligan, Renee A; Sharps, Phyllis W; White, Davene B; Rodan, Margaret F; Rossi, Maryann; Murray, Kennan B

    2008-01-01

    Background African American women are at increased risk for poor pregnancy outcomes compared to other racial-ethnic groups. Single or multiple psychosocial and behavioral factors may contribute to this risk. Most interventions focus on singular risks. This paper describes the design, implementation, challenges faced, and acceptability of a behavioral counseling intervention for low income, pregnant African American women which integrated multiple targeted risks into a multi-component format. Methods Six academic institutions in Washington, DC collaborated in the development of a community-wide, primary care research study, DC-HOPE, to improve pregnancy outcomes. Cigarette smoking, environmental tobacco smoke exposure, depression and intimate partner violence were the four risks targeted because of their adverse impact on pregnancy. Evidence-based models for addressing each risk were adapted and integrated into a multiple risk behavior intervention format. Pregnant women attending six urban prenatal clinics were screened for eligibility and risks and randomized to intervention or usual care. The 10-session intervention was delivered in conjunction with prenatal and postpartum care visits. Descriptive statistics on risk factor distributions, intervention attendance and length (i.e., with < 4 sessions considered minimal adherence) for all enrolled women (n = 1,044), and perceptions of study participation from a sub-sample of those enrolled (n = 152) are reported. Results Forty-eight percent of women screened were eligible based on presence of targeted risks, 76% of those eligible were enrolled, and 79% of those enrolled were retained postpartum. Most women reported a single risk factor (61%); 39% had multiple risks. Eighty-four percent of intervention women attended at least one session (60% attended ≥ 4 sessions) without disruption of clinic scheduling. Specific risk factor content was delivered as prescribed in 80% or more of the sessions; 78% of sessions were

  5. Opportunity, risk, and success recognizing, addressing, and balancing multiple factors crucial to the success of a project management system deployed to support multi-lateral decommissioning programs

    SciTech Connect

    Funk, Greg; Longsworth, Paul

    2007-07-01

    This paper addresses the factors involved in effectively implementing a world-class program/project management information system funded by multiple nations. Along with many other benefits, investing in and utilizing such systems improves delivery and drive accountability for major expenditures. However, there are an equally large number of impediments to developing and using such systems. To be successful, the process requires a dynamic combining of elements and strategic sequencing of initiatives. While program/project-management systems involve information technologies, software and hardware, they represent only one element of the overall system.. Technology, process, people and knowledge must all be integrated and working in concert with one another to assure a fully capable system. Major system implementations occur infrequently, and frequently miss established targets in relatively small organizations (with the risk increasing with greater complexity). The European Bank of Reconstruction (EBRD) is midway through just such an implementation. The EBRD is using funds from numerous donor countries to sponsor development of an overarching program management system. The system will provide the Russian Federation with the tools to effectively manage prioritizing, planning, and physically decommissioning assets{sub i}n northwest Russia to mitigate risks associated the Soviet era nuclear submarine program. Project-management delivery using world-class techniques supported by aligned systems has been proven to increase the probability of delivering on-time and on-budget, assuring those funding such programs optimum value for money. However, systems deployed to manage multi-laterally funded projects must be developed with appropriate levels of consideration given to unique aspects such as: accommodation of existing project management methods, consideration for differences is management structures and organizational behaviors, incorporation of unique strengths, and

  6. Marine and Human Systems: Addressing Multiple Scales and Multiple Stressors

    NASA Astrophysics Data System (ADS)

    Hofmann, E. E.; Bundy, A.; Chuenpagdee, R.; Maddison, L.; Svendsen, E.

    2015-12-01

    The Integrated Marine Biogeochemistry and Ecosystem Research (IMBER) project aims to develop a comprehensive understanding of, and predictive capacity of ocean responses to accelerating global change and the consequent effects on the Earth System and human society. Understanding the changing ecology and biogeochemistry of marine ecosystems and their sensitivity and resilience to multiple drivers, pressures and stressors is critical to developing responses that will help reduce the vulnerability of marine-dependent human communities. The cumulative pressure of anthropogenic activities on marine systems is already apparent and is projected to increase in the next decades. Policy- and decision-makers need assessments of the status and trends of marine habitats, species, and ecosystems to promote sustainable human activities in the marine environment, particularly in light of global environmental change and changing social systems and human pressures. The IMBER community recently undertook a synthesis and evaluation of approaches for ecosystem-based marine governance, integrated modeling of marine social-ecological systems, and the social and ecological consequences of changing marine ecosystems. The outcomes of this activity provide assessments of current understanding, indicate approaches needed to predict the effects of multiple stressors, at multiple scales, on marine ecosystems and dependent human populations, and highlight approaches for developing innovative societal responses to changing marine ecosystems.

  7. Sequence Factorization with Multiple References

    PubMed Central

    Wandelt, Sebastian; Leser, Ulf

    2015-01-01

    The success of high-throughput sequencing has lead to an increasing number of projects which sequence large populations of a species. Storage and analysis of sequence data is a key challenge in these projects, because of the sheer size of the datasets. Compression is one simple technology to deal with this challenge. Referential factorization and compression schemes, which store only the differences between input sequence and a reference sequence, gained lots of interest in this field. Highly-similar sequences, e.g., Human genomes, can be compressed with a compression ratio of 1,000:1 and more, up to two orders of magnitude better than with standard compression techniques. Recently, it was shown that the compression against multiple references from the same species can boost the compression ratio up to 4,000:1. However, a detailed analysis of using multiple references is lacking, e.g., for main memory consumption and optimality. In this paper, we describe one key technique for the referential compression against multiple references: The factorization of sequences. Based on the notion of an optimal factorization, we propose optimization heuristics and identify parameter settings which greatly influence 1) the size of the factorization, 2) the time for factorization, and 3) the required amount of main memory. We evaluate a total of 30 setups with a varying number of references on data from three different species. Our results show a wide range of factorization sizes (optimal to an overhead of up to 300%), factorization speed (0.01 MB/s to more than 600 MB/s), and main memory usage (few dozen MB to dozens of GB). Based on our evaluation, we identify the best configurations for common use cases. Our evaluation shows that multi-reference factorization is much better than single-reference factorization. PMID:26422374

  8. A single fluorophore to address multiple logic gates.

    PubMed

    Sahu, Saugata; Sil, Timir Baran; Das, Minati; Krishnamoorthy, G

    2015-09-01

    Logic gates with different radixes have been constructed using a biologically active molecule, 2-(4'-N,N-dimethylaminophenyl)imidazo[4,5-b]pyridine (DMAPIP-b). Taking advantage of the multiple binding sites of the fluorophore, a series of different molecular logic gates are developed using fluorescence intensities at different wavelengths. The high emission of the molecule is drastically quenched in the presence of Fe(3+). It is regained by the addition of an equivalent amount of F(-). The fluorescence On-Off nature has been used to construct molecular full subtractor and molecular keypad lock system with Boolean logic. A ternary system is generated by considering three defined fluorescence intensities at particular wavelengths. The smooth dependency of emission intensities with analyte concentration is utilized to construct an infinite-valued fuzzy logic system. The fuzzy logic system is further coupled with a neuro-adaptation method to predict more accurately the dependency of molecular intensity on external inputs. PMID:26215476

  9. Environmental factors in multiple sclerosis.

    PubMed

    Pantazou, Vasiliki; Schluep, Myriam; Du Pasquier, Renaud

    2015-04-01

    Although multiple sclerosis (MS) is recognized as a disorder involving the immune system, the interplay of environmental factors and individual genetic susceptibility seems to influence MS onset and clinical expression, as well as therapeutic responsiveness. Multiple human epidemiological and animal model studies have evaluated the effect of different environmental factors, such as viral infections, vitamin intake, sun exposure, or still dietary and life habits on MS prevalence. Previous Epstein-Barr virus infection, especially if this infection occurs in late childhood, and lack of vitamin D (VitD) currently appear to be the most robust environmental factors for the risk of MS, at least from an epidemiological standpoint. Ultraviolet radiation (UVR) activates VitD production but there are also some elements supporting the fact that insufficient UVR exposure during childhood may represent a VitD-independent risk factor of MS development, as well as negative effect on the clinical and radiological course of MS. Recently, there has been a growing interest in the gut-brain axis, a bidirectional neuro-hormonal communication system between the intestinal microbiota and the central nervous system (CNS). Indeed, components of the intestinal microbiota may be pro-inflammatory, promote the migration of immune cells into the CNS, and thus be a key parameter for the development of autoimmune disorders such as MS. Interestingly most environmental factors seem to play a role during childhood. Thus, if childhood is the most fragile period to develop MS later in life, preventive measures should be applied early in life. For example, adopting a diet enriched in VitD, playing outdoor and avoiding passive smoking would be extremely simple measures of primary prevention for public health strategies. However, these hypotheses need to be confirmed by prospective evaluations, which are obviously difficult to conduct. In addition, it remains to be determined whether and how Vit

  10. Factors Influencing Black Churches' Readiness to Address HIV.

    PubMed

    Pichon, Latrice C; Powell, Terrinieka Williams; Ogg, Siri A; Williams, Andrea L; Becton-Odum, Nicole

    2016-06-01

    This study employed a community-based participatory research approach to understand factors that influence church readiness to engage in HIV prevention and treatment activities. A convenience sample of twenty-six Black faith leaders participated in four focus groups. Data analysis was done through qualitative content analysis. Three themes emerged. First, the pastor's blessing and authority as the church's decision-maker determines readiness to engage in HIV prevention. Second, the church's purview of sexual health as part of a holistic ministry facilitates faith leader's readiness. Lastly, securing financial and human resources makes it feasible for faith leaders to implement activities. Findings suggest HIV-related stigma alone does not explain readiness to address HIV. Participants also discussed activities their churches are equipped to handle, including HIV testing events and health fairs. PMID:26345680

  11. An Approach for Addressing the Multiple Testing Problem in Social Policy Impact Evaluations

    ERIC Educational Resources Information Center

    Schochet, Peter Z.

    2009-01-01

    In social policy evaluations, the multiple testing problem occurs due to the many hypothesis tests that are typically conducted across multiple outcomes and subgroups, which can lead to spurious impact findings. This article discusses a framework for addressing this problem that balances Types I and II errors. The framework involves specifying…

  12. The fallacy of Ratio Correction to address confounding factors

    PubMed Central

    Karp, Natasha A; Segonds-Pichon, Anne; Gerdin, Anna-Karin B; Ramírez-Solis, Ramiro; White, Jacqueline K

    2014-01-01

    Scientists aspire to measure cause and effect. Unfortunately confounding variables, ones that are associated with both the probable cause and the outcome, can lead to an association that is true but potentially misleading. For example, altered body weight is often observed in a gene knockout, however many other variables, such as lean mass, will also change as the body weight changes. This leaves the researcher asking whether the change in that variable is expected for that change in weight. Ratio Correction, which is often referred to as Normalization, is a method used commonly to remove the effect of a confounding variable. Although Ratio Correction is used widely in biological research, it is not the method recommended in the statistical literature to address confounding factors; instead regression methods such as the analysis of covariance (ANCOVA) are proposed. This method examines the difference in means after adjusting for the confounding relationship. Using real data, this manuscript demonstrates how the Ratio Correction approach is flawed and can result in erroneous calls of significance leading to inappropriate biological conclusions. This arises as some of the underlying assumptions are not met. The manuscript goes on to demonstrate that researchers should use ANCOVA, and discusses how graphical tools can be used readily to judge the robustness of this method. This study is therefore a clear example of why assumption testing is an important component of a study and thus why it is included in the Animal Research: reporting of In Vivo Experiment (ARRIVE) guidelines. PMID:22829707

  13. Addressing multiple relationships between clients and therapists in lesbian, gay, bisexual, transgender communities.

    PubMed

    Kessler, Laura E; Waehler, Charles A

    2005-02-01

    Therapists working in lesbian, gay, bisexual, and transgender (LGBT) communities are likely to experience the potential to engage in multiple relationships with their clients. Currently, the American Psychological Association's (2002) ethics code and the related literature base offer minimal direct guidance to therapists practicing in LGBT communities. In this article, the authors review current literature regarding multiple relationships in psychotherapy, considering how this literature addresses issues specific to practitioners working within LGBT communities, present a case study highlighting the negotiation of a multiple relationship between a client and therapist who both identify as lesbian, and offer recommendations for practitioners working within LGBT communities. PMID:17073035

  14. Addressing the Multiplication Makes Bigger and Division Makes Smaller Misconceptions via Prediction and Clickers

    ERIC Educational Resources Information Center

    Lim, Kien H.

    2011-01-01

    This article presents a lesson that uses prediction items, clickers and visuals via PowerPoint slides to help prospective middle-school teachers address two common misconceptions: multiplication makes bigger and division makes smaller (MMB-DMS). Classroom research was conducted to explore the viability of such a lesson. Results show that the…

  15. [Personal factors and participation - How should professionals address them?].

    PubMed

    Kraus de Camargo, Olaf

    2016-09-01

    Controversy exists around the application of personal factors within the International Classification of Functioning, Disability and Health. In the framework, they are represented by one of the boxes, but without content. They are part of the model, but cannot be coded or collected statistically. This article clarifies the rationale for the inclusion of personal factors in the classification, describes the controversies related to it and provides a personal statement about the utility of personal factors in clinical practice. PMID:27534546

  16. Patellofemoral Pain Syndrome and Modifiable Intrinsic Risk Factors; How to Assess and Address?

    PubMed Central

    Halabchi, Farzin; Mazaheri, Reza; Seif-Barghi, Tohid

    2013-01-01

    Patellofemoral pain syndrome (PFPS) is a very common disorder of the knee. Due to multiple forces influencing the patellofemoral joint, clinical management of this ailment is particularly intricate. Patellofemoral pain syndrome has a multifactorial nature and multiple parameters have been proposed as potential risk factors, classified as intrinsic or extrinsic. Some of the intrinsic risk factors are modifiable and may be approached in treatment. A number of modifiable risk factors have been suggested, including quadriceps weakness, tightness of hamstring, iliopsoas and gastrosoleus muscles, hip muscles dysfunction, foot overpronation, tightness of iliotibial band, generalised joint laxity, limb length discrepancy, patellar malalignment and hypermobility. In general, the routine approach of physicians to this problem does not include assessment and modification of these risk factors and therefore, it may negatively affect the management outcomes. Changing this approach necessitates an easy and practical protocol for assessment of modifiable risk factors and effective and feasible measures to address them. In this review, we aimed to introduce assessment and intervention packages appropriate for this purpose. PMID:23802050

  17. Addressing the human factors issues associated with control room modifications

    SciTech Connect

    O`Hara, J.; Stubler, W.; Kramer, J.

    1998-03-01

    Advanced human-system interface (HSI) technology is being integrated into existing nuclear plants as part of plant modifications and upgrades. The result of this trend is that hybrid HSIs are created, i.e., HSIs containing a mixture of conventional (analog) and advanced (digital) technology. The purpose of the present research is to define the potential effects of hybrid HSIs on personnel performance and plant safety and to develop human factors guidance for safety reviews of them where necessary. In support of this objective, human factors issues associated with hybrid HSIs were identified. The issues were evaluated for their potential significance to plant safety, i.e., their human performance concerns have the potential to compromise plant safety. The issues were then prioritized and a subset was selected for design review guidance development.

  18. Addressing the Hard Factors for Command File Errors by Probabilistic Reasoning

    NASA Technical Reports Server (NTRS)

    Bryant, Larry; Meshkat, Leila

    2014-01-01

    Command File Errors (CFE) are managed using standard risk management approaches at the Jet Propulsion Laboratory. Over the last few years, more emphasis has been made on the collection, organization, and analysis of these errors for the purpose of reducing the CFE rates. More recently, probabilistic modeling techniques have been used for more in depth analysis of the perceived error rates of the DAWN mission and for managing the soft factors in the upcoming phases of the mission. We broadly classify the factors that can lead to CFE's as soft factors, which relate to the cognition of the operators and hard factors which relate to the Mission System which is composed of the hardware, software and procedures used for the generation, verification & validation and execution of commands. The focus of this paper is to use probabilistic models that represent multiple missions at JPL to determine the root cause and sensitivities of the various components of the mission system and develop recommendations and techniques for addressing them. The customization of these multi-mission models to a sample interplanetary spacecraft is done for this purpose.

  19. Addressing the multiplication makes bigger and division makes smaller misconceptions via prediction and clickers

    NASA Astrophysics Data System (ADS)

    Lim, Kien H.

    2011-12-01

    This article presents a lesson that uses prediction items, clickers and visuals via PowerPoint slides to help prospective middle-school teachers address two common misconceptions: multiplication makes bigger and division makes smaller (MMB-DMS). Classroom research was conducted to explore the viability of such a lesson. Results show that the lesson was effective in creating awareness that multiplication does not always make bigger and division does not always makes smaller, uncovering students' misconceptions, and providing opportunities for students to learn from mistakes. Students liked the activity for various reasons, such as getting to learn certain mathematical ideas, to think about the problems, to work in groups and to have fun. The lesson was implemented slightly differently in two classes. The class with an additional phase involving prediction and voting via clickers in the PowerPoint lesson showed a gain of 36 points (an effect size of 1.3 standard deviations, SDs) from the pre-test to the exit-test whereas, the comparison class showed a gain of 25 points (an effect size of 0.87 SDs). In terms of students' written responses with regards to addressing the MMB-DMS misconceptions, there was however not much difference between the two classes.

  20. Addressing the Multiple Drivers of Wetland Ecosystems Degradation in Lagos, Nigeria

    NASA Astrophysics Data System (ADS)

    Agboola, J.; Ndimele, P. E.; Odunuga, S.; Akanni, A.; Kosemani, B.; Ahove, M.

    2015-12-01

    Several body of knowledge have noted the importance of wetland ecosystems in climate moderation, resource supply and flood risk reduction amongst others. Relevant as it may, rapidly increasing population and uncontrolled urban development poses a challenge in some regions and require understanding of the ecosystem components and drivers of change over a long period of time. Thus, the main thrust of this paper is to analyse multiple drivers of wetland ecosystems degradation in the last 30 years in the Lagos megacity using field study, desktop review, satellite data and laboratory analysis. Key drivers identified includes: conversion of wetlands to settlements and waste sink, land use planning that neglects wetland conservation and restoration, ineffective legal status for wetlands, over exploitation leading to degradation and fragmentation of wetland ecosystems governance. In stemming further loss of this vital ecosystem, this study adopted and proposed respectively, the Drivers, Pressure, State, Impact and Response (DPSIR) and Integrated Planning Approach (IPA) frameworks in analysing policy and governance issues in wetland development. These analyses figured out amongst others, strict conservation and sustainable use of wetland resources, habitat restoration, climate adaptation measures, legal protection and wetland management institution as major responses to current multiple pressures facing wetland ecosystems in Lagos. For these frameworks to be made meaningful, weak coordination among government agencies and institutional capacity in implementation and law enforcement, unsustainable resource extraction by private/business organization and issues on alternative sources of income on the part of the local communities amongst others needs to be addressed.

  1. Multiple factors drive regional agricultural abandonment.

    PubMed

    Osawa, Takeshi; Kohyama, Kazunori; Mitsuhashi, Hiromune

    2016-01-15

    An understanding of land-use change and its drivers in agroecosystems is important when developing adaptations to future environmental and socioeconomic pressures. Agricultural abandonment occurs worldwide with multiple potentially positive and negative consequences; however, the main factors causing agricultural abandonment in a country i.e., at the macro scale, have not been identified. We hypothesized that socio-environmental factors driving agricultural abandonment could be summarized comprehensively into two, namely "natural" and "social", and the relative importance of these differs among regions. To test this postulate, we analyzed the factors currently leading to agricultural abandonment considering ten natural environment variables (e.g., temperature) and five social variables (e.g., number of farmers) using the random forest machine learning method after dividing Japan into eight regions. Our results showed that agricultural abandonment was driven by various socio-environmental factors, and the main factors leading to agricultural abandonment differed among regions, especially in Hokkaido in northern Japan. Hokkaido has a relatively large area of concentrated farmland, and abandonment might have resulted from the effectiveness of cultivation under specific climate factors, whereas the other regions have relatively small areas of farmland with many elderly part-time farmers. In such regions, abandonment might have been caused by the decreasing numbers of potential farmers. Thus, two different drivers of agricultural abandonment were found: inefficient cultivation and decreasing numbers of farmers. Therefore, agricultural abandonment cannot be prevented by adopting a single method or policy. Agricultural abandonment is a significant problem not only for food production but also for several ecosystem services. Governments and decision-makers should develop effective strategies to prevent further abandonment to ensure sustainable future management of agro

  2. Addressable single-spin control in multiple quantum dots coupled in series

    NASA Astrophysics Data System (ADS)

    Nakajima, Takashi

    2015-03-01

    Electron spin in semiconductor quantum dots (QDs) is promising building block of quantum computers for its controllability and potential scalability. Recent experiments on GaAs QDs have demonstrated necessary ingredients of universal quantum gate operations: single-spin rotations by electron spin resonance (ESR) which is virtually free from the effect of nuclear spin fluctuation, and pulsed control of two-spin entanglement. The scalability of this architecture, however, has remained to be demonstrated in the real world. In this talk, we will present our recent results on implementing single-spin-based qubits in triple, quadruple, and quintuple QDs based on a series coupled architecture defined by gate electrodes. Deterministic initialization of individual spin states and spin-state readout were performed by the pulse operation of detuning between two neighboring QDs. The spin state was coherently manipulated by ESR, where each spin in different QDs is addressed by the shift of the resonance frequency due to the inhomogeneous magnetic field induced by the micro magnet deposited on top of the QDs. Control of two-spin entanglement was also demonstrated. We will discuss key issues for implementing quantum algorithms based on three or more qubits, including the effect of a nuclear spin bath, single-shot readout fidelity, and tuning of multiple qubit devices. Our approaches to these issues will be also presented. This research is supported by Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST) from JSPS, IARPA project ``Multi-Qubit Coherent Operations'' through Copenhagen University, and Grant-in-Aid for Scientific Research from JSPS.

  3. Prognostic factors and classification in multiple myeloma.

    PubMed Central

    San Miguel, J. F.; Sànchez, J.; Gonzalez, M.

    1989-01-01

    Analyses of prognostic factors have allowed the design of staging systems in different haematological disorders. In a series of 220 patients with multiple myeloma, univariate analysis showed that nine parameters had a significant adverse effect on survival; poor performance status (Karnowsky scaling system less than 70%), infections before diagnosis, renal impairment (assessed either by creatinine clearance greater than 2 mg dl-1 or urea greater than 40 mg dl-1), serum calcium (greater than 10 mg dl-1), severe anaemia (less than 8.5 g dl-1), the presence of Bence-Jones proteinuria, failure to achieve complete remission, more than 40% plasma cells in bone marrow and a low paraprotein index (monoclonal component/% plasma cells: P less than 0.09). In addition, this index correlated significantly with all the other prognostic factors except performance status. The best combination of disease characteristics selected by means of the Cox regression proportional hazards method were performance status and creatinine levels. Additionally, by factor analysis of principal components we obtained a regression equation that included creatinine levels, haemoglobin, performance status and paraprotein index. Using this it was possible to separate the series of patients into three risk categories: A (65 patients), B (69 patients) and C (65 patients) with a median survival of 41, 24 and 12 months, respectively. The model provided similar results to those of the British Medical Research Council, whereas the staging systems proposed by Durie and Salmon, Merlin et al. and Carbone et al. had a lower discriminant value in our series. PMID:2757917

  4. Food-Based Interventions to Modify Diet Quality and Diversity to Address Multiple Micronutrient Deficiency.

    PubMed

    Nair, Madhavan K; Augustine, Little Flower; Konapur, Archana

    2015-01-01

    Global data indicate a high prevalence of hidden hunger among population. Deficiencies of certain micronutrients such as folic acid, iodine, iron, and vitamin A have long lasting effects on growth and development and therefore have been a National priority from many decades. The strategy implemented so far limits to the use of supplemental sources or fortified foods in alleviating the burden of deficiencies. These approaches however undermine the food-based strategies involving dietary diversification as the long-term sustainable strategy. There is lack of understanding on the level of evidence needed to implement such strategies and the level of monitoring required for impact evaluation. Dietary diversity concerns how to ensure access for each individual to a quality and safe diet with adequate macro- and micronutrients. The key to success in using dietary diversity as a strategy to tackle hidden hunger is in integrating it with the principles of bioavailability, translated to efficient food synergies with due emphasis on food accessibility, affordability, and outdoor physical activity/life style modifications. Promoting enabling environment and sustainable agriculture is crucial for practicing dietary diversification with behavior change communication as an integral segment. It can be concluded that food-based strategies require careful understanding of the factors associated with it and moderate it to form an effective strategy for controlling multiple micronutrient deficiencies. PMID:26779472

  5. Food-Based Interventions to Modify Diet Quality and Diversity to Address Multiple Micronutrient Deficiency

    PubMed Central

    Nair, Madhavan K.; Augustine, Little Flower; Konapur, Archana

    2016-01-01

    Global data indicate a high prevalence of hidden hunger among population. Deficiencies of certain micronutrients such as folic acid, iodine, iron, and vitamin A have long lasting effects on growth and development and therefore have been a National priority from many decades. The strategy implemented so far limits to the use of supplemental sources or fortified foods in alleviating the burden of deficiencies. These approaches however undermine the food-based strategies involving dietary diversification as the long-term sustainable strategy. There is lack of understanding on the level of evidence needed to implement such strategies and the level of monitoring required for impact evaluation. Dietary diversity concerns how to ensure access for each individual to a quality and safe diet with adequate macro- and micronutrients. The key to success in using dietary diversity as a strategy to tackle hidden hunger is in integrating it with the principles of bioavailability, translated to efficient food synergies with due emphasis on food accessibility, affordability, and outdoor physical activity/life style modifications. Promoting enabling environment and sustainable agriculture is crucial for practicing dietary diversification with behavior change communication as an integral segment. It can be concluded that food-based strategies require careful understanding of the factors associated with it and moderate it to form an effective strategy for controlling multiple micronutrient deficiencies. PMID:26779472

  6. Addressing Dropout Related Factors at the Local Level: Recommendations for Teachers

    ERIC Educational Resources Information Center

    Smith, Sandra Covington

    2008-01-01

    As educators and practitioners continue to seek effective interventions to prevent dropout, they must focus on identifying, monitoring, and addressing risk factors that are influenced by teachers (e.g., academic performance, peer and adult interactions, attendance, and behavior). As a result, teachers' roles in dropout prevention are critical.…

  7. Science and the Nonscience Major: Addressing the Fear Factor in the Chemical Arena Using Forensic Science

    ERIC Educational Resources Information Center

    Labianca, Dominick A.

    2007-01-01

    This article describes an approach to minimizing the "fear factor" in a chemistry course for the nonscience major, and also addresses relevant applications to other science courses, including biology, geology, and physics. The approach emphasizes forensic science and affords students the opportunity to hone their analytical skills in an…

  8. Addressing Gender-Based Violence at Schools for Learners with Intellectual Disability in Gauteng, South Africa: A Multiple Case Study

    ERIC Educational Resources Information Center

    Phasha, T. N.; Nyokangi, D.

    2012-01-01

    This paper reports part of the findings of the study which investigated sexual violence at two schools catering specifically for learners with mild intellectual disability in Gauteng Province. It looks particularly on participants' suggestions for addressing sexual violence in such school. A multiple case study within the qualitative research…

  9. Interactive actuation of multiple opto-thermocapillary flow-addressed bubble microrobots

    PubMed Central

    Hu, Wenqi; Fan, Qihui; Ohta, Aaron T

    2014-01-01

    Opto-thermocapillary flow-addressed bubble (OFB) microrobots are a potential tool for the efficient transportation of micro-objects. This microrobot system uses light patterns to generate thermal gradients within a liquid medium, creating thermocapillary forces that actuate the bubble microrobots. An interactive control system that includes scanning mirrors and a touchscreen interface was developed to address up to ten OFB microrobots. Using this system, the parallel and cooperative transportation of 20-μm-diameter polystyrene beads was demonstrated. PMID:25678988

  10. Multiple Rescue Factors Within a Wolbachia Strain

    PubMed Central

    Zabalou, Sofia; Apostolaki, Angeliki; Pattas, Savvas; Veneti, Zoe; Paraskevopoulos, Charalampos; Livadaras, Ioannis; Markakis, George; Brissac, Terry; Merçot, Hervé; Bourtzis, Kostas

    2008-01-01

    factors specific to each variant. This study shows that a given Wolbachia variant can possess multiple rescue determinants corresponding to different CI systems. In addition, our results: (a) suggest that wTei appears to behave in D. simulans as a suicide mod+ resc− strain, (b) unravel unique CI properties, and (c) provide a framework to understand the diversity and the evolution of new CI-compatibility types. PMID:18430940

  11. Multiple views to address diversity issues: an initial dialog to advance the chiropractic profession

    PubMed Central

    Johnson, Claire; Killinger, Lisa Zaynab; Christensen, Mark G.; Hyland, John K.; Mrozek, John P.; Zuker, R. Fred; Kizhakkeveettil, Anupama; Perle, Stephen M.; Oyelowo, Tolu

    2012-01-01

    The purpose of this article is to provide expert viewpoints on the topic of diversity in the chiropractic profession, including cultural competency, diversity in the profession, educational and clinical practice strategies for addressing diversity, and workforce issues. Over the next decades, changing demographics in North America will alter how the chiropractic profession functions on many levels. As the population increases in diversity, we will need to prepare our workforce to meet the needs of future patients and society. PMID:23966884

  12. Factors Associated with Multiple-Partner Fertility among Fathers

    ERIC Educational Resources Information Center

    Manlove, Jennifer; Logan, Cassandra; Ikramullah, Erum; Holcombe, Emily

    2008-01-01

    This article uses a sample of 1,731 fathers aged 16 - 45 from the 2002 National Survey of Family Growth to identify factors associated with multiple-partner fertility. Almost one third of fathers who reported multiple-partner fertility did so across a series of nonmarital relationships, and nonmarital-only multiple-partner fertility has been…

  13. The Role of Multiple Transcription Factors In Archaeal Gene Expression

    SciTech Connect

    Charles J. Daniels

    2008-09-23

    Since the inception of this research program, the project has focused on two central questions: What is the relationship between the 'eukaryal-like' transcription machinery of archaeal cells and its counterparts in eukaryal cells? And, how does the archaeal cell control gene expression using its mosaic of eukaryal core transcription machinery and its bacterial-like transcription regulatory proteins? During the grant period we have addressed these questions using a variety of in vivo approaches and have sought to specifically define the roles of the multiple TATA binding protein (TBP) and TFIIB-like (TFB) proteins in controlling gene expression in Haloferax volcanii. H. volcanii was initially chosen as a model for the Archaea based on the availability of suitable genetic tools; however, later studies showed that all haloarchaea possessed multiple tbp and tfb genes, which led to the proposal that multiple TBP and TFB proteins may function in a manner similar to alternative sigma factors in bacterial cells. In vivo transcription and promoter analysis established a clear relationship between the promoter requirements of haloarchaeal genes and those of the eukaryal RNA polymerase II promoter. Studies on heat shock gene promoters, and the demonstration that specific tfb genes were induced by heat shock, provided the first indication that TFB proteins may direct expression of specific gene families. The construction of strains lacking tbp or tfb genes, coupled with the finding that many of these genes are differentially expressed under varying growth conditions, provided further support for this model. Genetic tools were also developed that led to the construction of insertion and deletion mutants, and a novel gene expression scheme was designed that allowed the controlled expression of these genes in vivo. More recent studies have used a whole genome array to examine the expression of these genes and we have established a linkage between the expression of specific tfb

  14. Multiple factor analysis with continuous and dichotomous variables

    NASA Astrophysics Data System (ADS)

    Thanoon, Thanoon Y.; Adnan, Robiah; Saffari, Seyed Ehsan

    2014-12-01

    In this paper, continuous and dichotomous variables are used in multiple factor analysis method. When all variables within the same group are continuous, we use principal component analysis method in factor analysis, if all variables within the same group are dichotomous we use multiple correspondence analysis method in factor analysis. Statistical analyses, which involve Eigen roots, Eigen vectors, multiple factor loadings, correlation coefficient RV, contribution table, are discussed. The proposed procedure is illustrated by a lung cancer data consists of four groups "group of personal variables", "group of therapeutic variables", "group of nutritional variables", "group of genetic variables". Analysis are done by using XLSTAT program.

  15. Multiple-scattering lidar from both sides of the clouds: Addressing internal structure

    NASA Astrophysics Data System (ADS)

    Davis, A. B.

    2008-07-01

    Multiple-scattering (a.k.a. "off-beam") lidar is an emerging technology in cloud remote sensing. It delivers, as in classic lidar ceilometry, cloud base altitude but also the cloud's physical thickness H as well as its optical depth τ (averaged over horizontal scales on the order of H). The value of τ in fact must lie beyond the range accessible by standard (i.e., single-scattering/on-beam) lidar profiling, namely, up to 3-4. A refined diffusion-theoretical model is presented here for signals from multiple-scattering lidar and applied, on the one hand, to retrieval algorithm development and, on the other hand, signal-to-noise ratio (SNR) estimation. SNRs are computed for LANL's ground-based Wide-Angle Imaging Lidar (WAIL) system and NASA's space-based Lidar-In-space Technology Experiment (LITE). The refinements are threefold and all about internal structure. First, the laser source is modeled as a collimated anisotropic exponentially distributed internal source rather than an isotropic point source at the cloud boundary; this opens the possibility of using δ-Eddington rescaling to capture the forward peaked phase function more effectively within the diffusion framework. Second, stratification of the scattering coefficient is modeled as an increasing function of distance to cloud base; this strongly differentiates the signals when observed from above or from below. Finally, Cairns' rescaling is applied to this conservative scattering problem to account for the systematic effects of random (turbulence-driven) internal variability at scales up to a few mean free paths.

  16. Sociodemographic predictors of multiple non-communicable disease risk factors among older adults in South Africa

    PubMed Central

    Phaswana-Mafuya, Nancy; Peltzer, Karl; Chirinda, Witness; Musekiwa, Alfred; Kose, Zamakayise

    2013-01-01

    Background and objective Unhealthy lifestyle behaviours are important risk factors of morbidity and mortality. This study aimed to explore the sociodemographic predictors of multiple non-communicable disease (NCD) risk factors experienced by elderly South Africans. Methods We conducted a national population-based cross-sectional survey with a sample of 3,840 individuals aged 50 years or above in South Africa in 2008. The outcome variable was the co-existence of multiple NCD risk factors (tobacco use, alcohol, physical inactivity, fruit and vegetable intake, overweight or obesity, and hypertension) in each individual. The exposure variables were sociodemographic characteristics, namely, age, gender, education, wealth status, population group, marital status, and residence. Multivariate linear regression was used to assess the association between sociodemographic variables and multiple NCD risk factors. Results The mean number of NCD risk factors among all participants was three (95% confidence interval: 2.81–3.10). Multivariate linear regression analysis revealed that being female, being in the age group of 60–69 years, and being from the Coloured and Black African race were associated with a higher number of NCD risk factors. Marital status, educational level, wealth, and residence were not significantly associated with the number of NCD risk factors experienced. Conclusions The co-existence of multiple lifestyle NCD risk factors among the elderly is a public health concern. Comprehensive health-promotion interventions addressing the co-existence of multiple NCD risk factors tailored for specific sociodemographic groups are needed. PMID:24044582

  17. Experimental demonstration of a single-carrier frequency division multiple address based PON (SCFDMA-PON) architecture.

    PubMed

    Zhang, Cheng; Li, Juhao; Zhang, Fan; He, Yongqi; Wu, Hequan; Chen, Zhangyuan

    2010-11-22

    We introduce a novel architecture for next generation passive optical network (PON) base on the Single-carrier Frequency Division Multiple Address (SC-FDMA) technique. Both downstream and upstream SCFDMA-PON transmissions (5 Gb/s total, 2.5 Gb/s for each user) are experimentally demonstrated over 22.2 km standard single mode fiber and an additional simulated 1:32 optical splitter. We also test the tolerance range of the synchronization error and prove it matches the cyclic prefix period in our scheme, which means the packet transmission accuracy from different optical network units can be relaxed in the upstream. PMID:21164802

  18. Multiple Sclerosis Associated Risk Factors: A Case-Control Study

    PubMed Central

    POOROLAJAL, Jalal; MAZDEH, Mehrdokht; SAATCHI, Mohammad; TALEBI GHANE, Elaheh; BIDERAFSH, Azam; LOTFI, Bahar; FERYADRES, Mohammad; PAJOHI, Khabat

    2015-01-01

    Background: Hamadan Province is one of the high-risk regions in Iran for Multiple sclerosis (MS). A majority of the epidemiological studies conducted in Iran addressing MS are descriptive. This study was conducted to assess MS and its associated risk factors in Hamadan Province, the west of Iran. Methods: This case-control study compared 100 patients with MS (case group) and 100 patients with acute infectious diseases (control group) from September 2013 to March 2014. A checklist was used to assess the demographic, medical, and family history of the patients. The Friedman-Rosenman questionnaire was also used to assess personality type. Statistical analysis was performed using logistic regression model with Stata 11 software program. Results: The adjusted odds ratio (OR) estimate of MS was 4.37 (95% CI: 2.33, 8.20) for females compared to males; 0.15 (95% CI: 0.06, 0.43) for people aged above 50 years compared to aged 14 to 29 years; 0.44 (95% CI: 0.21, 0.91) for overweight or obese people compared to normal weights. Crude OR indicated a significant association between the occurrence of MS and exclusive breast feeding, season of birth, and smoking. However, the association was not statistically significant after adjustment for other covariates. Conclusion: The risk of MS is significantly lower in male gender, obese/overweight, and old people. Furthermore, non-smoking, non-exclusive breast-feeding, and born in autumn may increase the risk of MS but need further investigation. However, long-term large prospective cohort studies are needed to investigate the true effect of the potential risk factors on MS. PMID:26744707

  19. Interventions addressing risk factors of ischaemic heart disease in sub-Saharan Africa: a systematic review

    PubMed Central

    Ebireri, Jennifer; Aderemi, Adewale V; Omoregbe, Nicholas; Adeloye, Davies

    2016-01-01

    Background Ischaemic heart disease (IHD) is currently ranked eighth among the leading causes of deaths in sub-Saharan Africa (sSA). Yet, effective population-wide preventive measures targeting risks in the region are still largely unavailable. We aimed to review population-wide and individual-level interventions addressing risk factors of IHD among adults in sSA. Methods A systematic search of MEDLINE, EMBASE, Global Health and AJOL was conducted to identify studies focusing on population-wide and individual-level interventions targeting risks of IHD among adults in sSA. We conducted a detailed synthesis of basic findings of selected studies. Results A total of 2311 studies were identified, with only 9 studies meeting our selection criteria. 3 broad interventions were identified: dietary modifications, physical activity and community-based health promotion measures on tobacco and alcohol cessation. 3 studies reported significant reduction in blood pressure (BP), and another study reported statistically significant reduction in mean total cholesterol. Other outcome measures observed ranged from mild to no reduction in BP, blood glucose, body mass index and total cholesterol, respectively. Conclusions We cannot specify with all certainty contextually feasible interventions that can be effective in modifying IHD risk factors in population groups across sSA. We recommend more research on IHD, particularly on the understanding of the burden, geared towards developing and/or strengthening preventive and treatment interventions for the disease in sSA. PMID:27381212

  20. Factors associated with early growth in Egyptian infants: implications for addressing the dual burden of malnutrition.

    PubMed

    Kavle, Justine A; Flax, Valerie L; Abdelmegeid, Ali; Salah, Farouk; Hafez, Seham; Ramzy, Magda; Hamed, Doaa; Saleh, Gulsen; Galloway, Rae

    2016-01-01

    Optimal nutrition is critical to the attainment of healthy growth, human capital and sustainable development. In Egypt, infants and young children face overlapping forms of malnutrition, including micronutrient deficiencies, stunting and overweight. Yet, in this setting, little is known about the factors associated with growth during the first year of life. A rise in stunting in Lower Egypt from 2005 to 2008 prompted this implementation research study, which followed a longitudinal cohort of infants from birth to 1 year of age within the context of a USAID-funded maternal and child health integrated programme. We sought to determine if growth patterns and factors related to early growth differed in Lower and Upper Egypt, and examined the relationship between weight loss and subsequent stunting at 12 months of age. Growth patterns revealed that length-for-age z-score (LAZ) decreased and weight-for-length z-score (WLZ) increased from 6 to 12 months of age in both regions. One-quarter of infants were stunted and nearly one-third were overweight by 12 months of age in lower Egypt. Minimum dietary diversity was significantly associated with WLZ in Lower Egypt (β = 0.22, P < 0.05), but not in Upper Egypt. Diarrhoea, fever and programme exposure were not associated with any growth outcome. Weight loss during any period was associated with a twofold likelihood of stunting at 12 months in Lower Egypt, but not Upper Egypt. In countries, like Egypt, facing the nutrition transition, infant and young child nutrition programmes need to address both stunting and overweight through improving dietary quality and reducing reliance on energy-dense foods. PMID:26373408

  1. Multiplication factors in ethylene-filled proportional counters.

    PubMed

    Loyola, H; Birstein, L; Hevia, A

    2008-01-01

    Gas multiplication factors were measured in a proportional counter filled with high-purity ethylene in the pressure range 10-40 Torr. The multiplication factors were measured as a function of the reduced electric field S(a). The results show that, within the range of the high values of reduced electric field applied in this work (2648 < or = S(a) < or = 6455 V cm(-1) Torr(-1)), the reduced first Townsend coefficient alpha/P for ethylene may still be considered a function of S(a) alone. Good agreement was found with a model proposed by Akande. PMID:18682404

  2. Addressing risk factors, screening, and preventative treatment for diabetic retinopathy in developing countries: a review.

    PubMed

    Lin, Stephanie; Ramulu, Pradeep; Lamoureux, Ecosse L; Sabanayagam, Charumathi

    2016-05-01

    The number of people with diabetic retinopathy (DR) has increased with the increasing prevalence of diabetes mellitus worldwide, especially in developing countries. In recent years, the successful implementation of public health programs in developed countries has been thought to contribute to decreases in blindness from DR. Developing countries, however, have not seen the same improvements, and their public health interventions still face significant challenges. In this review we describe the current state of public health approaches including risk factor control, screening and treatment techniques for DR in developing countries, and suggest recommendations. While the awareness of DR is variable, specific knowledge about DR is low, such that many patients have already experienced vision loss by the time they are screened. Attempts to improve rates of screening, in particular through non-mydriatic cameras and tele-screening, are ongoing and promising, although challenges include collaboration with healthcare systems and technology failures. Laser treatment is the most readily available, with anti-VEGF therapy and vitreo-retinal surgery increasingly sought after and provided. Recommendations include the use of 'targeted mydriasis' for fundus imaging to address high rates of ungradable images, increased communication with diabetes management services to improve patient retention and mobilization of access to DR treatments. PMID:26991970

  3. Use of information visualization methods eliminating cross talk in multiple sensing units investigated for a light-addressable potentiometric sensor.

    PubMed

    Siqueira, José R; Maki, Rafael M; Paulovich, Fernando V; Werner, Carl F; Poghossian, Arshak; de Oliveira, Maria C F; Zucolotto, Valtencir; Oliveira, Osvaldo N; Schöning, Michael J

    2010-01-01

    The integration of nanostructured films containing biomolecules and silicon-based technologies is a promising direction for reaching miniaturized biosensors that exhibit high sensitivity and selectivity. A challenge, however, is to avoid cross talk among sensing units in an array with multiple sensors located on a small area. In this letter, we describe an array of 16 sensing units of a light-addressable potentiometric sensor (LAPS), which was made with layer-by-layer (LbL) films of a poly(amidomine) dendrimer (PAMAM) and single-walled carbon nanotubes (SWNTs), coated with a layer of the enzyme penicillinase. A visual inspection of the data from constant-current measurements with liquid samples containing distinct concentrations of penicillin, glucose, or a buffer indicated a possible cross talk between units that contained penicillinase and those that did not. With the use of multidimensional data projection techniques, normally employed in information visualization methods, we managed to distinguish the results from the modified LAPS, even in cases where the units were adjacent to each other. Furthermore, the plots generated with the interactive document map (IDMAP) projection technique enabled the distinction of the different concentrations of penicillin, from 5 mmol L(-1) down to 0.5 mmol L(-1). Data visualization also confirmed the enhanced performance of the sensing units containing carbon nanotubes, consistent with the analysis of results for LAPS sensors. The use of visual analytics, as with projection methods, may be essential to handle a large amount of data generated in multiple sensor arrays to achieve high performance in miniaturized systems. PMID:20041720

  4. Hypoxia inducible factor-1 alpha and multiple myeloma

    PubMed Central

    Tiwary, Bhupendra Nath

    2016-01-01

    Rapid tumor growth creates a state of hypoxia in the tumor microenvironment and results in release of hypoxia inducible factor-1 alpha (HiF-1α) in the local milieu. Hypoxia inducible factor activity is deregulated in many human cancers, especially those that are highly hypoxic. In multiple myeloma (MM) in initial stages of disease establishment, the hypoxic bone marrow microenvironment supports the initial survival and growth of the myeloma cells. Hypoxic tumour cells are usually resistant to radiotherapy and most conventional chemotherapeutic agents, rendering them highly aggressive and metastatic. Therefore, HIF is an attractive, although challenging, therapeutic target in MM directly or indirectly in recent years. PMID:26900575

  5. Factors associated with reporting multiple causes of death

    PubMed Central

    Wall, Melanie M; Huang, Jinzhou; Oswald, John; McCullen, Diane

    2005-01-01

    Background There is analytical potential for multiple cause of death data collected from death certificates. This study examines relationships of multiple causes of death as a function of factors available on the death certificate (demographics of decedent, place of death, type of certifier, disposal method, whether an autopsy was performed, and year of death). Methods Data from 326,332 Minnesota death certificates from 1990–1998 are examined. Underlying and non-underlying causes of death are examined (based on record axis codes) as well as demographic and death-related covariates. Associations between covariates and prevalence of multiple causes of death and conditional probability of underlying compared to non-underlying causes of death are examined. The occurrence of ischemic heart disease or diabetes as underlying causes are specifically examined. Results Both the probability of multiple causes of death and the proportion of underlying cause compared to non-underlying cause of death are associated with demographic characteristics of the deceased and other non-medical conditions related to filing death certificate such as place of death. Conclusions Multiple cause of death data provide a potentially useful way of looking for inaccuracies in reporting of causes of death. Differences across demographics in the proportion of time a cause is selected as underlying compared to non-underlying exist and can potentially provide useful information about the overall impact of causes of death in different populations. PMID:15655070

  6. Forecast of irrigation water demand considering multiple factors

    NASA Astrophysics Data System (ADS)

    Wang, X.; Lei, X.; Guo, X.; You, J.; Wang, H.

    2015-05-01

    Many factors influence irrigation water requirement on the basin scale, which make it difficult to obtain comprehensive data. Despite the advantage of less needing historical data, the prediction precision of traditional trend prediction methods is hard to guarantee. For water scarce basins, the artificial influence on irrigation requirement should be thought of as important impact factors. In this paper, the PCA (principal component analysis) method is used to identify the main influencing factors, such as precipitation, irrigation area, water saving technology and so on. Based on that, an irrigation water demand prediction model considering multiple factors is developed for water shortage regions. The method is applied in the Haihe River basin as an example. The study results show that the irrigation water demand forecasting method considering multiple factors in this paper can achieve higher modelling accuracy, compared with the traditional trend prediction method and the method that does not consider the human influence. In view of the small average relative error, 1.32%, it has good values for application.

  7. Intake Procedures as a Factor in Identifying and Addressing Barriers to Attendance of Adult Education Students.

    ERIC Educational Resources Information Center

    Hubble, Judy Hafley

    A study explored the nature of intake procedures of Texas adult education programs. Research on barriers to attendance and strategies for retention were reviewed, and the current use of intake procedures to identify and address barriers to attendance was summarized through a survey of 374 Literacy, Even Start Family Literacy, Adult Basic Education…

  8. Other High-Risk Factors for Young Drivers--How Graduated Licensing Does, Doesn't, or Could Address Them.

    ERIC Educational Resources Information Center

    Ferguson, Susan A.

    2003-01-01

    Examines the risk factors underlying the high crash rates of newly licensed drivers and assesses the extent to which existing graduated driver-licensing programs address these risks. Discusses such risks as driver fatigue, not using seat belts, high speeds, high-powered vehicles, and in-vehicle distractions. (Contains 66 references.) (AUTHOR/WFA)

  9. Space adaptation syndrome: multiple etiological factors and individual differences

    NASA Technical Reports Server (NTRS)

    Lackner, J. R.; DiZio, P.

    1991-01-01

    Space motion sickness is a significant operational concern in the American and Soviet space programs. Nearly 70% of all astronauts and cosmonauts are affected to some degree during their first several days of flight. It is now beginning to appear that space motion sickness like terrestrial motion sickness is the consequence of multiple etiological factors. As we come to understand basic mechanisms of spatial orientation and sensory-motor adaptation we can begin to predict etiological factors in different motion environments. Individuals vary greatly in the extent to which they are susceptible to these different factors. However, individuals seem to be relatively self-consistent in terms of their rates of adaptation to provocative stimulation and their retention of adaptation. Attempts to relate susceptibility to motion sickness during the microgravity phases of parabolic flight maneuvers to vestibular function under 1G and 0G test conditions are described.

  10. Modifiable factors influencing relapses and disability in multiple sclerosis.

    PubMed

    D'hooghe, M B; Nagels, G; Bissay, V; De Keyser, J

    2010-07-01

    A growing body of literature indicates that the natural course of multiple sclerosis can be influenced by a number of factors. Strong evidence suggests that relapses can be triggered by infections, the postpartum period and stressful life events. Vaccinations against influenza, hepatitis B and tetanus appear to be safe. Surgery, general and epidural anaesthesia, and physical trauma are not associated with an increased risk of relapses. Factors that have been associated with a reduced relapse rate are pregnancy, exclusive breastfeeding, sunlight exposure and higher vitamin D levels. A number of medications, including hormonal fertility treatment, seem to be able to trigger relapses. Factors that may worsen progression of disability include stressful life events, radiotherapy to the head, low levels of physical activity and low vitamin D levels. Strong evidence suggests that smoking promotes disease progression, both clinically and on brain magnetic resonance imaging. There is no evidence for an increased progression of disability following childbirth in women with multiple sclerosis. Moderate alcohol intake and exercise might have a neuroprotective effect, but this needs to be confirmed. PMID:20483884

  11. HUMAN SUBJECT AGE AND ACTIVITY LEVEL: FACTORS ADDRESSED IN A BIOMATHEMATICAL DEPOSITION PROGRAM FOR EXTRAPOLATION MODELING

    EPA Science Inventory

    A deterministic aerosol deposition model, previously validated by data from adult inhalation exposure experiments, is used to study factors affecting particle behavior within the developing human lung. ere, an age dependent lung morphology is presented in which the number of trac...

  12. Potential Risk Factors of Death in Multiple Trauma Patients

    PubMed Central

    Jelodar, Sina; Jafari, Peyman; Yadollahi, Mahnaz; Sabetian Jahromi, Golnar; Khalili, Hoseynali; Abbasi, Hamidreza; Bolandparvaz, Shahram; Paydar, Shahram

    2014-01-01

    Introduction: rauma has been recognized as one of the leading causes of death in many countries for decades. Reduction in mortality and morbidity rate of trauma cases is one of the most important attitudes in this field. Evaluation of different risk factors have been considered as the main goal of some studies. The purpose of this study was determining potential risk factors of death in trauma patients. Method: In a retrograde study, data of 740 patients admitted during three years (2009-2011) were studied. Demographic data (sex and age), clinical factors (blood pressure, pulse rate, respiratory rate, Glasgow coma scale (GCS)), trauma characteristics (location, type of injury, etc.), as well as outcome of patients were evaluated. Data analyses was done using SPSS 18.0. Stepwise multivariate regression analysis was used for recognition of independent predictive factors of death in multiple trauma patients. Results: Of those admitted, majority of patients were male (81.4%), 68% between 18 to 60 years, and 11.2% of them died during the course of treatment. Age; type of trauma; abnormal respiration rate, pulse rate, blood pressure; total GCS ≤8; abnormal pupil size; and head and neck; vertebral, and extremities fractures were obtained as significant predictive factor of death. GCS≤8, head and neck fracture, and abnormal pulse rate were independent death predictors. Conclusion: We identified GCS≤8, head and neck fracture, and abnormal pulse rate as predictive factors of mortality after trauma, which remained independent in the presence of all other factors and potentially treatable. PMID:26495375

  13. Multiple response optimization for higher dimensions in factors and responses

    DOE PAGESBeta

    Lu, Lu; Chapman, Jessica L.; Anderson-Cook, Christine M.

    2016-07-19

    When optimizing a product or process with multiple responses, a two-stage Pareto front approach is a useful strategy to evaluate and balance trade-offs between different estimated responses to seek optimum input locations for achieving the best outcomes. After objectively eliminating non-contenders in the first stage by looking for a Pareto front of superior solutions, graphical tools can be used to identify a final solution in the second subjective stage to compare options and match with user priorities. Until now, there have been limitations on the number of response variables and input factors that could effectively be visualized with existing graphicalmore » summaries. We present novel graphical tools that can be more easily scaled to higher dimensions, in both the input and response spaces, to facilitate informed decision making when simultaneously optimizing multiple responses. A key aspect of these graphics is that the potential solutions can be flexibly sorted to investigate specific queries, and that multiple aspects of the solutions can be simultaneously considered. As a result, recommendations are made about how to evaluate the impact of the uncertainty associated with the estimated response surfaces on decision making with higher dimensions.« less

  14. 2005 Shneidman Award Address. Integratively assessing risk and protective factors for adolescent suicide.

    PubMed

    Gutierrez, Peter M

    2006-04-01

    This article briefly reviews key issues in adolescent suicide risk assessment and proposes that assessing risk and protective factors in combination has the best probability of informing the field's understanding of this complex problem. Several newer measures are described along with summaries of their psychometric properties. A recommended protocol utilizing 4 developmentally appropriate, valid, and reliable self-report measures is suggested as a parsimonious way of gathering information on the range of risk and protective factors. Finally, a novel approach of employing short-term longitudinal studies to test models of adolescent suicide attempts is described along with a rationale for not focusing research efforts on completed suicide. Implications of this approach for prevention efforts conclude the article. PMID:16704319

  15. Factors Associated with Employment Status in Individuals with Multiple Sclerosis

    PubMed Central

    Arnett, Peter

    2015-01-01

    Background: Unemployment is common in individuals with multiple sclerosis (MS) and is associated with substantial socioeconomic burden. Several MS-related factors have been found to be associated with employment status, including fatigue, depression, cognitive problems, and motor difficulties. However, few studies have examined these factors collectively in predicting employment. The present study aimed to explore these variables together in predicting employment status in MS. Methods: Fifty-three individuals with MS participating in a research study of cognitive, emotional, and social factors related to MS were examined. Composite scores were created using factor analysis that represented cognition, fatigue, depression, and motor function. These composite scores, along with the Expanded Disability Status Scale score, were explored as predictors of employment status (working, not working) via logistic regression. Models of mediation were also investigated. Results: A model including composite scores of motor function, cognition, depression, and fatigue significantly distinguished those who are unemployed versus employed. However, only the cognitive, motor, and fatigue composite scores were found to be significantly associated with unemployment individually. Results of a mediation analysis using 1000 bootstrap samples indicated that the cognitive and fatigue composite scores significantly mediated the effect of disability on work status. Conclusions: Cognitive function and fatigue mediate the effect of MS disability on employment status. Interventions targeting cognitive difficulties and fatigue in MS may be effective in helping individuals maintain employment. PMID:26664334

  16. Insights into the Interactions between Educational Messages: Looking across Multiple Organizations Addressing Water Issues in Maricopa County, Arizona

    ERIC Educational Resources Information Center

    Cutts, Bethany; Saltz, Charlene; Elser, Monica

    2008-01-01

    The public receives environmental information from a variety of sources. Evaluation of a single program or one organization's effort is incomplete. Through surveys and interviews, we evaluate the cumulative impact of outreach by 20 water-related organizations in Maricopa County, Arizona. Household water conservation is a topic addressed by 18…

  17. Environmental Factors and Multiple Sclerosis Severity: A Descriptive Study

    PubMed Central

    Mandia, Daniele; Ferraro, Ottavia E.; Nosari, Guido; Montomoli, Cristina; Zardini, Elisabetta; Bergamaschi, Roberto

    2014-01-01

    Growing evidence suggests that environmental factors play a key role in the onset of multiple sclerosis (MS). This study was conducted to examine whether environmental factors may also be associated with the evolution of the disease. We collected data on smoking habits, sunlight exposure and diet (particularly consumption of vitamin D-rich foods) from a sample of 131 MS patients. We also measured their serum vitamin D concentration. The clinical impact of MS was quantified using the Multiple Sclerosis Severity Score (MSSS); MS was considered “severe” in patients with MSSS ≥ 6, and “mild” in patients with MSSS ≤ 1. The results showed a strong association between serum vitamin D concentration and both sunlight exposure (26.4 ± 11.9 ng/mL vs. 16.5 ± 12.1 ng/mL, p = 0.0004) and a fish-rich diet (23.5 ± 12.1 ng/mL vs. 16.1 ± 12.4 ng/mL, p = 0.005). Patients reporting frequent sunlight exposure had a lower MSSS (2.6 ± 2.4 h vs. 4.6 ± 2.6 h, p < 0.001). The mild MS patients reported much more frequent sunlight exposure (75% mild MS vs. 25% severe MS p = 0.004, Chi square test). A higher serum vitamin D concentration determined a lower risk of developing severe MS, adjusted for sunlight exposure (OR = 0.92 for one unit increase in vitamin D, 95% CI: 0.86–0.97, p = 0.005). A stronger inverse association emerged between frequent sunlight exposure and the risk of severe MS (OR = 0.26, 95% CI: 0.09–0.71, p = 0.009). Our data show that an appropriate diet and adequate expose to sunlight are associated with less aggressive MS. PMID:24950063

  18. Photonic-assisted microwave frequency multiplication with a tunable multiplication factor.

    PubMed

    Gao, Liang; Liu, Weilin; Chen, Xiangfei; Yao, Jianping

    2013-11-01

    Photonic-assisted microwave frequency multiplication with a tunable multiplication factor (MF) based on an optical comb generator and an embedded single-passband microwave photonic filter (MPF) is proposed and demonstrated. The optical comb is generated using two cascaded modulators which are driven by a microwave reference signal. By applying the optical comb to a photodetector, a fundamental frequency corresponding to the comb spacing and its harmonics is generated. Thanks to the embedded single-passband MPF, only one harmonic is selected by the single-passband MPF. Thus, a single-frequency frequency-multiplied microwave signal is generated. In the proposed system, the embedded single-passband MPF is formed by using a sliced broadband optical source and a section of dispersion-compensating fiber (DCF). By tuning the central frequency of the passband at a frequency corresponding to that of a specific harmonic, a microwave signal at that specific frequency is generated. The proposed system is experimentally demonstrated. A frequency-multiplied microwave signal with an MF from 1 to 5 is generated. The phase noise and frequency tunability of the generated microwave signal are also investigated. PMID:24177126

  19. Addressing astronomy misconceptions and achieving national science standards utilizing aspects of multiple intelligences theory in the classroom and the planetarium

    NASA Astrophysics Data System (ADS)

    Sarrazine, Angela Renee

    The purpose of this study was to incorporate multiple intelligences techniques in both a classroom and planetarium setting to create a significant increase in student learning about the moon and lunar phases. Utilizing a free-response questionnaire and a 25 item multiple choice pre-test/post-test design, this study identified middle school students' misconceptions and measured increases in student learning about the moon and lunar phases. The study spanned two semesters and contained six treatment groups which consisted of both single and multiple interventions. One group only attended the planetarium program. Two groups attended one of two classes a week prior to the planetarium program, and two groups attended one of two classes a week after the planetarium program. The most rigorous treatment group attended a class both a week before and after the planetarium program. Utilizing Rasch analysis techniques and parametric statistical tests, all six groups exhibited statistically significant gains in knowledge at the 0.05 level. There were no significant differences between students who attended only a planetarium program versus a single classroom program. Also, subjects who attended either a pre-planetarium class or a post- planetarium class did not show a statistically significant gain over the planetarium only situation. Equivalent effects on student learning were exhibited by the pre-planetarium class groups and post-planetarium class groups. Therefore, it was determined that the placement of the second intervention does not have a significant impact on student learning. However, a decrease in learning was observed with the addition of a third intervention. Further instruction and testing appeared to hinder student learning. This is perhaps an effect of subject fatigue.

  20. Multiple Interacting Risk Factors: On Methods for Allocating Risk Factor Interactions.

    PubMed

    Price, Bertram; MacNicoll, Michael

    2015-05-01

    A persistent problem in health risk analysis where it is known that a disease may occur as a consequence of multiple risk factors with interactions is allocating the total risk of the disease among the individual risk factors. This problem, referred to here as risk apportionment, arises in various venues, including: (i) public health management, (ii) government programs for compensating injured individuals, and (iii) litigation. Two methods have been described in the risk analysis and epidemiology literature for allocating total risk among individual risk factors. One method uses weights to allocate interactions among the individual risk factors. The other method is based on risk accounting axioms and finding an optimal and unique allocation that satisfies the axioms using a procedure borrowed from game theory. Where relative risk or attributable risk is the risk measure, we find that the game-theory-determined allocation is the same as the allocation where risk factor interactions are apportioned to individual risk factors using equal weights. Therefore, the apportionment problem becomes one of selecting a meaningful set of weights for allocating interactions among the individual risk factors. Equal weights and weights proportional to the risks of the individual risk factors are discussed. PMID:25644783

  1. Population genetics suggest that multiple invasion processes need to be addressed in the management plan of a plant disease vector

    PubMed Central

    Anderson, Kylie L; Congdon, Bradley C

    2013-01-01

    The use of a multidisciplinary approach is becoming increasingly important when developing management strategies that mitigate the economic and biological costs associated with invasive pests. A framework of simulated dispersal is combined with life-history information and analyses of population genetic structure to investigate the invasion dynamics of a plant disease vector, the island sugarcane planthopper (Eumetopina flavipes), through an archipelago of significant Australian quarantine concern. Analysis of eight microsatellite loci from 648 individuals suggests that frequent, wind-assisted immigration from multiple sources in Papua New Guinea contributes significantly to repeated colonization of far northern islands. However, intermittent wind-assisted immigration better explains patterns of genetic diversity and structure in the southern islands and on the tip of mainland Australia. Significant population structuring associated with the presence of clusters of highly related individuals results from breeding in-situ following colonization, with little postestablishment movement. Results also suggest that less important secondary movements occur between islands; these appear to be human mediated and restricted by quarantine zones. Control of the planthopper may be very difficult on islands close to Papua New Guinea given the apparent propensity for multiple invasion, but may be achievable further south where local populations appear highly independent and isolated. PMID:23789032

  2. Multiple Factors Drive Replicating Strand Composition Bias in Bacterial Genomes

    PubMed Central

    Zhao, Hai-Long; Xia, Zhong-Kui; Zhang, Fa-Zhan; Ye, Yuan-Nong; Guo, Feng-Biao

    2015-01-01

    Composition bias from Chargaff’s second parity rule (PR2) has long been found in sequenced genomes, and is believed to relate strongly with the replication process in microbial genomes. However, some disagreement on the underlying reason for strand composition bias remains. We performed an integrative analysis of various genomic features that might influence composition bias using a large-scale dataset of 1111 genomes. Our results indicate (1) the bias was stronger in obligate intracellular bacteria than in other free-living species (p-value = 0.0305); (2) Fusobacteria and Firmicutes had the highest average bias among the 24 microbial phyla analyzed; (3) the strength of selected codon usage bias and generation times were not observably related to strand composition bias (p-value = 0.3247); (4) significant negative relationships were found between GC content, genome size, rearrangement frequency, Clusters of Orthologous Groups (COG) functional subcategories A, C, I, Q, and composition bias (p-values < 1.0 × 10−8); (5) gene density and COG functional subcategories D, F, J, L, and V were positively related with composition bias (p-value < 2.2 × 10−16); and (6) gene density made the most important contribution to composition bias, indicating transcriptional bias was associated strongly with strand composition bias. Therefore, strand composition bias was found to be influenced by multiple factors with varying weights. PMID:26404268

  3. Environmental Factors Related to Multiple Sclerosis in Indian Population

    PubMed Central

    D’Cunha, Anita; Mustafa, Sharik

    2015-01-01

    Background Multiple sclerosis (MS) is less prevalent among Indians when compared to white populations. Genetic susceptibility remaining the same it is possible that environmental associations may have a role in determining disease prevalence. Aims To determine whether childhood infections, vaccination status, past infection with Helicobacter pylori (H.pylori), diet, socioeconomic and educational status were associated with MS. Material and Methods 139 patients and 278 matched control subjects were selected. A validated environmental exposure questionnaire was administered. Estimation of serum H.pylori IgG antibody was done by ELISA. Patients and controls were genotyped for HLA-DRB1*15:01. Results In our cohort a significant association was seen with measles (p <0.007), vegetarian diet (p < 0.001, higher educational status (p <0.0001) and urban living (p <0.0001). An inverse relationship was seen with H.Pylori infection and MS (p <0.001). Measles infection (OR 6.479, CI 1.21- 34.668, p< 0.029) and high educational status (OR 3.088, CI 1.212- 7.872, p< 0.018) were significant risk factors associated with MS. H.pylori infection was inversely related to MS (OR 0. 319, CI 0.144- 0.706, p <0.005). Conclusions Environmental influences may be important in determining MS prevalence. PMID:25902359

  4. [Factors of multiple resistance to antibiotics in nodule bacteria].

    PubMed

    Pariĭskaia, A N; Gorelova, O P

    1976-01-01

    Multiple resistance to antibiotics (penicillin, levomycetin, neomycin, tetracycline) was found in 15% of collection strains of nodule bacteria and in strains isolated from natural environment. PMID:1050635

  5. Is Hypovitaminosis D One of the Environmental Risk Factors for Multiple Sclerosis?

    ERIC Educational Resources Information Center

    Pierrot-Deseilligny, Charles; Souberbielle, Jean-Claude

    2010-01-01

    The role of hypovitaminosis D as a possible risk factor for multiple sclerosis is reviewed. First, it is emphasized that hypovitaminosis D could be only one of the risk factors for multiple sclerosis and that numerous other environmental and genetic risk factors appear to interact and combine to trigger the disease. Secondly, the classical…

  6. Identifying cooperative transcription factors in yeast using multiple data sources

    PubMed Central

    2014-01-01

    Background Transcriptional regulation of gene expression is usually accomplished by multiple interactive transcription factors (TFs). Therefore, it is crucial to understand the precise cooperative interactions among TFs. Various kinds of experimental data including ChIP-chip, TF binding site (TFBS), gene expression, TF knockout and protein-protein interaction data have been used to identify cooperative TF pairs in existing methods. The nucleosome occupancy data is not yet used for this research topic despite that several researches have revealed the association between nucleosomes and TFBSs. Results In this study, we developed a novel method to infer the cooperativity between two TFs by integrating the TF-gene documented regulation, TFBS and nucleosome occupancy data. TF-gene documented regulation and TFBS data were used to determine the target genes of a TF, and the genome-wide nucleosome occupancy data was used to assess the nucleosome occupancy on TFBSs. Our method identifies cooperative TF pairs based on two biologically plausible assumptions. If two TFs cooperate, then (i) they should have a significantly higher number of common target genes than random expectation and (ii) their binding sites (in the promoters of their common target genes) should tend to be co-depleted of nucleosomes in order to make these binding sites simultaneously accessible to TF binding. Each TF pair is given a cooperativity score by our method. The higher the score is, the more likely a TF pair has cooperativity. Finally, a list of 27 cooperative TF pairs has been predicted by our method. Among these 27 TF pairs, 19 pairs are also predicted by existing methods. The other 8 pairs are novel cooperative TF pairs predicted by our method. The biological relevance of these 8 novel cooperative TF pairs is justified by the existence of protein-protein interactions and co-annotation in the same MIPS functional categories. Moreover, we adopted three performance indices to compare our predictions

  7. Novel Drosophila receptor that binds multiple growth factors

    SciTech Connect

    Rosner, M.R.; Thompson, K.L.; Garcia, V.; Decker, S.J.

    1986-05-01

    The authors have recently reported the identification of a novel growth factor receptor from Drosophila cell cultures that has dual binding specificity for both insulin and epidermal growth factor (EGF). This 100 kDa protein is also antigenically related to the cytoplasmic region of the mammalian EGF receptor-tyrosine kinase. They now report that this protein binds to mammalian nerve growth factor and human transforming growth factor alpha as well as insulin and EGF with apparent dissociation constants ranging from 10/sup -6/ to 10/sup -8/ M. The 100 kDa protein can be affinity-labeled with these /sup 125/I-labeled growth factors after immunoprecipitation with anti-EGF receptor antiserum. These four growth factors appear to share a common binding site, as evidenced by their ability to block affinity labelling by /sup 125/I-insulin. No significant binding to the 100 kDa protein was observed with platelet-derived growth factor, transforming growth factor beta, or glucagon. The 100 kDa Drosophila protein has a unique ligand-binding spectrum with no direct counterpart in mammalian cells and may represent an evolutionary precursor of the mammalian receptors for these growth factors.

  8. Multiplicity in Supervision Relationships: A Factor in Improving throughput Success?

    ERIC Educational Resources Information Center

    van Biljon, J. A.; de Kock, E.

    2011-01-01

    Supervision has been identified as an important factor in the success of postgraduate students, even as the most significant variable and a large number of studies have been conducted to identify factors that contribute to supervision success. However the dependent variable in these studies--supervision success--has been an elusive one to define.…

  9. Latino risk-adjusted mortality in the men screened for the Multiple Risk Factor Intervention Trial.

    PubMed

    Thomas, Avis J; Eberly, Lynn E; Neaton, James D; Smith, George Davey

    2005-09-15

    Latinos are now the largest minority in the United States, but their distinctive health needs and mortality patterns remain poorly understood. Proportional hazards regressions were used to compare Latino versus White risk- and income-adjusted mortality over 25 years' follow-up from 5,846 Latino and 300,647 White men screened for the Multiple Risk Factor Intervention Trial. Men were aged 35-57 years and residing in 14 states when screened in 1973-1975. Data on coronary heart disease risk factors, self-reported race/ethnicity, and home addresses were obtained at baseline; income was estimated by linking addresses to census data. Mortality follow-up through 1999 was obtained using the National Death Index. The fully adjusted Latino/White hazard ratio for all-cause mortality was 0.82 (95% confidence interval (CI): 0.77, 0.87), based on 1,085 Latino and 73,807 White deaths; this pattern prevailed over time and across states (thus, likely across Latino subgroups). Hazard ratios were significantly greater than one for stroke (hazard ratio = 1.30, 95% CI: 1.01, 1.68), liver cancer (hazard ratio = 2.02, 95% CI: 1.21, 3.37), and infection (hazard ratio = 1.69, 95% CI: 1.24, 2.32). A substudy found only minor racial/ethnic differences in the quality of Social Security numbers, birth dates, soundex-adjusted names, and National Death Index searches. Results were not likely an artifact of return migration or incomplete mortality data. PMID:16076831

  10. Identifying and Addressing Vaccine Hesitancy

    PubMed Central

    Kestenbaum, Lori A.; Feemster, Kristen A.

    2015-01-01

    In the 20th century, the introduction of multiple vaccines significantly reduced childhood morbidity, mortality, and disease outbreaks. Despite, and perhaps because of, their public health impact, an increasing number of parents and patients are choosing to delay or refuse vaccines. These individuals are described as vaccine hesitant. This phenomenon has developed due to the confluence of multiple social, cultural, political and personal factors. As immunization programs continue to expand, understanding and addressing vaccine hesitancy will be crucial to their successful implementation. This review explores the history of vaccine hesitancy, its causes, and suggested approaches for reducing hesitancy and strengthening vaccine acceptance. PMID:25875982

  11. Identifying and addressing vaccine hesitancy.

    PubMed

    Kestenbaum, Lori A; Feemster, Kristen A

    2015-04-01

    In the 20th century, the introduction of multiple vaccines significantly reduced childhood morbidity, mortality, and disease outbreaks. Despite, and perhaps because of, their public health impact, an increasing number of parents and patients are choosing to delay or refuse vaccines. These individuals are described as "vaccine hesitant." This phenomenon has developed due to the confluence of multiple social, cultural, political, and personal factors. As immunization programs continue to expand, understanding and addressing vaccine hesitancy will be crucial to their successful implementation. This review explores the history of vaccine hesitancy, its causes, and suggested approaches for reducing hesitancy and strengthening vaccine acceptance. PMID:25875982

  12. Multiple Transcription Factor Families Regulate Axon Growth and Regeneration

    PubMed Central

    Moore, Darcie L.; Goldberg, Jeffrey L.

    2011-01-01

    Understanding axon regenerative failure remains a major goal in neuroscience, and reversing this failure remains a major goal for clinical neurology. While an inhibitory CNS environment clearly plays a role, focus on molecular pathways within neurons has begun to yield fruitful insights. Initial steps forward investigated the receptors and signaling pathways immediately downstream of environmental cues, but recent work has also shed light on transcriptional control mechanisms that regulate intrinsic axon growth ability, presumably through whole cassettes of gene target regulation. Here we will discuss transcription factors that regulate neurite growth in vitro and in vivo, including p53, SnoN, E47, CREB, STAT3, NFAT, c-Jun, ATF3, Sox11, NFκB, and Kruppel-like factors (KLFs). Revealing the similarities and differences among the functions of these transcription factors may further our understanding of the mechanisms of transcriptional regulation in axon growth and regeneration. PMID:21674813

  13. Teachers' Grading Decision Making: Multiple Influencing Factors and Methods

    ERIC Educational Resources Information Center

    Cheng, Liying; Sun, Youyi

    2015-01-01

    This study investigated Chinese secondary school English language teachers' grading decision making, focusing on the factors they considered and types of assessment they used for grading. A questionnaire was issued to 350 secondary school English language teachers in China. Descriptive analyses of the questionnaire data showed that these teachers…

  14. Investigation of Multiple Human Factors in Personalized Learning

    ERIC Educational Resources Information Center

    Chen, Sherry Y.; Huang, Pei-Ren; Shih, Yu-Cheng; Chang, Li-Ping

    2016-01-01

    In the past decade, a number of personalized learning systems have been developed and they mainly focus on learners' prior knowledge. On the other hand, previous research suggested that gender differences and cognitive styles have great effects on student learning. To this end, this study examines how human factors, especially gender differences…

  15. Multiple jeopardy: Risk and protective factors among addicted mothers' offspring

    PubMed Central

    LUTHAR, SUNIYA S.; CUSHING, GRETTA; MERIKANGAS, KATHLEEN R.; ROUNSAVILLE, BRUCE J.

    2012-01-01

    Objectives of this study were to ascertain risk and protective factors in the adjustment of 78 school-age and teenage offspring of opioid- and cocaine-abusing mothers. Using a multimethod, multiinformant approach, child outcomes were operationalized via lifetime psychiatric diagnoses and everyday social competence (each based on both mother and child reports), and dimensional assessments of symptoms (mother report). Risk/protective factors examined included the child sociodemographic attributes of gender, age, and ethnicity, aspects of maternal psychopathology, and both mother's and children's cognitive functioning. Results revealed that greater child maladjustment was linked with increasing age, Caucasian (as opposed to African American) ethnicity, severity of maternal psychiatric disturbance, higher maternal cognitive abilities (among African Americans) and lower child cognitive abilities (among Caucasians). Limitations of the study are discussed, as are implications of findings for future research. PMID:9524811

  16. Multiple risk factor evaluation in a hypertension clinic.

    PubMed

    Thom, S; Bunker, J; Callister, W; Poulter, N; Sever, P; Zographos, D

    1989-12-01

    Hypertension is associated with abnormal lipoprotein metabolism, which may be exacerbated by some groups of antihypertensive drugs and represents an additional powerful coronary heart disease risk factor. Of our Hypertension Clinic population, 75% had a total fasting serum cholesterol greater than 5.2 mmol/l. Dietary advice and adjustment of antihypertensive therapy has achieved significant reductions in total cholesterol, serum triglycerides and body weight (14%, 18% and 4.3%, respectively) in a cohort of 65 patients reassessed over a period of 3-21 months. The reduction in cholesterol is likely to represent at least a 28% reduction in the risk of a major coronary heart disease event, even before taking account of any improvement in other coronary heart disease risk factors. PMID:2632734

  17. Multiple birth risk factors and the distribution of handedness.

    PubMed

    Hicks, R A; Elliott, D; Garbesi, L; Martin, S

    1979-03-01

    In this study, we attempted to maximize the likelihood of replicating Bakan's (1971, 1977a) observations that left-handedness was more probable in college students who were the progeny of "high-risk" births. To do this, the relationships between handedness and a combination of factors known to be associated with birth risk were computed. The observed relationships proved to be trivial and thus the validity of Bakan's hypothesis was questionned. PMID:571779

  18. Impact of Multiple Factors on the Degree of Tinnitus Distress

    PubMed Central

    Brüggemann, Petra; Szczepek, Agnieszka J.; Rose, Matthias; McKenna, Laurence; Olze, Heidi; Mazurek, Birgit

    2016-01-01

    Objective: The primary cause of subjective tinnitus is a dysfunction of the auditory system; however, the degree of distress tinnitus causes depends largely on the psychological status of the patient. Our goal was to attempt to associate the grade of tinnitus-related distress with the psychological distress, physical, or psychological discomfort patients experienced, as well as potentially relevant social parameters, through a simultaneous analysis of these factors. Methods: We determined the level of tinnitus-related distress in 531 tinnitus patients using the German version of the tinnitus questionnaire (TQ). In addition, we used the Perceived Stress Questionnaire (PSQ); General Depression Scale Allgemeine Depression Skala (ADS), Berlin Mood Questionnaire (BSF); somatic symptoms inventory (BI), and SF-8 health survey as well as general information collected through a medical history. Results: The TQ score significantly correlated with a score obtained using PSQ, ADS, BSF, BI, and SF-8 alongside psychosocial factors such as age, gender, and marital status. The level of hearing loss and the auditory properties of the specific tinnitus combined with perceived stress and the degree of depressive mood and somatic discomfort of a patient were identified as medium-strong predictors of chronic tinnitus. Social factors such as gender, age, or marital status also had an impact on the degree of tinnitus distress. The results that were obtained were implemented in a specific cortical distress network model. Conclusions: Using a large representative sample of patients with chronic tinnitus permitted a simultaneous statistical measurement of psychometric and audiological parameters in predicting tinnitus distress. We demonstrate that single factors can be distinguished in a manner that explains their causative association and influence on the induction of tinnitus-related distress. PMID:27445776

  19. On Studying Common Factor Variance in Multiple-Component Measuring Instruments

    ERIC Educational Resources Information Center

    Raykov, Tenko; Pohl, Steffi

    2013-01-01

    A method for examining common factor variance in multiple-component measuring instruments is outlined. The procedure is based on an application of the latent variable modeling methodology and is concerned with evaluating observed variance explained by a global factor and by one or more additional component-specific factors. The approach furnishes…

  20. Elk-1 a Transcription Factor with Multiple Facets in the Brain

    PubMed Central

    Besnard, Antoine; Galan-Rodriguez, Beatriz; Vanhoutte, Peter; Caboche, Jocelyne

    2011-01-01

    The ternary complex factor (TCF) Elk-1 is a transcription factor that regulates immediate early gene (IEG) expression via the serum response element (SRE) DNA consensus site. Elk-1 is associated with a dimer of serum response factor (SRF) at the SRE site, and its phosphorylation occurs at specific residues in response to mitogen-activated protein kinases (MAPKs), including c-Jun-N terminal kinase (JNK), p38/MAPK, and extracellular-signal regulated kinase (ERK). This phosphorylation event is critical for triggering SRE-dependent transcription. Although MAPKs are fundamental actors for the instatement and maintenance of memory, and much investigation of their downstream signaling partners have been conducted, no data yet clearly implicate Elk-1 in these processes. This is partly due to the complexity of Elk-1 sub-cellular localization, and hence functions, within neurons. Elk-1 is present in its resting state in the cytoplasm, where it colocalizes with mitochondrial proteins or microtubules. In this particular sub-cellular compartment, overexpression of Elk-1 is toxic for neuronal cells. When phosphorylated by the MAPK/ERK, Elk-1 translocates to the nucleus where it is implicated in regulating chromatin remodeling, SRE-dependent transcription, and neuronal differentiation. Another post-translational modification is the conjugation to SUMO (Small Ubiquitin-like MOdifier), which relocalizes Elk-1 in the cytoplasm. Thus, Elk-1 plays a dual role in neuronal functions: pro-apoptotic within the cytoplasm, and pro-differentiation within the nucleus. To address the role of Elk-1 in the brain, one must be aware of its multiple facets, and design molecular tools that will shut down Elk-1 expression, trafficking, or activation, in specific neuronal compartments. We summarize in this review the known molecular functions of Elk-1, its regulation in neuronal cells, and present evidence of its possible implication in model systems of synaptic plasticity, learning, but also in

  1. Genetic factors influencing the risk of multiple myeloma bone disease

    PubMed Central

    Johnson, D C; Weinhold, N; Mitchell, J; Chen, B; Stephens, O W; Försti, A; Nickel, J; Kaiser, M; Gregory, W A; Cairns, D; Jackson, G H; Hoffmann, P; Noethen, M M; Hillengass, J; Bertsch, U; Barlogie, B; Davis, F E; Hemminki, K; Goldschmidt, H; Houlston, R S; Morgan, G J

    2016-01-01

    A major complication of multiple myeloma (MM) is the development of osteolytic lesions, fractures and bone pain. To identify genetic variants influencing the development of MM bone disease (MBD), we analyzed MM patients of European ancestry (totaling 3774), which had been radiologically surveyed for MBD. Each patient had been genotyped for ~6 00 000 single-nucleotide polymorphisms with genotypes for six million common variants imputed using 1000 Genomes Project and UK10K as reference. We identified a locus at 8q24.12 for MBD (rs4407910, OPG/TNFRSF11B, odds ratio=1.38, P=4.09 × 10–9) and a promising association at 19q13.43 (rs74676832, odds ratio=1.97, P=9.33 × 10–7). Our findings demonstrate that germline variation influences MBD and highlights the importance of RANK/RANKL/OPG pathway in MBD development. These findings will contribute to the development of future strategies for prevention of MBD in the early precancerous phases of MM. PMID:26669972

  2. Complete Effect-Profile Assessment in Association Studies with Multiple Genetic and Multiple Environmental Factors

    PubMed Central

    Wang, Zhi; Maity, Arnab; Luo, Yiwen; Neely, Megan L.; Tzeng, Jung-Ying

    2014-01-01

    Studying complex diseases in the post GWAS era has led to developing methods that consider factor-sets rather than individual genetic/environmental factors (i.e., Multi-G-Multi-E studies), and mining for potential gene-environment (GxE) interactions has proven to be an invaluable aid in both discovery and deciphering underlying biological mechanisms. Current approaches for examining effect profiles in Multi-G-Multi-E analyses are either underpowered due to large degrees of freedom, ill-suited for detecting GxE interactions due to imprecise modeling of the G and E effects, or lack of capacity for modeling interactions between two factor sets (e.g., existing methods focus primarily on a single E factor). In this work, we illustrate the issues encountered in constructing kernels for investigating interactions between two factor-sets, and propose a simple yet intuitive solution to construct the GxE kernel that retains the ease-of-interpretation of classic regression. We also construct a series of KM score tests to evaluate the complete effect profile (i.e., the G, E, and GxE effects individually or in combination). We show, via simulations and a data application, that the proposed KM methods outperform the classic and PC regressions across a range of scenarios, including varying effect size, effect structure, and interaction complexity. The largest power gain was observed when the underlying effect structure involved complex GxE interactions; however, the proposed methods have consistent, powerful performance when the effect profile is simple or complex, suggesting that the proposed method could be a useful tool for exploratory or confirmatory GxE analysis. PMID:25538034

  3. Dynamic Visual Computer Design for Factors and Multiples Word Problem Learning

    ERIC Educational Resources Information Center

    Hsieh, Chejen; Lin, Shouhua

    2008-01-01

    This study employs the Excel function to design dynamic visual activities for factors and multiples word problem learning. A teaching experiment was carried out eight times in 4 weeks on three fifth grade students. The result showed that after using multiple-linked representations activities, students made greater progress in understanding target…

  4. Single and Multiple Suicide Attempts and Associated Health Risk Factors in New Hampshire Adolescents

    ERIC Educational Resources Information Center

    Rosenberg, Harriet J.; Jankowski, Mary K.; Sengupta, Anjana; Wolfe, Rosemarie S.; Wolford, George L., II; Rosenberg, Stanley D.

    2005-01-01

    In this study we examined self-reported suicide attempts and their relationship to other health risk factors in a community sample of 16,644 adolescents. Fifteen percent endorsed suicide attempts (10% single; 5% multiple attempts). We hypothesized that multiple attempters would show higher prevalence of comorbid health risks than single or…

  5. Multiple Weather Factors Affect Apparent Survival of European Passerine Birds

    PubMed Central

    Salewski, Volker; Hochachka, Wesley M.; Fiedler, Wolfgang

    2013-01-01

    Weather affects the demography of animals and thus climate change will cause local changes in demographic rates. In birds numerous studies have correlated demographic factors with weather but few of those examined variation in the impacts of weather in different seasons and, in the case of migrants, in different regions. Using capture-recapture models we correlated weather with apparent survival of seven passerine bird species with different migration strategies to assess the importance of selected facets of weather throughout the year on apparent survival. Contrary to our expectations weather experienced during the breeding season did not affect apparent survival of the target species. However, measures for winter severity were associated with apparent survival of a resident species, two short-distance/partial migrants and a long-distance migrant. Apparent survival of two short distance migrants as well as two long-distance migrants was further correlated with conditions experienced during the non-breeding season in Spain. Conditions in Africa had statistically significant but relatively minor effects on the apparent survival of the two long-distance migrants but also of a presumably short-distance migrant and a short-distance/partial migrant. In general several weather effects independently explained similar amounts of variation in apparent survival for the majority of species and single factors explained only relatively low amounts of temporal variation of apparent survival. Although the directions of the effects on apparent survival mostly met our expectations and there are clear predictions for effects of future climate we caution against simple extrapolations of present conditions to predict future population dynamics. Not only did weather explains limited amounts of variation in apparent survival, but future demographics will likely be affected by changing interspecific interactions, opposing effects of weather in different seasons, and the potential for

  6. Presidential address.

    PubMed

    Vohra, U

    1993-07-01

    The Secretary of India's Ministry of Health and Family Welfare serves as Chair of the Executive Council of the International Institute for Population Sciences in Bombay. She addressed its 35th convocation in 1993. Global population stands at 5.43 billion and increases by about 90 million people each year. 84 million of these new people are born in developing countries. India contributes 17 million new people annually. The annual population growth rate in India is about 2%. Its population size will probably surpass 1 billion by the 2000. High population growth rates are a leading obstacle to socioeconomic development in developing countries. Governments of many developing countries recognize this problem and have expanded their family planning programs to stabilize population growth. Asian countries that have done so and have completed the fertility transition include China, Japan, Singapore, South Korea, and Thailand. Burma, Malaysia, North Korea, Sri Lanka, and Vietnam have not yet completed the transition. Afghanistan, Bangladesh, Iran, Nepal, and Pakistan are half-way through the transition. High population growth rates put pressure on land by fragmenting finite land resources, increasing the number of landless laborers and unemployment, and by causing considerable rural-urban migration. All these factors bring about social stress and burden civic services. India has reduced its total fertility rate from 5.2 to 3.9 between 1971 and 1991. Some Indian states have already achieved replacement fertility. Considerable disparity in socioeconomic development exists among states and districts. For example, the states of Bihar, Madhya Pradesh, Rajasthan, and Uttar Pradesh have female literacy rates lower than 27%, while that for Kerala is 87%. Overall, infant mortality has fallen from 110 to 80 between 1981 and 1990. In Uttar Pradesh, it has fallen from 150 to 98, while it is at 17 in Kerala. India needs innovative approaches to increase contraceptive prevalence rates

  7. Multiple genetic factors in the heterogeneity of thyroid hormone resistance

    SciTech Connect

    Weiss, R.E.; Refetoff, S. ); Marcocci, C.; Bruno-Bossio, G. )

    1993-01-01

    Generalized resistance to thyroid hormone (GRTH), a syndrome of inherited tissue hyposensitivity to thyroid hormone, is linked to thyroid hormone receptor (TR) mutations. A typical feature of GRTH is variable severity of organ involvement among families that, surprisingly, does not correlate with the degree of T[sub 3]-binding impairment of the corresponding in vitro synthesized mutant TRs. Furthermore, variations in the clinical severity among family members harboring identical TR[beta] mutations have been reported. The authors compared serum levels of thyroid hormones that maintained a normal TSH in members of a large family with GRTH divided in three groups: Group A, 8 affected subjects with a mutation replacing arginine-320 with a histidine in the T[sub 3]-binding domain of TR[beta]; Group B, 11 first degree relatives (sibs and children of affected subjects) with no TR[beta] mutation; Group C, 16 controls related by marriage. TSH values were not different among the three groups. As expected, total and free T[sub 4] and T[sub 3], and rT[sub 3] levels were significantly higher in Group A vs Groups B and C. However, with the exception of T[sub 3], the same tests were also significantly higher in Group B vs Group C. The latter differences are not due to thyroid hormone transport in serum since TBG concentrations were not different. It is postulated that genetic variability of factors that contribute to the action of thyroid hormone modulate the phenotype of GRTH associated with TR[beta] mutations. 23 refs., 2 figs., 1 tab.

  8. Confounding factors in HGT detection: statistical error, coalescent effects, and multiple solutions.

    PubMed

    Than, Cuong; Ruths, Derek; Innan, Hideki; Nakhleh, Luay

    2007-05-01

    Prokaryotic organisms share genetic material across species boundaries by means of a process known as horizontal gene transfer (HGT). This process has great significance for understanding prokaryotic genome diversification and unraveling their complexities. Phylogeny-based detection of HGT is one of the most commonly used methods for this task, and is based on the fundamental fact that HGT may cause gene trees to disagree with one another, as well as with the species phylogeny. Using these methods, we can compare gene and species trees, and infer a set of HGT events to reconcile the differences among these trees. In this paper, we address three factors that confound the detection of the true HGT events, including the donors and recipients of horizontally transferred genes. First, we study experimentally the effects of error in the estimated gene trees (statistical error) on the accuracy of inferred HGT events. Our results indicate that statistical error leads to overestimation of the number of HGT events, and that HGT detection methods should be designed with unresolved gene trees in mind. Second, we demonstrate, both theoretically and empirically, that based on topological comparison alone, the number of HGT scenarios that reconcile a pair of species/gene trees may be exponential. This number may be reduced when branch lengths in both trees are estimated correctly. This set of results implies that in the absence of additional biological information, and/or a biological model of how HGT occurs, multiple HGT scenarios must be sought, and efficient strategies for how to enumerate such solutions must be developed. Third, we address the issue of lineage sorting, how it confounds HGT detection, and how to incorporate it with HGT into a single stochastic framework that distinguishes between the two events by extending population genetics theories. This result is very important, particularly when analyzing closely related organisms, where coalescent effects may not be

  9. The 2011 Leona Tyler Award Address: The Relationship--And Its Relationship to the Common and Specific Factors of Psychotherapy

    ERIC Educational Resources Information Center

    Wampold, Bruce E.; Budge, Stephanie L.

    2012-01-01

    A debate exists about whether the common factors or specific ingredients are critical to producing the benefits of psychotherapy. A model of the relationship, based on evolved human characteristics related to healing, is presented that integrates common factors and specific ingredients. After the initial bond is formed, the relationship involves…

  10. Science Teaching Efficacy of Preservice Elementary Teachers: Examination of the Multiple Factors Reported as Influential

    ERIC Educational Resources Information Center

    Tastan Kirik, Özgecan

    2013-01-01

    This study explores the science teaching efficacy beliefs of preservice elementary teachers and the relationship between efficacy beliefs and multiple factors such as antecedent factors (participation in extracurricular activities and number of science and science teaching methods courses taken), conceptual understanding, classroom management…

  11. Investigating the Nature of Method Factors through Multiple Informants: Evidence for a Specific Factor?

    ERIC Educational Resources Information Center

    Alessandri, Guido; Vecchione, Michele; Tisak, John; Barbaranelli, Claudio

    2011-01-01

    When a self-report instrument includes a balanced number of positively and negatively worded items, factor analysts often use method factors to aid model fitting. The nature of these factors, often referred to as acquiescence, is still debated. Relying upon previous results (Alessandri et al., 2010; DiStefano & Motl, 2006, 2008; Rauch, Schweizer,…

  12. Therapeutic targets of multiple angiogenic factors for the treatment of cancer and metastasis.

    PubMed

    Cao, Yihai; Liu, Qi

    2007-01-01

    Like any growing healthy tissues, tumors build up their blood vessels by three mechanisms: angiogenesis, vasculogenesis, and intersucception. Vascular endothelial growth factor-A (VEGF-A) is one of the key factors responsible for stimulation and maintenance of the disorganized, leaky, and torturous tumor vasculature. In addition to VEGF-A, tumors produce multiple other factors to stimulate blood vessel growth. These include members in the platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), VEGF-C, insulin-like growth factor (IGF), angiopoietin (Ang), and hepatocyte growth factor (HGF) families. Recent studies show that these angiogenic factors can also promote lymphangiogenesis and potentially lymphatic metastasis. Understanding the roles of individual and combined angiogenic factors in promoting tumor angiogenesis is crucial for defining therapeutic targets and antiangiogenic drug development for the treatment of cancer. PMID:17419947

  13. Multiple NUCLEAR FACTOR Y transcription factors respond to abiotic stress in Brassica napus L.

    PubMed

    Xu, Li; Lin, Zhongyuan; Tao, Qing; Liang, Mingxiang; Zhao, Gengmao; Yin, Xiangzhen; Fu, Ruixin

    2014-01-01

    Members of the plant NUCLEAR FACTOR Y (NF-Y) family are composed of the NF-YA, NF-YB, and NF-YC subunits. In Brassica napus (canola), each of these subunits forms a multimember subfamily. Plant NF-Ys were reported to be involved in several abiotic stresses. In this study, we demonstrated that multiple members of thirty three BnNF-Ys responded rapidly to salinity, drought, or ABA treatments. Transcripts of five BnNF-YAs, seven BnNF-YBs, and two BnNF-YCs were up-regulated by salinity stress, whereas the expression of thirteen BnNF-YAs, ten BnNF-YBs, and four BnNF-YCs were induced by drought stress. Under NaCl treatments, the expression of one BnNF-YA10 and four NF-YBs (BnNF-YB3, BnNF-YB7, BnNF-YB10, and BnNF-YB14) were greatly increased. Under PEG treatments, the expression levels of four NF-YAs (BnNF-YA9, BnNF-YA10, BnNF-YA11, and BnNF-YA12) and five NF-YBs (BnNF-YB1, BnNF-YB8, BnNF-YB10, BnNF-YB13, and BnNF-YB14) were greatly induced. The expression profiles of 20 of the 27 salinity- or drought-induced BnNF-Ys were also affected by ABA treatment. The expression levels of six NF-YAs (BnNF-YA1, BnNF-YA7, BnNF-YA8, BnNF-YA9, BnNF-YA10, and BnNF-YA12) and seven BnNF-YB members (BnNF-YB2, BnNF-YB3, BnNF-YB7, BnNF-YB10, BnNF-YB11, BnNF-YB13, and BnNF-YB14) and two NF-YC members (BnNF-YC2 and BnNF-YC3) were greatly up-regulated by ABA treatments. Only a few BnNF-Ys were inhibited by the above three treatments. Several NF-Y subfamily members exhibited collinear expression patterns. The promoters of all stress-responsive BnNF-Ys harbored at least two types of stress-related cis-elements, such as ABRE, DRE, MYB, or MYC. The cis-element organization of BnNF-Ys was similar to that of Arabidopsis thaliana, and the promoter regions exhibited higher levels of nucleotide sequence identity with Brassica rapa than with Brassica oleracea. This work represents an entry point for investigating the roles of canola NF-Y proteins during abiotic stress responses and provides insight into

  14. [A factor analysis method for contingency table data with unlimited multiple choice questions].

    PubMed

    Toyoda, Hideki; Haiden, Reina; Kubo, Saori; Ikehara, Kazuya; Isobe, Yurie

    2016-02-01

    The purpose of this study is to propose a method of factor analysis for analyzing contingency tables developed from the data of unlimited multiple-choice questions. This method assumes that the element of each cell of the contingency table has a binominal distribution and a factor analysis model is applied to the logit of the selection probability. Scree plot and WAIC are used to decide the number of factors, and the standardized residual, the standardized difference between the sample, and the proportion ratio, is used to select items. The proposed method was applied to real product impression research data on advertised chips and energy drinks. Since the results of the analysis showed that this method could be used in conjunction with conventional factor analysis model, and extracted factors were fully interpretable, and suggests the usefulness of the proposed method in the study of psychology using unlimited multiple-choice questions. PMID:26964368

  15. Protective Factors Associated with Fewer Multiple Problem Behaviors Among Homeless/Runaway Youth

    PubMed Central

    Lightfoot, Marguerita; Stein, Judith A.; Tevendale, Heather; Preston, Kathleen

    2015-01-01

    Although homeless youth exhibit numerous problem behaviors, protective factors that can be targeted and modified by prevention programs to decrease the likelihood of involvement in risky behaviors are less apparent. The current study tested a model of protective factors for multiple problem behavior in a sample of 474 homeless youth (42% girls; 83% minority) ages 12 to 24 years. Higher levels of problem solving and planning skills were strongly related to lower levels of multiple problem behaviors in homeless youth, suggesting both the positive impact of preexisting personal assets of these youth and important programmatic targets for further building their resilience and decreasing problem behaviors. Indirect relationships between the background factors of self-esteem and social support and multiple problem behaviors were significantly mediated through protective skills. The model suggests that helping youth enhance their skills in goal setting, decision making, and self-reliant coping could lessen a variety of problem behaviors commonly found among homeless youth. PMID:22023279

  16. Are major behavioral and sociodemographic risk factors for mortality additive or multiplicative in their effects?

    PubMed

    Mehta, Neil; Preston, Samuel

    2016-04-01

    All individuals are subject to multiple risk factors for mortality. In this paper, we consider the nature of interactions between certain major sociodemographic and behavioral risk factors associated with all-cause mortality in the United States. We develop the formal logic pertaining to two forms of interaction between risk factors, additive and multiplicative relations. We then consider the general circumstances in which additive or multiplicative relations might be expected. We argue that expectations about interactions among socio-demographic variables, and their relation to behavioral variables, have been stated in terms of additivity. However, the statistical models typically used to estimate the relation between risk factors and mortality assume that risk factors act multiplicatively. We examine empirically the nature of interactions among five major risk factors associated with all-cause mortality: smoking, obesity, race, sex, and educational attainment. Data were drawn from the cross-sectional NHANES III (1988-1994) and NHANES 1999-2010 surveys, linked to death records through December 31, 2011. Our analytic sample comprised 35,604 respondents and 5369 deaths. We find that obesity is additive with each of the remaining four variables. We speculate that its additivity is a reflection of the fact that obese status is generally achieved later in life. For all pairings of socio-demographic variables, risks are multiplicative. For survival chances, it is much more dangerous to be poorly educated if you are black or if you are male. And it is much riskier to be a male if you are black. These traits, established at birth or during childhood, literally result in deadly combinations. We conclude that the identification of interactions among risk factors can cast valuable light on the nature of the process being studied. It also has public health implications by identifying especially vulnerable groups and by properly identifying the proportion of deaths

  17. Addressing healthcare.

    PubMed

    Daly, Rich

    2013-02-11

    Though President Barack Obama has rarely made healthcare references in his State of the Union addresses, health policy experts are hoping he changes that strategy this year. "The question is: Will he say anything? You would hope that he would, given that that was the major issue he started his presidency with," says Dr. James Weinstein, left, of the Dartmouth-Hitchcock health system. PMID:23487896

  18. The use of adjustment factors to address the impact of inflammation on vitamin A and iron status in humans.

    PubMed

    Thurnham, David I; Northrop-Clewes, Christine A; Knowles, Jacqueline

    2015-05-01

    Many nutrient biomarkers are altered by inflammation. We calculated adjustment factors for retinol and ferritin by using meta-analyses of studies containing the respective biomarker and 2 acute phase proteins in serum, C-reactive protein (CRP), and α1-acid glycoprotein (AGP). With the use of CRP and AGP we identified 4 groups in each study: reference (CRP ≤5 mg/L, AGP ≤1 g/L), incubation (CRP >5 mg/L, AGP ≤1 g/L), early convalescence (CRP >5 mg/L, AGP >1 g/L), and late convalescence (CRP ≤5 mg/L, AGP >1 g/L). For each biomarker, ratios of the geometric means of the reference to each inflammation group concentration were used to calculate adjustment factors for retinol (1.13, 1.24, and 1.11) and ferritin (0.77, 0.53, and 0.75) for the incubation, early, and late convalescent groups, respectively. The application of the meta-analysis factors in more recent studies compares well with study-specific factors. The same method was used to calculate adjustment factors for soluble transferrin receptor (sTfR) and body iron stores (BISs) in Lao children. We found no advantage in adjusting sTfR for inflammation; in fact, adjustment decreased iron deficiency. Neither adjusted (10% <0 mg/kg) nor nonadjusted (12% <0 mg/kg) BISs detected as much iron deficiency as did ferritin (18% <12 μg/L) and adjusted ferritin (21% <12 μg/L) unless the cutoff for BISs was increased from 0 to <3 mg/kg. However, we could find no evidence that the larger number of children identified as having BISs <3 mg/kg had risks of anemia comparable to those identified by using ferritin <12 μg/L. In conclusion, both corrected and uncorrected ferritin concentrations <12 μg/L are associated with more iron deficiency and anemia than either sTfR >8.3 mg/L or BISs <0 mg/kg in Lao children. PMID:25833890

  19. Community Stakeholders' Perceptions of Major Factors Influencing Childhood Obesity, the Feasibility of Programs Addressing Childhood Obesity, and Persisting Gaps.

    PubMed

    Ganter, Claudia; Aftosmes-Tobio, Alyssa; Chuang, Emmeline; Blaine, Rachel E; Land, Thomas; Davison, Kirsten K

    2016-04-01

    Prior research has identified numerous factors contributing to increased rates of childhood obesity. However, few studies have focused explicitly on the experience of community stakeholders in low-income communities. This study sought to capture the perspectives of these on-the-ground experts regarding major factors contributing to childhood obesity as well as gaps in current prevention and control efforts. We conducted semi-structured interviews with 39 stakeholders from different community sectors (e.g., healthcare providers, childcare providers, teachers). Data were drawn from the Massachusetts Childhood Obesity Research Demonstration project, a multi-level, multi-sector intervention designed to reduce childhood obesity being implemented in two low-income communities in Massachusetts. Interviews were conducted at baseline, transcribed, coded using grounded theory approach, and analyzed in NVivo 10.0. The vast majority of stakeholders had recently participated in obesity prevention strategies, and nearly all of them identified gaps in prevention efforts either within their organizations or in the broader community. In addition to factors previously identified in the literature, several themes emerged including the need to change policies to increase physical activity during school, offer healthier snacks in schools and afterschool programs, and increase communication and collaboration within the community in prevention efforts. Community stakeholders can impact the success of interventions by bridging the gap between science and lived experience. The results of this study can guide future research by highlighting the importance of including stakeholders' frontline experiences with target populations, and using information on identified gaps to augment intervention planning efforts. PMID:26433725

  20. Addressing Structural and Environmental Factors for Adolescent Sexual and Reproductive Health in Low- and Middle-Income Countries.

    PubMed

    Sommer, Marni; Mmari, Kristin

    2015-10-01

    A deeper understanding of how structure and environment shape the sexual and reproductive health vulnerabilities of youths across a range of outcomes has implications for the development of successful policies and programs. We have discussed some of the key structural and environmental factors that influence the sexual and reproductive health of adolescents, particularly in low- and middle-income countries, and the importance of engaging adolescents in identifying solutions. We have highlighted 2 case studies that describe structural or environmental approaches to improving adolescent sexual and reproductive health and made recommendations to more systematically incorporate attention to structure and environment to improve global adolescent health. PMID:26270290

  1. Stress Intensity Factor Solutions for Multiple Edge Cracks in Ceramic Matrix Composites

    NASA Technical Reports Server (NTRS)

    Ghosn, Louis

    1997-01-01

    NASA Lewis Research Center conducted a study to determine the stress intensity factor solutions for periodic arrays of bridged cracks for various crack spacings and crack lengths. Initially, the stress intensity factor of an array of unbridged multiple edge cracks was determined under constant global displacement as well as at a point load along the crack wake. These solutions are expected to contribute toward the development of a damage-based life-prediction methodology for CMC engine components.

  2. Common risk factor approach to address socioeconomic inequality in the oral health of preschool children – a prospective cohort study

    PubMed Central

    2014-01-01

    Background Dental caries remains the most prevalent chronic condition in children and a major contributor to poor general health. There is ample evidence of a skewed distribution of oral health, with a small proportion of children in the population bearing the majority of the burden of the disease. This minority group is comprised disproportionately of socioeconomically disadvantaged children. An in-depth longitudinal study is needed to better understand the determinants of child oral health, in order to support effective evidence-based policies and interventions in improving child oral health. The aim of the Study of Mothers’ and Infants’ Life Events Affecting Oral Health (SMILE) project is to identify and evaluate the relative importance and timing of critical factors that shape the oral health of young children and then to seek to evaluate those factors in their inter-relationship with socioeconomic influences. Methods/Design This investigation will apply an observational prospective study design to a cohort of socioeconomically-diverse South Australian newborns and their mothers, intensively following these dyads as the children grow to toddler age. Mothers of newborn children will be invited to participate in the study in the early post-partum period. At enrolment, data will be collected on parental socioeconomic status, mothers’ general and dental health conditions, details of the pregnancy, infant feeding practice and parental health behaviours and practices. Data on diet and feeding practices, oral health behaviours and practices, and dental visiting patterns will be collected at 3, 6, 12 and 24 months of age. When children turn 24-30 months, the children and their mothers/primary care givers will be invited to an oral examination to record oral health status. Anthropometric assessment will also be conducted. Discussion This prospective cohort study will examine a wide range of determinants influencing child oral health and related general conditions

  3. C/EBPβ regulates transcription factors critical for proliferation and survival of multiple myeloma cells

    PubMed Central

    Pal, Rekha; Janz, Martin; Galson, Deborah L.; Gries, Margarete; Li, Shirong; Jöhrens, Korinna; Anagnostopoulos, Ioannis; Dörken, Bernd; Mapara, Markus Y.; Borghesi, Lisa; Kardava, Lela; Roodman, G. David; Milcarek, Christine

    2009-01-01

    CCAAT/enhancer-binding protein β (C/EBPβ), also known as nuclear factor–interleukin-6 (NF-IL6), is a transcription factor that plays an important role in the regulation of growth and differentiation of myeloid and lymphoid cells. Mice deficient in C/EBPβ show impaired generation of B lymphocytes. We show that C/EBPβ regulates transcription factors critical for proliferation and survival in multiple myeloma. Multiple myeloma cell lines and primary multiple myeloma cells strongly expressed C/EBPβ, whereas normal B cells and plasma cells had little or no detectable levels of C/EBPβ. Silencing of C/EBPβ led to down-regulation of transcription factors such as IRF4, XBP1, and BLIMP1 accompanied by a strong inhibition of proliferation. Further, silencing of C/EBPβ led to a complete down-regulation of antiapoptotic B-cell lymphoma 2 (BCL2) expression. In chromatin immunoprecipitation assays, C/EBPβ directly bound to the promoter region of IRF4, BLIMP1, and BCL2. Our data indicate that C/EBPβ is involved in the regulatory network of transcription factors that are critical for plasma cell differentiation and survival. Targeting C/EBPβ may provide a novel therapeutic strategy in the treatment of multiple myeloma. PMID:19717648

  4. On Highest Common Factor and Least Common Multiple in the Secondary School Mathematics Curriculum.

    ERIC Educational Resources Information Center

    Davies, H. B.

    1980-01-01

    Attention is drawn to an ancient Greek method for finding the least common multiple (LCM) of two numbers. A link is established between this method and a well-known method of obtaining the highest common factor (HCF) numbers. This leads to consideration of some relationships between HCF and LCM. (Author/MK)

  5. The Effect of Auxiliary Variables and Multiple Imputation on Parameter Estimation in Confirmatory Factor Analysis

    ERIC Educational Resources Information Center

    Yoo, Jin Eun

    2009-01-01

    This Monte Carlo study investigates the beneficiary effect of including auxiliary variables during estimation of confirmatory factor analysis models with multiple imputation. Specifically, it examines the influence of sample size, missing rates, missingness mechanism combinations, missingness types (linear or convex), and the absence or presence…

  6. Mathematical Model for Addiction: Application to Multiple Risk Factor Intervention Trial Data for Smoking.

    ERIC Educational Resources Information Center

    Fan, David P.; Elketroussi, Mehdi

    1989-01-01

    Describes habituation and addiction, both psychological and physiological, using simple equations of mathematical model of ideodynamics, optimized to smoking data from Multiple Risk Factor Intervention Trial (MRFIT) program. With only four constant parameters, it was possible to calculate accurate time trends for recidivism to smoking among…

  7. Primary Factors Related to Multiple Placements for Children in Out-of-Home Care

    ERIC Educational Resources Information Center

    Eggertsen, Lars

    2008-01-01

    Using an ecological framework, this study identified which factors related to out-of-home placements significantly influenced multiple placements for children in Utah during 2000, 2001, and 2002. Multinomial logistic regression statistical procedures and a geographical information system (GIS) were used to analyze the data. The final model…

  8. Effects of dietary factors on energy regulation: Consideration of multiple- versus single-dietary-factor models

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While short-term studies demonstrate consistent effects of dietary protein, fiber, glycemic index and energy density on energy intake, long-term effectiveness trials typically indicate small or non-significant effects of these dietary factors on long-term weight change. In consequence, most lifestyl...

  9. Use of Therapeutic Neuroscience Education to address psychosocial factors associated with acute low back pain: a case report.

    PubMed

    Zimney, Kory; Louw, Adriaan; Puentedura, Emilio J

    2014-04-01

    Acute low back pain (LBP) from injuries is prevalent in the work place. It has been shown that patients with psychosocial factors often progress with persistent pain and lead to significant workers compensation costs. Therapeutic Neuroscience Education (TNE) has been shown to be beneficial in changing a patient's cognition regarding their pain state, which may result in decrease fear, anxiety and catastrophization. A 19-year-old female who developed LBP from a work injury was the patient for this case report. A physical examination, Numeric Pain Rating Scale (NRPS), Oswestry Disability Index (ODI), Fear-Avoidance Beliefs Questionnaire (FABQ), Keele STarT Back Screening Tool (Keele SBST) and Acute Low Back Pain Screening (ALBPS) Questionnaires were assessed during initial physical therapy visit and discharge. Treatment consisted of use of TNE, manual therapy and exercises. She attended five total visits over a 2-week period prior to full discharge. During the initial visit the patient reported NRPS = 3/10, ODI = 36%, FABQ-PA = 23, FABQ-W = 30, Keele SBST = 4/9, ALBPS = 101. At discharge the patient reported a 0 on all outcome questionnaires with ability to return to full work and no pain complaints. PMID:24252071

  10. Genetic, Epigenetic, and Environmental Factors Influencing Neurovisceral Integration of Cardiovascular Modulation: Focus on Multiple Sclerosis.

    PubMed

    Sternberg, Zohara

    2016-03-01

    Thought to be an autoimmune inflammatory CNS disease, multiple sclerosis (MS) involves multiple pathologies with heterogeneous clinical presentations. An impaired neurovisceral integration of cardiovascular modulation, indicated by sympathetic and parasympathetic autonomic nervous system (ANS) dysfunction, is among common MS clinical presentations. ANS dysfunction could not only enhance MS inflammatory and neurodegenerative processes, but can also lead to clinical symptoms such as depression, fatigue, sleep disorder, migraine, osteoporosis, and cerebral hemodynamic impairments. Therefore, factors influencing ANS functional activities, in one way or another, will have a significant impact on MS disease course. This review describes the genetic and epigenetic factors, and their interactions with a number of environmental factors contributing to the neurovisceral integration of cardiovascular modulation, with a focus on MS. Future studies should investigate the improvement in cardiovascular ANS function, as a strategy for preventing and minimizing MS-related morbidities, and improving patients' quality of life. PMID:26502224

  11. Environmental factors in multiple sclerosis: Epstein-Barr virus, vitamin D, and cigarette smoking.

    PubMed

    Wingerchuk, Dean M

    2011-01-01

    Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. Although its cause is not known, genetic and environmental factors both influence susceptibility to the disease. From the large array of environmental risk factors that have been examined over the past century, infection with Epstein-Barr virus, ultraviolet light exposure/vitamin D status, and cigarette smoking stand out because of the strength of supporting evidence. Epstein-Barr virus infection early in life appears to be necessary permissive step for disease development and probably acts in adolescence and early adulthood. Vitamin D-related mechanisms and cigarette smoking probably modify baseline disease risk and could plausibly do so at several stages of life; smoking appears to negatively affect disease course. This review summarizes current evidence for these 3 putative multiple sclerosis risk factors and early attempts to develop risk models and examine gene-environment interactions for this complex disease. PMID:21425266

  12. Inaugural address

    NASA Astrophysics Data System (ADS)

    Joshi, P. S.

    2014-03-01

    From jets to cosmos to cosmic censorship P S Joshi Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, India E-mail: psj@tifr.res.in 1. Introduction At the outset, I should like to acknowledge that part of the title above, which tries to capture the main flavour of this meeting, and has been borrowed from one of the plenary talks at the conference. When we set out to make the programme for the conference, we thought of beginning with observations on the Universe, but then we certainly wanted to go further and address deeper questions, which were at the very foundations of our inquiry, and understanding on the nature and structure of the Universe. I believe, we succeeded to a good extent, and it is all here for you in the form of these Conference Proceedings, which have been aptly titled as 'Vishwa Mimansa', which could be possibly translated as 'Analysis of the Universe'! It is my great pleasure and privilege to welcome you all to the ICGC-2011 meeting at Goa. The International Conference on Gravitation and Cosmology (ICGC) series of meetings are being organized by the Indian Association for General Relativity and Gravitation (IAGRG), and the first such meeting was planned and conducted in Goa in 1987, with subsequent meetings taking place at a duration of about four years at various locations in India. So, it was thought appropriate to return to Goa to celebrate the 25 years of the ICGC meetings. The recollections from that first meeting have been recorded elsewhere here in these Proceedings. The research and teaching on gravitation and cosmology was initiated quite early in India, by V V Narlikar at the Banares Hindu University, and by N R Sen in Kolkata in the 1930s. In course of time, this activity grew and gained momentum, and in early 1969, at the felicitation held for the 60 years of V V Narlikar at a conference in Ahmedabad, P C Vaidya proposed the formation of the IAGRG society, with V V Narlikar being the first President. This

  13. Opening addresses.

    PubMed

    Chukudebelu, W O; Lucas, A O; Ransome-kuti, O; Akinla, O; Obayi, G U

    1988-01-01

    The theme of the 3rd International Conference of the Society of Gynecology and Obstetrics of Nigeria (SOGON) held October 26, 1986 in Enugu was maternal morbidity and mortality in Africa. The opening addresses emphasize the high maternal mortality rate in Africa and SOGON's dedication to promoting women's health and welfare. In order to reduce maternal mortality, the scope of this problem must be made evident by gathering accurate mortality rates through maternity care monitoring and auditing. Governments, health professionals, educators, behavioral scientists, and communication specialists have a responsibility to improve maternal health services in this country. By making the population aware of this problem through education, measures can be taken to reduce the presently high maternal mortality rates. Nigerian women are physically unprepared for childbirth; therefore, balanced diets and disease prevention should be promoted. Since about 40% of deliveries are unmanaged, training for traditional birth attendants should be provided. Furthermore, family planning programs should discourage teenage pregnancies, encourage birth spacing and small families, and promote the use of family planning techniques among men. The problem of child bearing and rearing accompanied by hard work should also be investigated. For practices to change so that maternal mortality rates can be reduced, attitudes must be changed such that the current rates are viewed as unacceptable. PMID:12179275

  14. Opening Address

    NASA Astrophysics Data System (ADS)

    Yamada, T.

    2014-12-01

    Ladies and Gentlemen, it is my great honor and pleasure to present an opening address of the 3rd International Workshop on "State of the Art in Nuclear Cluster Physics"(SOTANCP3). On the behalf of the organizing committee, I certainly welcome all your visits to KGU Kannai Media Center belonging to Kanto Gakuin University, and stay in Yokohama. In particular, to whom come from abroad more than 17 countries, I would appreciate your participations after long long trips from your homeland to Yokohama. The first international workshop on "State of the Art in Nuclear Cluster Physics", called SOTANCP, was held in Strasbourg, France, in 2008, and the second one was held in Brussels, Belgium, in 2010. Then the third workshop is now held in Yokohama. In this period, we had the traditional 10th cluster conference in Debrecen, Hungary, in 2012. Thus we have the traditional cluster conference and SOTANCP, one after another, every two years. This obviously shows our field of nuclear cluster physics is very active and flourishing. It is for the first time in about 10 years to hold the international workshop on nuclear cluster physics in Japan, because the last cluster conference held in Japan was in Nara in 2003, about 10 years ago. The president in Nara conference was Prof. K. Ikeda, and the chairpersons were Prof. H. Horiuchi and Prof. I. Tanihata. I think, quite a lot of persons in this room had participated at the Nara conference. Since then, about ten years passed. So, this workshop has profound significance for our Japanese colleagues. The subjects of this workshop are to discuss "the state of the art in nuclear cluster physics" and also discuss the prospect of this field. In a couple of years, we saw significant progresses of this field both in theory and in experiment, which have brought better and new understandings on the clustering aspects in stable and unstable nuclei. I think, the concept of clustering has been more important than ever. This is true also in the

  15. Multiple substitutions in the von Willebrand factor gene that mimic the pseudogene sequence

    SciTech Connect

    Eikenboom, J.C.; Brieet, E.; Reitsma, P.H.; Vink, T.; Sixma, J.J.

    1994-03-15

    The authors have analyzed a type IIB and a type I von Willebrand disease family for the presence of mutations in the region coding for the glycoprotein Ib binding domain of the von Willebrand factor. Since this sequence is also present in the highly homologous von Willebrand factor pseudogene, the authors have studied genomic DNA as well as cDNA, which was produced from RNA isolated from endothelial cells or platelets. In both families, they have detected multiple consecutive nucleotide substitutions in the 5{prime} end of exon 28 that result in a sequence identical to the von Willebrand factor pseudogene. These substitutions were also found in cDNA, which proves that they are present in the active gene. The occurrence of multiple adjacent substitutions that exactly reflect a part of the sequence of the von Willebrand factor pseudogene is difficult to reconcile with sequential single mutational events. They therefore hypothesize that each of these multiple substitutions arose from one recombinational event between gene and pseudogene. 34 refs., 4 figs., 2 tabs.

  16. A Hematological Menace: Multiple Venous Thrombosis Complicated by Acquired Factor VIII Deficiency

    PubMed Central

    Paudel, Robin; Dominguez, Luis W.; Dogra, Prerna; Suman, Saurav; Badin, Simon; Wasserman, Carrie

    2016-01-01

    Patient: Male, 21 Final Diagnosis: Acquired Factor VIII Deficiency Symptoms: Abdominal hematoma • DVT • life threatening bleeding Medication: — Clinical Procedure: Life saving medical therapy Specialty: Hematology Objective: Rare disease Background: Acquired hemophilia A (AHA) classically presents with spontaneous bleeding of mucosal sites, GI tract, and sub-cutaneous tissues, often leading to large hematomas and ecchymosis. Among documented cases, 50% are idiopathic and few have been associated with trauma or surgery. We present a case of life-threatening bleeding caused by AHA, following trauma and complicated by multiple venous thrombi. Case Report: A 21-year-old man presented with multiple injuries secondary to trauma leading to extensive life-saving surgery. Two weeks post-operatively, he developed multiple deep venous thrombi and was started on anticoagulation. Twenty-four days post-operatively, he started bleeding from multiple mucosal sites and developed an abdominal hematoma. Anticoagulation was stopped, with administration of fresh frozen plasma and vitamin K. Diagnosis of AHA was made based on low factor VIII level and presence of factor VIII inhibitors after an appropriate battery of tests ruled out other possible diagnoses. He was started on steroids and recombinant factor VIIa, leading to immediate improvement. Once stable, Rituximab infusions resulted in decreasing factor VIII inhibitor levels, with gradual normalization of PTT. Conclusions: AHA remains a diagnostic challenge because of its rarity, leading to delay in diagnosis and causing significant morbidity and mortality. Elevated PTT relative to PT/INR is a strong clue which should be followed by mixing studies. Very few cases have been associated with surgery or trauma and relatively few large, controlled trials have compared different treatment modalities for AHA. Growing evidence supports anti-CD20 (Rituximab) as an effective treatment option, as in this case. PMID:27040655

  17. Incidence and risk factors for retinopathy of prematurity in multiple gestations: a Chinese population study.

    PubMed

    Yau, Gordon S K; Lee, Jacky W Y; Tam, Victor T Y; Yip, Stan; Cheng, Edith; Liu, Catherine C L; Chu, Benjamin C Y; Wong, Ian Y H

    2015-05-01

    To determine the incidence and risk factors of retinopathy of prematurity (ROP) among new-born Chinese infants of multiple gestations.A retrospective review of medical records was performed for all neonates of multiple gestations screened for ROP between January 2007 and December 2012 in 2 neonatal intensive care units in Hong Kong. Screening was offered to very low birth weight (VLBW; ≤1500 g) and/or preterm (gestation ≤32 weeks) neonates using the Royal College of Ophthalmologists ROP guideline and the International Classification of ROP by 3 pediatric ophthalmologists. Maternal and neonatal covariates were analyzed using univariate and multivariate regression analyses for both ROP and Type 1 ROP.A total of 153 Chinese infants of multiple gestations were included in the study. The mean gestational age (GA) was 30.8 ± 2.4 weeks and the mean birth weight (BW) was 1284.8 ± 267.4 g. The incidence of ROP and Type 1 ROP was 11.8% and 3.9%, respectively. On univariate analysis, younger GA, lighter birth weight, postnatal hypotension, inotropes use, bronchopulmonary disease, and intraventricular hemorrhage were common independent risk factors for the development of ROP and Type 1 ROP (all P ≤ 0.04). On multivariate analysis, younger GA, surfactant use, invasive mechanical ventilation, higher mean oxygen concentration, thrombocytopenia, intraventricular hemorrhage, total parental nutrition, and hypoglycemia were significant risk factors for ROP. For Type 1 ROP, there were no significant dependent risk factors.In preterm Chinese infants born from multiple gestations, prematurity, lighter weight, postnatal hypotension, inotropes use, bronchopulmonary dysplasia, and an intraventricular hemorrhage were common independent risk factors for the development of ROP and Type 1 ROP. PMID:25950699

  18. Welcome Address

    NASA Astrophysics Data System (ADS)

    Kiku, H.

    2014-12-01

    Ladies and Gentlemen, It is an honor for me to present my welcome address in the 3rd International Workshop on "State of the Art in Nuclear Cluster Physics"(SOTANCP3), as the president of Kanto Gakuin University. Particularly to those from abroad more than 17 countries, I am very grateful for your participation after long long trips from your home to Yokohama. On the behalf of the Kanto Gakuin University, we certainly welcome your visit to our university and stay in Yokohama. First I would like to introduce Kanto Gakuin University briefly. Kanto Gakuin University, which is called KGU, traces its roots back to the Yokohama Baptist Seminary founded in 1884 in Yamate, Yokohama. The seminary's founder was Albert Arnold Bennett, alumnus of Brown University, who came to Japan from the United States to establish a theological seminary for cultivating and training Japanese missionaries. Now KGU is a major member of the Kanto Gakuin School Corporation, which is composed of two kindergartens, two primary schools, two junior high schools, two senior high schools as well as KGU. In this university, we have eight faculties with graduate school including Humanities, Economics, Law, Sciences and Engineering, Architecture and Environmental Design, Human and Environmental Studies, Nursing, and Law School. Over eleven thousands students are currently learning in our university. By the way, my major is the geotechnical engineering, and I belong to the faculty of Sciences and Engineering in my university. Prof. T. Yamada, here, is my colleague in the same faculty. I know that the nuclear physics is one of the most active academic fields in the world. In fact, about half of the participants, namely, more than 50 scientists, come from abroad in this conference. Moreover, I know that the nuclear physics is related to not only the other fundamental physics such as the elementary particle physics and astrophysics but also chemistry, medical sciences, medical cares, and radiation metrology

  19. Comparison of different multiple flow algorithms for topographic RUSLE factor (LS) calculation in Switzerland

    NASA Astrophysics Data System (ADS)

    Bircher, Pascal; Liniger, Hanspeter; Prasuhn, Volker

    2016-04-01

    Soil erosion is a well-known challenge both from a global perspective and in Switzerland, and it is assessed and discussed in many projects (e.g. national or European erosion risk maps). Meaningful assessment of soil erosion requires models that adequately reflect surface water flows. Various studies have attempted to achieve better modelling results by including multiple flow algorithms in the topographic length and slope factor (LS-factor) of the Revised Universal Soil Loss Equation (RUSLE). The choice of multiple flow algorithms is wide, and many of them have been implemented in programs or tools like Saga-Gis, GrassGis, ArcGIS, ArcView, Taudem, and others. This study compares six different multiple flow algorithms with the aim of identifying a suitable approach to calculating the LS factor for a new soil erosion risk map of Switzerland. The comparison of multiple flow algorithms is part of a broader project to model soil erosion for the entire agriculturally used area in Switzerland and to renew and optimize the current erosion risk map of Switzerland (ERM2). The ERM2 was calculated in 2009, using a high resolution digital elevation model (2 m) and a multiple flow algorithm in ArcView. This map has provided the basis for enforcing soil protection regulations since 2010 and has proved its worth in practice, but it has become outdated (new basic data are now available, e.g. data on land use change, a new rainfall erosivity map, a new digital elevation model, etc.) and is no longer user friendly (ArcView). In a first step towards its renewal, a new data set from the Swiss Federal Office of Topography (Swisstopo) was used to generate the agricultural area based on the existing field block map. A field block is an area consisting of farmland, pastures, and meadows which is bounded by hydrological borders such as streets, forests, villages, surface waters, etc. In our study, we compared the six multiple flow algorithms with the LS factor calculation approach used in

  20. Race/Ethnicity and Multiple Cancer Risk Factors among Individuals Seeking Smoking Cessation Treatment

    PubMed Central

    Kendzor, Darla E.; Costello, Tracy J.; Li, Yisheng; Vidrine, Jennifer Irvin; Mazas, Carlos A.; Reitzel, Lorraine R.; Cinciripini, Paul M.; Cofta-Woerpel, Ludmila M.; Businelle, Michael S.; Wetter, David W.

    2016-01-01

    Smoking in combination with other behavioral risk factors is known to have a negative influence on health, and individuals who smoke typically engage in multiple risk behaviors. However, little is known about the clustering of risk behaviors among smokers of varying race/ethnicity. The purpose of this study was to examine patterns of cancer risk behaviors and to identify predictors of multiple risk behaviors in a racially/ethnically diverse sample of individuals seeking smoking cessation treatment. Overweight/obesity, at-risk alcohol consumption, and insufficient physical activity were measured in 424 smokers (African American, n = 144; Latino, n = 141; Caucasian, n = 139). Results indicated that 90% of participants reported behavioral cancer risk factors in addition to smoking. Approximately 70% of participants were overweight or obese, 48% engaged in at-risk drinking, and 27% were insufficiently physically active. Univariate analyses indicated that race/ethnicity, p < .001, smoking level, p = .03, and marital status, p = .04, were significant predictors of multiple risk behaviors, although only race/ethnicity remained a significant predictor, p < .001, when gender, smoking level, age, education, household income, marital status, and health insurance status were included in a multivariate model. Multivariate analysis indicated that the odds of engaging in multiple risk behaviors were significantly higher among Latinos, OR = 2.85, and African Americans, OR = 1.86, than Caucasians. Our findings highlight the need for research aimed at identifiying determinants of racial/ethnic differences in multiple risk behaviors, and indicate the importance of developing culturally sensitive interventions that target multiple risk behaviors. PMID:18990734

  1. Using multiple risk factors to assess the behavioral, cognitive, and affective effects of learned helplessness.

    PubMed

    McKean, K J

    1994-03-01

    Rather than examining the effect of the pessimistic explanatory style on an outcome variable reflecting a single domain, I studied the effects of multiple learned-helplessness risk factors on behavioral, cognitive, and affective variables. Undergraduate students completed the Learned Helplessness Scale (Quinless & McDermott-Nelson, 1988) as a measure of their expectation of uncontrollability and the Explanatory Style Questionnaire (Peterson et al., 1982) to determine their explanations for both positive and negative events. Results revealed a significant effect for risk level, with students at greater risk of helplessness reporting significantly more procrastination, lower grade point averages, and more dysphoria. These results support the use of multiple risk factors representing all learned-helplessness precursors and the assessment of learned-helplessness deficits drawn simultaneously from behavioral, cognitive, and affective domains. PMID:8189396

  2. The Causal Factors Associated with the Loving Care of the Mothers of Children with Multiple Disabilities

    PubMed Central

    Sadati, Ahmad Kalateh; Salehzade, Hamze; Hemmati, Soroor; Darvish, Manijeh; Heydari, Seyed Taghi; Tabrizi, Reza

    2015-01-01

    Background: Families with disabled children need more psycho-social considerations. Motherhood care of the children with multiple disabilities is difficult. Due to its importance, the aim of this study was to investigate the causal factors affecting loving care of mothers of children with multiple disabilities. Methods: The study used a cross-sectional method in which 75 mothers of exceptional children with multiple disabilities (physical and mental) in elementary schools in Shiraz, Iran. The data were collected through questionnaires which, besides demographical factors, evaluated the relationship between mothers’ loving care of children with multiple disabilities and four other variables including purpose in life, life satisfaction, religious attitude, and sense of coherence. Mann-Whitney U was used for comparison between mothers’ loving care and other variables. Results: Results revealed that demographic variables did not have a significant relationship with loving care. In the case of social variables, there was a significant relationship between mothers’ loving care and purpose in life (P<0.001), religious attitude (P<0.001), and life satisfaction (P=0.01). Conclusion: Motherhood care of disabled children is a unique phenomenon which is due to attachment of mother-child situation. Nevertheless, these mothers are vulnerable and marginalized people who need more attention and social supports provided by related governmental institutions and also NGOs actors. PMID:26448958

  3. An analysis of content in comprehensive cancer control plans that address chronic hepatitis B and C virus infections as major risk factors for liver cancer.

    PubMed

    Momin, Behnoosh; Richardson, Lisa

    2012-08-01

    Chronic hepatitis B and hepatitis C virus (HBV and HCV) infections are among the leading causes of preventable death worldwide. Chronic viral hepatitis is the cause of most primary liver cancer, which is the third leading cause of cancer deaths globally and the ninth leading cause of cancer deaths in the United States. The extent to which comprehensive cancer control (CCC) programs in states, tribal governments and organizations, territories, and Pacific Island jurisdictions address chronic hepatitis B and/or hepatitis C infections as risk factors for liver cancer or recommend interventions for liver cancer prevention in their CCC plans remains unknown. We searched CCC plans for this information using the search tool at http://www.cdc.gov/cancer/ncccp/ to access the content of plans for this information. A combination of key search terms including "liver cancer", "hepatitis", "chronic alcohol", and "alcohol abuse" were used to identify potential content regarding liver cancer risk factors and prevention. Relevant content was abstracted for further review and classification. Of 66 (Although CDC funds 65 programs, one of the Pacific Island Jurisdiction grantees is the Federated States of Micronesia (FSM). This national program supports four FSM states, each of which submits a cancer plan to CDC for a total of 69 plans. During this time period, 66 plans were available on the website.) CCC plans, 27% (n = 18) addressed liver cancer using the above-mentioned search terms. In the 23 plans that addressed HBV and/or HCV, there were 25 goals, objectives, strategies, and outcomes aimed at reducing the incidence or prevalence of HBV and/or HCV infection. While nearly a third of CCC programs identify at least one goal, objective, strategy, outcome, or prevention program to reduce cancer burden in their CCC plans, few plans discuss specific actions needed to reduce the burden of liver cancer. PMID:22160788

  4. Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel.

    PubMed

    Bruggeman, Kiara F; Rodriguez, Alexandra L; Parish, Clare L; Williams, Richard J; Nisbet, David R

    2016-09-23

    Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine. PMID:27517970

  5. Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel

    NASA Astrophysics Data System (ADS)

    Bruggeman, Kiara F.; Rodriguez, Alexandra L.; Parish, Clare L.; Williams, Richard J.; Nisbet, David R.

    2016-09-01

    Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine.

  6. Orthogonal matrix factorization enables integrative analysis of multiple RNA binding proteins

    PubMed Central

    Stražar, Martin; Žitnik, Marinka; Zupan, Blaž; Ule, Jernej; Curk, Tomaž

    2016-01-01

    Motivation: RNA binding proteins (RBPs) play important roles in post-transcriptional control of gene expression, including splicing, transport, polyadenylation and RNA stability. To model protein–RNA interactions by considering all available sources of information, it is necessary to integrate the rapidly growing RBP experimental data with the latest genome annotation, gene function, RNA sequence and structure. Such integration is possible by matrix factorization, where current approaches have an undesired tendency to identify only a small number of the strongest patterns with overlapping features. Because protein–RNA interactions are orchestrated by multiple factors, methods that identify discriminative patterns of varying strengths are needed. Results: We have developed an integrative orthogonality-regularized nonnegative matrix factorization (iONMF) to integrate multiple data sources and discover non-overlapping, class-specific RNA binding patterns of varying strengths. The orthogonality constraint halves the effective size of the factor model and outperforms other NMF models in predicting RBP interaction sites on RNA. We have integrated the largest data compendium to date, which includes 31 CLIP experiments on 19 RBPs involved in splicing (such as hnRNPs, U2AF2, ELAVL1, TDP-43 and FUS) and processing of 3’UTR (Ago, IGF2BP). We show that the integration of multiple data sources improves the predictive accuracy of retrieval of RNA binding sites. In our study the key predictive factors of protein–RNA interactions were the position of RNA structure and sequence motifs, RBP co-binding and gene region type. We report on a number of protein-specific patterns, many of which are consistent with experimentally determined properties of RBPs. Availability and implementation: The iONMF implementation and example datasets are available at https://github.com/mstrazar/ionmf. Contact: tomaz.curk@fri.uni-lj.si Supplementary information: Supplementary data are available

  7. The association of reproductive and lifestyle factors with a score of multiple endogenous hormones

    PubMed Central

    Shafrir, Amy L.; Zhang, Xuehong; Poole, Elizabeth M.; Hankinson, Susan E.; Tworoger, Shelley S.

    2014-01-01

    Introduction We recently reported that high levels of multiple sex and growth hormones were associated with increased postmenopausal breast cancer risk. Limited research has explored the relationship between reproductive, anthropometric, and lifestyle factors and levels of multiple hormones simultaneously. Methods This cross-sectional analysis included 738 postmenopausal Nurses' Health Study participants who were controls in a breast cancer nested case-control study and had measured levels of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone sulfate, prolactin and sex hormone binding globulin (SHBG). A score was created by summing the number of hormones a woman had above (below for SHBG) each hormone's age-adjusted geometric mean. The association between lifestyle, anthropometric, and reproductive exposures and the score was assessed using generalized linear models. Results The hormone score ranged from 0 to 8 with a mean of 4.0 (standard deviation=2.2). Body mass index (BMI) and alcohol consumption at blood draw were positively associated with the hormone score: a 5 unit increase in BMI was associated with a 0.79 (95%CI: 0.63, 0.95) unit increase in the score (p<0.0001) and each 15 grams/day increase in alcohol consumption was associated with a 0.41 (95%CI: 0.18, 0.63) unit increase in the score (p=0.0004). Family history of breast cancer, age at menarche, and physical activity were not associated with the score. Conclusions Reproductive breast cancer risk factors were not associated with elevated levels of multiple endogenous hormones, whereas anthropometric and lifestyle factors, particularly BMI and alcohol consumption, tended to be associated with higher levels of multiple hormones. PMID:25048255

  8. Parent Involvement in School Conceptualizing Multiple Dimensions and Their Relations with Family and Demographic Risk Factors.

    PubMed

    Kohl, Gwynne O; Lengua, Liliana J; McMahon, Robert J

    2000-11-01

    Parent involvement (PI) in school is associated with more positive academic performance and social competence in children. However, there are inadequacies in current measures of PI and a need for a better understanding of predictors of PI. In this study, measures were obtained from a normative sample of 387 children in kindergarten and first grade from high-risk neighborhoods in 4 different sites. First, a confirmatory factor analysis of a theoretical factor model of PI identified 6 reliable multiple-reporter PI factors: Parent-Teacher Contact, Parent Involvement at School, Quality of Parent-Teacher Relationship, Teacher's Perception of the Parent, Parent Involvement at Home, and Parent Endorsement of School. Next, the relations among 3 specific family and demographic risk factors-parental education level, maternal depression, and single-parent status-and these 6 PI factors were examined using path analyses in structural equation modeling. Results indicated that the 3 risk factors were differentially associated with the 6 PI factors: Parental education was significantly associated with 4 PI outcomes, maternal depression was significantly associated with 5 PI outcomes, and single-parent status was significantly associated with 3 PI outcomes. No significant ethnic group differences between African American and Caucasian families were found in these relations. PMID:20357900

  9. Factors influencing municipal solid waste generation in China: a multiple statistical analysis study.

    PubMed

    Liu, Chen; Wu, Xin-wu

    2011-04-01

    A relationship between the waste production and socio-economic factors is essential in waste management. In the present study, the factors influencing municipal solid waste generation in China were investigated by multiple statistical analysis. Twelve items were chosen for investigation: GDP, per capita GDP, urban population, the proportion of urban population, the area of urban construction, the area of paved roads, the area of urban gardens and green areas, the number of the large cities, annual per capita disposable income of urban households, annual per capita consumption expenditure of urban households, total energy consumption and annual per capital consumption for households. Two methodologies from multiple statistical analysis were selected; specifically principal components analysis (PCA) and cluster analysis (CA). Three new dimensions were identified by PCA: component 1: economy and urban development; component 2: energy consumption; and component 3: urban scale. The three components together accounted for 99.1% of the initial variance. The results show that economy and urban development are important items influencing MSW generation. The proportion of urban population and urban population had the highest loadings in all factors. The relationship between growth of gross domestic product (GDP) and production of MSW was not as clear-cut as often assumed in China, a situation that is more likely to apply to developed countries. Energy consumption was another factor considered in our study of MSW generation. In addition, the annual MSW quantity variation was investigated by cluster analysis. PMID:20699292

  10. Monitoring a Nuclear Factor-κB Signature of Drug Resistance in Multiple Myeloma*

    PubMed Central

    Xiang, Yun; Remily-Wood, Elizabeth R.; Oliveira, Vasco; Yarde, Danielle; He, Lili; Cheng, Jin Q.; Mathews, Linda; Boucher, Kelly; Cubitt, Christopher; Perez, Lia; Gauthier, Ted J.; Eschrich, Steven A.; Shain, Kenneth H.; Dalton, William S.; Hazlehurst, Lori; Koomen, John M.

    2011-01-01

    The emergence of acquired drug resistance results from multiple compensatory mechanisms acting to prevent cell death. Simultaneous monitoring of proteins involved in drug resistance is a major challenge for both elucidation of the underlying biology and development of candidate biomarkers for assessment of personalized cancer therapy. Here, we have utilized an integrated analytical platform based on SDS-PAGE protein fractionation prior to liquid chromatography coupled to multiple reaction monitoring mass spectrometry, a versatile and powerful tool for targeted quantification of proteins in complex matrices, to evaluate a well-characterized model system of melphalan resistance in multiple myeloma (MM). Quantitative assays were developed to measure protein expression related to signaling events and biological processes relevant to melphalan resistance in multiple myeloma, specifically: nuclear factor-κB subunits, members of the Bcl-2 family of apoptosis-regulating proteins, and Fanconi Anemia DNA repair components. SDS-PAGE protein fractionation prior to liquid chromatography coupled to multiple reaction monitoring methods were developed for quantification of these selected target proteins in amounts of material compatible with direct translation to clinical specimens (i.e. less than 50,000 cells). As proof of principle, both relative and absolute quantification were performed on cell line models of MM to compare protein expression before and after drug treatment in naïve cells and in drug resistant cells; these liquid chromatography-multiple reaction monitoring results are compared with existing literature and Western blots. The initial stage of a systems biology platform for examining drug resistance in MM has been implemented in cell line models and has been translated to MM cells isolated from a patient. The ultimate application of this platform could assist in clinical decision-making for individualized patient treatment. Although these specific assays have

  11. An Evaluation of Multiple Behavioral Risk Factors for Cancer in a Working Class, Multi-Ethnic Population

    PubMed Central

    Goodman, Melody S.; Li, Yi; Bennett, Gary G.; Stoddard, Anne M.; Emmons, Karen M.

    2012-01-01

    Behavioral risk factors for cancer tend to cluster within individuals, which can compound risk beyond that associated with the individual risk factors alone. There has been increasing attention paid to the prevalence of multiple risk factors (MRF) for cancer, and to the importance of designing interventions that help individuals reduce their risks across multiple behaviors simultaneously. The purpose of this paper is to develop methodology to identify an optimal linear combination of multiple risk factors (score function) which would facilitate evaluation of cancer interventions. PMID:23227033

  12. Critical factors for achieving multiple goals with water tariff systems: Combining limited data sources and expert testimony

    NASA Astrophysics Data System (ADS)

    Dalhuisen, Jasper; Nijkamp, Peter

    2002-07-01

    Price instruments are well-known policy handles to influence effectively residential water demand. Prices used to be set by water authorities in such a way that the principle of cost coverage was respected; they acted as prominent instruments in residential water policies in the past decades. More recently, however, price instruments are increasingly used to meet simultaneously financial, environmental, and social goals. This paper addresses four conditions for an appropriate tariff system for residential water use which are often found in the recent literature on the economics of water use. The paper analyzes the importance of background factors (e.g., low water availability) of these four principles as well as the extent to which actual tariff systems are employed in five mutually contrasting cities (Amsterdam, Athens, London, Seville, and Tel Aviv). Meta-analytic techniques, in particular, rough set analysis stemming from artificial intelligence, are applied to identify the common underlying relations between background factors and success of achieving multiple goals in these five urban case studies. The paper concludes with policy recommendations.

  13. Factors that influence adherence and strategies to maintain adherence to injected therapies for patients with multiple sclerosis.

    PubMed

    Saunders, Carol; Caon, Christina; Smrtka, Jennifer; Shoemaker, Jennifer

    2010-10-01

    A key aspect of the management of care for patients with multiple sclerosis (MS) is identifying which patients are struggling with adherence. Disease-modifying therapies for the treatment of MS are primarily preventative, with modest efficacy, and they can possibly cause significant side effects. These factors can lead patients to stop taking their medication because they continue to experience symptoms or relapses of the disease, and/or they have painful injection-site reactions on most parts of their bodies. However, striving for 100% adherence to the prescribed treatment regimen remains the goal and is the surest way to reap all the benefits associated with immunomodulatory therapy. Building trust, promoting injection self-efficacy, and educating patients about proper injection techniques to prevent injection-site reactions have the greatest impact on patient adherence. Factors including family involvement, financial stability and support, hope, and faith can also have a positive impact on adherence. Identifying patients who may be struggling with depression, which is easily treatable but often not well addressed, and providing access to mental health services are important. Although many strides have been made with regard to MS patient care, outlining strategies that can maintain or encourage adherence can provide practitioners with tools to facilitate their patients' health and well-being. PMID:21049829

  14. Fuzzy based power factor improvement strategy for a multiple connected AC-DC converter fed drive

    NASA Astrophysics Data System (ADS)

    Radhakrishnan, N.; Muthiah, Ramaswamy

    2012-01-01

    The main focus of this paper is to design a Fuzzy based control algorithm to realize an improvement in the input power factor of a multiple connected AC-DC converter fed drive system. It incorporates the role of fuzzy inference principles to generate appropriate PWM pulses for the power switches at the second stage of the power module. The philosophy is developed, with a view to reshape the input current phasor and enables it to align with the supply voltage wave in the perspective of improving the input power factor. The closed loop scheme evaluated using MATLAB based simulation exhibits an enhancement in supply power factor over a range of operating loads in addition to illustrating the speed regulating capability of the drive.

  15. High-power optical millimeter-wave signal generation with tunable frequency multiplication factor

    NASA Astrophysics Data System (ADS)

    Han, Yi-shi; Zheng, Zhenyu; Luo, Zhixiao; Min, Zhixuan; Xu, Ou; Liu, Jie

    2015-01-01

    This work demonstrates a simple and novel scheme for millimeter-wave (MMW) signal generation using optical multi-sidebands (OMSB) modulation. In the proposed methods, several pairs of optical sidebands can be generated by employing parallel phase modulators driven by a low frequency radio frequency (RF) signal. The optical sidebands will beat at a photodetector (PD) to generate high frequency MMW signal with tunable frequency multiplication factor, such as frequency octupling, 12-tupling, 16-tupling and 18-tupling. Since no optical filters or DC bias are used, the MMW signal has the evident character of high-power output. A generalized analytic expression and simulation verification for generating the frequency multi-tupling MMW signal are developed. The influences caused by non-ideal factors are discussed in detail, and undesired power ratios versus non-ideal factors are plotted and analyzed.

  16. Robustness of the fractal regime for the multiple-scattering structure factor

    NASA Astrophysics Data System (ADS)

    Katyal, Nisha; Botet, Robert; Puri, Sanjay

    2016-08-01

    In the single-scattering theory of electromagnetic radiation, the fractal regime is a definite range in the photon momentum-transfer q, which is characterized by the scaling-law behavior of the structure factor: S(q) ∝ 1 /q df. This allows a straightforward estimation of the fractal dimension df of aggregates in Small-Angle X-ray Scattering (SAXS) experiments. However, this behavior is not commonly studied in optical scattering experiments because of the lack of information on its domain of validity. In the present work, we propose a definition of the multiple-scattering structure factor, which naturally generalizes the single-scattering function S(q). We show that the mean-field theory of electromagnetic scattering provides an explicit condition to interpret the significance of multiple scattering. In this paper, we investigate and discuss electromagnetic scattering by three classes of fractal aggregates. The results obtained from the TMatrix method show that the fractal scaling range is divided into two domains: (1) a genuine fractal regime, which is robust; (2) a possible anomalous scaling regime, S(q) ∝ 1 /qδ, with exponent δ independent of df, and related to the way the scattering mechanism uses the local morphology of the scatterer. The recognition, and an analysis, of the latter domain is of importance because it may result in significant reduction of the fractal regime, and brings into question the proper mechanism in the build-up of multiple-scattering.

  17. Uranium mass and neutron multiplication factor estimates from time-correlation coincidence counts

    NASA Astrophysics Data System (ADS)

    Xie, Wenxiong; Li, Jiansheng; Zhu, Jianyu

    2015-10-01

    Time-correlation coincidence counts of neutrons are an important means to measure attributes of nuclear material. The main deficiency in the analysis is that an attribute of an unknown component can only be assessed by comparing it with similar known components. There is a lack of a universal method of measurement suitable for the different attributes of the components. This paper presents a new method that uses universal relations to estimate the mass and neutron multiplication factor of any uranium component with known enrichment. Based on numerical simulations and analyses of 64 highly enriched uranium components with different thicknesses and average radii, the relations between mass, multiplication and coincidence spectral features have been obtained by linear regression analysis. To examine the validity of the method in estimating the mass of uranium components with different sizes, shapes, enrichment, and shielding, the features of time-correlation coincidence-count spectra for other objects with similar attributes are simulated. Most of the masses and multiplications for these objects could also be derived by the formulation. Experimental measurements of highly enriched uranium castings have also been used to verify the formulation. The results show that for a well-designed time-dependent coincidence-count measuring system of a uranium attribute, there are a set of relations dependent on the uranium enrichment by which the mass and multiplication of the measured uranium components of any shape and size can be estimated from the features of the source-detector coincidence-count spectrum.

  18. Targeted Quantitative Analysis of Streptococcus pyogenes Virulence Factors by Multiple Reaction Monitoring*S⃞

    PubMed Central

    Lange, Vinzenz; Malmström, Johan A.; Didion, John; King, Nichole L.; Johansson, Björn P.; Schäfer, Juliane; Rameseder, Jonathan; Wong, Chee-Hong; Deutsch, Eric W.; Brusniak, Mi-Youn; Bühlmann, Peter; Björck, Lars; Domon, Bruno; Aebersold, Ruedi

    2008-01-01

    In many studies, particularly in the field of systems biology, it is essential that identical protein sets are precisely quantified in multiple samples such as those representing differentially perturbed cell states. The high degree of reproducibility required for such experiments has not been achieved by classical mass spectrometry-based proteomics methods. In this study we describe the implementation of a targeted quantitative approach by which predetermined protein sets are first identified and subsequently quantified at high sensitivity reliably in multiple samples. This approach consists of three steps. First, the proteome is extensively mapped out by multidimensional fractionation and tandem mass spectrometry, and the data generated are assembled in the PeptideAtlas database. Second, based on this proteome map, peptides uniquely identifying the proteins of interest, proteotypic peptides, are selected, and multiple reaction monitoring (MRM) transitions are established and validated by MS2 spectrum acquisition. This process of peptide selection, transition selection, and validation is supported by a suite of software tools, TIQAM (Targeted Identification for Quantitative Analysis by MRM), described in this study. Third, the selected target protein set is quantified in multiple samples by MRM. Applying this approach we were able to reliably quantify low abundance virulence factors from cultures of the human pathogen Streptococcus pyogenes exposed to increasing amounts of plasma. The resulting quantitative protein patterns enabled us to clearly define the subset of virulence proteins that is regulated upon plasma exposure. PMID:18408245

  19. Multiple risk factor interventions for primary prevention of coronary heart disease

    PubMed Central

    Ebrahim, Shah; Beswick, Andrew; Burke, Margaret; Smith, George Davey

    2014-01-01

    Background Primary prevention programmes in many countries attempt to reduce mortality and morbidity due to coronary heart disease (CHD) through risk factor modification. It is widely believed that multiple risk factor intervention using counselling and educational methods is efficacious and cost-effective and should be expanded. Recent trials examining risk factor changes have cast considerable doubt on the effectiveness of these multiple risk factor interventions. Objectives To assess the effects of multiple risk factor intervention for reducing cardiovascular risk factors, total mortality, and mortality from CHD among adults without clinical evidence of established cardiovascular disease. Search strategy MEDLINE was searched for the original review to 1995. This was updated by searching the Cochrane Central Register of Controlled Trials on The Cochrane Library Issue 3 2001, MEDLINE(2000 to September 2001) and EMBASE (1998 to September 2001). Selection criteria Intervention studies using counselling or education to modify more than one cardiovascular risk factor in adults from general populations, occupational groups, or high risk groups. Trials of less than 6 months duration were excluded. Data collection and analysis Data were extracted by two reviewers independently. Investigators were contacted to obtain missing information. Main results A total of 39 trials were found of which ten reported clinical event data. In the ten trials with clinical event end-points, the pooled odds ratios for total and CHD mortality were 0.96 (95% confidence intervals (CI) 0.92 to 1.01) and 0.96 (95% CI 0.89 to 1.04) respectively. Net changes in systolic and diastolic blood pressure, and blood cholesterol were (weighted mean differences) −3.6 mmHg (95% CI −3.9 to −3.3 mmHg), −2.8 mmHg (95% CI −2.9 to −2.6 mmHg) and −0.07 mMol/l (95% CI −0.8 to −0.06 mMol/l) respectively. Odds of reduction in smoking prevalence was 20% (95% CI 8% to 31%). Statistical heterogeneity

  20. Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma.

    PubMed

    Breitkreutz, I; Raab, M S; Vallet, S; Hideshima, T; Raje, N; Mitsiades, C; Chauhan, D; Okawa, Y; Munshi, N C; Richardson, P G; Anderson, K C

    2008-10-01

    Osteolytic bone disease in multiple myeloma (MM) is caused by enhanced osteoclast (OCL) activation and inhibition of osteoblast function. Lenalidomide and bortezomib have shown promising response rates in relapsed and newly diagnosed MM, and bortezomib has recently been reported to inhibit OCLs. We here investigated the effect of lenalidomide on OCL formation and osteoclastogenesis in comparison with bortezomib. Both drugs decreased alpha V beta 3-integrin, tartrate-resistant acid phosphatase-positive cells and bone resorption on dentin disks. In addition, both agents decreased receptor activator of nuclear factor-kappaB ligand (RANKL) secretion of bone marrow stromal cells (BMSCs) derived from MM patients. We identified PU.1 and pERK as major targets of lenalidomide, and nuclear factor of activated T cells of bortezomib, resulting in inhibition of osteoclastogenesis. Furthermore, downregulation of cathepsin K, essential for resorption of the bone collagen matrix, was observed. We demonstrated a significant decrease of growth and survival factors including macrophage inflammatory protein-alpha, B-cell activating factor and a proliferation-inducing ligand. Importantly, in serum from MM patients treated with lenalidomide, the essential bone-remodeling factor RANKL, as well as the RANKL/OPG ratio, were significantly reduced, whereas osteoprotegerin (OPG) was increased. We conclude that both agents specifically target key factors in osteoclastogenesis, and could directly affect the MM-OCL-BMSCs activation loop in osteolytic bone disease. PMID:18596740

  1. Prediagnosis biomarkers of insulin-like growth factor-1, insulin, and interleukin-6 dysregulation and multiple myeloma risk in the Multiple Myeloma Cohort Consortium

    PubMed Central

    Neuhouser, Marian L.; Rosner, Bernard; Albanes, Demetrius; Buring, Julie E.; Giles, Graham G.; Lan, Qing; Lee, I-Min; Purdue, Mark P.; Rothman, Nathaniel; Severi, Gianluca; Yuan, Jian-Min; Anderson, Kenneth C.; Pollak, Michael; Rifai, Nader; Hartge, Patricia; Landgren, Ola; Lessin, Lawrence; Virtamo, Jarmo; Wallace, Robert B.; Manson, JoAnn E.; Colditz, Graham A.

    2012-01-01

    Insulin-like growth factor-1 (IGF-1), insulin, and IL-6 are dysregulated in multiple myeloma pathogenesis and may also contribute to multiple myeloma etiology. To examine their etiologic role, we prospectively analyzed concentrations of serologic markers in 493 multiple myeloma cases and 978 controls from 8 cohorts in the Multiple Myeloma Cohort Consortium. We computed odds ratios (ORs) and 95% confidence intervals (CIs) for multiple myeloma per 1-SD increase in biomarker concentration using conditional logistic regression. We examined heterogeneity by time since blood collection (≤ 3, 4- ≤ 6, and > 6 years) in stratified models. Fasting IGF binding protein-1 concentration was associated with multiple myeloma risk within 3 years (OR, 95% CI per 1-SD increase: 2.3, 1.4-3.8, P = .001) and soluble IL-6 receptor level was associated within 6 years after blood draw (OR ≤ 3 years, 95% CI, 1.4, 1.1-1.9, P = .01; OR4- ≤ 6 years, 95% CI, 1.4, 1.1-1.7, P = .002). No biomarker was associated with longer-term multiple myeloma risk (ie, > 6 years). Interactions with time were statistically significant (IGF binding protein-1, P-heterogeneity = .0016; sIL6R, P-heterogeneity = .016). The time-restricted associations probably reflect the bioactivity of tumor and microenvironment cells in transformation from monoclonal gammopathy of undetermined significance or smoldering multiple myeloma to clinically manifest multiple myeloma. PMID:23074271

  2. Science Teaching Efficacy of Preservice Elementary Teachers: Examination of the Multiple Factors Reported as Influential

    NASA Astrophysics Data System (ADS)

    Taştan Kırık, Özgecan

    2013-12-01

    This study explores the science teaching efficacy beliefs of pr-service elementary teachers and the relationship between efficacy beliefs and multiple factors such as antecedent factors (participation in extracurricular activities and number of science and science teaching methods courses taken), conceptual understanding, classroom management beliefs and science teaching attitudes. Science education majors ( n = 71) and elementary education majors ( n = 262) were compared with respect to these variables. Finally, the predictors of two constructs of science teaching efficacy beliefs, personal science teaching efficacy (PSTE) and science teaching outcome expectancy (STOE), were examined by multiple linear regression analysis. According to the results, participation in extracurricular activities has a significant but low correlation with science concept knowledge, science teaching attitudes, PSTE and STOE. In addition, there is a small but significant correlation between science concept knowledge and outcome expectancy, which leads the idea that preservice elementary teachers' conceptual understanding in science contributes to their science teaching self-efficacy. This study reveals a moderate correlation between science teaching attitudes and STOE and a high correlation between science teaching attitudes and PSTE. Additionally, although the correlation coefficient is low, the number of methodology courses was found to be one of the correlates of science teaching attitudes. Furthermore, students of both majors generally had positive self-efficacy beliefs on both the STOE and PSTE. Specifically, science education majors had higher science teaching self-efficacy than elementary education majors. Regression results showed that science teaching attitude is the major factor in predicting both PSTE and STOE for both groups.

  3. Multiple roles of tumor necrosis factor-alpha in fracture healing.

    PubMed

    Karnes, Jonathan M; Daffner, Scott D; Watkins, Colleen M

    2015-09-01

    This review presents a summary of basic science evidence examining the influence of tumor necrosis factor-alpha (TNF-α) on secondary fracture healing. Multiple studies suggest that TNF-α, in combination with the host reservoir of peri-fracture mesenchymal stem cells, is a main determinant in the success of bone healing. Disease states associated with poor bone healing commonly have inappropriate TNF-α responses, which likely contributes to the higher incidence of delayed and nonunions in these patient populations. Appreciation of TNF-α in fracture healing may lead to new therapies to augment recovery and reduce the incidence of complications. PMID:25959413

  4. Epidemiology of Multiple Sclerosis: From Risk Factors to Prevention-An Update.

    PubMed

    Ascherio, Alberto; Munger, Kassandra L

    2016-04-01

    Although genetic susceptibility explains the clustering of multiple sclerosis (MS) within families and the sharp decline in risk with increasing genetic distance, it cannot fully explain the geographical variations in MS frequency and the changes in risk that occur with migration, which support the action of strong environmental factors. Among these, vitamin D status, obesity in early life, infection with the Epstein-Barr virus, and cigarette smoking are the most consistent environmental predictors of MS risk. The authors review the epidemiological data, critically discuss the evidence for causality of these and other associations, and briefly review the possibility of interventions to reduce MS risk. PMID:27116717

  5. Spatiotemporal patterns of evapotranspiration in response to multiple environmental factors simulated by the Community Land Model

    SciTech Connect

    Shi, Xiaoying; Mao, Jiafu; Thornton, Peter E; Huang, Maoyi; Hoffman, Forrest

    2013-01-01

    In this study, spatial and temporal patterns of evapotranspiration (ET) over the period of 1982-2008 are investigated and attributed to multiple environmental factors using the Community Land Model version 4 (CLM4). Our results show that CLM4 captures the spatial distribution and interannual variability of ET well when compared to observation-based estimates derived from the FLUXNET network of eddy covariance towers using the model tree ensembles (MTE) approach. We find that climate trends and variability dominate predicted variability in ET. Elevated atmospheric CO2 concentration also plays an important role in modulating the trend of predicted ET over most land areas, and functions as the dominant factor controlling ET changes over North America, South America and Asia regions. Compared to the effect of climate change and CO2 concentration, the roles of other factors such as nitrogen deposition, land use change and aerosol deposition are less pronounced and regionally dependent. For example, the aerosol deposition contribution is the third-most important factor for trends of ET over Europe, while it has the smallest impact on ET trend over other regions. As ET is a dominant component of the terrestrial water cycle, our results suggest that environmental factors like elevated CO2, nitrogen and aerosol depositions, and land use and land cover change, in addition to climate, could have significant impact on future projections of water resources and water cycle dynamics at global and regional scales.

  6. Spatiotemporal Patterns of Evapotranspiration in Response to Multiple Environmental Factors Simulated by the Community Land Model

    SciTech Connect

    Shi, Xiaoying; Mao, Jiafu; Thornton, P.; Huang, Maoyi

    2013-04-25

    Spatiotemporal patterns of evapotranspiration (ET) over the period from 1982 to 2008 are investigated and attributed to multiple environmental factors using the Community Land Model version 4 (CLM4). Our results show that CLM4 captures the spatial distribution and interannual variability of ET well when compared to observation-based estimates. We find that climate dominates the predicted variability in ET. Elevated atmospheric CO2 concentration also plays an important role in modulating the trend of predicted ET over most land areas, and replaces climate to function as the dominant factor controlling ET changes over the North America, South America and Asia regions. Compared to the effect of climate and CO2 concentration, the roles of other factors such as nitrogen deposition, land use change and aerosol deposition are less pronounced and regionally dependent. The aerosol deposition contribution is the third most important factor for trends of ET over Europe, while it has the smallest impact over other regions. As ET is a dominant component of the terrestrial water cycle, our results suggest that environmental factors like elevated CO2, nitrogen and aerosol depositions, and land use change, in addition to climate, could have significant impact on future projections of water resources and water cycle dynamics at global and regional scales.

  7. Hepatocyte nuclear factor 1 coordinates multiple processes in a model of intestinal epithelial cell function.

    PubMed

    Yang, Rui; Kerschner, Jenny L; Harris, Ann

    2016-04-01

    Mutations in hepatocyte nuclear factor 1 transcription factors (HNF1α/β) are associated with diabetes. These factors are well studied in the liver, pancreas and kidney, where they direct tissue-specific gene regulation. However, they also have an important role in the biology of many other tissues, including the intestine. We investigated the transcriptional network governed by HNF1 in an intestinal epithelial cell line (Caco2). We used chromatin immunoprecipitation followed by direct sequencing (ChIP-seq) to identify HNF1 binding sites genome-wide. Direct targets of HNF1 were validated using conventional ChIP assays and confirmed by siRNA-mediated depletion of HNF1, followed by RT-qPCR. Gene ontology process enrichment analysis of the HNF1 targets identified multiple processes with a role in intestinal epithelial cell function, including properties of the cell membrane, cellular response to hormones, and regulation of biosynthetic processes. Approximately 50% of HNF1 binding sites were also occupied by other members of the intestinal transcriptional network, including hepatocyte nuclear factor 4A (HNF4A), caudal type homeobox 2 (CDX2), and forkhead box A2 (FOXA2). Depletion of HNF1 in Caco2 cells increases FOXA2 abundance and decreases levels of CDX2, illustrating the coordinated activities of the network. These data suggest that HNF1 plays an important role in regulating intestinal epithelial cell function, both directly and through interactions with other intestinal transcription factors. PMID:26855178

  8. Identification of subunits of gonococcal RNA polymerase by immunoblot analysis: evidence for multiple sigma factors.

    PubMed Central

    Klimpel, K W; Lesley, S A; Clark, V L

    1989-01-01

    Heparin-agarose and single-stranded DNA-cellulose chromatography were used to purify RNA polymerase 25-fold from Neisseria gonorrhoeae, and the activity of the polymerase was characterized in altered assay systems. The core subunits (beta, beta', and alpha) were tentatively identified as major proteins copurifying with polymerase activity. The identification of the core subunits was confirmed by Western (immunoblot) analysis with polyclonal antisera to Escherichia coli core RNA polymerase. Gonococcal sigma factor heterogeneity was examined by Western blot analysis with polyclonal antiserum to the major E. coli sigma factor, sigma 70, to the E. coli heat shock sigma factor, sigma 32, and with a monoclonal antiserum to Salmonella typhimurium NtrA (sigma 54). Purified RNA polymerase and whole-cell extracts from type 1, type 4, heat-shocked, and anaerobically grown gonococci were examined. Four putative gonococcal sigma factors were detected in purified RNA polymerase preparations and in whole-cell extracts from all cell types. Two of these bands appeared as a doublet, which had an estimated Mr of 80,000. A single lower-Mr band, estimated to be 40,000, was also present. All three of these bands reacted with antisera to E. coli sigma 70 and to E. coli sigma 32. A fourth gonococcal protein reacted solely with a highly specific monoclonal antibody to sigma 54 and had an Mr of 90,000. We conclude that N. gonorrhoeae may contain multiple sigma factors, which it may use to regulate gene expression. Images PMID:2472377

  9. Risk factors for neutropenia with lenalidomide plus dexamethasone therapy for multiple myeloma.

    PubMed

    Mitani, Y; Usami, E; Kimura, M; Nakao, T; Okada, K; Matsuoka, T; Kokuryou, T; Yoshimura, T; Yamakawa, M

    2016-06-01

    Neutropenia may develop as an adverse event in patients with multiple myeloma receiving lenalidomide (LEN) plus dexamethasone (DEX) therapy. In the present study, we examined the risk factors associated with grade 3/4 neutropenia during the first cycle of LEN plus DEX therapy. We observed that hemoglobin level (≤ 8.5 g/dl) was a significant risk factor for grade 3/4 neutropenia during the first cycle of therapy (odds ratio: 19.40; 95% confidence interval: 2.68-141.00; p < 0.01). thus, our findings suggest that determining the hemoglobin level could be useful in the risk management for neutropenia in patients receiving LEN plus DEX therapy. PMID:27455556

  10. Reversal of Ischemic Cardiomyopathy with Sca-1+ Stem Cells Modified with Multiple Growth Factors

    PubMed Central

    Li, Ning; Pasha, Zeeshan; Ashraf, Muhammad

    2014-01-01

    Background We hypothesized that bone marrow derived Sca-1+ stem cells (BM Sca-1+) transduced with multiple therapeutic cytokines with diverse effects will induce faster angiomyogenic differentiation in the infarcted myocardium. Methods and Results BM Sca-1+ were purified from transgenic male mice expressing GFP. Plasmids encoding for select quartet of growth factors, i.e., human IGF-1, VEGF, SDF-1α and HGF were prepared and used for genetic modification of Sca-1+ cells (GFSca-1+). Scramble transfected cells (ScSca-1+) were used as a control. RT-PCR and western blotting showed significantly higher expression of the growth factors in GFSca-1+. Besides the quartet of the therapeutic growth factors, PCR based growth factor array showed upregulation of multiple angiogenic and prosurvival factors such as Ang-1, Ang-2, MMP9, Cx43, BMP2, BMP5, FGF2, and NGF in GFSca-1+ (p<0.01 vs ScSca-1+). LDH and TUNEL assays showed enhanced survival of GFSca-1+ under lethal anoxia (p<0.01 vs ScSca-1+). MTS assay showed significant increased cell proliferation in GFSca-1+ (p<0.05 vs ScSca-1+). For in vivo study, female mice were grouped to receive the intramyocardial injection of 15 μl DMEM without cells (group-1) or containing 2.5×105 ScSca-1+ (group-2) or GFSca-1+ (group-3) immediately after coronary artery ligation. As indicated by Sry gene, a higher survival of GFSca-1+ in group-3 on day4 (2.3 fold higher vs group-2) was observed with massive mobilization of stem and progenitor cells (cKit+, Mdr1+, Cxcr4+ cells). Heart tissue sections immunostained for actinin and Cx43 at 4 weeks post engraftment showed extensive myofiber formation and expression of gap junctions. Immunostaining for vWF showed increased blood vessel density in both peri-infarct and infarct regions in group-3. Infarct size was attenuated and the global heart function was improved in group-3 as compared to group-2. Conclusions Administration of BM Sca-1+ transduced with multiple genes is a novel approach to treat

  11. Multiple Landscape Factors Affect the Resilience of a Mixed Land Cover Watershed

    NASA Astrophysics Data System (ADS)

    Golden, H. E.; Lane, C.; Prues, A. G.; D'Amico, E.

    2015-12-01

    Human activities can stimulate the physical and chemical properties of streams to move beyond their background conditions, thereby facilitating the transition of these factors to stressors that affect watershed resilience. This is particularly true in mixed land cover watersheds. We quantify and explore the statistical nonlinear relationships between watershed and buffer-scale factors and nutrient (nitrite-nitrate (NO2-NO3), total Kjeldahl nitrogen (TKN), total phosphorus (TP)) concentrations, in addition to a multi-metric Index of Biotic Integrity (IBI), in a mesoscale mixed land cover watershed. Our goal is to contribute to a better understanding of the potentially numerous landscape and near-stream hydrological and biogeochemical factors that affect watershed resiliency - as inferred from in-stream nutrient levels and biological condition. We used a boosted regression tree approach, which quantifies nonlinear relationships and variable interactions, to develop watershed and 200 m buffer scale models for each chemical constituent and the annual IBI score. We developed nutrient models for the spring and summer seasons. Two primary factors - location within the watershed and percentage of urban land cover in the watershed or buffer - emerged as important explanatory variables in most nutrient and IBI models. Geographic location (i.e., latitude and longitude) interacted with other factors to explain the variability in summer NO2-NO3 concentrations and IBI scores and suggested that location might be associated with indicators of sources (e.g., land cover) and runoff potential (e.g., soil and topographic factors). Runoff indicators (e.g., Hydrologic Soil Group D and Topographic Wetness Indices) explained a substantial portion of the variability in nutrient concentrations as did point sources for TP in the summer months. Our overall approach confirms that it is important to consider multiple and often interacting factors when managing for watershed resilience.

  12. Infections in Hospitalised Patients with Multiple Myeloma: Main Characteristics and Risk Factors

    PubMed Central

    Valković, Toni; Gačić, Vedrana; Ivandić, Jelena; Petrov, Božo; Dobrila-Dintinjana, Renata; Dadić-Hero, Elizabeta; Načinović-Duletić, Antica

    2015-01-01

    Objective: Multiple myeloma is a common haematological malignancy and immune dysfunction is the hallmark of the disease. It leads to an increased infection risk, which is still a major cause of mortality. The infection spectrum and characteristics have evolved with the introduction of novel agents. An understanding of risk factors that increase susceptibility to infections is critical in fighting them. This retrospective investigation aimed to establish the incidence and main characteristics of infections in non-transplanted hospitalised myeloma patients in our department over a 3-year period, as well as factors associated with infections. Materials and Methods: A total of 240 hospitalised patients with multiple myeloma (120 males and 120 females; average age: 69 years, range: 41-89 years) who were diagnosed or treated in our department from January 2008 to December 2010 were included in this study and their data were retrospectively analysed. Results: Infections were identified in 17.9% of hospitalised patients. The most common pathogen found was Pseudomonas aeruginosa. The frequency of gram-positive and gram-negative pathogens was similar. In 37.2% of cases, the agent was not isolated. The most common sites of infections were the urinary system and the blood (septicemia). The frequency of infection increased with duration of disease and the rate of reinfection was 41.9%. The patients treated with bortezomib had the highest infection occurrence. Fatal outcome occurred in 9.3% of cases. Conclusion: The factors associated with infections in this investigation were female sex, 3B clinical stage of disease, increased serum creatinine and ferritin levels, neutropenia, poor general condition, and presence of catheters. Myeloma patients with one or more of these mentioned risk factors should be monitored with particular care in order to decrease the incidence and severity of infective complications. PMID:26376590

  13. Positive regulatory domain I binding factor 1 silences class II transactivator expression in multiple myeloma cells.

    PubMed

    Ghosh, N; Gyory, I; Wright, G; Wood, J; Wright, K L

    2001-05-01

    The major histocompatibility complex (MHC) class II transactivator (CIITA) acts as a master switch to activate expression of the genes required for MHC-II antigen presentation. During B-cell to plasma cell differentiation, MHC-II expression is actively silenced, but the mechanism has been unknown. In plasma cell tumors such as multiple myeloma the repression of MHC-II is associated with the loss of CIITA. We have identified that positive regulatory domain I binding factor 1 (PRDI-BF1), a transcriptional repressor, inhibits CIITA expression in multiple myeloma cell lines. Repression of CIITA depends on the DNA binding activity of PRDI-BF1 and its specific binding site in the CIITA promoter. Deletion of a histone deacetylase recruitment domain in PRDI-BF1 does not inhibit repression of CIITA nor does blocking histone deacetylase activity. This is in contrast to PRDI-BF1 repression of the c-myc promoter. Repression of CIITA requires either the N-terminal acidic and conserved PR motif or the proline-rich domain. PRDI-BF1 has been shown to be a key regulator of B-cell and macrophage differentiation. These findings now indicate that PRDI-BF1 has at least two mechanisms of repression whose function is dependent on the nature of the target promoter. Importantly, PRDI-BF1 is defined as the key molecule in silencing CIITA and thus MHC-II in multiple myeloma cells. PMID:11279146

  14. Hydrogeological factors affecting the multiple plumes of chlorinated contaminants in an industrial complex, Wonju, Korea

    NASA Astrophysics Data System (ADS)

    Yang, J.; Kaown, D.; Lee, H.; Lee, K.

    2010-12-01

    Apparent plume attenuations of multiple chlorinated contaminants such as TCE, carbon tetrachloride, and its daughter products at an industrial complex, Wonju, Korea were examined through various hydraulic tests and six rounds of groundwater quality analyses. Aquifer media properties and hydrogeologic factors affecting the distribution and attenuation of multiple contaminants were investigated and key attributes were evaluated. The study area has vertically heterogeneous properties from top alluvial layer to crystalline rocks while the weathered fractured layer above intact Jurassic biotite granite acts as the main layer for groundwater flow and aqueous phase multiple contaminants migration. Aerial heterogeneity in surface conditions plays an important role for groundwater recharge because the industrial complex is mostly paved by asphalt and concrete. Due to limited recharge area and concentrated precipitation in summer season, seasonal effects of contaminant plume distribution diminish as the distance increase from the area of recharge. This study analyzed how differently the solute and contaminant concentrations response to the seasonal recharge. For the analyses, the study site was divided into three zones and four transects were established. Groundwater and solute mass balances were estimated by computing groundwater and solute mass flux through transects. The effects of groundwater pumping, groundwater flow and contaminant degradation were examined to simulate the solutes and contaminant concentrations. General tendency of the water quality and contaminant concentration were reproducible with the effects of major components such as groundwater recharge, pumping and estimated degradation rate.

  15. NAC transcription factors in plant multiple abiotic stress responses: progress and prospects

    PubMed Central

    Shao, Hongbo; Wang, Hongyan; Tang, Xiaoli

    2015-01-01

    Abiotic stresses adversely affect plant growth and agricultural productivity. According to the current climate prediction models, crop plants will face a greater number of environmental stresses, which are likely to occur simultaneously in the future. So it is very urgent to breed broad-spectrum tolerant crops in order to meet an increasing demand for food productivity due to global population increase. As one of the largest families of transcription factors (TFs) in plants, NAC TFs play vital roles in regulating plant growth and development processes including abiotic stress responses. Lots of studies indicated that many stress-responsive NAC TFs had been used to improve stress tolerance in crop plants by genetic engineering. In this review, the recent progress in NAC TFs was summarized, and the potential utilization of NAC TFs in breeding abiotic stress tolerant transgenic crops was also be discussed. In view of the complexity of field conditions and the specificity in multiple stress responses, we suggest that the NAC TFs commonly induced by multiple stresses should be promising candidates to produce plants with enhanced multiple stress tolerance. Furthermore, the field evaluation of transgenic crops harboring NAC genes, as well as the suitable promoters for minimizing the negative effects caused by over-expressing some NAC genes, should be considered. PMID:26579152

  16. Systematic review of randomised controlled trials of multiple risk factor interventions for preventing coronary heart disease.

    PubMed Central

    Ebrahim, S.; Smith, G. D.

    1997-01-01

    OBJECTIVE: To assess the effectiveness of multiple risk factor intervention in reducing cardiovascular risk factors, total mortality, and mortality from coronary heart disease among adults. DESIGN: Systematic review and meta-analysis of randomised controlled trials in workforces and in primary care in which subjects were randomly allocated to more than one of six interventions (stopping smoking, exercise, dietary advice, weight control, antihypertensive drugs, and cholesterol lowering drugs) and followed up for at least six months. SUBJECTS: Adults aged 17-73 years, 903000 person years of observation were included in nine trials with clinical event outcomes and 303000 person years in five trials with risk factor outcomes alone. MAIN OUTCOME MEASURES: Changes in systolic and diastolic blood pressure, smoking rates, blood cholesterol concentrations, total mortality, and mortality from coronary heart disease. RESULTS: Net decreases in systolic and diastolic blood pressure, smoking prevalence, and blood cholesterol were 4.2 mm Hg (SE 0.19 mm Hg), 2.7 mm Hg (0.09 mm Hg), 4.2% (0.3%), and 0.14 mmol/l (0.01 mmol/l) respectively. In the nine trials with clinical event end points the pooled odds ratios for total and coronary heart disease mortality were 0.97 (95% confidence interval 0.92 to 1.02) and 0.96 (0.88 to 1.04) respectively. Statistical heterogeneity between the studies with respect to changes in mortality and risk factors was due to trials focusing on hypertensive participants and those using considerable amounts of drug treatment, with only these trials showing significant reductions in mortality. CONCLUSIONS: The pooled effects of multiple risk factor intervention on mortality were insignificant and a small, but potentially important, benefit of treatment (about a 10% reduction in mortality) may have been missed. Changes in risk factors were modest, were related to the amount of pharmacological treatment used, and in some cases may have been overestimated

  17. Associated Risk Factors of STIs and Multiple Sexual Relationships among Youths in Malawi

    PubMed Central

    N, Wilson Chialepeh; A, Sathiyasusuman

    2015-01-01

    Background Having unprotected sex with multiple sexual partners (MSP) is the greatest risk factor for human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs) among youths. Young people with MSPs are less likely to use a condom and the greater the risk for STIs. This study examines the associated risk factors of STIs and multiple sexual partnerships among youths aged 15–24 years. Data and Methods The Malawi Demographic Health Survey 2010 data was used. Out of a sample of 2,987 males and 9,559 females aged 15–24 years, 2,026 males and 6,470 females were considered in the study. Chi square test and logistic regression techniques were performed. Analysis was performed using Statistical Package for Social Sciences (SPSS) version 22. Findings The results indicate that 1,399 (69.0%) males and 2,290 (35.4%) females reported multiple sexual partnerships (MSP). Within the rural area, females (n = 1779) were more likely to report MSP than males (n = 1082) and within the urban areas, a higher proportion of females (n = 511) still reported MSP, with males (n = 316). About 78% rural females aged 20–24 years, and about 79% rural males aged 15–19 years reported MSP. The likelihood of MSP was higher among females in the poorest households (OR = 1.31), being married (OR = 5.71) and Catholic males (OR = 1.63), who were married (OR = 1.59). Catholic males (OR = 1.82) in the rural areas, who were married (OR = 1.80) and rural females in the northern region (OR = 1.26) were more likely to have MSP. The odds ratios were higher among urban females in the poorest (OR = 3.45) households who were married (OR = 4.22). Conclusions Having more than one sexual partner increases the risk of STIs and sexuality education programs should be introduced that emphasize the danger that surrounds MSP. PMID:26248328

  18. Multiple risk factors for work-related injuries and illnesses in korean-chinese migrant workers.

    PubMed

    Lee, Hyeonkyeong; Chae, Duckhee; Yi, Kwan Hyung; Im, Soye; Cho, Sung Hye

    2015-01-01

    Korean-Chinese currently represent the largest group of migrant workers in Korea. The purpose of this study was to investigate the influence of risk factors on the occurrence of work-related injuries and illnesses (WII). Data for 486 Korean-Chinese migrant workers were drawn from the 2010 Migrant Workers' Health and Safety Survey in Korea. Logistic regression was used to identify the association between WII and multiple risk factors. Individual health status (OR = 3.83, 95% CI [2.01, 7.30]), safety training (OR = 0.39, 95% CI [0.18, 0.85]), job satisfaction (OR = 1.90, 95% CI [1.07, 3.38]), physical and chemical hazard exposure (OR = 1.05, 95% CI [1.02, 1.08]), and length of stay (OR = 1.01, 95% CI [1.00, 1.01]) were identified as risk factors for WII. The findings suggest the need for a comprehensive approach to assess WII risk factors, including personal, work organization and psychosocial demands, and acculturation in Korean-Chinese migrant workers. PMID:25791407

  19. Population Heterogeneity in the Salience of Multiple Risk Factors for Adolescent Delinquency

    PubMed Central

    Lanza, Stephanie T.; Cooper, Brittany R.; Bray, Bethany C.

    2014-01-01

    Purpose To present mixture regression analysis as an alternative to more standard regression analysis for predicting adolescent delinquency. We demonstrate how mixture regression analysis allows for the identification of population subgroups defined by the salience of multiple risk factors. Methods We identified population subgroups (i.e., latent classes) of individuals based on their coefficients in a regression model predicting adolescent delinquency from eight previously established risk indices drawn from the community, school, family, peer, and individual levels. The study included N = 37,763 tenth-grade adolescents who participated in the Communities that Care Youth Survey. Standard, zero-inflated, and mixture Poisson and negative binomial regression models are considered. Results Standard and mixture negative binomial regression models are selected as optimal. The five-class regression model is interpreted based on the class-specific regression coefficients, indicating that risk factors have varying salience across classes of adolescents. Conclusions Standard regression shows that all risk factors are significantly associated with delinquency. Mixture regression provides more nuanced information, suggesting a unique set of risk factors that are salient for different subgroups of adolescents. Implications for the design of subgroup-specific interventions are discussed. PMID:24231260

  20. A Risk Analysis Methodology to Address Human and Organizational Factors in Offshore Drilling Safety: With an Emphasis on Negative Pressure Test

    NASA Astrophysics Data System (ADS)

    Tabibzadeh, Maryam

    According to the final Presidential National Commission report on the BP Deepwater Horizon (DWH) blowout, there is need to "integrate more sophisticated risk assessment and risk management practices" in the oil industry. Reviewing the literature of the offshore drilling industry indicates that most of the developed risk analysis methodologies do not fully and more importantly, systematically address the contribution of Human and Organizational Factors (HOFs) in accident causation. This is while results of a comprehensive study, from 1988 to 2005, of more than 600 well-documented major failures in offshore structures show that approximately 80% of those failures were due to HOFs. In addition, lack of safety culture, as an issue related to HOFs, have been identified as a common contributing cause of many accidents in this industry. This dissertation introduces an integrated risk analysis methodology to systematically assess the critical role of human and organizational factors in offshore drilling safety. The proposed methodology in this research focuses on a specific procedure called Negative Pressure Test (NPT), as the primary method to ascertain well integrity during offshore drilling, and analyzes the contributing causes of misinterpreting such a critical test. In addition, the case study of the BP Deepwater Horizon accident and their conducted NPT is discussed. The risk analysis methodology in this dissertation consists of three different approaches and their integration constitutes the big picture of my whole methodology. The first approach is the comparative analysis of a "standard" NPT, which is proposed by the author, with the test conducted by the DWH crew. This analysis contributes to identifying the involved discrepancies between the two test procedures. The second approach is a conceptual risk assessment framework to analyze the causal factors of the identified mismatches in the previous step, as the main contributors of negative pressure test

  1. A Risk Analysis Methodology to Address Human and Organizational Factors in Offshore Drilling Safety: With an Emphasis on Negative Pressure Test

    NASA Astrophysics Data System (ADS)

    Tabibzadeh, Maryam

    According to the final Presidential National Commission report on the BP Deepwater Horizon (DWH) blowout, there is need to "integrate more sophisticated risk assessment and risk management practices" in the oil industry. Reviewing the literature of the offshore drilling industry indicates that most of the developed risk analysis methodologies do not fully and more importantly, systematically address the contribution of Human and Organizational Factors (HOFs) in accident causation. This is while results of a comprehensive study, from 1988 to 2005, of more than 600 well-documented major failures in offshore structures show that approximately 80% of those failures were due to HOFs. In addition, lack of safety culture, as an issue related to HOFs, have been identified as a common contributing cause of many accidents in this industry. This dissertation introduces an integrated risk analysis methodology to systematically assess the critical role of human and organizational factors in offshore drilling safety. The proposed methodology in this research focuses on a specific procedure called Negative Pressure Test (NPT), as the primary method to ascertain well integrity during offshore drilling, and analyzes the contributing causes of misinterpreting such a critical test. In addition, the case study of the BP Deepwater Horizon accident and their conducted NPT is discussed. The risk analysis methodology in this dissertation consists of three different approaches and their integration constitutes the big picture of my whole methodology. The first approach is the comparative analysis of a "standard" NPT, which is proposed by the author, with the test conducted by the DWH crew. This analysis contributes to identifying the involved discrepancies between the two test procedures. The second approach is a conceptual risk assessment framework to analyze the causal factors of the identified mismatches in the previous step, as the main contributors of negative pressure test

  2. Multiple pregnancy: factors contributing to early infant's breast-feeding--own experience.

    PubMed

    Czeszyńska, M B; Kowalik, K

    1998-01-01

    The aims of the study were as follows: 1. to evaluate the effectiveness of current program to promote breast-feeding in our population of infants from multiple pregnancy; 2. to define factors responsible for failure in early breast-feeding establishing and/or maintaining breast-feed during the hospitalization of the babies in neonatal department. 122 newborn infants (2 sets of triplets and 58 twin pairs) born in the Clinic for Pathology of Pregnancy and Labor in Szczecin, Poland, in the years 1995 (January)-1999 (May) from multiple pregnancy were included in the study. In the examined material there were estimated neonatal conditions at birth, neonatal complications, which may disturb successful breast-feeding as well as other factors contributing to early breast-feeding, the way of feeding the babies during neonatal period and the mean time of starting breast-feeding. It was found that most of the examined babies were born with the features of prematurity: mean gestational age was 35.6 +/- 2.2 weeks and mean birthweight--2225.3 +/- 193.2 grams. Only 57.4% of babies were born in good conditions according to Apgar scores. Factors which influence in a negative way early breast-feeding were as follows: respiratory disturbance (22.1%), temporary oral nutrition intolerance due to sickness of the baby or early onset of infections (27.5%), operative delivery (62.3%), medicine taken by mothers (13.9%) and failure in maternal lactation (8.2%). Factors disturbing a normal course of breast-feeding were: phototherapy due to hyperbilirubinemia (20.5%) and late onset of infections (1.6%). In most cases breast-feeding was started 3-4 days after birth and the most frequent way of feeding was formula followed or in combination with maternal milk (at discharge in 86.9% of babies). We concluded that exclusive breast-feeding, despite program of promotion, is a rarity in population of newborn babies born from multiple pregnancy; time to start breast-feeding in this population is

  3. Analytical expressions for the gate utilization factors of passive multiplicity counters including signal build-up

    SciTech Connect

    Croft, Stephen; Evans, Louise G; Schear, Melissa A

    2010-01-01

    In the realm of nuclear safeguards, passive neutron multiplicity counting using shift register pulse train analysis to nondestructively quantify Pu in product materials is a familiar and widely applied technique. The approach most commonly taken is to construct a neutron detector consisting of {sup 3}He filled cylindrical proportional counters embedded in a high density polyethylene moderator. Fast neutrons from the item enter the moderator and are quickly slowed down, on timescales of the order of 1-2 {micro}s, creating a thermal population which then persists typically for several 10's {micro}s and is sampled by the {sup 3}He detectors. Because the initial transient is of comparatively short duration it has been traditional to treat it as instantaneous and furthermore to approximate the subsequent capture time distribution as exponential in shape. With these approximations simple expressions for the various Gate Utilization Factors (GUFs) can be obtained. These factors represent the proportion of time correlated events i.e. Doubles and Triples signal present in the pulse train that is detected by the coincidence gate structure chosen (predelay and gate width settings of the multiplicity shift register). More complicated expressions can be derived by generalizing the capture time distribution to multiple time components or harmonics typically present in real systems. When it comes to applying passive neutron multiplicity methods to extremely intense (i.e. high emission rate and highly multiplying) neutron sources there is a drive to use detector types with very fast response characteristics in order to cope with the high rates. In addition to short pulse width, detectors with a short capture time profile are also desirable so that a short coincidence gate width can be set in order to reduce the chance or Accidental coincidence signal. In extreme cases, such as might be realized using boron loaded scintillators, the dieaway time may be so short that the build

  4. Clinically Significant Fatigue: Prevalence and Associated Factors in an International Sample of Adults with Multiple Sclerosis Recruited via the Internet

    PubMed Central

    Weiland, Tracey J.; Jelinek, George A.; Marck, Claudia H.; Hadgkiss, Emily J.; van der Meer, Dania M.; Pereira, Naresh G.; Taylor, Keryn L.

    2015-01-01

    Background Fatigue contributes a significant burden of disease for people with multiple sclerosis (PwMS). Modifiable lifestyle factors have been recognized as having a role in a range of morbidity outcomes in PwMS. There is significant potential to prevent and treat fatigue in PwMS by addressing modifiable risk factors. Objectives To explore the associations between clinically significant fatigue and demographic factors, clinical factors (health-related quality of life, disability and relapse rate) and modifiable lifestyle, disease-modifying drugs (DMD) and supplement use in a large international sample of PwMS. Methods PwMS were recruited to the study via Web 2.0 platforms and completed a comprehensive survey measuring demographic, lifestyle and clinical characteristics, including health-related quality of life, disability, and relapse rate. Results Of 2469 participants with confirmed MS, 2138 (86.6%) completed a validated measure of clinically significant fatigue, the Fatigue Severity Scale. Participants were predominantly female from English speaking countries, with relatively high levels of education, and due to recruitment methods may have been highly pro-active about engaging in lifestyle management and self-help. Approximately two thirds of our sample (1402/2138; 65.6% (95% CI 63.7–67.7)) screened positive for clinically significant fatigue. Bivariate associations were present between clinically significant fatigue and several demographic, clinical, lifestyle, and medication variables. After controlling for level of disability and a range of stable socio-demographic variables, we found increased odds of fatigue associated with obesity, DMD use, poor diet, and reduced odds of fatigue with exercise, fish consumption, moderate alcohol use, and supplementation with vitamin D and flaxseed oil. Conclusion This study supports strong and significant associations between clinically significant fatigue and modifiable lifestyle factors. Longitudinal follow-up of this

  5. Serum Parathyroid Hormone Is a New Potential Risk Factor in Multiple Myeloma

    PubMed Central

    Won, Eun-Jeong; Kim, Hye-Ran; Choi, Hyun-Jung; Park, Hye-Ri; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Shin, Myung-Geun

    2014-01-01

    We hypothesized that serum PTH might be associated with various clinicopathological parameters in multiple myeloma (MM). So we investigated the implications of serum PTH in MM patients and the relationship with other risk factors of MM. A total of 115 patients who were newly diagnosed with MM were enrolled. Serum PTH level was 24.7 ± 34.9 (ranged 0.0–284.1) pg/mL. Serum levels of IgG, IgM, FLC-lambda, albumin, and LDH were in positive correlation with serum PTH. Compared to non-high PTH (<68.3 pg/mL) group, the hazard ratio (HR) for overall survival was higher for group with high PTH level (≥68.3 pg/mL) (HR, 1.710). Furthermore, the patient group with high PTH level showed inferior progression-free survival than non-high PTH group (P = 0.056). Interestingly, subgroup analysis showed that serum PTH level at diagnosis was associated with risk factors and clinical outcome in MM patients, especially in complete remission group, transplantation cases, ISS stage II cases, and cases without chromosome abnormality. In conclusion, this study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients. PMID:24967406

  6. Multiple factors contribute to anautogenous reproduction by the mosquito Aedes aegypti.

    PubMed

    Gulia-Nuss, Monika; Elliot, Anne; Brown, Mark R; Strand, Michael R

    2015-11-01

    Aedes aegypti is an anautogenous mosquito that must blood feed on a vertebrate host to produce and lay a clutch of eggs. The rockpool mosquito, Georgecraigius atropalpus, is related to A. aegypti but is a facultatively autogenous species that produces its first clutch of eggs shortly after emerging without blood feeding. Consumption of a blood meal by A. aegypti triggers the release of ovary ecdysteroidogenic hormone (OEH) and insulin-like peptide 3 (ILP3) from the brain, which stimulate egg formation. OEH and ILP3 also stimulate egg formation in G. atropalpus but are released at eclosion independently of blood feeding. These results collectively suggest that blood meal dependent release of OEH and ILP3 is one factor that prevents A. aegypti from reproducing autogenously. Here, we examined two other factors that potentially inhibit autogeny in A. aegypti: teneral nutrient reserves and the ability of OEH and ILP3 to stimulate egg formation in the absence of blood feeding. Measures of nutrient reserves showed that newly emerged A. aegypti females had similar wet weights but significantly lower protein and glycogen reserves than G. atropalpus females when larvae were reared under identical conditions. OEH stimulated non-blood fed A. aegypti females to produce ecdysteroid hormone and package yolk into oocytes more strongly than ILP3. OEH also reduced host seeking and blood feeding behavior, yet females produced few mature eggs. Overall, our results indicate that multiple factors prevent A. aegypti from reproducing autogenously. PMID:26255841

  7. [Multiple stepwise regression analysis of etiological factors of esophageal cancer in Cixian county].

    PubMed

    Hou, J

    1989-01-01

    Cixian county, one of the high-risk counties of esophageal cancer in the world, has a standardized mortality of 142.19/10(5) population, 1969-1971. The incidence of esophageal cancer had dropped year by year from 1974 to 1982. The significance of the incidence tendency was studied. The results are highly significant (P less than 0.001). The causative factors of esophageal cancer including five independent variables: X1 (number of people taking sanitized water), X2 (number of people on pickled Chinese cabbage), X3 (annual output of fruit), X4 (annual output of fresh vegetable) and X5 (annual output of sweet potato) and one dependent variable Y (morbidity of esophageal cancer) were studied by correlative analysis and multiple stepwise regression. Three correlative factors (X1, X2, and X5) with significant effect on the esophageal cancer were selected from the five suspected factors. The result indicated that taking sanitized water, reducing the number of people on pickled Chinese cabbage, changing the structure of food and keeping the nutrient balance, might decrease the incidence of esophageal cancer. PMID:2789130

  8. The environmental risk factors in multiple sclerosis susceptibility: A case-control study

    PubMed Central

    Shaygannejad, Vahid; Rezaie, Nooshin; Paknahad, Zamzam; Ashtari, Freshteh; Maghzi, Helia

    2016-01-01

    Background: Multiple sclerosis (MS) is a demyelinating and degenerating disease which involves central nervous system. Environmental risk factors have a key role in MS susceptibility. Here we aim to investigate different risk factors effect on MS susceptibility in a large population of MS patients in Isfahan, Iran. Materials and Methods: This study is a cross-sectional hospital-based study, which was conducted on a large group of MS patients registered in Kashani hospital and a control group from normal healthy population. Demographic data, age at onset of the disease, history of viral infections, vaccination, history of trauma to head, recent stressful events, alimentation, familial history, method of delivery (caesarean section, normal vaginal delivery), disability score and history of smoking were gathered using a designed questionnaire. Results: Totally 536 MS patient with the mean age of 34.37 ± 9.22 and 399 individuals from healthy population with the mean age of 32.53 ± 9.91 were recruited. Significant difference in history of measles infection (control = 15.5%, case = 22.4%, P = 0.009), consumption of dairy products (case = 56.6%, control = 67.5%, P = 0.01) and major stressful life events (case = 62.2%, control = 52.7%, P < 0.05) between these two groups were demonstrated. Conclusion: A significant relation between stress, history of infection and milk consumption was reached that highlights the importance of environmental risk factors in MS pathogenesis. PMID:27376037

  9. Regulatory approaches to obesity prevention: A systematic overview of current laws addressing diet-related risk factors in the European Union and the United States.

    PubMed

    Sisnowski, Jana; Handsley, Elizabeth; Street, Jackie M

    2015-06-01

    High prevalence of overweight and obesity remains a significant international public health problem. Law has been identified as a tool for obesity prevention and selected high-profile measures have been reported. However, the nature and extent of enacted legislation internationally are unclear. This research provides an overview of regulatory approaches enacted in the United States, the European Union, and EU Member States since 2004. To this end, relevant databases of primary and secondary legislation were systematically searched to identify and explore laws addressing dietary risk factors for obesity. Across jurisdictions, current regulatory approaches to obesity prevention are limited in reach and scope. Target groups are rarely the general population, but instead sub-populations in government-supported settings. Consumer information provision is preferred over taxation and marketing restrictions other than the regulation of health and nutrition claims. In the EU in particular, product reformulation with industry consent has also emerged as a popular small-scale measure. While consistent and widespread use of law is lacking, governments have employed a range of regulatory measures in the name of obesity prevention, indicating that there is, in principle, political will. Results from this study may serve as a starting point for future research and policy development. PMID:25963556

  10. Scattering from phase-separated vesicles. I. An analytical form factor for multiple static domains

    SciTech Connect

    Heberle, Frederick A.; Anghel, Vinicius N. P.; Katsaras, John

    2015-08-18

    This is the first in a series of studies considering elastic scattering from laterally heterogeneous lipid vesicles containing multiple domains. Unique among biophysical tools, small-angle neutron scattering can in principle give detailed information about the size, shape and spatial arrangement of domains. A general theory for scattering from laterally heterogeneous vesicles is presented, and the analytical form factor for static domains with arbitrary spatial configuration is derived, including a simplification for uniformly sized round domains. The validity of the model, including series truncation effects, is assessed by comparison with simulated data obtained from a Monte Carlo method. Several aspects of the analytical solution for scattering intensity are discussed in the context of small-angle neutron scattering data, including the effect of varying domain size and number, as well as solvent contrast. Finally, the analysis indicates that effects of domain formation are most pronounced when the vesicle's average scattering length density matches that of the surrounding solvent.

  11. Mathematical model for addiction: application to multiple risk factor intervention trial data for smoking.

    PubMed

    Fan, D P; Elketroussi, M

    1989-06-01

    Describes habituation and addiction, both psychological and physiological, using the simple equations of the mathematical model of ideodynamics. The parameters in these equations were optimized to smoking data from the Multiple Risk Factor Intervention Trial (MRFIT) program. With only 4 constant parameters, it was possible to calculate accurate time trends for recidivism to smoking among quitters, time trends for secondary cessation among recidivists, and final percentage of smokers in a population with both recidivism and secondary cessation occurring simultaneously. These same parameters further permit predictions for the long-range success of intervention programs to decrease substance dependency. Ideodynamics can also predict time trends of public opinion based on stories in the mass media. PMID:2661613

  12. The multiple lives of NMD factors: balancing roles in gene and genome regulation

    PubMed Central

    Isken, Olaf; Maquat, Lynne E.

    2013-01-01

    Nonsense-mediated mRNA decay (NMD) largely functions to ensure the quality of gene expression. However, NMD is also crucial to regulating appropriate expression levels for certain genes and for maintaining genome stability. Furthermore, just as NMD serves cells in multiple ways, so do its constituent proteins. Recent studies have clarified that UPF and SMG proteins, which were originally discovered to function in NMD, also have roles in other pathways, including specialized pathways of mRNA decay, DNA synthesis and cell-cycle progression, and the maintenance of telomeres. These findings suggest a delicate balance of metabolic events — some not obviously related to NMD — that can be influenced by the cellular abundance, location and activity of NMD factors and their binding partners. PMID:18679436

  13. Multiple infections and associated risk factors among non-injecting cocaine users in Argentina.

    PubMed

    Rossi, Diana; Radulich, Graciela; Muzzio, Estela; Naveira, Jorge; Sosa-Estani, Sergio; Rey, Jorge; Griemberg, Gloria; Friedman, Samuel R; Martínez-Peralta, Liliana; Weissenbacher, Mercedes

    2008-05-01

    The aim of this study was to estimate the seroprevalence rates of human immunodeficiency virus (HIV), hepatitis B virus (HBV, core antibody), hepatitis C virus (HCV), and syphilis infections and analyze associated risk factors among 504 non-injecting cocaine users (NICU) in Buenos Aires, Argentina. Participants were interviewed in face-to-face sessions through a short structured questionnaire. Using venipuncture, 10 mL of blood was collected. Seroprevalence rates were: HIV (6.3%), HBV (9%), HCV (7.5%), and VDRL (4.2%). The risk of being infected with HIV, HBV, and HCV was significantly associated with having had a sex partner who was either a drug injector or who was known to be HIV positive. HIV and HCV infections were associated with former imprisonment, and HCV was associated with having been tattooed. Because of the rising number of NICU and the multiple infections detected, it is essential to implement prevention strategies focused on this population. PMID:18461225

  14. Accelerated multiplicative updates and hierarchical ALS algorithms for nonnegative matrix factorization.

    PubMed

    Gillis, Nicolas; Glineur, François

    2012-04-01

    Nonnegative matrix factorization (NMF) is a data analysis technique used in a great variety of applications such as text mining, image processing, hyperspectral data analysis, computational biology, and clustering. In this letter, we consider two well-known algorithms designed to solve NMF problems: the multiplicative updates of Lee and Seung and the hierarchical alternating least squares of Cichocki et al. We propose a simple way to significantly accelerate these schemes, based on a careful analysis of the computational cost needed at each iteration, while preserving their convergence properties. This acceleration technique can also be applied to other algorithms, which we illustrate on the projected gradient method of Lin. The efficiency of the accelerated algorithms is empirically demonstrated on image and text data sets and compares favorably with a state-of-the-art alternating nonnegative least squares algorithm. PMID:22168561

  15. Statistical mechanical model of coupled transcription from multiple promoters due to transcription factor titration

    NASA Astrophysics Data System (ADS)

    Rydenfelt, Mattias; Cox, Robert Sidney, III; Garcia, Hernan; Phillips, Rob

    2014-01-01

    Transcription factors (TFs) with regulatory action at multiple promoter targets is the rule rather than the exception, with examples ranging from the cAMP receptor protein (CRP) in E. coli that regulates hundreds of different genes simultaneously to situations involving multiple copies of the same gene, such as plasmids, retrotransposons, or highly replicated viral DNA. When the number of TFs heavily exceeds the number of binding sites, TF binding to each promoter can be regarded as independent. However, when the number of TF molecules is comparable to the number of binding sites, TF titration will result in correlation (“promoter entanglement”) between transcription of different genes. We develop a statistical mechanical model which takes the TF titration effect into account and use it to predict both the level of gene expression for a general set of promoters and the resulting correlation in transcription rates of different genes. Our results show that the TF titration effect could be important for understanding gene expression in many regulatory settings.

  16. Young adult Ecstasy users and multiple sexual partners: understanding the factors underlying this HIV risk practice.

    PubMed

    Sterk, Claire E; Klein, Hugh; Elifson, Kirk W

    2008-09-01

    The purposes of this study are to (1) examine the extent to which young adult Ecstasy users recently reported having had multiple sex partners and (2) identify the factors predictive of engaging in this behavior. Potential predictors included demographic characteristics, background and experiences measures, childhood maltreatment experiences, substance use variables, and measures assessing psychological/psychosocial functioning. This research is based on a sample of 283 young adult recurrent users of the drug, Ecstasy. Study participants were recruited in Atlanta, Georgia between August 2002 and August 2004 using a targeted sampling and ethnographic mapping approach. Interviews took approximately two hours to complete. Nearly one-third of the study participants had more than one sex partner during the preceding month, and sexual protection rates tended to be low. Multivariate logistic regression analysis revealed seven predictors associated with an increased likelihood of having multiple sex partners: (1) being nonwhite, (2) knowing someone who was HIV-positive, (3) younger age of first sexual experience, (4) using Ecstasy for its touch-enhancing qualities, (5) higher self-esteem, (6) handling disagreements more dysfunctionally, and (7) not being involved in a romantic relationship. The HIV prevention- and intervention-related implications of these findings are discussed. PMID:19004415

  17. The multiple life of nerve growth factor: tribute to rita levi-montalcini (1909-2012).

    PubMed

    Aloe, Luigi; Chaldakov, George N

    2013-03-01

    At the end of the 19(th) century, it was envisaged by Santiago Ramon y Cajal, but not, proven, that life at the neuronal level requires trophic support. The proof was obtained in the early 1950's by work initiated by Rita Levi-Montalcini (RLM) discovering the nerve growth factor (NGF). Today, NGF and its relatives, collectively designated neurotrophins, are well recognized as mediators of multiple biological phenomena in health and disease, ranging from the neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects. Consequently, NGF and other neurotrophins are implicated in the pathogenesis of a large spectrum of neuronal and non-neuronal diseases, from Alzheimer's and other neurodegenerative diseases to atherosclerosis and other cardiometabolic diseases. Recent studies demonstrated the therapeutic potentials of NGF in these diseases, including ocular and cutaneous diseases. Furthermore, NGF TrkA receptor antagonists emerged as novel drugs for pain, prostate and breast cancer, melanoma, and urinary bladder syndromes. Altogether, NGF's multiple potential in health and disease is briefly described here. PMID:25207059

  18. Young Adult Ecstasy Users and Multiple Sexual Partners: Understanding the Factors Underlying this HIV Risk Practice†

    PubMed Central

    Sterk, Claire E.; Klein, Hugh; Elifson, Kirk W.

    2013-01-01

    The purposes of this study are to (1) examine the extent to which young adult Ecstasy users recently reported having had multiple sex partners and (2) identify the factors predictive of engaging in this behavior. Potential predictors included demographic characteristics, background and experiences measures, childhood maltreatment experiences, substance use variables, and measures assessing psychological/psychosocial functioning. This research is based on a sample of 283 young adult recurrent users of the drug, Ecstasy. Study participants were recruited in Atlanta, Georgia between August 2002 and August 2004 using a targeted sampling and ethnographic mapping approach. Interviews took approximately two hours to complete. Nearly one-third of the study participants had more than one sex partner during the preceding month, and sexual protection rates tended to be low. Multivariate logistic regression analysis revealed seven predictors associated with an increased likelihood of having multiple sex partners: (1) being nonwhite, (2) knowing someone who was HIV-positive, (3) younger age of first sexual experience, (4) using Ecstasy for its touch-enhancing qualities, (5) higher self-esteem, (6) handling disagreements more dysfunctionally, and (7) not being involved in a romantic relationship. The HIV prevention- and intervention-related implications of these findings are discussed. PMID:19004415

  19. Muscle Tissue Engineering Using Gingival Mesenchymal Stem Cells Encapsulated in Alginate Hydrogels Containing Multiple Growth Factors.

    PubMed

    Ansari, Sahar; Chen, Chider; Xu, Xingtian; Annabi, Nasim; Zadeh, Homayoun H; Wu, Benjamin M; Khademhosseini, Ali; Shi, Songtao; Moshaverinia, Alireza

    2016-06-01

    Repair and regeneration of muscle tissue following traumatic injuries or muscle diseases often presents a challenging clinical situation. If a significant amount of tissue is lost the native regenerative potential of skeletal muscle will not be able to grow to fill the defect site completely. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material, present an advantageous alternative therapeutic option for muscle tissue engineering in comparison to current treatment modalities available. To date, there has been no report on application of gingival mesenchymal stem cells (GMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of the current study were to develop an injectable 3D RGD-coupled alginate scaffold with multiple growth factor delivery capacity for encapsulating GMSCs, and to evaluate the capacity of encapsulated GMSCs to differentiate into myogenic tissue in vitro and in vivo where encapsulated GMSCs were transplanted subcutaneously into immunocompromised mice. The results demonstrate that after 4 weeks of differentiation in vitro, GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited muscle cell-like morphology with high levels of mRNA expression for gene markers related to muscle regeneration (MyoD, Myf5, and MyoG) via qPCR measurement. Our quantitative PCR analyzes revealed that the stiffness of the RGD-coupled alginate regulates the myogenic differentiation of encapsulated GMSCs. Histological and immunohistochemical/fluorescence staining for protein markers specific for myogenic tissue confirmed muscle regeneration in subcutaneous transplantation in our in vivo animal model. GMSCs showed significantly greater capacity for myogenic regeneration in comparison to hBMMSCs (p < 0.05). Altogether, our findings confirmed that GMSCs encapsulated in RGD-modified alginate hydrogel with multiple growth factor delivery capacity is a promising

  20. Multiple Nuclear Localization Signals Mediate Nuclear Localization of the GATA Transcription Factor AreA

    PubMed Central

    Hunter, Cameron C.; Siebert, Kendra S.; Downes, Damien J.; Wong, Koon Ho; Kreutzberger, Sara D.; Fraser, James A.; Clarke, David F.; Hynes, Michael J.; Davis, Meryl A.

    2014-01-01

    The Aspergillus nidulans GATA transcription factor AreA activates transcription of nitrogen metabolic genes in response to nitrogen limitation and is known to accumulate in the nucleus during nitrogen starvation. Sequence analysis of AreA revealed multiple nuclear localization signals (NLSs), five putative classical NLSs conserved in fungal AreA orthologs but not in the Saccharomyces cerevisiae functional orthologs Gln3p and Gat1p, and one putative noncanonical RRX33RXR bipartite NLS within the DNA-binding domain. In order to identify the functional NLSs in AreA, we constructed areA mutants with mutations in individual putative NLSs or combinations of putative NLSs and strains expressing green fluorescent protein (GFP)-AreA NLS fusion genes. Deletion of all five classical NLSs individually or collectively did not affect utilization of nitrogen sources or AreA-dependent gene expression and did not prevent AreA nuclear localization. Mutation of the bipartite NLS conferred the inability to utilize alternative nitrogen sources and abolished AreA-dependent gene expression likely due to effects on DNA binding but did not prevent AreA nuclear localization. Mutation of all six NLSs simultaneously prevented AreA nuclear accumulation. The bipartite NLS alone strongly directed GFP to the nucleus, whereas the classical NLSs collaborated to direct GFP to the nucleus. Therefore, AreA contains multiple conserved NLSs, which show redundancy and together function to mediate nuclear import. The noncanonical bipartite NLS is conserved in GATA factors from Aspergillus, yeast, and mammals, indicating an ancient origin. PMID:24562911

  1. Risk factors for increased multiple sclerosis susceptibility in the Iranian population.

    PubMed

    Mansouri, Behnam; Asadollahi, Shadi; Heidari, Kamran; Fakhri, Mohammad; Assarzadegan, Farhad; Nazari, Maryam; Divani, Afshin

    2014-12-01

    Multiple sclerosis (MS) is a complex autoimmune disease with increasing prevalence. Many factors have been assessed in relation to its development and its worldwide geographical and racial distribution. Therefore, we decided to conduct a nationwide case-control matched study to estimate the possible influence of putative risk factors on MS status in an Iranian MS population. Between January 2008 and September 2013, 1403 patients diagnosed with MS according to the Poser or McDonald criteria and 883 controls were studied. Of all patients, there were 921 women and 296 men (ratio 3.1:1) with a mean age of 32.6 ± 8.7 years. In the multivariate model adjusted for sex and age (±2years), we found associated risk factors of MS to be: history of any allergic condition (Odds ratio (OR): 1.92, 95% Confidence interval (CI): 1.55-2.47, p<0.001), and smoking (OR: 1.93, 95% CI: 1.31-2.73, p<0.001). Sunlight exposure ⩾ 3 hours was found to be associated with a reduced risk of MS (OR: 0.23, 95% CI: 0.15-0.31, p<0.001). As expected, cases were more likely to have a positive family history of MS than controls (OR: 1.91, 95% CI: 1.33-2.75, p<0.001). A significant association was found between family history of other autoimmune diseases and MS risk (OR: 1.57, 95% CI: 1.18-2.09, p=0.002). These results support the hypothesis that sun exposure is associated with a decreased risk of MS while smoking, autoimmune family history, MS family history, and personal allergy history are risk factors for MS susceptibility. PMID:25082407

  2. Concomitant Factors Leading to an Atypical Osteonecrosis of the Jaw in a Patient with Multiple Myeloma

    PubMed Central

    Miranda-Rius, Jaume; Brunet-Llobet, Lluís; Lahor-Soler, Eduard; Giménez-Rubio, Josep Anton

    2014-01-01

    Osteonecrosis of the jaw (ONJ) is a site specific osseous pathology, characterized by chronic exposed bone in the mouth, which needs to be reinforced periodically within the medical literature. ONJ is a clinical entity with many possible aetiologies and its pathogenesis is not well understood. The risk factors for ONJ include bisphosphonates treatments, head and neck radiotherapy, dental procedures involving bone surgery, and trauma. Management of ONJ has centred on efforts to eliminate or reduce severity of symptoms, to slow or prevent the progression of disease, and to eradicate diseased bone. This case describes a rare case of ONJ in a 64-year-old Caucasian male diagnosed with multiple myeloma stage III. The lesion was related to a traumatic injury during mastication. Eighteen months ago in the same area the molar 37 was extracted, achieving a complete satisfactory healing, when only 2 doses of zoledronic acid had been administered. Actinomyces bacterial aggregates were also identified in the microscopic analysis. The management of this osteonecrotic lesion included antibiotic treatment and chlorhexidine topical gel administration. The evolution was monitored every two weeks until patient's death. The authors provide a discussion of the etiology, pathogenesis, diagnosis, and management. This case report may shed light on the controversies about concomitant factors and mechanisms inducing ONJ. PMID:25140178

  3. Multiple intrinsic factors act in concert with Lhx2 to direct retinal gliogenesis

    PubMed Central

    de Melo, Jimmy; Clark, Brian S.; Blackshaw, Seth

    2016-01-01

    Müller glia (MG) are the principal glial cell type in the vertebrate retina. Recent work has identified the LIM homeodomain factor encoding gene Lhx2 as necessary for both Notch signaling and MG differentiation in late-stage retinal progenitor cells (RPCs). However, the extent to which Lhx2 interacts with other intrinsic regulators of MG differentiation is unclear. We investigated this question by investigating the effects of overexpression of multiple transcriptional regulators that are either known or hypothesized to control MG formation, in both wildtype and Lhx2-deficient RPCs. We observe that constitutively elevated Notch signaling, induced by N1ICD electroporation, inhibited gliogenesis in wildtype animals, but rescued MG development in Lhx2-deficient retinas. Electroporation of Nfia promoted the formation of cells with MG-like radial morphology, but did not drive expression of MG molecular markers. Plagl1 and Sox9 did not induce gliogenesis in wildtype animals, but nonetheless activated expression of the Müller marker P27Kip1 in Lhx2-deficient cells. Finally, Sox2, Sox8, and Sox9 promoted amacrine cell formation in Lhx2-deficient cells, but not in wildtype retinas. These findings demonstrate that overexpression of individual gliogenic factors typically regulates only a subset of characteristic MG markers, and that these effects are differentially modulated by Lhx2. PMID:27605455

  4. Multiple intrinsic factors act in concert with Lhx2 to direct retinal gliogenesis.

    PubMed

    de Melo, Jimmy; Clark, Brian S; Blackshaw, Seth

    2016-01-01

    Müller glia (MG) are the principal glial cell type in the vertebrate retina. Recent work has identified the LIM homeodomain factor encoding gene Lhx2 as necessary for both Notch signaling and MG differentiation in late-stage retinal progenitor cells (RPCs). However, the extent to which Lhx2 interacts with other intrinsic regulators of MG differentiation is unclear. We investigated this question by investigating the effects of overexpression of multiple transcriptional regulators that are either known or hypothesized to control MG formation, in both wildtype and Lhx2-deficient RPCs. We observe that constitutively elevated Notch signaling, induced by N1ICD electroporation, inhibited gliogenesis in wildtype animals, but rescued MG development in Lhx2-deficient retinas. Electroporation of Nfia promoted the formation of cells with MG-like radial morphology, but did not drive expression of MG molecular markers. Plagl1 and Sox9 did not induce gliogenesis in wildtype animals, but nonetheless activated expression of the Müller marker P27(Kip1) in Lhx2-deficient cells. Finally, Sox2, Sox8, and Sox9 promoted amacrine cell formation in Lhx2-deficient cells, but not in wildtype retinas. These findings demonstrate that overexpression of individual gliogenic factors typically regulates only a subset of characteristic MG markers, and that these effects are differentially modulated by Lhx2. PMID:27605455

  5. Risk factors for multiple sclerosis and associations with anti-EBV antibody titers.

    PubMed

    Mouhieddine, Tarek H; Darwish, Hala; Fawaz, Lama; Yamout, Bassem; Tamim, Hani; Khoury, Samia J

    2015-05-01

    Multiple sclerosis (MS) is an inflammatory demyelination of the central nervous system. We investigated the prevalence of EBV seropositivity and other known risk factors for MS (age, smoking, low vitamin D) and their effect on anti-EBV antibody titers. We retrospectively studied 249 MS patients receiving care at the American University of Beirut Medical Center and 230 controls, during 2010-2014. EBV seropositivity was higher in MS patients compared to controls for both anti-VCA (99.5%; 97.2%) and anti-EBNA-1 (96.3%; 89.4%), and the titers were significantly higher in MS patients. MS patients had a significantly lower vitamin D level (15.5 ± 8.3 ng/ml) compared to controls (20.4 ± 11.3 ng/ml). The proportion of heavy smokers and overweight individuals was significantly higher in MS patients. Lebanese MS patients have risk factors similar to those in western countries. Older age and female gender were associated with a higher anti-VCA titer and male gender with a higher anti-EBNA-1. PMID:25805657

  6. Hypoxia inducible factor-1 alpha as a therapeutic target in multiple myeloma

    PubMed Central

    Terragna, Carolina; Martello, Marina; Dico, Angela F.; Solaini, Giancarlo; Baracca, Alessandra; Sgarbi, Gianluca; Pasquinelli, Gianandrea; Valente, Sabrina; Zamagni, Elena; Tacchetti, Paola; Martinelli, Giovanni; Cavo, Michele

    2014-01-01

    The increasing importance of hypoxia-inducible factor-1α (HIF-1α) in tumorigenesis raises the possibility that agents which specifically inhibit this transcription factor, would provide significant therapeutic benefit. The constitutive expression of HIF-1α in about 35% of Multiple Myeloma (MM) patients suggests HIF-1α suppression might be part of a therapeutic strategy. Accordingly, we explored the effect of EZN-2968, a small 3rd generation antisense oligonucleotide against HIF-1α, in a panel of MM cell lines and primary patients samples. Here, we demonstrated that EZN-2968 is highly specific for HIF-1α mRNA and that exposure of MM cells to EZN-2968 resulted in an efficient and homogeneous loading of the cells showing a long lasting low HIF-1α protein level. In MM cells, HIF-1α suppression induced a permanent cell cycle arrest by prolonging S-phase through cyclin A modulation and in addition it induced a mild apoptotic cell death. Moreover, HIF-1α suppression caused a metabolic shift that leaded to increased production of ATP by oxidative phosphorylation (i.e. Warburg effect reversion), that was confirmed by the observed mitochondrial membrane potential decrease. These results show that HIF-1α is an important player in MM homeostasis and that its inhibition by small antisense oligonucleotides provides a rationale for novel therapeutic strategy to improving MM treatment. PMID:24732040

  7. Multiple Factors Related to the Secretion of Glucagon-Like Peptide-1

    PubMed Central

    Wang, XingChun; Liu, Huan; Chen, Jiaqi; Li, Yan; Qu, Shen

    2015-01-01

    The glucagon-like peptide-1 is secreted by intestinal L cells in response to nutrient ingestion. It regulates the secretion and sensitivity of insulin while suppressing glucagon secretion and decreasing postprandial glucose levels. It also improves beta-cell proliferation and prevents beta-cell apoptosis induced by cytotoxic agents. Additionally, glucagon-like peptide-1 delays gastric emptying and suppresses appetite. The impaired secretion of glucagon-like peptide-1 has negative influence on diabetes, hyperlipidemia, and insulin resistance related diseases. Thus, glucagon-like peptide-1-based therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) are now well accepted in the management of type 2 diabetes. The levels of glucagon-like peptide-1 are influenced by multiple factors including a variety of nutrients. The component of a meal acts as potent stimulants of glucagon-like peptide-1 secretion. The levels of its secretion change with the intake of different nutrients. Some drugs also have influence on GLP-1 secretion. Bariatric surgery may improve metabolism through the action on GLP-1 levels. In recent years, there has been a great interest in developing effective methods to regulate glucagon-like peptide-1 secretion. This review summarizes the literature on glucagon-like peptide-1 and related factors affecting its levels. PMID:26366173

  8. 'Hidden' factors influencing quality of life in patients with multiple sclerosis.

    PubMed

    Lysandropoulos, A P; Havrdova, E

    2015-10-01

    Traditional outcome measures for patients with multiple sclerosis (MS), whether in clinical trials or clinical practice, are currently in question. The combination of relapses, physical disability progression and magnetic resonance imaging (MRI) disease activity reflect only part of the impact that MS has on a patient's daily life. Quality of life (QoL) is considered by many to be the ideal outcome measure. Since it captures the patient's own perspective of well-being, QoL should be the primary focus when evaluating a patient and the main objective of MS management. Nevertheless, whilst numerous instruments to measure QoL in MS patients are available or proposed, there is no current consensus regarding which is the best tool to use and under what circumstances. QoL in patients with MS is determined by several factors beyond the more obvious; these include coping with the MS diagnosis, understanding the disease and the disease process, dealing with so-called 'hidden' symptoms such as fatigue, cognitive impairment and sexual disturbances, and managing the many associated personal challenges such as social isolation, family issues and working difficulties. Evidence is emerging that psychological interventions may be beneficial in MS patients although more research is required to confirm their utility. This article examines some factors that influence QoL in MS patients which may be overlooked in the general busyness of routine clinical practice. PMID:26374511

  9. Associations between the big five personality factors and multiple mini-interviews.

    PubMed

    Griffin, B; Wilson, I

    2012-08-01

    Given the accumulating evidence that performance in medical school and beyond is related to personality, it is important for research to consider how personality assessment can be included as part of the process of selecting medical students. Interviews are one way of measuring personality and this study extends prior research investigating whether the multiple mini interview (MMI) is related to the five factor model of personality. In contrast to prior results (Kulasegaram et al. in Adv Health Sci Edu 15:415-423, 2010), examination of MMI scores for 868 applicants to an Australian medical school over 3 years showed significant uncorrected correlations every year with extraversion (.19, .19, .30) and conscientiousness (.20, .22, .25) and with agreeableness in 2 years (.17, .19). Investigation of personality at a facet-level revealed differing relationships with the MMI within the five factors of personality. MMI scores were also correlated in 2 years (.17, .22) with a situational judgment test of interpersonal understanding (UMAT Section 2) but were unrelated to tests of logical reasoning ability (UMAT Section 1), non-verbal reasoning (Section 3), or past academic performance (Higher School Certificate results). PMID:21751103

  10. Ethylene Response Factors Are Controlled by Multiple Harvesting Stresses in Hevea brasiliensis.

    PubMed

    Putranto, Riza-Arief; Duan, Cuifang; Kuswanhadi; Chaidamsari, Tetty; Rio, Maryannick; Piyatrakul, Piyanuch; Herlinawati, Eva; Pirrello, Julien; Dessailly, Florence; Leclercq, Julie; Bonnot, François; Tang, Chaorong; Hu, Songnian; Montoro, Pascal

    2015-01-01

    Tolerance of recurrent mechanical wounding and exogenous ethylene is a feature of the rubber tree. Latex harvesting involves tapping of the tree bark and ethephon is applied to increase latex flow. Ethylene is an essential element in controlling latex production. The ethylene signalling pathway leads to the activation of Ethylene Response Factor (ERF) transcription factors. This family has been identified in Hevea brasiliensis. This study set out to understand the regulation of ERF genes during latex harvesting in relation to abiotic stress and hormonal treatments. Analyses of the relative transcript abundance were carried out for 35 HbERF genes in latex, in bark from mature trees and in leaves from juvenile plants under multiple abiotic stresses. Twenty-one HbERF genes were regulated by harvesting stress in laticifers, revealing an overrepresentation of genes in group IX. Transcripts of three HbERF-IX genes from HbERF-IXc4, HbERF-IXc5 and HbERF-IXc6 were dramatically accumulated by combining wounding, methyl jasmonate and ethylene treatments. When an ethylene inhibitor was used, the transcript accumulation for these three genes was halted, showing ethylene-dependent induction. Subcellular localization and transactivation experiments confirmed that several members of HbERF-IX are activator-type transcription factors. This study suggested that latex harvesting induces mechanisms developed for the response to abiotic stress. These mechanisms probably depend on various hormonal signalling pathways. Several members of HbERF-IX could be essential integrators of complex hormonal signalling pathways in Hevea. PMID:25906196

  11. Distribution Patterns of Infection with Multiple Types of Human Papillomaviruses and Their Association with Risk Factors

    PubMed Central

    Soto-De Leon, Sara; Camargo, Milena; Sanchez, Ricardo; Munoz, Marina; Perez-Prados, Antonio; Purroy, Antonio; Patarroyo, Manuel Elkin; Patarroyo, Manuel Alfonso

    2011-01-01

    Background Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. Principal Findings The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (−31.1%), or were of mestizo (−24.6%) or black (−40.9%) ethnicity. Conclusions According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2–4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies. PMID:21379574

  12. Regulation of complement factor H (CFH) by multiple miRNAs in Alzheimer's disease (AD) brain.

    PubMed

    Lukiw, Walter J; Alexandrov, Peter N

    2012-08-01

    Human brain cells rely on a specific subset of microRNAs (miRNAs or miRs) to shape their gene expression patterns, and this is mediated through microRNA effects on messenger RNA (mRNA) speciation and complexity. In recent studies (a) in short post-mortem interval Alzheimer's disease (AD) brain tissues versus age-matched controls, and (b) in pro-inflammatory cytokine- and Aβ42 peptide-stressed human neuronal-glial (HNG) cells in primary culture, we have identified several brain-abundant miRNA species found to be significantly up-regulated, including miR-125b and miR-146a. Both of these nuclear factor kappa B (NF-κB)-activated, 22 nucleotide small non-coding RNAs (sncRNAs) target the mRNA of the key, innate-immune- and inflammation-related regulatory protein, complement factor-H (CFH; chr 1q32), resulting in significant decreases in CFH expression (p < 0.01, ANOVA). Our results further indicate that HNG cells respond to IL-1β + Aβ42-peptide-induced stress by significant NF-κB-modulated up-regulation of miRNA-125b- and miRNA-146a. The complex interactive signaling of NF-κB, miR-125b, miR-146a, and perhaps other miRNAs, further illustrate interplay between inducible transcription factors and multiple pro-inflammatory sncRNAs that regulate CFH expression. The novel concept of miRNA actions involving mRNA target convergence and divergence are proposed and discussed. The combinatorial use of NF-кB inhibitors with anti-miRNAs (AMs; antagomirs) may have potential against CFH-driven pathogenic signaling in neurodegenerative disease, and may redirect our therapeutic perspectives to novel treatment strategies that have not yet been considered. PMID:22302353

  13. Multiple factors affect a population of Agassiz's desert tortoise (Gopherus agassizii) in the Northwestern Mojave Desert

    USGS Publications Warehouse

    Berry, Kristin H.; Yee, Julie L.; Coble, Ashley A.; Perry, William M.; Shields, Timothy A.

    2013-01-01

    Numerous factors have contributed to declines in populations of the federally threatened Agassiz's Desert Tortoise (Gopherus agassizii) and continue to limit recovery. In 2010, we surveyed a low-density population on a military test facility in the northwestern Mojave Desert of California, USA, to evaluate population status and identify potential factors contributing to distribution and low densities. Estimated densities of live tortoises ranged spatially from 1.2/km2 to 15.1/km2. Although only one death of a breeding-age tortoise was recorded for the 4-yr period prior to the survey, remains of 16 juvenile and immature tortoises were found, and most showed signs of predation by Common Ravens (Corvus corax) and mammals. Predation may have limited recruitment of young tortoises into the adult size classes. To evaluate the relative importance of different types of impacts to tortoises, we developed predictive models for spatially explicit densities of tortoise sign and live tortoises using topography (i.e., slope), predators (Common Raven, signs of mammalian predators), and anthropogenic impacts (distances from paved road and denuded areas, density of ordnance fragments) as covariates. Models suggest that densities of tortoise sign increased with slope and signs of mammalian predators and decreased with Common Ravens, while also varying based on interaction effects involving these predictors as well as distances from paved roads, denuded areas, and ordnance. Similarly, densities of live tortoises varied by interaction effects among distances to denuded areas and paved roads, density of ordnance fragments, and slope. Thus multiple factors predict the densities and distribution of this population.

  14. Factors influencing long-term outcomes in relapsing–remitting multiple sclerosis: PRISMS-15

    PubMed Central

    Kappos, Ludwig; Kuhle, Jens; Multanen, Juha; Kremenchutzky, Marcelo; Verdun di Cantogno, Elisabetta; Cornelisse, Peter; Lehr, Lorenz; Casset-Semanaz, Florence; Issard, Delphine; Uitdehaag, Bernard M J

    2015-01-01

    Aim An exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) β-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing–remitting multiple sclerosis (RRMS). Methods Patients in the original PRISMS study were invited to a single follow-up visit 15 years after initial randomisation (PRISMS-15). Outcomes over 15 years were compared in the lowest and highest quartile of the cumulative sc IFN β-1a dose groups, and according to total time receiving sc IFN β-1a as a continuous variable per 5 years of treatment. Potential prognostic factors for outcomes were analysed. Results Of 560 patients randomised in PRISMS, 291 returned for PRISMS-15 and 290 (51.8%) were analysed. Higher cumulative dose exposure and longer treatment time appeared to be associated with better outcomes on: annualised relapse rate, number of relapses, time to Expanded Disability Status Scale (EDSS) progression, change in EDSS, proportions of patients with EDSS ≥4 or ≥6, ≤5 relapses and EDSS <4 or <6, and time to conversion to secondary-progressive MS (SPMS). Higher dose exposure was associated with lower proportions of patients with EDSS progression and conversion to SPMS, and longer time on treatment with lower risk of first relapse. Change in EDSS from baseline to 24 months was a strong predictor of evaluated clinical outcomes over 15 years. Conclusions These findings suggest that higher cumulative exposure to sc IFN β-1a may be associated with better clinical outcomes, and early change in EDSS score may have prognostic value, over many years, in RRMS. PMID:26374702

  15. Multiple phosphorylation events control chicken ovalbumin upstream promoter transcription factor I orphan nuclear receptor activity.

    PubMed

    Gay, Frédérique; Baráth, Peter; Desbois-Le Péron, Christine; Métivier, Raphaël; Le Guével, Rémy; Birse, Darcy; Salbert, Gilles

    2002-06-01

    Chicken ovalbumin upstream promoter transcription factor I (COUP-TFI) is an orphan member of the nuclear hormone receptor superfamily that comprises key regulators of many biological functions, such as embryonic development, metabolism, homeostasis, and reproduction. Although COUP-TFI can both actively silence gene transcription and antagonize the functions of various other nuclear receptors, the COUP-TFI orphan receptor also acts as a transcriptional activator in certain contexts. Moreover, COUP-TFI has recently been shown to serve as an accessory factor for some ligand-bound nuclear receptors, suggesting that it may modulate, both negatively and positively, a wide range of hormonal responses. In the absence of any identified cognate ligand, the mechanisms involved in the regulation of COUP-TFI activity remain unclear. The elucidation of several putative phosphorylation sites for MAPKs, PKC, and casein kinase II within the sequence of this orphan receptor led us to investigate phosphorylation events regulating the various COUP-TFI functions. After showing that COUP-TFI is phosphorylated in vivo, we provide evidence that in vivo inhibition of either MAPK or PKC signaling pathway leads to a specific and pronounced decrease in COUP-TFI-dependent transcriptional activation of the vitronectin gene promoter. Focusing on the molecular mechanisms underlying the MAPK- and PKC-mediated regulation of COUP-TFI activity, we show that COUP-TFI can be directly targeted by PKC and MAPK. These phosphorylation events differentially modulate COUP-TFI functions: PKC-mediated phosphorylation enhances COUP-TFI affinity for DNA and MAPK-mediated phosphorylation positively regulates the transactivation function of COUP-TFI, possibly through enhancing specific coactivator recruitment. These data provide evidence that COUP-TFI is likely to integrate distinct signaling pathways and raise the possibility that multiple extracellular signals influence biological processes controlled by COUP

  16. Smouldering retinopathy of prematurity: a case treated by multiple antivascular endothelial growth factor therapy.

    PubMed

    Balakrishnan, Divya; Ambiya, Vikas; Jalali, Subhadra; Rani, Padmaja Kumari

    2016-01-01

    A 13 months old female baby born at 24 weeks of gestational age (GA) presented with stage 4A retinopathy of prematurity (ROP) with plus disease in the right eye and stage 3 with plus disease in the left eye. The baby was diagnosed with stage 3 zone 2 ROP in both eyes with plus disease at 32 weeks of GA and received intravitreal bevacizumab in both eyes. The baby received intravitreal bevacizumab and ranibizumab injections at 39 and 57 weeks of postmenstrual age (PMA), respectively for recurrence. Laser treatment to peripheral avascular retina was carried out at 67 weeks of PMA. The right eye progressed to stage 4A and left eye developed pre-retinal haemorrhages. This case reports late recurrence treated with initial multiple antivascular endothelial growth factor (VEGF) injections alone. One should be cautious in using anti-VEGF agents as a monotherapy in cases of ROP that appear different from the current understanding of the natural course of the disease. PMID:27571916

  17. The Autographa californica multiple nucleopolyhedrovirus ac110 gene encodes a new per os infectivity factor.

    PubMed

    Jiantao Liu; Zhu, Leyuan; Zhang, Shan; Deng, Zihao; Huang, Zhihong; Yuan, Meijin; Wu, Wenbi; Yang, Kai

    2016-08-01

    The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac110 gene is especially conserved in lepidopteran-specific baculoviruses and is uncharacterized. To investigate the role of ac110 in the baculovirus life cycle, an ac110-knockout (vAc110KO) and a repair (vAc110:HA) viruses were constructed in this study. Budded virion production and occlusion body formation were unaffected in vAc110KO-transfected or infected Sf9 cells. Intrahemocoelic injection of budded virions of vAc110KO killed Trichoplusia ni larvae as efficiently as the repair or the wild-type viruses. However, per os inoculation of occlusion bodies of vAc110KO failed to establish infection in T. ni larvae, while the repair virus was as efficient as the wild-type virus. Treatment with calcofluor white, a reagent that damages the peritrophic membrane, did not rescue the oral infectivity of vAc110KO. These results suggested that Ac110 is a new per os infectivity factor that may play a role after occlusion-derived virions pass through the peritrophic membrane during oral infection. PMID:27212681

  18. Multiple Signaling Pathways of the Insulin-Like Growth Factor 1 Receptor in Protection from Apoptosis

    PubMed Central

    Peruzzi, Francesca; Prisco, Marco; Dews, Michael; Salomoni, Paolo; Grassilli, Emanuela; Romano, Gaetano; Calabretta, Bruno; Baserga, Renato

    1999-01-01

    The type 1 insulin-like growth factor receptor (IGF-1R), activated by its ligands, protects several cell types from a variety of apoptotic injuries. The main signaling pathway for IGF-1R-mediated protection from apoptosis has been previously elucidated and rests on the activation of phosphatidylinositol 3-kinase, Akt/protein kinase B, and the phosphorylation and inactivation of BAD, a member of the Bcl-2 family of proteins. In 32D cells (a murine hemopoietic cell line devoid of insulin receptor substrate 1 [IRS-1]), the IGF-1R activates alternative pathways for protection from apoptosis induced by withdrawal of interleukin-3. One of these pathways leads to the activation of mitogen-activated protein kinase, while a third pathway results in the mitochondrial translocation of Raf and depends on the integrity of a group of serines in the C terminus of the receptor that are known to interact with 14.3.3 proteins. All three pathways, however, result in BAD phosphorylation. The presence of multiple antiapoptotic pathways may explain the remarkable efficacy of the IGF-1R in protecting cells from apoptosis. PMID:10490655

  19. [Children with Multiple Risk Factor Exposition Benefit from the German "Strengthening Families Program"].

    PubMed

    Bröning, Sonja; Sack, Peter-Michael; Thomsen, Monika; Thomasius, Rainer

    2016-09-01

    Children with Multiple Risk Factor Exposition Benefit from the German "Strengthening Families Program" The German adaptation of the substance use-preventive family-based Strengthening Families Program 10-14 (SFP, Iowa version) was evaluated in a longitudinal two-year follow-up trial. Participants were N = 292 children with a mean age of twelve years at baseline, and N = 292 parents. We employed a multi-centric, randomized-controlled, two-armed (SFP vs. minimal control condition) study design. Following a "risk moderation hypothesis", we assumed that children with an elevated risk-exposition R(+) would benefit more than children with a low risk-exposition R(-) irrespective of the preventive intervention, and that R(+) under SFP would benefit more than R(+) under the minimal control condition. "Risk-exposition" was measured in correspondence with the Communities That Care Youth Survey-questionnaire. A total of 28 % of children were classified with an elevated risk level. Children's reports confirmed our hypothesis: R(+) report a total of eleven improvements, four of these being significantly more distinct than in the other groups (Anxiety-Depressivity, Punitive Parenting of mother, Punitive Parenting of father, Unbalanced family functioning). In three measures an improvement appears solely in R(+) under SFP (Satisfaction with family functioning, School Attachment and Peer Relationship Quality, Quality of Life). Parents' reports showed a similar tendency, but were less pronounced. PMID:27595812

  20. Multiple interdependent sequence elements control splicing of a fibroblast growth factor receptor 2 alternative exon.

    PubMed Central

    Del Gatto, F; Plet, A; Gesnel, M C; Fort, C; Breathnach, R

    1997-01-01

    The fibroblast growth factor receptor 2 gene contains a pair of mutually exclusive alternative exons, one of which (K-SAM) is spliced specifically in epithelial cells. We have described previously (F. Del Gatto and R. Breathnach, Mol. Cell. Biol. 15:4825-4834, 1995) some elements controlling K-SAM exon splicing, namely weak exon splice sites, an exon-repressing sequence, and an intron-activating sequence. We identify here two additional sequences in the intron downstream from the K-SAM exon which activate splicing of the exon. The first sequence (intron-activating sequence 2 [IAS2]) lies 168 to 186 nucleotides downstream from the exon's 5' splice site. The second sequence (intron-activating sequence 3 [IAS3]) lies 933 to 1,052 nucleotides downstream from the exon's 5' splice site. IAS3 is a complex region composed of several parts, one of which (nucleotides 963 to 983) can potentially form an RNA secondary structure with IAS2. This structure is composed of two stems separated by an asymmetric bulge. Mutations which disrupt either stem decrease activation, while compensatory mutations which reestablish the stem restore activation, either completely or partially, depending on the mutation. We present a model for K-SAM exon splicing involving the intervention of multiple, interdependent pre-mRNA sequence elements. PMID:9271388

  1. Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting

    PubMed Central

    Zhu, Yuanjun; Li, Ruyi; Lin, Yuan; Shui, Mengyang; Liu, Xiaoyan; Chen, Huan; Wang, Yinye

    2016-01-01

    Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency. PMID:27432161

  2. Discovery of Enhancers of the Secretion of Leukemia Inhibitory Factor for the Treatment of Multiple Sclerosis.

    PubMed

    Vela, Laura; Caballero, Iván; Fang, Leiping; Liu, Qin; Ramón, Fernando; Díez, Emilio; de Los Frailes, Maite

    2016-06-01

    Multiple sclerosis (MS) is an autoimmune neurodegenerative disease that involves activation of T cells, microglia, and astrocytes. There is a clear unmet medical need for MS, as current therapies reduce the relapse rate, but are unable to prevent the neurological deterioration. Leukemia inhibitory factor (LIF) is a proinflammatory cytokine that can also positively modulate the immune response, by inducing the inhibition of myelin-reactive TH17 differentiation, and by promoting oligodendrocyte-mediated myelination. The aim of this project was to find central nervous system (CNS)-permeable and orally available small molecules that upregulate production of endogenous LIF. We describe here the development of a phenotypic assay and screening of 1.7 million compounds to identify LIF enhancers using U87 MG cells. Five chemically tractable series of compounds and a few singletons were selected for further progression. Some of them were also active in a different LIF-expressing cell line and in primary rat astrocytes. Although further studies would be required to deconvolute the targets involved in LIF induction and to confirm activity of hits in more disease-relevant assays, our results have demonstrated the potential of the phenotypic approach to identify specific and chemically tractable small molecules that trigger the production of LIF in relevant cell lines. PMID:26984928

  3. Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor.

    PubMed

    Anandhakumar, Jayamani; Moustafa, Yara W; Chowdhary, Surabhi; Kainth, Amoldeep S; Gross, David S

    2016-07-15

    Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the "anchor away" (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. PMID:27185874

  4. Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting.

    PubMed

    Zhu, Yuanjun; Li, Ruyi; Lin, Yuan; Shui, Mengyang; Liu, Xiaoyan; Chen, Huan; Wang, Yinye

    2016-01-01

    Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency. PMID:27432161

  5. Multiple post-translational modifications in hepatocyte nuclear factor 4{alpha}

    SciTech Connect

    Yokoyama, Atsushi; Katsura, Shogo; Ito, Ryo; Hashiba, Waka; Sekine, Hiroki; Fujiki, Ryoji; Kato, Shigeaki

    2011-07-15

    Highlights: {yields} We performed comprehensive PTM analysis for HNF4{alpha} protein. {yields} We identified 8 PTMs in HNF4{alpha} protein including newly identified PTMs. {yields} Among them, we found acetylation at lysine 458 was one of the prime PTMs for HNF4{alpha} function. {yields} Acetylation at lysine 458 was inhibitory for HNF4{alpha} transcription function. {yields} This modification fluctuated in response to extracellular condition. -- Abstract: To investigate the role of post-translational modifications (PTMs) in the hepatocyte nuclear factor 4{alpha} (HNF4{alpha})-mediated transcription, we took a comprehensive survey of PTMs in HNF4{alpha} protein by massspectrometry and identified totally 8 PTM sites including newly identified ubiquitilation and acetylation sites. To assess the impact of identified PTMs in HNF4{alpha}-function, we introduced point mutations at the identified PTM sites and, tested transcriptional activity of the HNF4{alpha}. Among the point-mutations, an acetylation site at lysine 458 was found significant in the HNF4{alpha}-mediated transcriptional control. An acetylation negative mutant at lysine 458 showed an increased transcriptional activity by about 2-fold, while an acetylation mimic mutant had a lowered transcriptional activation. Furthermore, this acetylation appeared to be fluctuated in response to extracellular nutrient conditions. Thus, by applying an comprehensive analysis of PTMs, multiple PTMs were newly identified in HNF4{alpha} and unexpected role of an HNF4{alpha} acetylation could be uncovered.

  6. Rgg influences the expression of multiple regulatory loci to coregulate virulence factor expression in Streptococcus pyogenes.

    PubMed

    Chaussee, Michael S; Sylva, Gail L; Sturdevant, Daniel E; Smoot, Laura M; Graham, Morag R; Watson, Robert O; Musser, James M

    2002-02-01

    The human pathogen Streptococcus pyogenes secretes many proteins to the cell wall and extracellular environment that contribute to virulence. Rgg regulates the expression of several exoproteins including a cysteine protease (SPE B), a nuclease (MF-1), a putative nuclease (MF-3), and autolysin. The functional heterogeneity of Rgg-regulated exoproteins and the lack of a conserved regulatory motif in the promoter regions of the genes suggested that Rgg interacts with additional regulatory networks to influence gene expression. DNA microarrays were used to test this hypothesis by comparing genomewide transcript profiles of S. pyogenes NZ131 and isogenic derivative NZ131 rgg during the exponential phase of growth. Transcripts of known and putative virulence-associated genes were more abundant in the rgg mutant, including emm, scpA, orfX, scl1, hasAB, slo, sagA, ska, speH, grab, mac, mf-1, and mf-3. Increased transcription of emm, scpA, and orfX in the rgg mutant was associated with increased production of the corresponding proteins. Differences in the expression of virulence-associated genes were associated with changes in the expression of several regulatory genes, including mga, sagA, csrRS, and fasBCA. The results show that Rgg influences the expression of multiple regulatory networks to coregulate virulence factor expression in S. pyogenes. PMID:11796609

  7. Multiplication factor for open ground storey buildings-a reliability based evaluation

    NASA Astrophysics Data System (ADS)

    Haran Pragalath, D. C.; Avadhoot, Bhosale; Robin, Davis P.; Pradip, Sarkar

    2016-06-01

    Open Ground Storey (OGS) framed buildings where the ground storey is kept open without infill walls, mainly to facilitate parking, is increasing commonly in urban areas. However, vulnerability of this type of buildings has been exposed in past earthquakes. OGS buildings are conventionally designed by a bare frame analysis that ignores the stiffness of the infill walls present in the upper storeys, but doing so underestimates the inter-storey drift (ISD) and thereby the force demand in the ground storey columns. Therefore, a multiplication factor (MF) is introduced in various international codes to estimate the design forces (bending moments and shear forces) in the ground storey columns. This study focuses on the seismic performance of typical OGS buildings designed by means of MFs. The probabilistic seismic demand models, fragility curves, reliability and cost indices for various frame models including bare frames and fully infilled frames are developed. It is found that the MF scheme suggested by the Israel code is better than other international codes in terms of reliability and cost.

  8. [Brain-derived and ciliary neurotrophic factors in patients with multiple sclerosis].

    PubMed

    Trushnikova, T N; Medvedeva, E L; Baĭdina, T V; Danilova, M A

    2014-01-01

    Objective. To study serum concentrations of BDNF and CNTF in patients with multiple sclerosis (MS) and compare them to clinical characteristics of MS. Material and methods. We examined 43 patients with confirmed diagnosis of MS according to McDonald's criteria with remitting type of disease course. Patients were in a stable condition and did not receive hormone treatment during the last 30 days. Serum concentrations of BDNF and CNTF were measured using ELISA. Results. Mean serum BDNF concentration was 7.9 (5.21; 14.7) ng/ml that was significantly lower (p=0.0001) compared to control values and was correlated with depression severity (r= -0.31, p=0.04) and physical asthenia (r= -0.32, p=0.04). CNTF concentration was 69.9 (31.2; 123.3) pg/ml (CNTF was not found in healthy people) and was correlated with the results of cognitive function assessment (the PASAT test) (r= -0.30, p=0.046). Conclusion. The difference in BDNF and CNTF serum concentrations between MS patients and healthy people and correlations with some clinical characteristics of MS provide evidence for the involvement of these factors in MS pathogenesis. PMID:25591532

  9. Scattering from phase-separated vesicles. I. An analytical form factor for multiple static domains

    DOE PAGESBeta

    Heberle, Frederick A.; Anghel, Vinicius N. P.; Katsaras, John

    2015-08-18

    This is the first in a series of studies considering elastic scattering from laterally heterogeneous lipid vesicles containing multiple domains. Unique among biophysical tools, small-angle neutron scattering can in principle give detailed information about the size, shape and spatial arrangement of domains. A general theory for scattering from laterally heterogeneous vesicles is presented, and the analytical form factor for static domains with arbitrary spatial configuration is derived, including a simplification for uniformly sized round domains. The validity of the model, including series truncation effects, is assessed by comparison with simulated data obtained from a Monte Carlo method. Several aspects ofmore » the analytical solution for scattering intensity are discussed in the context of small-angle neutron scattering data, including the effect of varying domain size and number, as well as solvent contrast. Finally, the analysis indicates that effects of domain formation are most pronounced when the vesicle's average scattering length density matches that of the surrounding solvent.« less

  10. Causes of Death and Prognostic Factors in Multiple Endocrine Neoplasia Type 1: A Prospective Study

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato; Uehara, Hirotsugu; Berna, Marc J.; Jensen, Robert T.

    2013-01-01

    Abstract Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking. To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%–14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled

  11. Bax: Addressed to kill.

    PubMed

    Renault, Thibaud T; Manon, Stéphen

    2011-09-01

    The pro-apoptototic protein Bax (Bcl-2 Associated protein X) plays a central role in the mitochondria-dependent apoptotic pathway. In healthy mammalian cells, Bax is essentially cytosolic and inactive. Following a death signal, the protein is translocated to the outer mitochondrial membrane, where it promotes a permeabilization that favors the release of different apoptogenic factors, such as cytochrome c. The regulation of Bax translocation is associated to conformational changes that are under the control of different factors. The evidences showing the involvement of different Bax domains in its mitochondrial localization are presented. The interactions between Bax and its different partners are described in relation to their ability to promote (or prevent) Bax conformational changes leading to mitochondrial addressing and to the acquisition of the capacity to permeabilize the outer mitochondrial membrane. PMID:21641962

  12. [Single-donor protocol: Transfusion practices and multiple transfusion risk factors in neonatal intensive care unit].

    PubMed

    Dollat, C; Pierron, C; Keslick, A; Billoir, E; François, A; Jarreau, P-H

    2016-09-01

    In France since 2002, the single-donor transfusion protocol, using four pediatric units from the same adult donor's packed red blood cells (PRBCs) in multiply transfused newborns, is recommended in preterm neonates to reduce the risks of infection and alloimmunization. This protocol is controversial, however, because it causes the transfusion of stored blood, which could have adverse consequences. Before the new recommendations of the French Haute Autorité de santé (National authority for health) in 2015, we conducted a national practice survey in 63 neonatal intensive care units (NICU) and a retrospective study of the characteristics of 103 children transfused within our unit, to better target beneficiaries. The practice survey showed that 30 % of French NICUs no longer used the protocol in 2014, due to logistical or financial problems, or concerns about the transfusion of stored blood. The practices were heterogeneous. Few NICUs used a written protocol. In our NICU, the use of single-donor protocol involved the use of units stored for more than 20 days in half of the cases beginning with the third unit used. Six-term newborns were mainly transfused once, which does not seem to warrant the single-donor transfusion protocol. The use of this protocol caused the loss of 50 % of the manufactured units, which go unused. In multivariate analysis, two factors were predictive of multiple transfusion within our population of 95 premature neonates undergoing transfusion: low-term and a high Clinical Risk Index for Babies (CRIB) score. The risk of multiple transfusions would be reduced by about 15 % for each additional week of gestation and approximately 16 % per point within the CRIB score. These variables integrated into a statistical model predict the risk of multiplying transfusions. According to the ROC curve, a calculated risk higher than 50 % is the appropriate cut-off value to transfuse with the single-donor transfusion protocol. This would limit its

  13. A structure-based Multiple-Instance Learning approach to predicting in vitro transcription factor-DNA interaction

    PubMed Central

    2015-01-01

    Background Understanding the mechanism of transcriptional regulation remains an inspiring stage of molecular biology. Recently, in vitro protein-binding microarray experiments have greatly improved the understanding of transcription factor-DNA interaction. We present a method - MIL3D - which predicts in vitro transcription factor binding by multiple-instance learning with structural properties of DNA. Results Evaluation on in vitro data of twenty mouse transcription factors shows that our method outperforms a method based on simple-instance learning with DNA structural properties, and the widely used k-mer counting method, for nineteen out of twenty of the transcription factors. Our analysis showed that the MIL3D approach can utilize subtle structural similarities when a strong sequence consensus is not available. Conclusion Combining multiple-instance learning and structural properties of DNA has promising potential for studying biological regulatory networks. PMID:25917392

  14. Endothelial dysfunction and progressive coronary atherosclerosis: sequential invasive studies in a patient with multiple cardiac risk factors.

    PubMed

    Chander, R; Kuhner, P A; Laws Houghton, J

    2001-08-01

    This manuscript describes sequential angiographic, endothelial and vasoreactivity characteristics of the coronary arterial circulation in a middle-aged patient with multiple cardiac risk factors who developed hemodynamically significant coronary atherosclerosis over a 6-year period. A 56-year-old woman demonstrated marked angiographic progression of coronary atherosclerosis over time beginning with minor luminal irregularities in the setting of severe endothelial dysfunction. The association of endothelial dysfunction, ineffective cardiac risk factor management and progressive atherosclerosis is discussed. PMID:11481511

  15. Renin-angiotensin system gene polymorphisms as risk factors for multiple sclerosis.

    PubMed

    Živković, Maja; Kolaković, Ana; Stojković, Ljiljana; Dinčić, Evica; Kostić, Smiljana; Alavantić, Dragan; Stanković, Aleksandra

    2016-04-15

    The components of renin-angiotensin system, such as angiotensin-converting enzyme (ACE), angiotensin II and angiotensin II receptor type 1 and 2 (AT1R and AT2R), are expressed in the central nervous system and leukocytes and proposed to be involved in the inflammation and pathogenesis of multiple sclerosis (MS). ACE I/D, AT1R 1166A/C and AT2R -1332A/G are functional polymorphisms associated with phenotypes of diverse chronic inflammatory diseases. The aim of this study was to investigate the association between ACE I/D, AT1R 1166A/C and AT2R -1332A/G gene polymorphisms and MS in Serbian population. A total of 470 MS patients and 478 controls participated in the study. Allele-specific polymerase chain reaction (PCR) was performed for genotyping of the ACE polymorphism. The AT1R and AT2R genotyping was done by duplex PCR and restriction fragment length polymorphism analysis. Both ACE homozygotes, II and DD, were significantly overrepresented in MS patients, compared to controls (χ(2) test p=0.03). Neither genotype nor allele frequencies of AT1R 1166A/C polymorphism were significantly different between patients and controls. Significant overrepresentation of AT2R -1332 AA genotype in female patients, compared to female controls, was detected (OR=1.67, 95%CI=1.13-2.49, χ(2) test p=0.01), suggesting that this genotype could be a gender-specific genetic risk factor for MS. PMID:27000216

  16. Decreased Endothelin-1 Plasma Levels in Multiple Sclerosis Patients: A Possible Factor of Vascular Dysregulation?

    PubMed Central

    Jankowska-Lech, Irmina; Terelak-Borys, Barbara; Grabska-Liberek, Iwona; Palasik, Witold; Bik, Wojciech; Wolińska-Witort, Ewa

    2015-01-01

    Background Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system with possible involvement of vascular dysregulation secondary to endothelial dysfunction caused by destruction of the vessel wall. Vascular dysregulation leads to excessive vasoconstriction or insufficient vasodilatation, resulting in vasospasm mediated by endothelin-1 (ET-1), the most potent and long-lasting mediator. Vascular dysregulation can play an important role in the pathogenesis of some eye disorders and it has been hypothesized that it is a vascular risk factor for glaucomatous optic neuropathy. The aim of this study was to estimate endothelin-1 (ET-1) plasma levels in patients with MS. Material/Methods The MS group consisted of 39 patients (9 males, 30 females), mean age: 38.8±10.02 years, range: 22–62. The control group consisted of 27 healthy volunteers (3 males and 24 females), mean age: 37.4±10.88 years, range: 20–62; clinically, in a non-active stage of the disease. ET-1 plasma levels were measured using the Endothelin-1 ELISA Kit (Immuno-Biological Laboratories Co., Japan). Statistical analysis was performed with the nonparametric Mann-Whitney U test for independent groups. Results Endothelin-1 (ET-1) plasma levels were significantly lower in MS patients compared to healthy controls: mean value 0.55±0.44 pg/ml (146.05±118.27 fmol/ml) vs. 0.95±0.48 pg/ml (252.83±127.16 fmol/ml); P=0.012. Conclusions Significantly decreased ET-1 plasma levels in the MS patients could reflect the non-active disease at the time of ET-1 measurements or the effects of immunomodulatory treatment, but it cannot be excluded that decreased ET-1 plasma levels in these patients might result from vascular dysregulation. PMID:25864450

  17. Global effect of indole-3-acetic acid biosynthesis on multiple virulence factors of Erwinia chrysanthemi 3937.

    PubMed

    Yang, Shihui; Zhang, Qiu; Guo, Jianhua; Charkowski, Amy O; Glick, Bernard R; Ibekwe, A Mark; Cooksey, Donald A; Yang, Ching-Hong

    2007-02-01

    Production of the plant hormone indole-3-acetic acid (IAA) is widespread among plant-associated microorganisms. The non-gall-forming phytopathogen Erwinia chrysanthemi 3937 (strain Ech3937) possesses iaaM (ASAP16562) and iaaH (ASAP16563) gene homologues. In this work, the null knockout iaaM mutant strain Ech138 was constructed. The IAA production by Ech138 was reduced in M9 minimal medium supplemented with l-tryptophan. Compared with wild-type Ech3937, Ech138 exhibited reduced ability to produce local maceration, but its multiplication in Saintpaulia ionantha was unaffected. The pectate lyase production of Ech138 was diminished. Compared with wild-type Ech3937, the expression levels of an oligogalacturonate lyase gene, ogl, and three endopectate lyase genes, pelD, pelI, and pelL, were reduced in Ech138 as determined by a green fluorescent protein-based fluorescence-activated cell sorting promoter activity assay. In addition, the transcription of type III secretion system (T3SS) genes, dspE (a putative T3SS effector) and hrpN (T3SS harpin), was found to be diminished in the iaaM mutant Ech138. Compared with Ech3937, reduced expression of hrpL (a T3SS alternative sigma factor) and gacA but increased expression of rsmA in Ech138 was also observed, suggesting that the regulation of T3SS and pectate lyase genes by IAA biosynthesis might be partially due to the posttranscriptional regulation of the Gac-Rsm regulatory pathway. PMID:17189441

  18. Multiple Immune Factors Are Involved in Controlling Acute and Chronic Chikungunya Virus Infection

    PubMed Central

    Poo, Yee Suan; Rudd, Penny A.; Gardner, Joy; Wilson, Jane A. C.; Larcher, Thibaut; Colle, Marie-Anne; Le, Thuy T.; Nakaya, Helder I.; Warrilow, David; Allcock, Richard; Bielefeldt-Ohmann, Helle; Schroder, Wayne A.; Khromykh, Alexander A.; Lopez, José A.; Suhrbier, Andreas

    2014-01-01

    The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA) in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells) in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection) was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA. PMID:25474568

  19. Resource factors for mental health resilience in early childhood: An analysis with multiple methodologies

    PubMed Central

    2013-01-01

    Background Given that relatively little is known about the development of resilience in early childhood, this longitudinal study aimed to identify preschool resource factors associated with young children’s mental health resilience to family adversity. Methods A community sample of 474 young Australian children was assessed in preschool (mean age 4.59 years, 49% male), and again two years later after their transition into formal schooling. At each assessment, standard questionnaires were used to obtain ratings from both parents and teachers about the quality of children’s relationships with parents and teachers, children’s self-concept and self-control, mental health (Strengths and Difficulties Questionnaire), and family adversities (including stressful life events and socioeconomic disadvantage). Results Greater exposure to cumulative family adversities was associated with both greater teacher- and parent-reported child mental health difficulties two years later. Multiple methodologies for operationalizing resilience were used to identify resources associated with resilient mental health outcomes. Higher quality child–parent and child-teacher relationships, and greater child self-concept and self-control were associated with resilient mental health outcomes. With the exception of child-teacher relationships, these resources were also prospective antecedents of subsequent resilient mental health outcomes in children with no pre-existing mental health difficulties. Child–parent relationships and child self-concept generally had promotive effects, being equally beneficial for children facing both low- and high-adversity. Child self-control demonstrated a small protective effect on teacher-reported outcomes, with greater self-control conferring greater protection to children under conditions of high-adversity. Conclusions Findings suggest that early intervention and prevention strategies that focus on fostering child-adult relationship quality, self

  20. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.

    PubMed

    Poo, Yee Suan; Rudd, Penny A; Gardner, Joy; Wilson, Jane A C; Larcher, Thibaut; Colle, Marie-Anne; Le, Thuy T; Nakaya, Helder I; Warrilow, David; Allcock, Richard; Bielefeldt-Ohmann, Helle; Schroder, Wayne A; Khromykh, Alexander A; Lopez, José A; Suhrbier, Andreas

    2014-12-01

    The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA) in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells) in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection) was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA. PMID:25474568

  1. Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells.

    PubMed

    Hideshima, Teru; Ikeda, Hiroshi; Chauhan, Dharminder; Okawa, Yutaka; Raje, Noopur; Podar, Klaus; Mitsiades, Constantine; Munshi, Nikhil C; Richardson, Paul G; Carrasco, Ruben D; Anderson, Kenneth C

    2009-07-30

    Bortezomib is a proteasome inhibitor with remarkable preclinical and clinical antitumor activity in multiple myeloma (MM) patients. The initial rationale for its use in MM was inhibition of nuclear factor (NF)-kappaB activity by blocking proteasomal degradation of inhibitor of kappaBalpha (IkappaBalpha). Bortezomib inhibits inducible NF-kappaB activity; however, its impact on constitutive NF-kappaB activity in MM cells has not yet been defined. In this study, we demonstrate that bortezomib significantly down-regulated IkappaBalpha expression and triggered NF-kappaB activation in MM cell lines and primary tumor cells from MM patients. Importantly, no inhibition of p65 (RelA) nuclear translocation was recognized after bortezomib treatment in a murine xenograft model bearing human MM cells. Bortezomib-induced NF-kappaB activation was mediated via the canonical pathway. Moreover, other classes of proteasome inhibitors also induced IkappaBalpha down-regulation associated with NF-kappaB activation. Molecular mechanisms whereby bortezomib induced IkappaBalpha down-regulation were further examined. Bortezomib triggered phosphorylation of IkappaB kinase (IKKbeta) and its upstream receptor-interacting protein 2, whereas IKKbeta inhibitor MLN120B blocked bortezomib-induced IkappaBalpha down-regulation and NF-kappaB activation, indicating receptor-interacting protein 2/IKKbeta signaling plays crucial role in bortezomib-induced NF-kappaB activation. Moreover, IKKbeta inhibitors enhanced bortezomib-induced cytotoxicity. Our studies therefore suggest that bortezomib-induced cytotoxicity cannot be fully attributed to inhibition of canonical NF-kappaB activity in MM cells. PMID:19436050

  2. Multiple-Group Confirmatory Factor Analysis in R--A Tutorial in Measurement Invariance with Continuous and Ordinal Indicators

    ERIC Educational Resources Information Center

    Hirschfeld, Gerrit; von Brachel, Ruth

    2014-01-01

    Multiple-group confirmatory factor analysis (MG-CFA) is among the most productive extensions of structural equation modeling. Many researchers conducting cross-cultural or longitudinal studies are interested in testing for measurement and structural invariance. The aim of the present paper is to provide a tutorial in MG-CFA using the freely…

  3. A Multiple Risk Factors Model of the Development of Aggression among Early Adolescents from Urban Disadvantaged Neighborhoods

    ERIC Educational Resources Information Center

    Kim, Sangwon; Orpinas, Pamela; Kamphaus, Randy; Kelder, Steven H.

    2011-01-01

    This study empirically derived a multiple risk factors model of the development of aggression among middle school students in urban, low-income neighborhoods, using Hierarchical Linear Modeling (HLM). Results indicated that aggression increased from sixth to eighth grade. Additionally, the influences of four risk domains (individual, family,…

  4. Risk factors for fecal colonization with multiple distinct strains of Escherichia coli among long-term care facility residents.

    PubMed

    Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N

    2009-05-01

    Of 49 long-term care facility residents, 21 (43%) were colonized with 2 or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest that future efforts to efficiently identify the diversity of colonizing strains will be challenging. PMID:19292660

  5. Physical and Cognitive-Affective Factors Associated with Fatigue in Individuals with Fibromyalgia: A Multiple Regression Analysis

    ERIC Educational Resources Information Center

    Muller, Veronica; Brooks, Jessica; Tu, Wei-Mo; Moser, Erin; Lo, Chu-Ling; Chan, Fong

    2015-01-01

    Purpose: The main objective of this study was to determine the extent to which physical and cognitive-affective factors are associated with fibromyalgia (FM) fatigue. Method: A quantitative descriptive design using correlation techniques and multiple regression analysis. The participants consisted of 302 members of the National Fibromyalgia &…

  6. Risk Factors for Fecal Colonization with Multiple Distinct Strains of Escherichia coli Among Long-Term Care Facility Residents

    PubMed Central

    Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N.

    2009-01-01

    Of 49 long-term care facility residents, 21 (43%) were colonized with two or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest future efforts to efficiently identify diversity of colonizing strains will be challenging. PMID:19292660

  7. Multiple Risk Factor Intervention in the Delivery of Primary Health Care to the Elderly: Lessons from Community-Based Programs.

    ERIC Educational Resources Information Center

    Kligman, Evan W.

    Within the past decade the role of the primary care physician caring for older patients has expanded to include counseling and "healthy aging" education to reduce multiple behavior risk factors. Project AGE WELL was a longitudinal study of the impact of a comprehensive and team delivered health promotion program on the health status of the…

  8. [Influence on the spatial distribution of fish in Taizi River basin by environmental factors at multiple scales].

    PubMed

    Ding, Sen; Zhang, Yuan; Qu, Xiao-Dong; Kong, Wei-Jing; Liu, Si-Si; Meng, Wei

    2012-07-01

    The deterioration of fish is influenced by various types of environmental factors. To develop protection plans that are more suitable, non-metric multidimensional scaling analysis (NMS) was used to investigate the influence of environmental factors at multiple scales on the spatial distribution of fish. The results of cluster analysis showed that there were three types of spatial distribution of fish, i.e. upstream timber and tributary headstream area, midstream hilly area, and downstream plain area. Results of NMS analysis indicated the significant correlations between spatial distribution of fish and environmental factors at multiple scales. Altitude, stream order and land use were three important factors influencing the fish distribution at the watershed scale. Combination of velocity and depth, habitat inhomogeneity and electrical conductivity significantly affected fish distribution at the reach scale, whereas the quality of bottom material showed significant influence at the microhabitat scale. Therefore, the effect of specific environmental factors at multiple scales should be taken into consideration in the basin fish conversation management. PMID:23002601

  9. Factors associated with the presence of multiple Lugol-voiding lesions in patients with esophageal squamous-cell carcinoma.

    PubMed

    Katada, C; Muto, M; Tanabe, S; Higuchi, K; Sasaki, T; Azuma, M; Ishido, K; Katada, N; Sakuramoto, S; Yamashita, K; Masaki, T; Nakayama, M; Okamoto, M; Koizumi, W

    2014-07-01

    Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol-voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence-specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84-122.45: P = 0.011), presence of the ALDH2-2 allele (OR 4.5, 95% CI 1.55-13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02-6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13-88.44: P = 0.038) and presence of the ALDH2-2 allele (OR 4.56, 95% CI 1.4-14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2-2 allele (OR 17.5, 95% CI 1.97-155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2-2 allele (OR 8.85, 95% CI 1.68-46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2-2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2-2 allele (OR 4.0, 95% CI 0.54-29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2-2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal

  10. Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9.

    PubMed

    Lindner, Maren; Thümmler, Katja; Arthur, Ariel; Brunner, Sarah; Elliott, Christina; McElroy, Daniel; Mohan, Hema; Williams, Anna; Edgar, Julia M; Schuh, Cornelia; Stadelmann, Christine; Barnett, Susan C; Lassmann, Hans; Mücklisch, Steve; Mudaliar, Manikhandan; Schaeren-Wiemers, Nicole; Meinl, Edgar; Linington, Christopher

    2015-07-01

    Remyelination failure plays an important role in the pathophysiology of multiple sclerosis, but the underlying cellular and molecular mechanisms remain poorly understood. We now report actively demyelinating lesions in patients with multiple sclerosis are associated with increased glial expression of fibroblast growth factor 9 (FGF9), which we demonstrate inhibits myelination and remyelination in vitro. This inhibitory activity is associated with the appearance of multi-branched 'pre-myelinating' MBP+ / PLP+ oligodendrocytes that interact with axons but fail to assemble myelin sheaths; an oligodendrocyte phenotype described previously in chronically demyelinated multiple sclerosis lesions. This inhibitory activity is not due to a direct effect of FGF9 on cells of the oligodendrocyte lineage but is mediated by factors secreted by astrocytes. Transcriptional profiling and functional validation studies demonstrate that these include effects dependent on increased expression of tissue inhibitor of metalloproteinase-sensitive proteases, enzymes more commonly associated with extracellular matrix remodelling. Further, we found that FGF9 induces expression of Ccl2 and Ccl7, two pro-inflammatory chemokines that contribute to recruitment of microglia and macrophages into multiple sclerosis lesions. These data indicate glial expression of FGF9 can initiate a complex astrocyte-dependent response that contributes to two distinct pathogenic pathways involved in the development of multiple sclerosis lesions. Namely, induction of a pro-inflammatory environment and failure of remyelination; a combination of effects predicted to exacerbate axonal injury and loss in patients. PMID:25907862

  11. Evaluating local indirect addressing in SIMD proc essors

    NASA Technical Reports Server (NTRS)

    Middleton, David; Tomboulian, Sherryl

    1989-01-01

    In the design of parallel computers, there exists a tradeoff between the number and power of individual processors. The single instruction stream, multiple data stream (SIMD) model of parallel computers lies at one extreme of the resulting spectrum. The available hardware resources are devoted to creating the largest possible number of processors, and consequently each individual processor must use the fewest possible resources. Disagreement exists as to whether SIMD processors should be able to generate addresses individually into their local data memory, or all processors should access the same address. The tradeoff is examined between the increased capability and the reduced number of processors that occurs in this single instruction stream, multiple, locally addressed, data (SIMLAD) model. Factors are assembled that affect this design choice, and the SIMLAD model is compared with the bare SIMD and the MIMD models.

  12. Multiple syndemic psychosocial factors are associated with reduced engagement in HIV care among a multinational, online sample of HIV-infected MSM in Latin America

    PubMed Central

    Biello, Katie B.; Oldenburg, Catherine E.; Safren, Steven A.; Rosenberger, Joshua G.; Novak, David S.; Mayer, Kenneth H.; Mimiaga, Matthew J.

    2016-01-01

    ABSTRACT Latin America has some of the highest levels of antiretroviral therapy (ART) coverage of any developing region in the world. Early initiation and optimal adherence to ART are necessary for improved health outcomes and reduction in onward transmission. Previous work has demonstrated the role of psychosocial problems as barriers to uptake and adherence to ART, and recently, a syndemic framework has been applied to the role of multiple psychosocial syndemic factors and adherence to ART, in the USA. However, to our knowledge, these associations have not been investigated outside of the USA, nor in a multi-country context. To address these gaps, we assessed the association between multiple co-occurring psychosocial factors and engagement in HIV-related medical care and adherence to ART among a large, multinational sample of sexually-active HIV-infected men who have sex with men in Latin America. Among the 2020 respondents, 80.7% reported currently receiving HIV-related medical care, 72.3% reported currently receiving ART; among those, 62.5% reported 100% adherence. Compared with experiencing no psychosocial health problems, experiencing five or more psychosocial health problems is associated with 42% lower odds of currently receiving HIV-related medical care (adjusted odds ratio, aOR = 0.58, 95% CI 0.36, 0.95) and of currently receiving ART (aOR = 0.58, 95% CI 0.38, 0.91). The number of psychosocial health problems experienced was associated with self-reported ART adherence in a dose–response relationship; compared to those with none of the factors, individuals with one syndemic factor had 23% lower odds (aOR = 0.77, 95% CI 0.60, 0.97) and individuals with five or more syndemic factors had 72% lower odds (aOR = 0.28, 95% CI 0.14, 0.55) of reporting being 100% adherent to ART. Addressing co-occurring psychosocial problems as potential barriers to uptake and adherence of ART in Latin America may improve the effectiveness of secondary prevention

  13. Multiple syndemic psychosocial factors are associated with reduced engagement in HIV care among a multinational, online sample of HIV-infected MSM in Latin America.

    PubMed

    Biello, Katie B; Oldenburg, Catherine E; Safren, Steven A; Rosenberger, Joshua G; Novak, David S; Mayer, Kenneth H; Mimiaga, Matthew J

    2016-03-01

    Latin America has some of the highest levels of antiretroviral therapy (ART) coverage of any developing region in the world. Early initiation and optimal adherence to ART are necessary for improved health outcomes and reduction in onward transmission. Previous work has demonstrated the role of psychosocial problems as barriers to uptake and adherence to ART, and recently, a syndemic framework has been applied to the role of multiple psychosocial syndemic factors and adherence to ART, in the USA. However, to our knowledge, these associations have not been investigated outside of the USA, nor in a multi-country context. To address these gaps, we assessed the association between multiple co-occurring psychosocial factors and engagement in HIV-related medical care and adherence to ART among a large, multinational sample of sexually-active HIV-infected men who have sex with men in Latin America. Among the 2020 respondents, 80.7% reported currently receiving HIV-related medical care, 72.3% reported currently receiving ART; among those, 62.5% reported 100% adherence. Compared with experiencing no psychosocial health problems, experiencing five or more psychosocial health problems is associated with 42% lower odds of currently receiving HIV-related medical care (adjusted odds ratio, aOR = 0.58, 95% CI 0.36, 0.95) and of currently receiving ART (aOR = 0.58, 95% CI 0.38, 0.91). The number of psychosocial health problems experienced was associated with self-reported ART adherence in a dose-response relationship; compared to those with none of the factors, individuals with one syndemic factor had 23% lower odds (aOR = 0.77, 95% CI 0.60, 0.97) and individuals with five or more syndemic factors had 72% lower odds (aOR = 0.28, 95% CI 0.14, 0.55) of reporting being 100% adherent to ART. Addressing co-occurring psychosocial problems as potential barriers to uptake and adherence of ART in Latin America may improve the effectiveness of secondary prevention interventions

  14. Weighing Evidence from Mendelian Randomization-Early-Life Obesity as a Causal Factor in Multiple Sclerosis?

    PubMed

    Ascherio, Alberto; Munger, Kassandra L

    2016-06-01

    In this Perspective, Alberto Ascherio and Kassandra Munger discuss the implications of Richards and colleagues' study exploring the role of early-life obesity in risk of multiple sclerosis. PMID:27351631

  15. Low levels of cobalamin, epidermal growth factor, and normal prions in multiple sclerosis spinal cord.

    PubMed

    Scalabrino, G; Veber, D; De Giuseppe, R; Roncaroli, F

    2015-07-01

    We have previously demonstrated that multiple sclerosis (MS) patients have abnormal cerebrospinal fluid (CSF) levels of the key myelin-related molecules cobalamin (Cbl), epidermal growth factor (EGF), and normal cellular prions (PrP(C)s), thus confirming that some CSF abnormalities may be co-responsible for remyelination failure. We determined the levels of these three molecules in post-mortem spinal cord (SC) samples taken from MS patients and control patients. The control SC samples, almost all of which came from non-neurological patients, did not show any microscopic lesions of any type. All of the samples were supplied by the U.K. MS Tissue Bank. The Cbl, EGF, and PrP(C) levels were determined using enzyme-linked immunosorbent assays. The SC total homocysteine level was determined using a competitive immunoenzymatic assay. CSF samples, taken from a further group of MS patients, were used for the assay of holo-transcobalamin (holo-TC) levels. The Cbl, EGF, and PrP(C) levels were significantly decreased in MS SCs in comparison with controls and, paradoxically, the decreased Cbl levels were associated with decreased SC levels of homocysteine, a biochemical marker of Cbl deficiency. The trends of EGF and PrP(C) levels paralleled those previously found in CSF, whereas that of Cbl was the opposite. There was no significant difference in CSF holo-TC levels between the MS patients and the controls. Given that we have previously demonstrated that Cbl positively regulates central nervous system EGF levels, it is conceivable that the low EGF levels in the MS SC may be causally related to a local decrease in Cbl levels. Only PrP(C) levels were invariably decreased in both the SC and CSF regardless of the clinical course of the disease. These findings suggest that the simultaneous lack of Cbl, EGF, and PrP(C)s may greatly hamper the remyelination process in MS patients, because they are key molecules of the machinery for remyelination. PMID:25888933

  16. Oral rabies vaccination of raccoons and striped skunks with ONRAB® baits: multiple factors influence field immunogenicity.

    PubMed

    Mainguy, Julien; Rees, Erin E; Canac-Marquis, Pierre; Bélanger, Denise; Fehlner-Gardiner, Christine; Séguin, Guylaine; Larrat, Sylvain; Lair, Stéphane; Landry, François; Côté, Nathalie

    2012-10-01

    Multiple control methods have been used in North America to manage the spread of rabies caused by the raccoon (Procyon lotor) rabies virus variant (RRVV). Recently, oral vaccination with ONRAB(®) vaccine baits, which contain an adenovirus rabies glycoprotein recombinant, has been made available as an additional tool for rabies control. Our objectives were to estimate rabies antibody prevalence in wild-caught raccoons and striped skunks (Mephitis mephitis), and identify factors influencing the probability of being antibody positive at the individual level in these species, following oral rabies vaccination (ORV) campaigns in which ONRAB was distributed aerially in 2007-2009 in southern Québec, Canada. Following the aerial distribution of 43-155 ONRAB baits/km(2), the annual percentages of antibody-positive raccoons and skunks varied between 35% and 56% and 11% and 17%, respectively. In raccoons, the probability of being antibody positive was positively associated with age and density of ONRAB distributed, and influenced by the number of previous ORV campaigns conducted. Conversely, this probability was negatively associated with estimated abundance of raccoons in the trapping cell and proportion of residential areas near the raccoon capture location. None of the variables examined explained variation in the probability of being antibody positive in skunks. Our results indicate that the ONRAB density applied during ORV campaigns should be adjusted to account for variations in raccoon population density and presence of residential areas to increase the likelihood of creating an effective immunological barrier against RRVV. The high percentage of juvenile raccoons (annual mean =45 ± 3 [SE]%) and skunks (66 ± 2%) captured during post-ORV monitoring suggests that ORV campaigns should be conducted at least annually to account for the recruitment of naïve individuals into the populations. In Québec, the increasing use of ONRAB coincided with the elimination of rabies

  17. Awards and Addresses Summary

    PubMed Central

    2008-01-01

    Each year at the annual ASHG meeting, addresses are given in honor of the society and a number of award winners. A summary of each of these addresses is given below. On the next pages, we have printed the Presidential Address and the addresses for the William Allan Award. The other addresses, accompanied by pictures of the speakers, can be found at www.ashg.org.

  18. Real-time particle monitor calibration factors and PM2.5 emission factors for multiple indoor sources.

    PubMed

    Dacunto, Philip J; Cheng, Kai-Chung; Acevedo-Bolton, Viviana; Jiang, Ruo-Ting; Klepeis, Neil E; Repace, James L; Ott, Wayne R; Hildemann, Lynn M

    2013-08-01

    Indoor sources can greatly contribute to personal exposure to particulate matter less than 2.5 μm in diameter (PM2.5). To accurately assess PM2.5 mass emission factors and concentrations, real-time particle monitors must be calibrated for individual sources. Sixty-six experiments were conducted with a common, real-time laser photometer (TSI SidePak™ Model AM510 Personal Aerosol Monitor) and a filter-based PM2.5 gravimetric sampler to quantify the monitor calibration factors (CFs), and to estimate emission factors for common indoor sources including cigarettes, incense, cooking, candles, and fireplaces. Calibration factors for these indoor sources were all significantly less than the factory-set CF of 1.0, ranging from 0.32 (cigarette smoke) to 0.70 (hamburger). Stick incense had a CF of 0.35, while fireplace emissions ranged from 0.44-0.47. Cooking source CFs ranged from 0.41 (fried bacon) to 0.65-0.70 (fried pork chops, salmon, and hamburger). The CFs of combined sources (e.g., cooking and cigarette emissions mixed) were linear combinations of the CFs of the component sources. The highest PM2.5 emission factors per time period were from burned foods and fireplaces (15-16 mg min(-1)), and the lowest from cooking foods such as pizza and ground beef (0.1-0.2 mg min(-1)). PMID:23784066

  19. Insulin-like growth factor-1- and interleukin-6-related gene variation and risk of multiple myeloma

    PubMed Central

    Birmann, Brenda M.; Tamimi, Rulla M.; Giovannucci, Edward; Rosner, Bernard; Hunter, David J.; Kraft, Peter; Mitsiades, Constantine; Anderson, Kenneth C.; Colditz, Graham A.

    2009-01-01

    Insulin-like growth factor (IGF)-1 and interleukin (IL)-6 promote the proliferation and survival of multiple myeloma cells. Variation in genes related to IGF-1 and IL-6 signaling may influence susceptibility to multiple myeloma. To assess their etiologic role, we examined the association of 70 tagging single nucleotide polymorphisms (SNP) in seven IGF-1 and three IL-6 pathway genes with multiple myeloma risk in two prospective cohorts, the Nurses' Health Study and Health Professionals Follow-up Study. Among participants who provided DNA specimens, we identified 58 women and 24 men with multiple myeloma and matched two controls per case. We used multivariable logistic regression models to assess the association of the SNPs or tagged haplotypes with multiple myeloma risk. Several SNPs had suggestive associations with multiple myeloma based on large odds ratios (OR), although corresponding omnibus p-values were not more than nominally significant (i.e., at p<0.05). These SNPs included rs1801278 in the gene encoding insulin receptor substrate-1 (IRS1; C/T v. C/C genotypes; OR=4.3, 95% confidence interval (CI)=1.5-12.1), and three IL-6 receptor SNPs: rs6684439 (T/T v. C/C: 2.9, 1.2-7.0), rs7529229 (C/C v. T/T; 2.5, 1.1-6.0), and rs8192284 (C/C v. A/A; 2.5, 1.1-6.0). Additional SNPs in genes encoding IGF-1, IGF binding protein-2, IRS2, and gp130 also demonstrated suggestive associations with multiple myeloma risk. We conducted a large number of statistical tests, and the findings may be due to chance. Nonetheless, the data are consistent with the hypothesis that IGF-1- and IL-6-related gene variation influences susceptibility to multiple myeloma and warrant confirmation in larger populations. PMID:19124510

  20. Las Matematicas: Lenguaje Universal. Nivel 2c: Factores y Multiplos (Mathematics: A Universql Language. Level 2c: Factors and Multiples).

    ERIC Educational Resources Information Center

    Dissemination and Assessment Center for Bilingual Education, Austin, TX.

    This is one of a series of student booklets designed for use in a bilingual mathematics program in grades 6-8. The general format is to present each page in both Spanish and English. The mathematical topics in this booklet include factors, prime and composite numbers, divisibility, and exponents. (MK)

  1. Common Factors Predicting Long-term Changes in Multiple Health Behaviors

    PubMed Central

    BLISSMER, BRYAN; PROCHASKA, JAMES O.; VELICER, WAYNE F.; REDDING, COLLEEN A.; ROSSI, JOSEPH S.; GREENE, GEOFFREY W.; PAIVA, ANDREA; ROBBINS, MARK

    2010-01-01

    This study was designed to assess if there are consistent treatment, stage, severity, effort and demographic effects which predict long-term changes across the multiple behaviors of smoking, diet and sun exposure. A secondary data analysis integrated data from four studies on smoking cessation (N = 3927), three studies on diet (N = 4824) and four studies on sun exposure (N = 6465). Across all three behaviors, behavior change at 24 months was related to treatment, stage of change, problem severity and effort effects measured at baseline. There were no consistent demographic effects. Across multiple behaviors, long-term behavior changes are consistently related to four effects that are dynamic and open to change. Behavior changes were not consistently related to static demographic variables. Future intervention research can target the four effects to determine if breakthroughs can be produced in changing single and multiple behaviors. PMID:20207664

  2. On the inclusion of prime factors to calculate the theoretical lower bounds in multiplierless single constant multiplications

    NASA Astrophysics Data System (ADS)

    Troncoso Romero, David E.; Meyer-Baese, Uwe; Dolecek, Gordana Jovanovic

    2014-12-01

    This paper presents an extension to the theoretical lower bounds for the number of adders and for the adder depth in multiplierless single constant multiplications (SCM). It is shown that the number of prime factors of the constants is key information to extend the current lower bounds in certain cases that have not yet been exposed. Additionally, the hidden theoretical lower bound for the number of adders required to preserve the minimum adder depth is revealed.

  3. [Successful treatment of venous thromboembolism with a Factor Xa inhibitor, edoxaban, in patients with lenalidomide-treated multiple myeloma].

    PubMed

    Kawaguchi, Masato; Uchimura, Norio; Okuda, Yuko; Konuma, Satomi; Nehashi, Yoshio

    2015-08-01

    Two multiple myeloma (MM) patients developed venous thromboembolism (VTE) while being treated with lenalidomide and low-dose dexamethasone. Aspirin is recommended for VTE prophylaxis when using lenalidomide/dexamethasone for MM patients with a standard risk of VTE. Despite aspirin administration, however, these two patients experienced VTE. Following VTE development, warfarin and then a Factor Xa inhibitor, edoxaban, were administered. The edoxaban treatment, especially, resulted in favorable and effective control of VTE. Considering these observations, Factor Xa inhibitors may in future become a preferred option for prevention and treatment of VTE when managing MM patients. PMID:26345573

  4. Elevated Translation Initiation Factor eIF4E Is an Attractive Therapeutic Target in Multiple Myeloma.

    PubMed

    Li, Shirong; Fu, Jing; Lu, Caisheng; Mapara, Markus Y; Raza, Shahzad; Hengst, Ulrich; Lentzsch, Suzanne

    2016-04-01

    eIF4E is the key regulator of protein translation and critical for translation. The oncogenic potential of tumorigenesis, which is highly contingent on cap-dependent eIF4E, also arises from the critical role in the nuclear export and cytosolic translation of oncogenic transcripts. Inhibition of Exportin1 (XPO1), which is the major nuclear export protein for eIF4E-bound oncoprotein mRNAs, results in decreased tumor cell growth in vitro and in vivo, suggesting that eIF4E is critical in multiple myeloma. Indeed, we found that eIF4E is overexpressed in myeloma cell lines and primary myeloma cells compared with normal plasma cells. Although stable overexpression of eIF4E in multiple myeloma cells significantly increases tumorigenesis, knockdown of eIF4E impairs multiple myeloma tumor progression in a human xenograft mouse model. Using a tet-on-inducible eIF4E-knockdown system, eIF4E downregulation blocks multiple myeloma tumor growth in vivo, correlating with decreased eIF4E expression. Further overexpression and knockdown of eIF4E revealed that eIF4E regulates translation of mRNAs with highly complex 5'-untranslated regions, such as c-MYC and C/EBPβ, and subsequently proliferation in multiple myeloma cells, but not in nonmalignant bone marrow stromal cells. Because many transcription factors that are critical for multiple myeloma proliferation exhibit a higher dependency on protein translation, eIF4E is an ideal and selective tool to target multiple myeloma cell growth. Mol Cancer Ther; 15(4); 711-9. ©2016 AACR. PMID:26939700

  5. Familial Factors Associated with the Use of Multiple Child-Care Arrangements

    ERIC Educational Resources Information Center

    Morrissey, Taryn W.

    2008-01-01

    This study examined the use of multiple, concurrent, nonparental child-care arrangements among children under 5 with employed mothers in the NICHD Study of Early Child Care and Youth Development (N= 759). Older children, those primarily cared for in informal child care, those living in cohabitating or single-parent households, and those whose…

  6. Multiple Regression Analysis of Factors that May Influence Middle School Science Scores

    ERIC Educational Resources Information Center

    Glover, Judith

    2012-01-01

    The purpose of this quantitative multiple regression study was to determine whether a relationship existed between Maryland State Assessment (MSA) reading scores, MSA math scores, gender, ethnicity, age, and MSA science scores. Also examined was if MSA reading scores, MSA math scores, gender, ethnicity, and age can be used in combination or alone…

  7. Prospective Mathematics Teachers' Sense Making of Polynomial Multiplication and Factorization Modeled with Algebra Tiles

    ERIC Educational Resources Information Center

    Caglayan, Günhan

    2013-01-01

    This study is about prospective secondary mathematics teachers' understanding and sense making of representational quantities generated by algebra tiles, the quantitative units (linear vs. areal) inherent in the nature of these quantities, and the quantitative addition and multiplication operations--referent preserving versus referent…

  8. Magnetic content addressable memories

    NASA Astrophysics Data System (ADS)

    Jiang, Zhenye

    Content Addressable Memories are designed with comparison circuits built into every bit cell. This parallel structure can increase the speed of searching from O(n) (as with Random Access Memories) to O(1), where n is the number of entries being searched. The high cost in hardware limits the application of CAM within situations where higher searching speed is extremely desired. Spintronics technology can build non-volatile Magnetic RAM with only one device for one bit cell. There are various technologies involved, like Magnetic Tunnel Junctions, off-easy-axis programming method, Synthetic Anti-Ferromagnetic tri-layers, Domain Wall displacement, Spin Transfer Torque tri-layers and etc. With them, particularly the Tunnel Magneto-Resistance variation in MTJ due to difference in magnetization polarity of the two magnets, Magnetic CAM can be developed with reduced hardware cost. And this is demonstrated by the discussion in this dissertation. Six MCAM designs are discussed. In the first design, comparand (C), local information (S) and their complements are stored into 4 MTJs connected in XOR gate pattern. The other five designs have one or two stacks for both information storage and comparison, and full TMR ratio can be taken advantage of. Two challenges for the five are specifically programming C without changing S and selectively programming a cell out of an array. The solutions to specific programming are: by confining the programming field for C in a ring structure design; by using field programming and spin polarized current programming respectively for C and S in the SAF+DW and SAF+STT tri-layer design; by making use of the difference in thresholds between direct mode and toggle mode switching in the SAF+SAF design. The problem of selective programming is addressed by off-easy-axis method and by including SAF tri-layers. Cell with STT tri-layers for both C and S can completely avoid the problems of specific and selective programming, but subject to the limit of

  9. Fatigue in multiple sclerosis: association with disease-related, behavioural and psychosocial factors.

    PubMed

    Trojan, D A; Arnold, D; Collet, J-P; Shapiro, S; Bar-Or, A; Robinson, A; Le Cruguel, J-P; Ducruet, T; Narayanan, S; Arcelin, K; Wong, A N; Tartaglia, M C; Lapierre, Y; Caramanos, Z; Da Costa, D

    2007-09-01

    We determined biopsychosocial correlates of general, physical, and mental fatigue in MS patients, by evaluating the additional contribution of potentially modifiable factors after accounting for non-modifiable disease-related factors. Fifty-three ambulatory MS patients, along with 28 normal controls were recruited for a cross-sectional study. Subjects completed the Multidimensional Fatigue Inventory (MFI) and Fatigue Severity Scale. Potential correlates evaluated were: disease-related factors (disease duration and type, immunomodulating treatment, muscle strength, pain, forced vital capacity (FVC), respiratory muscle strength, body mass index, disability, fibromyalgia), behavioural factors (physical activity, sleep quality) and psychosocial factors (depression, stress, self-efficacy). Multivariate models were calculated for MFI General, Physical, and Mental Fatigue. Age-adjusted multivariate models with non-modifiable factors included the following predictors (P < or = 0.10) of 1) MFI General and Mental Fatigue: none; and 2) MFI Physical Fatigue: FVC and disability. The following potentially modifiable predictors (P < or = 0.10) made an additional contribution to the models 1) MFI General Fatigue: sleep quality, self-efficacy, pain; 2) MFI Physical Fatigue: self-efficacy, physical activity; and 3) MFI Mental Fatigue: stress, self-efficacy. Fatigue in MS is multidimensional. Correlates of general and physical fatigue are disease-related, behavioural and psychosocial factors. Correlates of mental fatigue are psychosocial factors. Potentially modifiable factors account for a considerable portion of fatigue. PMID:17468448

  10. An Analysis of Multiple Factors Affecting Retention in Web-Based Community College Courses

    ERIC Educational Resources Information Center

    Doherty, William

    2006-01-01

    The current study examined four factors affecting retention in Web-based community college courses. Analyses were conducted on student demographics, student learning styles, course communication and external factors. The results suggest that Web-based courses are more attractive to busy students who are also more likely to fail or drop the course.…

  11. Parent Involvement in School: Conceptualizing Multiple Dimensions and Their Relations with Family and Demographic Risk Factors.

    ERIC Educational Resources Information Center

    Kohl, Gwynne O.; Lengua, Liliana J.; McMahon, Robert J.

    2000-01-01

    Explores the association between parental involvement (PI) and children's positive academic performance and social competence. Study examines the relations between a set of family and demographic risk factors and PI. Results reveal different patterns of relations between the risk factors studied-parental education, maternal depression, and…

  12. Reassessing the Behavior of Principals as a Multiple-Factor in Teachers' Job Satisfaction.

    ERIC Educational Resources Information Center

    Bogler, Ronit

    This paper reports on a study that examined the effects of three factors on teacher satisfaction: principal leadership style (transformational or transactional), principal decision-making strategy (autocratic versus participative), and teachers' perceptions of their occupation. An overview of each of the three factors is provided. For the study, a…

  13. Multiple steps in the regulation of transcription-factor level and activity.

    PubMed Central

    Calkhoven, C F; Ab, G

    1996-01-01

    This review focuses on the regulation of transcription factors, many of which are DNA-binding proteins that recognize cis-regulatory elements of target genes and are the most direct regulators of gene transcription. Transcription factors serve as integration centres of the different signal-transduction pathways affecting a given gene. It is obvious that the regulation of these regulators themselves is of crucial importance for differential gene expression during development and in terminally differentiated cells. Transcription factors can be regulated at two, principally different, levels, namely concentration and activity, each of which can be modulated in a variety of ways. The concentrations of transcription factors, as of intracellular proteins in general, may be regulated at any of the steps leading from DNA to protein, including transcription, RNA processing, mRNA degradation and translation. The activity of a transcription factor is often regulated by (de) phosphorylation, which may affect different functions, e.g. nuclear localization DNA binding and trans-activation. Ligand binding is another mode of transcription-factor activation. It is typical for the large super-family of nuclear hormone receptors. Heterodimerization between transcription factors adds another dimension to the regulatory diversity and signal integration. Finally, non-DNA-binding (accessory) factors may mediate a diverse range of functions, e.g. serving as a bridge between the transcription factor and the basal transcription machinery, stabilizing the DNA-binding complex or changing the specificity of the target sequence recognition. The present review presents an overview of different modes of transcription-factor regulation, each illustrated by typical examples. PMID:8713055

  14. Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor.

    PubMed

    Ban, Maria; Goris, An; Lorentzen, Aslaug R; Baker, Amie; Mihalova, Tania; Ingram, Gillian; Booth, David R; Heard, Robert N; Stewart, Graeme J; Bogaert, Elke; Dubois, Bénédicte; Harbo, Hanne F; Celius, Elisabeth G; Spurkland, Anne; Strange, Richard; Hawkins, Clive; Robertson, Neil P; Dudbridge, Frank; Wason, James; De Jager, Philip L; Hafler, David; Rioux, John D; Ivinson, Adrian J; McCauley, Jacob L; Pericak-Vance, Margaret; Oksenberg, Jorge R; Hauser, Stephen L; Sexton, David; Haines, Jonathan; Sawcer, Stephen; Compston, Alastair

    2009-10-01

    In a recent genome-wide association study (GWAS) based on 12,374 non-synonymous single nucleotide polymorphisms we identified a number of candidate multiple sclerosis susceptibility genes. Here, we describe the extended analysis of 17 of these loci undertaken using an additional 4234 patients, 2983 controls and 2053 trio families. In the final analysis combining all available data, we found that evidence for association was substantially increased for one of the 17 loci, rs34536443 from the tyrosine kinase 2 (TYK2) gene (P=2.7 x 10(-6), odds ratio=1.32 (1.17-1.47)). This single nucleotide polymorphism results in an amino acid substitution (proline to alanine) in the kinase domain of TYK2, which is predicted to influence the levels of phosphorylation and therefore activity of the protein and so is likely to have a functional role in multiple sclerosis. PMID:19293837

  15. Female pseudohermaphroditism with multiple caudal anomalies: Absence of Y-specific DNA sequences as pathogenetic factors

    SciTech Connect

    Seaver, L.H.; Grimes, J.; Erickson, R.P.

    1994-05-15

    46,XX female pseudohermaphrodites have been previously described with nearly complete masculinization of the external genitalia and no apparent source of testosterone. Multiple malformations of internal genital, urinary, and gastrointestinal tracts are associated. We have evaluated four such infants with female pseudohermaphroditism and multiple caudal anomalies. Three cases had apparently normal chromosome (46,XX); one had a 46,XX,del(10)(q25.3{yields}qter) chromosome constitution. The chromosome breakpoint is in the region of PAX2, a developmentally important paired box gene which is expressed in urogenital tissue. Using the polymerase chain reaction, we screened for the presence of multiple Y specific sequences, including SRY (sex determining region, Y chromosome), that could explain masculinization of the external genitalia. All were negative for Y centromeric sequences, ZFY (Zinc finger Y), and SRY. Furthermore, there was no evidence for adrenal or other sources of testosterone. We suggest that the masculinization in these cases is the result of abnormal expression of genes which would normally be regulated by testosterone. 32 refs., 1 fig., 2 tabs.

  16. [The role of multiple physical environmental factors on health of the population].

    PubMed

    Zviniatskovskiĭ, Ia I; Petrichenko, A E; Berdnik, O V; Zaĭkovskaia, V Iu; Serykh, L V

    1989-10-01

    Physical factors of urban environment (noise, electromagnetic fields) affect the process of the pathology development in children exposed to their effect at all the levels starting from the onset of early deviations in body nonspecific protection indices and up to the formation of chronic pathology. It has been established that all physical environmental factors negatively affect practically all the analyzed health indicators because of their nonspecific influence. At the same time it is demonstrated that the same factors have the most distinct effect on this or that system. Thus it becomes possible to exercise goal-oriented planning of environmental protection measures. PMID:2599411

  17. Addressing the Question of Disorder-Specific Risk Factors of Internet Addiction: A Comparison of Personality Traits in Patients with Addictive Behaviors and Comorbid Internet Addiction

    PubMed Central

    Müller, K. W.; Koch, A.; Dickenhorst, U.; Beutel, M. E.; Duven, E.; Wölfling, K.

    2013-01-01

    Uncontrolled use of the internet has been reported to affect the lives of some users in a negative way. According to epidemiological studies, about 1% of the general population is showing signs of internet addiction. Since internet addiction is becoming a growing health concern, research on potential risk factors is becoming more important in order to develop strategies for prevention and to adopt therapeutic treatment. Although there are some studies investigating personality traits in internet addiction, most of these studies are based on samples of healthy subjects. In this research project, we compared personality profiles of a sample of patients in different rehabilitation centers. 70 patients with an addiction disorder that additionally met the criteria for internet addiction were compared to 48 patients suffering from alcohol dependence. Besides Big Five personality traits, we also assessed depressive symptoms. It was shown that patients with comorbid internet addiction can be discriminated from other patients by higher neuroticism and lower extraversion as well as lower conscientiousness. After controlling for depressive symptoms, lower conscientiousness especially turned out to be a disorder-specific risk factor. As internet addiction is related to unique patterns of personality traits and can be discriminated from alcohol dependence, treatment approaches are needed that meet the specific requirements of patients with internet addiction. PMID:23865056

  18. Nasal administration of interleukin-33 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma surrogate.

    PubMed

    Shan, Shan; Li, Yan; Wang, Jingjing; Lv, Zhe; Yi, Dawei; Huang, Qiong; Corrigan, Chris J; Wang, Wei; Quangeng, Zhang; Ying, Sun

    2016-05-01

    The T-helper cell type 2-promoting cytokine interleukin-33 (IL-33) has been implicated in asthma pathogenesis. Angiogenesis is a feature of airways remodelling in asthma. We hypothesized that IL-33 induces airways angiogenesis and expression of angiogenic factors in an established murine surrogate of asthma. In the present study, BALB/c mice were subjected to serial intranasal challenge with IL-33 alone for up to 70 days. In parallel, ovalbumin (OVA) -sensitized mice were subjected to serial intranasal challenge with OVA or normal saline to serve as positive and negative controls, respectively. Immunohistochemical analysis of expression of von Willebrand factor and erythroblast transformation-specific-related gene, both blood vessel markers, and angiogenic factors angiogenin, insulin-like growth factor-1, endothelin-1, epidermal growth factor and amphiregulin was performed in lung sections ex vivo. An established in-house assay was used to test whether IL-33 was able to induce microvessel formation by human vascular endothelial cells. Results showed that serial intranasal challenge of mice with IL-33 or OVA resulted in proliferation of peribronchial von Willebrand factor-positive blood vessels to a degree closely related to the total expression of the angiogenic factors amphiregulin, angiogenin, endothelin-1, epidermal growth factor and insulin-like growth factor-1. IL-33 also induced microvessel formation by human endothelial cells in a concentration-dependent fashion in vitro. Our data are consistent with the hypothesis that IL-33 has the capacity to induce angiogenesis at least partly by increasing local expression of multiple angiogenic factors in an allergen-independent murine asthma surrogate, and consequently that IL-33 or its receptor is a potential novel molecular target for asthma therapy. PMID:27035894

  19. Evaluating the Evidence for the General Factor of Personality across Multiple Inventories

    PubMed Central

    Hopwood, Christopher J.; Wright, Aidan G.C.; Donnellan, M. Brent

    2012-01-01

    A general factor of personality (GFP) has been proposed as the apex of a personality trait hierarchy that explains covariance among the lower-order factors measured by various personality inventories. In this study we evaluated the GFP hypothesis across several personality inventories, unlike most previous research in which the GFP has been derived from individual instruments in isolation. Exploratory analyses did not produce substantial evidence for the existence of a single cross-instrument higher-order factor of factors and efforts to specify a range of GFP-inspired models in a confirmatory framework led to significant estimation difficulties and poor fit to the data. Overall these results fail to support a common GFP that is positioned at the top of a personality trait hierarchy. PMID:22879686

  20. Multiple Phytochrome-Interacting bHLH Transcription Factors Repress Premature Seedling Photomorphogenesis in Darkness

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An important contributing factor to the success of terrestrial flowering plants in colonizing the land was the evolution of a developmental strategy, termed skotomorphogenesis, whereby postgerminative seedlings emerging from buried seed grow vigorously upward in the subterranean darkness toward the ...

  1. Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

    SciTech Connect

    Yoon, Hyunjin; Ansong, Charles; McDermott, Jason E.; Gritsenko, Marina A.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.

    2011-06-28

    Background: Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity. Results: In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two of these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism. Conclusions: Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.

  2. Action of multiple intra-QTL genes concerted around a co-localized transcription factor underpins a large effect QTL.

    PubMed

    Dixit, Shalabh; Kumar Biswal, Akshaya; Min, Aye; Henry, Amelia; Oane, Rowena H; Raorane, Manish L; Longkumer, Toshisangba; Pabuayon, Isaiah M; Mutte, Sumanth K; Vardarajan, Adithi R; Miro, Berta; Govindan, Ganesan; Albano-Enriquez, Blesilda; Pueffeld, Mandy; Sreenivasulu, Nese; Slamet-Loedin, Inez; Sundarvelpandian, Kalaipandian; Tsai, Yuan-Ching; Raghuvanshi, Saurabh; Hsing, Yue-Ie C; Kumar, Arvind; Kohli, Ajay

    2015-01-01

    Sub-QTLs and multiple intra-QTL genes are hypothesized to underpin large-effect QTLs. Known QTLs over gene families, biosynthetic pathways or certain traits represent functional gene-clusters of genes of the same gene ontology (GO). Gene-clusters containing genes of different GO have not been elaborated, except in silico as coexpressed genes within QTLs. Here we demonstrate the requirement of multiple intra-QTL genes for the full impact of QTL qDTY12.1 on rice yield under drought. Multiple evidences are presented for the need of the transcription factor 'no apical meristem' (OsNAM12.1) and its co-localized target genes of separate GO categories for qDTY12.1 function, raising a regulon-like model of genetic architecture. The molecular underpinnings of qDTY12.1 support its effectiveness in further improving a drought tolerant genotype and for its validity in multiple genotypes/ecosystems/environments. Resolving the combinatorial value of OsNAM12.1 with individual intra-QTL genes notwithstanding, identification and analyses of qDTY12.1has fast-tracked rice improvement towards food security. PMID:26507552

  3. Action of multiple intra-QTL genes concerted around a co-localized transcription factor underpins a large effect QTL

    PubMed Central

    Dixit, Shalabh; Kumar Biswal, Akshaya; Min, Aye; Henry, Amelia; Oane, Rowena H.; Raorane, Manish L.; Longkumer, Toshisangba; Pabuayon, Isaiah M.; Mutte, Sumanth K.; Vardarajan, Adithi R.; Miro, Berta; Govindan, Ganesan; Albano-Enriquez, Blesilda; Pueffeld, Mandy; Sreenivasulu, Nese; Slamet-Loedin, Inez; Sundarvelpandian, Kalaipandian; Tsai, Yuan-Ching; Raghuvanshi, Saurabh; Hsing, Yue-Ie C.; Kumar, Arvind; Kohli, Ajay

    2015-01-01

    Sub-QTLs and multiple intra-QTL genes are hypothesized to underpin large-effect QTLs. Known QTLs over gene families, biosynthetic pathways or certain traits represent functional gene-clusters of genes of the same gene ontology (GO). Gene-clusters containing genes of different GO have not been elaborated, except in silico as coexpressed genes within QTLs. Here we demonstrate the requirement of multiple intra-QTL genes for the full impact of QTL qDTY12.1 on rice yield under drought. Multiple evidences are presented for the need of the transcription factor ‘no apical meristem’ (OsNAM12.1) and its co-localized target genes of separate GO categories for qDTY12.1 function, raising a regulon-like model of genetic architecture. The molecular underpinnings of qDTY12.1 support its effectiveness in further improving a drought tolerant genotype and for its validity in multiple genotypes/ecosystems/environments. Resolving the combinatorial value of OsNAM12.1 with individual intra-QTL genes notwithstanding, identification and analyses of qDTY12.1has fast-tracked rice improvement towards food security. PMID:26507552

  4. Level of education and multiple sclerosis risk after adjustment for known risk factors: The EnvIMS study

    PubMed Central

    Bjørnevik, Kjetil; Riise, Trond; Cortese, Marianna; Holmøy, Trygve; Kampman, Margitta T; Magalhaes, Sandra; Myhr, Kjell-Morten; Wolfson, Christina; Pugliatti, Maura

    2016-01-01

    Background: Several recent studies have found a higher risk of multiple sclerosis (MS) among people with a low level of education. This has been suggested to reflect an effect of smoking and lower vitamin D status in the social class associated with lower levels of education. Objective: The objective of this paper is to investigate the association between level of education and MS risk adjusting for the known risk factors smoking, infectious mononucleosis, indicators of vitamin D levels and body size. Methods: Within the case-control study on Environmental Factors In MS (EnvIMS), 953 MS patients and 1717 healthy controls from Norway reported educational level and history of exposure to putative environmental risk factors. Results: Higher level of education were associated with decreased MS risk (p trend = 0.001) with an OR of 0.53 (95% CI 0.41–0.68) when comparing those with the highest and lowest level of education. This association was only moderately reduced after adjusting for known risk factors (OR 0.61, 95% CI 0.44–0.83). The estimates remained similar when cases with disease onset before age 28 were excluded. Conclusion: These findings suggest that factors related to lower socioeconomic status other than established risk factors are associated with MS risk. PMID:26014605

  5. The role of multiple scattering in twilight zenith sky observations of atmospheric absorbers: Diurnal photochemistry and airmass factors

    NASA Astrophysics Data System (ADS)

    Perliski, Lori Mac

    The ability to properly interpret UV-visible twilight absorption measurements of atmospheric chemical constituents is dependent on how well the optical path, or airmass factor, of light collected by the spectrometer is understood. In the case of direct light measurement, the airmass factor may be calculated from simple geometrical considerations for a spherical atmosphere. In the case of scattered light, a spherical radiative transfer model must be used. A simple single scattering model and a Monte Carlo radiative transfer scheme were developed to study the effects of multiple scattering, aerosol scattering, albedo and refraction on scattered light airmass factors. Stratospheric airmass factors are found to be relatively insensitive to multiple scattering, albedo, refraction and aerosol scattering by background aerosols at fairly short visible wavelengths (about 450 nm). Tropospheric airmass factors, on the other hand, are very sensitive to these processes. Ground albedo, refraction, multiple scattering and aerosol scattering are also important in determining photolysis rates of atmospheric species. It is found that one-dimensional photochemical model calculations of vertical column abundances of several stratospheric chemical constituents are relatively insensitive to changes in photolysis rates due to albedo, refraction and background aerosol scattering, although they are sensitive to multiple scattering. Following the June 1991 eruption of Mt. Pinatubo, OClO and BrO were observed at Fritz Peak Observatory for the first time every. The radiative and photochemical effects of the presence of Pinatubo volcanic aerosols are examined using a one-dimensional photochemical model coupled to a spherical matrix inversion radiative transfer model. Although the heterogeneous removal of NO(x) is not explicitly considered in the photochemical model, the photochemical effects of NO(x) removal may be studied by prescribing the amount of NO(x) removed by heterogeneous chemistry

  6. [Effect of environmental factors on fish community structure in the Huntai River Basin at multiple scales].

    PubMed

    Li, Yan-li; Li, Yan-fen; Xu, Zong-xue

    2014-09-01

    In June 2012, fishes was investigated at 65 sampling sites in the Huntai River basin in Northeast of China. Forty species were collected, belonging to 9 orders, 14 families,33 genera. Cobitidae and Cyprinidae were the dominant fishes in the community structure in the Huntai River basin, accounting for 13. 21% and 65. 83% of the fish community, respectively. There were two types of spatial distribution of fish community, one was distributed in the head water and tributaries in the upstream, and the other was in the plain rivers. Nemachilus nudus, Cobitis granoei and Phoxinus lagowskii dominated the local community in the upper reaches of the Dahuofang Reservoir and shenwo River, while Carassius ayratus and Hemiculter leucisculdus dominated the local community in the plain rivers. CCA (canonical correspondence analysis) was used to distinguish the primary environmental variables that affected the fish community structure. The results indicated fish community was mainly affected by environment factors at watershed and reach scales. Proportions of woodland and urban land, and altitude were three important environmental factors affecting the fish community at the watershed scale. Dissolved oxygen, total nitrogen, pH and habitat inhomogeneity significantly affected the fish community at the reach scale, whereas substrate didn't show significant influence at the microhabitat scale. Environmental factors at watershed scale explained 7. 66% of the variation of fish community structure, environmental factors at reach scale explained 10. 57% of the variation of fish community structure. Environmental factors at reach scale influenced the fish community more significantly. PMID:25518673

  7. Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.

    PubMed

    Mast, Alan E

    2016-01-01

    Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF-factor VIIa complexes that initiate blood coagulation. The TFPIα isoform is present in platelets. TFPIα contains a stretch of 9 amino acids nearly identical to those found in the B-domain of factor V that are well conserved in mammals. These amino acids provide exosite binding to activated factor V, which allows for TFPIα to inhibit prothrombinase during the initiation phase of blood coagulation. Endogenous inhibition at this point in the coagulation cascade was only recently recognized and has provided a biochemical rationale to explain the pathophysiological mechanisms underlying several clinical disorders. These include the east Texas bleeding disorder that is caused by production of an altered form of factor V with high affinity for TFPI and a paradoxical procoagulant effect of heparins. In addition, these findings have led to ideas for pharmacological targeting of TFPI that may reduce bleeding in hemophilia patients. PMID:26603155

  8. Shared risk factors for multiple livestock diseases: a case study of bovine tuberculosis and brucellosis.

    PubMed

    Cowie, C E; Marreos, N; Gortázar, C; Jaroso, R; White, P C L; Balseiro, A

    2014-12-01

    Livestock diseases can result in reduced farm productivity. The bacterial diseases tuberculosis (TB) and brucellosis may share some transmission characteristics which, if managed in common, would result in more cost-effective management. Here, we identify risk factors shared between these diseases using a case-control approach and information theoretic modelling. One-hundred cattle farmers in Atlantic Spain were interviewed about farm characteristics and management practices. The risk factor shared between both diseases was intra- and inter-herd contact between cattle. Disease-specific risk factors were the presence of wildlife for TB, and cattle movement between farms for brucellosis. An integrated approach to disease management needs to consider cattle movement and farm biosecurity, reinforced by an education campaign to increase farmer awareness. This would be likely to bring benefits in reducing both diseases and improve the efficiency of any interventions. PMID:25267287

  9. Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels

    NASA Astrophysics Data System (ADS)

    Wylie, Ryan G.; Ahsan, Shoeb; Aizawa, Yukie; Maxwell, Karen L.; Morshead, Cindi M.; Shoichet, Molly S.

    2011-10-01

    Three-dimensional (3D) protein-patterned scaffolds provide a more biomimetic environment for cell culture than traditional two-dimensional surfaces, but simultaneous 3D protein patterning has proved difficult. We developed a method to spatially control the immobilization of different growth factors in distinct volumes in 3D hydrogels, and to specifically guide differentiation of stem/progenitor cells therein. Stem-cell differentiation factors sonic hedgehog (SHH) and ciliary neurotrophic factor (CNTF) were simultaneously immobilized using orthogonal physical binding pairs, barnase-barstar and streptavidin-biotin, respectively. Barnase and streptavidin were sequentially immobilized using two-photon chemistry for subsequent concurrent complexation with fusion proteins barstar-SHH and biotin-CNTF, resulting in bioactive 3D patterned hydrogels. The technique should be broadly applicable to the patterning of a wide range of proteins.

  10. A review of critical factors for assessing the dermal absorption of metal oxide nanoparticles from sunscreens applied to humans, and a research strategy to address current deficiencies.

    PubMed

    Gulson, Brian; McCall, Maxine J; Bowman, Diana M; Pinheiro, Teresa

    2015-11-01

    Metal oxide nanoparticles in sunscreens provide broad-spectrum ultraviolet protection to skin. All studies to assess dermal penetration of nanoparticles have unanimously concluded that the overwhelming majority of nanoparticles remain on the outer surface of the skin. However, possibly due to many different experimental protocols in use, conclusions over the potential penetration to viable skin are mixed. Here, we review several factors that may influence experimental results for dermal penetration including the species studied (human, or animal model), size and coating of the metal oxide nanoparticles, composition of the sunscreen formulation, site of sunscreen application, dose and number of applications, duration of the study, types of biological samples analysed, methods for analysing samples, exposure to UV and skin flexing. Based on this information, we suggest an appropriate research agenda involving international collaboration that maximises the potential for dermal absorption of nanoparticles, and their detection, under normal conditions of sunscreen use by humans. If results from this research agenda indicate no absorption is observed, then concerns over adverse health effects from the dermal absorption of nanoparticles in sunscreens may be allayed. PMID:26140917

  11. A dynamic factor modeling framework for analyzing multiple groundwater head series simultaneously

    NASA Astrophysics Data System (ADS)

    Berendrecht, W. L.; van Geer, F. C.

    2016-05-01

    In this paper we present an approach in which we combine a dynamic factor model (DFM) and predefined response functions to analyze a set of groundwater head series simultaneously. Each groundwater head series is decomposed into: (a) one or more deterministic components as a response to known driving forces, (b) one or more common dynamic factors, representing spatial patterns not related to any of the input series and (c) one specific dynamic factor for each groundwater head series, describing unique variation for that series. The approach reduces the degrees of freedom for each response function, enables the application to irregular observed data, and exploits the correlation between residual series of a set of groundwater head series. The common dynamic factors may be interpreted as spatial patterns due to e.g. limitations in the model specification or concept, spatially correlated errors in input variables, or driving forces which have not been included in the model. In the latter case the model can be applied in the context of an alarming system, e.g. to monitor regional trends. The specific dynamic factor depicts the variation of a particular groundwater head series that cannot be related to any other time series of the set nor to any input series. Therefore the specific dynamic factor is suitable for analyzing local variations and detecting incidental measurement errors, for example in a quality control procedure. The DFM framework is illustrated with a set of 8 groundwater head series and applied for filling gaps in time series, reconstructing high-frequency data, and detecting outliers.

  12. Multiple Factors Supporting the Transition to ICT-Rich Learning Environments in India, Turkey, and Chile

    ERIC Educational Resources Information Center

    Light, Daniel

    2010-01-01

    This research project used instrumental case studies of successful schools from the Intel® Teach Essentials Course in Turkey, India and Chile to examine what contextual factors might facilitate teachers' ability to transfer a professional development program about ICT and innovative teaching strategies into their classrooms given the school…

  13. "It Takes a Village" to Support the Vocabulary Development of Children with Multiple Risk Factors

    ERIC Educational Resources Information Center

    Baydar, Nazli; Küntay, Aylin C.; Yagmurlu, Bilge; Aydemir, Nuran; Cankaya, Dilek; Göksen, Fatos; Cemalcilar, Zeynep

    2014-01-01

    Data from a nationally representative sample from Turkey (N = 1,017) were used to investigate the environmental factors that support the receptive vocabulary of 3-year-old children who differ in their developmental risk due to family low economic status and elevated maternal depressive symptoms. Children's vocabulary knowledge was strongly…

  14. Factors Influencing New York Doctoral Graduate Student Satisfaction: A Quantitative Multiple Regression Analysis

    ERIC Educational Resources Information Center

    Nwenyi, Sabina E.

    2013-01-01

    Higher education administrators face challenges in providing a welcoming environment for doctoral students in higher education institutions. Administrators need to identify factors influencing satisfaction of this group of students to provide a supportive environment, reduce attrition rates, and promote persistence. The purpose of this…

  15. Factors Affecting University Entrants' Performance in High-Stakes Tests: A Multiple Regression Analysis

    ERIC Educational Resources Information Center

    Uy, Chin; Manalo, Ronaldo A.; Cabauatan, Ronaldo R.

    2015-01-01

    In the Philippines, students seeking admission to a university are usually required to meet certain entrance requirements, including passing the entrance examinations with questions on IQ and English, mathematics, and science. This paper aims to determine the factors that affect the performance of entrants into business programmes in high-stakes…

  16. Multivariate meta-analysis of prognostic factor studies with multiple cut-points and/or methods of measurement.

    PubMed

    Riley, Richard D; Elia, Eleni G; Malin, Gemma; Hemming, Karla; Price, Malcolm P

    2015-07-30

    A prognostic factor is any measure that is associated with the risk of future health outcomes in those with existing disease. Often, the prognostic ability of a factor is evaluated in multiple studies. However, meta-analysis is difficult because primary studies often use different methods of measurement and/or different cut-points to dichotomise continuous factors into 'high' and 'low' groups; selective reporting is also common. We illustrate how multivariate random effects meta-analysis models can accommodate multiple prognostic effect estimates from the same study, relating to multiple cut-points and/or methods of measurement. The models account for within-study and between-study correlations, which utilises more information and reduces the impact of unreported cut-points and/or measurement methods in some studies. The applicability of the approach is improved with individual participant data and by assuming a functional relationship between prognostic effect and cut-point to reduce the number of unknown parameters. The models provide important inferential results for each cut-point and method of measurement, including the summary prognostic effect, the between-study variance and a 95% prediction interval for the prognostic effect in new populations. Two applications are presented. The first reveals that, in a multivariate meta-analysis using published results, the Apgar score is prognostic of neonatal mortality but effect sizes are smaller at most cut-points than previously thought. In the second, a multivariate meta-analysis of two methods of measurement provides weak evidence that microvessel density is prognostic of mortality in lung cancer, even when individual participant data are available so that a continuous prognostic trend is examined (rather than cut-points). PMID:25924725

  17. Evidence for multiple sequences and factors involved in c-myc RNA stability during amphibian oogenesis.

    PubMed

    Lefresne, J; Lemaitre, J M; Selo, M; Goussard, J; Mouton, C; Andeol, Y

    2001-04-01

    To investigate the molecular mechanisms regulating c-myc RNA stability during late amphibian oogenesis, a heterologous system was used in which synthetic Xenopus laevis c-myc transcripts, progressively deleted from their 3' end, were injected into the cytoplasm of two different host axolotl (Ambystoma mexicanum) cells: stage VI oocytes and progesterone-matured oocytes (unfertilized eggs; UFE). This in vivo strategy allowed the behavior of the exogenous c-myc transcripts to be followed and different regions involved in the stability of each intermediate deleted molecule to be identified. Interestingly, these specific regions differ in the two cellular contexts. In oocytes, two stabilizing regions are located in the 3' untranslated region (UTR) and two in the coding sequence (exons II and III) of the RNA. In UFE, the stabilizing regions correspond to the first part of the 3' UTR and to the first part of exon II. However, in UFE, the majority of synthetic transcripts are degraded. This degradation is a consequence of nuclear factors delivered after germinal vesicle breakdown and specifically acting on targeted regions of the RNA. To test the direct implication of these nuclear factors in c-myc RNA degradation, an in vitro system was set up using axolotl germinal vesicle extracts that mimic the in vivo results and confirm the existence of specific destabilizing factors. In vitro analysis revealed that two populations of nuclear molecules are implicated: one of 4.4-5S (50-65 kDa) and the second of 5.4-6S (90-110 kDa). These degrading nuclear factors act preferentially on the coding region of the c-myc RNA and appear to be conserved between axolotl and Xenopus. Thus, this experimental approach has allowed the identification of specific stabilizing sequences in c-myc RNA and the temporal identification of the different factors (cytoplasmic and/or nuclear) involved in post-transcriptional regulation of this RNA during oogenesis. PMID:11284969

  18. A new method to improve multiplication factor in micro-pixel avalanche photodiodes with high pixel density

    NASA Astrophysics Data System (ADS)

    Sadygov, Z.; Ahmadov, F.; Khorev, S.; Sadigov, A.; Suleymanov, S.; Madatov, R.; Mehdiyeva, R.; Zerrouk, F.

    2016-07-01

    Presented is a new model describing development of the avalanche process in time, taking into account the dynamics of electric field within the depleted region of the diode and the effect of parasitic capacitance shunting individual quenching micro-resistors on device parameters. Simulations show that the effective capacitance of a single pixel, which defines the multiplication factor, is the sum of the pixel capacitance and a parasitic capacitance shunting its quenching micro-resistor. Conclusions obtained as a result of modeling open possibilities of improving the pixel gain in micropixel avalanche photodiodes with high pixel density (or low pixel capacitance).

  19. Reverse engineering of the multiple launch rocket system. Human factors, manpower, personnel, and training in the weapons system acquisition process

    NASA Astrophysics Data System (ADS)

    Arabian, J. M.; Hartel, C. R.; Kaplan, J. D.; Marcus, A.; Promisel, D. M.

    1984-06-01

    In a briefing format, this report on the Multiple Launch Rocket System summarizes an examination of human factors, manpower, personnel and training (HMPT) issues during the systems acquisition process. The report is one of four reverse engineering studies prepared at the request of Gen. M. R. Thurman, Army Vice Chief of Staff. The four systems were studied as a representative sample of Army weapons systems. They serve as the basis for drawing conclusions about aspects of the weapons system acquisition process which most affect HMPT considerations. A synthesis of the four system studies appears in the final report of the Reverse Engineering Task Force U.S. Army Research Institute.

  20. Analyses of prognostic factors in cases of non-small cell lung cancer with multiple brain metastases

    PubMed Central

    Gong, Xiaomei; Zhou, Daoan; Liang, Shixiong; Zhou, Caicun

    2016-01-01

    Aim To observe the therapeutic efficacy and prognostic factors that influence survival rates in non-small cell lung cancer (NSCLC) patients with multiple brain metastases (BMs), (more than three and less than ten). Methods Retrospective analyses were conducted on the clinical data of 209 NSCLC patients with multiple BMs and were admitted to our hospital between March 2007 and November 2012. All BM patients received whole-brain radiotherapy. Two hundred patients received combined chemotherapy during the treatment process; 99 received targeted drug therapy; and nine got only symptomatic and supportive treatment. Survival time was defined as the period from the start of BM therapy to the patient’s death or end of the follow-up period. The Kaplan–Meier method was used to calculate the median survival time, and the 6-month, 1-, and 2-year cumulative survival rates, as well as to plot the survival curves. The patients’ cultural background included their socioeconomic status, level of education, their understanding of the disease, and the degree of care and support they received from their family members. Log-rank test was employed to test the differences in the survival rates between the subgroups. Cox multivariate regression analyses were used to analyze the various factors influencing the prognoses of NSCLC with multiple BMs. Results The follow-up duration was between 1 and 87 months. The median survival time for all BM patients was 12.1 months (95% confidence interval 9.37–14.83). The 6-month, 1-, and 2-year cumulative survival rates were 80%, 50.2%, and 10.7%, respectively. Univariate analyses revealed that the independent factors influencing survival prognoses included Karnofsky Performance Status score, control of the primary lung tumor, interval between the confirmed diagnoses of lung cancer and BM, presence of extracranial metastasis, number of chemotherapy cycles undergone, Graded Prognostic Assessment class, administration of combined targeted drug

  1. Geophysical Factor Resolving of Rainfall Mechanism for Super Typhoons by Using Multiple Spatiotemporal Components Analysis

    NASA Astrophysics Data System (ADS)

    Huang, Chien-Lin; Hsu, Nien-Sheng

    2016-04-01

    This study develops a novel methodology to resolve the geophysical cause of typhoon-induced rainfall considering diverse dynamic co-evolution at multiple spatiotemporal components. The multi-order hidden patterns of complex hydrological process in chaos are detected to understand the fundamental laws of rainfall mechanism. The discovered spatiotemporal features are utilized to develop a state-of-the-art descriptive statistical model for mechanism validation, modeling and further prediction during typhoons. The time series of hourly typhoon precipitation from different types of moving track, atmospheric field and landforms are respectively precede the signal analytical process to qualify each type of rainfall cause and to quantify the corresponding affected degree based on the measured geophysical atmospheric-hydrological variables. This study applies the developed methodology in Taiwan Island which is constituted by complex diverse landform formation. The identified driving-causes include: (1) cloud height to ground surface; (2) co-movement effect induced by typhoon wind field with monsoon; (3) stem capacity; (4) interaction between typhoon rain band and terrain; (5) structural intensity variance of typhoon; and (6) integrated cloudy density of rain band. Results show that: (1) for the central maximum wind speed exceeding 51 m/sec, Causes (1) and (3) are the primary ones to generate rainfall; (2) for the typhoon moving toward the direction of 155° to 175°, Cause (2) is the primary one; (3) for the direction of 90° to 155°, Cause (4) is the primary one; (4) for the typhoon passing through mountain chain which above 3500 m, Cause (5) is the primary one; and (5) for the moving speed lower than 18 km/hr, Cause (6) is the primary one. Besides, the multiple geophysical component-based precipitation modeling can achieve 81% of average accuracy and 0.732 of average correlation coefficient (CC) within average 46 hours of duration, that improve their predictability.

  2. Variation partitioning of diatom species data matrices: Understanding the influence of multiple factors on benthic diatom communities in tropical streams.

    PubMed

    Bere, Taurai; Mangadze, Tinotenda; Mwedzi, Tongai

    2016-10-01

    Elucidating the confounding influence of multiple environmental factors on benthic diatom communities is important in developing water quality predictive models for better guidance of stream management efforts. The objective of this study was to explore the relative impact of metal pollution and hydromorphological alterations in, addition to nutrient enrichment and organic pollution, on diatom taxonomic composition with the view to improve stream diatom-based water quality inference models. Samples were collected twice at 20 sampling stations in the tropical Manyame Catchment, Zimbabwe. Diatom, macroinvertebrate communities and environmental factors were sampled and analysed. The variations in diatom community composition explained by different categories of environmental factors were analysed using canonical correspondence analysis using variance partitioning (partial CCA). The following variations were explained by the different predictor matrices: nutrient levels and organic pollution - 10.4%, metal pollution - 8.3% and hydromorphological factors - 7.9%. Thus, factors other than nutrient levels and organic pollution explain additional significant variation in these diatom communities. Development of diatom-based stream water quality inference models that incorporate metal pollution and hydromorphological alterations, where these are key issues, is thus deemed necessary. PMID:27320742

  3. Multiple Growth Factors, But Not VEGF, Stimulate Glycosaminoglycan Hyperelongation in Retinal Choroidal Endothelial Cells

    PubMed Central

    Al Gwairi, Othman; Osman, Narin; Getachew, Robel; Zheng, Wenhua; Liang, X-L.; Kamato, Danielle; Thach, Lyna; Little, Peter J.

    2016-01-01

    A major feature of early age-related macular degeneration (AMD) is the thickening of Bruch's membrane in the retina and an alteration in its composition with increased lipid deposition. In certain pathological conditions proteoglycans are responsible for lipid retention in tissues. Growth factors are known to increase the length of glycosaminoglycan chains and this can lead to a large increase in the interaction between proteoglycans and lipids. Using choroidal endothelial cells, we investigated the effects of a number of AMD relevant growth factors TGFβ, thrombin, PDGF, IGF and VEGF on proteoglycan synthesis. Cells were characterized as of endothelial origin using the specific cell markers endothelial nitric oxide synthesis and von Willebrand factor and imaged using confocal microscopy. Cells were treated with growth factors in the presence and absence of the appropriate inhibitors and were radiolabeled with [35S]-SO4. Proteoglycans were isolated by ion exchange chromatography and sized using SDS-PAGE. Radiosulfate incorporation was determined by the cetylpyridinium chloride (CPC) precipitation technique. To measure cellular glycosaminoglycan synthesizing capacity we added xyloside and assessed the xyloside-GAGs by SDS-PAGE. TGFβ, thrombin, PDGF & IGF dose-dependently stimulated radiosulfate incorporation and GAG elongation as well as xyloside-GAG synthesis, however VEGF treatment did not stimulate any changes in proteoglycan synthesis. VEGF did not increase pAKT but caused a large increase in pERK relative to the response to PDGF. Thus, AMD relevant agonists cause glycosaminoglycan hyperelongation of proteoglycans synthesised and secreted by retinal choroidal endothelial cells. The absence of a response to VEGF is intriguing and identifies proteoglycans as a novel potential target in AMD. Future studies will examine the relevance of these changes to enhanced lipid binding and the development of AMD. PMID:27570478

  4. Multiple requirements for SHPTP2 in epidermal growth factor-mediated cell cycle progression.

    PubMed Central

    Bennett, A M; Hausdorff, S F; O'Reilly, A M; Freeman, R M; Neel, B G

    1996-01-01

    Using transient overexpression and microinjection approaches, we examined SHPTP2's function in growth factor signaling. Overexpression of catalytically inactive SHPTP2 (PTP2CS) but not catalytically inactive SHPTP1, inhibited mitogen-activated protein (MAP) kinase activation and Elk-1 transactivation following epidermal growth factor (EGF) stimulation of 293 cells. An SHPTP2 mutant with both C-terminal tyrosyl phosphorylation sites converted to phenylalanine (PTP2YF) was also without effect; moreover, PTP2YF rescued PTP2CS-induced inhibition of EGF-induced Elk-1 transactivation. PTP2CS did not inhibit transactivation by activated Ras, suggesting that SHPTP2 acts upstream of or parallel to Ras. Neither PTP2CS nor PTP2YF inhibited platelet-derived growth factor (PDGF)-induced Elk-1 transactivation. Thus, protein-tyrosine phosphatase activity, but not tyrosyl phosphorylation of SHPTP2, is required for the immediate-early responses to EGF but not to PDGF. To determine whether SHPTP2 is required later in the cell cycle, we assessed S-phase entry in NIH 3T3 cells microinjected with anti-SHPTP2 antibodies or with a glutathione S-transferase (GST) fusion protein encoding both SH2 domains (GST-SH2). Microinjection of anti-SHPTP2 antibodies prior to stimulation inhibited EGF- but no PDGF- or serum-induced S-phase entry. Anti-SHPTP2 antibodies or GST-SH2 fusion protein could inhibit EGF-induced S-phase entry for up to 8 h after EGF addition. Although MAP kinase activation was detected shortly after EGF stimulation, no MAP kinase activation was detected around the restriction point. Therefore, SHPTP2 is absolutely required for immediate-early and late events induced by some, but not all, growth factors, and the immediate-early and late signal transduction pathways regulated by SHPTP2 are distinguishable. PMID:8622663

  5. Multiple Growth Factors, But Not VEGF, Stimulate Glycosaminoglycan Hyperelongation in Retinal Choroidal Endothelial Cells.

    PubMed

    Al Gwairi, Othman; Osman, Narin; Getachew, Robel; Zheng, Wenhua; Liang, X-L; Kamato, Danielle; Thach, Lyna; Little, Peter J

    2016-01-01

    A major feature of early age-related macular degeneration (AMD) is the thickening of Bruch's membrane in the retina and an alteration in its composition with increased lipid deposition. In certain pathological conditions proteoglycans are responsible for lipid retention in tissues. Growth factors are known to increase the length of glycosaminoglycan chains and this can lead to a large increase in the interaction between proteoglycans and lipids. Using choroidal endothelial cells, we investigated the effects of a number of AMD relevant growth factors TGFβ, thrombin, PDGF, IGF and VEGF on proteoglycan synthesis. Cells were characterized as of endothelial origin using the specific cell markers endothelial nitric oxide synthesis and von Willebrand factor and imaged using confocal microscopy. Cells were treated with growth factors in the presence and absence of the appropriate inhibitors and were radiolabeled with [35S]-SO4. Proteoglycans were isolated by ion exchange chromatography and sized using SDS-PAGE. Radiosulfate incorporation was determined by the cetylpyridinium chloride (CPC) precipitation technique. To measure cellular glycosaminoglycan synthesizing capacity we added xyloside and assessed the xyloside-GAGs by SDS-PAGE. TGFβ, thrombin, PDGF & IGF dose-dependently stimulated radiosulfate incorporation and GAG elongation as well as xyloside-GAG synthesis, however VEGF treatment did not stimulate any changes in proteoglycan synthesis. VEGF did not increase pAKT but caused a large increase in pERK relative to the response to PDGF. Thus, AMD relevant agonists cause glycosaminoglycan hyperelongation of proteoglycans synthesised and secreted by retinal choroidal endothelial cells. The absence of a response to VEGF is intriguing and identifies proteoglycans as a novel potential target in AMD. Future studies will examine the relevance of these changes to enhanced lipid binding and the development of AMD. PMID:27570478

  6. Energy propagation by transverse waves in multiple flux tube systems using filling factors

    SciTech Connect

    Van Doorsselaere, T.; Gijsen, S. E.; Andries, J.; Verth, G. E-mail: stief.gijsen@wis.kuleuven.be E-mail: g.verth@sheffield.ac.uk

    2014-11-01

    In the last few years, it has been found that transverse waves are present at all times in coronal loops or spicules. Their energy has been estimated with an expression derived for bulk Alfvén waves in homogeneous media, with correspondingly uniform wave energy density and flux. The kink mode, however, is localized in space with the energy density and flux dependent on the position in the cross-sectional plane. The more relevant quantities for the kink mode are the integrals of the energy density and flux over the cross-sectional plane. The present paper provides an approximation to the energy propagated by kink modes in an ensemble of flux tubes by means of combining the analysis of single flux tube kink oscillations with a filling factor for the tube cross-sectional area. This finally allows one to compare the expressions for energy flux of Alfvén waves with an ensemble of kink waves. We find that the correction factor for the energy in kink waves, compared to the bulk Alfvén waves, is between f and 2f, where f is the density filling factor of the ensemble of flux tubes.

  7. Heterophilic antibody interference affecting multiple hormone assays: Is it due to rheumatoid factor?

    PubMed

    Mongolu, Shiva; Armston, Annie E; Mozley, Erin; Nasruddin, Azraai

    2016-05-01

    Assay interference with heterophilic antibodies has been well described in literature. Rheumatoid factor is known to cause similar interference leading to falsely elevated hormone levels when measured by immunometric methods like enzyme-linked immunosorbent assay (ELISA) or multiplex immunoasays (MIA). We report a case of a 60-year-old male patient with a history of rheumatoid arthritis referred to our endocrine clinic for investigation of hypogonadism and was found to have high serum levels of LH, FSH, SHBG, Prolactin, HCG and TSH. We suspected assay interference and further tests were performed. We used Heteroblock tubes and PEG precipitation to eliminate the interference and the hormone levels post treatment were in the normal range. We believe the interference was caused by high serum levels of rheumatoid factor. Although he was treated with thyroxine for 3 years, we believe he may have been treated inappropriately as his Free T4 level was always normal despite high TSH due to assay interference. Our case illustrates the phenomenon of heterophilic antibody interference likely due to high levels of rheumatoid factor. It is essential for clinicians and endocrinologists in particular to be aware of this possibility when making treatment decisions in these groups of patients. PMID:26924790

  8. Imbalance between macrophage migration inhibitory factor and cortisol induces multiple organ dysfunction in patients with blunt trauma.

    PubMed

    Hayakawa, Mineji; Katabami, Kenichi; Wada, Takeshi; Minami, Yousuke; Sugano, Masahiro; Shimojima, Hidekazu; Kubota, Nobuhiko; Uegaki, Shinji; Sawamura, Atsushi; Gando, Satoshi

    2011-06-01

    Migration inhibitory factor (MIF) is associated with multiple organ dysfunction syndrome (MODS) in patients with systemic inflammatory response syndrome (SIRS). Our purposes were to determine the serum MIF, cortisol, and tumor narcosis factor-α (TNF-α) and to investigate the influences of the balance between the levels of MIF and cortisol in patients with blunt trauma. The cortisol levels were identical between the patients with and without MODS. However, the MIF and TNF-α levels in the patients with MODS were statistically higher than those of the patients without MODS. The cortisol/MIF ratios in the patients with MODS were statistically higher than those of the patients without MODS. The results show that MIF and TNF-α play an important role together in posttraumatic inflammatory response. An excessive serum MIF elevation overrides the anti-inflammatory effects of cortisol and leads to persistent SIRS followed by MODS in blunt trauma patients. PMID:20499270

  9. Impacts of test factors on heavy ion single event multiple-cell upsets in nanometer-scale SRAM

    NASA Astrophysics Data System (ADS)

    Yinhong, Luo; Fengqi, Zhang; Hongxia, Guo; Yao, Xiao; Wen, Zhao; Lili, Ding; Yuanming, Wang

    2015-11-01

    Single event multiple-cell upsets (MCU) increase sharply with the semiconductor devices scaling. The impacts of several test factors on heavy ion single event MCU in 65 nm SRAM are studied based on the buildup of MCU test data acquiring and processing technique, including the heavy ion LET, the tilt angle, the device orientation, the test pattern and the supply voltage; the MCU physical bitmaps are extracted correspondingly. The dependencies of parameters such as the MCU percentage, MCU mean and topological pattern on these factors are summarized and analyzed. This work is meaningful for developing a more reasonable single event test method and assessing the effectiveness of anti-MCU strategies on nanometer-scale devices.

  10. Multiple PAR and E4BP4 bZIP transcription factors in zebrafish: diverse spatial and temporal expression patterns.

    PubMed

    Ben-Moshe, Zohar; Vatine, Gad; Alon, Shahar; Tovin, Adi; Mracek, Philipp; Foulkes, Nicholas S; Gothilf, Yoav

    2010-09-01

    Circadian rhythms of physiology and behavior are generated by an autonomous circadian oscillator that is synchronized daily with the environment, mainly by light input. The PAR subfamily of transcriptional activators and the related E4BP4 repressor belonging to the basic leucine zipper (bZIP) family are clock-controlled genes that are suggested to mediate downstream circadian clock processes and to feedback onto the core oscillator. Here, the authors report the characterization of these genes in the zebrafish, an increasingly important model in the field of chronobiology. Five novel PAR and six novel e4bp4 zebrafish homolog genes were identified using bioinformatic tools and their coding sequences were cloned. Based on their evolutionary relationships, these genes were annotated as ztef2, zhlf1 and zhlf2, zdbp1 and zdbp2, and ze4bp4-1 to -6. The spatial and temporal mRNA expression pattern of each of these factors was characterized in zebrafish embryos in the context of a functional circadian clock and regulation by light. Nine of the factors exhibited augmented and rhythmic expression in the pineal gland, a central clock organ in zebrafish. Moreover, these genes were found to be regulated, to variable extents, by the circadian clock and/or by light. Differential expression patterns of multiple paralogs in zebrafish suggest multiple roles for these factors within the vertebrate circadian clock. This study, in the genetically accessible zebrafish model, lays the foundation for further research regarding the involvement and specific roles of PAR and E4BP4 transcription factors in the vertebrate circadian clock mechanism. PMID:20854132

  11. Determination of the QCD color factor ratio CA/CF from the scale dependence of multiplicity in three jet events

    NASA Astrophysics Data System (ADS)

    Gary, J. William

    2000-06-01

    I examine the determination of the QCD color factor ratio CA/CF from the scale evolution of particle multiplicity in e+e- three jet events. I fit an analytic expression for the multiplicity in three jet events to event samples generated with QCD multihadronic event generators. I demonstrate that a one parameter fit of CA/CF yields the expected result CA/CF=2.25 in the limit of asymptotically large energies if energy conservation is included in the calculation. In contrast, a two parameter fit of CA/CF and a constant offset to the gluon jet multiplicity, proposed in a recent study, does not yield CA/CF=2.25 in this limit. I apply the one parameter fit method to recently published data of the DELPHI experiment at the e+e- collider LEP at CERN and determine the effective value of CA/CF from this technique, at the finite energy of the Z0 boson, to be 1.74+/-0.03+/-0.10, where the first uncertainty is statistical and the second is systematic.

  12. Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma

    PubMed Central

    Lonial, Sagar; Waller, Edmund K.; Richardson, Paul G.; Jagannath, Sundar; Orlowski, Robert Z.; Giver, Cynthia R.; Jaye, David L.; Francis, Dixil; Giusti, Sara; Torre, Claire; Barlogie, Bart; Berenson, James R.; Singhal, Seema; Schenkein, David P.; Esseltine, Dixie-Lee W.; Anderson, Jessica; Xiao, Hugh; Heffner, Leonard T.; Anderson, Kenneth C.

    2005-01-01

    Bortezomib, a proteasome inhibitor with efficacy in multiple myeloma, is associated with thrombocytopenia, the cause and kinetics of which are different from those of standard cytotoxic agents. We assessed the frequency, kinetics, and mechanism of thrombocytopenia following treatment with bortezomib 1.3 mg/m2 in 228 patients with relapsed and/or refractory myeloma in 2 phase 2 trials. The mean platelet count decreased by approximately 60% during treatment but recovered rapidly between treatments in a cyclic fashion. Among responders, the pretreatment platelet count increased significantly during subsequent cycles of therapy. The mean percent reduction in platelets was independent of baseline platelet count, M-protein concentration, and marrow plasmacytosis. Plasma thrombopoietin levels inversely correlated with platelet count. Murine studies demonstrated a reduction in peripheral platelet count following a single bortezomib dose without negative effects on megakaryocytic cellularity, ploidy, or morphology. These data suggest that bortezomib-induced thrombocytopenia is due to a reversible effect on megakaryocytic function rather than a direct cytotoxic effect on megakaryocytes or their progenitors. The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be related to marrow injury or decreased thrombopoietin production. PMID:16099887

  13. Multiple factors dictate target selection by Hfq-binding small RNAs

    PubMed Central

    Beisel, Chase L; Updegrove, Taylor B; Janson, Ben J; Storz, Gisela

    2012-01-01

    Hfq-binding small RNAs (sRNAs) in bacteria modulate the stability and translational efficiency of target mRNAs through limited base-pairing interactions. While these sRNAs are known to regulate numerous mRNAs as part of stress responses, what distinguishes targets and non-targets among the mRNAs predicted to base pair with Hfq-binding sRNAs is poorly understood. Using the Hfq-binding sRNA Spot 42 of Escherichia coli as a model, we found that predictions using only the three unstructured regions of Spot 42 substantially improved the identification of previously known and novel Spot 42 targets. Furthermore, increasing the extent of base-pairing in single or multiple base-pairing regions improved the strength of regulation, but only for the unstructured regions of Spot 42. We also found that non-targets predicted to base pair with Spot 42 lacked an Hfq-binding site, folded into a secondary structure that occluded the Spot 42 targeting site, or had overlapping Hfq-binding and targeting sites. By modifying these features, we could impart Spot 42 regulation on non-target mRNAs. Our results thus provide valuable insights into the requirements for target selection by sRNAs. PMID:22388518

  14. Sequencing of LRP2 reveals multiple rare variants associated with urinary trefoil factor-3.

    PubMed

    McMahon, Gearoid M; Olden, Matthias; Garnaas, Maija; Yang, Qiong; Liu, Xuan; Hwang, Shih-Jen; Larson, Martin G; Goessling, Wolfram; Fox, Caroline S

    2014-12-01

    Novel biomarkers are being investigated to identify patients with kidney disease. We measured a panel of 13 urinary biomarkers in participants from the Offspring Cohort of the Framingham Heart Study. Using an Affymetrix chip with imputation to 2.5 M single-nucleotide polymorphisms (SNPs), we conducted a GWAS of these biomarkers (n=2640) followed by exonic sequencing and genotyping. Functional studies in zebrafish were used to investigate histologic correlation with renal function. Across all 13 biomarkers, there were 97 significant SNPs at three loci. Lead SNPs at each locus were rs6555820 (P=6.7×10(-49); minor allele frequency [MAF]=0.49) in HAVCR1 (associated with kidney injury molecule-1), rs7565788 (P=2.15×10(-16); MAF=0.22) in LRP2 (associated with trefoil factor 3 [TFF3]), and rs11048230 (P=4.77×10(-8); MAF=0.10) in an intergenic region near RASSF8 (associated with vascular endothelial growth factor). Validation in the CKDGen Consortium (n=67,093) showed that only rs7565788 at LRP2, which encodes megalin, was associated with eGFR (P=0.003). Sequencing of exons 16-72 of LRP2 in 200 unrelated individuals at extremes of urinary TFF3 levels identified 197 variants (152 rare; MAF<0.05), 31 of which (27 rare) were nonsynonymous. In aggregate testing, rare variants were associated with urinary TFF3 levels (P=0.003), and the lead GWAS signal was not explained by these variants. Knockdown of LRP2 in zebrafish did not alter the renal phenotype in static or kidney injury models. In conclusion, this study revealed common variants associated with urinary levels of TFF3, kidney injury molecule-1, and vascular endothelial growth factor and identified a cluster of rare variants independently associated with TFF3. PMID:24876117

  15. Phytic Acid: From Antinutritional to Multiple Protection Factor of Organic Systems.

    PubMed

    Silva, Elisângela O; Bracarense, Ana Paula F R L

    2016-06-01

    Several studies have shown the benefits of natural antioxidants on health and food preservation. Phytic acid (IP6) is a natural antioxidant that is found mainly in cereals and vegetables and, for a long period of time, was considered an antinutritional factor. However, in vitro and in vivo studies have demonstrated its beneficial effects in the prevention and treatment of several pathological conditions and cancer. Despite the numerous benefits of IP6, the signs and intracellular interactions mediated by this antioxidant remain poorly understood. This review describes the main chemical and biological aspects of IP6, as well as its actions in the prevention and treatment of various diseases. PMID:27272247

  16. Nanoscale content-addressable memory

    NASA Technical Reports Server (NTRS)

    Davis, Bryan (Inventor); Principe, Jose C. (Inventor); Fortes, Jose (Inventor)

    2009-01-01

    A combined content addressable memory device and memory interface is provided. The combined device and interface includes one or more one molecular wire crossbar memories having spaced-apart key nanowires, spaced-apart value nanowires adjacent to the key nanowires, and configurable switches between the key nanowires and the value nanowires. The combination further includes a key microwire-nanowire grid (key MNG) electrically connected to the spaced-apart key nanowires, and a value microwire-nanowire grid (value MNG) electrically connected to the spaced-apart value nanowires. A key or value MNGs selects multiple nanowires for a given key or value.

  17. Multiple risk factors associated with arsenic-induced skin cancer: effects of chronic liver disease and malnutritional status.

    PubMed Central

    Hsueh, Y. M.; Cheng, G. S.; Wu, M. M.; Yu, H. S.; Kuo, T. L.; Chen, C. J.

    1995-01-01

    In order to evaluate the prevalence and multiple risk factors of arsenic-induced skin cancer among residents in Taiwanese villages in which chronic arseniasis is hyperendemic, a total of 1571 subjects aged 30 or more years were recruited between September 1988 and March 1989. All of them were interviewed personally by a public health nurse using a structured questionnaire, and 1081 interviewed study subjects, including 468 men and 613 women, participated in physical examination, giving a participation rate of 68.8%. The overall prevalence of skin cancer was as high as 6.1%, showing an increase with age in both men and women. There was a significant dose-response relation between skin cancer prevalence and chronic arsenic exposure as indexed by duration of residence in the endemic area, duration of consumption of high-arsenic artesian well water, average arsenic exposure in parts per million (p.p.m.) and cumulative arsenic exposure in p.p.m.-years. Chronic carriers of hepatitis B surface antigen with liver dysfunction had an increased prevalence of skin cancer. Undernourishment, indexed by a high consumption of dried sweet potato as a staple food, was also significantly associated with an increased prevalence of arsenic-induced skin cancer. All these risk factors remained statistically significant in the multiple logistic regression analysis. Consistent with animal experiments, the findings imply that liver function and nutritional status may affect the metabolism of inorganic arsenic and the development of subsequent skin cancers. PMID:7819025

  18. Pre-B Cell Colony Enhancing Factor (PBEF), a Cytokine with Multiple Physiological Functions

    PubMed Central

    Sun, Zhongjie; Lei, Han; Zhang, Zhonge

    2013-01-01

    Pre-B cell colony enhancing factor (PBEF) is regarded as a proinflammatory cytokine. Named for its first discovered function as a pre-B cell colony enhancing factor, it has since been found to have many other functions relating to cell metabolism, inflammation, and immune modulation. It has also been found to have intracellular and extracellular forms, with the two overlapping in function. Most of the intracellular functions of PBEF are due to its role as a nicotinamide phosphoribosyltransferase (Nampt). It has been found in human endothelial cells, where it is able to induce angiogenesis through upregulation of VEGF and VEGFR and secretion of MCP-1. In human umbilical endothelial cells, PBEF increases levels of the protease MMP 2/9. PBEF has also been found in a variety of immune cells other than B cells and has been shown to inhibit apoptosis of macrophages. Extracellular PBEF has been shown to increase inflammatory cytokines, such as TNF-α, IL-1β, IL-16, and TGF-β1, and the chemokine receptor CCR3. PBEF also increases the production of IL-6, TNF-α, and IL-1β in CD14+ monocyctes, macrophages, and dendritic cells, enhances the effectiveness of T cells, and is vital to the development of both B and T lymphocytes. The purpose of this review is to summarize the recent advances in PBEF research. PMID:23787158

  19. Multiple conversion between the genes encoding bacterial class-I release factors

    PubMed Central

    Ishikawa, Sohta A.; Kamikawa, Ryoma; Inagaki, Yuji

    2015-01-01

    Bacteria require two class-I release factors, RF1 and RF2, that recognize stop codons and promote peptide release from the ribosome. RF1 and RF2 were most likely established through gene duplication followed by altering their stop codon specificities in the common ancestor of extant bacteria. This scenario expects that the two RF gene families have taken independent evolutionary trajectories after the ancestral gene duplication event. However, we here report two independent cases of conversion between RF1 and RF2 genes (RF1-RF2 gene conversion), which were severely examined by procedures incorporating the maximum-likelihood phylogenetic method. In both cases, RF1-RF2 gene conversion was predicted to occur in the region encoding nearly entire domain 3, of which functions are common between RF paralogues. Nevertheless, the ‘direction’ of gene conversion appeared to be opposite from one another—from RF2 gene to RF1 gene in one case, while from RF1 gene to RF2 gene in the other. The two cases of RF1-RF2 gene conversion prompt us to propose two novel aspects in the evolution of bacterial class-I release factors: (i) domain 3 is interchangeable between RF paralogues, and (ii) RF1-RF2 gene conversion have occurred frequently in bacterial genome evolution. PMID:26257102

  20. A Pilot Study on Factors Involved with Work Participation in the Early Stages of Multiple Sclerosis

    PubMed Central

    Van der Hiele, Karin; Middelkoop, Huub A. M.; Ruimschotel, Rob; Kamminga, Noëlle G. A.; Visser, Leo H.

    2014-01-01

    Background Up to 30% of recently diagnosed MS patients lose their jobs in the first four years after diagnosis. Taking into account the personal and socio-economic importance of sustaining employment, it is of the utmost importance to examine factors involved with work participation. Objective To investigate differences in self-reported functioning in recently diagnosed MS patients with and without a paid job. Methods Self-reports of physical and cognitive functioning, depression, anxiety and fatigue were gathered from 44 relapsing-remitting MS patients diagnosed within 3 years. Results Patients with a paid job (57%) reported better physical functioning (p<0.001), better memory functioning (p = 0.01) and a lower physical impact of fatigue (p = 0.018) than patients without a paid job. Physical functioning was the main predictor of employment status in a logistic regression model. In those with a paid job better memory functioning (r = 0.54, p = 0.005) and a lower social impact of fatigue (r = −0.46, p = 0.029) correlated with an increased number of working hours. Conclusion Better physical functioning is the primary factor involved with increased work participation in early MS. Better self-reported memory functioning and less social fatigue were associated with increased working hours. These findings highlight the importance of battling these symptoms in the early stages of MS. PMID:25153710

  1. Risk Factors Associated with the Onset of Relapsing-Remitting and Primary Progressive Multiple Sclerosis: A Systematic Review

    PubMed Central

    McKay, Kyla A.; Kwan, Vivian; Duggan, Thomas; Tremlett, Helen

    2015-01-01

    Multiple sclerosis (MS) is a chronic central nervous system disease with a highly heterogeneous course. The aetiology of MS is not well understood but is likely a combination of both genetic and environmental factors. Approximately 85% of patients present with relapsing-remitting MS (RRMS), while 10–15% present with primary progressive MS (PPMS). PPMS is associated with an older onset age, a different sex ratio, and a considerably more rapid disease progression relative to RRMS. We systematically reviewed the literature to identify modifiable risk factors that may be associated with these different clinical courses. We performed a search of six databases and integrated twenty observational studies into a descriptive review. Exposure to Epstein-Barr virus (EBV) appeared to increase the risk of RRMS, but its association with PPMS was less clear. Other infections, such as human herpesvirus-6 and chlamydia pneumoniae, were not consistently associated with a specific disease course nor was cigarette smoking. Despite the vast literature examining risk factors for the development of MS, relatively few studies reported findings by disease course. This review exposes a gap in our understanding of the risk factors associated with the onset of PPMS, our current knowledge being predominated by relapsing-onset MS. PMID:25802867

  2. Multiple sclerosis and environmental factors: the role of vitamin D, parasites, and Epstein-Barr virus infection.

    PubMed

    Correale, J; Gaitán, M I

    2015-01-01

    Pathogenic mechanisms underlying multiple sclerosis development have yet to be clearly identified, but considerable evidence indicates that autoimmunity plays an important role in the etiology of the disease. It is generally accepted that autoimmune diseases like MS arise from complex interactions between genetic susceptibility and environmental factors. Although environmental factors unequivocally influencing MS development have yet to be established, accumulating evidence singles out several candidates, including sunlight-UV exposure or vitamin D deficiency, viral infections, hygiene, and cigarette smoking. Vitamin D deficiency has been associated with different autoimmune diseases. Several investigations indicate 125 (OH)2 vitamin D plays a critical role in shaping T-cell response and inducing T cells with immunosuppressive properties. Likewise, helminth infections represent another potential environmental factor exerting immunomodulatory properties. Both epidemiological and experimental data provide evidence to support autoimmune down-regulation secondary to parasite infections in patients with MS, through regulatory T- and B-cell action, with effects extending beyond simple response to an infectious agent. Finally, different epidemiological studies have demonstrated that Epstein-Barr virus infection confers added risk of developing MS. Proposed mechanisms responsible for this association include activation and expansion of self-reactive T and B cells, lower threshold for self-tolerance breakdown, and enhanced autoreactive B-cell survival, all to be discussed in this review. Understanding environmental factors influencing propensity to MS will lead to new and more effective approaches to prevent and treat the disease. PMID:26046559

  3. Navigating the “liberation procedure”: a qualitative study of motivating and hesitating factors among people with multiple sclerosis

    PubMed Central

    Ploughman, Michelle; Harris, Chelsea; Hogan, Stephen H; Murray, Cynthia; Murdoch, Michelle; Austin, Mark W; Stefanelli, Mark

    2014-01-01

    Background The debate within the multiple sclerosis (MS) community initiated by the chronic cerebrospinal venous insufficiency (CCSVI) hypothesis and the subsequent liberation procedure placed some people with MS at odds with health care professionals and researchers. Objective This study explored decision making regarding the controversial liberation procedure among people with MS. Subjects and methods Fifteen people with MS (procedure, n=7; no procedure, n=8) participated in audiotaped semistructured interviews exploring their thoughts and experiences related to the liberation procedure. Data were transcribed and analyzed using an iterative, consensus-based, thematic content-analysis approach. Results Participants described an imbalance of motivating factors affirming the procedure compared to hesitating factors that provoked the participant to pause or reconsider when deciding to undergo the procedure. Collegial conversational relationships with trusted sources (eg, MS nurse, neurologist) and ability to critically analyze the CCSVI hypothesis were key hesitating factors. Fundraising, family enthusiasm, and the ease of navigation provided by medical tourism companies helped eliminate barriers to the procedure. Conclusion Knowledge of factors that helped to popularize the liberation procedure in Canada may inform shared decision making concerning this and future controversies in MS. PMID:25228799

  4. The prognostic factors and multiple biomarkers in young patients with colorectal cancer

    PubMed Central

    Wang, Mo-Jin; Ping, Jie; Li, Yuan; Adell, Gunnar; Arbman, Gunnar; Nodin, Bjorn; Meng, Wen-Jian; Zhang, Hong; Yu, Yong-Yang; Wang, Cun; Yang, Lie; Zhou, Zong-Guang; Sun, Xiao-Feng

    2015-01-01

    The incidence of colorectal cancer (CRC) in young patients (≤50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linköping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients. PMID:26013439

  5. Multiple organ damage caused by tumor necrosis factor and prevented by prior neutrophil depletion

    SciTech Connect

    Mallick, A.A.; Ishizaka, A.; Stephens, K.E.; Hatherill, J.R.; Tazelaar, H.D.; Raffin, T.A. )

    1989-05-01

    The effect of TNF on nonpulmonary multiple organ damage (MOD) was studied. Since polymorphonuclear leukocytes (PMN) are thought to play an important role in septic or TNF-induced MOD, we investigated both neutrophil sufficient (PMN+) and neutropenic (PMN-) guinea pigs. Sepsis was induced by Escherichia coli administration (2 x 10(9)/kg) or recombinant human TNF (1.4 x 10(6) U/kg) was infused into PMN+ and PMN- guinea pigs. During necropsy, the PMN+/TNF and PMN+/E coli animals exhibited marked damage in the adrenal glands, kidneys and liver as evidenced by hemorrhage, congestion, and PMN sequestration on histopathologic examination. There was also increased tissue albumin accumulation in the adrenal glands, kidneys, spleen, heart, and liver as demonstrated by {sup 125}I-labeled albumin determinations. In contrast, the PMN-/TNF group did not reveal histopathologic damage in any organ system and there was no abnormal organ accumulation of {sup 125}I-albumin. However, in PMN-/E coli animals, marked histopathologic damage in the adrenal glands and liver was evident. Furthermore, there were marked accumulations of {sup 125}I-albumin in the adrenals, heart, kidneys, liver, and spleen. Moreover, the PMN-/E coli guinea pigs had a much greater accumulation (p less than 0.01) of {sup 125}I-albumin in the kidneys than any other group including the PMN+/E coli group. Thus, nonpulmonary MOD in guinea pigs is caused by TNF administration and can be prevented by PMN depletion. However, while E coli administration also caused marked nonpulmonary MOD in neutrophil sufficient guinea pigs, equivalent or greater damage was produced in neutropenic animals. This suggests that while TNF-induced MOD may be primarily mediated by PMN, E coli-induced MOD seems to be mediated by more than PMN.

  6. Multiple factors affect diversity and abundance of ammonia-oxidizing microorganisms in iron mine soil.

    PubMed

    Xing, Yi; Si, Yan-Xiao; Hong, Chen; Li, Yang

    2015-07-01

    Ammonia oxidation by microorganisms is a critical process in the nitrogen cycle. In this study, four soil samples collected from a desert zone in an iron-exploration area and others from farmland and planted forest soil in an iron mine surrounding area. We analyzed the abundance and diversity of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in iron-mining area near the Miyun reservoir using ammonia monooxygenase. A subunit gene (amoA) as molecular biomarker. Quantitative polymerase chain reaction was applied to explore the relationships between the abundance of AOA and AOB and soil physicochemical parameters. The results showed that AOA were more abundant than AOB and may play a more dominant role in the ammonia-oxidizing process in the whole region. PCR-denaturing gradient gel electrophoresis was used to analyze the structural changes of AOA and AOB. The results showed that AOB were much more diverse than AOA. Nitrosospira cluster three constitute the majority of AOB, and AOA were dominated by group 1.1b in the soil. Redundancy analysis was performed to explore the physicochemical parameters potentially important to AOA and AOB. Soil characteristics (i.e. water, ammonia, organic carbon, total nitrogen, available phosphorus, and soil type) were proposed to potentially contribute to the distributions of AOB, whereas Cd was also closely correlated to the distributions of AOB. The community of AOA correlated with ammonium and water contents. These results highlight the importance of multiple drivers in microbial niche formation as well as their affect on ammonia oxidizer composition, both which have significant consequences for ecosystem nitrogen functioning. PMID:25860433

  7. Factors predicting depression across multiple domains in a national longitudinal sample of Canadian youth.

    PubMed

    Bellamy, Sherry; Hardy, Cindy

    2015-05-01

    This prospective longitudinal study aimed to investigate the strength and relative importance of multiple predictors of depression in youth aged 16 to 20 years. Data were drawn from Statistics Canada's National Longitudinal Survey of Children and Youth (Statistics Canada 2007a, b). Hierarchical regressions were conducted separately by child gender (N = 796 boys; N = 919 girls) for two overlapping samples: mixed parent-child dyads (e.g., biological mothers, fathers and other caregivers; N = 1,715) and a subsample containing only biological mother-child dyads (N = 1,425). Parent-reported data were used from Cycle 1 when the children were aged 4 to 8 years. Parent and child-reported data were used from Cycle 4 when children were aged 10 to 14 years. The outcome measure of depressive symptoms was taken from Cycle 7 when the youth were aged 16 to 20 years. Adolescents reported more depression symptoms than young adults and girls reported more than boys. For boys, higher anxiety/depression scores at ages 4 to 8 years and 10 to 14 years, along with lower self-esteem at 10 to 14 years, predicted higher depression scores. Girls' depression was predicted by loss of a parent by ages 4 to 8 years and higher self-reported anxiety/depression and aggression at ages 10 to 14 years. Among biological mother-child dyads, maternal depression reported by mother when child was aged 4 to 8 years and 10 to 14 years significantly predicted depression for girls. At 10 to 14 years, child-reported lower parental monitoring (girls only) and greater parental rejection (boys and girls) predicted depression at ages 16 to 20 years. PMID:25240908

  8. Addressivity in cogenerative dialogues

    NASA Astrophysics Data System (ADS)

    Hsu, Pei-Ling

    2014-03-01

    Ashraf Shady's paper provides a first-hand reflection on how a foreign teacher used cogens as culturally adaptive pedagogy to address cultural misalignments with students. In this paper, Shady drew on several cogen sessions to showcase his journey of using different forms of cogens with his students. To improve the quality of cogens, one strategy he used was to adjust the number of participants in cogens. As a result, some cogens worked and others did not. During the course of reading his paper, I was impressed by his creative and flexible use of cogens and at the same time was intrigued by the question of why some cogens work and not others. In searching for an answer, I found that Mikhail Bakhtin's dialogism, especially the concept of addressivity, provides a comprehensive framework to address this question. In this commentary, I reanalyze the cogen episodes described in Shady's paper in the light of dialogism. My analysis suggests that addressivity plays an important role in mediating the success of cogens. Cogens with high addressivity function as internally persuasive discourse that allows diverse consciousnesses to coexist and so likely affords productive dialogues. The implications of addressivity in teaching and learning are further discussed.

  9. Multiple cis elements and GATA factors regulate a cuticle collagen gene in C. elegans

    PubMed Central

    Yin, Jianghua; Madaan, Uday; Park, Amy; Aftab, Neelum; Savage-Dunn, Cathy

    2015-01-01

    The cuticle of the nematode Caenorhabditis elegans is a specialized extracellular matrix whose major component is collagen. Cuticle collagens are encoded by a large multi-gene family consisting of more than 150 members. Cuticle collagen genes are expressed in epidermis (hypodermis) and may be stage-specific or cyclically expressed. We identified cuticle collagen genes as transcriptional targets of the DBL-1 TGF-β-related signaling pathway. These studies prompted us to investigate the cis-regulatory sequences required for transcription of one of the target genes, col-41. We generated reporter constructs that reproduce stage- and tissue-specific expression of fluorescent markers. We identify four conserved sequence elements that are required for transcription of reporters. Finally, we provide evidence that col-41 expression is controlled by a sequence element containing two GATA sites and by the epidermal GATA transcription factors ELT-1 and ELT-3. PMID:25711168

  10. "It takes a village" to support the vocabulary development of children with multiple risk factors.

    PubMed

    Baydar, Nazli; Küntay, Aylin C; Yagmurlu, Bilge; Aydemir, Nuran; Cankaya, Dilek; Göksen, Fatos; Cemalcilar, Zeynep

    2014-04-01

    Data from a nationally representative sample from Turkey (N = 1,017) were used to investigate the environmental factors that support the receptive vocabulary of 3-year-old children who differ in their developmental risk due to family low economic status and elevated maternal depressive symptoms. Children's vocabulary knowledge was strongly associated with language stimulation and learning materials in all families regardless of risk status. Maternal warmth and responsiveness supported vocabulary competence in families of low economic status only when maternal depressive symptoms were low. In families with the highest levels of risk, that is, with depression and economic distress jointly present, support by the extended family and neighbors for caring for the child protected children's vocabulary development against these adverse conditions. The empirical evidence on the positive contribution of extrafamilial support to young children's receptive vocabulary under adverse conditions allows an expansion of our current theorizing about influences on language development. PMID:24188041

  11. Apparatus for measuring the decontamination factor of a multiple filter air-cleaning system

    DOEpatents

    Ortiz, J.P.

    1985-07-03

    An apparatus for measuring the overall decontamination factors of first and second filters located in a plenum. The first filter separates the plenum's upstream and intermediate chambers. The second filter separates the plenum's intermediate and downstream chambers. The apparatus comprises an aerosol generator that generates a challenge aerosol. An upstream collector collects unfiltered aerosol which is piped to first and second dilution stages and then to a laser aerosol spectrometer. An intermediate collector collects challenge aerosol that penetrates the first filter. The filtered aerosol is piped to the first dilution stage, diluted, and then piped to the laser aerosol spectrometer which detects single particles. A downstream collector collects challenge aerosol that penetrates both filters. The twice-filtered aerosol is piped to the aerosol spectrometer. A pump and several valves control the movement of aerosol within the apparatus.

  12. Apparatus for measuring the decontamination factor of a multiple filter air-cleaning system

    DOEpatents

    Ortiz, John P.

    1986-01-01

    An apparatus for measuring the overall decontamination factor of first and second filters located in a plenum. The first filter separates the plenum's upstream and intermediate chambers. The second filter separates the plenum's intermediate and downstream chambers. The apparatus comprises an aerosol generator that generates a challenge aerosol. An upstream collector collects unfiltered aerosol which is piped to first and second dilution stages and then to a laser aerosol spectrometer. An intermediate collector collects challenge aerosol that penetrates the first filter. The filtered aerosol is piped to the first dilution stage, diluted, and then piped to the laser aerosol spectrometer which detects single particles. A downstream collector collects challenge aerosol that penetrates both filters. The twice-filtered aerosol is piped to the aerosol spectrometer. A pump and several valves control the movement of aerosol within the apparatus.

  13. Multiple identification and risks: examination of peer factors across multiracial and single-race youth.

    PubMed

    Choi, Yoonsun; He, Michael; Herrenkohl, Todd I; Catalano, Richard F; Toumbourou, John W

    2012-07-01

    Multiracial youth are thought to be more vulnerable to peer-related risk factors than are single-race youth. However, there have been surprisingly few well-designed studies on this topic. This study empirically investigated the extent to which multiracial youth are at higher risk for peer influenced problem behavior. Data are from a representative and longitudinal sample of youth from Washington State (N = 1,760, mean age = 14.13, 50.9% girls). Of those in the sample, 225 youth self-identified as multiracial (12.8%), 1,259 as White (71.5%), 152 as Latino (8.6%), and 124 as Asian American (7.1%). Results show that multiracial youth have higher rates of violence and alcohol use than Whites and more marijuana use than Asian Americans. Higher levels of socioeconomic disadvantage and single-parent family status partly explained the higher rates of problem behaviors among multiracial youth. Peer risk factors of substance-using or antisocial friends were higher for multiracial youth than Whites, even after socioeconomic variables were accounted for, demonstrating a higher rate of peer risks among multiracial youth. The number of substance-using friends was the most consistently significant correlate and predictor of problems and was highest among multiracial youth. However, interaction tests did not provide consistent evidence of a stronger influence of peer risks among multiracial youth. Findings underscore the importance of a differentiated understanding of vulnerability in order to better target prevention and intervention efforts as well as the need for further research that can help identify and explain the unique experiences and vulnerabilities of multiracial youth. PMID:22395776

  14. Relative importance of multiple factors on terrestrial loading of DOC to Arctic river networks

    SciTech Connect

    Kicklighter, David W.; Hayes, Daniel J; Mcclelland, James W; Peterson, Bruce; Mcguire, David; Melillo, Jerry

    2014-01-01

    Terrestrial carbon dynamics influence the contribution of dissolved organic carbon (DOC) to river networks in addition to controlling carbon fluxes between the land surface and the atmosphere. In this study, we use a biogeochemical process model to simulate the lateral transfer of DOC from land to the Arctic Ocean via riverine transport. We estimate that the pan-arctic watershed has contributed, on average, 32 Tg C/yr of DOC to the Arctic Ocean over the 20th century with most coming from the extensive area of boreal deciduous needle-leaved forests and forested wetlands in Eurasian watersheds. We also estimate that the rate of terrestrial DOC loading has been increasing by 0.037 Tg C/yr2 over the 20th century primarily as a result of increases in air temperatures and precipitation. These increases have been partially compensated by decreases in terrestrial DOC loading caused by wildfires. Other environmental factors (CO2 fertilization, ozone pollution, atmospheric nitrogen deposition, timber harvest, agriculture) are estimated to have relatively small effects on terrestrial DOC loading to arctic rivers. The effects of the various environmental factors on terrestrial carbon dynamics have both compensated and enhanced concurrent effects on hydrology to influence terrestrial DOC loading. Future increases in riverine DOC concentrations and export may occur from warming-induced increases in terrestrial DOC production associated with enhanced microbial metabolism and the exposure of additional organic matter from permafrost degradation along with decreases in water yield associated with warming-induced increases in evapotranspiration. Improvements in simulating terrestrial DOC loading to pan-arctic rivers in the future will require better information on the spatial distribution of precipitation and its temporal trends, carbon dynamics of larch-dominated ecosystems in eastern Siberia, and the role of industrial organic effluents on carbon budgets of rivers in western

  15. Vascular Factors and Multiple Measures of Early Brain Health: CARDIA Brain MRI Study

    PubMed Central

    Launer, Lenore J.; Lewis, Cora E.; Schreiner, Pamela J.; Sidney, Steve; Battapady, Harsha; Jacobs, David R.; Lim, Kelvin O.; D’Esposito, Mark; Zhang, Qian; Reis, Jared; Davatzikos, Christos; Bryan, R. Nick

    2015-01-01

    Objective To identify early changes in brain structure and function that are associated with cardiovascular risk factors (CVRF). Design Cross-sectional brain Magnetic Resonance I (MRI) study. Setting Community based cohort in three U.S. sites. Participants A Caucasian and African-American sub-sample (n= 680; mean age 50.3 yrs) attending the 25 year follow-up exam of the Coronary Artery Risk Development in Young Adults Study. Primary and Secondary Outcomes 3T brain MR images processed for quantitative estimates of: total brain (TBV) and abnormal white matter (AWM) volume; white matter fractional anisotropy (WM-FA); and gray matter cerebral blood flow (GM-CBF). Total intracranial volume is TBV plus cerebral spinal fluid (TICV). A Global Cognitive Function (GCF) score was derived from tests of speed, memory and executive function. Results Adjusting for TICV and demographic factors, current smoking was significantly associated with lower GM-CBF and TBV, and more AWM (all <0.05); SA with lower GM-CBF, WM-FA and TBV (p=0.01); increasing BMI with decreasing GM-CBF (p<0003); hypertension with lower GM-CBF, WM-FA, and TBV and higher AWM (all <0.05); and diabetes with lower TBV (p=0.007). The GCS was lower as TBV decreased, AWM increased, and WM-FA (all p<0.01). Conclusion In middle age adults, CVRF are associated with brain health, reflected in MRI measures of structure and perfusion, and cognitive functioning. These findings suggest markers of mid-life cardiovascular and brain health should be considered as indication for early intervention and future risk of late-life cerebrovascular disease and dementia. PMID:25812012

  16. Six-Minute Walk Test for Persons with Mild or Moderate Disability from Multiple Sclerosis: Performance and Explanatory Factors

    PubMed Central

    Fry, Donna K.; Pfalzer, Lucinda A.

    2011-01-01

    ABSTRACT Purpose: The primary purpose of this study was to determine the extent to which health factors, functional measures, and pulmonary impairment explain performance on 6-Minute Walk Test (6MWT) distance in ambulatory persons with multiple sclerosis (MS). Another purpose was to determine the effect of disability and age on 6MWT performance and explanatory factors. Methods: A cross-sectional study design was used to evaluate factors that explain performance on the 6MWT in 64 community-dwelling persons with MS-related disability (Expanded Disability Status Scale [EDSS] 3.8±1.6). Of the 64 participants, 43 (67.2%) exhibited mild disability (EDSS <4.0) and 21 (32.8%) had moderate disability (EDSS 4.0–6.5). A regression analysis compared 6MWT performance to measures of health factors (EDSS, number of medications, number of comorbidities, resting HR, systolic and diastolic blood pressure [BP]); physical performance (functional stair test [FST], sit-to-stand test [SST], static standing balance [BAL], Fatigue Severity Scale [FSS], Activities-specific Balance Confidence [ABC] Scale); and pulmonary function (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], maximal voluntary ventilation [MVV], maximal inspiratory pressure [MIP], maximal expiratory pressure [MEP]). Results: EDSS, ABC, FST, SST, BAL, MVV, MIP, and MEP were significantly associated with 6MWT distance after adjusting for age. Multiple step-wise linear regression analysis revealed that ABC, FST, and BAL were significant and independent explanatory factors of 6MWT distance. ABC and FST explained 75% of the variance in 6MWT performance (R2=0.75). Curvilinear regression analysis revealed that the FST is the most significant explanatory factor for 6MWT distance, explaining 79% of the variance (R2=0.79). Conclusions: 6MWT performance in persons with MS was explained by balance confidence (ABC) and stair-climbing ability (FST). The ABC and FST may be practical clinical measures for

  17. Nuclear factor-κB regulates the expression of multiple genes encoding liver transport proteins.

    PubMed

    Balasubramaniyan, Natarajan; Ananthanarayanan, Meenakshisundaram; Suchy, Frederick J

    2016-04-15

    In this study we identified the mechanisms underlying the inhibitory effects of NF-κB on the expression of genes encoding multiple liver transport proteins. Well-conserved NF-κB binding sites were found in the promoters of farnesoid X receptor (FXR)-target genes. An electromobility shift assay (EMSA) demonstrated the specific interaction between the NF-κB p65 protein and a (32)P-labeled BSEP NF-κB response element (NF-κBE). Chromatin immunoprecipitation (ChIP) analysis confirmed binding of NF-κB p65 to the BSEP locus but not the FXRE in vitro. NF-κB p65 overexpression in Huh-7 cells markedly repressed FXR/RXR transactivation of the BSEP, ABCG5/G8, MRP2, and FXR promoters, which was totally reversed by expression of the IκBα super-repressor. NF-κB interacted directly with FXR on coimmunoprecipitation, suggesting another level for the inhibitory effects of NF-κB on FXR-target genes. In vivo ChIP analysis with liver nuclei obtained from mice after 3 days of common bile duct ligation (BDL) or 6 h post-lipopolysaccharide (LPS) injection showed a markedly increased recruitment of NF-κB p65 to the Bsep promoter compared with controls. There was also increased recruitment of the corepressor silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) and histone deacetylase (HDAC)3 and HDAC2 to the NF-κB sites. We also found that NF-κB p65 was recruited to NF-κB binding sites in the promoters of organic solute transporter, OSTα and OSTβ, and unexpectedly activated rather than repressed gene expression. In mouse liver after BDL NF-κB recruitment to Ostα and Ostβ promoters was associated with increased binding of the potent coactivator cAMP response element binding protein (CREB)-binding protein (CBP)/p300 to the NF-κBE and depletion of CBP/p300 at the FXR element. Overall, these studies demonstrate a novel role for NF-κB in adaptation to obstructive and LPS-induced cholestasis acting through recruitment to specific NF-κB binding sites in

  18. Structural basis for activation of trimeric Gi proteins by multiple growth factor receptors via GIV/Girdin

    PubMed Central

    Lin, Changsheng; Ear, Jason; Midde, Krishna; Lopez-Sanchez, Inmaculada; Aznar, Nicolas; Garcia-Marcos, Mikel; Kufareva, Irina; Abagyan, Ruben; Ghosh, Pradipta

    2014-01-01

    A long-standing issue in the field of signal transduction is to understand the cross-talk between receptor tyrosine kinases (RTKs) and heterotrimeric G proteins, two major and distinct signaling hubs that control eukaryotic cell behavior. Although stimulation of many RTKs leads to activation of trimeric G proteins, the molecular mechanisms behind this phenomenon remain elusive. We discovered a unifying mechanism that allows GIV/Girdin, a bona fide metastasis-related protein and a guanine-nucleotide exchange factor (GEF) for Gαi, to serve as a direct platform for multiple RTKs to activate Gαi proteins. Using a combination of homology modeling, protein–protein interaction, and kinase assays, we demonstrate that a stretch of ∼110 amino acids within GIV C-terminus displays structural plasticity that allows folding into a SH2-like domain in the presence of phosphotyrosine ligands. Using protein–protein interaction assays, we demonstrated that both SH2 and GEF domains of GIV are required for the formation of a ligand-activated ternary complex between GIV, Gαi, and growth factor receptors and for activation of Gαi after growth factor stimulation. Expression of a SH2-deficient GIV mutant (Arg 1745→Leu) that cannot bind RTKs impaired all previously demonstrated functions of GIV—Akt enhancement, actin remodeling, and cell migration. The mechanistic and structural insights gained here shed light on the long-standing questions surrounding RTK/G protein cross-talk, set a novel paradigm, and characterize a unique pharmacological target for uncoupling GIV-dependent signaling downstream of multiple oncogenic RTKs. PMID:25187647

  19. Protection by and anti-oxidant mechanism of berberine against rat liver fibrosis induced by multiple hepatotoxic factors.

    PubMed

    Zhang, Ben-Jian; Xu, Dan; Guo, Yu; Ping, Jie; Chen, Liao-Bin; Wang, Hui

    2008-03-01

    1. The aim of the present study was to investigate the effect and mechanism of berberine, an alkaloid extracted from the traditional Chinese medicine coptis, on rat liver fibrosis induced by multiple hepatotoxic factors. 2. Male Wistar rats were separated into five groups, a normal control group, a fibrotic control group and fibrotic groups treated with three different doses of berberine. The fibrotic models were established by introduction of multiple hepatotoxic factors, including CCl(4), ethanol and high cholesterol. Rats in the treatment groups were administered 50, 100 or 200 mg/kg berberine, intragastrically, daily for 4 weeks. Serum levels of alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST), hepatic activity of superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) and hepatic hydroxyproline (Hyp) content were determined. Liver biopsies were obtained for histological and immunohistochemical studies to detect the expressions of alpha-smooth muscle actin (SMA) and transforming growth factor (TGF)-beta1. 3. The results showed that, compared with the fibrotic control group, serum levels of ALT and AST and hepatic content of MDA and Hyp were markedly decreased, but the activity of hepatic SOD was significantly increased in berberine-treated groups in a dose-dependent manner. In addition, histopathological changes, such as steatosis, necrosis and myofibroblast proliferation, were reduced and the expression of a-SMA and TGF-b1 was significantly downregulated in the berberine-treated groups (P < 0.01). 4. These results suggest that berberine could be used to prevent experimental liver fibrosis through regulation of the anti-oxidant system and lipid peroxidation. PMID:17973934

  20. Multiple Sexual Partners as a Potential Independent Risk Factor for Cervical Cancer: a Meta-analysis of Epidemiological Studies.

    PubMed

    Liu, Zhi-Chang; Liu, Wei-Dong; Liu, Yan-Hui; Ye, Xiao-Hua; Chen, Si-Dong

    2015-01-01

    It's known that having multiple sexual partners is one of the risk factors of human papillomavirus (HPV) infection which is a major cause of cervical cancer. However, it is not clear whether the number of sexual partners is an independent risk factor for cervical cancer. We identified relevant studies by searching the databases of MEDLINE, PubMed and ScienceDirect published in English from January 1980 to January 2014. We analyzed those studies by combining the study-specific odds ratios (ORs) using random-effects models. Forty-one studies were included in this meta-analysis. We observed that the number of sexual partners was associated with the occurrence of non-malignant cervical disease (OR=1.82, 95%CI 1.63-2.00) and invasive cervical carcinoma (OR=1.77, 95%CI 1.50-2.05). Subgroup analyses revealed that the association remained significant after controlling for HPV infection (OR=1.52, 95%CI 1.21-1.83 for non-malignant disease; OR=1.53, 95%CI 1.30- 1.76 for invasive cervical carcinoma). We found that there was a non-linear relation of the number of sexual partners with both non-malignant cervical disease and invasive cervical carcinoma. The risk of both malignant and non-malignant disease is relatively stable in women with more than 4-7 sexual partners. Furthermore, the frequency-risk of disease remained significant after controlling for HPV infection.The study suggested that having multiple sexual partners, with or without HPV infection, is a potential risk factor of cervical cancer. PMID:25987056

  1. Inherited prion disease with 4-octapeptide repeat insertion: disease requires the interaction of multiple genetic risk factors.

    PubMed

    Kaski, Diego N; Pennington, Catherine; Beck, Jon; Poulter, Mark; Uphill, James; Bishop, Matthew T; Linehan, Jaqueline M; O'Malley, Catherine; Wadsworth, Jonathan D F; Joiner, Susan; Knight, Richard S G; Ironside, James W; Brandner, Sebastian; Collinge, John; Mead, Simon

    2011-06-01

    Genetic factors are implicated in the aetiology of sporadic late-onset neurodegenerative diseases. Whether these genetic variants are predominantly common or rare, and how multiple genetic factors interact with each other to cause disease is poorly understood. Inherited prion diseases are highly heterogeneous and may be clinically mistaken for sporadic Creutzfeldt-Jakob disease because of a negative family history. Here we report our investigation of patients from the UK with four extra octapeptide repeats, which suggest that the risk of clinical disease is increased by a combination of the mutation and a susceptibility haplotype on the wild-type chromosome. The predominant clinical syndrome is a progressive cortical dementia with pyramidal signs, myoclonus and cerebellar abnormalities that closely resemble sporadic Creutzfeldt-Jakob disease. Autopsy shows perpendicular deposits of prion protein in the molecular layer of the cerebellum. Identity testing, PRNP microsatellite haplotyping and genealogical work confirm no cryptic close family relationships and suggests multiple progenitor disease haplotypes. All patients were homozygous for methionine at polymorphic codon 129. In addition, at a single nucleotide polymorphism upstream of PRNP thought to confer susceptibility to sporadic Creutzfeldt-Jakob disease (rs1029273), all patients were homozygous for the risk allele (combined P=5.9×10(-5)). The haplotype identified may also be a risk factor in other partially penetrant inherited prion diseases although it does not modify age of onset. Blood expression of PRNP in healthy individuals was modestly higher in carriers of the risk haplotype. These findings may provide a precedent for understanding apparently sporadic neurodegenerative diseases caused by rare high-risk mutations. PMID:21616973

  2. The soybean GmbZIP1 transcription factor enhances multiple abiotic stress tolerances in transgenic plants.

    PubMed

    Gao, Shi-Qing; Chen, Ming; Xu, Zhao-Shi; Zhao, Chang-Ping; Li, Liancheng; Xu, Hui-jun; Tang, Yi-miao; Zhao, Xin; Ma, You-Zhi

    2011-04-01

    Abscisic acid (ABA)-responsive element binding proteins (AREBs) are basic domain/leucine zipper transcription factors that bind to the ABA-responsive element (ABRE) in the promoter regions of ABA-inducible genes in plants. A novel bZIP transcription factor gene, GmbZIP1, encoding 438 amino acids with a conserved bZIP domain composed of 60 amino acids was isolated from salt-tolerant soybean cv. Tiefeng 8. Southern blotting showed that only one copy was present in the soybean genome. Phylogenetic analyses showed that GmbZIP1 belonged to the AREB subfamily of the bZIP family and was most closely related to AtABF2 and OsTRAB1. The expression of GmbZIP1 was highly induced by ABA, drought, high salt and low temperature; and GmbZIP1 was expressed in soybean roots, stems and leaves under different stress conditions. GmbZIP1 was localized inside the nuclei of transformed onion epidermal cells. Overexpression of GmbZIP1 enhanced the responses of transgenic plants to ABA and triggered stomatal closure under stresses, potentially leading to improved tolerances to several abiotic stresses such as high salt, low temperature and drought in transgenic plants. Furthermore, overexpression of GmbZIP1 affected the expression of some ABA or stress-related genes involved in regulating stomatal closure in Arabidopsis under ABA, drought and high salt stress conditions. A few AREB elements were detected in the promoter region of those ABA or stress-related genes, suggesting that GmbZIP1 regulates the ABA response or stomatal closure mediated by those downstream genes in transgenic Arabidopsis. Moreover, GmbZIP1 was used to improve the drought tolerance trait of Chinese wheat varieties BS93. Functional analysis showed that overexpression of GmbZIP1 enhanced the drought tolerance of transgenic wheat, and transcripts of GmbZIP1 were detected in transgenic wheat using RT-PCR. In addition, GmbZIP1 overexpression did not result in growth retardation in all transgenic plants, suggesting that Gmb

  3. Maintenance of Tissue Pluripotency by Epigenetic Factors Acting at Multiple Levels

    PubMed Central

    Sadasivam, Devendran A.; Huang, Der-Hwa

    2016-01-01

    Pluripotent stem cells often adopt a unique developmental program while retaining certain flexibility. The molecular basis of such properties remains unclear. Using differentiation of pluripotent Drosophila imaginal tissues as assays, we examined the contribution of epigenetic factors in ectopic activation of Hox genes. We found that over-expression of Trithorax H3K4 methyltransferase can induce ectopic adult appendages by selectively activating the Hox genes Ultrabithorax and Sex comb reduced in wing and leg discs, respectively. This tissue-specific inducibility correlates with the presence of paused RNA polymerase II in the promoter-proximal region of these genes. Although the Antennapedia promoter is paused in eye-antenna discs, it cannot be induced by Trx without a reduction in histone variants or their chaperones, suggesting additional control by the nucleosomal architecture. Lineage tracing and pulse-chase experiments revealed that the active state of Hox genes is maintained substantially longer in mutants deficient for HIRA, a chaperone for the H3.3 variant. In addition, both HIRA and H3.3 appeared to act cooperatively with the Polycomb group of epigenetic repressors. These results support the involvement of H3.3-mediated nucleosome turnover in restoring the repressed state. We propose a regulatory framework integrating transcriptional pausing, histone modification, nucleosome architecture and turnover for cell lineage maintenance. PMID:26926299

  4. Multiple transcription factor binding sites predict AID targeting in non-immunoglobulin genes

    PubMed Central

    Duke, Jamie L.; Liu, Man; Yaari, Gur; Khalil, Ashraf M.; Tomayko, Mary M.; Shlomchik, Mark J.; Schatz, David G.; Kleinstein, Steven H.

    2013-01-01

    Aberrant targeting of the enzyme Activation Induced Cytidine Deaminase (AID) results in the accumulation of somatic mutations in approximately 25% of expressed genes in germinal center B cells. Observations in Ung−/− Msh2−/− mice suggest that many other genes efficiently repair AID-induced lesions, so that up to 45% of genes may actually be targeted by AID. It is important to understand the mechanisms that recruit AID to certain genes, as this mis-targeting represents an important risk for genome instability. We hypothesize that several mechanisms will combine to target AID to each locus. In order to resolve which mechanisms affect AID targeting, we analyze 7.3Mb of sequence data, along with the regulatory context, from 83 genes in Ung−/− Msh2−/− mice to identify common properties of AID targets. This analysis identifies the involvement of three transcription factor binding sites (E-box motifs, along with YY1 and C/EBP-beta binding sites) that may work together to recruit AID. Based on previous knowledge and these newly discovered features, a classification tree model was built to predict genome-wide AID targeting. Using this predictive model we were able to identify a set of 101 high-interest genes that are likely targets of AID. PMID:23514741

  5. Maintenance of Tissue Pluripotency by Epigenetic Factors Acting at Multiple Levels.

    PubMed

    Sadasivam, Devendran A; Huang, Der-Hwa

    2016-02-01

    Pluripotent stem cells often adopt a unique developmental program while retaining certain flexibility. The molecular basis of such properties remains unclear. Using differentiation of pluripotent Drosophila imaginal tissues as assays, we examined the contribution of epigenetic factors in ectopic activation of Hox genes. We found that over-expression of Trithorax H3K4 methyltransferase can induce ectopic adult appendages by selectively activating the Hox genes Ultrabithorax and Sex comb reduced in wing and leg discs, respectively. This tissue-specific inducibility correlates with the presence of paused RNA polymerase II in the promoter-proximal region of these genes. Although the Antennapedia promoter is paused in eye-antenna discs, it cannot be induced by Trx without a reduction in histone variants or their chaperones, suggesting additional control by the nucleosomal architecture. Lineage tracing and pulse-chase experiments revealed that the active state of Hox genes is maintained substantially longer in mutants deficient for HIRA, a chaperone for the H3.3 variant. In addition, both HIRA and H3.3 appeared to act cooperatively with the Polycomb group of epigenetic repressors. These results support the involvement of H3.3-mediated nucleosome turnover in restoring the repressed state. We propose a regulatory framework integrating transcriptional pausing, histone modification, nucleosome architecture and turnover for cell lineage maintenance. PMID:26926299

  6. Microfluidic channel structures speed up mixing of multiple emulsions by a factor of ten.

    PubMed

    Land, Kevin J; Mbanjwa, Mesuli; Korvink, Jan G

    2014-09-01

    We present a novel use for channel structures in microfluidic devices, whereby two two-phase emulsions, one created on-chip, the other off-chip, are rapidly mixed with each other in order to allow for the coalescence of one emulsion with the other. This approach has been motivated by the difficulty in introducing aqueous cross linking agents into droplets by utilising conventional approaches. These conventional approaches include continuous introduction of the different aqueous reagents before droplet formation or alternatively formation of individual droplets of each reagent and subsequent droplet merging later in the microfluidic device. We show that our approach can decrease the mixing time for these fluidic systems by a factor greater than 10 times when compared to a standard microfluidic channel without structures, thereby also allowing for additional reaction time within the microfluidic device. This method shows an application for microfluidic channel structures not before demonstrated, also demonstrating an alternative method for introducing reagents such as cross linkers which link polymer chains to form particles, and provides an example where enzymes are immobilized in monodisperse particles. PMID:25332738

  7. Microfluidic channel structures speed up mixing of multiple emulsions by a factor of ten

    PubMed Central

    Mbanjwa, Mesuli; Korvink, Jan G.

    2014-01-01

    We present a novel use for channel structures in microfluidic devices, whereby two two-phase emulsions, one created on-chip, the other off-chip, are rapidly mixed with each other in order to allow for the coalescence of one emulsion with the other. This approach has been motivated by the difficulty in introducing aqueous cross linking agents into droplets by utilising conventional approaches. These conventional approaches include continuous introduction of the different aqueous reagents before droplet formation or alternatively formation of individual droplets of each reagent and subsequent droplet merging later in the microfluidic device. We show that our approach can decrease the mixing time for these fluidic systems by a factor greater than 10 times when compared to a standard microfluidic channel without structures, thereby also allowing for additional reaction time within the microfluidic device. This method shows an application for microfluidic channel structures not before demonstrated, also demonstrating an alternative method for introducing reagents such as cross linkers which link polymer chains to form particles, and provides an example where enzymes are immobilized in monodisperse particles. PMID:25332738

  8. Patterns in foliar nutrient resorption stoichiometry at multiple scales: controlling factors and ecosystem consequences (Invited)

    NASA Astrophysics Data System (ADS)

    Reed, S.; Cleveland, C. C.; Davidson, E. A.; Townsend, A. R.

    2013-12-01

    During leaf senescence, nutrient rich compounds are transported to other parts of the plant and this 'resorption' recycles nutrients for future growth, reducing losses of potentially limiting nutrients. Variations in leaf chemistry resulting from nutrient resorption also directly affect litter quality, in turn, regulating decomposition rates and soil nutrient availability. Here we investigated stoichiometric patterns of nitrogen (N) and phosphorus (P) resorption efficiency at multiple spatial scales. First, we assembled a global database to explore nutrient resorption among and within biomes and to examine potential relationships between resorption stoichiometry and ecosystem nutrient status. Next, we used a forest regeneration chronosequence in Brazil to assess how resorption stoichiometry linked with a suite of other nutrient cycling measures and with ideas of how nutrient limitation may change over secondary forest regrowth. Finally, we measured N:P resorption ratios of six canopy tree species in a Costa Rican tropical forest. We calculated species-specific resorption ratios and compared them with patterns in leaf litter and topsoil nutrient concentrations. At the global scale, N:P resorption ratios increased with latitude and decreased with mean annual temperature (MAT) and precipitation (MAP; P<0.001 for each). In particular, we observed a notable switch across latitudes: N:P resorption ratios were generally <1 in latitudes <23° and >1 in latitudes >23°. Focusing on tropical sites in our global dataset we found that, despite fewer data and a restricted latitudinal range, a significant relationship between latitude and N:P resorption ratios persisted (P<0.001). In contrast, tropical N:P resorption ratios did not vary with MAT (P=0.965) and the relationship with MAP was only marginally significant (P=0.089). Data suggest that soil type, at least in part, helps explain N:P resorption patterns across tropical latitudes: plants on more weathered soils (Oxisols

  9. Multiple Risk Factors of Alcoholic and Non-Alcoholic Myocardial Infarction Patients

    PubMed Central

    Harisharan; Singh, Awnish Kumar; Dangal, Nidhu Ram; Surapaneni, Krishna Mohan; Joshi, Ashish

    2016-01-01

    Background: Myocardial infarction (MI) is one of the most critical medical emergency and contributor to morbidity and mortality worldwide. Myocardial infarction is the most common form of coronary heart disease and leading cause of premature death. Past century has seen substantial advancement in the field of medical sciences but still mortality trends due to myocardial infarction is increasing in developing countries including India. We have conducted this study to compare the Sociodemographic characteristics of alcoholic and non alcoholic MI patients admitted in coronary care unit of Saveetha Medical College, Chennai, India. Methods: An exploratory cross sectional study was performed by enrolling a convenient sample of 100 Myocardial Infarction patients. Information about Sociodemographic characteristics, past medical history, alcohol and tobacco intake, physical activity, psychological stress and biochemical measurements was gathered. Results: The mean age of the respondents was 46 (SD=6) years and majority of them were male i.e. 82%. 100% married and 89% literate, there were 24% past and 22% present alcoholics. Consumption of alcohol on a monthly, weekly and daily basis was 8%, 11% and 5% respectively. Preference to brandy was 67%, rum was 21% and that the beer was 12%. Current smoker were 20% and former were 11%. 93% and 52% respondents were under medication of beta blocker and angiotensin-converting-enzyme (ACE) inhibitors respectively. Conclusion: Worldwide, MI is the most common cause of mortality and morbidity and hence early diagnosis and management is most essential. Results from our study revealed that, participants had sedentary lifestyles where risk factors of MI such as alcohol consumption, and smoking does existed. PMID:26234988

  10. The multiple roles of epidermal growth factor repeat O-glycans in animal development.

    PubMed

    Haltom, Amanda R; Jafar-Nejad, Hamed

    2015-10-01

    The epidermal growth factor (EGF)-like repeat is a common, evolutionarily conserved motif found in secreted proteins and the extracellular domain of transmembrane proteins. EGF repeats harbor six cysteine residues which form three disulfide bonds and help generate the three-dimensional structure of the EGF repeat. A subset of EGF repeats harbor consensus sequences for the addition of one or more specific O-glycans, which are initiated by O-glucose, O-fucose or O-N-acetylglucosamine. These glycans are relatively rare compared to mucin-type O-glycans. However, genetic experiments in model organisms and cell-based assays indicate that at least some of the glycosyltransferases involved in the addition of O-glycans to EGF repeats play important roles in animal development. These studies, combined with state-of-the-art biochemical and structural biology experiments have started to provide an in-depth picture of how these glycans regulate the function of the proteins to which they are linked. In this review, we will discuss the biological roles assigned to EGF repeat O-glycans and the corresponding glycosyltransferases. Since Notch receptors are the best studied proteins with biologically-relevant O-glycans on EGF repeats, a significant part of this review is devoted to the role of these glycans in the regulation of the Notch signaling pathway. We also discuss recently identified proteins other than Notch which depend on EGF repeat glycans to function properly. Several glycosyltransferases involved in the addition or elongation of O-glycans on EGF repeats are mutated in human diseases. Therefore, mechanistic understanding of the functional roles of these carbohydrate modifications is of interest from both basic science and translational perspectives. PMID:26175457

  11. Multiple variants in UGT1A1 gene are factors to develop indirect hyper-bilirubinemia.

    PubMed

    Hu, Rei-Ting; Wang, Nai-Yuan; Huang, May-Jen; Huang, Ching-Shan; Chen, Ding-Shinn; Yang, Sien-Sing

    2014-08-01

    Most Taiwanese patients with hyper-bilirubinemia have genetic abnormalities in the uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene beyond the variants in the TATA box upstream of UGT1A1 associated with Gilbert's syndrome. To investigate the role of UGT1A1 in the pathogenesis of indirect hyper-bilirubinemia, we prospectively studied 97 consecutive patients with indirect hyper-bilirubinemia for genotypes of promoter [(TA)6TAA6, (TA)7TAA7] and coding region [nucleotide (nt)-211, nt-686, nt-1,091 and nt-1,456] of UGT1A1. Thirty-six of the patients (45.6%) were found to have Gilbert's syndrome with 7/7 genotype; among them, 14 also carried variants at nt-686. Forty-two patients (43.3%) had the 6/7 genotype; among them, 36 patients were found to have one or more variants in the coding region. Patients with higher serum total bilirubin are associated with higher likelihood of carrying Gilbert's syndrome genotype: 60.0% (P=0.007) patients with serum total bilirubin level ≥2.5 mg/dL carried the Gilbert's syndrome genotype, while only 23.9% of patients with serum total bilirubin level <2.5 mg/dL carry the same genotype (P=0.0006). Forty-one of the 61 non-Gilbert's patients had one homogenous variants or two or more heterozygous variants in UGT1A1. Further studies are necessary to confirm the role of one homo-zygous variant or two or more hetero-zygous variants in UGT1A1 gene as factors for indirect hyper-bilirubinemia. PMID:25202696

  12. ATP hydrolysis catalyzed by human replication factor C requires participation of multiple subunits.

    PubMed

    Cai, J; Yao, N; Gibbs, E; Finkelstein, J; Phillips, B; O'Donnell, M; Hurwitz, J

    1998-09-29

    Human replication factor C (hRFC) is a five-subunit protein complex (p140, p40, p38, p37, and p36) that acts to catalytically load proliferating cell nuclear antigen onto DNA, where it recruits DNA polymerase delta or epsilon to the primer terminus at the expense of ATP, leading to processive DNA synthesis. We have previously shown that a subcomplex of hRFC consisting of three subunits (p40, p37, and p36) contained DNA-dependent ATPase activity. However, it is not clear which subunit(s) hydrolyzes ATP, as all five subunits include potential ATP binding sites. In this report, we introduced point mutations in the putative ATP-binding sequences of each hRFC subunit and examined the properties of the resulting mutant hRFC complex and the ATPase activity of the hRFC or the p40.p37.p36 complex. A mutation in any one of the ATP binding sites of the p36, p37, p40, or p140 subunits markedly reduced replication activity of the hRFC complex and the ATPase activity of the hRFC or the p40.p37.p36 complex. A mutation in the ATP binding site of the p38 subunit did not alter the replication activity of hRFC. These findings indicate that the replication activity of hRFC is dependent on efficient ATP hydrolysis contributed to by the action of four hRFC subunits. PMID:9751713

  13. ABI-like transcription factor gene TaABL1 from wheat improves multiple abiotic stress tolerances in transgenic plants.

    PubMed

    Xu, Dong-Bei; Gao, Shi-Qing; Ma, You-Zhi; Xu, Zhao-Shi; Zhao, Chang-Ping; Tang, Yi-Miao; Li, Xue-Yin; Li, Lian-Cheng; Chen, Yao-Feng; Chen, Ming

    2014-12-01

    The phytohormone abscisic acid (ABA) plays crucial roles in adaptive responses of plants to abiotic stresses. ABA-responsive element binding proteins (AREBs) are basic leucine zipper transcription factors that regulate the expression of downstream genes containing ABA-responsive elements (ABREs) in promoter regions. A novel ABI-like (ABA-insensitive) transcription factor gene, named TaABL1, containing a conserved basic leucine zipper (bZIP) domain was cloned from wheat. Southern blotting showed that three copies were present in the wheat genome. Phylogenetic analyses indicated that TaABL1 belonged to the AREB subfamily of the bZIP transcription factor family and was most closely related to ZmABI5 in maize and OsAREB2 in rice. Expression of TaABL1 was highly induced in wheat roots, stems, and leaves by ABA, drought, high salt, and low temperature stresses. TaABL1 was localized inside the nuclei of transformed wheat mesophyll protoplast. Overexpression of TaABL1 enhanced responses of transgenic plants to ABA and hastened stomatal closure under stress, thereby improving tolerance to multiple abiotic stresses. Furthermore, overexpression of TaABL1 upregulated or downregulated the expression of some stress-related genes controlling stomatal closure in transgenic plants under ABA and drought stress conditions, suggesting that TaABL1 might be a valuable genetic resource for transgenic molecular breeding. PMID:25344442

  14. Lmo4 and Other LIM domain only factors are necessary and sufficient for multiple retinal cell type development.

    PubMed

    Jin, Kangxin; Xiao, Dongchang; Andersen, Bogi; Xiang, Mengqing

    2016-08-01

    Understanding the molecular basis by which distinct cell types are specified is a central issue in retinogenesis and retinal disease development. Here we examined the role of LIM domain only 4 (Lmo4) in retinal development using both gain-of-function and loss-of-function approaches. By immunostaining, Lmo4 was found to be expressed in mouse retina from E10.5 to mature stages. Retroviral delivery of Lmo4 into retinal progenitor cells could promote the amacrine, bipolar and Müller cell fates at the expense of photoreceptors. It also inhibited the fate of early-born retinal ganglion cells. Using a dominant-negative form of Lmo4 which suppresses transcriptional activities of all LIM domain only factors, we demonstrated that LIM domain only factors are both necessary and sufficient for promoting amacrine and bipolar cell development, but not for the differentiation of ganglion, horizontal, Müller, or photoreceptor cells. Taken together, our study uncovers multiple roles of Lmo4 during retinal development and demonstrates the importance of LIM domain only factors in ensuring proper retinal cell specification and differentiation. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 900-915, 2016. PMID:26579872

  15. Assessing the Risk Factors for Multiple Sclerosis in Women of Reproductive Age Suffering the Disease in Isfahan Province

    PubMed Central

    Rejali, Mehri; Hosseini, Sayed Mohsen; Kazemi Tabaee, Maryam Sadat; Etemadifar, Masoud

    2016-01-01

    Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Etiology of the disease is not well understood; however, it is more common in women than in men and occurs mainly during reproductive age. The aim of this study was to evaluate some risk factors in women of childbearing age with MS in Isfahan Province. Methods: This analytic case–control study was conducted in MS Clinic in Isfahan, 2014. The study was done on 200 patients with MS and 200 nonpatients (matched controls) that were randomly selected for inclusion in the study. The data collection tool was a researcher-designed questionnaire consisting of three parts: Demographics, disease characteristics, and some risk factors related to reproductive age. Data were analyzed by SPSS version 20, using descriptive and inferential statistics. Results: The results showed that risk of MS had a significant relationship with age at menarche (P < 0.001), prior use of oral contraceptives (OCs) (P = 0.002), duration of use of OCs (P = 0.008), and number of pregnancies (P < 0.001). However, there was no significant relationship between age of onset of use of OCs (P = 0.80) and age at the first pregnancy (P = 0.45) with the risk of MS. Conclusions: Results of this research determined that the following risk factors were associated with developing MS, age at menarche, history, and duration of use of OCs and number of pregnancies. PMID:27076896

  16. Genotype-Based Bayesian Analysis of Gene-Environment Interactions with Multiple Genetic Markers and Misclassification in Environmental Factors

    PubMed Central

    Lobach, Iryna; Fan, Ruzong

    2015-01-01

    A key component to understanding etiology of complex diseases, such as cancer, diabetes, alcohol dependence, is to investigate gene-environment interactions. This work is motivated by the following two concerns in the analysis of gene-environment interactions. First, multiple genetic markers in moderate linkage disequilibrium may be involved in susceptibility to a complex disease. Second, environmental factors may be subject to misclassification. We develop a genotype based Bayesian pseudolikelihood approach that accommodates linkage disequilibrium in genetic markers and misclassification in environmental factors. Since our approach is genotype based, it allows the observed genetic information to enter the model directly thus eliminating the need to infer haplotype phase and simplifying computations. Bayesian approach allows shrinking parameter estimates towards prior distribution to improve estimation and inference when environmental factors are subject to misclassification. Simulation experiments demonstrated that our method produced parameter estimates that are nearly unbiased even for small sample sizes. An application of our method is illustrated using a case-control study of interaction between early onset of drinking and genes involved in dopamine pathway. PMID:26180529

  17. Growth differentiating factor 15 enhances the tumor-initiating and self-renewal potential of multiple myeloma cells

    PubMed Central

    Tanno, Toshihiko; Lim, Yiting; Wang, Qiuju; Chesi, Marta; Bergsagel, P. Leif; Matthews, Geoff; Johnstone, Ricky W.; Ghosh, Nilanjan; Borrello, Ivan; Huff, Carol Ann

    2014-01-01

    Disease relapse remains a major factor limiting the survival of cancer patients. In the plasma cell malignancy multiple myeloma (MM), nearly all patients ultimately succumb to disease relapse and progression despite new therapies that have improved remission rates. Tumor regrowth indicates that clonogenic growth potential is continually maintained, but the determinants of self-renewal in MM are not well understood. Normal stem cells are regulated by extrinsic niche factors, and the tumor microenvironment (TME) may similarly influence tumor cell clonogenic growth and self-renewal. Growth differentiation factor 15 (GDF15) is aberrantly secreted by bone marrow stromal cells (BMSCs) in MM. We found that GDF15 is produced by BMSCs after direct contact with plasma cells and enhances the tumor-initiating potential and self-renewal of MM cells in a protein kinase B- and SRY (sex-determining region Y)-box–dependent manner. Moreover, GDF15 induces the expansion of MM tumor-initiating cells (TICs), and changes in the serum levels of GDF15 were associated with changes in the frequency of clonogenic MM cells and the progression-free survival of MM patients. These findings demonstrate that GDF15 plays a critical role in mediating the interaction among mature tumor cells, the TME, and TICs, and strategies targeting GDF15 may affect long-term clinical outcomes in MM. PMID:24345755

  18. A wheat WRKY transcription factor TaWRKY10 confers tolerance to multiple abiotic stresses in transgenic tobacco.

    PubMed

    Wang, Chen; Deng, Pengyi; Chen, Liulin; Wang, Xiatian; Ma, Hui; Hu, Wei; Yao, Ningcong; Feng, Ying; Chai, Ruihong; Yang, Guangxiao; He, Guangyuan

    2013-01-01

    WRKY transcription factors are reported to be involved in defense regulation, stress response and plant growth and development. However, the precise role of WRKY transcription factors in abiotic stress tolerance is not completely understood, especially in crops. In this study, we identified and cloned 10 WRKY genes from genome of wheat (Triticum aestivum L.). TaWRKY10, a gene induced by multiple stresses, was selected for further investigation. TaWRKY10 was upregulated by treatment with polyethylene glycol, NaCl, cold and H2O2. Result of Southern blot indicates that the wheat genome contains three copies of TaWRKY10. The TaWRKY10 protein is localized in the nucleus and functions as a transcriptional activator. Overexpression of TaWRKY10 in tobacco (Nicotiana tabacum L.) resulted in enhanced drought and salt stress tolerance, mainly demonstrated by the transgenic plants exhibiting of increased germination rate, root length, survival rate, and relative water content under these stress conditions. Further investigation showed that transgenic plants also retained higher proline and soluble sugar contents, and lower reactive oxygen species and malonaldehyde contents. Moreover, overexpression of the TaWRKY10 regulated the expression of a series of stress related genes. Taken together, our results indicate that TaWRKY10 functions as a positive factor under drought and salt stresses by regulating the osmotic balance, ROS scavenging and transcription of stress related genes. PMID:23762295

  19. A dynamic RNA loop in an IRES affects multiple steps of elongation factor-mediated translation initiation.

    PubMed

    Ruehle, Marisa D; Zhang, Haibo; Sheridan, Ryan M; Mitra, Somdeb; Chen, Yuanwei; Gonzalez, Ruben L; Cooperman, Barry S; Kieft, Jeffrey S

    2015-01-01

    Internal ribosome entry sites (IRESs) are powerful model systems to understand how the translation machinery can be manipulated by structured RNAs and for exploring inherent features of ribosome function. The intergenic region (IGR) IRESs from the Dicistroviridae family of viruses are structured RNAs that bind directly to the ribosome and initiate translation by co-opting the translation elongation cycle. These IRESs require an RNA pseudoknot that mimics a codon-anticodon interaction and contains a conformationally dynamic loop. We explored the role of this loop and found that both the length and sequence are essential for translation in different types of IGR IRESs and from diverse viruses. We found that loop 3 affects two discrete elongation factor-dependent steps in the IRES initiation mechanism. Our results show how the IRES directs multiple steps after 80S ribosome placement and highlights the often underappreciated significance of discrete conformationally dynamic elements within the context of structured RNAs. PMID:26523395

  20. Multiple-component remediation for developmental reading disabilities: IQ, socioeconomic status, and race as factors in remedial outcome.

    PubMed

    Morris, Robin D; Lovett, Maureen W; Wolf, Maryanne; Sevcik, Rose A; Steinbach, Karen A; Frijters, Jan C; Shapiro, Marla B

    2012-01-01

    Results from a controlled evaluation of remedial reading interventions are reported: 279 young disabled readers were randomly assigned to a program according to a 2 × 2 × 2 factorial design (IQ, socioeconomic status [SES], and race). The effectiveness of two multiple-component intervention programs for children with reading disabilities (PHAB + RAVE-O; PHAB + WIST) was evaluated against alternate (CSS, MATH) and phonological control programs. Interventions were taught an hour daily for 70 days on a 1:4 ratio at three different sites. Multiple-component programs showed significant improvements relative to control programs on all basic reading skills after 70 hours and at 1-year follow-up. Equivalent gains were observed for different racial, SES, and IQ groups. These factors did not systematically interact with program. Differential outcomes for word identification, fluency, comprehension, and vocabulary were found between the multidimensional programs, although equivalent long-term outcomes and equal continued growth confirmed that different pathways exist to effective reading remediation. PMID:20445204

  1. Factors influencing the survival of outmigrating juvenile salmonids through multiple dam passages: an individual-based approach.

    PubMed

    Elder, Timothy; Woodley, Christa M; Weiland, Mark A; Strecker, Angela L

    2016-08-01

    Substantial declines of Pacific salmon populations have occurred over the past several decades related to large-scale anthropogenic and climatic changes in freshwater and marine environments. In the Columbia River Basin, migrating juvenile salmonids may pass as many as eight large-scale hydropower projects before reaching the ocean; however, the cumulative effects of multiple dam passages are largely unknown. Using acoustic transmitters and an extensive system of hydrophone arrays in the Lower Columbia River, we calculated the survival of yearling Chinook salmon (Oncorhynchus tshawytscha) and steelhead (O. mykiss) passing one, two, or three dams. We applied a unique index of biological characteristics and environmental exposures, experienced by each fish individually as it migrated downstream, in order to examine which factors most influence salmonid survival. High outflow volumes led to involuntary spill in 2011 and created an environment of supersaturated dissolved gas concentrations. In this environment, migrating smolt survival was strongly influenced by barometric pressure, fish velocity, and water temperature. The effect of these variables on survival was compounded by multiple dam passages compared to fish passing a single dam. Despite spatial isolation between dams in the Lower Columbia River hydrosystem, migrating smolt appear to experience cumulative effects akin to a press disturbance. In general, Chinook salmon and steelhead respond similarly in terms of survival rates and responses to altered environmental conditions. Management actions that limit dissolved gas concentrations in years of high flow will benefit migrating salmonids at this life stage. PMID:27547362

  2. Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh

    PubMed Central

    Gernand, Alison D.; Schulze, Kerry J.; Nanayakkara-Bind, Ashika; Arguello, Margia; Shamim, Abu Ahmed; Ali, Hasmot; Wu, Lee; West, Keith P.; Christian, Parul

    2015-01-01

    Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA) supplementation, we measured placental growth hormone (PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5 (2.4) kg/m2 and birth weight was 2.68 (0.41) kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction); and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies. Trial Registration ClinicalTrials.gov NCT00860470 PMID:26431336

  3. The Drosophila homeodomain transcription factor, Vnd, associates with a variety of co-factors, is extensively phosphorylated and forms multiple complexes in embryos.

    PubMed

    Zhang, Huanqing; Syu, Li-Jyun; Modica, Vicky; Yu, Zhongxin; Von Ohlen, Tonia; Mellerick, Dervla M

    2008-10-01

    Vnd is a dual transcriptional regulator that is essential for Drosophila dorsal-ventral patterning. Yet, our understanding of the biochemical basis for its regulatory activity is limited. Consistent with Vnd's ability to repress target expression in embryos, endogenously expressed Vnd physically associates with the co-repressor, Groucho, in Drosophila Kc167 cells. Vnd exists as a single complex in Kc167 cells, in contrast with embryonic Vnd, which forms multiple high-molecular-weight complexes. Unlike its vertebrate homolog, Nkx2.2, full-length Vnd can bind its target in electrophoretic mobility shift assay, suggesting that co-factor availability may influence Vnd's weak regulatory activity in transient transfections. We identify the high mobility group 1-type protein, D1, and the novel helix-loop-helix protein, Olig, as novel Vnd-interacting proteins using co-immunoprecipitation assays. Furthermore, we demonstrate that both D1 and Olig are co-expressed with Vnd during Drosophila embryogenesis, consistent with a biological basis for this interaction. We also suggest that the phosphorylation state of Vnd influences its ability to interact with co-factors, because Vnd is extensively phosphorylated in embryos and can be phosphorylated by activated mitogen-activated protein kinase in vitro. These results highlight the complexities of Vnd-mediated regulation. PMID:18795949

  4. Interferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations

    PubMed Central

    Kristjansdottir, G; Sandling, J K; Bonetti, A; Roos, I M; Milani, L; Wang, C; Gustafsdottir, S M; Sigurdsson, S; Lundmark, A; Tienari, P J; Koivisto, K; Elovaara, I; Pirttilä, T; Reunanen, M; Peltonen, L; Saarela, J; Hillert, J; Olsson, T; Landegren, U; Alcina, A; Fernández, O; Leyva, L; Guerrero, M; Lucas, M; Izquierdo, G; Matesanz, F; Syvänen, A-C

    2008-01-01

    Background: IRF5 is a transcription factor involved both in the type I interferon and the toll-like receptor signalling pathways. Previously, IRF5 has been found to be associated with systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel diseases. Here we investigated whether polymorphisms in the IRF5 gene would be associated with yet another disease with features of autoimmunity, multiple sclerosis (MS). Methods: We genotyped nine single nucleotide polymorphisms and one insertion-deletion polymorphism in the IRF5 gene in a collection of 2337 patients with MS and 2813 controls from three populations: two case–control cohorts from Spain and Sweden, and a set of MS trio families from Finland. Results: Two single nucleotide polymorphism (SNPs) (rs4728142, rs3807306), and a 5 bp insertion-deletion polymorphism located in the promoter and first intron of the IRF5 gene, showed association signals with values of p<0.001 when the data from all cohorts were combined. The predisposing alleles were present on the same common haplotype in all populations. Using electrophoretic mobility shift assays we observed allele specific differences in protein binding for the SNP rs4728142 and the 5 bp indel, and by a proximity ligation assay we demonstrated increased binding of the transcription factor SP1 to the risk allele of the 5 bp indel. Conclusion: These findings add IRF5 to the short list of genes shown to be associated with MS in more than one population. Our study adds to the evidence that there might be genes or pathways that are common in multiple autoimmune diseases, and that the type I interferon system is likely to be involved in the development of these diseases. PMID:18285424

  5. Addressing Social Issues.

    ERIC Educational Resources Information Center

    Schoebel, Susan

    1991-01-01

    Maintains that advertising can help people become more aware of social responsibilities. Describes a successful nationwide newspaper advertising competition for college students in which ads address social issues such as literacy, drugs, teen suicide, and teen pregnancy. Notes how the ads have helped grassroots programs throughout the United…

  6. States Address Achievement Gaps.

    ERIC Educational Resources Information Center

    Christie, Kathy

    2002-01-01

    Summarizes 2 state initiatives to address the achievement gap: North Carolina's report by the Advisory Commission on Raising Achievement and Closing Gaps, containing an 11-point strategy, and Kentucky's legislation putting in place 10 specific processes. The North Carolina report is available at www.dpi.state.nc.us.closingthegap; Kentucky's…

  7. Address of the President

    ERIC Educational Resources Information Center

    Ness, Frederic W.

    1976-01-01

    The president of the Association of American Colleges addresses at the 62nd annual meeting the theme of the conference: "Looking to the Future--Liberal Education in a Radically Changing Society." Contributions to be made by AAC are examined. (LBH)

  8. Addressing Sexual Harassment

    ERIC Educational Resources Information Center

    Young, Ellie L.; Ashbaker, Betty Y.

    2008-01-01

    This article discusses ways on how to address the problem of sexual harassment in schools. Sexual harassment--simply defined as any unwanted and unwelcome sexual behavior--is a sensitive topic. Merely providing students, parents, and staff members with information about the school's sexual harassment policy is insufficient; schools must take…

  9. Space sciences - Keynote address

    NASA Technical Reports Server (NTRS)

    Alexander, Joseph K.

    1990-01-01

    The present status and projected future developments of the NASA Space Science and Applications Program are addressed. Emphasis is given to biochemistry experiments that are planned for the Space Station. Projects for the late 1990s which will study the sun, the earth's magnetosphere, and the geosphere are briefly discussed.

  10. Sociocultural and Demographic Risk Factors for the Development of Multiple Sclerosis in Kuwait: A Case - Control Study

    PubMed Central

    Al-Shammri, Suhail N.; Hanna, Magdy G.; Chattopadhyay, Arpita; Akanji, Abayomi O.

    2015-01-01

    Introduction Immunological, genetic and environmental factors are believed to play important roles in the pathogenesis of Multiple Sclerosis (MS). There have been many studies on risk factors for MS but these have been mainly in Caucasian populations; robust studies in Arab populations remain relatively uncommon. This study therefore aimed to identify behavioral, socio-cultural, and demographic factors associated with development of MS in Kuwait, a high income Arab country, currently undergoing a demographic transition. Subjects and methods In this case- control study, 195 Kuwaiti MS patients and 146 healthy age and sex-matched controls were recruited. Both groups of subjects were interviewed using a structured questionnaire, in relation to anthropometric, socio-cultural and demographic data, residence during the 1990/91 Gulf War and current and past medical history, including medications. We also clinically evaluated, and retrospectively reviewed medical records of patients to derive appropriate clinical information, including associated chronic medical illness requiring long-term treatment. Results On multiple logistic regression analysis after adjustment for potential confounders including age, gender and BMI, in all the subjects, a positive associations prevail with presence of MS and some sociocultural and demographic factors, which included non-Bedouin ethnicity (AOR 2, 95% CI 1.0-3.9, p 0.049), positive family history of MS (AOR 10.6, 95% CI 3.0-36.9), p < 0.001), and low daily sunlight exposure of < 15min/day (AOR 5.3, 95% CI 2.7-10.5 p < 0.001). In addition, while 41.8% of MS patients indicated at least one comorbidity, only 26.8% of the controls reported any associated physical illness, with the suggestion that presence of certain comorbidities might increase MS risk (AOR 2.4, 95% CI 1.3-4.7, p < 0.001). Other risk variables such as smoking status and mode of routine outdoor dressing were not significant in all the MS subjects taken as a whole, but

  11. Main and interactive effects of multiple global-change factors on soil respiration and its components: a meta-analysis

    NASA Astrophysics Data System (ADS)

    Zhou, Xuhui

    2014-05-01

    Global change usually involves simultaneous changes in multiple environmental factors, which may considerably affect ecosystem structure and functioning and alter ecosystem services to human society. With increased awareness of their potential interactions, some multi-factorial studies have been conducted to investigate their main and interactive effects on carbon (C) cycling in terrestrial ecosystem. However, how multiple global-change factors affected soil respiration (Rs) and its components (i.e., autotrophic (Ra) and heterotrophic respiration (Rh)) remains controversial among individual studies. In this study, we conducted a meta-analysis to examine the main and possible 2- or 3-factor interactive effects with warming (W), elevated CO2 (E), nitrogen addition (N), increased precipitation (I) and drought (D) on Rs and its components from 150 published papers. Our results show that E, W, I and N significantly stimulated Rs by 29.23%, 7.19%, 22.95%, and 16.90% (p<0.05), respectively, while I depressed it by 16.90% (p<0.01). E consistently induced a significant positive effect on both Ra and Rh, while I affected them with an opposite trend. Among nine two-way interactive effects on Rs, synergistic interaction (i.e., the effect of combined treatment > the additive effects of single two main factors) occurred in E×N, E×W, I×N, and D×W, while neutral interaction (i.e., the effect of combined treatment ≡ the additive one) and antagonistic interaction (i.e., the effect of combined treatment < the additive one)was rare, only in I×W for neutral one and in N×W and I×E for the latter. In addition, E×W and E×N displayed synergistic interactions on Rh. The more dominance of synergistic interactions in two-way interactive effects on Rs and Rh may determine a central positive tendency of Rs in future, and affect the feedback of terrestrial C cycle to the climate system correspondingly.

  12. To Fish or Not to Fish: Factors at Multiple Scales Affecting Artisanal Fishers' Readiness to Exit a Declining Fishery

    PubMed Central

    Daw, Tim M.; Cinner, Joshua E.; McClanahan, Timothy R.; Brown, Katrina; Stead, Selina M.; Graham, Nicholas A. J.; Maina, Joseph

    2012-01-01

    Globally, fisheries are challenged by the combined impacts of overfishing, degradation of ecosystems and impacts of climate change, while fisheries livelihoods are further pressured by conservation policy imperatives. Fishers' adaptive responses to these pressures, such as exiting from a fishery to pursue alternative livelihoods, determine their own vulnerability, as well as the potential for reducing fishing effort and sustaining fisheries. The willingness and ability to make particular adaptations in response to change, such as exiting from a declining fishery, is influenced by economic, cultural and institutional factors operating at scales from individual fishers to national economies. Previous studies of exit from fisheries at single or few sites, offer limited insight into the relative importance of individual and larger-scale social and economic factors. We asked 599 fishers how they would respond to hypothetical scenarios of catch declines in 28 sites in five western Indian Ocean countries. We investigated how socioeconomic variables at the individual-, household- and site-scale affected whether they would exit fisheries. Site-level factors had the greatest influence on readiness to exit, but these relationships were contrary to common predictions. Specifically, higher levels of infrastructure development and economic vitality - expected to promote exit from fisheries - were associated with less readiness to exit. This may be due to site level histories of exit from fisheries, greater specialisation of fishing households, or higher rewards from fishing in more economically developed sites due to technology, market access, catch value and government subsidies. At the individual and household scale, fishers from households with more livelihood activities, and fishers with lower catch value were more willing to exit. These results demonstrate empirically how adaptive responses to change are influenced by factors at multiple scales, and highlight the importance

  13. To fish or not to fish: factors at multiple scales affecting artisanal fishers' readiness to exit a declining fishery.

    PubMed

    Daw, Tim M; Cinner, Joshua E; McClanahan, Timothy R; Brown, Katrina; Stead, Selina M; Graham, Nicholas A J; Maina, Joseph

    2012-01-01

    Globally, fisheries are challenged by the combined impacts of overfishing, degradation of ecosystems and impacts of climate change, while fisheries livelihoods are further pressured by conservation policy imperatives. Fishers' adaptive responses to these pressures, such as exiting from a fishery to pursue alternative livelihoods, determine their own vulnerability, as well as the potential for reducing fishing effort and sustaining fisheries. The willingness and ability to make particular adaptations in response to change, such as exiting from a declining fishery, is influenced by economic, cultural and institutional factors operating at scales from individual fishers to national economies. Previous studies of exit from fisheries at single or few sites, offer limited insight into the relative importance of individual and larger-scale social and economic factors. We asked 599 fishers how they would respond to hypothetical scenarios of catch declines in 28 sites in five western Indian Ocean countries. We investigated how socioeconomic variables at the individual-, household- and site-scale affected whether they would exit fisheries. Site-level factors had the greatest influence on readiness to exit, but these relationships were contrary to common predictions. Specifically, higher levels of infrastructure development and economic vitality - expected to promote exit from fisheries - were associated with less readiness to exit. This may be due to site level histories of exit from fisheries, greater specialisation of fishing households, or higher rewards from fishing in more economically developed sites due to technology, market access, catch value and government subsidies. At the individual and household scale, fishers from households with more livelihood activities, and fishers with lower catch value were more willing to exit. These results demonstrate empirically how adaptive responses to change are influenced by factors at multiple scales, and highlight the importance

  14. Household trends in access to improved water sources and sanitation facilities in Vietnam and associated factors: findings from the Multiple Indicator Cluster Surveys, 2000–2011

    PubMed Central

    Tuyet-Hanh, Tran Thi; Lee, Jong-Koo; Oh, Juhwan; Van Minh, Hoang; Ou Lee, Chul; Hoan, Le Thi; Nam, You-Seon; Long, Tran Khanh

    2016-01-01

    Background Despite progress made by the Millennium Development Goal (MDG) number 7.C, Vietnam still faces challenges with regard to the provision of access to safe drinking water and basic sanitation. Objective This paper describes household trends in access to improved water sources and sanitation facilities separately, and analyses factors associated with access to improved water sources and sanitation facilities in combination. Design Secondary data from the Vietnam Multiple Indicator Cluster Survey in 2000, 2006, and 2011 were analyzed. Descriptive statistics and tests of significance describe trends over time in access to water and sanitation by location, demographic and socio-economic factors. Binary logistic regressions (2000, 2006, and 2011) describe associations between access to water and sanitation, and geographic, demographic, and socio-economic factors. Results There have been some outstanding developments in access to improved water sources and sanitation facilities from 2000 to 2011. In 2011, the proportion of households with access to improved water sources and sanitation facilities reached 90% and 77%, respectively, meeting the 2015 MDG targets for safe drinking water and basic sanitation set at 88% and 75%, respectively. However, despite these achievements, in 2011, only 74% of households overall had access to combined improved drinking water and sanitation facilities. There were also stark differences between regions. In 2011, only 47% of households had access to both improved water and sanitation facilities in the Mekong River Delta compared with 94% in the Red River Delta. In 2011, households in urban compared to rural areas were more than twice as likely (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.9–2.5) to have access to improved water and sanitation facilities in combination, and households in the highest compared with the lowest wealth quintile were over 40 times more likely (OR: 42.3; 95% CI: 29.8–60.0). Conclusions More

  15. Proliferation of endothelial component of parathyroid gland in multiple endocrine neoplasia type 1. Potential relationship with a mitogenic factor.

    PubMed Central

    D'Adda, T.; Amorosi, A.; Bussolati, G.; Brandi, M. L.; Bordi, C.

    1993-01-01

    The basic fibroblast growth factor-like mitogen detected in the plasma of patients with the multiple endocrine neoplasia type 1 (MEN-1) syndrome was found to have a specific mitogenic effect on parathyroid endothelial cells in vitro. To investigate its pathogenic role in humans, the endothelial component of parathyroid glands was evaluated by ultrastructural morphometry in six MEN-1 patients. The results were compared with those found in six patients with uremic hyperparathyroidism (UHPT) and in three subjects with histologically normal glands. Plasma mitogenic activity was found in all MEN-1 patients but not in those with UHPT or in normal subjects. All morphometric parameters investigated (fractional volume and nuclear density of capillary endothelial cells, volume fraction and number per unit area of capillaries) showed 1.5- to 2-fold higher values in patients with MEN-1 than in those with UHPT (P < 0.05). In contrast, no difference was found between MEN-1 cases and normal subjects. Quantitative evaluation of parathyroid pericytes yielded results similar to those of endothelial cells. These data indicate that the proliferation of parathyroid cells in MEN-1 patients is accompanied by parallel increase in the associated endothelial component that does not occur in patients with UHPT and may support the hypothesis of an in vivo role of the MEN-1 mitogen factor on the endothelial component of parathyroid glands in MEN-1 patients. Images Figure 1 PMID:8102033

  16. Excerpts from keynote address

    SciTech Connect

    Creel, G.C.

    1995-06-01

    Excerpts from the keynote principally address emissions issues in the fossil power industry as related to heat rate improvements. Stack emissions of both sulfur and nitrogen oxides are discussed, and a number of examples are given: (1) PEPCO`s Potomac River Station, and (2) Morgantown station`s NOX reduction efforts. Circulating water emissions are also briefly discussed, as are O & M costs of emission controls.

  17. Holographic content addressable storage

    NASA Astrophysics Data System (ADS)

    Chao, Tien-Hsin; Lu, Thomas; Reyes, George

    2015-03-01

    We have developed a Holographic Content Addressable Storage (HCAS) architecture. The HCAS systems consists of a DMD (Digital Micromirror Array) as the input Spatial Light Modulator (SLM), a CMOS (Complementary Metal-oxide Semiconductor) sensor as the output photodetector and a photorefractive crystal as the recording media. The HCAS system is capable of performing optical correlation of an input image/feature against massive reference data set stored in the holographic memory. Detailed system analysis will be reported in this paper.

  18. Forms of Address in Chilean Spanish

    ERIC Educational Resources Information Center

    Bishop, Kelley; Michnowicz, Jim

    2010-01-01

    The present investigation examines possible social and linguistic factors that influence forms of address used in Chilean Spanish with various interlocutors. A characteristic of the Spanish of Chile is the use of a variety of forms of address for the second person singular, "tu", "vos", and "usted", with corresponding verb conjugations (Lipski…

  19. MicroRNA miR-8 regulates multiple growth factor hormones produced from Drosophila fat cells.

    PubMed

    Lee, G J; Jun, J W; Hyun, S

    2015-06-01

    Metabolic organs such as the liver and adipose tissue produce several peptide hormones that influence metabolic homeostasis. Fat bodies, the Drosophila counterpart of liver and adipose tissues, have been thought to analogously secrete several hormones that affect organismal physiology, but their identity and regulation remain poorly understood. Previous studies have indicated that microRNA miR-8, functions in the fat body to non-autonomously regulate organismal growth, suggesting that fat body-derived humoral factors are regulated by miR-8. Here, we found that several putative peptide hormones known to have mitogenic effects are regulated by miR-8 in the fat body. Most members of the imaginal disc growth factors and two members of the adenosine deaminase-related growth factors are up-regulated in the absence of miR-8. Drosophila insulin-like peptide 6 (Dilp6) and imaginal morphogenesis protein-late 2 (Imp-L2), a binding partner of Dilp, are also up-regulated in the fat body of miR-8 null mutant larvae. The fat body-specific reintroduction of miR-8 into the miR-8 null mutants revealed six peptides that showed fat-body organ-autonomous regulation by miR-8. Amongst them, only Imp-L2 was found to be regulated by U-shaped, the miR-8 target for body growth. However, a rescue experiment by knockdown of Imp-L2 indicated that Imp-L2 alone does not account for miR-8's control over the insect's growth. Our findings suggest that multiple peptide hormones regulated by miR-8 in the fat body may collectively contribute to Drosophila growth. PMID:25492518

  20. Psychosocial factors associated with pain intensity, pain-related interference, and psychological functioning in persons with multiple sclerosis and pain.

    PubMed

    Osborne, Travis L; Jensen, Mark P; Ehde, Dawn M; Hanley, Marisol A; Kraft, George

    2007-01-01

    Biopsychosocial models of chronic pain that recognize psychological and environmental factors as important aspects of adjustment to pain have been proposed for understanding chronic pain and related suffering in persons with multiple sclerosis (MS), but such models have not been empirically tested. The objective of this study was to test such a model by evaluating the associations of several psychosocial variables (i.e., pain-related catastrophizing, perceived social support, pain beliefs, and pain coping) with pain intensity, pain interference with functioning, and psychological functioning in persons with chronic pain and MS, after controlling for demographic and disease-related factors. Participants were 125 community-dwelling persons with MS and pain who completed a mailed questionnaire that included measures of pain intensity and interference, psychological functioning, catastrophizing, social support, and pain beliefs and coping. The psychosocial variables accounted for an additional 25% of the variance in average pain intensity after controlling for demographic and disease-related variables (p<.001). These variables explained an additional 22% of the variance in pain-related interference (p<.001) and 43% of the variance in psychological functioning (p<.001), after adjusting for demographic and MS-related variables and average pain intensity. Catastrophizing was consistently and independently associated with all criterion measures, whereas social support, pain beliefs, and pain coping were associated with some criterion measures but not others. The results provide empirical support for a biopsychosocial understanding of chronic pain in MS and suggest that specific psychosocial factors (e.g., catastrophizing) may be important regarding adjustment to pain in persons with MS. PMID:16950570

  1. Equivalence factors for standardizing catch data across multiple beach seine nets to account for differences in relative bias

    NASA Astrophysics Data System (ADS)

    Hallett, Chris S.; Hall, Norm G.

    2012-06-01

    We describe a method for modelling the relative effects of seine net biases and for deriving equivalence factors to standardize fish abundance data sets collected using multiple sampling gears. Nearshore fish communities were sampled from 10 sites in each of the basin and riverine portions of the Swan-Canning Estuary, Western Australia, using beach seine nets of three different lengths (21.5, 41.5 and 133 m). The resulting data were subjected to generalized linear modelling to derive equivalence factors relating catches from the two larger net types to those from the 21.5 m net. Equivalence factors were derived on the basis of functional habitat guilds of fish (small benthic, small pelagic, demersal, pelagic). Prior to standardization, catches from the 41.5 and 133 m nets consistently underestimated fish densities relative to those from the 21.5 m net. Following standardization, the degree to which fish densities were underestimated by the two larger nets was reduced and/or eliminated for most guilds, and particularly in the case of the 133 m net. For both of the larger nets, standardized estimates of total fish density across all species were far closer to those recorded using the 21.5 m seine, thus indicating that standardization of the fish abundance data had greatly reduced the overall effects of the biases introduced by the different net types. This approach could be applied to other systems and sampling methods, to facilitate more robust comparisons of fish abundances between studies with divergent sampling methodologies.

  2. Prediction of the processing factor for pesticides in apple juice by principal component analysis and multiple linear regression.

    PubMed

    Martin, L; Mezcua, M; Ferrer, C; Gil Garcia, M D; Malato, O; Fernandez-Alba, A R

    2013-01-01

    The main objective of this work was to establish a mathematical function that correlates pesticide residue levels in apple juice with the levels of the pesticides applied on the raw fruit, taking into account some of their physicochemical properties such as water solubility, the octanol/water partition coefficient, the organic carbon partition coefficient, vapour pressure and density. A mixture of 12 pesticides was applied to an apple tree; apples were collected after 10 days of application. After harvest, apples were treated with a mixture of three post-harvest pesticides and the fruits were then processed in order to obtain apple juice following a routine industrial process. The pesticide residue levels in the apple samples were analysed using two multi-residue methods based on LC-MS/MS and GC-MS/MS. The concentration of pesticides was determined in samples derived from the different steps of processing. The processing factors (the coefficient between residue level in the processed commodity and the residue level in the commodity to be processed) obtained for the full juicing process were found to vary among the different pesticides studied. In order to investigate the relationships between the levels of pesticide residue found in apple juice samples and their physicochemical properties, principal component analysis (PCA) was performed using two sets of samples (one of them using experimental data obtained in this work and the other including the data taken from the literature). In both cases the correlation was found between processing factors of pesticides in the apple juice and the negative logarithms (base 10) of the water solubility, octanol/water partition coefficient and organic carbon partition coefficient. The linear correlation between these physicochemical properties and the processing factor were established using a multiple linear regression technique. PMID:23281800

  3. Continuum of Care in a Maternal, Newborn and Child Health Program in Ghana: Low Completion Rate and Multiple Obstacle Factors

    PubMed Central

    Yeji, Francis; Shibanuma, Akira; Oduro, Abraham; Debpuur, Cornelius; Kikuchi, Kimiyo; Owusu-Agei, Seth; Gyapong, Margaret; Okawa, Sumiyo; Ansah, Evelyn; Asare, Gloria Quansah; Nanishi, Keiko; Williams, John; Addei, Sheila; Tawiah, Charlotte; Yasuoka, Junko; Enuameh, Yeetey; Sakeah, Evelyn; Wontuo, Peter; Jimba, Masamine; Hodgson, Abraham

    2015-01-01

    Background Slow progress has been made in achieving the Millennium Development Goals 4 and 5 in Ghana. Ensuring continuum of care (at least four antenatal visits; skilled birth attendance; postnatal care within 48 hours, at two weeks, and six weeks) for mother and newborn is crucial in helping Ghana achieve these goals and beyond. This study examined the levels and factors associated with continuum of care (CoC) completion among Ghanaian women aged 15–49. Methods A retrospective cross-sectional survey was conducted among women who experienced live births between January 2011 and April 2013 in three regions of Ghana. In a two-stage random sampling method, 1,500 women with infants were selected and interviewed about maternal and newborn service usage in line with CoC. Multiple logistic regression models were used to assess factors associated with CoC completion. Results Only 8.0% had CoC completion; the greatest gap and contributor to the low CoC was detected between delivery and postnatal care within 48 hours postpartum. About 95% of women had a minimum of four antenatal visits and postnatal care at six weeks postpartum. A total of 75% had skilled assisted delivery and 25% received postnatal care within 48 hours. Factors associated with CoC completion at 95% CI were geographical location (OR = 0.35, CI 0.13–0.39), marital status (OR = 0.45; CI 0.22–0.95), education (OR = 2.71; CI 1.11–6.57), transportation (OR = 1.97; CI 1.07–3.62), and beliefs about childhood illnesses (OR = 0.34; CI0.21–0.61). Conclusion The continuum of care completion rate is low in the study site. Efforts should focus on increasing postnatal care within 48 hours and overcoming the known obstacles to increasing the continuum of care completion rate. PMID:26650388

  4. Multiple Orientia tsutsugamushi Ankyrin Repeat Proteins Interact with SCF1 Ubiquitin Ligase Complex and Eukaryotic Elongation Factor 1 α

    PubMed Central

    Min, Chan-Ki; Kwon, Ye-Jin; Ha, Na-Young; Cho, Bon-A; Kim, Jo-Min; Kwon, Eun-Kyung; Kim, Yeon-Sook; Choi, Myung-Sik; Kim, Ik-Sang; Cho, Nam-Hyuk

    2014-01-01

    Background Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular bacterium. Previously, a large number of genes that encode proteins containing eukaryotic protein-protein interaction motifs such as ankyrin-repeat (Ank) domains were identified in the O. tsutsugamushi genome. However, little is known about the Ank protein function in O. tsutsugamushi. Methodology/Principal Findings To characterize the function of Ank proteins, we investigated a group of Ank proteins containing an F-box–like domain in the C-terminus in addition to the Ank domains. All nine selected ank genes were expressed at the transcriptional level in host cells infected with O. tsutsugamushi, and specific antibody responses against three Ank proteins were detected in the serum from human patients, indicating an active expression of the bacterial Ank proteins post infection. When ectopically expressed in HeLa cells, the Ank proteins of O. tsutsugamushi were consistently found in the nucleus and/or cytoplasm. In GST pull-down assays, multiple Ank proteins specifically interacted with Cullin1 and Skp1, core components of the SCF1 ubiquitin ligase complex, as well as the eukaryotic elongation factor 1 α (EF1α). Moreover, one Ank protein co-localized with the identified host targets and induced downregulation of EF1α potentially via enhanced ubiquitination. The downregulation of EF1α was observed consistently in diverse host cell types infected with O. tsutsugamushi. Conclusion/Significance These results suggest that conserved targeting and subsequent degradation of EF1α by multiple O. tsutsugamushi Ank proteins could be a novel bacterial strategy for replication and/or pathogenesis during mammalian host infection. PMID:25166298

  5. Plasticity in above- and belowground resource acquisition traits in response to single and multiple environmental factors in three tree species.

    PubMed

    Freschet, Grégoire T; Bellingham, Peter J; Lyver, Philip O'B; Bonner, Karen I; Wardle, David A

    2013-04-01

    Functional trait plasticity is a major component of plant adjustment to environmental stresses. Here, we explore how multiple local environmental gradients in resources required by plants (light, water, and nutrients) and soil disturbance together influence the direction and amplitude of intraspecific changes in leaf and fine root traits that facilitate capture of these resources. We measured population-level analogous above- and belowground traits related to resource acquisition, i.e. "specific leaf area"-"specific root length" (SLA-SRL), and leaf and root N, P, and dry matter content (DMC), on three dominant understory tree species with contrasting carbon and nutrient economics across 15 plots in a temperate forest influenced by burrowing seabirds. We observed similar responses of the three species to the same single environmental influences, but partially species-specific responses to combinations of influences. The strength of intraspecific above- and belowground trait responses appeared unrelated to species resource acquisition strategy. Finally, most analogous leaf and root traits (SLA vs. SRL, and leaf versus root P and DMC) were controlled by contrasting environmental influences. The decoupled responses of above- and belowground traits to these multiple environmental factors together with partially species-specific adjustments suggest complex responses of plant communities to environmental changes, and potentially contrasting feedbacks of plant traits with ecosystem properties. We demonstrate that despite the growing evidence for broadly consistent resource-acquisition strategies at the whole plant level among species, plants also show partially decoupled, finely tuned strategies between above- and belowground parts at the intraspecific level in response to their environment. This decoupling within species suggests a need for many species-centred ecological theories on how plants respond to their environments (e.g. competitive/stress-tolerant/ruderal and

  6. Content addressable memory project

    NASA Technical Reports Server (NTRS)

    Hall, J. Storrs; Levy, Saul; Smith, Donald E.; Miyake, Keith M.

    1992-01-01

    A parameterized version of the tree processor was designed and tested (by simulation). The leaf processor design is 90 percent complete. We expect to complete and test a combination of tree and leaf cell designs in the next period. Work is proceeding on algorithms for the computer aided manufacturing (CAM), and once the design is complete we will begin simulating algorithms for large problems. The following topics are covered: (1) the practical implementation of content addressable memory; (2) design of a LEAF cell for the Rutgers CAM architecture; (3) a circuit design tool user's manual; and (4) design and analysis of efficient hierarchical interconnection networks.

  7. Bioreactors Addressing Diabetes Mellitus

    PubMed Central

    Minteer, Danielle M.; Gerlach, Jorg C.

    2014-01-01

    The concept of bioreactors in biochemical engineering is a well-established process; however, the idea of applying bioreactor technology to biomedical and tissue engineering issues is relatively novel and has been rapidly accepted as a culture model. Tissue engineers have developed and adapted various types of bioreactors in which to culture many different cell types and therapies addressing several diseases, including diabetes mellitus types 1 and 2. With a rising world of bioreactor development and an ever increasing diagnosis rate of diabetes, this review aims to highlight bioreactor history and emerging bioreactor technologies used for diabetes-related cell culture and therapies. PMID:25160666

  8. Addressing Environmental Health Inequalities.

    PubMed

    Gouveia, Nelson

    2016-01-01

    Environmental health inequalities refer to health hazards disproportionately or unfairly distributed among the most vulnerable social groups, which are generally the most discriminated, poor populations and minorities affected by environmental risks. Although it has been known for a long time that health and disease are socially determined, only recently has this idea been incorporated into the conceptual and practical framework for the formulation of policies and strategies regarding health. In this Special Issue of the International Journal of Environmental Research and Public Health (IJERPH), "Addressing Environmental Health Inequalities-Proceedings from the ISEE Conference 2015", we incorporate nine papers that were presented at the 27th Conference of the International Society for Environmental Epidemiology (ISEE), held in Sao Paulo, Brazil, in 2015. This small collection of articles provides a brief overview of the different aspects of this topic. Addressing environmental health inequalities is important for the transformation of our reality and for changing the actual development model towards more just, democratic, and sustainable societies driven by another form of relationship between nature, economy, science, and politics. PMID:27618906

  9. Total joint replacement: A multiple risk factor analysis of physical activity level 1-2 years postoperatively.

    PubMed

    Paxton, Elizabeth W; Torres, Andy; Love, Rebecca M; Barber, Thomas C; Sheth, Dhiren S; Inacio, Maria C S

    2016-07-01

    Background and purpose - The effect of total joint arthroplasty (TJA) on physical activity is not fully understood. We investigated the change in physical activity after TJA and patient factors associated with change. Patients and methods - Using a total joint replacement registry, primary total hip arthroplasty (THA) patients (n = 5,678) and knee arthroplasty (TKA) patients (n = 11,084) between January 1, 2010 and December 31, 2012 were identified. Median age at THA was 68 and median age at TKA was 67. Change in self-reported physical activity (minutes per week) from before TJA (within 1 year of surgery) to after TJA (1-2 years) was the outcome of interest. Patient demographics and comorbidities were evaluated as risk factors. Multiple linear regression was used. Results - Median physical activity before surgery was 50 min/week (IQR: 0-140) for THA patients and 58 (IQR: 3-143) for TKA patients. Median physical activity after surgery was 150 min/week (IQR: 60-280) for both THA patients and TKA patients. Following TJA, 50% of patients met CDC/WHO physical activity guideline criteria. Higher body mass index was associated with lower change in physical activity (THA: -7.1 min/week; TKA: -5.9 min/week). Females had lower change than males (THA: -11 min/week; TKA: -9.1 min/week). In TKA patients, renal failure was associated with lower change (-17 min/week), as were neurological disorders (-30 min/week). Interpretation - Self-reported minutes of physical activity increased from before to after TJA, but 50% of TJA patients did not meet recommended physical activity guideline criteria. Higher body mass index, female sex, and specific comorbidities were found to be associated with low change in physical activity. Patient education on the benefits of physical activity should concentrate on these subgroups of patients. PMID:27299567

  10. Long Term Clinical Prognostic Factors in Relapsing-Remitting Multiple Sclerosis: Insights from a 10-Year Observational Study

    PubMed Central

    Ehling, Rainer; Lutterotti, Andreas; Hegen, Harald; Di Pauli, Franziska; Auer, Michael; Deisenhammer, Florian; Reindl, Markus; Berger, Thomas

    2016-01-01

    Background Multiple sclerosis (MS) has a highly heterogenic course making prediction of long term outcome very difficult. Objective The objective was to evaluate current and identify additional clinical factors that are linked to long term outcome of relapsing-remitting MS assessed by disability status 10 years after disease onset. Methods This observational study included 793 patients with relapsing-remitting MS. Clinical factors hypothesized to influence long term outcome measured by EDSS scores 10 years after disease onset were analysed by Kaplan-Meier-estimates. Multinomial logistic regression models regarding mild (EDSS ≤2.5), moderate (EDSS 3.0–5.5) or severe (EDSS ≥6.0) disability were calculated to correct for confounders. Results Secondary progression was the strongest predictor of severe disability (Hazard ratio [HR] 503.8, 95% confidence interval [CI] 160.0–1580.1); p<0.001). Complete remission of neurological symptoms at onset reduced the risk of moderate disability (HR 0.42; CI 0.23–0.77; p = 0.005), while depression (HR 3.59; CI 1.14–11.24; p = 0.028) and cognitive dysfunction (HR 4.64; CI 1.11–19.50; p = 0.036) 10 years after disease onset were associated with severe disability. Oligoclonal bands and pregnancy were not correlated with disability. Conclusion We were able to identify clinically apparent chronic depression and cognitive dysfunction to be associated with adverse long term outcome in MS and to confirm that pregnancy has no negative impact. Additionally, we emphasize the positive predictive value of complete remission of initial symptoms. PMID:27391947

  11. A comparison of the risk factors of intrahepatic recurrence, early recurrencen, and multiple recurrences after resection for single nodular hepatocellular carcinoma

    PubMed Central

    An, Hyun Joon; Shin, Woo Young; Ahn, Seung-Ik

    2015-01-01

    Backgrounds/Aims Intrahepatic recurrence is one of the most important causes of compromised prognosis after surgical resection of hepatocellular carcinoma (HCC). This retrospective study was designed to identify and compare the risks of recurrence, early recurrence and multiple recurrences in a single patient population. Methods A series of 92 consecutive patients, who received resection for single nodular HCC at our institute from January 2007 to December 2013, were enrolled in this study. The patients were divided into recurrent and non-recurrent groups; the recurrent group was further divided into subgroups by applying two criteria: early and late recurrence (with a cutoff of 18 months), and single and multiple (≥2) recurrence. The potential risk factors were compared using univariate and multivariate analyses. The subgroup analysis was performed to determine the effects of different cut-off values on the analysis. Results 41 recurrences (44.6%) occurred during a mean follow-up of 42.4 months. The Child-Pugh score, and the portal vein invasion were found to be independent risk factors of recurrence, but differentiation was the only independent risk factor of early recurrence. The serum alpha-fetoprotein, tumor size, tumor necrosis, and hemorrhage were found to be the risk factors of multiple recurrences according to the univariate analysis, but lacked significance according to the multivariate analysis. When the cutoffs for early and multiple recurrences were changed to ≤10 months and >3 nodules, respectively, different risk factors were identified. Conclusions Our results implicated that different factors can predict the recurrence, timing, and multiplicity of an HCC recurrence. Further studies should be conducted to prove the complex relationships between tumor burden, invasiveness, and underlying liver cirrhosis for initial tumors, and the timing and multiplicity of recurrent HCC. PMID:26379729

  12. Biological impact of vascular endothelial growth factor on vessel density and survival in multiple myeloma and plasmacytoma.

    PubMed

    Swelam, Wael M; Al Tamimi, Dalal M

    2010-11-15

    We compared the differences in a number of angiogenesis-related immunohistochemical parameters, including microvascular density (MVD) and tumor cell activity, between multiple myeloma (MM) and solitary plasmacytoma (SP). Tissue sections from tumors of MM and SP were immunohistochemically stained and analyzed using ImageJ image analysis software for the expression of vascular endothelial growth factor (VEGF), VEGF receptors (Flt-1 and Flk-1), inducible nitric oxide (iNOS), and anti-apoptotic (Bcl-2) protein. Tumor tissues were cytologically graded as high-, intermediate-, or low-grade. Two pathologists determined the MVD of each section independently by recording the average number of CD34+ blood vessels in 500 unit fields. The arithmetic means for MVD were statistically analyzed using the Student's t-test and the significance level was calculated at P-value <0.001. The results indicate a direct correlation between upregulation of iNOS/VEGF in high-grade tumors. For MM, an increase in MVD is also correlated with a high-grade. Tumor survival signaling by Bcl-2 in both SP and MM emphasizes the fact that VEGF has a bimodal role that is mainly angiogenic in MM and tumorigenic, promoting tumor cell survival in SP. PMID:20709463

  13. The town of Cabar, Croatia, a high risk area for multiple sclerosis--analytic epidemiology of dietary factors.

    PubMed

    Perković, Olivio; Jurjević, Ante; Rudez, Josip; Antoncić, Igor; Bralić, Marina; Kapović, Miljenko

    2010-04-01

    Multiple sclerosis (MS) is demyelization disease of central nervous system of unidentified causes. Analytic epidemiological research of 19 patients, clinically approved cases of MS and 25 controls, autochthonic inhabitants of town of Cabar, Croatia, the high-risk zone for the disease, was made. The research plan included case-control investigation--the "door to door" questionnaire--about nutrition habits. An odds ratio (OR) was calculated for all the factors which were more frequently found in the patients than in the controls, and vice versa. The variables that were connected with significant risk for MS in the town of Cabar included: alcohol consumption (p = 0.05), animal fats/dried meat products consumption (p = 0.007), nitrate salting (p = 0.03), strong spices (p = 0.007), mixed bread (p = 0.002), oat and oat products consumption (p = 0.0075). No connection was found with regular consumption of vegetables and fruit (p = 0.009), blue fresh fish (p = 0.028), other fresh fish (p = 0.03), freshwater fish (p = 0.002), canned fish (p = 0.004), dormouse meat (p = 0.007), air-dried meat products (p = 0.004) and using the water from water supply (p = 0.011). In the town of Cabar nutritional customs, primarily food rich in animal fats, alcohol-abuse, and oat consumption could have an influence on MS pathogenesis in genetically inclined individuals. PMID:21305732

  14. Targeting the insulin-like growth factor-1 receptor to overcome bortezomib resistance in preclinical models of multiple myeloma.

    PubMed

    Kuhn, Deborah J; Berkova, Zuzana; Jones, Richard J; Woessner, Richard; Bjorklund, Chad C; Ma, Wencai; Davis, R Eric; Lin, Pei; Wang, Hua; Madden, Timothy L; Wei, Caimiao; Baladandayuthapani, Veerabhadran; Wang, Michael; Thomas, Sheeba K; Shah, Jatin J; Weber, Donna M; Orlowski, Robert Z

    2012-10-18

    Proteasome inhibition with bortezomib is a validated approach to the treatment of multiple myeloma, but drug resistance often emerges and limits its utility in the retreatment setting. To begin to identify some of the mechanisms involved, we developed bortezomib-resistant myeloma cell lines that, unlike previously reported models, showed no β5 subunit mutations. Instead, up-regulation of the insulin-like growth factor (IGF)-1 axis was identified, with increased autocrine and paracrine secretion of IGF-1, leading to increased activation of the IGF-1 receptor (IGF-1R). Exogenous IGF-1 reduced cellular sensitivity to bortezomib, whereas pharmacologic or small hairpin RNA-mediated IGF-1R suppression enhanced bortezomib sensitivity in cell lines and patient samples. In vitro studies with OSI-906, a clinically relevant dual IGF-1R and insulin receptor inhibitor, showed it acted synergistically with bortezomib, and potently resensitized bortezomib-resistant cell lines and patient samples to bortezomib. Importantly, OSI-906 in combination with bortezomib also overcame bortezomib resistance in an in vivo model of myeloma. Taken together, these data support the hypothesis that signaling through the IGF-1/IGF-1R axis contributes to acquired bortezomib resistance, and provide a rationale for combining bortezomib with IGF-1R inhibitors like OSI-906 to overcome or possibly prevent the emergence of bortezomib-refractory disease in the clinic. PMID:22932796

  15. Nucleosome eviction and multiple co-factor binding predict estrogen-receptor-alpha-associated long-range interactions

    PubMed Central

    He, Chao; Wang, Xiaowo; Zhang, Michael Q.

    2014-01-01

    Many enhancers regulate their target genes via long-distance interactions. High-throughput experiments like ChIA-PET have been developed to map such largely cell-type-specific interactions between cis-regulatory elements genome-widely. In this study, we integrated multiple types of data in order to reveal the general hidden patterns embedded in the ChIA-PET data. We found characteristic distance features related to promoter–promoter, enhancer–enhancer and insulator–insulator interactions. Although a protein may have many binding sites along the genome, our hypothesis is that those sites that share certain open chromatin structure can accommodate relatively larger protein complex consisting of specific regulatory and ‘bridging’ factors, and may be more likely to form robust long-range deoxyribonucleic acid (DNA) loops. This hypothesis was validated in the estrogen receptor alpha (ERα) ChIA-PET data. An efficient classifier was built to predict ERα-associated long-range interactions solely from the related ChIP-seq data, hence linking distal ERα-dependent enhancers to their target genes. We further applied the classifier to generate additional novel interactions, which were undetected in the original ChIA-PET paper but were validated by other independent experiments. Our work provides a new insight into the long-range chromatin interactions through deeper and integrative ChIA-PET data analysis and demonstrates DNA looping predictability from ordinary ChIP-seq data. PMID:24782518

  16. More than just one: multiplicity of Hirudins and Hirudin-like Factors in the Medicinal Leech, Hirudo medicinalis.

    PubMed

    Müller, Christian; Mescke, Katharina; Liebig, Stephanie; Mahfoud, Hala; Lemke, Sarah; Hildebrandt, Jan-Peter

    2016-02-01

    Blood-sucking leeches like the medicinal leech, Hirudo medicinalis, have been used for medical purposes since ancient times. During feeding, medicinal leeches transfer a broad range of bioactive substances into the host's wound to prevent premature hemostasis and blood coagulation. Hirudin is probably the best known of these substances. Despite its long history of investigation, recombinant production and clinical use, there still exist conflicting data regarding the primary structure of hirudin. Entirely unclear is the potential biological significance of three different subtypes and many isoforms of hirudins that have been characterized so far. Furthermore, there is only incomplete information on their cDNA sequences and no information at all on gene structures and DNA sequences are available in the databases. Our efforts to fill these gaps revealed the presence of multiple hirudin-encoding genes in the genome of Hirudo medicinalis. We have strong evidence for the expression of all three subtypes of hirudin within individual leeches and for the expression of additional hirudins or hirudin-like factors that may have different biological functions and may be promising candidates for new drugs. PMID:26267058

  17. Multiple post-domestication origins of kabuli chickpea through allelic variation in a diversification-associated transcription factor.

    PubMed

    Varma Penmetsa, R; Carrasquilla-Garcia, Noelia; Bergmann, Emily M; Vance, Lisa; Castro, Brenna; Kassa, Mulualem T; Sarma, Birinchi K; Datta, Subhojit; Farmer, Andrew D; Baek, Jong-Min; Coyne, Clarice J; Varshney, Rajeev K; von Wettberg, Eric J B; Cook, Douglas R

    2016-09-01

    Chickpea (Cicer arietinum) is among the founder crops domesticated in the Fertile Crescent. One of two major forms of chickpea, the so-called kabuli type, has white flowers and light-colored seed coats, properties not known to exist in the wild progenitor. The origin of the kabuli form has been enigmatic. We genotyped a collection of wild and cultivated chickpea genotypes with 538 single nucleotide polymorphisms (SNPs) and examined patterns of molecular diversity relative to geographical sources and market types. In addition, we examined sequence and expression variation in candidate anthocyanin biosynthetic pathway genes. A reduction in genetic diversity and extensive genetic admixture distinguish cultivated chickpea from its wild progenitor species. Among germplasm, the kabuli form is polyphyletic. We identified a basic helix-loop-helix (bHLH) transcription factor at chickpea's B locus that conditions flower and seed colors, orthologous to Mendel's A gene of garden pea, whose loss of function is associated invariantly with the kabuli type of chickpea. From the polyphyletic distribution of the kabuli form in germplasm, an absence of nested variation within the bHLH gene and invariant association of loss of function of bHLH among the kabuli type, we conclude that the kabuli form arose multiple times during the phase of phenotypic diversification after initial domestication of cultivated chickpea. PMID:27193699

  18. MULTIPASS, a rice R2R3-type MYB transcription factor, regulates adaptive growth by integrating multiple hormonal pathways.

    PubMed

    Schmidt, Romy; Schippers, Jos H M; Mieulet, Delphine; Obata, Toshihiro; Fernie, Alisdair R; Guiderdoni, Emmanuel; Mueller-Roeber, Bernd

    2013-10-01

    Growth regulation is an important aspect of plant adaptation during environmental perturbations. Here, the role of MULTIPASS (OsMPS), an R2R3-type MYB transcription factor of rice, was explored. OsMPS is induced by salt stress and expressed in vegetative and reproductive tissues. Over-expression of OsMPS reduces growth under non-stress conditions, while knockdown plants display increased biomass. OsMPS expression is induced by abscisic acid and cytokinin, but is repressed by auxin, gibberellin and brassinolide. Growth retardation caused by OsMPS over-expression is partially restored by auxin application. Expression profiling revealed that OsMPS negatively regulates the expression of EXPANSIN (EXP) and cell-wall biosynthesis as well as phytohormone signaling genes. Furthermore, the expression of OsMPS-dependent genes is regulated by auxin, cytokinin and abscisic acid. Moreover, we show that OsMPS is a direct upstream regulator of OsEXPA4, OsEXPA8, OsEXPB2, OsEXPB3, OsEXPB6 and the endoglucanase genes OsGLU5 and OsGLU14. The multiple responses of OsMPS and its target genes to various hormones suggest an integrative function of OsMPS in the cross-talk between phytohormones and the environment to regulate adaptive growth. PMID:23855375

  19. Regulatory network analysis of transcription factors, microRNAs, target genes and host genes in human multiple myeloma.

    PubMed

    Huang, Zhuoyan; Xu, Zhiwen; Kunhao Wang, Kunhao Wang; Wang, Ning; Wang, Shang

    2015-11-01

    In recent years, molecular biologists have achieved great advance in micro RNA (miRNA) and gene investigation about the pathogenesis of multiple myeloma (MM). Existing research data of the transcription factors (TFs) and miRNAs is disperse and unorganized, which prevents researchers from investigating the mechanism and analyze regulatory pathways of MM systematically. In our research, regulatory interactions among miRNAs, TFs, host genes and target genes were imported to construct regulatory networks at three levels, including the abnormally expressed network and the related network as well as the global network. The abnormally expressed network was primary investigated cause it was an experimentally validated topological network, and it systematically explained the regulatory mechanism of MM. Its outstanding significance lies in that if we correct each abnormally expressed gene and miRNA to normal expression level by transcriptional control adjustment, thus the whole genetic expression network will return to normal state, and MM may not relapse. Additionally, analyses and comparisons to upstream as well as downstream of abnormally expressed miRNAs and genes in three networks highlighted some important regulators and key signaling pathways. For example, STAT3 and hsa-miR-125b, PIAS3 and hsa-miR-21 respectively formed self adaptation feedback regulations. The current research proposed a novel perspective to systematically explained the regulatory mechanism of MM and may contribute to further research and therapy of carcinomas. PMID:26687742

  20. A dynamic RNA loop in an IRES affects multiple steps of elongation factor-mediated translation initiation

    PubMed Central

    Ruehle, Marisa D; Zhang, Haibo; Sheridan, Ryan M; Mitra, Somdeb; Chen, Yuanwei; Gonzalez, Ruben L; Cooperman, Barry S; Kieft, Jeffrey S

    2015-01-01

    Internal ribosome entry sites (IRESs) are powerful model systems to understand how the translation machinery can be manipulated by structured RNAs and for exploring inherent features of ribosome function. The intergenic region (IGR) IRESs from the Dicistroviridae family of viruses are structured RNAs that bind directly to the ribosome and initiate translation by co-opting the translation elongation cycle. These IRESs require an RNA pseudoknot that mimics a codon-anticodon interaction and contains a conformationally dynamic loop. We explored the role of this loop and found that both the length and sequence are essential for translation in different types of IGR IRESs and from diverse viruses. We found that loop 3 affects two discrete elongation factor-dependent steps in the IRES initiation mechanism. Our results show how the IRES directs multiple steps after 80S ribosome placement and highlights the often underappreciated significance of discrete conformationally dynamic elements within the context of structured RNAs. DOI: http://dx.doi.org/10.7554/eLife.08146.001 PMID:26523395

  1. The amplification of 1q21 is an adverse prognostic factor in patients with multiple myeloma in a Chinese population

    PubMed Central

    Yu, Wenjun; Guo, Rui; Qu, Xiaoyan; Qiu, Hairong; Li, Jianyong; Zhang, Run; Chen, Lijuan

    2016-01-01

    The prognostic heterogeneity of multiple myeloma (MM) is largely due to different genetic abnormalities. Cytogenetic analysis has revealed that most of MM harbor chromosome aberrations. Amplification of 1q21 is one of the most common chromosomal aberrations. Interphase fluorescence in situ hybridization was applied to detect the 1q21 amplification in 86 Chinese patients with newly diagnosed MM. Amp(1q21) was found in totally 40 of 86 (46.5%) cases, among which 29 with three copies of 1q21 and eleven with at least four copies of 1q21. Further analysis revealed a significant difference of overall survival and progression-free survival among the three arms (P<0.05). Bortezomib could not significantly improve the overall survival for patients with 1q21 amplification (P>0.05). These findings suggest that 1q21 amplification with four copies or more is prognostic factor for adverse outcomes of MM patients. Furthermore, chromosome 1q21 gains predicted a poor overall survival even in those receiving bortezomib-based regimens. PMID:26834489

  2. Targeting the insulin-like growth factor-1 receptor to overcome bortezomib resistance in preclinical models of multiple myeloma

    PubMed Central

    Kuhn, Deborah J.; Berkova, Zuzana; Jones, Richard J.; Woessner, Richard; Bjorklund, Chad C.; Ma, Wencai; Davis, R. Eric; Lin, Pei; Wang, Hua; Madden, Timothy L.; Wei, Caimiao; Baladandayuthapani, Veerabhadran; Wang, Michael; Thomas, Sheeba K.; Shah, Jatin J.; Weber, Donna M.

    2012-01-01

    Proteasome inhibition with bortezomib is a validated approach to the treatment of multiple myeloma, but drug resistance often emerges and limits its utility in the retreatment setting. To begin to identify some of the mechanisms involved, we developed bortezomib-resistant myeloma cell lines that, unlike previously reported models, showed no β5 subunit mutations. Instead, up-regulation of the insulin-like growth factor (IGF)–1 axis was identified, with increased autocrine and paracrine secretion of IGF-1, leading to increased activation of the IGF-1 receptor (IGF-1R). Exogenous IGF-1 reduced cellular sensitivity to bortezomib, whereas pharmacologic or small hairpin RNA–mediated IGF-1R suppression enhanced bortezomib sensitivity in cell lines and patient samples. In vitro studies with OSI-906, a clinically relevant dual IGF-1R and insulin receptor inhibitor, showed it acted synergistically with bortezomib, and potently resensitized bortezomib-resistant cell lines and patient samples to bor-tezomib. Importantly, OSI-906 in combination with bortezomib also overcame bor-tezomib resistance in an in vivo model of myeloma. Taken together, these data support the hypothesis that signaling through the IGF-1/IGF-1R axis contributes to acquired bortezomib resistance, and provide a rationale for combining bortezomib with IGF-1R inhibitors like OSI-906 to overcome or possibly prevent the emergence of bortezomib-refractory disease in the clinic. PMID:22932796

  3. Genes encoding isoforms of transcription elongation factor TFIIS in Xenopus and the use of multiple unusual RNA processing signals.

    PubMed Central

    Plant, K E; Hair, A; Morgan, G T

    1996-01-01

    We have identified cDNAs encoding three related forms of transcription elongation factor TFIIS (S-II) in Xenopus laevis ovary. Comparison of Xenopus and mammalian sequences identifies likely diagnostic amino acids that distinguish classes of vertebrate TFIIS. The diversity of TFIIS polypeptides in Xenopus is due partly to the presence of two diverged genes in this tetraploid genome. We isolated genomic clones containing one of the genes, xTFIIS.oA, and, unlike a previously described vertebrate TFIIS gene, found that it contains introns. Alternative splicing at a CAG/CAG motif containing the 3' splice site of intron 4 produces the third form of xTFIIS, which differs from one of the others simply in lacking Ser109. Intron 6 of xTFIIS.oA contains splice and branch site consensus sequences conforming to those of the minor class of AT-AC introns and this was confirmed for the homeologous xTFIIS.oB gene by genomic PCR. Other unusual but functional variants of RNA processing signals were found in xTFIIS genes at the 5' splice site of intron 8 and the polyadenylation hexanucleotides. Utilization of multiple unusual processing signals may make the generation of mature xTFIIS.o mRNAs inefficient and the possible regulatory consequences of this are discussed. PMID:8836176

  4. Factors that retard remyelination in multiple sclerosis with a focus on TIP30: a novel therapeutic target.

    PubMed

    Nakahara, Jin; Aiso, Sadakazu; Suzuki, Norihiro

    2009-12-01

    In the CNS oligodendrocytes produce myelin and ensheath individual axons after birth. Demyelination disables saltatory conduction and leads to loss of neural functions. Oligodendrocyte precursor cells (OPCs) are immature and abundant reservoir cells in the adult brain that are capable of differentiating into myelinating oligodendrocytes. Upon demyelination insults, OPCs are spontaneously induced to differentiate in order to remyelinate denuded axons and promote functional recovery. While remyelination is an efficient regenerative process in the CNS, it often fails in the chronic phase of multiple sclerosis (MS). OPCs are nonetheless preserved in many MS lesions, suggesting that arrested OPC differentiation underlies remyelination failure in chronic MS. Understanding the molecular pathology of this arrested differentiation and remyelination failure in chronic MS is critical for developing remyelination medicines that will promote a full functional recovery in these patients. Recently, TIP30 was identified as an inhibitor of OPC differentiation in MS. TIP30 inhibits proper nucleocytoplasmic transport and thus disables nuclear import of transcription factors that are required for differentiation. TIP30 may also increase susceptibility of OPCs to cell death. In this review, we examine the pathophysiological nature of remyelination failure in chronic MS and discuss the role of TIP30 as a novel therapeutic target. PMID:19839715

  5. Content addressable memory project

    NASA Technical Reports Server (NTRS)

    Hall, Josh; Levy, Saul; Smith, D.; Wei, S.; Miyake, K.; Murdocca, M.

    1991-01-01

    The progress on the Rutgers CAM (Content Addressable Memory) Project is described. The overall design of the system is completed at the architectural level and described. The machine is composed of two kinds of cells: (1) the CAM cells which include both memory and processor, and support local processing within each cell; and (2) the tree cells, which have smaller instruction set, and provide global processing over the CAM cells. A parameterized design of the basic CAM cell is completed. Progress was made on the final specification of the CPS. The machine architecture was driven by the design of algorithms whose requirements are reflected in the resulted instruction set(s). A few of these algorithms are described.

  6. Development of a modified factor analysis/multiple regression model to apportion suspended particulate matter in a complex urban airshed

    NASA Astrophysics Data System (ADS)

    Morandi, Maria T.; Daisey, Joan M.; Lioy, Paul J.

    A modified factor analysis/multiple regression (FA/MR) receptor-oriented source apportionment model has been developed which permits application of FA/MR statistical methods when some of the tracers are not unique to an individual source type. The new method uses factor and regression analyses to apportion non-unique tracer ambient concentrations in situations where there are unique tracers for all sources contributing to the non-unique tracer except one, and ascribes the residual concentration to that source. This value is then used as the source tracer in the final FA/MR apportionment model for ambient paniculate matter. In addition, factor analyses results are complemented with examination of regression residuals in order to optimize the number of identifiable sources. The new method has been applied to identify and apportion the sources of inhalable particulate matter (IPM; D5015 μm), Pb and Fe at a site in Newark, NJ. The model indicated that sulfate/secondary aerosol contributed an average of 25.8 μ -3 (48%) to IPM concentrations, followed by soil resuspension (8.2 μ -3 or 15%), paint spraying/paint pigment (6.7/gmm -3or 13%), fuel oil burning/space heating (4.3 μ -3 or 8 %), industrial emissions (3.6 μm -3 or 7 %) and motor vehicle exhaust (2.7 μ -3 or 15 %). Contributions to ambient Pb concentrations were: motor vehicle exhaust (0.16μm -3or 36%), soil resuspension (0.10μm -3 or 24%), fuel oil burning/space heating (0.08μm -3or 18%), industrial emissions (0.07 μ -3 or 17 %), paint spraying/paint pigment (0.036 μm -3or 9 %) and zinc related sources (0.022 μ -3 or 5 %). Contributions to ambient Fe concentrations were: soil resuspension (0.43μ -3or 51%), paint spraying/paint pigment (0.28 μm -3or 33 %) and industrial emissions (0.15 μ -3or 18 %). The models were validated by comparing partial source profiles calculated from modeling results with the corresponding published source emissions composition.

  7. Genome-Wide Identification and Expression Analysis of WRKY Transcription Factors under Multiple Stresses in Brassica napus.

    PubMed

    He, Yajun; Mao, Shaoshuai; Gao, Yulong; Zhu, Liying; Wu, Daoming; Cui, Yixin; Li, Jiana; Qian, Wei

    2016-01-01

    WRKY transcription factors play important roles in responses to environmental stress stimuli. Using a genome-wide domain analysis, we identified 287 WRKY genes with 343 WRKY domains in the sequenced genome of Brassica napus, 139 in the A sub-genome and 148 in the C sub-genome. These genes were classified into eight groups based on phylogenetic analysis. In the 343 WRKY domains, a total of 26 members showed divergence in the WRKY domain, and 21 belonged to group I. This finding suggested that WRKY genes in group I are more active and variable compared with genes in other groups. Using genome-wide identification and analysis of the WRKY gene family in Brassica napus, we observed genome duplication, chromosomal/segmental duplications and tandem duplication. All of these duplications contributed to the expansion of the WRKY gene family. The duplicate segments that were detected indicated that genome duplication events occurred in the two diploid progenitors B. rapa and B. olearecea before they combined to form B. napus. Analysis of the public microarray database and EST database for B. napus indicated that 74 WRKY genes were induced or preferentially expressed under stress conditions. According to the public QTL data, we identified 77 WRKY genes in 31 QTL regions related to various stress tolerance. We further evaluated the expression of 26 BnaWRKY genes under multiple stresses by qRT-PCR. Most of the genes were induced by low temperature, salinity and drought stress, indicating that the WRKYs play important roles in B. napus stress responses. Further, three BnaWRKY genes were strongly responsive to the three multiple stresses simultaneously, which suggests that these 3 WRKY may have multi-functional roles in stress tolerance and can potentially be used in breeding new rapeseed cultivars. We also found six tandem repeat pairs exhibiting similar expression profiles under the various stress conditions, and three pairs were mapped in the stress related QTL regions

  8. Genome-Wide Identification and Expression Analysis of WRKY Transcription Factors under Multiple Stresses in Brassica napus

    PubMed Central

    He, Yajun; Mao, Shaoshuai; Gao, Yulong; Zhu, Liying; Wu, Daoming; Cui, Yixin; Li, Jiana; Qian, Wei

    2016-01-01

    WRKY transcription factors play important roles in responses to environmental stress stimuli. Using a genome-wide domain analysis, we identified 287 WRKY genes with 343 WRKY domains in the sequenced genome of Brassica napus, 139 in the A sub-genome and 148 in the C sub-genome. These genes were classified into eight groups based on phylogenetic analysis. In the 343 WRKY domains, a total of 26 members showed divergence in the WRKY domain, and 21 belonged to group I. This finding suggested that WRKY genes in group I are more active and variable compared with genes in other groups. Using genome-wide identification and analysis of the WRKY gene family in Brassica napus, we observed genome duplication, chromosomal/segmental duplications and tandem duplication. All of these duplications contributed to the expansion of the WRKY gene family. The duplicate segments that were detected indicated that genome duplication events occurred in the two diploid progenitors B. rapa and B. olearecea before they combined to form B. napus. Analysis of the public microarray database and EST database for B. napus indicated that 74 WRKY genes were induced or preferentially expressed under stress conditions. According to the public QTL data, we identified 77 WRKY genes in 31 QTL regions related to various stress tolerance. We further evaluated the expression of 26 BnaWRKY genes under multiple stresses by qRT-PCR. Most of the genes were induced by low temperature, salinity and drought stress, indicating that the WRKYs play important roles in B. napus stress responses. Further, three BnaWRKY genes were strongly responsive to the three multiple stresses simultaneously, which suggests that these 3 WRKY may have multi-functional roles in stress tolerance and can potentially be used in breeding new rapeseed cultivars. We also found six tandem repeat pairs exhibiting similar expression profiles under the various stress conditions, and three pairs were mapped in the stress related QTL regions

  9. Identification of multiple cellular uptake pathways of polystyrene nanoparticles and factors affecting the uptake: relevance for drug delivery systems.

    PubMed

    Firdessa, Rebuma; Oelschlaeger, Tobias A; Moll, Heidrun

    2014-01-01

    Nanoparticles may address challenges by human diseases through improving diagnosis, vaccination and treatment. The uptake mechanism regulates the type of threat a particle poses on the host cells and how a cell responds to it. Hence, understanding the uptake mechanisms and cellular interactions of nanoparticles at the cellular and subcellular level is a prerequisite for their effective biomedical applications. The present study shows the uptake mechanisms of polystyrene nanoparticles and factors affecting their uptake in bone marrow-derived macrophages, 293T kidney epithelial cells and L929 fibroblasts. Labeling with the endocytic marker FM4-64 and transmission electron microscopy studies show that the nanoparticles were internalized rapidly via endocytosis and accumulated in intracellular vesicles. Soon after their internalizations, nanoparticles trafficked to organelles with acidic pH. Analysis of the ultrastructural morphology of the plasma membrane invaginations or extravasations provides clear evidence for the involvement of several uptake routes in parallel to internalize a given type of nanoparticles by mammalian cells, highlighting the complexity of the nanoparticle-cell interactions. Blocking the specific endocytic pathways by different pharmacological inhibitors shows similar outcomes. The potential to take up nanoparticles varies highly among different cell types in a particle sizes-, time- and energy-dependent manner. Furthermore, infection and the activation status of bone marrow-derived macrophages significantly affect the uptake potential of the cells, indicating the need to understand the diseases' pathogenesis to establish effective and rational drug-delivery systems. This study enhances our understanding of the application of nanotechnology in biomedical sciences. PMID:25224362

  10. Addressing Software Security

    NASA Technical Reports Server (NTRS)

    Bailey, Brandon

    2015-01-01

    Historically security within organizations was thought of as an IT function (web sites/servers, email, workstation patching, etc.) Threat landscape has evolved (Script Kiddies, Hackers, Advanced Persistent Threat (APT), Nation States, etc.) Attack surface has expanded -Networks interconnected!! Some security posture factors Network Layer (Routers, Firewalls, etc.) Computer Network Defense (IPS/IDS, Sensors, Continuous Monitoring, etc.) Industrial Control Systems (ICS) Software Security (COTS, FOSS, Custom, etc.)

  11. Treatment Results of Postoperative Radiotherapy on Squamous Cell Carcinoma of the Oral Cavity: Coexistence of Multiple Minor Risk Factors Results in Higher Recurrence Rates

    SciTech Connect

    Fan, Kang-Hsing; Wang, Hung-Ming; Kang, Chung-Jan

    2010-07-15

    Purpose: The aim of this study was to investigate the treatment results of postoperative radiotherapy (PORT) on squamous cell carcinoma of the oral cavity (OSCC). Materials and Methods: This study included 302 OSCC patients who were treated by radical surgery and PORT. Indications for PORT include Stage III or IV OSCC according to the 2002 criteria of the American Joint Committee on Cancer, the presence of perineural invasion or lymphatic invasion, the depth of tumor invasion, or a close surgical margin. Patients with major risk factors, such as multiple nodal metastases, a positive surgical margin, or extracapsular spreading, were excluded. The prescribed dose of PORT ranged from 59.4 to 66.6Gy (median, 63Gy). Results: The 3-year overall and recurrence-free survival rates were 73% and 70%, respectively. Univariate analysis revealed that differentiation, perineural invasion, lymphatic invasion, bone invasion, location (hard palate and retromolar trigone), invasion depths {>=}10mm, and margin distances {<=}4mm were significant prognostic factors. The presence of multiple significant factors of univariate analysis correlated with disease recurrence. The 3-year recurrence-free survival rates were 82%, 76%, and 45% for patients with no risk factors, one or two risk factors, and three or more risk factors, respectively. After multivariate analysis, the number of risk factors and lymphatic invasion were significant prognostic factors. Conclusion: PORT may be an adequate adjuvant therapy for OSCC patients with one or two risk factors of recurrence. The presence of multiple risk factors and lymphatic invasion correlated with poor prognosis, and more aggressive treatment may need to be considered.

  12. Brain-derived neurotrophic and immunologic factors: beneficial effects of riboflavin on motor disability in murine model of multiple sclerosis

    PubMed Central

    Naghashpour, Mahshid; Amani, Reza; Sarkaki, Alireza; Ghadiri, Ata; Samarbafzadeh, Alireza; Jafarirad, Sima; Malehi, Amal Saki

    2016-01-01

    Objective(s): In the present study, C57BL/6 female mice (n=56) were used to explore the neuroprotective effects of riboflavin in motor disability of experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis. Materials and Methods: The animals were assigned into 7 groups: sham-operated 1 (SO1), healthy mice receiving PBS (phosphate buffer saline); sham-operated 2 (SO2), healthy mice receiving PBS and riboflavin; sham treatment 1 (ST1), EAE mice receiving water; sham treatment 2 (ST2), EAE mice receiving sodium acetate buffer; treatment 1 (T1), EAE mice receiving interferon beta-1a (INFβ-1a); treatment 2 (T2), EAE mice receiving riboflavin; treatment 3 (T3), EAE mice receiving INFβ-1a and riboflavin. After EAE induction, scoring was performed based on clinical signs. Upon detecting score 0.5, riboflavin at 10 mg/kg of body weight and/or INFβ-1a at 150 IU/g of body weight administration was started for two weeks. The brain and spinal cord levels of brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and interleukin-17A (IL-17A) were studied using real-time PCR and ELISA methods. Results: BDNF expression and protein levels were increased in the brain and spinal cord of the T3 group compared with the other groups (P<0.01). IL-6 and IL-17A expressions were increased in the brains of the T3 and T1 groups, respectively, compared to the other groups (P<0.01). The daily clinical score was reduced significantly by riboflavin in both effector and chronic phases of the disease compared with that of the controls (P<0.05). Conclusion: Our findings showed that riboflavin is capable of suppressing the neurological disability mediated by BDNF and IL-6. PMID:27279989

  13. Global Effect of Indole-3-Acetic Acid Biosynthesis on Multiple Virulence Factors of Erwinia chrysanthemi 3937▿

    PubMed Central

    Yang, Shihui; Zhang, Qiu; Guo, Jianhua; Charkowski, Amy O.; Glick, Bernard R.; Ibekwe, A. Mark; Cooksey, Donald A.; Yang, Ching-Hong

    2007-01-01

    Production of the plant hormone indole-3-acetic acid (IAA) is widespread among plant-associated microorganisms. The non-gall-forming phytopathogen Erwinia chrysanthemi 3937 (strain Ech3937) possesses iaaM (ASAP16562) and iaaH (ASAP16563) gene homologues. In this work, the null knockout iaaM mutant strain Ech138 was constructed. The IAA production by Ech138 was reduced in M9 minimal medium supplemented with l-tryptophan. Compared with wild-type Ech3937, Ech138 exhibited reduced ability to produce local maceration, but its multiplication in Saintpaulia ionantha was unaffected. The pectate lyase production of Ech138 was diminished. Compared with wild-type Ech3937, the expression levels of an oligogalacturonate lyase gene, ogl, and three endopectate lyase genes, pelD, pelI, and pelL, were reduced in Ech138 as determined by a green fluorescent protein-based fluorescence-activated cell sorting promoter activity assay. In addition, the transcription of type III secretion system (T3SS) genes, dspE (a putative T3SS effector) and hrpN (T3SS harpin), was found to be diminished in the iaaM mutant Ech138. Compared with Ech3937, reduced expression of hrpL (a T3SS alternative sigma factor) and gacA but increased expression of rsmA in Ech138 was also observed, suggesting that the regulation of T3SS and pectate lyase genes by IAA biosynthesis might be partially due to the posttranscriptional regulation of the Gac-Rsm regulatory pathway. PMID:17189441

  14. Mangiferin induces apoptosis in multiple myeloma cell lines by suppressing the activation of nuclear factor kappa B-inducing kinase.

    PubMed

    Takeda, Tomoya; Tsubaki, Masanobu; Kino, Toshiki; Yamagishi, Misa; Iida, Megumi; Itoh, Tatsuki; Imano, Motohiro; Tanabe, Genzoh; Muraoka, Osamu; Satou, Takao; Nishida, Shozo

    2016-05-01

    Mangiferin is a naturally occurring glucosyl xanthone, which induces apoptosis in various cancer cells. However, the molecular mechanism underlying mangiferin-induced apoptosis has not been clarified thus far. Therefore, we examined the molecular mechanism underlying mangiferin-induced apoptosis in multiple myeloma (MM) cell lines. We found that mangiferin decreased the viability of MM cell lines in a concentration-dependent manner. We also observed an increased number of apoptotic cells, caspase-3 activation, and a decrease in the mitochondrial membrane potential. In addition, mangiferin inhibited the nuclear translocation of nuclear factor kappa B (NF-κB) and expression of phosphorylated inhibitor kappa B (IκB) and increased the expression of IκB protein, whereas no changes were observed in the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase 1/2 (JNK1/2), and mammalian target of rapamycin (mTOR). The molecular mechanism responsible for mangiferin-induced inhibition of nuclear translocation of NF-κB was a decrease in the expression of phosphorylated NF-κB-inducing kinase (NIK). Moreover, mangiferin decreased the expression of X-linked inhibitor of apoptosis protein (XIAP), survivin, and Bcl-xL proteins. Knockdown of NIK expression showed results similar to those observed with mangiferin treatment. Our results suggest that mangiferin induces apoptosis through the inhibition of nuclear translocation of NF-κB by suppressing NIK activation in MM cell lines. Our results provide a new insight into the molecular mechanism of mangiferin-induced apoptosis. Importantly, since the number of reported NIK inhibitors is limited, mangiferin, which targets NIK, may be a potential anticancer agent for the treatment of MM. PMID:26996543

  15. Hand washing behavior and associated factors in Vietnam based on the Multiple Indicator Cluster Survey, 2010–2011

    PubMed Central

    To, Kien Gia; Lee, Jong-Koo; Nam, You-Seon; Trinh, Oanh Thi Hoang; Van Do, Dung

    2016-01-01

    Background Handwashing is a cost-effective way of preventing communicable diseases such as respiratory and food-borne illnesses. However, handwashing rates are low in developing countries. Target 7C of the seventh Millennium Development Goals was to increase by half the proportion of people with sustainable access to safe drinking water and basic sanitation by 2015. Studies have found that better access to improved water sources and sanitation is associated with higher rates of handwashing. Objective Our goal was to describe handwashing behaviour and identify the associated factors in Vietnamese households. Design Data from 12,000 households participating in the Vietnam Multiple Indicator Cluster Survey 2011 were used. The survey used a multistage sampling method to randomly select 100 clusters and 20 households per cluster. Self-administered questionnaires were used to collect data from a household representative. Demographic variables, the presence of a specific place for handwashing, soap and water, access to improved sanitation, and access to improved water sources were tested for association with handwashing behaviour in logistic regression. Results Almost 98% of households had a specific place for handwashing, and 85% had cleansing materials and water at such a place. The prevalence of handwashing in the sample was almost 85%. Educational level, ethnicity of the household head, and household wealth were factors associated with handwashing practice (p<0.05). Those having access to an improved sanitation facility were more likely to practise handwashing [odds ratio (OR)=1.69, 95% confidence interval (CI): 1.37–2.09, p<0.001], as were those with access to improved water sources (OR=1.74, 95% CI: 1.37–2.21, p<0.001). Conclusions Households with low education, low wealth, belonging to ethnic minorities, and with low access to improved sanitation facilities and water sources should be targeted for interventions implementing handwashing practice. In addition

  16. Total joint replacement: A multiple risk factor analysis of physical activity level 1–2 years postoperatively

    PubMed Central

    Torres, Andy; Love, Rebecca M; Barber, Thomas C; Sheth, Dhiren S; Inacio, Maria C S

    2016-01-01

    Background and purpose — The effect of total joint arthroplasty (TJA) on physical activity is not fully understood. We investigated the change in physical activity after TJA and patient factors associated with change. Patients and methods — Using a total joint replacement registry, primary total hip arthroplasty (THA) patients (n = 5,678) and knee arthroplasty (TKA) patients (n = 11,084) between January 1, 2010 and December 31, 2012 were identified. Median age at THA was 68 and median age at TKA was 67. Change in self-reported physical activity (minutes per week) from before TJA (within 1 year of surgery) to after TJA (1–2 years) was the outcome of interest. Patient demographics and comorbidities were evaluated as risk factors. Multiple linear regression was used. Results — Median physical activity before surgery was 50 min/week (IQR: 0–140) for THA patients and 58 (IQR: 3–143) for TKA patients. Median physical activity after surgery was 150 min/week (IQR: 60–280) for both THA patients and TKA patients. Following TJA, 50% of patients met CDC/WHO physical activity guideline criteria. Higher body mass index was associated with lower change in physical activity (THA: −7.1 min/week; TKA: −5.9 min/week). Females had lower change than males (THA: −11 min/week; TKA: −9.1 min/week). In TKA patients, renal failure was associated with lower change (−17 min/week), as were neurological disorders (−30 min/week). Interpretation — Self-reported minutes of physical activity increased from before to after TJA, but 50% of TJA patients did not meet recommended physical activity guideline criteria. Higher body mass index, female sex, and specific comorbidities were found to be associated with low change in physical activity. Patient education on the benefits of physical activity should concentrate on these subgroups of patients. PMID:27299567

  17. Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

    PubMed Central

    Santo, Vítor E.; Mano, João F.; Reis, Rui L.

    2013-01-01

    The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors. PMID:23249320

  18. Impact of multiple cardiovascular risk factors on femoral artery intima-media thickness in asymptomatic young adults (the Bogalusa Heart Study).

    PubMed

    Paul, Timir K; Srinivasan, Sathanur R; Chen, Wei; Li, Shengxu; Bond, M Gene; Tang, Rong; Berenson, Gerald S

    2005-02-15

    Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases in middle-aged and older adults. Although risk factors for coronary artery disease are also associated with increased IMT, especially as measured in carotid arteries, there is a paucity of information with respect to the femoral artery in this regard in the asymptomatic, younger adult population. This study examined the impact of multiple risk factors on the common femoral artery IMT as measured by B-mode ultrasonography in 1,080 black and white subjects aged 24 to 43 years (71% white and 43% men) enrolled in the Bogalusa Heart Study. Femoral IMT showed gender difference (men more than women, p = 0.001), but no racial difference. In a multivariate model, systolic blood pressure, age, male gender, cigarette smoking, and total cholesterol/high-density lipoprotein cholesterol ratios related independently, in that order, to IMT. Mean IMT increased with an increasing number of risk factors defined as values above the age-, race-, and gender-specific 75th percentile of systolic blood pressure, waist circumference, total cholesterol/high-density lipoprotein cholesterol ratio, and insulin along with smoking status (p for trend = 0.003), with respective mean IMT values of 0.66, 0.69, 0.73, and 0.79 mm for 0, 1 to 2, 3, and 4 to 5 risk factors. The odds ratio for patients with >/=3 risk factors versus no risk factors having IMT in the top fifth percentile was 4.7 (p = 0.01). The observed adverse trend of increasing femoral IMT with an increasing number of risk factors in free-living, asymptomatic young subjects underscores the need for multiple risk factors profiling in early life. Further, ultrasonography of the femoral artery in conjunction with multiple risk factor profiling can be helpful in risk stratification. PMID:15695130

  19. Addressing neurological disorders with neuromodulation.

    PubMed

    Oluigbo, Chima O; Rezai, Ali R

    2011-07-01

    Neurological disorders are becoming increasingly common in developed countries as a result of the aging population. In spite of medications, these disorders can result in progressive loss of function as well as chronic physical, cognitive, and emotional disability that ultimately places enormous emotional and economic on the patient, caretakers, and the society in general. Neuromodulation is emerging as a therapeutic option in these patients. Neuromodulation is a field, which involves implantable devices that allow for the reversible adjustable application of electrical, chemical, or biological agents to the central or peripheral nervous system with the objective of altering its functioning with the objective of achieving a therapeutic or clinically beneficial effect. It is a rapidly evolving field that brings together many different specialties in the fields of medicine, materials science, computer science and technology, biomedical, and neural engineering as well as the surgical or interventional specialties. It has multiple current and emerging indications, and an enormous potential for growth. The main challenges before it are in the need for effective collaboration between engineers, basic scientists, and clinicians to develop innovations that address specific problems resulting in new devices and clinical applications. PMID:21193369

  20. Presidential address: imagination trumps knowledge.

    PubMed

    Moore, Frederick A

    2010-12-01

    Multiple organ failure (MOF) emerged 30 years ago and became our research focus. Over the years, we have proposed a series of cartoons that rallied multidisciplinary translational research teams around common themes to generate "win-win" hypotheses that when tested (right or wrong) have advanced our understanding of MOF. MOF has a bimodal trajectory, and the gut plays a role in both trajectories. Early MOF occurs because of excessive proinflammation (ie, systemic inflammatory response syndrome [SIRS]), and early gut ischemia-reperfusion can amplify SIRS and contribute to the early fulminant SIRS-MOF trajectory. Fortunately, most patients survive early SIRS, but some develop excessive anti-inflammation (ie, compensatory anti-inflammatory response syndrome). The gut also plays a role in this late indolent compensatory anti-inflammatory response syndrome-MOF trajectory. Multiple factors cause progressive gut dysfunction such that the gut (an important immunologic organ) worsens compensatory anti-inflammatory response syndrome and becomes the reservoir for pathogens and toxins that cause late sepsis. PMID:21146000

  1. Geomagnetic disturbances may be environmental risk factor for multiple sclerosis: an ecological study of 111 locations in 24 countries

    PubMed Central

    2012-01-01

    Background We noticed that a hypothesis based on the effect of geomagnetic disturbances (GMD) has the ability to explain special features of multiple sclerosis (MS). Areas around geomagnetic 60 degree latitude (GM60L) experience the greatest amount of GMD. The easiest way to evaluate our hypothesis was to test the association of MS prevalence (MSP) with angular distance to geomagnetic 60 degree latitude (AMAG60) and compare it with the known association of MS with geographical latitude (GL). We did the same with angular distance to geographic 60 degree latitude (AGRAPH60) as a control. Methods English written papers with MSP keywords, done in Europe (EUR), North America (NA) or Australasia (AUS) were retrieved from the PubMed. Geomagnetic coordinates were determined for each location and AMAG60 was calculated as absolute value of numerical difference between its geomagnetic latitude from GM60L. By an ecological study with using meta-regression analyses, the relationship of MSP with GL, AMAG60 and AGRAPH60 were evaluated separately. MSP data were weighted by square root of number of prevalent cases. Models were compared by their adjusted R square (AR2) and standard error of estimate (SEE). Results 111 MSP data were entered in the study. In each continent, AMAG60 had the best correlation with MSP, the largest AR2 (0.47, 0.42 and 0.84 for EUR, NA and AUS, respectively) and the least SEE. Merging both hemispheres data, AMAG60 explained 56% of MSP variations with the least SEE (R = 0.75, AR2 = 0.56, SEE = 57), while GL explained 17% (R = 0.41, AR2 = 0.17, SEE = 78.5) and AGRAPH60 explained 12% of that variations with the highest SEE (R = 0.35, AR2 = 0.12, SEE = 80.5). Conclusions Our results confirmed that AMAG60 is the best describer of MSP variations and has the strongest association with MSP distribution. They clarified that the well-known latitudinal gradient of MSP may be actually a gradient related to GM60L. Moreover, the

  2. Characterization of concentration, particle size distribution, and contributing factors to ambient hexavalent chromium in an area with multiple emission sources

    NASA Astrophysics Data System (ADS)

    Yu, Chang Ho; Huang, Lihui; Shin, Jin Young; Artigas, Francisco; Fan, Zhi-hua (Tina)

    2014-09-01

    Airborne hexavalent chromium (Cr(VI)) is a known pulmonary carcinogen and can be emitted from both natural and anthropogenic sources, including diesel emissions. However, there is limited knowledge about ambient Cr(VI) concentration levels and its particle size distribution. This pilot study characterized ambient Cr(VI) concentrations in the New Jersey Meadowlands (NJ ML) district, which is close to the heavily trafficked New Jersey Turnpike (NJTPK) as well as Chromium Ore Processing Residue (COPR) waste sites. Monitoring was simultaneously conducted at two sites, William site (∼50 m from NJTPK) and MERI site (∼700 m from NJTPK). The distance between the two sites is approximately 6.2 km. Ambient Cr(VI) concentrations and PM2.5 mass concentrations were concurrently measured at both sites during summer and winter. The summer concentrations (mean ± S.D. [median]), 0.13 ± 0.06 [0.12] ng/m3 at the MERI site and 0.08 ± 0.05 [0.07] ng/m3 at the William site, were all significantly higher than the winter concentrations, 0.02 ± 0.01 [0.02] ng/m3 and 0.03 ± 0.01 [0.03] ng/m3 at the MERI and William sites, respectively. The site difference (i.e., MERI > William) was observed for summer Cr(VI) concentrations; however, no differences for winter and pooled datasets. These results suggest higher Cr(VI) concentrations may be attributed from stronger atmospheric reactions such as photo-oxidation of Cr(III) to Cr(VI) in the summer. The Cr(VI) distribution as a function of particle size, ranging from 0.18 to 18 μm, was determined at the William site. It was found that Cr(VI) was enriched in the particles less than 2.5 μm in diameter (PM2.5). This finding suggested potential health concerns, because PM2.5 are easily inhaled and deposited in the alveoli. A multiple linear regression analysis confirmed ambient Cr(VI) concentrations were significantly affected by meteorological factors (i.e., temperature and humidity) and reactive gases/particles (i.e., O3, Fe and Mn).

  3. Characterization of concentration, particle size distribution, and contributing factors to ambient hexavalent chromium in an area with multiple emission sources

    PubMed Central

    Yu, Chang Ho; Huang, Lihui; Shin, Jin Young; Artigas, Francisco; Fan, Zhi-hua (Tina)

    2015-01-01

    Airborne hexavalent chromium (Cr(VI)) is a known pulmonary carcinogen and can be emitted from both natural and anthropogenic sources, including diesel emissions. However, there is limited knowledge about ambient Cr(VI) concentration levels and its particle size distribution. This pilot study characterized ambient Cr(VI) concentrations in the New Jersey Meadowlands (NJ ML) district, which is close to the heavily trafficked New Jersey Turnpike (NJTPK) as well as Chromium Ore Processing Residue (COPR) waste sites. Monitoring was simultaneously conducted at two sites, William site (~50 m from NJTPK) and MERI site (~700 m from NJTPK). The distance between the two sites is approximately 6.2 km. Ambient Cr(VI) concentrations and PM2.5 mass concentrations were concurrently measured at both sites during summer and winter. The summer concentrations (mean ± S.D. [median]), 0.13 ± 0.06 [0.12] ng/m3 at the MERI site and 0.08 ± 0.05 [0.07] ng/m3 at the William site, were all significantly higher than the winter concentrations, 0.02 ± 0.01 [0.02] ng/m3 and 0.03 ± 0.01 [0.03] ng/m3 at the MERI and William sites, respectively. The site difference (i.e., MERI > William) was observed for summer Cr(VI) concentrations; however, no differences for winter and pooled datasets. These results suggest higher Cr(VI) concentrations may be attributed from stronger atmospheric reactions such as photo-oxidation of Cr(III) to Cr(VI) in the summer. The Cr(VI) distribution as a function of particle size, ranging from 0.18 to 18 μm, was determined at the William site. It was found that Cr(VI) was enriched in the particles less than 2.5 μm in diameter (PM2.5). This finding suggested potential health concerns, because PM2.5 are easily inhaled and deposited in the alveoli. A multiple linear regression analysis confirmed ambient Cr(VI) concentrations were significantly affected by meteorological factors (i.e., temperature and humidity) and reactive gases/particles (i.e., O3, Fe and Mn). PMID

  4. Image compression using address-vector quantization

    NASA Astrophysics Data System (ADS)

    Nasrabadi, Nasser M.; Feng, Yushu

    1990-12-01

    A novel vector quantization scheme, the address-vector quantizer (A-VQ), is proposed which exploits the interblock correlation by encoding a group of blocks together using an address-codebook (AC). The AC is a set of address-codevectors (ACVs), each representing a combination of addresses or indices. Each element of the ACV is an address of an entry in the LBG-codebook, representing a vector-quantized block. The AC consists of an active (addressable) region and an inactive (nonaddressable) region. During encoding the ACVs in the AC are reordered adaptively to bring the most probable ACVs into the active region. When encoding an ACV, the active region is checked, and if such an address combination exists, its index is transmitted to the receiver. Otherwise, the address of each block is transmitted individually. The SNR of the images encoded by the A-VQ method is the same as that of a memoryless vector quantizer, but the bit rate is by a factor of approximately two.

  5. Multiplicity of hypoxia-inducible transcription factors and their connection to the circadian clock in the zebrafish.

    PubMed

    Pelster, Bernd; Egg, Margit

    2015-01-01

    In zebrafish, as in most vertebrates, three different isoforms of the hypoxia-inducible transcription factor, Hif-1α, Hif-2α, and Hif-3α, have been identified. The expression data of genes encoding these three proteins, as analyzed so far, show distinct expression patterns for all three isoforms during early development, under hypoxic conditions, and during exercise, suggesting differential roles for all three proteins under these different conditions. While isoform-specific functions for Hif-1α and Hif-2α have been identified in recent years, the role of Hif-3α remains somewhat elusive. Several studies mostly using mammalian cells or tissues discussed Hif-3α as a competitive inhibitor of Hif-1α and Hif-2α. In zebrafish, the expression changes for Hif-1α and Hif-3α observed during development and under environmental stress conditions do not support this hypothesis, and recent studies indicate that Hif-3α is also able to directly control transcriptional activity of certain genes. The Hif signaling pathway is tightly connected to cell circuitries such as glucose and lipid metabolism, and only very recently a further linkage to the circadian clock has been described. In this context a detailed analysis of the mRNA concentrations of hif-1α, hif-2α, and hif-3α also revealed a circadian expression pattern for hif-3α mRNA under normoxic conditions in zebrafish larvae. In addition, accumulation of Hif-1α protein during short-term hypoxia was found to depend on the time within the daily light and dark cycle at which hypoxia was encountered, suggesting that the hypoxia signaling pathway may be regulated by the circadian clock. This is supported by the fact that some of the downstream genes of the Hif signaling pathway, namely, erythropoietin and vascular endothelial growth factor, are known to be clock controlled as well. Furthermore, in developing zebrafish, the disruption of the circadian rhythm was shown to result in a diminished hypoxic response with a

  6. Predicting Prostate Cancer Mortality Among Men With Intermediate to High-Risk Disease and Multiple Unfavorable Risk Factors

    SciTech Connect

    Nguyen, Paul L. Chen Minghui; Catalona, William J.; Moul, Judd W.; Sun, Leon; D'Amico, Anthony V.

    2009-03-01

    Purpose: To determine whether the number of unfavorable risk factors could be used to predict the risk of prostate cancer-specific mortality (PCSM) among men with intermediate- to high-risk prostate cancer. Methods and Materials: We studied 1,063 men who underwent radical prostatectomy (n = 559), external beam radiotherapy (n = 288), or radiotherapy plus androgen suppression therapy (n = 116) for prostate cancer between 1965 and 2002. Fine and Gray's regression analysis was used to determine whether an increasing number of unfavorable risk factors (prostate-specific antigen level >10 ng/mL, Gleason score of {>=}7, clinical Stage T2b or greater, or pretreatment prostate-specific antigen velocity >2.0 ng/mL/y) was associated with the interval to PCSM and all-cause mortality. Results: Median follow-up was 5.6 years. Compared with those with one risk factor, the adjusted hazard ratio for PCSM was 2.3 (95% confidence interval 1.1-4.8; p = 0.03) for two risk factors, 5.4 (95% confidence interval 2.7-10.7; p < 0.0001) for three risk factors, and 13.6 (95% confidence interval 6.3-29.2; p < 0.0001) for all four risk factors. The 5-year cumulative incidence of PCSM was 2.4% for one factor, 2.4% for two factors, 7.0% for three factors, and 14.7% for all four factors. Prostate cancer deaths as a proportion of all deaths was 19% for one factor, 33% for two factors, 53% for three factors, and 80% for four factors. Conclusion: The number of unfavorable risk factors was significantly associated with PCSM. Prostate cancer was the major cause of death in men with at least three risk factors. Therefore, these men should be considered for clinical trials designed to assess whether survival is prolonged with the addition of novel agents to current standards of practice.

  7. Assessment of factors which affect multiple uses of water sources at household level in rural Zimbabwe - A case study of Marondera, Murehwa and Uzumba Maramba Pfungwe districts

    NASA Astrophysics Data System (ADS)

    Katsi, Luckson; Siwadi, Japson; Guzha, Edward; Makoni, Fungai S.; Smits, Stef

    Water with all its multiple uses plays a pivotal role in the sustenance of rural livelihoods, especially the poor. As such, the provision of water which go beyond domestic to include water for small-scale productive uses should be encouraged to enhance peoples’ livelihood options by making significant contribution to household income, food security, improved nutrition and health. All these multiple benefits, if combined can assist in the fight against hunger and poverty. This study was conducted in Mashonaland East province, covering Marondera, Murehwa and Uzumba Maramba Pfungwe districts in Zimbabwe for the period December 2005-May 2006 to assess factors which affect multiple uses of water sources at household level. Participatory Rural Appraisal tools such as discussions, observations and interviews were used for data collection. The survey found that people indeed require water for productive purposes apart from domestic uses, which are often given top priority. The study found out that multiple uses of water sources at household level can be affected by segmentation of water services into domestic and productive water supply schemes, technology and system design, water quality and quantity and distance to water sources among other factors. The study recommends that water service providers to be able to provide appropriate, efficient and sustainable services, they should understand and appreciate that people’s water needs are integrated and are part and parcel of their multifaceted livelihood strategies.

  8. A 3D point-kernel multiple scatter model for parallel-beam SPECT based on a gamma-ray buildup factor

    NASA Astrophysics Data System (ADS)

    Marinkovic, Predrag; Ilic, Radovan; Spaic, Rajko

    2007-09-01

    A three-dimensional (3D) point-kernel multiple scatter model for point spread function (PSF) determination in parallel-beam single-photon emission computed tomography (SPECT), based on a dose gamma-ray buildup factor, is proposed. This model embraces nonuniform attenuation in a voxelized object of imaging (patient body) and multiple scattering that is treated as in the point-kernel integration gamma-ray shielding problems. First-order Compton scattering is done by means of the Klein-Nishina formula, but the multiple scattering is accounted for by making use of a dose buildup factor. An asset of the present model is the possibility of generating a complete two-dimensional (2D) PSF that can be used for 3D SPECT reconstruction by means of iterative algorithms. The proposed model is convenient in those situations where more exact techniques are not economical. For the proposed model's testing purpose calculations (for the point source in a nonuniform scattering object for parallel beam collimator geometry), the multiple-order scatter PSF generated by means of the proposed model matched well with those using Monte Carlo (MC) simulations. Discrepancies are observed only at the exponential tails mostly due to the high statistic uncertainty of MC simulations in this area, but not because of the inappropriateness of the model.

  9. 2014 ASHG Awards and Addresses

    PubMed Central

    2015-01-01

    Each year at the annual meeting of The American Society of Human Genetics (ASHG), addresses are given in honor of The Society and a number of award winners. A summary of each of these addresses is given below. On the following pages, we have printed the presidential address and the addresses for the William Allan Award, the Curt Stern Award, and the Victor A. McKusick Leadership Award. Webcasts of these addresses, as well as those of many other presentations, can be found at http://www.ashg.org.

  10. 2013 ASHG Awards and Addresses

    PubMed Central

    2014-01-01

    Each year at the annual meeting of The American Society of Human Genetics (ASHG), addresses are given in honor of The Society and a number of award winners. A summary of each of these addresses is given below. On the following pages, we have printed the Presidential Address and the addresses for the William Allan Award, the Curt Stern Award, and the Victor A. McKusick Leadership Award. Webcasts of these addresses, as well as those of many other presentations, can be found at http://www.ashg.org.

  11. A registry-based case-control study of risk factors for the development of multiple non-fatal injuries on the job.

    PubMed

    Li, C Y; Du, C L; Chen, C J; Sung, F C

    1999-07-01

    Using compensation records of Taiwan, we conducted a case-control study nested within a cohort of 77,846 active workers who experienced at least one incidence of non-fatal work-related injury between 1994 and 1996 in order to explore factors associated with risk of sustaining multiple non-fatal injuries in the workplace. Cases (n = 2,616) were workers with more than three incidences of non-fatal injury during the study period and controls (n = 3,974) were randomly sampled from workers who experienced only one incidence of non-fatal injury during the same period. Compared with construction workers, workers employed in mining and quarrying (OR = 2.7), manufacturing (OR = 1.2), commerce (OR = 1.6), transport, storage and communication (OR = 1.3) and social, personal and community service (OR = 1.4) were all at significantly elevated risk of multiple non-fatal injuries. Both age and wage showed a significant dose-response effect on the risk of developing multiple non-fatal injuries. The preliminary analysis suggests that workers in certain industries are at significantly elevated risks of multiple work-related non-fatal injuries, in particular those in the mining and quarry industries. Additionally, further preventive measures should be aimed at protecting older workers from such injuries and further studies would help provide more specific interpretations on the positive association between higher wage earning and risk of multiple non-fatal injuries. PMID:10628060

  12. Examining the Factor Structure and Psychometric Properties of the Quality of Life Scale among People with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Fitzgerald, Shawn M.; Li, Jian; Rumrill, Phillip D., Jr.; Bishop, Malachy; Merchant, William R.

    2015-01-01

    Rehabilitation counseling researchers seeking to more fully understand the phenomenon of psychosocial adaptation to disability are devoting increased attention to the impact of disability on quality of life (QOL). This impact has been of particular interest among multiple sclerosis (MS) researchers. The complex etiology, unpredictable nature, and…

  13. The Relationship of Selected Supply- and Demand-Side Factors to Forms of Perceived Discrimination among Adults with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Roessler, Richard T.; Neath, Jeanne; McMahon, Brian T.; Rumrill, Phillip D.

    2007-01-01

    Single-predictor and stepwise multinomial logistic regression analyses and an external validation were completed on 3,082 allegations of employment discrimination by adults with multiple sclerosis. Women filed two thirds of the allegations, and individuals between 31 and 50 made the vast majority of discrimination charges (73%). Allegations…

  14. Predicting probability of occurrence and factors affecting distribution and abundance of three Ozark endemic crayfish species at multiple spatial scales

    USGS Publications Warehouse

    Nolen, Matthew S.; Magoulick, Daniel D.; DiStefano, Robert J.; Imhoff, Emily M.; Wagner, Brian K.

    2014-01-01

    We found that a range of environmental variables were important in predicting crayfish distribution and abundance at multiple spatial scales and their importance was species-, response variable- and scale dependent. We would encourage others to examine the influence of spatial scale on species distribution and abundance patterns.

  15. Multiple-Component Remediation for Developmental Reading Disabilities: IQ, Socioeconomic Status, and Race as Factors in Remedial Outcome

    ERIC Educational Resources Information Center

    Morris, Robin D.; Lovett, Maureen W.; Wolf, Maryanne; Sevcik, Rose A.; Steinbach, Karen A.; Frijters, Jan C.; Shapiro, Marla B.

    2012-01-01

    Results from a controlled evaluation of remedial reading interventions are reported: 279 young disabled readers were randomly assigned to a program according to a 2 x 2 x 2 factorial design (IQ, socioeconomic status [SES], and race). The effectiveness of two multiple-component intervention programs for children with reading disabilities (PHAB +…

  16. Assessing the Impact of Faking on Binary Personality Measures: An IRT-Based Multiple-Group Factor Analytic Procedure

    ERIC Educational Resources Information Center

    Ferrando, Pere J.; Anguiano-Carrasco, Cristina

    2009-01-01

    This article proposes a model-based multiple-group procedure for assessing the impact of faking on personality measures and the scores derived from these measures. The assessment is at the item level and the base model, which is intended for binary items, can be parameterized both as an Item Response Theory (IRT) model and as an Item…

  17. Patterns of Service Use, Individual and Contextual Risk Factors, and Resilience among Adolescents Using Multiple Psychosocial Services

    ERIC Educational Resources Information Center

    Ungar, Michael; Liebenberg, Linda; Dudding, Peter; Armstrong, Mary; van de Vijver, Fons J. R.

    2013-01-01

    Background: Very little research has examined the relationship between resilience, risk, and the service use patterns of adolescents with complex needs who use multiple formal and mandated services such as child welfare, mental health, juvenile justice, and special educational supports. This article reports on a study of 497 adolescents in…

  18. Growth differentiation factor 6 derived from mesenchymal stem/stromal cells reduces age-related functional deterioration in multiple tissues

    PubMed Central

    Hisamatsu, Daisuke; Ohno-Oishi, Michiko; Nakamura, Shiho; Mabuchi, Yo; Naka-Kaneda, Hayato

    2016-01-01

    The senescence-associated secretory phenotype (SASP) has attracted attention as a mechanism that connects cellular senescence to tissue dysfunction, and specific SASP factors have been identified as systemic pro-aging factors. However, little is known about the age-dependent changes in the secretory properties of stem cells. Young, but not old, mesenchymal stem/stromal cells (MSCs) are a well-known source of critical regenerative factors, but the identity of these factors remains elusive. In this study, we identified growth differentiation factor 6 (Gdf6; also known as Bmp13 and CDMP-2) as a regenerative factor secreted from young MSCs. The expression of specific secretory factors, including Gdf6, was regulated by the microRNA (miRNA) miR-17, whose expression declined with age. Upregulation of Gdf6 restored the osteogenic capacity of old MSCs in vitro and exerted positive effects in vivo on aging-associated pathologies such as reduced lymphopoiesis, insufficient muscle repair, reduced numbers of neural progenitors in the brain, and chronic inflammation. Our results suggest that manipulation of miRNA could enable control of the SASP, and that regenerative factors derived from certain types of young cells could be used to treat geriatric diseases. PMID:27311402

  19. Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and. alpha. 1-antitrypsin genes

    SciTech Connect

    Costa, R.H. ); Grayson, D.R. ); Darnell, J.E. Jr. )

    1989-04-01

    Transthyretin (TTR) and {alpha}1-antitrypsin ({alpha}1-AT) are expressed at high levels in the liver and also in at least one other cell type. The authors report here a detailed analysis of the proximal regulatory region of the TTR gene, which has uncovered two new DNA-binding factors that are present mainly (or only) in hepatocytes. One of these new factors, hepatocyte nuclear factor 3 (HNF-3), binds to two sites that are crucial in TTR expression as well as to two additional sites in the {alpha}1-AT proximal enhancer region. The second new factor, HNF-4, binds to two sites in TTR that are required for gene activity. The authors had previously identified binding sites for another hepatocyte-enriched DNA-binding protein (C/EBP or a relative thereof), and additional promoter-proximal sites for that protein in both TTR and {alpha}1-AT are also reported here. From these results it seems clear that cell-specific expression is not simply the result of a single cell-specific factor for each gene but the results of a combination of such factors. The variation and distribution of such factors among different cell types could be an important basis for the coordinate expression of the TTR and {alpha}1-AT genes in the liver or the discordant transcriptional activation of these genes in a few other cell types. The identification of such cell-enriched factors is a necessary prelude to understanding the basis for cell specificity.

  20. Short communication: comparison of virulence factors in Klebsiella pneumoniae strains associated with multiple or single cases of mastitis.

    PubMed

    Kanevsky-Mullarky, I; Nedrow, A J; Garst, S; Wark, W; Dickenson, M; Petersson-Wolfe, C S; Zadoks, R N

    2014-01-01

    Klebsiella pneumoniae mastitis in dairy cattle is generally due to an opportunistic infection from the environment, resulting in large heterogeneity among mastitis-causing strains within a herd. However, in mastitis outbreaks in 4 herds, several strains of K. pneumoniae were identified as the cause of infection in multiple cows, suggesting increased ability to either cause disease or evade host defenses. In this study, differences in capsule formation and immune evasion were compared in 5 pairs of K. pneumoniae strains, where one strain in each pair was associated with multiple cases of mastitis and the other with a single case of mastitis. Production of capsular polysaccharide, ability to evade killing by polymorphonuclear neutrophilic leukocytes (PMNL), and the relationship between the 2 were evaluated for each strain grown in broth or milk. Growth of isolates in skim milk increased capsule size and ability to evade killing by PMNL, depending on strain type. Specifically, strains associated with multiple cases of mastitis had increased capsule size in skim milk. Strains associated with single cases of mastitis were better able to evade killing by PMNL when grown in skim milk. Our results, although preliminary, suggest that the 2 groups of strains may constitute different subpopulations of K. pneumoniae. However, our findings do not indicate that capsule or evasions of killing by PMNL explain increased mastitis outbreaks with Klebsiella. Further work will explain the enhanced ability of some strains to cause mastitis in dairy cows. PMID:24534505

  1. Event-related potentials to tones show differences between children with multiple risk factors for dyslexia and control children before the onset of formal reading instruction.

    PubMed

    Hämäläinen, Jarmo A; Lohvansuu, Kaisa; Ervast, Leena; Leppänen, Paavo H T

    2015-02-01

    Multiple risk factors can affect the development of specific reading problems or dyslexia. In addition to the most prevalent and studied risk factor, phonological processing, auditory discrimination problems have also been found in children and adults with reading difficulties. The present study examined 37 children between the ages of 5 and 6, 11 of which had multiple risk factors for developing reading problems. The children participated in a passive oddball EEG experiment with sinusoidal sounds with changes in sound frequency, duration, or intensity. The responses to the standard stimuli showed a negative voltage shift in children at risk for reading problems compared to control children at 107-215 ms in frontocentral areas corresponding to P1 offset and N250 onset. Source analyses showed that the difference originated from the left and right auditory cortices. Additionally, the children at risk for reading problems had a larger late discriminative negativity (LDN) response in amplitude for sound frequency change than the control children. The amplitudes at the P1-N250 time window showed correlations to letter knowledge and phonological identification whereas the amplitudes at the LDN time window correlated with verbal short-term memory and rapid naming. These results support the view that problems in basic auditory processing abilities precede the onset of reading instruction and can act as one of the risk factors for dyslexia. PMID:24746550

  2. Constraining the factor analytical solutions obtained from multiple-year receptor modeling of ambient PM2.5 data from five speciation sites in Ontario, Canada

    NASA Astrophysics Data System (ADS)

    Sofowote, Uwayemi M.; Su, Yushan; Dabek-Zlotorzynska, Ewa; Rastogi, Ankit K.; Brook, Jeff; Hopke, Philip K.

    2015-05-01

    Rotational ambiguity in factor analyses leads to solutions that are not always consistent with reality. The inherent non-negativity constraints in positive matrix factorization (PMF) help to prevent factor solutions from becoming overly unrealistic, but they are not sufficient to prevent unwanted rotations that could manifest in factors that should have similar compositions varying across multiple sites. The Canadian National Air Pollution Surveillance (NAPS) network operates five fine particulate matter (PM2.5) speciation sites in Ontario. Data from these sites from 2005 to 2010 were subjected to PMF to obtain factors representing sources of particulate matter. Eight factors were found to be common across these sites. These factors had profiles that varied greatly from one site to the other, suggesting that the PMF solutions were impacted by some rotational ambiguity. New features in the EPA PMF V5 program allow the use of a priori information to impose mathematical constraints that guide the evolution of the factor solutions. These constraints reduce the rotational space. In situations where major emissions sources are known and located in the neighborhood of receptors, or emissions inventories and literature source profiles exist, it is easy to use these profiles to force the factor solutions to conform to the expected signatures. In our case, reported source profiles were neither available nor applicable due to the large spatial span of potential sources and receptor sites. This work describes how such constraints can be generated and used in these complex situations. The fundamental principle explored in this work is the concept of 'stiffness' of PMF solutions to identify the desirable non-rotating factors.

  3. MONKEY: Identifying conserved transcription-factor binding sitesin multiple alignments using a binding site-specific evolutionarymodel

    SciTech Connect

    Moses, Alan M.; Chiang, Derek Y.; Pollard, Daniel A.; Iyer, VenkyN.; Eisen, Michael B.

    2004-10-28

    We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.

  4. [Multiple meningiomas].

    PubMed

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. PMID:27234913

  5. Mental stress and psychosocial factors at work in relation to multiple-site musculoskeletal pain: a longitudinal study of kitchen workers.

    PubMed

    Haukka, Eija; Leino-Arjas, Päivi; Ojajärvi, Anneli; Takala, Esa-Pekka; Viikari-Juntura, Eira; Riihimäki, Hilkka

    2011-04-01

    Among 385 female kitchen workers, we examined (1) whether mental stress and psychosocial factors at work (job control, skill discretion, supervisor support, co-worker relationships, and hurry) predict multiple-site musculoskeletal pain (MSP; defined as pain at ≥ 3 of seven sites) and (2) reversedly, whether MSP predicts these psychosocial factors. Data were collected by questionnaire at 3-month intervals during 2 years. Trajectory analysis was applied. Four trajectories of MSP prevalence emerged: Low, Descending, Ascending, and High. For the psychosocial factors, a two-trajectory model (Ascending or High vs. Low) yielded the best fit. In logistic regression analysis, with the Low MSP trajectory as reference, poor co-worker relationships (odds ratio [OR] 3.9), mental stress (3.1) and hurry (2.1) at baseline predicted belonging to the High MSP trajectory. Also MSP at baseline predicted the trajectories (Ascending vs. Low) of low job control (2.2) and mental stress (3.2). Adverse changes in most psychosocial factors were associated with belonging to the High (ORs between 2.3 and 8.6) and Ascending (2.7-5.5) MSP trajectories. In generalized estimating equations, time-lagged by 3 months, all psychosocial factors but two predicted MSP (1.4-2.1), allowing, e.g. for MSP at baseline, and vice versa, MSP predicted low job control, low supervisor support, and mental stress (1.4-2.0), after adjustment for e.g. the relevant psychosocial factor at baseline. In conclusion, we found that several psychosocial factors predicted MSP and that MSP predicted several psychosocial factors. The results suggest a cumulative process in which adverse psychosocial factors and MSP influence each other. PMID:20932789

  6. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors

    PubMed Central

    Benson, Andrew K.; Kelly, Scott A.; Legge, Ryan; Ma, Fangrui; Low, Soo Jen; Kim, Jaehyoung; Zhang, Min; Oh, Phaik Lyn; Nehrenberg, Derrick; Hua, Kunjie; Kachman, Stephen D.; Moriyama, Etsuko N.; Walter, Jens; Peterson, Daniel A.; Pomp, Daniel

    2010-01-01

    In vertebrates, including humans, individuals harbor gut microbial communities whose species composition and relative proportions of dominant microbial groups are tremendously varied. Although external and stochastic factors clearly contribute to the individuality of the microbiota, the fundamental principles dictating how environmental factors and host genetic factors combine to shape this complex ecosystem are largely unknown and require systematic study. Here we examined factors that affect microbiota composition in a large (n = 645) mouse advanced intercross line originating from a cross between C57BL/6J and an ICR-derived outbred line (HR). Quantitative pyrosequencing of the microbiota defined a core measurable microbiota (CMM) of 64 conserved taxonomic groups that varied quantitatively across most animals in the population. Although some of this variation can be explained by litter and cohort effects, individual host genotype had a measurable contribution. Testing of the CMM abundances for cosegregation with 530 fully informative SNP markers identified 18 host quantitative trait loci (QTL) that show significant or suggestive genome-wide linkage with relative abundances of specific microbial taxa. These QTL affect microbiota composition in three ways; some loci control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. These data provide clear evidence for the importance of host genetic control in shaping individual microbiome diversity in mammals, a key step toward understanding the factors that govern the assemblages of gut microbiota associated with complex diseases. PMID:20937875

  7. Identification of Specific and Universal Virulence Factors in Burkholderia cenocepacia Strains by Using Multiple Infection Hosts▿ †

    PubMed Central

    Uehlinger, Susanne; Schwager, Stephan; Bernier, Steve P.; Riedel, Kathrin; Nguyen, David T.; Sokol, Pamela A.; Eberl, Leo

    2009-01-01

    Over the past few decades, strains of the Burkholderia cepacia complex have emerged as important pathogens for patients suffering from cystic fibrosis. Identification of virulence factors and assessment of the pathogenic potential of Burkholderia strains have increased the need for appropriate infection models. In previous studies, different infection hosts, including mammals, nematodes, insects, and plants, have been used. At present, however, the extent to which the virulence factors required to infect different hosts overlap is not known. The aim of this study was to analyze the roles of various virulence factors of two closely related Burkholderia cenocepacia strains, H111 and the epidemic strain K56-2, in a multihost pathogenesis system using four different model organisms, namely, Caenorhabditis elegans, Galleria mellonella, the alfalfa plant, and mice or rats. We demonstrate that most of the identified virulence factors are specific for one of the infection models, and only three factors were found to be essential for full pathogenicity in several hosts: mutants defective in (i) quorum sensing, (ii) siderophore production, and (iii) lipopolysaccharide biosynthesis were attenuated in at least three of the infection models and thus may represent promising targets for the development of novel anti-infectives. PMID:19528212

  8. Pre-operative factors indicating risk of multiple operations versus a single operation in women undergoing surgery for screen detected breast cancer.

    PubMed

    O'Flynn, E A M; Currie, R J; Mohammed, K; Allen, S D; Michell, M J

    2013-02-01

    We aim to identify preoperative factors at diagnosis which could predict whether women undergoing wide local excision (WLE) would require further operations. 1593 screen-detected invasive and non-invasive breast cancers were reviewed. Age, presence of ductal carcinoma in situ (DCIS), invasive cancer size on mammography, mammographic sign, tumour type, grade and confidence of the radiologist in malignancy were compared. 83%(1315/1593) of women had a WLE. Of these, 70%(919/1315) had a single operation, and 30%(396/1315) multiple operations. These included repeat WLE to clear margins (60%(238/396)), mastectomy (34%(133/396)) and axillary dissection (6%(25/396)). The presence of mammographic microcalcification, lobular carcinoma and grade 2 malignancy on core biopsy were independent risk factors for multiple operations on multivariate analysis. Women with mammographic DCIS >30 mm were 3.4 times more likely to undergo repeat surgery than those with smaller foci. The multidisciplinary team should pay particular attention to these factors when planning surgery. PMID:22789490

  9. Choosing among Multiple Achievement Measures: Applying Multitrait--Multimethod Confirmatory Factor Analysis to State Assessment, ACT, and Student GPA Data

    ERIC Educational Resources Information Center

    Dickinson, Emily R.; Adelson, Jill L.

    2016-01-01

    Practitioners and researchers interested in understanding student achievement, its predictors, and how it relates to other student outcomes are likely unaware of how the source information about achievement may offer subtly different pictures. This study applies multitrait-multimethod (MTMM) confirmatory factor analysis (CFA) within a structural…

  10. Sexual Orientation-Based Disparities in School and Juvenile Justice Discipline: A Multiple Group Comparison of Contributing Factors

    ERIC Educational Resources Information Center

    Poteat, V. Paul; Scheer, Jillian R.; Chong, Eddie S. K.

    2016-01-01

    There is little data on whether school discipline or juvenile justice sanctions are directed disproportionately toward sexual minority youth (e.g., lesbian, gay, bisexual, or questioning; LGBQ) compared with heterosexual youth and even less on factors that may relate to such disparities. We tested for sexual orientation-based disparities in school…

  11. Acculturation and Adjustment in Latino Adolescents: How Cultural Risk Factors and Assets Influence Multiple Domains of Adolescent Mental Health

    ERIC Educational Resources Information Center

    Smokowski, Paul; Buchanan, Rachel L.; Bacallao, Martica L.

    2009-01-01

    The purpose of this study was to examine the relationships among risk factors, cultural assets, and Latino adolescent mental health outcomes. We extend past research by using a longitudinal design and evaluating direct and moderated acculturation effects across a range of internalizing, externalizing, and academic engagement outcomes. The sample…

  12. Multiple environmental chemical exposures to lead, mercury and polychlorinated biphenyls among childbearing-aged women (NHANES 1999–2004): Body burden and risk factors

    PubMed Central

    Thompson, Marcella Remer; Boekelheide, Kim

    2013-01-01

    Background Lead, mercury and polychlorinated biphenyls (PCBs) are neurotoxicants with intergenerational health consequences from maternal body burden and gestational exposures. Little is known about multiple chemical exposures among childbearing-aged women. Objectives To determine the percentage of women aged 16–49 of diverse races and ethnicities whose body burdens for all three xenobiotics were at or above the median; to identify mixed exposures; and to describe those women disproportionately burdened by two or more of these chemicals based on susceptibility- and exposure-related attributes, socioeconomic factors and race-ethnicity. Methods Secondary data analysis of National Health and Nutrition Examination Survey (1999–2004). Results The best-fit logistic regression model without interactions contained 12 variables. Four risk factors associated with body burden were notable (P ≤ 0.05). An exponential relationship was demonstrated with increasing age. Any fish consumption in past 30 days more than doubled the odds. Heavy alcohol consumption increased the relative risk. History of breastfeeding reduced this risk. These women were more likely to have two xenobiotics at or above the median than one. More than one-fifth of these childbearing-aged women had three xenobiotic levels at or above the median. Conclusions These findings are among the first description of US childbearing-aged women’s body burden and risk factors for multiple chemical exposures. This study supports increasing age, any fish consumption and heavy alcohol consumption as significant risk factors for body burden. History of breastfeeding lowered the body burden. Limited evidence was found of increased risk among minority women independent of other risk factors. PMID:23158727

  13. Aging and multiple sclerosis.

    PubMed

    Sanai, Shaik Ahmed; Saini, Vasu; Benedict, Ralph Hb; Zivadinov, Robert; Teter, Barbara E; Ramanathan, Murali; Weinstock-Guttman, Bianca

    2016-05-01

    The life expectancy and average age of persons with multiple sclerosis (MS) have increased significantly during the last two decades. The introduction of disease-modifying therapies and a better delineation and understanding of the superimposed comorbidities often diagnosed in MS patients are probably the most important factors accountable for the increase in aging MS population worldwide. Healthcare teams must therefore address the problems arising due to advancing age superimposed on this chronic neurologic disease. In this review, we focus on the physiology of aging, its effects on MS disease course, and the pathological and immunological changes associated with aging and disease progression. Additionally, we discuss the common comorbidities that occur in aging persons with MS that may arise either as a result of the aging process or from relentless chronic MS disease progression as well as the challenges on differentiating the two processes for a more appropriate therapeutic approach. PMID:26895718

  14. Socioeconomic and gender group differences in early literacy skills: a multiple-group confirmatory factor analysis approach

    PubMed Central

    Lee, Julia Ai Cheng; Otaiba, Stephanie Al

    2015-01-01

    Socioeconomic status and gender are important demographic variables that strongly relate to academic achievement. This study examined the early literacy skills differences between 4 sociodemographic groups, namely, boys ineligible for free or reduced-price lunch (FRL), girls ineligible for FRL, boys eligible for FRL, and girls eligible for FRL. Data on kindergarteners (N = 462) were analysed using multiple-group confirmatory factory analysis. Early literacy skill differences between boys and girls are more nuanced than previously reported; subsidy status and gender interact. Both boys and girls from high-poverty households performed significantly lower than the girls from low-poverty households in alphabet knowledge, phonological awareness, and spelling. There were gender gaps, with a female advantage, among children from high-poverty households in alphabet knowledge and spelling and among children from low-poverty households in alphabet knowledge. These results highlight the importance of employing methodologically sound techniques to ascertain group differences in componential early literacy skills. PMID:25750582

  15. Shared Service Center vs. Shared Service Network: A Multiple Case Study Analysis of Factors Impacting on Shared Service Configurations

    NASA Astrophysics Data System (ADS)

    Becker, Jörg; Niehaves, Björn; Krause, Andreas

    Shared services have proven to be a key element when it comes to increasing government efficiency by collaboration. Here, we seek to investigate into the shared services phenomenon in the context of government reforms. For this purpose, an interview and document analysis-based multiple case study has been conducted in Germany. The qualitative analysis covers two shared service implementations on the local government level and identifies important preconditions for shared service emergence, namely cost pressure as motive, the existence of key actors promoting the topic and the existence of prior cooperation. Moreover, it is shown that the structure of such previous cooperation determines, if shared services are being organised in a centralised (shared service centre) or decentralised format (shared service network).

  16. Host proteins interacting with the Moloney murine leukemia virus integrase: Multiple transcriptional regulators and chromatin binding factors

    PubMed Central

    Studamire, Barbara; Goff, Stephen P

    2008-01-01

    Background A critical step for retroviral replication is the stable integration of the provirus into the genome of its host. The viral integrase protein is key in this essential step of the retroviral life cycle. Although the basic mechanism of integration by mammalian retroviruses has been well characterized, the factors determining how viral integration events are targeted to particular regions of the genome or to regions of a particular DNA structure remain poorly defined. Significant questions remain regarding the influence of host proteins on the selection of target sites, on the repair of integration intermediates, and on the efficiency of integration. Results We describe the results of a yeast two-hybrid screen using Moloney murine leukemia virus integrase as bait to screen murine cDNA libraries for host proteins that interact with the integrase. We identified 27 proteins that interacted with different integrase fusion proteins. The identified proteins include chromatin remodeling, DNA repair and transcription factors (13 proteins); translational regulation factors, helicases, splicing factors and other RNA binding proteins (10 proteins); and transporters or miscellaneous factors (4 proteins). We confirmed the interaction of these proteins with integrase by testing them in the context of other yeast strains with GAL4-DNA binding domain-integrase fusions, and by in vitro binding assays between recombinant proteins. Subsequent analyses revealed that a number of the proteins identified as Mo-MLV integrase interactors also interact with HIV-1 integrase both in yeast and in vitro. Conclusion We identify several proteins interacting directly with both MoMLV and HIV-1 integrases that may be common to the integration reaction pathways of both viruses. Many of the proteins identified in the screen are logical interaction partners for integrase, and the validity of a number of the interactions are supported by other studies. In addition, we observe that some of the

  17. Name-Based Address Mapping for Virtual Private Networks

    NASA Astrophysics Data System (ADS)

    Surányi, Péter; Shinjo, Yasushi; Kato, Kazuhiko

    IPv4 private addresses are commonly used in local area networks (LANs). With the increasing popularity of virtual private networks (VPNs), it has become common that a user connects to multiple LANs at the same time. However, private address ranges for LANs frequently overlap. In such cases, existing systems do not allow the user to access the resources on all LANs at the same time. In this paper, we propose name-based address mapping for VPNs, a novel method that allows connecting to hosts through multiple VPNs at the same time, even when the address ranges of the VPNs overlap. In name-based address mapping, rather than using the IP addresses used on the LANs (the real addresses), we assign a unique virtual address to each remote host based on its domain name. The local host uses the virtual addresses to communicate with remote hosts. We have implemented name-based address mapping for layer 3 OpenVPN connections on Linux and measured its performance. The communication overhead of our system is less than 1.5% for throughput and less than 0.2ms for each name resolution.

  18. Identifying sexual health protective factors among Northern Plains American Indian youth: An ecological approach utilizing multiple perspectives.

    PubMed

    Griese, Emily R; Kenyon, DenYelle Baete; McMahon, Tracey R

    2016-01-01

    This study examined aspects of the sociocultural context in which American Indian (AI) teen pregnancy occurs, focusing specifically on protective factors for Northern Plains AI youth. Principles of community-based participatory research guided the qualitative data collection from 185 community members (focus groups with AI youth, youth parents, and elders; interviews with health care providers and school personnel) from a reservation and an urban community. Results indicated three protective systems impacted the sexual health and behaviors of AI youth: school, family, and enculturation. These findings provide a better understanding of how specific protective factors within these systems may buffer AI youth from involvement in risky sexual behaviors and work to inform culturally relevant prevention and intervention efforts. PMID:27536896

  19. Okadaic acid mimics multiple changes in early protein phosphorylation and gene expression induced by tumor necrosis factor or interleukin-1.

    PubMed

    Guy, G R; Cao, X; Chua, S P; Tan, Y H

    1992-01-25

    Okadaic acid, a phosphatase inhibitor from a marine organism, mimics tumor necrosis factor/interleukin-1 (TNF/IL-1) in inducing changes in early cellular protein phosphorylation. A total of approximately 116 proteins exhibit significant and concordant changes in phosphorylation or dephosphorylation within 15 min in human fibroblasts activated by either okadaic acid, TNF, or IL-1. The fidelity of this mimicry by okadaic acid extends to the phosphorylation of the 27 hsp complex, stathmin, eIF-4E, myosin light chain, nucleolin, epidermal growth factor receptor, and other cdc2-kinase substrates (c-abl, RB, and p53). The okadaic acid-induced pattern of protein phosphorylation is distinct from that observed in cells treated with phorbol 12-myristate 13-acetate or with ligands like epidermal growth factor, cyclic AMP agonists, bradykinin, or interferons. Like TNF, okadaic acid also induces the transcription of immediate early response genes like c-jun and Egr-1 as well as the interleukin-6 genes. The overall early effects of okadaic acid uniquely parallel those of TNF/IL-1 and not those of other cytokines or ligands. Regulation of protein phosphatase inhibition is discussed as a mechanism for TNF/IL-1 signal transduction. PMID:1370482

  20. Q-factor of (In,Ga)N containing III-nitride microcavity grown by multiple deposition techniques

    SciTech Connect

    Gačević, Ž. Calleja, E.; Réveret, F.

    2013-12-21

    A 3λ/2 (In,Ga)N/GaN resonant cavity, designed for ∼415 nm operation, is grown by molecular beam epitaxy and is sandwiched between a 39.5-period (In,Al)N/GaN distributed Bragg reflector (DBR), grown on c-plane GaN-on-sapphire pseudo-substrate by metal-organic vapor phase epitaxy and an 8-period SiO{sub 2}/ZrO{sub 2} DBR, deposited by electron beam evaporation. Optical characterization reveals an improvement in the cavity emission spectral purity of approximately one order of magnitude due to resonance effects. The combination of spectrophotometric and micro-reflectivity measurements confirms the strong quality (Q)-factor dependence on the excitation spot size. We derive simple analytical formulas to estimate leak and residual absorption losses and propose a simple approach to model the Q-factor and to give a quantitative estimation of the weight of cavity disorder. The model is in good agreement with both transfer-matrix simulation and the experimental findings. We point out that the realization of high Q-factor (In,Ga)N containing microcavities on GaN pseudo-substrates is likely to be limited by the cavity disorder.

  1. Addressing contrasting cognitive models in scientific collaboration

    NASA Astrophysics Data System (ADS)

    Diviacco, P.

    2012-04-01

    If the social aspects of scientific communities and their internal dynamics is starting to be recognized and acknowledged in the everyday lives of scientists, it is rather difficult for them to find tools that could support their activities consistently with this perspective. Issues span from gathering researchers to mutual awareness, from information sharing to building meaning, with the last one being particularly critical in research fields as the geo-sciences, that deal with the reconstruction of unique, often non-reproducible, and contingent processes. Reasoning here is, in fact, mainly abductive, allowing multiple and concurrent explanations for the same phenomenon to coexist. Scientists bias one hypothesis over another not only on strictly logical but also on sociological motivations. Following a vision, scientists tend to evolve and isolate themselves from other scientists creating communities characterized by different cognitive models, so that after some time these become incompatible and scientists stop understanding each other. We address these problems as a communication issue so that the classic distinction into three levels (syntactic, semantic and pragmatic) can be used. At the syntactic level, we highlight non-technical obstacles that condition interoperability and data availability and transparency. At the semantic level, possible incompatibilities of cognitive models are particularly evident, so that using ontologies, cross-domain reconciliation should be applied. This is a very difficult task to perform since the projection of knowledge by scientists, in the designated community, is political and thus can create a lot of tension. The strategy we propose to overcome these issues pertains to pragmatics, in the sense that it is intended to acknowledge the cultural and personal factors each partner brings into the collaboration and is based on the idea that meaning should remain a flexible and contingent representation of possibly divergent views

  2. Interleukin-10 but not transforming growth factor-β1 gene expression is up-regulated by vitamin D treatment in multiple sclerosis patients.

    PubMed

    Farsani, Zeinab Shirvani; Behmanesh, Mehrdad; Sahraian, Mohammad Ali

    2015-03-15

    Multiple sclerosis (MS) is an inflammatory and autoimmune disease. Variety of different genetics and environmental factors are involved in MS pathology. The epidemiological studies demonstrated that vitamin D has immune and immunomodulating effects on MS disease. Therefore, this study aims to evaluate the effect of vitamin D treatment on the expression of interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) genes in MS patients. We found that, the expression level of IL-10 gene in treated patients was up-regulated 3.84 times more than before treatment, but the expression level of TGF-β1 was not affected by vitamin D treatment. Also, a significant relationship was observed between vitamin D level and EDSS in MS patients. Our results indicated that the increased level of serum vitamin D and IL-10 gene expression may be associated with the reduction of EDSS scores in MS patients. PMID:25680585

  3. The autoimmune disease-associated transcription factors EOMES and TBX21 are dysregulated in multiple sclerosis and define a molecular subtype of disease.

    PubMed

    Parnell, Grant P; Gatt, Prudence N; Krupa, Malgorzata; Nickles, Dorothee; McKay, Fiona C; Schibeci, Stephen D; Batten, Marcel; Baranzini, Sergio; Henderson, Andrew; Barnett, Michael; Slee, Mark; Vucic, Steve; Stewart, Graeme J; Booth, David R

    2014-03-01

    We have identified a marked over-representation of transcription factors controlling differentiation of T, B, myeloid and NK cells among the 110 MS genes now known to be associated with multiple sclerosis (MS). To test if the expression of these genes might define molecular subtypes of MS, we interrogated their expression in blood in three independent cohorts of untreated MS (from Sydney and Adelaide) or clinically isolated syndrome (CIS, from San Francisco) patients. Expression of the transcription factors (TF) controlling T and NK cell differentiation, EOMES, TBX21 and other TFs was significantly lower in MS/CIS compared to healthy controls in all three cohorts. Expression was tightly correlated between these TFs, with other T/NK cell TFs, and to another downregulated gene, CCL5. Expression was stable over time, but did not predict disease phenotype. Optimal response to therapy might be indicated by normalization of expression of these genes in blood. PMID:24495857

  4. Importance of Simultaneous Evaluation of Multiple Risk Factors for Hemodialysis Patients’ Mortality and Development of a Novel Index: Dialysis Outcomes and Practice Patterns Study

    PubMed Central

    2015-01-01

    Background For hemodialysis (HD) patients, many risk factors for death are associated with each other intricately. However, they are often considered separately in clinical settings. We evaluated the maintenance HD patients’ risk of death within one year from multiple risk factors simultaneously considering their interrelationships using a novel index (survival index, SI) for HD patients in the United States developed using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Methods We analyzed data from 3899 and 3765 patients to develop and validate SI, respectively. To predict death within one year, candidate models were developed using logistic regression models. The final model was determined by comparing the accuracy among the models for the prediction of deaths. Results The model included age; body mass index; serum creatinine, albumin, total cholesterol and phosphorus levels; history of cardiovascular diseases; and arteriovenous fistula use. SI showed a higher accuracy in predicting death (c-statistic, 0.739) than geriatric nutritional risk index (0.647) and serum albumin level (0.637). The probability of death predicted on the basis of SI matched the observed number of deaths. Cox proportional hazard models for time-dependent SI showed that patients with low SI had a higher risk of death than patients with high SI [reference, Group 4 (26.1≤SI)]; Group 1 (SI<12.7), adjusted hazard ratio, 7.97 (95% CI, 5.02, 12.65); Group 2 (12.7≤SI<19.0), 3.18 (95% CI, 1.96, 5.16); Group 3 (19.0≤SI<26.1), 2.20 (95% CI, 1.33, 3.66). Conclusion Results of this study suggest that the simultaneous evaluation of multiple risk factors can more accurately assess patients’ prognosis and identify patients at an increased risk of death than single factors. PMID:26030526

  5. Interferon-alpha and transfer factor in the treatment of multiple sclerosis: a double-blind, placebo-controlled trial. AUSTIMS Research Group.

    PubMed Central

    1989-01-01

    The role of interferon-alpha (IFN-alpha) and transfer factor (TF) in the treatment of multiple sclerosis was investigated in a prospective, multi-centric, three year, double-blind, placebo-controlled trial. One hundred and eighty two patients with clinically definite multiple sclerosis were randomised into three treatment groups whose compositions were found to be similar for demographic and prognostic variables including HLA status. Subcutaneous injections of IFN-alpha (3 x 10(6) units), TF (0.5 units) manufactured from leucocytes of cohabiting donors, or placebo were given twice weekly for two months, once weekly for 10 months then fortnightly for 24 months. One hundred and fifty three patients completed the injection regimen. There was no significant difference in the progression of disability for multiple sclerosis patients in either the IFN-alpha or TF-treated groups compared with the placebo group. Similarly, change in visual evoked responses (VER), and in number of oligoclonal bands (OCB) and the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) over the trial period did not differ significantly between the three groups. However, the IFN-alpha-treated group had significantly more reported adverse drug reactions and patient withdrawals than either of the other two groups. PMID:2659737

  6. The importance of systems thinking to address obesity.

    PubMed

    Finegood, Diane T

    2012-01-01

    Obesity is clearly a complex problem for both the individual and for society. Complex or 'wicked' problems have common characteristics such as heterogeneity, nonlinearity, interdependence, and self-organization. As such they require solutions appropriate for complex problems, rather than a reductionist search for the causes. 'Systems thinking' provides new ways to consider how to collectively address complex societal problems like obesity, where biology interacts with social, cultural and built environmental factors in infinite permutations and combinations. The systems that give rise to the obesity epidemic function at multiple levels, and there are important interactions between these levels. At any given level, individual actors and organizations matter and system function is optimized when individual and organizational capacity to respond is well matched to the complexity of individual tasks. Providing system supports to help networks of individuals become 'communities of practice' and 'systems of influence' may also help to accelerate the pace of effective action against obesity. Research efforts need to move away from the relentless search for the specific isolated causes of obesity and focus on solutions that have been shown to work in addressing other 'wicked' problems. PMID:23128771

  7. Experimental determination of multiple thermodynamic and kinetic risk factors for nephrolithiasis in the urine of healthy controls and calcium oxalate stone formers: does a universal discriminator exist?

    PubMed

    Rodgers, A L; Webber, D; Hibberd, B

    2015-11-01

    Nephrolithiasis is thought to be governed by urinary thermodynamic and kinetic risk factors. However, identification of one or more of these factors which consistently and unambiguously differentiates between healthy subjects (N) and calcium oxalate (CaOx) renal stone patients (SF) remains elusive. The present study addresses this challenge. 24 h urines were collected from 15 N and 10 SF. Urine compositions were used to compute thermodynamic risk indices including urinary ratios, quotients and supersaturation (SS) values, while CaOx metastable limits (MSL) were determined experimentally. Crystallisation kinetics was determined by measuring rates of particle formation (number, volume, size) using a Coulter counter multisizer (CC) and a Coulter flow cytometer (FC). Particle shapes were qualitatively differentiated by FC and were viewed directly by scanning electron microscopy. Several urinary composition ratios and risk quotients were significantly different between the groups. However, there were no significant differences between CaOx MSL or SS values. Using transformed FC data, the rate of CaOx crystallisation in SF was significantly greater than in N. This was not supported by CC measurements. There were no significant differences between the groups with respect to particle size or CaOx crystal growth rates. Single and aggregated CaOx dihydrate crystals were observed in both groups with equal frequency and there were no differences in the kinetic properties of these deposits. A few CaOx monohydrate crystals were observed in SF. Although several risk factors were found to be significantly different between the groups, none of them were consistently robust when compared to other cognate factors. Arguments were readily invoked which demonstrated inter-factor inconsistencies and conflicts. We suspect that a unique discriminatory factor, such as any of those which we investigated in the present study, may not exist. PMID:26198547

  8. Intimate Partner Violence, Relationship Power Inequity and the Role of Sexual and Social Risk Factors in the Production of Violence among Young Women Who Have Multiple Sexual Partners in a Peri-Urban Setting in South Africa

    PubMed Central

    Zembe, Yanga Z.; Townsend, Loraine; Thorson, Anna; Silberschmidt, Margrethe; Ekstrom, Anna Mia

    2015-01-01

    Introduction This paper aims to assess the extent and correlates of intimate partner violence (IPV), explore relationship power inequity and the role of sexual and social risk factors in the production of violence among young women aged 16–24 reporting more than one partner in the past three months in a peri-urban setting in the Western Cape, South Africa. Recent estimates suggest that every six hours a woman is killed by an intimate partner in South Africa, making IPV a leading public health problem in the country. While there is mounting evidence that levels of IPV are high in peri-urban settings in South Africa, not much is known about how it manifests among women who engage in concomitantly high HIV risk behaviours such as multiple sexual partnering, transactional sex and age mixing. We know even less about how such women negotiate power and control if exposed to violence in such sexual networks. Methods Two hundred and fifty nine women with multiple sexual partners, residing in a predominantly Black peri-urban community in the Western Cape, South Africa, were recruited into a bio-behavioural survey using Respondent Driven Sampling (RDS). After the survey, focus group discussions and individual interviews were conducted among young women and men to understand the underlying factors informing their risk behaviours and experiences of violence. Findings 86% of the young women experienced IPV in the past 12 months. Sexual IPV was significantly correlated with sex with a man who was 5 years or older than the index female partner (OR 1.7, 95% CI 1.0–3.2) and transactional sex with most recent casual partner (OR 2.1, 95% CI 1.1–3.8). Predictably, women experienced high levels of relationship power inequity. However, they also identified areas in their controlling relationships where they shared decision making power. Discussion Levels of IPV among young women with multiple sexual partners were much higher than what is reported among women in the general

  9. The Conserved Polarity Factor PodJ1 Impacts Multiple Cell Envelope-Associated Functions in Sinorhizobium meliloti

    PubMed Central

    Fields, Alexander T.; Navarrete, Charlene S.; Zare, Alaa Ziad; Huang, Zhenzhong; Mostafavi, Mina; Lewis, Jainee C.; Rezaeihaghighi, Yasha; Brezler, Benjamin J.; Ray, Shatarupa; Rizzacasa, Anne L.; Barnett, Melanie J.; Long, Sharon R.; Chen, Esther J.; Chen, Joseph C.

    2012-01-01

    Summary Although diminutive in size, bacteria possess highly diverse and spatially confined cellular structures. Two related alpha-proteobacteria, Sinorhizobium meliloti and Caulobacter crescentus, serve as models for investigating the genetic basis of morphologic variations. S. meliloti, a symbiont of leguminous plants, synthesizes multiple flagella and no prosthecae, whereas C. crescentus, a freshwater bacterium, has a single polar flagellum and stalk. The podJ gene, originally identified in C. crescentus for its role in polar organelle development, is split into two adjacent open reading frames, podJ1 and podJ2, in S. meliloti. Deletion of podJ1 interferes with flagellar motility, exopolysaccharide production, cell envelope integrity, cell division, and normal morphology, but not symbiosis. As in C. crescentus, the S. meliloti PodJ1 protein appears to act as a polarity beacon and localizes to the newer cell pole. Microarray analysis indicates that podJ1 affects the expression of at least 129 genes, the majority of which correspond to observed mutant phenotypes. Together, phenotypic characterization, microarray analysis, and suppressor identification suggest that PodJ1 controls a core set of conserved elements, including flagellar and pili genes, the signaling proteins PleC and DivK, and the transcriptional activator TacA, while alternate downstream targets have evolved to suit the distinct lifestyles of individual species. PMID:22553970

  10. The impact of selected factors on early diagnosis of multiple primary cancers in patients with uveal melanoma

    PubMed Central

    Romanowska-Dixon, Bożena

    2013-01-01

    Aim of the study To find differences between a group of patients with intraocular melanoma and another primary cancer and a group of patients with no identifiable second primary cancer. Material and methods The analysis involved 240 participants, selected from patients who were treated for uveal melanoma at the Department of Ophthalmology and Ocular Oncology of the Jagiellonian University Medical College between the year 1998 and 2007. Among those patients 97 were diagnosed with one or more independent primary cancers. Those patients were subject to a comparative analysis with a second group of 143 patients who had uveal melanoma with no identifiable second primary cancer. Results Statistically significant differences between the group of patients with intraocular melanoma and another primary cancer, and the group of patients with uveal melanoma (but without another diagnosed primary neoplasm) were as follows: more common family history of cancer, better education, living in cities (especially with a population over 500 thousand), previous surgery except for uveal melanoma, and two or less than two pregnancies in the case of women. Conclusions This analysis revealed that more common family history of cancer, better education, living in cities (especially with a population over 500 thousand), previous surgery, except for uveal melanoma, and two or less than two pregnancies in the case of women, were associated with a higher rate of detection of multiple primary cancers. PMID:24592138

  11. The Alfin-like homeodomain finger protein AL5 suppresses multiple negative factors to confer abiotic stress tolerance in Arabidopsis.

    PubMed

    Wei, Wei; Zhang, Yu-Qin; Tao, Jian-Jun; Chen, Hao-Wei; Li, Qing-Tian; Zhang, Wan-Ke; Ma, Biao; Lin, Qing; Zhang, Jin-Song; Chen, Shou-Yi

    2015-03-01

    Plant homeodomain (PHD) finger proteins affect processes of growth and development by changing transcription and reading epigenetic histone modifications, but their functions in abiotic stress responses remain largely unclear. Here we characterized seven Arabidopsis thaliana Alfin1-like PHD finger proteins (ALs) in terms of the responses to abiotic stresses. ALs localized to the nucleus and repressed transcription. Except AL6, all the ALs bound to G-rich elements. Mutations of the amino acids at positions 34 and 35 in AL6 caused loss of ability to bind to G-rich elements. Expression of the AL genes responded differentially to osmotic stress, salt, cold and abscisic acid treatments. AL5-over-expressing plants showed higher tolerance to salt, drought and freezing stress than Col-0. Consistently, al5 mutants showed reduced stress tolerance. We used ChIP-Seq assays to identify eight direct targets of AL5, and found that AL5 binds to the promoter regions of these genes. Knockout mutants of five of these target genes exhibited varying tolerances to stresses. These results indicate that AL5 inhibits multiple signaling pathways to confer stress tolerance. Our study sheds light on mechanisms of AL5-mediated signaling in abiotic stress responses, and provides tools for improvement of stress tolerance in crop plants. PMID:25619813

  12. Multiple Myeloma Symptoms

    MedlinePlus

    ... it is multiple myeloma . Stay on top of discoveries, trials, research and more. Click here to sign up for the MMRF Newsletter First name Last name E-mail address CLOSE News & Press Multiple Myeloma Knowledge Center Privacy Policy Donor Privacy Policy Terms of ...

  13. Spatial distribution of bacterial communities driven by multiple environmental factors in a beach wetland of the largest freshwater lake in China

    PubMed Central

    Ding, Xia; Peng, Xiao-Jue; Jin, Bin-Song; Xiao, Ming; Chen, Jia-Kuan; Li, Bo; Fang, Chang-Ming; Nie, Ming

    2015-01-01

    The spatial distributions of bacterial communities may be driven by multiple environmental factors. Thus, understanding the relationships between bacterial distribution and environmental factors is critical for understanding wetland stability and the functioning of freshwater lakes. However, little research on the bacterial communities in deep sediment layers exists. In this study, thirty clone libraries of 16S rRNA were constructed from a beach wetland of the Poyang Lake along both horizontal (distance to the water-land junction) and vertical (sediment depth) gradients to assess the effects of sediment properties on bacterial community structure and diversity. Our results showed that bacterial diversity increased along the horizontal gradient and decreased along the vertical gradient. The heterogeneous sediment properties along gradients substantially affected the dominant bacterial groups at the phylum and species levels. For example, the NH+4 concentration decreased with increasing depth, which was positively correlated with the relative abundance of Alphaproteobacteria. The changes in bacterial diversity and dominant bacterial groups showed that the top layer had a different bacterial community structure than the deeper layers. Principal component analysis revealed that both gradients, not each gradient independently, contributed to the shift in the bacterial community structure. A multiple linear regression model explained the changes in bacterial diversity and richness along the depth and distance gradients. Overall, our results suggest that spatial gradients associated with sediment properties shaped the bacterial communities in the Poyang Lake beach wetland. PMID:25767466

  14. The AP-1 transcription factor homolog Pf-AP-1 activates transcription of multiple biomineral proteins and potentially participates in Pinctada fucata biomineralization

    PubMed Central

    Zheng, Xiangnan; Cheng, Minzhang; Xiang, Liang; Liang, Jian; Xie, Liping; Zhang, Rongqing

    2015-01-01

    Activator protein-1 (AP-1) is an important bZIP transcription factor that regulates a series of physiological processes by specifically activating transcription of several genes, and one of its well-chartered functions in mammals is participating in bone mineralization. We isolated and cloned the complete cDNA of a Jun/AP-1 homolog from Pinctada fucata and called it Pf-AP-1. Pf-AP-1 had a highly conserved bZIP region and phosphorylation sites compared with those from mammals. A tissue distribution analysis showed that Pf-AP-1 was ubiquitously expressed in P. fucata and the mRNA level of Pf-AP-1 is extremely high in mantle. Pf-AP-1 expression was positively associated with multiple biomineral proteins in the mantle. The luciferase reporter assay in a mammalian cell line showed that Pf-AP-1 significantly up-regulates the transcriptional activity of the promoters of KRMP, Pearlin, and Prisilkin39. Inhibiting the activity of Pf-AP-1 depressed the expression of multiple matrix proteins. Pf-AP-1 showed a unique expression pattern during shell regeneration and pearl sac development, which was similar to the pattern observed for biomineral proteins. These results suggest that the Pf-AP-1 AP-1 homolog is an important transcription factor that regulates transcription of several biomineral proteins simultaneously and plays a role in P. fucata biomineralization, particularly during pearl and shell formation. PMID:26404494

  15. Septic hematogenous lumbar spondylodiscitis in elderly patients with multiple risk factors: efficacy of posterior stabilization and interbody fusion with iliac crest bone graft

    PubMed Central

    Mater, Eckhardt; Schön, Ralph

    2010-01-01

    The conservative and operative treatment strategies of hematogenous spondylodiscitis in septic patients with multiple risk factors are controversial. The present series demonstrates the outcome of 18 elderly patients (median age, 72 years) with septic hematogenous spondylodiscitis and intraspinal abscess treated with microsurgical decompression and debridement of the infective tissue, followed by posterior stabilization and interbody fusion with iliac crest bone graft in one or two lumbar segments. The majority of the patients were unsuccessfully treated with intravenous antibiotics prior to the operation. Antibiotic therapy was continued for more than 6 weeks postoperatively. Morbidity and early mortality amounted to 50 and 17%, respectively. Three patients died in the hospital from internal complications after an initial postoperative improvement of the inflammatory clinical signs and laboratory parameters. Fifteen patients recovered from the spinal infection. Three of them died several months after discharge (cerebral hemorrhage, malignancy and unknown cause). Twelve patients had excellent or good outcomes during the follow-up period of at least 1 year. The series shows that operative decompression and eradication of the intraspinal and intervertebral infective tissue with fusion and stabilization via a posterior approach is possible in septic patients with multiple risk factors and leads to good results in those patients, who survive the initial severe stage of the septic disease. However, the morbidity and mortality suggest that this surgical treatment is not the therapy of first choice in high-risk septic patients, but may be considered in patients when conservative management has failed. PMID:20495933

  16. Predictive factors of neutralizing antibodies development in relapsing-remitting multiple sclerosis patients on interferon Beta-1b therapy.

    PubMed

    Lanzillo, R; Orefice, G; Prinster, A; Ventrella, G; Liuzzi, R; Scarano, V; Florio, C; Vacca, G; Brunetti, A; Alfano, B; Brescia Morra, V; Bonavita, V

    2011-04-01

    The identification of predictive factors of NAbs development might have a relevant impact on clinical practice. Our objective is to look after predictive factors of NAbs development in MS IFN Beta-1b-treated patients. Database was screened for patients on IFN Beta-1b treatment with an Expanded Disability Status Scale (EDSS) at a baseline between 1 and 3.5, disease duration shorter than 15 years, and NAbs analysis performed every 6 months. The NAbs positive status was analysed in relation to baseline clinical, neuropsychological and brain imaging measures. Forty-nine patients were included. Sixteen patients had become NAbs positive at some point on IFN therapy (35%). NAbs producers differed from not producers for higher incidence of cognitive deficit and higher lesion load (OR = 5.0 and 5.6, respectively). Our study suggests that NAbs development might be a marker of a more aggressive disease and that worse outcome in NAbs producers might be biased by baseline condition. PMID:21308385

  17. Multiple-factor influences upon feeding flight rates at wading bird colonies (Alias: Are flight-line counts useful?)

    USGS Publications Warehouse

    Erwin, R.M.; Ogden, J.C.

    1979-01-01

    The temporal patterns of feeding, resting, and reproductive behavior in colonial wading birds have been studied by a number of investigators, both on a short-term (daily) and long-term (annual) basis. In coastal marine environments, activities at colonies are influenced by tides, time of day and phase of the nesting cycle. The purpose of this paper is twofold: (1) to examine the effects of tide, time of day (physical factors), nesting phase, colony site, and species identity (biological factors) on feeding flight rates at breeding colonies and, as a result of this, (2) to evaluate the usefulness of feeding flight counts as an index of the number of nests in the colony. Earlier work suggests that the relationship between the number of individuals flying to and from the nesting colony may be quite consistent with nest numbers. Thus, by monitoring flights from remote locations, observers might obtain relatively accurate census data while minimizing time and disturbance at colonies. Recent concern for the deleterious impact of humans at waterbird colonies underscores the need to investigate alternative census methods.

  18. TaNAC2, a NAC-type wheat transcription factor conferring enhanced multiple abiotic stress tolerances in Arabidopsis

    PubMed Central

    Mao, Xinguo; Zhang, Hongying; Qian, Xueya; Li, Ang; Zhao, Guangyao; Jing, Ruilian

    2012-01-01

    Environmental stresses such as drought, salinity, and cold are major factors that significantly limit agricultural productivity. NAC transcription factors play essential roles in response to various abiotic stresses. However, the paucity of wheat NAC members functionally characterized to date does not match the importance of this plant as a world staple crop. Here, the function of TaNAC2 was characterized in Arabidopsis thaliana. A fragment of TaNAC2 was obtained from suppression subtractive cDNA libraries of wheat treated with polyethylene glycol, and its full-length cDNA was obtained by searching a full-length wheat cDNA library. Gene expression profiles indicated that TaNAC2 was involved in response to drought, salt, cold, and abscisic acid treatment. To test its function, transgenic Arabidopsis lines overexpressing TaNAC2–GFP controlled by the cauliflower mosaic virus 35S promoter were generated. Overexpression of TaNAC2 resulted in enhanced tolerances to drought, salt, and freezing stresses in Arabidopsis, which were simultaneously demonstrated by enhanced expression of abiotic stress-response genes and several physiological indices. Therefore, TaNAC2 has potential for utilization in transgenic breeding to improve abiotic stress tolerances in crops. PMID:22330896

  19. Global Identification of SMAD2 Target Genes Reveals a Role for Multiple Co-regulatory Factors in Zebrafish Early Gastrulas*

    PubMed Central

    Liu, Zhaoting; Lin, Xiwen; Cai, Zhaoping; Zhang, Zhuqiang; Han, Chunsheng; Jia, Shunji; Meng, Anming; Wang, Qiang

    2011-01-01

    Nodal and Smad2/3 signals play pivotal roles in mesendoderm induction and axis determination during late blastulation and early gastrulation in vertebrate embryos. However, Smad2/3 direct target genes during those critical developmental stages have not been systematically identified. Here, through ChIP-chip assay, we show that the promoter/enhancer regions of 679 genes are bound by Smad2 in the zebrafish early gastrulas. Expression analyses confirm that a significant proportion of Smad2 targets are indeed subjected to Nodal/Smad2 regulation at the onset of gastrulation. The co-existence of DNA-binding sites of other transcription factors in the Smad2-bound regions allows the identification of well known Smad2-binding partners, such as FoxH1 and Lef1/β-catenin, as well as many previously unknown Smad2 partners, including Oct1 and Gata6, during embryogenesis. We demonstrate that Oct1 physically associates with and enhances the transcription and mesendodermal induction activity of Smad2, whereas Gata6 exerts an inhibitory role in Smad2 signaling and mesendodermal induction. Thus, our study systemically uncovers a large number of Smad2 targets in early gastrulas and suggests cooperative roles of Smad2 and other transcription factors in controlling target gene transcription, which will be valuable for studying regulatory cascades during germ layer formation and patterning of vertebrate embryos. PMID:21669877

  20. Virus-induced gene silencing unravels multiple transcription factors involved in floral growth and development in Phalaenopsis orchids

    PubMed Central

    Hsieh, Ming-Hsien; Pan, Zhao-Jun; Lai, Pei-Han; Lu, Hsiang-Chia; Yeh, Hsin-Hung; Hsu, Chia-Chi; Wu, Wan-Lin; Chung, Mei-Chu; Wang, Shyh-Shyan; Chen, Wen-Huei; Chen, Hong-Hwa

    2013-01-01

    Orchidaceae, one of the largest angiosperm families, has significant commercial value. Isolation of genes involved in orchid floral development and morphogenesis, scent production, and colouration will advance knowledge of orchid flower formation and facilitate breeding new varieties to increase the commercial value. With high-throughput virus-induced gene silencing (VIGS), this study identified five transcription factors involved in various aspects of flower morphogenesis in the orchid Phalaenopsis equestris. These genes are PeMADS1, PeMADS7, PeHB, PebHLH, and PeZIP. Silencing PeMADS1 and PebHLH resulted in reduced flower size together with a pelaloid column containing petal-like epidermal cells and alterations of epidermal cell arrangement in lip lateral lobes, respectively. Silencing PeMADS7, PeHB, and PeZIP alone resulted in abortion of the first three fully developed flower buds of an inflorescence, which indicates the roles of the genes in late flower development. Furthermore, double silencing PeMADS1 and PeMADS6, C- and B-class MADS-box genes, respectively, produced a combinatorial phenotype with two genes cloned in separate vectors. Both PeMADS1 and PeMADS6 are required to ensure the normal development of the lip and column as well as the cuticle formation on the floral epidermal cell surface. Thus, VIGS allows for unravelling the interaction between two classes of MADS transcription factors for dictating orchid floral morphogenesis. PMID:23956416

  1. Nitric Oxide-cGMP Signaling Stimulates Erythropoiesis through Multiple Lineage-Specific Transcription Factors: Clinical Implications and a Novel Target for Erythropoiesis

    PubMed Central

    Ikuta, Tohru; Sellak, Hassan; Odo, Nadine; Adekile, Adekunle D.; Gaensler, Karin M. L.

    2016-01-01

    Much attention has been directed to the physiological effects of nitric oxide (NO)-cGMP signaling, but virtually nothing is known about its hematologic effects. We reported for the first time that cGMP signaling induces human γ-globin gene expression. Aiming at developing novel therapeutics for anemia, we examined here the hematologic effects of NO-cGMP signaling in vivo and in vitro. We treated wild-type mice with NO to activate soluble guanylate cyclase (sGC), a key enzyme of cGMP signaling. Compared to untreated mice, NO-treated mice had higher red blood cell counts and total hemoglobin but reduced leukocyte counts, demonstrating that when activated, NO-cGMP signaling exerts hematopoietic effects on multiple types of blood cells in vivo. We next generated mice which overexpressed rat sGC in erythroid and myeloid cells. The forced expression of sGCs activated cGMP signaling in both lineage cells. Compared with non-transgenic littermates, sGC mice exhibited hematologic changes similar to those of NO-treated mice. Consistently, a membrane-permeable cGMP enhanced the differentiation of hematopoietic progenitors toward erythroid-lineage cells but inhibited them toward myeloid-lineage cells by controlling multiple lineage-specific transcription factors. Human γ-globin gene expression was induced at low but appreciable levels in sGC mice carrying the human β-globin locus. Together, these results demonstrate that NO-cGMP signaling is capable of stimulating erythropoiesis in both in vitro and vivo settings by controlling the expression of multiple lineage-specific transcription factors, suggesting that cGMP signaling upregulates erythropoiesis at the level of gene transcription. The NO-cGMP signaling axis may constitute a novel target to stimulate erythropoiesis in vivo. PMID:26727002

  2. Deconvolving temperature and substrate effects on soil heterotrophic respiration under multiple global change factors in mixed grass prairie

    NASA Astrophysics Data System (ADS)

    Tucker, C.; Nie, M.; Pendall, E. G.

    2013-12-01

    in temperature sensitivity of SOM decomposition. Overall, the temperature sensitivity of the fast pool was highly sensitive to global change factors and their interactions. On the other hand, there were no differences in temperature sensitivity of the slow pool in response to the global change factors. Similarly, the base rate of the fast pool was sensitive to the global change factors, while the slow pool base rate was not. However, the overall size of the slow pool was significantly affected by the global change factors. Vegetation removal reduced the slow pool by ~19% across all warming x CO2 treatments. This effect was greatest under elevated CO2 (both warmed and control), but non-significant under ambient CO2 and temperature. Importantly, effects mediated through the vegetation were the primary factor determining whether slow pool C was gained or lost under elevated CO2 and warming. Our data-model fusion approach allowed us to deconvolve the effect of reduced substrate availability from temperature sensitivity, and to demonstrate that global change may lead to strong positive C cycling feedbacks.

  3. Multiple copies of eukaryotic translation initiation factors in Brassica rapa facilitate redundancy, enabling diversification through variation in splicing and broad-spectrum virus resistance.

    PubMed

    Nellist, Charlotte F; Qian, Wei; Jenner, Carol E; Moore, Jonathan D; Zhang, Shujiang; Wang, Xiaowu; Briggs, William H; Barker, Guy C; Sun, Rifei; Walsh, John A

    2014-01-01

    Recessive strain-specific resistance to a number of plant viruses in the Potyvirus genus has been found to be based on mutations in the eukaryotic translation initiation factor 4E (eIF4E) and its isoform, eIF(iso)4E. We identified three copies of eIF(iso)4E in a number of Brassica rapa lines. Here we report broad-spectrum resistance to the potyvirus Turnip mosaic virus (TuMV) due to a natural mechanism based on the mis-splicing of the eIF(iso)4E allele in some TuMV-resistant B. rapa var. pekinensis lines. Of the splice variants, the most common results in a stop codon in intron 1 and a much truncated, non-functional protein. The existence of multiple copies has enabled redundancy in the host plant's translational machinery, resulting in diversification and emergence of the resistance. Deployment of the resistance is complicated by the presence of multiple copies of the gene. Our data suggest that in the B. rapa subspecies trilocularis, TuMV appears to be able to use copies of eIF(iso)4E at two loci. Transformation of different copies of eIF(iso)4E from a resistant B. rapa line into an eIF(iso)4E knockout line of Arabidopsis thaliana proved misleading because it showed that, when expressed ectopically, TuMV could use multiple copies which was not the case in the resistant B. rapa line. The inability of TuMV to access multiple copies of eIF(iso)4E in B. rapa and the broad spectrum of the resistance suggest it may be durable. PMID:24274163

  4. MELISSE, a large multicentric observational study to determine risk factors of venous thromboembolism in patients with multiple myeloma treated with immunomodulatory drugs.

    PubMed

    Leleu, Xavier; Rodon, Philippe; Hulin, Cyrille; Daley, Laurent; Dauriac, Charles; Hacini, Maya; Decaux, Olivier; Eisemann, Jean-Claude; Fitoussi, Olivier; Lioure, Bruno; Voillat, Laurent; Slama, Borhane; Al Jijakli, Ahmad; Benramdane, Riad; Chaleteix, Carinne; Costello, Régis; Thyss, Antoine; Mathiot, Claire; Boyle, Eileen; Maloisel, Frédéric; Stoppa, Anne-Marie; Kolb, Brigitte; Michallet, Mauricette; Lamblin, Anne; Natta, Patrick; Facon, Thierry; Elalamy, Ismail; Fermand, Jean-Paul; Moreau, Philippe

    2013-10-01

    Immunomodulatory drugs (IMiDs) are associated with an increased risk of venous thromboembolism (VTE) in multiple myeloma (MM) patients. We designed MELISSE, a multicentre prospective observational study, to evaluate VTE incidence and identify risk factors in IMiDs-treated MM. Our objective was to determine the real-life practice of VTE prophylaxis strategy. A total of 524 MM patients were included, and we planned to collect information at baseline, at four and at 12 months, on MM therapy, on VTE risk factors and management. VTE incidence was 7% (n=31), including 2.5% pulmonary embolism (PE) (n=11), similar at four or 12 months. VTE was observed at all risk assessment levels, although the increased risk assessment level correlated to a lower rate of VTE, maybe due to the implemented thromboprophylaxis strategy. VTE occurred in 7% on aspirin vs 3% on low-molecular-weight heparin (LMWH) prophylaxis, and none on vitamin K antagonists (VKA). New risk factors for VTE in IMiDs-treated MM were identified. In conclusion, VTE prophylaxis is compulsory in IMiDs-treated MM, based on individualised VTE risk assessment. Anticoagulation prophylaxis with LMWH should clearly be prioritised in MM patients with high VTE risk, along with VKA. Further prospective studies will identify most relevant VTE risk factors in IMiDs-treated MM to select accurately which MM patients should receive LMWH prophylaxis and for which duration to optimise VTE risk reduction. PMID:23903204

  5. Efficacy of deferred dosing of granulocyte colony-stimulating factor in autologous hematopoietic transplantation for multiple myeloma.

    PubMed

    Cox, J E; Campos, S; Wu, J; May, R; Liu, H; Ramos, C A; Carrum, G; Heslop, H E; Brenner, M K; Kamble, R T

    2014-02-01

    Routine administration of G-CSF following autologous hematopoietic SCT (ASCT) expedites ANC recovery and reduces hospitalization by 1-2 days; it has no impact on febrile neutropenia, infections, morbidity, mortality, event-free survival or OS. To determine whether delayed G-CSF dosage could result in equivalent ANC recovery and thereby improve cost effectiveness, we deferred the administration of G-CSF until WBC recovery had begun. A total of 117 patients with multiple myeloma received ASCT from January 2005 to September 2012. Of these, 52 were in the conventional dosing group (CGD) and received G-CSF from Day +7 for a median of five doses. In the deferred dosing group (DGD), 65 patients received G-CSF from median day 14 post transplant for a median of zero doses. There was no difference between groups in the incidence or duration of febrile neutropenia, duration of grade III mucositis, weight gain, rash, engraftment syndrome or early death (100 days). The DGD group had a significantly longer time to neutrophil engraftment than the CGD group (15 days vs 12 days; P<0.0001), a longer period of severe neutropenia (<100/μL; 8 days vs 6 days; P<0.0001), longer treatment with intravenous antibiotics (7 days vs 5 days; P=0.016) and longer hospital stay (19 days vs 17 days; P=<0.0001). Although the cost of G-CSF was lower in the DGD group (mean $308 vs $2467), the additional hospitalization raised the median total cost of ASCT in this group by 17%. There was, however, no adverse effect of deferred dosing on the rate of febrile neuropenic episodes or Day 100 survival, so that deferred dosing of G-CSF may be suitable for patients receiving ASCT as outpatients, for whom longer hospital stay would not be an offsetting cost. PMID:24096822

  6. Alcohol Use among Adolescent Youth: The Role of Friendship Networks and Family Factors in Multiple School Studies

    PubMed Central

    Wang, Cheng; Hipp, John R.; Butts, Carter T.; Jose, Rupa; Lakon, Cynthia M.

    2015-01-01

    To explore the co-evolution of friendship tie choice and alcohol use behavior among 1,284 adolescents from 12 small schools and 976 adolescents from one big school sampled in the National Longitudinal Study of Adolescent to Adult Health (AddHealth), we apply a Stochastic Actor-Based (SAB) approach implemented in the R-based Simulation Investigation for Empirical Network Analysis (RSiena) package. Our results indicate the salience of both peer selection and peer influence effects for friendship tie choice and adolescent drinking behavior. Concurrently, the main effect models indicate that parental monitoring and the parental home drinking environment affected adolescent alcohol use in the small school sample, and that parental home drinking environment affected adolescent drinking in the large school sample. In the small school sample, we detect an interaction between the parental home drinking environment and choosing friends that drink as they multiplicatively affect friendship tie choice. Our findings suggest that future research should investigate the synergistic effects of both peer and parental influences for adolescent friendship tie choices and drinking behavior. And given the tendency of adolescents to form ties with their friends' friends, and the evidence of local hierarchy in these networks, popular youth who do not drink may be uniquely positioned and uniquely salient as the highest rank of the hierarchy to cause anti-drinking peer influences to diffuse down the social hierarchy to less popular youth. As such, future interventions should harness prosocial peer influences simultaneously with strategies to increase parental support and monitoring among parents to promote affiliation with prosocial peers. PMID:25756364

  7. The mechanical properties of high speed GTAW weld and factors of nonlinear multiple regression model under external transverse magnetic field

    NASA Astrophysics Data System (ADS)

    Lu, Lin; Chang, Yunlong; Li, Yingmin; He, Youyou

    2013-05-01

    A transverse magnetic field was introduced to the arc plasma in the process of welding stainless steel tubes by high-speed Tungsten Inert Gas Arc Welding (TIG for short) without filler wire. The influence of external magnetic field on welding quality was investigated. 9 sets of parameters were designed by the means of orthogonal experiment. The welding joint tensile strength and form factor of weld were regarded as the main standards of welding quality. A binary quadratic nonlinear regression equation was established with the conditions of magnetic induction and flow rate of Ar gas. The residual standard deviation was calculated to adjust the accuracy of regression model. The results showed that, the regression model was correct and effective in calculating the tensile strength and aspect ratio of weld. Two 3D regression models were designed respectively, and then the impact law of magnetic induction on welding quality was researched.

  8. [Long-term survival and prognostic factors in multiple myeloma treated with conventional chemotherapy. Report of 109 cases].

    PubMed

    Ben Abid, H; Meddeb, B; Ben Abdallah, M; Bel Hadj Ali, Z; Hafsia, R; Ben Lakhal, R; Gouider, E; Aissaoui, L; Landoulsi, I; ben Abdeladhim, A; Hafsia, A

    2000-12-01

    Our study is retrospective. We report the results of conventional chemotherapy ins previosly untreated patients with myeloma. Survival and prognostic factors were analysed in 109 patients diagnosed from 1983 to 1992. The median age was 65 years, 87 patients (80%) were including in the stage III according the Durie Salmon staging system. The median survival time was 27 months and 10 years survival rate is 3.66%. In the univariate analysis, two prognostic variables were retained namely the hemoglobin and creatinine level. The study suggest that conventional therapy is a good treatment for old patients. However, patients younger than 55 years, must benefit from intensive chemotherapy supported by autologous bone marrow, pheripheral blood stem cells, or allogenic bone marrow transplantation. A considerable encrace in duration of remission and survival is possible. PMID:11155374

  9. The wheat transcription factor, TabHLH39, improves tolerance to multiple abiotic stressors in transgenic plants.

    PubMed

    Zhai, Yiqian; Zhang, Lichao; Xia, Chuan; Fu, Silu; Zhao, Guangyao; Jia, Jizeng; Kong, Xiuying

    2016-05-13

    Although bHLH transcription factors play important roles regulating plant development and abiotic stress response and tolerance, few functional studies have been performed in wheat. In this study, we isolated and characterized a bHLH gene, TabHLH39, from wheat. The TabHLH39 gene is located on wheat chromosome 5DL, and the protein localized to the nucleus and activated transcription. TabHLH39 showed variable expression in roots, stems, leaves, glumes, pistils and stamens and was induced by polyethylene glycol, salt and cold treatments. Further analysis revealed that TabHLH39 overexpression in Arabidopsis significantly enhanced tolerance to drought, salt and freezing stress during the seedling stage, which was also demonstrated by enhanced abiotic stress-response gene expression and changes to several physiological indices. Therefore, TabHLH39 has potential in transgenic breeding applications to improve abiotic stress tolerance in crops. PMID:27091431

  10. Shifts in Arctic phenology in response to climate and anthropogenic factors as detected from multiple satellite time series

    NASA Astrophysics Data System (ADS)

    Zeng, Heqing; Jia, Gensuo; Forbes, Bruce C.

    2013-09-01

    There is an urgent need to reduce the uncertainties in remotely sensed detection of phenological shifts of high latitude ecosystems in response to climate changes in past decades. In this study, vegetation phenology in western Arctic Russia (the Yamal Peninsula) was investigated by analyzing and comparing Normalized Difference Vegetation Index (NDVI) time series derived from the Advanced Very High Resolution Radiometer (AVHRR), the Moderate Resolution Imaging Spectroradiometer (MODIS), and SPOT-Vegetation (VGT) during the decade 2000-2010. The spatial patterns of key phenological parameters were highly heterogeneous along the latitudinal gradients based on multi-satellite data. There was earlier SOS (start of the growing season), later EOS (end of the growing season), longer LOS (length of the growing season), and greater MaxNDVI from north to south in the region. The results based on MODIS and VGT data showed similar trends in phenological changes from 2000 to 2010, while quite a different trend was found based on AVHRR data from 2000 to 2008. A significantly delayed EOS (p < 0.01), thus increasing the LOS, was found from AVHRR data, while no similar trends were detected from MODIS and VGT data. There were no obvious shifts in MaxNDVI during the last decade. MODIS and VGT data were considered to be preferred data for monitoring vegetation phenology in northern high latitudes. Temperature is still a key factor controlling spatial phenological gradients and variability, while anthropogenic factors (reindeer husbandry and resource exploitation) might explain the delayed SOS in southern Yamal. Continuous environmental damage could trigger a positive feedback to the delayed SOS.

  11. A wheat salinity-induced WRKY transcription factor TaWRKY93 confers multiple abiotic stress tolerance in Arabidopsis thaliana.

    PubMed

    Qin, Yuxiang; Tian, Yanchen; Liu, Xiuzhi

    2015-08-21

    Wheat is an important crop in the world. But most of the cultivars are salt sensitive, and often adversely affected by salt stress. WRKY transcription factors play a major role in plant responses to salt stress, but the effective salinity regulatory WRKYs identified in bread wheat are limited and the mechanism of salt stress tolerance is also not well explored. Here, we identified a salt (NaCl) induced class II WRKY transcription factor TaWRKY93. Its transcript level was strongly induced by salt (NaCl) and exogenous abscisic acid (ABA). Over-expression of TaWRKY93 in Arabidopsis thaliana enhanced salt (NaCl), drought, low temperature and osmotic (mannitol) stress tolerance, mainly demonstrated by transgenic plants forming longer primary roots or more lateral roots on MS plates supplemented with NaCl and mannitol individually, higher survival rate under drought and low temperature stress. Further, transgenic plants maintained a more proline content, higher relative water content and less electrolyte leakage than the wild type plants. The transcript abundance of a series of abiotic stress-related genes was up-regulated in the TaWRKY93 transgenic plants. In summary, TaWRKY93 is a new positive regulator of abiotic stress, it may increase salinity, drought and low temperature stress tolerance through enhancing osmotic adjustment, maintaining membrane stability and increasing transcription of stress related genes, and contribute to the superior agricultural traits of SR3 through promoting root development. It can be used as a candidate gene for wheat transgenic engineering breeding against abiotic stress. PMID:26106823

  12. Multiple risk factors and ischaemic stroke in the elderly Asian population with and without atrial fibrillation. An analysis of 425,600 Chinese individuals without prior stroke.

    PubMed

    Guo, Yutao; Wang, Hao; Tian, Yingchun; Wang, Yutang; Lip, Gregory Y H

    2016-01-01

    Ischaemic stroke risk rises with the increasing cardiovascular risk factors. How atrial fibrillation (AF) incrementally contributes to the risk for ischaemic stroke with increasing age and multiple cardiovascular risk factors is unclear. In an individual patient with AF the mechanism of ischaemic stroke may be related directly to AF itself or to risk factors associated with AF. It was this study's objective to investigate incident ischaemic stroke in relation to age and increasing cardiovascular risk factor(s), and the incremental impact of AF on stroke rates. We studied a 5% random sampling from Chinese medical insurance data covering more than 10 million individuals, for the years 2001 to 2012. The rate of ischaemic stroke was calculated amongst the individuals with no prior history of ischaemic stroke, in relation to age groups (aged < 65, 65-74, ≥ 75 years old; n = 348,431, n = 56,952, n = 20,217, respectively), and increasing risk factors using the CHA2DS2-VASc score. Among the randomly sampled 425,600 individuals with total follow-up of 1,864,232 patient-years [63.8% male, mean age 60 years; 880 with AF, vs 424,720 non-AF], there were 13,242 (3.1%) ischaemic strokes after 64,834 person-years follow-up. Overall, ischaemic stroke incidence (per 100 person-years) was 0.35 (95%CI 0.34-0.35) in the non-AF population and 1.11 (0.84-1.45) with AF. The AF population age < 65 and 65-74 had higher CHA2DS2-VASc scores than the non-AF population (p< 0.001), but this was non-significant between the non-AF and AF population age ≥ 75 (p=0.086). For the population age ≥ 75 years, incident stroke rates were 2.07 (0.86-4.76) and 4.29 (4.08-4.51) in non-AF and AF populations, respectively. The non-AF population age ≥ 65 years with ≥ 2 additional comorbidities (hypertension, vascular disease, diabetic, or heart failure) had ischaemic stroke rates similar to an AF population with CHA2DS2-VASc ≥ 4. In both non-AF and AF populations, those with CHA2DS2

  13. Addressing problems of employee performance.

    PubMed

    McConnell, Charles R

    2011-01-01

    Employee performance problems are essentially of 2 kinds: those that are motivational in origin and those resulting from skill deficiencies. Both kinds of problems are the province of the department manager. Performance problems differ from problems of conduct in that traditional disciplinary processes ordinarily do not apply. Rather, performance problems are addressed through educational and remedial processes. The manager has a basic responsibility in ensuring that everything reasonable is done to help each employee succeed. There are a number of steps the manager can take to address employee performance problems. PMID:21537142

  14. Addressable parallel cavity-based quantum memory

    NASA Astrophysics Data System (ADS)

    Vetlugin, Anton N.; Sokolov, Ivan V.

    2014-09-01

    We elaborate theoretically a model of addressable parallel cavity-based quantum memory for light able to store multiple transverse spatial modes of the input light signal of finite duration and, at the same time, a time sequence of the signals by side illumination. Having in mind possible applications for, e.g., quantum repeaters, we reveal the addressability of our memory, that is, its handiness for the read-out on demand of a given transverse quantized signal mode and of a given signal from the time sequence. The addressability is achieved by making use of different spatial configurations of pump wave during the write-in and the readout. We also demonstrate that for the signal durations of the order of few cavity decay times, better efficiency is achieved when one excites the cavity with zero light-matter coupling and finally performs fast excitation transfer from the intracavity field to the collective spin. On the other hand, the light-matter coupling control in time, based on dynamical impedance matching, allows to store and retrieve time restricted signals of the on-demand smooth time shape.

  15. Matching Alternative Addresses: a Semantic Web Approach

    NASA Astrophysics Data System (ADS)

    Ariannamazi, S.; Karimipour, F.; Hakimpour, F.

    2015-12-01

    Rapid development of crowd-sourcing or volunteered geographic information (VGI) provides opportunities for authoritatives that deal with geospatial information. Heterogeneity of multiple data sources and inconsistency of data types is a key characteristics of VGI datasets. The expansion of cities resulted in the growing number of POIs in the OpenStreetMap, a well-known VGI source, which causes the datasets to outdate in short periods of time. These changes made to spatial and aspatial attributes of features such as names and addresses might cause confusion or ambiguity in the processes that require feature's literal information like addressing and geocoding. VGI sources neither will conform specific vocabularies nor will remain in a specific schema for a long period of time. As a result, the integration of VGI sources is crucial and inevitable in order to avoid duplication and the waste of resources. Information integration can be used to match features and qualify different annotation alternatives for disambiguation. This study enhances the search capabilities of geospatial tools with applications able to understand user terminology to pursuit an efficient way for finding desired results. Semantic web is a capable tool for developing technologies that deal with lexical and numerical calculations and estimations. There are a vast amount of literal-spatial data representing the capability of linguistic information in knowledge modeling, but these resources need to be harmonized based on Semantic Web standards. The process of making addresses homogenous generates a helpful tool based on spatial data integration and lexical annotation matching and disambiguating.

  16. Temporal uncertainty analysis of human errors based on interrelationships among multiple factors: a case of Minuteman III missile accident.

    PubMed

    Rong, Hao; Tian, Jin; Zhao, Tingdi

    2016-01-01

    In traditional approaches of human reliability assessment (HRA), the definition of the error producing conditions (EPCs) and the supporting guidance are such that some of the conditions (especially organizational or managerial conditions) can hardly be included, and thus the analysis is burdened with incomprehensiveness without reflecting the temporal trend of human reliability. A method based on system dynamics (SD), which highlights interrelationships among technical and organizational aspects that may contribute to human errors, is presented to facilitate quantitatively estimating the human error probability (HEP) and its related variables changing over time in a long period. Taking the Minuteman III missile accident in 2008 as a case, the proposed HRA method is applied to assess HEP during missile operations over 50 years by analyzing the interactions among the variables involved in human-related risks; also the critical factors are determined in terms of impact that the variables have on risks in different time periods. It is indicated that both technical and organizational aspects should be focused on to minimize human errors in a long run. PMID:26360211

  17. Resistance to transforming growth factor β-mediated tumor suppression in melanoma: are multiple mechanisms in place?

    PubMed Central

    Lasfar, Ahmed; Cohen-Solal, Karine A.

    2010-01-01

    Resistance to transforming growth factor (TGF) β-mediated tumor suppression in melanoma appears to be a crucial step in tumor aggressiveness since it is usually coupled with the ability of TGFβ to drive the oncogenic process via autocrine and paracrine effects. In this review, we will focus mainly on the mechanisms of escape from TGFβ-induced cell cycle arrest because the mechanisms of resistance to TGFβ-mediated apoptosis are still essentially speculative. As expected, some of these mechanisms can directly affect the function of the main downstream effectors of TGFβ, Smad2 and Smad3, resulting in compromised Smad-mediated antiproliferative activity. Other mechanisms can counteract or overcome TGFβ-mediated cell cycle arrest independently of the Smads. In melanoma, some models of resistance to TGFβ have been suggested and will be described. In addition, we propose additional models of resistance taking into consideration the information available on the dysregulation of fundamental cellular effectors and signaling pathways in melanoma. PMID:20656791

  18. Effects of multiple climate change factors on the tall fescue-fungal endophyte symbiosis: infection frequency and tissue chemistry.

    SciTech Connect

    Brosi, Glade; McCulley, Rebecca L; Bush, L P; Nelson, Jim A; Classen, Aimee T; Norby, Richard J

    2011-01-01

    Climate change (altered CO{sub 2}, warming, and precipitation) may affect plant-microbial interactions, such as the Lolium arundinaceum-Neotyphodium coenophialum symbiosis, to alter future ecosystem structure and function. To assess this possibility, tall fescue tillers were collected from an existing climate manipulation experiment in a constructed old-field community in Tennessee (USA). Endophyte infection frequency (EIF) was determined, and infected (E+) and uninfected (E-) tillers were analysed for tissue chemistry. The EIF of tall fescue was higher under elevated CO{sub 2} (91% infected) than with ambient CO{sub 2} (81%) but was not affected by warming or precipitation treatments. Within E+ tillers, elevated CO{sub 2} decreased alkaloid concentrations of both ergovaline and loline, by c. 30%; whereas warming increased loline concentrations 28% but had no effect on ergovaline. Independent of endophyte infection, elevated CO{sub 2} reduced concentrations of nitrogen, cellulose, hemicellulose, and lignin. These results suggest that elevated CO{sub 2}, more than changes in temperature or precipitation, may promote this grass-fungal symbiosis, leading to higher EIF in tall fescue in old-field communities. However, as all three climate factors are likely to change in the future, predicting the symbiotic response and resulting ecological consequences may be difficult and dependent on the specific atmospheric and climatic conditions encountered.

  19. NMR conformational properties of an Anthrax Lethal Factor domain studied by multiple amino acid-selective labeling

    SciTech Connect

    Vourtsis, Dionysios J.; Chasapis, Christos T.; Pairas, George; Bentrop, Detlef; Spyroulias, Georgios A.

    2014-07-18

    Highlights: • A polypeptide, N-ALF{sub 233}, was overexpressed in E. coli and successfully isolated. • We produced {sup 2}H/{sup 15}N/{sup 13}C labeled protein samples. • Amino acid selective approaches were applied. • We acquired several heteronuclear NMR spectra, to complete the backbone assignment. • Prediction of the secondary structure was performed. - Abstract: NMR-based structural biology urgently needs cost- and time-effective methods to assist both in the process of acquiring high-resolution NMR spectra and their subsequent analysis. Especially for bigger proteins (>20 kDa) selective labeling is a frequently used means of sequence-specific assignment. In this work we present the successful overexpression of a polypeptide of 233 residues, corresponding to the structured part of the N-terminal domain of Anthrax Lethal Factor, using Escherichia coli expression system. The polypeptide was subsequently isolated in pure, soluble form and analyzed structurally by solution NMR spectroscopy. Due to the non-satisfying quality and resolution of the spectra of this 27 kDa protein, an almost complete backbone assignment became feasible only by the combination of uniform and novel amino acid-selective labeling schemes. Moreover, amino acid-type selective triple-resonance NMR experiments proved to be very helpful.

  20. Conformational Transition Pathways of Epidermal Growth Factor Receptor Kinase Domain from Multiple Molecular Dynamics Simulations and Bayesian Clustering

    PubMed Central

    2015-01-01

    The epidermal growth factor receptor (EGFR) is aberrantly activated in various cancer cells and an important target for cancer treatment. Deep understanding of EGFR conformational changes between the active and inactive states is of pharmaceutical interest. Here we present a strategy combining multiply targeted molecular dynamics simulations, unbiased molecular dynamics simulations, and Bayesian clustering to investigate transition pathways during the activation/inactivation process of EGFR kinase domain. Two distinct pathways between the active and inactive forms are designed, explored, and compared. Based on Bayesian clustering and rough two-dimensional free energy surfaces, the energy-favorable pathway is recognized, though DFG-flip happens in both pathways. In addition, another pathway with different intermediate states appears in our simulations. Comparison of distinct pathways also indicates that disruption of the Lys745-Glu762 interaction is critically important in DFG-flip while movement of the A-loop significantly facilitates the conformational change. Our simulations yield new insights into EGFR conformational transitions. Moreover, our results verify that this approach is valid and efficient in sampling of protein conformational changes and comparison of distinct pathways. PMID:25136273

  1. The Novel Wheat Transcription Factor TaNAC47 Enhances Multiple Abiotic Stress Tolerances in Transgenic Plants

    PubMed Central

    Zhang, Lina; Zhang, Lichao; Xia, Chuan; Zhao, Guangyao; Jia, Jizeng; Kong, Xiuying

    2016-01-01

    NAC transcription factors play diverse roles in plant development and responses to abiotic stresses. However, the biological roles of NAC family members in wheat are not well understood. Here, we reported the isolation and functional characterization of a novel wheat TaNAC47 gene. TaNAC47 encoded protein, localizing in the nucleus, is able to bind to the ABRE cis-element and transactivate transcription in yeast, suggesting that it likely functions as a transcriptional activator. We also showed that TaNAC47 is differentially expressed in different tissues, and its expression was induced by the stress treatments of salt, cold, polyethylene glycol and exogenous abscisic acid. Furthermore, overexpression of TaNAC47 in Arabidopsis resulted in ABA hypersensitivity and enhancing tolerance of transgenic plants to drought, salt, and freezing stresses. Strikingly, overexpression of TaNAC47 was found to activate the expression of downstream genes and change several physiological indices that may enable transgenic plants to overcome unfavorable environments. Taken together, these results uncovered an important role of wheat TaNAC47 gene in response to ABA and abiotic stresses. PMID:26834757

  2. MADS-box transcription factor AGL21 regulates lateral root development and responds to multiple external and physiological signals.

    PubMed

    Yu, Lin-Hui; Miao, Zi-Qing; Qi, Guo-Feng; Wu, Jie; Cai, Xiao-Teng; Mao, Jie-Li; Xiang, Cheng-Bin

    2014-11-01

    Plant root system morphology is dramatically influenced by various environmental cues. The adaptation of root system architecture to environmental constraints, which mostly depends on the formation and growth of lateral roots, is an important agronomic trait. Lateral root development is regulated by the external signals coordinating closely with intrinsic signaling pathways. MADS-box transcription factors are known key regulators of the transition to flowering and flower development. However, their functions in root development are still poorly understood. Here we report that AGL21, an AGL17-clade MADS-box gene, plays a crucial role in lateral root development. AGL21 was highly expressed in root, particularly in the root central cylinder and lateral root primordia. AGL21 overexpression plants produced more and longer lateral roots while agl21 mutants showed impaired lateral root development, especially under nitrogen-deficient conditions. AGL21 was induced by many plant hormones and environmental stresses, suggesting a function of this gene in root system plasticity in response to various signals. Furthermore, AGL21 was found positively regulating auxin accumulation in lateral root primordia and lateral roots by enhancing local auxin biosynthesis, thus stimulating lateral root initiation and growth. We propose that AGL21 may be involved in various environmental and physiological signals-mediated lateral root development and growth. PMID:25122697

  3. Multiple Linear Regression Analysis of Factors Affecting Real Property Price Index From Case Study Research In Istanbul/Turkey

    NASA Astrophysics Data System (ADS)

    Denli, H. H.; Koc, Z.

    2015-12-01

    Estimation of real properties depending on standards is difficult to apply in time and location. Regression analysis construct mathematical models which describe or explain relationships that may exist between variables. The problem of identifying price differences of properties to obtain a price index can be converted into a regression problem, and standard techniques of regression analysis can be used to estimate the index. Considering regression analysis for real estate valuation, which are presented in real marketing process with its current characteristics and quantifiers, the method will help us to find the effective factors or variables in the formation of the value. In this study, prices of housing for sale in Zeytinburnu, a district in Istanbul, are associated with its characteristics to find a price index, based on information received from a real estate web page. The associated variables used for the analysis are age, size in m2, number of floors having the house, floor number of the estate and number of rooms. The price of the estate represents the dependent variable, whereas the rest are independent variables. Prices from 60 real estates have been used for the analysis. Same price valued locations have been found and plotted on the map and equivalence curves have been drawn identifying the same valued zones as lines.

  4. Polynucleotide Phosphorylase Regulates Multiple Virulence Factors and the Stabilities of Small RNAs RsmY/Z in Pseudomonas aeruginosa

    PubMed Central

    Chen, Ronghao; Weng, Yuding; Zhu, Feng; Jin, Yongxin; Liu, Chang; Pan, Xiaolei; Xia, Bin; Cheng, Zhihui; Jin, Shouguang; Wu, Weihui

    2016-01-01

    Post-transcriptional regulation enables bacteria to quickly response to environmental stresses. Polynucleotide phosphorylase (PNPase), which contains an N-terminal catalytic core and C-terminal RNA binding KH-S1 domains, is involved in RNA processing. Here we demonstrate that in Pseudomonas aeruginosa the KH-S1 domains of PNPase are required for the type III secretion system (T3SS) and bacterial virulence. Transcriptome analysis revealed a pleiotropic role of PNPase in gene regulation. Particularly, the RNA level of exsA was decreased in the ΔKH-S1 mutant, which was responsible for the reduced T3SS expression. Meanwhile, the pilus biosynthesis genes were down regulated and the type VI secretion system (T6SS) genes were up regulated in the ΔKH-S1 mutant, which were caused by increased levels of small RNAs, RsmY, and RsmZ. Further studies revealed that deletion of the KH-S1 domains did not affect the transcription of RsmY/Z, but increased their stabilities. An in vivo pull-down and in vitro electrophoretic mobility shift assay (EMSA) demonstrated a direct interaction between RsmY/Z and the KH-S1 fragment. Overall, this study reveals the roles of PNPase in the regulation of virulence factors and stabilities of small RNAs in P. aeruginosa. PMID:26973625

  5. MADS-Box Transcription Factor AGL21 Regulates Lateral Root Development and Responds to Multiple External and Physiological Signals

    PubMed Central

    Yu, Lin-Hui; Miao, Zi-Qing; Qi, Guo-Feng; Wu, Jie; Cai, Xiao-Teng; Mao, Jie-Li; Xiang, Cheng-Bin

    2014-01-01

    Plant root system morphology is dramatically influenced by various environmental cues. The adaptation of root system architecture to environmental constraints, which mostly depends on the formation and growth of lateral roots, is an important agronomic trait. Lateral root development is regulated by the external signals coordinating closely with intrinsic signaling pathways. MADS-box transcription factors are known key regulators of the transition to flowering and flower development. However, their functions in root development are still poorly understood. Here we report that AGL21, an AGL17-clade MADS-box gene, plays a crucial role in lateral root development. AGL21 was highly expressed in root, particularly in the root central cylinder and lateral root primordia. AGL21 overexpression plants produced more and longer lateral roots while agl21 mutants showed impaired lateral root development, especially under nitrogen-deficient conditions. AGL21 was induced by many plant hormones and environmental stresses, suggesting a function of this gene in root system plasticity in response to various signals. Furthermore, AGL21 was found positively regulating auxin accumulation in lateral root primordia and lateral roots by enhancing local auxin biosynthesis, thus stimulating lateral root initiation and growth. We propose that AGL21 may be involved in various environmental and physiological signals-mediated lateral root development and growth. PMID:25122697

  6. Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions.

    PubMed

    Sanderson, N; Factor, V; Nagy, P; Kopp, J; Kondaiah, P; Wakefield, L; Roberts, A B; Sporn, M B; Thorgeirsson, S S

    1995-03-28

    Aberrant expression of transforming growth factor beta 1 (TGF-beta 1) has been implicated in a number of disease processes, particularly those involving fibrotic and inflammatory lesions. To determine the in vivo effects of overexpression of TGF-beta 1 on the function and structure of hepatic as well as extrahepatic tissues, transgenic mice were generated containing a fusion gene (Alb/TGF-beta 1) consisting of modified porcine TGF-beta 1 cDNA under the control of the regulatory elements of the mouse albumin gene. Five transgenic lines were developed, all of which expressed the Alb/TGF-beta 1 transgene selectively in hepatocytes. The transgenic line 25 expressing the highest level of the transgene in the liver also had high (> 10-fold over control) plasma levels of TGF-beta 1. Hepatic fibrosis and apoptotic death of hepatocytes developed in all the transgenic lines but was more pronounced in line 25. The fibrotic process was characterized by deposition of collagen around individual hepatocytes and within the space of Disse in a radiating linear pattern. Several extrahepatic lesions developed in line 25, including glomerulonephritis and renal failure, arteritis and myocarditis, as well as atrophic changes in pancreas and testis. The results from this transgenic model strongly support the proposed etiological role for TGF-beta 1 in a variety of fibrotic and inflammatory disorders. The transgenic model may also provide an appropriate paradigm for testing therapeutic interventions aimed at neutralizing the detrimental effects of this important cytokine. PMID:7708687

  7. Multidimensional Family Therapy: Addressing Co-Occurring Substance Abuse and Other Problems among Adolescents with Comprehensive Family-Based Treatment

    PubMed Central

    Rowe, Cynthia L.

    2010-01-01

    Synopsis Adolescent substance abuse rarely occurs without other psychiatric and developmental problems, yet it is often treated and researched as if it can be isolated from comorbid conditions. Few comprehensive interventions are available that effectively address the range of co-occurring problems associated with adolescent substance abuse. This article reviews the clinical interventions and research evidence supporting the use of Multidimensional Family Therapy (MDFT) for adolescents with substance abuse and co-occurring problems. MDFT is uniquely suited to addres