WorldWideScience

Sample records for supervision regulations progression

  1. 48 CFR 32.503-2 - Supervision of progress payments.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Supervision of progress... GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Progress Payments Based on Costs 32.503-2 Supervision of progress payments. (a) The extent of progress payments supervision, by prepayment review...

  2. Measuring progressive independence with the resident supervision index: empirical approach.

    Science.gov (United States)

    Kashner, T Michael; Byrne, John M; Chang, Barbara K; Henley, Steven S; Golden, Richard M; Aron, David C; Cannon, Grant W; Gilman, Stuart C; Holland, Gloria J; Kaminetzky, Catherine P; Keitz, Sheri A; Muchmore, Elaine A; Kashner, Tetyana K; Wicker, Annie B

    2010-03-01

    A Resident Supervision Index (RSI) developed by our research team quantifies the intensity of resident supervision in graduate medical education, with the goal of testing for progressive independence. The 4-part RSI method includes a survey instrument for staff and residents (RSI Inventory), a strategy to score survey responses, a theoretical framework (patient centered optimal supervision), and a statistical model that accounts for the presence or absence of supervision and the intensity of patient care. The RSI Inventory data came from 140 outpatient encounters involving 57 residents and 37 attending physicians during a 3-month period at a Department of Veterans Affairs outpatient clinic. Responses are scored to quantitatively measure the intensity of resident supervision across 10 levels of patient services (staff is absent, is present, participated, or provided care with or without a resident), case discussion (resident-staff interaction), and oversight (staff reviewed case, reviewed medical chart, consulted with staff, or assessed patient). Scores are analyzed by level and for patient care using a 2-part model (supervision initiated [yes or no] versus intensity once supervision was initiated). All resident encounters had patient care supervision, resident oversight, or both. Consistent with the progressive independence hypothesis, residents were 1.72 (P  =  .019) times more likely to be fully responsible for patient care with each additional postgraduate year. Decreasing case complexity, increasing clinic workload, and advanced nonmedical degrees among attending staff were negatively associated with supervision intensity, although associations varied by supervision level. These data are consistent with the progressive independence hypothesis in graduate medical education and offer empirical support for the 4-part RSI method to quantify the intensity of resident supervision for research, program evaluation, and resident assessment purposes. Before

  3. Regulation and supervision of microfinance in Albania

    Directory of Open Access Journals (Sweden)

    Rezart Hoxhaj

    2010-07-01

    Full Text Available This paper describes important regulation issues that concern microfinance. It starts byconsidering literature on how and why to regulate and supervise microfinance. Considering thespecific case of microfinance in Albania, it analyzes the context of this industry and someparticular issues that might influence its growth. Related regulation in Albania seems to be notactivity-oriented since a real definition of microfinance is lacking in the Albanian law. Therefor,Albanian microfinance sector needs, first of all, a microcredit and microfinance definition toimplement the right development policies and avoid confusion and license misuse. Moreover, theregulatory framework seems to be too restrictive for institutions supposed to be engaged inmicrofinance example high capital requirement and provisioning. Possible interventions can be inlowering minimum capital requirements for NBFIs to improve entrance, simplifying procedures,documentation and harmonization of the taxation treatment of institutions to enhancedevelopment, encourage access and avoid market distortions. There is the need to implementregulation considering microfinance as an activity, and develop a regulatory framework to inducecommercial banks integrate downward into the microfinance market and help informal start-upsinstitutions develop and get formalized.

  4. Fundamental principles of financial regulation and supervision

    OpenAIRE

    Kregel, Jan A.; Mario Tonveronachi

    2014-01-01

    The financial system is a private-public partnership coming from government ceding the right to produce means of payment with the related permission on leveraged lending services, against the acceptance of rules designed to ensure stability for both individual institutions and the financial system. The experience shows that market-based regulation does not produce the wanted results, while rules-based and principle-based regulatory systems are prone to regulatory avoidance and capture, especi...

  5. Regulation and Supervision of The Global Financial System. A Proposal for Institutional Reform

    NARCIS (Netherlands)

    Denters, H.M.G.

    2009-01-01

    nternational financial markets are supervised primarily by national authorities. However, national authorities are inherently incapable to regulate and supervise seamless globalised financial markets. To the extent international regulators exist, they constitute a disorderly patchwork of

  6. [Administrative reform thinking on the regulations on the supervision and administration of medical devices].

    Science.gov (United States)

    Yue, Wei

    2014-09-01

    This paper learned and interpreted the regulations on the supervision and administration of medical devices, carded the thoughts of administrative reform, then put forward the "ten principles", including full supervision, classification supervision, risk classification, safety-effective-save, to encourage innovation, simplified license, scientific-standard, sincerity & self-discipline, clear responsibility, severe punishment, and discussed these priciples.

  7. Views of Educational Supervisors Concerning the Feasibility of Educational Supervision Regulation

    Science.gov (United States)

    Akbasli, Sait; Ozbas, Mehmet

    2012-01-01

    The main purpose of this study is to determine the level in which educational supervisors who carry out the regulations concerning the feasibility conditions of educational supervision regulation views arise. The research was carried out in 2010 to 2011 academic year; the research population included 3150 educational supervisors and the research…

  8. Market Supervision New Super Regulator in the Pipeline

    Institute of Scientific and Technical Information of China (English)

    WANG PEI

    2006-01-01

    @@ The establishment of a new regulator or coordinating body for China's financial industry is reported to be on the horizon. While the exact positioning and function of the proposed body are still not clear, some already question the need to form a new regulator on the top of the existing regulatory and supervisory bodies.

  9. Supervised progressive cross-continuum strength training compared with usual care in older medical patients

    DEFF Research Database (Denmark)

    Pedersen, Mette Merete; Petersen, Janne; Beyer, Nina;

    2016-01-01

    on the model), combined with post-training protein supplementation initiated during hospitalization and continued at home for 4 weeks, is superior to usual care on change in mobility 4 weeks after discharge in older medical patients. Methods: Eighty older medical patients (65 years or older) acutely admitted...... hospitalization and continued after discharge. We conducted a feasibility study prior to this trial and found a progression model for loaded sit-to-stands feasible in older medical patients. This study aims to determine whether a simple supervised strength training program for the lower extremities (based...... hospitalization and three times per week for 4 weeks after discharge. Both exercises follow pre-defined models for progression and will be performed for three sets of 8–12 repetitions maximum in each training session. Thereafter, the patient will be asked to consume a protein supplement given orally containing 18...

  10. Bank Risk-Taking Abroad : Does Home-Country Regulation and Supervision Matter

    NARCIS (Netherlands)

    Ongena, S.; Popov, A.; Udell, G.F.

    2011-01-01

    This paper provides the first empirical evidence on how home-country regulation and supervision affects bank risk-tailing in host-country markets. We analyze lending by 136 banks to 8,253 firms in 1,513 different localities across 13 countries. We find strong evidence that laxer regulatory restricti

  11. Bank Risk-Taking Abroad : Does Home-Country Regulation and Supervision Matter

    NARCIS (Netherlands)

    Ongena, S.; Popov, A.; Udell, G.F.

    2011-01-01

    This paper provides the first empirical evidence on how home-country regulation and supervision affects bank risk-tailing in hostr-country markets. We analyze lending by 136 banks to 8,253 firms in 1,513 different localities across 13 countries. We find strong evidence that laxer regulatory restrict

  12. Bank Risk-Taking Abroad : Does Home-Country Regulation and Supervision Matter

    NARCIS (Netherlands)

    Ongena, S.; Popov, A.; Udell, G.F.

    2011-01-01

    This paper provides the first empirical evidence on how home-country regulation and supervision affects bank risk-tailing in host-country markets. We analyze lending by 136 banks to 8,253 firms in 1,513 different localities across 13 countries. We find strong evidence that laxer regulatory

  13. Bank Risk-Taking Abroad : Does Home-Country Regulation and Supervision Matter

    NARCIS (Netherlands)

    Ongena, S.; Popov, A.; Udell, G.F.

    2011-01-01

    This paper provides the first empirical evidence on how home-country regulation and supervision affects bank risk-tailing in hostr-country markets. We analyze lending by 136 banks to 8,253 firms in 1,513 different localities across 13 countries. We find strong evidence that laxer regulatory

  14. Outsourcing, managing, supervising, and regulating private military companies in contingency operations

    OpenAIRE

    2010-01-01

    Approved for public release; distribution is unlimited This thesis examines the utilization of private military companies (PMCs) by government agencies of the United States in contingency operations in Iraq and Afghanistan. The aim of this thesis is to investigate the roles that PMCs play in current contingency operations, and to analyze how PMCs can become more useful instruments in contingency operations if they are properly outsourced, managed, supervised, and regulated. In this regar...

  15. Progress toward risk informed regulation

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, K.C.

    1997-01-01

    For the last several years, the NRC, with encouragement from the industry, has been moving in the direction of risk informed regulation. This is consistent with the regulatory principle of efficiency, formally adopted by the Nuclear Regulatory Commission in 1991, which requires that regulatory activities be consistent with the degree of risk reduction they achieve. Probabilistic risk analysis has become the tool of choice for selecting the best of several alternatives. Closely related to risk informed regulation is the development of performance based rules. Such rules focus on the end result to be achieved. They do not specify the process, but instead establish the goals to be reached and how the achievement of those goals is to be judged. The inspection and enforcement activity is based on whether or not the goals have been met. The author goes on to offer comments on the history of the development of this process and its probable development in the future. He also addresses some issues which must be resolved or at least acknowledged. The success of risk informed regulation ultimately depends on having sufficiently reliable data to allow quantification of regulatory alternatives in terms of relative risk. Perhaps the area of human reliability and organizational performance has the greatest potential for improvement in reactor safety. The ability to model human performance is significantly less developed that the ability to model mechanical or electrical systems. The move toward risk informed, performance based regulation provides an unusual, perhaps unique, opportunity to establish a more rational, more effective basis for regulation.

  16. Capital regulations, supervision and the international harmonization of bank capital ratios

    Directory of Open Access Journals (Sweden)

    Kevin T. Jacques

    2017-06-01

    Full Text Available In recent decades, despite the Basel Committee’s effort to develop internationally uniform regulatory capital standards, the capital ratios of banks across countries continue to exhibit significant differences. This paper examines the fundamental question of whether, given a uniform regulatory capital standard, regulators should expect similar banks to exhibit similar risk-based capital ratios. More specifically, this study develops a one-period theoretical model to examine the level playing field argument in light of not only uniform regulatory capital standards but also differences in bank supervision. The results of the theoretical model suggest that even with an internationally uniform risk-based capital requirement, it is unreasonable to expect banks in different countries to hold similar capital ratios. This occurs, in part, because regulators have discretion in how they apply the risk-based capital standards. Furthermore, the results suggest that a necessary condition for banks to exhibit similar capital ratios is that uniform capital requirements must be accompanied by a uniform stringency and application of regulatory supervision.

  17. Discussion on Supervision of Village Regulations and Folk Conventions%论村规民约的监督

    Institute of Scientific and Technical Information of China (English)

    许晓琼; 张居盛

    2011-01-01

    Village regulations and folk conventions is a code of conduct in rural society and play an important role in the new rural development. Tlie supervision of village regulations and folk conventions can ensure die validity, prevention, error correction and efficiency of village regulations and folk conventions. At present, diere are still supervision of consciousness, lack of supervision, supervision principal is not clear, the supervisory measures do not reach the designated position and other issues. Therefore, for the problems in the supervision of village regulations and folk conventions, administrative supervision, judicial oversight and supervision of social are put forward, the methods for supervising village regulations and folk conventions are adopted, namely, strict record review, eliminating unlawful pacts and strengthening the judicial application. Thus, it not only can ensure effective supervision, but also can not interfere the self-government of villagers.%村规民约是一种存在于乡村社会中的行为规范,在新农村建设中发挥着重要作用.对村规民约进行监督具有保障村规民约的合法性、预防、纠错以及增效的作用.目前村规民约监督还存在监督意识淡薄,缺乏监督依据、监督主体不明确和监督措施不力的问题.针对村规民约的监督中存在的问题,提出应通过行政监督、司法监督和社会监督多种途径,采取严格备案审查、消除不合法的村规民约和加强判决审查等方式监督村规民约,做到既有效监督,又不至于干涉村民自治.

  18. La vigilanza sul sistema finanziario: obiettivi, assetti e approcci (Financial-Sector Regulation and Supervision: Targets, Frameworks and Approaches

    Directory of Open Access Journals (Sweden)

    Mario Sarcinelli

    2012-04-01

    Full Text Available The scandals that have tarnished the reputation of Wall Street and in Italy have damaged those who have invested their savings in Parmalat or Cirio corporate bonds or in Argentinean Government securities justify revisiting the objectives to be achieved by regulation and supervision of the financial sector. Stability is still regarded as paramount for banking, to be secured through an appropriate capital cushion, extensive supervisory arrangements, and market discipline, as agreed by Basel 2. Other financial intermediaries need to conduct their business with great transparency, openness and respect of the rules. However, an ever expanding and innovative financial sector, the blurring of traditional segmentations and globalisation make the task of regulating and supervising the financial sector more difficult and challenging, thus requiring new frameworks, for instance a single agency, in various jurisdictions and more international co-ordination and co-operation among regulating and supervising agencies. Up to now, the approach followed by the latter has been microeconomic, but the growing financial instability and the greater relevance of systemic risk may ask for a macroeconomic management of prudential regulation and supervision, thus complementing monetary policy in securing financial stability.  JEL Codes: E52, G18, G21, G28Keywords: Banking; Regulation; Securities

  19. 76 FR 39246 - List of Office of Thrift Supervision Regulations to be Enforced by the Office of the Comptroller...

    Science.gov (United States)

    2011-07-06

    ... accordingly as OCC rules, with nomenclature and other technical amendments to reflect OCC supervision. The OCC... of Federal Regulations with nomenclature and other technical amendments. After the transfer date, and.... Part 533 Disclosure and Reporting of CRA-related Agreements. Part 536 Consumer Protection in Sales...

  20. La vigilanza sul sistema finanziario: obiettivi, assetti e approcci (Financial-Sector Regulation and Supervision: Targets, Frameworks and Approaches

    Directory of Open Access Journals (Sweden)

    Mario Sarcinelli

    2004-09-01

    Full Text Available The scandals that have tarnished the reputation of Wall Street and in Italy have damaged those who have invested their savings in Parmalat or Cirio corporate bonds or in Argentinean Government securities justify revisiting the objectives to be achieved by regulation and supervision of the financial sector. Stability is still regarded as paramount for banking, to be secured through an appropriate capital cushion, extensive supervisory arrangements, and market discipline, as agreed by Basel 2. Other financial intermediaries need to conduct their business with great transparency, openness and respect of the rules. However, an ever expanding and innovative financial sector, the blurring of traditional segmentations and globalisation make the task of regulating and supervising the financial sector more difficult and challenging, thus requiring new frameworks, for instance a single agency, in various jurisdictions and more international co-ordination and co-operation among regulating and supervising agencies. Up to now, the approach followed by the latter has been microeconomic, but the growing financial instability and the greater relevance of systemic risk may ask for a macroeconomic management of prudential regulation and supervision, thus complementing monetary policy in securing financial stability.

  1. Anti-crisis Regulation, Banking Supervision and Monetary Policy in the Mechanism of Ensuring Financial Stability of the Banking System

    OpenAIRE

    Dovgan Zhanna N.

    2013-01-01

    The article develops a scheme of correlations of subjects of anti-crisis regulation and tools of support of financial stability of the banking system of Ukraine (FSBS). It analyses instruments of influence of the bodies of state regulation on financial stability of the banking system of Ukraine. It develops proposals with respect to improvement of the banking supervision in the context of ensuring FSBS of Ukraine. It studies interdependence between the type of the mode of national regulatory ...

  2. CONCEPTUAL BASES OF MACRO PRUDENTIAL OF SUPERVISION AND REGULATION OF INSURANCE ACTIVITIES

    Directory of Open Access Journals (Sweden)

    А. Zaletov

    2014-03-01

    Full Text Available The substantive provisions of macro prudential supervision and adjusting, certain basic problems of his realization for adjusting of domestic market of bank services and the process of realization of conception of macro prudential supervision and adjusting is considered, are considered in the article.

  3. SRC kinase regulation in progressively invasive cancer.

    Directory of Open Access Journals (Sweden)

    Weichen Xu

    Full Text Available Metastatic progression is a multistep process that involves tumor growth and survival, motility and invasion, and subsequent proliferation in an inappropriate environment. The Src protein tyrosine kinase has been implicated in many of the biochemical pathways that drive these behaviors. Although Src itself is only rarely mutated in human tumors, its aberrant activity has been noted in various cancers and suggested to serve as a barometer of metastatic potential. With these features in mind, we examined Src kinase regulation at the structural, enzymatic, and expression levels as a function of progressively invasive prostate cancer cell lines. Surprisingly, both total Src content and kinase activity decrease with increasing cell line aggressiveness, an observation that appears to be inconsistent with the well-documented role of Src in the signaling pathways that drive growth and invasion. However, we do observe a direct correlation between Src kinase specific activity (total Src kinase activity/total Src content and metastatic aggressiveness, possibly suggesting that in highly aggressive cell lines, key signaling enzymes are globally recruited to drive the cancerous phenotype. In addition, although the expected enhanced phosphorylation of Src at Tyr-416 (activation site is present in the most aggressive prostate cancer cell lines, unexpectedly high phosphorylation levels at the Tyr-527 inhibitory site are observed as well. The latter, rather than representative of inhibited enzyme, is more indicative of primed Src responsive to local phosphorylated binding partners.

  4. Kollegial supervision

    DEFF Research Database (Denmark)

    Andersen, Ole Dibbern; Petersson, Erling

    Publikationen belyser, hvordan kollegial supervision i en kan organiseres i en uddannelsesinstitution......Publikationen belyser, hvordan kollegial supervision i en kan organiseres i en uddannelsesinstitution...

  5. The Regulation of Technology-Assisted Distance Counseling and Supervision in the United States: An Analysis of Current Extent, Trends, and Implications

    Science.gov (United States)

    McAdams, Charles R.; Wyatt, Kristi Lee

    2010-01-01

    Counseling licensure boards report emerging needs to regulate technology-assisted distance counseling and supervision. An analysis of published regulations and telephone interviews with board administrators nationwide suggests that boards agree generally on 7 aspects of technology-assisted distance practice that need to be regulated. Nevertheless,…

  6. Classification models for clear cell renal carcinoma stage progression, based on tumor RNAseq expression trained supervised machine learning algorithms.

    Science.gov (United States)

    Jagga, Zeenia; Gupta, Dinesh

    2014-01-01

    Clear-cell Renal Cell Carcinoma (ccRCC) is the most- prevalent, chemotherapy resistant and lethal adult kidney cancer. There is a need for novel diagnostic and prognostic biomarkers for ccRCC, due to its heterogeneous molecular profiles and asymptomatic early stage. This study aims to develop classification models to distinguish early stage and late stage of ccRCC based on gene expression profiles. We employed supervised learning algorithms- J48, Random Forest, SMO and Naïve Bayes; with enriched model learning by fast correlation based feature selection to develop classification models trained on sequencing based gene expression data of RNAseq experiments, obtained from The Cancer Genome Atlas. Different models developed in the study were evaluated on the basis of 10 fold cross validations and independent dataset testing. Random Forest based prediction model performed best amongst the models developed in the study, with a sensitivity of 89%, accuracy of 77% and area under Receivers Operating Curve of 0.8. We anticipate that the prioritized subset of 62 genes and prediction models developed in this study will aid experimental oncologists to expedite understanding of the molecular mechanisms of stage progression and discovery of prognostic factors for ccRCC tumors.

  7. PROBLEMS OF FORMATION OF OPTIMAL MODEL OF GOVERNMENTAL REGULATION AND SUPERVISION IN THE FINANCIAL SECTOR OF UKRAINE IN THE CONTEXT OF CREDIT COOPERATION

    Directory of Open Access Journals (Sweden)

    Oleksandra OSADETS

    2016-07-01

    Full Text Available In the presented scientific practical research we considered and explored the role and problems of state regulation and supervision of the financial sector of Ukraine, in particular of credit unions because they are inalienable participants in the financial market. In current conditions that have been established during the inancial crisis, one of the most urgent problems is the effective functioning of the regulation and supervision of the financial sector. The crisis that negatively affected the activities of financial sector participants discovered the discrepancy of regulation and supervision of them, which caused the negative trend of development of financial market of Ukraine, as evidenced by official data of the National Commission, which performs state regulation in the sphere of financial services. In the presented scientific practical research we identified the strengths and weaknesses of the modern system of state regulation and supervision in the financial sector of Ukraine, particularly in the sector of credit cooperation, and we formed suggestions on improving its model in the context of the concentration of regulatory and supervisory efforts in state financial regulators

  8. PROBLEMS OF FORMATION OF OPTIMAL MODEL OF GOVERNMENTAL REGULATION AND SUPERVISION IN THE FINANCIAL SECTOR OF UKRAINE IN THE CONTEXT OF CREDIT COOPERATION

    Directory of Open Access Journals (Sweden)

    Oleksandra OSADETS

    2016-07-01

    Full Text Available In the presented scientific practical research we considered and explored the role and problems of state regulation and supervision of the financial sector of Ukraine, in particular of credit unions because they are inalienable participants in the financial market. In current conditions that have been established during the financial crisis, one of the most urgent problems is the effective functioning of the regulation and supervision of the financial sector. The crisis that negatively affected the activities of financial sector participants discovered the discrepancy of regulation and supervision of them, which caused the negative trend of development of financial market of Ukraine, as evidenced by official data of the National Commission, which performs state regulation in the sphere of financial services. In the presented scientific practical research we identified the strengths and weaknesses of the modern system of state regulation and supervision in the financial sector of Ukraine, particularly in the sector of credit cooperation, and we formed suggestions on improving its model in the context of the concentration of regulatory and supervisory efforts in state financial regulators.

  9. (Regulation of terpene metabolism. ) Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1984-01-01

    This research program represents a very broad-based approach to understanding the biochemistry of the monoterpene and sesquiterpene constituents of the essential oils. This program includes basic research on the pathways, enzymes and mechanisms of terpene biosynthesis and catabolism, on the physiology of essential oil production, and on the morphology and development of oil glands, as well as practical approaches to manipulating essential oil composition and yield. As a natural extension of research on monoterpene biosynthesis and catabolism in sage and peppermint we have explored some aspects of possible regulatory mechanisms. Tentative evidence has been obtained for developmental regulation of the levels of biosynthetic and catabolic enzymes. 10 refs., 8 figs.

  10. 76 FR 4555 - Authority To Require Supervision and Regulation of Certain Nonbank Financial Companies

    Science.gov (United States)

    2011-01-26

    ... those activities most prone to systemic risk through contagion. To measure interconnectedness, commenters suggested evaluating, among other things, liquidity profile, contagion risk, counterparty credit... prudential regulators or the Office of Financial Research to make its determinations. 11. Should the degree...

  11. The efficacy of early initiated, supervised, progressive resistance training compared to unsupervised, home-based exercise after unicompartmental knee arthroplasty: a single-blinded randomized controlled trial.

    Science.gov (United States)

    Jørgensen, Peter B; Bogh, Søren B; Kierkegaard, Signe; Sørensen, Henrik; Odgaard, Anders; Søballe, Kjeld; Mechlenburg, Inger

    2017-01-01

    To examine if supervised progressive resistance training was superior to home-based exercise in rehabilitation after unicompartmental knee arthroplasty. Single blinded, randomized clinical trial. Surgery, progressive resistance training and testing was carried out at Aarhus University Hospital and home-based exercise was carried out in the home of the patient. Fifty five patients were randomized to either progressive resistance training or home-based exercise. Patients were randomized to either progressive resistance training (home based exercise five days/week and progressive resistance training two days/week) or control group (home based exercise seven days/week). Preoperative assessment, 10-week (primary endpoint) and one-year follow-up were performed for leg extension power, spatiotemporal gait parameters and knee injury and osteoarthritis outcome score (KOOS). Forty patients (73%) completed 1-year follow-up. Patients in the progressive resistance training group participated in average 11 of 16 training sessions. Leg extension power increased from baseline to 10-week follow-up in progressive resistance training group (progressive resistance training: 0.28 W/kg, P= 0.01, control group: 0.01 W/kg, P=0.93) with no between-group difference. Walking speed and KOOS scores increased from baseline to 10-week follow-up in both groups with no between-group difference (six minutes walk test P=0.63, KOOS P>0.29). Progressive resistance training two days/week combined with home based exercise five days/week was not superior to home based exercise seven days/week in improving leg extension power of the operated leg.

  12. Mir-33 regulates cell proliferation and cell cycle progression.

    Science.gov (United States)

    Cirera-Salinas, Daniel; Pauta, Montse; Allen, Ryan M; Salerno, Alessandro G; Ramírez, Cristina M; Chamorro-Jorganes, Aranzazu; Wanschel, Amarylis C; Lasuncion, Miguel A; Morales-Ruiz, Manuel; Suarez, Yajaira; Baldan, Ángel; Esplugues, Enric; Fernández-Hernando, Carlos

    2012-03-01

    Cholesterol metabolism is tightly regulated at the cellular level and is essential for cellular growth. microRNAs (miRNAs), a class of noncoding RNAs, have emerged as critical regulators of gene expression, acting predominantly at posttranscriptional level. Recent work from our group and others has shown that hsa-miR-33a and hsa-miR-33b, miRNAs located within intronic sequences of the Srebp genes, regulate cholesterol and fatty acid metabolism in concert with their host genes. Here, we show that hsa-miR-33 family members modulate the expression of genes involved in cell cycle regulation and cell proliferation. MiR-33 inhibits the expression of the cyclin-dependent kinase 6 (CDK6) and cyclin D1 (CCND1), thereby reducing cell proliferation and cell cycle progression. Overexpression of miR-33 induces a significant G 1 cell cycle arrest in Huh7 and A549 cell lines. Most importantly, inhibition of miR-33 expression using 2'fluoro/methoxyethyl-modified (2'F/MOE-modified) phosphorothioate backbone antisense oligonucleotides improves liver regeneration after partial hepatectomy (PH) in mice, suggesting an important role for miR-33 in regulating hepatocyte proliferation during liver regeneration. Altogether, these results suggest that Srebp/miR-33 locus may cooperate to regulate cell proliferation, cell cycle progression and may also be relevant to human liver regeneration.

  13. 48 CFR 836.572 - Government supervision.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Government supervision. 836.572 Section 836.572 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SPECIAL... supervision. The contracting officer shall insert the clause at 852.236-78, Government supervision,...

  14. Liechtenstein; Assessment of the Supervision and Regulation of the Financial Sector Volume II-Detailed Assessment of Observance of Standards and Codes

    OpenAIRE

    International Monetary Fund

    2003-01-01

    This report on the offshore financial center program contains technical advice and recommendations given by the staff team of the International Monetary Fund in response to Liechtenstein’s request for technical assistance. It provides detailed assessment of observance of the Basel Core Principles for effective banking supervision, implementation of the International Organization of Securities Commissions (IOSCO) Objectives And Principles Of Securities Regulation, and observance of the Inter...

  15. Clinical supervision.

    Science.gov (United States)

    Goorapah, D

    1997-05-01

    The introduction of clinical supervision to a wider sphere of nursing is being considered from a professional and organizational point of view. Positive views are being expressed about adopting this concept, although there are indications to suggest that there are also strong reservations. This paper examines the potential for its success amidst the scepticism that exists. One important question raised is whether clinical supervision will replace or run alongside other support systems.

  16. Mechanism of genetic regulation. Comprehensive progress report, 1965-1967

    Energy Technology Data Exchange (ETDEWEB)

    Doi, R H

    1968-04-22

    Research progress is reported for the period 1965 through 1967. In order to obtain a biological system for the study of gene regulation, a study of the phage-bacterium complex and the uninfected host was begun. Accomplishments include the isolation and characterization of phages for B. subtilis for studies on transcriptional and translational controls, the identification of factors which control the functional capacity of transfer RNA, and the analysis of the initiation of protein synthesis in B. subtilis. (ACR)

  17. 19 CFR 146.4 - Operator responsibility and supervision.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Operator responsibility and supervision. 146.4... and supervision. (a) Supervision. The operator shall supervise all admissions, transfers, removals... conditions of storage in the zone as required by law and regulations. Supervision by the operator shall...

  18. Discussion on supervision implementation regulation problems and countermeasures%谈监理实施细则存在的问题及对策

    Institute of Scientific and Technical Information of China (English)

    杨富金

    2015-01-01

    简述了国内相关法律、法规对监理实施细则的编制要求,通过分析当前监理实施细则存在的问题,提出了一些解决对策,以促进监理行业朝着科学管理、规范管理的方向健康发展。%The paper briefly illustrates supervision implementation regulations compiling demands according to domestic relevant laws and rules, analyzes current supervision implementation problems,and puts forward some solving countermeasures,with a view to promote its scientific and regular development.

  19. Malta; Financial System Stability Assessment, including Reports on the Observance of Standards and Codes on the following topics: Monetary and Financial Policy Transparency, Banking Supervision, Securities Regulation, Insurance Regulation, Corporate Governance, and Payment Systems

    OpenAIRE

    International Monetary Fund

    2003-01-01

    The report provides the details of the Malta Financial Stability Assessment (MFSA). It defines its roles, responsibilities, and objectives for financial policies. It reviews the reports on the observance of standards and codes on monetary and financial policy transparency, banking supervision, securities regulation, insurance regulation, corporate governance, and payment systems. It assesses the macroeconomic environment and risks, soundness and vulnerabilities of the financial system, and al...

  20. Whither Supervision?

    Directory of Open Access Journals (Sweden)

    Duncan Waite

    2006-11-01

    Full Text Available This paper inquires if the school supervision is in decadence. Dr. Waite responds that the answer will depend on which perspective you look at it. Dr. Waite suggests taking in consideration three elements that are related: the field itself, the expert in the field (the professor, the theorist, the student and the administrator, and the context. When these three elements are revised, it emphasizes that there is not a consensus about the field of supervision, but there are coincidences related to its importance and that it is related to the improvement of the practice of the students in the school for their benefit. Dr. Waite suggests that the practice on this field is not always in harmony with what the theorists affirm. When referring to the supervisor or the skilled person, the author indicates that his or her perspective depends on his or her epistemological believes or in the way he or she conceives the learning; that is why supervision can be understood in different ways. About the context, Waite suggests that there have to be taken in consideration the social or external forces that influent the people and the society, because through them the education is affected. Dr. Waite concludes that the way to understand the supervision depends on the performer’s perspective. He responds to the initial question saying that the supervision authorities, the knowledge on this field, the performers, and its practice, are maybe spread but not extinct because the supervision will always be part of the great enterprise that we called education.

  1. 76 FR 81942 - Federal Acquisition Regulation; Information Collection; Progress Payments (SF-1443)

    Science.gov (United States)

    2011-12-29

    ... Regulation; Information Collection; Progress Payments (SF-1443) AGENCIES: Department of Defense (DOD... ``Progress Payments,'' contractors are required to request progress payments on Standard Form (SF) 1443... information, reasonably requested by the Contracting Officer. The contractual requirement for submission of...

  2. 7 CFR 56.6 - Supervision.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Supervision. 56.6 Section 56.6 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections... Grading of Shell Eggs General § 56.6 Supervision. All grading service shall be subject to supervision...

  3. CYTOKINE REGULATION IN THE COURSE OF MULTIPLE MYELOMA PROGRESSION

    Directory of Open Access Journals (Sweden)

    O. V. Smirnova

    2015-01-01

    Full Text Available Cytokines are wide-range modifiers of biological reactions. Cytokine regulation provides proliferation, differentiation, cell function, cell-cell and inter-systemic interaction, direction and nature of immune response to invasion of infectious and non-infectious pathogens. There are several distinct groups of cytokines: pro-inflammatory, anti-inflammatory factors, regulators of cellular and humoral immunity etc. A distinct role of cytokines is not excluded for infectious complications accompanying multiple myeloma (MM. Cytokine regulatory effects on immune defense in the organism as a whole, and a balance between proand anti-inflammatory cytokines in blood of MM patients depend on the stage of multiple myeloma progression and possibility of infectious complications. Therefore, the aim of our study was to evaluate proand anti-inflammatory cytokines and cytokine regulation in patients with MM G-immunochemical option. Our study involved 101 patients with MM (IgG-variant, their age ranging between 40 and 76 years. The diagnosis was verified by clinical and laboratory examinations. The G-variant of MM was verified by immunofixation and electrophoresis. The definite diagnosis and disease staging was confirmed by a combination of diagnostic criteria. Heparinized blood samples were taken from the cubital vein in the morning (8 to 9 hours, in fasting state upon admission, prior to the starting a pathogenetic therapy. Dynamic monitoring of patients was carried out over the period of their staying in hospital. All patients were staged according to Durie and Salmon (1975 (stages II, III. At each stage, we discerned two sub-groups: A, without renal disease, B, with renal impairment. The control group consisted of 125 healthy volunteers matched for age and sex with the main group. IL-2, IL-4, IL-8, TNFα, and IFNγ levels in sera of the patients and healthy individuals were determined by enzyme immunoassay kits (JSC “Vector-Best”,Novosibirsk. In the

  4. Daxx regulates mitotic progression and prostate cancer predisposition.

    Science.gov (United States)

    Kwan, Pak Shing; Lau, Chi Chiu; Chiu, Yung Tuen; Man, Cornelia; Liu, Ji; Tang, Kai Dun; Wong, Yong Chuan; Ling, Ming-Tat

    2013-04-01

    Mitotic progression of mammalian cells is tightly regulated by the E3 ubiquitin ligase anaphase promoting complex (APC)/C. Deregulation of APC/C is frequently observed in cancer cells and is suggested to contribute to chromosome instability and cancer predisposition. In this study, we identified Daxx as a novel APC/C inhibitor frequently overexpressed in prostate cancer. Daxx interacts with the APC/C coactivators Cdc20 and Cdh1 in vivo, with the binding of Cdc20 dependent on the consensus destruction boxes near the N-terminal of the Daxx protein. Ectopic expression of Daxx, but not the D-box deleted mutant (DaxxΔD-box), inhibited the degradation of APC/Cdc20 and APC/Cdh1 substrates, leading to a transient delay in mitotic progression. Daxx is frequently upregulated in prostate cancer tissues; the expression level positively correlated with the Gleason score and disease metastasis (P = 0.027 and 0.032, respectively). Furthermore, ectopic expression of Daxx in a non-malignant prostate epithelial cell line induced polyploidy under mitotic stress. Our data suggest that Daxx may function as a novel APC/C inhibitor, which promotes chromosome instability during prostate cancer development.

  5. 48 CFR 52.247-12 - Supervision, Labor, or Materials.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Supervision, Labor, or....247-12 Supervision, Labor, or Materials. As prescribed in 47.207-5(b), insert a clause substantially... when the contractor is required to furnish supervision, labor, or materials: Supervision, Labor,...

  6. Regulation of microtubule stability and mitotic progression by survivin.

    Science.gov (United States)

    Giodini, Alessandra; Kallio, Marko J; Wall, Nathan R; Gorbsky, Gary J; Tognin, Simona; Marchisio, Pier Carlo; Symons, Marc; Altieri, Dario C

    2002-05-01

    Survivin is a member of the inhibitor of apoptosis (IAP) gene family, which has been implicated in both preservation of cell viability and regulation of mitosis in cancer cells. Here, we show that HeLa cells microinjected with a polyclonal antibody to survivin exhibited delayed progression in prometaphase (31.5 +/- 6.9 min) and metaphase (126.8 +/- 73.8 min), as compared with control injected cells (prometaphase, 21.5 +/- 3.3 min; metaphase, 18.9 +/- 4.5 min; P mitotic spindles severely depleted of microtubules and occasionally underwent apoptosis without exiting the mitotic block or thereafter. Forced expression of survivin in HeLa cells profoundly influenced microtubule dynamics with reduction of pole-to-pole distance at metaphase (8.57 +/- 0.21 microm versus 10.58 +/- 0.19 microm; P microtubules against nocodazole-induced depolymerization in vivo. These data demonstrate that survivin functions at cell division to control microtubule stability and assembly of a normal mitotic spindle. This pathway may facilitate checkpoint evasion and promote resistance to chemotherapy in cancer.

  7. 48 CFR 852.236-78 - Government supervision.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Government supervision. 852.236-78 Section 852.236-78 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... Government supervision. As prescribed in 836.572, insert the following clause: Government Supervision...

  8. Rules for Supervision and Inspection of Offshore Oil Industry

    Institute of Scientific and Technical Information of China (English)

    Dai Zhongliang; Song Lisong

    1994-01-01

    @@ In short,safety supervision and technique inspection mean the safety supervision by the government,and the inspection by technical organization,and those are put into practice by a series of administrative rules and regulations.

  9. Challenges for Better thesis supervision.

    Science.gov (United States)

    Ghadirian, Laleh; Sayarifard, Azadeh; Majdzadeh, Reza; Rajabi, Fatemeh; Yunesian, Masoud

    2014-01-01

    Conduction of thesis by the students is one of their major academic activities. Thesis quality and acquired experiences are highly dependent on the supervision. Our study is aimed at identifing the challenges in thesis supervision from both students and faculty members point of view. This study was conducted using individual in-depth interviews and Focus Group Discussions (FGD). The participants were 43 students and faculty members selected by purposive sampling. It was carried out in Tehran University of Medical Sciences in 2012. Data analysis was done concurrently with data gathering using content analysis method. Our data analysis resulted in 162 codes, 17 subcategories and 4 major categories, "supervisory knowledge and skills", "atmosphere", "bylaws and regulations relating to supervision" and "monitoring and evaluation". This study showed that more attention and planning in needed for modifying related rules and regulations, qualitative and quantitative improvement in mentorship training, research atmosphere improvement and effective monitoring and evaluation in supervisory area.

  10. REGULATION AND SUPERVISION SHADOW BANKING INSTITUTIONS WHICH IS POTENTIALLY GIVES SYSTEMIC RISK AS AN EFFORT TO GIVE LAW PROTECTION TO CONSUMERS (Study in Banyumas Ex-Residency

    Directory of Open Access Journals (Sweden)

    Sulistyandari

    2016-01-01

    Full Text Available Shadow banking practice there is a tendency to increase, then the regulator should be set. Some cases have led to financial stability system disorders and cause systemic risk. This study aims to reveal weaknesses in the regulation and implementation of shadow banking institutions that have the potential for systemic risk and the protection of customers both normative and implementation in the Ex-residency of Banyumas. This study is a qualitative study with normative juridical approach and the study of law as the law in action, a social science studies that non-doctrinal and empirical. The results showed that the implementation of the supervision of shadow banking in the former residency of Banyumas potential harm to customers primarily in LJKNB shaped KSP / KJKS that provide services to non members, LJKNB who misuse their permissions business activities, LJKNB that has not been incorporated, but no potential systemic. Factors law, law enforcement, facilities, people and culture affect the implementation of surveillance in the area of Ex-residency of Banyumas.

  11. 36 CFR 25.3 - Supervision; suspensions.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Supervision; suspensions. 25.3 Section 25.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL MILITARY PARKS; LICENSED GUIDE SERVICE REGULATIONS § 25.3 Supervision; suspensions. (a) The...

  12. 77 FR 19287 - Federal Acquisition Regulation; Submission for OMB Review; Progress Payments (SF-1443)

    Science.gov (United States)

    2012-03-30

    ... Register at 76 FR 81942, on December 29, 2011. No comments were received. Public comments are particularly... Regulation; Submission for OMB Review; Progress Payments (SF-1443) AGENCY: Department of Defense...

  13. Bone marrow myeloid cells in regulation of multiple myeloma progression.

    Science.gov (United States)

    Herlihy, Sarah E; Lin, Cindy; Nefedova, Yulia

    2017-08-01

    Survival, growth, and response to chemotherapy of cancer cells depends strongly on the interaction of cancer cells with the tumor microenvironment. In multiple myeloma, a cancer of plasma cells that localizes preferentially in the bone marrow, the microenvironment is highly enriched with myeloid cells. The majority of myeloid cells are represented by mature and immature neutrophils. The contribution of the different myeloid cell populations to tumor progression and chemoresistance in multiple myeloma is discussed.

  14. Regulation of prostate cancer progression by the tumor microenvironment.

    Science.gov (United States)

    Shiao, Stephen L; Chu, Gina Chia-Yi; Chung, Leland W K

    2016-09-28

    Prostate cancer remains the most frequently diagnosed cancer in men in North America, and despite recent advances in treatment patients with metastatic disease continue to have poor five-year survival rates. Recent studies in prostate cancer have revealed the critical role of the tumor microenvironment in the initiation and progression to advanced disease. Experimental data have uncovered a reciprocal relationship between the cells in the microenvironment and malignant tumor cells in which early changes in normal tissue microenvironment can promote tumorigenesis and in turn tumor cells can promote further pro-tumor changes in the microenvironment. In the tumor microenvironment, the presence of persistent immune infiltrates contributes to the recruitment and reprogramming of other non-immune stromal cells including cancer-associated fibroblasts and a unique recently identified population of metastasis-initiating cells (MICs). These MICs, which can also be found as part of the circulating tumor cell (CTC) population in PC patients, promote cancer cell transformation, enhance metastatic potential and confer therapeutic resistance. MICs act can on other cells within the tumor microenvironment in part by secreting exosomes that reprogram adjacent stromal cells to create a more favorable tumor microenvironment to support continued cancer growth and progression. We review here the current data on the intricate relationship between inflammation, reactive stroma, tumor cells and disease progression in prostate cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. The Role of pH Regulation in Cancer Progression.

    Science.gov (United States)

    McIntyre, Alan; Harris, Adrian L

    Frequently observed phenotypes of tumours include high metabolic activity, hypoxia and poor perfusion; these act to produce an acidic microenvironment. Cellular function depends on pH homoeostasis, and thus, tumours become dependent on pH regulatory mechanisms. Many of the proteins involved in pH regulation are highly expressed in tumours, and their expression is often of prognostic significance. The more acidic tumour microenvironment also has important implications with regard to chemotherapeutic and radiotherapeutic interventions. In addition, we review pH-sensing mechanisms, the role of pH regulation in tumour phenotype and the use of pH regulatory mechanisms as therapeutic targets.

  16. 7 CFR 1944.665 - Supervision and inspection of work.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Supervision and inspection of work. 1944.665 Section 1944.665 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE... Supervision and inspection of work. Grantees are responsible for supervising all rehabilitation and...

  17. NFIX as a Master Regulator for Lung Cancer Progression

    Directory of Open Access Journals (Sweden)

    Nor I. A. Rahman

    2017-08-01

    Full Text Available About 40% of lung cancer cases globally are diagnosed at the advanced stage. Lung cancer has a high mortality and overall survival in stage I disease is only 70%. This study was aimed at finding a candidate of transcription regulator that initiates the mechanism for metastasis by integrating computational and functional studies. The genes involved in lung cancer were retrieved using in silico software. 10 kb promoter sequences upstream were scanned for the master regulator. Transient transfection of shRNA NFIXs were conducted against A549 and NCI-H1299 cell lines. qRT-PCR and functional assays for cell proliferation, migration and invasion were carried out to validate the involvement of NFIX in metastasis. Genome-wide gene expression microarray using a HumanHT-12v4.0 Expression BeadChip Kit was performed to identify differentially expressed genes and construct a new regulatory network. The in silico analysis identified NFIX as a master regulator and is strongly associated with 17 genes involved in the migration and invasion pathways including IL6ST, TIMP1 and ITGB1. Silencing of NFIX showed reduced expression of IL6ST, TIMP1 and ITGB1 as well as the cellular proliferation, migration and invasion processes. The data was integrated with the in silico analyses to find the differentially expressed genes. Microarray analysis showed that 18 genes were expressed differentially in both cell lines after statistical analyses integration between t-test, LIMMA and ANOVA with Benjamini-Hochberg adjustment at p-value < 0.05. A transcriptional regulatory network was created using all 18 genes, the existing regulated genes including the new genes PTCH1, NFAT5 and GGCX that were found highly associated with NFIX, the master regulator of metastasis. This study suggests that NFIX is a promising target for therapeutic intervention that is expected to inhibit metastatic recurrence and improve survival rate.

  18. 对特殊监管区域出入境检验检疫监管规定的分析与探讨%Analysis and probing of special supervision district entry-exit inspection and quarantme supervision regulation

    Institute of Scientific and Technical Information of China (English)

    李文青; 刘宏波; 阎青

    2012-01-01

    Due to the General Administration of Quality Supervision for special areas’ supervision is according to the old and single fact,which is not match with its development status.And current Entry and Exit Inspection and Quarantine are found,which can’t satisfy the inspection of special supervision areas’ need.In this situation,the Quality Administration issued the"On the Supervision and Management of Special Inspection and Quarantine Area(drafts)",to seek the advice from the internals of Inspection and Quarantine.By careful analysis the Inspection and Quarantine agencies’ historic evolution and advantages and disadvantages of custom clearance management,the author puts forward some ideas and opinions;hopes these ideas can help the inspection work keep pace with The Times,and more in line with the actual business needs.%由于出入境检验检疫机构对海关特殊监管区域进行监管的依据陈旧单一,与特殊监管区域的发展现状并不匹配,并且已经越来越不能满足特殊监管区域监管工作的实际需要。在上述情况下,质检总局下发了《关于对〈特殊监管区域检验检疫监督管理办法〉(征求意见稿)征求意见的函》,向检验检疫系统内征求对该办法的修改意见和建议。笔者通过认真分析检验检疫机构对特殊监管区域监督管理方面的历史沿革和利弊,提出了自己的一些见解和观点,希望能够对该办法的修订有所帮助并使检验检疫机构对特殊监管区域的监管工作能做到与时俱进,更加符合实际的业务需求。

  19. Supervision as Metaphor

    Science.gov (United States)

    Lee, Alison; Green, Bill

    2009-01-01

    This article takes up the question of the language within which discussion of research degree supervision is couched and framed, and the consequences of such framings for supervision as a field of pedagogical practice. It examines the proliferation and intensity of metaphor, allegory and allusion in the language of candidature and supervision,…

  20. A Supervision of Solidarity

    Science.gov (United States)

    Reynolds, Vikki

    2010-01-01

    This article illustrates an approach to therapeutic supervision informed by a philosophy of solidarity and social justice activism. Called a "Supervision of Solidarity", this approach addresses the particular challenges in the supervision of therapists who work alongside clients who are subjected to social injustice and extreme marginalization. It…

  1. PHD2: from hypoxia regulation to disease progression.

    Science.gov (United States)

    Meneses, Ana M; Wielockx, Ben

    2016-01-01

    Oxygen represents one of the major molecules required for the development and maintenance of life. An adequate response to hypoxia is therefore required for the functioning of the majority of living organisms and relies on the activation of the hypoxia-inducible factor (HIF) pathway. HIF prolyl hydroxylase domain-2 (PHD2) has long been recognized as the major regulator of this response, controlling a myriad of outcomes that range from cell death to proliferation. However, this enzyme has been associated with more pathways, making the role of this protein remarkably complex under distinct pathologies. While a protective role seems to exist in physiological conditions such as erythropoiesis; the picture is more complex during pathologies such as cancer. Since the regulation of this enzyme and its closest family members is currently considered as a possible therapy for various diseases, understanding the different particular roles of this protein is essential.

  2. Regulation of replication fork progression through histone supply and demand

    DEFF Research Database (Denmark)

    Groth, Anja; Corpet, Armelle; Cook, Adam J L

    2007-01-01

    DNA replication in eukaryotes requires nucleosome disruption ahead of the replication fork and reassembly behind. An unresolved issue concerns how histone dynamics are coordinated with fork progression to maintain chromosomal stability. Here, we characterize a complex in which the human histone...... chaperone Asf1 and MCM2-7, the putative replicative helicase, are connected through a histone H3-H4 bridge. Depletion of Asf1 by RNA interference impedes DNA unwinding at replication sites, and similar defects arise from overproduction of new histone H3-H4 that compromises Asf1 function. These data link Asf......1 chaperone function, histone supply, and replicative unwinding of DNA in chromatin. We propose that Asf1, as a histone acceptor and donor, handles parental and new histones at the replication fork via an Asf1-(H3-H4)-MCM2-7 intermediate and thus provides a means to fine-tune replication fork...

  3. MUC1 Regulates PDGFA Expression During Pancreatic Cancer Progression

    Science.gov (United States)

    Sahraei, Mahnaz; Roy, Lopamudra Das; Curry, Jennifer M; Teresa, Tinder L; Nath, Sritama; Besmer, Dahlia; Kidiyoor, Amritha; Dalia, Ritu; Gendler, Sandra J; Mukherjee, Pinku

    2012-01-01

    Pancreatic Ductal Adenocarcinoma (PDA) has one of the worst prognoses of all cancers. Mucin 1 (MUC1), a transmembrane mucin glycoprotein, is a key modulator of several signaling pathways that affect oncogenesis, motility, and metastasis. Its expression is known to be associated with poor prognosis in patients. However, the precise mechanism remains elusive. We report a novel association of MUC1 with Platelet-Derived Growth Factor-A (PDGFA). PDGFA is one of the many drivers of tumor growth, angiogenesis, and metastasis in PDA. Using mouse PDA models as well as human samples, we show clear evidence that MUC1 regulates the expression and secretion of PDGFA. This, in turn, influences proliferation and invasion of pancreatic cancer cells leading to higher tumor burden in vivo. In addition, we reveal that MUC1 over expressing cells are heavily dependent on PDGFA both for proliferation and invasion while MUC1-null cells are not. Moreover, PDGFA and MUC1 are critical for translocation of βcatenin to the nucleus for oncogenesis to ensue. Finally, we elucidate the underlying mechanism by which MUC1 regulates PDGFA expression and secretion in pancreatic cancer cells. We show that MUC1 associates with Hif1-α, a known transcription factor involved in controlling PDGFA expression. Furthermore, MUC1 facilitates Hif1-α translocation to the nucleus. In summary, we have demonstrated that MUC1-induced invasion and proliferation occurs via increased exogenous production of PDGFA. Thus, impeding MUC1 regulation of PDGFA signaling may be therapeutically beneficial for patients with PDA. PMID:22266848

  4. Good supervision and PBL

    DEFF Research Database (Denmark)

    Otrel-Cass, Kathrin

    This field study was conducted at the Faculty of Social Sciences at Aalborg University with the intention to investigate how students reflect on their experiences with supervision in a PBL environment. The overall aim of this study was to inform about the continued work in strengthening supervision...... at this faculty. This particular study invited Master level students to discuss: • How a typical supervision process proceeds • How they experienced and what they expected of PBL in the supervision process • What makes a good supervision process...

  5. Smooth muscle FGF/TGFβ cross talk regulates atherosclerosis progression.

    Science.gov (United States)

    Chen, Pei-Yu; Qin, Lingfeng; Li, Guangxin; Tellides, George; Simons, Michael

    2016-07-01

    The conversion of vascular smooth muscle cells (SMCs) from contractile to proliferative phenotype is thought to play an important role in atherosclerosis. However, the contribution of this process to plaque growth has never been fully defined. In this study, we show that activation of SMC TGFβ signaling, achieved by suppression of SMC fibroblast growth factor (FGF) signaling input, induces their conversion to a contractile phenotype and dramatically reduces atherosclerotic plaque size. The FGF/TGFβ signaling cross talk was observed in vitro and in vivo In vitro, inhibition of FGF signaling increased TGFβ activity, thereby promoting smooth muscle differentiation and decreasing proliferation. In vivo, smooth muscle-specific knockout of an FGF receptor adaptor Frs2α led to a profound inhibition of atherosclerotic plaque growth when these animals were crossed on Apoe(-/-) background and subjected to a high-fat diet. In particular, there was a significant reduction in plaque cellularity, increase in fibrous cap area, and decrease in necrotic core size. In agreement with these findings, examination of human coronary arteries with various degrees of atherosclerosis revealed a strong correlation between the activation of FGF signaling, loss of TGFβ activity, and increased disease severity. These results identify SMC FGF/TGFβ signaling cross talk as an important regulator of SMC phenotype switch and document a major contribution of medial SMC proliferation to atherosclerotic plaque growth.

  6. Discovery of a Splicing Regulator Required for Cell Cycle Progression

    Energy Technology Data Exchange (ETDEWEB)

    Suvorova, Elena S.; Croken, Matthew; Kratzer, Stella; Ting, Li-Min; Conde de Felipe, Magnolia; Balu, Bharath; Markillie, Lye Meng; Weiss, Louis M.; Kim, Kami; White, Michael W.

    2013-02-01

    In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.

  7. Organisation of the state supervision and regulation of storage facilities for low- and intermediate level radioactive waste in the Northwest region of Russia

    Energy Technology Data Exchange (ETDEWEB)

    Novikov, Sergey

    1999-07-01

    The North-European Interregional Territorial District of Gosatomnadzor of Russia was established in 1992. It supervises the fulfilment of the legislative requirements of the Russian Federation on nuclear and radiation safety in production, management and use of nuclear energy, and nuclear materials and radioactive substances. Among the subjects supervised are four nuclear power plants operating RBMK type of reactors. Gosatomnazdor also issues licences for working with radioactive materials. This presentation discusses some of the issues in waste treatment and management in the District.

  8. NPAT expression is regulated by E2F and is essential for cell cycle progression

    DEFF Research Database (Denmark)

    Gao, Guang; Bracken, Adrian P; Burkard, Karina

    2003-01-01

    NPAT is an in vivo substrate of cyclin E-Cdk2 kinase and is thought to play a critical role in coordinated transcriptional activation of histone genes during the G(1)/S-phase transition and in S-phase entry in mammalian cells. Here we show that NPAT transcription is up-regulated at the G(1)/S...... by small interfering RNA duplexes impedes cell cycle progression and histone gene expression in tissue culture cells. Thus, NPAT is an important E2F target that is required for cell cycle progression in mammalian cells. As NPAT is involved in the regulation of S-phase-specific histone gene transcription...

  9. Beyond an oncogene, Lin28 is a master regulator of cancer progression.

    Science.gov (United States)

    Wang, Xuefei; Weng, Mingjiao; Jin, Yinji; Yang, Weiwei; Wang, Xin; Wu, Di; Wang, Tianzhen; Li, Xiaobo

    2017-07-26

    The RNA binding protein Lin28 is increased in most human malignancies, and elevated Lin28 is a biomarker for poor prognosis and contributes to cancer progression. Lin28 functions as a master oncogene and is involved in almost all hallmarks of cancer. In this review, we summarize the aberrant molecular expression mechanisms and pathological roles of Lin28 in cancer progression. Moreover, we elaborate on the established molecular mechanisms, from the transcriptional level to the post-transcriptional and translational levels, by which Lin28 regulates cancer progression.

  10. Integrated Financial Supervision: Experiences in Selected Countries

    OpenAIRE

    Edgardo Demaestri; Diego Sourrouille

    2003-01-01

    This paper represents one of the first comparative analyses of experiences of integrated supervision. It discusses how several countries around the world have developed the processes of integrating financial regulation and supervision, and covers numerous relevant technical issues as well as the policy options. It describes the scope of the activities, institutions, responsibilities, and regulatory powers that integrated supervisors are expected to cover. Issues related to the organizational ...

  11. 互联网众筹融资监管法律规制%Supervision Regulations on Crowdfunding on the Internet

    Institute of Scientific and Technical Information of China (English)

    张亚珊

    2016-01-01

    Crowdfunding, as a new financing model, mainly relies on the Internet with the rapid development on a global scale in recent years. In the environment of Chinese Internet + era crowdfunding, the new rules of the US SEC crowdfunding are to be understood. Its remaining subject qualification is uncertain, and its moral hazard involves some issues: legal risks, lack of supporting legal environment and other issues. Combined with the developing situation of Chinese crowdfunding mentioned above, this paper puts forward a sound legislative system framework of the legal framework, establishes and improves the management and supervision mechanism, improves the information disclosure system, the establishment of the amount of funding cap system, the establishment funders protection mechanism, and the recommendation of social credit system construction. Comprehensive legal regulations on crowdfunding promotes sustainable healthy development of China's Internet crowdfunding.%众筹作为一种融资新模式,众筹平台主要以互联网为依托,近年来在全球范围内发展迅速。在中国互联网+时代众筹的大环境下,对美国的SEC众筹新规进行了解,结合中国众筹发展现状,存在主体资格的不确定,众筹平台本身存在道德风险涉及法律风险,众筹融资缺乏配套的法律环境等问题,提出完善立法体系构架法律框架,建立完善的管理和监督机制,完善信息披露制度,设立筹资金额上限制度,建立出资者保护机制,完善社会信用体系建设的建议,对众筹融资进行全面的法律规制,推动中国互联网众筹的可持续良性发展。

  12. [Regulation of terpene metabolism]. Annual progress report, March 15, 1988--March 14, 1989

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1989-12-31

    Progress in understanding of the metabolism of monoterpenes by peppermint and spearmint is recorded including the actions of two key enzymes, geranyl pyrophosphate:limonene cyclase and a UDP-glucose dependent glucosyl transferase; concerning the ultrastructure of oil gland senescence; enzyme subcellular localization; regulation of metabolism; and tissue culture systems.

  13. Developmental Regulation with Progressive Vision Loss: Use of Control Strategies and Affective Well-Being

    Science.gov (United States)

    Schilling, Oliver K.; Wahl, Hans-Werner; Boerner, Kathrin; Horowitz, Amy; Reinhardt, Joann P.; Cimarolli, Verena R.; Brennan-Ing, Mark; Heckhausen, Jutta

    2016-01-01

    The present study addresses older adults' developmental regulation when faced with progressive and irreversible vision loss. We used the motivational theory of life span development as a conceptual framework and examined changes in older adults' striving for control over everyday goal achievement, and their association with affective well-being,…

  14. Rho proteins − the key regulators of cytoskeleton in the progression of mitosis and cytokinesis

    Directory of Open Access Journals (Sweden)

    Anna Klimaszewska

    2011-11-01

    Full Text Available The Rho proteins are members of the Ras superfamily of small GTPases. They are thought to be crucial regulators of multiple signal transduction pathways that influence a wide range of cellular functions, including migration, membrane trafficking, adhesion, polarity and cell shape changes. Thanks to their ability to control the assembly and organization of the actin and microtubule cytoskeletons, Rho GTPases are known to regulate mitosis and cytokinesis progression. These proteins are required for formation and rigidity of the cortex during mitotic cell rounding, mitotic spindle formation and attachment of the spindle microtubules to the kinetochore. In addition, during cytokinesis, they are involved in promoting division plane determination, contractile ring and cleavage furrow formation and abscission. They are also known as regulators of cell cycle progression at the G1/S and G2/M transition. Thus, the signal transduction pathways in which Rho proteins participate, appear to connect dynamics of actin and microtubule cytoskeletons to cell cycle progression. We review the current state of knowledge concerning the molecular mechanisms by which Rho GTPase signaling regulates remodeling of actin and microtubule cytoskeletons in order to control cell division progression.

  15. Social Possible Selves, Self-Regulation, and Social Goal Progress in Older Adulthood

    Science.gov (United States)

    Ko, Han-Jung; Mejía, Shannon; Hooker, Karen

    2014-01-01

    Lifespan development involves setting and pursuing self-guided goals. This study examines how in the social domain, possible selves, a future-oriented self-concept, and self-regulation, including self-regulatory beliefs and intraindividual variability in self-regulatory behavior, relate to differences in overall daily social goal progress. An…

  16. 依法规范和监督县级党委权力的行使%On the Regulation and Supervision of the Power Exercising of County Party Committee According to the Law

    Institute of Scientific and Technical Information of China (English)

    张红

    2011-01-01

    县委及县委书记权力过于集中,监督乏力,并无限扩张、滥用,"县委书记腐败现象"折射出县级党政权责错位。改变这一现象,需要完善县权改革,界定党政权责,强化党内外监督和法律监督,改革现有监督体制,规范县党委依法正确行使权力。%The power of County Party Committee or secretary of CPC is too concentrative and lacks of good supervision, which causes its unlimited extension and abuse. The Corruption of secretary of CPC reflects the misplacement in rights and responsibilities of CPC. To improve it, we need to perfect the reformation of county power, define the rights and responsibilities of the County Party Committee, strengthen the supervision of Party inside and outside and of law, reform the current supervision system and regulate the power exercising of CPC according to the law.

  17. Networks of Professional Supervision

    Science.gov (United States)

    Annan, Jean; Ryba, Ken

    2013-01-01

    An ecological analysis of the supervisory activity of 31 New Zealand school psychologists examined simultaneously the theories of school psychology, supervision practices, and the contextual qualities that mediated participants' supervisory actions. The findings indicated that the school psychologists worked to achieve the supervision goals of…

  18. Forskellighed i supervision

    DEFF Research Database (Denmark)

    Petersen, Birgitte; Beck, Emma

    2009-01-01

    Indtryk og tendenser fra den anden danske konference om supervision, som blev holdt på Københavns Universitet i oktober 2008......Indtryk og tendenser fra den anden danske konference om supervision, som blev holdt på Københavns Universitet i oktober 2008...

  19. Experiments in Virtual Supervision.

    Science.gov (United States)

    Walker, Rob

    This paper examines the use of First Class conferencing software to create a virtual culture among research students and as a vehicle for supervision and advising. Topics discussed include: computer-mediated communication and research; entry to cyberculture, i.e., research students' induction into the research community; supervision and the…

  20. História, regulação e poder disciplinar no campo da supervisão escolar History, regulation and disciplinary power in the school supervision field

    Directory of Open Access Journals (Sweden)

    Adriana Bergold Leal

    2010-08-01

    Full Text Available Este artigo tem como tema a supervisão escolar, sendo ela questionada por ângulos diferentes daqueles recorrentemente anunciados nas bibliografias específicas e até então raramente colocados sob suspeita. Como resultado das análises, problematiza a história da supervisão como uma narração linear que continua regulando o trabalho docente, mesmo negando essa função. Entendendo a regulação como uma forma de conduzir a ação docente, aproxima desta o conceito de poder disciplinar e os instrumentos de que, segundo Michel Foucault, esse poder faz uso para agir sobre os sujeitos: a vigilância hierárquica, a sanção normalizadora e o exame. Ressalta ainda a produtividade do fazer docente como justificativa da regulação provocada pela função supervisora. Interrompendo o curso natural da história da supervisão, é possível perceber que, embora pertencendo a ordens discursivas diferentes, as fases históricas narradas atendem à mesma estratégia de ação reguladora e ao mesmo solo epistêmico.The presented article is about School Supervision, which is questioned by different angles from those announced again and again in specific bibliographies and until now rarely having been put under suspicion. As a result of the analysis, we problematize the history of supervision as a linear narrative that continues regulating the work of teaching, even denying this function. Regulation being understood as a way of conducting the act of teaching approximates, from this act of teaching, the concept of disciplinary power and the instruments which, according to Michel Foucault, are used by this power to act upon the individuals: hierarchical vigilance, normalizing sanction and exam. This study also emphasizes the productivity of teaching as a justification for the regulation provoked by the supervising function. When the natural course of supervision history is interrupted, it is possible for us to see that the historical phases narrated, even

  1. Supervision som undervisningsform i voksenspecialundervisningen

    DEFF Research Database (Denmark)

    Kristensen, René

    2000-01-01

    Supervision som undervisningsform i voksenspecialundervisningen. Procesarbejde i undervisning af voksne.......Supervision som undervisningsform i voksenspecialundervisningen. Procesarbejde i undervisning af voksne....

  2. Assembly and interrogation of Alzheimer's disease genetic networks reveal novel regulators of progression.

    Directory of Open Access Journals (Sweden)

    Soline Aubry

    Full Text Available Alzheimer's disease (AD is a complex multifactorial disorder with poorly characterized pathogenesis. Our understanding of this disease would thus benefit from an approach that addresses this complexity by elucidating the regulatory networks that are dysregulated in the neural compartment of AD patients, across distinct brain regions. Here, we use a Systems Biology (SB approach, which has been highly successful in the dissection of cancer related phenotypes, to reverse engineer the transcriptional regulation layer of human neuronal cells and interrogate it to infer candidate Master Regulators (MRs responsible for disease progression. Analysis of gene expression profiles from laser-captured neurons from AD and controls subjects, using the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe, yielded an interactome consisting of 488,353 transcription-factor/target interactions. Interrogation of this interactome, using the Master Regulator INference algorithm (MARINa, identified an unbiased set of candidate MRs causally responsible for regulating the transcriptional signature of AD progression. Experimental assays in autopsy-derived human brain tissue showed that three of the top candidate MRs (YY1, p300 and ZMYM3 are indeed biochemically and histopathologically dysregulated in AD brains compared to controls. Our results additionally implicate p53 and loss of acetylation homeostasis in the neurodegenerative process. This study suggests that an integrative, SB approach can be applied to AD and other neurodegenerative diseases, and provide significant novel insight on the disease progression.

  3. Several Thoughts on the Institutional Structure of Regulation and Supervision of Quasi-Financial Institutions%关于准金融机构监管体制的若干思考

    Institute of Scientific and Technical Information of China (English)

    俞燕

    2014-01-01

    Quasi-financial institutions engaged in business financing are regulated and supervised by departments of gov-ernment rather than financial regulatory authorities.As a useful supplement of the formal system, they have a huge space for development.A discussion on the institutional structure of regulation and supervision of these institutions reveals that the struc-ture is flawed with some problems, and the key issue is the allocation of regulatory power.This paper addresses the issue from two dimensions, the vertical and horizontal allocation of the regulatory power.It suggests that the local governments should be given total regulatory power, and the provincial governments should establish a single regulatory agency to supervise all types of quasi-financial institutions to improve the institutional structure and achieve effective regulation and supervision of the quasi-fi-nancial institutions.%我国现对准金融机构采取“多头分层”监管模式,但是,监管主体缺乏专业性且监管力量不足、监管主体不独立、监管权配置不充分等问题突出。准金融机构监管体制的核心问题是监管权的配置。监管权的纵向配置涉及中央和地方之间的关系。监管权的横向配置涉及监管主体的选择。本文建议将准金融机构监管权下放至地方政府,由省级政府成立具有独立性的地方金融监管机构实施统一监管,以完善准金融机构监管体制,实现有效监管。

  4. Research progress of photoperiod regulated genes on flowering time in rice.

    Science.gov (United States)

    Deyan, Kong; Shoujun, Chen; Liguo, Zhou; Huan, Gao; Lijun, Luo; Zaochang, Liu

    2016-06-20

    Rice flowering regulation is an extremely complex process, which is controlled by genetic factors and external environment. Photoperiodic regulatory pathway is pivotal to control flowering in rice, in which florigen genes Hd3a and RTF1 are at the core and they are regulated by upstream Hd1-dependent, Ehd1-dependent, as well as both Hd1- and Ehd1-independent pathways. The three pathways bring a variety of light signal information together to Hd3a and RTF1 for further integration, and then transmit the signals in the form of florigen to the downstream flowering related genes. In this review, we summarize the research progress of photoperiod regulated genes on flowering time in rice, including the photoreceptors and circadian rhythm genes, the florigens, its upstream, downstream and interacting genes. We hope to provide a reference for in-depth study of rice flowering regulation.

  5. Autophagy regulated by miRNAs in colorectal cancer progression and resistance

    Directory of Open Access Journals (Sweden)

    Andrew Fesler

    2017-01-01

    Full Text Available The catabolic process of autophagy is an essential cellular function that allows for the breakdown and recycling of cellular macromolecules. In recent years, the impact of epigenetic regulation of autophagy by noncoding miRNAs has been recognized in human cancer. In colorectal cancer, autophagy plays critical roles in cancer progression as well as resistance to chemotherapy, and recent evidence demonstrates that miRNAs are directly involved in mediating these functions. In this review, we focus on the recent advancements in the field of miRNA regulation of autophagy in colorectal cancer.

  6. CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients

    DEFF Research Database (Denmark)

    Fløyel, Tina; Brorsson, Caroline; Nielsen, Lotte B;

    2014-01-01

    (CTSH) affects disease mechanisms and progression in T1D. The T allele of rs3825932 was associated with lower CTSH expression in human lymphoblastoid cell lines and pancreatic tissue. Proinflammatory cytokines decreased the expression of CTSH in human islets and primary rat β-cells, and overexpression...... of CTSH protected insulin-secreting cells against cytokine-induced apoptosis. Mechanistic studies indicated that CTSH exerts its antiapoptotic effects through decreased JNK and p38 signaling and reduced expression of the proapoptotic factors Bim, DP5, and c-Myc. CTSH overexpression also up-regulated Ins2...... the experimental and clinical data. In line with these observations, healthy human subjects carrying the T allele have lower β-cell function, which was evaluated by glucose tolerance testing. The data provide strong evidence that CTSH is an important regulator of β-cell function during progression of T1D...

  7. SON controls cell-cycle progression by coordinated regulation of RNA splicing.

    Science.gov (United States)

    Ahn, Eun-Young; DeKelver, Russell C; Lo, Miao-Chia; Nguyen, Tuyet Ann; Matsuura, Shinobu; Boyapati, Anita; Pandit, Shatakshi; Fu, Xiang-Dong; Zhang, Dong-Er

    2011-04-22

    It has been suspected that cell-cycle progression might be functionally coupled with RNA processing. However, little is known about the role of the precise splicing control in cell-cycle progression. Here, we report that SON, a large Ser/Arg (SR)-related protein, is a splicing cofactor contributing to efficient splicing of cell-cycle regulators. Downregulation of SON leads to severe impairment of spindle pole separation, microtubule dynamics, and genome integrity. These molecular defects result from inadequate RNA splicing of a specific set of cell-cycle-related genes that possess weak splice sites. Furthermore, we show that SON facilitates the interaction of SR proteins with RNA polymerase II and other key spliceosome components, suggesting its function in efficient cotranscriptional RNA processing. These results reveal a mechanism for controlling cell-cycle progression through SON-dependent constitutive splicing at suboptimal splice sites, with strong implications for its role in cancer and other human diseases.

  8. Clinical Supervision in Denmark

    DEFF Research Database (Denmark)

    Jacobsen, Claus Haugaard

    Data fra den danske undersøgelse af psykoterapeuters faglige udvikling indsamlet ved hjælp af DPCCQ. Oplægget fokuserer på supervision (modtaget, givet, uddannelse i) blandt danske psykoterapeutiske arbejdende psykologer....

  9. Supervision af psykoterapi

    DEFF Research Database (Denmark)

    SUPERVISION AF PSYKOTERAPI indtager en central position i uddannelsen og udviklingen af psykoterapeuter. Trods flere lighedspunkter med psykoterapi, undervisning og konsultation er psykoterapisupervision et selvstændigt virksomhedsområde. Supervisor må foruden at være en trænet psykoterapeut kende...... supervisionens rammer og indplacering i forhold til organisation og samfund. En række kapitler drejer sig om supervisors opgaver, roller og kontrolfunktion, supervision set fra supervisandens perspektiv samt betragtninger over relationer og processer i supervision. Der drøftes fordele og ulemper ved de...... forskellige måder, hvorpå en sag kan fremlægges. Bogens første del afsluttes med refleksioner over de etiske aspekter ved psykoterapisupervision. Bogens anden del handler om de særlige forhold, der gør sig gældende ved supervision af en række specialiserede behandlingsformer eller af psykoterapi med bestemte...

  10. Psykoterapi og supervision

    DEFF Research Database (Denmark)

    Jacobsen, Claus Haugaard

    2014-01-01

    Kapitlet beskriver supervisionen funktioner i forhold til psykoterapi. Supervision af psykoterapi henviser i almindelighed til, at en psykoterapeut konsulterer en ofte mere erfaren kollega (supervisor) med henblik på drøftelse af et konkret igangværende psykoterapeutisk behandlingsforløb. Formålet...... er at fremme denne fagpersons (psykoterapeutens) faglige udvikling samt sikre kvaliteten af behandlingen.kan defineres som i. Der redegøres for, hvorfor supervision er vigtig del af psykoterapeutens profession samt vises, hvorledes supervision foruden den faglige udvikling også er vigtigt redskab i...... psykoterapiens kvalitetssikring. Efter at have drøftet nogle etiske forhold ved supervision, fremlægges endelig nogle få forskningsresultater vedr. psykoterapisupervision af danske psykologer....

  11. Supervision and group dynamics

    DEFF Research Database (Denmark)

    Hansen, Søren; Jensen, Lars Peter

    2004-01-01

    as well as at Aalborg University. The first visible result has been participating supervisors telling us that the course has inspired them to try supervising group dynamics in the future. This paper will explore some aspects of supervising group dynamics as well as, how to develop the Aalborg model...... An important aspect of the problem based and project organized study at Aalborg University is the supervision of the project groups. At the basic education (first year) it is stated in the curriculum that part of the supervisors' job is to deal with group dynamics. This is due to the experience...... that many students are having difficulties with practical issues such as collaboration, communication, and project management. Most supervisors either ignore this demand, because they do not find it important or they find it frustrating, because they do not know, how to supervise group dynamics...

  12. Regulation network analysis of testicular seminoma at various stages of progression.

    Science.gov (United States)

    Sha, J-J; Dong, Y-H; Liu, D-M; Bo, J-J; Huang, Y-R; Li, Z; Ping, P

    2013-03-11

    Testicular seminoma has become the most common solid malignancy in young men, especially in the 20s group. We obtained the gene expression profile of human testicular seminoma cells from NCBI, identified the differentially expressed genes of testicular seminoma cells of different stages, and constructed the regulation networks of different stages of testicular seminoma using bioinformatics methodology. Forty differentially expressed genes of testicular seminoma cells of different stages were identified. These genes and pathways are apparently involved in the progression of testicular seminoma.

  13. LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice.

    Science.gov (United States)

    Kim, Jeesun; Singh, Anup Kumar; Takata, Yoko; Lin, Kevin; Shen, Jianjun; Lu, Yue; Kerenyi, Marc A; Orkin, Stuart H; Chen, Taiping

    2015-12-02

    Mammalian oocytes are arrested at prophase I until puberty when hormonal signals induce the resumption of meiosis I and progression to meiosis II. Meiotic progression is controlled by CDK1 activity and is accompanied by dynamic epigenetic changes. Although the signalling pathways regulating CDK1 activity are well defined, the functional significance of epigenetic changes remains largely unknown. Here we show that LSD1, a lysine demethylase, regulates histone H3 lysine 4 di-methylation (H3K4me2) in mouse oocytes and is essential for meiotic progression. Conditional deletion of Lsd1 in growing oocytes results in precocious resumption of meiosis and spindle and chromosomal abnormalities. Consequently, most Lsd1-null oocytes fail to complete meiosis I and undergo apoptosis. Mechanistically, upregulation of CDC25B, a phosphatase that activates CDK1, is responsible for precocious meiotic resumption and also contributes to subsequent spindle and chromosomal defects. Our findings uncover a functional link between LSD1 and the major signalling pathway governing meiotic progression.

  14. Progression to impaired glucose regulation and diabetes in the population-based Inter99 study

    DEFF Research Database (Denmark)

    Engberg, Susanne; Vistisen, Dorte; Lau, Cathrine;

    2009-01-01

    Objective: To estimate the progression rates to impaired glucose regulation (impaired fasting glucose or impaired glucose tolerance) and diabetes in the Danish population-based Inter99 study and in a high-risk subpopulation, separately. Research Design and Methods: From a population-based primary...... glucose regulation using the current World Health Organization classification criteria were calculated for the first time in a large European population-based study. The progression rates to diabetes show the same pattern as seen in the few similar European studies.......Objective: To estimate the progression rates to impaired glucose regulation (impaired fasting glucose or impaired glucose tolerance) and diabetes in the Danish population-based Inter99 study and in a high-risk subpopulation, separately. Research Design and Methods: From a population-based primary...... prevention study, the Inter99 study, 4,615 individuals without diabetes at baseline and with relevant follow-up data were divided into a low- and a high-risk group based on a risk estimate of ischemic heart disease or the presence of risk factors (smoking, hypertension, hypercholesterolemia, obesity...

  15. Investigating the regulation of stem and progenitor cell mitotic progression by in situ imaging.

    Science.gov (United States)

    Gerhold, Abigail R; Ryan, Joël; Vallée-Trudeau, Julie-Nathalie; Dorn, Jonas F; Labbé, Jean-Claude; Maddox, Paul S

    2015-05-01

    Genome stability relies upon efficacious chromosome congression and regulation by the spindle assembly checkpoint (SAC). The study of these fundamental mitotic processes in adult stem and progenitor cells has been limited by the technical challenge of imaging mitosis in these cells in situ. Notably, how broader physiological changes, such as dietary intake or age, affect mitotic progression in stem and/or progenitor cells is largely unknown. Using in situ imaging of C. elegans adult germlines, we describe the mitotic parameters of an adult stem and progenitor cell population in an intact animal. We find that SAC regulation in germline stem and progenitor cells is distinct from that found in early embryonic divisions and is more similar to that of classical tissue culture models. We further show that changes in organismal physiology affect mitotic progression in germline stem and progenitor cells. Reducing dietary intake produces a checkpoint-dependent delay in anaphase onset, and inducing dietary restriction when the checkpoint is impaired increases the incidence of segregation errors in mitotic and meiotic cells. Similarly, developmental aging of the germline stem and progenitor cell population correlates with a decline in the rate of several mitotic processes. These results provide the first in vivo validation of models for SAC regulation developed in tissue culture systems and demonstrate that several fundamental features of mitotic progression in adult stem and progenitor cells are highly sensitive to organismal physiological changes.

  16. Two Approaches to Clinical Supervision.

    Science.gov (United States)

    Anderson, Eugene M.

    Criteria are established for a definition of "clinical supervision" and the effectiveness of such supervisory programs in a student teaching context are considered. Two differing genres of clinical supervision are constructed: "supervision by pattern analysis" is contrasted with "supervision by performance objectives." An outline of procedural…

  17. Counselor Supervision: A Consumer's Guide.

    Science.gov (United States)

    Yager, Geoffrey G.; Littrell, John M.

    This guide attempts to solve problems caused when a certain designated "brand" of supervision is forced on the counselor trainee with neither choice nor checklist of important criteria. As a tentative start on a guide to supervision the paper offers the following: a definition of supervision; a summary of the various types of supervision; a…

  18. Regulation of p53 by ING family members in suppression of tumor initiation and progression.

    Science.gov (United States)

    Jafarnejad, Seyed Mehdi; Li, Gang

    2012-06-01

    The INhibitor of Growth (ING) family is an evolutionarily conserved set of proteins, implicated in suppression of initiation and progression of cancers in various tissues. They promote cell cycle arrest, cellular senescence and apoptosis, participate in stress responses, regulate DNA replication and DNA damage responses, and inhibit cancer cell migration, invasion, and angiogenesis of the tumors. At the molecular level, ING proteins are believed to participate in chromatin remodeling and transcriptional regulation of their target genes. However, the best known function of ING proteins is their cooperation with p53 tumor suppressor protein in tumor suppression. All major isoforms of ING family members can promote the transactivition of p53 and the majority of them are shown to directly interact with p53. In addition, ING proteins are thought to interact with and modulate the function of auxiliary members of p53 pathway, such as MDM2, ARF , p300, and p21, indicating their widespread involvement in the regulation and function of this prominent tumor suppressor pathway. It seems that p53 pathway is the main mechanism by which ING proteins exert their functions. Nevertheless, regulation of other pathways which are not relevant to p53, yet important for tumorigenesis such as TGF-β and NF-κB, by ING proteins is also observed. This review summarizes the current understanding of the mutual interactions and cooperation between different members of ING family with p53 pathway and implications of this cooperation in the suppression of cancer initiation and progression.

  19. MMSET is dynamically regulated during cell-cycle progression and promotes normal DNA replication.

    Science.gov (United States)

    Evans, Debra L; Zhang, Haoxing; Ham, Hyoungjun; Pei, Huadong; Lee, SeungBaek; Kim, JungJin; Billadeau, Daniel D; Lou, Zhenkun

    2016-01-01

    The timely and precise duplication of cellular DNA is essential for maintaining genome integrity and is thus tightly-regulated. During mitosis and G1, the Origin Recognition Complex (ORC) binds to future replication origins, coordinating with multiple factors to load the minichromosome maintenance (MCM) complex onto future replication origins as part of the pre-replication complex (pre-RC). The pre-RC machinery, in turn, remains inactive until the subsequent S phase when it is required for replication fork formation, thereby initiating DNA replication. Multiple myeloma SET domain-containing protein (MMSET, a.k.a. WHSC1, NSD2) is a histone methyltransferase that is frequently overexpressed in aggressive cancers and is essential for normal human development. Several studies have suggested a role for MMSET in cell-cycle regulation; however, whether MMSET is itself regulated during cell-cycle progression has not been examined. In this study, we report that MMSET is degraded during S phase in a cullin-ring ligase 4-Cdt2 (CRL4(Cdt2)) and proteasome-dependent manner. Notably, we also report defects in DNA replication and a decreased association of pre-RC factors with chromatin in MMSET-depleted cells. Taken together, our results suggest a dynamic regulation of MMSET levels throughout the cell cycle, and further characterize the role of MMSET in DNA replication and cell-cycle progression.

  20. 监督学习的发展动态%Current Directions in Supervised Learning Research

    Institute of Scientific and Technical Information of China (English)

    蒋艳凰; 周海芳; 杨学军

    2003-01-01

    Supervised learning is very important in machine learning area. It has been making great progress in manydirections. This article summarizes three of these directions ,which are the hot problems in supervised learning field.These three directions are (a) improving classification accuracy by learning ensembles of classifiers, (b) methods forscaling up supervised learning algorithm, (c) extracting understandable rules from classifiers.

  1. Intratesticular signals regulate germ cell progression and production of qualitatively mature spermatozoa in vertebrates

    Directory of Open Access Journals (Sweden)

    Rosaria eMeccariello

    2014-05-01

    Full Text Available Spermatogenesis, a highly conserved process in vertebrates, is mainly under the hypothalamic-pituitary control, being regulated by the secretion of pituitary gonadotropins, FSH and LH, in response to stimulation exerted by Gonadotropin Releasing Hormone (GnRH from hypothalamic neurons. At testicular level, gonadotropins bind specific receptors located on the somatic cells regulating the production of steroids and factors necessary to ensure a correct spermatogenesis. Indeed, besides the endocrine route, a complex network of cell-to-cell communications regulates germ cell progression, and a combination of endocrine and intragonadal signals sustains the production of high quality mature spermatozoa. In this review we focus on the recent advances in the area of the intragonadal signals supporting sperm development.

  2. Deciphering the spatio-temporal regulation of entry and progression through mitosis.

    Science.gov (United States)

    Gheghiani, Lilia; Gavet, Olivier

    2014-02-01

    Mitosis has been studied since the early 1880s as a key event of the cell division cycle where remarkable changes in cellular architecture take place and ultimately lead to an equal segregation of duplicated chromosomes into two daughter cells. A detailed description of the complex and highly ordered cellular events taking place is now available. Many regulators involved in key steps including entry into mitosis, nuclear envelope breakdown, microtubule (MT) spindle formation, and chromosome attachment, as well as mitotic exit and cytokinesis, have also been identified. However, understanding the precise spatio-temporal contribution of each regulator in the cell reorganization process has been technically challenging. This review will focus on a number of recent advances in our understanding of the spatial distribution of protein activities and the temporal regulation of their activation and inactivation during entry and progression through mitosis by the use of intramolecular Förster resonance energy transfer (FRET)-based biosensors.

  3. Mitochondrial regulation of cell cycle progression through SLC25A43

    Energy Technology Data Exchange (ETDEWEB)

    Gabrielson, Marike; Reizer, Edwin [School of Health and Medical Sciences, Faculty of Medicine and Health, Örebro University, SE 70182 Örebro (Sweden); Stål, Olle [Department of Clinical and Experimental Medicine, Linköping University, SE 58185 Linköping (Sweden); Department of Oncology, Linköping University, SE 58185 Linköping (Sweden); Tina, Elisabet, E-mail: elisabet.tina@regionorebrolan.se [Department of Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, SE 70182 Örebro (Sweden)

    2016-01-22

    An increasing body of evidence is pointing towards mitochondrial regulation of the cell cycle. In a previous study of HER2-positive tumours we could demonstrate a common loss in the gene encoding for the mitochondrial transporter SLC25A43 and also a significant relation between SLC25A43 protein expression and S-phase fraction. Here, we investigated the consequence of suppressed SLC25A43 expression on cell cycle progression and proliferation in breast epithelial cells. In the present study, we suppressed SLC25A43 using siRNA in immortalised non-cancerous breast epithelial MCF10A cells and HER2-positive breast cancer cells BT-474. Viability, apoptosis, cell proliferation rate, cell cycle phase distribution, and nuclear Ki-67 and p21, were assessed by flow cytometry. Cell cycle related gene expressions were analysed using real-time PCR. We found that SLC25A43 knockdown in MCF10A cells significantly inhibited cell cycle progression during G{sub 1}-to-S transition, thus significantly reducing the proliferation rate and fraction of Ki-67 positive MCF10A cells. In contrast, suppressed SLC25A43 expression in BT-474 cells resulted in a significantly increased proliferation rate together with an enhanced G{sub 1}-to-S transition. This was reflected by an increased fraction of Ki-67 positive cells and reduced level of nuclear p21. In line with our previous results, we show a role for SLC25A43 as a regulator of cell cycle progression and proliferation through a putative mitochondrial checkpoint. These novel data further strengthen the connection between mitochondrial function and the cell cycle, both in non-malignant and in cancer cells. - Highlights: • Proposed cell cycle regulation through the mitochondrial transporter SLC25A43. • SLC25A43 alters cell proliferation rate and cell cycle progression. • Suppressed SLC25A43 influences transcription of cell cycle regulatory genes.

  4. Rho/ROCK signaling in regulation of corneal epithelial cell cycle progression.

    Science.gov (United States)

    Chen, Jian; Guerriero, Emily; Lathrop, Kira; SundarRaj, Nirmala

    2008-01-01

    The authors' previous study showed that the expression of a Rho-associated serine/threonine kinase (ROCK) is regulated during cell cycle progression in corneal epithelial cells. The present study was conducted to determine whether and how Rho/ROCK signaling regulates cell cycle progression. Rabbit corneal epithelial cells (RCECs) in culture were arrested in the G(0) phase of the cell cycle by serum deprivation and then allowed to re-enter the cell cycle in the presence or absence of the ROCK inhibitor (Y27632) in serum-supplemented medium. The number of cells in the S phase, the relative levels of specific cyclins and CDKs and their intracellular distribution, and the relative levels of mRNAs were determined by BrdU labeling, Western blot and immunocytochemical analyses, and real-time RT-PCR, respectively. ROCK inhibition delayed the progression of G(1) to S phase and led to a decrease in the number of RCECs entering the S phase between 12 and 24 hours from 31.5% +/- 4.5% to 8.1% +/- 2.6%. During the cell cycle progression, protein and mRNA levels of cyclin-D1 and -D3 and cyclin-dependent kinases CDK4 and CDK6 were significantly lower, whereas the protein levels of the CDK inhibitor p27(Kip1) were higher in ROCK-inhibited cells. Intracellular mRNA or protein levels of cyclin-E and protein levels of CDK2 were not significantly affected, but their nuclear translocation was delayed by ROCK inhibition. ROCK signaling is involved in cell cycle progression in RCECs, possibly by upregulation of cyclin-D1 and -D3 and CDK4, -6, and -2; nuclear translocation of CDK2 and cyclin-E; and downregulation of p27(Kip1).

  5. 34 CFR 303.171 - Supervision and monitoring of programs.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Supervision and monitoring of programs. 303.171 Section 303.171 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF...-Application Requirements § 303.171 Supervision and monitoring of programs. Each application must...

  6. 49 CFR 176.57 - Supervision of handling and stowage.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Supervision of handling and stowage. 176.57 Section 176.57 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS... VESSEL General Handling and Stowage § 176.57 Supervision of handling and stowage. (a) Hazardous...

  7. 7 CFR 761.102 - Borrower recordkeeping, reporting, and supervision.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Borrower recordkeeping, reporting, and supervision. 761.102 Section 761.102 Agriculture Regulations of the Department of Agriculture (Continued) FARM... Credit § 761.102 Borrower recordkeeping, reporting, and supervision. (a) A borrower must...

  8. Studies on PPAR α and γ participating in progression of liver fibrosis by regulating ACSL1

    Directory of Open Access Journals (Sweden)

    XIN Xuan

    2014-08-01

    Full Text Available During the development and procession of liver fibrosis, peroxisome proliferator-activated receptor (PPAR α and γ are in charge of the regulation of lipid metabolism, fatty acid metabolism, anti-liver fibrosis, etc., and are closely related to fat metabolism-related enzymes. As a key enzyme in fat metabolism, acyl-CoA synthetase long-chain family member 1 (ACSL1 is involved in lipid synthesis and catabolism and then causes lipid deposition and inflammation in the liver, so it directly or indirectly promotes hepatic fibrosis. The biological functions and roles of PPAR α and γ and ACSL1 are reviewed; the action mechanisms of PPAR α and γ in the transcriptional regulation of ACSL1 are briefly described; the regulatory effects of PPAR α and γ on ACSL1 and their effects on the progression of hepatic fibrosis are analyzed from the aspects of liver lipid metabolism and hepatic stellate cell activation. It is pointed out that in the liver PPAR α and γ are directly or indirectly involved in the progression of hepatic fibrosis by regulating ACSL1.

  9. Plac8 Links Oncogenic Mutations to Regulation of Autophagy and Is Critical to Pancreatic Cancer Progression

    Directory of Open Access Journals (Sweden)

    Conan Kinsey

    2014-05-01

    Full Text Available Mutations in p53 and RAS potently cooperate in oncogenic transformation, and correspondingly, these genetic alterations frequently coexist in pancreatic ductal adenocarcinoma (PDA and other human cancers. Previously, we identified a set of genes synergistically activated by combined RAS and p53 mutations as frequent downstream mediators of tumorigenesis. Here, we show that the synergistically activated gene Plac8 is critical for pancreatic cancer growth. Silencing of Plac8 in cell lines suppresses tumor formation by blocking autophagy, a process essential for maintaining metabolic homeostasis in PDA, and genetic inactivation in an engineered mouse model inhibits PDA progression. We show that Plac8 is a critical regulator of the autophagic machinery, localizing to the lysosomal compartment and facilitating lysosome-autophagosome fusion. Plac8 thus provides a mechanistic link between primary oncogenic mutations and the induction of autophagy, a central mechanism of metabolic reprogramming, during PDA progression.

  10. Microcephaly disease gene Wdr62 regulates mitotic progression of embryonic neural stem cells and brain size.

    Science.gov (United States)

    Chen, Jian-Fu; Zhang, Ying; Wilde, Jonathan; Hansen, Kirk C; Lai, Fan; Niswander, Lee

    2014-05-30

    Human genetic studies have established a link between a class of centrosome proteins and microcephaly. Current studies of microcephaly focus on defective centrosome/spindle orientation. Mutations in WDR62 are associated with microcephaly and other cortical abnormalities in humans. Here we create a mouse model of Wdr62 deficiency and find that the mice exhibit reduced brain size due to decreased neural progenitor cells (NPCs). Wdr62 depleted cells show spindle instability, spindle assembly checkpoint (SAC) activation, mitotic arrest and cell death. Mechanistically, Wdr62 associates and genetically interacts with Aurora A to regulate spindle formation, mitotic progression and brain size. Our results suggest that Wdr62 interacts with Aurora A to control mitotic progression, and loss of these interactions leads to mitotic delay and cell death of NPCs, which could be a potential cause of human microcephaly.

  11. Resistance to group clinical supervision

    DEFF Research Database (Denmark)

    Buus, Niels; Delgado, Cynthia; Traynor, Michael

    2017-01-01

    This present study is a report of an interview study exploring personal views on participating in group clinical supervision among mental health nursing staff members who do not participate in supervision. There is a paucity of empirical research on resistance to supervision, which has traditiona......This present study is a report of an interview study exploring personal views on participating in group clinical supervision among mental health nursing staff members who do not participate in supervision. There is a paucity of empirical research on resistance to supervision, which has...... traditionally been theorized as a supervisee's maladaptive coping with anxiety in the supervision process. The aim of the present study was to examine resistance to group clinical supervision by interviewing nurses who did not participate in supervision. In 2015, we conducted semistructured interviews with 24...

  12. Self-Supervised Dynamical Systems

    Science.gov (United States)

    Zak, Michail

    2003-01-01

    Some progress has been made in a continuing effort to develop mathematical models of the behaviors of multi-agent systems known in biology, economics, and sociology (e.g., systems ranging from single or a few biomolecules to many interacting higher organisms). Living systems can be characterized by nonlinear evolution of probability distributions over different possible choices of the next steps in their motions. One of the main challenges in mathematical modeling of living systems is to distinguish between random walks of purely physical origin (for instance, Brownian motions) and those of biological origin. Following a line of reasoning from prior research, it has been assumed, in the present development, that a biological random walk can be represented by a nonlinear mathematical model that represents coupled mental and motor dynamics incorporating the psychological concept of reflection or self-image. The nonlinear dynamics impart the lifelike ability to behave in ways and to exhibit patterns that depart from thermodynamic equilibrium. Reflection or self-image has traditionally been recognized as a basic element of intelligence. The nonlinear mathematical models of the present development are denoted self-supervised dynamical systems. They include (1) equations of classical dynamics, including random components caused by uncertainties in initial conditions and by Langevin forces, coupled with (2) the corresponding Liouville or Fokker-Planck equations that describe the evolutions of probability densities that represent the uncertainties. The coupling is effected by fictitious information-based forces, denoted supervising forces, composed of probability densities and functionals thereof. The equations of classical mechanics represent motor dynamics that is, dynamics in the traditional sense, signifying Newton s equations of motion. The evolution of the probability densities represents mental dynamics or self-image. Then the interaction between the physical and

  13. Feedback regulation of NEUROG2 activity by MTGR1 is required for progression of neurogenesis.

    Science.gov (United States)

    Aaker, Joshua D; Patineau, Andrea L; Yang, Hyun-Jin; Ewart, David T; Gong, Wuming; Li, Tongbin; Nakagawa, Yasushi; McLoon, Steven C; Koyano-Nakagawa, Naoko

    2009-12-01

    The sequential steps of neurogenesis are characterized by highly choreographed changes in transcription factor activity. In contrast to the well-studied mechanisms of transcription factor activation during neurogenesis, much less is understood regarding how such activity is terminated. We previously showed that MTGR1, a member of the MTG family of transcriptional repressors, is strongly induced by a proneural basic helix-loop-helix transcription factor, NEUROG2 in developing nervous system. In this study, we describe a novel feedback regulation of NEUROG2 activity by MTGR1. We show that MTGR1 physically interacts with NEUROG2 and represses transcriptional activity of NEUROG2. MTGR1 also prevents DNA binding of the NEUROG2/E47 complex. In addition, we provide evidence that proper termination of NEUROG2 activity by MTGR1 is necessary for normal progression of neurogenesis in the developing spinal cord. These results highlight the importance of feedback regulation of proneural gene activity in neurodevelopment.

  14. [Progress of studies on mechanisms of acupuncture underlying regulation of cardiac function via autonomic nervous system].

    Science.gov (United States)

    Wang, Ya-Li; Yu, Zhi; Xu, Bin

    2014-02-01

    Acupuncture therapy has been confirmed to be effective in treating cardiovascular diseases in clinical practice. Acupuncture-induced balance of the autonomic nervous system activities is one of its key mechanisms. In the present paper, the authors review progress of studies on acupuncture treatment of cardiovascular diseases from 1) regulating cardiac sympathetic-beta-adrenergic receptor activity and myocardial intracellular GTP-binding protein (Gs)-adenylylcyclase (AC)-cyclic adenosine monophosphate (cAMP)-protein kinase (PKA) signaling, and 2) balancing cardiac sympathetic and vagal nerve activities. Due to limited experimental conditions, in-depth studies about the mechanisms of acupuncture intervention underlying improvement of cardiovascular functions are relatively fewer up to now. Along with the further development of modern biology, the mechanism of acupuncture intervention underlying regulation of cardiac function via autonomic nerve system will be revealed in detail.

  15. 7α-Hydroxypregnenolone, a new key regulator of amphibian locomotion: discovery, progress and prospect.

    Science.gov (United States)

    Tsutsui, Kazuyoshi; Haraguchi, Shogo; Matsunaga, Masahiro; Koyama, Teppei; Do Rego, Jean-Luc; Vaudry, Hubert

    2012-05-01

    Seasonally-breeding amphibians have served as excellent animal models to investigate the biosynthesis and biological actions of neurosteroids. Previous studies have demonstrated that the brain of amphibians possesses key steroidogenic enzymes and produces pregnenolone, a precursor of steroid hormones, and other various neurosteroids. We recently found that the brain of seasonally-breeding newts actively produces 7α-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. This novel amphibian neurosteroid acts as a neuronal modulator to stimulate locomotor activity in newts. Subsequently, the mode of action of 7α-hydroxypregnenolone has been demonstrated in the newt brain. 7α-Hydroxypregnenolone stimulates locomotor activity through activation of the dopaminergic system. To understand the functional significance of 7α-hydroxypregnenolone in the regulation of locomotor activity, diurnal and seasonal changes in synthesis of 7α-hydroxypregnenolone have also been demonstrated in the newt brain. Melatonin derived from the pineal gland and eyes regulates 7α-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7α-hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor changes. In addition, 7α-hydroxypregnenolone mediates corticosterone action to increase locomotor activity under stress. This review summarizes the discovery, progress and prospect of 7α-hydroxypregnenolone, a new key regulator of amphibian locomotion.

  16. Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yi-Ju [Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan (China); Jan, Yee-Jee [Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Ko, Bor-Sheng [Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan (China); Liang, Shu-Man; Liou, Jun-Yang, E-mail: jliou@nhri.org.tw [Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan (China)

    2015-06-15

    There are seven mammalian isoforms of the 14-3-3 protein, which regulate multiple cellular functions via interactions with phosphorylated partners. Increased expression of 14-3-3 proteins contributes to tumor progression of various malignancies. Several isoforms of 14-3-3 are overexpressed and associate with higher metastatic risks and poorer survival rates of hepatocellular carcinoma (HCC). 14-3-3β and 14-3-3ζ regulate HCC cell proliferation, tumor growth and chemosensitivity via modulating mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and p38 signal pathways. Moreover, 14-3-3ε suppresses E-cadherin and induces focal adhesion kinase (FAK) expression, thereby enhancing epithelial-mesenchymal transition (EMT) and HCC cell migration. 14-3-3ζ forms complexes with αB-crystallin, which induces EMT and is the cause of sorafenib resistance in HCC. Finally, a recent study has indicated that 14-3-3σ induces heat shock protein 70 (HSP70) expression, which increases HCC cell migration. These results suggest that selective 14-3-3 isoforms contribute to cell proliferation, EMT and cell migration of HCC by regulating distinct targets and signal pathways. Targeting 14-3-3 proteins together with specific downstream effectors therefore has potential to be therapeutic and prognostic factors of HCC. In this article, we will overview 14-3-3’s regulation of its downstream factors and contributions to HCC EMT, cell migration and proliferation.

  17. Collective academic supervision

    DEFF Research Database (Denmark)

    Nordentoft, Helle Merete; Thomsen, Rie; Wichmann-Hansen, Gitte

    2013-01-01

    are interconnected. Collective Academic Supervision provides possibilities for systematic interaction between individual master students in their writing process. In this process they learn core academic competencies, such as the ability to assess theoretical and practical problems in their practice and present them...

  18. Reflecting reflection in supervision

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    Reflection has moved from the margins to the mainstream in supervision. Notions of reflection have become well established since the late 1980s. These notions have provided useful framing devices to help conceptualize some important processes in guidance and counseling. However, some applications...

  19. Clinical Supervision in Denmark

    DEFF Research Database (Denmark)

    Jacobsen, Claus Haugaard

    2011-01-01

    on giving and receiving clinical supervision as reported by therapists in Denmark. Method: Currently, the Danish sample consists of 350 clinical psychologist doing psychotherapy who completed DPCCQ. Data are currently being prepared for statistical analysis. Results: This paper will focus primarily...

  20. Kontraktetablering i supervision

    DEFF Research Database (Denmark)

    Mortensen, Karen Vibeke; Jacobsen, Claus Haugaard

    2007-01-01

    Kapitlet behandler kontraktetablering i supervision, et element, der ofte er blevet negligeret eller endog helt forbigået ved indledningen af supervisionsforløb. Sikre aftaler om emner som tid, sted, procedurer for fremlæggelse, fortrolighed, ansvarsfordeling og evaluering skaber imidlertid tryghed...

  1. Etiske betragtninger ved supervision

    DEFF Research Database (Denmark)

    Jacobsen, Claus Haugaard; Agerskov, Kirsten

    2007-01-01

    Kapitlet præsenterer nogle etiske betragtninger ved supervision. Mens der længe har eksisteret etiske retningslinjer for psykoterapeutisk arbejde, har der overraskende nok manglet tilsvarende vejledninger på supervisionsområdet. Det betyder imidlertid ikke, at de ikke er relevante. I kapitlet gøres...

  2. MMed cohort supervision: A path out of the swamp?

    African Journals Online (AJOL)

    One possible path to be explored is that of joint supervision. There are four options by ... applied by academic administrators as a way of complying with the regulations without any ... functional elements of proposal writing, data gathering and ...

  3. HMGA1: a master regulator of tumor progression in triple-negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Sandeep N Shah

    Full Text Available Emerging evidence suggests that tumor cells metastasize by co-opting stem cell transcriptional networks, although the molecular underpinnings of this process are poorly understood. Here, we show for the first time that the high mobility group A1 (HMGA1 gene drives metastatic progression in triple negative breast cancer cells (MDA-MB-231, Hs578T by reprogramming cancer cells to a stem-like state. Silencing HMGA1 expression in invasive, aggressive breast cancer cells dramatically halts cell growth and results in striking morphologic changes from mesenchymal-like, spindle-shaped cells to cuboidal, epithelial-like cells. Mesenchymal genes (Vimentin, Snail are repressed, while E-cadherin is induced in the knock-down cells. Silencing HMGA1 also blocks oncogenic properties, including proliferation, migration, invasion, and orthotopic tumorigenesis. Metastatic progression following mammary implantation is almost completely abrogated in the HMGA1 knock-down cells. Moreover, silencing HMGA1 inhibits the stem cell property of three-dimensional mammosphere formation, including primary, secondary, and tertiary spheres. In addition, knock-down of HMGA1 depletes cancer initiator/cancer stem cells and prevents tumorigenesis at limiting dilutions. We also discovered an HMGA1 signature in triple negative breast cancer cells that is highly enriched in embryonic stem cells. Together, these findings indicate that HMGA1 is a master regulator of tumor progression in breast cancer by reprogramming cancer cells through stem cell transcriptional networks. Future studies are needed to determine how to target HMGA1 in therapy.

  4. Multiple markers for melanoma progression regulated by DNA methylation: insights from transcriptomic studies.

    Science.gov (United States)

    Gallagher, William M; Bergin, Orla E; Rafferty, Mairin; Kelly, Zoë D; Nolan, Ilse-Maria; Fox, Edward J P; Culhane, Aedin C; McArdle, Linda; Fraga, Mario F; Hughes, Linda; Currid, Caroline A; O'Mahony, Fiona; Byrne, Aileen; Murphy, Alison A; Moss, Catherine; McDonnell, Susan; Stallings, Raymond L; Plumb, Jane A; Esteller, Manel; Brown, Robert; Dervan, Peter A; Easty, David J

    2005-11-01

    The incidence of melanoma is increasing rapidly, with advanced lesions generally failing to respond to conventional chemotherapy. Here, we utilized DNA microarray-based gene expression profiling techniques to identify molecular determinants of melanoma progression within a unique panel of isogenic human melanoma cell lines. When a poorly tumorigenic cell line, derived from an early melanoma, was compared with two increasingly aggressive derivative cell lines, the expression of 66 genes was significantly changed. A similar pattern of differential gene expression was found with an independently derived metastatic cell line. We further examined these melanoma progression-associated genes via use of a tailored TaqMan Low Density Array (LDA), representing the majority of genes within our cohort of interest. Considerable concordance was seen between the transcriptomic profiles determined by DNA microarray and TaqMan LDA approaches. A range of novel markers were identified that correlated here with melanoma progression. Most notable was TSPY, a Y chromosome-specific gene that displayed extensive down-regulation in expression between the parental and derivative cell lines. Examination of a putative CpG island within the TSPY gene demonstrated that this region was hypermethylated in the derivative cell lines, as well as metastatic melanomas from male patients. Moreover, treatment of the derivative cell lines with the DNA methyltransferase inhibitor, 2'-deoxy-5-azacytidine (DAC), restored expression of the TSPY gene to levels comparable with that found in the parental cells. Additional DNA microarray studies uncovered a subset of 13 genes from the above-mentioned 66 gene cohort that displayed re-activation of expression following DAC treatment, including TSPY, CYBA and MT2A. DAC suppressed tumor cell growth in vitro. Moreover, systemic treatment of mice with DAC attenuated growth of melanoma xenografts, with consequent re-expression of TSPY mRNA. Overall, our data support

  5. miR-340 and ZEB1 negative feedback loop regulates TGF-β- mediated breast cancer progression

    Science.gov (United States)

    Xie, Ye-Gong; Wang, Jie; Mao, Jie-Fei; Zhang, Bin; Wang, Xin; Cao, Xu-Chen

    2016-01-01

    MicroRNAs act as key regulators in carcinogenesis and progression in various cancers. In present study, we explored the role of miR-340 in the breast cancer progression. Our results showed that overexpression of miR-340 inhibits breast cancer cell proliferation and invasion, whereas depletion of miR-340 promotes breast cancer progression. Molecularly, ZEB1 was identified as a target gene of miR-340 and miR-340 suppressed the expression of ZEB1 by directly binding to the 3′-UTR of ZEB1. Furthermore, ZEB1 transcriptionally suppresses miR-340 expression. The negative feedback loop regulated TGF-β-mediated breast cancer progression. In conclusion, our data suggested that miR-340 acted as a tumor suppressor in breast cancer progression. PMID:27036021

  6. Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program.

    Science.gov (United States)

    Lee, Eun Ju; Jan, Arif Tasleem; Baig, Mohammad Hassan; Ashraf, Jalaluddin Mohammad; Nahm, Sang-Soep; Kim, Yong-Woon; Park, So-Young; Choi, Inho

    2016-08-01

    Differentiation of muscle satellite cells (MSCs) involves interaction of the proteins present in the extracellular matrix (ECM) with MSCs to regulate their activity, and therefore phenotype. Herein, we report fibromodulin (FMOD), a member of the proteoglycan family participating in the assembly of ECM, as a novel regulator of myostatin (MSTN) during myoblast differentiation. In addition to having a pronounced effect on the expression of myogenic marker genes [myogenin (MYOG) and myosin light chain 2 (MYL2)], FMOD was found to maintain the transcriptional activity of MSTN Moreover, coimmunoprecipitation and in silico studies performed to investigate the interaction of FMOD helped confirm that it antagonizes MSTN function by distorting its folding and preventing its binding to activin receptor type IIB. Furthermore, in vivo studies revealed that FMOD plays an active role in healing by increasing satellite cell recruitment to sites of injury. Together, these findings disclose a hitherto unrecognized regulatory role for FMOD in MSCs and highlight new mechanisms whereby FMOD circumvents the inhibitory effects of MSTN and triggers myoblast differentiation. These findings offer a basis for the design of novel MSTN inhibitors that promote muscle regeneration after injury or for the development of pharmaceutical agents for the treatment of different muscle atrophies.-Lee, E. J., Jan, A. T., Baig, M. H., Ashraf, J. M., Nahm, S.-S., Kim, Y.-W., Park, S.-Y., Choi, I. Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program.

  7. An intrinsic microRNA timer regulates progressive decline in shoot regenerative capacity in plants.

    Science.gov (United States)

    Zhang, Tian-Qi; Lian, Heng; Tang, Hongbo; Dolezal, Karel; Zhou, Chuan-Miao; Yu, Sha; Chen, Juan-Hua; Chen, Qi; Liu, Hongtao; Ljung, Karin; Wang, Jia-Wei

    2015-02-01

    Plant cells are totipotent and competent to regenerate from differentiated organs. It has been shown that two phytohormones, auxin and cytokinin, play critical roles within this process. As in animals, the regenerative capacity declines with age in plants, but the molecular basis for this phenomenon remains elusive. Here, we demonstrate that an age-regulated microRNA, miR156, regulates shoot regenerative capacity. As a plant ages, the gradual increase in miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors leads to the progressive decline in shoot regenerative capacity. In old plants, SPL reduces shoot regenerative capacity by attenuating the cytokinin response through binding with the B-type ARABIDOPSIS RESPONSE REGULATORs, which encode the transcriptional activators in the cytokinin signaling pathway. Consistently, the increased amount of exogenous cytokinin complements the reduced shoot regenerative capacity in old plants. Therefore, the recruitment of age cues in response to cytokinin contributes to shoot regenerative competence. © 2015 American Society of Plant Biologists. All rights reserved.

  8. Netrin-1 up-regulation in inflammatory bowel diseases is required for colorectal cancer progression.

    Science.gov (United States)

    Paradisi, Andrea; Maisse, Carine; Coissieux, Marie-May; Gadot, Nicolas; Lépinasse, Florian; Delloye-Bourgeois, Céline; Delcros, Jean-Guy; Svrcek, Magali; Neufert, Clemens; Fléjou, Jean-François; Scoazec, Jean-Yves; Mehlen, Patrick

    2009-10-06

    Chronic inflammation and cancer are intimately associated. This is particularly true for inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, which show a major increased risk for colorectal cancer. While the understanding of the molecular pathogenesis of IBD has recently improved, the mechanisms that link these chronic inflammatory states to colorectal cancer development are in large part unknown. One of these mechanisms is NF-kappaB pathway activation which in turn may contribute to tumor formation by providing anti-apoptotic survival signals to the epithelial cells. Based on the observation that netrin-1, the anti-apoptotic ligand for the dependence receptors DCC and UNC5H is up-regulated in colonic crypts in response to NF-kappaB, we show here that colorectal cancers from inflammatory bowel diseases patients have selected up-regulation of netrin-1. Moreover, we demonstrate that this inflammation-driven netrin-1 up-regulation is causal for colorectal cancer development as interference with netrin-1 autocrine loop in a mouse model for ulcerative colitis-associated colorectal cancer, while showing no effect on inflammation, inhibits colorectal cancer progression.

  9. Social networks in supervision

    DEFF Research Database (Denmark)

    Lystbæk, Christian Tang

    and practice have focused on conceptual frameworks and practical techniques of promoting reflection through conversation in general and questioning in particular. However, in recent years, supervision research has started to focus on the social and technological aspects of supervision. This calls...... is constituted by the relationality of the actors, not by the actors themselves. In other words, no one acts in a vacuum but rather always under the influence of a wide range of surrounding and interconnected factors. Actors are actors because they are in a networked relationship. Thus, focusing on social...... and space. That involves mobilised an denrolled actos, both animate and inanimate (e.g. books, computers, etc. Actor-network theory defines a symmetry between animate and inanimate, i.e. subjects and objects, because ”human powers increasingly derive from the complex interconnections if human with material...

  10. Ethics in education supervision

    Directory of Open Access Journals (Sweden)

    Fatma ÖZMEN

    2008-06-01

    Full Text Available Supervision in education plays a crucial role in attaining educational goals. In addition to determining the present situation, it has a theoretical and practical function regarding the actions to be taken in general and the achievement of teacher development in particular to meet the educational goals in the most effective way. For the education supervisors to act ethically in their tasks while achieving this vital mission shall facilitate them to build up trust, to enhance the level of collaboration and sharing, thus it shall contribute to organizational effectiveness. Ethics is an essential component of educational supervision. Yet, it demonstrates rather vague quality due to the conditions, persons, and situations. Therefore, it is a difficult process to develop the ethical standards in institutions. This study aims to clarify the concept of ethics, to bring up its importance, and to make recommendations for more effective supervisions from the aspect of ethics, based on the literature review, some research results, and sample cases reported by teachers and supervisors.

  11. Overexpression of NOTCH-regulated Ankyrin Repeat Protein is associated with papillary thyroid carcinoma progression

    Science.gov (United States)

    Zhang, Mingdi; Qin, Yiyu; Zuo, Bin; Gong, Wei; Zhang, Shenglai; Gong, Yurong; Quan, Zhiwei; Chu, Bingfeng

    2017-01-01

    Papillary thyroid cancer (PTC) is one of the endocrine cancers with high clinical and genetic heterogeneity. NOTCH signaling and its downstream NOTCH-Regulated Ankyrin Repeat Protein (NRARP) have been implicated in oncogenesis of many cancers, but the roles in PTCs are less studied. In this study, we show that NRARP is frequently over-expressed in thyroid carcinoma. The over-activation of NRARP is highly and positively correlated with NOTCH genes. Moreover, we find that the expression of NRARP is highly associated with several epithelial mesenchymal transition (EMT) markers and contributes to poor survival outcomes. Therefore, these results indicate that NRARP is an important clinical biomarker in thyroid carcinoma and it promotes EMT induction as well as the progression of PTCs via NOTCH signaling activation. PMID:28207739

  12. miR-107 regulates tumor progression by targeting NF1 in gastric cancer.

    Science.gov (United States)

    Wang, Shizhi; Ma, Gaoxiang; Zhu, Haixia; Lv, Chunye; Chu, Haiyan; Tong, Na; Wu, Dongmei; Qiang, Fulin; Gong, Weida; Zhao, Qinghong; Tao, Guoquan; Zhou, Jianwei; Zhang, Zhengdong; Wang, Meilin

    2016-11-09

    Our previous genome-wide miRNA microarray study revealed that miR-107 was upregulated in gastric cancer (GC). In this study we aimed to explore its biological role in the pathogenesis of GC. Integrating in silico prediction algorithms with western blotting assays revealed that miR-107 inhibition enhanced NF1 (neurofibromin 1) mRNA and protein levels, suggesting that NF1 is one of miR-107 targets in GC. Luciferase reporter assay revealed that miR-107 suppressed NF1 expression by binding to the first potential binding site within the 3'-UTR of NF1 mRNA. mRNA stable assay indicated this binding could result in NF1 mRNA instability, which might contribute to its abnormal protein expression. Functional analyses such as cell growth, transwell migration and invasion assays were used to investigate the role of interaction between miR-107 and its target on GC development and progression. Moreover, We investigated the association between the clinical phenotype and the status of miR-107 expression in 55 GC tissues, and found the high expression contributed to the tumor size and depth of invasion. The results exhibited that down regulation of miR-107 opposed cell growth, migration, and invasion, whereas NF1 repression promoted these phenotypes. Our findings provide a mechanism by which miR-107 regulates NF1 in GC, as well as highlight the importance of interaction between miR-107 and NF1 in GC development and progression.

  13. HABP2 is a novel regulator of hyaluronan-mediated human lung cancer progression

    Directory of Open Access Journals (Sweden)

    Tamara eMirzapoiazova

    2015-07-01

    Full Text Available Background: Lung cancer is a devastating disease with limited treatment options. Many lung cancers have changes in their microenvironment including upregulation of the extracellular matrix glycosaminoglycan, hyaluronan (HA, which we have previously demonstrated can regulate the activity of the extracellular serine protease, Hyaluronan Binding Protein 2 (HABP2. This study examined the functional role of HABP2 on HA-mediated human lung cancer dynamics.Methods: Immunohistochemical analysis was performed on lung cancer patient samples using anti-HABP2 antibody. Stable control, shRNA and HABP2 overexpressing human lung adenocarcinoma cells were evaluated using immunoblot analysis, migration, extravasation and urokinase plasminogen activator (uPA activation assays with or without high molecular weight HA (HMW-HA or low molecular weight HA (LMW-HA. In human lung cancer xenograft models, primary tumor growth rates and lung metastasis were analyzed using consecutive tumor volume measurements and nestin immunoreactivity in nude mouse lungs.Results: We provide evidence that HABP2 is an important regulator of lung cancer progression. HABP2 expression was increased in several subtypes of patient non-small cell lung cancer samples. Further, HABP2 overexpression increased LMW-HA-induced uPA activation, migration and extravasation in human lung adenocarcinoma cells. In vivo, overexpression of HABP2 in human lung adenocarcinoma cells increased primary tumor growth rates in nude mice by ~2 fold and lung metastasis by ~10 fold compared to vector control cells (n=5 per condition.Conclusions: Our data suggests a possible direct effect of HABP2 on uPA activation and lung cancer progression. Our observations suggest that exploration of HABP2 in non-small cell lung carcinoma merits further study both as a diagnostic and therapeutic option.

  14. NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes.

    Science.gov (United States)

    Teixeira, Leonardo K; Carrossini, Nina; Sécca, Cristiane; Kroll, José E; DaCunha, Déborah C; Faget, Douglas V; Carvalho, Lilian D S; de Souza, Sandro J; Viola, João P B

    2016-09-01

    The NFAT family of transcription factors has been primarily related to T cell development, activation, and differentiation. Further studies have shown that these ubiquitous proteins are observed in many cell types inside and outside the immune system, and are involved in several biological processes, including tumor growth, angiogenesis, and invasiveness. However, the specific role of the NFAT1 family member in naive B cell proliferation remains elusive. Here, we demonstrate that NFAT1 transcription factor controls Cyclin E expression, cell proliferation, and tumor growth in vivo. Specifically, we show that inducible expression of NFAT1 inhibits cell cycle progression, reduces colony formation, and controls tumor growth in nude mice. We also demonstrate that NFAT1-deficient naive B lymphocytes show a hyperproliferative phenotype and high levels of Cyclin E1 and E2 upon BCR stimulation when compared to wild-type B lymphocytes. NFAT1 transcription factor directly regulates Cyclin E expression in B cells, inhibiting the G1/S cell cycle phase transition. Bioinformatics analysis indicates that low levels of NFAT1 correlate with high expression of Cyclin E1 in different human cancers, including Diffuse Large B-cell Lymphomas (DLBCL). Together, our results demonstrate a repressor role for NFAT1 in cell cycle progression and Cyclin E expression in B lymphocytes, and suggest a potential function for NFAT1 protein in B cell malignancies.

  15. Bax Inhibitor-1 down-regulation in the progression of chronic liver diseases

    Directory of Open Access Journals (Sweden)

    Burra Patrizia

    2010-04-01

    Full Text Available Abstract Background Bax inhibitor-1 (BI-1 is an evolutionary conserved endoplasmic reticulum protein that, when overexpressed in mammalian cells, suppresses the apoptosis induced by Bax, a pro-apoptotic member of the Bcl-2 family. The aims of this study were: (1 to clarify the role of intrinsic anti- and pro-apoptotic mediators, evaluating Bax and BI-1 mRNA and protein expressions in liver tissues from patients with different degrees of liver damage; (2 to determine whether HCV and HBV infections modulate said expression. Methods We examined 62 patients: 39 with chronic hepatitis (CH (31 HCV-related and 8 HBV-related; 7 with cirrhosis (6 HCV-related and 1 HBV-related; 13 with hepatocellular carcinoma (HCC [7 in viral cirrhosis (6 HCV- and 1 HBV-related, 6 in non-viral cirrhosis]; and 3 controls. Bax and BI-1 mRNAs were quantified by real-time PCR, and BI-1 protein expression by Western blot. Results CH tissues expressed significantly higher BI-1 mRNA levels than cirrhotic tissues surrounding HCC (P Conclusions BI-1 expression is down-regulated as liver damage progresses. The high BI-1 mRNAs levels observed in early liver disease may protect virus-infected cells against apoptosis, while their progressive downregulation may facilitate hepatocellular carcinogenesis. HCV genotype seems to have a relevant role in Bax transcript expression.

  16. Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment.

    Science.gov (United States)

    Panagopoulos, Vasilios; Leach, Damien A; Zinonos, Irene; Ponomarev, Vladimir; Licari, Giovanni; Liapis, Vasilios; Ingman, Wendy V; Anderson, Peter; DeNichilo, Mark O; Evdokiou, Andreas

    2017-04-01

    Myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are heme-containing enzymes, well known for their antimicrobial activity, are released in high quantities by infiltrating immune cells in breast cancer. However, the functional importance of their presence within the tumour microenvironment is unclear. We have recently described a new role for peroxidases as key regulators of fibroblast and endothelial cell functionality. In the present study, we investigate for the first time, the ability of peroxidases to promote breast cancer development and progression. Using the 4T1 syngeneic murine orthotopic breast cancer model, we examined whether increased levels of peroxidases in developing mammary tumours influences primary tumour growth and metastasis. We showed that MPO and EPO stimulation increased mammary tumour growth and enhanced lung metastases, effects that were associated with reduced tumour necrosis, increased collagen deposition and neo-vascularisation within the primary tumour. In vitro, peroxidase treatment, robustly stimulated human mammary fibroblast migration and collagen type I and type VI secretion. Mechanistically, peroxidases induced the transcription of pro-tumorigenic and metastatic MMP1, MMP3 and COX-2 genes. Taken together, these findings identify peroxidases as key contributors to cancer progression by augmenting pro-tumorigenic collagen production and angiogenesis. Importantly, this identifies inflammatory peroxidases as therapeutic targets in breast cancer therapy.

  17. Protein tyrosine phosphatase PTPRB regulates Src phosphorylation and tumour progression in NSCLC.

    Science.gov (United States)

    Qi, Yinliang; Dai, Yuanchang; Gui, Shuyu

    2016-10-01

    Protein tyrosine-phosphatases (PTPs) play important roles in various biological processes. Deregulation in PTP function has been implicated in carcinogenesis and tumour progression in many cancer types. However, the role of protein tyrosine phosphatase receptor type B (PTPRB) in non-small-cell lung cancer (NSCLC) tumorigenesis has not been investigated. Lentiviral vector expressing PTPRB cDNA or shRNA was infected into A549 and H1299 cell lines, followed by cell proliferation, colony formation, soft agar and invasion assays. A549 xenograft mouse model was used to evaluate in vivo function of PTPRB. Quantitative polymerase chain reaction (PCR) was used to measure PTPRB expression in NSCLC patient samples. Kaplan Meier analysis was performed to assess association between PTPRB expression and patient overall survival (OS). Multivariate analysis was performed to evaluate prognostic significance of PTPRB. Overexpression of PTPRB reduced cell proliferation rate, colony formation efficiency, soft agar growth and cell invasion in A549 and H1299 cells, as well as tumour growth rate in A549 xenograft. Knockdown of PTPRB increased Src phosphorylation and cell invasion, which was reversed by Src inhibitor PP2. Additionally, PTPRB was down-regulated in NSCLC patient and was associated with patient OS. PTPRB regulates Src phosphorylation and tumorigenesis in NSCLC. PTPRB may serve as an independent prognostic biomarker for NSCLC patients.

  18. PCAF-primed EZH2 acetylation regulates its stability and promotes lung adenocarcinoma progression

    Institute of Scientific and Technical Information of China (English)

    Wan Junhu; Chin Y Eugene; Zhang Hongquan; Zhan Jun; Li Shuai; Ma Ji; Xu Weizhi; Liu Chang; Xue Xiaowei; Xie Yuping; Fang Weigang

    2015-01-01

    Enhancer of zeste homolog 2 ( EZH2 ) is a key epigenetic regulator that catalyzes the trimethyla-tion of H3K27 and is modulated by post-translational modifications (PTMs). However, the precise regulation of EZH2 PTMs remains elusive. We, herein, report that EZH2 is acetylated by acetyltransferase P300/CBP-associat-ed factor (PCAF) and is deacetylated by deacetylase SIRT1. We identified that PCAF interacts with and acetylates EZH2 mainly at lysine 348 (K348). Mechanistically, K348 acetylation decreases EZH2 phosphorylation at T345 and T487 and increases EZH2 stability without disrupting the formation of polycomb repressive complex 2 ( PRC2 ) . Functionally, EZH2 K348 acetylation enhances its capacity in suppression of the target genes and promotes lung cancer cell migration and invasion. Further, elevated EZH2 K348 acetylation in lung adenocarcinoma patients pre-dicts a poor prognosis. Our findings define a new mechanism underlying EZH2 modulation by linking EZH2 acety-lation to its phosphorylation that stabilizes EZH2 and promotes lung adenocarcinoma progression.

  19. RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Houcai; Yu, Jing; Zhang, Lixia; Xiong, Yuanyuan; Chen, Shuying; Xing, Haiyan; Tian, Zheng; Tang, Kejing; Wei, Hui; Rao, Qing; Wang, Min; Wang, Jianxiang, E-mail: wangjx@ihcams.ac.cn

    2014-04-18

    Highlights: • RPS27a expression was up-regulated in advanced-phase CML and AL patients. • RPS27a knockdown changed biological property of K562 and K562/G01 cells. • RPS27a knockdown affected Raf/MEK/ERK, P21 and BCL-2 signaling pathways. • RPS27a knockdown may be applicable for new combination therapy in CML patients. - Abstract: Ribosomal protein S27a (RPS27a) could perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The high expression level of RPS27a was reported in solid tumors, and we found that the expression level of RPS27a was up-regulated in advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL) patients. In this study, we explored the function of RPS27a in leukemia cells by using CML cell line K562 cells and its imatinib resistant cell line K562/G01 cells. It was observed that the expression level of RPS27a was high in K562 cells and even higher in K562/G01 cells. Further analysis revealed that RPS27a knockdown by shRNA in both K562 and K562G01 cells inhibited the cell viability, induced cell cycle arrest at S and G2/M phases and increased cell apoptosis induced by imatinib. Combination of shRNA with imatinib treatment could lead to more cleaved PARP and cleaved caspase-3 expression in RPS27a knockdown cells. Further, it was found that phospho-ERK(p-ERK) and BCL-2 were down-regulated and P21 up-regulated in RPS27a knockdown cells. In conclusion, RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells. It appears that drugs targeting RPS27a combining with tyrosine kinase inhibitor (TKI) might represent a novel therapy strategy in TKI resistant CML patients.

  20. Researching online supervision

    DEFF Research Database (Denmark)

    Smedegaard Ernst Bengtsen, Søren; Mathiasen, Helle

    2014-01-01

    , or a poor substitution of such. This one-sidedness on the conceptual level makes it challenging to empirically study the deeper implications digital tools have for the supervisory dialogue. Drawing on phenomenology and systems theory we argue that we need new concepts in qualitative methodology that allow...... us to research the digital tools on their own premises as autonomous things in themselves, possessing an ontological creativity of their own. In order for qualitative research to match the ontological nature of digital tools we conclude the article by formulating three criteria of a ‘torn......’ methodology that makes room for new approaches to researching online supervision at the university....

  1. Researching online supervision

    DEFF Research Database (Denmark)

    Bengtsen, Søren S. E.; Mathiasen, Helle

    2014-01-01

    us to research the digital tools on their own premises as autonomous things in themselves, possessing an ontological creativity of their own. In order for qualitative research to match the ontological nature of digital tools we conclude the article by formulating three criteria of a ‘torn......’ methodology that makes room for new approaches to researching online supervision at the university......., or a poor substitution of such. This one-sidedness on the conceptual level makes it challenging to empirically study the deeper implications digital tools have for the supervisory dialogue. Drawing on phenomenology and systems theory we argue that we need new concepts in qualitative methodology that allow...

  2. Online supervision at the university

    DEFF Research Database (Denmark)

    Bengtsen, Søren Smedegaard; Jensen, Gry Sandholm

    2015-01-01

    The article presents and condenses the background, findings and results of a one yearlong research project on online supervision and feedback at the university. The article builds on presentations and discussions in different research environments and conferences on higher education research...... supervision proves unhelpful when trying to understand how online supervision and feedback is a pedagogical phenomenon in its own right, and irreducible to the face-to-face context. Secondly we show that not enough attention has been given to the way different digital tools and platforms influence...... the supervisory dialogue in the specific supervision context. We conclude by terming this challenge in online supervision a form of ‘torn pedagogy’; that online tools and platforms destabilise and ‘tear’ traditional understandings of supervision pedagogy ‘apart’. Also, we conclude that on the backdrop of a torn...

  3. Co-expression of mitosis-regulating genes contributes to malignant progression and prognosis in oligodendrogliomas.

    Science.gov (United States)

    Liu, Yanwei; Hu, Huimin; Zhang, Chuanbao; Wang, Haoyuan; Zhang, Wenlong; Wang, Zheng; Li, Mingyang; Zhang, Wei; Zhou, Dabiao; Jiang, Tao

    2015-11-10

    The clinical prognosis of patients with glioma is determined by tumor grades, but tumors of different subtypes with equal malignancy grade usually have different prognosis that is largely determined by genetic abnormalities. Oligodendrogliomas (ODs) are the second most common type of gliomas. In this study, integrative analyses found that distribution of TCGA transcriptomic subtypes was associated with grade progression in ODs. To identify critical gene(s) associated with tumor grades and TCGA subtypes, we analyzed 34 normal brain tissue (NBT), 146 WHO grade II and 130 grade III ODs by microarray and RNA sequencing, and identified a co-expression network of six genes (AURKA, NDC80, CENPK, KIAA0101, TIMELESS and MELK) that was associated with tumor grades and TCGA subtypes as well as Ki-67 expression. Validation of the six genes was performed by qPCR in additional 28 ODs. Importantly, these genes also were validated in four high-grade recurrent gliomas and the initial lower-grade gliomas resected from the same patients. Finally, the RNA data on two genes with the highest discrimination potential (AURKA and NDC80) and Ki-67 were validated on an independent cohort (5 NBTs and 86 ODs) by immunohistochemistry. Knockdown of AURKA and NDC80 by siRNAs suppressed Ki-67 expression and proliferation of gliomas cells. Survival analysis showed that high expression of the six genes corporately indicated a poor survival outcome. Correlation and protein interaction analysis provided further evidence for this co-expression network. These data suggest that the co-expression of the six mitosis-regulating genes was associated with malignant progression and prognosis in ODs.

  4. Notch pathway regulates female germ cell meiosis progression and early oogenesis events in fetal mouse.

    Science.gov (United States)

    Feng, Yan-Min; Liang, Gui-Jin; Pan, Bo; Qin, Xun-Si; Zhang, Xi-Feng; Chen, Chun-Lei; Li, Lan; Cheng, Shun-Feng; De Felici, Massimo; Shen, Wei

    2014-01-01

    A critical process of early oogenesis is the entry of mitotic oogonia into meiosis, a cell cycle switch regulated by a complex gene regulatory network. Although Notch pathway is involved in numerous important aspects of oogenesis in invertebrate species, whether it plays roles in early oogenesis events in mammals is unknown. Therefore, the rationale of the present study was to investigate the roles of Notch signaling in crucial processes of early oogenesis, such as meiosis entry and early oocyte growth. Notch receptors and ligands were localized in mouse embryonic female gonads and 2 Notch inhibitors, namely DAPT and L-685,458, were used to attenuate its signaling in an in vitro culture system of ovarian tissues from 12.5 days post coitum (dpc) fetus. The results demonstrated that the expression of Stra8, a master gene for germ cell meiosis, and its stimulation by retinoic acid (RA) were reduced after suppression of Notch signaling, and the other meiotic genes, Dazl, Dmc1, and Rec8, were abolished or markedly decreased. Furthermore, RNAi of Notch1 also markedly inhibited the expression of Stra8 and SCP3 in cultured female germ cells. The increased methylation status of CpG islands within the Stra8 promoter of the oocytes was observed in the presence of DAPT, indicating that Notch signaling is probably necessary for maintaining the epigenetic state of this gene in a way suitable for RA stimulation. Furthermore, in the presence of Notch inhibitors, progression of oocytes through meiosis I was markedly delayed. At later culture periods, the rate of oocyte growth was decreased, which impaired subsequent primordial follicle assembly in cultured ovarian tissues. Taken together, these results suggested new roles of the Notch signaling pathway in female germ cell meiosis progression and early oogenesis events in mammals.

  5. Supervised Transfer Sparse Coding

    KAUST Repository

    Al-Shedivat, Maruan

    2014-07-27

    A combination of the sparse coding and transfer learn- ing techniques was shown to be accurate and robust in classification tasks where training and testing objects have a shared feature space but are sampled from differ- ent underlying distributions, i.e., belong to different do- mains. The key assumption in such case is that in spite of the domain disparity, samples from different domains share some common hidden factors. Previous methods often assumed that all the objects in the target domain are unlabeled, and thus the training set solely comprised objects from the source domain. However, in real world applications, the target domain often has some labeled objects, or one can always manually label a small num- ber of them. In this paper, we explore such possibil- ity and show how a small number of labeled data in the target domain can significantly leverage classifica- tion accuracy of the state-of-the-art transfer sparse cod- ing methods. We further propose a unified framework named supervised transfer sparse coding (STSC) which simultaneously optimizes sparse representation, domain transfer and classification. Experimental results on three applications demonstrate that a little manual labeling and then learning the model in a supervised fashion can significantly improve classification accuracy.

  6. Advanced Music Therapy Supervision Training

    DEFF Research Database (Denmark)

    2009-01-01

    supervision training excerpts live in the workshop will be offered. The workshop will include demonstrating a variety of supervision methods and techniques used in A) post graduate music therapy training programs b) a variety of work contexts such as psychiatry and somatic music psychotherapy. The workshop......The presentation will illustrate training models in supervision for experienced music therapists where transference/counter transference issues are in focus. Musical, verbal and body related tools will be illustrated from supervision practice by the presenters. A possibility to experience small...

  7. Advanced Music Therapy Supervision Training

    DEFF Research Database (Denmark)

    2009-01-01

    supervision training excerpts live in the workshop will be offered. The workshop will include demonstrating a variety of supervision methods and techniques used in A) post graduate music therapy training programs b) a variety of work contexts such as psychiatry and somatic music psychotherapy. The workshop......The presentation will illustrate training models in supervision for experienced music therapists where transference/counter transference issues are in focus. Musical, verbal and body related tools will be illustrated from supervision practice by the presenters. A possibility to experience small...

  8. Processes regulating progressive nitrogen limitation under elevated carbon dioxide: a meta-analysis

    Science.gov (United States)

    Liang, Junyi; Qi, Xuan; Souza, Lara; Luo, Yiqi

    2016-05-01

    The nitrogen (N) cycle has the potential to regulate climate change through its influence on carbon (C) sequestration. Although extensive research has explored whether or not progressive N limitation (PNL) occurs under CO2 enrichment, a comprehensive assessment of the processes that regulate PNL is still lacking. Here, we quantitatively synthesized the responses of all major processes and pools in the terrestrial N cycle with meta-analysis of CO2 experimental data available in the literature. The results showed that CO2 enrichment significantly increased N sequestration in the plant and litter pools but not in the soil pool, partially supporting one of the basic assumptions in the PNL hypothesis that elevated CO2 results in more N sequestered in organic pools. However, CO2 enrichment significantly increased the N influx via biological N fixation and the loss via N2O emission, but decreased the N efflux via leaching. In addition, no general diminished CO2 fertilization effect on plant growth was observed over time up to the longest experiment of 13 years. Overall, our analyses suggest that the extra N supply by the increased biological N fixation and decreased leaching may potentially alleviate PNL under elevated CO2 conditions in spite of the increases in plant N sequestration and N2O emission. Moreover, our syntheses indicate that CO2 enrichment increases soil ammonium (NH4+) to nitrate (NO3-) ratio. The changed NH4+/NO3- ratio and subsequent biological processes may result in changes in soil microenvironments, above-belowground community structures and associated interactions, which could potentially affect the terrestrial biogeochemical cycles. In addition, our data synthesis suggests that more long-term studies, especially in regions other than temperate ones, are needed for comprehensive assessments of the PNL hypothesis.

  9. Role of NOD1 in Heart Failure Progression via Regulation of Ca(2+) Handling.

    Science.gov (United States)

    Val-Blasco, Almudena; Piedras, María Jose G M; Ruiz-Hurtado, Gema; Suarez, Natalia; Prieto, Patricia; Gonzalez-Ramos, Silvia; Gómez-Hurtado, Nieves; Delgado, Carmen; Pereira, Laetitia; Benito, Gemma; Zaragoza, Carlos; Domenech, Nieves; Crespo-Leiro, María Generosa; Vasquez-Echeverri, Daniel; Nuñez, Gabriel; Lopez-Collazo, Eduardo; Boscá, Lisardo; Fernández-Velasco, María

    2017-01-31

    Heart failure (HF) is a complex syndrome associated with a maladaptive innate immune system response that leads to deleterious cardiac remodeling. However, the underlying mechanisms of this syndrome are poorly understood. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a newly recognized innate immune sensor involved in cardiovascular diseases. This study evaluated the role of NOD1 in HF progression. NOD1 was examined in human failing myocardium and in a post-myocardial infarction (PMI) HF model evaluated in wild-type (wt-PMI) and Nod1(-/-) mice (Nod1(-/-)-PMI). The NOD1 pathway was up-regulated in human and murine failing myocardia. Compared with wt-PMI, hearts from Nod1(-/-)-PMI mice had better cardiac function and attenuated structural remodeling. Ameliorated cardiac function in Nod1(-/-)-PMI mice was associated with prevention of Ca(2+) dynamic impairment linked to HF, including smaller and longer intracellular Ca(2+) concentration transients and a lesser sarcoplasmic reticulum Ca(2+) load due to a down-regulation of the sarcoplasmic reticulum Ca(2+)-adenosine triphosphatase pump and by augmented levels of the Na(+)/Ca(2+) exchanger. Increased diastolic Ca(2+) release in wt-PMI cardiomyocytes was related to hyperphosphorylation of ryanodine receptors, which was blunted in Nod1(-/-)-PMI cardiomyocytes. Pharmacological blockade of NOD1 also prevented Ca(2+) mishandling in wt-PMI mice. Nod1(-/-)-PMI mice showed significantly fewer ventricular arrhythmias and lower mortality after isoproterenol administration. These effects were associated with lower aberrant systolic Ca(2+) release and with a prevention of the hyperphosphorylation of ryanodine receptors under isoproterenol administration in Nod1(-/-)-PMI mice. NOD1 modulated intracellular Ca(2+) mishandling in HF, emerging as a new target for HF therapy. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Public Supervision over Private Relationships : Towards European Supervision Private Law?

    NARCIS (Netherlands)

    Cherednychenko, O.O.

    2014-01-01

    The rise of public supervision over private relationships in many areas of private law has led to the development of what, in the author’s view, could be called ‘European supervision private law’. This emerging body of law forms part of European regulatory private law and is made up of contract-rela

  11. Supervising PETE Candidates Using the Situational Supervision Model

    Science.gov (United States)

    Levy, Linda S.; Johnson, Lynn V.

    2012-01-01

    Physical education teacher candidates (PETCs) often, as part of their curricular requirements, engage in early field experiences that prepare them for student teaching. Matching the PETC's developmental level with the mentor's supervision style enhances this experience. The situational supervision model, based on the situational leadership model,…

  12. Exploring Clinical Supervision as Instrument for Effective Teacher Supervision

    Science.gov (United States)

    Ibara, E. C.

    2013-01-01

    This paper examines clinical supervision approaches that have the potential to promote and implement effective teacher supervision in Nigeria. The various approaches have been analysed based on the conceptual framework of instructional supervisory behavior. The findings suggest that a clear distinction can be made between the prescriptive and…

  13. Supervision Learning as Conceptual Threshold Crossing: When Supervision Gets "Medieval"

    Science.gov (United States)

    Carter, Susan

    2016-01-01

    This article presumes that supervision is a category of teaching, and that we all "learn" how to teach better. So it enquires into what novice supervisors need to learn. An anonymised digital questionnaire sought data from supervisors [n226] on their experiences of supervision to find out what was difficult, and supervisor interviews…

  14. Supervision Learning as Conceptual Threshold Crossing: When Supervision Gets "Medieval"

    Science.gov (United States)

    Carter, Susan

    2016-01-01

    This article presumes that supervision is a category of teaching, and that we all "learn" how to teach better. So it enquires into what novice supervisors need to learn. An anonymised digital questionnaire sought data from supervisors [n226] on their experiences of supervision to find out what was difficult, and supervisor interviews…

  15. Supervision of Supervised Agricultural Experience Programs: A Synthesis of Research.

    Science.gov (United States)

    Dyer, James E.; Williams, David L.

    1997-01-01

    A review of literature from 1964 to 1993 found that supervised agricultural experience (SAE) teachers, students, parents, and employers value the teachers' supervisory role. Implementation practices vary widely and there are no cumulative data to guide policies and standards for SAE supervision. (SK)

  16. [Ribozyme riboswitch based gene expression regulation systems for gene therapy applications: progress and challenges].

    Science.gov (United States)

    Feng, Jing-Xian; Wang, Jia-wen; Lin, Jun-sheng; Diao, Yong

    2014-11-01

    Robust and efficient control of therapeutic gene expression is needed for timing and dosing of gene therapy drugs in clinical applications. Ribozyme riboswitch provides a promising building block for ligand-controlled gene-regulatory system, based on its property that exhibits tunable gene regulation, design modularity, and target specificity. Ribozyme riboswitch can be used in various gene delivery vectors. In recent years, there have been breakthroughs in extending ribozyme riboswitch's application from gene-expression control to cellular function and fate control. High throughput screening platforms were established, that allow not only rapid optimization of ribozyme riboswitch in a microbial host, but also straightforward transfer of selected devices exhibiting desired activities to mammalian cell lines in a predictable manner. Mathematical models were employed successfully to explore the performance of ribozyme riboswitch quantitively and its rational design predictably. However, to progress toward gene therapy relevant applications, both precision rational design of regulatory circuits and the biocompatibility of regulatory ligand are still of crucial importance.

  17. Supervision Legislation for Foreign Capital Financial Institutions Starting up

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Supervision over foreign capital banks should reflect the new concept of equalattention paid to the fully open up and prudent supervision. China Banking Regulatory Commission (CBRC) held "2005National Meeting of Regulating Foreign Capital Banks" from April 7 to 8 in Shenzhen. There were 19leaders from local Banking Regulatory Bureaus, who deal with foreign capital regulating business, attended the meeting.At the meeting, Shi Jiliang, Vice-President of CBRC, said that CBRC is going to set up a trans-department statute cleaning up group, and start the revision of"Administrating Statutes for Foreign Capital Financial Institutions" and "Detailed Rules and Regulations in Implementing".

  18. VCP/p97, down-regulated by microRNA-129-5p, could regulate the progression of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Yu Liu

    Full Text Available Valosin containing protein (VCP/p97 plays various important roles in cells. Moreover, elevated expression of VCP in hepatocellular carcinoma (HCC is correlated with increased incidence of recurrence. But the role of VCP in HCC progression in vitro and in vivo is unclear. And there are few reports about the regulation mechanism on the expression of VCP in HCC. In this study, it was identified that the level of VCP was frequently increased in human HCC tissues. In addition, down-regulation of VCP with siRNAs could dramatically suppress the genesis and progression of tumor in vivo. It was found that miR-129-5p directly inhibited the expression of VCP in several HCC cell lines. Meanwhile, the level of VCP in HCC tissues was negatively associated with the level of miR-129-5p. Our further investigation showed that the enhanced expression of miR-129-5p also suppressed tumor growth in vivo. Moreover, it was revealed that miR-129-5p could inhibit the degradation of IκBα and increase the apoptosis and reduce the migration of HCC cells by suppressing the expression of VCP. Our results revealed that the expression of VCP was directly regulated by miR-129-5p and this regulation played an important role in the progression of HCC.

  19. Inductive Supervised Quantum Learning

    Science.gov (United States)

    Monràs, Alex; Sentís, Gael; Wittek, Peter

    2017-05-01

    In supervised learning, an inductive learning algorithm extracts general rules from observed training instances, then the rules are applied to test instances. We show that this splitting of training and application arises naturally, in the classical setting, from a simple independence requirement with a physical interpretation of being nonsignaling. Thus, two seemingly different definitions of inductive learning happen to coincide. This follows from the properties of classical information that break down in the quantum setup. We prove a quantum de Finetti theorem for quantum channels, which shows that in the quantum case, the equivalence holds in the asymptotic setting, that is, for large numbers of test instances. This reveals a natural analogy between classical learning protocols and their quantum counterparts, justifying a similar treatment, and allowing us to inquire about standard elements in computational learning theory, such as structural risk minimization and sample complexity.

  20. Supervision in Special Language Programs.

    Science.gov (United States)

    Florez-Tighe, Viola

    Too little emphasis is placed on instructional supervision in special language programs for limited-English-proficient students. Such supervision can provide a mechanism to promote the growth of instructional staff, improve the instructional program, and lead to curriculum development. Many supervisors are undertrained and unable to provide…

  1. Unfinished Business: Subjectivity and Supervision

    Science.gov (United States)

    Green, Bill

    2005-01-01

    Within the now burgeoning literature on doctoral research education, postgraduate research supervision continues to be a problematical issue, practically and theoretically. This paper seeks to explore and understand supervision as a distinctive kind of pedagogic practice. Informed by a larger research project, it draws on poststructuralism,…

  2. Supervision af psykoterapi via Skype

    DEFF Research Database (Denmark)

    Jacobsen, Claus Haugaard; Grünbaum, Liselotte

    2011-01-01

    clinical experience of Skype™ in supervision, mainly of psychoanalytic child psychotherapy, is presented and reflected upon. Finally, the reluctance of the Danish Board for Psychologists’s to recognize audiovisual distance supervision as part of the required training demands is discussed. It is concluded...

  3. Supervisees' Perception of Clinical Supervision

    Science.gov (United States)

    Willis, Lisa

    2010-01-01

    Supervisors must become aware of the possible conflicts that could arise during clinical supervision. It is important that supervisors communicate their roles and expectations effectively with their supervisees. This paper supports the notion that supervision is a mutual agreement between the supervisee and the supervisor and the roles of…

  4. Assessment of Counselors' Supervision Processes

    Science.gov (United States)

    Ünal, Ali; Sürücü, Abdullah; Yavuz, Mustafa

    2013-01-01

    The aim of this study is to investigate elementary and high school counselors' supervision processes and efficiency of their supervision. The interview method was used as it was thought to be better for realizing the aim of the study. The study group was composed of ten counselors who were chosen through purposeful sampling method. Data were…

  5. Tværfaglig supervision

    DEFF Research Database (Denmark)

    Tværfaglig supervision dækker over supervision af forskellige faggrupper. Det er en kompleks disciplin der stiller store krav tl supervisor. Bogens første del præsenterer fire faglige supervisionsmodeller: En almen, en psykodynamisk, en kognitiv adfærdsterapeutisk og en narrativ. Anden del...

  6. Tværfaglig supervision

    DEFF Research Database (Denmark)

    Tværfaglig supervision dækker over supervision af forskellige faggrupper. Det er en kompleks disciplin der stiller store krav tl supervisor. Bogens første del præsenterer fire faglige supervisionsmodeller: En almen, en psykodynamisk, en kognitiv adfærdsterapeutisk og en narrativ. Anden del henven...

  7. Supervision Duty of School Principals

    Directory of Open Access Journals (Sweden)

    Kürşat YILMAZ

    2009-04-01

    Full Text Available Supervision by school administrators is becoming more and more important. The change in the roles ofschool administrators has a great effect on that increase. At present, school administrators are consideredmore than as technical directors, but as instructional leaders. This increased the importance of schooladministrators’ expected supervision acts. In this respect, the aim of this study is to make a conceptualanalysis about school administrators’ supervision duties. For this reason, a literature review related withsupervision and contemporary supervision approaches was done, and the official documents concerningsupervision were examined. As a result, it can be said that school administrators’ supervision duties havebecome very important. And these duties must certainly be carried out by school administrators.

  8. Group supervision for general practitioners

    DEFF Research Database (Denmark)

    Galina Nielsen, Helena; Sofie Davidsen, Annette; Dalsted, Rikke;

    2013-01-01

    AIM: Group supervision is a sparsely researched method for professional development in general practice. The aim of this study was to explore general practitioners' (GPs') experiences of the benefits of group supervision for improving the treatment of mental disorders. METHODS: One long...... considered important prerequisites for disclosing and discussing professional problems. CONCLUSION: The results of this study indicate that participation in a supervision group can be beneficial for maintaining and developing GPs' skills in dealing with patients with mental health problems. Group supervision......-established supervision group was studied closely for six months by observing the group sessions, and by interviewing GPs and their supervisors, individually and collectively. The interviews were recorded digitally and transcribed verbatim. The data were analysed using systematic text condensation. RESULTS: The GPs found...

  9. China to Step up Supervision of Futures Market

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China will intensify its supervision and regulation of the futures market,and severely crack down on insider trading and market manipulation,according to the country’ssecurities regulator. Jiang Yang,Assistant to Chairman of the China Securities Regulatory Commission(CSRC),said Friday at the sixth International

  10. Regulator of G protein signaling 6 is a novel suppressor of breast tumor initiation and progression.

    Science.gov (United States)

    Maity, Biswanath; Stewart, Adele; O'Malley, Yunxia; Askeland, Ryan W; Sugg, Sonia L; Fisher, Rory A

    2013-08-01

    Breast cancer is a large global health burden and the most frequently diagnosed malignancy in women worldwide. Here, we utilize RGS6(-/-) mice to interrogate the role of regulator of G protein signaling 6 (RGS6), localized to the ductal epithelium in mouse and human breast, as a novel tumor suppressor in vivo. RGS6(-/-) mice exhibit accelerated 7,12-dimethylbenza[α]anthracene (DMBA)-induced tumor initiation and progression, as well as decreased overall survival. Analysis of carcinogenic aberrations in the mammary glands of DMBA-treated mice revealed a failure of the DNA damage response concurrent with augmented oncogenesis in RGS6(-/-) animals. Furthermore, RGS6 suppressed cell growth induced by either human epidermal growth factor receptor 2 or estrogen receptor activation in both MCF-7 breast cancer cells and mammary epithelial cells (MECs). MECs isolated from RGS6(-/-) mice also showed a deficit in DMBA-induced ATM/p53 activation, reactive oxygen species generation and apoptosis confirming that RGS6 is required for effective activation of the DNA damage response in these cells, a critical countermeasure against carcinogen-mediated genotoxic stress. The ability of RGS6 to simultaneously enhance DNA-damage-induced apoptotic signaling and suppress oncogenic cell growth likely underlie the accelerated tumorigenesis and cellular transformation observed in DMBA-treated RGS6(-/-) mice and isolated MECs, respectively. Unsurprisingly, spontaneous tumor formation was also seen in old female RGS6(-/-) but not in wild-type mice. Our finding that RGS6 is downregulated in all human breast cancer subtypes independent of their molecular classification indicates that obtaining a means to restore the growth suppressive and pro-apoptotic actions of RGS6 in breast might be a viable means to treat a large spectrum of breast tumors.

  11. Hormonally up-regulated neu-associated kinase: A novel target for breast cancer progression.

    Science.gov (United States)

    Zambrano, Joelle N; Neely, Benjamin A; Yeh, Elizabeth S

    2017-05-01

    Hormonally up-regulated neu-associated Kinase (Hunk) is a protein kinase that was originally identified in the murine mammary gland and has been shown to be highly expressed in Human Epidermal Growth Factor Receptor 2 positive (HER2(+)/ErbB2(+)) breast cancer cell lines as well as MMTV-neu derived mammary tumor cell lines. However, the physiological role of Hunk has been largely elusive since its identification. Though Hunk is predicted to be a Serine/Threonine (Ser/Thr) protein kinase with homology to the SNF1/AMPK family of protein kinases, there are no known Hunk substrates that have been identified to date. Recent work demonstrates a role for Hunk in HER2(+)/ErbB2(+) breast cancer progression, including drug resistance to HER2/ErbB2 inhibitors, with Hunk potentially acting downstream of HER2/ErbB2 and the PI3K/Akt pathway. These studies have collectively shown that Hunk plays a vital role in promoting mammary tumorigenesis, as Hunk knockdown via shRNA in xenograft tumor models or crossing MMTV-neu or Pten-deficient genetically engineered mouse models into a Hunk knockout (Hunk-/-) background impairs mammary tumor growth in vivo. Because the majority of HER2(+)/ErbB2(+) breast cancer patients acquire drug resistance to HER2/ErbB2 inhibitors, the characterization of novel drug targets like Hunk that have the potential to simultaneously suppress tumorigenesis and potentially enhance efficacy of current therapeutics is an important facet of drug development. Therefore, work aimed at uncovering specific regulatory functions for Hunk that could contribute to this protein kinase's role in both tumorigenesis and drug resistance will be informative. This review focuses on what is currently known about this under-studied protein kinase, and how targeting Hunk may prove to be a potential therapeutic target for the treatment of breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. The regulation of skeletal muscle protein turnover during the progression of cancer cachexia in the Apc(Min/+ mouse.

    Directory of Open Access Journals (Sweden)

    James P White

    Full Text Available Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The Apc(Min/+ mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the Apc(Min/+ mouse is not known. Cachexia progression was studied in Apc(Min/+ mice that were either weight stable (WS or had initial (≤5%, intermediate (6-19%, or extreme (≥20% body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172, AMPK activity, and raptor phosphorylation (Ser 792 were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process.

  13. Understanding Trust as an Essential Element of Trainee Supervision and Learning in the Workplace

    Science.gov (United States)

    Hauer, Karen E.; ten Cate, Olle; Boscardin, Christy; Irby, David M.; Iobst, William; O'Sullivan, Patricia S.

    2014-01-01

    Clinical supervision requires that supervisors make decisions about how much independence to allow their trainees for patient care tasks. The simultaneous goals of ensuring quality patient care and affording trainees appropriate and progressively greater responsibility require that the supervising physician trusts the trainee. Trust allows the…

  14. Molecular mechanisms and clinical applications of miR-22 in regulating malignant progression in human cancer (Review)

    Science.gov (United States)

    Wang, Jingyu; Li, Yuan; Ding, Meiman; Zhang, Honghe; Xu, Xiaoming; Tang, Jinlong

    2017-01-01

    miRNAs (microRNAs) have been validated to play fateful roles in the occurrence and development of cancers by post-transcriptionally targeting 3′-untranslated regions of the downstream gene mRNAs to repress mRNA expression. Mounting investigations forcefully document that not only does miR-22 biologically impinge on the processes of senescence, energy supply, angiogenesis, EMT (epithelial-mesenchymal transition), proliferation, migration, invasion, metastasis and apoptosis, but also it genetically or epigenetically exerts dual (inhibitory/promoting cancer) effects in various cancers via CNAs (copy number alterations), SNPs (single nucleotide polymorphisms), methylation, acetylation and even more momentously hydroxymethylation. Additionally, miR-22 expression may fluctuate with cancer progression in the body fluids of cancer patients and miR-22 could amplify its inhibitory or promoting effects through partaking in positive or negative feedback loops and interplaying with many other related miRNAs in the cascade of events, making it possible for miR-22 to be a promising and complementary or even independent cancer biomarker in some cancers and engendering profound influences on the early diagnosis, therapeutics, supervising curative effects and prognosis. PMID:28000852

  15. THE COMPARISON OF BANKING SUPERVISION MODEL IN INDONESIA, UNITED KINGDOM, SOUTH KOREA AS EFORTS TO IMPROVE INDONESIAN SUPERVISION SYSTEM

    Directory of Open Access Journals (Sweden)

    Sulistyandari

    2015-05-01

    Full Text Available This study aims to revise banking supervision by conducting comparative studies research model of banking supervision in Indonesia, the UK, South Korea and the aspirations of the respondents (Bank, OJK, theorist in Central Java on efforts to improve banking supervision is now done in Indonesia. The results show Indonesian comparison with the UK and South Korea gives the idea that the OJK in charge of education and consumer protection to enhance its role as practiced by the FCA in the UK, and the LPS assignments need to be expanded in order to ensure that all consumers of financial institutions as was done by the FSCS in the UK and KDIC in South Korea. Aspirations of the people of the regulation and supervision of banking include aspects of regulatory, law enforcement, infrastructure, community (the Bank and culture.

  16. The Wicked Problem of the Intersection between Supervision and Evaluation

    Directory of Open Access Journals (Sweden)

    Ian M. METTE

    2017-03-01

    Full Text Available The purpose of this research was to explore how principals in eight high-functioning elementary schools in one American school district balanced teacher supervision and evaluation in their role as an instructional leader. Using the theoretical framework of ‘wicked problems’, to unpack the circular used to problematize teacher supervision and evaluation, the findings analyse how elementary principals in these eight buildings acknowledge the tensions and conflicts between supervision and evaluation, specifically as they relate to improving teacher instruction. Specifically, the results of this study highlight not only the differences between supervision and evaluation, but also the intersection between the two functions, as well as how high-performing elementary school principals serve as an instructional coach rather than a manager of teachers. While the two functions of supervision and evaluation are inherently different, it is the acknowledgement of the intersection between the two functions that can allow building principals to progress as instructional coaches who can better develop human resources and create higher-functioning school systems. Overall, this study points toward the importance of elementary principals having the instructional leadership skills to differentiate supervision and professional development need for teachers, which in turn influences the evaluation of a teacher is in her/his respective career.

  17. Quality of supervision: postgraduate dental research trainees' perspectives.

    Science.gov (United States)

    Beaudin, A; Emami, E; Palumbo, M; Tran, S D

    2016-02-01

    Supervision is a pillar in enhancing the student's learning environment throughout her/his higher education. Multiple studies qualify graduate supervision among the most important contributors to the successful completion of a higher education degree and to graduate students' positive academic experience. The aim of this study was to assess the views of graduate students enrolled in the Dental Sciences and Craniofacial Research Graduate Programs at McGill University (n = 64) regarding the quality of supervision they are receiving. An online questionnaire composed of 22 open and closed-ended format items was used and covered five domains: student profile, supervisory relationship, conflict resolution, student progress/thesis writing and career development. Descriptive statistics, chi-square tests and interpretative qualitative analysis were used to evaluate students' perspectives. Fifty-nine students completed the survey (92.2%). The distribution of sample in regard to the graduate student level was almost identical (M.Sc. level n = 28, Ph.D. n = 31). Overall, most graduate students appeared satisfied with the supervision they received and had similar perspectives about the surveyed domains. There was one statistically significant difference (P supervision they received. The main elements contributing to a positive supervision experience were support, guidance, availability and good communication between supervisees and supervisors. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Nuclear FAK and Runx1 Cooperate to Regulate IGFBP3, Cell-Cycle Progression, and Tumor Growth.

    Science.gov (United States)

    Canel, Marta; Byron, Adam; Sims, Andrew H; Cartier, Jessy; Patel, Hitesh; Frame, Margaret C; Brunton, Valerie G; Serrels, Bryan; Serrels, Alan

    2017-08-14

    Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition of the surrounding tumor microenvironment. Here, we report in a murine model of skin squamous cell carcinoma (SCC) that nuclear FAK regulates Runx1-dependent transcription of insulin-like growth factor binding protein 3 (IGFBP3), and that this regulates SCC cell-cycle progression and tumor growth in vivo Furthermore, we identified a novel molecular complex between FAK and Runx1 in the nucleus of SCC cells and showed that FAK interacted with a number of Runx1-regulatory proteins, including Sin3a and other epigenetic modifiers known to alter Runx1 transcriptional function through posttranslational modification. These findings provide important new insights into the role of FAK as a scaffolding protein in molecular complexes that regulate gene transcription. Cancer Res; 77(19); 1-12. ©2017 AACR. ©2017 American Association for Cancer Research.

  19. Supervision--The Most Variable of Variables: Student Perspectives

    Science.gov (United States)

    McAlpine, Lynn; McKinnon, Margot

    2013-01-01

    The supervision literature often conceptualizes the supervisor as the primary person in doctoral students' progress. Yet, there is growing evidence that the supervisor is but one of many resources that students draw on. Our study takes up this idea in answering the question: What is students' experience of their supervisory relationships over…

  20. The Economic Analysis of Law on the To-be-expired Food Sales and Supervision

    Directory of Open Access Journals (Sweden)

    Gao Guilin

    2015-07-01

    Full Text Available To-be-expired food sold in shops and supermarkets without supervision run the certain risks of the security of people’s lives and health. However, under the current legal system, it is very difficult for the supervision departments on food safety to take fruitful/effective supervision measures. This exposes the contradiction and conflict of legality and rationality in food safety supervision. From the point of Law and Economics, this study analyzes in detail the causes of market self-regulation failure towards business behavior in selling the approaching expired food and problems in government regulation. The study also puts forward the legal governance mechanism of dealing with selling approaching expired food in order to provide some guidance to the legislation of supervision of food safety supervision.

  1. Foxn1 regulates lineage progression in cortical and medullary thymic epithelial cells but is dispensable for medullary sublineage divergence.

    Directory of Open Access Journals (Sweden)

    Craig S Nowell

    2011-11-01

    Full Text Available The forkhead transcription factor Foxn1 is indispensable for thymus development, but the mechanisms by which it mediates thymic epithelial cell (TEC development are poorly understood. To examine the cellular and molecular basis of Foxn1 function, we generated a novel and revertible hypomorphic allele of Foxn1. By varying levels of its expression, we identified a number of features of the Foxn1 system. Here we show that Foxn1 is a powerful regulator of TEC differentiation that is required at multiple intermediate stages of TE lineage development in the fetal and adult thymus. We find no evidence for a role for Foxn1 in TEC fate-choice. Rather, we show it is required for stable entry into both the cortical and medullary TEC differentiation programmes and subsequently is needed at increasing dosage for progression through successive differentiation states in both cortical and medullary TEC. We further demonstrate regulation by Foxn1 of a suite of genes with diverse roles in thymus development and/or function, suggesting it acts as a master regulator of the core thymic epithelial programme rather than regulating a particular aspect of TEC biology. Overall, our data establish a genetics-based model of cellular hierarchies in the TE lineage and provide mechanistic insight relating titration of a single transcription factor to control of lineage progression. Our novel revertible hypomorph system may be similarly applied to analyzing other regulators of development.

  2. Complex networks and banking systems supervision

    Science.gov (United States)

    Papadimitriou, Theophilos; Gogas, Periklis; Tabak, Benjamin M.

    2013-10-01

    Comprehensive and thorough supervision of all banking institutions under a Central Bank’s regulatory control has become necessary as recent banking crises show. Promptly identifying bank distress and contagion issues is of great importance to the regulators. This paper proposes a methodology that can be used additionally to the standard methods of bank supervision or the new ones proposed to be implemented. By this, one can reveal the degree of banks’ connectedness and thus identify “core” instead of just “big” banks. Core banks are central in the network in the sense that they are shown to be crucial for network supervision. Core banks can be used as gauges of bank distress over a sub-network and promptly raise a red flag so that the central bank can effectively and swiftly focus on the corresponding neighborhood of financial institutions. In this paper we demonstrate the proposed scheme using as an example the asset returns variable. The method may and should be used with alternative variables as well.

  3. The regulatory beta-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis

    DEFF Research Database (Denmark)

    Yde, C W; Olsen, B B; Meek, D

    2008-01-01

    Cell-cycle transition from the G(2) phase into mitosis is regulated by the cyclin-dependent protein kinase 1 (CDK1) in complex with cyclin B. CDK1 activity is controlled by both inhibitory phosphorylation, catalysed by the Myt1 and Wee1 kinases, and activating dephosphorylation, mediated by the CDC...... interference results in delayed cell-cycle progression at the onset of mitosis. Knockdown of CK2beta causes stabilization of Wee1 and increased phosphorylation of CDK1 at the inhibitory Tyr15. PLK1-Wee1 association is an essential event in the degradation of Wee1 in unperturbed cell cycle. We have found...... regulatory subunit, identifying it as a new component of signaling pathways that regulate cell-cycle progression at the entry of mitosis.Oncogene advance online publication, 12 May 2008; doi:10.1038/onc.2008.146....

  4. PRR11 regulates late-S to G2/M phase progression and induces premature chromatin condensation (PCC)

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Chundong; Zhang, Ying; Li, Yi; Zhu, Huifang; Wang, Yitao; Cai, Wei [Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016 (China); Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China); Zhu, Jiang [Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China); Ozaki, Toshinori [Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuohku, Chiba 260-8717 (Japan); Bu, Youquan, E-mail: buyqcn@aliyun.com [Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016 (China); Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China)

    2015-03-13

    Recently, we have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene product likely implicated in the regulation of cell cycle progression as well as lung cancer development. However, its precise role in cell cycle progression remains unclear. In the present study, we have further investigated the expression pattern and functional implication of PRR11 during cell cycle in detail in human lung carcinoma-derived H1299 cells. According to our immunofluorescence study, PRR11 was expressed largely in cytoplasm, the amount of PRR11 started to increase in the late S phase, and was retained until just before mitotic telophase. Consistent with those observations, siRNA-mediated knockdown of PRR11 caused a significant cell cycle arrest in the late S phase. Intriguingly, the treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. Moreover, knockdown of PRR11 also resulted in a remarkable retardation of G2/M progression, and PRR11-knockdown cells subsequently underwent G2 phase cell cycle arrest accompanied by obvious mitotic defects such as multipolar spindles and multiple nuclei. In addition, forced expression of PRR11 promoted the premature Chromatin condensation (PCC), and then proliferation of PRR11-expressing cells was massively attenuated and induced apoptosis. Taken together, our current observations strongly suggest that PRR11, which is strictly regulated during cell cycle progression, plays a pivotal role in the regulation of accurate cell cycle progression through the late S phase to mitosis. - Highlights: • PRR11 started to increase in the late S phase and was retained until just before mitotic telophase. • PRR11-knockdown caused a significant cell cycle arrest in the late S phase and G2 phase. • The treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. • PRR11-knockdown led to multipolar spindles and multiple nuclei. • Forced expression of PRR11 promoted the PCC and inhibited

  5. Fibronectin Matrix Remodeling in the Regulation of the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression

    Science.gov (United States)

    2011-09-01

    the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression PRINCIPAL INVESTIGATOR: Paula J. McKeown-Longo, Ph.D...2011 4. TITLE AND SUBTITLE Fibronectin Matrix Remodeling in the Regulation of the 5a. CONTRACT NUMBER W81XWH-10-1-0755 Inflammatory Response within...hypothesis that force dependent unfolding of fibronectin in the tumor stroma drives an inflammatory response within the lung tumor microenvironment

  6. Wildland fire as a self-regulating mechanism: the role of previous burns and weather in limiting fire progression.

    Science.gov (United States)

    Parks, Sean A; Holsinger, Lisa M; Miller, Carol; Nelson, Cara R

    2015-09-01

    Theory suggests that natural fire regimes can result in landscapes that are both self-regulating and resilient to fire. For example, because fires consume fuel, they may create barriers to the spread of future fires, thereby regulating fire size. Top-down controls such as weather, however, can weaken this effect. While empirical examples demonstrating this pattern-process feedback between vegetation and fire exist, they have been geographically limited or did not consider the influence of time between fires and weather. The availability of remotely sensed data identifying fire activity over the last four decades provides an opportunity to explicitly quantify-the ability of wildland fire to limit the progression of subsequent fire. Furthermore, advances in fire progression mapping now allow an evaluation of how daily weather as a top-down control modifies this effect. In this study, we evaluated the ability of wildland fire to create barriers that limit the spread of subsequent fire along a gradient representing time between fires in four large study areas in the western United States. Using fire progression maps in conjunction with weather station data, we also evaluated the influence of daily weather. Results indicate that wildland fire does limit subsequent fire spread in all four study areas, but this effect decays over time; wildland fire no longer limits subsequent fire spread 6-18 years after fire, depending on the study area. We also found that the ability of fire to regulate, subsequent fire progression was substantially reduced under extreme conditions compared to moderate weather conditions in all four study areas. This study increases understanding of the spatial feedbacks that can lead to self-regulating landscapes as well as the effects of top-down controls, such as weather, on these feedbacks. Our results will be useful to managers who seek to restore natural fire regimes or to exploit recent burns when managing fire.

  7. A Brief History of the Institutional Design of Banking Supervision in the Netherlands

    OpenAIRE

    2002-01-01

    This paper describes how banking supervision in the Netherlands has evolved over time. It concentrates on how legal and institutional arrangements and the practice of banking regulation and supervision have responded to developments in the financial environment since the Bank Act of 1948 formally entrusted banking supervision to the Nederlandsche Bank. To put the developments of the last fifty years in a broader perspective, this study also contains a brief history of the Bank and the commerc...

  8. Trade Supervision Adjustment in 2012

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    China revised its supervision policies on import and export trades again, with 13 notices approved by related government ministries and administrations as well as 15 catalogues of import and export licenses being involved.

  9. Learning Dynamics in Doctoral Supervision

    DEFF Research Database (Denmark)

    Kobayashi, Sofie

    This doctoral research explores doctoral supervision within life science research in a Danish university. From one angle it investigates doctoral students’ experiences with strengthening the relationship with their supervisors through a structured meeting with the supervisor, prepared as part...... investigates learning opportunities in supervision with multiple supervisors. This was investigated through observations and recording of supervision, and subsequent analysis of transcripts. The analyses used different perspectives on learning; learning as participation, positioning theory and variation theory....... The research illuminates how learning opportunities are created in the interaction through the scientific discussions. It also shows how multiple supervisors can contribute to supervision by providing new perspectives and opinions that have a potential for creating new understandings. The combination...

  10. Supervising undergraduate research: a collective approach utilising groupwork and peer support.

    Science.gov (United States)

    Baker, Mary-Jane; Cluett, Elizabeth; Ireland, Lorraine; Reading, Sheila; Rourke, Susan

    2014-04-01

    Nursing education now requires graduate entry for professional registration. The challenge is to ensure that students develop independence and team working in a resource effective manner. The dissertation is one opportunity for this. To evaluate changing from individual dissertation supervision to group peer supervision. Group supervision was implemented for one cohort. Dissertation outcomes were compared with two previous cohorts. Student evaluative data was assessed. Group supervision did not adversely affect dissertation outcomes (p=0.85). 88% of students reported peer supervision to be helpful, with themes being 'support and sharing', and 'progress and moving forward'. Peer group support provided consistent supervision harnessing the energy and resources of the students and Faculty, without adversely affecting outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  12. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  13. 20 CFR 656.21 - Supervised recruitment.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Supervised recruitment. 656.21 Section 656.21... Supervised recruitment. (a) Supervised recruitment. Where the Certifying Officer determines it appropriate, post-filing supervised recruitment may be required of the employer for the pending application or...

  14. Educational Supervision Appropriate for Psychiatry Trainee's Needs

    Science.gov (United States)

    Rele, Kiran; Tarrant, C. Jane

    2010-01-01

    Objective: The authors studied the regularity and content of supervision sessions in one of the U.K. postgraduate psychiatric training schemes (Mid-Trent). Methods: A questionnaire sent to psychiatry trainees assessed the timing and duration of supervision, content and protection of supervision time, and overall quality of supervision. The authors…

  15. 32 CFR 727.11 - Supervision.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Supervision. 727.11 Section 727.11 National... Supervision. The Judge Advocate General will exercise supervision over all legal assistance activities in the Department of the Navy. Subject to the supervision of the Judge Advocate General, officers in charge of...

  16. An Effective Supervision Model of a Standard Clause for Consumer Protection in the Business Transactions

    Directory of Open Access Journals (Sweden)

    M. Syamsudin

    2017-03-01

    Full Text Available This research aims to form an effective supervision model of a standard clause to protect consumer’s rights and interests. This study answers the questions the effectiveness of a standard clause supervision carried out by Otoritas Jasa Keuangan [Financial Services Authority (OJK] and Badan Penyelesaian Sengketa Konsumen [Consumer Dispute Settlement Agency (BPSK]; effective supervision model of a standard clause which can protect the rights and interest of the consumer. The object of this study are OJK and BPSK as a supervision of a standard clause. The result of this research shows that the supervision of standard clause done by those institutions has not been effective yet, this caused by several factors to wit the weakness of implementing regulation in terms of supervision, unclear supervision mechanism, the weakness of socialization related to the rules of standard clause towards business actors, and other weakness and obstacles faced by both institutions. The effective supervision model of standard clause is being formed that based on five points, namely: (1 the needs of institution/agency reformation who authorize to do supervision of standard clause; (2 the needs to determine the scope of duty and authority of standard clause supervision institution; (3 the needs of determination of material range about standard clause subjected to supervision which comprises: the content, the form, the position and the expression; (4 the needs of precise mechanism of standard clause supervision conducted by supervision institution; (5 the needs of following up the supervision results, especially to the business actors who break the standard clause rules.

  17. Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells

    Science.gov (United States)

    Ugarte, Fernando; Sousae, Rebekah; Cinquin, Bertrand; Martin, Eric W.; Krietsch, Jana; Sanchez, Gabriela; Inman, Margaux; Tsang, Herman; Warr, Matthew; Passegué, Emmanuelle; Larabell, Carolyn A.; Forsberg, E. Camilla

    2015-01-01

    Summary Epigenetic regulation serves as the basis for stem cell differentiation into distinct cell types, but it is unclear how global epigenetic changes are regulated during this process. Here, we tested the hypothesis that global chromatin organization affects the lineage potential of stem cells and that manipulation of chromatin dynamics influences stem cell function. Using nuclease sensitivity assays, we found a progressive decrease in chromatin digestion among pluripotent embryonic stem cells (ESCs), multipotent hematopoietic stem cells (HSCs), and mature hematopoietic cells. Quantitative high-resolution microscopy revealed that ESCs contain significantly more euchromatin than HSCs, with a further reduction in mature cells. Increased cellular maturation also led to heterochromatin localization to the nuclear periphery. Functionally, prevention of heterochromatin formation by inhibition of the histone methyltransferase G9A resulted in delayed HSC differentiation. Our results demonstrate global chromatin rearrangements during stem cell differentiation and that heterochromatin formation by H3K9 methylation regulates HSC differentiation. PMID:26489895

  18. Multivoiced Supervision of Master's Students: A Case Study of Alternative Supervision Practices in Higher Education

    Science.gov (United States)

    Dysthe, Olga; Samara, Akylina; Westrheim, Kariane

    2006-01-01

    This article describes and analyzes an alternative supervision model at the Master of Education Programme at the University of Bergen aimed at improving research supervision. A three-pronged approach was introduced, combining supervision groups, student colloquia and individual supervision. The supervision groups consisted of two supervisors and…

  19. Terrorism and financial supervision

    Directory of Open Access Journals (Sweden)

    Anatoli van der Krans

    2005-12-01

    Full Text Available This article presents an analysis of how legislators on international, European and national level combat the financing of terrorism. The central question in this article is whether European regulations concerning the prevention of money laundering and the financing of terrorism, are effective, proportional and mutually harmonious. Now that many regulations in this field have been established by intra-national bodies, it is important to examine how these regulations are further elaborated in the respective national systems. This article gives a broad overview of legislative initiatives of the UN, USA, FATF, EU and Council of Europe. The Netherlands for numerous reasons serves as a legal example. It is concluded that measures taken or proposed to avoid or at least reduce the financing of terrorism are quite effective to prevent abuse of the financial system. On the other hand, these measures increase the risk of underground or illegal financing, which is even more difficult to control.

  20. Terrorism and financial supervision

    Directory of Open Access Journals (Sweden)

    Anatoli van der Krans

    2005-12-01

    Full Text Available This article presents an analysis of how legislators on international, European and national level combat the financing of terrorism. The central question in this article is whether European regulations concerning the prevention of money laundering and the financing of terrorism, are effective, proportional and mutually harmonious. Now that many regulations in this field have been established by intra-national bodies, it is important to examine how these regulations are further elaborated in the respective national systems. This article gives a broad overview of legislative initiatives of the UN, USA, FATF, EU and Council of Europe. The Netherlands for numerous reasons serves as a legal example. It is concluded that measures taken or proposed to avoid or at least reduce the financing of terrorism are quite effective to prevent abuse of the financial system. On the other hand, these measures increase the risk of underground or illegal financing, which is even more difficult to control.

  1. Clinical supervision in a community setting.

    Science.gov (United States)

    Evans, Carol; Marcroft, Emma

    Clinical supervision is a formal process of professional support, reflection and learning that contributes to individual development. First Community Health and Care is committed to providing clinical supervision to nurses and allied healthcare professionals to support the provision and maintenance of high-quality care. In 2012, we developed new guidelines for nurses and AHPs on supervision, incorporating a clinical supervision framework. This offers a range of options to staff so supervision accommodates variations in work settings and individual learning needs and styles.

  2. Clinical supervision: the state of the art.

    Science.gov (United States)

    Falender, Carol A; Shafranske, Edward P

    2014-11-01

    Since the recognition of clinical supervision as a distinct professional competence and a core competence, attention has turned to ensuring supervisor competence and effective supervision practice. In this article, we highlight recent developments and the state of the art in supervision, with particular emphasis on the competency-based approach. We present effective clinical supervision strategies, providing an integrated snapshot of the current status. We close with consideration of current training practices in supervision and challenges.

  3. Human Cdc14B promotes progression through mitosis by dephosphorylating Cdc25 and regulating Cdk1/cyclin B activity.

    Directory of Open Access Journals (Sweden)

    Indra Tumurbaatar

    Full Text Available Entry into and progression through mitosis depends on phosphorylation and dephosphorylation of key substrates. In yeast, the nucleolar phosphatase Cdc14 is pivotal for exit from mitosis counteracting Cdk1-dependent phosphorylations. Whether hCdc14B, the human homolog of yeast Cdc14, plays a similar function in mitosis is not yet known. Here we show that hCdc14B serves a critical role in regulating progression through mitosis, which is distinct from hCdc14A. Unscheduled overexpression of hCdc14B delays activation of two master regulators of mitosis, Cdc25 and Cdk1, and slows down entry into mitosis. Depletion of hCdc14B by RNAi prevents timely inactivation of Cdk1/cyclin B and dephosphorylation of Cdc25, leading to severe mitotic defects, such as delay of metaphase/anaphase transition, lagging chromosomes, multipolar spindles and binucleation. The results demonstrate that hCdc14B-dependent modulation of Cdc25 phosphatase and Cdk1/cyclin B activity is tightly linked to correct chromosome segregation and bipolar spindle formation, processes that are required for proper progression through mitosis and maintenance of genomic stability.

  4. Terrorism and financial supervision

    NARCIS (Netherlands)

    Krans, Anatoli van der

    2005-01-01

    This article presents an analysis of how legislators on international, European and national level combat the financing of terrorism. The central question in this article is whether European regulations concerning the prevention of money laundering and the financing of terrorism, are effective, prop

  5. 78 FR 67361 - Public Water System Supervision Program Revision for the Commonwealth of Kentucky

    Science.gov (United States)

    2013-11-12

    ... AGENCY Public Water System Supervision Program Revision for the Commonwealth of Kentucky AGENCY: U.S... that the Commonwealth of Kentucky is revising its approved Public Water System Supervision Program... corresponding federal regulations. Therefore, the EPA is tentatively approving this revision to the Commonwealth...

  6. 77 FR 23246 - Public Water System Supervision Program Revision for the Commonwealth of Kentucky

    Science.gov (United States)

    2012-04-18

    ... AGENCY Public Water System Supervision Program Revision for the Commonwealth of Kentucky AGENCY... that the Commonwealth of Kentucky is revising its approved Public Water System Supervision Program... regulations. Therefore, the EPA is tentatively approving this revision to the Commonwealth of Kentucky's...

  7. 7 CFR 1205.25 - Supervision of sign-up period.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Supervision of sign-up period. 1205.25 Section 1205.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING... RESEARCH AND PROMOTION Procedures for Conduct of Sign-up Period Procedures § 1205.25 Supervision of...

  8. 75 FR 69662 - Public Water System Supervision Program Revision for the State of Colorado

    Science.gov (United States)

    2010-11-15

    ... [Federal Register Volume 75, Number 219 (Monday, November 15, 2010)] [Notices] [Page 69662] [FR Doc No: 2010-28497] ENVIRONMENTAL PROTECTION AGENCY [FRL-9225-3] Public Water System Supervision... Public Water System Supervision (PWSS) Primacy Program by adopting Federal regulations for the Lead...

  9. 76 FR 45253 - Public Water Supply Supervision Program; Program Revision for the State of Alaska

    Science.gov (United States)

    2011-07-28

    ... AGENCY Public Water Supply Supervision Program; Program Revision for the State of Alaska AGENCY... State of Alaska has revised its approved State Public Water Supply Supervision Primacy Program. Alaska has adopted regulations analogous to the EPA's Ground Water Rule. The EPA has determined that...

  10. 食品安全自媒体监督:现状、问题及其法律规制%Supervision of We Media over Food Safety:Its Present Situation,Problems and Legal Regulations

    Institute of Scientific and Technical Information of China (English)

    郭兰英; 单飞跃; 赵文焕

    2014-01-01

    以微博、微信、个人网站等为代表的自媒体,具有重构公共话语平台的现实功能,能够拓展食品安全信息的传播和监督空间,成为公众参与食品安全监督的新方式。但在«食品安全法»确立的现行食品安全监督法律机制中并无包括自媒体在内的公众参与食品安全监督的位置,再加之自媒体传导食品安全信息存在的缺陷,导致公众在使用自媒体进行食品安全监督时产生新的问题。这些问题需要法律对其作出回应。完善自媒体监督的规范,可以鼓励公众参与食品安全监督,提升食品安全监督效果。%We Media,represented by micro-blogs,Wechat and personal websites,has the realistic function of reconstructing a public discourse platform,which has gradually become a new and effective way for the public to participate in the supervision over food safety,such as expanding the space of spreading the information of and making supervision over food safety.However,the existing legal mechanism of food safety supervision established by the Food Safety Law of the People's Republic of China does not provide for any public participation in supervision over food safety;in addition,the defects of spreading information of food safety by employing we media have aroused new problems about public supervision over food safety.So new legal norms are demanded to improve the supervision of we media so as to encourage the public participation in and enhance the effect of supervision over food safety.

  11. Clinical supervision in the provision of intensive home visiting by health visitors.

    Science.gov (United States)

    Jarrett, Patricia; Barlow, Jane

    2014-02-01

    The objective of this paper is to explore the perceptions of health visitors working in frontline child protection concerning the role of clinical supervision. Fifteen health visitors ('home visitors') providing an intensive home visiting service to high-risk families in the south east of England were interviewed about their experience of receiving supervision. The model of clinical supervision used was based on the Family Partnership Programme and delivered by two trained psychotherapists. The data were analysed using thematic analysis. Home visitors believed that clinical supervision enabled them to maintain boundaries, regulate and reflect on their practice, and develop a better understanding of the issues clients were facing. The model of supervision used and the organisational context were believed to be important factors in the delivery of clinical supervision and to have contributed to its success.

  12. 77 FR 32881 - Supervised Securities Holding Company Registration

    Science.gov (United States)

    2012-06-04

    ... 81 Supervised Securities Holding Company Registration AGENCY: Board of Governors of the Federal...'' or ``Act''), which permits nonbank companies that own at least one registered securities broker or dealer, and that are required by a foreign regulator or provision of foreign law to be subject to...

  13. 7 CFR 1822.279 - Loan supervision and servicing.

    Science.gov (United States)

    2010-01-01

    ... LOANS AND GRANTS PRIMARILY FOR REAL ESTATE PURPOSES RURAL HOUSING LOANS AND GRANTS Rural Housing Site....279 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL... supervision and loan servicing will be provided according to 7 CFR part 3560....

  14. Recent Progress in Understanding Subtype Specific Regulation of NMDA Receptors by G Protein Coupled Receptors (GPCRs

    Directory of Open Access Journals (Sweden)

    Kai Yang

    2014-02-01

    Full Text Available G Protein Coupled Receptors (GPCRs are the largest family of receptors whose ligands constitute nearly a third of prescription drugs in the market. They are widely involved in diverse physiological functions including learning and memory. NMDA receptors (NMDARs, which belong to the ionotropic glutamate receptor family, are likewise ubiquitously expressed in the central nervous system (CNS and play a pivotal role in learning and memory. Despite its critical contribution to physiological and pathophysiological processes, few pharmacological interventions aimed directly at regulating NMDAR function have been developed to date. However, it is well established that NMDAR function is precisely regulated by cellular signalling cascades recruited downstream of G protein coupled receptor (GPCR stimulation. Accordingly, the downstream regulation of NMDARs likely represents an important determinant of outcome following treatment with neuropsychiatric agents that target selected GPCRs. Importantly, the functional consequence of such regulation on NMDAR function varies, based not only on the identity of the GPCR, but also on the cell type in which relevant receptors are expressed. Indeed, the mechanisms responsible for regulating NMDARs by GPCRs involve numerous intracellular signalling molecules and regulatory proteins that vary from one cell type to another. In the present article, we highlight recent findings from studies that have uncovered novel mechanisms by which selected GPCRs regulate NMDAR function and consequently NMDAR-dependent plasticity.

  15. SDF-1/CXCR4 Axis Regulates Cell Cycle Progression and Epithelial-Mesenchymal Transition via Up-regulation of Survivin in Glioblastoma.

    Science.gov (United States)

    Liao, Anyan; Shi, Ranran; Jiang, Yuliang; Tian, Suqing; Li, Panpan; Song, Fuxi; Qu, Yalan; Li, Jinna; Yun, Haiqin; Yang, Xiangshan

    2016-01-01

    Stromal cell-derived factor 1 (SDF-1)/CXCR4 ligand-receptor axis is widely recommended as an attractive target for cancer therapy. Meanwhile, epithelial-mesenchymal transition (EMT) process is linked to disease pathophysiology. As one of inhibitors of apoptosis proteins, survivin is implicated in the onset and development of cancer. In the present study, we tried to determine the cause-effect associations between SDF-1/CXCR4 axis and survivin expression in glioblastoma U-251 cell line. Survivin activation and inhibition were induced with exogenous SDF-1 and survivin small interfering RNA (survivin siRNA), respectively. Western blot was used to detect relevant proteins in SDF-1/CXCR4 axis. Western blot analysis revealed that survivin expression in U-251 increased in a dose- and time-dependent manner in response to SDF-1 treatment. However, the interference with MEK/ERK and PI3K/AKT pathway prohibited SDF-1-induced survivin up-regulation. Importantly, survivin knockdown abrogated cell cycle progression and the expression of snail and N-cadherin, compared with non-transfectants. In conclusion, the present study shows that SDF-1 up-regulates survivin via MEK/ERK and PI3K/AKT pathway, leading to cell cycle progression and EMT occurrence dependent on survivin. The blockade of survivin will allow for the treatment of glioblastoma.

  16. Urgency of Community Supervision Organization by Government

    Directory of Open Access Journals (Sweden)

    Catur Wibowo Budi Santoso

    2015-03-01

    Full Text Available Urgency Surveillance Study of Social Organization aims to describe the reality of the problems in the a real of Social Organization; describe the implementation of the role of government (including local government in controlling the Social Organization; and provider recommendations on matters that need to be regulated in the draft regulations on the supervision of organizations. This study used a qualitative approach, with the aim that can be obtained in-depth and complete information about matters relating to the existence and dynamics in regional organizations. The study results presented can be: that on the one hand the existence of organizations that do not contribute little in development, but on the other hand there are many community organizations that act an archaic and disturbing in society; for the entire operational provisions for the implementation of Social Organization must be available; things that need to be arranged substantially in the surveillance by the government.

  17. Regulation Effectiveness Evaluation Model for New Rural Cooperative Medical Scheme Fund Supervision%新型农村合作医疗基金监管有效性评价指标体系构建与方法选定

    Institute of Scientific and Technical Information of China (English)

    张新瑞; 薛兴利

    2012-01-01

    The thesis stated the concept of new rural cooperative medical fund supervision effectiveness and the evaluation principle. On the basis of establishment principle, the thesis constructed the evaluation index system for the new rural cooperative medical fund supervision effectiveness with 30 performance indicators, mainly from the 3 areas, namely the supervisory ability, the regulatory efficiency and the external supervision. Finally, according to the characteristics of new rural cooperative medical fund supervision, the thesis selected fuzzy comprehensive evaluation method as evaluation method, discussed the steps and emphasized the evaluation results of treatment, to provide references for regulation effectiveness evaluation.%文章在阐明新型农村合作医疗基金监管有效性基本内涵与评价原则的基础上,从监管能力、监管效率和外部监督等3个方面,选取30个指标构建了新型农村合作医疗基金监管有效性评价指标体系;从新型农村合作医疗基金监管的特点出发,通过比较,选取模糊综合评价法作为适宜方法,介绍了模糊综合评价法的操作步骤及其评价结果的分析和处理,以期为实现新型农村合作医疗基金的有效监管提供依据.

  18. Mechanisms of bioluminescence, chemiluminescence and of their regulation. Progress report, one year period through March 1976

    Energy Technology Data Exchange (ETDEWEB)

    Seliger, H H

    1976-01-01

    Progress is reported on a 10-yr study of the production and role of excited states in biological systems and the mechanisms involved in bioluminescence and chemoluminescence. An hypothesis of the origin of bioluminescence is presented that is based on the mixed function oxygenase reaction. Techniques of absolute measurements of light intensities and spectral composition were applied in studies of bioluminescence of marine dinoflagellates and the chemiluminescence of carcinogenic polycyclic aromatic hydrocarbons as the result of enzymatic hydroxylation. (CH)

  19. Targeting pH regulating proteins for cancer therapy-Progress and limitations.

    Science.gov (United States)

    Parks, Scott K; Pouysségur, Jacques

    2017-01-27

    Tumour acidity induced by metabolic alterations and incomplete vascularisation sets cancer cells apart from normal cellular physiology. This distinguishing tumour characteristic has been an area of intense study, as cellular pH (pHi) disturbances disrupt protein function and therefore multiple cellular processes. Tumour cells effectively utilise pHi regulating machinery present in normal cells with enhancements provided by additional oncogenic or hypoxia induced protein modifications. This overall improvement of pH regulation enables maintenance of an alkaline pHi in the continued presence of external acidification (pHe). Considerable experimentation has revealed targets that successfully disrupt tumour pHi regulation in efforts to develop novel means to weaken or kill tumour cells. However, redundancy in these pH-regulating proteins, which include Na(+)/H(+) exchangers (NHEs), carbonic anhydrases (CAs), Na(+)/HCO3(-) co-transporters (NBCs) and monocarboxylate transporters (MCTs) has prevented effective disruption of tumour pHi when individual protein targeting is performed. Here we synthesise recent advances in understanding both normoxic and hypoxic pH regulating mechanisms in tumour cells with an ultimate focus on the disruption of tumour growth, survival and metastasis. Interactions between tumour acidity and other cell types are also proving to be important in understanding therapeutic applications such as immune therapy. Promising therapeutic developments regarding pH manipulation along with current limitations are highlighted to provide a framework for future research directives.

  20. Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis.

    Directory of Open Access Journals (Sweden)

    Jeffrey M Skerker

    2005-10-01

    Full Text Available Two-component signal transduction systems, comprised of histidine kinases and their response regulator substrates, are the predominant means by which bacteria sense and respond to extracellular signals. These systems allow cells to adapt to prevailing conditions by modifying cellular physiology, including initiating programs of gene expression, catalyzing reactions, or modifying protein-protein interactions. These signaling pathways have also been demonstrated to play a role in coordinating bacterial cell cycle progression and development. Here we report a system-level investigation of two-component pathways in the model organism Caulobacter crescentus. First, by a comprehensive deletion analysis we show that at least 39 of the 106 two-component genes are required for cell cycle progression, growth, or morphogenesis. These include nine genes essential for growth or viability of the organism. We then use a systematic biochemical approach, called phosphotransfer profiling, to map the connectivity of histidine kinases and response regulators. Combining these genetic and biochemical approaches, we identify a new, highly conserved essential signaling pathway from the histidine kinase CenK to the response regulator CenR, which plays a critical role in controlling cell envelope biogenesis and structure. Depletion of either cenK or cenR leads to an unusual, severe blebbing of cell envelope material, whereas constitutive activation of the pathway compromises cell envelope integrity, resulting in cell lysis and death. We propose that the CenK-CenR pathway may be a suitable target for new antibiotic development, given previous successes in targeting the bacterial cell wall. Finally, the ability of our in vitro phosphotransfer profiling method to identify signaling pathways that operate in vivo takes advantage of an observation that histidine kinases are endowed with a global kinetic preference for their cognate response regulators. We propose that this

  1. A novel "four-component" two-component signal transduction mechanism regulates developmental progression in Myxococcus xanthus.

    Science.gov (United States)

    Jagadeesan, Sakthimala; Mann, Petra; Schink, Christian W; Higgs, Penelope I

    2009-08-07

    Histidine-aspartate phosphorelays are employed by two-component signal transduction family proteins to mediate responses to specific signals or stimuli in microorganisms and plants. The RedCDEF proteins constitute a novel signaling system in which four two-component proteins comprising a histidine kinase, a histidine-kinase like protein, and two response regulators function together to regulate progression through the elaborate developmental program of Myxococcus xanthus. A combination of in vivo phenotypic analyses of in-frame deletions and non-functional point mutations in each gene as well as in vitro autophosphorylation and phosphotransfer analyses of recombinant proteins indicate that the RedC histidine kinase protein autophosphorylates and donates a phosphoryl group to the single domain response regulator, RedF, to repress progression through the developmental program. To relieve this developmental repression, RedC instead phosphorylates RedD, a dual receiver response regulator protein. Surprisingly, RedD transfers the phosphoryl group to the histidine kinase-like protein RedE, which itself appears to be incapable of autophosphorylation. Phosphorylation of RedE may render RedE accessible to RedF, where it removes the phosphoryl group from RedF-P, which is otherwise an unusually stable phosphoprotein. These analyses reveal a novel "four-component" signaling mechanism that has probably arisen to temporally coordinate signals controlling the developmental program in M. xanthus. The RedCDEF signaling system provides an important example of how the inherent plasticity and modularity of the basic two-component signaling domains comprise a highly adaptable framework well suited to expansion into complex signaling mechanisms.

  2. Two-Component Signal Transduction Pathways Regulating Growth and Cell Cycle Progression in a Bacterium: A System-Level Analysis

    Science.gov (United States)

    Skerker, Jeffrey M; Prasol, Melanie S; Perchuk, Barrett S; Biondi, Emanuele G

    2005-01-01

    Two-component signal transduction systems, comprised of histidine kinases and their response regulator substrates, are the predominant means by which bacteria sense and respond to extracellular signals. These systems allow cells to adapt to prevailing conditions by modifying cellular physiology, including initiating programs of gene expression, catalyzing reactions, or modifying protein–protein interactions. These signaling pathways have also been demonstrated to play a role in coordinating bacterial cell cycle progression and development. Here we report a system-level investigation of two-component pathways in the model organism Caulobacter crescentus. First, by a comprehensive deletion analysis we show that at least 39 of the 106 two-component genes are required for cell cycle progression, growth, or morphogenesis. These include nine genes essential for growth or viability of the organism. We then use a systematic biochemical approach, called phosphotransfer profiling, to map the connectivity of histidine kinases and response regulators. Combining these genetic and biochemical approaches, we identify a new, highly conserved essential signaling pathway from the histidine kinase CenK to the response regulator CenR, which plays a critical role in controlling cell envelope biogenesis and structure. Depletion of either cenK or cenR leads to an unusual, severe blebbing of cell envelope material, whereas constitutive activation of the pathway compromises cell envelope integrity, resulting in cell lysis and death. We propose that the CenK–CenR pathway may be a suitable target for new antibiotic development, given previous successes in targeting the bacterial cell wall. Finally, the ability of our in vitro phosphotransfer profiling method to identify signaling pathways that operate in vivo takes advantage of an observation that histidine kinases are endowed with a global kinetic preference for their cognate response regulators. We propose that this system

  3. Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis

    DEFF Research Database (Denmark)

    Aszodi, Attila; Hunziker, Ernst B; Brakebusch, Cord;

    2003-01-01

    -actin organization. In addition, mutant chondrocytes show decreased proliferation caused by a defect in G1/S transition and cytokinesis. The G1/S defect is, at least partially, caused by overexpression of Fgfr3, nuclear translocation of Stat1/Stat5a, and up-regulation of the cell cycle inhibitors p16 and p21...

  4. Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus.

    Science.gov (United States)

    Gora, Kasia G; Cantin, Amber; Wohlever, Matthew; Joshi, Kamal K; Perchuk, Barrett S; Chien, Peter; Laub, Michael T

    2013-03-01

    Cell cycle transitions are often triggered by the proteolysis of key regulatory proteins. In Caulobacter crescentus, the G1-S transition involves the degradation of an essential DNA-binding response regulator, CtrA, by the ClpXP protease. Here, we show that another critical cell cycle regulator, SciP, is also degraded during the G1-S transition, but by the Lon protease. SciP is a small protein that binds directly to CtrA and prevents it from activating target genes during G1. We demonstrate that SciP must be degraded during the G1-S transition so that cells can properly activate CtrA-dependent genes following DNA replication initiation and the reaccumulation of CtrA. These results indicate that like CtrA, SciP levels are tightly regulated during the Caulobacter cell cycle. In addition, we show that formation of a complex between CtrA and SciP at target promoters protects both proteins from their respective proteases. Degradation of either protein thus helps trigger the destruction of the other, facilitating a cooperative disassembly of the complex. Collectively, our results indicate that ClpXP and Lon each degrade an important cell cycle regulator, helping to trigger the onset of S phase and prepare cells for the subsequent programmes of gene expression critical to polar morphogenesis and cell division.

  5. The Impact of Regulations, Safety Considerations and Physical Limitations on Research Progress at Maximum Biocontainment

    OpenAIRE

    2012-01-01

    We describe herein, limitations on research at biosafety level 4 (BSL-4) containment laboratories, with regard to biosecurity regulations, safety considerations, research space limitations, and physical constraints in executing experimental procedures. These limitations can severely impact the number of collaborations and size of research projects investigating microbial pathogens of biodefense concern. Acquisition, use, storage, and transfer of biological select agents and toxins (BSAT) are ...

  6. Hypoxia Up-Regulates Galectin-3 in Mammary Tumor Progression and Metastasis.

    Directory of Open Access Journals (Sweden)

    Joana T de Oliveira

    Full Text Available The tumor microenvironment encompasses several stressful conditions for cancer cells such as hypoxia, oxidative stress and pH alterations. Galectin-3, a well-studied member of the beta-galactoside-binding animal family of lectins has been implicated in multiple steps of metastasis as cell-cell and cell-ECM adhesion, promotion of angiogenesis, cell proliferation and resistance to apoptosis. However, both its aberrantly up- and down-regulated expression was observed in several types of cancer. Thus, the mechanisms that regulate galectin-3 expression in neoplastic settings are not clear. In order to demonstrate the putative role of hypoxia in regulating galectin-3 expression in canine mammary tumors (CMT, in vitro and in vivo studies were performed. In malignant CMT cells, hypoxia was observed to induce expression of galectin-3, a phenomenon that was almost completely prevented by catalase treatment of CMT-U27 cells. Increased galectin-3 expression was confirmed at the mRNA level. Under hypoxic conditions the expression of galectin-3 shifts from a predominant nuclear location to cytoplasmic and membrane expressions. In in vivo studies, galectin-3 was overexpressed in hypoxic areas of primary tumors and well-established metastases. Tumor hypoxia thus up-regulates the expression of galectin-3, which may in turn increase tumor aggressiveness.

  7. TTIP as a Platform for Progress in Pharma and Medtech Regulations

    DEFF Research Database (Denmark)

    Van Vooren, Bart; Ryckmann, Charlotte

    2016-01-01

    Opponents of the transatlantic trade and investment partnership treaty (TTIP) fear that, the EU might lose the capacity to protect public health as it deems appropriate. The freedom to regulate would be jeopardized because TTIP would bind the EU to the United States’ regulatory interests, which...

  8. Allelic deletions of cell growth regulators during progression of bladder cancer

    DEFF Research Database (Denmark)

    Primdahl, H; von der Maase, H; Christensen, M

    2000-01-01

    Cell growth regulators include proteins of the p53 pathway encoded by the genes CDKN2A (p16, p14arf), MDM2, TP53, and CDKN1A (p21) as well as proteins encoded by genes like RB1, E2F, and MYCL. In the present study we investigated allelic deletions of all these genes in each recurrent bladder tumor...

  9. Regulation of polyamine synthesis in plants. Final progress report, July 1, 1991--December 31, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Malmberg, R.L.

    1995-07-01

    This research focused on unusual post-translational modifications occuring in a arginine decarboxylase cDNA clone in oats. A novel regulatory mechanism for polyamines was explored and an attempt was made to characterize it. A plant ornithine decarboxylase cDNA was identified in Arabidopsis. Further work remains on the mechanisms of polyamine regulation and function in plants.

  10. Ethics in Rehabilitation Counselor Supervision.

    Science.gov (United States)

    Blackwell, Terry L.; Strohmer, Douglas C.; Belcas, Eva M.; Burton, Kathryn A.

    2002-01-01

    Article is an exploration of some of the ethical issues facing rehabilitation counselors who provide clinical supervision. Ethical issues related to competence, evaluation and due process, dual relationships, confidentiality, and informed consent are discussed. (Contains 28references, 2 tables, and 1 appendix.) (Author)

  11. The role of miRNA regulation in cancer progression and drug resistance

    DEFF Research Database (Denmark)

    Joshi, Tejal

    RNAs in the context of cancer biology, drug resistance and disease progression. The first project described in Chapter 6 addresses the problem of tamoxifen resistance, an anti-estrogen drug that is generally highly effective in the treatment of ER-positive breast cancers. The underlying molecular mechanisms...... the role of miRNAs in the transformation of ocular mucosa associated lymphoid tissue lymphoma (MALT) to the high-grade diffuse large B-cell lymphoma (DLBCL) of eye. Several tumor suppressive miRNAs were found to be dysregulated in DLBCL, suggesting their possible role in disease transformation. Many...

  12. Influence of Tumor Microenvironment on the Molecular Regulation of Prostate Cancer Progression

    Science.gov (United States)

    2011-08-01

    well plates. Lysates were prepared from cultured cells in a solution containing 50 mM Tris, pH 7.5; 120 mM NaCl; 0.5% Nonidet p - 40 ; 40 M...metastatic progression. Adv Cancer Res, 2007. 97: p . 225-46. 40 . Mimori, K., et al., Coexpression of matrix metalloproteinase-7 (MMP-7) and epidermal...day period. Results are means ± SE of three independent experiments. * P , 0.05 (students t-test) compared to cell number at day 1 ±SEM (B

  13. A genetic analysis of Adh1 regulation. Progress report, June 1991--February 1992

    Energy Technology Data Exchange (ETDEWEB)

    Freeling, M.

    1992-03-01

    The overall goal of our research proposal is to understand the meaning of the various cis-acting sites responsible for AdH1 expression in the entire maize plant. Progress is reported in the following areas: Studies on the TATA box and analysis of revertants of the Adh1-3F1124 allele; screening for more different mutants that affect Adh1 expression differentially; studies on cis-acting sequences required for root-specific Adh1 expression; refinement of the use of the particle gun; and functional analysis of a non- glycolytic anaerobic protein.

  14. Role of the tumor microenvironment in regulating apoptosis and cancer progression.

    Science.gov (United States)

    Yaacoub, Katherine; Pedeux, Remy; Tarte, Karin; Guillaudeux, Thierry

    2016-08-10

    Apoptosis is a gene-directed program that is engaged to efficiently eliminate dysfunctional cells. Evasion of apoptosis may be an important gate to tumor initiation and therapy resistance. Like any other developmental program, apoptosis can be disrupted by several genetic aberrations driving malignant cells into an uncontrolled progression and survival. For its sustained growth, cancer develops in a complex environment, which provides survival signals and rescues malignant cells from apoptosis. Recent studies have clearly shown a wide interaction between tumor cells and their microenvironment, confirming the influence of the surrounding cells on tumor expansion and invasion. These non-malignant cells not only intensify tumor cells growth but also upgrade the process of metastasis. The strong crosstalk between malignant cells and a reactive microenvironment is mediated by soluble chemokines and cytokines, which act on tumor cells through surface receptors. Disturbing the microenvironment signaling might be an encouraging approach for patient's treatment. Therefore, the ultimate knowledge of "tumor-microenvironment" interactions facilitates the identification of novel therapeutic procedures that mobilize cancer cells from their supportive cells. This review focuses on cancer progression mediated by the dysfunction of apoptosis and by the fundamental relationship between tumor and reactive cells. New insights and valuable targets for cancer prevention and therapy are also presented. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. RNA metabolism in the regulation of protein synthesis in plants. Progress report, 1975-1979

    Energy Technology Data Exchange (ETDEWEB)

    Key, J L

    1979-01-01

    The major objectives of the research for the contract period covered by this report were (1) to gain an insight into the sequence organization of the DNA of soybean, emphasizing the arrangement of single copy or unique sequences and repetitive sequences of DNA throughout the genome, (2) to characterize soybean RNAs relative to nucleotide sequence complexity and kinetics of synthesis and turnover of poly A/sup +/ mRNA, and (3) to study ribosomal proteins directed to an analysis of possible changes in proteins which relate to the activation of 80S ribosomes and thus mRNA utilization and protein synthesis in response to environmental stimuli. Even with greatly reduced funding compared to that requested, objectives 1 and 2 were substantially accomplished. Because of reduced funding and the 20-month no cost extension, relatively little progress was made on objective 3. Accordingly objectives 1 and 2 will be summarized in some detail; a brief account of progress is presented on objective 3.

  16. AS101 prevents diabetic nephropathy progression and mesangial cell dysfunction: regulation of the AKT downstream pathway.

    Directory of Open Access Journals (Sweden)

    Itay Israel Shemesh

    Full Text Available Diabetic nephropathy (DN is characterized by proliferation of mesangial cells, mesangial expansion, hypertrophy and extracellular matrix accumulation. Previous data have cross-linked PKB (AKT to TGFβ induced matrix modulation. The non-toxic compound AS101 has been previously shown to favorably affect renal pathology in various animal models and inhibits AKT activity in leukemic cells. Here, we studied the pharmacological properties of AS101 against the progression of rat DN and high glucose-induced mesangial dysfunction. In-vivo administration of AS101 to Streptozotocin injected rats didn't decreased blood glucose levels but ameliorated kidney hypotrophy, proteinuria and albuminuria and downregulated cortical kidney phosphorylation of AKT, GSK3β and SMAD3. AS101 treatment of primary rat glomerular mesangial cells treated with high glucose significantly reduced their elevated proliferative ability, as assessed by XTT assay and cell cycle analysis. This reduction was associated with decreased levels of p-AKT, increased levels of PTEN and decreased p-GSK3β and p-FoxO3a expression. Pharmacological inhibition of PI3K, mTORC1 and SMAD3 decreased HG-induced collagen accumulation, while inhibition of GSK3β did not affect its elevated levels. AS101 also prevented HG-induced cell growth correlated to mTOR and (rpS6 de-phosphorylation. Thus, pharmacological inhibition of the AKT downstream pathway by AS101 has clinical potential in alleviating the progression of diabetic nephropathy.

  17. Nfix Regulates Temporal Progression of Muscle Regeneration through Modulation of Myostatin Expression

    Directory of Open Access Journals (Sweden)

    Giuliana Rossi

    2016-03-01

    Full Text Available Nfix belongs to a family of four highly conserved proteins that act as transcriptional activators and/or repressors of cellular and viral genes. We previously showed a pivotal role for Nfix in regulating the transcriptional switch from embryonic to fetal myogenesis. Here, we show that Nfix directly represses the Myostatin promoter, thus controlling the proper timing of satellite cell differentiation and muscle regeneration. Nfix-null mice display delayed regeneration after injury, and this deficit is reversed upon in vivo Myostatin silencing. Conditional deletion of Nfix in satellite cells results in a similar delay in regeneration, confirming the functional requirement for Nfix in satellite cells. Moreover, mice lacking Nfix show reduced myofiber cross sectional area and a predominant slow twitching phenotype. These data define a role for Nfix in postnatal skeletal muscle and unveil a mechanism for Myostatin regulation, thus providing insights into the modulation of its complex signaling pathway.

  18. Nfix Regulates Temporal Progression of Muscle Regeneration through Modulation of Myostatin Expression

    Science.gov (United States)

    Rossi, Giuliana; Antonini, Stefania; Bonfanti, Chiara; Monteverde, Stefania; Vezzali, Chiara; Tajbakhsh, Shahragim; Cossu, Giulio; Messina, Graziella

    2016-01-01

    Summary Nfix belongs to a family of four highly conserved proteins that act as transcriptional activators and/or repressors of cellular and viral genes. We previously showed a pivotal role for Nfix in regulating the transcriptional switch from embryonic to fetal myogenesis. Here, we show that Nfix directly represses the Myostatin promoter, thus controlling the proper timing of satellite cell differentiation and muscle regeneration. Nfix-null mice display delayed regeneration after injury, and this deficit is reversed upon in vivo Myostatin silencing. Conditional deletion of Nfix in satellite cells results in a similar delay in regeneration, confirming the functional requirement for Nfix in satellite cells. Moreover, mice lacking Nfix show reduced myofiber cross sectional area and a predominant slow twitching phenotype. These data define a role for Nfix in postnatal skeletal muscle and unveil a mechanism for Myostatin regulation, thus providing insights into the modulation of its complex signaling pathway. PMID:26923583

  19. HABP2 is a novel regulator of hyaluronan-mediated human lung cancer progression

    OpenAIRE

    Tamara eMirzapoiazova; Nurbek eMambetsariev; Frances E Lennon; Bolot eMambetsariev; Joshua E. Berlind; Ravi eSalgia; Singleton, Patrick A.

    2015-01-01

    Background: Lung cancer is a devastating disease with limited treatment options. Many lung cancers have changes in their microenvironment including upregulation of the extracellular matrix glycosaminoglycan, hyaluronan (HA), which we have previously demonstrated can regulate the activity of the extracellular serine protease, Hyaluronan Binding Protein 2 (HABP2). This study examined the functional role of HABP2 on HA-mediated human lung cancer dynamics.Methods: Immunohistochemical analysis was...

  20. HABP2 is a Novel Regulator of Hyaluronan-Mediated Human Lung Cancer Progression

    OpenAIRE

    Mirzapoiazova, Tamara; Mambetsariev, Nurbek; Frances E Lennon; Mambetsariev, Bolot; Joshua E. Berlind; Salgia, Ravi; Singleton, Patrick A.

    2015-01-01

    Background Lung cancer is a devastating disease with limited treatment options. Many lung cancers have changes in their microenvironment including upregulation of the extracellular matrix glycosaminoglycan, hyaluronan (HA), which we have previously demonstrated can regulate the activity of the extracellular serine protease, hyaluronan binding protein 2 (HABP2). This study examined the functional role of HABP2 on HA-mediated human lung cancer dynamics. Methods Immunohistochemical an...

  1. Microarray analysis of differentially expressed genes regulating lipid metabolism during melanoma progression.

    Science.gov (United States)

    Sumantran, Venil N; Mishra, Pratik; Sudhakar, N

    2015-04-01

    A new hallmark of cancer involves acquisition of a lipogenic phenotype which promotes tumorigenesis. Little is known about lipid metabolism in melanomas. Therefore, we used BRB (Biometrics Research Branch) class comparison tool with multivariate analysis to identify differentially expressed genes in human cutaneous melanomas, compared with benign nevi and normal skin derived from the microarray dataset (GDS1375). The methods were validated by identifying known melanoma biomarkers (CITED1, FGFR2, PTPRF, LICAM, SPP1 and PHACTR1) in our results. Eighteen genes regulating metabolism of fatty acids, lipid second messengers and gangliosides were 2-9 fold upregulated in melanomas of GDS-1375. Out of the 18 genes, 13 were confirmed by KEGG pathway analysis and 10 were also significantly upregulated in human melanoma cell lines of NCI-60 Cell Miner database. Results showed that melanomas upregulated PPARGC1A transcription factor and its target genes regulating synthesis of fatty acids (SCD) and complex lipids (FABP3 and ACSL3). Melanoma also upregulated genes which prevented lipotoxicity (CPT2 and ACOT7) and regulated lipid second messengers, such as phosphatidic acid (AGPAT-4, PLD3) and inositol triphosphate (ITPKB, ITPR3). Genes for synthesis of pro-tumorigenic GM3 and GD3 gangliosides (UGCG, HEXA, ST3GAL5 and ST8SIA1) were also upregulated in melanoma. Overall, the microarray analysis of GDS-1375 dataset indicated that melanomas can become lipogenic by upregulating genes, leading to increase in fatty acid metabolism, metabolism of specific lipid second messengers, and ganglioside synthesis.

  2. The impact of regulations, safety considerations and physical limitations on research progress at maximum biocontainment.

    Science.gov (United States)

    Shurtleff, Amy C; Garza, Nicole; Lackemeyer, Matthew; Carrion, Ricardo; Griffiths, Anthony; Patterson, Jean; Edwin, Samuel S; Bavari, Sina

    2012-12-01

    We describe herein, limitations on research at biosafety level 4 (BSL-4) containment laboratories, with regard to biosecurity regulations, safety considerations, research space limitations, and physical constraints in executing experimental procedures. These limitations can severely impact the number of collaborations and size of research projects investigating microbial pathogens of biodefense concern. Acquisition, use, storage, and transfer of biological select agents and toxins (BSAT) are highly regulated due to their potential to pose a severe threat to public health and safety. All federal, state, city, and local regulations must be followed to obtain and maintain registration for the institution to conduct research involving BSAT. These include initial screening and continuous monitoring of personnel, controlled access to containment laboratories, accurate and current BSAT inventory records. Safety considerations are paramount in BSL-4 containment laboratories while considering the types of research tools, workflow and time required for conducting both in vivo and in vitro experiments in limited space. Required use of a positive-pressure encapsulating suit imposes tremendous physical limitations on the researcher. Successful mitigation of these constraints requires additional time, effort, good communication, and creative solutions. Test and evaluation of novel vaccines and therapeutics conducted under good laboratory practice (GLP) conditions for FDA approval are prioritized and frequently share the same physical space with important ongoing basic research studies. The possibilities and limitations of biomedical research involving microbial pathogens of biodefense concern in BSL-4 containment laboratories are explored in this review.

  3. The Impact of Regulations, Safety Considerations and Physical Limitations on Research Progress at Maximum Biocontainment

    Directory of Open Access Journals (Sweden)

    Jean Patterson

    2012-12-01

    Full Text Available We describe herein, limitations on research at biosafety level 4 (BSL-4 containment laboratories, with regard to biosecurity regulations, safety considerations, research space limitations, and physical constraints in executing experimental procedures. These limitations can severely impact the number of collaborations and size of research projects investigating microbial pathogens of biodefense concern. Acquisition, use, storage, and transfer of biological select agents and toxins (BSAT are highly regulated due to their potential to pose a severe threat to public health and safety. All federal, state, city, and local regulations must be followed to obtain and maintain registration for the institution to conduct research involving BSAT. These include initial screening and continuous monitoring of personnel, controlled access to containment laboratories, accurate and current BSAT inventory records. Safety considerations are paramount in BSL-4 containment laboratories while considering the types of research tools, workflow and time required for conducting both in vivo and in vitro experiments in limited space. Required use of a positive-pressure encapsulating suit imposes tremendous physical limitations on the researcher. Successful mitigation of these constraints requires additional time, effort, good communication, and creative solutions. Test and evaluation of novel vaccines and therapeutics conducted under good laboratory practice (GLP conditions for FDA approval are prioritized and frequently share the same physical space with important ongoing basic research studies. The possibilities and limitations of biomedical research involving microbial pathogens of biodefense concern in BSL-4 containment laboratories are explored in this review.

  4. [Iron regulation of gene expression in the Bradyrhizobium japonicum/soybean symbiosis]. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Guerinot, M.L.

    1992-06-01

    We wish to address the question of whether iron plays a regulatory role in the Bradyrhizobium japonicum/soybeam symbiosis. Iron may be an important regulatory signal in planta as the bacteria must acquire iron from their plant hosts and iron-containing proteins figure prominently in all nitrogen-fixing symbioses. For example, the bacterial partner is believed to synthesize the heme moiety of leghemoglobin, which may represent as much as 25--30% of the total soluble protein in an infected plant cell. For this reason, we have focused our attention on the regulation by iron of the first step in the bacterial heme biosynthetic pathway. The enzyme which catalyzes this step, 5-aminolevulinic acid synthase, is encoded by the hemA gene which we had previously cloned and sequenced. Specific objectives include: to define the cis-acting sequences which confer iron regulation on the B. japonicum hemA gene; to identify trans-acting factors which regulate the expression of hemA by iron; to identify new loci which are transcriptionally responsive to changes in iron availability; and to examine the effects of mutations in various known regulatory genes for their effect on the expression of hemA.

  5. Meiotic regulation of TPX2 protein levels governs cell cycle progression in mouse oocytes.

    Directory of Open Access Journals (Sweden)

    Stéphane Brunet

    Full Text Available Formation of female gametes requires acentriolar spindle assembly during meiosis. Mitotic spindles organize from centrosomes and via local activation of the RanGTPase on chromosomes. Vertebrate oocytes present a RanGTP gradient centred on chromatin at all stages of meiotic maturation. However, this gradient is dispensable for assembly of the first meiotic spindle. To understand this meiosis I peculiarity, we studied TPX2, a Ran target, in mouse oocytes. Strikingly, TPX2 activity is controlled at the protein level through its accumulation from meiosis I to II. By RNAi depletion and live imaging, we show that TPX2 is required for spindle assembly via two distinct functions. It controls microtubule assembly and spindle pole integrity via the phosphorylation of TACC3, a regulator of MTOCs activity. We show that meiotic spindle formation in vivo depends on the regulation of at least a target of Ran, TPX2, rather than on the regulation of the RanGTP gradient itself.

  6. 20 CFR 655.30 - Supervised recruitment.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Supervised recruitment. 655.30 Section 655.30... Workers) § 655.30 Supervised recruitment. (a) Supervised recruitment. Where an employer is found to have... failed to adequately conduct recruitment activities or failed in any obligation of this part, the CO may...

  7. 40 CFR 35.935-8 - Supervision.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Supervision. 35.935-8 Section 35.935-8... ASSISTANCE Grants for Construction of Treatment Works-Clean Water Act § 35.935-8 Supervision. In the case of... supervision and inspection of the project to ensure that the construction conforms with the approved plans...

  8. Supervision Experiences of New Professional School Counselors

    Science.gov (United States)

    Bultsma, Shawn A.

    2012-01-01

    This qualitative study examined the supervision experiences of 11 new professional school counselors. They reported that their supervision experiences were most often administrative in nature; reports of clinical and developmental supervision were limited to participants whose supervisors were licensed as professional counselors. In addition,…

  9. 10 CFR 35.27 - Supervision.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Supervision. 35.27 Section 35.27 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL General Administrative Requirements § 35.27 Supervision. (a) A... under the supervision of an authorized user, as allowed by § 35.11(b)(1), shall— (1) In addition to...

  10. 28 CFR 2.91 - Supervision responsibility.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Supervision responsibility. 2.91 Section 2.91 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT OF....91 Supervision responsibility. (a) Pursuant to D.C. Code 24-133(c), the District of Columbia...

  11. 75 FR 59799 - Office of Thrift Supervision

    Science.gov (United States)

    2010-09-28

    ... Office of Thrift Supervision Purchase of Branch Office(s) and/or Transfer of Assets/Liabilities AGENCY: Office of Thrift Supervision (OTS), Treasury. ACTION: Notice and request for comment. SUMMARY: The... Supervision within the Department of the Treasury will submit the proposed information collection...

  12. 7 CFR 70.12 - Supervision.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Supervision. 70.12 Section 70.12 Agriculture... PRODUCTS AND RABBIT PRODUCTS Grading of Poultry Products and Rabbit Products General § 70.12 Supervision. All grading service shall be subject to supervision at all times by the responsible State...

  13. 7 CFR 550.33 - Administrative supervision.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Administrative supervision. 550.33 Section 550.33... Agreements Program Management § 550.33 Administrative supervision. REE employees are prohibited from engaging... management issues. The cooperator is solely responsible for the administrative supervision of its employees....

  14. 27 CFR 46.79 - Supervision.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Supervision. 46.79 Section... § 46.79 Supervision. Before payment is made under this subpart in respect of the tax, or tax and duty... under the supervision of an appropriate TTB officer who will be assigned for that purpose by...

  15. 24 CFR 200.105 - Mortgagor supervision.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Mortgagor supervision. 200.105... supervision. (a) As long as the Commissioner is the insurer or holder of the mortgage, the Commissioner shall... Regulatory Agreement or other instrument granting the Commissioner supervision of the mortgagor....

  16. The Learning Alliance: Ethics in Doctoral Supervision

    Science.gov (United States)

    Halse, Christine; Bansel, Peter

    2012-01-01

    This paper is concerned with the ethics of relationships in doctoral supervision. We give an overview of four paradigms of doctoral supervision that have endured over the past 25 years and elucidate some of their strengths and limitations, contextualise them historically and consider their implications for doctoral supervision in the contemporary…

  17. 32 CFR 631.3 - Supervision.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Supervision. 631.3 Section 631.3 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL....3 Supervision. The following will develop and have staff supervision over AFDCB and...

  18. 9 CFR 354.13 - Supervision.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Supervision. 354.13 Section 354.13... CERTIFICATION VOLUNTARY INSPECTION OF RABBITS AND EDIBLE PRODUCTS THEREOF Basis of Service § 354.13 Supervision. All inspection service shall be subject to supervision at all times by the station supervisor,...

  19. Skærpet bevidsthed om supervision

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This article presents a historical survey of the initiatives which have taken place in european music therapy towards developing a deeper consciousness about supervision. Supervision as a disciplin in music therapy training, as a maintenance of music therapy profession and as a postgraduate...... training for examined music therapists. Definitions are presented and methods developed by working groups in european music therapy supervision are presented....

  20. Multicultural Supervision: What Difference Does Difference Make?

    Science.gov (United States)

    Eklund, Katie; Aros-O'Malley, Megan; Murrieta, Imelda

    2014-01-01

    Multicultural sensitivity and competency represent critical components to contemporary practice and supervision in school psychology. Internship and supervision experiences are a capstone experience for many new school psychologists; however, few receive formal training and supervision in multicultural competencies. As an increased number of…

  1. A National Survey of School Counselor Supervision Practices: Administrative, Clinical, Peer, and Technology Mediated Supervision

    Science.gov (United States)

    Perera-Diltz, Dilani M.; Mason, Kimberly L.

    2012-01-01

    Supervision is vital for personal and professional development of counselors. Practicing school counselors (n = 1557) across the nation were surveyed to explore current supervision practices. Results indicated that 41.1% of school counselors provide supervision. Although 89% receive some type of supervision, only 10.3% of school counselors receive…

  2. [Regulation of terpene metabolism]. Annual progress report, March 15, 1991--March 14, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1992-12-31

    This report describes accomplishments over the past year on understanding of terpene synthesis in mint plants and sage. Specifically reported are the fractionation of 4-S-limonene synthetase, the enzyme responsible for the first committed step to monoterpene synthesis, along with isolation of the corresponding RNA and DNA cloning of its gene; the localization of the enzyme within the oil glands, regulation of transcription and translation of the synthetase, the pathway to camphor biosynthesis,a nd studies on the early stages and branch points of the isoprenoid pathway.

  3. Supervision Experiences of Professional Counselors Providing Crisis Counseling

    Science.gov (United States)

    Dupre, Madeleine; Echterling, Lennis G.; Meixner, Cara; Anderson, Robin; Kielty, Michele

    2014-01-01

    In this phenomenological study, the authors explored supervision experiences of 13 licensed professional counselors in situations requiring crisis counseling. Five themes concerning crisis and supervision were identified from individual interviews. Findings support intensive, immediate crisis supervision and postlicensure clinical supervision.

  4. [Regulation of terpene metabolism]. Annual progress report, March 15, 1990--March 14, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1991-12-31

    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target ``regulatory`` enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C{sub 15}-C{sub 30}) produced by oil glands.

  5. Rho GTPase-independent regulation of mitotic progression by the RhoGEF Net1.

    Science.gov (United States)

    Menon, Sarita; Oh, Wonkyung; Carr, Heather S; Frost, Jeffrey A

    2013-09-01

    Neuroepithelial transforming gene 1 (Net1) is a RhoA-subfamily-specific guanine nucleotide exchange factor that is overexpressed in multiple human cancers and is required for proliferation. Molecular mechanisms underlying its role in cell proliferation are unknown. Here we show that overexpression or knockdown of Net1 causes mitotic defects. Net1 is required for chromosome congression during metaphase and generation of stable kinetochore microtubule attachments. Accordingly, inhibition of Net1 expression results in spindle assembly checkpoint activation. The ability of Net1 to control mitosis is independent of RhoA or RhoB activation, as knockdown of either GTPase does not phenocopy effects of Net1 knockdown on nuclear morphology, and effects of Net1 knockdown are effectively rescued by expression of catalytically inactive Net1. We also observe that Net1 expression is required for centrosomal activation of p21-activated kinase and its downstream kinase Aurora A, which are critical regulators of centrosome maturation and spindle assembly. These results identify Net1 as a novel regulator of mitosis and indicate that altered expression of Net1, as occurs in human cancers, may adversely affect genomic stability.

  6. PFTK1 Promotes Gastric Cancer Progression by Regulating Proliferation, Migration and Invasion.

    Science.gov (United States)

    Yang, Lei; Zhu, Jia; Huang, Hua; Yang, Qichang; Cai, Jing; Wang, Qiuhong; Zhu, Junya; Shao, Mengting; Xiao, Jinzhang; Cao, Jie; Gu, Xiaodan; Zhang, Shusen; Wang, Yingying

    2015-01-01

    PFTK1, also known as PFTAIRE1, CDK14, is a novel member of Cdc2-related serine/threonine protein kinases. Recent studies show that PFTK1 is highly expressed in several malignant tumors such as hepatocellular carcinoma, esophageal cancer, breast cancer, and involved in regulation of cell cycle, tumors proliferation, migration, and invasion that further influence the prognosis of tumors. However, the expression and physiological significance of PFTK1 in gastric cancer remain unclear. In this study, we analyzed the expression and clinical significance of PFTK1 by Western blot in 8 paired fresh gastric cancer tissues, nontumorous gastric mucosal tissues and immunohistochemistry on 161 paraffinembedded slices. High PFTK1 expression was correlated with the tumor grade, lymph node invasion as well as Ki-67. Through Cell Counting Kit (CCK)-8 assay, flow cytometry, colony formation, wound healing and transwell assays, the vitro studies demonstrated that PFTK1 overexpression promoted proliferation, migration and invasion of gastric cancer cells, while PFTK1 knockdown led to the opposite results. Our findings for the first time supported that PFTK1 might play an important role in the regulation of gastric cancer proliferation, migration and would provide a novel promising therapeutic strategy against human gastric cancer.

  7. Gamma-actin is involved in regulating centrosome function and mitotic progression in cancer cells.

    Science.gov (United States)

    Po'uha, Sela T; Kavallaris, Maria

    2015-01-01

    Reorganization of the actin cytoskeleton during mitosis is crucial for regulating cell division. A functional role for γ-actin in mitotic arrest induced by the microtubule-targeted agent, paclitaxel, has recently been demonstrated. We hypothesized that γ-actin plays a role in mitosis. Herein, we investigated the effect of γ-actin in mitosis and demonstrated that γ-actin is important in the distribution of β-actin and formation of actin-rich retraction fibers during mitosis. The reduced ability of paclitaxel to induce mitotic arrest as a result of γ-actin depletion was replicated with a range of mitotic inhibitors, suggesting that γ-actin loss reduces the ability of broad classes of anti-mitotic agents to induce mitotic arrest. In addition, partial depletion of γ-actin enhanced centrosome amplification in cancer cells and caused a significant delay in prometaphase/metaphase. This prolonged prometaphase/metaphase arrest was due to mitotic defects such as uncongressed and missegregated chromosomes, and correlated with an increased presence of mitotic spindle abnormalities in the γ-actin depleted cells. Collectively, these results demonstrate a previously unknown role for γ-actin in regulating centrosome function, chromosome alignment and maintenance of mitotic spindle integrity.

  8. ERG Cooperates with Androgen Receptor in Regulating Trefoil Factor 3 in Prostate Cancer Disease Progression

    Directory of Open Access Journals (Sweden)

    David S. Rickman

    2010-12-01

    Full Text Available To elucidate the role of ETS gene fusions in castration-resistant prostate cancer (CRPC, we characterized the transcriptome of 54 CRPC tumor samples from men with locally advanced or metastatic disease. Trefoil factor 3 (TFF3 emerged as the most highly differentially regulated gene with respect to ERG rearrangement status and resistance to hormone ablation therapy. Conventional chromatin immunoprecipitation (ChIP-polymerase chain reaction and ChIP followed by DNA sequencing (ChIP-seq revealed direct binding of ERG to ETS binding sites in the TFF3 promoter in ERG-rearranged prostate cancer cell lines. These results were confirmed in ERG-rearranged hormone-naive prostate cancer (HNPC and CRPC tissue samples. Functional studies demonstrated that ERG has an inhibitory effect on TFF3 expression in hormone-naive cancer but not in the castration-resistant state. In addition, we provide evidence suggesting an effect of androgen receptor signaling on ERG-regulated TFF3 expression. Furthermore, TFF3 overexpression enhances ERG-mediated cell invasion in CRPC prostate cancer cells. Taken together, our findings reveal a novel mechanism for enhanced tumor cell aggressiveness resulting from ERG rearrangement in the castration-resistant setting through TFF3 gene expression.

  9. ERG cooperates with androgen receptor in regulating trefoil factor 3 in prostate cancer disease progression.

    Science.gov (United States)

    Rickman, David S; Chen, Ying-Bei; Banerjee, Samprit; Pan, Yihang; Yu, Jindan; Vuong, Terry; Perner, Sven; Lafargue, Christopher J; Mertz, Kirsten D; Setlur, Sunita R; Sircar, Kanishka; Chinnaiyan, Arul M; Bismar, Tarek A; Rubin, Mark A; Demichelis, Francesca

    2010-12-01

    To elucidate the role of ETS gene fusions in castration-resistant prostate cancer (CRPC), we characterized the transcriptome of 54 CRPC tumor samples from men with locally advanced or metastatic disease. Trefoil factor 3 (TFF3) emerged as the most highly differentially regulated gene with respect to ERG rearrangement status and resistance to hormone ablation therapy. Conventional chromatin immunoprecipitation (ChIP)-polymerase chain reaction and ChIP followed by DNA sequencing (ChIP-seq) revealed direct binding of ERG to ETS binding sites in the TFF3 promoter in ERG-rearranged prostate cancer cell lines. These results were confirmed in ERG-rearranged hormone-naive prostate cancer (HNPC) and CRPC tissue samples. Functional studies demonstrated that ERG has an inhibitory effect on TFF3 expression in hormone-naive cancer but not in the castration-resistant state. In addition, we provide evidence suggesting an effect of androgen receptor signaling on ERG-regulated TFF3 expression. Furthermore, TFF3 overexpression enhances ERG-mediated cell invasion in CRPC prostate cancer cells. Taken together, our findings reveal a novel mechanism for enhanced tumor cell aggressiveness resulting from ERG rearrangement in the castration-resistant setting through TFF3 gene expression.

  10. Clinical group supervision in yoga therapy: model effects, and lessons learned.

    Science.gov (United States)

    Forbes, Bo; Volpe Horii, Cassandra; Earls, Bethany; Mashek, Stephanie; Akhtar, Fiona

    2012-01-01

    Clinical supervision is an integral component of therapist training and professional development because of its capacity for fostering knowledge, self-awareness, and clinical acumen. Individual supervision is part of many yoga therapy training programs and is referenced in the IAYT Standards as "mentoring." Group supervision is not typically used in the training of yoga therapists. We propose that group supervision effectively supports the growth and development of yoga therapists-in-training. We present a model of group supervision for yoga therapist trainees developed by the New England School of Integrative Yoga Therapeutics™ (The NESIYT Model) that includes the background, structure, format, and development of our inaugural 18-month supervision group. Pre-and post-supervision surveys and analyzed case notes, which captured key didactic and process themes, are discussed. Clinical issues, such as boundaries, performance anxiety, sense of self efficacy, the therapeutic alliance, transference and counter transference, pacing of yoga therapy sessions, evaluation of client progress, and adjunct therapist interaction are reviewed. The timing and sequence of didactic and process themes and benefits for yoga therapist trainees' professional development, are discussed. The NESIYT group supervision model is offered as an effective blueprint for yoga therapy training programs.

  11. Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

    Directory of Open Access Journals (Sweden)

    R. A. Contreras

    2016-01-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studied in vitro and in vivo in experimental animal model of autoimmune and inflammatory disorders. Based on these studies, MSCs are currently widely used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA characterized by complex deregulation of the immune systems. However, the therapeutic properties of MSCs in arthritis are still controverted. These controversies might be due to the diversity of MSC sources and isolation protocols used, the time, the route and dose of MSC administration, the variety of the mechanisms involved in the MSCs suppressive effects, and the complexity of arthritis pathogenesis. In this review, we discuss the role of the interactions between MSCs and the different immune cells associated with arthritis pathogenesis and the possible means described in the literature that could enhance MSCs therapeutic potential counteracting arthritis development and progression.

  12. Lin28/let-7 axis regulates aerobic glycolysis and cancer progression via PDK1.

    Science.gov (United States)

    Ma, Xiaoyu; Li, Chenchen; Sun, Linchong; Huang, De; Li, Tingting; He, Xiaoping; Wu, Gongwei; Yang, Zheng; Zhong, Xiuying; Song, Libing; Gao, Ping; Zhang, Huafeng

    2014-10-10

    Aberrant expression of Lin28 and let-7 has been observed in many human malignancies. However, its functions and underlying mechanisms remain largely elusive. Here we show that aberrant expression of Lin28 and let-7 facilitates aerobic glycolysis, or Warburg effect, in cancer cells. Mechanistically, we discover that Lin28A and Lin28B enhance, whereas let-7 suppresses, aerobic glycolysis via targeting pyruvate dehydrogenase kinase 1, or PDK1, in a hypoxia- or hypoxia-inducible factor-1 (HIF-1)-independent manner, illustrating a novel pathway to mediate aerobic glycolysis of cancer cells even in ambient oxygen levels. Importantly, we further demonstrate that PDK1 is critical for Lin28A- and Lin28B-mediated cancer proliferation both in vitro and in vivo, establishing a previously unappreciated mechanism by which Lin28/let-7 axis facilitates Warburg effect to promote cancer progression. Our findings suggest a potential rationale to target PDK1 for cancer therapy in malignancies with aberrant expression of Lin28 and let-7.

  13. Microsomal PGE2 synthase-1 regulates melanoma cell survival and associates with melanoma disease progression.

    Science.gov (United States)

    Kim, Sun-Hee; Hashimoto, Yuuri; Cho, Sung-Nam; Roszik, Jason; Milton, Denái R; Dal, Fulya; Kim, Sangwon F; Menter, David G; Yang, Peiying; Ekmekcioglu, Suhendan; Grimm, Elizabeth A

    2016-05-01

    COX-2 and its product PGE2 enhance carcinogenesis and tumor progression, which has been previously reported in melanoma. As most COX inhibitors cause much toxicity, the downstream microsomal PGE2 synthase-1 (mPGES1) is a consideration for targeting. Human melanoma TMAs were employed for testing mPGES1 protein staining intensity and percentage levels, and both increased with clinical stage; employing a different Stage III TMA, mPGES1 intensity (not percentage) associated with reduced patient survival. Our results further show that iNOS was also highly expressed in melanoma tissues with high mPGES1 levels, and iNOS-mediated NO promoted mPGES1 expression and PGE2 production. An mPGES1-specific inhibitor (CAY10526) as well as siRNA attenuated cell survival and increased apoptosis. CAY10526 significantly suppressed tumor growth and increased apoptosis in melanoma xenografts. Our findings support the value of a prognostic and predictive role for mPGES1, and suggest targeting this molecule in the PGE2 pathway as another avenue toward improving melanoma therapy.

  14. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

    Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

  15. Mesenchymal Stem Cells Regulate the Innate and Adaptive Immune Responses Dampening Arthritis Progression

    Science.gov (United States)

    Contreras, R. A.; Djouad, F.

    2016-01-01

    Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to immunomodulate cells from both the innate and the adaptive immune systems promoting an anti-inflammatory environment. During the last decade, MSCs have been intensively studied in vitro and in vivo in experimental animal model of autoimmune and inflammatory disorders. Based on these studies, MSCs are currently widely used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) characterized by complex deregulation of the immune systems. However, the therapeutic properties of MSCs in arthritis are still controverted. These controversies might be due to the diversity of MSC sources and isolation protocols used, the time, the route and dose of MSC administration, the variety of the mechanisms involved in the MSCs suppressive effects, and the complexity of arthritis pathogenesis. In this review, we discuss the role of the interactions between MSCs and the different immune cells associated with arthritis pathogenesis and the possible means described in the literature that could enhance MSCs therapeutic potential counteracting arthritis development and progression. PMID:27847522

  16. B cells promote tumor progression via STAT3 regulated-angiogenesis.

    Directory of Open Access Journals (Sweden)

    Chunmei Yang

    Full Text Available The role of B cells in cancer and the underlying mechanisms remain to be further explored. Here, we show that tumor-associated B cells with activated STAT3 contribute to tumor development by promoting tumor angiogenesis. B cells with or without Stat3 have opposite effects on tumor growth and tumor angiogenesis in both B16 melanoma and Lewis Lung Cancer mouse models. Ex vivo angiogenesis assays show that B cell-mediated tumor angiogenesis is mainly dependent on the induction of pro-angiogenic gene expression, which requires Stat3 signaling in B cells. Furthermore, B cells with activated STAT3 are mainly found in or near tumor vasculature and correlate significantly with overall STAT3 activity in human tumors. Moreover, the density of B cells in human tumor tissues correlates significantly with expression levels of several STAT3-downstream pro-angiogenic genes, as well as the degree of tumor angiogenesis. Together, these findings define a novel role of B cells in promoting tumor progression through angiogenesis and identify STAT3 in B cells as potential therapeutic target for anti-angiogenesis therapy.

  17. [Software version and medical device software supervision].

    Science.gov (United States)

    Peng, Liang; Liu, Xiaoyan

    2015-01-01

    The importance of software version in the medical device software supervision does not cause enough attention at present. First of all, the effect of software version in the medical device software supervision is discussed, and then the necessity of software version in the medical device software supervision is analyzed based on the discussion of the misunderstanding of software version. Finally the concrete suggestions on software version naming rules, software version supervision for the software in medical devices, and software version supervision scheme are proposed.

  18. Coordination of Recombination with Meiotic Progression in the Caenorhabditis elegans Germline by KIN-18, a TAO Kinase That Regulates the Timing of MPK-1 Signaling.

    Science.gov (United States)

    Yin, Yizhi; Donlevy, Sean; Smolikove, Sarit

    2016-01-01

    Meiosis is a tightly regulated process requiring coordination of diverse events. A conserved ERK/MAPK-signaling cascade plays an essential role in the regulation of meiotic progression. The Thousand And One kinase (TAO) kinase is a MAPK kinase kinase, the meiotic role of which is unknown. We have analyzed the meiotic functions of KIN-18, the homolog of mammalian TAO kinases, in Caenorhabditis elegans. We found that KIN-18 is essential for normal meiotic progression; mutants exhibit accelerated meiotic recombination as detected both by analysis of recombination intermediates and by crossover outcome. In addition, ectopic germ-cell differentiation and enhanced levels of apoptosis were observed in kin-18 mutants. These defects correlate with ectopic activation of MPK-1 that includes premature, missing, and reoccurring MPK-1 activation. Late progression defects in kin-18 mutants are suppressed by inhibiting an upstream activator of MPK-1 signaling, KSR-2. However, the acceleration of recombination events observed in kin-18 mutants is largely MPK-1-independent. Our data suggest that KIN-18 coordinates meiotic progression by modulating the timing of MPK-1 activation and the progression of recombination events. The regulation of the timing of MPK-1 activation ensures the proper timing of apoptosis and is required for the formation of functional oocytes. Meiosis is a conserved process; thus, revealing that KIN-18 is a novel regulator of meiotic progression in C. elegans would help to elucidate TAO kinase's role in germline development in higher eukaryotes.

  19. [Regulation of terpene metabolism]. Annual progress report, March 15, 1989--March 14, 1990

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1989-11-09

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C{sub 10}) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C{sub 15} C{sub 20}, C{sub 30}, C{sub 40}) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C{sub 15}) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  20. Progressive effects of silver nanoparticles on hormonal regulation of reproduction in male rats.

    Science.gov (United States)

    Dziendzikowska, K; Krawczyńska, A; Oczkowski, M; Królikowski, T; Brzóska, K; Lankoff, A; Dziendzikowski, M; Stępkowski, T; Kruszewski, M; Gromadzka-Ostrowska, J

    2016-12-15

    The growing use of silver nanoparticles (AgNPs) in various applications, including consumer, agriculture and medicine products, has raised many concerns about the potential risks of nanoparticles (NPs) to human health and the environment. An increasing body of evidence suggests that AgNPs may have adverse effects of humans, thus the aim of this study was to investigate the effects of AgNPs on the male reproductive system. Silver particles (20nm AgNPs (groups Ag I and Ag II) and 200nm Ag sub-micron particles (SPs) (group Ag III)) were administered intravenously to male Wistar rats at a dose of 5 (groups Ag I and Ag III) or 10 (group Ag II) mg/kg of body weight. The biological material was sampled 24h, 7days and 28days after injection. The obtained results revealed that the AgNPs had altered the luteinising hormone concentration in the plasma and the sex hormone concentration in the plasma and testes. Plasma and intratesticular levels of testosterone and dihydrotestosterone were significantly decreased both 7 and 28days after treatment. No change in the prolactin and sex hormone-binding globulin concentration was observed. Exposure of the animals to AgNPs resulted in a considerable decrease in 5α-reductase type 1 and the aromatase protein level in the testis. Additionally, expression analysis of genes involved in steroidogenesis and the steroids metabolism revealed significant down-regulation of Star, Cyp11a1, Hsd3b1, Hsd17b3 and Srd5a1 mRNAs in AgNPs/AgSPs-exposed animals. The present study demonstrates the potential adverse effect on the hormonal regulation of the male reproductive function following AgNP/AgSP administration, in particular alterations of the sex steroid balance and expression of genes involved in steroidogenesis and the steroids metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Heme oxygenase-1 regulates the progression of K/BxN serum transfer arthritis.

    Directory of Open Access Journals (Sweden)

    Rita Brines

    Full Text Available BACKGROUND: Heme oxygenase-1 (HO-1 is induced in many cell types as a defense mechanism against stress. We have investigated the possible role of endogenous HO-1 in the effector phase of arthritis using the K/BxN serum transfer model of arthritis in HO-1 heterozygous and homozygous knock-out mice. METHODOLOGY/PRINCIPAL FINDINGS: Arthritis was induced in C57/Black-6 xFVB (HO-1(+/+, HO-1(+/- and HO-1(-/- mice by intraperitoneal injection of 150 µl serum from arthritic K/BxN mice at days 0 and 2. Blood was collected and animals were sacrificed at day 10. Histological analysis was performed in ankle sections. The levels of inflammatory mediators were measured in serum and paw homogenates by enzyme-linked immunosorbent assay or Multiplex technology. The incidence of arthritis was higher in HO-1(+/- and HO-1(-/- groups compared with HO-1(+/+. The inflammatory response was aggravated in HO-1(+/- mice as shown by arthritic score and the migration of inflammatory cells that could be related to the enhancement of CXCL-1 production. In addition, the HO-1(+/- group showed proteoglycan depletion significantly higher than HO-1(+/+ mice. Serum levels of matrix metalloproteinase-3, monocyte chemotactic protein-1, plasminogen activator inhibitor-1, E-selectin and intercellular adhesion molecule-1 were increased in arthritic HO-1(-/- mice, whereas vascular endothelial growth factor and some cytokines such as interferon-γ showed a reduction compared to HO-1(+/+ or HO-1(+/- mice. In addition, down-regulated gene expression of ferritin, glutathione S-reductase A1 and superoxide dismutase-2 was observed in the livers of arthritic HO-1(+/- animals. CONCLUSION/SIGNIFICANCE: Endogenous HO-1 regulates the production of systemic and local inflammatory mediators and plays a protective role in K/BxN serum transfer arthritis.

  2. Clinical supervision training across contexts.

    Science.gov (United States)

    Tai, Joanna; Bearman, Margaret; Edouard, Vicki; Kent, Fiona; Nestel, Debra; Molloy, Elizabeth

    2016-08-01

    Clinicians require specific skills to teach or supervise students in the workplace; however, there are barriers to accessing faculty member development, such as time, cost and suitability. The Clinical Supervision Support Across Contexts (ClinSSAC) programme was designed to provide accessible interprofessional educator training to clinical supervisors across a wide range of clinical settings. In Australia there are increasing numbers of health care students, creating pressure on existing placements. Students are now increasingly learning in community settings, where clinicians have traditionally had less access to faculty member development. An interprofessional team collaborated in the development and implementation of ClinSSAC. A total of 978 clinicians participated in a face-to-face, interactive, introductory module to clinical supervision; 672 people accessed the equivalent online core module, with 23 per cent completing all activities. Additional profession-and discipline-specific modules were also developed. Formal project evaluation found that most participants rated the workshops as helpful or very helpful for their roles as clinical supervisors. Interdisciplinary learning from the workshops was reported to enable cross-discipline supervision. Large participant numbers and favourable ratings indicate a continuing need for basic training in education. Key factors to workshop success included expert facilitators, the interprofessional context and interactive model. The online modules were an important adjunct, and provided context-specific resources, but the low online completion rate suggests protected face-to-face time for faculty member development is still required. Programmes such as ClinSSAC have the capacity to promote interprofessional education and practice. There are barriers to accessing faculty member development, such as time, cost and suitability. © 2015 John Wiley & Sons Ltd.

  3. Learning Dynamics in Doctoral Supervision

    DEFF Research Database (Denmark)

    Kobayashi, Sofie

    This doctoral research explores doctoral supervision within life science research in a Danish university. From one angle it investigates doctoral students’ experiences with strengthening the relationship with their supervisors through a structured meeting with the supervisor, prepared as part...... of an introduction course for new doctoral students. This study showed how the course provides an effective way build supervisee agency and strengthening supervisory relationships through clarification and alignment of expectations and sharing goals about doctoral studies. From the other angle the research...

  4. Semi-supervised sparse coding

    KAUST Repository

    Wang, Jim Jing-Yan

    2014-07-06

    Sparse coding approximates the data sample as a sparse linear combination of some basic codewords and uses the sparse codes as new presentations. In this paper, we investigate learning discriminative sparse codes by sparse coding in a semi-supervised manner, where only a few training samples are labeled. By using the manifold structure spanned by the data set of both labeled and unlabeled samples and the constraints provided by the labels of the labeled samples, we learn the variable class labels for all the samples. Furthermore, to improve the discriminative ability of the learned sparse codes, we assume that the class labels could be predicted from the sparse codes directly using a linear classifier. By solving the codebook, sparse codes, class labels and classifier parameters simultaneously in a unified objective function, we develop a semi-supervised sparse coding algorithm. Experiments on two real-world pattern recognition problems demonstrate the advantage of the proposed methods over supervised sparse coding methods on partially labeled data sets.

  5. Effect of Shensong Yangxin on the Progression of Paroxysmal Atrial Fibrillation is Correlated with Regulation of Autonomic Nerve Activity

    Science.gov (United States)

    Zhao, Hong-Yi; Zhang, Shu-Di; Zhang, Kai; Wang, Xi; Zhao, Qing-Yan; Zhang, Shu-Juan; Dai, Zi-Xuan; Qian, Yong-Sheng; Zhang, You-Jing; Wei, Hao-Tian; Tang, Yan-Hong; Huang, Cong-Xin

    2017-01-01

    Background: Shensong Yangxin (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the mechanism of SSYX on atrial fibrillation (AF) is unknown. In this study, we tested the hypothesis that the effect of SSYX on the progression of paroxysmal AF is correlated with the regulation of autonomic nerve activity. Methods: Eighteen mongrel dogs were randomly divided into control group (n = 6), pacing group (n = 6), and pacing + SSYX group (n = 6). The control group was implanted with pacemakers without pacing; the pacing group was implanted with pacemakers with long-term intermittent atrial pacing; the pacing + SSYX group underwent long-term intermittent atrial pacing and SSYX oral administration. Results: Compared to the pacing group, the parameters of heart rate variability were lower after 8 weeks in the pacing + SSYX group (low-frequency [LF] component: 20.85 ± 3.14 vs. 15.3 ± 1.89 ms2, P = 0.004; LF component/high-frequency component: 1.34 ± 0.33 vs. 0.77 ± 0.15, P dogs in the pacing group had more episodes and longer durations of AF than that in the pacing + SSYX group. SSYX markedly inhibited the increase in sympathetic nerves and upregulation of tumor necrosis factor-alpha and interleukin-6 expression in the pacing + SSYX group. Furthermore, SSYX suppressed the decrease of acetylcholine and α7 nicotinic acetylcholine receptor protein induced by long-term intermittent atrial pacing. Conclusions: SSYX substantially prevents atrial electrical remodeling and the progression of AF. These effects of SSYX may have association with regulating the imbalance of autonomic nerve activity and the cholinergic anti-inflammatory pathway. PMID:28091409

  6. Inhibitory Effect of 1,8-Cineol on β-Catenin Regulation, WNT11 Expression, and Cellular Progression in HNSCC

    Directory of Open Access Journals (Sweden)

    Anna Roettger

    2017-05-01

    Full Text Available ObjectivesHead and neck squamous cell carcinoma (HNSCC is one of the most common tumors worldwide. The high mortality rates have not changed during the last three decades, and thus there is an enormous need for innovative therapy approaches. Several recent studies suggest an important role of the Wnt/β-catenin signaling pathway in the tumorigenesis of HNSCC. We analyzed the effect of the monoterpene oxide 1,8-cineol on the regulation of the Wnt/β-catenin signaling pathway and the cellular progression of different HNSCC cell lines.MethodsPermanent HNSCC cell lines were exposed to varying concentrations and times of 1,8-cineol. Regulation and activity profiles of the Wnt/β-catenin signaling cascade were analyzed using Western hybridization experiments, MTT assays, real-time PCR-based epithelial to mesenchymal transition array, and immunohistochemistry.ResultsExposure of different cell lines to 1,8-cineol treatment resulted in a dose-dependent inhibition of proliferation and a decreased activity of the WNT/β-catenin pathway. We can show the inhibition of glycogen synthase kinase 3 (GSK-3α/β (Ser-9/21 as well as a corresponding decreased endolysosomal localization, leading to a decreased β-catenin activity. Furthermore, we can show that exposure to cineol functionally results in a reduced expression of WNT11.ConclusionIn this work, we demonstrate for the first time that 1,8-cineol acts as an inhibitor of the Wnt/β-catenin activity in HNSCC via a decreased inhibition of GSK-3, which lead to reduced levels of WNT11 and a dose-dependent decrease of the cellular progression. Our data represent a new mechanism of 1,8-cineol activity, which may lead to novel molecular targets and treatment approaches of this natural drug.

  7. Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: a novel mechanistic insight into progressive obesity.

    Science.gov (United States)

    Dai, Zhiyu; Qi, Weiwei; Li, Cen; Lu, Juling; Mao, Yuling; Yao, Yachao; Li, Lei; Zhang, Ting; Hong, Honghai; Li, Shuai; Zhou, Ti; Yang, Zhonghan; Yang, Xia; Gao, Guoquan; Cai, Weibin

    2013-09-05

    Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Specific changes in the expression of imprinted genes in prostate cancer-implications for cancer progression and epigenetic regulation

    Institute of Scientific and Technical Information of China (English)

    Teodora Ribarska; Klaus-Marius Bastian; Annemarie Koch; Wolfgang A Schulz

    2012-01-01

    Epigenetic dysregulation comprising DNA hypermethylation and hypomethylation,enhancer of zeste homologue 2 (EZH2)overexpression and altered patterns of histone modifications is associated with the progression of prostate cancer.DNA methylation,EZH2 and histone modifications also ensure the parental-specific monoallelic expression of at least 62 imprinted genes.Although it is therefore tempting to speculate that epigenetic dysregulation may extend to imprinted genes,expression changes in cancerous prostates are only well documented for insulin-like growth factor 2 (IGF2).A literature and database survey on imprinted genes in prostate cancer suggests that the expression of most imprinted genes remains unchanged despite global disturbances in epigenetic mechanisms.Instead,selective genetic and epigenetic changes appear to lead to the inactivation of a sub-network of imprinted genes,which might function in the prostate to limit cell growth induced viathe PI3K/Akt pathway,modulate androgen responses and regulate differentiation.Whereas dysregulation of IG F2 may constitute an early change in prostate carcinogenesis,inactivation of this imprinted gene network is rather associated with cancer progression.

  9. Feedback regulation between atypical E2Fs and APC/CCdh1 coordinates cell cycle progression.

    Science.gov (United States)

    Boekhout, Michiel; Yuan, Ruixue; Wondergem, Annelotte P; Segeren, Hendrika A; van Liere, Elsbeth A; Awol, Nesibu; Jansen, Imke; Wolthuis, Rob M F; de Bruin, Alain; Westendorp, Bart

    2016-03-01

    E2F transcription factors control the oscillating expression pattern of multiple target genes during the cell cycle. Activator E2Fs, E2F1-3, induce an upswing of E2F targets, which is essential for the G1-to-S phase transition, whereas atypical E2Fs, E2F7 and E2F8, mediate a downswing of the same targets during late S, G2, and M phases. Expression of atypical E2Fs is induced by E2F1-3, but it is unknown how atypical E2Fs are inactivated in a timely manner. Here, we demonstrate that E2F7 and E2F8 are substrates of the anaphase-promoting complex/cyclosome (APC/C). Removal of CDH1, or mutating the CDH1-interacting KEN boxes, stabilized E2F7/8 from anaphase onwards and during G1. Expressing KEN mutant E2F7 during G1 impairs S phase entry and eventually results in cell death. Furthermore, we show that E2F8, but not E2F7, interacts also with APC/C(C) (dc20). Importantly, atypical E2Fs can activate APC/C(C) (dh1) by repressing its inhibitors cyclin A, cyclin E, and Emi1. In conclusion, we discovered a feedback loop between atypical E2Fs and APC/C(C) (dh1), which ensures balanced expression of cell cycle genes and normal cell cycle progression.

  10. Ski regulates Hippo and TAZ signaling to suppress breast cancer progression.

    Science.gov (United States)

    Rashidian, Juliet; Le Scolan, Erwan; Ji, Xiaodan; Zhu, Qingwei; Mulvihill, Melinda M; Nomura, Daniel; Luo, Kunxin

    2015-02-10

    Ski, the transforming protein of the avian Sloan-Kettering retrovirus, inhibits transforming growth factor-β (TGF-β)/Smad signaling and displays both pro-oncogenic and anti-oncogenic activities in human cancer. Inhibition of TGF-β signaling is likely responsible for the pro-oncogenic activity of Ski. We investigated the mechanism(s) underlying the tumor suppressor activity of Ski and found that Ski suppressed the activity of the Hippo signaling effectors TAZ and YAP to inhibit breast cancer progression. TAZ and YAP are transcriptional coactivators that can contribute to cancer by promoting proliferation, tumorigenesis, and cancer stem cell expansion. Hippo signaling activates the the Lats family of kinases, which phosphorylate TAZ and YAP, resulting in cytoplasmic retention and degradation and inhibition of their transcriptional activity. We showed that Ski interacted with multiple components of the Hippo pathway to facilitate activation of Lats2, resulting in increased phosphorylation and subsequent degradation of TAZ. Ski also promoted the degradation of a constitutively active TAZ mutant that is not phosphorylated by Lats, suggesting the existence of a Lats2-independent degradation pathway. Finally, we showed that Ski repressed the transcriptional activity of TAZ by binding to the TAZ partner TEAD and recruiting the transcriptional co-repressor NCoR1 to the TEAD-TAZ complex. Ski effectively reversed transformation and epithelial-to-mesenchyme transition in cultured breast cancer cells and metastasis in TAZ-expressing xenografted tumors. Thus, Ski inhibited the function of TAZ through multiple mechanisms in human cancer cells.

  11. Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

    Directory of Open Access Journals (Sweden)

    Martinez Fernando J

    2010-09-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.

  12. Nursing supervision for care comprehensiveness.

    Science.gov (United States)

    Chaves, Lucieli Dias Pedreschi; Mininel, Vivian Aline; Silva, Jaqueline Alcântara Marcelino da; Alves, Larissa Roberta; Silva, Maria Ferreira da; Camelo, Silvia Helena Henriques

    2017-01-01

    To reflect on nursing supervision as a management tool for care comprehensiveness by nurses, considering its potential and limits in the current scenario. A reflective study based on discourse about nursing supervision, presenting theoretical and practical concepts and approaches. Limits on the exercise of supervision are related to the organization of healthcare services based on the functional and clinical model of care, in addition to possible gaps in the nurse training process and work overload. Regarding the potential, researchers emphasize that supervision is a tool for coordinating care and management actions, which may favor care comprehensiveness, and stimulate positive attitudes toward cooperation and contribution within teams, co-responsibility, and educational development at work. Nursing supervision may help enhance care comprehensiveness by implying continuous reflection on including the dynamics of the healthcare work process and user needs in care networks. refletir a supervisão de enfermagem como instrumento gerencial do enfermeiro para integralidade do cuidado, considerando suas potencialidades e limitações no cenário atual. estudo reflexivo baseado na formulação discursiva sobre a supervisão de enfermagem, apresentando conceitos e enfoques teóricos e/ou práticos. limitações no exercício da supervisão estão relacionadas à organização dos serviços de saúde embasada no modelo funcional e clínico de atenção, assim como possíveis lacunas no processo de formação do enfermeiro e sobrecarga de trabalho. Quanto às potencialidades, destaca-se a supervisão como instrumento de articulação de ações assistenciais e gerenciais, que pode favorecer integralidade da atenção, estimular atitudes de cooperação e colaboração em equipe, além da corresponsabilização e promoção da educação no trabalho. supervisão de enfermagem pode contribuir para fortalecimento da integralidade do cuidado, pressupondo reflexão cont

  13. Regulation and market power in the Spanish liquefied petroleum gas industry: Progress or failure?

    Energy Technology Data Exchange (ETDEWEB)

    Bello, Alejandro; Huerta, Emilio [Departamento de Gestion de Empresas, Universidad Publica de Navarra, Campus de Arrosadia, 31006 Pamplona, Navarra (Spain)

    2007-07-15

    This paper presents a detailed study of the structure, market power and competition in the distribution sector for liquefied petroleum gas (LPG), within Spain. It is a segment of energy consumption and supply that is not often given serious attention, despite the fact that LPG is a crucial source of energy to many households, in many countries in Europe and in the rest of the world. Despite formally being an open and liberalized sector, the Spanish LPG market is characterized by high concentration within the industry; Repsol Butano, the dominant operator, practically controls the entire value chain. These structural characteristics probably justify state intervention in the form of price fixing, in order to guarantee accessible prices for final consumers. Nevertheless, applying this tool has had negative effects on the opening and liberalization process. On the one hand, it fails to encourage entry or an increase in the participation of new operators; on the other, it has considerably deteriorated the economic and financial performance of the distribution agents that are subjected to two strong forces. First, the dominant operator looks after its own interests and its income; and second, the Government tries to defend the interests of final consumers by fixing prices that inadequately remunerate the activity. This shows the contradictory regulatory actions that try to promote competition, and then establish mechanisms to regulate activity by fixing prices that act as price limits. These government set prices discourage new competitors from entering. (author)

  14. Structure and regulation of an archaebacterial promoter: An in vivo study. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, C.J.

    1993-12-31

    In the initial grant period the authors have devised an in vivo assay system for the analysis of gene expression in the halophilic archaea. This system has been used to analyzed the H. volcanii tRNALys promoter where it was found that the a 40 bp fragment carrying BoxA and BoxB sequences in sufficient for in vivo expression. Detailed analysis of the BoxA element indicates that the BoxA TA sequence is essential for efficient expression. Support for the hypothesis that all archaea share common transcriptional signals was obtained when a methanogen tRNAGln gene, with its associated BoxA sequence, was found to direct its own transcription in H. volcanii. In related experiments a eukaryotic RNA polymerase 3 terminator was found to act as a strong termination signal in H. volcanii. Sequence comparisons between this element and mapped RNA 3{prime} ends indicates that T-rich sequences may be important role in directing termination in vivo. Finally, in an attempt to establish a model system to study regulated gene expression, the authors have isolated a DNA fragment that encodes a heat shock inaudible transcript. This gene will not serve as a model for detailed studies of the mechanisms of gene expression in the archaea.

  15. Ubiquitin-specific protease 14 regulates cardiac hypertrophy progression by increasing GSK-3β phosphorylation.

    Science.gov (United States)

    Liu, Ningning; Chai, Renjie; Liu, Bin; Zhang, Zhenhui; Zhang, Shuangwei; Zhang, Jingzhi; Liao, Yuning; Cai, Jianyu; Xia, Xiaohong; Li, Aiqun; Liu, Jinbao; Huang, Hongbiao; Liu, Shiming

    2016-09-23

    Cardiac hypertrophy, a compensatory response to various stimuli in the heart, independently predicts cardiovascular ailments and related deaths. Increasing evidence indicates ubiquitin-proteasome signaling contributes to cardiac hypertrophy regulation. Here, we identified ubiquitin-specific protease 14 (USP14), a 19S proteasome associated deubiquitinase (DUB), as a novel target for cardiac hypertrophy therapy via inhibition of the GSK-3β pathway. Indeed, USP14 expression was increased in an animal model of abdominal aorta constriction. In an angiotensin II (AngII) induced primary neonatal rat cardiomyocyte hypertrophy model, USP14 expression was increased in a time-dependent manner, and reduced USP14 deubiquitinase activity or USP14 knockdown resulted in lower expression levels of the myocardial hypertrophy specific marker β-MHC, and subsequent decreased GSK-3β phosphorylation. In conclusion, USP14 mediates the development of cardiac hypertrophy by promoting GSK-3β phosphorylation, suggesting that USP14 might represent a novel therapeutic target for cardiac hypertrophy treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Progress in the Study of Acupuncture in Regulating Post-Cerebral Ischemia/Reperfusion Cell-Apoptosis Related Gene Expression

    Institute of Scientific and Technical Information of China (English)

    卜渊; 耿德勤; 曾因明

    2003-01-01

    @@ Cerebralvascular disease has already become one of the serious illnesses that threatens human health. Along with the development of medicine, although the therapeutic method harvested huge progress, currently ideal therapeutic methods are lacking. The conventional acupuncture has definite therapeutic effect on cerebropathy. Clinical practice and various animal experiments confirmed that acupuncture could alleviate the pathologic damage after cerebral ischemic injury and promote the nerve function recovery. Past studies showed that the role of acupuncture in treating cerebral ischemia is realized through alleviating post-ischemic neuron necrosis, while recent study discovered that acupuncture has inhibitory effect on post-ischemia induced neuronal necrosis(1), which brought the mechanism of acupuncture in treating cerebral ischemia from the biochemical and metabolical level to the molecular biologic level. The studies revealed that after cerebral ischemia, many genes were induced to express themselves, protein product they coded directly or indirectly participated in the regulation of post-cerebral ischemia apoptosis of neuron, some promoting the apoptosis, while others inhibiting apoptosis with some of the function still unclear. The anti-apoptotic effect of acupuncture is accomplished through regulating the relevant apoptotic gene expression(2), and now it is reviewed as follows:

  17. Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle Progression through Def Recruitment of Calpain3

    Science.gov (United States)

    Tao, Ting; Shi, Hui; Lo, Li Jan; Wang, Yingchun; Chen, Jun; Peng, Jinrong

    2016-01-01

    Digestive organ expansion factor (Def) is a nucleolar protein that plays dual functions: it serves as a component of the ribosomal small subunit processome for the biogenesis of ribosomes and also mediates p53 degradation through the cysteine proteinase calpain-3 (CAPN3). However, nothing is known about the exact relationship between Def and CAPN3 or the regulation of the Def function. In this report, we show that CAPN3 degrades p53 and its mutant proteins p53A138V, p53M237I, p53R248W, and p53R273P but not the p53R175H mutant protein. Importantly, we show that Def directly interacts with CAPN3 in the nucleoli and determines the nucleolar localisation of CAPN3, which is a prerequisite for the degradation of p53 in the nucleolus. Furthermore, we find that Def is modified by phosphorylation at five serine residues: S50, S58, S62, S87, and S92. We further show that simultaneous phosphorylations at S87 and S92 facilitate the nucleolar localisation of Capn3 that is not only essential for the degradation of p53 but is also important for regulating cell cycle progression. Hence, we propose that the Def-CAPN3 pathway serves as a nucleolar checkpoint for cell proliferation by selective inactivation of cell cycle-related substrates during organogenesis. PMID:27657329

  18. Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1.

    Science.gov (United States)

    Champhekar, Ameya; Damle, Sagar S; Freedman, George; Carotta, Sebastian; Nutt, Stephen L; Rothenberg, Ellen V

    2015-04-15

    The ETS family transcription factor PU.1 is essential for the development of several blood lineages, including T cells, but its function in intrathymic T-cell precursors has been poorly defined. In the thymus, high PU.1 expression persists through multiple cell divisions in early stages but then falls sharply during T-cell lineage commitment. PU.1 silencing is critical for T-cell commitment, but it has remained unknown how PU.1 activities could contribute positively to T-cell development. Here we employed conditional knockout and modified antagonist PU.1 constructs to perturb PU.1 function stage-specifically in early T cells. We show that PU.1 is needed for full proliferation, restricting access to some non-T fates, and controlling the timing of T-cell developmental progression such that removal or antagonism of endogenous PU.1 allows precocious access to T-cell differentiation. Dominant-negative effects reveal that this repression by PU.1 is mediated indirectly. Genome-wide transcriptome analysis identifies novel targets of PU.1 positive and negative regulation affecting progenitor cell signaling and cell biology and indicating distinct regulatory effects on different subsets of progenitor cell transcription factors. Thus, in addition to supporting early T-cell proliferation, PU.1 regulates the timing of activation of the core T-lineage developmental program.

  19. Over-expression of tetraspanin 8 in malignant glioma regulates tumor cell progression

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Si-Jian [Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025 (China); Wu, Yue-Bing [Department of Internal Medicine Oncology, Hubei Cancer Hospital, Wuhan, Hubei 430079 (China); Cai, Shang [Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Suzhou 21500 (China); Pan, Yi-Xin; Liu, Wei [Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Bian, Liu-Guan [Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025 (China); Sun, Bomin [Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Sun, Qing-Fang, E-mail: sunqingfang11@163.com [Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025 (China)

    2015-03-13

    Tumor cell invasion and proliferation remain the overwhelming causes of death for malignant glioma patients. To establish effective therapeutic methods, new targets implied in these processes have to be identified. Tetraspanin 8 (Tspn8) forms complexes with a large variety of trans-membrane and/or cytosolic proteins to regulate several important cellular functions. In the current study, we found that Tspn8 was over-expressed in multiple clinical malignant glioma tissues, and its expression level correlated with the grade of tumors. Tspn8 expression in malignant glioma cells (U251MG and U87MG lines) is important for cell proliferation and migration. siRNA-mediated knockdown of Tspn8 markedly reduced in vitro proliferation and migration of U251MG and U87MG cells. Meanwhile, Tspn8 silencing also increased the sensitivity of temozolomide (TMZ), and significantly increased U251MG or U87MG cell death and apoptosis by TMZ were achieved with Tspn8 knockdown. We observed that Tspn8 formed a complex with activated focal adhesion kinase (FAK) in both human malignant glioma tissues and in above glioma cells. This complexation appeared required for FAK activation, since Tspn8 knockdown inhibited FAK activation in U251MG and U87MG cells. These results provide evidence that Tspn8 contributes to the pathogenesis of glioblastoma probably by promoting proliferation, migration and TMZ-resistance of glioma cells. Therefore, targeting Tspn8 may provide a potential therapeutic intervention for malignant glioma. - Highlights: • Tspn8 is over-expressed in multiple clinical malignant glioma tissues. • Tspn8 expression is correlated with the grade of malignant gliomas. • Tspn8 knockdown suppresses U251MG/U87MG proliferation and in vitro migration. • Tspn8 knockdown significantly increases TMZ sensitivity in U251MG/U87MG cells. • Tspn8 forms a complex with FAK, required for FAK activation.

  20. Chromofungin Ameliorates the Progression of Colitis by Regulating Alternatively Activated Macrophages

    Directory of Open Access Journals (Sweden)

    Nour Eissa

    2017-09-01

    Full Text Available Ulcerative colitis (UC is characterized by a functional dysregulation of alternatively activated macrophage (AAM and intestinal epithelial cells (IECs homeostasis. Chromogranin-A (CHGA secreted by neuroendocrine cells is implicated in intestinal inflammation and immune dysregulation. CHGA undergoes proteolytic processing to generate CHGA-derived peptides. Chromofungin (CHR: CHGA47–66 is a short CHGA-derived peptide encoded by CHGA Exon-IV and is involved in innate immune regulation, but the basis is poorly investigated. We investigated the expression of CHR in colonic tissue of patients with active UC and assessed the effects of the CHR in dextran sulfate sodium (DSS colitis in mice and on macrophages and human colonic epithelial cells. We found that mRNA expression of CHR correlated positively with mRNA levels of AAM markers and gene expression of tight junction (TJ proteins and negatively with mRNA levels of interleukin (IL-8, IL-18, and collagen in patients with active UC. Moreover, AAM markers correlated positively with gene expression of TJ proteins and negatively with IL-8, IL-18, and collagen gene expression. Experimentally, intracolonic administration of CHR protected against DSS-induced colitis by priming macrophages into AAM, reducing colonic collagen deposition, and maintaining IECs homeostasis. This effect was associated with a significant increase of AAM markers, reduction of colonic IL-18 release and conservation of gene expression of TJ proteins. In vitro, CHR enhanced AAM polarization and increased the production of anti-inflammatory mediators. CHR-treated AAM conditioned medium increased Caco-2 cell migration, viability, proliferation, and mRNA levels of TJ proteins, and decreased oxidative stress-induced apoptosis and proinflammatory cytokines release. Direct CHR treatments had the same effect. In conclusion, CHR treatment reduces the severity of colitis and the inflammatory process via enhancing AAM functions and maintaining

  1. Efficacy of a randomized controlled self-regulation based physical activity intervention for chronic fatigue: Mediation effects of physical activity progress and self-regulation skills.

    Science.gov (United States)

    Marques, M M; de Gucht, V; Leal, I; Maes, S

    2017-03-01

    Examine the medium-term effects of a brief physical activity (PA) self-regulation (SR) based intervention (4-STEPS program) for chronic fatigue, and explore the mediating effects of PA related variables and SR skills. A two-arm randomized controlled trial (Usual Care vs 4-STEPS) was carried out. The 4-STEPS program consisted of Motivational Interviewing and SR-skills training. Fatigue severity (primary outcome) and impact, PA, health-related quality of life (HrQoL), and somatic and psychological distress were assessed at baseline, post-treatment (12weeks) and 12months follow-up. Ninety-one patients (45 intervention and 46 controls) were included. At follow-up, there were significant treatment effects on fatigue severity (g=0.72) and fatigue impact, leisure-time PA, and physical and psychological HrQoL. No significant effects were found for number of daily steps and somatic and psychological distress. Fatigue severity at follow-up was partially mediated by post-treatment progress on a personal PA goal (effect ratio=18%). Results suggest that a brief intervention, focusing on the formulation and pursuit of personal PA goals and the use of SR skills, produces sustained benefits for fatigue severity. Despite these promising results, dropout was high and the intervention was not beneficial for all secondary outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Sundhedsfaglig supervision som klinisk metode

    DEFF Research Database (Denmark)

    Nordentoft, Helle Merete

    2011-01-01

    Kapitlet gennemgår og diskuterer sundhedsfaglig supervision (SFS) som metode. Formålet med kapitlet er at give læseren indsigt i og et kritisk blik på metodens muligheder og begrænsninger. Indledningsvis uddyber kapitlet den historiske baggrund for SFS og hvordan metoden udfolder sig i praksis me...... metodens fremtidige perspektiver - set i lyset af de mange nye metoder, der 'kæmper' om de samme målgrupper i vejledningslandskabet så som f.eks. coaching, debriefing og mentoring....

  3. Supervised Object Class Colour Normalisation

    DEFF Research Database (Denmark)

    Riabchenko, Ekatarina; Lankinen, Jukka; Buch, Anders Glent;

    2013-01-01

    Colour is an important cue in many applications of computer vision and image processing, but robust usage often requires estimation of the unknown illuminant colour. Usually, to obtain images invariant to the illumination conditions under which they were taken, color normalisation is used....... In this work, we develop a such colour normalisation technique, where true colours are not important per se but where examples of same classes have photometrically consistent appearance. This is achieved by supervised estimation of a class specic canonical colour space where the examples have minimal variation...

  4. The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation

    Science.gov (United States)

    The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G2/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 depositi...

  5. Status Quo Of Drug Supervision in China

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Drugs are a special kind of commodity used to prevent,treat and diagnose diseases.Effective supervision of drugs has a great bearing on ensuring the safe use of pharmaceuticals by consumers and on safeguarding the right to lire and health of the general public.The Chinese government has always attached great importance to supervision over drug safety,and has always been commltted to the goal of strengthening such supervision and guaranteeing public drug safety.

  6. On Training Targets for Supervised Speech Separation

    OpenAIRE

    Wang, Yuxuan; Narayanan, Arun; Wang, DeLiang

    2014-01-01

    Formulation of speech separation as a supervised learning problem has shown considerable promise. In its simplest form, a supervised learning algorithm, typically a deep neural network, is trained to learn a mapping from noisy features to a time-frequency representation of the target of interest. Traditionally, the ideal binary mask (IBM) is used as the target because of its simplicity and large speech intelligibility gains. The supervised learning framework, however, is not restricted to the...

  7. GRP78 as a regulator of liver steatosis and cancer progression mediated by loss of the tumor suppressor PTEN.

    Science.gov (United States)

    Chen, W-T; Zhu, G; Pfaffenbach, K; Kanel, G; Stiles, B; Lee, A S

    2014-10-16

    Glucose-regulated protein 78 (GRP78), a molecular chaperone widely elevated in human cancers, is critical for endoplasmic reticulum (ER) protein folding, stress signaling and PI3K/AKT activation. Genetic knockout models of GRP78 revealed that GRP78 maintains homeostasis of metabolic organs, including liver, pancreas and adipose tissues. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the most common liver cancers. There is a lack of effective therapeutics for HCC and CC, highlighting the need to further understand liver tumorigenic mechanisms. PTEN (phosphatase and tenson homolog deleted on chromosome 10), a tumor suppressor that antagonizes the PI3K/AKT pathway, is inactivated in a wide range of tumors, including 40-50% of human liver cancers. To elucidate the role of GRP78 in liver cancer, we created a mouse model with biallelic liver-specific deletion of Pten and Grp78 mediated by Albumin-Cre-recombinase (cP(f/f)78(f/f)). Interestingly, in contrast to PTEN, deletion of GRP78 was progressive but incomplete. At 3 months, cP(f/f)78(f/f) livers showed hepatomegaly, activation of lipogenic genes, exacerbated steatosis and liver injury, implying that GRP78 protects the liver against PTEN-null-mediated pathogenesis. Furthermore, in response to liver injury, we observed increased proliferation and expansion of bile duct and liver progenitor cells in cP(f/f)78(f/f) livers. Strikingly, bile duct cells in cP(f/f)78(f/f) livers maintained wild-type (WT) GRP78 level, whereas adjacent areas showed GRP78 reduction. Analysis of signaling pathways revealed selective JNK activation, β-catenin downregulation, along with PDGFRα upregulation, which was unique to cP(f/f)78(f/f) livers at 6 months. Development of both HCC and CC was accelerated and was evident in cP(f/f)78(f/f) livers at 8-9 months, coinciding with intense GRP78 expression in the cancer lesions, and GRP78 expression in adjacent normal areas reverted back to the WT level. In contrast, c78(f/f) livers

  8. Supervised Discrete Hashing With Relaxation.

    Science.gov (United States)

    Gui, Jie; Liu, Tongliang; Sun, Zhenan; Tao, Dacheng; Tan, Tieniu

    2016-12-29

    Data-dependent hashing has recently attracted attention due to being able to support efficient retrieval and storage of high-dimensional data, such as documents, images, and videos. In this paper, we propose a novel learning-based hashing method called ''supervised discrete hashing with relaxation'' (SDHR) based on ''supervised discrete hashing'' (SDH). SDH uses ordinary least squares regression and traditional zero-one matrix encoding of class label information as the regression target (code words), thus fixing the regression target. In SDHR, the regression target is instead optimized. The optimized regression target matrix satisfies a large margin constraint for correct classification of each example. Compared with SDH, which uses the traditional zero-one matrix, SDHR utilizes the learned regression target matrix and, therefore, more accurately measures the classification error of the regression model and is more flexible. As expected, SDHR generally outperforms SDH. Experimental results on two large-scale image data sets (CIFAR-10 and MNIST) and a large-scale and challenging face data set (FRGC) demonstrate the effectiveness and efficiency of SDHR.

  9. Semi-supervised clustering methods

    Science.gov (United States)

    Bair, Eric

    2013-01-01

    Cluster analysis methods seek to partition a data set into homogeneous subgroups. It is useful in a wide variety of applications, including document processing and modern genetics. Conventional clustering methods are unsupervised, meaning that there is no outcome variable nor is anything known about the relationship between the observations in the data set. In many situations, however, information about the clusters is available in addition to the values of the features. For example, the cluster labels of some observations may be known, or certain observations may be known to belong to the same cluster. In other cases, one may wish to identify clusters that are associated with a particular outcome variable. This review describes several clustering algorithms (known as “semi-supervised clustering” methods) that can be applied in these situations. The majority of these methods are modifications of the popular k-means clustering method, and several of them will be described in detail. A brief description of some other semi-supervised clustering algorithms is also provided. PMID:24729830

  10. Clinical supervision by consultants in teaching hospitals.

    Science.gov (United States)

    Hore, Craig T; Lancashire, William; Fassett, Robert G

    2009-08-17

    Clinical supervision is a vital part of postgraduate medical education. Without it, trainees may not learn effectively from their experiences; this may lead to acceptance by registrars and junior doctors of lower standards of care. Currently, supervision is provided by consultants to registrars and junior doctors, and by registrars to junior doctors. Evidence suggests that the clinical supervision provided to postgraduate doctors is inadequate. Registrars and juniors doctors have the right to expect supervision in the workplace. Impediments to the provision of clinical supervision include competing demands of hospital service provision on trainees and supervisors, lack of clarity of job descriptions, private versus public commitments of supervisors and lack of interest. Supervisors should be trained in the process of supervision and provided with the time and resources to conduct it. Those being supervised should be provided with clear expectations of the process. We need to create and develop systems, environments and cultures that support high standards of conduct and effective clinical supervision. These systems must ensure the right to supervision, feedback, support, decent working conditions and respect for both trainees and their supervisors.

  11. EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression

    Directory of Open Access Journals (Sweden)

    Lescaille Géraldine

    2012-03-01

    Full Text Available Abstract Backgrounds An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC progression. Methods Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat. Results OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner. Conclusions Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion.

  12. The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression

    Science.gov (United States)

    He, Chunbo; Mao, Dagan; Hua, Guohua; Lv, Xiangmin; Chen, Xingcheng; Angeletti, Peter C; Dong, Jixin; Remmenga, Steven W; Rodabaugh, Kerry J; Zhou, Jin; Lambert, Paul F; Yang, Peixin; Davis, John S; Wang, Cheng

    2015-01-01

    The Hippo signaling pathway controls organ size and tumorigenesis through a kinase cascade that inactivates Yes-associated protein (YAP). Here, we show that YAP plays a central role in controlling the progression of cervical cancer. Our results suggest that YAP expression is associated with a poor prognosis for cervical cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo signaling pathway and activate YAP to induce cervical cancer cell proliferation and migration. Activated YAP allows for up-regulation of TGF-α, AREG, and EGFR, forming a positive signaling loop to drive cervical cancer cell proliferation. HPV E6 protein, a major etiological molecule of cervical cancer, maintains high YAP protein levels in cervical cancer cells by preventing proteasome-dependent YAP degradation to drive cervical cancer cell proliferation. Results from human cervical cancer genomic databases and an accepted transgenic mouse model strongly support the clinical relevance of the discovered feed-forward signaling loop. Our study indicates that combined targeting of the Hippo and the ERBB signaling pathways represents a novel therapeutic strategy for prevention and treatment of cervical cancer. PMID:26417066

  13. Diversity Competent Group Work Supervision: An Application of the Supervision of Group Work Model (SGW)

    Science.gov (United States)

    Okech, Jane E. Atieno; Rubel, Deborah

    2007-01-01

    This article emphasizes the need for concrete descriptions of supervision to promote diversity-competent group work and presents an application of the supervision of group work model (SGW) to this end. The SGW, a supervision model adapted from the discrimination model, is uniquely suited for promoting diversity competence in group work, since it…

  14. Diversity Competent Group Work Supervision: An Application of the Supervision of Group Work Model (SGW)

    Science.gov (United States)

    Okech, Jane E. Atieno; Rubel, Deborah

    2007-01-01

    This article emphasizes the need for concrete descriptions of supervision to promote diversity-competent group work and presents an application of the supervision of group work model (SGW) to this end. The SGW, a supervision model adapted from the discrimination model, is uniquely suited for promoting diversity competence in group work, since it…

  15. Implementability of Instructional Supervision as a Contemporary Educational Supervision Model in Turkish Education System

    OpenAIRE

    2012-01-01

    In this study, implementability of instructional supervision as one of contemporary educational supervision models in Turkish Education System was evaluated. Instructional supervision which aims to develop instructional processes and increase the quality of student learning based on observation of classroom activities requires collaboration among supervisors and teachers. In this literature review, significant problems have been detected due to structural organization, structural and control-...

  16. Empirical study of supervised gene screening

    Directory of Open Access Journals (Sweden)

    Ma Shuangge

    2006-12-01

    Full Text Available Abstract Background Microarray studies provide a way of linking variations of phenotypes with their genetic causations. Constructing predictive models using high dimensional microarray measurements usually consists of three steps: (1 unsupervised gene screening; (2 supervised gene screening; and (3 statistical model building. Supervised gene screening based on marginal gene ranking is commonly used to reduce the number of genes in the model building. Various simple statistics, such as t-statistic or signal to noise ratio, have been used to rank genes in the supervised screening. Despite of its extensive usage, statistical study of supervised gene screening remains scarce. Our study is partly motivated by the differences in gene discovery results caused by using different supervised gene screening methods. Results We investigate concordance and reproducibility of supervised gene screening based on eight commonly used marginal statistics. Concordance is assessed by the relative fractions of overlaps between top ranked genes screened using different marginal statistics. We propose a Bootstrap Reproducibility Index, which measures reproducibility of individual genes under the supervised screening. Empirical studies are based on four public microarray data. We consider the cases where the top 20%, 40% and 60% genes are screened. Conclusion From a gene discovery point of view, the effect of supervised gene screening based on different marginal statistics cannot be ignored. Empirical studies show that (1 genes passed different supervised screenings may be considerably different; (2 concordance may vary, depending on the underlying data structure and percentage of selected genes; (3 evaluated with the Bootstrap Reproducibility Index, genes passed supervised screenings are only moderately reproducible; and (4 concordance cannot be improved by supervised screening based on reproducibility.

  17. Consolidated supervision of financial institutions and financial market in the Republic of Croatia

    Directory of Open Access Journals (Sweden)

    Bojana Olgić Draženović

    2005-06-01

    Full Text Available The question of regulation and supervision of all parts of financial system is of major importance for any country. In order to protect the interest of the society and to accelerate the economic development, it is necessary to provide adequate legal framework as well as independent supervision institutions. The regulations refer mostly to maintenance of financial stability and consumer protection. The article points out that the structure of the financial sector in the Republic of Croatia is underdeveloped and characterized by domination of the banking sector. Therefore, bank supervision is one of the main tasks of Croatian national bank and all other financial institutions (except banks are regulated by other regulatory institutions. The problems of authority overlapping and insufficient regulation are becoming more complex by the development of financial sector and especially by the deregulation of financial markets. Because of that, it is reasonable to investigate the existing regulatory framework of Croatian financial system concerning its structure and development.

  18. 基于互联网金融创新与监管关系新特点下的监督政策研究%The Research on Regulation and Supervision Policy Based on the New Features of the Relationship between Internet Financial Innovation and Regulation

    Institute of Scientific and Technical Information of China (English)

    陆岷峰; 吴建平

    2016-01-01

    . One view is that the traditional financial regulation and financial innovation is a kind of positive game relation. Another view is that with the informatization and increased competition, the traditional financial organization’s social function gradually evolves to the dual role of fund resources allocation subject and risk resources allocation subject, so the financial innovation and financial regulation is complementary. Compared with the traditional finance, on the one hand, the nature of the Internet finance is still a kind of finance, so the relationship between Internet financial innovation and regulation is closed to the relationship between the traditional financial innovation and regulation. On the other hand, the Internet finance has its own unique existence and is different from the traditional financial industry, therefore the regulation on the Internet finance should be moderately different from that on the traditional finance. So treatment of the Internet financial innovation and regulation should depend on the different situations, and the Internet finance regulators should respect the market, care for innovations, and promote the healthy development of the Internet finance and better serve for the real economy by mutual support of encouraging the innovation and strengthening the supervision.

  19. The human RNA polymerase II-associated factor 1 (hPaf1): a new regulator of cell-cycle progression.

    Science.gov (United States)

    Moniaux, Nicolas; Nemos, Christophe; Deb, Shonali; Zhu, Bing; Dornreiter, Irena; Hollingsworth, Michael A; Batra, Surinder K

    2009-09-22

    The human PAF (hPAF) complex is part of the RNA polymerase II transcription apparatus and regulates multiple steps in gene expression. Further, the yeast homolog of hPaf1 has a role in regulating the expression of a subset of genes involved in the cell-cycle. We therefore investigated the role of hPaf1 during progression of the cell-cycle. Herein, we report that the expression of hPaf1, a subunit of the hPAF complex, increases with cell-cycle progression and is regulated in a cell-cycle dependant manner. hPaf1 specifically regulates a subclass of genes directly implicated in cell-cycle progression during G1/S, S/G2, and G2/M. In prophase, hPaf1 aligns in filament-like structures, whereas in metaphase it is present within the pole forming a crown-like structure, surrounding the centrosomes. Moreover, hPaf1 is degraded during the metaphase to anaphase transition. In the nucleus, hPaf1 regulates the expression of cyclins A1, A2, D1, E1, B1, and Cdk1. In addition, expression of hPaf1 delays DNA replication but favors the G2/M transition, in part through microtubule assembly and mitotic spindle formation. Our results identify hPaf1 and the hPAF complex as key regulators of cell-cycle progression. Mutation or loss of stoichiometry of at least one of the members may potentially lead to cancer development.

  20. A Gestalt Approach to Group Supervision

    Science.gov (United States)

    Melnick, Joseph; Fall, Marijane

    2008-01-01

    The authors define and then describe the practice of group supervision. The role of creative experiment in assisting supervisees who perceive themselves as confused, moving in circles, or immobilized is described. Fictional case examples illustrate these issues in supervision. The authors posit the "good fit" of Gestalt theory and techniques with…

  1. 19 CFR 146.3 - Customs supervision.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Customs supervision. 146.3 Section 146.3 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) FOREIGN TRADE ZONES General Provisions § 146.3 Customs supervision. (a) Assignment of...

  2. 27 CFR 70.609 - Supervision.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Supervision. 70.609... From Disaster, Vandalism, or Malicious Mischief Destruction of Liquors § 70.609 Supervision. When... official or made unmarketable, the liquors shall be destroyed by suitable means under...

  3. 28 CFR 551.32 - Staff supervision.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Staff supervision. 551.32 Section 551.32 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT MISCELLANEOUS Inmate Organizations § 551.32 Staff supervision. (a) The Warden shall appoint a staff member as...

  4. 17 CFR 166.3 - Supervision.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Supervision. 166.3 Section 166.3 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION CUSTOMER PROTECTION RULES § 166.3 Supervision. Each Commission registrant, except an associated person who has no...

  5. 9 CFR 146.10 - Supervision.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Supervision. 146.10 Section 146.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Supervision. (a) The Official State Agency may designate qualified persons as Authorized Agents to do...

  6. The real relationship in psychotherapy supervision.

    Science.gov (United States)

    Watkins, C Edward

    2011-01-01

    While the real relationship has long been addressed in psychoanalysis and psychotherapy, the matter of the real relationship in psychotherapy supervision has yet to receive any attention. Ample supervisory focus has indeed been given to the working alliance and transference-countertransference configuration (including parallel processes), but after a century of psychotherapy supervision, any mention whatsoever of real relationship phenomena is absent. In this paper, the following hypotheses are proposed: The real relationship (1) is a crucial component of the supervision relationship that has transtheoretical implications; (2) exists from the moment supervision begins until its end; (3) is the forever silent yet forever substantive contributor to supervisory process and outcome; (4) exerts a significant impact on (a) the development and establishment of the supervisory working alliance and (b) the unfolding and eventual utilization of the transference-countertransference experience in the supervisory situation; (5) consists of at least two dimensions in supervision--realism and genuineness--that vary along valence and magnitude continua (building on the works of Greenson and Gelso), and (6) deserves a place of eminence equal to the working alliance and transference-countertransference configuration if supervision theory, practice, and research are to be most fully informed. The possibility of using recent real relationship research in psychotherapy as a prototype to inform future research in supervision is presented, and two case examples are provided to illustrate the seeming power of real relationship phenomena in psychotherapy supervision.

  7. 21 CFR 640.62 - Medical supervision.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Medical supervision. 640.62 Section 640.62 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Source Plasma § 640.62 Medical supervision....

  8. Teacher Supervision Practices and Principals' Characteristics

    Science.gov (United States)

    April, Daniel; Bouchamma, Yamina

    2015-01-01

    A questionnaire was used to determine the individual and collective teacher supervision practices of school principals and vice-principals in Québec (n = 39) who participated in a research-action study on pedagogical supervision. These practices were then analyzed in terms of the principals' sociodemographic and socioprofessional characteristics…

  9. 32 CFR 552.65 - Command supervision.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Command supervision. 552.65 Section 552.65 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY RESERVATIONS AND....65 Command supervision. (a) All insurance business conducted on Army installation will be...

  10. 9 CFR 145.11 - Supervision.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Supervision. 145.11 Section 145.11 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Supervision. (a) The Official State Agency may designate qualified persons as Authorized Agents to do...

  11. Experiencing Higher Degree Research Supervision as Teaching

    Science.gov (United States)

    Bruce, Christine; Stoodley, Ian

    2013-01-01

    This article describes higher degree research supervisors' experiences of supervision as teaching. While research education is considered central to the higher degree research experience, comparatively little is known to date of the teaching lenses adopted by supervisors as they go about their supervision. We worked with 35 supervisors engaged in…

  12. The Agile Approach with Doctoral Dissertation Supervision

    Science.gov (United States)

    Tengberg, Lars Göran Wallgren

    2015-01-01

    Several research findings conclude that many doctoral students fail to complete their studies within the allowable time frame, in part because of problems related to the research and supervision process. Surveys show that most doctoral students are generally satisfied with their dissertation supervision. However, these surveys also reveal some…

  13. Applying Services Marketing Principles to Postgraduate Supervision

    Science.gov (United States)

    Dann, Stephen

    2008-01-01

    Purpose: The paper aims to describe the application of two key service quality frameworks for improving the delivery of postgraduate research supervision. The services quality frameworks are used to identify key areas of overlap between services marketing practice and postgraduate supervision that can be used by the supervisor to improve research…

  14. Applying Services Marketing Principles to Postgraduate Supervision

    Science.gov (United States)

    Dann, Stephen

    2008-01-01

    Purpose: The paper aims to describe the application of two key service quality frameworks for improving the delivery of postgraduate research supervision. The services quality frameworks are used to identify key areas of overlap between services marketing practice and postgraduate supervision that can be used by the supervisor to improve research…

  15. The School Counselor, the Cactus, and Supervision

    Science.gov (United States)

    Boyd, John D.; Walter, Paul B.

    1975-01-01

    The authors suggest that counselor supervision is a viable way to assist school counselors in dealing with lack of professional development opportunities. Supervision can facilitate the counselor's personal and professional development and can promote counselor competencies, accountability and the improvement of guidance services and programs. (SE)

  16. A Gestalt Approach to Group Supervision

    Science.gov (United States)

    Melnick, Joseph; Fall, Marijane

    2008-01-01

    The authors define and then describe the practice of group supervision. The role of creative experiment in assisting supervisees who perceive themselves as confused, moving in circles, or immobilized is described. Fictional case examples illustrate these issues in supervision. The authors posit the "good fit" of Gestalt theory and techniques with…

  17. State Supervision and Control of Radiation Protection

    CERN Document Server

    2001-01-01

    Radiation Protection Centre is carrying state supervision and control of radiation protection. The main objective of state supervision and control of radiation protection is assessing how licensees comply with requirements of the appropriate legislation and enforcement. Summary of inspections conducted in 1999-2001 is presented.

  18. State Radiation Protection Supervision and Control

    CERN Document Server

    2002-01-01

    Radiation Protection Centre is carrying state supervision and control of radiation protection. The main objective of state supervision and control of radiation protection is assessing how licensees comply with requirements of the appropriate legislation and enforcement. Summary of inspections conducted in 2002 is presented.

  19. The Consolidation on Banking Supervision in the Context of a Pan European Banking System

    Directory of Open Access Journals (Sweden)

    Teodora Barbu

    2007-03-01

    Full Text Available The diversity of national banking systems in the European banking system and the absence of consolidated supervision creates the premises for a series of interrogations whose essence is the same: Is it possible to discuss about a Pan European Banking System? The starting point in answering this question was the efforts to create a single banking market, which took place in 1973-1999, and the impact of integration on the European Banking Industry. Among the most representative aspects, it must be emphasized the necessity of consolidating banking supervision at an European level, considering that the International Banking Community studies the problematic of banking regulations at a global level. The two dimensions of the prudential and European bank supervision device – the geographic and the institutional – demand the creation of a structural reform in order to ensure the functioning of a Pan European system of banking supervision and regulations. The considerations on the Consolidation of European Banking Supervision draws into discussion the Financial Supervision Authority which has generalized as an applicable model in numerous European countries and has been mentioned as an alternative of Pan European banking supervision. In the process of the integration of the banking sector, the Basel II Accord represents an opportunity in reaching a convergence of national regulations and practices in matters of risk management, considering that these actions are in line with the preoccupations of realizing a Pan European banking system. Thus, the creation of Pan European banking system involves actions in more directions: legal, institutional, operational meant to ensure the consolidation of banking supervision.

  20. Supervised and unsupervised classification - The case of IRAS point sources

    Science.gov (United States)

    Adorf, Hans-Martin; Meurs, E. J. A.

    Progress is reported on a project which aims at mapping the extragalactic sky in order to derive the large scale distribution of luminous matter. The approach consists in selecting from the IRAS Point Source Catalog a set of galaxies which is as clean and as complete as possible. The decision and discrimination problems involved lend themselves to a treatment using methods from multivariate statistics, in particular statistical pattern recognition. Two different approaches, one based on supervised Bayesian classification, the other on unsupervised data-driven classification, are presented and some preliminary results are reported.

  1. Soluble common gamma chain exacerbates COPD progress through the regulation of inflammatory T cell response in mice

    Directory of Open Access Journals (Sweden)

    Lee B

    2017-03-01

    Full Text Available Byunghyuk Lee,1 Eunhee Ko,1 Jiyeon Lee,2 Yuna Jo,1 Hyunju Hwang,1 Tae Sik Goh,1,3 Myungsoo Joo,2 Changwan Hong1 1Department of Anatomy and Cell Biology, Pusan National University School of Medicine, 2Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, 3Department of Orthopedic Surgery, Medical Research Institute, Pusan National University School of Medicine, Busan, South Korea Abstract: Cigarette smoking (CS is a major cause of considerable morbidity and mortality by inducing lung cancer and COPD. COPD, a smoking-related disorder, is closely related to the alteration of immune system and inflammatory processes that are specifically mediated by T cells. Soluble common gamma chain (sγc has recently been identified as a critical regulator of the development and differentiation of T cells. We examined the effects of sγc in a cigarette smoke extract (CSE mouse model. The sγc level in CSE mice serum is significantly downregulated, and the cellularity of lymph node (LN is systemically reduced in the CSE group. Overexpression of sγc enhances the cellularity and IFNγ production of CD8 T cells in LN and also enhances Th1 and Th17 differentiation of CD4 T cells in the respiratory tract. Mechanistically, the downregulation of sγc expression mediated by CSE is required to prevent excessive inflammatory T cell responses. Therefore, our data suggest that sγc may be one of the target molecules for the control of immunopathogenic progresses in COPD. Keywords: COPD, T cell, soluble common gamma chain, cytokine

  2. The role of supervision in the training of behavior therapists: Case study

    Directory of Open Access Journals (Sweden)

    Raquel Martins Sartori

    2014-08-01

    Full Text Available The therapeutic process therapist requires skills that go beyond the theoretical and technical knowledge, the therapeutic relationship is a prerequisite for the success of behavioral psychotherapy variable. Supervision of clinical care is a fundamental skill development of the future therapist educational resource as well as to increase the supply conditions of a more appropriate psychotherapeutic customer service. The article reports on supervisory experience in the first client of a therapist in training showed behavioral patterns of aggression. The default client produced in therapist behaviors and feelings that hindered progress and therapeutic success. Supervision thus occupied a role in analyzing and modeling the behavior therapist as a strategy to increase the chances of success of the case. As a result of the strategies adopted in supervision, there were changes in the pattern of interaction between therapist and client training with his progress in the case.

  3. Malignant progressive tumor cell clone exhibits significant up-regulation of cofilin-2 and 27-kDa modified form of cofilin-1 compared to regressive clone.

    Science.gov (United States)

    Kuramitsu, Yasuhiro; Wang, Yufeng; Okada, Futoshi; Baron, Byron; Tokuda, Kazuhiro; Kitagawa, Takao; Akada, Junko; Nakamura, Kazuyuki

    2013-09-01

    QR-32 is a regressive murine fibrosarcoma cell clone which cannot grow when they are transplanted in mice; QRsP-11 is a progressive malignant tumor cell clone derived from QR-32 which shows strong tumorigenicity. A recent study showed there to be differentially expressed up-regulated and down-regulated proteins in these cells, which were identified by proteomic differential display analyses by using two-dimensional gel electrophoresis and mass spectrometry. Cofilins are small proteins of less than 20 kDa. Their function is the regulation of actin assembly. Cofilin-1 is a small ubiquitous protein, and regulates actin dynamics by means of binding to actin filaments. Cofilin-1 plays roles in cell migration, proliferation and phagocytosis. Cofilin-2 is also a small protein, but it is mainly expressed in skeletal and cardiac muscles. There are many reports showing the positive correlation between the level of cofilin-1 and cancer progression. We have also reported an increased expression of cofilin-1 in pancreatic cancer tissues compared to adjacent paired normal tissues. On the other hand, cofilin-2 was significantly less expressed in pancreatic cancer tissues. Therefore, the present study investigated the comparison of the levels of cofilin-1 and cofilin-2 in regressive QR-32 and progressive QRsP-11cells by western blotting. Cofilin-2 was significantly up-regulated in QRsP-11 compared to QR-32 cells (p<0.001). On the other hand, the difference of the intensities of the bands of cofilin-1 (18 kDa) in QR-32 and QRsP-11 was not significant. However, bands of 27 kDa showed a quite different intensity between QR-32 and QRsP-11, with much higher intensities in QRsP-11 compared to QR-32 (p<0.001). These results suggested that the 27-kDa protein recognized by the antibody against cofilin-1 is a possible biomarker for progressive tumor cells.

  4. Is it possible to strengthen psychiatric nursing staff's clinical supervision?

    DEFF Research Database (Denmark)

    Gonge, Henrik; Buus, Niels

    2015-01-01

    AIM: To test the effects of a meta-supervision intervention in terms of participation, effectiveness and benefits of clinical supervision of psychiatric nursing staff. BACKGROUND: Clinical supervision is regarded as a central component in developing mental health nursing practices, but the evidence...... on individuals or wards already actively engaged in clinical supervision, which suggested that individuals and wards without well-established supervision practices may require more comprehensive interventions targeting individual and organizational barriers to clinical supervision....

  5. Supervision over technological and measurement processes

    Directory of Open Access Journals (Sweden)

    T. Karkoszka

    2011-01-01

    Full Text Available Purpose: of the paper has been an attainment of the thesis: “If there is something we can define, we can measure it. If there is something we can measure, we can analyse that. If there is something we can analyse, we can supervise that. If there is something we can supervise, we can improve that [1]”.Design/methodology/approach: used for the analysis has covered proposition of the supervision over measurement processes system that can be applied in quality assurance.Findings: of analysis are as follows: system of supervision over measurement processes performed (in compliance with real, realised in an organisation processes, can assure the achievement of the accurate and reliable results that, being the base of any feedback in any process, have fundamental meaning in making appropriate decisions.Practical implications: can be applied in case of any organisation, wanting to demonstrate the conformity of processes in the range of requirements that apply to: products, workers, natural environment and others by supervision over measurement equipment.Originality/value: of the presented paper has been obtained by working out the design of supervision over measurement system, also measurement system capability, which should be supplement for supervision over processes system in the assurance of processes and products quality.

  6. Providing effective supervision in clinical neuropsychology.

    Science.gov (United States)

    Stucky, Kirk J; Bush, Shane; Donders, Jacobus

    2010-01-01

    A specialty like clinical neuropsychology is shaped by its selection of trainees, educational standards, expected competencies, and the structure of its training programs. The development of individual competency in this specialty is dependent to a considerable degree on the provision of competent supervision to its trainees. In clinical neuropsychology, as in other areas of professional health-service psychology, supervision is the most frequently used method for teaching a variety of skills, including assessment, report writing, differential diagnosis, and treatment. Although much has been written about the provision of quality supervision in clinical and counseling psychology, very little published guidance is available regarding the teaching and provision of supervision in clinical neuropsychology. The primary focus of this article is to provide a framework and guidance for the development of suggested competency standards for training of neuropsychological supervisors, particularly at the residency level. In this paper we outline important components of supervision for neuropsychology trainees and suggest ways in which clinicians can prepare for supervisory roles. Similar to Falender and Shafranske (2004), we propose a competency-based approach to supervision that advocates for a science-informed, formalized, and objective process that clearly delineates the competencies required for good supervisory practice. As much as possible, supervisory competencies are related to foundational and functional competencies in professional psychology, as well as recent legislative initiatives mandating training in supervision. It is our hope that this article will foster further discussion regarding this complex topic, and eventually enhance training in clinical neuropsychology.

  7. Colleague Supervision--"Ignored and Undervalued"? The Views of Students and Supervisors in a New University

    Science.gov (United States)

    Watson, Tom

    2012-01-01

    Colleague supervision is increasingly used in UK modern (post-92) universities to support the progress of academic staff to doctoral qualifications. Denicolo (2004) argues that it is a "role relationship that has been largely ignored or undervalued by administration" (p. 693) and colleague students and supervisors "felt more…

  8. Design of the multicenter standardized supervised exercise training intervention for the claudication: exercise vs endoluminal revascularization (CLEVER) study.

    Science.gov (United States)

    Bronas, Ulf G; Hirsch, Alan T; Murphy, Timothy; Badenhop, Dalynn; Collins, Tracie C; Ehrman, Jonathan K; Ershow, Abby G; Lewis, Beth; Treat-Jacobson, Diane J; Walsh, M Eileen; Oldenburg, Niki; Regensteiner, Judith G

    2009-11-01

    The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

  9. MicroRNA-574-5p was pivotal for TLR9 signaling enhanced tumor progression via down-regulating checkpoint suppressor 1 in human lung cancer.

    Directory of Open Access Journals (Sweden)

    Qinchuan Li

    Full Text Available Accumulating data suggested that functional expression of Toll-like receptors (TLRs in tumor cells was involved in tumor progression. Our previous study demonstrated that TLR9 signaling could enhance the tumor progression of human lung cancer cells in vitro and in vivo. We further showed that miR-574-5p was the mostly up-regulated miRNA in human lung cancer cells under TLR9 signaling by miRNA array analysis. Here we characterized the potential role of miRNA-574-5p in enhanced tumor progression induced by TLR9 signaling in human lung cancer. We confirmed that TLR9 signaling effectively elevated the expression of miR-574-5p in human lung cancer cells. Notably, we found that down-regulation of miRNA-574-5p using miR-574-5p inhibitor in vitro or miR-574-5p sponge in vivo significantly abrogated the enhanced tumor progression induced by TLR9 signaling. Further studies showed that miR-574-5p was an important player associated with enhanced tumor progression of human lung cancer cells. Notably, we identified checkpoint suppressor 1 (Ches1 as the dominant direct target for miRNA-574-5p to confer the TLR9 signaling enhanced tumor progression. We revealed that over-expression of Ches1 significantly inhibited the cell cycle entry of human lung cancer cells. Finally, we revealed that the expression of miR-574-5p was positively correlated with TLR9 and reversely correlated with Ches1 in lung cancer patients. Our findings not only facilitated the further understanding of the crosstalk between miRNAs and TLRs in tumor biology, but also provided novel potential candidates for treatment of cancer.

  10. ARTD1 regulates cyclin E expression and consequently cell-cycle re-entry and G1/S progression in T24 bladder carcinoma cells.

    Science.gov (United States)

    Léger, Karolin; Hopp, Ann-Katrin; Fey, Monika; Hottiger, Michael O

    2016-08-02

    ADP-ribosylation is involved in a variety of biological processes, many of which are chromatin-dependent and linked to important functions during the cell cycle. However, any study on ADP-ribosylation and the cell cycle faces the problem that synchronization with chemical agents or by serum starvation and subsequent growth factor addition already activates ADP-ribosylation by itself. Here, we investigated the functional contribution of ARTD1 in cell cycle re-entry and G1/S cell cycle progression using T24 urinary bladder carcinoma cells, which synchronously re-enter the cell cycle after splitting without any additional stimuli. In synchronized cells, ARTD1 knockdown, but not inhibition of its enzymatic activity, caused specific down-regulation of cyclin E during cell cycle re-entry and G1/S progression through alterations of the chromatin composition and histone acetylation, but not of other E2F-1 target genes. Although Cdk2 formed a functional complex with the residual cyclin E, p27(Kip 1) protein levels increased in G1 upon ARTD1 knockdown most likely due to inappropriate cyclin E-Cdk2-induced phosphorylation-dependent degradation, leading to decelerated G1/S progression. These results provide evidence that ARTD1 regulates cell cycle re-entry and G1/S progression via cyclin E expression and p27(Kip 1) stability independently of its enzymatic activity, uncovering a novel cell cycle regulatory mechanism.

  11. Down-regulation of neogenin accelerated glioma progression through promoter Methylation and its overexpression in SHG-44 Induced Apoptosis.

    Directory of Open Access Journals (Sweden)

    Xinmin Wu

    Full Text Available BACKGROUND: Dependence receptors have been proved to act as tumor suppressors in tumorigenesis. Neogenin, a DCC homologue, well known for its fundamental role in axon guidance and cellular differentiation, is also a dependence receptor functioning to control apoptosis. However, loss of neogenin has been reported in several kinds of cancers, but its role in glioma remains to be further investigated. METHODOLOGY/PRINCIPAL FINDINGS: Western blot analysis showed that neogenin level was lower in glioma tissues than in their matching surrounding non-neoplastic tissues (n = 13, p<0.01. By immunohistochemical analysis of 69 primary and 16 paired initial and recurrent glioma sections, we found that the loss of neogenin did not only correlate negatively with glioma malignancy (n = 69, p<0.01, but also glioma recurrence (n = 16, p<0.05. Kaplan-Meier plot and Cox proportional hazards modelling showed that over-expressive neogenin could prolong the tumor latency (n = 69, p<0.001, 1187.6 ± 162.6 days versus 687.4 ± 254.2 days and restrain high-grade glioma development (n = 69, p<0.01, HR: 0.264, 95% CI: 0.102 to 0.687. By Methylation specific polymerase chain reaction (MSP, we reported that neogenin promoter was methylated in 31.0% (9/29 gliomas, but absent in 3 kinds of glioma cell lines. Interestingly, the prevalence of methylation in high-grade gliomas was higher than low-grade gliomas and non-neoplastic brain tissues (n = 33, p<0.05 and overall methylation rate increased as glioma malignancy advanced. Furthermore, when cells were over-expressed by neogenin, the apoptotic rate in SHG-44 was increased to 39.7% compared with 8.1% in the blank control (p<0.01 and 9.3% in the negative control (p<0.01. CONCLUSIONS/SIGNIFICANCE: These observations recapitulated the proposed role of neogenin as a tumor suppressor in gliomas and we suggest its down-regulation owing to promoter methylation is a selective advantage for glioma genesis, progression and recurrence

  12. Colleague supervision – “ignored and undervalued”? The views of students and supervisors in a new university

    OpenAIRE

    2012-01-01

    Colleague supervision is increasingly used in UK modern (post-92) universities to support the progress of academic staff to doctoral qualifications. Denicolo (2004) argues that it is a ‘role relationship that has been\\ud largely ignored or undervalued by administration’ (p. 693) and colleague students and supervisors ‘felt more vulnerable’ than other students/supervisors (p. 706). This small-scale research amongst students and staff in a colleague supervision relationship at a single UK moder...

  13. Social constructionism and supervision: experiences of AAMFT supervisors and supervised therapists.

    Science.gov (United States)

    Hair, Heather J; Fine, Marshall

    2012-10-01

    A phenomenological research process was used to investigate the supervision experience for supervisors and therapists when supervisors use a social constructionist perspective. Participants of the one-to-one interviews were six AAMFT Approved Supervisors and six therapists providing counseling to individuals, couples and families. The findings suggest supervisors were committed to their self-identified supervision philosophy and intentionally sought out congruence between epistemology and practice. The shared experience of therapists indicates they associated desirable supervision experiences with their supervisors' social constructionist perspective. Our findings also indicated that supervisors' and therapists' understanding of social constructionism included the more controversial concepts of agency and extra-discursiveness. This research has taken an empirical step in the direction of understanding what the social constructionist supervision experience is like for supervisors and therapists. Our findings suggest a linkage between epistemology and supervision practice and a satisfaction with the supervision process. © 2012 American Association for Marriage and Family Therapy.

  14. Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett's esophagus to adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Yan Li; John M Wo; Mukunda B Ray; Whitney Jones; Ruifeng R Su; Susan Ellis; Robert C G Martin

    2006-01-01

    AIM: To investigate the expression of cyclooxygenase-2(COX-2) and epithelial growth factor receptor (EGFR)throughout the progression of Barrett's esophagus (BE).METHODS: COX-2 and EGFR protein expressions were detected by using immunohistochemical method. A detailed cytomorphological changes were determined.Areas of COX-2 and EGFR expression were quantified by using computer Imaging System.RESULTS: The expressions of both COX-2 and EGFR increased along with the progression from BE to esophagus adenocarcinoma (EAC). A positive correlation was found between COX-2 expression and EGFR expression.CONCLUSION: COX-2 and EGFR may be cooperative in the stepwise progression from BE to EAC, thereby leading to carcinogenesis.

  15. Androgen receptor regulated microRNA miR-182-5p promotes prostate cancer progression by targeting the ARRDC3/ITGB4 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Jingjing [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433 (China); Xu, Chen [Research Center of Developmental Biology, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433 (China); Department of Orthopedics, Changzheng Hospital Affiliated to Second Military Medical University, 415th Feng Yang Road, Shanghai, 200003 (China); Fang, Ziyu; Li, Yaoming [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433 (China); Liu, Houqi; Wang, Yue [Research Center of Developmental Biology, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433 (China); Translational Medicine Center, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433 (China); Xu, Chuanliang [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433 (China); Sun, Yinghao, E-mail: sunyh@medmail.com.cn [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433 (China)

    2016-05-20

    Abstracts: MicroRNAs (miRNAs) are important endogenous gene regulators that play key roles in prostate cancer development and metastasis. However, specific miRNA expression patterns in prostate cancer tissues from Chinese patients remain largely unknown. In this study, we compared miRNA expression patterns in 65 pairs of prostate cancer and para-cancer tissues by RNA sequencing and found that miR-182-5p was the most up-regulated miRNA in prostate cancer tissues. The result was validated using realtime PCR in 18 pairs of prostate cancer and para-cancer tissues. In in vitro analysis, it was confirmed that miR-182-5p promotes prostate cancer cell proliferation, invasion and migration and inhibit apoptosis. In addition, the androgen receptor directly regulated the transcription of miR-182-5p, which could target to the 3′UTR of ARRDC3 mRNA and affect the expression of ARRDC3 and its downstream gene ITGB4. For the in vivo experiment, miR-182-5p overexpression also promoted the growth and progression of prostate cancer tumors. In this regard, we suggest that miR-182-5p may be a key androgen receptor-regulated factor that contributes to the development and metastasis of Chinese prostate cancers and may be a potential target for the early diagnosis and therapeutic studies of prostate cancer. -- Highlights: •miR-182-5p is the mostly up-regulated miRNA in Chinese prostate cancer. •miR-182-5p is regulated by androgen receptor. •miR-182-5p promotes prostate cancer progression. •miR-182-5p regulates ARRDC3/ITGB4 pathway.

  16. Effective School Management and Supervision: Imperative for ...

    African Journals Online (AJOL)

    To provide quality education requires effective management of the human and material resources in the industry. ... examines the twin concepts of school management and supervision as the vital factors in providing quality education services.

  17. Factors affecting frontline workers' satisfaction with supervision.

    Science.gov (United States)

    Noelker, Linda S; Ejaz, Farida K; Menne, Heather L; Bagaka's, Joshua G

    2009-02-01

    Objective. This research was guided by a stress and support model to examine the effects of frontline workers' background characteristics, personal stressors, job-related stressors, and workplace support on satisfaction with supervision. Method. Survey data were collected from 644 workers in 49 long-term-care settings that employed them. Regression analysis were used to determine the effects of worker level and then Hierarchical Linear Modeling (HLM) and organizational factors on the outcome. Results. Although all four variable categories made significant contributions to explaining satisfaction with supervision, the most powerful were personal stressors and job-related stressors. Results from HLM analysis showed frontline workers in nursing homes and those employed in for-profit organizations had lower levels of satisfaction with supervision. Discussion. Findings suggest organizational interventions to address workers' financial and health issues and management practices such as better training programs and peer mentoring could enhance workers' satisfaction with supervision.

  18. Results of Evolution Supervised by Genetic Algorithms

    CERN Document Server

    Jäntschi, Lorentz; Bălan, Mugur C; Sestraş, Radu E

    2010-01-01

    A series of results of evolution supervised by genetic algorithms with interest to agricultural and horticultural fields are reviewed. New obtained original results from the use of genetic algorithms on structure-activity relationships are reported.

  19. The Cryogenic Supervision System in NSRRC

    CERN Document Server

    Li, Hsing-Chieh; Chiou, Wen-Song; Hsiao, Feng-Zone; Tsai, Zong-Da

    2005-01-01

    The helium cryogenic system in NSRRC is a fully automatic PLC system using the Siemens SIMATIC 300 controller. Modularization in both hardware and software makes it easy in the program reading, the system modification and the problem debug. Based on the Laview program we had developed a supervision system taking advantage of the Internet technology to get system's real-time information in any place. The functions of this supervision system include the real-time data accessing with more than 300 digital/analog signals, the data restore, the history trend display, and the human machine interface. The data is accessed via a Profibus line connecting the PLC system and the supervision system with a maximum baud rate 1.5 Mbit/s. Due to this supervision system, it is easy to master the status of the cryogenic system within a short time and diagnose the problem.

  20. Supervision of Curriculum at the Middle Level.

    Science.gov (United States)

    Kienapfel, Bruce

    1984-01-01

    Effective curriculum supervision is essential to a good middle school and curriculum program, and principals can do this job through preparation, curriculum review and development, taking advantage of supervisory opportunities, and curriculum evaluation. (DCS)

  1. Exploring My Style of Teacher Supervision

    OpenAIRE

    2009-01-01

    This is a report on a pilot study regarding language teacher supervision styles. The author holds a certificate in language program administration, and the pilot involved teachers of the Japanese language one of whom was also involved in the certificate program. The teachers teach at an American language institute and they agreed to be observed by the author, following procedures detailed in clinical supervision. After the lesson observation, a one-on-one conference was held with the author a...

  2. The Commitment decision according to paragraph 29 EnWG - a standardizing regulation under the supervision of the courts; Die Festlegungsentscheidung nach paragraph 29 EnWG - normierende Regulierung unter den Augen der Gerichte

    Energy Technology Data Exchange (ETDEWEB)

    Attendorn, Thorsten [Bezirksregierung Arnsberg (Germany)

    2009-03-15

    With the commitment decision according to paragraph 29 Energy Economy Act, the regulation authority has an effective instrument, which enables a one-sided determination of the entrance conditions and entrance methods as well as tariffs. This is an application of the standardizing regulation. The desired result is not caused ex post, but ex-ante. This is due to a uniform decision instead of a multiplicity of abuse decisions. The first commitment decisions passed the court instances. In the meantime, there are several decisions of the higher regional court and the Federal High Court. That gives cause to a stock-taking. The author of the contribution under consideration reports on this stock-tacking.

  3. On psychoanalytic supervision as signature pedagogy.

    Science.gov (United States)

    Watkins, C Edward

    2014-04-01

    What is signature pedagogy in psychoanalytic education? This paper examines that question, considering why psychoanalytic supervision best deserves that designation. In focusing on supervision as signature pedagogy, I accentuate its role in building psychoanalytic habits of mind, habits of hand, and habits of heart, and transforming theory and self-knowledge into practical product. Other facets of supervision as signature pedagogy addressed in this paper include its features of engagement, uncertainty, formation, and pervasiveness, as well as levels of surface, deep, and implicit structure. Epistemological, ontological, and axiological in nature, psychoanalytic supervision engages trainees in learning to do, think, and value what psychoanalytic practitioners in the field do, think, and value: It is, most fundamentally, professional preparation for competent, "good work." In this paper, effort is made to shine a light on and celebrate the pivotal role of supervision in "making" or developing budding psychoanalysts and psychoanalytic psychotherapists. Now over a century old, psychoanalytic supervision remains unparalleled in (1) connecting and integrating conceptualization and practice, (2) transforming psychoanalytic theory and self-knowledge into an informed analyzing instrument, and (3) teaching, transmitting, and perpetuating the traditions, practice, and culture of psychoanalytic treatment.

  4. 9 CFR 355.31 - Supervision by inspector.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Supervision by inspector. 355.31..., CERTIFICATION, AND IDENTIFICATION AS TO CLASS, QUALITY, QUANTITY, AND CONDITION Supervision § 355.31 Supervision... filled in whole or in part and no such label shall be affixed thereto except under the supervision of...

  5. 28 CFR 2.94 - Supervision reports to Commission.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Supervision reports to Commission. 2.94 Section 2.94 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT... Parolees § 2.94 Supervision reports to Commission. An initial supervision report to confirm...

  6. 10 CFR 34.46 - Supervision of radiographers' assistants.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Supervision of radiographers' assistants. 34.46 Section 34... REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.46 Supervision of... personal supervision of a radiographer. The personal supervision must include: (a) The...

  7. Opportunities to Learn Scientific Thinking in Joint Doctoral Supervision

    Science.gov (United States)

    Kobayashi, Sofie; Grout, Brian W.; Rump, Camilla Østerberg

    2015-01-01

    Research into doctoral supervision has increased rapidly over the last decades, yet our understanding of how doctoral students learn scientific thinking from supervision is limited. Most studies are based on interviews with little work being reported that is based on observation of actual supervision. While joint supervision has become widely…

  8. 28 CFR 2.207 - Supervision reports to Commission.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Supervision reports to Commission. 2.207 Section 2.207 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT....207 Supervision reports to Commission. A regular supervision report shall be submitted to...

  9. 28 CFR 810.1 - Supervision contact requirements.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Supervision contact requirements. 810.1 Section 810.1 Judicial Administration COURT SERVICES AND OFFENDER SUPERVISION AGENCY FOR THE DISTRICT OF COLUMBIA COMMUNITY SUPERVISION: ADMINISTRATIVE SANCTIONS § 810.1 Supervision contact requirements. If...

  10. Exploring Supervisor and Supervisee Experiences of Triadic Supervision

    Science.gov (United States)

    Derrick, Emily C.

    2010-01-01

    This dissertation research focused on supervisor and supervisee experiences within the triadic supervision triad. Triadic supervision is an emerging method of supervision within counselor education. It is fast becoming the preferred mode of supervision in counselor education programs. Unfortunately, there is very little research to support the…

  11. A Model for Using Triadic Supervision in Counselor Preparation Programs

    Science.gov (United States)

    Lawson, Gerard; Hein, Serge F.; Getz, Hildy

    2009-01-01

    The Council for Accreditation of Counseling and Related Educational Programs (2001) has approved the use of triadic supervision as an alternative to individual supervision in clinical instruction. However, literature describing this mode of supervision is very limited. A model for triadic supervision is described, including presession planning,…

  12. Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis

    National Research Council Canada - National Science Library

    Skerker, Jeffrey M; Prasol, Melanie S; Perchuk, Barrett S; Biondi, Emanuele G; Laub, Michael T

    2005-01-01

    Two-component signal transduction systems, comprised of histidine kinases and their response regulator substrates, are the predominant means by which bacteria sense and respond to extracellular signals...

  13. Multicultural supervision: lessons learned about an ongoing struggle.

    Science.gov (United States)

    Christiansen, Abigail Tolhurst; Thomas, Volker; Kafescioglu, Nilufer; Karakurt, Gunnur; Lowe, Walter; Smith, William; Wittenborn, Andrea

    2011-01-01

    This article examines the experiences of seven diverse therapists in a supervision course as they wrestled with the real-world application of multicultural supervision. Existing literature on multicultural supervision does not address the difficulties that arise in addressing multicultural issues in the context of the supervision relationship. The experiences of six supervisory candidates and one mentoring supervisor in addressing multicultural issues in supervision are explored. Guidelines for conversations regarding multicultural issues are provided.

  14. Group Supervision in Graduate Education: A Process of Supervision Skill Development and Text Improvement

    Science.gov (United States)

    Samara, Akylina

    2006-01-01

    This paper is an investigation of group supervision of the Master of Education thesis at the University of Bergen, Norway. Four recorded group supervision sessions are analysed. The group participants are five students and three supervisors. The sessions are analysed from a qualitative, phenomenological perspective. The results show that group…

  15. Classroom Supervision and Informal Analysis of Behavior. A Manual for Supervision.

    Science.gov (United States)

    Hull, Ray; Hansen, John

    This manual for supervision addresses itself to those with responsibility for helping teachers develop into skilled professionals through use of a rational plan of feedback and assistance. It describes the supervision cycle and outline simple and practical techniques to collect effective data that will assist the classroom teacher. The manual has…

  16. Group Supervision in Graduate Education: A Process of Supervision Skill Development and Text Improvement

    Science.gov (United States)

    Samara, Akylina

    2006-01-01

    This paper is an investigation of group supervision of the Master of Education thesis at the University of Bergen, Norway. Four recorded group supervision sessions are analysed. The group participants are five students and three supervisors. The sessions are analysed from a qualitative, phenomenological perspective. The results show that group…

  17. General Duties Medical Officer Role 1 remote supervision in the era of Army Contingency Operations.

    Science.gov (United States)

    Martin-Bates, Alexander James; Jefferys, S E

    2016-08-01

    The return to contingency after Operation HERRICK (2002-2014 Afghanistan conflict) has seen an emerging trend for small-scale rapidly developing expeditionary operations. The associated small, remote medical footprint for such operations, often within a coalition construct, reliant on host nation support is in direct conflict with the General Medical Council (GMC) guidelines for junior doctor supervision in an 'approved practice setting'. If a General Duties Medical Officer (GDMO) is nominated to support future operations, the provision of assured patient care and supervision within GMC guidelines, while ensuring career progression and ongoing education, may prove a challenge. Recently published British Army Policy aims to provide a framework to meet these challenges. The authors' first-hand experience in implementing this policy is explored further. The deployment of a remotely supervised GDMO, in line with British Army Policy, is both suitable and safe. This should assure quality medical care delivery during the era of Army Contingency Operations.

  18. CLASP1, astrin and Kif2b form a molecular switch that regulates kinetochore-microtubule dynamics to promote mitotic progression and fidelity.

    Science.gov (United States)

    Manning, Amity L; Bakhoum, Samuel F; Maffini, Stefano; Correia-Melo, Clara; Maiato, Helder; Compton, Duane A

    2010-10-20

    Accurate chromosome segregation during mitosis requires precise coordination of various processes, such as chromosome alignment, maturation of proper kinetochore-microtubule (kMT) attachments, correction of erroneous attachments, and silencing of the spindle assembly checkpoint (SAC). How these fundamental aspects of mitosis are coordinately and temporally regulated is poorly understood. In this study, we show that the temporal regulation of kMT attachments by CLASP1, astrin and Kif2b is central to mitotic progression and chromosome segregation fidelity. In early mitosis, a Kif2b-CLASP1 complex is recruited to kinetochores to promote chromosome movement, kMT turnover, correction of attachment errors, and maintenance of SAC signalling. However, during metaphase, this complex is replaced by an astrin-CLASP1 complex, which promotes kMT stability, chromosome alignment, and silencing of the SAC. We show that these two complexes are differentially recruited to kinetochores and are mutually exclusive. We also show that other kinetochore proteins, such as Kif18a, affect kMT attachments and chromosome movement through these proteins. Thus, CLASP1-astrin-Kif2b complex act as a central switch at kinetochores that defines mitotic progression and promotes fidelity by temporally regulating kMT attachments.

  19. 生长素调节植物花发育的研究进展%Research Progress on Auxin Regulation in Flower DeveloPment

    Institute of Scientific and Technical Information of China (English)

    严希; 彭剑涛

    2015-01-01

    花是被子植物的繁殖器官,花的发育是植物繁衍后代的关键环节。大量研究表明,花发育受到基因、植物激素、温度等多种内外因素的调控,生长素在此过程中扮演着不可或缺的角色。本文介绍了国内外生长素调控花发育研究的进展,尤其是生长素极性运输、生长素含量变化以及生长素信号转导在花器官发育过程中的作用。%Flower is the reproductive organ of angiosperm,and flower development is the key step in the progress of reproduction. Numerous researches have indicated that flower development is regulated by genes,plant hor-mones,temperature,and so on. Plant hormones,especially auxin,play indispensable roles in regulation of flow-er development. In this review we introduced the research progress on auxin regulation in flower development. Effects of polar auxin transport,changes in auxin contents and auxin signal transduction on the development of flower were reviewed in particular.

  20. ATP-binding cassette G-subfamily transporter 2 regulates cell cycle progression and asymmetric division in mouse cardiac side population progenitor cells.

    Science.gov (United States)

    Sereti, Konstantina-Ioanna; Oikonomopoulos, Angelos; Unno, Kazumasa; Cao, Xin; Qiu, Yiling; Liao, Ronglih

    2013-01-04

    After cardiac injury, cardiac progenitor cells are acutely reduced and are replenished in part by regulated self-renewal and proliferation, which occurs through symmetric and asymmetric cellular division. Understanding the molecular cues controlling progenitor cell self-renewal and lineage commitment is critical for harnessing these cells for therapeutic regeneration. We previously have found that the cell surface ATP-binding cassette G-subfamily transporter 2 (Abcg2) influences the proliferation of cardiac side population (CSP) progenitor cells, but through unclear mechanisms. To determine the role of Abcg2 on cell cycle progression and mode of division in mouse CSP cells. Herein, using CSP cells isolated from wild-type and Abcg2 knockout mice, we found that Abcg2 regulates G1-S cell cycle transition by fluorescence ubiquitination cell cycle indicators, cell cycle-focused gene expression arrays, and confocal live-cell fluorescent microscopy. Moreover, we found that modulation of cell cycle results in transition from symmetric to asymmetric cellular division in CSP cells lacking Abcg2. Abcg2 modulates CSP cell cycle progression and asymmetric cell division, establishing a mechanistic link between this surface transporter and cardiac progenitor cell function. Greater understanding of progenitor cell biology and, in particular, the regulation of resident progenitor cell homeostasis is vital for guiding the future development of cell-based therapies for cardiac regeneration.

  1. DACH1 regulates cell cycle progression of myeloid cells through the control of cyclin D, Cdk 4/6 and p21{sup Cip1}

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae-Woong; Kim, Hyeng-Soo; Kim, Seonggon; Hwang, Junmo; Kim, Young Hun; Lim, Ga Young [School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Sohn, Wern-Joo [Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu 700-412 (Korea, Republic of); Yoon, Suk-Ran [Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Kim, Jae-Young [Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu 700-412 (Korea, Republic of); Park, Tae Sung [Department of Laboratory Medicine, Kyung Hee University School of Medicine, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702 (Korea, Republic of); Park, Kwon Moo [Department of Anatomy, Kyungpook National University School of Medicine, Daegu 700-422 (Korea, Republic of); Ryoo, Zae Young [School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Lee, Sanggyu, E-mail: slee@knu.ac.kr [School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer DACH1 increases cyclin D, F and Cdk 1, 4, 6 in mouse myeloid progenitor cells. Black-Right-Pointing-Pointer The knockdown of DACH1 blocked the cell cycle progression of HL-60 cells. Black-Right-Pointing-Pointer The novel effect of DACH1 related with cell cycle regulation and leukemogenesis. -- Abstract: The cell-fate determination factor Dachshund, a component of the Retinal Determination Gene Network (RDGN), has a role in breast tumor proliferation through the repression of cyclin D1 and several key regulators of embryonic stem cell function, such as Nanog and Sox2. However, little is known about the role of DACH1 in a myeloid lineage as a cell cycle regulator. Here, we identified the differential expression levels of extensive cell cycle regulators controlled by DACH1 in myeloid progenitor cells. The forced expression of DACH1 induced p27{sup Kip1} and repressed p21{sup Cip1}, which is a pivotal characteristic of the myeloid progenitor. Furthermore, DACH1 significantly increased the expression of cyclin D1, D3, F, and Cdk 1, 4, and 6 in myeloid progenitor cells. The knockdown of DACH1 blocked the cell cycle progression of HL-60 promyeloblastic cells through the decrease of cyclin D1, D3, F, and Cdk 1, 4, and 6 and increase in p21{sup Cip1}, which in turn decreased the phosphorylation of the Rb protein. The expression of Sox2, Oct4, and Klf4 was significantly up-regulated by the forced expression of DACH1 in mouse myeloid progenitor cells.

  2. Intuitive expertise in ICT graduate supervision

    Directory of Open Access Journals (Sweden)

    Jill Jameson

    2002-12-01

    Full Text Available Intuitive expertise in the application of advanced interdisciplinary facilitation is the subject of this personal reflection on the graduate supervisory style of Professor David Squires in computers in education. This single-case reflective study examines the characteristics of effective supervision observed during masters and doctoral supervision at King's College in the years 1990-9. Interdisciplinarity in ICT graduate studies particularly requires a fluency of supervisory expertise in enabling supervisees to combine multiple complex perspectives from a number of fields of knowledge. Intuitive combinatory aspects of supervision are highlighted in this reflection on the role carried out by an academic expert in facilitating student success. This is examined from a perspective incorporating affective as well as intellectual elements, informed by characteristics identified in professional sports and performing arts coaching/mentoring. Key characteristics comprising a model of intuitive expertise in ICT graduate supervision were outlined. The resultant portrait aims to complement existing literature on graduate supervision, with reference to the field of ICTI computers in education relating to student hypermedia composition.

  3. Appreciative Perspectives on Supervision in Social Work

    Directory of Open Access Journals (Sweden)

    Elena UNGURU

    2017-06-01

    Full Text Available Supervision is considered to be an extremly important stage in the professional development of the specialists in the fields with asistential nature, such as: psychotherapy, coaching, personal development, counselling, etc. In Romania, the supervision of social services has become compulsory through the Order 288/2006. A great part of the content of standards for the case management, including those referred to supervision, namely to the theoretical and methodological development of some teachers, such as: Professor PhD Ştefan Cojocaru, Professor PhD Ana Muntean, Professor PhD Elena Zamfir. In this review, we will synthesize a part of Professor Ştefan Cojocaru’s contribution to the development of the field of appreciative supervision, as it is presented in the volume Appreciative methods in social work. Survey, supervision and case management, published with Polirom Publishing House in 2005. We will aim to also synthesize a series of echos of his work in the Romanian scientific literature.

  4. 7 CFR 1220.617 - Supervision of the process for requesting a referendum.

    Science.gov (United States)

    2010-01-01

    ... referendum. 1220.617 Section 1220.617 Agriculture Regulations of the Department of Agriculture (Continued... AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.617 Supervision of the process for requesting a referendum. The Administrator, AMS, shall...

  5. 7 CFR 1280.621 - Supervision of the process for conducting a referendum.

    Science.gov (United States)

    2010-01-01

    ... referendum. 1280.621 Section 1280.621 Agriculture Regulations of the Department of Agriculture (Continued... AGRICULTURE LAMB PROMOTION, RESEARCH, AND INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.621 Supervision of the process for conducting a referendum. The Administrator, AMS, shall be...

  6. Sulindac and Celecoxib regulate cell cycle progression by p53/p21 up regulation to induce apoptosis during initial stages of experimental colorectal cancer.

    Science.gov (United States)

    Vaish, Vivek; Rana, Chandan; Piplani, Honit; Vaiphei, Kim; Sanyal, Sankar Nath

    2014-03-01

    In the present study we have elaborated the putative mechanisms could be followed by the non-steroidal anti-inflammatory drugs (NSAIDs) viz. Sulindac and Celecoxib in the regulation of cell cycle checkpoints along with tumor suppressor proteins to achieve their chemopreventive effects in the initial stages of experimental colorectal cancer. Male Sprague-Dawley rats were administered with 1,2-dimethylhydrazine dihydrochloride (DMH) to produce early stages of colorectal carcinogenesis. The mRNA expression profiles of various target genes were analyzed by RT-PCR and validated by quantitative real-time PCR, whereas protein expression was analyzed by Western blotting. Nuclear localization of transcription factors or other nuclear proteins was analyzed by electrophoretic mobility shift assay and immunofluorescence. Flowcytometry was performed to analyze the differential apoptotic events and cell cycle regulation. Molecular docking studies with different target proteins were also performed to deduce the various putative mechanisms of action followed by Sulindac and Celecoxib. We observed that DMH administration has abruptly increased the proliferation of colonic cells which is macroscopically visible in the form of multiple plaque lesions and co-relates with the disturbed molecular mechanisms of cell cycle regulation. However, co-administration of NSAIDs has shown regulatory effects on cell cycle checkpoints via induction of various tumor suppressor proteins. We may conclude that Sulindac and Celecoxib could possibly follow p53/p21 mediated regulation of cell proliferation, where down regulation of NF-κB signaling and activation of PPARγ might serve as important additional events in vivo.

  7. Regulations of enzymes in animals: effects of developmental processes, cancer and radiation. Progress report XI, 1 May 1976--30 April 1977

    Energy Technology Data Exchange (ETDEWEB)

    Knox, W.E.

    1977-06-01

    Two outstandingly successful studies were among those outlined in the proposal last year. They are the first and last topics summarized in this progress report: the first evidence that the chemical composition of human tumors can probably be predicted on the basis of our previous studies in the rat, and the elucidation of the function of the arginine-proline pathway, its importance in fetal and tumor tissues, and its regulation. The variety of other studies are summarized under headings somewhat different from those used in the original proposal, in order to denote more clearly what was actually found, but all proposed topics have been studied to some extent.

  8. Project Supervision – An Engineering Approach

    DEFF Research Database (Denmark)

    Paulsen, Rasmus Reinhold; Larsen, Rasmus; Ersbøll, Bjarne Kjær

    2011-01-01

    of their master thesis writing. The supervision principles are: Ownership: The student should feel that their project is their own. Ideally, they should formulate the project themselves. Write early: We strongly encourage the students to write and generate figures and images already from the first week......For more than twenty years, a group based supervision strategy has been used when supervising engineering bachelor- and master thesis students at our research group. In recent years, we have formalised the approach and used our industry experience to create a very successful framework for project...... at all meetings. Weekly meetings are scheduled to be at a specific day at a specific place for the entire process....

  9. Multi-Instance Learning from Supervised View

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hua Zhou

    2006-01-01

    In multi-instance learning, the training set comprises labeled bags that are composed of unlabeled instances,and the task is to predict the labels of unseen bags. This paper studies multi-instance learning from the view of supervised learning. First, by analyzing some representative learning algorithms, this paper shows that multi-instance learners can be derived from supervised learners by shifting their focuses from the discrimination on the instances to the discrimination on the bags. Second, considering that ensemble learning paradigms can effectively enhance supervised learners, this paper proposes to build multi-instance ensembles to solve multi-instance problems. Experiments on a real-world benchmark test show that ensemble learning paradigms can significantly enhance multi-instance learners.

  10. Core ethical issues of clinical nursing supervision.

    Science.gov (United States)

    Berggren, Ingela; Barbosa da Silva, António; Severinsson, Elisabeth

    2005-03-01

    Clinical nursing supervision enables supervisees to reflect on ethically difficult caring situations, thereby strengthening their professional identity, integrating nursing theory and practice, and leading to the development of ethical competence. The aim of this study was to develop an understanding of the core ethical issues of clinical nursing supervision, using previous research as well as philosophical analysis of the theories of three moral philosophers: Harald Ofstad, Richard Hare and Carol Gilligan. The ultimate aim of this study was to develop a general model for ethical decision-making and to establish its relevance for clinical nursing supervision. The findings highlight four important values for the development of a basis for ethical decision-making. These values are caring, dignity, responsibility and virtue.

  11. Guidelines for clinical supervision in health service psychology.

    Science.gov (United States)

    2015-01-01

    This document outlines guidelines for supervision of students in health service psychology education and training programs. The goal was to capture optimal performance expectations for psychologists who supervise. It is based on the premises that supervisors (a) strive to achieve competence in the provision of supervision and (b) employ a competency-based, meta-theoretical approach to the supervision process. The Guidelines on Supervision were developed as a resource to inform education and training regarding the implementation of competency-based supervision. The Guidelines on Supervision build on the robust literatures on competency-based education and clinical supervision. They are organized around seven domains: supervisor competence; diversity; relationships; professionalism; assessment/evaluation/feedback; problems of professional competence, and ethical, legal, and regulatory considerations. The Guidelines on Supervision represent the collective effort of a task force convened by the American Psychological Association (APA) Board of Educational Affairs (BEA). PsycINFO Database Record (c) 2015 APA, all rights reserved.

  12. High-Intensity Progressive Resistance Training Increases Strength With No Change in Cardiovascular Function and Autonomic Neural Regulation in Older Adults.

    Science.gov (United States)

    Kanegusuku, Hélcio; Queiroz, Andréia C; Silva, Valdo J; de Mello, Marco T; Ugrinowitsch, Carlos; Forjaz, Cláudia L

    2015-07-01

    The effects of high-intensity progressive resistance training (HIPRT) on cardiovascular function and autonomic neural regulation in older adults are unclear. To investigate this issue, 25 older adults were randomly divided into two groups: control (CON, N = 13, 63 ± 4 years; no training) and HIPRT (N = 12, 64 ± 4 years; 2 sessions/week, 7 exercises, 2–4 sets, 10–4 RM). Before and after four months, maximal strength, quadriceps cross-sectional area (QCSA), clinic and ambulatory blood pressures (BP), systemic hemodynamics, and cardiovascular autonomic modulation were measured. Maximal strength and QCSA increased in the HIPRT group and did not change in the CON group. Clinic and ambulatory BP, cardiac output, systemic vascular resistance, stroke volume, heart rate, and cardiac sympathovagal balance did not change in the HIPRT group or the CON group. In conclusion, HIPRT was effective at increasing muscle mass and strength without promoting changes in cardiovascular function or autonomic neural regulation.

  13. Thermal regulation of functional groups in running water ecosystems. Progress report, October 1, 1975--June 30, 1976

    Energy Technology Data Exchange (ETDEWEB)

    Cummins, K.W.; Klug, M.J.

    1976-07-01

    Progress is reported on the following research projects: characterization of functional groups of running water organisms, particularly macroconsumers; studies on relationship of functional groups to qualitative and quantitative characteristics of organic inputs to stream ecosystems; studies on relationship of functional groups to thermal regimes; and dimensioning the control of feeding and growth by temperature and food quality and quantity and determining the extent of compensatory action of each. (HLW)

  14. Incremental Supervised Subspace Learning for Face Recognition

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Subspace learning algorithms have been well studied in face recognition. Among them, linear discriminant analysis (LDA) is one of the most widely used supervised subspace learning method. Due to the difficulty of designing an incremental solution of the eigen decomposition on the product of matrices, there is little work for computing LDA incrementally. To avoid this limitation, an incremental supervised subspace learning (ISSL) algorithm was proposed, which incrementally learns an adaptive subspace by optimizing the maximum margin criterion (MMC). With the dynamically added face images, ISSL can effectively constrain the computational cost. Feasibility of the new algorithm has been successfully tested on different face data sets.

  15. EEM{sup TM} wireless supervision

    Energy Technology Data Exchange (ETDEWEB)

    Bilic, H. [Ericsson-Nikola Tesla d.d. Zagreb (Croatia)

    2000-07-01

    By adding the GSM network to the communication level of Energy Management systems, energy operating centres (EOC) can offer wireless access to the supervised equipment. Furthermore EOC can profit from rapid service development in the GSM networks. With implementation of GPRS to the GSM network EOC can instantly offer wireless access to external IP based networks such as Internet and corporate Intranets. The author describes architecture and key characteristic of Ericsson EnergyMaster{sup TM} (EEM{sup TM}) system for Energy Management, how and where to implement wireless supervision, wireless access to IP addresses and also how to implement new services provided by the GSM network. (orig.)

  16. Supervised Learning in Multilayer Spiking Neural Networks

    CERN Document Server

    Sporea, Ioana

    2012-01-01

    The current article introduces a supervised learning algorithm for multilayer spiking neural networks. The algorithm presented here overcomes some limitations of existing learning algorithms as it can be applied to neurons firing multiple spikes and it can in principle be applied to any linearisable neuron model. The algorithm is applied successfully to various benchmarks, such as the XOR problem and the Iris data set, as well as complex classifications problems. The simulations also show the flexibility of this supervised learning algorithm which permits different encodings of the spike timing patterns, including precise spike trains encoding.

  17. The collagen triple helix repeat containing 1 facilitates hepatitis B virus-associated hepatocellular carcinoma progression by regulating multiple cellular factors and signal cascades.

    Science.gov (United States)

    Zhang, Rui; Cao, Yanhua; Bai, Lan; Zhu, Chengliang; Li, Rui; He, Hui; Liu, Yingle; Wu, Kailang; Liu, Fang; Wu, Jianguo

    2015-12-01

    Hepatitis B virus (HBV) infection is one of the major causes of acute and chronic liver diseases, fulminant hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HCC accounts for more than 85% of primary liver cancers and is the seventh most common cancer and the third leading cause of cancer-related deaths. However, the mechanism by which HBV induces HCC is largely unknown. Collagen triple helixes repeat containing 1 (CTHRC1) is a secreted protein and has characteristics of a circulating hormone with potentially broad implications for cell metabolism and physiology. CTHRC1 is associated with human cancers, but its effect on HCC is unknown. Here, we revealed that CTHRC1 expression is highly correlated with HCC progression in HBV-infected patients, and demonstrated that HBV stimulates CTHRC1 expression by activating nuclear factor-kappa B (NF-κB) and cAMP response element binding protein (CREB), through extracellular signal-regulated kinase/c-Jun N-terminal kinase (ERK/c-JNK) pathway. In addition, CTHRC1 activates hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) through regulating phosphoinosmde-3-kinase/protein kinase B/mammalian target of rapamycin (PI-3K/AKT/mTOR) pathway. More interestingly, CTHRC1 enhances colony formation, migration, and invasion of hepatoma cells by regulating p53 and stimulating matrix metalloproteinase-9 (MMP-9) expression. In addition, knock-down of CTHRC1 results in the repression of HBV-associated carcinogenesis in nude mice. Thus, we revealed a novel mechanism by which HBV facilitates HCC development through activating the oncoprotein CTHRC1, which in turn enhances HBV-related HCC progression by stimulates colony formation, migration, and invasion of hepatoma cells through regulating multiple cellular factors and signal cascades.

  18. Latest Developments in China's Banking Reform, Opening-up and Supervision

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

      China Banking Regulatory Commission (CBRC) was authorized by law to regulate and supervise all the banking institutions in China and their business activities. CBRC plays an active role in China's banking reform. According to a press release by the State Council on December 5, under the leadership of the central government and the guidance of Deng Xiaoping Theory and the important thought of" Three Represents," the CBRC continues to practise the scientific concept of development, deepen the banking reform, further the opening up and enhance banking supervision, so as to ensure a safe and sound development of China's banking sector.……

  19. Latest Developments in China's Banking Reform, Opening-up and Supervision

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ China Banking Regulatory Commission (CBRC) was authorized by law to regulate and supervise all the banking institutions in China and their business activities. CBRC plays an active role in China's banking reform. According to a press release by the State Council on December 5, under the leadership of the central government and the guidance of Deng Xiaoping Theory and the important thought of" Three Represents," the CBRC continues to practise the scientific concept of development, deepen the banking reform, further the opening up and enhance banking supervision, so as to ensure a safe and sound development of China's banking sector.

  20. Supervision of Waste Management and Environmental Protection at the Swedish Nuclear Facilities 2001

    CERN Document Server

    Persson, M

    2003-01-01

    The report summarizes the supervision of waste management and environmental protection at the nuclear facilities that was carried out by the Swedish Radiation Protection Authority in 2001. A summary of the inspections and a description of important issues connected with the supervision of the nuclear facilities are given.The inspections during 2001 have focused on theme inspections of waste management, environmental inspections considering the environmental monitoring at the Swedish nuclear facilities and review safety analysis and research programs from the Swedish Nuclear Fuel and Waste Management Co.The Swedish Radiation Protection Authority finds that the operations are mainly performed according to current regulations

  1. NEED OF FINANCIAL INSTITUTIONS SUPERVISION THROUGH AN SINGLE FRAMEWORK OF MACRO-PRUDENTIAL SUPERVISION

    Directory of Open Access Journals (Sweden)

    MEDAR LUCIAN-ION

    2013-12-01

    Full Text Available Joint Committee of the European Supervisory Authorities required Member States to implement new macro-prudential indicators.through national authorities of prudential supervision will be perform activities concerning the supplementary supervision of credit institutions, insurance companies or reinsurance companies, investment services firms and investment management firms, from a financial conglomerate. The most popular ways that give stability to the financial system are related to normal functioning of markets, to ensure implementation of payments in the economy and especially achieving a quality financial intermediation. Activities concerning macroprudential supervision concern, first of all, of managerial strengthening of internal control, assessment and management of risks

  2. The job-search grind: perceived progress, self-reactions, and self-regulation of search effort

    NARCIS (Netherlands)

    Wanberg, C.; Zhu, J.; van Hooft, E.A.J.

    2010-01-01

    Guided by theory and research on self-regulation and goal pursuit, we offer a framework for studying the dynamics of unemployed individuals’ job search. A daily survey over three weeks demonstrated vacillation in job seeker affect and, to a lesser extent, "reemployment efficacy." Daily perceived job

  3. A semi-supervised approach uncovers thousands of intragenic enhancers differentially activated in human cells

    OpenAIRE

    2015-01-01

    Background Transcriptional enhancers are generally known to regulate gene transcription from afar. Their activation involves a series of changes in chromatin marks and recruitment of protein factors. These enhancers may also occur inside genes, but how many may be active in human cells and their effects on the regulation of the host gene remains unclear. Results We describe a novel semi-supervised method based on the relative enrichment of chromatin signals between 2 conditions to predict act...

  4. Recent progress of appetite regulation in central nervous system%中枢食欲调节研究进展

    Institute of Scientific and Technical Information of China (English)

    程笑冰; 宁光

    2009-01-01

    Concordant ingestion of appetite regulation internet is the basic physiological activity of human. Appetite regulation relates to complicate mechanisms and involves many systems and factors. Their impacting and controlling formed the appetite regulation internet. The hypothalamus plays a crucial role in re-cepting,integrating and releasing signals of energy status in central nervous system. The consummated con-struction of hypothalamus about appetite regulation and the finding of new regulation factors are very impor-tant for the learning of mechanism of obesity and diabetes and the development of drugs.%食欲调节网络的协调性摄食活动是维持人类生命的基本生理活动,食欲调节具有复杂而精细的调节机制,而下丘脑正是接受、整合与发放食欲调节信号、维持体重稳定的重要中枢.中枢神经系统或外周组织产生的具有促/抑食欲作用的神经内分泌因子在下丘脑形成复杂的食欲调节网络和相互投射的神经环路,对食欲进行精确的调控.不断完善下丘脑食欲调节区域,不断发现新的调控因子及其作用机制,对深入了解肥胖及糖尿病的病理生理机制及设计开发各种有效控制体重和血糖的药物有重大意义.

  5. Autocrine regulation of glioblastoma cell cycle progression, viability and radioresistance through the VEGF-VEGFR2 (KDR) interplay.

    Science.gov (United States)

    Knizetova, Petra; Ehrmann, Jiri; Hlobilkova, Alice; Vancova, Iveta; Kalita, Ondrej; Kolar, Zdenek; Bartek, Jiri

    2008-08-15

    Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and progression of malignant brain tumors. Given the significance of tumor microenvironment in general, and the established role of paracrine VEGF signaling in glioblastoma (GBM) biology in particular, we explored the potential autocrine control of human astrocytoma behavior by VEGF. Using a range of cell and molecular biology approaches to study a panel of astrocytoma (grade III and IV/GBM)-derived cell lines and a series of clinical specimens from low- and high-grade astrocytomas, we show that co-expression of VEGF and VEGF receptors (VEGFRs) occurs commonly in astrocytoma cells. We found VEGF secretion and VEGF-induced biological effects (modulation of cell cycle progression and enhanced viability of glioblastoma cells) to function in an autocrine manner. Morevover, we demonstrated that the autocrine VEGF signaling is mediated via VEGFR2 (KDR), and involves co-activation of the c-Raf/MAPK, PI3K/Akt and PLC/PKC pathways. Blockade of VEGFR2 by the selective inhibitor (SU1498) abrogated the VEGF-mediated enhancement of astrocytoma cell growth and viability under unperturbed culture conditions. In addition, such interference with VEGF-VEGFR2 signaling potentiated the ionizing radiation-induced tumor cell death. In clinical specimens, both VEGFRs and VEGF were co-expressed in astroglial tumor cells, and higher VEGF expression correlated with tumor progression, thereby supporting the relevance of functional VEGF-VEGFR signaling in vivo. Overall, our results are consistent with a potential autocrine role of the VEGF-VEGFR2 (KDR) interplay as a factor contributing to malignant astrocytoma growth and radioresistance, thereby supporting the candidacy of this signaling cascade as a therapeutic target, possibly in combination with radiotherapy.

  6. CIP2A modulates cell-cycle progression in human cancer cells by regulating the stability and activity of Plk1.

    Science.gov (United States)

    Kim, Jae-Sung; Kim, Eun Ju; Oh, Jeong Su; Park, In-Chul; Hwang, Sang-Gu

    2013-11-15

    Abnormal cell-cycle control can lead to aberrant cell proliferation and cancer. The oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) is an inhibitor of protein phosphatase 2A (PP2A) that stabilizes c-Myc. However, the precise role of CIP2A in cell division is not understood. Herein, we show that CIP2A is required for mitotic progression by regulating the polo-like kinase (Plk1). With mitotic entry, CIP2A translocated from the cytoplasm to the nucleus, where it was enriched at spindle poles. CIP2A depletion delayed mitotic progression, resulting in mitotic abnormalities independent of PP2A activity. Unexpectedly, CIP2A interacted directly with the polo-box domain of Plk1 during mitosis. This interaction was required to maintain Plk1 stability by blocking APC/C-Cdh1-dependent proteolysis, thereby enhancing the kinase activity of Plk1 during mitosis. We observed strong correlation and in vivo interactions between these two proteins in multiple human cancer specimens. Overall, our results established a novel function for CIP2A in facilitating the stability and activity of the pivotal mitotic kinase Plk1 in cell-cycle progression and tumor development.

  7. Capital and Portfolio Risk under the Solvency Regulation Supervision Analysis of Partial Adjustment Model based on Property-liability Companies%偿付能力监管下韵资本与组合风险——基于产险公司局部联立调整模型的分析

    Institute of Scientific and Technical Information of China (English)

    王丽珍; 李秀芳

    2012-01-01

    Ever since 2007, capital and stock increases trend m insurance compamc~ o~ ,~ , the required capital size are expanding, and also the frequency of capital increasing is improving. Although the ap- pearance of this phenomenon is inevitable, owing to the costliness and scarcity of capital, insurance industry and China Insurance Regulatory Commission all have paid more attention to the upsurge about capital. Furthermore, if the insurance companies can' t raise capital timely, they will not operate normally, and then it is bound to endanger social stability and the interest of insurance consumers. So it is meaningful to study the capital under the solvency regulation supervision and the special development stage. The capital is applicable to withstand unexpected loss, in this sense, the adjustment of capital is corresponding with risk level. Thus, we combine capital with risk to re- search the development of china' s property-liability companies. According to the research paradigm of banking studies about capital structure and portfolio risk, we employ partial adjustment model to the insurance area. Through the panel data of 34 Property-Liability insurance companies, this paper conduct the Three-stage least square ( 3 SLS) procedure to estimate a simultaneous equations model and examines the impact of capital determina- tion and portfolio risk under solvency regulation. In addition to this, we also consider the other factors, such as the structure of lines, the scale of asset, the reinsurance ratio, the return of asset under the research framework. Based on this, robustness tests with two broad heading including five types subsamples also present consistent results. Our key findings include four aspects. First of all, we find that capitalized insurers increase capital faster than under- capitalized insurers, which is different from the condition of American. This result implies that, on account of the rapid development of insurance industry currently, insurance

  8. Epigenetic modification regulates both expression of tumor-associated genes and cell cycle progressing in human colon cancer cell lines:Colo-320 and SW1116

    Institute of Scientific and Technical Information of China (English)

    Jing Yuan FANG; Ying Xuan CHEN; Juan LU; Rong LU; Li YANG; Hong Yin ZHU; Wei Qi GU; Lun Gen LU

    2004-01-01

    The aim of this study is to assess the effects of DNA methylation and histone acetylation, alone or in combination, on the expression of several tumor-associated genes and cell cycle progression in two established human colon cancer cell lines: Colo-320 and SW1116. Treatments with 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin A, alone or in combination, were applied respectively. The methylation status of the CDKN2A promoter was determined by methylation-specific PCR, and the acetylated status of the histones associated with the p21wAF1 and CDKN2A genes was examined by chromatin immunoprecipitation. The expression of the CDKN2A, p21WAF1, p53, p73, APC, c-myc, c-Ki-ras and survivin genes was detected by real-time RT-PCR and RT-PCR. The cell cycle profile was established by flow cytometry.We found that along with the demethylation of the CDKN2A gene promoter in both cell lines induced by 5-aza-dC alone or in combination with TSA, the expression of both CDKN2A and APC genes increased. The treatment of TSA or sodium butyrate up-regulated the transcription of p21 WAF1 significantly by inducing the acetylation of histones H4 and H3, but failed to alter the acetylation level of CDKN2A-associated histones. No changes in transcription of p53, p73,c-myc, c-Ki-ras and survivin genes were observed. In addition, TSA or sodium butyrate was shown to arrest cells at the G1 phase. However, 5-aza-dC was not able to affect the cell cycle progression. In conclusion, regulation by epigenetic modification of the transcription of tumor-associated genes and the cell cycle progression in both human colon cancer cell lines Colo-320 and SW1116 is gene-specific.

  9. N-glycosylation at Asn residues 554 and 566 of E-cadherin affects cell cycle progression through extracellular signal-regulated protein kinase signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Hongbo Zhao; Xiliang Zha; Lidong Sun; Liying Wang; Zhibin Xu; Feng Zhou; Jianmin Su; Jiawei Jin; Yong Yang; Yali Hu

    2008-01-01

    E-cadherin, which has a widely acknowledged role in mediating calcium-dependent cell-cell adhesion between epithelial cells, also functions as a tumor suppressor. The ectodomain of human E-cadherin contains four potential N-glycosylation sites at Asn residues 554, 566, 618, and 633.We investigated the role of E-cadherin N-glycosylation in cell cycle progression by site-directed mutagenesis. We showed previously that all four potential N-glycosylation sites of E-cadherin were N-glycosylated in human breast carcinoma MDA-MB-435 cells. Removal of N-glycan at Asn633 dramatically affected E-cadherin stability. In this study we showed that E-cadherin mutant missing N-glycans at Asn554, Asn566 and Asn618 failed to induce cell cycle arrest in G1 phase and to suppress cell proliferation in comparison with wild-type E-cadherin. Moreover, N-glycans at Asn554 and Asn566, but not at Asn618, seemed to be indispensable for E-cadherin-mediated suppression of cell cycle progression.Removal of N-glycans at either Asn554 or Asn566 of E-cadherin was accompanied with the activation of the extracellular signal-regulated protein kinase signaling pathway. After treatment with PD98059, an inhibitor of the extraceilular signal-regulated protein kinase signaling pathway, wild-type E-cadherin transfected MDA-MB-435 and E-cadherin N-glycosylation-deficient mutant transfected MDA-MB-435 cells had equivalent numbers of cells in G1 phase. These findings implied that N-glycosylation might be crucial for E-cadherin-mediated suppression of cell cycle progression.

  10. Theory of Multiple Intelligences at Teacher Supervision

    Directory of Open Access Journals (Sweden)

    İzzet Döş

    2012-07-01

    Full Text Available This study aims to determine views of teachers and supervisors related to the multiple intelligences in students’ learning that they took into consideration in the evaluation of teachers during lesson supervision. The study was conducted with 5 supervisors who work at Kahramanmaraş provincial directorate of national education and 10 teachers who work at primary schools in the centre of Kahramanmaraş in 2011-2012 year. Data was gathered with the help of interview form consisting of five open-ended questions. In the analysis of the data content analysis which is one of the qualitative research methods. According to the results of the analysis, it has been found that usage of multiple intelligences theory in the evaluation students’ learning during supervision enabled them to evaluate students’ learning in a more detailed way. It also made it possible for the supervisors to examine supervision evaluations at different levels. It was also mentioned that supervisions made according to multiple intelligence theory has some limitations.

  11. On Restraint of and Supervision over Power

    Institute of Scientific and Technical Information of China (English)

    DONG YUNHU

    2007-01-01

    @@ Power is the nucleus of social and political life. Effective restraint on and supervision over the operation of power is the fundamental way of preventing corruption of power, which at the same time constitutes an important indication to democracy and its development in a given country.

  12. Peer Supervision: Toward More Effective Training.

    Science.gov (United States)

    Wagner, Carol A.; Smith, James P., Jr.

    1979-01-01

    Discusses peer supervision as a vehicle for increasing student responsibility for self-assessment and peer assessment, and increasing independence and interdependence among students for professional and personal growth. The article also explains a model of a master's degree program in counseling and includes rationale, definition, implementation,…

  13. Case Studies in Middle Management Supervision

    Science.gov (United States)

    White, Lori S.

    2011-01-01

    This chapter presents a series of supervision-related case studies of situations that midlevel managers might face. Individuals enrolled in a midlevel management professional development course recommended the topics selected for this chapter. Drawing upon her experience teaching the course, the author selected four case studies that individuals…

  14. 19 CFR 111.28 - Responsible supervision.

    Science.gov (United States)

    2010-04-01

    ... TREASURY CUSTOMS BROKERS Duties and Responsibilities of Customs Brokers § 111.28 Responsible supervision... the broker intends to transact customs business, a list of the names of persons currently employed by... the broker already has a permit, and before the broker begins to transact customs business as a...

  15. Magazine Picture Collage in Group Supervision

    Science.gov (United States)

    Shepard, Blythe C.; Guenette, Francis L.

    2010-01-01

    A magazine picture collage activity was used with three female counsellor education students as a vehicle to support them in processing their experience as counsellors in training. The use of magazine picture collage in group supervision is described, and the benefits and challenges are presented. The collages served as jumping-off points for…

  16. 19 CFR 19.34 - Customs supervision.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Customs supervision. 19.34 Section 19.34 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CUSTOMS WAREHOUSES, CONTAINER STATIONS AND CONTROL OF MERCHANDISE THEREIN Space Bonded for the Storage...

  17. Cybersupervision: Conducting Supervision on the Information Superhighway.

    Science.gov (United States)

    Coursol, Diane

    The internship experience is an integral part of the graduate program for counselor education students. The APA Code of Ethics and Standards of Practice and the ACPA code of ethics require that students receive regular supervision from site and faculty supervisors during the practicum and internship experiences. However, when student counselors…

  18. Supporting Placement Supervision in Clinical Exercise Physiology

    Science.gov (United States)

    Sealey, Rebecca M.; Raymond, Jacqueline; Groeller, Herb; Rooney, Kieron; Crabb, Meagan; Watt, Kerrianne

    2015-01-01

    The continued engagement of the professional workforce as supervisors is critical for the sustainability and growth of work-integrated learning activities in university degrees. This study investigated factors that influence the willingness and ability of clinicians to continue to supervise clinical exercise physiology work-integrated learning…

  19. 27 CFR 24.30 - Supervision.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Supervision. 24.30 Section 24.30 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS WINE Administrative and Miscellaneous Provisions Authorities § 24.30...

  20. Remote Video Supervision in Adapted Physical Education

    Science.gov (United States)

    Kelly, Luke; Bishop, Jason

    2013-01-01

    Supervision for beginning adapted physical education (APE) teachers and inservice general physical education teachers who are learning to work with students with disabilities poses a number of challenges. The purpose of this article is to describe a project aimed at developing a remote video system that could be used by a university supervisor to…

  1. Spirituality and School Counselor Education and Supervision

    Science.gov (United States)

    Gallo, Laura L.

    2014-01-01

    Spirituality is an area that has not received a great deal of attention in supervision, yet it can have substantial effects on the counseling process. A definition of spirituality that allows for a variety of worldviews can be useful to both counselor and client as it helps strengthen the counseling relationship and lessen differences between…

  2. Performance Monitoring Applied to System Supervision

    Directory of Open Access Journals (Sweden)

    Bertille Somon

    2017-07-01

    Full Text Available Nowadays, automation is present in every aspect of our daily life and has some benefits. Nonetheless, empirical data suggest that traditional automation has many negative performance and safety consequences as it changed task performers into task supervisors. In this context, we propose to use recent insights into the anatomical and neurophysiological substrates of action monitoring in humans, to help further characterize performance monitoring during system supervision. Error monitoring is critical for humans to learn from the consequences of their actions. A wide variety of studies have shown that the error monitoring system is involved not only in our own errors, but also in the errors of others. We hypothesize that the neurobiological correlates of the self-performance monitoring activity can be applied to system supervision. At a larger scale, a better understanding of system supervision may allow its negative effects to be anticipated or even countered. This review is divided into three main parts. First, we assess the neurophysiological correlates of self-performance monitoring and their characteristics during error execution. Then, we extend these results to include performance monitoring and error observation of others or of systems. Finally, we provide further directions in the study of system supervision and assess the limits preventing us from studying a well-known phenomenon: the Out-Of-the-Loop (OOL performance problem.

  3. Computer Monitor Supervision: A Clinical Note.

    Science.gov (United States)

    Scherl, Charles R.; Haley, Jay

    2000-01-01

    Presents communication procedures for supervisors and therapy trainees that have been developed as a result of the use of computer technology. Using the computer as a supervision tool, therapy can be influenced by the supervisor while minimizing disruption. Successes and pitfalls in a master's level practicum course in family therapy are…

  4. Computer Monitor Supervision: A Clinical Note.

    Science.gov (United States)

    Scherl, Charles R.; Haley, Jay

    2000-01-01

    Presents communication procedures for supervisors and therapy trainees that have been developed as a result of the use of computer technology. Using the computer as a supervision tool, therapy can be influenced by the supervisor while minimizing disruption. Successes and pitfalls in a master's level practicum course in family therapy are…

  5. Enhancing Adult Learning in Clinical Supervision

    Science.gov (United States)

    Goldman, Stuart

    2011-01-01

    Objective/Background: For decades, across almost every training site, clinical supervision has been considered "central to the development of skills" in psychiatry. The crucial supervisor/supervisee relationship has been described extensively in the literature, most often framed as a clinical apprenticeship of the novice to the master craftsman.…

  6. Supervision That Improves Teaching: Strategies and Techniques.

    Science.gov (United States)

    Sullivan, Susan; Glanz, Jeffrey

    This book offers a plan for improved classroom practice through the supervisory process. It includes hands-on practices for developing a personalized supervision strategy, research-based and empirically tested strategies, field-tested tools and techniques for qualitative and quantitative observation, a comprehensive resource of traditional and…

  7. Instructional Supervision: The Policy-Practice Rift.

    Science.gov (United States)

    Tunison, Scott D.

    2001-01-01

    Discusses the results of a recent Canadian study in which the perceptions of superintendents, principals, and teachers were analyzed and compared in order to determine the actual level of agreement between the practices for instructional supervision outlined in the school division's policy manual and the actual practice in the schools governed by…

  8. On Training Targets for Supervised Speech Separation

    Science.gov (United States)

    Wang, Yuxuan; Narayanan, Arun; Wang, DeLiang

    2014-01-01

    Formulation of speech separation as a supervised learning problem has shown considerable promise. In its simplest form, a supervised learning algorithm, typically a deep neural network, is trained to learn a mapping from noisy features to a time-frequency representation of the target of interest. Traditionally, the ideal binary mask (IBM) is used as the target because of its simplicity and large speech intelligibility gains. The supervised learning framework, however, is not restricted to the use of binary targets. In this study, we evaluate and compare separation results by using different training targets, including the IBM, the target binary mask, the ideal ratio mask (IRM), the short-time Fourier transform spectral magnitude and its corresponding mask (FFT-MASK), and the Gammatone frequency power spectrum. Our results in various test conditions reveal that the two ratio mask targets, the IRM and the FFT-MASK, outperform the other targets in terms of objective intelligibility and quality metrics. In addition, we find that masking based targets, in general, are significantly better than spectral envelope based targets. We also present comparisons with recent methods in non-negative matrix factorization and speech enhancement, which show clear performance advantages of supervised speech separation. PMID:25599083

  9. Making Supervision Relationships Accountable: Graduate Student Logs.

    Science.gov (United States)

    Yeatman, Anna

    1995-01-01

    Graduate student journals of research projects and their supervision are suggested as a means of structuring the supervisory process, making it more accountable, and facilitating students' successful completion of their academic and research tasks. However, the method also requires skill in successful thesis production on the supervisor's part.…

  10. How to Supervise a Ph.D.

    Science.gov (United States)

    Connell, R. W.

    1985-01-01

    A discussion of the process and problems of supervising a doctoral candidate examines the nature of the task and relationship, the stages of research (defining the topic, design, gathering material, writing, defense, and dissemination), criticism and intellectual growth, and references and sponsorship. (MSE)

  11. Parallelprocesser og deres tilblivelse i supervision

    DEFF Research Database (Denmark)

    Jacobsen, Claus Haugaard

    2006-01-01

    Kapitlet beskæftiger sig med ”Parallelprocesser og deres tilblivelse i supervision”. Først indkredses parallelprocesbegrebet i dets mange variationer. Der er tale om et nøglebegreb i psykoanalytisk supervision, der overordnet set henviser til en relationel positionering eller tematik i...

  12. Exploring Principals' Perceptions of Supervised Agricultural Experience

    Science.gov (United States)

    Rayfield, John; Wilson, Elizabeth

    2009-01-01

    This study explored the perceptions of principals at high schools with agricultural education programs in regard to Supervised Agricultural Experience (SAE). There is evidence that suggests that high school principals' attitudes may both directly and indirectly affect factors that influence school climate and student achievement. In this study,…

  13. A Social Reconstruction Model of Supervision.

    Science.gov (United States)

    Seda, E. Elliott

    This paper presents a social reconstructionist model of supervision. The model connects schools and society, and considers the vital role teachers, students, staff, and others play in developing, designing, and implementing reforms in school and society. The model is based on the philosophy of social reconstructionism, which views schools as…

  14. Experiences of Supervision at Practice Placement Sites

    Directory of Open Access Journals (Sweden)

    Lesley Diack

    2014-01-01

    Full Text Available Background. Whilst placement supervision and clinical education programmes are of significant value in shaping the behaviours of undergraduate healthcare students, appropriate provisions which are efficacious to the learner are somewhat lacking, particularly for students studying on UK MPharm programmes. Objectives. To explore and explain the value of placement supervision to the personal development and employability of undergraduate pharmacy students. Methods. Students participated in a week long community pharmacy pilot programme, a result of a collaborative effort between the School of Pharmacy and Life Sciences and a small consortium of community pharmacies. Students and stakeholders were asked to evaluate their experiences via separate questionnaires which had been developed to elicit views and attitudes. Key Findings. Feedback from students and stakeholders towards the experience was overwhelmingly positive with multiple benefits being reported. Of particular prominence was the emphasis in student feedback on the value of placement supervision to their professional and personal development. Findings were indicative of a development in clinical practice proficiencies, core skills, and improvement in decision-making practice. Conclusions. The benefits of clinical supervision to the professional and personal development of MPharm students are well documented, although attracting professional pharmacy supervisors is proving a problematic task for educational providers in the UK.

  15. Extracting microRNA-gene relations from biomedical literature using distant supervision.

    Science.gov (United States)

    Lamurias, Andre; Clarke, Luka A; Couto, Francisco M

    2017-01-01

    Many biomedical relation extraction approaches are based on supervised machine learning, requiring an annotated corpus. Distant supervision aims at training a classifier by combining a knowledge base with a corpus, reducing the amount of manual effort necessary. This is particularly useful for biomedicine because many databases and ontologies have been made available for many biological processes, while the availability of annotated corpora is still limited. We studied the extraction of microRNA-gene relations from text. MicroRNA regulation is an important biological process due to its close association with human diseases. The proposed method, IBRel, is based on distantly supervised multi-instance learning. We evaluated IBRel on three datasets, and the results were compared with a co-occurrence approach as well as a supervised machine learning algorithm. While supervised learning outperformed on two of those datasets, IBRel obtained an F-score 28.3 percentage points higher on the dataset for which there was no training set developed specifically. To demonstrate the applicability of IBRel, we used it to extract 27 miRNA-gene relations from recently published papers about cystic fibrosis. Our results demonstrate that our method can be successfully used to extract relations from literature about a biological process without an annotated corpus. The source code and data used in this study are available at https://github.com/AndreLamurias/IBRel.

  16. Extracting microRNA-gene relations from biomedical literature using distant supervision

    Science.gov (United States)

    Clarke, Luka A.; Couto, Francisco M.

    2017-01-01

    Many biomedical relation extraction approaches are based on supervised machine learning, requiring an annotated corpus. Distant supervision aims at training a classifier by combining a knowledge base with a corpus, reducing the amount of manual effort necessary. This is particularly useful for biomedicine because many databases and ontologies have been made available for many biological processes, while the availability of annotated corpora is still limited. We studied the extraction of microRNA-gene relations from text. MicroRNA regulation is an important biological process due to its close association with human diseases. The proposed method, IBRel, is based on distantly supervised multi-instance learning. We evaluated IBRel on three datasets, and the results were compared with a co-occurrence approach as well as a supervised machine learning algorithm. While supervised learning outperformed on two of those datasets, IBRel obtained an F-score 28.3 percentage points higher on the dataset for which there was no training set developed specifically. To demonstrate the applicability of IBRel, we used it to extract 27 miRNA-gene relations from recently published papers about cystic fibrosis. Our results demonstrate that our method can be successfully used to extract relations from literature about a biological process without an annotated corpus. The source code and data used in this study are available at https://github.com/AndreLamurias/IBRel. PMID:28263989

  17. A microRNA/Runx1/Runx2 network regulates prostate tumor progression from onset to adenocarcinoma in TRAMP mice.

    Science.gov (United States)

    Farina, Nicholas H; Zingiryan, Areg; Akech, Jacqueline A; Callahan, Cody J; Lu, Huimin; Stein, Janet L; Languino, Lucia R; Stein, Gary S; Lian, Jane B

    2016-10-25

    While decades of research have identified molecular pathways inducing and promoting stages of prostate cancer malignancy, studies addressing dynamic changes of cancer-related regulatory factors in a prostate tumor progression model are limited. Using the TRAMP mouse model of human prostate cancer, we address mechanisms of deregulation for the cancer-associated transcription factors, Runx1 and Runx2 by identifying microRNAs with reciprocal expression changes at six time points during 33 weeks of tumorigenesis. We molecularly define transition stages from PIN lesions to hyperplasia/neoplasia and progression to adenocarcinoma by temporal changes in expression of human prostate cancer markers, including the androgen receptor and tumor suppressors, Nkx3.1 and PTEN. Concomitant activation of PTEN, AR, and Runx factors occurs at early stages. At late stages, PTEN and AR are downregulated, while Runx1 and Runx2 remain elevated. Loss of Runx-targeting microRNAs, miR-23b-5p, miR-139-5p, miR-205-5p, miR-221-3p, miR-375-3p, miR-382-5p, and miR-384-5p, contribute to aberrant Runx expression in prostate tumors. Our studies reveal a Runx/miRNA interaction axis centered on PTEN-PI3K-AKT signaling. This regulatory network translates to mechanistic understanding of prostate tumorigenesis that can be developed for diagnosis and directed therapy.

  18. Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer

    Science.gov (United States)

    Heger, Zbynek; Merlos Rodrigo, Miguel Angel; Michalek, Petr; Polanska, Hana; Masarik, Michal; Vit, Vitezslav; Plevova, Mariana; Pacik, Dalibor; Eckschlager, Tomas; Stiborova, Marie

    2016-01-01

    The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential. PMID:27824899

  19. Supervisor's HEXACO personality traits and subordinate perceptions of abusive supervision

    NARCIS (Netherlands)

    Breevaart, Kimberley; Vries, de Reinout E.

    2017-01-01

    Abusive supervision is detrimental to both subordinates and organizations. Knowledge about individual differences in personality related to abusive supervision may improve personnel selection and potentially reduce the harmful effects of this type of leadership. Using the HEXACO personality framewor

  20. Sirtuin1功能及调控研究进展%PROGRESS IN FUNCTIONS AND REGULATION OF SIRTUIN 1

    Institute of Scientific and Technical Information of China (English)

    赵雯; 李方晖; 肖冰

    2012-01-01

    Sirtuin 1 (SIR.T1) is the largest among the seven members of the sirtuin family of class HI nicoiinamide ade-nine dinucleoude (NAD ( + ))-dependent protein deacetylases, which is the most widely studied longevity factor in recent studies. In addition to achieve the epigenelic regulation by the acetylation of lysine residues in histories, SIRT1 can also regulate the activity of several other key cellular proteins, which have emerged as critical regulators of cell growth, differentiation, and apoptolic programs. Recent studies have found that SIRT1 regulation on cell functions is not only through the level of its activity, but also through subcellular localization. SIRT1 shuttles between nucleus and cytoplasm and the level of SIRT1 activity and its physiological function regulation still need to be further studied.%Sirtuin 1(SIRTl)是依赖于烟酰胺腺(嘿)呤二核苷酸辅酶(nicotinamide adenine dinucleotide,NAD+)的去乙酰化酶(Sirtuins,SIRTs)家族7个成员中最大的一个,是近年来研究最为广泛的长寿因子.SIRT1除了对组蛋里赖氨酸残基去乙酰化修饰调节表现遗传外,SIRT1还可以调节细胞其他关键蛋白活性,控制细胞增殖、分化和细胞凋亡等生理功能.量近研究发现,SIRT1调控细胞功能除了与其酶活性水平有关,也可能风其在细胞中的定位有关.SIRT1在细胞核质之间穿梭和SIRT1活性水平及其相对应的生理功能仍需深入研究.

  1. How to contribute to the progress of neuroendocrinology: New insights from discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions.

    Science.gov (United States)

    Tsutsui, Kazuyoshi

    2016-02-01

    Obtaining new insights by discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions is essential for the progress of neuroendocrinology. At the beginning of 1970s, gonadotropin-releasing hormone (GnRH) was discovered in mammals. Since then, it was generally accepted that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in vertebrates. In 2000, however, gonadotropin-inhibitory hormone (GnIH), a novel hypothalamic neuropeptide that actively inhibits gonadotropin release, was discovered in quail. The follow-up studies demonstrated that GnIH acts as a new key player for regulation of reproduction across vertebrates. It now appears that GnIH acts on the pituitary and the brain to serve a number of behavioral and physiological functions. On the other hand, a new concept has been established that the brain synthesizes steroids, called neurosteroids. The formation of neurosteroids in the brain was originally demonstrated in mammals and subsequently in other vertebrates. Recently, 7α-hydroxypregnenolone was discovered as a novel bioactive neurosteroid inducing locomotor behavior of vertebrates, indicating that neurosteroidogenesis in the brain is still incompletely elucidated in vertebrates. At the beginning of 2010s, it was further found that the pineal gland actively produces neurosteroids. Pineal neurosteroids act on the brain to regulate locomotor rhythms and neuronal survival. Furthermore, the interaction of neuropeptides and neurosteroids is becoming clear. GnIH decreases aggressive behavior by regulating neuroestrogen synthesis in the brain. This review summarizes these new insights by discovering novel neuropeptides and neurosteroids in the field of neuroendocrinology.

  2. Deep Learning at 15PF: Supervised and Semi-Supervised Classification for Scientific Data

    OpenAIRE

    Kurth, Thorsten; Zhang, Jian; Satish, Nadathur; Mitliagkas, Ioannis; Racah, Evan; Patwary, Mostofa Ali; Malas, Tareq; Sundaram, Narayanan; Bhimji, Wahid; Smorkalov, Mikhail; Deslippe, Jack; Shiryaev, Mikhail; Sridharan, Srinivas; Prabhat; Dubey, Pradeep

    2017-01-01

    This paper presents the first, 15-PetaFLOP Deep Learning system for solving scientific pattern classification problems on contemporary HPC architectures. We develop supervised convolutional architectures for discriminating signals in high-energy physics data as well as semi-supervised architectures for localizing and classifying extreme weather in climate data. Our Intelcaffe-based implementation obtains $\\sim$2TFLOP/s on a single Cori Phase-II Xeon-Phi node. We use a hybrid strategy employin...

  3. Development of well construction and workover supervising in Russian Federation

    Science.gov (United States)

    Sizov, A.; Boyarko, G.; Shenderova, I.

    2014-08-01

    Despite long history of drilling supervising it still has a number of uncertainties. The period of rapid rise in supervising development at the beginning of the 90's changed in the 2000's. The necessity in the development of this sphere is obvious. The author describes the history of supervising, period of its market condition adaptation. The research also gives principles methods of supervising development and first steps for its position improvement.

  4. Beta-endorphin neuron regulates stress response and innate immunity to prevent breast cancer growth and progression.

    Science.gov (United States)

    Sarkar, Dipak K; Zhang, Changqing

    2013-01-01

    Body and mind interact extensively with each other to control health. Emerging evidence suggests that chronic neurobehavioral stress can promote various tumor growth and progression. The biological reaction to stress involves a chemical cascade initiated within the central nervous system and extends to the periphery, encompassing the immune, endocrine, and autonomic systems. Activation of sympathetic nervous system, such as what happens in the "fight or flight" response, downregulates tumor-suppressive genes, inhibits immune function, and promotes tumor growth. On the other hand, an optimistic attitude or psychological intervention helps cancer patients to survive longer via increase in β-endorphin neuronal suppression of stress hormone levels and sympathetic outflows and activation of parasympathetic control of tumor suppressor gene and innate immune cells to destroy and clear tumor cells.

  5. PTHrP produced by myeloma plasma cells regulates their survival and pro-osteoclast activity for bone disease progression.

    Science.gov (United States)

    Cafforio, Paola; Savonarola, Annalisa; Stucci, Stefania; De Matteo, Monica; Tucci, Marco; Brunetti, Anna Elisabetta; Vecchio, Vita Mariagrazia; Silvestris, Francesco

    2014-01-01

    To promote their survival and progression in the skeleton, osteotropic malignancies of breast, lung, and prostate produce parathyroid hormone-related protein (PTHrP), which induces hypercalcemia. PTHrP serum elevations have also been described in multiple myeloma (MM), although their role is not well defined. When we investigated MM cells from patients and cell lines, we found that PTHrP and its receptor (PTH-R1) are highly expressed, and that PTHrP is secreted both as a full-length molecule and as small subunits. Among these subunits, the mid-region, including the nuclear localization sequence (NLS), exerted a proliferative effect because it was accumulated in nuclei of MM cells surviving in starvation conditions. This was confirmed by increased transcription of several genes enrolled in proliferation and apoptosis control. PTHrP was also found to stimulate PTH-R1 in MM cells. PTH-R1's selective activation by the full-length PTHrP molecule or the NH2 -terminal fragment resulted in a significant increase of intracellular Ca(2+) influx, cyclic adenosine monophosphate (cAMP) content, and expression of receptor activator of NF-κB ligand (RANKL) and monocyte chemoattractant protein-1 (MCP-1). Our data definitely clarify the role of PTHrP in MM. The PTHrP peptide is functionally secreted by malignant plasma cells and contributes to MM tumor biology and progression, both by intracrine maintenance of cell proliferation in stress conditions and by autocrine or paracrine stimulation of PTH-R1, which in turn reinforces the production of osteoclastogenic factors. © 2014 American Society for Bone and Mineral Research. © 2014 American Society for Bone and Mineral Research.

  6. Allele loss and down-regulation of heparanase gene are associated with the progression and poor prognosis of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Guo-Liang Huang

    Full Text Available OBJECTIVES: The role of heparanase (HPSE gene in cancers including hepatocellular carcinoma (HCC is currently controversial. This study was aimed at investigating the impact of genetic alteration and expression change of HPSE on the progression and prognosis of HCC. METHODS: The HPSE gene was studied in three different aspects: (1 loss of heterozygosity (LOH by a custom SNP microarray and DNA copy number by real-time PCR; (2 mRNA level by qRT-PCR; and (3 protein expression by immunohistochemistry. The clinical significances of allele loss and expression change of HPSE were analyzed. RESULTS: Microarray analysis showed that the average LOH frequency for 10 SNPs located within HPSE gene was 31.6%, three of which were significantly correlated with tumor grade, serum HBV-DNA level, and AFP concentration. In agreement with SNP LOH data, DNA copy number loss of HPSE was observed in 38.74% (43/111 of HCC cases. HPSE mRNA level was notably reduced in 74.1% (83/112 of tumor tissues compared with non-tumor liver tissues, which was significantly associated with DNA copy number loss, increased tumor size, and post-operative metastasis. HPSE protein level was also remarkably reduced in 66.3% (53/80 of tumor tissues, which was correlated with tumor grade. Patients with lower expression level of HPSE mRNA or protein had a significantly lower survival rate than those with higher expression. Cox regression analysis suggested that HPSE protein was an independent predictor of overall survival in HCC patients. CONCLUSIONS: The results in this study demonstrate that genetic alteration and reduction of HPSE expression are associated with tumor progression and poor prognosis of HCCs, suggesting that HPSE behaves like a tumor suppressor gene and is a potential prognostic marker for HCC patients.

  7. Research Progress in Regulation of Pokemon and MicroRNA on Carcinogensis and Progress for Colon Cancer%Pokemon及microRNA调控结肠癌发生发展的研究进展

    Institute of Scientific and Technical Information of China (English)

    别延红

    2013-01-01

    Pokemon蛋白(也被称为LRF、ZBTB7、OCZF、FBI-1),即POK红系髓性致癌因子(erythroid ontogenic factor),是转录抑制因子POK家族的一员,现已被确认为原癌基因.微小核糖核酸microRNA (miRNA)是近年来研究最活跃的细胞调控因子,miRNA是一种22~25个核苷酸之间的非编码RNA,能在转录和翻译水平上调控基因表达,它们都在结肠癌中发挥作用.文章对Pokemon、miRNA调控结肠癌发生发展的研究进行综述.%POK erythroid myeloid ontogenic factor (Pokemon),also called as LRF,ZBTB7,OCZF or FBI-1,has been identified as an oncogene.MicroRNAs (miRNAs) are 22~25 nucleotides long,non-coding RNAs,which could regulate transcriptional and translational gene expression.Both Pokemon and miRNAs play very important roles in colon cancer.This paper reviews on Pokemon and miRNA regulating carcinogensis and progress for colon cancer.

  8. Exposure to 9,10-phenanthrenequinone accelerates malignant progression of lung cancer cells through up-regulation of aldo-keto reductase 1B10

    Energy Technology Data Exchange (ETDEWEB)

    Matsunaga, Toshiyuki, E-mail: matsunagat@gifu-pu.ac.jp [Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196 (Japan); Morikawa, Yoshifumi; Haga, Mariko; Endo, Satoshi [Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196 (Japan); Soda, Midori; Yamamura, Keiko [Laboratory of Clinical Pharmacy, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650 (Japan); El-Kabbani, Ossama [Monash Institute of Pharmaceutical Sciences, Monash University, Victoria 3052 (Australia); Tajima, Kazuo [Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa 920-1181 (Japan); Ikari, Akira [Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196 (Japan); Hara, Akira [Faculty of Engineering, Gifu University, Gifu 501-1193 (Japan)

    2014-07-15

    Inhalation of 9,10-phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust, exerts fatal damage against a variety of cells involved in respiratory function. Here, we show that treatment with high concentrations of 9,10-PQ evokes apoptosis of lung cancer A549 cells through production of reactive oxygen species (ROS). In contrast, 9,10-PQ at its concentrations of 2 and 5 μM elevated the potentials for proliferation, invasion, metastasis and tumorigenesis, all of which were almost completely inhibited by addition of an antioxidant N-acetyl-L-cysteine, inferring a crucial role of ROS in the overgrowth and malignant progression of lung cancer cells. Comparison of mRNA expression levels of six aldo-keto reductases (AKRs) in the 9,10-PQ-treated cells advocated up-regulation of AKR1B10 as a major cause contributing to the lung cancer malignancy. In support of this, the elevation of invasive, metastatic and tumorigenic activities in the 9,10-PQ-treated cells was significantly abolished by the addition of a selective AKR1B10 inhibitor oleanolic acid. Intriguingly, zymographic and real-time PCR analyses revealed remarkable increases in secretion and expression, respectively, of matrix metalloproteinase 2 during the 9,10-PQ treatment, and suggested that the AKR1B10 up-regulation and resultant activation of mitogen-activated protein kinase cascade are predominant mechanisms underlying the metalloproteinase induction. In addition, HPLC analysis and cytochrome c reduction assay in in vitro 9,10-PQ reduction by AKR1B10 demonstrated that the enzyme catalyzes redox-cycling of this quinone, by which ROS are produced. Collectively, these results suggest that AKR1B10 is a key regulator involved in overgrowth and malignant progression of the lung cancer cells through ROS production due to 9,10-PQ redox-cycling. - Highlights: • 9,10-PQ promotes invasion, metastasis and tumorigenicity in lung cancer cells. • The 9,10-PQ-elicited promotion is possibly due to AKR1B10 up-regulation

  9. Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling.

    Science.gov (United States)

    Guo, Huabei; Nagy, Tamas; Pierce, Michael

    2014-11-01

    Deletion of GnT-V (MGAT5), which synthesizes N-glycans with β(1,6)-branched glycans, reduced the compartment of cancer stem cells (CSC) in the her-2 mouse model of breast cancer, leading to delay of tumor onset. Because GnT-V levels are also commonly up-regulated in colon cancer, we investigated their regulation of colon CSC and adenoma development. Anchorage-independent cell growth and tumor formation induced by injection of colon tumor cells into NOD/SCID mice were positively associated with GnT-V levels, indicating regulation of proliferation and tumorigenicity. Using Apc(min/+) mice with different GnT-V backgrounds, knock-out of GnT-V had no significant effect on the number of adenoma/mouse, but adenoma size was significantly reduced and accompanied increased survival of Apc(min/+) mice with GnT-V deletion (p cells, we found that FZD-7 receptors expressed N-linked β(1,6) branching, indicating that FZD-7 can be modified by GnT-V. The aberrant Wnt signaling observed after modulating GnT-V levels is likely to result from altered N-linked β(1,6) branching on FZD-7, thereby affecting Wnt signaling, the compartment of CSC, and tumor progression.

  10. Clients' Views of Live Supervision and Satisfaction with Therapy.

    Science.gov (United States)

    Locke, Lisa D.; McCollum, Eric E.

    2001-01-01

    Examines clients' perceptions of live supervision and their satisfaction with therapy in a university-based training clinic for marriage and family therapists. Results indicate that clients were generally satisfied with therapy and found the live-supervision process satisfactory as long as the perceived helpfulness of live supervision outweighed…

  11. Supervising development in petroleum industry of the Russian Federation

    OpenAIRE

    Sizov, Aleksey Valentinovich; Tretyakov, Konstantin Nikolaevich; Boyarko, Grigory Yurievich; Shenderova, Inna Vladimirovna; Shakirov, A.

    2015-01-01

    Supervising has strongly consolidated in the domestic petroleum services market of the Russian Federation. But despite the rapid growth of the supervising services market, there is a definite need for its further development. In the article, the developments of supervising in petroleum industry of the Russian Federation, as well as possible ways of its improvement are considered.

  12. Does Live Supervision Make a Difference? A Multilevel Analysis

    Science.gov (United States)

    Silverthorn, Brandon C.; Bartle-Haring, Suzanne; Meyer, Kevin; Toviessi, Paula

    2009-01-01

    While the benefit of live supervision on clinical training is largely unquestioned, research that examines how live supervision affects the therapeutic process is lacking. Although marriage and family therapy has embraced this method of supervision, there is little empirical evidence suggesting it "works." This study uses hierarchical linear…

  13. A Delphi Study and Initial Validation of Counselor Supervision Competencies

    Science.gov (United States)

    Neuer Colburn, Anita A.; Grothaus, Tim; Hays, Danica G.; Milliken, Tammi

    2016-01-01

    The authors addressed the lack of supervision training standards for doctoral counseling graduates by developing and validating an initial list of supervision competencies. They used content analysis, Delphi polling, and content validity methods to generate a list, vetted by 2 different panels of supervision experts, of 33 competencies grouped…

  14. Style and Quality in Research Supervision: The Supervisor Dependency Factor.

    Science.gov (United States)

    Kam, Booi Hon

    1997-01-01

    A survey of 250 graduate research students examined the extent of dependency on supervisors in a range of research-related tasks, and how that dependency affected the research supervision process. Results suggest appropriate research supervision has no set prescription, but interactions among quality and style of supervision, role expectations of…

  15. Testing Group Supervision in Fieldwork Training for Social Work Students

    Science.gov (United States)

    Zeira, Anat; Schiff, Miriam

    2010-01-01

    This study monitors group supervision for students' field training in a Bachelor's Degree in Social Work (BSW) program and compares it with the experience of the students receiving the traditional individual supervision. The experimental group supervision model is implemented in two consecutive years. Students' experiences are compared at three…

  16. 18 CFR 367.9110 - Account 911, Supervision.

    Science.gov (United States)

    2010-04-01

    ..., Supervision. 367.9110 Section 367.9110 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... ACT Operation and Maintenance Expense Chart of Accounts § 367.9110 Account 911, Supervision. This account must include the cost of labor and expenses incurred in the general direction and supervision...

  17. 28 CFR 2.95 - Early termination from supervision.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Early termination from supervision. 2.95 Section 2.95 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND RECOMMITMENT... Parolees § 2.95 Early termination from supervision. (a)(1) Upon its own motion or upon request of a...

  18. Testing Group Supervision in Fieldwork Training for Social Work Students

    Science.gov (United States)

    Zeira, Anat; Schiff, Miriam

    2010-01-01

    This study monitors group supervision for students' field training in a Bachelor's Degree in Social Work (BSW) program and compares it with the experience of the students receiving the traditional individual supervision. The experimental group supervision model is implemented in two consecutive years. Students' experiences are compared at three…

  19. 25 CFR 213.43 - Relinquishment of Government supervision.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Relinquishment of Government supervision. 213.43 Section... Relinquishment of Government supervision. All oil and gas leases hereafter executed shall contain the following relinquishment of supervision clause and terms operative after such relinquishment, or other provisions...

  20. 34 CFR 303.501 - Supervision and monitoring of programs.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Supervision and monitoring of programs. 303.501 Section... INFANTS AND TODDLERS WITH DISABILITIES State Administration General § 303.501 Supervision and monitoring... supervision of programs and activities receiving assistance under this part; and (2) The monitoring...

  1. 7 CFR 27.73 - Supervision of transfers of cotton.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Supervision of transfers of cotton. 27.73 Section 27... Supervision of transfers of cotton. Whenever the owner of any cotton inspected and sampled for classification... be effected under the supervision of an exchange inspection agency or a supervisor of...

  2. 28 CFR 570.44 - Supervision and restraint requirements.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Supervision and restraint requirements... PROGRAMS AND RELEASE COMMUNITY PROGRAMS Escorted Trips § 570.44 Supervision and restraint requirements. Inmates under escort will be within the constant and immediate visual supervision of escorting staff...

  3. 18 CFR 367.9070 - Account 907, Supervision.

    Science.gov (United States)

    2010-04-01

    ..., Supervision. 367.9070 Section 367.9070 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... ACT Operation and Maintenance Expense Chart of Accounts § 367.9070 Account 907, Supervision. This account must include the cost of labor and expenses incurred in the general direction and supervision...

  4. 9 CFR 590.418 - Supervision of marking and packaging.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Supervision of marking and packaging...) Identifying and Marking Product § 590.418 Supervision of marking and packaging. (a) Evidence of label approval... container except by an inspector or under the supervision of an inspector or other person authorized by...

  5. 49 CFR 237.133 - Supervision of repairs and modifications.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Supervision of repairs and modifications. 237.133... Supervision of repairs and modifications. Each repair or modification pursuant to this part shall be performed under the immediate supervision of a railroad bridge supervisor as defined in § 237.55 of this part...

  6. 7 CFR 27.80 - Fees; classification, Micronaire, and supervision.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Fees; classification, Micronaire, and supervision. 27... Classification and Micronaire § 27.80 Fees; classification, Micronaire, and supervision. For services rendered by... classification and Micronaire determination results certified on cotton class certificates.) (e) Supervision,...

  7. 46 CFR 380.23 - Supervision of records.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Supervision of records. 380.23 Section 380.23 Shipping... § 380.23 Supervision of records. (a) Contractors and others subject to the provisions of this subpart... shall be responsible for supervision of its document retention and disposal program. Immediately...

  8. 18 CFR 367.9010 - Account 901, Supervision.

    Science.gov (United States)

    2010-04-01

    ..., Supervision. 367.9010 Section 367.9010 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... ACT Operation and Maintenance Expense Chart of Accounts § 367.9010 Account 901, Supervision. This account must include the cost of labor and expenses incurred in the general direction and supervision...

  9. 46 CFR 131.420 - Manning and supervision.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Manning and supervision. 131.420 Section 131.420 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS OPERATIONS Sufficiency and Supervision of Crew of Survival Craft § 131.420 Manning and supervision. (a) There must...

  10. 33 CFR 6.12-1 - General supervision and control.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false General supervision and control... GENERAL PROTECTION AND SECURITY OF VESSELS, HARBORS, AND WATERFRONT FACILITIES Supervision and Control of Explosives or Other Dangerous Cargo § 6.12-1 General supervision and control. The Captain of the Port...

  11. 34 CFR 300.149 - SEA responsibility for general supervision.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false SEA responsibility for general supervision. 300.149... EDUCATION OF CHILDREN WITH DISABILITIES State Eligibility Sea Responsibility for General Supervision and Implementation of Procedural Safeguards § 300.149 SEA responsibility for general supervision. (a) The SEA...

  12. 7 CFR 58.6 - Supervision of service.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Supervision of service. 58.6 Section 58.6 Agriculture... Grading Service § 58.6 Supervision of service. All inspection or grading service shall be subject to supervision by a supervisory inspector or grader, Area Supervisor, or by the Chief, or such other person...

  13. 7 CFR 27.16 - Inspection; weighing; samples; supervision.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Inspection; weighing; samples; supervision. 27.16... Samples § 27.16 Inspection; weighing; samples; supervision. The inspection, weighing, and sampling of... Services Office shall be (a) under the supervision of a supervisor of cotton inspection, or (b) by or...

  14. 9 CFR 592.340 - Supervision of marking and packaging.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Supervision of marking and packaging... § 592.340 Supervision of marking and packaging. (a) Evidence of label approval. Inspection program... product or container thereof except by an inspection program employee or under the supervision of...

  15. Status of Clinical Supervision among School Counselors in Southeast Georgia

    Science.gov (United States)

    Black, Anna Lila; Bailey, Carrie Lynn; Bergin, James J.

    2011-01-01

    Previous studies have investigated the role of clinical supervision in school counseling practice. This research explored the status and meaning of clinical supervision to school counselors employed in two southeastern Georgia counties. Results indicate that participants value clinical supervision even though their employers did not necessarily…

  16. 30 CFR 250.1616 - Supervision, surveillance, and training.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Supervision, surveillance, and training. 250.1616 Section 250.1616 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR... Supervision, surveillance, and training. (a) The lessee shall provide onsite supervision of...

  17. 12 CFR 905.13 - Office of Supervision.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Office of Supervision. 905.13 Section 905.13... OPERATIONS DESCRIPTION OF ORGANIZATION AND FUNCTIONS General Organization § 905.13 Office of Supervision. (a) General. The Office of Supervision is responsible for conducting on-site examinations of the...

  18. 27 CFR 19.970 - Supervision of operations.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Supervision of operations..., DEPARTMENT OF THE TREASURY LIQUORS DISTILLED SPIRITS PLANTS Distilled Spirits For Fuel Use Supervision § 19.970 Supervision of operations. The appropriate TTB officer may assign appropriate TTB officers...

  19. 33 CFR 326.4 - Supervision of authorized activities.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Supervision of authorized..., DEPARTMENT OF DEFENSE ENFORCEMENT § 326.4 Supervision of authorized activities. (a) Inspections. District... Government unless daily supervision or other unusual expenses are involved. In such unusual cases,...

  20. Higher Degree Research Supervision: From Practice toward Theory

    Science.gov (United States)

    Maxwell, T. W.; Smyth, Robyn

    2011-01-01

    This paper presents our theorizing about the complex nature of higher degree research supervision. The intent is to make a contribution to the current debates about higher education generally, and supervision of higher degree research students in particular. We add to the pedagogy of supervision by extending its scope to and beyond the supervisory…

  1. Integrating Creativity into Supervision Using Bernard's Discrimination Model

    Science.gov (United States)

    Koltz, Rebecca L.

    2008-01-01

    Clinical supervision is an important aspect of counselor education. Much of traditional supervision is conducted from a logical standpoint; however, some supervisees may be better served when supervisors integrate both logic and creativity. This article presents the integration of creative activities into supervision using Bernard's Discrimination…

  2. Effective Yard Supervision: From Needs Assessment to Customized Training

    Science.gov (United States)

    Sharkey, Jill D.; Hunnicutt, Kayleigh L.; Mayworm, Ashley M.; Schiedel, K. Chris; Calcagnotto, Leandro

    2014-01-01

    Most educational scholars agree that appropriate supervision of children is critical for positive youth development. Supervision is especially important during situations where children have a large degree of freedom and unstructured interaction, such as during recess. Despite the apparent importance of supervision of children at recess, there is…

  3. Educational Technology and Distance Supervision in Counselor Education

    Science.gov (United States)

    Carlisle, Robert Milton; Hays, Danica G.; Pribesh, Shana L.; Wood, Chris T.

    2017-01-01

    The authors used a nonexperimental descriptive design to examine the prevalence of distance supervision in counselor education programs, educational technology used in supervision, training on technology in supervision, and participants' (N = 673) perceptions of legal and ethical compliance. Program policies are recommended to guide the training…

  4. Counseling Supervision within a Feminist Framework: Guidelines for Intervention

    Science.gov (United States)

    Degges-White, Suzanne E.; Colon, Bonnie R.; Borzumato-Gainey, Christine

    2013-01-01

    Feminist supervision is based on the principles of feminist theory. Goals include sharing responsibility for the supervision process, empowering the supervisee, attending to the contextual assumptions about clients, and analyzing gender roles. This article explores feminist supervision and guidelines for providing counseling supervision…

  5. 19 CFR 19.38 - Supervision of exportation.

    Science.gov (United States)

    2010-04-01

    ... the sales ticket procedure for exportation shall be exported only under Customs supervision as... exportation transactions, examination of articles being exported, and audits of the proprietor's records. (b) Supervision of ATF bonded exports. Customs officers may conduct general supervision of exportations...

  6. Regulation of H-Ras-driven MAPK signaling, transformation and tumorigenesis, but not PI3K signaling and tumor progression, by plasma membrane microdomains.

    Science.gov (United States)

    Michael, J V; Wurtzel, J G T; Goldfinger, L E

    2016-05-30

    In this study, we assessed the contributions of plasma membrane (PM) microdomain targeting to the functions of H-Ras and R-Ras. These paralogs have identical effector-binding regions, but variant C-terminal targeting domains (tDs) which are responsible for lateral microdomain distribution: activated H-Ras targets to lipid ordered/disordered (Lo/Ld) domain borders, and R-Ras to Lo domains (rafts). We hypothesized that PM distribution regulates Ras-effector interactions and downstream signaling. We used tD swap mutants, and assessed effects on signal transduction, cell proliferation, transformation and tumorigenesis. R-Ras harboring the H-Ras tD (R-Ras-tH) interacted with Raf, and induced Raf and ERK phosphorylation similar to H-Ras. R-Ras-tH stimulated proliferation and transformation in vitro, and these effects were blocked by both MEK and PI3K inhibition. Conversely, the R-Ras tD suppressed H-Ras-mediated Raf activation and ERK phosphorylation, proliferation and transformation. Thus, Ras access to Raf at the PM is sufficient for MAPK activation and is a principal component of Ras mitogenesis and transformation. Fusion of the R-Ras extended N-terminal domain to H-Ras had no effect on proliferation, but inhibited transformation and tumor progression, indicating that the R-Ras N-terminus also contributes negative regulation to these Ras functions. PI3K activation was tD independent; however, H-Ras was a stronger activator of PI3K than R-Ras, with either tD. PI3K inhibition nearly ablated transformation by R-Ras-tH, H-Ras and H-Ras-tR, whereas MEK inhibition had a modest effect on Ras-tH-driven transformation but no effect on H-Ras-tR transformation. R-Ras-tH supported tumor initiation, but not tumor progression. While H-Ras-tR-induced transformation was reduced relative to H-Ras, tumor progression was robust and similar to H-Ras. H-Ras tumor growth was moderately suppressed by MEK inhibition, which had no effect on H-Ras-tR tumor growth. In contrast, PI3K inhibition

  7. United Kingdom; The Future of Regulation and Supervision Technical Note

    OpenAIRE

    International Monetary Fund

    2011-01-01

    In recent years, the IMF has released a growing number of reports and other documents covering economic and financial developments and trends in member countries. Each report, prepared by a staff team after discussions with government officials, is published at the option of the member country.

  8. Association of Interferon- and Transforming Growth Factor β–Regulated Genes and Macrophage Activation With Systemic Sclerosis–Related Progressive Lung Fibrosis

    Science.gov (United States)

    Christmann, Romy B.; Sampaio-Barros, Percival; Stifano, Giuseppina; Borges, Claudia L.; de Carvalho, Carlos R.; Kairalla, Ronaldo; Parra, Edwin R.; Spira, Avrum; Simms, Robert; Capellozzi, Vera L.; Lafyatis, Robert

    2015-01-01

    Objective Systemic sclerosis (SSc)–related interstitial lung disease (ILD) is one of the leading causes of mortality. We undertook this study to analyze the gene expression of lung tissue in a prospective cohort of patients with SSc-related ILD and to compare it with that in control lungs and with 2 prospective clinical parameters in order to understand the molecular pathways implicated in progressive lung disease. Methods Lung tissue was obtained by open lung biopsy in 28 consecutive patients with SSc-related ILD and in 4 controls. High-resolution computed tomography (HRCT) and pulmonary function testing (PFT) were performed at baseline and 2–3 years after treatment based on lung histologic classification. Microarray analysis was performed, and the results were correlated with changes in the HRCT score (FibMax) and PFT values. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to confirm differential levels of messenger RNA and protein. Results Lung microarray data distinguished patients with SSc-related ILD from healthy controls. In the lungs of patients with SSc-related ILD who had nonspecific interstitial pneumonia (NSIP), expressed genes included macrophage markers, chemokines, collagen, and transforming growth factor β (TGFβ)– and interferon (IFN)–regulated genes. Expression of these genes correlated with progressive lung fibrosis defined by the change in FibMax. Immunohistochemistry confirmed increased markers of collagen (COL1A1), IFN (OAS1 and IFI44), and macrophages (CCL18 and CD163), and the positive correlation with the change in FibMax was confirmed by qPCR in a larger group of SSc patients with NSIP. Several genes correlated with both the change in FibMax (r > 0.4) and the change in % predicted forced vital capacity (r < −0.1), including IFN and macrophage markers, chemokines, and heat-shock proteins. Conclusion These results highlight major pathogenic pathways relevant to progressive pulmonary fibrosis in SSc

  9. Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease

    Directory of Open Access Journals (Sweden)

    Eric D. Abston

    2012-01-01

    Full Text Available Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3 myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL-4-dominant T helper (Th2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis.

  10. Pervasive Modes of Thinking That Affect Our Conduct of Teaching, Supervision, and Research: Are We Stuck in an Old Paradigm?

    Science.gov (United States)

    Krugman, Martin; Andrews, Sharon Vincz

    This paper identifies the major modes of thought that have characterized the conduct of teaching, research, and supervision at institutions of higher education, focusing specifically on the fields of psychology and education. These frameworks for thinking (paradigms) in both the social and "hard" sciences have progressed through three…

  11. Glutathione transferases P1/P2 regulate the timing of signaling pathway activations and cell cycle progression during mouse liver regeneration.

    Science.gov (United States)

    Pajaud, J; Ribault, C; Ben Mosbah, I; Rauch, C; Henderson, C; Bellaud, P; Aninat, C; Loyer, P; Morel, F; Corlu, A

    2015-01-15

    Glutathione transferases (GST) are phase II enzymes catalyzing the detoxification of endogenous noxious compounds and xenobiotics. They also regulate phosphorylation activities of MAPKinases in a catalytic-independent manner. Previous studies have demonstrated the regulation of JNK-dependent pathway by GSTP1/2. Considering the crucial role of JNK in the early steps of the hepatocyte cell cycle, we sought to determine whether GSTP1/2 were essential for hepatocyte proliferation following partial hepatectomy (PH). Using a conventional double knockout mouse model for the Gstp1 and Gstp2 genes, we found that the lack of GSTP1/P2 reduced the rate of DNA replication and mitotic index during the first wave of hepatocyte proliferation. The lowered proliferation was associated with the decrease in TNFalpha and IL-6 plasma concentrations, reduced hepatic HGF expression and delayed and/or altered activation of STAT3, JNK and ERK1/2 signaling pathways. In addition, the expression and/or activation of cell cycle regulators such as Cyclin D1, CDK4, E2F1 and MCM7 was postponed demonstrating that the absence of GSTP1/2 delayed the entry into and progression through the G1 phase of the cell cycle and impaired the synchrony of proliferation in hepatocytes following PH. Furthermore, while JNK and its downstream targets c-Jun and ATF2 were activated during the early steps of the liver regeneration in wild-type animals, the constitutively active JNK found in the quiescent liver of Gstp1/2 knockout mice underwent a decrease in its activity after PH. Transient induction of antioxidant enzymes and nitric oxide synthase were also delayed or repressed during the regenerative response. Altogether our results demonstrate that GSTP1/2 are a critical regulators of hepatocyte proliferation in the initial phases of liver regeneration.

  12. Regulators of Trypanosoma brucei cell cycle progression and differentiation identified using a kinome-wide RNAi screen.

    Directory of Open Access Journals (Sweden)

    Nathaniel G Jones

    2014-01-01

    Full Text Available The African trypanosome, Trypanosoma brucei, maintains an integral link between cell cycle regulation and differentiation during its intricate life cycle. Whilst extensive changes in phosphorylation have been documented between the mammalian bloodstream form and the insect procyclic form, relatively little is known about the parasite's protein kinases (PKs involved in the control of cellular proliferation and differentiation. To address this, a T. brucei kinome-wide RNAi cell line library was generated, allowing independent inducible knockdown of each of the parasite's 190 predicted protein kinases. Screening of this library using a cell viability assay identified ≥42 PKs that are required for normal bloodstream form proliferation in culture. A secondary screen identified 24 PKs whose RNAi-mediated depletion resulted in a variety of cell cycle defects including in G1/S, kinetoplast replication/segregation, mitosis and cytokinesis, 15 of which are novel cell cycle regulators. A further screen identified for the first time two PKs, named repressor of differentiation kinase (RDK1 and RDK2, depletion of which promoted bloodstream to procyclic form differentiation. RDK1 is a membrane-associated STE11-like PK, whilst RDK2 is a NEK PK that is essential for parasite proliferation. RDK1 acts in conjunction with the PTP1/PIP39 phosphatase cascade to block uncontrolled bloodstream to procyclic form differentiation, whilst RDK2 is a PK whose depletion efficiently induces differentiation in the absence of known triggers. Thus, the RNAi kinome library provides a valuable asset for functional analysis of cell signalling pathways in African trypanosomes as well as drug target identification and validation.

  13. Supervised Learning with Complex-valued Neural Networks

    CERN Document Server

    Suresh, Sundaram; Savitha, Ramasamy

    2013-01-01

    Recent advancements in the field of telecommunications, medical imaging and signal processing deal with signals that are inherently time varying, nonlinear and complex-valued. The time varying, nonlinear characteristics of these signals can be effectively analyzed using artificial neural networks.  Furthermore, to efficiently preserve the physical characteristics of these complex-valued signals, it is important to develop complex-valued neural networks and derive their learning algorithms to represent these signals at every step of the learning process. This monograph comprises a collection of new supervised learning algorithms along with novel architectures for complex-valued neural networks. The concepts of meta-cognition equipped with a self-regulated learning have been known to be the best human learning strategy. In this monograph, the principles of meta-cognition have been introduced for complex-valued neural networks in both the batch and sequential learning modes. For applications where the computati...

  14. Balancing Design Project Supervision and Learning Facilitation

    DEFF Research Database (Denmark)

    Nielsen, Louise Møller

    2012-01-01

    set of demands to the design lecturer. On one hand she is the facilitator of the learning process, where the students are in charge of their own projects, and where learning happens through the students’ own experiences, successes and mistakes and on the other hand she is a supervisor, who uses her...... experiences and expertise to guide the students’ decisions in relation to the design project. This paper focuses on project supervision in the context of design education – and more specifically on how this supervision is unfolded in a Problem Based Learning culture. The paper explores the supervisor......In design there is a long tradition for apprenticeship, as well as tradition for learning through design projects. Today many design educations are positioned within the University context, and have to be aligned with the learning culture and structure, which they represent. This raises a specific...

  15. Bias Modeling for Distantly Supervised Relation Extraction

    Directory of Open Access Journals (Sweden)

    Yang Xiang

    2015-01-01

    Full Text Available Distant supervision (DS automatically annotates free text with relation mentions from existing knowledge bases (KBs, providing a way to alleviate the problem of insufficient training data for relation extraction in natural language processing (NLP. However, the heuristic annotation process does not guarantee the correctness of the generated labels, promoting a hot research issue on how to efficiently make use of the noisy training data. In this paper, we model two types of biases to reduce noise: (1 bias-dist to model the relative distance between points (instances and classes (relation centers; (2 bias-reward to model the possibility of each heuristically generated label being incorrect. Based on the biases, we propose three noise tolerant models: MIML-dist, MIML-dist-classify, and MIML-reward, building on top of a state-of-the-art distantly supervised learning algorithm. Experimental evaluations compared with three landmark methods on the KBP dataset validate the effectiveness of the proposed methods.

  16. Balancing Design Project Supervision and Learning Facilitation

    DEFF Research Database (Denmark)

    Nielsen, Louise Møller

    2012-01-01

    experiences and expertise to guide the students’ decisions in relation to the design project. This paper focuses on project supervision in the context of design education – and more specifically on how this supervision is unfolded in a Problem Based Learning culture. The paper explores the supervisor......’s balance between the roles: 1) Design Project Supervisor – and 2) Learning Facilitator – with the aim to understand when to apply the different roles, and what to be aware of when doing so. This paper represents the first pilot-study of a larger research effort. It is based on a Lego Serious Play workshop......In design there is a long tradition for apprenticeship, as well as tradition for learning through design projects. Today many design educations are positioned within the University context, and have to be aligned with the learning culture and structure, which they represent. This raises a specific...

  17. The Supervised Learning Gaussian Mixture Model

    Institute of Scientific and Technical Information of China (English)

    马继涌; 高文

    1998-01-01

    The traditional Gaussian Mixture Model(GMM)for pattern recognition is an unsupervised learning method.The parameters in the model are derived only by the training samples in one class without taking into account the effect of sample distributions of other classes,hence,its recognition accuracy is not ideal sometimes.This paper introduces an approach for estimating the parameters in GMM in a supervising way.The Supervised Learning Gaussian Mixture Model(SLGMM)improves the recognition accuracy of the GMM.An experimental example has shown its effectiveness.The experimental results have shown that the recognition accuracy derived by the approach is higher than those obtained by the Vector Quantization(VQ)approach,the Radial Basis Function (RBF) network model,the Learning Vector Quantization (LVQ) approach and the GMM.In addition,the training time of the approach is less than that of Multilayer Perceptrom(MLP).

  18. Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.

    Science.gov (United States)

    Azevedo, Hátylas; Fujita, André; Bando, Silvia Yumi; Iamashita, Priscila; Moreira-Filho, Carlos Alberto

    2014-01-01

    Gliomas are aggressive primary brain tumors with high infiltrative potential. The expression of Angiotensin II (Ang II) receptors has been associated with poor prognosis in human astrocytomas, the most common type of glioma. In this study, we investigated the role of Angiotensin II in glioma malignancy through transcriptional profiling and network analysis of cultured C6 rat glioma cells exposed to Ang II and to inhibitors of its membrane receptor subtypes. C6 cells were treated with Ang II and specific antagonists of AT1 and AT2 receptors. Total RNA was isolated after three and six hours of Ang II treatment and analyzed by oligonucleotide microarray technology. Gene expression data was evaluated through transcriptional network modeling to identify how differentially expressed (DE) genes are connected to each other. Moreover, other genes co-expressing with the DE genes were considered in these analyses in order to support the identification of enriched functions and pathways. A hub-based network analysis showed that the most connected nodes in Ang II-related networks exert functions associated with cell proliferation, migration and invasion, key aspects for glioma progression. The subsequent functional enrichment analysis of these central genes highlighted their participation in signaling pathways that are frequently deregulated in gliomas such as ErbB, MAPK and p53. Noteworthy, either AT1 or AT2 inhibitions were able to down-regulate different sets of hub genes involved in protumoral functions, suggesting that both Ang II receptors could be therapeutic targets for intervention in glioma. Taken together, our results point out multiple actions of Ang II in glioma pathogenesis and reveal the participation of both Ang II receptors in the regulation of genes relevant for glioma progression. This study is the first one to provide systems-level molecular data for better understanding the protumoral effects of Ang II in the proliferative and infiltrative behavior of

  19. Transcriptional network analysis reveals that AT1 and AT2 angiotensin II receptors are both involved in the regulation of genes essential for glioma progression.

    Directory of Open Access Journals (Sweden)

    Hátylas Azevedo

    Full Text Available Gliomas are aggressive primary brain tumors with high infiltrative potential. The expression of Angiotensin II (Ang II receptors has been associated with poor prognosis in human astrocytomas, the most common type of glioma. In this study, we investigated the role of Angiotensin II in glioma malignancy through transcriptional profiling and network analysis of cultured C6 rat glioma cells exposed to Ang II and to inhibitors of its membrane receptor subtypes. C6 cells were treated with Ang II and specific antagonists of AT1 and AT2 receptors. Total RNA was isolated after three and six hours of Ang II treatment and analyzed by oligonucleotide microarray technology. Gene expression data was evaluated through transcriptional network modeling to identify how differentially expressed (DE genes are connected to each other. Moreover, other genes co-expressing with the DE genes were considered in these analyses in order to support the identification of enriched functions and pathways. A hub-based network analysis showed that the most connected nodes in Ang II-related networks exert functions associated with cell proliferation, migration and invasion, key aspects for glioma progression. The subsequent functional enrichment analysis of these central genes highlighted their participation in signaling pathways that are frequently deregulated in gliomas such as ErbB, MAPK and p53. Noteworthy, either AT1 or AT2 inhibitions were able to down-regulate different sets of hub genes involved in protumoral functions, suggesting that both Ang II receptors could be therapeutic targets for intervention in glioma. Taken together, our results point out multiple actions of Ang II in glioma pathogenesis and reveal the participation of both Ang II receptors in the regulation of genes relevant for glioma progression. This study is the first one to provide systems-level molecular data for better understanding the protumoral effects of Ang II in the proliferative and infiltrative

  20. Association of protein kinase FA/GSK-3alpha (a proline-directed kinase and a regulator of protooncogenes) with human cervical carcinoma dedifferentiation/progression.

    Science.gov (United States)

    Yang, S D; Yu, J S; Lee, T T; Ni, M H; Yang, C C; Ho, Y S; Tsen, T Z

    1995-10-01

    Computer analysis of protein phosphorylation-sites sequence revealed that most transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) (a particular member of PDPK family) has been optimized for human cervical tissue and used to demonstrate for the first time significantly increased (P < 0.001) activity in poorly differentiated cervical carcinoma (82.8 +/- 6.6 U/mg of protein), moderately differentiated carcinoma (36.2 +/- 3.4 U/mg of protein), and well-differentiated carcinoma (18.3 +/- 2.4 U/mg of protein) from 36 human cervical carcinoma samples when compared to 12 normal controls (4.9 +/- 0.6 U/mg of protein). Immunoblotting analysis further revealed that increased activity of kinase FA/GSK-3alpha in cervical carcinoma is due to overexpression of protein synthesis of the kinase. Taken together, the results provide initial evidence that overexpression of protein synthesis and cellular activity of kinase FA/GSK-3alpha may be involved in human cervical carcinoma dedifferentiation/progression, supporting an association of proline-directed protein kinase with neoplastic transformation and tumorigenesis. Since protein kinase FA/GSK-3alpha may function as a possible regulator of transcription factors/proto-oncogenes, the results further suggest that kinase FA/GSK-3alpha may play a potential role in human cervical carcinogenesis, especially in its dedifferentiation and progression.