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,…

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.

Performance-based regulation. Panel Discussion

International Nuclear Information System (INIS)

Youngblood, Robert; Bier, Vicki M.; Bukowski, Richard W.; Prasad Kadambi, N.; Koonce, James F.

2001-01-01

Full text of publication follows: Performance-based regulation is a part of the NRC's Strategic Plan and is realizing steady progress in conceptual development for actual applications. For example, high-level, conceptual guidelines have been proposed that would apply to reactors, materials, and waste areas. Performance-based approaches are also being applied in other regulated industries such as FAA and OSHA. The discussion will include comments from speakers from different parts of the nuclear industry and other industries regarding benefits and weaknesses of performance-based regulation. (authors)

Prostate Cancer Epigenetics: A Review on Gene Regulation

Directory of Open Access Journals (Sweden)

Lena Diaw

2007-01-01

Full Text Available Prostate cancer is the most common cancer in men in western countries, and its incidence is increasing steadily worldwide. Molecular changes including both genetic and epigenetic events underlying the development and progression of this disease are still not well understood. Epigenetic events are involved in gene regulation and occur through different mechanisms such as DNA methylation and histone modifi cations. Both DNA methylation and histone modifi cations affect gene regulation and play important roles either independently or by interaction in tumor initiation and progression. This review will discuss the genes associated with epigenetic alterations in prostate cancer progression: their regulation and importance as possible markers for the disease.

Parent-Child Attachment and Emotion Regulation

Science.gov (United States)

Brumariu, Laura E.

2015-01-01

Given the centrality of both parent-child attachment and emotion regulation in children's development and adjustment, it is important to evaluate the relations between these constructs. This article discusses conceptual and empirical links between attachment and emotion regulation in middle childhood, highlights progress and challenges in the…

cAMP Signaling Regulates Histone H3 Phosphorylation and Mitotic Entry Through a Disruption of G2 Progression

OpenAIRE

Rodriguez-Collazo, Pedro; Snyder, Sara K.; Chiffer, Rebecca C.; Bressler, Erin A.; Voss, Ty C.; Anderson, Eric P.; Genieser, Hans-Gottfried; Smith, Catharine L.

2008-01-01

cAMP signaling is known to have significant effects on cell growth, either inhibitory or stimulatory depending on the cell type. Study of cAMP-induced growth inhibition in mammalian somatic cells has focused mainly on the combined role of protein kinase A (PKA) and mitogen-activated protein (MAP) kinases in regulation of progression through the G1 phase of the cell cycle. Here we show that cAMP signaling regulates histone H3 phosphorylation in a cell cycle-dependent fashion, increasing it in ...

Self-regulation in the mining industry

DEFF Research Database (Denmark)

Sinding, Knud; Peck, Philip

2013-01-01

Many industries have established their own systems for self-regulation. They often do so when companies involved in the industry operate in countries where financial, technical, environmental and social regulation is weak and when the industry is challenged by legitimacy issues related to behaviour...... in one of these areas. One industry that has progressed unevenly down the road of self-regulation in these areas is mining. Developing self-regulation for mines and mining companies involves difficult questions of scope, rules, membership, assessment criteria and performance evaluation. While self-regulation...... may bring benefits to members, they are likely to take a long time coming; but when they do arrive they may be substantial. Using a range of theoretical and empirical results from research on self-regulation, performance rating and corporate strategy, this paper analyses the strategic and operational...

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

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

International Nuclear Information System (INIS)

Zhang, Chundong; Zhang, Ying; Li, Yi; Zhu, Huifang; Wang, Yitao; Cai, Wei; Zhu, Jiang; Ozaki, Toshinori; Bu, Youquan

2015-01-01

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

PTPRZ1 regulates calmodulin phosphorylation and tumor progression in small-cell lung carcinoma

International Nuclear Information System (INIS)

Makinoshima, Hideki; Ishii, Genichiro; Kojima, Motohiro; Fujii, Satoshi; Higuchi, Youichi; Kuwata, Takeshi; Ochiai, Atsushi

2012-01-01

Small-cell lung carcinoma (SCLC) is a neuroendocrine tumor subtype and comprises approximately 15% of lung cancers. Because SCLC is still a disease with a poor prognosis and limited treatment options, there is an urgent need to develop targeted molecular agents for this disease. We screened 20 cell lines from a variety of pathological phenotypes established from different organs by RT-PCR. Paraffin-embedded tissue from 252 primary tumors was examined for PTPRZ1 expression using immunohistochemistry. shRNA mediated PTPRZ1 down-regulation was used to study impact on tyrosine phosphorylation and in vivo tumor progression in SCLC cell lines. Here we show that PTPRZ1, a member of the protein tyrosine- phosphatase receptor (PTPR) family, is highly expressed in SCLC cell lines and specifically exists in human neuroendocrine tumor (NET) tissues. We also demonstrate that binding of the ligand of PTPRZ1, pleiotrophin (PTN), activates the PTN/PTPRZ1 signaling pathway to induce tyrosine phosphorylation of calmodulin (CaM) in SCLC cells, suggesting that PTPRZ1 is a regulator of tyrosine phosphorylation in SCLC cells. Furthermore, we found that PTPRZ1 actually has an important oncogenic role in tumor progression in the murine xenograft model. PTPRZ1 was highly expressed in human NET tissues and PTPRZ1 is an oncogenic tyrosine phosphatase in SCLCs. These results imply that a new signaling pathway involving PTPRZ1 could be a feasible target for treatment of NETs

Tetraspanin CD9 regulates osteoclastogenesis via regulation of p44/42 MAPK activity

International Nuclear Information System (INIS)

Yi, TacGhee; Kim, Hye-Jin; Cho, Je-Yoel; Woo, Kyung Mi; Ryoo, Hyun-Mo; Kim, Gwan-Shik; Baek, Jeong-Hwa

2006-01-01

Tetraspanin CD9 has been shown to regulate cell-cell fusion in sperm-egg fusion and myotube formation. However, the role of CD9 in osteoclast, another multinucleated cell type, is not still clear. Therefore, we investigated the role of CD9 in osteoclast differentiation. CD9 was expressed in osteoclast lineage cells and its expression level increased during the progression of RANKL-induced osteoclastogenesis. KMC8, a neutralizing antibody specific to CD9, significantly suppressed RANKL-induced multinucleated osteoclast formation and the mRNA expression of osteoclast differentiation marker genes. To define CD9-regulated osteoclastogenic signaling pathway, MAPK pathways were examined. KMC8 induced long-term phosphorylation of p44/42 MAPK, but not of p38 MAPK. Constitutive activation of p44/42 MAPK by overexpressing constitutive-active mutant of MEK1 almost completely blocked osteoclast differentiation. Taken together, these results suggest that CD9 expressed on osteoclast lineage cells might positively regulate osteoclastogenesis via the regulation of p44/42 MAPK activity

Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms.

Science.gov (United States)

Royston, Kendra J; Paul, Bidisha; Nozell, Susan; Rajbhandari, Rajani; Tollefsbol, Trygve O

2018-07-01

Little is known about the effects of combinatorial dietary compounds on the regulation of epigenetic mechanisms involved in breast cancer prevention. The human diet consists of a multitude of components, and there is a need to elucidate how certain compounds interact in collaboration. Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyltransferase (DNMT) inhibitor, and sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor found in cruciferous vegetables, are two epigenetic modifying compounds that have only recently been studied in conjunction. The use of DNMT and HDAC inhibitors to reverse the malignant expression of certain genes in breast cancer has shown considerable promise. Previously, we found that SFN + WA synergistically promote breast cancer cell death. Herein, we determined that these compounds inhibit cell cycle progression from S to G2 phase in MDA-MB-231 and MCF-7 breast cancer. Furthermore, we demonstrate that this unique combination of epigenetic modifying compounds down-regulates the levels of Cyclin D1 and CDK4, and pRB; conversely, the levels of E2F mRNA and tumor suppressor p21 are increased independently of p53. We find these events coincide with an increase in unrestricted histone methylation. We propose SFN + WA-induced breast cancer cell death is attributed, in part, to epigenetic modifications that result in the modulated expression of key genes responsible for the regulation of cancer cell senescence. Copyright © 2018 Elsevier Inc. All rights reserved.

The regulation effect of STAT 5 signaling pathway on the cell cycle progression of irradiated KG-1 cells

International Nuclear Information System (INIS)

Guo Dehuang; Dong Bo; Luo Qingliang; Wen Gengyun; Mao Bingzhi

2000-01-01

The author investigated the role of the JAK/STAT signaling pathway regulating cell cycle progression in the irradiated KG-1 cells. By permanent transfecting the cells with DN-STAT 5 cDNA to block the JAK/STAT signaling pathway and then transient transfecting with cyclin D 1 or cyclin B 1 cDNA, the effects of cyclin D 1 protein and cyclin B 1 protein on the cell cycle progression were examined. Results showed that after irradiation with 8Gy 60 Co rays, the irradiated KG-1 cells transfected with only DN-STAT 5 cDNA can not recover form the G 1 arrest, even though GM-CSF was added. Meanwhile, the cells transfected with both the DN-STAT 5 cDNA and cyclin D 1 cDNA or cyclin B 1 cDNA can recover from the G 1 arrest or the G 2 arrest to a great extent. Thus, it was proved indirectly that the JAK/STAT signaling pathway activated by GM-CSF regulated the cell cycle progression through cyclin D 1 and cyclin B 1 protein

p53 regulates cytoskeleton remodeling to suppress tumor progression.

Science.gov (United States)

Araki, Keigo; Ebata, Takahiro; Guo, Alvin Kunyao; Tobiume, Kei; Wolf, Steven John; Kawauchi, Keiko

2015-11-01

Cancer cells possess unique characteristics such as invasiveness, the ability to undergo epithelial-mesenchymal transition, and an inherent stemness. Cell morphology is altered during these processes and this is highly dependent on actin cytoskeleton remodeling. Regulation of the actin cytoskeleton is, therefore, important for determination of cell fate. Mutations within the TP53 (tumor suppressor p53) gene leading to loss or gain of function (GOF) of the protein are often observed in aggressive cancer cells. Here, we highlight the roles of p53 and its GOF mutants in cancer cell invasion from the perspective of the actin cytoskeleton; in particular its reorganization and regulation by cell adhesion molecules such as integrins and cadherins. We emphasize the multiple functions of p53 in the regulation of actin cytoskeleton remodeling in response to the extracellular microenvironment, and oncogene activation. Such an approach provides a new perspective in the consideration of novel targets for anti-cancer therapy.

A review of building energy regulation and policy for energy conservation in developing countries

International Nuclear Information System (INIS)

Iwaro, Joseph; Mwasha, Abraham

2010-01-01

The rapid growth of energy use, worldwide, hfs raised concerns over problems of energy supply and exhaustion of energy resources. Most of the developed countries are implementing building energy regulations such as energy standards, codes etc., to reduce building energy consumption. The position of developing countries with respect to energy regulations implementation and enforcement is either poorly documented or not documented at all. In addition, there is a lack of consistent data, which makes it difficult to understand the underlying changes that affect energy regulation implementation in developing countries. In that respect, this paper investigates the progress of building energy regulations in developing countries and its implication for energy conservation and efficiency. The present status of building energy regulations in 60 developing countries around the world was analysed through a survey of building energy regulations using online survey. The study revealed the present progress made on building energy regulations in relation to implementation, development and compliance; at the same time the study recommends possible solutions to the barriers facing building energy regulation implementation in the developing world. - Research Highlights: →Progress and implications of energy regulations in developing countries. →Investigation assessed the progress made on energy regulations using online survey. →Energy regulation activities is progressively increasing in developing countries. →The study identified 25 developing countries without energy regulatory standards. →The study shows relationship between energy regulation and energy consumption.

Selective Regulation of Oocyte Meiotic Events Enhances Progress in Fertility Preservation Methods

Directory of Open Access Journals (Sweden)

Onder Celik

2015-01-01

persistence of the GV oocyte, which reduces the number of good quality eggs. Selective regulation of somatic cell signals and oocyte meiotic events enhance progress in fertility preservation methods, which may give us the opportunity to prevent follicle loss in prematurely aging women and young women with cancer are undergoing chemoradiotherapy.

Cell Cycle Regulation of Stem Cells by MicroRNAs.

Science.gov (United States)

Mens, Michelle M J; Ghanbari, Mohsen

2018-06-01

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of gene expression. They are involved in the fine-tuning of fundamental biological processes such as proliferation, differentiation, survival and apoptosis in many cell types. Emerging evidence suggests that miRNAs regulate critical pathways involved in stem cell function. Several miRNAs have been suggested to target transcripts that directly or indirectly coordinate the cell cycle progression of stem cells. Moreover, previous studies have shown that altered expression levels of miRNAs can contribute to pathological conditions, such as cancer, due to the loss of cell cycle regulation. However, the precise mechanism underlying miRNA-mediated regulation of cell cycle in stem cells is still incompletely understood. In this review, we discuss current knowledge of miRNAs regulatory role in cell cycle progression of stem cells. We describe how specific miRNAs may control cell cycle associated molecules and checkpoints in embryonic, somatic and cancer stem cells. We further outline how these miRNAs could be regulated to influence cell cycle progression in stem cells as a potential clinical application.

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.

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.

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

International Nuclear Information System (INIS)

Yao, Jingjing; Xu, Chen; Fang, Ziyu; Li, Yaoming; Liu, Houqi; Wang, Yue; Xu, Chuanliang; Sun, Yinghao

2016-01-01

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.

Curcumin inhibits bladder cancer progression via regulation of β-catenin expression.

Science.gov (United States)

Shi, Jing; Wang, Yunpeng; Jia, Zhuomin; Gao, Yu; Zhao, Chaofei; Yao, Yuanxin

2017-07-01

Bladder cancer has a considerable morbidity and mortality impact with particularly poor prognosis. Curcumin has been recently noticed as a polyphenolic compound separated from turmeric to regulate tumor progression. However, the precise molecular mechanism by which curcumin inhibits the invasion and metastasis of bladder cancer cells is not fully elucidated. In this study, we investigate the effect of curcumin on the bladder cancer as well as possible mechanisms of curcumin. The expression of β-catenin was detected by quantitative real-time polymerase chain reaction and immunohistochemical analysis in a series of bladder cancer tissues. In addition, bladder cancer cell lines T24 and 5637 cells were treated with different concentrations of curcumin. The cytotoxic effect of curcumin on cell proliferation of T24 and 5637 cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The migration and invasion capacity of T24 and 5637 cells were measured by transwell assay. The effects of curcumin on expression levels of β-catenin and epithelial-mesenchymal transition marker were determined by western blotting. The β-catenin expression was significantly upregulated in bladder cancer tissues when compared with corresponding peri-tumor tissues. Furthermore, curcumin inhibited the cell proliferation of T24 and 5637 cells, and curcumin reduced the migration and invasive ability of T24 and 5637 cells via regulating β-catenin expression and reversing epithelial-mesenchymal transition. Curcumin may be a new drug for bladder cancer.

miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells.

Science.gov (United States)

Kuhn, Stephanie; Johnson, Stuart L; Furness, David N; Chen, Jing; Ingham, Neil; Hilton, Jennifer M; Steffes, Georg; Lewis, Morag A; Zampini, Valeria; Hackney, Carole M; Masetto, Sergio; Holley, Matthew C; Steel, Karen P; Marcotti, Walter

2011-02-08

MicroRNAs (miRNAs) are small noncoding RNAs able to regulate a broad range of protein-coding genes involved in many biological processes. miR-96 is a sensory organ-specific miRNA expressed in the mammalian cochlea during development. Mutations in miR-96 cause nonsyndromic progressive hearing loss in humans and mice. The mouse mutant diminuendo has a single base change in the seed region of the Mir96 gene leading to widespread changes in the expression of many genes. We have used this mutant to explore the role of miR-96 in the maturation of the auditory organ. We found that the physiological development of mutant sensory hair cells is arrested at around the day of birth, before their biophysical differentiation into inner and outer hair cells. Moreover, maturation of the hair cell stereocilia bundle and remodelling of auditory nerve connections within the cochlea fail to occur in miR-96 mutants. We conclude that miR-96 regulates the progression of the physiological and morphological differentiation of cochlear hair cells and, as such, coordinates one of the most distinctive functional refinements of the mammalian auditory system.

The fidelity of synaptonemal complex assembly is regulated by a signaling mechanism that controls early meiotic progression.

Science.gov (United States)

Silva, Nicola; Ferrandiz, Nuria; Barroso, Consuelo; Tognetti, Silvia; Lightfoot, James; Telecan, Oana; Encheva, Vesela; Faull, Peter; Hanni, Simon; Furger, Andre; Snijders, Ambrosius P; Speck, Christian; Martinez-Perez, Enrique

2014-11-24

Proper chromosome segregation during meiosis requires the assembly of the synaptonemal complex (SC) between homologous chromosomes. However, the SC structure itself is indifferent to homology, and poorly understood mechanisms that depend on conserved HORMA-domain proteins prevent ectopic SC assembly. Although HORMA-domain proteins are thought to regulate SC assembly as intrinsic components of meiotic chromosomes, here we uncover a key role for nuclear soluble HORMA-domain protein HTP-1 in the quality control of SC assembly. We show that a mutant form of HTP-1 impaired in chromosome loading provides functionality of an HTP-1-dependent checkpoint that delays exit from homology search-competent stages until all homolog pairs are linked by the SC. Bypassing of this regulatory mechanism results in premature meiotic progression and licensing of homology-independent SC assembly. These findings identify nuclear soluble HTP-1 as a regulator of early meiotic progression, suggesting parallels with the mode of action of Mad2 in the spindle assembly checkpoint. Copyright © 2014 Elsevier Inc. All rights reserved.

Regulative environmental policy. Regulative Umweltpolitik

Energy Technology Data Exchange (ETDEWEB)

Goerlitz, A; Voigt, R [Universitaet der Bundeswehr Muenchen, Neubiberg (Germany, F.R.). Fakultaet fuer Sozialwissenschaften; eds.

1991-01-01

Regulative policy means those governmental attempts to steer the course of things which can fall back on a certain repertoire of instruments for actions in order to warrant the causal and temporal connection between the making available and the employment of means. The fact that environmental protection needs regulative policy is substantiated by the thesis that the market has failed; consequently only government can manage the public goods 'environment' in a suitable way, and it is a matter of fact that environmental protection at present is operated preferably via regulative policy. The problems of regulative enviromental policy are manifold. Its implementation often miscarries because of limited administrative resources on the one hand - making sufficient control impossible for instance -, and because of poor quality regulative instruments on the other hand. One way out would be to increase the efficiency of regulative policy by sophisticating judicial techniques. Other ways out point to the executing level and aim at improving implementation strategies or are concerned with post-regulative law. The latter refers to a new legal quality which demonstrates itself already in corporatistical crisis regulation or in induction programs such as pollution limits. A final way out favours deregulation strategies which includes the introduction of environmental levies or the allocation of environmental licences. An interdisciplinary discourse is to find out what would happen if these ways were taken. Pointers to solutions from varying scientific disciplines resulting from this discourse are to be found in this volume. (orig./HSCH).

Phytohormone and Light Regulation of Chlorophyll Degradation

Directory of Open Access Journals (Sweden)

Xiaoyu Zhu

2017-11-01

Full Text Available Degreening, due to the net loss of chlorophyll (Chl, is the most prominent symptom during the processes of leaf senescence, fruit ripening, and seed maturation. Over the last decade or so, extensive identifications of Chl catabolic genes (CCGs have led to the revelation of the biochemical pathway of Chl degradation. As such, exploration of the regulatory mechanism of the degreening process is greatly facilitated. During the past few years, substantial progress has been made in elucidating the regulation of Chl degradation, particularly via the mediation of major phytohormones' signaling. Intriguingly, ethylene and abscisic acid's signaling have been demonstrated to interweave with light signaling in mediating the regulation of Chl degradation. In this review, we briefly summarize this progress, with an effort on providing a framework for further investigation of multifaceted and hierarchical regulations of Chl degradation.

Regulation of ROCK Activity in Cancer

DEFF Research Database (Denmark)

Morgan-Fisher, Marie; Wewer, Ulla M; Yoneda, Atsuko

2013-01-01

, these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer.......Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key...... regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active...

The general technical regulation and the standardization

International Nuclear Information System (INIS)

Laverie, Michel; Houze, Christian; Lebouleux, Philippe

1980-01-01

Through a certain number of procedures, the thorough appreciation of the safety of a nuclear installation relies more on a specific appreciation taking into account the references as a whole, than on a technical regulation which claims to cover all the problems. Nevertheless, a French technical regulation structure regarding the safety domain must be built up progressively. The authors consider the principles of such a structure, and together they make the inventory of the works, finished, in progress or contemplated. The description of this specifically French approach emphazises the multiple and complementary forms given to statutory implements [fr

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...... difference in the numbers of gene loci hit by deletions muscle-invasive versus noninvasive tumors (P = 0.0000002), with the genes most often hit by deletions in muscle-invasive tumors being TP53, RB1, and MYCL. A number of novel findings were made. Losses of MYCL and RB1 alleles were more pronounced...... that a characteristic difference between recurrent noninvasive and recurrent progressing bladder tumors is loss of cell cycle-regulatory genes in the latter group....

Down-regulation of S100C is associated with bladder cancer progression and poor survival

DEFF Research Database (Denmark)

Memon, Ashfaque Ahmed; Sorensen, Boe Sandahl; Meldgaard, Peter

2005-01-01

cancer biopsy samples obtained from 88 patients followed for a median of 23 months (range, 1-97 months). RESULTS: We found a significantly lower mRNA expression of S100C in connective tissue invasive tumors (T1, P = 0.0030) and muscle invasive tumors [(T2-T4), P ...PURPOSE: The goal of this study was to identify proteins down-regulated during bladder cancer progression. EXPERIMENTAL DESIGN: By using comparative proteome analysis and measurement of mRNA, we found a significant down-regulation of S100C, a member of the S100 family of proteins, in T24 (grade 3......) as compared with RT4 (grade 1) bladder cancer cell lines. Moreover, quantification of the mRNA level revealed that decreased expression of the protein reflects a low level of transcription of the S100C gene. Based on this observation, we quantified the S100C mRNA expression level with real-time PCR in bladder...

Introduction: Self-Regulation of Learning in Postsecondary Education

Science.gov (United States)

Bembenutty, Hefer

2011-01-01

Self-regulation of learning occupies a fundamental place in postsecondary education. "Self-regulation of learning" refers to learners' beliefs about their capability to engage in appropriate actions, thoughts, feelings, and behaviors in order to pursue valuable academic goals while self-monitoring and self-reflecting on their progress toward goal…

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.

Regulation of beta cell replication

DEFF Research Database (Denmark)

Lee, Ying C; Nielsen, Jens Høiriis

2008-01-01

Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

Down-regulated miR-448 relieves spinal cord ischemia/reperfusion injury by up-regulating SIRT1

Directory of Open Access Journals (Sweden)

Yun Wang

2018-03-01

Full Text Available MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII. The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.

Federal Aviation Regulations - National Aviation Regulations of Russia

Science.gov (United States)

Chernykh, O.; Bakiiev, M.

2018-03-01

Chinese Aerospace Engineering is currently developing cooperation with Russia on a wide-body airplane project that has directed the work towards better understanding of Russian airworthiness management system. The paper introduces national Aviation regulations of Russia, presents a comparison of them with worldwide recognized regulations, and highlights typical differences. They have been found to be: two general types of regulations used in Russia (Aviation Regulations and Federal Aviation Regulations), non-unified structure of regulations on Aircraft Operation management, various separate agencies responsible for regulation issuance instead of one national aviation authority, typical confusions in references. The paper also gives a list of effective Russian Regulations of both types.

Redox regulation of cell proliferation: Bioinformatics and redox proteomics approaches to identify redox-sensitive cell cycle regulators.

Science.gov (United States)

Foyer, Christine H; Wilson, Michael H; Wright, Megan H

2018-03-29

Plant stem cells are the foundation of plant growth and development. The balance of quiescence and division is highly regulated, while ensuring that proliferating cells are protected from the adverse effects of environment fluctuations that may damage the genome. Redox regulation is important in both the activation of proliferation and arrest of the cell cycle upon perception of environmental stress. Within this context, reactive oxygen species serve as 'pro-life' signals with positive roles in the regulation of the cell cycle and survival. However, very little is known about the metabolic mechanisms and redox-sensitive proteins that influence cell cycle progression. We have identified cysteine residues on known cell cycle regulators in Arabidopsis that are potentially accessible, and could play a role in redox regulation, based on secondary structure and solvent accessibility likelihoods for each protein. We propose that redox regulation may function alongside other known posttranslational modifications to control the functions of core cell cycle regulators such as the retinoblastoma protein. Since our current understanding of how redox regulation is involved in cell cycle control is hindered by a lack of knowledge regarding both which residues are important and how modification of those residues alters protein function, we discuss how critical redox modifications can be mapped at the molecular level. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

[Regulation of terpene metabolism.] Progress report

International Nuclear Information System (INIS)

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

3-D bioprinting law regulation perspectives.

Science.gov (United States)

Pashkov, Vitalii; Harkusha, Andrii

Achieved level of technical progress moves us closer and closer to practical use of 3-d bioprinting technologies in real life. Such perspective raise a wide variety of crucial legal issues from the acceptable model of regulation of the science and its' societal effects to problems of the commercialization of the technology and potential restrictions of its use. Some key points on concept of legal regulation of abovementioned sphere is a base of this study. Scientific discussion on 3-D bioprinting, European Union`s and US experience in patenting of 3-D bioprinting technologies, European Medicine Agency (EMA) or the US Food and Drug Administration (FDA) regulations, European Medical Technology Industry Association (EUCOMED) Acts. Article is based on dialectical, comparative, analytic, synthetic and comprehensive research methods. General debate of last few years comes down to an attempt to resolve hesitation between legal attempts for regulation of 3-D biobrinting and concept of complete prohibition of such activities. An adequate response to the mentioned challenge is a reasonable position between some aspects of prohibition and self-regulation, resulting in a moderate number of regulations and standards for developing and marketing. Such regulations may concern an intellectual property (IP) rights, regulation of distribution, premarket restrictions, control mechanism etc. Scientific approach and regulatory settlement of 3-D bioprinting sphere must unite to achieve a fair balance between the interests of humanity and of individuals - on the one hand, and development of science and business benefits for stakeholders - on the other. The main instruments for this must be balanced regulation of intellectual property (IP) rights, regulation of access and distribution, premarket restrictions, control mechanism etc.

Experimentation and mathematical simulation of the operation of a 300-kW boiler, equipped with a progressive regulation or on/off burner

Energy Technology Data Exchange (ETDEWEB)

Anglesio, P [Politecnico di Torino, Italy; Perthuis, E

1980-04-01

The results of an experimental study undertaken during tests run with domestic fuel oil and natural gas, are described. Losses via wall surfaces and exhaust gases are determined, and according to variations in output with the effective power of the boiler and the advantage of progressive regulation mode operation, from the energy point of view, are demonstrated. The mathematical model developed is presented. Simulation is obtained by considering thermal transfers in the hearth, and then the exchanger of the boiler. For continuous operation, two programs are presented. The first is used for adjustment to experimental results. A third program simulates discontinuous operation. Theoretical results slightly overestimate actual output, but confirm the advantage of progressive regulation. The economic study shows that the excess cost of a progressive modulation type burner tends to direct choice towards a compromise, in the form of a dual-rate (high/low) type burner.

Branded prescription drug fee. Final regulations, temporary regulations, and removal of temporary regulations.

Science.gov (United States)

2014-07-28

This document contains final regulations that provide guidance on the annual fee imposed on covered entities engaged in the business of manufacturing or importing branded prescription drugs. This fee was enacted by section 9008 of the Patient Protection and Affordable Care Act, as amended by section 1404 of the Health Care and Education Reconciliation Act of 2010. This document also withdraws the Branded Prescription Drug Fee temporary regulations and contains new temporary regulations regarding the definition of controlled group that apply beginning on January 1, 2015. The final regulations and the new temporary regulations affect persons engaged in the business of manufacturing or importing certain branded prescription drugs. The text of the temporary regulations in this document also serves as the text of proposed regulations set forth in a notice of proposed rulemaking (REG-123286-14) on this subject in the Proposed Rules section in this issue of the Federal Register.

Mining in the Northern Territory: evolution of regulation

International Nuclear Information System (INIS)

McGill, T.

2002-01-01

The Northern Territory Government is shifting away from the traditional command and control prescriptive style regulation, to self-regulation with its increased emphasis on company responsibility. Benchmarking in the areas of environment, health and safety are key steps in this shift. It is widely recognised that heavy-handed regulatory systems are not a particularly effective way to achieve best practice outcomes, a more holistic approach to regulation is required. The ideal situation is to have Government and industry jointly setting goals and reviewing progress towards those goals

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...

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. © FASEB.

Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation

Energy Technology Data Exchange (ETDEWEB)

Cho, Seong-Jun; Kang, Hana [KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul (Korea, Republic of); Kim, Min Young [Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan (Korea, Republic of); Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun [KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul (Korea, Republic of); Pyo, Suhkneung [College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do (Korea, Republic of); Yang, Kwang Hee, E-mail: kwangheey@khnp.co.kr [KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul (Korea, Republic of)

2016-04-01

Purpose: To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Methods and Materials: Splenocytes and IM-9 cells were uniformly irradiated with various doses of a {sup 137}Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. Results: First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Conclusion: Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast.

Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation.

Science.gov (United States)

Cho, Seong-Jun; Kang, Hana; Kim, Min Young; Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun; Pyo, Suhkneung; Yang, Kwang Hee

2016-04-01

To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Splenocytes and IM-9 cells were uniformly irradiated with various doses of a (137)Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast. Copyright © 2016 Elsevier Inc. All rights reserved.

Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation

International Nuclear Information System (INIS)

Cho, Seong-Jun; Kang, Hana; Kim, Min Young; Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun; Pyo, Suhkneung; Yang, Kwang Hee

2016-01-01

Purpose: To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Methods and Materials: Splenocytes and IM-9 cells were uniformly irradiated with various doses of a "1"3"7Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. Results: First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Conclusion: Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast.

MicroRNAs regulate osteogenesis and chondrogenesis

International Nuclear Information System (INIS)

Dong, Shiwu; Yang, Bo; Guo, Hongfeng; Kang, Fei

2012-01-01

Highlights: ► To focus on the role of miRNAs in chondrogenesis and osteogenesis. ► Involved in the regulation of miRNAs in osteoarthritis. ► To speculate some therapeutic targets for bone diseases. -- Abstract: MicroRNAs (miRNAs) are a class of small molecules and non-coding single strand RNAs that regulate gene expression at the post-transcriptional level by binding to specific sequences within target genes. miRNAs have been recognized as important regulatory factors in organism development and disease expression. Some miRNAs regulate the proliferation and differentiation of osteoblasts, osteoclasts and chondrocytes, eventually influencing metabolism and bone formation. miRNAs are expected to provide potential gene therapy targets for the clinical treatment of metabolic bone diseases and bone injuries. Here, we review the recent research progress on the regulation of miRNAs in bone biology, with a particular focus on the miRNA-mediated control mechanisms of bone and cartilage formation.

MicroRNAs regulate osteogenesis and chondrogenesis

Energy Technology Data Exchange (ETDEWEB)

Dong, Shiwu, E-mail: shiwudong@gmail.com [Laboratory of Biomechanics, Department of Anatomy, The Third Military Medical University, Chongqing (China); Yang, Bo; Guo, Hongfeng; Kang, Fei [Laboratory of Biomechanics, Department of Anatomy, The Third Military Medical University, Chongqing (China)

2012-02-24

Highlights: Black-Right-Pointing-Pointer To focus on the role of miRNAs in chondrogenesis and osteogenesis. Black-Right-Pointing-Pointer Involved in the regulation of miRNAs in osteoarthritis. Black-Right-Pointing-Pointer To speculate some therapeutic targets for bone diseases. -- Abstract: MicroRNAs (miRNAs) are a class of small molecules and non-coding single strand RNAs that regulate gene expression at the post-transcriptional level by binding to specific sequences within target genes. miRNAs have been recognized as important regulatory factors in organism development and disease expression. Some miRNAs regulate the proliferation and differentiation of osteoblasts, osteoclasts and chondrocytes, eventually influencing metabolism and bone formation. miRNAs are expected to provide potential gene therapy targets for the clinical treatment of metabolic bone diseases and bone injuries. Here, we review the recent research progress on the regulation of miRNAs in bone biology, with a particular focus on the miRNA-mediated control mechanisms of bone and cartilage formation.

[Regulation of terpene metabolism]. Progress report

International Nuclear Information System (INIS)

Croteau, R.

1986-01-01

Studies on the regulation of monoterpene metabolism in M. piperita were conducted. All of the steps from the acyclic precursor geranyl pyrophosphate to the various menthol isomers have been demonstrated. The first intermediate to accumulate in vivo is d-pulegone. The emphasis has been on the demonstration, partial purification and characterization of the relevant enzymes in the pathway. The studies on the isopiperitenol dehydrogenase and isopiperitenone isomerase have been completed. We are not studying the endocyclic double-bond reductase (NADPH-dependent) and, based on substrate specificity studies and the previously demonstrated isomerization of cis- isopulegone to pulegone, are now virtually convinced that the major pathway to menthol(s) in peppermint involves reduction of isopiperitenone to isopulegone and isomerication of isopulegone to pulegone. 16 refs., 1 fig

Regulation of translation during cancer progression

International Nuclear Information System (INIS)

Petz, M.

2012-01-01

Laminin B1 (LamB1) is a main component of the extracellular matrix and is involved in the regulation of tumor cell migration and invasion of during carcinogenesis. Metastasis of carcinoma cells is crucially linked to the process of epithelial to mesenchymal transition (EMT), which allows tumor cells to acquire a more motile phenotype and to dissociate from the epithelial cell cluster of the tumor. Expression profiling of polysome-associated mRNA revealed LamB1 to be translationally upregulated upon EMT of malignant hepatocytes. The enhanced translation of LamB1 in metastatic hepatocytes proved to be regulated by an internal ribosome entry site (IRES) located within the 5’-untranslated region (UTR) of the LamB1 transcript. IRES activity was detected by employing two independent reporter systems and verified by stringent assays for the presence of cryptic promoter or splice sites. The minimal cis-acting IRES sequence of 293 nucleotides that is required for cap-independent translation was localized directly upstream of the start codon. Notably, the IRES trans-acting factor (ITAF) La was identified by RNA affinity purification as regulatory factor that interacts with LamB1 5’-UTR. This interaction was verified by RNA-immunoprecipitation in vivo, which revealed enhanced binding of La to the minimal IRES motif of LamB1 after EMT. Consistently, cytoplasmic levels of La were elevated in EMT-transformed cells and correlated with increased LamB1 protein expression. Furthermore, IRES-driven translation of LamB1 was elevated in the presence of La in vitro. Importantly, the EMT-induced cytoplasmic translocation of La was found to be triggered by platelet derived growth factor (PDGF) that is downstream of transforming growth factor (TGF)-β signaling. Together, these data demonstrate that La interacts with the LamB1 IRES in the cytoplasm, resulting in enhanced cap-independent translation of LamB1 in malignant hepatocytes that have undergone EMT. (author) [de

Alteration of Epigenetic Regulation by Long Noncoding RNAs in Cancer

Directory of Open Access Journals (Sweden)

Mariangela Morlando

2018-02-01

Full Text Available Long noncoding RNAs (lncRNAs are important regulators of the epigenetic status of the human genome. Besides their participation to normal physiology, lncRNA expression and function have been already associated to many diseases, including cancer. By interacting with epigenetic regulators and by controlling chromatin topology, their misregulation may result in an aberrant regulation of gene expression that may contribute to tumorigenesis. Here, we review the functional role and mechanisms of action of lncRNAs implicated in the aberrant epigenetic regulation that has characterized cancer development and progression.

Toward a Personalized Science of Emotion Regulation

Science.gov (United States)

Doré, Bruce P.; Silvers, Jennifer A.; Ochsner, Kevin N.

2018-01-01

The ability to successfully regulate emotion plays a key role in healthy development and the maintenance of psychological well-being. Although great strides have been made in understanding the nature of regulatory processes and the consequences of deploying them, a comprehensive understanding of emotion regulation that can specify what strategies are most beneficial for a given person in a given situation is still a far-off goal. In this review, we argue that moving toward this goal represents a central challenge for the future of the field. As an initial step, we propose a concrete framework that (i) explicitly considers emotion regulation as an interaction of person, situation, and strategy, (ii) assumes that regulatory effects vary according to these factors, and (iii) sets as a primary scientific goal the identification of person-, situation-, and strategy-based contingencies for successful emotion regulation. Guided by this framework, we review current questions facing the field, discuss examples of contextual variation in emotion regulation success, and offer practical suggestions for continued progress in this area. PMID:29750085

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.

Regulation of ROCK Activity in Cancer

Science.gov (United States)

Morgan-Fisher, Marie; Wewer, Ulla M.

2013-01-01

Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active conformation by the direct binding of guanosine triphosphate (GTP)–loaded Rho. In recent years, a number of ROCK isoform-specific binding partners have been found to modulate the kinase activity through direct interactions with the catalytic domain or via altered cellular localization of the kinases. Thus, these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer. PMID:23204112

Choosing to regulate: does choice enhance craving regulation?

Science.gov (United States)

Mobasser, Arian; Zeithamova, Dagmar; Pfeifer, Jennifer H

2018-01-01

Abstract Goal-directed behavior and lifelong well-being often depend on the ability to control appetitive motivations, such as cravings. Cognitive reappraisal is an effective way to modulate emotional states, including cravings, but is often studied under explicit instruction to regulate. Despite the strong prediction from Self-Determination Theory that choice should enhance task engagement and regulation success, little is known empirically about whether and how regulation is different when participants choose (vs are told) to exert control. To investigate how choice affects neural activity and regulation success, participants reappraised their responses to images of personally-craved foods while undergoing functional neuroimaging. Participants were either instructed to view or reappraise (‘no-choice’) or chose freely to view or reappraise (‘yes-choice’). Choice increased activity in the frontoparietal control network. We expected this activity would be associated with increased task engagement, resulting in better regulation success. However, contrary to this prediction, choice slightly reduced regulation success. Follow-up multivariate functional neuroimaging analyses indicated that choice likely disrupted allocation of limited cognitive resources during reappraisal. While unexpected, these results highlight the importance of studying upstream processes such as regulation choice, as they may affect the ability to regulate cravings and other emotional states. PMID:29462475

QUANTITATIVE ANALYSIS OF FLUX REGULATION THROUGH HIERARCHICAL REGULATION ANALYSIS

NARCIS (Netherlands)

van Eunen, Karen; Rossell, Sergio; Bouwman, Jildau; Westerhoff, Hans V.; Bakker, Barbara M.; Jameson, D; Verma, M; Westerhoff, HV

2011-01-01

Regulation analysis is a methodology that quantifies to what extent a change in the flux through a metabolic pathway is regulated by either gene expression or metabolism. Two extensions to regulation analysis were developed over the past years: (i) the regulation of V(max) can be dissected into the

Quantitative analysis of flux regulation through hierarchical regulation analysis

NARCIS (Netherlands)

Eunen, K. van; Rossell, S.; Bouwman, J.; Westerhoff, H.V.; Bakker, B.M.

2011-01-01

Regulation analysis is a methodology that quantifies to what extent a change in the flux through a metabolic pathway is regulated by either gene expression or metabolism. Two extensions to regulation analysis were developed over the past years: (i) the regulation of Vmax can be dissected into the

Building strong bones: molecular regulation of the osteoblast lineage.

Science.gov (United States)

Long, Fanxin

2011-12-22

The past 15 years have witnessed tremendous progress in the molecular understanding of osteoblasts, the main bone-forming cells in the vertebrate skeleton. In particular, all of the major developmental signals (including WNT and Notch signalling), along with an increasing number of transcription factors (such as RUNX2 and osterix), have been shown to regulate the differentiation and/or function of osteoblasts. As evidence indicates that osteoblasts may also regulate the behaviour of other cell types, a clear understanding of the molecular identity and regulation of osteoblasts is important beyond the field of bone biology.

[Research progress on phosphorus budgets and regulations in reservoirs].

Science.gov (United States)

Shen, Xiao; Li, Xu; Zhang, Wang-shou

2014-12-01

Phosphorus is an important limiting factor of water eutrophication. A clear understanding of its budget and regulated method is fundamental for reservoir ecological health. In order to pro- mote systematic research further and improve phosphorus regulation system, the budget balance of reservoir phosphorus and its influencing factors were concluded, as well as conventional regulation and control measures. In general, the main phosphorus sources of reservoirs include upstream input, overland runoff, industrial and domestic wastewater, aquaculture, atmospheric deposition and sediment release. Upstream input is the largest phosphorus source among them. The principal output path of phosphorus is the flood discharge, the emission load of which is mainly influenced by drainage patterns. In addition, biological harvest also can export a fraction of phosphorus. There are some factors affecting the reservoir phosphorus balance, including reservoirs' function, hydrological conditions, physical and chemical properties of water, etc. Therefore, the phosphorus budgets of different reservoirs vary greatly, according to different seasons and regions. In order to reduce the phosphorus loading in reservoirs, some methods are carried out, including constructed wetlands, prefix reservoir, sediment dredging, biomanipulation, etc. Different methods need to be chosen and combined according to different reservoirs' characteristics and water quality management goals. Thus, in the future research, it is reasonable to highlight reservoir ecological characteristics and proceed to a complete and systematic analysis of the inherent complexity of phosphorus budget and its impact factors for the reservoirs' management. Besides, the interaction between phosphorus budget and other nutrients in reservoirs also needs to be conducted. It is fundamental to reduce the reservoirs' phosphorus loading to establish a scientific and improved management system based on those researches.

Expression of cyclophilin B is associated with malignant progression and regulation of genes implicated in the pathogenesis of breast cancer.

Science.gov (United States)

Fang, Feng; Flegler, Ayanna J; Du, Pan; Lin, Simon; Clevenger, Charles V

2009-01-01

Cyclophilin B (CypB) is a 21-kDa protein with peptidyl-prolyl cis-trans isomerase activity that functions as a transcriptional inducer for Stat5 and as a ligand for CD147. To better understand the global function of CypB in breast cancer, T47D cells with a small interfering RNA-mediated knockdown of CypB were generated. Subsequent expression profiling analysis showed that 663 transcripts were regulated by CypB knockdown, and that many of these gene products contributed to cell proliferation, cell motility, and tumorigenesis. Real-time PCR confirmed that STMN3, S100A4, S100A6, c-Myb, estrogen receptor alpha, growth hormone receptor, and progesterone receptor were all down-regulated in si-CypB cells. A linkage analysis of these array data to protein networks resulted in the identification of 27 different protein networks that were impacted by CypB knockdown. Functional assays demonstrated that CypB knockdown also decreased cell growth, proliferation, and motility. Immunohistochemical and immunofluorescent analyses of a matched breast cancer progression tissue microarray that was labeled with an anti-CypB antibody demonstrated a highly significant increase in CypB protein levels as a function of breast cancer progression. Taken together, these results suggest that the enhanced expression of CypB in malignant breast epithelium may contribute to the pathogenesis of this disease through its regulation of the expression of hormone receptors and gene products that are involved in cell proliferation and motility.

Constructing regulation and regulating for energy efficient construction

Energy Technology Data Exchange (ETDEWEB)

Shove, Elizabeth [Lancaster University (United Kingdom). Centre for the Study of Environmental Change

1998-07-01

This project considers the process of formulating energy-related building regulation in the light of the revisions to Part L (Conservation of Fuel and Power) of the Building Regulations for England and Wales. Details are given of the main objectives of the research, namely, the examination of the roles of the UK government, local government and pressure groups in shaping energy efficiency standards, the impacts of environmental regulations, the limits of energy-related regulation, environmental regulation of the building sector, and the features of energy related building control. This control is compared with current practice in other European countries. The methodology of the project involving the review of governmental documents and interviews is described. (UK)

Post-translational regulation enables robust p53 regulation.

Science.gov (United States)

Shin, Yong-Jun; Chen, Kai-Yuan; Sayed, Ali H; Hencey, Brandon; Shen, Xiling

2013-08-30

The tumor suppressor protein p53 plays important roles in DNA damage repair, cell cycle arrest and apoptosis. Due to its critical functions, the level of p53 is tightly regulated by a negative feedback mechanism to increase its tolerance towards fluctuations and disturbances. Interestingly, the p53 level is controlled by post-translational regulation rather than transcriptional regulation in this feedback mechanism. We analyzed the dynamics of this feedback to understand whether post-translational regulation provides any advantages over transcriptional regulation in regard to disturbance rejection. When a disturbance happens, even though negative feedback reduces the steady-state error, it can cause a system to become less stable and transiently overshoots, which may erroneously trigger downstream reactions. Therefore, the system needs to balance the trade-off between steady-state and transient errors. Feedback control and adaptive estimation theories revealed that post-translational regulation achieves a better trade-off than transcriptional regulation, contributing to a more steady level of p53 under the influence of noise and disturbances. Furthermore, post-translational regulation enables cells to respond more promptly to stress conditions with consistent amplitude. However, for better disturbance rejection, the p53- Mdm2 negative feedback has to pay a price of higher stochastic noise. Our analyses suggest that the p53-Mdm2 feedback favors regulatory mechanisms that provide the optimal trade-offs for dynamic control.

Prostate Cancer Epigenetics: A Review on Gene Regulation

OpenAIRE

Diaw, Lena; Woodson, Karen; Gillespie, John W.

2007-01-01

Prostate cancer is the most common cancer in men in western countries, and its incidence is increasing steadily worldwide. Molecular changes including both genetic and epigenetic events underlying the development and progression of this disease are still not well understood. Epigenetic events are involved in gene regulation and occur through different mechanisms such as DNA methylation and histone modifi cations. Both DNA methylation and histone modifi cations affect gene regulation and play ...

Regulating the Regulator

Energy Technology Data Exchange (ETDEWEB)

1992-08-26

The article reports on a challenge to the UK electricity regulator to defend his record by the Coalition for Fair Electricity Regulation (COFFER). The challenge centres on whether the obligation for the regional electric companies (REC) to purchase power from the cheapest source is being enforced. This is related to the wider issue of whether the REC's support of combined-cycle gas turbine (CCGT) is economic. COFFER considers that uneconomic gas-fired power plants are being allowed to displace economic coal-fired stations. Aspects discussed include the background to the dispute and the costs of CCGT and coal fired power generation. 1 fig., 1 tab.

EZH2: a pivotal regulator in controlling cell differentiation.

Science.gov (United States)

Chen, Ya-Huey; Hung, Mien-Chie; Li, Long-Yuan

2012-01-01

Epigenetic regulation plays an important role in stem cell self-renewal, maintenance and lineage differentiation. The epigenetic profiles of stem cells are related to their transcriptional signature. Enhancer of Zeste homlog 2 (EZH2), a catalytic subunit of epigenetic regulator Polycomb repressive complex 2 (PRC2), has been shown to be a key regulator in controlling cellular differentiation. EZH2 is a histone methyltransferase that not only methylates histone H3 on Lys 27 (H3K27me3) but also interacts with and recruits DNA methyltransferases to methylate CpG at certain EZH2 target genes to establish firm repressive chromatin structures, contributing to tumor progression and the regulation of development and lineage commitment both in embryonic stem cells (ESCs) and adult stem cells. In addition to its well-recognized epigenetic gene silencing function, EZH2 also directly methylates nonhistone targets such as the cardiac transcription factor, GATA4, resulting in attenuated GATA4 transcriptional activity and gene repression. This review addresses recent progress toward the understanding of the biological functions and regulatory mechanisms of EZH2 and its targets as well as their roles in stem cell maintenance and cell differentiation.

Lysophosphatidic acid signaling via LPA_1 and LPA_3 regulates cellular functions during tumor progression in pancreatic cancer cells

International Nuclear Information System (INIS)

Fukushima, Kaori; Takahashi, Kaede; Yamasaki, Eri; Onishi, Yuka; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

2017-01-01

Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors exhibits a variety of biological effects, such as cell proliferation, motility and differentiation. The aim of this study was to evaluate the roles of LPA_1 and LPA_3 in cellular functions during tumor progression in pancreatic cancer cells. LPA_1 and LPA_3 knockdown cells were generated from PANC-1 cells. The cell motile and invasive activities of PANC-1 cells were inhibited by LPA_1 and LPA_3 knockdown. In gelatin zymography, LPA_1 and LPA_3 knockdown cells indicated the low activation of matrix metalloproteinase-2 (MMP-2) in the presence of LPA. Next, to assess whether LPA_1 and LPA_3 regulate cellular functions induced by anticancer drug, PANC-1 cells were treated with cisplatin (CDDP) for approximately 6 months. The cell motile and invasive activities of long-term CDDP treated cells were markedly higher than those of PANC-1 cells, correlating with the expression levels of LPAR1 and LPAR3 genes. In soft agar assay, the long-term CDDP treated cells formed markedly large sized colonies. In addition, the cell motile and invasive activities enhanced by CDDP were significantly suppressed by LPA_1 and LPA_3 knockdown as well as colony formation. These results suggest that LPA signaling via LPA_1 and LPA_3 play an important role in the regulation of cellular functions during tumor progression in PANC-1 cells. - Highlights: • The cell motile and invasive activities of PANC-1 cells were stimulated by LPA_1 and LPA_3. • LPA_1 and LPA_3 enhanced MMP-2 activation in PANC-1 cells. • The expressions of LPAR1 and LPAR3 genes were elevated in PANC-1 cells treated with cisplatin. • The cell motile and invasive activities of PANC-1 cells treated with cisplatin were suppressed by LPA_1 and LPA_3 knockdown. • LPA_1 and LPA_3 are involved in the regulation of cellular functions during tumor progression in PANC-1 cells.

Safety regulation of geological disposal of radioactive waste: progress since Cordoba and remaining challenges

International Nuclear Information System (INIS)

Duncan, A.; Pescatore, C.

2010-01-01

Claudio Pescatore, Deputy Division Head (NEA) presented a paper, the purpose of which was to recall where we stood at the time of the Cordoba Workshop (1997) on the regulation of disposal of long-lived radioactive waste, to review developments since then, to present the key existing issues, and reflect on the remaining challenges and possible responses. The overview study on progress in regulation for geological disposal since the Cordoba workshop [NEA/RWMC/RF(2008)6], provides a good list of references regarding the first two issues. The presentation of the existing issues takes advantage of the synthesis of the responses to a questionnaire completed by the regulatory organisations in preparation for this workshop. It warns regulators and implementers that international work to date seems to have created an expectation in the mind of the public and in some organisations that nothing less than a guarantee by the regulator is needed of maintaining current levels of protection of both individuals and populations practically forever, regardless of the impracticality of this. This expectation needs to be replaced with a carefully and clearly explained understanding of the choices involved in dealing with long-lived radioactive waste against a background of our responsibilities to both current and future generations and our practical capacity to deliver them. Concerning the current major challenges faced in regulation, the paper comes back to the issue of the 'guarantee' by the regulator and it observes that there is no doubt that there is a willingness to do the best to comply with the principle of protection and that we are broadly convinced that current concepts for geological disposal, supported by multiple lines of reasoning and application of best available techniques (BAT) will meet that principle. However, we do not have the capacity to prove or guarantee this, nor do we believe that it is possible in practice. Although we are advised that it is neither

The international radioactive transportation regulations: A model for national regulations

International Nuclear Information System (INIS)

Pope, R.B.; Rawl, R.R.

1990-06-01

The International Atomic Energy Agency's (IAEA) Regulations for the Safe Transport of Radioactive Material, Safety Series No. 6 (herein after denoted as the ''International Regulations'') serve as the model for the regulations for individual countries and international modal organizations controlling the packaging and transportation of radioactive materials. The purpose of this paper is to outline the background and history of the International Regulations, the general principles behind the requirements of the International Regulations, the structure and general contents of the latest edition of the International Regulations, and the roles of various international bodies in the development and implementation of the International Regulations and the current status of regulatory and supportive document development at both the international and domestic level. This review will provide a basis for users and potential users to better understand the source and application of the International Regulations. 1 tab

Hypothalamic mTOR signaling regulates food intake.

Science.gov (United States)

Cota, Daniela; Proulx, Karine; Smith, Kathi A Blake; Kozma, Sara C; Thomas, George; Woods, Stephen C; Seeley, Randy J

2006-05-12

The mammalian Target of Rapamycin (mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR signaling is controlled by energy status in specific regions of the hypothalamus and colocalizes with neuropeptide Y and proopiomelanocortin neurons in the arcuate nucleus. Central administration of leucine increases hypothalamic mTOR signaling and decreases food intake and body weight. The hormone leptin increases hypothalamic mTOR activity, and the inhibition of mTOR signaling blunts leptin's anorectic effect. Thus, mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake.

Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.

Directory of Open Access Journals (Sweden)

Kristin Mussar

Full Text Available Macrophages populate the mesenchymal compartment of all organs during embryogenesis and have been shown to support tissue organogenesis and regeneration by regulating remodeling of the extracellular microenvironment. Whether this mesenchymal component can also dictate select developmental decisions in epithelia is unknown. Here, using the embryonic pancreatic epithelium as model system, we show that macrophages drive the epithelium to execute two developmentally important choices, i.e. the exit from cell cycle and the acquisition of a migratory phenotype. We demonstrate that these developmental decisions are effectively imparted by macrophages activated toward an M2 fetal-like functional state, and involve modulation of the adhesion receptor NCAM and an uncommon "paired-less" isoform of the transcription factor PAX6 in the epithelium. Over-expression of this PAX6 variant in pancreatic epithelia controls both cell motility and cell cycle progression in a gene-dosage dependent fashion. Importantly, induction of these phenotypes in embryonic pancreatic transplants by M2 macrophages in vivo is associated with an increased frequency of endocrine-committed cells emerging from ductal progenitor pools. These results identify M2 macrophages as key effectors capable of coordinating epithelial cell cycle withdrawal and cell migration, two events critical to pancreatic progenitors' delamination and progression toward their differentiated fates.

Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.

Science.gov (United States)

Mussar, Kristin; Tucker, Andrew; McLennan, Linsey; Gearhart, Addie; Jimenez-Caliani, Antonio J; Cirulli, Vincenzo; Crisa, Laura

2014-01-01

Macrophages populate the mesenchymal compartment of all organs during embryogenesis and have been shown to support tissue organogenesis and regeneration by regulating remodeling of the extracellular microenvironment. Whether this mesenchymal component can also dictate select developmental decisions in epithelia is unknown. Here, using the embryonic pancreatic epithelium as model system, we show that macrophages drive the epithelium to execute two developmentally important choices, i.e. the exit from cell cycle and the acquisition of a migratory phenotype. We demonstrate that these developmental decisions are effectively imparted by macrophages activated toward an M2 fetal-like functional state, and involve modulation of the adhesion receptor NCAM and an uncommon "paired-less" isoform of the transcription factor PAX6 in the epithelium. Over-expression of this PAX6 variant in pancreatic epithelia controls both cell motility and cell cycle progression in a gene-dosage dependent fashion. Importantly, induction of these phenotypes in embryonic pancreatic transplants by M2 macrophages in vivo is associated with an increased frequency of endocrine-committed cells emerging from ductal progenitor pools. These results identify M2 macrophages as key effectors capable of coordinating epithelial cell cycle withdrawal and cell migration, two events critical to pancreatic progenitors' delamination and progression toward their differentiated fates.

IL-4 Receptor Alpha Signaling through Macrophages Differentially Regulates Liver Fibrosis Progression and Reversal

Directory of Open Access Journals (Sweden)

Shih-Yen Weng

2018-03-01

Full Text Available Chronic hepatitis leads to liver fibrosis and cirrhosis. Cirrhosis is a major cause of worldwide morbidity and mortality. Macrophages play a key role in fibrosis progression and reversal. However, the signals that determine fibrogenic vs fibrolytic macrophage function remain ill defined. We studied the role of interleukin-4 receptor α (IL-4Rα, a potential central switch of macrophage polarization, in liver fibrosis progression and reversal. We demonstrate that inflammatory monocyte infiltration and liver fibrogenesis were suppressed in general IL-4Rα−/− as well as in macrophage-specific IL-4Rα−/− (IL-4RαΔLysM mice. However, with deletion of IL-4RαΔLysM spontaneous fibrosis reversal was retarded. Results were replicated by pharmacological intervention using IL-4Rα-specific antisense oligonucleotides. Retarded resolution was linked to the loss of M2-type resident macrophages, which secreted MMP-12 through IL-4 and IL-13-mediated phospho-STAT6 activation. We conclude that IL-4Rα signaling regulates macrophage functional polarization in a context-dependent manner. Pharmacological targeting of macrophage polarization therefore requires disease stage-specific treatment strategies. Research in Context: Alternative (M2-type macrophage activation through IL-4Rα promotes liver inflammation and fibrosis progression but speeds up fibrosis reversal. This demonstrates context dependent, opposing roles of M2-type macrophages. During reversal IL-4Rα induces fibrolytic MMPs, especially MMP-12, through STAT6. Liver-specific antisense oligonucleotides efficiently block IL-4Rα expression and attenuate fibrosis progression. Keywords: Fibrosis, IL-4 receptor alpha, Liver, Macrophage, MMP12, Progression, Reversal

The Impact of Regulating Social Science Research with Biomedical Regulations

Science.gov (United States)

Durosinmi, Brenda Braxton

2011-01-01

The Impact of Regulating Social Science Research with Biomedical Regulations Since 1974 Federal regulations have governed the use of human subjects in biomedical and social science research. The regulations are known as the Federal Policy for the Protection of Human Subjects, and often referred to as the "Common Rule" because 18 Federal…

The Regulation of the Angiogenic Factor FGF Binding Protein (FGF-BP) by the APC/Beta-Catenin Signaling Pathway in the Progression of Breast Cancer

National Research Council Canada - National Science Library

Stylianou, Dora

2004-01-01

...) to study the expression of FGF-BP in mammary tumorigenesis progression of the APC/+ mouse and 2) to determine the mechanism of regulation of FGF-BP b the APC/beta-catenin signaling pathway in breast cancer...

The Regulation of the Angiogenic Factor FGF Binding Protein (FGF-BP) by the APC/Beta-Catenin Signaling Pathway in the Progression of Breast Cancer

National Research Council Canada - National Science Library

Stylianou, Dora

2003-01-01

...) to study the expression of FGF-BP in mammary tumorigenesis% progression of the APC/+ mouse and 2) to determine the mechanism of regulation of FGF-BP by the APC/beta- catenin signaling pathway in breast cancer...

To Regulate or Not to Regulate? Views on Electronic Cigarette Regulations and Beliefs about the Reasons for and against Regulation.

Science.gov (United States)

Sanders-Jackson, Ashley; Tan, Andy S L; Bigman, Cabral A; Mello, Susan; Niederdeppe, Jeff

2016-01-01

Policies designed to restrict marketing, access to, and public use of electronic cigarettes (e-cigarettes) are increasingly under debate in various jurisdictions in the US. Little is known about public perceptions of these policies and factors that predict their support or opposition. Using a sample of US adults from Amazon Mechanical Turk in May 2015, this paper identifies beliefs about the benefits and costs of regulating e-cigarettes and identifies which of these beliefs predict support for e-cigarette restricting policies. A higher proportion of respondents agreed with 8 different reasons to regulate e-cigarettes (48.5% to 83.3% agreement) versus 7 reasons not to regulate e-cigarettes (11.5% to 18.9%). The majority of participants agreed with 7 out of 8 reasons for regulation. When all reasons to regulate or not were included in a final multivariable model, beliefs about protecting people from secondhand vapor and protecting youth from trying e-cigarettes significantly predicted stronger support for e-cigarette restricting policies, whereas concern about government intrusion into individual choices was associated with reduced support. This research identifies key beliefs that may underlie public support or opposition to policies designed to regulate the marketing and use of e-cigarettes. Advocates on both sides of the issue may find this research valuable in developing strategic campaigns related to the issue. Specific beliefs of potential benefits and costs of e-cigarette regulation (protecting youth, preventing exposure to secondhand vapor, and government intrusion into individual choices) may be effectively deployed by policy makers or health advocates in communicating with the public.

To Regulate or Not to Regulate? Views on Electronic Cigarette Regulations and Beliefs about the Reasons for and against Regulation.

Directory of Open Access Journals (Sweden)

Ashley Sanders-Jackson

Full Text Available Policies designed to restrict marketing, access to, and public use of electronic cigarettes (e-cigarettes are increasingly under debate in various jurisdictions in the US. Little is known about public perceptions of these policies and factors that predict their support or opposition.Using a sample of US adults from Amazon Mechanical Turk in May 2015, this paper identifies beliefs about the benefits and costs of regulating e-cigarettes and identifies which of these beliefs predict support for e-cigarette restricting policies.A higher proportion of respondents agreed with 8 different reasons to regulate e-cigarettes (48.5% to 83.3% agreement versus 7 reasons not to regulate e-cigarettes (11.5% to 18.9%. The majority of participants agreed with 7 out of 8 reasons for regulation. When all reasons to regulate or not were included in a final multivariable model, beliefs about protecting people from secondhand vapor and protecting youth from trying e-cigarettes significantly predicted stronger support for e-cigarette restricting policies, whereas concern about government intrusion into individual choices was associated with reduced support.This research identifies key beliefs that may underlie public support or opposition to policies designed to regulate the marketing and use of e-cigarettes. Advocates on both sides of the issue may find this research valuable in developing strategic campaigns related to the issue.Specific beliefs of potential benefits and costs of e-cigarette regulation (protecting youth, preventing exposure to secondhand vapor, and government intrusion into individual choices may be effectively deployed by policy makers or health advocates in communicating with the public.

Impact of Lifestyle and Metformin Interventions on the Risk of Progression to Diabetes and Regression to Normal Glucose Regulation in Overweight or Obese People With Impaired Glucose Regulation.

Science.gov (United States)

Herman, William H; Pan, Qing; Edelstein, Sharon L; Mather, Kieren J; Perreault, Leigh; Barrett-Connor, Elizabeth; Dabelea, Dana M; Horton, Edward; Kahn, Steven E; Knowler, William C; Lorenzo, Carlos; Pi-Sunyer, Xavier; Venditti, Elizabeth; Ye, Wen

2017-12-01

Both lifestyle and metformin interventions can delay or prevent progression to type 2 diabetes mellitus (DM) in people with impaired glucose regulation, but there is considerable interindividual variation in the likelihood of receiving benefit. Understanding an individual's 3-year risk of progressing to DM and regressing to normal glucose regulation (NGR) might facilitate benefit-based tailored treatment. We used the values of 19 clinical variables measured at the Diabetes Prevention Program (DPP) baseline evaluation and Cox proportional hazards models to assess the 3-year risk of progression to DM and regression to NGR separately for DPP lifestyle, metformin, and placebo participants who were adherent to the interventions. Lifestyle participants who lost ≥5% of their initial body weight at 6 months and metformin and placebo participants who reported taking ≥80% of their prescribed medication at the 6-month follow-up were defined as adherent. Eleven of 19 clinical variables measured at baseline predicted progression to DM, and 6 of 19 predicted regression to NGR. Compared with adherent placebo participants at lowest risk of developing diabetes, participants at lowest risk of developing diabetes who adhered to a lifestyle intervention had an 8% absolute risk reduction (ARR) of developing diabetes and a 35% greater absolute likelihood of reverting to NGR. Participants at lowest risk of developing diabetes who adhered to a metformin intervention had no reduction in their risk of developing diabetes and a 17% greater absolute likelihood of reverting to NGR. Participants at highest risk of developing DM who adhered to a lifestyle intervention had a 39% ARR of developing diabetes and a 24% greater absolute likelihood of reverting to NGR, whereas those who adhered to the metformin intervention had a 25% ARR of developing diabetes and an 11% greater absolute likelihood of reverting to NGR. Unlike our previous analyses that sought to explain population risk, these

7 CFR 301.89-5 - Movement of regulated articles from regulated areas.

Science.gov (United States)

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Movement of regulated articles from regulated areas. 301.89-5 Section 301.89-5 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... § 301.89-5 Movement of regulated articles from regulated areas. (a) Any regulated article may be moved...

Substrate Curvature Regulates Cell Migration -A Computational Study

Science.gov (United States)

He, Xiuxiu; Jiang, Yi

Cell migration in host microenvironment is essential to cancer etiology, progression and metastasis. Cellular processes of adhesion, cytoskeletal polymerization, contraction, and matrix remodeling act in concert to regulate cell migration, while local extracellular matrix architecture modulate these processes. In this work we study how stromal microenvironment with native and cell-derived curvature at micron-meter scale regulate cell motility pattern. We developed a 3D model of single cell migration on a curved substrate. Mathematical analysis of cell morphological adaption to the cell-substrate interface shows that cell migration on convex surfaces deforms more than on concave surfaces. Both analytical and simulation results show that curved surfaces regulate the cell motile force for cell's protruding front through force balance with focal adhesion and cell contraction. We also found that cell migration on concave substrates is more persistent. These results offer a novel biomechanical explanation to substrate curvature regulation of cell migration. NIH 1U01CA143069.

Down-regulation of tricarboxylic acid (TCA) cycle genes blocks progression through the first mitotic division in Caenorhabditis elegans embryos.

Science.gov (United States)

Rahman, Mohammad M; Rosu, Simona; Joseph-Strauss, Daphna; Cohen-Fix, Orna

2014-02-18

The cell cycle is a highly regulated process that enables the accurate transmission of chromosomes to daughter cells. Here we uncover a previously unknown link between the tricarboxylic acid (TCA) cycle and cell cycle progression in the Caenorhabditis elegans early embryo. We found that down-regulation of TCA cycle components, including citrate synthase, malate dehydrogenase, and aconitase, resulted in a one-cell stage arrest before entry into mitosis: pronuclear meeting occurred normally, but nuclear envelope breakdown, centrosome separation, and chromosome condensation did not take place. Mitotic entry is controlled by the cyclin B-cyclin-dependent kinase 1 (Cdk1) complex, and the inhibitory phosphorylation of Cdk1 must be removed in order for the complex to be active. We found that following down-regulation of the TCA cycle, cyclin B levels were normal but CDK-1 remained inhibitory-phosphorylated in one-cell stage-arrested embryos, indicative of a G2-like arrest. Moreover, this was not due to an indirect effect caused by checkpoint activation by DNA damage or replication defects. These observations suggest that CDK-1 activation in the C. elegans one-cell embryo is sensitive to the metabolic state of the cell, and that down-regulation of the TCA cycle prevents the removal of CDK-1 inhibitory phosphorylation. The TCA cycle was previously shown to be necessary for the development of the early embryo in mammals, but the molecular processes affected were not known. Our study demonstrates a link between the TCA cycle and a specific cell cycle transition in the one-cell stage embryo.

Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain.

Science.gov (United States)

Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

2008-01-01

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

Involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells.

Science.gov (United States)

Takahashi, Kaede; Fukushima, Kaori; Onishi, Yuka; Minami, Kanako; Otagaki, Shiho; Ishimoto, Kaichi; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

2018-08-01

Free fatty acid receptor 1 (FFA1) and FFA4 mediate a variety of biological responses through binding of medium- and long-chain free fatty acids. The aim of this study was to investigate an involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells. The long-term fluorouracil (5-FU) and cisplatin (CDDP) treated cells were generated from DLD1 cells (DLD-5FU and DLD-CDDP cells, respectively). FFAR1 expressions were lower in DLD-5FU and DLD-CDDP cells than in DLD1 cells. In contrast, DLD-5FU and DLD-CDDP cells showed the high FFAR4 expressions, compared with DLD1 cells. The cell motile activities of DLD-5FU and DLD-CDDP cells were reduced by GW9508 which is an agonist of FFA1 and FFA4. Moreover, GW1100, an antagonist of FFA1, inhibited the cell motile activities of DLD-5FU and DLD-CDDP cells. To evaluate whether FFA1 and FFA4 regulate the enhancement of cell motility, invasion and colony formation, highly migratory (hmDLD1) cells were established from DLD1 cells. FFAR1 expression was significantly higher in hmDLD1 cells than in DLD1 cells, but no change of FFAR4 expression was observed. The elevated cell motile and invasive activities and colony formation of hmDLD1 cells were suppressed by FFA1 inhibition. These results suggest that FFA1 and FFA4 are involved in the regulation of cellular functions during tumor progression in colon cancer DLD1 cells. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Private regulation in EU better regulation : Past performance and future promises

NARCIS (Netherlands)

Verbruggen, Paul

The promotion of private regulation is frequently part of better regulation programmes. Also the Better Regulation programme of the European Union (EU) initiated in 2002 advocated forms of private regulation as important means to improve EU law-making activities. However, for various reasons the

Hmga2 regulates self-renewal of retinal progenitors.

Science.gov (United States)

Parameswaran, Sowmya; Xia, Xiaohuan; Hegde, Ganapati; Ahmad, Iqbal

2014-11-01

In vertebrate retina, histogenesis occurs over an extended period. To sustain the temporal generation of diverse cell types, retinal progenitor cells (RPCs) must self-renew. However, self-renewal and regulation of RPCs remain poorly understood. Here, we demonstrate that cell-extrinsic factors coordinate with the epigenetic regulator high-mobility group AT-hook 2 (Hmga2) to regulate self-renewal of late retinal progenitor cells (RPCs). We observed that a small subset of RPCs was capable of clonal propagation and retained multipotentiality of parents in the presence of endothelial cells (ECs), known self-renewal regulators in various stem cell niches. The self-renewing effects, also observed in vivo, involve multiple intercellular signaling pathways, engaging Hmga2. As progenitors exhaust during retinal development, expression of Hmga2 progressively decreases. Analyses of Hmga2-expression perturbation, in vitro and in vivo, revealed that Hmga2 functionally helps to mediate cell-extrinsic influences on late-retinal progenitor self-renewal. Our results provide a framework for integrating the diverse intercellular influences elicited by epigenetic regulators for self-renewal in a dynamic stem cell niche: the developing vertebrate retina. © 2014. Published by The Company of Biologists Ltd.

Frontiers of environmental regulation: environmental management systems: a regulator`s perspective

Energy Technology Data Exchange (ETDEWEB)

Stone, M.J. [South Australian Dept. of Mines and Energy, Adelaide, SA (Australia)

1996-12-31

Leading edge companies throughout the world have embraced management systems to achieve optimal sustainable performance in the ever changing business environment of the 1990s. Given that the natural environment and environmental performance have become major issues affecting organizations, the need for integrating environmental management with all the other components of an organization`s overall management approach is now widely recognized. This paper is organized in five parts. The first explores recently released environmental standards, the interim environmental management systems (EMS) general guidelines standard AS/NZS ISO 14004 (Int) and identifies how this has dealt with the regulator/community/company interface. The second identifies company requirements for addressing environmental issues. The third, considers regulatory theory to identify current requirements for an effective regulatory system and how this can interface with a company`s EMS. These form the basis in the fourth section for identifying some opportunities which occur at the company/ regulator interface. The fifth and final section draws a number of conclusions about the current frontiers of environmental regulation. The coincidence of the requirements of a regulatory framework with the areas of interface between what is referred to in the draft International Standard for EMS as `Interested Parties`, the regulators and community, are identified. (author). 1 tab., 2 figs., 20 refs.

Peak regulation right

International Nuclear Information System (INIS)

Gao, Z. |; Ren, Z.; Li, Z.; Zhu, R.

2005-01-01

A peak regulation right concept and corresponding transaction mechanism for an electricity market was presented. The market was based on a power pool and independent system operator (ISO) model. Peak regulation right (PRR) was defined as a downward regulation capacity purchase option which allowed PRR owners to buy certain quantities of peak regulation capacity (PRC) at a specific price during a specified period from suppliers. The PRR owner also had the right to decide whether or not they would buy PRC from suppliers. It was the power pool's responsibility to provide competitive and fair peak regulation trading markets to participants. The introduction of PRR allowed for unit capacity regulation. The PRR and PRC were rated by the supplier, and transactions proceeded through a bidding process. PRR suppliers obtained profits by selling PRR and PRC, and obtained downward regulation fees regardless of whether purchases are made. It was concluded that the peak regulation mechanism reduced the total cost of the generating system and increased the social surplus. 6 refs., 1 tab., 3 figs

Regulating through leverage: Civil regulation in China

NARCIS (Netherlands)

Fürst, K.

2016-01-01

The overarching goal of this study is to examine the efforts of Chinese NGOs to prevent and/or control industrial pollution risks and then use the findings of this research to study the nature of civil regulation in, and beyond, China’s authoritarian setting. It first argues that 'regulation through

Changing the regulation for regulating the change: Innovation-driven regulatory developments for smart grids, smart metering and e-mobility in Italy

International Nuclear Information System (INIS)

Lo Schiavo, Luca; Delfanti, Maurizio; Fumagalli, Elena; Olivieri, Valeria

2013-01-01

For a long time considered as technologically mature, electric systems are now facing a period of rapid evolution, inspired by climate change concerns. Several studies show that current regulation of natural monopolies does not offer sufficient incentives for network operators (and network users) to participate in this process. Taking Italy as a case study, this paper analyses how energy regulation can change to support the current transformation. We describe the recent regulatory interventions in the domain of smart grids, smart metering and electromobility, with a specific emphasis on the provisions aimed at fostering innovation—an issue that until recently has received almost no attention in the literature nor in the practice of regulation. The progress we observe is considerable in all new areas of concern, and, above all, in the regulator's commitment to provide the right incentives for investments in demonstration projects: the acquisition of experience is regarded as essential to move to more sophisticated regulatory instruments. Finally, regulation is also increasingly concerned with network users, both traditional and new, with the objective to stimulate more active behaviours. - Highlights: ► Regulatory changes in Italy: smart grids, smart metering and electromobility. ► Identification of indicators for regulating innovative investments. ► Demonstration projects for smart grids and EV recharging infrastructures. ► Proposal of an output-based regulation for smart grids. ► Time of Use pricing for residential and small commercial consumers

Cancers take their Toll--the function and regulation of Toll-like receptors in cancer cells

DEFF Research Database (Denmark)

Chen, R; Alvero, A B; Silasi, D-A

2008-01-01

proliferation, would also be key factors in regulating and enhancing cancer progression. The TLR pathways, which play a critical role in tissue repair, are also key regulators in cancer progression as well as chemoresistance. TLRs serve as cell surface sensors that can initiate pathways leading to proliferation......Cancer could be deemed as an abnormal and uncontrolled tissue repair process. Therefore, it would not be surprising that factors that function in the tissue repair process, such as cytokines, chemokines, growth factors and Toll-like receptor (TLR) ligands, as well as growth signals for compensatory...... and chemoresistance; as well as mediators that are able to regulate the infiltrating immune cells to provide further support for cancer progression....

Regulation for the decommissioning of nuclear power plants in U.S.A

International Nuclear Information System (INIS)

Oishi, Yuichi

2001-01-01

Since beginning of operation in nuclear reactor for practical power generation for the first one in Japan in 1966, the rector already passed more than 30 years are found and some investigations on its abolition method and its countermeasure accompanied with its permanent operation finishing of the reactor for future have been progressed by government and the relative organizations. The Japan Engineering and Inspection Corporation, under trust of the Ministry of Economy and Industry, has carried out some surveys on abolition measure regulation in the world. On the regulation in U.S.A. as a part of the surveys, abstract of the survey results performed before 1999 was introduced. Items in the survey were regulation system, definition and configuration of the abolition measure, legal procedures on the measure, and the last radiation survey and evaluating method. In U.S.A., as contents on legal procedure and document to be proposed are in detail and concretely regulated, the abolition measure activity can be progressed in standard according to the legal regulation, difference between every plants is thought to be very small. And, in spite of being regulated in details, participation of regulation agency on the procedures is less than that under operation, and there are some exempted items automatically. This is to say, it is a method to be processed under check of the abolition measure activity by NRC through its notice, inspection and approval, under agreeing with desires of applicants. (G.K.)

The KRAB Zinc Finger Protein Roma/Zfp157 Is a Critical Regulator of Cell-Cycle Progression and Genomic Stability

Directory of Open Access Journals (Sweden)

Teresa L.F. Ho

2016-04-01

Full Text Available Regulation of DNA replication and cell division is essential for tissue growth and maintenance of genomic integrity and is particularly important in tissues that undergo continuous regeneration such as mammary glands. We have previously shown that disruption of the KRAB-domain zinc finger protein Roma/Zfp157 results in hyperproliferation of mammary epithelial cells (MECs during pregnancy. Here, we delineate the mechanism by which Roma engenders this phenotype. Ablation of Roma in MECs leads to unscheduled proliferation, replication stress, DNA damage, and genomic instability. Furthermore, mouse embryonic fibroblasts (MEFs depleted for Roma exhibit downregulation of p21Cip1 and geminin and have accelerated replication fork velocities, which is accompanied by a high rate of mitotic errors and polyploidy. In contrast, overexpression of Roma in MECs halts cell-cycle progression, whereas siRNA-mediated p21Cip1 knockdown ameliorates, in part, this phenotype. Thus, Roma is an essential regulator of the cell cycle and is required to maintain genomic stability.

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.

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

Science.gov (United States)

Lescaille, Géraldine; Menashi, Suzanne; Cavelier-Balloy, Bénédicte; Khayati, Farah; Quemener, Cathy; Podgorniak, Marie Pierre; Naïmi, Benyoussef; Calvo, Fabien; Lebbe, Céleste; Mourah, Samia

2012-03-23

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. 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. 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. Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion.

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

International Nuclear Information System (INIS)

Lescaille, Géraldine; Mourah, Samia; Menashi, Suzanne; Cavelier-Balloy, Bénédicte; Khayati, Farah; Quemener, Cathy; Podgorniak, Marie Pierre; Naïmi, Benyoussef; Calvo, Fabien; Lebbe, Céleste

2012-01-01

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. 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. 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. Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion

miR-24-3p/FGFR3 Signaling as a Novel Axis Is Involved in Epithelial-Mesenchymal Transition and Regulates Lung Adenocarcinoma Progression

Directory of Open Access Journals (Sweden)

Pengyu Jing

2018-01-01

Full Text Available Our previous studies showed that Fibroblast growth factor receptor 3 (FGFR3 contributed to cell growth in lung cancer. However, the correlation between FGFR3 and tumor progression, coupled with the underlying mechanisms, are not fully understood. The clinical significance of FGFR3 was determined in two cohorts of clinical samples (n=22, n=78. A panel of biochemical assays and functional experiments was utilized to elucidate the underlying mechanisms and effects of FGFR3 and miR-24-3p on lung adenocarcinoma progression. Upregulated FGFR3 expression indicated an adverse prognosis for lung adenocarcinoma individuals and promoted metastatic potential of lung adenocarcinoma cells. Owing to the direct regulation towards FGFR3, miR-24-3p could interfere with the potential of proliferation, migration, and invasion in lung adenocarcinoma, following variations of EMT-related protein expression. As a significant marker of EMT, E-cadherin was negatively correlated with FGFR3, of which ectopic overexpression could neutralize the antitumour effects of miR-24-3p and reverse its regulatory effects on EMT markers. Taken together, these findings define a novel insight into the miR-24-3p/FGFR3 signaling axis in regulating lung adenocarcinoma progression and suggest that targeting the miR-24-3p/FGFR3 axis could be an effective and efficient way to prevent tumor progression.

Mechanism and regulation of epithelial–mesenchymal transition in cancer

Directory of Open Access Journals (Sweden)

Guttilla Reed IK

2015-08-01

Full Text Available Irene K Guttilla ReedDepartment of Biology, University of Saint Joseph, West Hartford, CT, USAAbstract: During development and the pathogenesis of certain diseases, including cancer, the epithelial–mesenchymal transition (EMT program is activated. It is hypothesized that EMT plays a major role in tumor invasion and the establishment of distant metastases. Metastatic disease is responsible for the vast majority of cancer-related deaths, which provides a precedent for elucidating pathways that regulate EMT. EMT is defined as the transition of cells with an epithelial phenotype into cells with a mesenchymal phenotype through a series of genetic and environmental events. This leads to the repression of epithelial-associated markers, upregulation of mesenchymal-associated markers, a loss of cell polarity and adhesion, and increased cell motility and invasiveness. EMT is a reversible and dynamic process, and can be regulated by signals from the microenvironment such as inflammation, hypoxia, and growth factors or epigenetically via microRNAs. These signals modulate key EMT-associated transcription factors and effector proteins that control cellular phenotype and regulate tumor plasticity in response to changing conditions in the microenvironment and the progressive nature of cancer. Understanding the complex regulatory networks controlling EMT can provide insight into tumor progression and metastasis.Keywords: EMT, metastasis, microRNA, transcription factor, growth factor, tumor progression

Exposure to 9,10-phenanthrenequinone accelerates malignant progression of lung cancer cells through up-regulation of aldo-keto reductase 1B10

International Nuclear Information System (INIS)

Matsunaga, Toshiyuki; Morikawa, Yoshifumi; Haga, Mariko; Endo, Satoshi; Soda, Midori; Yamamura, Keiko; El-Kabbani, Ossama; Tajima, Kazuo; Ikari, Akira; Hara, Akira

2014-01-01

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

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

Gaz de France and market regulation

International Nuclear Information System (INIS)

Carriere, J.F.; Balard, Th.

2004-01-01

Following an overview of the specific features of the European gas sector (characterised by highly concentrated production and increasing levels of production outside Europe and over long distances), the article describes the lead up to the opening of the market place in France. Following the application of the first directive in 2000, Gaz de France has carried out various measures, the aim of which was to achieve immediate efficiency (with the organizational separation of the transport and trading divisions, the separation of activities from an accounting viewpoint and the publication of a transparent TPA tariff as opposed to a discriminatory one). This opening of the gas sector has seen the start of a gradual process based on this experience. In addition to these initial measures, the opening of the gas markets has been subject to a regulatory framework as from January 2003, and the task of regulating the French gas sector has been given to the CRE (Commission de regulation de l'electricite). Thanks to the ongoing dialogue initiated by the latter with all key players in the market, progress has been achieved in various fields related to regulation. Even if this process is not complete, the French example demonstrates that the combined actions of the regulator and the market operators working together in a constructive manner and in stages, makes it possible to successfully introduce a genuinely open market. (authors)

Radiation regulation

International Nuclear Information System (INIS)

Braithwaite, J.; Grabosky, P.

1985-01-01

The five main areas of radiation regulation considered are radiation exposure in the mining of uranium and other minerals, exposure in the use of uranium in nuclear reactors, risks in the transport of radioactive materials and hazards associated with the disposal of used materials. In Australia these problems are regulated by mines departments, the Australian Atomic Energy Commission and radiation control branches in state health departments. Each of these instutional areas of regulation is examined

Chemical regulators of plant hormones and their applications in basic research and agriculture.

Science.gov (United States)

Jiang, Kai; Asami, Tadao

2018-04-20

Plant hormones are small molecules that play versatile roles in regulating plant growth, development, and responses to the environment. Classic methodologies, including genetics, analytic chemistry, biochemistry, and molecular biology, have contributed to the progress in plant hormone studies. In addition, chemical regulators of plant hormone functions have been important in such studies. Today, synthetic chemicals, including plant growth regulators, are used to study and manipulate biological systems, collectively referred to as chemical biology. Here, we summarize the available chemical regulators and their contributions to plant hormone studies. We also pose questions that remain to be addressed in plant hormone studies and that might be solved with the help of chemical regulators.

Regulation of Meiotic Recombination

Energy Technology Data Exchange (ETDEWEB)

Gregory p. Copenhaver

2011-11-09

Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

75 FR 75904 - Global Terrorism Sanctions Regulations; Terrorism Sanctions Regulations; Foreign Terrorist...

Science.gov (United States)

2010-12-07

... Terrorism Sanctions Regulations; Terrorism Sanctions Regulations; Foreign Terrorist Organizations Sanctions... Foreign Assets Control (``OFAC'') of the U.S. Department of the Treasury is amending the Global Terrorism Sanctions Regulations (``GTSR'') and the Terrorism Sanctions Regulations (``TSR'') to expand the scope of...

Experience with the 1985 UK ionizing radiation regulations: the regulators' viewpoint

International Nuclear Information System (INIS)

Bines, W.P.; Beaver, P.F.

1991-01-01

The Ionising Radiations Regulations 1985 achieved UK implementation of the Euratom Basic Safety Standards Directive; interim action has taken account of recent revisions of risk estimates and the regulations will not be revised in advance of renegotiation of the Euratom Directive. Wide ranging consultation, central to the development of health and safety legislation in the UK, leads to greater co-operation between regulators and regulated and more acceptable legislation. Examples of co-operation, also of methods of enforcement and the use made of them, are given. The authors conclude that the regulations have stood the test of experience well. (Author)

ZRF1 controls the retinoic acid pathway and regulates leukemogenic potential in acute myeloid leukemia.

Science.gov (United States)

Demajo, S; Uribesalgo, I; Gutiérrez, A; Ballaré, C; Capdevila, S; Roth, M; Zuber, J; Martín-Caballero, J; Di Croce, L

2014-11-27

Acute myeloid leukemia (AML) is frequently linked to epigenetic abnormalities and deregulation of gene transcription, which lead to aberrant cell proliferation and accumulation of undifferentiated precursors. ZRF1, a recently characterized epigenetic factor involved in transcriptional regulation, is highly overexpressed in human AML, but it is not known whether it plays a role in leukemia progression. Here, we demonstrate that ZRF1 depletion decreases cell proliferation, induces apoptosis and enhances cell differentiation in human AML cells. Treatment with retinoic acid (RA), a differentiating agent currently used to treat certain AMLs, leads to a functional switch of ZRF1 from a negative regulator to an activator of differentiation. At the molecular level, ZRF1 controls the RA-regulated gene network through its interaction with the RA receptor α (RARα) and its binding to RA target genes. Our genome-wide expression study reveals that ZRF1 regulates the transcription of nearly half of RA target genes. Consistent with our in vitro observations that ZRF1 regulates proliferation, apoptosis, and differentiation, ZRF1 depletion strongly inhibits leukemia progression in a xenograft mouse model. Finally, ZRF1 knockdown cooperates with RA treatment in leukemia suppression in vivo. Taken together, our data reveal that ZRF1 is a key transcriptional regulator in leukemia progression and suggest that ZRF1 inhibition could be a novel strategy to be explored for AML treatment.

Restructuring and regulating district heating and cogeneration in transition economies

International Nuclear Information System (INIS)

Brendow, Klaus

2004-01-01

In summer 2004, the World Energy Council published a Study on 'Regulating district heating and cogeneration in central and eastern Europe'2, prepared by representatives from eleven economies in transition and two Nordic countries. The Task Force analysed twelve regulatory issues, country-by-country, on all internationally comparable basis. Regulatory progress on the road to more efficient, profitable, competitive and service-oriented heat supplies was described. Common concerns were identified: the need for independence of the regulator from policy and industry, improved coordination between central and local regulators and between environmental and energy authorities, access to grids, and a 'fair' sharing of CHP benefits among heat and electricity generation. Looking forward, the Task Force advocated a continued dialogue between decision makers, regulators, regulated industries and customers on: 1)the internalisation of DH/CHP benefits; 2)the future reduction of the density of regulation; 3) Joint implementation; 4)the compensation for public service obligations; 5)the elimination of old debt and stranded investments; 6) DH/CHP taxation; 7)privatisation; 8)the integration of DH/CHP in urban planning. A concluding WEC workshop in Moscow in March 2004 addressed recommendations to policy makers('Moscow Statement'). (Author)

Competition between bank regulators

OpenAIRE

Schindler, Dirk; Eggert, Wolfgang

2004-01-01

This paper examines competition between bank regulators in open economies. We use a model where credit demand of firms is endogenous and show any tendency for downward competition in regulation policy is limited by the effect of regulation on profits of nonfinancial firms. Moreover, perfect mobility on loans and deposit markets fully eliminates the incentives of regulators to set bank regulation at ine±cient low levels.

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.

MFAP5 promotes tumor progression and bone metastasis by regulating ERK/MMP signaling pathways in breast cancer.

Science.gov (United States)

Wu, Zhiqiang; Wang, Ting; Fang, Meng; Huang, Wending; Sun, Zhengwang; Xiao, Jianru; Yan, Wangjun

2018-04-06

Breast cancer accounts for about 30% of all cancers in women, while approximately 70% breast cancer patients developed bone metastases throughout the course of their disease, highlighting the importance of exploring new therapeutic targets. Microfibrillar-associated protein 5 (MFAP5) is a component of extracellular elastic microfibril which has been confirmed to function in tissue development and cancer progression. But the role of MFAP5 in breast cancer remains unclear. The present study demonstrated that MFAP5 was up-regulated in breast cancers compared with that in normal breast tissues, and further increased in breast cancer bone metastasis. Functionally, MFAP5 overexpression accelerated breast cancer cell proliferation and migration, while an opposite effect was observed when MFAP5 was knocked down. In addition, up-regulation of MFAP5 increased the expression of MMP2 and MMP9 and activated the ERK signaling pathway. Conversely, inhibition of MFAP5 suppressed the expression of MMP2, MMP9, p-FAK, p-Erk1/2 and p-cJun. These findings may provide a better understanding about the mechanism of breast cancer and suggest that MFAP5 may be a potential prognostic biomarker and therapeutic target for breast cancer, especially for bone metastasis of breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Beyond the technical: The role of emotion regulation in lacrosse officiating.

Science.gov (United States)

Friesen, Andrew P; Devonport, Tracey J; Lane, Andrew M

2017-03-01

Emotions can influence the performance of referees leading to a need to examine emotions experienced, and regulation strategies used by referees. The present study assessed emotions and emotion regulation strategies of 19 referees officiating at an Under-19 Lacrosse World Championship. Using survey methods and focus group interviews, officials responded to five questions: (a) What emotions were experienced? (b) What events elicited emotions? (c) How did lacrosse officials manage their own emotional states prior to, throughout, and following a competitive game? (d) How did officials manage others' emotional states? (e) What were the perceived consequences of these strategies? Results indicate that emotions fluctuated throughout the tournament as referees encountered intrapersonal and interpersonal emotion-eliciting events. These fluctuations are suggested to come from a progressively diminished capacity for emotion regulation. Participants used emotion regulation strategies that could be classified into Gross' (1999) families of emotion regulation strategies, often relying on suppression, emotion contagion, and preventative refereeing. Collectively, the results offer new insights into referee emotion regulation at international events.

Study on the development of safety regulations for geological disposal of high-level radioactive waste

International Nuclear Information System (INIS)

Wei Fangxin

2012-01-01

The development of regulations under Regulations on Safety Management of Radioactive Waste has become necessary as the issuance of it. The regulations related to geological disposal of high-level radioactive waste can promote the progress of research and development on geological disposal of high-level radioactive waste in China. This paper has present suggestions on development of regulations on geological disposal of high-level radioactive waste by analyzing development of safety regulations on geological disposal of high-level radioactive waste in foreign countries and problems occurred in China and discussed important issues related to the development of safety regulations on geological disposal of high-level radioactive waste. (author)

Properties and regulation of biosynthesis of cottonseed storage proteins. Comprehensive progress report, December 1, 1976 to September 1, 1979

Energy Technology Data Exchange (ETDEWEB)

Dure, III, L S

1979-01-01

The regulation of gene expression in cotton seed embryogenesis was studied by attempting to define what gene products are likely to be highly regulated during this developmental progression. The flow of nitrogen into the free amino acids pools of the developing cotyledons, and into the principal nitrogen nutritional reserve of the seed, the storage proteins was measured. This was continued by following the flow of nitrogen from the storage proteins to the principal exported amino acid asparagine that occurs during the first several days of germination. In this fashion the rise and fall of certain enzymes of amino acid intermediary metabolism could be postulated, and in some cases, verified. The subsets of abundant mRNAs whose appearance and disappearance coincided with developmental events in cotyledon embryogenesis/germination with the short range goal of identifying proteins/enzyme activities were delineated as well as their mRNAs that represent specific developmental stages and the long range goal of using these representatives as probes for studying the mechanisms controlling the rise and fall of these mRNAs and their protein products.

78 FR 31551 - Federal Acquisition Regulation; Submission for OMB Review; Commerce Patent Regulations

Science.gov (United States)

2013-05-24

...; Submission for OMB Review; Commerce Patent Regulations AGENCIES: Department of Defense (DOD), General... collection requirement concerning Department of Commerce patent regulations. A notice was published in...- 0095, Commerce Patent Regulations, by any of the following methods: Regulations.gov : http://www...

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 a...

Identification of Hypoxia-Regulated Proteins Using MALDI-Mass Spectrometry Imaging Combined with Quantitative Proteomics

DEFF Research Database (Denmark)

Djidja, Marie-Claude; Chang, Joan; Hadjiprocopis, Andreas

2014-01-01

Hypoxia is present in most solid tumors and is clinically correlated with increased metastasis and poor patient survival. While studies have demonstrated the role of hypoxia and hypoxia-regulated proteins in cancer progression, no attempts have been made to identify hypoxia-regulated proteins using...

[Regulation of terpene metabolism]. [Mentha piperita, Mentha spicata

Energy Technology Data Exchange (ETDEWEB)

Croteau, R.

1989-01-01

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.

Interpersonal emotion regulation.

Science.gov (United States)

Zaki, Jamil; Williams, W Craig

2013-10-01

Contemporary emotion regulation research emphasizes intrapersonal processes such as cognitive reappraisal and expressive suppression, but people experiencing affect commonly choose not to go it alone. Instead, individuals often turn to others for help in shaping their affective lives. How and under what circumstances does such interpersonal regulation modulate emotional experience? Although scientists have examined allied phenomena such as social sharing, empathy, social support, and prosocial behavior for decades, there have been surprisingly few attempts to integrate these data into a single conceptual framework of interpersonal regulation. Here we propose such a framework. We first map a "space" differentiating classes of interpersonal regulation according to whether an individual uses an interpersonal regulatory episode to alter their own or another person's emotion. We then identify 2 types of processes--response-dependent and response-independent--that could support interpersonal regulation. This framework classifies an array of processes through which interpersonal contact fulfills regulatory goals. More broadly, it organizes diffuse, heretofore independent data on "pieces" of interpersonal regulation, and identifies growth points for this young and exciting research domain.

Volume regulation in epithelia

DEFF Research Database (Denmark)

Larsen, Erik Hviid; Hoffmann, Else Kay

2016-01-01

to amphibian skin and mammalian cortical collecting tubule of low and intermediate osmotic permeability. Crosstalk between entrance and exit mechanisms interferes with volume regulation both at aniso-osmotic and iso-osmotic volume perturbations. It has been proposed that cell volume regulation is an intrinsic...... regulation are cloned. The volume-regulated anion channel (VRAC) exhibiting specific electrophysiological characteristics seems exclusive to serve cell volume regulation. This is contrary to K+ channels as well as cotransporters and exchange mechanisms that may serve both transepithelial transport and cell...... volume regulation. In the same cell, these functions may be maintained by different ion pathways that are separately regulated. RVD is often preceded by increase in cytosolic free Ca2+, probably via influx through TRP channels, but Ca2+ release from intracellular stores has also been observed. Cell...

Why try (not to cry: Intra- and inter-personal motives for crying regulation

Directory of Open Access Journals (Sweden)

Gwenda eSimons

2013-01-01

Full Text Available This article discusses inter- and intra-personal motives for the regulation of crying, and presents illustrative findings from an online survey (N = 110 exploring why and how people regulate crying in their everyday lives. In line with current theorizing on emotion regulation and crying (e.g., Vingerhoets et al., 2000, we propose that emotional crying is regulated using both antecedent-focused techniques targeting the underlying emotion and response-focused techniques targeting the act of crying itself. Indeed, our survey respondents reported having used both antecedent- and response-focused strategies to either up-regulate or down-regulate their crying. Motives for crying regulation may be both inter- and intra-personal and may serve both immediate, pleasure motives and future, utility motives (Tamir, 2009. Our findings suggest that down-regulation attempts are often driven by inter-personal motives (e.g., protecting the well-being of others; impression management in addition to intra-personal motives such as maintaining subjective well-being, whereas up-regulation attempts are mostly driven by intra-personal motives. Further progress requires methodologies for manipulating or tracking regulation motives and strategies in real-time crying episodes.

Ex Post Regulation as the Method of Sectoral Regulation in Electricity Sector

Directory of Open Access Journals (Sweden)

Rafał Nagaj

2017-10-01

Full Text Available Aim/purpose - The aim of the article is to present the essence of ex post approach to sectoral regulation, to show the advantages and disadvantages of ex post regulation and to answer the question whether it is worth using in the electricity sector. Design/methodology/approach - For this purpose, a critical analysis of expert literature was made and an empirical analysis of countries that have applied ex post regulation in the electricity sector in the European Union. Two research methods were used: a case study and a comparison of changes in price and quality of services. The research period covered the period 2000-2016. Findings - It was found that ex post regulation reduces regulatory costs, does not adversely affect the quality of service and long-term rates, gives businesses the freedom of decision-making and the ability to react quickly to changes in the economy. The main disadvantages of ex post regulation are the tendency for companies to over-estimate bills for consumers, the difficulty of pursuing claims by consumers and the need to shift regulatory risk to consumers. Research implications/limitations - In the paper there was identified a research gap, i.e. the effects of ex post regulation in the electricity sector in European Union countries where such regulation was applied. Identifying the research gap will help us understand what are the advantages and disadvantages of ex post regulation and will create a model for when it is good moment to implement this in the economy. Besides identifying the research gap, further studies will be required over ex post regulation. Originality/value/contribution - The additional value of the paper is the study of ex post regulation, its essence and types. The article analyzed the effects of ex post regulation in the electricity sector and provided valuable insights into the potential risks associated with this approach to economic regulation.

Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases.

Science.gov (United States)

González, Hugo; Elgueta, Daniela; Montoya, Andro; Pacheco, Rodrigo

2014-09-15

Neuroinflammation constitutes a fundamental process involved in the progression of several neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. Microglial cells play a central role in neuroinflammation, promoting neuroprotective or neurotoxic microenvironments, thus controlling neuronal fate. Acquisition of different microglial functions is regulated by intercellular interactions with neurons, astrocytes, the blood-brain barrier, and T-cells infiltrating the central nervous system. In this study, an overview of the regulation of microglial function mediated by different intercellular communications is summarised and discussed. Afterward, we focus in T-cell-mediated regulation of neuroinflammation involved in neurodegenerative disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Autocrine-paracrine regulation of the mammary gland.

Science.gov (United States)

Weaver, S R; Hernandez, L L

2016-01-01

autocrine-paracrine regulation of the mammary gland, with an examination of both foundational work and the progress made within the last 10 to 20 yr of research. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Regulation as Rhetoric

DEFF Research Database (Denmark)

Boll, Karen; Györy, Csaba

This paper analyses the way regulatory agencies strategically use public ‘rhetoric’ and ‘management of appearance’ to strengthen their regulation. It reports a comparative study of the Securities and Exchange Commission (SEC) which is the US federal securities regulator and the Danish Tax...... and Customs Administration (SKAT) which is the national tax regulator in Denmark. SEC operates in a US context where the agency fights to get trust, while SKAT operates in a context where high trust in public agencies is a basic condition. We argue, however, that despite the radically different institutional...... engage reflectively in image promotion which serves two purposes: establishing and maintaining legitimacy in a particular social and political environment and producing compliance. Further, we argue that this regulation is a form of ‘post-bureaucratic’ regulation in which compliance is achieved...

Voltage regulator for generator

Energy Technology Data Exchange (ETDEWEB)

Naoi, K

1989-01-17

It is an object of this invention to provide a voltage regulator for a generator charging a battery, wherein even if the ambient temperature at the voltage regulator rises abnormally high, possible thermal breakage of the semiconductor elements constituting the voltage regulator can be avoided. A feature of this invention is that the semiconductor elements can be protected from thermal breakage, even at an abnormal ambient temperature rise at the voltage regulator for the battery charging generator, by controlling a maximum conduction ratio of a power transistor in the voltage regulator in accordance with the temperature at the voltage regulator. This is achieved through a switching device connected in series to the field coil of the generator and adapted to be controlled in accordance with an output voltage of the generator and the ambient temperature at the voltage regulator. 6 figs.

Molecular machinery of signal transduction and cell cycle regulation in Plasmodium

OpenAIRE

Koyama, Fernanda C.; Chakrabarti, Debopam; Garcia, Célia R.S.

2009-01-01

The regulation of the Plasmodium cell cycle is not understood. Although the Plasmodium falciparum genome is completely sequenced, about 60% of the predicted proteins share little or no sequence similarity with other eukaryotes. This feature impairs the identification of important proteins participating in the regulation of the cell cycle. There are several open questions that concern cell cycle progression in malaria parasites, including the mechanism by which multiple nuclear divisions is co...

Sortilin regulates progranulin action in castration-resistant prostate cancer cells.

Science.gov (United States)

Tanimoto, Ryuta; Morcavallo, Alaide; Terracciano, Mario; Xu, Shi-Qiong; Stefanello, Manuela; Buraschi, Simone; Lu, Kuojung G; Bagley, Demetrius H; Gomella, Leonard G; Scotlandi, Katia; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

2015-01-01

The growth factor progranulin is as an important regulator of transformation in several cellular systems. We have previously demonstrated that progranulin acts as an autocrine growth factor and stimulates motility, proliferation, and anchorage-independent growth of castration-resistant prostate cancer cells, supporting the hypothesis that progranulin may play a critical role in prostate cancer progression. However, the mechanisms regulating progranulin action in castration-resistant prostate cancer cells have not been characterized. Sortilin, a single-pass type I transmembrane protein of the vacuolar protein sorting 10 family, binds progranulin in neurons and negatively regulates progranulin signaling by mediating progranulin targeting for lysosomal degradation. However, whether sortilin is expressed in prostate cancer cells and plays any role in regulating progranulin action has not been established. Here, we show that sortilin is expressed at very low levels in castration-resistant PC3 and DU145 cells. Significantly, enhancing sortilin expression in PC3 and DU145 cells severely diminishes progranulin levels and inhibits motility, invasion, proliferation, and anchorage-independent growth. In addition, sortilin overexpression negatively modulates Akt (protein kinase B, PKB) stability. These results are recapitulated by depleting endogenous progranulin in PC3 and DU145 cells. On the contrary, targeting sortilin by short hairpin RNA approaches enhances progranulin levels and promotes motility, invasion, and anchorage-independent growth. We dissected the mechanisms of sortilin action and demonstrated that sortilin promotes progranulin endocytosis through a clathrin-dependent pathway, sorting into early endosomes and subsequent lysosomal degradation. Collectively, these results point out a critical role for sortilin in regulating progranulin action in castration-resistant prostate cancer cells, suggesting that sortilin loss may contribute to prostate cancer progression.

Grandfather regulations, new source bias, and state air toxics regulations

International Nuclear Information System (INIS)

Levinson, Arik

1999-01-01

This paper uses plant-level data from the Census of Manufactures and the variation in toxic air pollution regulations across states to measure the effects of laws that are more stringent for new sources of pollution than for existing sources (so-called 'grandfather' regulations). Of particular interest is the resulting 'new source bias' and its effects on capital vintage and investment. Two industries are examined: commercial printing, which has a local product market; and paint manufacturing, which has a more national market. In general, there seem to be no statistically significant differences in capital vintage or investment between plants in states that grandfather new sources of pollution, plants in states that have no air toxics regulations, and plants in states that regulate both new and existing sources

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.

Self-regulation – the key to progress in clinical reasoning? | Postma ...

African Journals Online (AJOL)

Both groups lauded the scaffolding that the case-based curriculum provided. Strategic thinking, goal orientation and self-regulation ability were identified in group 1. A lack of diligence, poor data-processing ability and a possible lack of interest were identified in group 2 students, who were unaware of learning opportunities.

Regulations concerning the radionuclides uses in France

International Nuclear Information System (INIS)

Vergne, J.

1955-01-01

The progress in the uses of radioisotopes has been conditioned by increasing the number of trained workers and researchers and developing theoretical teaching in universities since 1950 in France as well as developing a national control of the distribution and uses of radioisotopes. With the large diffusion and development of radioisotopes uses and applications, new rules and regulations came to control the importation, exportation, transport and utilization of radioisotopes. In the first part, it described the different French laws since 1934 and their successive modifications which ruled on the production, manipulation and utilization of radioisotopes. An inter-ministerial committee was created in 1952 to advise and inform of all the questions related to the preparation, importation, exportation, possession and distribution of radioisotopes. The transport regulations are in constant evolution and has got to meet with international recommendations. It distinguished three different type of transport: road, river and railway transport, postal transport and finally air transport. All the different transports have their specific packaging, maximum transportable quantity, maximum material intensity and labelling requirements. The regulations about customs duties are specified as well as the administrative formalities for non natural radioisotopes importation. Since 1950, diseases caused by irradiation to natural or artificial radioactive materials are recognised as professional diseases and a table of the actual regulations is presented. (M.P.)

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.

Lysophosphatidic acid signaling via LPA{sub 1} and LPA{sub 3} regulates cellular functions during tumor progression in pancreatic cancer cells

Energy Technology Data Exchange (ETDEWEB)

Fukushima, Kaori; Takahashi, Kaede; Yamasaki, Eri; Onishi, Yuka [Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Fukushima, Nobuyuki [Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Honoki, Kanya [Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Tsujiuchi, Toshifumi, E-mail: ttujiuch@life.kindai.ac.jp [Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)

2017-03-01

Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors exhibits a variety of biological effects, such as cell proliferation, motility and differentiation. The aim of this study was to evaluate the roles of LPA{sub 1} and LPA{sub 3} in cellular functions during tumor progression in pancreatic cancer cells. LPA{sub 1} and LPA{sub 3} knockdown cells were generated from PANC-1 cells. The cell motile and invasive activities of PANC-1 cells were inhibited by LPA{sub 1} and LPA{sub 3} knockdown. In gelatin zymography, LPA{sub 1} and LPA{sub 3} knockdown cells indicated the low activation of matrix metalloproteinase-2 (MMP-2) in the presence of LPA. Next, to assess whether LPA{sub 1} and LPA{sub 3} regulate cellular functions induced by anticancer drug, PANC-1 cells were treated with cisplatin (CDDP) for approximately 6 months. The cell motile and invasive activities of long-term CDDP treated cells were markedly higher than those of PANC-1 cells, correlating with the expression levels of LPAR1 and LPAR3 genes. In soft agar assay, the long-term CDDP treated cells formed markedly large sized colonies. In addition, the cell motile and invasive activities enhanced by CDDP were significantly suppressed by LPA{sub 1} and LPA{sub 3} knockdown as well as colony formation. These results suggest that LPA signaling via LPA{sub 1} and LPA{sub 3} play an important role in the regulation of cellular functions during tumor progression in PANC-1 cells. - Highlights: • The cell motile and invasive activities of PANC-1 cells were stimulated by LPA{sub 1} and LPA{sub 3}. • LPA{sub 1} and LPA{sub 3} enhanced MMP-2 activation in PANC-1 cells. • The expressions of LPAR1 and LPAR3 genes were elevated in PANC-1 cells treated with cisplatin. • The cell motile and invasive activities of PANC-1 cells treated with cisplatin were suppressed by LPA{sub 1} and LPA{sub 3} knockdown. • LPA{sub 1} and LPA{sub 3} are involved in the regulation of cellular functions during tumor

Towards trust in regulation. Moving to a public value regulation

Energy Technology Data Exchange (ETDEWEB)

Mitchell, Catherine; Woodman, Bridget [Energy Policy Group, University of Exeter Cornwall Campus, Treliever Road, Penryn, TR10 9EZ (United Kingdom)

2010-06-15

The UK Government has committed itself to reducing its carbon dioxide emissions. The challenge of successfully achieving a transition to a sustainable energy system, in the context of the UK's largely privately owned energy industry, rests on the ability of policy makers to encourage and enable the necessary changes or innovation at all levels of the energy system. This paper argues that the UK's current, dominant political paradigm or framework (the regulatory state paradigm (RSP)) and within it, the role of the economic regulator, Ofgem acts as a fundamental block to this challenge. The current economic regulatory system is based on trust in the market, or on predicted (albeit theoretical) known outcomes. To expand our regulatory system to one which can deliver a sustainable energy system requires innovation in a certain direction (as opposed to any innovation). That is the antithesis of the current process of regulation. Trust is required that Ofgem, the economic regulator, will develop rules and incentives which deliver an agreed sustainable energy goal, which is 'trusted' to be the 'right' goal. This requires Ofgem moving away from ex-ante regulation to a type of regulation where all costs, benefits and outcomes cannot be known beforehand and where they cannot necessarily be quantifiable. This has, very provisionally, been called Public Value Regulation (PVR). (author)

Towards trust in regulation-moving to a public value regulation

Energy Technology Data Exchange (ETDEWEB)

Mitchell, Catherine, E-mail: catherine.mitchell@exeter.ac.u [Energy Policy Group, University of Exeter Cornwall Campus, Treliever Road, Penryn, TR10 9EZ (United Kingdom); Woodman, Bridget [Energy Policy Group, University of Exeter Cornwall Campus, Treliever Road, Penryn, TR10 9EZ (United Kingdom)

2010-06-15

The UK Government has committed itself to reducing its carbon dioxide emissions. The challenge of successfully achieving a transition to a sustainable energy system, in the context of the UK's largely privately owned energy industry, rests on the ability of policy makers to encourage and enable the necessary changes or innovation at all levels of the energy system. This paper argues that the UK's current, dominant political paradigm or framework (the regulatory state paradigm (RSP)) and within it, the role of the economic regulator, Ofgem acts as a fundamental block to this challenge. The current economic regulatory system is based on trust in the market, or on predicted (albeit theoretical) known outcomes. To expand our regulatory system to one which can deliver a sustainable energy system requires innovation in a certain direction (as opposed to any innovation). That is the antithesis of the current process of regulation. Trust is required that Ofgem, the economic regulator, will develop rules and incentives which deliver an agreed sustainable energy goal, which is 'trusted' to be the 'right' goal. This requires Ofgem moving away from ex-ante regulation to a type of regulation where all costs, benefits and outcomes cannot be known beforehand and where they cannot necessarily be quantifiable. This has, very provisionally, been called Public Value Regulation (PVR).

Towards trust in regulation-moving to a public value regulation

International Nuclear Information System (INIS)

Mitchell, Catherine; Woodman, Bridget

2010-01-01

The UK Government has committed itself to reducing its carbon dioxide emissions. The challenge of successfully achieving a transition to a sustainable energy system, in the context of the UK's largely privately owned energy industry, rests on the ability of policy makers to encourage and enable the necessary changes or innovation at all levels of the energy system. This paper argues that the UK's current, dominant political paradigm or framework (the regulatory state paradigm (RSP)) and within it, the role of the economic regulator, Ofgem acts as a fundamental block to this challenge. The current economic regulatory system is based on trust in the market, or on predicted (albeit theoretical) known outcomes. To expand our regulatory system to one which can deliver a sustainable energy system requires innovation in a certain direction (as opposed to any innovation). That is the antithesis of the current process of regulation. Trust is required that Ofgem, the economic regulator, will develop rules and incentives which deliver an agreed sustainable energy goal, which is 'trusted' to be the 'right' goal. This requires Ofgem moving away from ex-ante regulation to a type of regulation where all costs, benefits and outcomes cannot be known beforehand and where they cannot necessarily be quantifiable. This has, very provisionally, been called Public Value Regulation (PVR).

Clinical research involving minors in international and serbian regulations.

Science.gov (United States)

Planojević, Nina; Zivojinović, Dragica

2013-07-01

Participation in clinical trials can be useful for the health of a person, in who it is conducted, but it does not have to be - it can even be harmful. Therefore, primary motive to accept such risk is humanity and human wish to contribute to the progress of medicine; this is expressed by personal consent. The consent, however, can be an expression of personal humanity, and for this, it is not logical that someone can give consent on behalf of someone else, as it is done by a legally authorized representative on behalf of a minor. Therefore, authors raise 3 questions: What are the reasons to consider representative's consent acceptable? How should a model of regulations look like in order to provide the most complete possible protection to a minor? Is actual regulation of minors' position within international and Serbian law, analyzed here by authors for their specific solutions, acceptable? Representative's consent is acceptable only for therapeutic research, because these can bring benefits to everyone's health, including a minor in which those are conducted - this is an acceptable (secondary) motive of participation in the research. Expression of humanity on other's behalf, typical for non-therapeutic research, is not acceptable; this makes ban of minors' participation in non-therapeutic research more appropriate regulation model. International regulations are not in accordance to results presented in the paper for allowing participation of minors both in therapeutic and non-therapeutic research. Serbian regulation is closer to the most acceptable regulation model.

Reconceptualizing Civil Regulation

DEFF Research Database (Denmark)

Galang, Roberto Martin; Castello, Itziar

2011-01-01

This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility litera....... Finally, we argue that, in Asia, governments act as a structuration mechanism which challenges the current understanding of CSR.......This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility...... and environmental standards; but also that local, small and medium companies play a key role in the development of Asian civil regulation. We call this second finding the “CSR importation trap”. Our findings are supported by evidence on the limitations in the interchangeable properties of business and governments...

The STAR protein QKI-7 recruits PAPD4 to regulate post-transcriptional polyadenylation of target mRNAs

OpenAIRE

Yamagishi, Ryota; Tsusaka, Takeshi; Mitsunaga, Hiroko; Maehata, Takaharu; Hoshino, Shin-ichi

2016-01-01

Emerging evidence has demonstrated that regulating the length of the poly(A) tail on an mRNA is an efficient means of controlling gene expression at the post-transcriptional level. In early development, transcription is silenced and gene expression is primarily regulated by cytoplasmic polyadenylation. In somatic cells, considerable progress has been made toward understanding the mechanisms of negative regulation by deadenylation. However, positive regulation through elongation of the poly(A)...

TGF-β Signaling Regulates Pancreatic β-Cell Proliferation through Control of Cell Cycle Regulator p27 Expression

International Nuclear Information System (INIS)

Suzuki, Tomoyuki; Dai, Ping; Hatakeyama, Tomoya; Harada, Yoshinori; Tanaka, Hideo; Yoshimura, Norio; Takamatsu, Tetsuro

2013-01-01

Proliferation of pancreatic β-cells is an important mechanism underlying β-cell mass adaptation to metabolic demands. Increasing β-cell mass by regeneration may ameliorate or correct both type 1 and type 2 diabetes, which both result from inadequate production of insulin by β-cells of the pancreatic islet. Transforming growth factor β (TGF-β) signaling is essential for fetal development and growth of pancreatic islets. In this study, we exposed HIT-T15, a clonal pancreatic β-cell line, to TGF-β signaling. We found that inhibition of TGF-β signaling promotes proliferation of the cells significantly, while TGF-β signaling stimulation inhibits proliferation of the cells remarkably. We confirmed that this proliferative regulation by TGF-β signaling is due to the changed expression of the cell cycle regulator p27. Furthermore, we demonstrated that there is no observed effect on transcriptional activity of p27 by TGF-β signaling. Our data show that TGF-β signaling mediates the cell-cycle progression of pancreatic β-cells by regulating the nuclear localization of CDK inhibitor, p27. Inhibition of TGF-β signaling reduces the nuclear accumulation of p27, and as a result this inhibition promotes proliferation of β-cells

Federal, state, and local regulation of radioactive-waste transportation: Progress toward a definition of regulatory authority

International Nuclear Information System (INIS)

Livingston-Behan, E.A.

1986-01-01

The supremacy clause, the commerce clause, and the equal-protection guarantees of the U.S. Constitution establish the basic framework for defining the authority of Federal, State, and local governments to regulate the transportation of radioactive waste. Court decisions and advisory rulings of the U.S. Department of Transportation (DOT) suggest that State and local regulation of the transportation of spent nuclear fuel and high-level radioactive waste is precluded under supremacy-clause principles to the extent that such regulation addresses nuclear safety or aspects of transportation that are already specifically regulated by the Federal government. Even where State and local requirements are found to be valid under the supremacy clause, they must still satisfy constitutional requirements under the commerce and equal-protection clauses. Despite stringent standards of review, State and local transportation requirements have been upheld where directly related to the traditional exercise of police powers in the area of transportation. Legitimate State and local police-power activities identified to date by the DOT and the courts include inspection and enforcement, immediate accident reporting, local regulation of traffic, and certain time-of-day curfews. The extent to which State and local permitting requirements and license fees may be determined valid by the DOT and the courts remains unclear. Continued clarification by the DOT and the courts as to the validity of permits and fees will serve to further define the appropriate balance for Federal, State, and local regulation of radioactive-waste transportation

NORM regulations

Energy Technology Data Exchange (ETDEWEB)

Gray, P. [ed.

1997-02-01

The author reviews the question of regulation for naturally occuring radioactive material (NORM), and the factors that have made this a more prominent concern today. Past practices have been very relaxed, and have often involved very poor records, the involvment of contractors, and the disposition of contaminated equipment back into commercial service. The rationale behind the establishment of regulations is to provide worker protection, to exempt low risk materials, to aid in scrap recycling, to provide direction for remediation and to examine disposal options. The author reviews existing regulations at federal and state levels, impending legislation, and touches on the issue of site remediation and potential liabilities affecting the release of sites contaminated by NORM.

UK medicines regulation: responding to current challenges.

Science.gov (United States)

Richards, Natalie; Hudson, Ian

2016-12-01

The medicines regulatory environment is evolving rapidly in response to the changing environment. Advances in science and technology have led to a vast field of increasingly complicated pharmaceutical and medical device products; increasing globalization of the pharmaceutical industry, advances in digital technology and the internet, changing patient populations, and shifts in society also affect the regulatory environment. In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicines, medical devices and blood products to protect and improve public health, and supports innovation through scientific research and development. It works closely with other bodies in a single medicines network across Europe and takes forward UK health priorities. This paper discusses the range of initiatives in the UK and across Europe to support innovation in medicines regulation. The MHRA leads a number of initiatives, such as the Innovation Office, which helps innovators to navigate the regulatory processes to progress their products or technologies; and simplification of the Clinical Trials Regulations and the Early Access to Medicines Scheme, to bring innovative medicines to patients faster. The Accelerated Access Review will identify reforms to accelerate access for National Health Service patients to innovative medicines and medical technologies. PRIME and Adaptive Pathways initiatives are joint endeavours within the European regulatory community. The MHRA runs spontaneous reporting schemes and works with INTERPOL to tackle counterfeiting and substandard products sold via the internet. The role of the regulator is changing rapidly, with new risk-proportionate, flexible approaches being introduced. International collaboration is a key element of the work of regulators, and is set to expand. © 2016 The British Pharmacological Society.

Epigenetic regulation of neural stem cell property from embryo to adult

Directory of Open Access Journals (Sweden)

Naoya Murao

2016-03-01

Full Text Available Neural stem cells (NSCs have the ability to self-renew and give rise to neurons and glial cells (astrocytes and oligodendrocytes in the mammalian central nervous system. This multipotency is acquired by NSCs during development and is maintained throughout life. Proliferation, fate specification, and maturation of NSCs are regulated by both cell intrinsic and extrinsic factors. Epigenetic modification is a representative intrinsic factor, being involved in many biological aspects of central nervous system development and adult neurogenesis through the regulation of NSC dynamics. In this review, we summarize recent progress in the epigenetic regulation of NSC behavior in the embryonic and adult brain, with particular reference to DNA methylation, histone modification, and noncoding RNAs.

MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes

OpenAIRE

He, Jie; Wu, Jiangbin; Xu, Naihan; Xie, Weidong; Li, Mengnan; Li, Jianna; Jiang, Yuyang; Yang, Burton B.; Zhang, Yaou

2012-01-01

MiR-210 is up-regulated in multiple cancer types but its function is disputable and further investigation is necessary. Using a bioinformatics approach, we identified the putative target genes of miR-210 in hypoxia-induced CNE cells from genome-wide scale. Two functional gene groups related to cell cycle and RNA processing were recognized as the major targets of miR-210. Here, we investigated the molecular mechanism and biological consequence of miR-210 in cell cycle regulation, particularly ...

Risk-informed regulation

International Nuclear Information System (INIS)

Hoffman, D.R.

2003-01-01

In assessing safety for nuclear facilities, regulators have traditionally used a deterministic approach. New techniques for assessing nuclear or radiological risks make it possible for regulators to incorporate risk insights into their regulations. By 'risk-informing' the regulatory processes, independent bodies tasked with protecting the health and safety of the public can focus on those design and operational issues most important to safety. Such an approach is a move away from prescriptive regulations that were based on conservative engineering judgments toward regulations focused on issues that contribute significantly to safety. Despite the availability of probabilistic risk assessment (PRA) tools, organisations often struggle with how to best use this capability. Most international regulations are still based largely on deterministic analyses that were developed without the benefit of quantitative or measurable estimates of risk. PRA considers issues of risk in a more comprehensive manner by examining a wider spectrum of initiating events and their frequency, and considers the likelihood of events in a rigorous and comprehensive manner. In some countries, nuclear regulators are actively moving toward increasing the use of risk insights in a variety of strategic arenas, including risk-informed technical specifications (operating limits and conditions), in-service inspection and testing, programs, and assessment and enforcement actions. A risk-informed approach enhances the traditional deterministic approach by explicitly considering a broader range of safety challenges, focusing resources on the basis of risk significance, considering a broader range of counter measures to mitigate challenges, and explicitly identifying and quantifying uncertainties in analyses. (author)

Positive Emotion Regulation and Psychopathology: A Transdiagnostic Cultural Neuroscience Approach

Science.gov (United States)

Hechtman, Lisa A.; Raila, Hannah; Chiao, Joan Y.; Gruber, June

2013-01-01

There is burgeoning interest in the study of positive emotion regulation and psychopathology. Given the significant public health costs and the tremendous variance in national prevalence rates associated with many disorders of positive emotion, it is critical to reach an understanding of how cultural factors, along with biological factors, mutually influence positive emotion regulation. Progress in this domain has been relatively unexplored, however, underscoring the need for an integrative review and empirical roadmap for investigating the cultural neuroscientific contributions to positive emotion disturbance for both affective and clinical science domains. The present paper thus provides a multidisciplinary, cultural neuroscience approach to better understand positive emotion regulation and psychopathology. We conclude with a future roadmap for researchers aimed at harnessing positive emotion and alleviating the burden of mental illness cross-culturally. PMID:24812583

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.

The Regulation of Skeletal Muscle Protein Turnover during the Progression of Cancer Cachexia in the ApcMin/+ Mouse

Science.gov (United States)

White, James P.; Baynes, John W.; Welle, Stephen L.; Kostek, Matthew C.; Matesic, Lydia E.; Sato, Shuichi; Carson, James A.

2011-01-01

Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The ApcMin/+ 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 ApcMin/+ mouse is not known. Cachexia progression was studied in ApcMin/+ 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. PMID:21949739

Expression of the central growth regulator BIG BROTHER is regulated by multiple cis-elements

Directory of Open Access Journals (Sweden)

Breuninger Holger

2012-03-01

Full Text Available Abstract Background Much of the organismal variation we observe in nature is due to differences in organ size. The observation that even closely related species can show large, stably inherited differences in organ size indicates a strong genetic component to the control of organ size. Despite recent progress in identifying factors controlling organ growth in plants, our overall understanding of this process remains limited, partly because the individual factors have not yet been connected into larger regulatory pathways or networks. To begin addressing this aim, we have studied the upstream regulation of expression of BIG BROTHER (BB, a central growth-control gene in Arabidopsis thaliana that prevents overgrowth of organs. Final organ size and BB expression levels are tightly correlated, implying the need for precise control of its expression. BB expression mirrors proliferative activity, yet the gene functions to limit proliferation, suggesting that it acts in an incoherent feedforward loop downstream of growth activators to prevent over-proliferation. Results To investigate the upstream regulation of BB we combined a promoter deletion analysis with a phylogenetic footprinting approach. We were able to narrow down important, highly conserved, cis-regulatory elements within the BB promoter. Promoter sequences of other Brassicaceae species were able to partially complement the A. thaliana bb-1 mutant, suggesting that at least within the Brassicaceae family the regulatory pathways are conserved. Conclusions This work underlines the complexity involved in precise quantitative control of gene expression and lays the foundation for identifying important upstream regulators that determine BB expression levels and thus final organ size.

The four and a half LIM domains 2 (FHL2) regulates ovarian granulosa cell tumor progression via controlling AKT1 transcription

OpenAIRE

Hua, G; He, C; Lv, X; Fan, L; Wang, C; Remmenga, S W; Rodabaugh, K J; Yang, L; Lele, S M; Yang, P; Karpf, A R; Davis, J S; Wang, C

2016-01-01

The four and a half LIM domains 2 (FHL2) has been shown to play important roles in the regulation of cell proliferation, survival, adhesion, motility and signal transduction in a cell type and tissue-dependent manner. However, the function of FHL2 in ovarian physiology and pathology is unclear. The aim of this study was to determine the role and functional mechanism of FHL2 in the progression of ovarian granulosa cell tumors (GCTs). Immunohistochemical analysis indicated that FHL2 was overexp...

Integrins Regulate Apical Constriction via Microtubule Stabilization in the Drosophila Eye Disc Epithelium

Directory of Open Access Journals (Sweden)

Vilaiwan M. Fernandes

2014-12-01

Full Text Available During morphogenesis, extracellular signals trigger actomyosin contractility in subpopulations of cells to coordinate changes in cell shape. To illuminate the link between signaling-mediated tissue patterning and cytoskeletal remodeling, we study the progression of the morphogenetic furrow (MF, the wave of apical constriction that traverses the Drosophila eye imaginal disc preceding photoreceptor neurogenesis. Apical constriction depends on actomyosin contractility downstream of the Hedgehog (Hh and bone morphogenetic protein (BMP pathways. We identify a role for integrin adhesion receptors in MF progression. We show that Hh and BMP regulate integrin expression, the loss of which disrupts apical constriction and slows furrow progression; conversely, elevated integrins accelerate furrow progression. We present evidence that integrins regulate MF progression by promoting microtubule stabilization, since reducing microtubule stability rescues integrin-mediated furrow acceleration. Thus, integrins act as a genetic link between tissue-level signaling events and morphological change at the cellular level, leading to morphogenesis and neurogenesis in the eye.

Culture and emotion regulation.

Science.gov (United States)

Ford, Brett Q; Mauss, Iris B

2015-06-01

While anthropological research has long emphasized cultural differences in whether emotions are viewed as beneficial versus harmful, psychological science has only recently begun to systematically examine those differences and their implications for emotion regulation and well-being. Underscoring the pervasive role of culture in people's emotions, we summarize research that has examined links between culture, emotion regulation, and well-being. Specifically, we focus on two questions. First, how does culture lead individuals to regulate their emotions? And second, how does culture modulate the link between emotion regulation and well-being? We finish by suggesting directions for future research to advance the study of culture and emotion regulation.

Radiation Control Regulation 1993

International Nuclear Information System (INIS)

1993-01-01

This Regulation (No. 434-1993) was made in pursuance of the Radiation Control Act 1990 and replaces the Active Substances Regulations 1959 repealed by the Act. It entered into force on 1 September 1993. The Regulation specifies that the technical radiation protection definitions have the same meaning as in the 1990 recommendations. The Regulation provides for the licensing of persons to use radioactive substances and radiation apparatus. It prescribes activities which may only be carried out by an accredited radiation expert and regulates the use of radiation apparatus and radioactive substances as well as the disposal and transport of radiation apparatus and radioactive substances. (NEA)

Load regulating expansion fixture

International Nuclear Information System (INIS)

Wagner, L.M.; Strum, M.J.

1998-01-01

A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils is disclosed. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located there between. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components. 1 fig

Is self-regulation possible

International Nuclear Information System (INIS)

Barkenbus, J.N.

1983-01-01

The Nuclear Regulatory Commission's increasingly prescriptive regulation of the nuclear industry can have deleterious effects, perhaps the most serious being the shift in responsibility for safety from the utility to the NRC. Several factors account for this type of regulation including the nature and structure of the nuclear industry, public opinion and bureaucratic incentives, and the nature of the technology itself. The opportunities to create heightened industry self-regulation (performance-based regulation) deserve further examination. The key to self-regulation is to structure incentives so that it is clearly within the nuclear utilities' interests to build and operate nuclear power facilities in the safest manner possible. 27 references

Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications.

Science.gov (United States)

Fasano, Alessio

2012-10-01

One of the most important and overlooked functions of the gastrointestinal tract is to provide a dynamic barrier to tightly controlled antigen trafficking through both the transcellular and paracellular pathways. Intercellular tight junctions (TJ) are the key structures regulating paracellular trafficking of macromolecules. Although steady progress has been made in understanding TJ ultrastructure, relatively little is known about their pathophysiological regulation. Our discovery of zonulin, the only known physiological modulator of intercellular TJ described so far, increased understanding of the intricate mechanisms that regulate gut permeability and led us to appreciate that its up-regulation in genetically susceptible individuals may lead to immune-mediated diseases. This information has translational implications, because the zonulin pathway is currently exploited to develop both diagnostic and therapeutic applications pertinent to a variety of immune-mediated diseases. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

The Development of Innovation Systems as an Object with the State Regulation

Directory of Open Access Journals (Sweden)

Melnyk Alexander G.

2017-09-01

Full Text Available The article examines the processes of structuring the environment for the development of innovation systems in terms of the formation of a State regulated object. A methodological approach to definition of the State regulation at the primary, secondary and tertiary levels of structuring the environment of innovation systems has been suggested, based on the premise of the objective nature of the integration of social environment and market mechanisms into the structure of an object with the State regulation for the development of innovation systems. The definition of innovative systems as an object with the State regulation in terms of structural-organizational and functional areas of their expansion has been presented. A model for the progressive extension of the State regulated object by means of the development of innovation systems at the primary, secondary and tertiary levels of the structuring of environment in the process of formation of the institutional and technological structures of innovation systems has been proposed.

Regulating hedge funds.

OpenAIRE

Daníelsson, J.; Zigrand, JP.

2007-01-01

Due to the ever-increasing amounts under management and their unregulated and opaque nature, hedge funds have emerged as a key concern for policymakers. While until now, hedge funds have been left essentially unregulated, we are seeing increasing calls for regulation for both microprudential and macroprudential reasons. In our view, most calls for the regulation of hedge funds are based on a misperception of the effectiveness of financial regulations, perhaps coupled with a lack of understand...

Self-Regulation Skills of Pre-Service Music Teachers

Science.gov (United States)

Akyüzlüer, Fatima

2014-01-01

The purpose of this study is to identify how a four-semester music teacher education programme on self-regulation changes as they progress through the programme. The participants of the study included a total of 101 music teachers in four different semesters of their teacher preparation programme. The instrument used in this study is the Motivated…

A SWI/SNF Chromatin Remodelling Protein Controls Cytokinin Production through the Regulation of Chromatin Architecture

KAUST Repository

Jégu, Teddy

2015-10-12

Chromatin architecture determines transcriptional accessibility to DNA and consequently gene expression levels in response to developmental and environmental stimuli. Recently, chromatin remodelers such as SWI/SNF complexes have been recognized as key regulators of chromatin architecture. To gain insight into the function of these complexes during root development, we have analyzed Arabidopsis knock-down lines for one sub-unit of SWI/SNF complexes: BAF60. Here, we show that BAF60 is a positive regulator of root development and cell cycle progression in the root meristem via its ability to down-regulate cytokinin production. By opposing both the deposition of active histone marks and the formation of a chromatin regulatory loop, BAF60 negatively regulates two crucial target genes for cytokinin biosynthesis (IPT3 and IPT7) and one cell cycle inhibitor (KRP7). Our results demonstrate that SWI/SNF complexes containing BAF60 are key factors governing the equilibrium between formation and dissociation of a chromatin loop controlling phytohormone production and cell cycle progression.

A SWI/SNF Chromatin Remodelling Protein Controls Cytokinin Production through the Regulation of Chromatin Architecture

KAUST Repository

Jé gu, Teddy; Domenichini, Sé verine; Blein, Thomas; Ariel, Federico; Christ, Auré lie; Kim, SoonKap; Crespi, Martin; Boutet-Mercey, Sté phanie; Mouille, Gré gory; Bourge, Mickaë l; Hirt, Heribert; Bergounioux, Catherine; Raynaud, Cé cile; Benhamed, Moussa

2015-01-01

Chromatin architecture determines transcriptional accessibility to DNA and consequently gene expression levels in response to developmental and environmental stimuli. Recently, chromatin remodelers such as SWI/SNF complexes have been recognized as key regulators of chromatin architecture. To gain insight into the function of these complexes during root development, we have analyzed Arabidopsis knock-down lines for one sub-unit of SWI/SNF complexes: BAF60. Here, we show that BAF60 is a positive regulator of root development and cell cycle progression in the root meristem via its ability to down-regulate cytokinin production. By opposing both the deposition of active histone marks and the formation of a chromatin regulatory loop, BAF60 negatively regulates two crucial target genes for cytokinin biosynthesis (IPT3 and IPT7) and one cell cycle inhibitor (KRP7). Our results demonstrate that SWI/SNF complexes containing BAF60 are key factors governing the equilibrium between formation and dissociation of a chromatin loop controlling phytohormone production and cell cycle progression.

Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention

International Nuclear Information System (INIS)

Chang, Aeson; Kim-Fuchs, Corina; Le, Caroline P.; Hollande, Frédéric; Sloan, Erica K.

2015-01-01

The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer

Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention

Energy Technology Data Exchange (ETDEWEB)

Chang, Aeson [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Kim-Fuchs, Corina [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Visceral Surgery and Medicine, University Hospital Bern, Bern 3010 (Switzerland); Le, Caroline P. [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Hollande, Frédéric [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Pathology, University of Melbourne, Parkville 3010 (Australia); Sloan, Erica K., E-mail: erica.sloan@monash.edu [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Cousins Center for PNI, UCLA Semel Institute, Jonsson Comprehensive Cancer Center, and UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095 (United States); Peter MacCallum Cancer Centre, Division of Cancer Surgery, East Melbourne, Victoria 3002 (Australia)

2015-07-17

The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer.

Cell cycle regulation of hematopoietic stem or progenitor cells.

Science.gov (United States)

Hao, Sha; Chen, Chen; Cheng, Tao

2016-05-01

The highly regulated process of blood production is achieved through the hierarchical organization of hematopoietic stem cell (HSC) subsets and their progenies, which differ in self-renewal and differentiation potential. Genetic studies in mice have demonstrated that cell cycle is tightly controlled by the complex interplay between extrinsic cues and intrinsic regulatory pathways involved in HSC self-renewal and differentiation. Deregulation of these cellular programs may transform HSCs or hematopoietic progenitor cells (HPCs) into disease-initiating stem cells, and can result in hematopoietic malignancies such as leukemia. While previous studies have shown roles for some cell cycle regulators and related signaling pathways in HSCs and HPCs, a more complete picture regarding the molecular mechanisms underlying cell cycle regulation in HSCs or HPCs is lacking. Based on accumulated studies in this field, the present review introduces the basic components of the cell cycle machinery and discusses their major cellular networks that regulate the dormancy and cell cycle progression of HSCs. Knowledge on this topic would help researchers and clinicians to better understand the pathogenesis of relevant blood disorders and to develop new strategies for therapeutic manipulation of HSCs.

Fibrocytes: A Novel Stromal Cells to Regulate Resistance to Anti-Angiogenic Therapy and Cancer Progression.

Science.gov (United States)

Goto, Hisatsugu; Nishioka, Yasuhiko

2017-12-29

An adequate blood supply is essential for cancer cells to survive and grow; thus, the concept of inhibiting tumor angiogenesis has been applied to cancer therapy, and several drugs are already in clinical use. It has been shown that treatment with those anti-angiogenic drugs improved the response rate and prolonged the survival of patients with various types of cancer; however, it is also true that the effect was mostly limited. Currently, the disappointing clinical results are explained by the existence of intrinsic or acquired resistance to the therapy mediated by both tumor cells and stromal cells. This article reviews the mechanisms of resistance mediated by stromal cells such as endothelial cells, pericytes, fibroblasts and myeloid cells, with an emphasis on fibrocytes, which were recently identified as the cell type responsible for regulating acquired resistance to anti-angiogenic therapy. In addition, the other emerging role of fibrocytes as mediator-producing cells in tumor progression is discussed.

Podoplanin promotes progression of malignant pleural mesothelioma by regulating motility and focus formation.

Science.gov (United States)

Takeuchi, Shinji; Fukuda, Koji; Yamada, Tadaaki; Arai, Sachiko; Takagi, Satoshi; Ishii, Genichiro; Ochiai, Atsushi; Iwakiri, Shotaro; Itoi, Kazumi; Uehara, Hisanori; Nishihara, Hiroshi; Fujita, Naoya; Yano, Seiji

2017-04-01

Malignant pleural mesothelioma (MPM) is characterized by dissemination and aggressive growth in the thoracic cavity. Podoplanin (PDPN) is an established diagnostic marker for MPM, but the function of PDPN in MPM is not fully understood. The purpose of this study was to determine the pathogenetic function of PDPN in MPM. Forty-seven of 52 tumors (90%) from Japanese patients with MPM and 3/6 (50%) MPM cell lines tested positive for PDPN. Knocking down PDPN in PDPN-high expressing MPM cells resulted in decreased cell motility. In contrast, overexpression of PDPN in PDPN-low expressing MPM cells enhanced cell motility. PDPN stimulated motility was mediated by activation of the RhoA/ROCK pathway. Moreover, knocking down PDPN with short hairpin (sh) RNA in PDPN-high expressing MPM cells resulted in decreased development of a thoracic tumor in mice with severe combined immune deficiency (SCID). In sharp contrast, transfection of PDPN in PDPN-low expressing MPM cells resulted in an increase in the number of Ki-67-positive proliferating tumor cells and it promoted progression of a thoracic tumor in SCID mice. Interestingly, PDPN promoted focus formation in vitro, and a low level of E-cadherin expression and YAP1 activation was observed in PDPN-high MPM tumors. These findings indicate that PDPN is a diagnostic marker as well as a pathogenetic regulator that promotes MPM progression by increasing cell motility and inducing focus formation. Therefore, PDPN might be a pathogenetic determinant of MPM dissemination and aggressive growth and may thus be an ideal therapeutic target. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

TOWARD MORE EFFECTIVE REGULATION

Energy Technology Data Exchange (ETDEWEB)

J. GRAF

2000-06-01

This paper proposes a model relationship between the operator engaged in a hazardous activity, the regulator of that activity, and the general public. The roles and responsibilities of each entity are described in a way that allows effective communication flow. The role of the regulator is developed using the steam boiler as an example of a hazard subject to regulation; however, the model applies to any regulated activity. In this model the safety analyst has the extremely important role of communicating sometimes difficult technical information to the regulator in a way that the regulator can provide credible assurance to the general public as to the adequacy of the control of the hazardous activity. The conclusion asserts that acceptance of the model, understanding of the roles and responsibilities and definition of who communicates what information to whom will mitigate frustration on the part of each of the three entities.

Ageing in relation to skeletal muscle dysfunction: redox homoeostasis to regulation of gene expression.

Science.gov (United States)

Goljanek-Whysall, Katarzyna; Iwanejko, Lesley A; Vasilaki, Aphrodite; Pekovic-Vaughan, Vanja; McDonagh, Brian

2016-08-01

Ageing is associated with a progressive loss of skeletal muscle mass, quality and function-sarcopenia, associated with reduced independence and quality of life in older generations. A better understanding of the mechanisms, both genetic and epigenetic, underlying this process would help develop therapeutic interventions to prevent, slow down or reverse muscle wasting associated with ageing. Currently, exercise is the only known effective intervention to delay the progression of sarcopenia. The cellular responses that occur in muscle fibres following exercise provide valuable clues to the molecular mechanisms regulating muscle homoeostasis and potentially the progression of sarcopenia. Redox signalling, as a result of endogenous generation of ROS/RNS in response to muscle contractions, has been identified as a crucial regulator for the adaptive responses to exercise, highlighting the redox environment as a potentially core therapeutic approach to maintain muscle homoeostasis during ageing. Further novel and attractive candidates include the manipulation of microRNA expression. MicroRNAs are potent gene regulators involved in the control of healthy and disease-associated biological processes and their therapeutic potential has been researched in the context of various disorders, including ageing-associated muscle wasting. Finally, we discuss the impact of the circadian clock on the regulation of gene expression in skeletal muscle and whether disruption of the peripheral muscle clock affects sarcopenia and altered responses to exercise. Interventions that include modifying altered redox signalling with age and incorporating genetic mechanisms such as circadian- and microRNA-based gene regulation, may offer potential effective treatments against age-associated sarcopenia.

UK: the current state of regulation of complementary and alternative medicine.

Science.gov (United States)

Walker, L A; Budd, S

2002-03-01

There is no legislation that restricts the practice of CAM in the UK apart from the practice of chiropractic and osteopathy and limits on advertising the treatments of certain conditions such as cancer and tuberculosis. The UK government has increasingly recognised the need for comprehensive regulation of CAM, though it abandoned its original plan for a single overarching regulatory body. Initiatives to examine and hasten the process of regulation have included setting up a central, well-recognised charitable body to facilitate progress for individual professions, and an authoritative survey of the existing professional organisations. One pathway open to individual professions is statutory self-regulation, which requires a single governing body, a systematic corpus of knowledge, recognised training courses and demonstrated efficacy. The other pathway is voluntary self-regulation. Chiropractic and osteopathy have adopted statutory self-regulation, though this has proved expensive for individual members of these professions. A recent House of Lords report on CAM has recommended that the herbal medicine and acupuncture professions should also develop a system of statutory regulation. Other professions, such as aromatherapy, are in the process of establishing single professional bodies as a first step towards self-regulation. Among the issues that remain to be resolved is the relationship between the CAM professions and statutory registered practitioners who also practise CAM.

Self-regulation in securities markets

OpenAIRE

Carson, John

2011-01-01

This paper canvasses the trends in self-regulation and the role of self-regulation in securities markets in different parts of the world. The paper also describes the conditions in which self-regulation might be an effective element of securities markets regulation, particularly in emerging markets. Use of self-regulation and self-regulatory organizations is often recommended in emerging m...

VanT, a central regulator of quorum sensing signalling in Vibrio anguillarum

OpenAIRE

Croxatto, Antony

2006-01-01

Many bacteria produce signal molecules that serve in a cell-to-cell communication system termed quorum sensing. This signalling system allows a bacterial population to co-ordinately regulate functions according to their cell number in a defined environment. As bacterial growth progresses towards the stationary phase, signalling molecules accumulate in the growth medium and, above a certain threshold level, regulate the expression of genes involved in diverse functions. Most of the functions m...

Leucine zipper, down regulated in cancer-1 gene expression in prostate cancer

OpenAIRE

Salemi, Michele; Barone, Nunziata; La Vignera, Sandro; Condorelli, Rosita A.; Recupero, Domenico; Galia, Antonio; Fraggetta, Filippo; Aiello, Anna Maria; Pepe, Pietro; Castiglione, Roberto; Vicari, Enzo; Calogero, Aldo E.

2016-01-01

Numerous genetic alterations have been implicated in the development of prostate cancer (PCa). DNA and protein microarrays have enabled the identification of genes associated with apoptosis, which is important in PCa development. Despite the molecular mechanisms are not entirely understood, inhibition of apoptosis is a critical pathophysiological factor that contributes to the onset and progression of PCa. Leucine zipper, down-regulated in cancer 1 (LDOC-1) is a known regulator of the nuclear...

Regulating chemicals: law, science, and the unbearable burdens of regulation.

Science.gov (United States)

Silbergeld, Ellen K; Mandrioli, Daniele; Cranor, Carl F

2015-03-18

The challenges of regulating industrial chemicals remain unresolved in the United States. The Toxic Substances Control Act (TSCA) of 1976 was the first legislation to extend coverage to the regulation of industrial chemicals, both existing and newly registered. However, decisions related to both law and science that were made in passing this law inevitably rendered it ineffectual. Attempts to fix these shortcomings have not been successful. In light of the European Union's passage of innovative principles and requirements for chemical regulation, it is no longer possible to deny the opportunity and need for reform in US law and practice.

Panel presentation: Should some type of incentive regulation replace traditional methods for regulating LDCs?

International Nuclear Information System (INIS)

Costello, K.W.

1992-01-01

State regulators should consider new approaches to regulating LDCs. They should seriously look at different incentive systems, even if only as an experiment, to address the major inefficiencies they see plaguing LDCs. Regulators have become more receptive in recent years to applying different incentive systems for historically heavily regulated industries such as the telecommunications and electric industries. In view of prevailing conditions in the natural gas industry, there is no good reason why regulators should not be as receptive to applying incentive systems for LDCs. For gas services offered in competitive markets, regulators should ask themselves whether regulation is necessary any longer. For services still requiring regulation, regulators should explore whether changes in traditional regulation are needed. While some PUCs have undertaken new regulatory practices, the question before them today is whether they should do more; whether, for example, states should accelerate their efforts toward adopting more flexible pricing and other incentive-based regulations or toward considering deregulating selected services. PUCs have different options. They can choose from among a large number of incentive systems. Their choices should hinge upon what they view as major sources of inefficiencies. For example, if uneconomical bypass is perceived as a problem then different price rules might constitute the cornerstone of an incentive-based policy. On the other hand, if excessive purchased-gas costs seem to be a major problem, a PUC may want to consider abolishing the PGA or modifying it in a form that would eliminate the cost-plus component

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

International Nuclear Information System (INIS)

Dziendzikowska, K.; Krawczyńska, A.; Oczkowski, M.; Królikowski, T.; Brzóska, K.; Lankoff, A.; Dziendzikowski, M.; Stępkowski, T.; Kruszewski, M.

2016-01-01

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 (20 nm AgNPs (groups Ag I and Ag II) and 200 nm 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 24 h, 7 days and 28 days 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 28 days 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. - Highlights: • Assessment of the toxic effects of AgNPs/AgSPs on the regulation of male reproductive function • AgNP −/AgSP-induced alterations of sex steroid status in male Wistar rats. �

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

Energy Technology Data Exchange (ETDEWEB)

Dziendzikowska, K., E-mail: k.dziendzikowska@gmail.com [Division of Nutrition Physiology, Department of Dietetics, Faculty of Human Nutrition and Consumer Science, Warsaw University of Life Sciences – SGGW, Nowoursynowska 159C, 02-776 Warsaw (Poland); Krawczyńska, A. [Laboratory of Molecular Biology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna (Poland); Oczkowski, M.; Królikowski, T. [Division of Nutrition Physiology, Department of Dietetics, Faculty of Human Nutrition and Consumer Science, Warsaw University of Life Sciences – SGGW, Nowoursynowska 159C, 02-776 Warsaw (Poland); Brzóska, K. [Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland); Lankoff, A. [Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland); Department of Radiobiology and Immunology, Institute of Biology, Jan Kochanowski University, Świetokrzyska 15, 25-406 Kielce (Poland); Dziendzikowski, M. [Airworthiness Division, Air Force Institute of Technology, Ks. Boleslawa 6, 01-494 Warsaw (Poland); Stępkowski, T. [Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland); Kruszewski, M. [Department of Medical Biology and Translational Research, Faculty of Medicine, University of Information Technology and Management, Sucharskiego 2, 35-225 Rzeszów (Poland); Department of Molecular Biology and Translational Research, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin (Poland); and others

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 (20 nm AgNPs (groups Ag I and Ag II) and 200 nm 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 24 h, 7 days and 28 days 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 28 days 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. - Highlights: • Assessment of the toxic effects of AgNPs/AgSPs on the regulation of male reproductive function • AgNP −/AgSP-induced alterations of sex steroid status in male Wistar rats. �

Selective Androgen Receptor Down-Regulators (SARDs): A New Prostate Cancer Therapy

National Research Council Canada - National Science Library

Bhattacharyya, Rumi S

2007-01-01

The androgen receptor (AR) plays a key role in the development and progression of prostate cancer Targeting the AR for down-regulation would be a useful strategy for treating prostate cancer, especially hormone-refractory...

Optimal Regulation of Lumpy Investments

NARCIS (Netherlands)

Zwart, G.; Broer, D.P.

2012-01-01

When a monopolist has discretion over the timing of infrastructure investments, regulation of post-investment prices interferes with incentivizing socially optimal investment timing. In a model of regulated lumpy investment under uncertainty, we study regulation when the regulator can condition

Health sector regulation in Thailand: recent progress and the future agenda.

Science.gov (United States)

Teerawattananon, Yot; Tangcharoensathien, Viroj; Tantivess, Sripen; Mills, Anne

2003-03-01

This paper reviews the current system of regulation and assesses its effectiveness in the health-care system of Thailand. In order to achieve this, extensive documentary reviews were performed and supplemented by in-depth interviews. We found the existing regulatory framework to be fairly comprehensive with rules and roles firmly established. Regulations cover almost all relevant private and public organisations including individuals. However, the incomplete performance of regulatory functions was detected resulting in problems of overburdened staff and delays in performance of functions. Our recommendations propose the promotion of professional ethics and continuing education, an effort to narrow the gap between expectation and reality through public education, and the empowering of consumer organisations. The increasing popularity of medical lawsuits and professional insurance, which in part reflects the imperfect administration of the system, highlights the need for careful consideration of how best to handle the increase in complaints. The mapping of the regulatory system in this paper, together with the discussion of how to cope with the expansion of medicine as a business and with greater consumerism, will be of interest to other middle income countries that seek to reform and strengthen their regulatory system.

The development of regulations

International Nuclear Information System (INIS)

Slokan Dusic, D.; Levstek, M.F.; Stritar, A.

2003-01-01

In October 2002, The Act on Protection Against Ionising Radiation and Nuclear Safety which regulates all aspects of protection against ionising radiation and nuclear safety entered into force in Slovenia. The Slovenian government and its responsible ministries shall issue several governmental and ministerial regulations to support the above - mentioned act. The Slovenian Nuclear Safety Administration (SNSA) which acts within the Ministry of the Environment, Spatial Planing and Energy takes an active part in drafting the regulations which are defined in the act. Due to a very comprehensive and pretentious task, that is to be completed in a relatively short period of time, taking into consideration the involvement of stakeholders and all competent ministries, the SNSA within the Quality Management System developed a special procedure that insures the systematic approach to the preparation of regulations. The article will briefly represent the process that: defines the preparation, development, harmonisation, review, approval and issue of regulations and uniforms the format of developed regulations. (author)

Taurine up-regulated gene 1 functions as a master regulator to coordinate glycolysis and metastasis in hepatocellular carcinoma.

Science.gov (United States)

Lin, Yang-Hsiang; Wu, Meng-Han; Huang, Ya-Hui; Yeh, Chau-Ting; Cheng, Mei-Ling; Chi, Hsiang-Cheng; Tsai, Chung-Ying; Chung, I-Hsiao; Chen, Ching-Ying; Lin, Kwang-Huei

2018-01-01

Cancer cells display altered glucose metabolism characterized by a preference for aerobic glycolysis. The aerobic glycolytic phenotype of hepatocellular carcinoma (HCC) is often correlated with tumor progression and poorer clinical outcomes. However, the issue of whether glycolytic metabolism influences metastasis in HCC remains unclear. In the current study, we showed that knockdown of taurine up-regulated gene 1 (TUG1) induces marked inhibition of cell migration, invasion, and glycolysis through suppression of microRNA (miR)-455-3p. MiR-455-3p, which is transcriptionally repressed by p21, directly targets the 3' untranslated region of adenosine monophosphate-activated protein kinase subunit beta 2 (AMPKβ2). The TUG1/miR-455-3p/AMPKβ2 axis regulates cell growth, metastasis, and glycolysis through regulation of hexokinase 2 (HK2). TUG1 is clearly associated with HK2 overexpression and unfavorable prognosis in HCC patients. Our data collectively highlight that novel regulatory associations among TUG1, miR-455-3p, AMPKβ2, and HK2 are an important determinant of glycolytic metabolism and metastasis in HCC cells and support the potential utility of targeting TUG1/HK2 as a therapeutic strategy for HCC. (Hepatology 2018;67:188-203). © 2017 by the American Association for the Study of Liver Diseases.

Molecular regulation and genetic improvement of seed oil content in Brassica napus L.

Directory of Open Access Journals (Sweden)

Wei HUA,Jing LIU,Hanzhong WANG

2016-09-01

Full Text Available As an important oil crop and a potential bioenergy crop, Brassica napus L. is becoming a model plant for basic research on seed lipid biosynthesis as well as seed oil content, which has always been the key breeding objective. In this review, we present current progress in understanding of the regulation of oil content in B. napus, including genetics, biosynthesis pathway, transcriptional regulation, maternal effects and QTL analysis. Furthermore, the history of breeding for high oil content in B. napus is summarized and the progress in breeding ultra-high oil content lines is described. Finally, prospects for breeding high oil content B. napus cultivars are outlined.

Personality and Emotion Regulation Strategies

Directory of Open Access Journals (Sweden)

Esti Hayu Purnamaningsih

2017-01-01

Full Text Available The emotions has many important functions in our life such as in relation of interpersonal communication, and health. In interpersonal communicative function aimed to signal to other information about internal state. Emotions manifests in specific cognitive, behavioural, and physiological reactions, thus closely related to health. There is wide variety of ways for individuals to regulate their emotion. In this regard, there are two kinds of emotion regulation strategy; first Antecedent-focused emotion regulation consisting of situation selection, situation modification, attentional deployment, cognitive change and second, Response-focused emotion regulation consisting of suppression. The purpose of this research is to investigate personality factors relate with emotion regulation strategies. 339 students from Faculty of Psychology, Universitas Gadjah Mada were participating in this study and given The Big Five Personality Factors (Ramdhani, 2012, adaptation, and the modified version of the Emotion Regulation Scale was used, Emotion Regulation Questionnaire (John & Gross, 2004 which measure personality and emotion regulation respectively. Using multiple regression analysis, the study indicated that personality predicts emotion regulation strategies.

Rapamycin up-regulates triglycerides in hepatocytes by down-regulating Prox1.

Science.gov (United States)

Kwon, Sora; Jeon, Ji-Sook; Kim, Su Bin; Hong, Young-Kwon; Ahn, Curie; Sung, Jung-Suk; Choi, Inho

2016-02-27

Although the prolonged use of rapamycin may cause unwanted side effects such as hyperlipidemia, the underlying mechanism remains unknown. Prox1 is a transcription factor responsible for the development of several tissues including lymphatics and liver. There is growing evidences that Prox1 participates in metabolism in addition to embryogenesis. However, whether Prox1 is directly related to lipid metabolism is currently unknown. HepG2 human hepatoma cells were treated with rapamycin and total lipids were analyzed by thin layer chromatography. The effect of rapamycin on the expression of Prox1 was determined by western blotting. To investigate the role of Prox1 in triglycerides regulation, siRNA and overexpression system were employed. Rapamycin was injected into mice for 2 weeks and total lipids and proteins in liver were measured by thin layer chromatography and western blot analysis, respectively. Rapamycin up-regulated the amount of triglyceride and down-regulated the expression of Prox1 in HepG2 cells by reducing protein half-life but did not affect its transcript. The loss-of-function of Prox1 was coincident with the increase of triglycerides in HepG2 cells treated with rapamycin. The up-regulation of triglycerides by rapamycin in HepG2 cells reverted to normal levels by the compensation of Prox1 using the overexpression system. Rapamycin also down-regulated Prox1 expression but increased triglycerides in mouse liver. This study suggests that rapamycin can increase the amount of triglycerides by down-regulating Prox1 expression in hepatocytes, which means that the mammalian target of rapamycin (mTOR) signaling is important for the regulation of triglycerides by maintaining Prox1 expression.

Regulation of Wnt/β-catenin signaling by posttranslational modifications

Science.gov (United States)

2014-01-01

The canonical Wnt signaling pathway (or Wnt/β-catenin pathway) plays a pivotal role in embryonic development and adult homeostasis; deregulation of the Wnt pathway contributes to the initiation and progression of human diseases including cancer. Despite its importance in human biology and disease, how regulation of the Wnt/β-catenin pathway is achieved remains largely undefined. Increasing evidence suggests that post-translational modifications (PTMs) of Wnt pathway components are essential for the activation of the Wnt/β-catenin pathway. PTMs create a highly dynamic relay system that responds to Wnt stimulation without requiring de novo protein synthesis and offer a platform for non-Wnt pathway components to be involved in the regulation of Wnt signaling, hence providing alternative opportunities for targeting the Wnt pathway. This review highlights the current status of PTM-mediated regulation of the Wnt/β-catenin pathway with a focus on factors involved in Wnt-mediated stabilization of β-catenin. PMID:24594309

Power-MOSFET Voltage Regulator

Science.gov (United States)

Miller, W. N.; Gray, O. E.

1982-01-01

Ninety-six parallel MOSFET devices with two-stage feedback circuit form a high-current dc voltage regulator that also acts as fully-on solid-state switch when fuel-cell out-put falls below regulated voltage. Ripple voltage is less than 20 mV, transient recovery time is less than 50 ms. Parallel MOSFET's act as high-current dc regulator and switch. Regulator can be used wherever large direct currents must be controlled. Can be applied to inverters, industrial furnaces photovoltaic solar generators, dc motors, and electric autos.

Regulating household financial advice

Directory of Open Access Journals (Sweden)

Benjamin F. Cummings

2012-08-01

Full Text Available This paper reviews economic theory related to investment advice. This theory explains 1 why financial advisors need to be carefully regulated for the benefit of both the investment advice industry and for consumers, 2 why principles-based regulation (e.g., a fiduciary standard is more efficient than rules-based regulation, 3 why dual regulation of financial professionals providing investment or insurance advice is inefficient and inequitable policy, and 4 why the application of a universal and uniform fiduciary standard will be difficult to implement.

let-7 miRNAs Can Act through Notch to Regulate Human Gliogenesis

Directory of Open Access Journals (Sweden)

M. Patterson

2014-11-01

Full Text Available It is clear that neural differentiation from human pluripotent stem cells generates cells that are developmentally immature. Here, we show that the let-7 plays a functional role in the developmental decision making of human neural progenitors, controlling whether these cells make neurons or glia. Through gain- and loss-of-function studies on both tissue and pluripotent derived cells, our data show that let-7 specifically regulates decision making in this context by regulation of a key chromatin-associated protein, HMGA2. Furthermore, we provide evidence that the let-7/HMGA2 circuit acts on HES5, a NOTCH effector and well-established node that regulates fate decisions in the nervous system. These data link the let-7 circuit to NOTCH signaling and suggest that this interaction serves to regulate human developmental progression.

The neuroendocrine regulation of food intake in fish: a review of current knowledge

Directory of Open Access Journals (Sweden)

Helene Volkoff

2016-11-01

Full Text Available Fish are the most diversified group of vertebrates and, although progress has been made in the past years, only relatively few fish species have been examined to date, with regards to the endocrine regulation of feeding in fish. In fish, as in mammals, feeding behavior is ultimately regulated by central effectors within feeding centers of the brain, which receive and process information from endocrine signals from both brain and peripheral tissues. Although basic endocrine mechanisms regulating feeding appear to be conserved among vertebrates, major physiological differences between fish and mammals and the diversity of fish, in particular in regard to feeding habits, digestive tract anatomy and physiology, suggest the existence of fish- and species-specific regulating mechanisms. This review provides an overview of hormones known to regulate food intake in fish, emphasizing on major hormones and the main fish groups studied to date.

From research to regulations

International Nuclear Information System (INIS)

Flury-Herard, A.

2000-01-01

from the beginning of nuclear energy utilization, the necessity arose to take into account the knowledge progress in order to give the best scientific base possible to the regulation protecting workers and the public against the potentially injurious effects of ionizing radiations. These next years, the experts should make their benefit of numerous new results with the conjunction of ultra precise experimental irradiation techniques and to global approach of the genome. The United Nations scientific committee on effect of atomic radiation (U.N.S.C.E.A.R.) plays an essential part in the analysis and the synthesis of the most recent researches to evaluate more precisely, these effects, especially for low radiations doses. (N.C.)

Moving from self-regulation to external regulation of Department of Energy facilities

International Nuclear Information System (INIS)

Wishau, R.J.; Dawson, J.; Lee, D.W.

1999-01-01

This paper discusses the initiative to transfer the regulation of Department of Energy (DOE) nuclear facilities to the US Nuclear Regulatory Commission (NRC). The paper gives an overview of some of the major technical, policy and legal issues that accompany this initiative. The paper focuses on specific issues and how they may be affected by external regulation of occupational radiation protection at DOE facilities. Differences between the NRC and the DOE approach to regulating nuclear safety are compared and contrasted. Some projected impacts from this transition are examined. Finally, recommendations are provided that may enhance the transition, increasing the likelihood of successful external NRC regulation

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.

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

2016-03-08

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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Status of mixed-waste regulation

International Nuclear Information System (INIS)

Bahadur, S.

1988-01-01

Mixed waste is waste containing radionuclides regulated by the US Nuclear Regulatory Commission (NRC) under the Atomic Energy Act, as well as hazardous waste materials regulated by the Environmental Protection Agency (EPA) under the Resource Conservation and Recovery Act (RCRA). This has led to a situation of dual regulation in which both NRC and EPA regulate the same waste under requirements that at times appear conflicting. The NRC has been working with the EPA to resolve the issues associated with the dual regulation of mixed waste. Discussions between the two agencies indicate that dual regulation of mixed wastes appears technically achievable, although the procedures may be complex and burdensome to the regulated community. The staffs of both agencies have been coordinating their efforts to minimize the burden of dual regulation on state agencies and the industry. Three major issues were identified as sources of potential regulatory conflict: (a) definition and identification of mixed waste, (b) siting guidelines for disposal facilities, and (c) design concepts for disposal units

Nuclear safety and regulation

International Nuclear Information System (INIS)

Kim, Hho Jung

2000-03-01

This book contains 12 chapters, which are atom and radiation, nuclear reactor and kinds of nuclear power plant, safeguard actuation system and stability evaluation for rock foundation of nuclear power plant, nuclear safety and principle, safety analysis and classification of incident, probabilistic safety assessment and major incident, nuclear safety regulation, system of nuclear safety regulation, main function and subject of safety regulation in nuclear facilities, regulation of fuel cycle and a nuclear dump site, protection of radiation and, safety supervision and, safety supervision and measurement of environmental radioactivity.

Genetic Regulation in the Aiptasia pallida Symbiosis - Performance Report, Year 1

National Research Council Canada - National Science Library

Tomb, Jean-Francois

1997-01-01

This report describes the progress of the project 'Genetic Regulation in A. pallida Symbiosis'. The main goal of the project in year 1 was to identify sequence tags for differentially expressed genes using the SAGE approach...

The transport systems of Ventricaria ventricosa: hypotonic and hypertonic turgor regulation.

Science.gov (United States)

Bisson, M A; Beilby, M J

2002-11-01

The time course of hypertonic and hypotonic turgor regulation was studied in Ventricaria (Valonia) using pressure probe and I/V(current-voltage) analysis. Of 11 cells, 9 exhibited hypertonic turgor regulation, ranging from 100% regulation in 150 min to 14% regulation (14% recovery of the decrease in turgor) in 314 min. Some cells began regulating immediately, others took up to 90 min to begin. The resting PD (potential difference) became more positive in most cells. The I/V characteristics became more nonlinear with high resistance between -150 and -20 mV and negative conductance region near -70 mV. Prolonged (16 sec) voltage clamps to negative levels (-100 to -150 mV) showed progressively more rapid current turn-off, but subsequent I/V characteristics were not affected. Clamping to +150 mV, however, abolished the high conductance between -50 and +100 mV to yield a uniform high resistance I/V characteristic, similar to that in high [K+]o. Decreasing illumination from 2.02 micromol sec(-1) m(-2) to 0.5 micromol sec(-1)1 m(-2) had a similar effect. Two out of a total of three cells exhibited hypotonic turgor regulation. Both cells started regulating within minutes and achieved near 50% regulation within 50 min. The PD became more negative. The I/V curves exhibited high resistance between +50 and +150 mV. The characteristics were similar to those in cells exposed to low [K+]o. Prolonged voltage clamps to both negative and positive levels showed slow current increase. Decreased illumination increased the membrane resistance.

Regulation of CNKSR2 protein stability by the HECT E3 ubiquitin ligase Smurf2, and its role in breast cancer progression.

Science.gov (United States)

David, Diana; Surendran, Arun; Thulaseedharan, Jissa V; Nair, Asha S

2018-03-13

Smurf2 E3 ubiquitin ligase physically associates with and regulate the stability of distinct cellular protein substrates. The multi-functional scaffold protein Connector enhancer of kinase suppressor of ras 2 (CNKSR2) plays a key role in regulating cell proliferation, and differentiation through multiple receptor tyrosine kinase pathways. The aim of this study was to investigate whether the interaction between Smurf2 and CNKSR2 has any significant role in the post transcriptional regulation of CNKSR2 expression in breast cancer. Here we demonstrate a novel interaction of CNKSR2 with Smurf2 by co-immunoprecipitation, indirect immunofluorescence studies, and surface plasmon resonance (SPR) analysis, which can ubiquitinate, but stabilize CNKSR2 by protecting it from proteasome mediated degradation. CNKSR2 protein levels were significantly increased upon forced overexpression of Smurf2, indicating the role of Smurf2 in regulating the stability of CNKSR2. Conversely, Smurf2 knockdown resulted in a marked decrease in the protein level expression of CNKSR2 by facilitating enhanced polyubiquitination and proteasomal degradation and reduced the proliferation and clonogenic survival of MDA-MB-231 breast cancer cell lines. Tissue microarray data from 84 patients with various stages of mammary carcinoma, including (in order of increasing malignant potential) normal, usual hyperplasia, fibrocystic changes, fibroadenoma, carcinoma-in-situ, and invasive ductal carcinoma showed a statistically significant association between Smurf2 and CNKSR2 expression, which is also well correlated with the ER, PR, and HER2 status of the tissue samples. A comparatively high expression of Smurf2 and CNKSR2 was observed when the expression of ER and PR was low, and HER2 was high. Consistently, both Smurf2 and CNKSR2 showed an integrated expression in MCF10 breast progression model cell lines. Altogether, our findings reveal that Smurf2 is a novel positive regulator of CNKSR2 and suggest that Smurf

Environmental Regulation, Foreign Direct Investment and Green Technological Progress—Evidence from Chinese Manufacturing Industries

Science.gov (United States)

Hu, Jiangfeng; Wang, Zhao; Lian, Yuehan; Huang, Qinghua

2018-01-01

This study examines the spillover effects of foreign direct investment (FDI) on green technology progress rate (as measured by the green total factor productivity). The analysis utilizes two measures of FDI, labor-based FDI and capital-based FDI, and separately investigates four sets of industry classifications—high/low discharge regulation and high/low emission standard regulation. The results indicate that in the low discharge regulation and low emission standard regulation industry, labor-based FDI has a significant negative spillover effect, and capital-based FDI has a significant positive spillover effect. However, in the high-intensity environmental regulation industry, the negative influence of labor-based FDI is completely restrained, and capital-based FDI continues to play a significant positive green technological spillover effects. These findings have clear policy implications: the government should be gradually reducing the labor-based FDI inflow or increasing stringency of environmental regulation in order to reduce or eliminate the negative spillover effect of the labor-based FDI. PMID:29382112

Environmental Regulation, Foreign Direct Investment and Green Technological Progress—Evidence from Chinese Manufacturing Industries

Directory of Open Access Journals (Sweden)

Jiangfeng Hu

2018-01-01

Full Text Available This study examines the spillover effects of foreign direct investment (FDI on green technology progress rate (as measured by the green total factor productivity. The analysis utilizes two measures of FDI, labor-based FDI and capital-based FDI, and separately investigates four sets of industry classifications—high/low discharge regulation and high/low emission standard regulation. The results indicate that in the low discharge regulation and low emission standard regulation industry, labor-based FDI has a significant negative spillover effect, and capital-based FDI has a significant positive spillover effect. However, in the high-intensity environmental regulation industry, the negative influence of labor-based FDI is completely restrained, and capital-based FDI continues to play a significant positive green technological spillover effects. These findings have clear policy implications: the government should be gradually reducing the labor-based FDI inflow or increasing stringency of environmental regulation in order to reduce or eliminate the negative spillover effect of the labor-based FDI.

The 5th Symposium on Post-Transcriptional Regulation of Plant Gene Expression (PTRoPGE)

Energy Technology Data Exchange (ETDEWEB)

Karen S. Browning; Marie Petrocek; Bonnie Bartel

2006-06-01

The 5th Symposium on Post-Transcriptional Regulation of Plant Gene Expression (PTRoPGE) will be held June 8-12, 2005 at the University of Texas at Austin. Exciting new and ongoing discoveries show significant regulation of gene expression occurs after transcription. These post-transcriptional control events in plants range from subtle regulation of transcribed genes and phosphorylation, to the processes of gene regulation through small RNAs. This meeting will focus on the regulatory role of RNA, from transcription, through translation and finally degradation. The cross-disciplinary design of this meeting is necessary to encourage interactions between researchers that have a common interest in post-transcriptional gene expression in plants. By bringing together a diverse group of plant molecular biologist and biochemists at all careers stages from across the world, this meeting will bring about more rapid progress in understanding how plant genomes work and how genes are finely regulated by post-transcriptional processes to ultimately regulate cells.

Negative Effects of Antimonopoly Regulation on the Russian Electric Power Industry

Directory of Open Access Journals (Sweden)

Elena NEPRINTSEVA

2017-07-01

Full Text Available With the antimonopoly regulation in the domestic economy getting more stringent an analysis of the current measures of antimonopoly regulation in terms of their efficiency is now becoming ever more relevant. The aim of the study - analyze how the measures of antimonopoly regulation affect competitive relationships in the electric power industry. The following methods have been used in this work: empirical method, cause-effect method and scientific abstraction method. The article sets out an analysis of the antimonopoly regulation measures that the antimonopoly authority applies. It also provides an assessment of consequences that follow from such methods being applied for the promotion of competitive relationships on the market of electric power and capacity. A conclusion has been reached that the antimonopoly regulation measures being applied impede the progress of competitive relationships on the market of electric power and capacity. The continuing process of reformation in electric power industry aims to liberalize relationships in the area of electric power production. Yet, as a result of this process, generating capacities are becoming increasingly more concentrated mainly around state companies. This is mainly caused by the lack of certainty regarding the results of the industry reformation and a more stringent state regulation over the last years of the reforms. At the same time, for the purposes of limiting the market force, measures of antimonopoly regulation are being applied to generating companies. Such measures have an adverse effect on competitive relationships and stimulate further concentration.

Comparison of series regulated neutral beam accel supplies with shunt regulated accel supplies

International Nuclear Information System (INIS)

Baker, W.; Smith, B.H.

1976-01-01

This study was undertaken to get a direct comparison between comparable series and shunt regulated power supplies. It is intended that the two supplies will be strictly equivalent with the same safety factors in the design of each type and the cost estimates made on the same basis. The series regulated power supply is simply a scaled up version of the 2XIIB Accel Supplies. Each supply provides 150 kV, 65 ampere, 500 ms pulse output such as will be used on the TFTR sources. The shunt regulated power supply uses high reactance transformers to provide the series impedance for the shunt regulator. The most significant difference in the performance of the two types of power supplies is that the shunt regulated supply has a minimum interrupt period of 16 ms, whereas the series regulated supply can have about 0.5 ms. Even this difference can be eliminated with a commutator circuit such as is being developed in Berkeley for the 150 kV, 20 ampere system. The 16 ms period is probably not a very serious limitation because it still permits up to 31 interrupts per 500 ms pulse. The shunt regulated system appears to be about 37 percent less expensive than the series system

Effect Mechanism of Penstock on Stability and Regulation Quality of Turbine Regulating System

Directory of Open Access Journals (Sweden)

Wencheng Guo

2014-01-01

Full Text Available This paper studies the effect mechanism of water inertia and head loss of penstock on stability and regulation quality of turbine regulating system with surge tank or not and proposes the construction method of equivalent model of regulating system. Firstly, the complete linear mathematical model of regulating system is established. Then, the free oscillation equation and time response of the frequency that describe stability and regulation quality, respectively, are obtained. Finally, the effects of penstock are analysed by using stability region and response curves. The results indicate that the stability and regulation quality of system without surge tank are determined by time response of frequency which only depends on water hammer wave in penstock, while, for system with surge tank, the time response of frequency depending on water hammer wave in penstock and water-level fluctuation in surge tank jointly determines the stability and regulation quality. Water inertia of penstock mainly affects the stability and time response of frequency of system without surge tank as well as the stability and head wave of time response of frequency with surge tank. Head loss of penstock mainly affects the stability and tail wave of time response of frequency with surge tank.

Transcriptional regulators of Na, K-ATPase subunits

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Zhiqin eLi

2015-10-01

Full Text Available The Na,K-ATPase classically serves as an ion pump creating an electrochemical gradient across the plasma membrane that is essential for transepithelial transport, nutrient uptake and membrane potential. In addition, Na,K-ATPase also functions as a receptor, a signal transducer and a cell adhesion molecule. With such diverse roles, it is understandable that the Na,K-ATPase subunits, the catalytic alpha-subunit, the beta-subunit and the FXYD proteins, are controlled extensively during development and to accommodate physiological needs. The spatial and temporal expression of Na,K-ATPase is partially regulated at the transcriptional level. Numerous transcription factors, hormones, growth factors, lipids and extracellular stimuli modulate the transcription of the Na,K-ATPase subunits. Moreover, epigenetic mechanisms also contribute to the regulation of Na,K-ATPase expression. With the ever growing knowledge about diseases associated with the malfunction of Na,K-ATPase, this review aims at summarizing the best-characterized transcription regulators that modulate Na,K-ATPase subunit levels. As abnormal expression of Na,K-ATPase subunits have been observed in many carcinoma, we will also discuss transcription factors that are associated with epithelial-to-mesenchymal transition, a crucial step in the progression of many tumors to malignant disease.

Understanding cell cycle and cell death regulation provides novel weapons against human diseases.

Science.gov (United States)

Wiman, K G; Zhivotovsky, B

2017-05-01

Cell division, cell differentiation and cell death are the three principal physiological processes that regulate tissue homoeostasis in multicellular organisms. The growth and survival of cells as well as the integrity of the genome are regulated by a complex network of pathways, in which cell cycle checkpoints, DNA repair and programmed cell death have critical roles. Disruption of genomic integrity and impaired regulation of cell death may both lead to uncontrolled cell growth. Compromised cell death can also favour genomic instability. It is becoming increasingly clear that dysregulation of cell cycle and cell death processes plays an important role in the development of major disorders such as cancer, cardiovascular disease, infection, inflammation and neurodegenerative diseases. Research achievements in these fields have led to the development of novel approaches for treatment of various conditions associated with abnormalities in the regulation of cell cycle progression or cell death. A better understanding of how cellular life-and-death processes are regulated is essential for this development. To highlight these important advances, the Third Nobel Conference entitled 'The Cell Cycle and Cell Death in Disease' was organized at Karolinska Institutet in 2016. In this review we will summarize current understanding of cell cycle progression and cell death and discuss some of the recent advances in therapeutic applications in pathological conditions such as cancer, neurological disorders and inflammation. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Serine/threonine/tyrosine phosphorylation regulates DNA binding of bacterial transcriptional regulators

DEFF Research Database (Denmark)

Kalantari, Aida; Derouiche, Abderahmane; Shi, Lei

2015-01-01

Reversible phosphorylation of bacterial transcriptional regulators (TRs) belonging to the family of two-component systems (TCSs) is a well-established mechanism for regulating gene expression. Recent evidence points to the fact that reversible phosphorylation of bacterial TRs on other types...

Analysis of meiosis regulators in human gonads

DEFF Research Database (Denmark)

Jørgensen, Anne; Nielsen, John E; Jensen, Martin Blomberg

2012-01-01

The mitosis-meiosis switch is a key event in the differentiation of germ cells. In humans, meiosis is initiated in fetal ovaries, whereas in testes meiotic entry is inhibited until puberty. The purpose of this study was to examine the expression pattern of meiosis regulators in human gonads...... with their role in initiation and progression of meiosis. The putative meiosis inhibitors, CYP26B1 and NANOS2, were primarily expressed in Leydig cells and spermatocytes, respectively. In conclusion, the expression pattern of the investigated meiotic regulators is largely conserved in the human gonads compared...... with rodents, but with some minor differences, such as a stable expression of CYP26B1 in human fetal ovaries. The sexually dimorphic expression pattern of DMRT1 indicates a similar role in the mitosis-meiosis switch in human gonads as previously demonstrated in mice. The biological importance of the changes...

A Pedagogical Note on the Superiority of Price-Cap Regulation to Rate-of-Return Regulation

Science.gov (United States)

Currier, Kevin M.; Jackson, Brian K.

2008-01-01

The two forms of natural monopoly regulation that are typically discussed in intermediate microeconomics textbooks are marginal cost pricing and average cost pricing (rate-of-return regulation). However, within the last 20 years, price-cap regulation has largely replaced rate-of-return regulation because of the former's potential to generate more…

Panel presentation: Should some type of incentive regulation replace traditional methods for regulating LDCs?

International Nuclear Information System (INIS)

Turner, J.L.

1992-01-01

This paper reviews the advantages and disadvantages of using incentive regulation to provide the best service and rates for natural gas consumers and compares it to the traditional rate-of-return regulation. It discusses some of the allegations used to prevent incentive regulation such as the rate-of-return regulation provides an incentive to over-build and pad rate base, thus creating inefficiencies. The author also feels that strict competition is not necessarily beneficial and that some form of regulation is necessary. The paper goes on to outline the author's ideas of how a successful incentive plan should work while emphasizing his preference for a rate-of-return regulation. From the ratepayers' view, the incentives granted should be rewards for improvement in a utility's performance. In other words, there must be clear goals set for management and the fulfillment or lack of fulfillment should result in rewards or penalties. The author feels that incentive regulation could prove to be appropriate in the areas of demand side management such as energy conservation programs

Optimum regulation of grid monopoly in the power trade; Optimal regulering av nettmonopoler i kraftomsetningen

Energy Technology Data Exchange (ETDEWEB)

Hope, E.

1994-06-01

The report discusses the organization and behaviour of grid monopolies in the Norwegian power trade and relations to the socio-economic effectiveness. The main attention is laid on analyzing regulation mechanisms and measures leading to an efficient short-term operation and to the investment of optimum production capacity in a long run. Regarding the management, measures are discussed for increasing the efficiency of total power trade by evaluating the existing marketing function of Statnett. Some basic conditions are accounted concerning the regulation problem of grid monopolies with a particular attention to asymmetric information between the authority and the monopoly. In addition, forms of regulation and regulation mechanisms together with the incentive characteristics of these, are discussed. The existing profit regulation principles in relation to an alternative system design such as maximum price regulation combined with standard regulation, are evaluated. 16 refs., 7 figs.

Tariffs regulation experiences in the Italian electricity industry

International Nuclear Information System (INIS)

Bianchi, A.

1997-01-01

This work tries to explain the tariff regulation experiences in the Italian electricity industry from the end of the second world war to now. These events, shown in the following tables, are divided into four phases: 1) the progressive standardization of electric power prices (1945-61); 2) the price control (1961-74); 3) the 'interferences' in the tariff system (1974-95); 4) the present deregulation (price-cap)

RNA-guided transcriptional regulation

Science.gov (United States)

Church, George M.; Mali, Prashant G.; Esvelt, Kevin M.

2016-02-23

Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

The regulation of hunting

DEFF Research Database (Denmark)

Abildtrup, Jens; Jensen, Frank

Within hunting, wildlife populations are estimated to be too high in many countries which is assumed to be due to the market failure, that each hunter harvests too little compared to what the regulator wants. This may be due to the existing regulation which, among other things, requires knowledge...... by an individual, variable tax rate. The variable tax rate is, among other things, based on the difference in marginal value of the population between the hunter and the regulator. The paper shows that the population tax/subsidy secures a first-best optimum. Thus, the population tax is a good alternative...... to the existing regulation....

7 CFR 987.48 - Container regulation.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Container regulation. 987.48 Section 987.48... IN RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Container Regulation § 987.48 Container regulation. Whenever the Committee deems it advisable to establish a container regulation for any variety of...

Regulated electricity retailing in Chile

Energy Technology Data Exchange (ETDEWEB)

Galetovic, Alexander, E-mail: alexander@galetovic.cl [Facultad de Ciencias Economicas y Empresariales, Universidad de los Andes, Santiago, Chile. Av. San Carlos de Apoquindo 2200, Las Condes, Santiago (Chile); Munoz, Cristian M., E-mail: cmunozm@aes.com [AES Gener and Departamento de Ingenieria Electrica, Universidad Catolica de Chile (Chile)

2011-10-15

While some countries have unbundled distribution and retailing, skeptics argue that the physical attributes of electricity make retailers redundant. Instead, it is claimed that passive pass through of wholesale prices plus regulated charges for transmission and distribution suffice for customers to benefit from competitive generation markets. We review the Chilean experience with regulated retailing and pass through of wholesale prices. We argue that when energy wholesale prices are volatile and prices are stabilized, distortions emerge. Regulated retailers gain little by mitigating or correcting them. On the contrary, sometimes price distortions increase their profits. We estimate the cost of three distortions that neither regulated retailers nor the regulator have shown any interest in correcting. - Highlights: > We review Chile's experience with regulated electricity retailing. > Distortions emerge when energy wholesale prices are volatile and prices stabilized. > Regulated retailers gain little by mitigating or correcting distortions. > Sometimes price distortions increase retailers' profits. > We estimate the cost of three distortions, which retailers have not corrected.

Regulated electricity retailing in Chile

International Nuclear Information System (INIS)

Galetovic, Alexander; Munoz, Cristian M.

2011-01-01

While some countries have unbundled distribution and retailing, skeptics argue that the physical attributes of electricity make retailers redundant. Instead, it is claimed that passive pass through of wholesale prices plus regulated charges for transmission and distribution suffice for customers to benefit from competitive generation markets. We review the Chilean experience with regulated retailing and pass through of wholesale prices. We argue that when energy wholesale prices are volatile and prices are stabilized, distortions emerge. Regulated retailers gain little by mitigating or correcting them. On the contrary, sometimes price distortions increase their profits. We estimate the cost of three distortions that neither regulated retailers nor the regulator have shown any interest in correcting. - Highlights: → We review Chile's experience with regulated electricity retailing. → Distortions emerge when energy wholesale prices are volatile and prices stabilized. → Regulated retailers gain little by mitigating or correcting distortions. → Sometimes price distortions increase retailers' profits. → We estimate the cost of three distortions, which retailers have not corrected.

Wrecked regulation of intrinsically disordered proteins in diseases: Pathogenicity of deregulated regulators

Directory of Open Access Journals (Sweden)

Vladimir N. Uversky

2014-07-01

Full Text Available Biologically active proteins without stable tertiary structure are common in all known proteomes. Functions of these intrinsically disordered proteins (IDPs are typically related to regulation, signaling and control. Cellular levels of these important regulators are tightly regulated by a variety mechanisms ranging from firmly controlled expression to precisely targeted degradation. Functions of IDPs are controlled by binding to specific partners, alternative splicing, and posttranslational modifications among other means. In the norm, right amounts of precisely activated IDPs have to be present in right time at right places. Wrecked regulation brings havoc to the ordered world of disordered proteins, leading to protein misfolding, misidentification, and missignaling that give rise to numerous human diseases, such as cancer, cardiovascular disease, neurodegenerative diseases, and diabetes. Among factors inducing pathogenic transformations of IDPs are various cellular mechanisms, such as chromosomal translocations, damaged splicing, altered expression, frustrated posttranslational modifications, aberrant proteolytic degradation, and defective trafficking. This review presents some of the aspects of deregulated regulation of IDPs leading to human diseases.

Redox Regulation in Amyotrophic Lateral Sclerosis

Science.gov (United States)

Parakh, Sonam; Spencer, Damian M.; Halloran, Mark A.; Soo, Kai Y.; Atkin, Julie D.

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS. PMID:23533690

Deleted in breast cancer 1 (DBC1) protein regulates hepatic gluconeogenesis.

Science.gov (United States)

Nin, Veronica; Chini, Claudia C S; Escande, Carlos; Capellini, Verena; Chini, Eduardo N

2014-02-28

Liver gluconeogenesis is essential to provide energy to glycolytic tissues during fasting periods. However, aberrant up-regulation of this metabolic pathway contributes to the progression of glucose intolerance in individuals with diabetes. Phosphoenolpyruvate carboxykinase (PEPCK) expression plays a critical role in the modulation of gluconeogenesis. Several pathways contribute to the regulation of PEPCK, including the nuclear receptor Rev-erbα and the histone deacetylase SIRT1. Deleted in breast cancer 1 (DBC1) is a nuclear protein that binds to and regulates both Rev-erbα and SIRT1 and, therefore, is a candidate to participate in the regulation of PEPCK. In this work, we provide evidence that DBC1 regulates glucose metabolism and the expression of PEPCK. We show that DBC1 levels decrease early in the fasting state. Also, DBC1 KO mice display higher gluconeogenesis in a normal and a high-fat diet. DBC1 absence leads to an increase in PEPCK mRNA and protein expression. Conversely, overexpression of DBC1 results in a decrease in PEPCK mRNA and protein levels. DBC1 regulates the levels of Rev-erbα, and manipulation of Rev-erbα activity or levels prevents the effect of DBC1 on PEPCK. In addition, Rev-erbα levels decrease in the first hours of fasting. Finally, knockdown of the deacetylase SIRT1 eliminates the effect of DBC1 knockdown on Rev-erbα levels and PEPCK expression, suggesting that the mechanism of PEPCK regulation is, at least in part, dependent on the activity of this enzyme. Our results point to DBC1 as a novel regulator of gluconeogenesis.

Extracellular Matrix as a Regulator of Epidermal Stem Cell Fate.

Science.gov (United States)

Chermnykh, Elina; Kalabusheva, Ekaterina; Vorotelyak, Ekaterina

2018-03-27

Epidermal stem cells reside within the specific anatomic location, called niche, which is a microenvironment that interacts with stem cells to regulate their fate. Regulation of many important processes, including maintenance of stem cell quiescence, self-renewal, and homeostasis, as well as the regulation of division and differentiation, are common functions of the stem cell niche. As it was shown in multiple studies, extracellular matrix (ECM) contributes a lot to stem cell niches in various tissues, including that of skin. In epidermis, ECM is represented, primarily, by a highly specialized ECM structure, basement membrane (BM), which separates the epidermal and dermal compartments. Epidermal stem cells contact with BM, but when they lose the contact and migrate to the overlying layers, they undergo terminal differentiation. When considering all of these factors, ECM is of fundamental importance in regulating epidermal stem cells maintenance, proper mobilization, and differentiation. Here, we summarize the remarkable progress that has recently been made in the research of ECM role in regulating epidermal stem cell fate, paying special attention to the hair follicle stem cell niche. We show that the destruction of ECM components impairs epidermal stem cell morphogenesis and homeostasis. A deep understanding of ECM molecular structure as well as the development of in vitro system for stem cell maintaining by ECM proteins may bring us to developing new approaches for regenerative medicine.

Soft Regulation with Crowd Recommendation: Coordinating Self-Interested Agents in Sociotechnical Systems under Imperfect Information.

Science.gov (United States)

Luo, Yu; Iyengar, Garud; Venkatasubramanian, Venkat

2016-01-01

Regulating emerging industries is challenging, even controversial at times. Under-regulation can result in safety threats to plant personnel, surrounding communities, and the environment. Over-regulation may hinder innovation, progress, and economic growth. Since one typically has limited understanding of, and experience with, the novel technology in practice, it is difficult to accomplish a properly balanced regulation. In this work, we propose a control and coordination policy called soft regulation that attempts to strike the right balance and create a collective learning environment. In soft regulation mechanism, individual agents can accept, reject, or partially accept the regulator's recommendation. This non-intrusive coordination does not interrupt normal operations. The extent to which an agent accepts the recommendation is mediated by a confidence level (from 0 to 100%). Among all possible recommendation methods, we investigate two in particular: the best recommendation wherein the regulator is completely informed and the crowd recommendation wherein the regulator collects the crowd's average and recommends that value. We show by analysis and simulations that soft regulation with crowd recommendation performs well. It converges to optimum, and is as good as the best recommendation for a wide range of confidence levels. This work sheds a new theoretical perspective on the concept of the wisdom of crowds.

Why Do People Regulate Their Emotions? A Taxonomy of Motives in Emotion Regulation.

Science.gov (United States)

Tamir, Maya

2016-08-01

Emotion regulation involves the pursuit of desired emotional states (i.e., emotion goals) in the service of superordinate motives. The nature and consequences of emotion regulation, therefore, are likely to depend on the motives it is intended to serve. Nonetheless, limited attention has been devoted to studying what motivates emotion regulation. By mapping the potential benefits of emotion to key human motives, this review identifies key classes of motives in emotion regulation. The proposed taxonomy distinguishes between hedonic motives that target the immediate phenomenology of emotions, and instrumental motives that target other potential benefits of emotions. Instrumental motives include behavioral, epistemic, social, and eudaimonic motives. The proposed taxonomy offers important implications for understanding the mechanism of emotion regulation, variation across individuals and contexts, and psychological function and dysfunction, and points to novel research directions. © 2015 by the Society for Personality and Social Psychology, Inc.

Recent progress on the traditional Chinese medicines that regulate the blood

Directory of Open Access Journals (Sweden)

Hsin-Yi Hung

2016-04-01

Full Text Available In traditional Chinese medicine, the herbs that regulate blood play a vital role. Here, nine herbs including Typhae Pollen, Notoginseng Root, Common Bletilla Tuber, India Madder Root and Rhizome, Chinese Arborvitae Twig, Lignum Dalbergiae Oderiferae, Chuanxiong Rhizoma, Corydalis Tuber, and Motherwort Herb were selected and reviewed for their recent studies on anti-tumor, anti-inflammatory and cardiovascular effects. Besides, the analytical methods developed to qualify or quantify the active compounds of the herbs are also summarized.

The Porphyromonas gingivalis ferric uptake regulator orthologue does not regulate iron homeostasis

Directory of Open Access Journals (Sweden)

Catherine Butler

2015-09-01

Full Text Available Porphyromonas gingivalis is a Gram-negative anaerobic bacterium that has an absolute requirement for iron which it transports from the host as heme and/or Fe2+. Iron transport must be regulated to prevent toxic effects from excess metal in the cell. P. gingivalis has one ferric uptake regulator (Fur orthologue encoded in its genome called Har, which would be expected to regulate the transport and usage of iron within this bacterium. As a gene regulator, inactivation of Har should result in changes in gene expression of several genes compared to the wild-type. This dataset (GEO accession number GSE37099 provides information on expression levels of genes in P. gingivalis in the absence of Har. Surprisingly, these genes do not relate to iron homeostasis.

Regulating deregulated energy markets

International Nuclear Information System (INIS)

Jackson, M.

2002-01-01

The North American gas and electricity markets are fast evolving, and regulators are currently faced with a host of issues such as market-based rates, unbundling, stranded costs, open access, and incentive regulation are surfacing as a result of deregulation. The regulatory environment in Ontario was reviewed by the author. Deregulated markets rule, from commodities to gas and electricity. Additionally, there is an evolution of traditional utility regulation. A look at deregulated markets revealed that there are regulations on boundary conditions on the deregulated market. Under the Ontario Energy Board (OEB), all generators, transmitters, distributors, and retailers of electricity must be licensed. The standard supply service (SSS) offered by electricity distributors and system gas which is still being sold by natural gas distributors continues to be regulated by OEB. One issue that was addressed was separation for revenues and costs of the utility's purchase and sale of gas business, at least for accounting purposes. The next issue discussed was cost of system gas and SSS, followed by timely signals and prudent incurred costs. Historical benefits were reviewed, such as historical commitments to low-cost electricity. Pooling transportation costs, transmission pricing continued, market-based rates, unbundling, stranded costs, open access, incentive regulation/ performance based regulation (PBR) were all discussed. Price cap on PBR, both partial and comprehensive were looked at. A requirement to review guidelines on cost of capital and an application to extend blanket approval provisions for gas storage were discussed, as they are amongst some of the challenges of the future. Other challenges include revised rules and practice and procedure; practice directions for cost awards, appeals, and other functions; confidentiality guidelines; and refinements to the role of and approaches to alternative dispute resolution. The future role of regulators was examined in light

Emerging Evidence for MicroRNAs as Regulators of Cancer Stem Cells

Energy Technology Data Exchange (ETDEWEB)

Sethi, Aisha [Department of Pathology, Henry Ford Hospital, Detroit, MI 48202 (United States); Sholl, Lynette M., E-mail: lmsholl@partners.org [Department of Pathology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

2011-10-24

Cancer stem cells are defined as a subpopulation of cells within a tumor that are capable of self-renewal and differentiation into the heterogeneous cell lineages that comprise the tumor. Many studies indicate that cancer stem cells may be responsible for treatment failure and relapse in cancer patients. The factors that regulate cancer stem cells are not well defined. MicroRNAs (miRNAs) are small non-coding RNAs that regulate translational repression and transcript degradation. miRNAs play a critical role in embryonic and inducible pluripotent stem cell regulation and emerging evidence supports their role in cancer stem cell evolution. To date, miRNAs have been shown to act either as tumor suppressor genes or oncogenes in driving critical gene expression pathways in cancer stem cells in a wide range of human malignancies, including hematopoietic and epithelial tumors and sarcomas. miRNAs involved in cancer stem cell regulation provide attractive, novel therapeutic targets for cancer treatment. This review attempts to summarize progress to date in defining the role of miRNAs in cancer stem cells.

Emerging Evidence for MicroRNAs as Regulators of Cancer Stem Cells

International Nuclear Information System (INIS)

Sethi, Aisha; Sholl, Lynette M.

2011-01-01

Cancer stem cells are defined as a subpopulation of cells within a tumor that are capable of self-renewal and differentiation into the heterogeneous cell lineages that comprise the tumor. Many studies indicate that cancer stem cells may be responsible for treatment failure and relapse in cancer patients. The factors that regulate cancer stem cells are not well defined. MicroRNAs (miRNAs) are small non-coding RNAs that regulate translational repression and transcript degradation. miRNAs play a critical role in embryonic and inducible pluripotent stem cell regulation and emerging evidence supports their role in cancer stem cell evolution. To date, miRNAs have been shown to act either as tumor suppressor genes or oncogenes in driving critical gene expression pathways in cancer stem cells in a wide range of human malignancies, including hematopoietic and epithelial tumors and sarcomas. miRNAs involved in cancer stem cell regulation provide attractive, novel therapeutic targets for cancer treatment. This review attempts to summarize progress to date in defining the role of miRNAs in cancer stem cells

Fisheries regulation

DEFF Research Database (Denmark)

Jensen, Frank; Frost, Hans Staby; Abildtrup, Jens

2017-01-01

Economists normally claim that a stock externality arises within fisheries because each individual fisherman does not take the effect on stock size into account when making harvest decisions. Due to the stock externality, it is commonly argued that fisheries regulation is necessary, but regulatory...... decisions are complicated by a tremendous amount of uncertainty and asymmetric information. This paper provides an overview of selected parts of the literature on the regulation of fisheries under uncertainty and asymmetric information, and possible areas for future research are identified. Specifically...

Recent Progress on Liver Kinase B1 (LKB1: Expression, Regulation, Downstream Signaling and Cancer Suppressive Function

Directory of Open Access Journals (Sweden)

Ren-You Gan

2014-09-01

Full Text Available Liver kinase B1 (LKB1, known as a serine/threonine kinase, has been identified as a critical cancer suppressor in many cancer cells. It is a master upstream kinase of 13 AMP-activated protein kinase (AMPK-related protein kinases, and possesses versatile biological functions. LKB1 gene is mutated in many cancers, and its protein can form different protein complexes with different cellular localizations in various cell types. The expression of LKB1 can be regulated through epigenetic modification, transcriptional regulation and post-translational modification. LKB1 dowcnstream pathways mainly include AMPK, microtubule affinity regulating kinase (MARK, salt-inducible kinase (SIK, sucrose non-fermenting protein-related kinase (SNRK and brain selective kinase (BRSK signalings, etc. This review, therefore, mainly discusses recent studies about the expression, regulation, downstream signaling and cancer suppressive function of LKB1, which can be helpful for better understanding of this molecular and its significance in cancers.

Lysosomal Regulation of mTORC1 by Amino Acids in Mammalian Cells

Directory of Open Access Journals (Sweden)

Yao Yao

2017-07-01

Full Text Available The mechanistic target of rapamycin complex 1 (mTORC1 is a master regulator of cell growth in eukaryotic cells. The active mTORC1 promotes cellular anabolic processes including protein, pyrimidine, and lipid biosynthesis, and inhibits catabolic processes such as autophagy. Consistent with its growth-promoting functions, hyper-activation of mTORC1 signaling is one of the important pathomechanisms underlying major human health problems including diabetes, neurodegenerative disorders, and cancer. The mTORC1 receives multiple upstream signals such as an abundance of amino acids and growth factors, thus it regulates a wide range of downstream events relevant to cell growth and proliferation control. The regulation of mTORC1 by amino acids is a fast-evolving field with its detailed mechanisms currently being revealed as the precise picture emerges. In this review, we summarize recent progress with respect to biochemical and biological findings in the regulation of mTORC1 signaling on the lysosomal membrane by amino acids.

Mechanisms of the Regulation of the Intestinal Na+/H+ Exchanger NHE3

Directory of Open Access Journals (Sweden)

Peijian He

2010-01-01

Full Text Available A major of Na+ absorptive process in the proximal part of intestine and kidney is electroneutral exchange of Na+ and H+ by Na+/H+ exchanger type 3 (NHE3. During the past decade, significant advance has been achieved in the mechanisms of NHE3 regulation. A bulk of the current knowledge on Na+/H+ exchanger regulation is based on heterologous expression of mammalian Na+/H+ exchangers in Na+/H+ exchanger deficient fibroblasts, renal epithelial, and intestinal epithelial cells. Based on the reductionist's approach, an understanding of NHE3 regulation has been greatly advanced. More recently, confirmations of in vitro studies have been made using animals deficient in one or more proteins but in some cases unexpected findings have emerged. The purpose of this paper is to provide a brief overview of recent progress in the regulation and functions of NHE3 present in the luminal membrane of the intestinal tract.

Ionising radiation: a guide to the Regulations

International Nuclear Information System (INIS)

Hughes, Donald.

1986-01-01

The author explains the basic requirements on health and safety personnel in relation to the Ionising Radiations Regulations 1985. The outline paper is presented under the following headings: Dose assessment, Interpretation and general regulations 1-5, Dose limitation regulations 6 and 7, Regulation of work - regulations 8-12, Dosimetry and medical surveillance - regulations 13-17, summary of records to be kept, entry to controlled areas, Control of radioactive substances -regulations 18-23, Monitoring of radiation regulation 24, Assessments and notifications - regulations 25-31, Safety of articles and equipment - regulations 32-34, Other guidance. (U.K.)

Retail experience in the de-regulated market

International Nuclear Information System (INIS)

Cummings, R.

2003-01-01

This paper describes the experience gained to date in the de-regulated electricity market through an examination of the commercial market. In 2001, chaos provided opportunity, while in 2002 the emphasis was on operations. In 2003, the landscape reflected hyper-competition, selling second services, and a changing landscape. A discussion followed on the residential market with a look at market structure, economics, and uncertainty concerning the future. The following components were identified as working well: wholesale market, commercial market, market model/data, and innovation in offerings and green supply. Areas requiring further improvement were also identified. It was suggested that the residential de-regulated roadmap should be clarified and retail friendly transactions should be imposed. Other improvements involve education and operations/system capabilities. The author concluded that the deregulated electricity market is still an immature market, where progress is being made in the commercial market. The residential market is in a critical period, with a market model still evolving. figs

Expression profiling of genes regulated by TGF-beta: Differential regulation in normal and tumour cells

Directory of Open Access Journals (Sweden)

Takahashi Takashi

2007-04-01

Full Text Available Abstract Background TGF-beta is one of the key cytokines implicated in various disease processes including cancer. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells and in contrast, acts as a pro-tumour cytokine by promoting tumour angiogenesis, immune-escape and metastasis. It is not clear if various actions of TGF-beta on normal and tumour cells are due to differential gene regulations. Hence we studied the regulation of gene expression by TGF-beta in normal and cancer cells. Results Using human 19 K cDNA microarrays, we show that 1757 genes are exclusively regulated by TGF-beta in A549 cells in contrast to 733 genes exclusively regulated in HPL1D cells. In addition, 267 genes are commonly regulated in both the cell-lines. Semi-quantitative and real-time qRT-PCR analysis of some genes agrees with the microarray data. In order to identify the signalling pathways that influence TGF-beta mediated gene regulation, we used specific inhibitors of p38 MAP kinase, ERK kinase, JNK kinase and integrin signalling pathways. The data suggest that regulation of majority of the selected genes is dependent on at least one of these pathways and this dependence is cell-type specific. Interestingly, an integrin pathway inhibitor, RGD peptide, significantly affected TGF-beta regulation of Thrombospondin 1 in A549 cells. Conclusion These data suggest major differences with respect to TGF-beta mediated gene regulation in normal and transformed cells and significant role of non-canonical TGF-beta pathways in the regulation of many genes by TGF-beta.

Neutrophils that infiltrate the central nervous system regulate T cell responses

DEFF Research Database (Denmark)

Zehntner, Simone P; Brickman, Cristina; Bourbonnière, Lyne

2005-01-01

Regulation of inflammatory responses is critical to progression of organ-specific autoimmune disease. Although many candidate cell types have been identified, immunoregulatory activity has rarely been directly assayed and never from the CNS. We have analyzed the regulatory capability of Gr-1high ...

PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at the inhibitory site

International Nuclear Information System (INIS)

Jung, Sujin; Kang, Jeong Gu; Lee, Ju Hee; Song, Kyoung Jin; Ko, Jeong-Heon; Kim, Yong-Sam

2014-01-01

Highlights: • PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at Thr 387 . • Overexpression of PHLPP1 sensitizes contact inhibition. • Tumor cells with suppressed PHLPP1 expression are refractory to apoptosis and highly proliferative. • Loss or down-regulation of PHLPP1 may drive tumor development and progression. - Abstract: Contact inhibition has been largely elusive despite that a loss of contact inhibition is a critical event for cancer development and progression. Here, we report that PHLPP1 is a binding protein for Mst1 and it modulates the Hippo pathway by dephosphorylating Mst1 at the inhibitory Thr 387 of Mst1. Yap1 was localized predominantly in the nucleus but marginally in the cytoplasm in HeLa cells under sparse conditions, whereas the functional protein was more directed to sequestration in the cytoplasm under dense environments. Furthermore, loss of PHLPP1 resulted in a failure of the apoptotic control. It is interesting that down-regulated expression of PHLPP1 appears to mimic the loss of contact inhibition, a hallmark of cancer

PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at the inhibitory site

Energy Technology Data Exchange (ETDEWEB)

Jung, Sujin; Kang, Jeong Gu [Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon (Korea, Republic of); Lee, Ju Hee [Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon (Korea, Republic of); Department of Biomolecular Science, University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon (Korea, Republic of); Song, Kyoung Jin [Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon (Korea, Republic of); Ko, Jeong-Heon [Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon (Korea, Republic of); Department of Biomolecular Science, University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon (Korea, Republic of); Kim, Yong-Sam, E-mail: omsys1@kribb.re.kr [Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon (Korea, Republic of); Department of Biomolecular Science, University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon (Korea, Republic of)

2014-01-24

Highlights: • PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at Thr{sup 387}. • Overexpression of PHLPP1 sensitizes contact inhibition. • Tumor cells with suppressed PHLPP1 expression are refractory to apoptosis and highly proliferative. • Loss or down-regulation of PHLPP1 may drive tumor development and progression. - Abstract: Contact inhibition has been largely elusive despite that a loss of contact inhibition is a critical event for cancer development and progression. Here, we report that PHLPP1 is a binding protein for Mst1 and it modulates the Hippo pathway by dephosphorylating Mst1 at the inhibitory Thr{sup 387} of Mst1. Yap1 was localized predominantly in the nucleus but marginally in the cytoplasm in HeLa cells under sparse conditions, whereas the functional protein was more directed to sequestration in the cytoplasm under dense environments. Furthermore, loss of PHLPP1 resulted in a failure of the apoptotic control. It is interesting that down-regulated expression of PHLPP1 appears to mimic the loss of contact inhibition, a hallmark of cancer.

PPARγ regulates exocrine pancreas lipase.

Science.gov (United States)

Danino, Hila; Naor, Ronny Peri-; Fogel, Chen; Ben-Harosh, Yael; Kadir, Rotem; Salem, Hagit; Birk, Ruth

2016-12-01

Pancreatic lipase (triacylglycerol lipase EC 3.1.1.3) is an essential enzyme in hydrolysis of dietary fat. Dietary fat, especially polyunsaturated fatty acids (PUFA), regulate pancreatic lipase (PNLIP); however, the molecular mechanism underlying this regulation is mostly unknown. As PUFA are known to regulate expression of proliferator-activated receptor gamma (PPARγ), and as we identified in-silico putative PPARγ binding sites within the putative PNLIP promoter sequence, we hypothesized that PUFA regulation of PNLIP might be mediated by PPARγ. We used in silico bioinformatics tools, reporter luciferase assay, PPARγ agonists and antagonists, PPARγ overexpression in exocrine pancreas AR42J and primary cells to study PPARγ regulation of PNLIP. Using in silico bioinformatics tools we mapped PPARγ binding sites (PPRE) to the putative promoter region of PNLIP. Reporter luciferase assay in AR42J rat exocrine pancreas acinar cells transfected with various constructs of the putative PNLIP promoter showed that PNLIP transcription is significantly enhanced by PPARγ dose-dependently, reaching maximal levels with multi PPRE sites. This effect was significantly augmented in the presence of PPARγ agonists and reduced by PPARγ antagonists or mutagenesis abrogating PPRE sites. Over-expression of PPARγ significantly elevated PNLIP transcript and protein levels in AR42J cells and in primary pancreas cells. Moreover, PNLIP expression was up-regulated by PPARγ agonists (pioglitazone and 15dPGJ2) and significantly down-regulated by PPARγ antagonists in non-transfected rat exocrine pancreas AR42J cell line cells. PPARγ transcriptionally regulates PNLIP gene expression. This transcript regulation resolves part of the missing link between dietary PUFA direct regulation of PNLIP. Copyright © 2016 Elsevier B.V. All rights reserved.

Regulation of nucleolus assembly by non-coding RNA polymerase II transcripts.

Science.gov (United States)

Caudron-Herger, Maïwen; Pankert, Teresa; Rippe, Karsten

2016-05-03

The nucleolus is a nuclear subcompartment for tightly regulated rRNA production and ribosome subunit biogenesis. It also acts as a cellular stress sensor and can release enriched factors in response to cellular stimuli. Accordingly, the content and structure of the nucleolus change dynamically, which is particularly evident during cell cycle progression: the nucleolus completely disassembles during mitosis and reassembles in interphase. Although the mechanisms that drive nucleolar (re)organization have been the subject of a number of studies, they are only partly understood. Recently, we identified Alu element-containing RNA polymerase II transcripts (aluRNAs) as important for nucleolar structure and rRNA synthesis. Integrating these findings with studies on the liquid droplet-like nature of the nucleolus leads us to propose a model on how RNA polymerase II transcripts could regulate the assembly of the nucleolus in response to external stimuli and during cell cycle progression.

Self-regulation: the need to succeed

International Nuclear Information System (INIS)

Sorenson, G.C.

1985-01-01

The nuclear industry has long complained that it is over-regulated. Others - including the regulator - are now beginning to accept this complaint and acknowledge that perhaps the industry is over regulated and something should be done to provide relief. It is clear that regulation will not simply go away. The industry is perceived by some as one that cannot be trusted and must be closely regulated or serious health and safety consequences will result. Headlines claiming coverup of design deficiencies, allegations concerning construction problems, cheating on exams, mismanagement, intimidation of QA/QC personnel, etc., do little to dispel these concerns for the layman. This paper looks at two areas that must be considered in attempting to decrease the amount of regulator-imposed activities and increase self-regulation: 1) establish greater trust and confidence in the industry's ability to do a good job and be responsible for self-regulation; and 2) establish industry initiatives to regulate itself

Nuclear regulation in transition

International Nuclear Information System (INIS)

Tomain, J.P.

1986-01-01

The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed. (author)

Nuclear regulation in transition

Energy Technology Data Exchange (ETDEWEB)

Tomain, J.P. (Cincinnati Univ., OH, US. Coll. of Law)

1986-01-01

The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed.

Drinking Water Contaminants -- Standards and Regulations

Science.gov (United States)

... and Research Centers Contact Us Share Drinking Water Contaminants – Standards and Regulations EPA identifies contaminants to regulate ... other partners to implement these SDWA provisions. Regulated Contaminants National Primary Drinking Water Regulations (NPDWRs) - table of ...

Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest

International Nuclear Information System (INIS)

Uchida, Fumihiko; Uzawa, Katsuhiro; Kasamatsu, Atsushi; Takatori, Hiroaki; Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Tanzawa, Hideki; Bukawa, Hiroki

2012-01-01

Cell division cycle associated 3 (CDCA3), part of the Skp1-cullin-F-box (SCF) ubiquitin ligase, refers to a trigger of mitotic entry and mediates destruction of the mitosis inhibitory kinase. Little is known about the relevance of CDCA3 to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of CDCA3 in OSCC. We evaluated CDCA3 mRNA and protein expression in both OSCC-derived cell lines and primary OSCCs and performed functional analyses of CDCA3 in OSCC-derived cells using the shRNA system. The CDCA3 expression at both the mRNA and protein levels was frequently up-regulated in all cell lines examined and primary tumors (mRNA, 51/69, 74 %; protein, 79/95, 83 %) compared to normal controls (p < 0.001). In contrast, no significant level of CDCA3 protein expression was seen in oral premalignant lesions (OPLs) (n = 20) compared with the expression in OSCCs. Among the clinical variables analyzed, the CDCA3 expression status was closely related to tumor size (p < 0.05). In addition, suppression of CDCA3 expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells by arresting cell-cycle progression at the G1 phase. Further, there was up-regulation of the cyclin-dependent kinase inhibitors (p21 Cip1 , p27 Kip1 , p15 INK4B , and p16 INK4A ) in the knockdown cells. The current results showed that overexpression of CDCA3 occurs frequently during oral carcinogenesis and this overexpression might be associated closely with progression of OSCCs by preventing the arrest of cell-cycle progression at the G1 phase via decreased expression of the cyclin-dependent kinase inhibitors

MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer

Science.gov (United States)

Cekaite, Lina; Eide, Peter W.; Lind, Guro E.; Skotheim, Rolf I.; Lothe, Ragnhild A.

2016-01-01

Gene expression is in part regulated by microRNAs (miRNAs). This review summarizes the current knowledge of miRNAs in colorectal cancer (CRC); their role as growth regulators, the mechanisms that regulate the miRNAs themselves and the potential of miRNAs as biomarkers. Although thousands of tissue samples and bodily fluids from CRC patients have been investigated for biomarker potential of miRNAs (>160 papers presented in a comprehensive tables), none single miRNA nor miRNA expression signatures are in clinical use for this disease. More than 500 miRNA-target pairs have been identified in CRC and we discuss how these regulatory nodes interconnect and affect signaling pathways in CRC progression. PMID:26623728

Epigenetic suppression of neprilysin regulates breast cancer invasion.

Science.gov (United States)

Stephen, H M; Khoury, R J; Majmudar, P R; Blaylock, T; Hawkins, K; Salama, M S; Scott, M D; Cosminsky, B; Utreja, N K; Britt, J; Conway, R E

2016-03-07

In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer

Regulation of semaphorin 4D expression and cell proliferation of ovarian cancer by ERalpha and ERbeta

Directory of Open Access Journals (Sweden)

Y. Liu

Full Text Available Ovarian cancer is one of the most common malignancies in women. Semaphorin 4D (sema 4D is involved in the progress of multiple cancers. In the presence of estrogen-like ligands, estrogen receptors (ERα and ERβ participate in the progress of breast and ovarian cancers by transcriptional regulation. The aim of the study was to investigate the role of sema 4D and elucidate the regulatory pattern of ERα and ERβ on sema 4D expression in ovarian cancers. Sema 4D levels were up-regulated in ovarian cancer SKOV-3 cells. Patients with malignant ovarian cancers had significantly higher sema 4D levels than controls, suggesting an oncogene role of sema 4D in ovarian cancer. ERα expressions were up-regulated in SKOV-3 cells compared with normal ovarian IOSE80 epithelial cells. Conversely, down-regulation of ERβ was observed in SKOV-3 cells. Forced over-expression of ERα and ERβ in SKOV-3 cells was manipulated to establish ERα+ and ERβ+ SKOV-3 cell lines. Incubation of ERα+ SKOV-3 cells with ERs agonist 17β-estradiol (E2 significantly enhanced sema 4D expression and rate of cell proliferation. Incubated with E2, ERβ+ SKOV-3 cells showed lower sema 4D expression and cell proliferation. Blocking ERα and ERβ activities with ICI182-780 inhibitor, sema 4D expressions and cell proliferation of ERα+ and ERβ+ SKOV-3 cells were recovered to control levels. Taken together, the data showed that sema 4D expression was positively correlated with the progress of ovarian cancer. ERα positively regulated sema 4D expression and accelerated cell proliferation. ERβ negatively regulated sema 4D expression and inhibited cell multiplication.

Trout Stream Special Regulations

Data.gov (United States)

Minnesota Department of Natural Resources — This layer shows Minnesota trout streams that have a special regulation as described in the 2006 Minnesota Fishing Regulations. Road crossings were determined using...

Global approaches to regulating electronic cigarettes

Science.gov (United States)

Kennedy, Ryan David; Awopegba, Ayodeji; De León, Elaine; Cohen, Joanna E

2017-01-01

Objectives Classify and describe the policy approaches used by countries to regulate e-cigarettes. Methods National policies regulating e-cigarettes were identified by (1) conducting web searches on Ministry of Health websites, and (2) broad web searches. The mechanisms used to regulate e-cigarettes were classified as new/amended laws, or existing laws. The policy domains identified include restrictions or prohibitions on product: sale, manufacturing, importation, distribution, use, product design including e-liquid ingredients, advertising/promotion/sponsorship, trademarks, and regulation requiring: taxation, health warning labels and child-safety standards. The classification of the policy was reviewed by a country expert. Results The search identified 68 countries that regulate e-cigarettes: 22 countries regulate e-cigarettes using existing regulations; 25 countries enacted new policies to regulate e-cigarettes; 7 countries made amendments to existing legislation; 14 countries use a combination of new/amended and existing regulation. Common policies include a minimum-age-of-purchase, indoor-use (vape-free public places) bans and marketing restrictions. Few countries are applying a tax to e-cigarettes. Conclusions A range of regulatory approaches are being applied to e-cigarettes globally; many countries regulate e-cigarettes using legislation not written for e-cigarettes. PMID:27903958

Strategic choices in the environmental debate: Environmental regulation and self-regulation

DEFF Research Database (Denmark)

Ulhøi, John Parm

Den aktuelle miljødebat, der føres i litteraturen, kan give direkte anledning til den uheldige opfattelse, at det overvejende er et spørgsmål om miljøregulering eller indirekte regulering baseret på markedskræfterne. Dette er i modstrid med den kendsgerning, at der findes mange kombinationer i...

Implications of Circadian Rhythm in Dopamine and Mood Regulation.

Science.gov (United States)

Kim, Jeongah; Jang, Sangwon; Choe, Han Kyoung; Chung, Sooyoung; Son, Gi Hoon; Kim, Kyungjin

2017-07-31

Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-erbα induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

Functional analysis of the cell cycle regulator Rca1 in Drosophila melanogaster

OpenAIRE

Zielke, Norman

2007-01-01

Tight regulation of APC/C activity is essential for cell cycle progression. An important class of negative APC/C regulators are the Rca1/Emi1 family proteins. All members of the Rca1/Emi1 family share a conserved zinc binding region (ZBR) which is essential for their inhibitory activity. The Rca1/Emi1 proteins belong to the class of F-box proteins that are known to act as substrate recognition subunits in SCF-E3-ligase complexes. Emi1 and Rca1 interact in vitro with members of the Skp family ...

Hepatocyte produced matrix metalloproteinases are regulated by CD147 in liver fibrogenesis.

Science.gov (United States)

Calabro, Sarah R; Maczurek, Annette E; Morgan, Alison J; Tu, Thomas; Wen, Victoria W; Yee, Christine; Mridha, Auvro; Lee, Maggie; d'Avigdor, William; Locarnini, Stephen A; McCaughan, Geoffrey W; Warner, Fiona J; McLennan, Susan V; Shackel, Nicholas A

2014-01-01

The classical paradigm of liver injury asserts that hepatic stellate cells (HSC) produce, remodel and turnover the abnormal extracellular matrix (ECM) of fibrosis via matrix metalloproteinases (MMPs). In extrahepatic tissues MMP production is regulated by a number of mechanisms including expression of the glycoprotein CD147. Previously, we have shown that CD147 is expressed on hepatocytes but not within the fibrotic septa in cirrhosis [1]. Therefore, we investigated if hepatocytes produce MMPs, regulated by CD147, which are capable of remodelling fibrotic ECM independent of the HSC. Non-diseased, fibrotic and cirrhotic livers were examined for MMP activity and markers of fibrosis in humans and mice. CD147 expression and MMP activity were co-localised by in-situ zymography. The role of CD147 was studied in-vitro with siRNA to CD147 in hepatocytes and in-vivo in mice with CCl4 induced liver injury using ãCD147 antibody intervention. In liver fibrosis in both human and mouse tissue MMP expression and activity (MMP-2, -9, -13 and -14) increased with progressive injury and localised to hepatocytes. Additionally, as expected, MMPs were abundantly expressed by activated HSC. Further, with progressive fibrosis there was expression of CD147, which localised to hepatocytes but not to HSC. Functionally significant in-vitro regulation of hepatocyte MMP production by CD147 was demonstrated using siRNA to CD147 that decreased hepatocyte MMP-2 and -9 expression/activity. Further, in-vivo α-CD147 antibody intervention decreased liver MMP-2, -9, -13, -14, TGF-β and α-SMA expression in CCl4 treated mice compared to controls. We have shown that hepatocytes produce active MMPs and that the glycoprotein CD147 regulates hepatocyte MMP expression. Targeting CD147 regulates hepatocyte MMP production both in-vitro and in-vivo, with the net result being reduced fibrotic matrix turnover in-vivo. Therefore, CD147 regulation of hepatocyte MMP is a novel pathway that could be targeted by

Hepatocyte produced matrix metalloproteinases are regulated by CD147 in liver fibrogenesis.

Directory of Open Access Journals (Sweden)

Sarah R Calabro

Full Text Available The classical paradigm of liver injury asserts that hepatic stellate cells (HSC produce, remodel and turnover the abnormal extracellular matrix (ECM of fibrosis via matrix metalloproteinases (MMPs. In extrahepatic tissues MMP production is regulated by a number of mechanisms including expression of the glycoprotein CD147. Previously, we have shown that CD147 is expressed on hepatocytes but not within the fibrotic septa in cirrhosis [1]. Therefore, we investigated if hepatocytes produce MMPs, regulated by CD147, which are capable of remodelling fibrotic ECM independent of the HSC.Non-diseased, fibrotic and cirrhotic livers were examined for MMP activity and markers of fibrosis in humans and mice. CD147 expression and MMP activity were co-localised by in-situ zymography. The role of CD147 was studied in-vitro with siRNA to CD147 in hepatocytes and in-vivo in mice with CCl4 induced liver injury using ãCD147 antibody intervention.In liver fibrosis in both human and mouse tissue MMP expression and activity (MMP-2, -9, -13 and -14 increased with progressive injury and localised to hepatocytes. Additionally, as expected, MMPs were abundantly expressed by activated HSC. Further, with progressive fibrosis there was expression of CD147, which localised to hepatocytes but not to HSC. Functionally significant in-vitro regulation of hepatocyte MMP production by CD147 was demonstrated using siRNA to CD147 that decreased hepatocyte MMP-2 and -9 expression/activity. Further, in-vivo α-CD147 antibody intervention decreased liver MMP-2, -9, -13, -14, TGF-β and α-SMA expression in CCl4 treated mice compared to controls.We have shown that hepatocytes produce active MMPs and that the glycoprotein CD147 regulates hepatocyte MMP expression. Targeting CD147 regulates hepatocyte MMP production both in-vitro and in-vivo, with the net result being reduced fibrotic matrix turnover in-vivo. Therefore, CD147 regulation of hepatocyte MMP is a novel pathway that could be

76 FR 62630 - Information Security Regulations

Science.gov (United States)

2011-10-11

... CENTRAL INTELLIGENCE AGENCY 32 CFR Part 1902 Information Security Regulations AGENCY: Central... information security regulations which have become outdated. The Executive Order upon which the regulations... CFR Part 1902 Information security regulations. PART 1902 [REMOVED AND RESERVED] Sec. 1902.13 [Removed...

Overview of OVATE FAMILY PROTEINS, a novel class of plant-specific growth regulators

Directory of Open Access Journals (Sweden)

Shucai eWang

2016-03-01

Full Text Available OVATE FAMILY PROTEINS (OFPs are a class of proteins with a conserved OVATE domain. OVATE protein was first identified in tomato as a key regulator of fruit shape. OFPs are plant-specific proteins that are widely distributed in the plant kingdom including mosses and lycophytes. Transcriptional activity analysis of Arabidopsis OFPs (AtOFPs in protoplasts suggests that they act as transcription repressors. Functional characterization of OFPs from different plant species including Arabidopsis, rice, tomato, pepper and banana suggests that OFPs regulate multiple aspects of plant growth and development, which is likely achieved by interacting with different types of transcription factors including the KNOX and BELL classes, and/or directly regulating the expression of target genes such as Gibberellin 20 oxidase (GA20ox. Here, we examine how OVATE was originally identified, summarize recent progress in elucidation of the roles of OFPs in regulating plant growth and development, and describe possible mechanisms underpinning this regulation. Finally, we review potential new research directions that could shed additional light on the functional biology of OFPs in plants.

miR-208-3p promotes hepatocellular carcinoma cell proliferation and invasion through regulating ARID2 expression

Energy Technology Data Exchange (ETDEWEB)

Yu, Peng; Wu, Dingguo; You, Yu; Sun, Jing; Lu, Lele; Tan, Jiaxing; Bie, Ping, E-mail: bieping2010@163.com

2015-08-15

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at post-transcriptional level. miRNA dysregulation plays a causal role in cancer progression. In this study, miR-208-3p was highly expressed and directly repressed ARID2 expression. As a result, ARID2 expression in hepatocellular carcinoma (HCC) was decreased. In vitro, miR-208-3p down-regulation and ARID2 over-expression elicited similar inhibitory effects on HCC cell proliferation and invasion. In vivo test results revealed that miR-208-3p down-regulation inhibited HCC tumorigenesis in Hep3B cells. Moreover, ARID2 was possibly a downstream element of transforming growth factor beta1 (TGFβ1)/miR-208-3p/ARID2 regulatory pathway. These findings suggested that miR-208-3p up-regulation is associated with HCC cell progression and may provide a new target for liver cancer treatment. - Highlights: • miR-208-3p was highly expressed and directly repressed the expression of ARID2 in HCC. • miR-208-3p contributed to HCC cell progression both in vitro and in vivo. • Over-expression of ARID2 inhibited the HCC cell proliferation and invasion. • Restoration of ARID2 partly reversed the the effect of miR-208-3p down-regulation on HCC cells. • Newly regulatory pathway: miR-208-3p mediated the repression of ARID2 by TGFβ1 in HCC cells.

Soft Regulation with Crowd Recommendation: Coordinating Self-Interested Agents in Sociotechnical Systems under Imperfect Information

Science.gov (United States)

2016-01-01

Regulating emerging industries is challenging, even controversial at times. Under-regulation can result in safety threats to plant personnel, surrounding communities, and the environment. Over-regulation may hinder innovation, progress, and economic growth. Since one typically has limited understanding of, and experience with, the novel technology in practice, it is difficult to accomplish a properly balanced regulation. In this work, we propose a control and coordination policy called soft regulation that attempts to strike the right balance and create a collective learning environment. In soft regulation mechanism, individual agents can accept, reject, or partially accept the regulator’s recommendation. This non-intrusive coordination does not interrupt normal operations. The extent to which an agent accepts the recommendation is mediated by a confidence level (from 0 to 100%). Among all possible recommendation methods, we investigate two in particular: the best recommendation wherein the regulator is completely informed and the crowd recommendation wherein the regulator collects the crowd’s average and recommends that value. We show by analysis and simulations that soft regulation with crowd recommendation performs well. It converges to optimum, and is as good as the best recommendation for a wide range of confidence levels. This work sheds a new theoretical perspective on the concept of the wisdom of crowds. PMID:26977699

Nanomaterials: Regulation and Risk Assessment

DEFF Research Database (Denmark)

Hansen, Steffen Foss; Grieger, Khara Deanne; Baun, Anders

2013-01-01

, the Water Framework Directive, pharmaceuticals regulation, and the Novel Foods Regulation. Current regulation of nanomaterials entail three overall challenges: 1) limitations in regard to terminology and definitions of key terms such as a “substance,” “novel food,” etc.; 2) safety assessment requirements...

International Religion Indexes: Government Regulation, Government Favoritism, and Social Regulation of Religion*

Science.gov (United States)

Grim, Brian J.; Finke, Roger

2014-01-01

The study of religion is severely handicapped by a lack of adequate cross-national data. Despite the prominence of religion in international events and recent theoretical models pointing to the consequences of regulating religion, cross-national research on religion has been lacking. We strive to fill this void by developing measurement models and indexes for government regulation, government favoritism, and social regulation of religion. The indexes rely on data from an extensive coding of the 2003 International Religious Freedom Report for 196 countries and territories. Using a series of tests to evaluate the new data and indexes, we find that the measures developed are highly reliable and valid. The three indexes will allow researchers and others to measure the government’s subsidy and regulation of religion as well as the restrictions placed on religion by social and cultural forces beyond the state. PMID:25484633

Differential regulation of HIF-1α and HIF-2α in neuroblastoma: Estrogen-related receptor alpha (ERRα) regulates HIF2A transcription and correlates to poor outcome

International Nuclear Information System (INIS)

Hamidian, Arash; Stedingk, Kristoffer von; Munksgaard Thorén, Matilda; Mohlin, Sofie; Påhlman, Sven

2015-01-01

Hypoxia-inducible factors (HIFs) are differentially regulated in tumor cells. While the current paradigm supports post-translational regulation of the HIF-α subunits, we recently showed that hypoxic HIF-2α is also transcriptionally regulated via insulin-like growth factor (IGF)-II in the childhood tumor neuroblastoma. Here, we demonstrate that transcriptional regulation of HIF-2α seems to be restricted to neural cell-derived tumors, while HIF-1α is canonically regulated at the post-translational level uniformly across different tumor forms. Enhanced expression of HIF2A mRNA at hypoxia is due to de novo transcription rather than increased mRNA stability, and chemical stabilization of the HIF-α proteins at oxygen-rich conditions unexpectedly leads to increased HIF2A transcription. The enhanced HIF2A levels do not seem to be dependent on active HIF-1. Using a transcriptome array approach, we identified members of the Peroxisome proliferator-activated receptor gamma coactivator (PGC)/Estrogen-related receptor (ERR) complex families as potential regulators of HIF2A. Knockdown or inhibition of one of the members, ERRα, leads to decreased expression of HIF2A, and high expression of the ERRα gene ESRRA correlates with poor overall and progression-free survival in a clinical neuroblastoma material consisting of 88 tumors. Thus, targeting of ERRα and pathways regulating transcriptional HIF-2α are promising therapeutic avenues in neuroblastoma. - Highlights: • Transcriptional control of HIF-2α is restricted to neural cell-derived tumors. • Enhanced transcription of HIF2A is not due to increased mRNA stability. • Chemical stabilization of the HIF-α subunits leads to increased HIF2A transcription. • ERRα regulates HIF2A mRNA expression in neuroblastoma. • High expression of ESRRA correlates to poor outcome in neuroblastoma

Differential regulation of HIF-1α and HIF-2α in neuroblastoma: Estrogen-related receptor alpha (ERRα) regulates HIF2A transcription and correlates to poor outcome

Energy Technology Data Exchange (ETDEWEB)

Hamidian, Arash; Stedingk, Kristoffer von; Munksgaard Thorén, Matilda; Mohlin, Sofie; Påhlman, Sven, E-mail: sven.pahlman@med.lu.se

2015-06-05

Hypoxia-inducible factors (HIFs) are differentially regulated in tumor cells. While the current paradigm supports post-translational regulation of the HIF-α subunits, we recently showed that hypoxic HIF-2α is also transcriptionally regulated via insulin-like growth factor (IGF)-II in the childhood tumor neuroblastoma. Here, we demonstrate that transcriptional regulation of HIF-2α seems to be restricted to neural cell-derived tumors, while HIF-1α is canonically regulated at the post-translational level uniformly across different tumor forms. Enhanced expression of HIF2A mRNA at hypoxia is due to de novo transcription rather than increased mRNA stability, and chemical stabilization of the HIF-α proteins at oxygen-rich conditions unexpectedly leads to increased HIF2A transcription. The enhanced HIF2A levels do not seem to be dependent on active HIF-1. Using a transcriptome array approach, we identified members of the Peroxisome proliferator-activated receptor gamma coactivator (PGC)/Estrogen-related receptor (ERR) complex families as potential regulators of HIF2A. Knockdown or inhibition of one of the members, ERRα, leads to decreased expression of HIF2A, and high expression of the ERRα gene ESRRA correlates with poor overall and progression-free survival in a clinical neuroblastoma material consisting of 88 tumors. Thus, targeting of ERRα and pathways regulating transcriptional HIF-2α are promising therapeutic avenues in neuroblastoma. - Highlights: • Transcriptional control of HIF-2α is restricted to neural cell-derived tumors. • Enhanced transcription of HIF2A is not due to increased mRNA stability. • Chemical stabilization of the HIF-α subunits leads to increased HIF2A transcription. • ERRα regulates HIF2A mRNA expression in neuroblastoma. • High expression of ESRRA correlates to poor outcome in neuroblastoma.

Post-transcriptional regulation of vascular endothelial growth factor: Implications for tumor angiogenesis

Institute of Scientific and Technical Information of China (English)

Peter S Yoo; Abby L Mulkeen; Charles H Cha

2006-01-01

Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization,translation, and differential cellular localization of various isoforms. Recent advances in our understanding of posttranscriptional regulation of VEGF include identification of the stabilizing mRNA binding protein, HuR, and the discovery of internal ribosomal entry sites in the 5'UTR of the VEGF mRNA. Monoclonal anti-VEGF antibody was recently approved for use in humans, but suffers from the need for high systemic doses. RNA interference (RNAi)technology is being used in vitro and in animal models with promising results. Here, we review the literature on post-transcriptional regulation of VEGF and describe recent progress in targeting these mechanisms for therapeutic benefit.

Mitochondrial activity in the regulation of stem cell self-renewal and differentiation.

Science.gov (United States)

Khacho, Mireille; Slack, Ruth S

2017-12-01

Mitochondria are classically known as the essential energy producers in cells. As such, the activation of mitochondrial metabolism upon cellular differentiation was deemed a necessity to fuel the high metabolic needs of differentiated cells. However, recent studies have revealed a direct role for mitochondrial activity in the regulation of stem cell fate and differentiation. Several components of mitochondrial metabolism and respiration have now been shown to regulate different aspects of stem cell differentiation through signaling, transcriptional, proteomic and epigenetic modulations. In light of these findings mitochondrial metabolism is no longer considered a consequence of cellular differentiation, but rather a key regulatory mechanism of this process. This review will focus on recent progress that defines mitochondria as the epicenters for the regulation of stem cell fate decisions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Correlation set analysis: detecting active regulators in disease populations using prior causal knowledge

Directory of Open Access Journals (Sweden)

Huang Chia-Ling

2012-03-01

Full Text Available Abstract Background Identification of active causal regulators is a crucial problem in understanding mechanism of diseases or finding drug targets. Methods that infer causal regulators directly from primary data have been proposed and successfully validated in some cases. These methods necessarily require very large sample sizes or a mix of different data types. Recent studies have shown that prior biological knowledge can successfully boost a method's ability to find regulators. Results We present a simple data-driven method, Correlation Set Analysis (CSA, for comprehensively detecting active regulators in disease populations by integrating co-expression analysis and a specific type of literature-derived causal relationships. Instead of investigating the co-expression level between regulators and their regulatees, we focus on coherence of regulatees of a regulator. Using simulated datasets we show that our method performs very well at recovering even weak regulatory relationships with a low false discovery rate. Using three separate real biological datasets we were able to recover well known and as yet undescribed, active regulators for each disease population. The results are represented as a rank-ordered list of regulators, and reveals both single and higher-order regulatory relationships. Conclusions CSA is an intuitive data-driven way of selecting directed perturbation experiments that are relevant to a disease population of interest and represent a starting point for further investigation. Our findings demonstrate that combining co-expression analysis on regulatee sets with a literature-derived network can successfully identify causal regulators and help develop possible hypothesis to explain disease progression.

The Regulation of Street Foods

DEFF Research Database (Denmark)

Forkour, John Boulard; Samuelsen, Helle; Yeboah, Eric Henry

2017-01-01

the challenges and negotiating strategies of regulators of street-vended foods in Ghana and analyses the implication for their relationship with street food vendors. The paper reveals that regulators operate in a context of limited resources, leading to a general feeling of neglect. In coping, regulators adopt...

Self-Regulation in Online Learning

Science.gov (United States)

Cho, Moon-Heum; Shen, Demei

2013-01-01

The purpose of this study was to examine the role of goal orientation and academic self-efficacy in student achievement mediated by effort regulation, metacognitive regulation, and interaction regulation in an online course. The results show that intrinsic goal orientation and academic self-efficacy predicted students' metacognitive…

A novel micromechanical flow regulator

NARCIS (Netherlands)

van Toor, M.W.; van Toor, M.W.; Lammerink, Theodorus S.J.; Gardeniers, Johannes G.E.; Elwenspoek, Michael Curt; Monsma, D.J.

1996-01-01

A new concept for a micromechanical flow regulator is presented. Regulation of the flow is achieved using variation of channel length instead of channel diameter. Several design concepts together with their application in fluidic systems are presented. A regulator for biomedical use, as a part of a

Regulation of the power sector

CERN Document Server

2013-01-01

Regulation of the Power Sector is a unified, consistent and comprehensive treatment of the theories and practicalities of regulation in modern power-supply systems. The need for generation to occur at the time of use occasioned by the impracticality of large-scale electricity storage coupled with constant and often unpredictable changes in demand make electricity-supply systems large, dynamic and complex and their regulation a daunting task. Conceptually arranged in four parts, this book addresses both traditional regulatory frameworks and also liberalized and re-regulated environments. First, an introduction gives a full characterization of power supply including engineering, economic and regulatory viewpoints. The second part presents the fundamentals of regulation and the third looks at the regulation of particular components of the power sector in detail. Advanced topics and subjects still open or subject to dispute form the content of the fourth part. In a sector where regulatory design is the key driver...

The Porphyromonas gingivalis ferric uptake regulator orthologue binds hemin and regulates hemin-responsive biofilm development.

Directory of Open Access Journals (Sweden)

Catherine A Butler

Full Text Available Porphyromonas gingivalis is a Gram-negative pathogen associated with the biofilm-mediated disease chronic periodontitis. P. gingivalis biofilm formation is dependent on environmental heme for which P. gingivalis has an obligate requirement as it is unable to synthesize protoporphyrin IX de novo, hence P. gingivalis transports iron and heme liberated from the human host. Homeostasis of a variety of transition metal ions is often mediated in Gram-negative bacteria at the transcriptional level by members of the Ferric Uptake Regulator (Fur superfamily. P. gingivalis has a single predicted Fur superfamily orthologue which we have designated Har (heme associated regulator. Recombinant Har formed dimers in the presence of Zn2+ and bound one hemin molecule per monomer with high affinity (Kd of 0.23 µM. The binding of hemin resulted in conformational changes of Zn(IIHar and residue 97Cys was involved in hemin binding as part of a predicted -97C-98P-99L- hemin binding motif. The expression of 35 genes was down-regulated and 9 up-regulated in a Har mutant (ECR455 relative to wild-type. Twenty six of the down-regulated genes were previously found to be up-regulated in P. gingivalis grown as a biofilm and 11 were up-regulated under hemin limitation. A truncated Zn(IIHar bound the promoter region of dnaA (PGN_0001, one of the up-regulated genes in the ECR455 mutant. This binding decreased as hemin concentration increased which was consistent with gene expression being regulated by hemin availability. ECR455 formed significantly less biofilm than the wild-type and unlike wild-type biofilm formation was independent of hemin availability. P. gingivalis possesses a hemin-binding Fur orthologue that regulates hemin-dependent biofilm formation.

Ocean Dumping Control Regulations

International Nuclear Information System (INIS)

1978-01-01

These Regulations were made further to the Ocean Dumping Control Act which provides for restrictions in dumping operations. The Regulations contain model applications for permits to dump or load a series of materials. (NEA)

Regulation of Genetic Tests

Science.gov (United States)

... for Genomics Research Intellectual Property Issues in Genetics Archive Online Bioethics Resources Privacy in Genomics Regulation of ... are not regulated, meaning that they go to market without any independent analysis to verify the claims ...

Virulence regulation in Staphylococcus aureus: the need for in vivo analysis of virulence factor regulation.

Science.gov (United States)

Pragman, Alexa A; Schlievert, Patrick M

2004-10-01

Staphylococcus aureus is a pathogenic microorganism that is responsible for a wide variety of clinical infections. These infections can be relatively mild, but serious, life-threatening infections may result from the expression of staphylococcal virulence factors that are coordinated by virulence regulators. Much work has been done to characterize the actions of staphylococcal virulence regulators in broth culture. Recently, several laboratories showed that transcriptional analyses of virulence regulators in in vivo animal models or in human infection did not correlate with transcriptional analyses accomplished in vitro. In describing the differences between in vitro and in vivo transcription of staphylococcal virulence regulators, we hope to encourage investigators to study virulence regulators using infection models whenever possible.

EU Regulation of Nanobiocides: Challenges in Implementing the Biocidal Product Regulation (BPR)

DEFF Research Database (Denmark)

Brinch, Anna; Hansen, Steffen Foss; Hartmann, Nanna B.

2016-01-01

The Biocidal Products Regulation (BPR) contains several provisions for nanomaterials (NMs) and is the first regulation in the European Union to require specific testing and risk assessment for the NM form of a biocidal substance as a part of the information requirements. Ecotoxicological data...

Progranulin, lysosomal regulation and neurodegenerative disease.

Science.gov (United States)

Kao, Aimee W; McKay, Andrew; Singh, Param Priya; Brunet, Anne; Huang, Eric J

2017-06-01

The discovery that heterozygous and homozygous mutations in the gene encoding progranulin are causally linked to frontotemporal dementia and lysosomal storage disease, respectively, reveals previously unrecognized roles of the progranulin protein in regulating lysosome biogenesis and function. Given the importance of lysosomes in cellular homeostasis, it is not surprising that progranulin deficiency has pleiotropic effects on neural circuit development and maintenance, stress response, innate immunity and ageing. This Progress article reviews recent advances in progranulin biology emphasizing its roles in lysosomal function and brain innate immunity, and outlines future avenues of investigation that may lead to new therapeutic approaches for neurodegeneration.

Into the void: Regulating pesticide use in Colorado's commercial cannabis markets.

Science.gov (United States)

Subritzky, Todd; Pettigrew, Simone; Lenton, Simon

2017-04-01

In 2014, Colorado implemented the world's first seed-to-sale recreational cannabis market under a commercial model. This paper aims to provide a thick descriptive account that gives insight into the issues and complexities of Colorado's pioneering and evolving attempt to regulate the use of pesticides on commercial cannabis plantations. The paper examines multiple data sets including: (i) Colorado State Government documents; (ii) recreational cannabis regulations; (iii) mass and niche media publications (n=175); (iv) face-to-face interviews with key stakeholders, including seniors, regulators and industry executives (n=8); and (v) field notes from relevant conferences and cultivation facility tours in Denver in October, 2016. Two key issues are identified. First, a public safety threat has arisen relating to application of pesticides on cannabis with intensified toxicity in concentrated products of particular concern. Second, as a pioneering jurisdiction, Colorado faces a considerable knowledge gap. To expand collective learning on this issue, for which no regulatory template and little research exists, state regulators tapped industry and other stakeholder expertise while attempting to ensure public safety goals were achieved and regulatory capture by industry was limited. Four years since the recreational cannabis market in Colorado was legalised, the State continues to grapple with the pesticide issue as testing regulations and cultivation standards are yet to be finalised. While more work is needed, Colorado has made significant progress in developing regulations relating to this complex matter. As governments of countries such as Canada and US states, including California, contemplate changes to recreational cannabis laws, Colorado's experience can assist regulators in other jurisdictions considering policy change. Copyright © 2017 Elsevier B.V. All rights reserved.

Designing Next Generation Telecom Regulation

DEFF Research Database (Denmark)

Henten, Anders; Samarajiva, Rohan

– ICT convergence regulation and multisector utility regulation. Whatever structure of next generation telecom regulation is adopted, all countries will need to pay much greater attention to the need for increased coordination of policy directions and regulatory activities both across the industries......Continuously expanding applications of information and communication technologies (ICT) are transforming local, national, regional and international economies into network economies, the foundation for information societies. They are being built upon expanded and upgraded national telecom networks...... to creating an environment to foster a massive expansion in the coverage and capabilities of the information infrastructure networks, with national telecom regulators as the key implementers of the policies of reform. The first phase of reform has focused on industry specific telecom policy and regulation...

The role of interest, self-efficacy and academic self-regulation in ...

African Journals Online (AJOL)

The role of interest, self-efficacy and academic self-regulation in predicting academic achievement of students of Islamic Azad University. ... academic achievement and among subtests of interest only subtests of confidence has ability to predict academic achievement, but self-efficacy is not able to predict students' progress.

Biophysical force regulation in 3D tumor cell invasion

Science.gov (United States)

Wu, Mingming

When embedded within 3D extracellular matrices (ECM), animal cells constantly probe and adapt to the ECM locally (at cell length scale) and exert forces and communicate with other cells globally (up to 10 times of cell length). It is now well accepted that mechanical crosstalk between animal cells and their microenvironment critically regulate cell function such as migration, proliferation and differentiation. Disruption of the cell-ECM crosstalk is implicated in a number of pathologic processes including tumor progression and fibrosis. Central to the problem of cell-ECM crosstalk is the physical force that cells generate. By measuring single cell generated force within 3D collagen matrices, we revealed a mechanical crosstalk mechanism between the tumor cells and the ECM. Cells generate sufficient force to stiffen collagen fiber network, and stiffer matrix, in return promotes larger cell force generation. Our work highlights the importance of fibrous nonlinear elasticity in regulating tumor cell-ECM interaction, and results may have implications in the rapid tissue stiffening commonly found in tumor progression and fibrosis. This work is partially supported by NIH Grants R21RR025801 and R21GM103388.

Regulation of Fanconi anemia protein FANCD2 monoubiquitination by miR-302

International Nuclear Information System (INIS)

Suresh, Bharathi; Kumar, A. Madhan; Jeong, Hoe-Su; Cho, Youl-Hee; Ramakrishna, Suresh; Kim, Kye-Seong

2015-01-01

Fanconi anemia (FA) is a recessively inherited multigene disease characterized by congenital defects, progressive bone marrow failure, and heightened cancer susceptibility. Monoubiquitination of the FA pathway member FANCD2 contributes to the repair of replication stalling DNA lesions. However, cellular regulation of FANCD2 monoubiquitination remains poorly understood. In the present study, we identified the miR-302 cluster as a potential regulator of FANCD2 by bioinformatics analysis. MicroRNAs (miRNAs) are the major posttranscriptional regulators of a wide variety of biological processes, and have been implicated in a number of diseases. Expression of the exogenous miR-302 cluster (without miR-367) reduced FANCD2 monoubiquitination and nuclear foci formation. Furthermore, miR-302 cells showed extensive chromosomal breakage upon MMC treatment when compared to mock control cells. Taken together, our results suggest that overexpression of miR-302 plays a critical role in the regulation of FANCD2 monoubiquitination, resulting in characteristic defects in DNA repair within cells. - Highlights: • miR-302 binds to the 3′UTR promoter of the FANCD2 gene to regulate gene expression. • miR-302 cluster down-regulates FANCD2 protein expression. • miR-302 cluster reduces FANCD2 monoubiquitination and nuclear foci formation. • miR-302 exhibits the characteristic defects in DNA repair in cells.

Regulation of Fanconi anemia protein FANCD2 monoubiquitination by miR-302

Energy Technology Data Exchange (ETDEWEB)

Suresh, Bharathi [Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); College of Medicine, Hanyang University, Seoul (Korea, Republic of); Kumar, A. Madhan [Center of Research Excellence in Corrosion, Research Institute King Fahd University of Petroleum and Minerals, Dhahran (Saudi Arabia); Jeong, Hoe-Su [Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Cho, Youl-Hee [College of Medicine, Hanyang University, Seoul (Korea, Republic of); Ramakrishna, Suresh, E-mail: suresh.ramakris@gmail.com [Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); College of Medicine, Hanyang University, Seoul (Korea, Republic of); Kim, Kye-Seong, E-mail: ks66kim@hanyang.ac.kr [Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); College of Medicine, Hanyang University, Seoul (Korea, Republic of)

2015-10-16

Fanconi anemia (FA) is a recessively inherited multigene disease characterized by congenital defects, progressive bone marrow failure, and heightened cancer susceptibility. Monoubiquitination of the FA pathway member FANCD2 contributes to the repair of replication stalling DNA lesions. However, cellular regulation of FANCD2 monoubiquitination remains poorly understood. In the present study, we identified the miR-302 cluster as a potential regulator of FANCD2 by bioinformatics analysis. MicroRNAs (miRNAs) are the major posttranscriptional regulators of a wide variety of biological processes, and have been implicated in a number of diseases. Expression of the exogenous miR-302 cluster (without miR-367) reduced FANCD2 monoubiquitination and nuclear foci formation. Furthermore, miR-302 cells showed extensive chromosomal breakage upon MMC treatment when compared to mock control cells. Taken together, our results suggest that overexpression of miR-302 plays a critical role in the regulation of FANCD2 monoubiquitination, resulting in characteristic defects in DNA repair within cells. - Highlights: • miR-302 binds to the 3′UTR promoter of the FANCD2 gene to regulate gene expression. • miR-302 cluster down-regulates FANCD2 protein expression. • miR-302 cluster reduces FANCD2 monoubiquitination and nuclear foci formation. • miR-302 exhibits the characteristic defects in DNA repair in cells.

Feedback regulation between autophagy and PKA.

Science.gov (United States)

Torres-Quiroz, Francisco; Filteau, Marie; Landry, Christian R

2015-01-01

Protein kinase A (PKA) controls diverse cellular processes and homeostasis in eukaryotic cells. Many processes and substrates of PKA have been described and among them are direct regulators of autophagy. The mechanisms of PKA regulation and how they relate to autophagy remain to be fully understood. We constructed a reporter of PKA activity in yeast to identify genes affecting PKA regulation. The assay systematically measures relative protein-protein interactions between the regulatory and catalytic subunits of the PKA complex in a systematic set of genetic backgrounds. The candidate PKA regulators we identified span multiple processes and molecular functions (autophagy, methionine biosynthesis, TORC signaling, protein acetylation, and DNA repair), which themselves include processes regulated by PKA. These observations suggest the presence of many feedback loops acting through this key regulator. Many of the candidate regulators include genes involved in autophagy, suggesting that not only does PKA regulate autophagy but that autophagy also sends signals back to PKA.

Present state of nuclear regulation organizations of main countries in the world. Importance of regulation staffs and requirements

International Nuclear Information System (INIS)

Nishida, Naoki

2013-01-01

After Fukushima accident, NRA (Nuclear Regulation Authority) was established in Japan as an independent organization from promotion. In order to perform effective and reliable nuclear regulation, it was important management organization such as nuclear regulation commission worked efficiently, and also requirements for nuclear regulation staffs engaged in actual regulatory works were of importance so as for appropriate decision making or judgments of management organization. Since regulation staffs needed professional expertise and technical judgment capabilities in wide areas including other than nuclear energy, various efforts had been done to get able regulation staffs in US, France and UK nuclear regulation organizations concerned, which became clarified after overseas investigation for this article. Since knowledge in nuclear industry could be used for effective regulation, mid-career recruitment had been employed in regulation organization of each country so as to take such knowledge and so it was important how to utilize industrial knowledge under appropriate conditions compatible with independence of regulation organization. (T. Tanaka)

Dealing with duplicate regulations and conflicting jurisdictions

International Nuclear Information System (INIS)

Aamodt, P.L.

1991-01-01

There are a number of situations where mixed wastes are regulated by dual regulations and regulators. This presentation attempts to show where such duplication exists and how it evolved historically through legislative actions. The presentation includes a discussion of strategies that have been used to deal with the problems that result from duplicate regulations and jurisdictional conflicts. The RCRA and AEA regulations are really more similar than dissimilar. There are significant issues that must be worked through with the regulators. It is most important to work with your regulators early in process. The following are suggestions for dealing with the regulators. (1) Know the regulations in advance of discussions. (2) Begin dialogue with the regulator(s) as early as possible and get to know the people you will be dealing with -- and let them know you. (3) Explain the technical/regulatory issues/problems that you face at your facility in sufficient detail that they are clearly understood, and work with the regulator(s) to reasonably address them in the language/requirements of the permit. (4) Always attempt to comply with the regulations first before going in with a variance request -- document your efforts, and be honest with your assessment of issues. (5) Don't be adversarial -- remember that the regulator has the same objectives as you do. 1 tab

Complement anaphylatoxins as immune regulators in cancer

OpenAIRE

Sayegh, Eli T; Bloch, Orin; Parsa, Andrew T

2014-01-01

The role of the complement system in innate immunity is well characterized. However, a recent body of research implicates the complement anaphylatoxins C3a and C5a as insidious propagators of tumor growth and progression. It is now recognized that certain tumors elaborate C3a and C5a and that complement, as a mediator of chronic inflammation and regulator of immune function, may in fact foster rather than defend against tumor growth. A putative mechanism for this function is complement-mediat...

Electrical installations and regulations

CERN Document Server

Whitfield, J F

1966-01-01

Electrical Installations and Regulations focuses on the regulations that apply to electrical installations and the reasons for them. Topics covered range from electrical science to alternating and direct current supplies, as well as equipment for providing protection against excess current. Cables, wiring systems, and final subcircuits are also considered, along with earthing, discharge lighting, and testing and inspection.Comprised of 12 chapters, this book begins with an overview of electrical installation work, traits of a good electrician, and the regulations governing installations. The r

Study on the Regulating Performance of Sliding Regulation-Valve

Science.gov (United States)

Hu, Wei; Peng, Xiaoyong; Zhang, Yuan; Zheng, Yulan; Zhu, Fangyao

2018-01-01

Using a proven reliable method of CFD to study the regulating performance of a sliding regulation valve with a conical spool and rugby body. The numerical simulation results indicate that no matter where the spool is located, the flow field always has a vortex at the center of the valve body; When the spool is at the origin, the vortex and resistance coefficient of the valve are the minimum; When the spool moves from the origin to the right (the opening of the valve becomes smaller) to reach a certain position later, vortex currents also begin to appear around the tube wall behind the orifice. In addition, the vortex increases as the throttling port decreases whereas the resistance coefficient of the valve ascends slowly with the increase of the deviation of the spool and the rise in series; This type of regulating valve has S type (slow at both ends, sensitive at the center) flow characteristics at the stroke, and is not affected by the size of Re.

Incentive regulation of nuclear power plants by state regulators

International Nuclear Information System (INIS)

Martin, R.L.; Baker, K.; Olson, J.

1991-02-01

The Nuclear Regulatory Commission (NRC) monitors incentive programs established by state regulators in order to obtain current information and to consider the potential safety effects of the incentive programs as applied to nuclear units. The current report is an update of NUREG/CR-5509, Incentive Regulation of Nuclear Power Plants by State Public Utility Commissions, published in December 1989. The information in this report was obtained from interviews conducted with each state regulator and each utility with a minimum entitlement of 10%. The agreements, orders, and settlements from which each incentive program was implemented were reviewed as required. The interviews and supporting documentation form the basis for the individual state reports describing the structure and financial impact of each incentive program. The programs currently in effect represent the adoption of an existing nuclear performance incentive program proposal and one new program. In addition, since 1989 a number of nuclear units have been included in one existing program; while one program was discontinued and another one concluded. 6 refs., 27 tabs

Safety evaluation and regulation of chemicals. 2. Impact of regulations - improvement of methods

Energy Technology Data Exchange (ETDEWEB)

Homburger, F [ed.

1985-01-01

This volume assesses the impact of new scientific knowledge on the testing and regulation of chemicals, including food additives, drugs, cosmetics, pesticides, and other commercial substances. Apart from describing the newest tests, regulations, and risk assessment strategies, chapters reflect changes forced by both the growing need for cost containment and the mounting pressure to find alternatives to animal testing. Based on an international congress, the book also brings the advantage of diversity in the background and nationality of the authors, thus allowing a view of central problems according to the different interests of academics, industry scientists, government scientists, and regulators. The book opens with coverage of national and international regulations designed to prevent and control damage to human health and the environment. Topics range from basic problems of policy design and enforcement to the specific requirements for chemical regulation in developing countries. The next chapters cover new tests, systems, and assays used in in vivo safety testing. Readers will find a critical assessment of tests used to determine teratogenicity, mutagenicity, carcinogenicity, neurotoxicity and chemical lethality. Other topics include factors operating in the public perception of chemical hazards, guidelines for decision making in the management and regulation of risks, and future trends in the methodology of safety evaluation. The volume concludes with an overview of in vitro methods for testing hepatotoxicity. Several short-term in vitro test models and limited in vivo bioassays are presented and evaluated in terms of their capacity to substitute for long-term animal studies. Expert and thorough in its coverage, the book offers a wealth of technical and practical information for toxicologists, pharmacologists, industrial policy makers, and government regulators. (orig.). With 67 figs., 34 tabs.

Environmental regulation and competitiveness

NARCIS (Netherlands)

Mulatu, A.; Florax, R.J.G.M.; Withagen, C.A.A.M.

2001-01-01

The potential relationship between domestic environmental regulation and international competitiveness has evoked various speculations. The common neoclassical train of thought is that strict environmental regulation is detrimental to the competitiveness of industry, and that it induces phenomena

Proactive and defensive self-regulation in learning

Directory of Open Access Journals (Sweden)

Darko Lončarić

2008-12-01

Full Text Available Although self-regulation research is fragmented over several interdisciplinary areas and theories, the concept of self-regulation could represent a cohesive force for integrating different areas of psychology, such as clinical, educational, or organisational psychology. This paper focuses on self-regulation within the educational framework and elaborates the concept of self-regulated learning. Current advances in self-regulated learning research indicated that concepts, such as cognition and motivation, need to be integrated into a coherent self-regulation model. Two models that integrate cognitive and motivational constructs are described in this paper, namely the motivational and cognitive self-regulation components described by Pintrich and colleagues (e.g., Garcia & Pintrich 1994, and a six component model of self-regulated learning provided by Boekaerts (1997. These models were used to formulate new and parsimonious organisational constructs that classify self-regulation components into proactive and defensive self-regulation patterns. At the end, the applicative value of the models and the need for further research, regarding the question of specific self-regulation failures (the depressive self-regulation pattern, are being discussed.

7 CFR 3.87 - Agency regulations.

Science.gov (United States)

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Agency regulations. 3.87 Section 3.87 Agriculture Office of the Secretary of Agriculture DEBT MANAGEMENT Federal Salary Offset § 3.87 Agency regulations. USDA agencies may issue regulations or policies not inconsistent with OPM regulations (5 CFR part 550...

Nuclear regulation - the Canadian approach

International Nuclear Information System (INIS)

Jennekens, J.

1981-09-01

Although the Atomic Energy Control Board was established 35 years ago the basic philosophy of nuclear regulation in Canada and the underlying principles of the regulatory process remain essentially unchanged. This paper outlines the Canadian approach to nuclear regulation and explains in practical terms how the principles of regulation are applied. (author)

Targeted genome regulation via synthetic programmable transcriptional regulators

KAUST Repository

Piatek, Agnieszka Anna

2016-04-19

Regulation of gene transcription controls cellular functions and coordinates responses to developmental, physiological and environmental cues. Precise and efficient molecular tools are needed to characterize the functions of single and multiple genes in linear and interacting pathways in a native context. Modular DNA-binding domains from zinc fingers (ZFs) and transcriptional activator-like proteins (TALE) are amenable to bioengineering to bind DNA target sequences of interest. As a result, ZF and TALE proteins were used to develop synthetic programmable transcription factors. However, these systems are limited by the requirement to re-engineer proteins for each new target sequence. The clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR associated 9 (Cas9) genome editing tool was recently repurposed for targeted transcriptional regulation by inactivation of the nuclease activity of Cas9. Due to the facile engineering, simplicity, precision and amenability to library construction, the CRISPR/Cas9 system is poised to revolutionize the functional genomics field across diverse eukaryotic species. In this review, we discuss the development of synthetic customizable transcriptional regulators and provide insights into their current and potential applications, with special emphasis on plant systems, in characterization of gene functions, elucidation of molecular mechanisms and their biotechnological applications. © 2016 Informa UK Limited, trading as Taylor & Francis Group

Re-Framing Biotechnology Regulation.

Science.gov (United States)

Peck, Alison

Biotechnology is about to spill the banks of federal regulation. New genetic engineering techniques like CRISPR-Cas9 promise revolutionary breakthroughs in medicine, agriculture, and public health—but those techniques would not be regulated under the terms of the Coordinated Framework for Regulation of Biotechnology. This revolutionary moment in biotechnology offers an opportunity to correct the flaws in the framework, which was hastily patched together at the advent of the technology. The framework has never captured all relevant technologies, has never satisfied the public that risk is being effectively managed, and has never been accessible to small companies and publicly-funded labs that increasingly are positioned to make radical, life-saving innovations. This Article offers a proposal for new legislation that would reshape biotechnology regulation to better meet these goals. Key reforms include tying regulation to risk rather than technology category; consolidating agency review; capturing distinct regulatory expertise through inter-agency consultations; creating a clearinghouse to help guide applicants and disseminate information; setting up more comprehensive monitoring of environmental effects; and providing federal leadership to fill key data gaps and address socio-economic impacts.

Natural Gas Regulation

International Nuclear Information System (INIS)

1995-01-01

The regulation of Natural Gas. Natural gas Regulation clarifies and consolidates the legal and institutional framework for development of the industry through six principal elements: 1) Establishment of a vision of the industry. 2) Development of regulatory objectives. 3) Determination of relationships among industry participants. 4) Clear specification of the role of PEMEX in the industry. 5) Definition of the functions of the Regulatory authority. 6) Creation of a transition regime. In parallel with the development of the substantive legal framework, the law of the Comision Reguladora de Energia (CRE) was also enacted by Congress in October 1995 to strength the institutional framework and implement the legal changes. This law defines the CRE as an agency of the Energy Ministry with technical, operational, and budgetary autonomy, and responsibility for implementing natural gas industry regulation. (Author)

Volume Regulated Channels

DEFF Research Database (Denmark)

Klausen, Thomas Kjær

of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume...... but are also essential for a number of physiological processes such as proliferation, controlled cell death, migration and endocrinology. The thesis have been focusing on two Channels, namely the swelling activated Cl- channel (ICl, swell) and the transient receptor potential Vanilloid (TRPV4) channel. I: Cl......- serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...

Culture as Mediator: Co-Regulation, Self-Regulation, and Middle School Mathematics Achievement

Science.gov (United States)

Hinnant-Crawford, Brandi Nicole; Faison, Morgan Z.; Chang, Mei-Lin

2016-01-01

Purpose: Self-regulation is defined as strategic, metacognitive behavior, motivation and cognition aimed at a goal (Zimmmerman and Schunk, 2011). Co-regulation, arguably more aligned with norms in communal cultures, is the process of learners sharing "a common problem-solving plane" through which self-regulatory strategies are learned…

Regulation of GMOs in China.

Science.gov (United States)

Liu, Yinliang

2008-12-01

Genetically modified organisms (GMOs) are created by biotechnology to serve people with much benefit while may impose risks to ecological environment and human health and therefore need careful regulation. During the past two decades, GMOs have been well developed in China and so has their corresponding regulation. This paper reviews and comments the multiple aspects of mainly the agricultural GMOs, including their safety assessment, control measures, trade activities, import, labels, and GM food, which have been prescribed by the corresponding laws, regulations and administrative measures. It is held that till present a framework for regulation of agricultural GMOs and GM food has been established basically in China, while a more comprehensive system for regulation of all kinds of GMOs and all kinds of related activities is still needed at present and in the future.

Atomic Energy Control Regulations

International Nuclear Information System (INIS)

1992-01-01

This is the consolidated text of the Atomic Energy Control Regulations of 17 March 1960, with amendments to 27 August 1992. The Regulations cover the licensing of nuclear facilities, radiation sources, including uranium mining, radiation protection questions, etc. (NEA)

„The Control” in View of International Accounting Regulation and Romanian Accounting Regulation

Directory of Open Access Journals (Sweden)

Cristina Ciuraru-Andrica

2010-12-01

Full Text Available In Romania, financial reporting accountant is governed by Accounting Low number 82/1991, republished, and O.M.F.P. 3.055/2009 approving the accounting regulation in accordance with European Directives. To these are added the International Financial Reporting Standards (IFRS, IAS and IFRIC of which must take into account certain Romanian legal persons in accordance with applicable regulations. Therefore this paper presents the main points of the control from the two types of accounting regulations perspective (national and international applied in our country.

Mortgage market regulation: Europe

NARCIS (Netherlands)

Aalbers, M.B.; Smith, S.J.

2012-01-01

Despite several European Union (EU) initiatives, there is only limited pan-European mortgage market regulation. The EU strategy can be characterised as one of parallel liberalisation and consolidation. This article highlights the key differences in regulation among European mortgage markets.

Complement anaphylatoxins as immune regulators in cancer.

Science.gov (United States)

Sayegh, Eli T; Bloch, Orin; Parsa, Andrew T

2014-08-01

The role of the complement system in innate immunity is well characterized. However, a recent body of research implicates the complement anaphylatoxins C3a and C5a as insidious propagators of tumor growth and progression. It is now recognized that certain tumors elaborate C3a and C5a and that complement, as a mediator of chronic inflammation and regulator of immune function, may in fact foster rather than defend against tumor growth. A putative mechanism for this function is complement-mediated suppression of immune effector cells responsible for immunosurveillance within the tumor microenvironment. This paradigm accords with models of immune dysregulation, such as autoimmunity and infectious disease, which have defined a pathophysiological role for abnormal complement signaling. Several types of immune cells express the cognate receptors for the complement anaphylatoxins, C3aR and C5aR, and demonstrate functional modulation in response to complement stimulation. In turn, impairment of antitumor immunity has been intimately tied to tumor progression in animal models of cancer. In this article, the literature was systematically reviewed to identify studies that have characterized the effects of the complement anaphylatoxins on the composition and function of immune cells within the tumor microenvironment. The search identified six studies based upon models of lymphoma and ovarian, cervical, lung, breast, and mammary cancer, which collectively support the paradigm of complement as an immune regulator in the tumor microenvironment. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

76 FR 70220 - New Jersey Regulations on Transportation of Regulated Medical Waste

Science.gov (United States)

2011-11-10

...., Director, Healthcare Waste Institute, 4301 Connecticut Avenue NW., Suite 300, Washington, DC 20008, and (2... Hazardous Waste Management Program, Mail Code 401-02C, P.O. Box 420, Trenton, NJ 08625-0420. A certification.... PHMSA-2011-0294 (PDA-35(R)] New Jersey Regulations on Transportation of Regulated Medical Waste AGENCY...

Mediator can regulate mitotic entry and direct periodic transcription in fission yeast.

Science.gov (United States)

Banyai, Gabor; Lopez, Marcela Davila; Szilagyi, Zsolt; Gustafsson, Claes M

2014-11-01

Cdk8 is required for correct timing of mitotic progression in fission yeast. How the activity of Cdk8 is regulated is unclear, since the kinase is not activated by T-loop phosphorylation and its partner, CycC, does not oscillate. Cdk8 is, however, a component of the multiprotein Mediator complex, a conserved coregulator of eukaryotic transcription that is connected to a number of intracellular signaling pathways. We demonstrate here that other Mediator components regulate the activity of Cdk8 in vivo and thereby direct the timing of mitotic entry. Deletion of Mediator components Med12 and Med13 leads to higher cellular Cdk8 protein levels, premature phosphorylation of the Cdk8 target Fkh2, and earlier entry into mitosis. We also demonstrate that Mediator is recruited to clusters of mitotic genes in a periodic fashion and that the complex is required for the transcription of these genes. We suggest that Mediator functions as a hub for coordinated regulation of mitotic progression and cell cycle-dependent transcription. The many signaling pathways and activator proteins shown to function via Mediator may influence the timing of these cell cycle events. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Self-regulation through Goal Setting

DEFF Research Database (Denmark)

Koch, Alexander; Nafziger, Julia

self-control problems. We show how goals permit self-regulation, but also that they are painful self-disciplining devices. Greater self-control problems therefore lead to stronger self-regulation through goals only up to a certain point. For severely present-biased preferences, the required goal...... for self-regulation is too painful and the individual rather gives up....

Fostering Self-Regulated Learning through Distance Education: A Case Study of M.Phil Secondary Teacher Education Program of Allama Iqbal Open University

Science.gov (United States)

Ambreen, Munazza; Haqdad, Ambreen; Saleem, Wajid A.

2016-01-01

Self-regulated learning (SLR) has been recognized as a pivotal antecedent of students' effective learning and academic achievement. A self-regulated learner can independently and effectively plan for learning, choose and use appropriate learning strategies and reflect and monitor learning progress. Self-regulated learning, for learners in general…

How do older adult drivers self-regulate? Characteristics of self-regulation classes defined by latent class analysis.

Science.gov (United States)

Bergen, Gwen; West, Bethany A; Luo, Feijun; Bird, Donna C; Freund, Katherine; Fortinsky, Richard H; Staplin, Loren

2017-06-01

Motor-vehicle crashes were the second leading cause of injury death for adults aged 65-84years in 2014. Some older drivers choose to self-regulate their driving to maintain mobility while reducing driving risk, yet the process remains poorly understood. Data from 729 older adults (aged ≥60years) who joined an older adult ride service program between April 1, 2010 and November 8, 2013 were analyzed to define and describe classes of driving self-regulation. Latent class analysis was employed to characterize older adult driving self-regulation classes using driving frequency and avoidance of seven driving situations. Logistic regression was used to explore associations between characteristics affecting mobility and self-regulation class. Three classes were identified (low, medium, and high self-regulation). High self-regulating participants reported the highest proportion of always avoiding seven risky driving situations and the lowest driving frequency followed by medium and low self-regulators. Those who were female, aged 80years or older, visually impaired, assistive device users, and those with special health needs were more likely to be high self-regulating compared with low self-regulating. Avoidance of certain driving situations and weekly driving frequency are valid indicators for describing driving self-regulation classes in older adults. Understanding the unique characteristics and mobility limitations of each class can guide optimal transportation strategies for older adults. Published by Elsevier Ltd.

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.

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

International Nuclear Information System (INIS)

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

A contextual model of self-regulation change mechanisms among individuals with addictive disorders.

Science.gov (United States)

Roos, Corey R; Witkiewitz, Katie

2017-11-01

Numerous behavioral treatments for addictive disorders include components explicitly aimed at targeting self-regulation (e.g., coping and emotion regulation). We first provide a summary of key findings to date among studies that have examined self-regulation as a mechanism of behavior change (MOBC) in behavioral treatments for addictive disorders. Based on our review, we conclude that the role of self-regulation as a MOBC across behavioral treatments for addictive disorders is not well-characterized and findings are inconsistent across studies. For example, our review indicates that there is still inconsistent evidence that coping is a unique MOBC in cognitive-behavioral approaches for addictive behaviors. We propose that there has been slow progress in understanding self-regulation as a MOBC in addiction treatment because of a lack of attention to contextual factors. Accordingly, in the second half of this paper, we propose a contextual model of self-regulation change mechanisms, which emphasizes that the role of various facets of self-regulation as MOBC may depend on contextual factors in the immediate situational context (e.g., fluctuating internal and external cues) and in the broader context in which an individual is embedded (e.g., major life stressors, environmental conditions, dispositions). Additionally, we provide specific recommendations to guide future research for understanding both between-person and within-person self-regulation MOBC in addiction treatment. In particular, we provide key recommendations for how to capitalize on intensive longitudinal measurement methods (e.g., ecological momentary assessment) when bringing a contextual perspective to the study of self-regulation as MOBC in various addiction treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ultra-Low-Dropout Linear Regulator

Science.gov (United States)

Thornton, Trevor; Lepkowski, William; Wilk, Seth

2011-01-01

A radiation-tolerant, ultra-low-dropout linear regulator can operate between -150 and 150 C. Prototype components were demonstrated to be performing well after a total ionizing dose of 1 Mrad (Si). Unlike existing components, the linear regulator developed during this activity is unconditionally stable over all operating regimes without the need for an external compensation capacitor. The absence of an external capacitor reduces overall system mass/volume, increases reliability, and lowers cost. Linear regulators generate a precisely controlled voltage for electronic circuits regardless of fluctuations in the load current that the circuit draws from the regulator.

Utility regulation and competition policy

International Nuclear Information System (INIS)

Robinson, Colin

2002-03-01

Contents: 1. The New Electricity Trading Arrangements in England and Wales: A Review - David Currie, 2. A Critique of Rail Regulation - Dieter Helm, 3. Moving to a Competitive Market in Water - Colin Robinson, 4. The New Gas Trading Arrangements - George Yarrow, 5. A Review of Privatization and Regulation Experience in Britain - Irwin M. Stelzer, 6. Converging Communications: Implications for Regulation - Mark Armstrong, 7. Opening European Electricity and Gas Markets - Graham Shuttleworth, 8. Concurrency or Convergence? Competition and Regulation Under the Competition Act 1998 - Tom Sharpe QC, 9. Ten Years of European Merger Control - Paul Seabright. (Author)

Parental Influences on Children's Self-Regulation of Energy Intake: Insights from Developmental Literature on Emotion Regulation

Directory of Open Access Journals (Sweden)

Leslie A. Frankel

2012-01-01

Full Text Available The following article examines the role of parents in the development of children's self-regulation of energy intake. Various paths of parental influence are offered based on the literature on parental influences on children's emotion self-regulation. The parental paths include modeling, responses to children's behavior, assistance in helping children self-regulate, and motivating children through rewards and punishments. Additionally, sources of variation in parental influences on regulation are examined, including parenting style, child temperament, and child-parent attachment security. Parallels in the nature of parents' role in socializing children's regulation of emotions and energy intake are examined. Implications for future research are discussed.

Emotion regulation in interpersonal problems: the role of cognitive-emotional complexity, emotion regulation goals, and expressivity.

Science.gov (United States)

Coats, Abby Heckman; Blanchard-Fields, Fredda

2008-03-01

Young, middle-aged, and older adults' emotion regulation strategies in interpersonal problems were examined. Participants imagined themselves in anger- or sadness-eliciting situations with a close friend. Factor analyses of a new questionnaire supported a 4-factor model of emotion regulation strategies, including passivity, expressing emotions, seeking emotional information or support, and solving the problem. Results suggest that age differences in emotion regulation (such as older adults' increased endorsement of passive emotion regulation relative to young adults) are partially due to older adults' decreased ability to integrate emotion and cognition, increased prioritization of emotion regulation goals, and decreased tendency to express anger. (c) 2008 APA, all rights reserved.

REGULATION OF NATIONAL QUALIFICATIONS SYSTEMS

Directory of Open Access Journals (Sweden)

Anna A. Muravyeva

2014-01-01

Full Text Available The paper looks into the diverse aspects of qualifications system regulation, designed for balancing the supply and demand in the labor and educational service markets. Both the objects and mechanisms of such regulation are described. Special attention is given to institutions, involved in regulation of qualifications, and their jurisdiction. Another emphasis is on the industry-related regulation of qualifications which proved to be effective both on the national and European level. Such structures were first established on the national levels to regulate the qualifications and ensure their comparability and compatibility, given the economic globalization and growing labor and academic mobility. The author points out the role of the ministries of education and labor in maintaining a steady qualifications system, and outlines the positive experience of Great Britain using the industry councils for continuing development of qualifications system.

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

Executive functioning, emotion regulation, eating self-regulation, and weight status in low-income preschool children: how do they relate?

Science.gov (United States)

Hughes, Sheryl O; Power, Thomas G; O'Connor, Teresia M; Orlet Fisher, Jennifer

2015-06-01

The purpose of the present study was to examine relationships between child eating self-regulation, child non-eating self-regulation, and child BMIz in a low-income sample of Hispanic families with preschoolers. The eating in the absence of hunger task as well as parent-report of child satiety responsiveness and food responsiveness were used to assess child eating self-regulation. Two laboratory tasks assessing executive functioning, a parent questionnaire assessing child effortful control (a temperament dimension related to executive functioning), and the delay of gratification and gift delay tasks assessing child emotion regulation were used to assess child non-eating self-regulation. Bivariate correlations were run among all variables in the study. Hierarchical linear regression analyses assessed: (1) child eating self-regulation associations with the demographic, executive functioning, effortful control, and emotion regulation measures; and (2) child BMI z-score associations with executive functioning, effortful control, emotion regulation measures, and eating self-regulation measures. Within child eating self-regulation, only the two parent-report measures were related. Low to moderate positive correlations were found between measures of executive functioning, effortful control, and emotion regulation. Only three relationships were found between child eating self-regulation and other forms of child self-regulation: eating in the absence of hunger was positively associated with delay of gratification, and poor regulation on the gift delay task was associated positively with maternal reports of food responsiveness and negatively with parent-reports of satiety responsiveness. Regression analyses showed that child eating self-regulation was associated with child BMIz but other forms of child self-regulation were not. Implications for understanding the role of self-regulation in the development of child obesity are discussed. Copyright © 2015 Elsevier Ltd. All

Pesticide regulations and farm worker safety: the need to improve pesticide regulations in Viet Nam.

Science.gov (United States)

Phung, Dung Tri; Connell, Des; Miller, Greg; Rutherford, Shannon; Chu, Cordia

2012-06-01

Agricultural pesticide use in Viet Nam has more than tripled since 1990. However, pesticide legislation and regulations have not been developed in response to this large increase in usage, as a result of which pesticides pose a serious threat to human health and the environment. This paper identifies the need to improve pesticide regulations in Viet Nam through a comparative analysis of pesticide regulations in Viet Nam and the United States of America, where the rate of acute poisoning among agricultural workers is much lower than in Viet Nam and where information pertaining to pesticide regulations is made accessible to the public. The analysis identified several measures that would help to improve Viet Nam's pesticide regulations. These include enhancing pesticide legislation, clarifying the specific roles and active involvement of both the environmental and health sectors; performing a comprehensive risk-benefit evaluation of pesticide registration and management practices; improving regulations on pesticide suspension and cancellation, transport, storage and disposal; developing import and export policies and enhancing pesticide-related occupational safety programmes.

Modeling microenvironmental regulation of glioblastoma stem cells: a biomaterials perspective

Science.gov (United States)

Heffernan, John M.; Sirianni, Rachael W.

2018-02-01

Following diagnosis of a glioblastoma (GBM) brain tumor, surgical resection, chemotherapy and radiation together yield a median patient survival of only 15 months. Importantly, standard treatments fail to address the dynamic regulation of the brain tumor microenvironment that actively supports tumor progression and treatment resistance. It is becoming increasingly recognized that specialized niches within the tumor microenvironment maintain a population of highly malignant glioblastoma stem-like cells (GSCs). GSCs are resistant to traditional chemotherapy and radiation therapy, suggesting that they may be responsible for the near universal rates of tumor recurrence and associated morbidity in GBM. Thus, disrupting microenvironmental support for GSCs could be critical to developing more effective GBM therapies. Three-dimensional (3D) culture models of the tumor microenvironment are powerful tools for identifying key biochemical and biophysical inputs that impact malignant behaviors. Such systems have been used effectively to identify conditions that regulate GSC proliferation, invasion, stem-specific phenotypes, and treatment resistance. Considering the significant role that GSC microenvironments play in regulating this tumorigenic sub-population, these models may be essential for uncovering mechanisms that limit GSCs malignancy.

TLX: A master regulator for neural stem cell maintenance and neurogenesis.

Science.gov (United States)

Islam, Mohammed M; Zhang, Chun-Li

2015-02-01

The orphan nuclear receptor TLX, also known as NR2E1, is an essential regulator of neural stem cell (NSC) self-renewal, maintenance, and neurogenesis. In vertebrates, TLX is specifically localized to the neurogenic regions of the forebrain and retina throughout development and adulthood. TLX regulates the expression of genes involved in multiple pathways, such as the cell cycle, DNA replication, and cell adhesion. These roles are primarily performed through the transcriptional repression or activation of downstream target genes. Emerging evidence suggests that the misregulation of TLX might play a role in the onset and progression of human neurological disorders making this factor an ideal therapeutic target. Here, we review the current understanding of TLX function, expression, regulation, and activity significant to NSC maintenance, adult neurogenesis, and brain plasticity. This article is part of a Special Issue entitled: Nuclear receptors in animal development. Copyright © 2014 Elsevier B.V. All rights reserved.

Regulation and inspection support radiation protection in nuclear and other installations

International Nuclear Information System (INIS)

Williams, M.K.; Potter, C.; Harbison, S.A.

1996-01-01

Over the past fifty years, radiation protection legislation in the UK has developed from a narrow industry-specific base to a comprehensive package of regulations and supporting Approved Code of Practice, with additional provisions for nuclear installations. Development of this legislation mirrors progress in international understanding about the risks from exposure to ionising radiation. The current Ionising Radiations Regulations 1985 largely implement the Euratom 1980 Basic Safety Standards Directive and place particular emphasis on the need to keep exposure as low as reasonably practicable. The regulations have been underpinned by the development of the concept of the Tolerability of Risk and the application of the ALARP/ALARA principle, particularly at nuclear installations. Analysis of dose data on HSE's Central Index of Dose Information has shown the general success of this approach in the UK; the data have also allowed targeting of inspection effort. Currently, the Health and Safety Commission and Executive are developing plans for implementing the revised EU Basic Safety Standards Directive. (author)

Regulation Development for Drinking Water Contaminants

Science.gov (United States)

To explain what process and information underlies regulations including how the Safe Drinking Water Act applies to regulation development i.e. how does the drinking water law translate into regulations.

Financial Private Regulation and Enforcement

OpenAIRE

MILLER, Geoffrey

2011-01-01

This paper has been delivered within the context of the research project "Transnational Private Regulatory Regimes: Constitutional foundations and governance design". This paper considers the topic of private regulation and enforcement for internationally active financial services firms. The paper documents the following types of regulation and enforcement that involve significant private input: house rules, contracts, internal compliance, management-based regulation, private standard-sett...

Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5 (ANGPTL6), Bmi-1 and E2F-3a, key regulators of brain cell proliferation.

Science.gov (United States)

Cui, J G; Zhao, Y; Sethi, P; Li, Y Y; Mahta, A; Culicchia, F; Lukiw, W J

2010-07-01

High density micro-RNA (miRNA) arrays, fluorescent-reporter miRNA assay and Northern miRNA dot-blot analysis show that a brain-enriched miRNA-128 is significantly down-regulated in glioblastoma multiforme (GBM) and in GBM cell lines when compared to age-matched controls. The down-regulation of miRNA-128 was found to inversely correlate with WHO tumor grade. Three bioinformatics-verified miRNA-128 targets, angiopoietin-related growth factor protein 5 (ARP5; ANGPTL6), a transcription suppressor that promotes stem cell renewal and inhibits the expression of known tumor suppressor genes involved in senescence and differentiation, Bmi-1, and a transcription factor critical for the control of cell-cycle progression, E2F-3a, were found to be up-regulated. Addition of exogenous miRNA-128 to CRL-1690 and CRL-2610 GBM cell lines (a) restored 'homeostatic' ARP5 (ANGPTL6), Bmi-1 and E2F-3a expression, and (b) significantly decreased the proliferation of CRL-1690 and CRL-2610 cell lines. Our data suggests that down-regulation of miRNA-128 may contribute to glioma and GBM, in part, by coordinately up-regulating ARP5 (ANGPTL6), Bmi-1 and E2F-3a, resulting in the proliferation of undifferentiated GBM cells.

ERK Regulates Renal Cell Proliferation and Renal Cyst Expansion in inv Mutant Mice

International Nuclear Information System (INIS)

Okumura, Yasuko; Sugiyama, Noriyuki; Tanimura, Susumu; Nishida, Masashi; Hamaoka, Kenji; Kohno, Michiaki; Yokoyama, Takahiko

2009-01-01

Nephronophthisis (NPHP) is the most frequent genetic cause of end-stage kidney disease in children and young adults. Inv mice are a model for human nephronophthisis type 2 (NPHP2) and characterized by multiple renal cysts and situs inversus. Renal epithelial cells in inv cystic kidneys show increased cell proliferation. We studied the ERK pathway to understand the mechanisms that induce cell proliferation and renal cyst progression in inv kidneys. We studied the effects of ERK suppression by administering PD184352, an oral mitogen-activated protein kinase kinase (MEK) inhibitor on renal cyst expansion, extracellular signal-regulated protein kinase (ERK) activity, bromo-deoxyuridine (BrdU) incorporation and expression of cell-cycle regulators in invΔC kidneys. Phosphorylated ERK (p-ERK) level increased along with renal cyst enlargement. Cell-cycle regulators showed a high level of expression in invΔC kidneys. PD184352 successfully decreased p-ERK level and inhibited renal cyst enlargement. The inhibitor also decreased expression of cell-cycle regulators and BrdU incorporation in renal epithelial cells. The present results showed that ERK regulated renal cell proliferation and cyst expansion in inv mutants

Know-How on design of switching regulator

International Nuclear Information System (INIS)

1985-08-01

This book introduces switching regulator from base to application, which deals with fundamentals of switching regulator such as the reason of boom about switching regulator, understanding simple circuit without electric transformer and decision of circuit type with input voltage and output voltage, configuration and characteristic of switching regulator, a concrete design of switching regulator, pulse width control circuit and protection circuit, concrete circuit examples of switching power and the point of switching regulator.

The Drosophila Perlecan gene trol regulates multiple signaling pathways in different developmental contexts

Directory of Open Access Journals (Sweden)

Perry Trinity L

2007-11-01

Full Text Available Abstract Background Heparan sulfate proteoglycans modulate signaling by a variety of growth factors. The mammalian proteoglycan Perlecan binds and regulates signaling by Sonic Hedgehog, Fibroblast Growth Factors (FGFs, Vascular Endothelial Growth Factor (VEGF and Platelet Derived Growth Factor (PDGF, among others, in contexts ranging from angiogenesis and cardiovascular development to cancer progression. The Drosophila Perlecan homolog trol has been shown to regulate the activity of Hedgehog and Branchless (an FGF homolog to control the onset of stem cell proliferation in the developing brain during first instar. Here we extend analysis of trol mutant phenotypes to show that trol is required for a variety of developmental events and modulates signaling by multiple growth factors in different situations. Results Different mutations in trol allow developmental progression to varying extents, suggesting that trol is involved in multiple cell-fate and patterning decisions. Analysis of the initiation of neuroblast proliferation at second instar demonstrated that trol regulates this event by modulating signaling by Hedgehog and Branchless, as it does during first instar. Trol protein is distributed over the surface of the larval brain, near the regulated neuroblasts that reside on the cortical surface. Mutations in trol also decrease the number of circulating plasmatocytes. This is likely to be due to decreased expression of pointed, the response gene for VEGF/PDGF signaling that is required for plasmatocyte proliferation. Trol is found on plasmatocytes, where it could regulate VEGF/PDGF signaling. Finally, we show that in second instar brains but not third instar brain lobes and eye discs, mutations in trol affect signaling by Decapentaplegic (a Transforming Growth Factor family member, Wingless (a Wnt growth factor and Hedgehog. Conclusion These studies extend the known functions of the Drosophila Perlecan homolog trol in both developmental and

Protective microglia and its regulation in Parkinson's disease

Directory of Open Access Journals (Sweden)

Weidong Le

2016-09-01

Full Text Available Microglia mediated neuroinflammation is a hallmark of Parkinson’s disease (PD. It has been reported that microglia in the brain of PD have both neurotoxic and neuroprotective effects, depending on the microglial activation states. In this review, we will focus on the recent research findings of the neuroprotective role of microglia-mediated neuroinflammation in PD. Accumulating new evidences have indicated that the protective mechanisms of microglia may result from its regulation of transrepression pathways via nuclear receptors, anti-inflammatory responses, neuron-microglia crosstalk, histone modification and microRNA regulation. All of these protective mechanisms of microglia orchestrate with each other to repress the production of neurotoxic inflammatory components. Since the detrimental effects of inflammation overwhelm the protective effects of microglia during the disease progression of PD, exploring an in-depth understanding of the protective mechanisms of microglia and promoting the transformation of beneficial microglia are urgently important for the treatment of PD.

Significance of Coaching in the Context of Emotion Regulation

Science.gov (United States)

Novotná, Ivana; Blahová, Jarmila; Šatanková, Sláva

2017-09-01

Coaching as a form of development has opened new possibilities and broadened the sphere of competence for personal or manager development since 1990s. At the beginning, there was not enough literature related to this topic, but progressively it has been popularized in so much that some authors have released their books in several languages. John Whitmore (2004) warns about the misuse of popularization of a new term (coaching), by using which many managers hide their reluctance against a modification or disability to change something in their traditional managerial style. Emotion regulation is the base for successful leadership, success in work life in general and satisfaction in any relationship. In the paper, the authors focus on the significance of coaching for the personal and professional growth as a systematic method using several strategies of emotion regulation.

Significance of Coaching in the Context of Emotion Regulation

Directory of Open Access Journals (Sweden)

Novotná Ivana

2017-09-01

Full Text Available Coaching as a form of development has opened new possibilities and broadened the sphere of competence for personal or manager development since 1990s. At the beginning, there was not enough literature related to this topic, but progressively it has been popularized in so much that some authors have released their books in several languages. John Whitmore (2004 warns about the misuse of popularization of a new term (coaching, by using which many managers hide their reluctance against a modification or disability to change something in their traditional managerial style. Emotion regulation is the base for successful leadership, success in work life in general and satisfaction in any relationship. In the paper, the authors focus on the significance of coaching for the personal and professional growth as a systematic method using several strategies of emotion regulation.

Regulation of gas infrastructure expansion

International Nuclear Information System (INIS)

De Joode, J.

2012-01-01

The topic of this dissertation is the regulation of gas infrastructure expansion in the European Union (EU). While the gas market has been liberalised, the gas infrastructure has largely remained in the regulated domain. However, not necessarily all gas infrastructure facilities - such as gas storage facilities, LNG import terminals and certain gas transmission pipelines - need to be regulated, as there may be scope for competition. In practice, the choice of regulation of gas infrastructure expansion varies among different types of gas infrastructure facilities and across EU Member States. Based on a review of economic literature and on a series of in-depth case studies, this study explains these differences in choices of regulation from differences in policy objectives, differences in local circumstances and differences in the intrinsic characteristics of the infrastructure projects. An important conclusion is that there is potential for a larger role for competition in gas infrastructure expansion.

Measuring Individual Differences in Emotion Regulation: The Emotion Regulation Profile-Revised (ERP-R

Directory of Open Access Journals (Sweden)

Delphine Nelis

2011-02-01

Full Text Available The main purpose of this study was to validate a new instrument aimed to assess emotion regulation: the Emotion Regulation Profile-Revised (ERP-R. Exploratory factor analyses yielded two theoretically meaningful factors: down-regulation of negative emotions and up-regulation of positive emotions. Internal reliability scores of the two factors were good. Findings showed evidence of convergent/discriminant validity, with ERP-R scores being independent of non verbal reasoning and verbal skills while positively related to emotional intelligence and to relevant personality dimensions. There was also preliminary evidence of criterion validity. ERP-R scores also demonstrated incremental validity to predict a number of criteria over and above emotional intelligence and emotional stability. Overall, the results show a clear 2 factors solution for the ERP-R and high correlations with convergent and divergent scales as well as good criterion and incremental validities.

Market reaction to bank liquidity regulation

OpenAIRE

Bruno, Brunella; Onali, Enrico; Schaeck, Klaus

2018-01-01

We measure market reactions to announcements concerning liquidity regulation, a key innovation in the Basel framework. Our initial results show that liquidity regulation attracts negative abnormal returns. However, the price responses are less pronounced when coinciding announcements concerning capital regulation are backed out, suggesting that markets do not consider liquidity regulation to be binding. Bank- and country-specific characteristics also matter. Liquid balance sheets and high cha...

Successful emotion regulation requires both conviction and skill: beliefs about the controllability of emotions, reappraisal, and regulation success.

Science.gov (United States)

Gutentag, Tony; Halperin, Eran; Porat, Roni; Bigman, Yochanan E; Tamir, Maya

2017-09-01

To succeed in self-regulation, people need to believe that it is possible to change behaviour and they also need to use effective means to enable such a change. We propose that this also applies to emotion regulation. In two studies, we found that people were most successful in emotion regulation, the more they believed emotions can be controlled and the more they used an effective emotion regulation strategy - namely, cognitive reappraisal. Cognitive reappraisal moderated the link between beliefs about the controllability of emotion and success in emotion regulation, when reappraisal was measured as a trait (Study 1) or manipulated (Study 2). Such moderation was found when examining the regulation of disgust elicited by emotion-inducing films (Study 1), and the regulation of anger elicited by real political events (Study 2). We discuss the implications of our findings for research and practice in emotion regulation.

Thermal flow regulator of refrigerant

International Nuclear Information System (INIS)

Dubinskij, S.I.; Savchenko, A.G.; Suplin, V.Z.

1988-01-01

A thermal flow regulator of refrigerant for helium flow-type temperature-controlled cryostats based on controlling the channel hydraulic resistance due to variation of the flow density and viscosity during liquid helium transformation into the gaseous state. Behind the regulator both two-phase flow and a heated gas can be produced. The regulator resolution is (7-15)x10 -4 l/mW of liquid helium

HIPPA privacy regulations: practical information for physicians.

Science.gov (United States)

McMahon, E B; Lee-Huber, T

2001-07-01

After much debate and controversy, the Bush administration announced on April 12, 2001, that it would implement the Health Insurance Portability and Accountability Act (HIPAA) privacy regulations issued by the Clinton administration in December of 2000. The privacy regulations became effective on April 14, 2001. Although the regulations are considered final, the Secretary of the Department of Health and Human Services has the power to modify the regulations at any time during the first year of implementation. These regulations affect how a patient's health information is used and disclosed, as well as how patients are informed of their privacy rights. As "covered entities," physicians have until April 14, 2003, to comply fully with the HIPAA privacy regulations, which are more than 1,500 pages in length. This article presents a basic overview of the new and complex regulations and highlights practical information about physicians' compliance with the regulations. However, this summary of the HIPAA privacy regulations should not be construed as legal advice or an opinion on specific situations. Please consult an attorney concerning your compliance with HIPAA and the regulations promulgated thereunder.

The Provisional Staff Regulations of the Agency. Amendment to Regulation 5.04(a)

International Nuclear Information System (INIS)

1973-01-01

On 20 February 1973 the Board of Governors approved the substitution of the figure '1500' for '1000' in the second sentence of Provisional Staff Regulation 5.04(a) as set forth in document INFCIRC/6/Rev.2/Mod.1, thus amending that Regulation to read

miR-193b Regulates Mcl-1 in Melanoma.

Science.gov (United States)

Chen, Jiamin; Zhang, Xiao; Lentz, Cindy; Abi-Daoud, Marie; Paré, Geneviève C; Yang, Xiaolong; Feilotter, Harriet E; Tron, Victor A

2011-11-01

MicroRNAs play important roles in gene regulation, and their expression is frequently dysregulated in cancer cells. In a previous study, we reported that miR-193b represses cell proliferation and regulates cyclin D1 in melanoma cells, suggesting that miR-193b could act as a tumor suppressor. Herein, we demonstrate that miR-193b also down-regulates myeloid cell leukemia sequence 1 (Mcl-1) in melanoma cells. MicroRNA microarray profiling revealed that miR-193b is expressed at a significantly lower level in malignant melanoma than in benign nevi. Consistent with this, Mcl-1 is detected at a higher level in malignant melanoma than in benign nevi. In a survey of melanoma samples, the level of Mcl-1 is inversely correlated with the level of miR-193b. Overexpression of miR-193b in melanoma cells represses Mcl-1 expression. Previous studies showed that Mcl-1 knockdown cells are hypersensitive to ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-X(L), and Bcl-w. Similarly, overexpression of miR-193b restores ABT-737 sensitivity to ABT-737-resistant cells. Furthermore, the effect of miR-193b on the expression of Mcl-1 seems to be mediated by direct interaction between miR-193b and seed and seedless pairing sequences in the 3' untranslated region of Mcl-1 mRNA. Thus, this study provides evidence that miR-193b directly regulates Mcl-1 and that down-regulation of miR-193b in vivo could be an early event in melanoma progression. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Protein kinase C signaling and cell cycle regulation

Directory of Open Access Journals (Sweden)

Adrian R Black

2013-01-01

Full Text Available A link between T cell proliferation and the protein kinase C (PKC family of serine/threonine kinases has been recognized for about thirty years. However, despite the wealth of information on PKC-mediated control of T cell activation, understanding of the effects of PKCs on the cell cycle machinery in this cell type remains limited. Studies in other systems have revealed important cell cycle-specific effects of PKC signaling that can either positively or negatively impact proliferation. The outcome of PKC activation is highly context-dependent, with the precise cell cycle target(s and overall effects determined by the specific isozyme involved, the timing of PKC activation, the cell type, and the signaling environment. Although PKCs can regulate all stages of the cell cycle, they appear to predominantly affect G0/G1 and G2. PKCs can modulate multiple cell cycle regulatory molecules, including cyclins, cyclin-dependent kinases (cdks, cdk inhibitors and cdc25 phosphatases; however, evidence points to Cip/Kip cdk inhibitors and D-type cyclins as key mediators of PKC-regulated cell cycle-specific effects. Several PKC isozymes can target Cip/Kip proteins to control G0/G1→S and/or G2→M transit, while effects on D-type cyclins regulate entry into and progression through G1. Analysis of PKC signaling in T cells has largely focused on its roles in T cell activation; thus, observed cell cycle effects are mainly positive. A prominent role is emerging for PKCθ, with non-redundant functions of other isozymes also described. Additional evidence points to PKCδ as a negative regulator of the cell cycle in these cells. As in other cell types, context-dependent effects of individual isozymes have been noted in T cells, and Cip/Kip cdk inhibitors and D-type cyclins appear to be major PKC targets. Future studies are anticipated to take advantage of the similarities between these various systems to enhance understanding of PKC-mediated cell cycle regulation in

Prediction of epigenetically regulated genes in breast cancer cell lines

Energy Technology Data Exchange (ETDEWEB)

Loss, Leandro A; Sadanandam, Anguraj; Durinck, Steffen; Nautiyal, Shivani; Flaucher, Diane; Carlton, Victoria EH; Moorhead, Martin; Lu, Yontao; Gray, Joe W; Faham, Malek; Spellman, Paul; Parvin, Bahram

2010-05-04

Methylation of CpG islands within the DNA promoter regions is one mechanism that leads to aberrant gene expression in cancer. In particular, the abnormal methylation of CpG islands may silence associated genes. Therefore, using high-throughput microarrays to measure CpG island methylation will lead to better understanding of tumor pathobiology and progression, while revealing potentially new biomarkers. We have examined a recently developed high-throughput technology for measuring genome-wide methylation patterns called mTACL. Here, we propose a computational pipeline for integrating gene expression and CpG island methylation profles to identify epigenetically regulated genes for a panel of 45 breast cancer cell lines, which is widely used in the Integrative Cancer Biology Program (ICBP). The pipeline (i) reduces the dimensionality of the methylation data, (ii) associates the reduced methylation data with gene expression data, and (iii) ranks methylation-expression associations according to their epigenetic regulation. Dimensionality reduction is performed in two steps: (i) methylation sites are grouped across the genome to identify regions of interest, and (ii) methylation profles are clustered within each region. Associations between the clustered methylation and the gene expression data sets generate candidate matches within a fxed neighborhood around each gene. Finally, the methylation-expression associations are ranked through a logistic regression, and their significance is quantified through permutation analysis. Our two-step dimensionality reduction compressed 90% of the original data, reducing 137,688 methylation sites to 14,505 clusters. Methylation-expression associations produced 18,312 correspondences, which were used to further analyze epigenetic regulation. Logistic regression was used to identify 58 genes from these correspondences that showed a statistically signifcant negative correlation between methylation profles and gene expression in the

Evolving Role of the Power Sector Regulator: A Clean Energy Regulators Initiative Report

Energy Technology Data Exchange (ETDEWEB)

Zinaman, O.; Miller, M.; Bazilian, M.

2014-04-01

This paper seeks to briefly characterize the evolving role of power sector regulation. Given current global dynamics, regulation of the power sector is undergoing dramatic changes. This transformation is being driven by various factors including technological advances and cost reductions in renewable energy, energy efficiency, and demand management; increasing air pollution and climate change concerns; and persistent pressure for ensuring sustainable economic development and increased access to energy services by the poor. These issues add to the already complex task of power sector regulation, of which the fundamental remit remains to objectively and transparently ensure least-cost service delivery at high quality. While no single regulatory task is trivial to undertake, it is the prioritization and harmonization of a multitude of objectives that exemplifies the essential challenge of power sector regulation. Evolving regulatory roles can be understood through the concept of existing objectives and an additional layer of emerging objectives. Following this categorization, we describe seven existing objectives of power sector regulators and nine emerging objectives, highlighting key challenges and outlining interdependencies. This essay serves as a preliminary installment in the Clean Energy Regulatory Initiative (CERI) series, and aims to lay the groundwork for subsequent reports and case studies that will explore these topics in more depth.

Helping Others Regulate Emotion Predicts Increased Regulation of One's Own Emotions and Decreased Symptoms of Depression.

Science.gov (United States)

Doré, Bruce P; Morris, Robert R; Burr, Daisy A; Picard, Rosalind W; Ochsner, Kevin N

2017-05-01

Although much research considers how individuals manage their own emotions, less is known about the emotional benefits of regulating the emotions of others. We examined this topic in a 3-week study of an online platform providing training and practice in the social regulation of emotion. We found that participants who engaged more by helping others (vs. sharing and receiving support for their own problems) showed greater decreases in depression, mediated by increased use of reappraisal in daily life. Moreover, social regulation messages with more other-focused language (i.e., second-person pronouns) were (a) more likely to elicit expressions of gratitude from recipients and (b) predictive of increased use of reappraisal over time for message composers, suggesting perspective-taking enhances the benefits of practicing social regulation. These findings unpack potential mechanisms of socially oriented training in emotion regulation and suggest that by helping others regulate, we may enhance our own regulatory skills and emotional well-being.

Mcl-1 Ubiquitination: Unique Regulation of an Essential Survival Protein

Directory of Open Access Journals (Sweden)

Barbara Mojsa

2014-05-01

Full Text Available Mcl-1 is an anti-apoptotic protein of the Bcl-2 family that is essential for the survival of multiple cell lineages and that is highly amplified in human cancer. Under physiological conditions, Mcl-1 expression is tightly regulated at multiple levels, involving transcriptional, post-transcriptional and post-translational processes. Ubiquitination of Mcl-1, that targets it for proteasomal degradation, allows for rapid elimination of the protein and triggering of cell death, in response to various cellular events. In the last decade, a number of studies have elucidated different pathways controlling Mcl-1 ubiquitination and degradation. Four different E3 ubiquitin-ligases (e.g., Mule, SCFβ-TrCP, SCFFbw7 and Trim17 and one deubiquitinase (e.g., USP9X, that respectively mediate and oppose Mcl-1 ubiquitination, have been formerly identified. The interaction between Mule and Mcl-1 can be modulated by other Bcl-2 family proteins, while recognition of Mcl-1 by the other E3 ubiquitin-ligases and deubiquitinase is influenced by phosphorylation of specific residues in Mcl-1. The protein kinases and E3 ubiquitin-ligases that are involved in the regulation of Mcl-1 stability vary depending on the cellular context, highlighting the complexity and pivotal role of Mcl-1 regulation. In this review, we attempt to recapitulate progress in understanding Mcl-1 regulation by the ubiquitin-proteasome system.

18 CFR 410.1 - Basin regulations-Water Code and Administrative Manual-Part III Water Quality Regulations.

Science.gov (United States)

2010-04-01

... Code and Administrative Manual-Part III Water Quality Regulations. 410.1 Section 410.1 Conservation of... CODE AND ADMINISTRATIVE MANUAL-PART III WATER QUALITY REGULATIONS § 410.1 Basin regulations—Water Code and Administrative Manual—Part III Water Quality Regulations. (a) The Water Code of the Delaware River...

The power of regulation

International Nuclear Information System (INIS)

Lewis, M.G.

1995-01-01

Slides accompanying a presentation at The Power of Change Conference in Vancouver, BC in April 1995 about regulations affecting the power industry were presented. Issues addressed included customer choice, incentive regulation changes (price-caps, revenue sharing and pricing flexibility), the reactions of Canadian industry to regulatory changes, and anticipated reactions of the financial markets to changes in regulations. The potential effects of competition and changes that will create competition were discussed. The level of readiness of Canadian financial, ownership and regulatory bodies was discussed. The needs and expectations of investors from a new regulatory regime were quesstimated. Possible alternatives to the present regulatory framework were suggested

Epigenetic Regulation of Adipokines

Directory of Open Access Journals (Sweden)

Tho X. Pham

2017-08-01

Full Text Available Adipose tissue expansion in obesity leads to changes in the expression of adipokines, adipocyte-specific hormones that can regulate whole body energy metabolism. Epigenetic regulation of gene expression is a mechanism by which cells can alter gene expression through the modifications of DNA and histones. Epigenetic mechanisms, such as DNA methylation and histone modifications, are intimately tied to energy metabolism due to their dependence on metabolic intermediates such as S-adenosylmethionine and acetyl-CoA. Altered expression of adipokines in obesity may be due to epigenetic changes. The goal of this review is to highlight current knowledge of epigenetic regulation of adipokines.

Microtubule affinity-regulating kinases are potential druggable targets for Alzheimer's disease.

Science.gov (United States)

Annadurai, Narendran; Agrawal, Khushboo; Džubák, Petr; Hajdúch, Marián; Das, Viswanath

2017-11-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects normal functions of the brain. Currently, AD is one of the leading causes of death in developed countries and the only one of the top ten diseases without a means to prevent, cure, or significantly slow down its progression. Therefore, newer therapeutic concepts are urgently needed to improve survival and the quality of life of AD patients. Microtubule affinity-regulating kinases (MARKs) regulate tau-microtubule binding and play a crucial role in neurons. However, their role in hyperphosphorylation of tau makes them potential druggable target for AD therapy. Despite the relevance of MARKs in AD pathogenesis, only a few small molecules are known to have anti-MARK activity and not much has been done to progress these compounds into therapeutic candidates. But given the diverse role of MARKs, the specificity of novel inhibitors is imperative for their successful translation from bench to bedside. In this regard, a recent co-crystal structure of MARK4 in association with a pyrazolopyrimidine-based inhibitor offers a potential scaffold for the development of more specific MARK inhibitors. In this manuscript, we review the biological role of MARKs in health and disease, and draw attention to the largely unexplored area of MARK inhibitors for AD.

Novel Molecules Regulating Energy Homeostasis: Physiology and Regulation by Macronutrient Intake and Weight Loss

Directory of Open Access Journals (Sweden)

Anna Gavrieli

2016-09-01

Full Text Available Excess energy intake, without a compensatory increase of energy expenditure, leads to obesity. Several molecules are involved in energy homeostasis regulation and new ones are being discovered constantly. Appetite regulating hormones such as ghrelin, peptide tyrosine-tyrosine and amylin or incretins such as the gastric inhibitory polypeptide have been studied extensively while other molecules such as fibroblast growth factor 21, chemerin, irisin, secreted frizzle-related protein-4, total bile acids, and heme oxygenase-1 have been linked to energy homeostasis regulation more recently and the specific role of each one of them has not been fully elucidated. This mini review focuses on the above mentioned molecules and discusses them in relation to their regulation by the macronutrient composition of the diet as well as diet-induced weight loss.

Soft Regulators, though judges

NARCIS (Netherlands)

de Geest, G.G.A.; Dari Mattiacci, G.

Judges have a tendency to be more demanding than regulators. In the United States, a majority of the courts has adopted the rule that the unexcused violation of a statutory standard is negligence per se. However, the converse does not hold: compliance with regulation does not relieve the injurer of

Safety supervision on high-pressure gas regulations

International Nuclear Information System (INIS)

Lee, Won Il

1991-01-01

The first part lists the regulation on safety supervision of high-pressure gas, enforcement ordinance on high-pressure gas safety supervision and enforcement regulations about high-pressure gas safety supervision. The second part indicates safety regulations on liquefied petroleum gas and business, enforcement ordinance of safety on liquefied petroleum gas and business, enforcement regulation of safety supervision over liquefied petroleum gas and business. The third part lists regulation on gas business, enforcement ordinance and enforcement regulations on gas business. Each part has theory and explanation for questions.

Comparison of some European regulations

Energy Technology Data Exchange (ETDEWEB)

Argyriadis, K [Germanisher Lloyd, Hamburg (Germany)

1996-09-01

Fatigue calculations are an essential part in certification of a wind turbine. Manufacturers have to fulfill recommendations of several different regulations throughout Europe with the result that the design has often to be altered to satisfy them. In general three national (D/GL, NL, DK), and two international (GL, IEC) regulations are in use, with the IEC standard getting more importance with wind energy deploying to more in regions with no yet clearly defined national standards (India, Spain). The Germanischer Lloyd made calculations for wind turbines they are certifying and in one case we compared the resulting damages for different regulations and classes on a 600 kW, three bladed, stall regulated wind turbine. (EG) 18 refs.

75 FR 10997 - Cuban Assets Control Regulations; Sudanese Sanctions Regulations; Iranian Transactions Regulations

Science.gov (United States)

2010-03-10

... specific license, or otherwise exempt, the exportation of such services and software from the United States... services and software. Paragraph (c) of each of these two sections provides that specific licenses may be... Iranian Transactions Regulations to authorize the exportation of certain services and software incident to...

Regulating a Monopoly Offering Priority Service

OpenAIRE

Matsukawa, Isamu

2006-01-01

This paper investigates the effects of alternative forms of regulation on the market penetration and capacity, which are determined by a profit-maximizing monopolist providing priority service to consumers. For continuous priority service, a minimum reliability standard, price cap and rate of return regulation lead to larger capacity than in the absence of regulation. A minimum reliability standard reduces the market penetration while price cap and rate of return regulation increase it. T...

Model of accounting regulation in Lithuania

OpenAIRE

Rudžionienė, Kristina; Gipienė, Gailutė

2008-01-01

This paper analyses the regulation of accounting system in Lithuania. There are different approaches to accounting regulation. For example, the "free market" approach is against any regulation; it says that each process in the market will be in equilibrium itself. Mostly it is clear that regulation is important and useful, especially in financial accounting. It makes information in financial reports understandable and comparable in one country or different countries. There are three theories ...

Policy and network regulation for the integration of distribution generation and renewables for electricity supply

International Nuclear Information System (INIS)

Ten Donkelaar, M.; Van Oostvoorn, F.

2005-08-01

This study has analysed the existing policy and regulation aimed at the integration of an increased share of Distributed Generation (DG) in electricity supply systems in the European Union. It illustrates the state of the art and progress in the development of support mechanisms and network regulation for large-scale integration of DG. Through a benchmark study a systematic comparison has been made of different DG support schemes and distribution network regulation in EU Member States to a predefined standard, the level playing field. This level playing field has been defined as the situation where energy markets, policy and regulation provide neutral incentives to central versus distributed generation, which results in an economically more efficient electricity supply to the consumer. In current regulation and policy a certain discrepancy can be noticed between the actual regulation and policy support systems in a number of countries, the medium to long term targets and the ideal situation described according to the level playing field objective. Policies towards DG and RES are now mainly aimed at removing short-term barriers, increasing the production share of DG/RES, but often ignoring the more complex barriers of integrating DG/RES that is created by the economic network regulation in current electricity markets

Dengue virus-induced regulation of the host cell translational machinery

Directory of Open Access Journals (Sweden)

C.S.A. Villas-Bôas

2009-11-01

Full Text Available Dengue virus (DV-induced changes in the host cell protein synthesis machinery are not well understood. We investigated the transcriptional changes related to initiation of protein synthesis. The human hepatoma cell line, HepG2, was infected with DV serotype 2 for 1 h at a multiplicity of infection of one. RNA was extracted after 6, 24 and 48 h. Microarray results showed that 36.5% of the translation factors related to initiation of protein synthesis had significant differential expression (Z-score ≥ ±2.0. Confirmation was obtained by quantitative real-time reverse transcription-PCR. Of the genes involved in the activation of mRNA for cap-dependent translation (eIF4 factors, eIF4A, eIF4G1 and eIF4B were up-regulated while the negative regulator of translation eIF4E-BP3 was down-regulated. This activation was transient since at 24 h post-infection levels were not significantly different from control cells. However, at 48 h post-infection, eIF4A, eIF4E, eIF4G1, eIF4G3, eIF4B, and eIF4E-BP3 were down-regulated, suggesting that cap-dependent translation could be inhibited during the progression of infection. To test this hypothesis, phosphorylation of p70S6K and 4E-BP1, which induce cap-dependent protein synthesis, was assayed. Both proteins remained phosphorylated when assayed at 6 h after infection, while infection induced dephosphorylation of p70S6K and 4E-BP1 at 24 and 48 h of infection, respectively. Taken together, these results provide biological evidence suggesting that in HepG2 cells DV sustains activation of the cap-dependent machinery at early stages of infection, but progression of infection switches protein synthesis to a cap-independent process.

The financial regulations of the Agency

International Nuclear Information System (INIS)

1994-01-01

On 14 September 1994, the Board of Governors approved revised Financial Regulations of the Agency, with implementation of these Regulations beginning 1 January 1995. The Financial Regulations, as revised, are reproduced in this document for the information of all Member States

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

Science.gov (United States)

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

2015-01-01

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-...

Role and regulation of apoptotic cell death in the kidney. Y2K update.

Science.gov (United States)

Ortiz, A; Lorz, C; Catalan, M P; Justo, P; Egido, J

2000-08-01

Apoptosis is an active form of cell death that, in balance with mitosis, regulates cell number. Cell number abnormalities are a frequent feature of renal disease. We now review current concepts on the molecular regulation of apoptotic cell death, including the influence of survival and lethal factors from the extracellular microenvironment as well as the role of intracellular regulators of apoptosis, such as death receptors, proapoptotic and antiapoptotic bcl2-related proteins, the mitochondria and caspases. In addition the role of apoptosis in the genesis, persistence and progression and remodeling and resolution of renal injury is discussed. Information on the expression and function of apoptosis regulatory proteins in specific renal syndromes is summarized. Finally, future perspectives in research and clinical intervention are discussed.

Toward Better Mapping between Regulations and Operations of Enterprises Using Vocabularies and Semantic Similarity

Directory of Open Access Journals (Sweden)

Sagar Sunkle

2015-12-01

Full Text Available Industry governance, risk, and compliance (GRC solutions stand to gain from various analyses offered by formal compliance checking approaches. Such adoption is made difficult by the fact that most formal approaches assume that a mapping between concepts of regulations and models of operational specifics exists. Industry solutions offer tagging mechanisms to map regulations to operational specifics; however, they are mostly semi-formal in nature and tend to rely extensively on experts. We propose to use Semantics of Business Vocabularies and Rules along with similarity measures to create an explicit mapping between concepts of regulations and models of operational specifics of the enterprise. We believe that our work-in-progress takes a step toward adapting and leveraging formal compliance checking approaches in industry GRC solutions.

Energy policy conference on the regulation of energy industries; Conference de politique energetique sur la regulation des industries energetiques

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-11-01

This document is the report of the conference meeting jointly organized by the French general plan commission and the general direction of energy and raw materials on the regulation of energy industries: 1 - the changes in the regulation of public utilities in competition: harmonization, respect of impartiality and social cohesion, organization of a loyal competition, specialized regulation and regulation of competition, open debates; 2 - towards an homogenous model of regulatory authority?: the US model (collegial and hybrid organizations), the UK model (individual and independent), missions of regulation and institutional 'meccano', theory and practice, draft classification of the institutional approaches of IEA countries (role of ministries and regulatory agencies), independent regulatory authorities or not, significant differences in converging models, dominant types of regulation in the different sectors, situation of the French energy regulatory system (institutional plan, regulation processes, relations of the regulation authority with the government), reasons of the differences between different countries, expected evolution of the regulation systems in the coming years. (J.S.)

Energy policy conference on the regulation of energy industries; Conference de politique energetique sur la regulation des industries energetiques

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-11-01

This document is the report of the conference meeting jointly organized by the French general plan commission and the general direction of energy and raw materials on the regulation of energy industries: 1 - the changes in the regulation of public utilities in competition: harmonization, respect of impartiality and social cohesion, organization of a loyal competition, specialized regulation and regulation of competition, open debates; 2 - towards an homogenous model of regulatory authority?: the US model (collegial and hybrid organizations), the UK model (individual and independent), missions of regulation and institutional 'meccano', theory and practice, draft classification of the institutional approaches of IEA countries (role of ministries and regulatory agencies), independent regulatory authorities or not, significant differences in converging models, dominant types of regulation in the different sectors, situation of the French energy regulatory system (institutional plan, regulation processes, relations of the regulation authority with the government), reasons of the differences between different countries, expected evolution of the regulation systems in the coming years. (J.S.)

Energy Density, Energy Intake, and Body Weight Regulation in Adults12345

Science.gov (United States)

Karl, J. Philip; Roberts, Susan B.

2014-01-01

The role of dietary energy density (ED) in the regulation of energy intake (EI) is controversial. Methodologically, there is also debate about whether beverages should be included in dietary ED calculations. To address these issues, studies examining the effects of ED on EI or body weight in nonelderly adults were reviewed. Different approaches to calculating dietary ED do not appear to alter the direction of reported relations between ED and body weight. Evidence that lowering dietary ED reduces EI in short-term studies is convincing, but there are currently insufficient data to determine long-term effectiveness for weight loss. The review also identified key barriers to progress in understanding the role of ED in energy regulation, in particular the absence of a standard definition of ED, and the lack of data from multiple long-term clinical trials examining the effectiveness of low-ED diet recommendations for preventing both primary weight gain and weight regain in nonobese individuals. Long-term clinical trials designed to examine the impact of dietary ED on energy regulation, and including multiple ED calculation methods within the same study, are still needed to determine the importance of ED in the regulation of EI and body weight. PMID:25398750

Microenvironmental regulation of hematopoietic stem cells and its implications in leukemogenesis.

Science.gov (United States)

Seshadri, Madhav; Qu, Cheng-Kui

2016-07-01

Hematopoietic stem cells (HSCs) are a population of cells in the bone marrow which can self-renew, differentiate into late lineage progenitors, or remain quiescent. HSCs exist alongside several cell types in the bone marrow microenvironment that comprise the stem cell niche. These cells regulate HSC function and can contribute to leukemogenesis. In this review we will discuss recent advances in this field. In the vascular niche, arteriolar and sinusoidal zones appear to play distinct roles in HSC function. Endothelial cells modulate HSC function via Notch and other signaling pathways. In the endosteal niche multiple cell types regulate HSCs. Osteoblasts promote HSC quiescence via secreted factors and possibly physical interactions, whereas adipocytes may oppose HSC quiescence. The balance of these opposing factors depends on metabolic cues. Feedback from HSC-derived cells, including macrophages and megakaryocytes also appears to regulate HSC quiescence. Dysfunction of the bone marrow microenvironment, including mesenchymal stem cell-derived stromal cells and the sympathetic nervous system can induce or alter the progression of hematologic malignancies. Many cell types in the bone marrow microenvironment affect HSC function and contribute to malignancy. Further understanding how HSCs are regulated by the microenvironment has clinical implications for stem cell transplantation and other therapies for hematologic malignancies.

A quantitative model of regulator's preference factor (RPF) in electricity-environment coordinated regulation system

Energy Technology Data Exchange (ETDEWEB)

Ren, Yulong; Fu, Shijun [Economy and Business Administration School of Chongqing University, Chongqing 400030 (China)

2010-12-15

This paper explores quantification of regulator's preference factor (RPF) in electricity-environment coordinated regulation system. Based on social welfare economics, we articulately depict RPF's qualitative concept and its economic meaning. Then, applying abstract functions (i.e., abstract social welfare function, abstract utility function, and abstract production function), we deduce the partial-social-welfare elasticity, and build the mathematics model of maximizing social welfare. We nest this elasticity into the model's Kuhn-Tucker conditions, and obtain RPF's definition formula. By solving the Kuhn-Tucker conditions, we get RPF's quantitative formula, which solves the problem of hard to quantify regulator's preference in electricity-environment coordinated regulation system. The result shows that RPF only has relationship to subsystems' production function, and is independent of social welfare function and subsystems' utility function. Finally, we provide an empirical research based on the western region of China from year 1995 to 2004. It reveals that regulator has relative stability preference to mitigating pollutants. And validity test confirms that the empirical result is fit well to the practice. The RPF is truly a more general and valid instrument to measure regulator's preference in its regulated field. (author)

An Age-Related Mechanism of Emotion Regulation: Regulating Sadness Promotes Children's Learning by Broadening Information Processing

Science.gov (United States)

Davis, Elizabeth L.

2016-01-01

Emotion regulation predicts positive academic outcomes like learning, but little is known about "why". Effective emotion regulation likely promotes learning by broadening the scope of what may be attended to after an emotional event. One hundred twenty-six 6- to 13-year-olds' (54% boys) regulation of sadness was examined for changes in…

Deciphering Transcriptional Regulation

DEFF Research Database (Denmark)

Valen, Eivind

The myriad of cells in the human body are all made from the same blueprint: the human genome. At the heart of this diversity lies the concept of gene regulation, the process in which it is decided which genes are used where and when. Genes do not function as on/off buttons, but more like a volume...... mostly near the start of the gene known as the promoter. This region contains patterns scattered in the DNA that the TFs can recognize and bind to. Such binding can prompt the assembly of the pre-initiation complex which ultimately leads to transcription of the gene. In order to achieve the regulation...... on what characterizes a hippocampus promoter. Pairing CAGE with TF binding site prediction we identi¿ed a likely key regulator of hippocampus. Finally, we developed a method for CAGE exploration. While the DeepCAGE library characterized a full 1.4 million transcription initiation events it did not capture...

Electricity regulation and economic growth

OpenAIRE

Costa, M. Teresa (Maria Teresa), 1951-; Garcia-Quevedo, Jose; Trujillo-Baute, Elisa

2018-01-01

The main objective of this paper is to analyse the effect of electricity regulation on economic growth. Although the relationship between electricity consumption and economic growth has been extensively analysed in the empirical literature, this framework has not been used to estimate the effect of electricity regulation on economic growth. Understanding this effect is essential for the assessment of regulatory policy. Specifically, we assess the effects of two major areas of regulation, rene...

Individual Differences in Automatic Emotion Regulation Interact with Primed Emotion Regulation during an Anger Provocation

OpenAIRE

Zhang, Jing; Lipp, Ottmar V.; Hu, Ping

2017-01-01

The current study investigated the interactive effects of individual differences in automatic emotion regulation (AER) and primed emotion regulation strategy on skin conductance level (SCL) and heart rate during provoked anger. The study was a 2 × 2 [AER tendency (expression vs. control) × priming (expression vs. control)] between subject design. Participants were assigned to two groups according to their performance on an emotion regulation-IAT (differentiating automatic emotion control tend...

Analysis of combinatorial regulation: scaling of partnerships between regulators with the number of governed targets.

Directory of Open Access Journals (Sweden)

Nitin Bhardwaj

2010-05-01

Full Text Available Through combinatorial regulation, regulators partner with each other to control common targets and this allows a small number of regulators to govern many targets. One interesting question is that given this combinatorial regulation, how does the number of regulators scale with the number of targets? Here, we address this question by building and analyzing co-regulation (co-transcription and co-phosphorylation networks that describe partnerships between regulators controlling common genes. We carry out analyses across five diverse species: Escherichia coli to human. These reveal many properties of partnership networks, such as the absence of a classical power-law degree distribution despite the existence of nodes with many partners. We also find that the number of co-regulatory partnerships follows an exponential saturation curve in relation to the number of targets. (For E. coli and Bacillus subtilis, only the beginning linear part of this curve is evident due to arrangement of genes into operons. To gain intuition into the saturation process, we relate the biological regulation to more commonplace social contexts where a small number of individuals can form an intricate web of connections on the internet. Indeed, we find that the size of partnership networks saturates even as the complexity of their output increases. We also present a variety of models to account for the saturation phenomenon. In particular, we develop a simple analytical model to show how new partnerships are acquired with an increasing number of target genes; with certain assumptions, it reproduces the observed saturation. Then, we build a more general simulation of network growth and find agreement with a wide range of real networks. Finally, we perform various down-sampling calculations on the observed data to illustrate the robustness of our conclusions.

ON THE ROLE OF PERIOD-2 IN THE CIRCADIAN AND HOMEOSTATIC REGULATION OF SLEEP

OpenAIRE

La Spada, F.

2013-01-01

Humans spend one third of their life sleeping, then we could raise the basic question: Why do we sleep? Despite the fact that we still don't fully understand its function, we made much progress in understanding at different levels how sleep is regulated. One model suggests that sleep is regulated by two processes: a homeostatic process that tracks the need for sleep and by a circadian rhythm that determines the preferred time-of-day sleep occurs. At the molecular level circadian rhythms ar...

Believing Is Doing: Emotion Regulation Beliefs Are Associated With Emotion Regulation Behavioral Choices and Subjective Well-Being

Directory of Open Access Journals (Sweden)

Catherine Nicole Marie Ortner

2017-03-01

Full Text Available Research in emotion regulation has begun to examine various predictors of emotion regulation choices, including individual differences and contextual variables. However, scant attention has been paid to the extent to which people’s beliefs about the specific consequences of emotion regulation strategies for the components of an emotional response and long-term well-being predict their behavioral regulatory choices and, in turn, their subjective well-being. Participants completed measures to assess their beliefs about the consequences of functional and dysfunctional strategies, behavioral choices of emotion regulation strategies in negative scenarios, and subjective well-being. The model that fit the data indicated partial mediation whereby beliefs were associated with approximately 9% of the variance in choices. Emotion regulation choices were related to subjective well-being, with an additional direct effect between beliefs and well-being. This suggests beliefs play a role in people’s regulatory choices. Future research should explore how beliefs interact with individual differences and contextual variables to better understand why people regulate their emotions in different ways and, ultimately, to help individuals make healthy emotion regulation choices.

Believing Is Doing: Emotion Regulation Beliefs Are Associated With Emotion Regulation Behavioral Choices and Subjective Well-Being.

Science.gov (United States)

Ortner, Catherine Nicole Marie; Briner, Esther Lydia; Marjanovic, Zdravko

2017-03-01

Research in emotion regulation has begun to examine various predictors of emotion regulation choices, including individual differences and contextual variables. However, scant attention has been paid to the extent to which people's beliefs about the specific consequences of emotion regulation strategies for the components of an emotional response and long-term well-being predict their behavioral regulatory choices and, in turn, their subjective well-being. Participants completed measures to assess their beliefs about the consequences of functional and dysfunctional strategies, behavioral choices of emotion regulation strategies in negative scenarios, and subjective well-being. The model that fit the data indicated partial mediation whereby beliefs were associated with approximately 9% of the variance in choices. Emotion regulation choices were related to subjective well-being, with an additional direct effect between beliefs and well-being. This suggests beliefs play a role in people's regulatory choices. Future research should explore how beliefs interact with individual differences and contextual variables to better understand why people regulate their emotions in different ways and, ultimately, to help individuals make healthy emotion regulation choices.

Definitional Issues in Emotion Regulation Research

Science.gov (United States)

Bridges, Lisa J.; Denham, Susanne A.; Ganiban, Jody M.

2004-01-01

Operational definitions of emotion regulation are frequently unclear, as are links between emotion regulation measures and underlying theoretical constructs. This is of concern because measurement decisions can have both intentional and unintentional implications for underlying conceptualizations of emotion regulation. This report examines the…

ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion.

Science.gov (United States)

Chen, Wei-Ta; Ebelt, Nancy D; Stracker, Travis H; Xhemalce, Blerta; Van Den Berg, Carla L; Miller, Kyle M

2015-06-01

Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression.

Regulating danger on the highways: hours of service regulations.

Science.gov (United States)

Mansfield, Daniel; Kryger, Meir

2015-12-01

Current hours of service regulations governing commercial truck drivers in place in the United States, Canada, Australia, and the European Union are summarized and compared to facilitate the assessment of the effectiveness of such provisions in preventing fatigue and drowsiness among truck drivers. Current hours of service provisions governing commercial truck drivers were derived from governmental sources. The commercial truck driver hours of service provisions in the United States, Canada, and the European Union permit drivers to work 14 hours and those of Australia permit drivers to work 12 hours a day on a regular basis. The regulations do not state what a driver may do with time off. They are consistent with a driver being able to drive after 24 hours without sleep. They do not take into account circadian rhythm by linking driving or rest to time of day. Current hours of service regulations governing commercial truck drivers leave gaps--permitting drivers to work long hours on a regular basis, permitting driving after no sleep for 24 hours, and failing to take into account the importance of circadian rhythm, endangering the public safety and the truck drivers themselves. Copyright © 2015 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

Novel insights into a retinoic-acid-induced cleft palate based on Rac1 regulation of the fibronectin arrangement.

Science.gov (United States)

Tang, Qinghuang; Li, Liwen; Lee, Min-Jung; Ge, Qing; Lee, Jong-Min; Jung, Han-Sung

2016-03-01

Retinoic acid (RA)-induced cleft palate results from both extrinsic obstructions by the tongue and internal factors within the palatal shelves. Our previous study showed that the spatiotemporal expression of Rac1 regulates the fibronectin (FN) arrangement through cell density alterations that play an important role in palate development. In this study, we investigate the involvement of the Rac1 regulation of the FN arrangement in RA-induced cleft palate. Our results demonstrate that RA-induced intrinsic alterations in palatal shelves, including a delayed progress of cell condensation, delay palate development, even after the removal of the tongue. Further analysis shows that RA treatment diminishes the region-distinctive expression of Rac1 within the palatal shelves, which reversely alters the fibrillar arrangement of FN. Furthermore, RA treatment disrupts the formation of lamellipodia, which are indicative structures of cell migration that are regulated by Rac1. These results suggest that the Rac1 regulation of the FN arrangement is involved in RA-induced cleft palate through the regulation of cell migration, which delays the progress of cell condensation and subsequently influences the FN arrangement, inducing a delay in palate development. Our study provides new insights into the RA-induced impairment of palatal shelf elevation based on cell migration dynamics.

Panel presentation: Should some type of incentive regulation replace traditional methods for regulating LDC's?

International Nuclear Information System (INIS)

Farman, R.D.

1992-01-01

This paper discusses the wants and fears of gas utility companies with regards to incentive regulation. The idea of replacing the traditional rate-of-return regulation with incentive regulation sound very desirous in that it should provide greater management flexibility, quicker and more streamlined regulatory processes, and utility financial rewards based on how well customer needs are met. However, the main fear is that this could result in arbitrary, inappropriate productivity or efficiency targets, or would embody a risk/reward ratio skewed more heavily toward financial penalties than opportunities to increase earnings. The paper presents some of the obstacles of traditional regulation which include a lack of incentive to minimize operational costs; a lack of incentive to introduce new technology, products, or services; prevent the need for flexibility to compete in contestable markets; and the diversion caused by utility managers having to manage the regulatory process rather than delivering value to customers. The paper concludes by comparing the incentive regulation program used in the telecommunications industry to the natural gas industry to demonstrate why the success of the telecommunications model doesn't apply to the gas utilities incentive model

History and future of genetically engineered food animal regulation: an open request.

Science.gov (United States)

Wells, Kevin D

2016-06-01

Modern biotechnology resulted from of a series of incremental improvements in the understanding of DNA and the enzymes that nature evolved to manipulate it. As the potential impact of genetic engineering became apparent, scientists began the process of trying to identify the potential unintended consequences. Restrictions to recombinant DNA experimentation were at first self-imposed. Collaborative efforts between scientists and lawyers formalized an initial set of guidelines. These guidelines have been used to promulgate regulations around world. However, the initial guidelines were only intended as a starting point and were motivated by a specific set of concerns. As new data became available, the guidelines and regulations should have been adapted to the new knowledge. Instead, other social drivers drove the development of regulations. For most species and most applications, the framework that was established has slowly allowed some products to reach the market. However, genetically engineered livestock that are intended for food have been left in a regulatory state of limbo. To date, no genetically engineered food animal is available in the marketplace. A short history and a U.S.-based genetic engineer's perspective are presented. In addition, a request to regulatory agencies is presented for consideration as regulation continues to evolve. Regulators appear to have shown preference for the slow, random progression of evolution over the efficiency of intentional design.

MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligo.

Science.gov (United States)

Sahoo, Anupama; Lee, Bongyong; Boniface, Katia; Seneschal, Julien; Sahoo, Sanjaya K; Seki, Tatsuya; Wang, Chunyan; Das, Soumen; Han, Xianlin; Steppie, Michael; Seal, Sudipta; Taieb, Alain; Perera, Ranjan J

2017-09-01

Vitiligo is a common chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic, environmental, and biochemical causes, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. In this study we characterized the human vitiligo cell line PIG3V and the normal human melanocyte line HEM-l by RNA sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched microRNA-211, a known metabolic switch in nonpigmented melanoma cells, was severely down-regulated in vitiligo cell line PIG3V and skin biopsy samples from vitiligo patients, whereas its predicted targets PPARGC1A, RRM2, and TAOK1 were reciprocally up-regulated. microRNA-211 binds to PGC1-α 3' untranslated region locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated microRNA-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of microRNA-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

MiRNA-mediated regulation of cell signaling and homeostasis in the early mouse embryo.

Science.gov (United States)

Pernaute, Barbara; Spruce, Thomas; Rodriguez, Tristan A; Manzanares, Miguel

2011-02-15

At the time of implantation the mouse embryo is composed of three tissues the epiblast, trophectoderm and primitive endoderm. As development progresses the epiblast goes on to form the foetus whilst the trophectoderm and primitive endoderm give rise to extra-embryonic structures with important roles in embryo patterning and nutrition. Dramatic changes in gene expression occur during early embryo development and these require regulation at different levels. miRNAs are small non coding RNAs that have emerged over the last decade as important post-transcriptional repressors of gene expression. The roles played by miRNAs during early mammalian development are only starting to be elucidated. In order to gain insight into the function of miRNAs in the different lineages of the early mouse embryo we have analysed in depth the phenotype of embryos and extra-embryonic stem cells mutant for the miRNA maturation protein Dicer. This study revealed that miRNAs are involved in regulating cell signaling and homeostasis in the early embryo. Specifically, we identified a role for miRNAs in regulating the Erk signaling pathway in the extra-embryonic endoderm, cell cycle progression in extra-embryonic tissues and apoptosis in the epiblast.

Exploring epigenetic regulation of fear memory and biomarkers associated with Post-traumatic stress disorder

Directory of Open Access Journals (Sweden)

Stephanie A. Maddox

2013-07-01

Full Text Available This review examines recent work on epigenetic mechanisms underlying animal models of fear learning as well as its translational implications in disorders of fear regulation, such as Posttraumatic Stress Disorder (PTSD. Specifically, we will examine work outlining roles of differential histone acetylation and DNA methylation associated with consolidation, reconsolidation and extinction in Pavlovian fear paradigms. We then focus on the numerous studies examining the epigenetic modifications of the Brain-derived neurotrophin factor (BDNF pathway and the extension of these findings from animal models to recent work in human clinical populations. We will also review recently published data on FKBP5 regulation of glucocorticoid receptor function, and how this is modulated in animal models of PTSD and in human clinical populations via epigenetic mechanisms. As glucocorticoid regulation of memory consolidation is well established in fear models, we examine how these recent data contribute to our broader understanding of fear memory formation. The combined recent progress in epigenetic modulation of memory with the advances in fear neurobiology suggest that this area may be critical to progress in our understanding of fear-related disorders with implications for new approaches to treatment and prevention.

Systematic Analysis of the Functions of Lysine Acetylation in the Regulation of Tat Activity.

Directory of Open Access Journals (Sweden)

Minghao He

Full Text Available The Tat protein of HIV-1 has several well-known properties, such as nucleocytoplasmic trafficking, transactivation of transcription, interaction with tubulin, regulation of mitotic progression, and induction of apoptosis. Previous studies have identified a couple of lysine residues in Tat that are essential for its functions. In order to analyze the functions of all the lysine residues in Tat, we mutated them individually to alanine, glutamine, and arginine. Through systematic analysis of the lysine mutants, we discovered several previously unidentified characteristics of Tat. We found that lysine acetylation could modulate the subcellular localization of Tat, in addition to the regulation of its transactivation activity. Our data also revealed that lysine mutations had distinct effects on microtubule assembly and Tat binding to bromodomain proteins. By correlation analysis, we further found that the effects of Tat on apoptosis and mitotic progression were not entirely attributed to its effect on microtubule assembly. Our findings suggest that Tat may regulate diverse cellular activities through binding to different proteins and that the acetylation of distinct lysine residues in Tat may modulate its interaction with various partners.

Cyclin D3 interacts with vitamin D receptor and regulates its transcription activity

International Nuclear Information System (INIS)

Jian Yongzhi; Yan Jun; Wang Hanzhou; Chen Chen; Sun Maoyun; Jiang Jianhai; Lu Jieqiong; Yang Yanzhong; Gu Jianxin

2005-01-01

D-type cyclins are essential for the progression through the G1 phase of the cell cycle. Besides serving as cell cycle regulators, D-type cyclins were recently reported to have transcription regulation functions. Here, we report that cyclin D3 is a new interacting partner of vitamin D receptor (VDR), a member of the superfamily of nuclear receptors for steroid hormones, thyroid hormone, and the fat-soluble vitamins A and D. The interaction was confirmed with methods of yeast two-hybrid system, in vitro binding analysis and in vivo co-immunoprecipitation. Cyclin D3 interacted with VDR in a ligand-independent manner, but treatment of the ligand, 1,25-dihydroxyvitamin D3, strengthened the interaction. Confocal microscopy analysis showed that ligand-activated VDR led to an accumulation of cyclin D3 in the nuclear region. Cyclin D3 up-regulated transcriptional activity of VDR and this effect was counteracted by overexpression of CDK4 and CDK6. These findings provide us a new clue to understand the transcription regulation functions of D-type cyclins

Ketamine and international regulations.

Science.gov (United States)

Liao, Yanhui; Tang, Yi-Lang; Hao, Wei

2017-09-01

Ketamine is an anesthetic commonly used in low-income countries and has recently been shown to be effective for treatment-resistant depression. However, the illicit manufacturing, trafficking, and nonmedical use of ketamine are increasing globally, and its illicit use poses major public health challenges in many countries. To review the nonmedical use of ketamine in selected countries and its regulatory control. We conducted a review of literature identified from searches of the China National Knowledge Infrastructure (CNKI) (1979-2016) and PubMed databases, supplemented by additional references identified by the authors. Special attention was given to the regulation of ketamine. Illicit manufacturing, trafficking, and use of ketamine appear to have begun on a large scale in several Asian nations, and it has subsequently spread to other regions. Regulations governing availability of ketamine vary across countries, but there is a clear trend toward tighter regulations. As nonmedical use of ketamine and its harmful consequences have worsened globally, stricter controls are necessary. Appropriate regulation of ketamine is important for international efforts to control ketamine's cross-border trafficking and its nonmedical use.

Regulating nuclear fuel waste

International Nuclear Information System (INIS)

1995-01-01

When Parliament passed the Atomic Energy Control Act in 1946, it erected the framework for nuclear safety in Canada. Under the Act, the government created the Atomic Energy Control Board and gave it the authority to make and enforce regulations governing every aspect of nuclear power production and use in this country. The Act gives the Control Board the flexibility to amend its regulations to adapt to changes in technology, health and safety standards, co-operative agreements with provincial agencies and policy regarding trade in nuclear materials. This flexibility has allowed the Control Board to successfully regulate the nuclear industry for more than 40 years. Its mission statement 'to ensure that the use of nuclear energy in Canada does not pose undue risk to health, safety, security and the environment' concisely states the Control Board's primary objective. The Atomic Energy Control Board regulates all aspects of nuclear energy in Canada to ensure there is no undue risk to health, safety, security or the environment. It does this through a multi-stage licensing process

Cystatin F as a regulator of immune cell cytotoxicity.

Science.gov (United States)

Kos, Janko; Nanut, Milica Perišić; Prunk, Mateja; Sabotič, Jerica; Dautović, Esmeralda; Jewett, Anahid

2018-05-10

Cysteine cathepsins are lysosomal peptidases involved in the regulation of innate and adaptive immune responses. Among the diverse processes, regulation of granule-dependent cytotoxicity of cytotoxic T-lymphocytes (CTLs) and natural killer (NK) cells during cancer progression has recently gained significant attention. The function of cysteine cathepsins is regulated by endogenous cysteine protease inhibitors-cystatins. Whereas other cystatins are generally cytosolic or extracellular proteins, cystatin F is present in endosomes and lysosomes and is thus able to regulate the activity of its target directly. It is delivered to endosomal/lysosomal vesicles as an inactive, disulphide-linked dimer. Proteolytic cleavage of its N-terminal part leads to the monomer, the only form that is a potent inhibitor of cathepsins C, H and L, involved in the activation of granzymes and perforin. In NK cells and CTLs the levels of active cathepsin C and of granzyme B are dependent on the concentration of monomeric, active cystatin F. In tumour microenvironment, inactive dimeric cystatin F can be secreted from tumour cells or immune cells and further taken up by the cytotoxic cells. Subsequent monomerization and inhibition of cysteine cathepsins within the endosomal/lysosomal vesicles impairs granzyme and perforin activation, and provokes cell anergy. Further, the glycosylation pattern has been shown to be important in controlling secretion of cystatin F from target cells, as well as internalization by cytotoxic cells and trafficking to endosomal/lysosomal vesicles. Cystatin F is therefore an important mediator used by bystander cells to reduce NK and T-cell cytotoxicity.

EWSR1 regulates mitosis by dynamically influencing microtubule acetylation.

Science.gov (United States)

Wang, Yi-Long; Chen, Hui; Zhan, Yi-Qun; Yin, Rong-Hua; Li, Chang-Yan; Ge, Chang-Hui; Yu, Miao; Yang, Xiao-Ming

2016-08-17

EWSR1, participating in transcription and splicing, has been identified as a translocation partner for various transcription factors, resulting in translocation, which in turn plays crucial roles in tumorigenesis. Recent studies have investigated the role of EWSR1 in mitosis. However, the effect of EWSR1 on mitosis is poorly understood. Here, we observed that depletion of EWSR1 resulted in cell cycle arrest in the mitotic phase, mainly due to an increase in the time from nuclear envelope breakdown to metaphase, resulting in a high percentage of unaligned chromosomes and multipolar spindles. We also demonstrated that EWSR1 is a spindle-associated protein that interacts with α-tubulin during mitosis. EWSR1 depletion increased the cold-sensitivity of spindle microtubules, and decreased the rate of spindle assembly. EWSR1 regulated the level of microtubule acetylation in the mitotic spindle; microtubule acetylation was rescued in EWSR1-depleted mitotic cells following suppression of HDAC6 activity by its specific inhibitor or siRNA treatment. In summary, these results suggest that EWSR1 regulates the acetylation of microtubules in a cell cycle-dependent manner through its dynamic location on spindle MTs, and may be a novel regulator for mitosis progress independent of its translocation.

Spatiotemporal Regulation of Nuclear Transport Machinery and Microtubule Organization

Science.gov (United States)

Okada, Naoyuki; Sato, Masamitsu

2015-01-01

Spindle microtubules capture and segregate chromosomes and, therefore, their assembly is an essential event in mitosis. To carry out their mission, many key players for microtubule formation need to be strictly orchestrated. Particularly, proteins that assemble the spindle need to be translocated at appropriate sites during mitosis. A small GTPase (hydrolase enzyme of guanosine triphosphate), Ran, controls this translocation. Ran plays many roles in many cellular events: nucleocytoplasmic shuttling through the nuclear envelope, assembly of the mitotic spindle, and reorganization of the nuclear envelope at the mitotic exit. Although these events are seemingly distinct, recent studies demonstrate that the mechanisms underlying these phenomena are substantially the same as explained by molecular interplay of the master regulator Ran, the transport factor importin, and its cargo proteins. Our review focuses on how the transport machinery regulates mitotic progression of cells. We summarize translocation mechanisms governed by Ran and its regulatory proteins, and particularly focus on Ran-GTP targets in fission yeast that promote spindle formation. We also discuss the coordination of the spatial and temporal regulation of proteins from the viewpoint of transport machinery. We propose that the transport machinery is an essential key that couples the spatial and temporal events in cells. PMID:26308057

Network Regulation and Support Schemes

DEFF Research Database (Denmark)

Ropenus, Stephanie; Schröder, Sascha Thorsten; Jacobsen, Henrik

2009-01-01

-in tariffs to market-based quota systems, and network regulation approaches, comprising rate-of-return and incentive regulation. National regulation and the vertical structure of the electricity sector shape the incentives of market agents, notably of distributed generators and network operators......At present, there exists no explicit European policy framework on distributed generation. Various Directives encompass distributed generation; inherently, their implementation is to the discretion of the Member States. The latter have adopted different kinds of support schemes, ranging from feed....... This article seeks to investigate the interactions between the policy dimensions of support schemes and network regulation and how they affect the deployment of distributed generation. Firstly, a conceptual analysis examines how the incentives of the different market agents are affected. In particular...

Attachment and Dyadic Regulation Processes.

Science.gov (United States)

Overall, Nickola C; Simpson, Jeffry A

2015-02-01

Insecurely attached people have relatively unhappy and unstable romantic relationships, but the quality of their relationships depends on how their partners regulate them. Some partners find ways to regulate the emotional and behavioral reactions of insecurely attached individuals, which promotes greater relationship satisfaction and security. We discuss attachment theory and interdependence dilemmas, and then explain how and why certain responses by partners assuage the cardinal concerns of insecure individuals in key interdependent situations. We then review recent studies illustrating how partners can successfully regulate the reactions of anxiously and avoidantly attached individuals, yielding more constructive interactions. We finish by considering how these regulation processes can create a more secure dyadic environment, which helps to improve relationships and attachment security across time.

Executive functions and self-regulation.

Science.gov (United States)

Hofmann, Wilhelm; Schmeichel, Brandon J; Baddeley, Alan D

2012-03-01

Self-regulation is a core aspect of adaptive human behavior that has been studied, largely in parallel, through the lenses of social and personality psychology as well as cognitive psychology. Here, we argue for more communication between these disciplines and highlight recent research that speaks to their connection. We outline how basic facets of executive functioning (working memory operations, behavioral inhibition, and task-switching) may subserve successful self-regulation. We also argue that temporary reductions in executive functions underlie many of the situational risk factors identified in the social psychological research on self-regulation and review recent evidence that the training of executive functions holds significant potential for improving poor self-regulation in problem populations. Copyright © 2012 Elsevier Ltd. All rights reserved.

Navigating the transcriptional roadmap regulating plant secondary cell wall deposition

Directory of Open Access Journals (Sweden)

Steven Grant Hussey

2013-08-01

Full Text Available The current status of lignocellulosic biomass as an invaluable resource in industry, agriculture and health has spurred increased interest in understanding the transcriptional regulation of secondary cell wall (SCW biosynthesis. The last decade of research has revealed an extensive network of NAC, MYB and other families of transcription factors regulating Arabidopsis SCW biosynthesis, and numerous studies have explored SCW-related transcription factors in other dicots and monocots. Whilst the general structure of the Arabidopsis network has been a topic of several reviews, they have not comprehensively represented the detailed protein-DNA and protein-protein interactions described in the literature, and an understanding of network dynamics and functionality has not yet been achieved for SCW formation. Furthermore the methodologies employed in studies of SCW transcriptional regulation have not received much attention, especially in the case of non-model organisms. In this review, we have reconstructed the most exhaustive literature-based network representations to date of SCW transcriptional regulation in Arabidopsis. We include a manipulable Cytoscape representation of the Arabidopsis SCW transcriptional network to aid in future studies, along with a list of supporting literature for each documented interaction. Amongst other topics, we discuss the various components of the network, its evolutionary conservation in plants, putative modules and dynamic mechanisms that may influence network function, and the approaches that have been employed in network inference. Future research should aim to better understand network function and its response to dynamic perturbations, whilst the development and application of genome-wide approaches such as ChIP-seq and systems genetics are in progress for the study of SCW transcriptional regulation in non-model organisms.

An Intrinsic MicroRNA Timer Regulates Progressive Decline in Shoot Regenerative Capacity in Plants

Czech Academy of Sciences Publication Activity Database

Zhang, T.Q.; Lian, H.; Tang, H.B.; Doležal, Karel; Zhou, E.M.; Yu, S.; Chen, J.H.; Chen, Q.; Liu, H.T.; Ljung, K.R.; Wang, J.W.

2015-01-01

Roč. 27, č. 2 (2015), s. 349-360 ISSN 1040-4651 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : CYTOKININ SIGNAL-TRANSDUCTION * B RESPONSE REGULATORS * ARABIDOPSIS-THALIANA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.538, year: 2015

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

5 CFR 179.301 - Scope of regulations.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Scope of regulations. 179.301 Section 179.301 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CLAIMS COLLECTION STANDARDS Administrative Offset § 179.301 Scope of regulations. These regulations apply to the...

Age discrimination: the new Regulations

OpenAIRE

Sprack, John

2006-01-01

A summary of the principal changes introduced by the Employment Equality (Age) Regulations 2006 as they came into effect in England and Wales. Extracts from the Regulations follow the commentary. Article by John Sprack (Barrister, part-time Chairman of Employment Tribunals and author of Tottel's Guide to the Age Discrimination Regulations 2006) published in Amicus Curiae – Journal of the Society for Advanced Legal Studies at the Institute of Advanced Legal Studies. The Journal is produced by ...

Regulations for RA reactor operation

International Nuclear Information System (INIS)

1980-09-01

Regulations for RA reactor operation are written in accordance with the legal regulations defined by the Law about radiation protection and related legal acts, as well as technical standards according to the IAEA recommendations. The contents of this book include: fundamental data about the reactor; legal regulations for reactor operation; organizational scheme for reactor operation; general and detailed instructions for operation, behaviour in the reactor building, performing experiments; operating rules for operation under steady state and accidental conditions [sr

Regulations and instructions; Propisi i uputstva

Energy Technology Data Exchange (ETDEWEB)

NONE

1960-07-01

Regulations and instructions for operating the RA reactor consist of the following chapters: general regulations with the fundamental RA reactor characteristics, operating regulations and instructions for the personnel on duty, regulations for accidental conditions, training program for the staff of the Laboratory for reactor operation. Propisi i uputstva za rad reaktora RA sadrze sledeca poglavlja: opsti deo sa kratkim opisom karakteristika reaktora RA, propisi za rad dezurnog osoblja, propisi za slucaj udesa, program obuke osoblja Laboratorije za eksploataciju reaktora RA.

Chemicals regulation and the Porter Hypothesis:a critical review of the new European chemicals regulation

OpenAIRE

Frohwein, T. (Torsten); Hansjürgens, B. (Bernd)

2005-01-01

In this contribution, discussions about the Porter Hypothesis and the pros and cons of the new European chemicals regulation system REACH are tied together. The contribution seeks to apply the Porter Hypothesis to the field of European chemicals regulation. Porter’s claim of positive effects of regulation on innovations seems especially important for the chemicals sector pursuing differentiation. But, understanding Porter’s concept of strategic management indicates that certain segments of th...

50 CFR 216.86 - Local regulations.

Science.gov (United States)

2010-10-01

... Pribilof Islands Administration § 216.86 Local regulations. Local regulations will be published from time... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Local regulations. 216.86 Section 216.86 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION...

The Self-Regulated Learning Model and Music Education

OpenAIRE

Maja Marijan

2017-01-01

Self-regulation and self-regulated learning (SRL) are important features in music education. In this research self-regulated learning model is presented as a complex, multidimensional structure. SRL starts with the self-regulation. Self-regulation is formed through interaction with the environment, thus self-learning, self-analysis, self-judgment, self-instruction, and self-monitoring are the main functions in self-regulatory structure. Co-regulation is needed, and helps self-regulation to be...

Initial state regulation of investor-owned utilities

International Nuclear Information System (INIS)

Savitski, D.W.

2001-01-01

This paper examines state initiation of public service (or utility) commission regulation of investor-owned utilities (IOUs) using an economic theory of regulation. The decision to regulate IOUs is assumed to have depended on the strength of competing interest groups, e.g. consumers and producers, and on institutional factors, e.g. whether commissioners were appointed or elected. Regulators, which then had jurisdiction over IOU rates, are assumed to have been optimizing agents. The potential benefits of regulation, in turn, translated into pressure to initiate regulation. To test this, a hazard model is applied to state-level data. On the demand side of the regulation market, the distribution of federal power and population density were unrelated, while a set of time dummies was positively related to the probability that a state initiated regulation. On the supply side, the fraction of the population that was urban and whether the governor was Republican or not were positively and negatively related to this probability

SIRT1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival

Science.gov (United States)

Becatti, Matteo; Fiorillo, Claudia; Barygina, Victoria; Cecchi, Cristina; Lotti, Torello; Prignano, Francesca; Silvestro, Agrippino; Nassi, Paolo; Taddei, Niccolò

2014-01-01

Vitiligo is an acquired and progressive hypomelanotic disease that manifests as circumscribed depigmented patches on the skin. The aetiology of vitiligo remains unclear, but recent experimental data underline the interactions between melanocytes and other typical skin cells, particularly keratinocytes. Our previous results indicate that keratinocytes from perilesional skin show the features of damaged cells. Sirtuins (silent mating type information regulation 2 homolog) 1, well-known modulators of lifespan in many species, have a role in gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection and healthy ageing. In the literature there is no evidence for SIRT1 signalling in vitiligo and its possible involvement in disease progression. Here, biopsies were taken from the perilesional skin of 16 patients suffering from non-segmental vitiligo and SIRT1 signalling was investigated in these cells. For the first time, a new SIRT1/Akt, also known as Protein Kinase B (PKB)/mitogen-activated protein kinase (MAPK) signalling has been revealed in vitiligo. SIRT1 regulates MAPK pathway via Akt-apoptosis signal-regulating kinase-1 and down-regulates pro-apoptotic molecules, leading to decreased oxidative stress and apoptotic cell death in perilesional vitiligo keratinocytes. We therefore propose SIRT1 activation as a novel way of protecting perilesional vitiligo keratinocytes from damage. PMID:24410795

Tumor-associated fibrosis as a regulator of tumor immunity and response to immunotherapy.

Science.gov (United States)

Jiang, Hong; Hegde, Samarth; DeNardo, David G

2017-08-01

Tumor-associated fibrosis is characterized by unchecked pro-fibrotic and pro-inflammatory signaling. The components of fibrosis including significant numbers of cancer-associated fibroblasts, dense collagen deposition, and extracellular matrix stiffness, are well appreciated regulators of tumor progression but may also be critical regulators of immune surveillance. While this suggests that the efficacy of immunotherapy may be limited in highly fibrotic cancers like pancreas, it also suggests a therapeutic opportunity to target fibrosis in these tumor types to reawaken anti-tumor immunity. This review discusses the mechanisms by which fibrosis might subvert tumor immunity and how to overcome these mechanisms.

Two new pollution regulations introduced

International Nuclear Information System (INIS)

Anon.

2000-01-01

A newly proposed regulation in Ontario will require the mandatory tracking of 358 airborne pollutants by the electricity sector as well as by other large industrial facilities such as iron and steel manufacturers and petroleum refiners. If passed, the regulation would make Ontario the first jurisdiction in the world to require monitoring and reporting of a full suite of major greenhouse gases, including smog and acid-rain causing emissions. The proposed regulation also provides for immediate public access to any reported information. Ontario residents can comment on the proposed regulation through the Environmental Bill of Rights registry. A new, more severe hazardous waste regulation will also take effect on March 31, 2001, whereby testing for 88 contaminants will be done according to a new standard called the Toxicity Characteristic Leaching Procedure (TCLP). This new regulation also introduces a new 'derived from' rule which requires that a listed hazardous waste keep its classification until it can be demonstrated otherwise. Ontario's list of hazardous wastes has been updated to include 129 new chemicals and industrial processes. The Ontario Ministry has also adopted the Canada-wide Standards for Particulate Matter and Ozone, as well as the Canada-wide Standards for mercury emissions from base metal smelters as well as from incineration of sewage sludge and municipal, medical, hazardous waste

The challenge of legitimizing spatially differentiated regulation

DEFF Research Database (Denmark)

Thorsøe, Martin Hvarregaard; Graversgaard, Morten; Noe, Egon

2017-01-01

Differentiating regulation is a promising approach to agri-environmental regulation that may potentially reduce the environmental impact of agriculture at the lowest possible costs for the farmers and society, but also possesses a number of challenges. In this article, we explore the challenges...... to the legitimacy of agri-environmental regulation that occurs when the regulatory regime changes from general regulation to differentiated regulation. The analysis is based on a case study of the implementation of the Buffer zone act in Denmark – a regulation that prevents agricultural production in a 10 (later 9......) meter fringe around selected waterbodies. We distinguish between two different ways of legitimizing: Producing knowledge and participation. We conclude that to harvest some of the obvious benefits of differentiated regulation a number of challenges must be resolved, 1) ensuring legitimacy...

Negative regulation of NOD1 mediated angiogenesis by PPARγ-regulated miR-125a

International Nuclear Information System (INIS)

Kang, Hyesoo; Park, Youngsook; Lee, Aram; Seo, Hyemin; Kim, Min Jung; Choi, Jihea; Jo, Ha-neul; Jeong, Ha-neul; Cho, Jin Gu; Chang, Woochul; Lee, Myeong-Sok; Jeon, Raok; Kim, Jongmin

2017-01-01

Infection with pathogens activates the endothelial cell and its sustained activation may result in impaired endothelial function. Endothelial dysfunction contributes to the pathologic angiogenesis that is characteristic of infection-induced inflammatory pathway activation. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor which recognizes bacterial molecules and stimulates an immune reaction in various cells; however, the underlying molecular mechanisms in the regulation of inflammation-triggered angiogenesis are not fully understood. Here we report that peroxisome proliferator-activated receptor gamma (PPARγ)-mediated miR-125a serves as an important regulator of NOD1 agonist-mediated angiogenesis in endothelial cells by directly targeting NOD1. Treatment of human umbilical vein endothelial cells with natural PPARγ ligand, 15-Deoxy-Delta12,14-prostaglandin J2, led to inhibition of NOD1 expression; contrarily, protein levels of NOD1 were significantly increased by PPARγ knockdown. We report that PPARγ regulation of NOD1 expression is a novel microRNA-mediated regulation in endothelial cells. MiR-125a expression was markedly decreased in human umbilical vein endothelial cells subjected to PPARγ knockdown while 15-Deoxy-Delta12,14-prostaglandin J2 treatment increased the level of miR-125a. In addition, NOD1 is closely regulated by miR-125a, which directly targets the 3′ untranslated region of NOD1. Moreover, both overexpression of miR-125a and PPARγ activation led to inhibition of NOD1 agonist-induced tube formation in endothelial cells. Finally, NOD1 agonist increased the formation of cranial and subintestinal vessel plexus in zebrafish, and this effect was abrogated by concurrent PPARγ activation. Overall, these findings identify a PPARγ-miR-125a-NOD1 signaling axis in endothelial cells that is critical in the regulation of inflammation-mediated angiogenesis. - Highlights: • Expression of NOD1 is regulated by

46 CFR 515.34 - Regulated Persons Index.

Science.gov (United States)

2010-10-01

... 46 Shipping 9 2010-10-01 2010-10-01 false Regulated Persons Index. 515.34 Section 515.34 Shipping FEDERAL MARITIME COMMISSION REGULATIONS AFFECTING OCEAN SHIPPING IN FOREIGN COMMERCE LICENSING, FINANCIAL... Commission § 515.34 Regulated Persons Index. The Regulated Persons Index is a database containing the names...

No. 434 - Radiation Control Regulation 1993

International Nuclear Information System (INIS)

1993-01-01

This Regulation, made under the Radiation Control Act 1990, replaces the Radioactive Substances Regulation 1959, repealed by the 1990 Act. It deals with licensing of the use of radioactive substances and radiation apparatus, regulates their use, disposal and transport. It also provides for radiation monitoring and emergency planning. (NEA)

25 CFR 275.4 - Implementing regulations.

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Implementing regulations. 275.4 Section 275.4 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR INDIAN SELF-DETERMINATION AND EDUCATION ASSISTANCE ACT PROGRAM STAFFING § 275.4 Implementing regulations. Regulations to implement section 105 of the Act...

Banking regulation and market making

OpenAIRE

Cimon, David A.; Garriott, Corey

2017-01-01

We present a model of market makers subject to recent banking regulations: liquidity and capital constraints in the style of Basel III and a position limit in the style of the Volcker Rule. Regulation causes market makers to reduce their intermediation by refusing principal positions. However, it can improve the bid-ask spread because it induces new market makers to enter. Since market makers intermediate less, asset prices exhibit a liquidity premium. Costs of regulation can be assessed by m...

pH regulation in sensitive and multidrug resistant Ehrlich ascites tumor cells

DEFF Research Database (Denmark)

Litman, Thomas; Pedersen, S F; Kramhøft, B

1998-01-01

Maintenance and regulation of intracellular pH (pHi) was studied in wild-type Ehrlich ascites tumor cells (EHR2) and five progressively daunorubicin-resistant, P-glycoprotein (P-gp)-expressing strains, the maximally resistant of which is EHR2/1.3. Steady-state pHi was similar in cells expressing...

7 CFR 319.77-2 - Regulated articles.

Science.gov (United States)

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 319.77-2 Section 319.77-2....77-2 Regulated articles. In order to prevent the spread of gypsy moth from Canada into noninfested... section are designated as regulated articles. Regulated articles may be imported into the United States...

7 CFR 301.91-2 - Regulated articles.

Science.gov (United States)

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.91-2 Section 301.91-2... Regulations § 301.91-2 Regulated articles. The following are regulated articles: (a) Logs, pulpwood, branches...) Any other product, article, or means of conveyance, of any character whatsoever, not covered by...

48 CFR Appendix - Federal Acquisition Regulation (FAR) Index

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Federal Acquisition Regulation (FAR) Index Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT... (IFMS) Contract clause. FAR Index Federal Acquisition Regulation (FAR) Index Editorial Note: This...

Repertoires of emotion regulation: A person-centered approach to assessing emotion regulation strategies and links to psychopathology.

Science.gov (United States)

Dixon-Gordon, Katherine L; Aldao, Amelia; De Los Reyes, Andres

2015-01-01

Despite growing research on emotion regulation (ER) strategies and psychopathology, research has primarily focused on identifying one-to-one associations between ER strategies and symptoms. Thus, little is known about how patterns in the repertoires of ER strategies are associated with different mental disorders. We utilised latent class analysis to identify distinct repertoires of ER strategies, and their links with various psychopathology domains (i.e., anxiety, depression, disordered eating, borderline personality). Participants (N = 531) reported on their use of seven ER strategies in six recalled stressful contexts, as well as on their symptoms of psychopathology. We identified five classes of ER strategies: Low Regulators (n = 168), High Regulators (n = 140), Adaptive Regulators (n = 99), Worriers/Ruminators (n = 96) and Avoiders (n = 28). Generally, High Regulators and Worriers/Ruminators endorsed greater levels of psychopathology, relative to Low and Adaptive Regulators. Our findings underscore the importance of characterising the dynamics of ER repertoires when seeking to understand links between ER strategies and psychopathology.

MeCP2 Promotes Gastric Cancer Progression Through Regulating FOXF1/Wnt5a/β-Catenin and MYOD1/Caspase-3 Signaling Pathways

Directory of Open Access Journals (Sweden)

Lingyu Zhao

2017-02-01

Full Text Available Methyl-CpG binding protein 2 (MeCP2 has recently been characterized as an oncogene frequently amplified in several types of cancer. However, its precise role in gastric cancer (GC and the molecular mechanism of MeCP2 regulation are still largely unknown. Here we report that MeCP2 is highly expressed in primary GC tissues and the expression level is correlated with the clinicopathologic features of GC. In our experiments, knockdown of MeCP2 inhibited tumor growth. Molecular mechanism of MeCP2 regulation was investigated using an integrated approach with combination of microarray analysis and chromatin immunoprecipitation sequencing (ChIP-Seq. The results suggest that MeCP2 binds to the methylated CpG islands of FOXF1 and MYOD1 promoters and inhibits their expression at the transcription level. Furthermore, we show that MeCP2 promotes GC cell proliferation via FOXF1-mediated Wnt5a/β-Catenin signaling pathway and suppresses apoptosis through MYOD1-mediated Caspase-3 signaling pathway. Due to its high expression level in GC and its critical function in driving GC progression, MeCP2 represents a promising therapeutic target for GC treatment.

The new Romanian regulation of undeclared labour

Directory of Open Access Journals (Sweden)

Raluca Dimitriu

2017-12-01

Full Text Available The “black” labour is an indicator of how efficient is the enforcement of the labour law. Irrespective of how progressive may the labour law system be in a society, the proliferation of work without employment contracts expresses the failure of the labour law system in the real market. In Romania, Labour Code has been dramatically changed in the summer of 2017, especially with the declared goal to better organize the fight against the undeclared work. This paper is an analysis of the impact of these changes in an attempt to highlight the consequences of the new regulation, which seems to be fighting undeclared work predominantly by punitive tools. Following a general approach to the vulnerability of the worker without an employment contract, as well as some of the reasons for such choice, the analysis starts from the identification of the practical difficulties raised by the new regulation. On the other hand, the paper highlights the benefits of returning to the consensual nature of the employment contract, as well as the disadvantages of the excessive widening of the definition of the concept of undeclared work.

Regulations for ionizing radiation protection

International Nuclear Information System (INIS)

1999-01-01

General regulations and principles of radiation protection and safety are presented. In addition, the regulations for licensing and occupational and medical exposure as well as for safe transport of radioactive materials and wastes are given

Radiation emitting devices regulations

International Nuclear Information System (INIS)

1970-01-01

The Radiation Emitting Devices Regulations are the regulations referred to in the Radiation Emitting Devices Act and relate to the operation of devices. They include standards of design and construction, standards of functioning, warning symbol specifications in addition to information relating to the seizure and detention of machines failing to comply with the regulations. The radiation emitting devices consist of the following: television receivers, extra-oral dental x-ray equipment, microwave ovens, baggage inspection x-ray devices, demonstration--type gas discharge devices, photofluorographic x-ray equipment, laser scanners, demonstration lasers, low energy electron microscopes, high intensity mercury vapour discharge lamps, sunlamps, diagnostic x-ray equipment, ultrasound therapy devices, x-ray diffraction equipment, cabinet x-ray equipment and therapeutic x-ray equipment

7 CFR 301.81-2 - Regulated articles.

Science.gov (United States)

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Regulated articles. 301.81-2 Section 301.81-2... Regulations § 301.81-2 Regulated articles. The following are regulated articles: (a) Imported fire ant queens... other articles, except potting soil that is shipped in original containers in which the soil was placed...

Regulation of T Cell Differentiation and Function by EZH2

Science.gov (United States)

Karantanos, Theodoros; Christofides, Anthos; Bardhan, Kankana; Li, Lequn; Boussiotis, Vassiliki A.

2016-01-01

The enhancer of zeste homolog 2 (EZH2), one of the polycomb-group proteins, is the catalytic subunit of Polycomb-repressive complex 2 (PRC2) and induces the trimethylation of the histone H3 lysine 27 (H3K27me3) promoting epigenetic gene silencing. EZH2 contains a SET domain promoting the methyltransferase activity, while the three other protein components of PRC2, namely EED, SUZ12, and RpAp46/48, induce compaction of the chromatin permitting EZH2 enzymatic activity. Numerous studies highlight the role of this evolutionary conserved protein as a master regulator of differentiation in humans involved in the repression of the homeotic gene and the inactivation of X-chromosome. Through its effects in the epigenetic regulation of critical genes, EZH2 has been strongly linked to cell cycle progression, stem cell pluripotency, and cancer biology, being currently at the cutting edge of research. Most recently, EZH2 has been associated with hematopoietic stem cell proliferation and differentiation, thymopoiesis and lymphopoiesis. Several studies have evaluated the role of EZH2 in the regulation of T cell differentiation and plasticity as well as its implications in the development of autoimmune diseases and graft-versus-host disease (GVHD). The aim of this review is to summarize the current knowledge regarding the role of EZH2 in the regulation of the differentiation and function of T cells focusing on possible applications in various immune-mediated conditions, including autoimmune disorders and GVHD. PMID:27199994

DUB3 Deubiquitylating Enzymes Regulate Hippo Pathway Activity by Regulating the Stability of ITCH, LATS and AMOT Proteins

DEFF Research Database (Denmark)

Nguyen, Thanh Hung; Kugler, Jan-Michael; Cohen, Stephen Michael

2017-01-01

/TAZ, is regulated by ubiquitin mediated protein turnover and several ubiquitin ligase complexes have been implicated in human cancer. However, little is known about the deubiquitylating enzymes that counteract these ubiquitin ligases in regulation of the Hippo pathway. Here we identify the DUB3 family...... deubiquitylating enzymes as regulators of Hippo pathway activity. We provide evidence that DUB3 proteins regulate YAP/TAZ activity by controlling the stability of the E3 ligase ITCH, the LATS kinases and the AMOT family proteins. As a novel Hippo pathway regulator, DUB3 has the potential to act a tumor suppressor...

Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer.

Science.gov (United States)

Centuori, Sara M; Martinez, Jesse D

2014-10-01

A high-fat diet coincides with increased levels of bile acids. This increase in bile acids, particularly deoxycholic acid (DCA), has been strongly associated with the development of colon cancer. Conversely, ursodeoxycholic acid (UDCA) may have chemopreventive properties. Although structurally similar, DCA and UDCA present different biological and pathological effects in colon cancer progression. The differential regulation of cancer by these two bile acids is not yet fully understood. However, one possible explanation for their diverging effects is their ability to differentially regulate signaling pathways involved in the multistep progression of colon cancer, such as the epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) pathway. This review will examine the biological effects of DCA and UDCA on colon cancer development, as well as the diverging effects of these bile acids on the oncogenic signaling pathways that play a role in colon cancer development, with a particular emphasis on bile acid regulation of the EGFR-MAPK pathway.

Distributed cooperative regulation for multiagent systems and its applications to power systems: a survey.

Science.gov (United States)

Hu, Jianqiang; Li, Yaping; Yong, Taiyou; Cao, Jinde; Yu, Jie; Mao, Wenbo

2014-01-01

Cooperative regulation of multiagent systems has become an active research area in the past decade. This paper reviews some recent progress in distributed coordination control for leader-following multiagent systems and its applications in power system and mainly focuses on the cooperative tracking control in terms of consensus tracking control and containment tracking control. Next, methods on how to rank the network nodes are summarized for undirected/directed network, based on which one can determine which follower should be connected to leaders such that partial followers can perceive leaders' information. Furthermore, we present a survey of the most relevant scientific studies investigating the regulation and optimization problems in power systems based on distributed strategies. Finally, some potential applications in the frequency tracking regulation of smart grids are discussed at the end of the paper.

Emotional Intelligence of Self Regulated Learners

Science.gov (United States)

Rathore, Ami

2018-01-01

The study was conducted on self regulated learners of senior secondary school. The main objectives of the study were to find out significant dimensions of emotional intelligence held by self regulated learners. To compare the emotional intelligence dimensions of self regulated learners, in terms of subject and gender. To find out the relationship…

Kyoto : implications for utility regulation

International Nuclear Information System (INIS)

Dunsky, P.

2003-01-01

The author provided a historical perspective of energy use and the role of carbon in the western hemisphere by displaying a series of graphs showing carbon intensity of energy, carbon emissions from energy, and the long path to green power. The 1990s represented a decade of progress. Almost three times as much wind capacity as nuclear capacity was added worldwide in 2001. The main challenge for the 21st century will be to bring under-developed countries into the fold while perpetuating the economic and human progress of the twentieth century. It was emphasized that environmental damage caused by utilities must be reversed. The contemporary context for the Kyoto Protocol was reviewed. Canada's commitment under the Kyoto Protocol is to reduce greenhouse gas emissions by 6 per cent below 1990 levels. The challenge for utility regulators to meet this commitment was examined. The costs are not entirely excessive. Some of the regulatory issues were discussed, namely revising a broad rate making framework, cost recovery and others. The Kyoto compliance plan was also reviewed with reference to internal options, external options, identification of regulatory barriers, and consideration of greenhouse gas credit markets. figs

Molecular Regulation of Histamine Synthesis

Directory of Open Access Journals (Sweden)

Hua Huang

2018-06-01

Full Text Available Histamine is a critical mediator of IgE/mast cell-mediated anaphylaxis, a neurotransmitter and a regulator of gastric acid secretion. Histamine is a monoamine synthesized from the amino acid histidine through a reaction catalyzed by the enzyme histidine decarboxylase (HDC, which removes carboxyl group from histidine. Despite the importance of histamine, transcriptional regulation of HDC gene expression in mammals is still poorly understood. In this review, we focus on discussing advances in the understanding of molecular regulation of mammalian histamine synthesis.

Down-regulation of Wild-type p53-induced Phosphatase 1 (Wip1) Plays a Critical Role in Regulating Several p53-dependent Functions in Premature Senescent Tumor Cells*

Science.gov (United States)

Crescenzi, Elvira; Raia, Zelinda; Pacifico, Francesco; Mellone, Stefano; Moscato, Fortunato; Palumbo, Giuseppe; Leonardi, Antonio

2013-01-01

Premature or drug-induced senescence is a major cellular response to chemotherapy in solid tumors. The senescent phenotype develops slowly and is associated with chronic DNA damage response. We found that expression of wild-type p53-induced phosphatase 1 (Wip1) is markedly down-regulated during persistent DNA damage and after drug release during the acquisition of the senescent phenotype in carcinoma cells. We demonstrate that down-regulation of Wip1 is required for maintenance of permanent G2 arrest. In fact, we show that forced expression of Wip1 in premature senescent tumor cells induces inappropriate re-initiation of mitosis, uncontrolled polyploid progression, and cell death by mitotic failure. Most of the effects of Wip1 may be attributed to its ability to dephosphorylate p53 at Ser15 and to inhibit DNA damage response. However, we also uncover a regulatory pathway whereby suppression of p53 Ser15 phosphorylation is associated with enhanced phosphorylation at Ser46, increased p53 protein levels, and induction of Noxa expression. On the whole, our data indicate that down-regulation of Wip1 expression during premature senescence plays a pivotal role in regulating several p53-dependent aspects of the senescent phenotype. PMID:23612976

Metabolic regulation of yeast

Science.gov (United States)

Fiechter, A.

1982-12-01

Metabolic regulation which is based on endogeneous and exogeneous process variables which may act constantly or time dependently on the living cell is discussed. The observed phenomena of the regulation are the result of physical, chemical, and biological parameters. These parameters are identified. Ethanol is accumulated as an intermediate product and the synthesis of biomass is reduced. This regulatory effect of glucose is used for the aerobic production of ethanol. Very high production rates are thereby obtained. Understanding of the regulation mechanism of the glucose effect has improved. In addition to catabolite repression, several other mechanisms of enzyme regulation have been described, that are mostly governed by exogeneous factors. Glucose also affects the control of respiration in a third class of yeasts which are unable to make use of ethanol as a substrate for growth. This is due to the lack of any anaplerotic activity. As a consequence, diauxic growth behavior is reduced to a one-stage growth with a drastically reduced cell yield. The pulse chemostat technique, a systematic approach for medium design is developed and medium supplements that are essential for metabolic control are identified.

76 FR 9988 - Improving EPA Regulations

Science.gov (United States)

2011-02-23

... suggestions do you have for how the Agency could change the regulations to be more flexible? 6. Benefits and... public input on the design of a plan to use for periodic retrospective review of its regulations. DATES... At this time, EPA seeks help in designing the plan it will use for periodic review of regulations...

Psychosocial and behavioural factors in the regulation of weight: Self-regulation, self-efficacy and locus control.

Science.gov (United States)

Menéndez-González, Lara; Orts-Cortés, María Isabel

To identify the relationship and behaviour of the variables of self-control, self-efficacy and locus control in weight regulation of obese, overweight and normal weight adults. Transversal study undertaken in the Health Centre of El Coto (Gijón) from 1st April to 30th July 2015. Subjects between 18-65 years of age with a body mass index recording within the last two years. serious medical illness, eating disorders or pregnant women. Behavioural variables: self-regulation of body weight (Inventory of self-control of body weight), perceived self-efficacy in weight regulation (Inventory of perceived self-efficacy in weight regulation) and locus control in weight regulation (Inventory of locus control in weight regulation). Anthropometric variables: weight (kg) and height (m), body mass index. One hundred and six participants were included: 32 were obese, 28 overweight and 46 normal weight. Significant differences were found between the 3 study groups for total scale of self-efficacy (F=61.77; pcontrol (F=13.92; p=.019), other weighty influences of locus control (F=9.21; pcontrol (F=3.50; p=.011). The relationship between body mass index and behavioural variables of self-efficacy, self-regulation and locus control, suggests the need for healthcare professionals to include psychological factors of behaviour in any preventive action and intervention directed at weight control. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Auxin-BR Interaction Regulates Plant Growth and Development

Science.gov (United States)

Tian, Huiyu; Lv, Bingsheng; Ding, Tingting; Bai, Mingyi; Ding, Zhaojun

2018-01-01

Plants develop a high flexibility to alter growth, development, and metabolism to adapt to the ever-changing environments. Multiple signaling pathways are involved in these processes and the molecular pathways to transduce various developmental signals are not linear but are interconnected by a complex network and even feedback mutually to achieve the final outcome. This review will focus on two important plant hormones, auxin and brassinosteroid (BR), based on the most recent progresses about these two hormone regulated plant growth and development in Arabidopsis, and highlight the cross-talks between these two phytohormones. PMID:29403511

Regulation of Autophagy by Kinases

International Nuclear Information System (INIS)

Sridharan, Savitha; Jain, Kirti; Basu, Alakananda

2011-01-01

Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets

Regulation of Autophagy by Kinases

Energy Technology Data Exchange (ETDEWEB)

Sridharan, Savitha; Jain, Kirti; Basu, Alakananda, E-mail: alakananda.basu@unthsc.edu [Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)

2011-06-09

Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

Regulation of Autophagy by Kinases

Science.gov (United States)

Sridharan, Savitha; Jain, Kirti; Basu, Alakananda

2011-01-01

Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets. PMID:24212825