A conserved serine residue regulates the stability of Drosophila Salvador and human WW domain-containing adaptor 45 through proteasomal degradation

Energy Technology Data Exchange (ETDEWEB)

Wu, Di, E-mail: DiWu@mail.nankai.edu.cn; Wu, Shian

2013-04-19

Highlights: •Ser-17 is key for the stability of Drosophila Sav. •Ala mutation of Ser-17 promotes the proteasomal degradation of Sav. •Ser-17 residue is not the main target of Hpo-induced Sav stabilization. •Hpo-dependent and -independent mechanisms regulate Sav stability. •This mechanism is conserved in the homologue of Sav, human WW45. -- Abstract: The Hippo (Hpo) pathway is a conserved tumor suppressor pathway that controls organ size through the coordinated regulation of apoptosis and proliferation. Drosophila Salvador (Sav), which limits organ size, is a core component of the Hpo pathway. In this study, Ser-17 was shown to be important for the stability of Sav. Alanine mutation of Ser-17 promoted the proteasomal degradation of Sav. Destabilization and stabilization of the Sav protein mediated by alanine mutation of Ser-17 and by Hpo, respectively, were independent of each other. This implies that the stability of Sav is controlled by two mechanisms, one that is Ser-17-dependent and Hpo-independent, and another that is Ser-17-independent and Hpo-dependent. These dual mechanisms also regulated the human counterpart of Drosophila Sav, WW domain-containing adaptor 45 (WW45). The conservation of this regulation adds to its significance in normal physiology and tumorigenesis.

Current regulator for stabilizing electrostatic generators; Regulateur de courant pour stabilisation de generateur electrostatique

Energy Technology Data Exchange (ETDEWEB)

Gabet, A; Taieb, J

1950-07-01

An instrument consisting of two electronic tubes, a triode and a pentode, connected in series, serves as a stabilizer of the current that charges a working model of a van de Graaff generator. The current is maintained at a level corresponding to an auxiliary variable voltage. The triode maintains that voltage, while the pentode regulates the current. Another application of the circuit, viz., the stabilizing of the generator voltage, will be described elsewhere. (author)

SUMOylation regulates nuclear localization and stability of TRAIP/RNF206

International Nuclear Information System (INIS)

Park, I. Seul; Han, Ye gi; Chung, Hee Jin; Jung, Yong Woo; Kim, Yonghwan; Kim, Hongtae

2016-01-01

TRAIP/RNF206 plays diverse roles in cell cycle progression, DNA damage response, and DNA repair pathways. Physiological importance of TRAIP is highlighted by the identification of pathogenic mutations of TRAIP gene in patients diagnosed with primordial dwarfism. Although the diverse functions of TRAIP in the nucleus have been well characterized, molecular mechanism of TRAIP retention in the nucleus has not been determined. Here, we discovered that TRAIP is post-translationally modified by the small ubiquitin-like protein (SUMO). In addition, we identified five SUMOylation sites in TRAIP, and successfully generated SUMOylation deficient mutant of TRAIP. In an attempt to define the functional roles of TRAIP SUMOylation, we discovered that SUMOylation deficient TRAIP is not retained in the nucleus. In addition, protein stability of SUMOylation deficient TRAIP is lower than wild type TRAIP, demonstrating that SUMOylation is critical for both proper subcellular localization and protein stability of TRAIP. Taken together, these findings improve the understanding clinical implication of TRAIP in various diseases including primordial dwarfism and cancers. - Highlights: • TRAIP is post-translationally modified by SUMO. • SUMOylation affects subcellular localization of TRAIP. • SUMOylation regulates protein stability of TRAIP.

SUMOylation regulates nuclear localization and stability of TRAIP/RNF206

Energy Technology Data Exchange (ETDEWEB)

Park, I. Seul; Han, Ye gi; Chung, Hee Jin [Department of Biological Sciences, Sungkyunkwan University (SKKU), Suwon 440-746 (Korea, Republic of); Jung, Yong Woo [College of Pharmacy, Korea University, Sejong City 339-700 (Korea, Republic of); Kim, Yonghwan, E-mail: yhkim@sookmyung.ac.kr [Department of Biological Sciences, Sookmyung Women' s University, Seoul 04310 (Korea, Republic of); Kim, Hongtae, E-mail: khtcat@skku.edu [Department of Biological Sciences, Sungkyunkwan University (SKKU), Suwon 440-746 (Korea, Republic of)

2016-02-19

TRAIP/RNF206 plays diverse roles in cell cycle progression, DNA damage response, and DNA repair pathways. Physiological importance of TRAIP is highlighted by the identification of pathogenic mutations of TRAIP gene in patients diagnosed with primordial dwarfism. Although the diverse functions of TRAIP in the nucleus have been well characterized, molecular mechanism of TRAIP retention in the nucleus has not been determined. Here, we discovered that TRAIP is post-translationally modified by the small ubiquitin-like protein (SUMO). In addition, we identified five SUMOylation sites in TRAIP, and successfully generated SUMOylation deficient mutant of TRAIP. In an attempt to define the functional roles of TRAIP SUMOylation, we discovered that SUMOylation deficient TRAIP is not retained in the nucleus. In addition, protein stability of SUMOylation deficient TRAIP is lower than wild type TRAIP, demonstrating that SUMOylation is critical for both proper subcellular localization and protein stability of TRAIP. Taken together, these findings improve the understanding clinical implication of TRAIP in various diseases including primordial dwarfism and cancers. - Highlights: • TRAIP is post-translationally modified by SUMO. • SUMOylation affects subcellular localization of TRAIP. • SUMOylation regulates protein stability of TRAIP.

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.

The Evolving Contingency Contracting Market: Private Sector Self regulation and United States Government Monitoring of Procurement of Stability Operations Services

Science.gov (United States)

2016-01-01

statements of work would be useful in ensuring ethical govern- ment procurement practices. Conclusions The United States conducts diplomatic, defense...THE EVOLVING CONTINGENCY CONTRACTING MARKET: PRIVATE SECTOR SELF-REGULATION AND UNITED STATES GOVERNMENT MONITORING OF PROCUREMENT OF STABILITY...MARKET: PRIVATE SECTOR SELF-REGULATION AND UNITED STATES GOVERNMENT MONITORING OF PROCUREMENT OF STABILITY OPERATIONS SERVICES Whitney Grespin January

Active Erk Regulates Microtubule Stability in H-ras-Transformed Cells

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Rene E. Harrison

2001-01-01

Full Text Available Increasing evidence suggests that activated erk regulates cell functions, at least in part, by mechanisms that do not require gene transcription. Here we show that the map kinase, erk, decorates microtubules (MTs and mitotic spindles in both parental and mutant active rastransfected 10T1 /2 fibroblasts and MCF10A breast epithelial cells. Approximately 20% of total cellular erk decorated MTs in both cell lines. A greater proportion of activated erk was associated with MTs in the presence of mutant active H-ras than in parental cells. Activation of erk by the ras pathway coincided with a decrease in the stability of MT, as detected by a stability marker. The MKK1 inhibitor, PD98059 and transfection of a dominant negative MKK1 blocked ras-induced instability of MTs but did not modify the association of erk with MTs or affect MT stability of the parental cells. These results indicate that the subset of active erk kinase that associates with MTs contributes to their instability in the presence of a mutant active ras. The MT-associated subset of active erk likely contributes to the enhanced invasive and proliferative abilities of cells containing mutant active H-ras.

Voltage regulator for on-board CMS ECAL powering : dynamic stability of the feedback loop

CERN Document Server

Wertelaers, P

2010-01-01

Traditionally, a capacitor is parallelled to the load of the regulator. Its main function is to steer (limit) the loop bandwidth. An ideal capacitor would provoke near-to-no dynamic stability. A typical remedy, not always elegant, is to select a device with appreciable parasitic series resistance. In this Note, and alternative method is proposed. The CMS ECAL regulator is of adjustable type, and adding a small capacitor at the divider there, brings about a "lead" type control action.

Stability identification for grid-connected inverters with LCL filters considering grid-voltage feedforward regulator

DEFF Research Database (Denmark)

Lu, Minghui; Blaabjerg, Frede

2017-01-01

This paper identifies stable resonance frequency range for grid-connected inverter with Grid-Voltage Feedforward Regulator (GVFR). Beginning with the current loop stability analysis without GVFR, system poles distribution is analytically studied in z-domain, the critical frequency is therefore...... calculated as well as the control gain limit. Then, this paper reveals the GVFR would change the system stability in the weak power system, two frequency boundaries and three typical resonance frequency ranges are identified and compared. System poles distribution shows that GVFR can offer damping effects...

Regulating Cortical Oscillations in an Inhibition-Stabilized Network.

Science.gov (United States)

Jadi, Monika P; Sejnowski, Terrence J

2014-04-21

Understanding the anatomical and functional architecture of the brain is essential for designing neurally inspired intelligent systems. Theoretical and empirical studies suggest a role for narrowband oscillations in shaping the functional architecture of the brain through their role in coding and communication of information. Such oscillations are ubiquitous signals in the electrical activity recorded from the brain. In the cortex, oscillations detected in the gamma range (30-80 Hz) are modulated by behavioral states and sensory features in complex ways. How is this regulation achieved? Although several underlying principles for the genesis of these oscillations have been proposed, a unifying account for their regulation has remained elusive. In a network of excitatory and inhibitory neurons operating in an inhibition-stabilized regime, we show that strongly superlinear responses of inhibitory neurons facilitate bidirectional regulation of oscillation frequency and power. In such a network, the balance of drives to the excitatory and inhibitory populations determines how the power and frequency of oscillations are modulated. The model accounts for the puzzling increase in their frequency with the salience of visual stimuli, and a decrease with their size. Oscillations in our model grow stronger as the mean firing level is reduced, accounting for the size dependence of visually evoked gamma rhythms, and suggesting a role for oscillations in improving the signal-to-noise ratio (SNR) of signals in the brain. Empirically testing such predictions is still challenging, and implementing the proposed coding and communication strategies in neuromorphic systems could assist in our understanding of the biological system.

An improved direct feedback linearization technique for transient stability enhancement and voltage regulation of power generators

Energy Technology Data Exchange (ETDEWEB)

Kenne, Godpromesse [Laboratoire d' Automatique et d' Informatique Appliquee (LAIA), Departement de Genie Electrique, Universite de Dschang, B.P. 134 Bandjoun, Cameroun; Goma, Raphael; Lamnabhi-Lagarrigue, Francoise [Laboratoire des Signaux et Systemes (L2S), CNRS-SUPELEC, Universite Paris XI, 3 Rue Joliot Curie, 91192 Gif-sur-Yvette (France); Nkwawo, Homere [Departement GEII, Universite Paris XIII, IUT Villetaneuse, 99 Avenue Jean Baptiste Clement, 93430 Villetaneuse (France); Arzande, Amir; Vannier, Jean Claude [Departement Energie, Ecole Superieure d' Electricite-SUPELEC, 3 Rue Joliot Curie, 91192 Gif-sur-Yvette (France)

2010-09-15

In this paper, a simple improved direct feedback linearization design method for transient stability and voltage regulation of power systems is discussed. Starting with the classical direct feedback linearization technique currently applied to power systems, an adaptive nonlinear excitation control of synchronous generators is proposed, which is new and effective for engineering. The power angle and mechanical power input are not assumed to be available. The proposed method is based on a standard third-order model of a synchronous generator which requires only information about the physical available measurements of angular speed, active electric power and generator terminal voltage. Experimental results of a practical power system show that fast response, robustness, damping, steady-state and transient stability as well as voltage regulation are all achieved satisfactorily. (author)

Troponin C Mutations Partially Stabilize the Active State of Regulated Actin and Fully Stabilize the Active State When Paired with Δ14 TnT.

Science.gov (United States)

Baxley, Tamatha; Johnson, Dylan; Pinto, Jose R; Chalovich, Joseph M

2017-06-13

Striated muscle contraction is regulated by the actin-associated proteins tropomyosin and troponin. The extent of activation of myosin ATPase activity is lowest in the absence of both Ca 2+ and activating cross-bridges (i.e., S1-ADP or rigor S1). Binding of activating species of myosin to actin at a saturating Ca 2+ concentration stabilizes the most active state (M state) of the actin-tropomyosin-troponin complex (regulated actin). Ca 2+ binding alone produces partial stabilization of the active state. The extent of stabilization at a saturating Ca 2+ concentration depends on the isoform of the troponin subunits, the phosphorylation state of troponin, and, in the case of cardiac muscle, the presence of hypertrophic cardiomyopathy-producing mutants of troponin T and troponin I. Cardiac dysfunction is also associated with mutations of troponin C (TnC). Troponin C mutants A8V, C84Y, and D145E increase the Ca 2+ sensitivity of ATPase activity. We show that these mutants change the distribution of regulated actin states. The A8V and C84Y TnC mutants decreased the inactive B state distribution slightly at low Ca 2+ concentrations, but the D145E mutants had no effect on that state. All TnC mutants increased the level of the active M state compared to that of the wild type, at a saturating Ca 2+ concentration. Troponin complexes that contained two mutations that stabilize the active M state, A8V TnC and Δ14 TnT, appeared to be completely in the active state in the presence of only Ca 2+ . Because Ca 2+ gives full activation, in this situation, troponin must be capable of positioning tropomyosin in the active M state without the need for rigor myosin binding.

Cell Cycle Regulates Nuclear Stability of AID and Determines the Cellular Response to AID.

Directory of Open Access Journals (Sweden)

Quy Le

2015-09-01

Full Text Available AID (Activation Induced Deaminase deaminates cytosines in DNA to initiate immunoglobulin gene diversification and to reprogram CpG methylation in early development. AID is potentially highly mutagenic, and it causes genomic instability evident as translocations in B cell malignancies. Here we show that AID is cell cycle regulated. By high content screening microscopy, we demonstrate that AID undergoes nuclear degradation more slowly in G1 phase than in S or G2-M phase, and that mutations that affect regulatory phosphorylation or catalytic activity can alter AID stability and abundance. We directly test the role of cell cycle regulation by fusing AID to tags that destabilize nuclear protein outside of G1 or S-G2/M phases. We show that enforced nuclear localization of AID in G1 phase accelerates somatic hypermutation and class switch recombination, and is well-tolerated; while nuclear AID compromises viability in S-G2/M phase cells. We identify AID derivatives that accelerate somatic hypermutation with minimal impact on viability, which will be useful tools for engineering genes and proteins by iterative mutagenesis and selection. Our results further suggest that use of cell cycle tags to regulate nuclear stability may be generally applicable to studying DNA repair and to engineering the genome.

[Regulation of thermal stability of enzymes by changing the composition of media. Native and modified alpha-chymotrypsin].

Science.gov (United States)

Levitskiĭ, V Iu; Melik-Nubarov, N S; Slepnev, V I; Shikshnis, V A; Mozhaev, V V

1990-01-01

Stabilizing effect of denaturing salts on irreversible thermoinactivation of native and modified alpha-chymotrypsin at elevated temperatures is observed. The effect is caused by a shift of conformational equilibrium, at the primary step of reversible unfolding in the course of thermoinactivation, to a more unfolded form which is not able to refold "incorrectly". The stability of alpha-chymotrypsin is regulated within a wide range by medium alteration: the stabilizing effects are similar to those achieved by multipoint attachment of the enzyme to a support or by hydrophilization of protein by covalent modification.

Regulation of mIκBNS stability through PEST-mediated degradation by proteasome

Energy Technology Data Exchange (ETDEWEB)

Park, Koog Chan; Jeong, Jiyeong; Kim, Keun Il, E-mail: kikim@sookmyung.ac.kr

2014-01-24

Highlights: • mIκBNS is degraded rapidly by proteasome without ubiquitylation. • N-terminal PEST sequence is responsible for the unstable nature of mIκBNS. • PEST sequence is not critical for nuclear localization of mIκBNS. • There is single bona fide NLS at the C-terminus of mIκBNS. - Abstract: Negative regulatory proteins in a cytokine signaling play a critical role in restricting unwanted excess activation of the signaling pathway. At the same time, negative regulatory proteins need to be removed rapidly from cells to respond properly to the next incoming signal. A nuclear IκB protein called IκBNS is known to inhibit a subset of NF-κB target genes upon its expression by NF-κB activation. Here, we show a mechanism to control the stability of mIκBNS which might be important for cells to prepare the next round signaling. We found that mIκBNS is a short-lived protein of which the stability is controlled by proteasome, independent of ubiquitylation process. We identified that the N-terminal PEST sequence in mIκBNS was critical for the regulation of stability.

The role of surface electrostatics on the stability, function and regulation of human cystathionine β-synthase, a complex multidomain and oligomeric protein.

Science.gov (United States)

Pey, Angel L; Majtan, Tomas; Kraus, Jan P

2014-09-01

Human cystathionine β-synthase (hCBS) is a key enzyme of sulfur amino acid metabolism, controlling the commitment of homocysteine to the transsulfuration pathway and antioxidant defense. Mutations in hCBS cause inherited homocystinuria (HCU), a rare inborn error of metabolism characterized by accumulation of toxic homocysteine in blood and urine. hCBS is a complex multidomain and oligomeric protein whose activity and stability are independently regulated by the binding of S-adenosyl-methionine (SAM) to two different types of sites at its C-terminal regulatory domain. Here we study the role of surface electrostatics on the complex regulation and stability of hCBS using biophysical and biochemical procedures. We show that the kinetic stability of the catalytic and regulatory domains is significantly affected by the modulation of surface electrostatics through noticeable structural and energetic changes along their denaturation pathways. We also show that surface electrostatics strongly affect SAM binding properties to those sites responsible for either enzyme activation or kinetic stabilization. Our results provide new insight into the regulation of hCBS activity and stability in vivo with implications for understanding HCU as a conformational disease. We also lend experimental support to the role of electrostatic interactions in the recently proposed binding modes of SAM leading to hCBS activation and kinetic stabilization. Copyright © 2014 Elsevier B.V. All rights reserved.

Brassinosteroids regulate pavement cell growth by mediating BIN2-induced microtubule stabilization.

Science.gov (United States)

Liu, Xiaolei; Yang, Qin; Wang, Yuan; Wang, Linhai; Fu, Ying; Wang, Xuelu

2018-02-23

Brassinosteroids (BRs), a group of plant steroid hormones, play important roles in regulating plant development. The cytoskeleton also affects key developmental processes and a deficiency in BR biosynthesis or signaling leads to abnormal phenotypes similar to those of microtubule-defective mutants. However, how BRs regulate microtubule and cell morphology remains unknown. Here, using liquid chromatography-tandem mass spectrometry, we identified tubulin proteins that interact with Arabidopsis BRASSINOSTEROID INSENSITIVE2 (BIN2), a negative regulator of BR responses in plants. In vitro and in vivo pull-down assays confirmed that BIN2 interacts with tubulin proteins. High-speed co-sedimentation assays demonstrated that BIN2 also binds microtubules. The Arabidopsis genome also encodes two BIN2 homologs, BIN2-LIKE 1 (BIL1) and BIL2, which function redundantly with BIN2. In the bin2-3 bil1 bil2 triple mutant, cortical microtubules were more sensitive to treatment with the microtubule-disrupting drug oryzalin than in wild-type, whereas in the BIN2 gain-of-function mutant bin2-1, cortical microtubules were insensitive to oryzalin treatment. These results provide important insight into how BR regulates plant pavement cell and leaf growth by mediating the stabilization of microtubules by BIN2.

On the development of the new harmonised damage stability regulations for dry cargo and passenger ships

International Nuclear Information System (INIS)

Papanikolaou, Apostolos; Eliopoulou, Eleftheria

2008-01-01

This paper outlines the methodological background and presents a summary of the main results of a series of undertaken international, IMO-led studies, on the harmonisation of the new probabilistic, risk-based regulations with the currently in-force regulatory provisions for assessing the damage stability of dry cargo and passenger ships. It reviews the historical development of the new regulations, to be applied to all new buildings on January 1, 2009, and the anticipated impact of the new rules on the design and indirect operation of various subcategories of dry cargo and passenger ships. It identifies certain loopholes in the existing regulations that appear cured by the new ones, though certain compromises adopted in the development of the new regulations, particularly those related to large passenger ships' survivability, have left some open issues to be addressed in the near future

Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2.

Directory of Open Access Journals (Sweden)

Kunihiko Hatanaka

Full Text Available The fibroblast growth factor (FGF system plays a critical role in the maintenance of vascular integrity via enhancing the stability of VE-cadherin at adherens junctions. However, the precise molecular mechanism is not well understood. In the present study, we aimed to investigate the detailed mechanism of FGF regulation of VE-cadherin function that leads to endothelial junction stabilization.In vitro studies demonstrated that the loss of FGF signaling disrupts the VE-cadherin-catenin complex at adherens junctions by increasing tyrosine phosphorylation levels of VE-cadherin. Among protein tyrosine phosphatases (PTPs known to be involved in the maintenance of the VE-cadherin complex, suppression of FGF signaling reduces SHP2 expression levels and SHP2/VE-cadherin interaction due to accelerated SHP2 protein degradation. Increased endothelial permeability caused by FGF signaling inhibition was rescued by SHP2 overexpression, indicating the critical role of SHP2 in the maintenance of endothelial junction integrity.These results identify FGF-dependent maintenance of SHP2 as an important new mechanism controlling the extent of VE-cadherin tyrosine phosphorylation, thereby regulating its presence in adherens junctions and endothelial permeability.

An Assessment of the Stability and the Potential for In-Situ Synthesis of Regulated Organic Compounds in High Level Radioactive Waste Stored at Hanford, Richland, Washington

Energy Technology Data Exchange (ETDEWEB)

Wiemers, K.D.; Babad, H.; Hallen, R.T.; Jackson, L.P.; Lerchen, M.E.

1999-01-04

The stability assessment examined 269 non-detected regulated compounds, first seeking literature references of the stability of the compounds, then evaluating each compound based upon the presence of functional groups using professional judgment. Compounds that could potentially survive for significant periods in the tanks (>1 year) were designated as stable. Most of the functional groups associated with the regulated organic compounds were considered unstable under tank waste conditions. The general exceptions with respect to functional group stability are some simple substituted aromatic and polycyclic aromatic compounds that resist oxidation and the multiple substituted aliphatic and aromatic halides that hydrolyze or dehydrohalogenate slowly under tank waste conditions. One-hundred and eighty-one (181) regulated, organic compounds were determined as likely unstable in the tank waste environment.

An Assessment of the Stability and the Potential for In-Situ Synthesis of Regulated Organic Compounds in High Level Radioactive Waste Stored at Hanford, Richland, Washington

International Nuclear Information System (INIS)

Wiemers, K.D.; Babad, H.; Hallen, R.T.; Jackson, L.P.; Lerchen, M.E.

1999-01-01

The stability assessment examined 269 non-detected regulated compounds, first seeking literature references of the stability of the compounds, then evaluating each compound based upon the presence of functional groups using professional judgment. Compounds that could potentially survive for significant periods in the tanks (>1 year) were designated as stable. Most of the functional groups associated with the regulated organic compounds were considered unstable under tank waste conditions. The general exceptions with respect to functional group stability are some simple substituted aromatic and polycyclic aromatic compounds that resist oxidation and the multiple substituted aliphatic and aromatic halides that hydrolyze or dehydrohalogenate slowly under tank waste conditions. One-hundred and eighty-one (181) regulated, organic compounds were determined as likely unstable in the tank waste environment

p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability

Directory of Open Access Journals (Sweden)

Giovanni Morelli

2018-05-01

Full Text Available Summary: The protein p27Kip1 plays roles that extend beyond cell-cycle regulation during cerebral cortex development, such as the regulation of neuronal migration and neurite branching via signaling pathways that converge on the actin and microtubule cytoskeletons. Microtubule-dependent transport is essential for the maturation of neurons and the establishment of neuronal connectivity though synapse formation and maintenance. Here, we show that p27Kip1 controls the transport of vesicles and organelles along the axon of mice cortical projection neurons in vitro. Moreover, suppression of the p27Kip1 ortholog, dacapo, in Drosophila melanogaster disrupts axonal transport in vivo, leading to the reduction of locomotor activity in third instar larvae and adult flies. At the molecular level, p27Kip1 stabilizes the α-tubulin acetyltransferase 1, thereby promoting the acetylation of microtubules, a post-translational modification required for proper axonal transport. : Morelli et al. report that p27Kip1/Dacapo modulates the acetylation of microtubules in axons via stabilization of ATAT1, the main α-tubulin acetyltransferase. Its conditional loss leads to the reduction of bidirectional axonal transport of vesicles and mitochondria in vitro in mice and in vivo in Drosophila. Keywords: p27Kip1, dacapo, acetylation, axonal transport, ATAT1, alpha-tubulin, HDAC6, Drosophila, mouse, cerebral cortex

The deubiquitinase USP9X regulates FBW7 stability and suppresses colorectal cancer

Science.gov (United States)

Khan, Omar M.; Carvalho, Joana; Spencer-Dene, Bradley; Mitter, Richard; Frith, David; Snijders, Ambrosius P.; Wood, Stephen A.

2018-01-01

The tumor suppressor FBW7 targets oncoproteins such as c-MYC for ubiquitylation and is mutated in several human cancers. We noted that in a substantial percentage of colon cancers, FBW7 protein is undetectable despite the presence of FBW7 mRNA. To understand the molecular mechanism of FBW7 regulation in these cancers, we employed proteomics and identified the deubiquitinase (DUB) USP9X as an FBW7 interactor. USP9X antagonized FBW7 ubiquitylation, and Usp9x deletion caused Fbw7 destabilization. Mice lacking Usp9x in the gut showed reduced secretory cell differentiation and increased progenitor proliferation, phenocopying Fbw7 loss. In addition, Usp9x inactivation impaired intestinal regeneration and increased tumor burden in colitis-associated intestinal cancer. c-Myc heterozygosity abrogated increased progenitor proliferation and tumor burden in Usp9x-deficient mice, suggesting that Usp9x suppresses tumor formation by regulating Fbw7 protein stability and thereby reducing c-Myc. Thus, we identify a tumor suppressor mechanism in the mammalian intestine that arises from the posttranslational regulation of FBW7 by USP9X independent of somatic FBW7 mutations. PMID:29346117

hSSB1 regulates both the stability and the transcriptional activity of p53

OpenAIRE

Xu, Shuangbing; Wu, Yuanzhong; Chen, Qiong; Cao, Jingying; Hu, Kaishun; Tang, Jianjun; Sang, Yi; Lai, Fenju; Wang, Li; Zhang, Ruhua; Li, Sheng-Ping; Zeng, Yi-Xin; Yin, Yuxin; Kang, Tiebang

2012-01-01

The tumor suppressor p53 is essential for several cellular processes that are involved in the response to diverse genotoxic stress, including cell cycle arrest, DNA repair, apoptosis and senescence. Studies of the regulation of p53 have mostly focused on its stability and transactivation; however, new regulatory molecules for p53 have also been frequently identified. Here, we report that human ssDNA binding protein SSB1 (hSSB1), a novel DNA damage-associated protein, can interact with p53 and...

Process stabilization by peak current regulation in reactive high-power impulse magnetron sputtering of hafnium nitride

International Nuclear Information System (INIS)

Shimizu, T; Villamayor, M; Helmersson, U; Lundin, D

2016-01-01

A simple and cost effective approach to stabilize the sputtering process in the transition zone during reactive high-power impulse magnetron sputtering (HiPIMS) is proposed. The method is based on real-time monitoring and control of the discharge current waveforms. To stabilize the process conditions at a given set point, a feedback control system was implemented that automatically regulates the pulse frequency, and thereby the average sputtering power, to maintain a constant maximum discharge current. In the present study, the variation of the pulse current waveforms over a wide range of reactive gas flows and pulse frequencies during a reactive HiPIMS process of Hf-N in an Ar–N 2 atmosphere illustrates that the discharge current waveform is a an excellent indicator of the process conditions. Activating the reactive HiPIMS peak current regulation, stable process conditions were maintained when varying the N 2 flow from 2.1 to 3.5 sccm by an automatic adjustment of the pulse frequency from 600 Hz to 1150 Hz and consequently an increase of the average power from 110 to 270 W. Hf–N films deposited using peak current regulation exhibited a stable stoichiometry, a nearly constant power-normalized deposition rate, and a polycrystalline cubic phase Hf-N with (1 1 1)-preferred orientation over the entire reactive gas flow range investigated. The physical reasons for the change in the current pulse waveform for different process conditions are discussed in some detail. (paper)

New aspects of protein stability and turnover in the regulation of genome integrity

DEFF Research Database (Denmark)

Gallina, Irene

of DNA repair is the control of protein abundance, both at a global cellular level, and locally at the site of damage. This is achieved through transcriptional regulation of protein synthesis and through the control of protein stability and turnover. In this study, we investigate the role of Rad56...... sensitivity when mutant. Prior to the work presented here,all these loci have been mapped to a specific gene except RAD56. We map the rad56-1 mutation to the NAT3 gene, which encodes the catalytic subunit of the NatB N-terminal acetyltransferase in yeast. Deletion of RAD56 causes sensitivity to X-rays, methyl......-scale studies investigating factors involved in DNA metabolism, but no specific function has been assigned to Cmr1. Taking advantage of a series of high-throughput screens we characterize Cmr1 as a chromatinassociated protein, involved in the regulation of fork progression in the presence of replication stress...

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

Tristetraprolin regulation of interleukin 23 mRNA stability prevents a spontaneous inflammatory disease.

Science.gov (United States)

Molle, Céline; Zhang, Tong; Ysebrant de Lendonck, Laure; Gueydan, Cyril; Andrianne, Mathieu; Sherer, Félicie; Van Simaeys, Gaetan; Blackshear, Perry J; Leo, Oberdan; Goriely, Stanislas

2013-08-26

Interleukin (IL) 12 and IL23 are two related heterodimeric cytokines produced by antigen-presenting cells. The balance between these two cytokines plays a crucial role in the control of Th1/Th17 responses and autoimmune inflammation. Most studies focused on their transcriptional regulation. Herein, we explored the role of the adenine and uridine-rich element (ARE)-binding protein tristetraprolin (TTP) in influencing mRNA stability of IL12p35, IL12/23p40, and IL23p19 subunits. LPS-stimulated bone marrow-derived dendritic cells (BMDCs) from TTP(-/-) mice produced normal levels of IL12/23p40. Production of IL12p70 was modestly increased in these conditions. In contrast, we observed a strong impact of TTP on IL23 production and IL23p19 mRNA stability through several AREs in the 3' untranslated region. TTP(-/-) mice spontaneously develop an inflammatory syndrome characterized by cachexia, myeloid hyperplasia, dermatitis, and erosive arthritis. We observed IL23p19 expression within skin lesions associated with exacerbated IL17A and IL22 production by infiltrating γδ T cells and draining lymph node CD4 T cells. We demonstrate that the clinical and immunological parameters associated with TTP deficiency were completely dependent on the IL23-IL17A axis. We conclude that tight control of IL23 mRNA stability by TTP is critical to avoid severe inflammation.

DBC1 promotes castration-resistant prostate cancer by positively regulating DNA binding and stability of AR-V7.

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Moon, Sue Jin; Jeong, Byong Chang; Kim, Hwa Jin; Lim, Joung Eun; Kwon, Ghee Young; Kim, Jeong Hoon

2018-03-01

Constitutively active AR-V7, one of the major androgen receptor (AR) splice variants lacking the ligand-binding domain, plays a key role in the development of castration-resistant prostate cancer (CRPC) and anti-androgen resistance. However, our understanding of the regulatory mechanisms of AR-V7-driven transcription is limited. Here we report DBC1 as a key regulator of AR-V7 transcriptional activity and stability in CRPC cells. DBC1 functions as a coactivator for AR-V7 and is required for the expression of AR-V7 target genes including CDH2, a mesenchymal marker linked to CRPC progression. DBC1 is required for recruitment of AR-V7 to its target enhancers and for long-range chromatin looping between the CDH2 enhancer and promoter. Mechanistically, DBC1 enhances DNA-binding activity of AR-V7 by direct interaction and inhibits CHIP E3 ligase-mediated ubiquitination and degradation of AR-V7 by competing with CHIP for AR-V7 binding, thereby stabilizing and activating AR-V7. Importantly, DBC1 depletion suppresses the tumorigenic and metastatic properties of CRPC cells. Our results firmly establish DBC1 as a critical AR-V7 coactivator that plays a key role in the regulation of DNA binding and stability of AR-V7 and has an important physiological role in CRPC progression.

ATM regulates Cdt1 stability during the unperturbed S phase to prevent re-replication

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Iwahori, Satoko; Kohmon, Daisuke; Kobayashi, Junya; Tani, Yuhei; Yugawa, Takashi; Komatsu, Kenshi; Kiyono, Tohru; Sugimoto, Nozomi; Fujita, Masatoshi

2014-01-01

Ataxia-telangiectasia mutated (ATM) plays crucial roles in DNA damage responses, especially with regard to DNA double-strand breaks (DSBs). However, it appears that ATM can be activated not only by DSB, but also by some changes in chromatin architecture, suggesting potential ATM function in cell cycle control. Here, we found that ATM is involved in timely degradation of Cdt1, a critical replication licensing factor, during the unperturbed S phase. At least in certain cell types, degradation of p27Kip1 was also impaired by ATM inhibition. The novel ATM function for Cdt1 regulation was dependent on its kinase activity and NBS1. Indeed, we found that ATM is moderately phosphorylated at Ser1981 during the S phase. ATM silencing induced partial reduction in levels of Skp2, a component of SCFSkp2 ubiquitin ligase that controls Cdt1 degradation. Furthermore, Skp2 silencing resulted in Cdt1 stabilization like ATM inhibition. In addition, as reported previously, ATM silencing partially prevented Akt phosphorylation at Ser473, indicative of its activation, and Akt inhibition led to modest stabilization of Cdt1. Therefore, the ATM-Akt-SCFSkp2 pathway may partly contribute to the novel ATM function. Finally, ATM inhibition rendered cells hypersensitive to induction of re-replication, indicating importance for maintenance of genome stability. PMID:24280901

RNase-L regulates the stability of mitochondrial DNA-encoded mRNAs in mouse embryo fibroblasts

International Nuclear Information System (INIS)

Chandrasekaran, Krish; Mehrabian, Zara; Li Xiaoling; Hassel, Bret

2004-01-01

Accelerated decrease in the levels of mitochondrial DNA-encoded mRNA (mt-mRNA) occurs in neuronal cells exposed either to the excitatory amino acid, glutamate or to the sodium ionophore, monensin, suggesting a role of mitochondrial RNase(s) on the stability of mt-mRNAs. Here we report that in mouse embryo fibroblasts that are devoid of the interferon-regulated RNase, RNase-L, the monensin-induced decrease in the half-life of mt-mRNA was reduced. In monensin (250 nM)-treated RNase-L +/+ cells the average half-life of mt-mRNA, determined after termination of transcription with actinomycin D, was found to be 3 h, whereas in monensin-treated RNase-L -/- cells the half-life of mt-mRNA was >6 h. In contrast, the stability of nuclear DNA-encoded β-actin mRNA was unaffected. Induction of RNase-L expression in mouse 3T3 fibroblasts further decreased the monensin-induced reduction in mt-mRNA half-life to 1.5 h. The results indicate that the RNase-L-dependent decrease in mtDNA-encoded mRNA transcript levels occurs through a decrease in the half-life of mt-mRNA, and that RNase-L may play a role in the stability of mt-mRNA

Tumor protein D52 expression is post-transcriptionally regulated by T-cell intercellular antigen (TIA) 1 and TIA-related protein via mRNA stability.

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Motohashi, Hiromi; Mukudai, Yoshiki; Ito, Chihiro; Kato, Kosuke; Shimane, Toshikazu; Kondo, Seiji; Shirota, Tatsuo

2017-05-04

Although tumor protein D52 (TPD52) family proteins were first identified nearly 20 years ago, their molecular regulatory mechanisms remain unclear. Therefore, we investigated the post-transcriptional regulation of TPD52 family genes. An RNA immunoprecipitation (RIP) assay showed the potential binding ability of TPD52 family mRNAs to several RNA-binding proteins, and an RNA degradation assay revealed that TPD52 is subject to more prominent post-transcriptional regulation than are TPD53 and TPD54. We subsequently focused on the 3'-untranslated region (3'-UTR) of TPD52 as a cis -acting element in post-transcriptional gene regulation. Several deletion mutants of the 3'-UTR of TPD52 mRNA were constructed and ligated to the 3'-end of a reporter green fluorescence protein gene. An RNA degradation assay revealed that a minimal cis -acting region, located in the 78-280 region of the 5'-proximal region of the 3'-UTR, stabilized the reporter mRNA. Biotin pull-down and RIP assays revealed specific binding of the region to T-cell intracellular antigen 1 (TIA-1) and TIA-1-related protein (TIAR). Knockdown of TIA-1/TIAR decreased not only the expression, but also the stability of TPD52 mRNA; it also decreased the expression and stability of the reporter gene ligated to the 3'-end of the 78-280 fragment. Stimulation of transforming growth factor-β and epidermal growth factor decreased the binding ability of these factors, resulting in decreased mRNA stability. These results indicate that the 78-280 fragment and TIA-1/TIAR concordantly contribute to mRNA stability as a cis -acting element and trans -acting factor(s), respectively. Thus, we here report the specific interactions between these elements in the post-transcriptional regulation of the TPD52 gene. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

The post-transcriptional regulator rsmA/csrA activates T3SS by stabilizing the 5' UTR of hrpG, the master regulator of hrp/hrc genes, in Xanthomonas.

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Maxuel O Andrade

2014-02-01

Full Text Available The RsmA/CsrA family of the post-transcriptional regulators of bacteria is involved in the regulation of many cellular processes, including pathogenesis. In this study, we demonstrated that rsmA not only is required for the full virulence of the phytopathogenic bacterium Xanthomonas citri subsp. citri (XCC but also contributes to triggering the hypersensitive response (HR in non-host plants. Deletion of rsmA resulted in significantly reduced virulence in the host plant sweet orange and a delayed and weakened HR in the non-host plant Nicotiana benthamiana. Microarray, quantitative reverse-transcription PCR, western-blotting, and GUS assays indicated that RsmA regulates the expression of the type 3 secretion system (T3SS at both transcriptional and post-transcriptional levels. The regulation of T3SS by RsmA is a universal phenomenon in T3SS-containing bacteria, but the specific mechanism seems to depend on the interaction between a particular bacterium and its hosts. For Xanthomonads, the mechanism by which RsmA activates T3SS remains unknown. Here, we show that RsmA activates the expression of T3SS-encoding hrp/hrc genes by directly binding to the 5' untranslated region (UTR of hrpG, the master regulator of the hrp/hrc genes in XCC. RsmA stabilizes hrpG mRNA, leading to increased accumulation of HrpG proteins and subsequently, the activation of hrp/hrc genes. The activation of the hrp/hrc genes by RsmA via HrpG was further supported by the observation that ectopic overexpression of hrpG in an rsmA mutant restored its ability to cause disease in host plants and trigger HR in non-host plants. RsmA also stabilizes the transcripts of another T3SS-associated hrpD operon by directly binding to the 5' UTR region. Taken together, these data revealed that RsmA primarily activates T3SS by acting as a positive regulator of hrpG and that this regulation is critical to the pathogenicity of XCC.

NEURO-SYSTEM OF AIMING AND STABILIZING WITH A REGULATOR ON THE BASIS OF STANDARD MODEL MODEL REFERENCE CONTROLLER

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B.I. Kuznetsov

2015-08-01

Full Text Available The aim of this work is the synthesis of neural network aiming and stabilization system for the special equipment of moving objects with neuro-controller on the basis of standard model and performance comparison of the neural network system with the neural network predictive control. Build a block diagram of the neural network aiming and stabilization system, based on the subject control principle with PD-regulator in the position loop and with neuro-controller on the basis of standard model in the in the velocity loop. The neuro-controller on the basis of standard model Model Reference Controller is synthesized in the MATLAB Neural Network Toolbox and system simulation is performed. The studies show that the transient state variables of the system are oscillatory. Therefore, the neuro-controller with the prediction NN Predictive Controller should be used for aiming and stabilizing system to provide high dynamic characteristics achieved at the cost of higher complexity and computational cost.

The Banana Fruit SINA Ubiquitin Ligase MaSINA1 Regulates the Stability of MaICE1 to be Negatively Involved in Cold Stress Response.

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Fan, Zhong-Qi; Chen, Jian-Ye; Kuang, Jian-Fei; Lu, Wang-Jin; Shan, Wei

2017-01-01

The regulation of ICE1 protein stability is important to ensure effective cold stress response, and is extensively studied in Arabidopsis . Currently, how ICE1 stability in fruits under cold stress is controlled remains largely unknown. Here, we reported the possible involvement of a SEVEN IN ABSENTIA (SINA) ubiquitin ligase MaSINA1 from banana fruit in affecting MaICE1 stability. MaSINA1 was identified based on a yeast two-hybrid screening using MaICE1 as bait. Further yeast two-hybrid, pull-down, bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation (CoIP) assays confirmed that MaSINA1 interacted with MaICE1. The expression of MaSINA1 was repressed by cold stress. Subcellular localization analysis in tobacco leaves showed that MaSINA1 was localized predominantly in the nucleus. In vitro ubiquitination assay showed that MaSINA1 possessed E3 ubiquitin ligase activity. More importantly, in vitro and semi- in vivo experiments indicated that MaSINA1 can ubiquitinate MaICE1 for the 26S proteasome-dependent degradation, and therefore suppressed the transcriptional activation of MaICE1 to MaNAC1, an important regulator of cold stress response of banana fruit. Collectively, our data reveal a mechanism in banana fruit for control of the stability of ICE1 and for the negative regulation of cold stress response by a SINA E3 ligase via the ubiquitin proteasome system.

Regulation of HTLV-1 Tax Stability, Cellular Trafficking and NF-κB Activation by the Ubiquitin-Proteasome Pathway

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Lavorgna, Alfonso; Harhaj, Edward William

2014-01-01

Human T-cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that infects CD4+ T cells and causes adult T-cell leukemia/lymphoma (ATLL) in 3%–5% of infected individuals after a long latent period. HTLV-1 Tax is a trans-activating protein that regulates viral gene expression and also modulates cellular signaling pathways to enhance T-cell proliferation and cell survival. The Tax oncoprotein promotes T-cell transformation, in part via constitutive activation of the NF-κB transcription factor; however, the underlying mechanisms remain unknown. Ubiquitination is a type of post-translational modification that occurs in a three-step enzymatic cascade mediated by E1, E2 and E3 enzymes and regulates protein stability as well as signal transduction, protein trafficking and the DNA damage response. Emerging studies indicate that Tax hijacks the ubiquitin machinery to activate ubiquitin-dependent kinases and downstream NF-κB signaling. Tax interacts with the E2 conjugating enzyme Ubc13 and is conjugated on C-terminal lysine residues with lysine 63-linked polyubiquitin chains. Tax K63-linked polyubiquitination may serve as a platform for signaling complexes since this modification is critical for interactions with NEMO and IKK. In addition to NF-κB signaling, mono- and polyubiquitination of Tax also regulate its subcellular trafficking and stability. Here, we review recent advances in the diverse roles of ubiquitin in Tax function and how Tax usurps the ubiquitin-proteasome pathway to promote oncogenesis. PMID:25341660

E2-EPF UCP regulates stability and functions of missense mutant pVHL via ubiquitin mediated proteolysis.

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Park, Kyeong-Su; Kim, Ju Hee; Shin, Hee Won; Chung, Kyung-Sook; Im, Dong-Soo; Lim, Jung Hwa; Jung, Cho-Rok

2015-10-26

Missense mutation of VHL gene is frequently detected in type 2 VHL diseases and linked to a wide range of pVHL functions and stability. Certain mutant pVHLs retain ability to regulate HIFs but lose their function by instability. In this case, regulating of degradation of mutant pVHLs, can be postulated as therapeutic method. The stability and cellular function of missense mutant pVHLs were determine in HEK293T transient expressing cell and 786-O stable cell line. Ubiquitination assay of mutant VHL proteins was performed in vitro system. Anticancer effect of adenovirus mediated shUCP expressing was evaluated using ex vivo mouse xenograft assay. Three VHL missense mutants (V155A, L158Q, and Q164R) are directly ubiquitinated by E2-EPF UCP (UCP) in vitro. Mutant pVHLs are more unstable than wild type in cell. Missense mutant pVHLs interact with UCP directly in both in vitro and cellular systems. Lacking all of lysine residues of pVHL result in resistance to ubiquitination thereby increase its stability. Missense mutant pVHLs maintained the function of E3 ligase to ubiquitinate HIF-1α in vitro. In cells expressing mutant pVHLs, Glut-1 and VEGF were relatively upregulated compared to their levels in cells expressing wild-type. Depletion of UCP restored missense mutant pVHLs levels and inhibited cell growth. Adenovirus-mediated shUCP RNA delivery inhibited tumor growth in ex vivo mouse xenograft model. These data suggest that targeting of UCP can be one of therapeutic method in type 2 VHL disease caused by unstable but functional missense mutant pVHL.

Uganda; Financial System Stability Assessment, including Reports on the Observance of Standards and Codes on the following topics: Monetary and Financial Policy Transparency, Banking Supervision, Securities Regulation, and Payment Systems

OpenAIRE

International Monetary Fund

2003-01-01

This paper presents findings of Uganda’s Financial System Stability Assessment, including Reports on the Observance of Standards and Codes on Monetary and Financial Policy Transparency, Banking Supervision, Securities Regulation, Insurance Regulation, Corporate Governance, and Payment Systems. The banking system in Uganda, which dominates the financial system, is fundamentally sound, more resilient than in the past, and currently poses no threat to macroeconomic stability. A major disruption ...

[RTEL1 (regulator of telomere elongation helicase 1), a DNA helicase essential for genome stability].

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Le Guen, Tangui; Jullien, Laurent; Schertzer, Mike; Lefebvre, Axelle; Kermasson, Laetitia; de Villartay, Jean-Pierre; Londoño-Vallejo, Arturo; Revy, Patrick

2013-12-01

RTEL1 (regulator of telomere length helicase 1) is a DNA helicase that has been identified more than 10 years ago. Many works since, mainly in the nematode Caenorhabditis elegans and the mouse, have highlighted its role in chromosomal stability, maintenance of telomere length, and DNA repair. Recently, four laboratories have characterized RTEL1 mutations in patients with dyskeratosis congenita (DC) and Hoyeraal-Hreidarsson (HH) syndrome, a rare and severe variant of DC. We here summarize the current knowledge on RTEL1 and discuss the possible other functions that RTEL1 could play. © 2013 médecine/sciences – Inserm.

Compound C prevents Hypoxia-Inducible Factor-1α protein stabilization by regulating the cellular oxygen availability via interaction with Mitochondrial Complex I

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Hagen Thilo

2011-04-01

Full Text Available Abstract The transcription factor Hypoxia-Inducible Factor-1α is a master regulator of the cellular response to low oxygen concentration. Compound C, an inhibitor of AMP-activated kinase, has been reported to inhibit hypoxia dependent Hypoxia-Inducible Factor-1α activation via a mechanism that is independent of AMP-activated kinase but dependent on its interaction with the mitochondrial electron transport chain. The objective of this study is to characterize the interaction of Compound C with the mitochondrial electron transport chain and to determine the mechanism through which the drug influences the stability of the Hypoxia-Inducible Factor-1α protein. We found that Compound C functions as an inhibitor of complex I of the mitochondrial electron transport chain as demonstrated by its effect on mitochondrial respiration. It also prevents hypoxia-induced Hypoxia-Inducible Factor-1α stabilization in a dose dependent manner. In addition, Compound C does not have significant effects on reactive oxygen species production from complex I via both forward and reverse electron flux. This study provides evidence that similar to other mitochondrial electron transport chain inhibitors, Compound C regulates Hypoxia-Inducible Factor-1α stability by controlling the cellular oxygen concentration.

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

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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...

Stepping strategies for regulating gait adaptability and stability.

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Hak, Laura; Houdijk, Han; Steenbrink, Frans; Mert, Agali; van der Wurff, Peter; Beek, Peter J; van Dieën, Jaap H

2013-03-15

Besides a stable gait pattern, gait in daily life requires the capability to adapt this pattern in response to environmental conditions. The purpose of this study was to elucidate the anticipatory strategies used by able-bodied people to attain an adaptive gait pattern, and how these strategies interact with strategies used to maintain gait stability. Ten healthy subjects walked in a Computer Assisted Rehabilitation ENvironment (CAREN). To provoke an adaptive gait pattern, subjects had to hit virtual targets, with markers guided by their knees, while walking on a self-paced treadmill. The effects of walking with and without this task on walking speed, step length, step frequency, step width and the margins of stability (MoS) were assessed. Furthermore, these trials were performed with and without additional continuous ML platform translations. When an adaptive gait pattern was required, subjects decreased step length (padaptations resulted in the preservation of equal MoS between trials, despite the disturbing influence of the gait adaptability task. When the gait adaptability task was combined with the balance perturbation subjects further decreased step length, as evidenced by a significant interaction between both manipulations (p=0.012). In conclusion, able-bodied people reduce step length and increase step width during walking conditions requiring a high level of both stability and adaptability. Although an increase in step frequency has previously been found to enhance stability, a faster movement, which would coincide with a higher step frequency, hampers accuracy and may consequently limit gait adaptability. Copyright © 2012 Elsevier Ltd. All rights reserved.

Microtubular stability affects pVHL-mediated regulation of HIF-1alpha via the p38/MAPK pathway in hypoxic cardiomyocytes.

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Miao Teng

Full Text Available BACKGROUND: Our previous research found that structural changes of the microtubule network influence glycolysis in cardiomyocytes by regulating the hypoxia-inducible factor (HIF-1α during the early stages of hypoxia. However, little is known about the underlying regulatory mechanism of the changes of HIF-1α caused by microtubule network alternation. The von Hippel-Lindau tumor suppressor protein (pVHL, as a ubiquitin ligase, is best understood as a negative regulator of HIF-1α. METHODOLOGY/PRINCIPAL FINDINGS: In primary rat cardiomyocytes and H9c2 cardiac cells, microtubule-stabilization was achieved by pretreating with paclitaxel or transfection of microtubule-associated protein 4 (MAP4 overexpression plasmids and microtubule-depolymerization was achieved by pretreating with colchicine or transfection of MAP4 siRNA before hypoxia treatment. Recombinant adenovirus vectors for overexpressing pVHL or silencing of pVHL expression were constructed and transfected in primary rat cardiomyocytes and H9c2 cells. With different microtubule-stabilizing and -depolymerizing treaments, we demonstrated that the protein levels of HIF-1α were down-regulated through overexpression of pVHL and were up-regulated through knockdown of pVHL in hypoxic cardiomyocytes. Importantly, microtubular structure breakdown activated p38/MAPK pathway, accompanied with the upregulation of pVHL. In coincidence, we found that SB203580, a p38/MAPK inhibitor decreased pVHL while MKK6 (Glu overexpression increased pVHL in the microtubule network altered-hypoxic cardiomyocytes and H9c2 cells. CONCLUSIONS/SIGNIFICANCE: This study suggests that pVHL plays an important role in the regulation of HIF-1α caused by the changes of microtubular structure and the p38/MAPK pathway participates in the process of pVHL change following microtubule network alteration in hypoxic cardiomyocytes.

Pilocarpine-induced seizures trigger differential regulation of microRNA-stability related genes in rat hippocampal neurons.

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Kinjo, Erika R; Higa, Guilherme S V; Santos, Bianca A; de Sousa, Erica; Damico, Marcio V; Walter, Lais T; Morya, Edgard; Valle, Angela C; Britto, Luiz R G; Kihara, Alexandre H

2016-02-12

Epileptogenesis in the temporal lobe elicits regulation of gene expression and protein translation, leading to reorganization of neuronal networks. In this process, miRNAs were described as being regulated in a cell-specific manner, although mechanistics of miRNAs activity are poorly understood. The specificity of miRNAs on their target genes depends on their intracellular concentration, reflecting the balance of biosynthesis and degradation. Herein, we confirmed that pilocarpine application promptly (PAPD4 gene expression in the hippocampus, two genes related to miRNA degradation and stability, respectively. Moreover, SE decreased the number of XRN2-positive cells in the hilus, while reduced the number of PAPD4-positive cells in CA1. XRN2 and PAPD4 levels did not change in calretinin- and CamKII-positive cells, although it was possible to determine that PAPD4, but not XRN2, was upregulated in parvalbumin-positive cells, revealing that SE induction unbalances the accumulation of these functional-opposed proteins in inhibitory interneurons that directly innervate distinct domains of pyramidal cells. Therefore, we were able to disclose a possible mechanism underlying the differential regulation of miRNAs in specific neurons during epileptogenesis.

Structural analysis of inter-genus complexes of V-antigen and its regulator and their stabilization by divalent metal ions.

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Basu, Abhishek; Das, Atanu; Mondal, Abhisek; Datta, Saumen

2016-03-01

Gram-negative bacteria like Yersinia, Pseudomonas, and Aeromonas need type III secretion system (T3SS) for their pathogenicity. V-antigen and its regulator are essential for functioning of T3SS. There is significant functional conservation amongst V-antigen and its regulator belonging to the Ysc family. In this study, we have structurally characterized the inter-genus complexes of V-antigen and its regulator. ConSurf analysis demonstrates that V-antigens belonging to the Ysc family show high structural identity predominantly confined to the two long helical regions. The regulator of V-antigen shows high conservation in its first intramolecular coiled-coil domain, responsible for interaction with V-antigen. ∆LcrG(1-70) localizes within the groove formed by long helices of LcrV, as observed in PcrV-∆PcrG(13-72) interaction. Inter-genus complexes of LcrV-PcrG and PcrV-LcrG exhibited elongated conformation and 1:1 heterodimeric state like the native complex of PcrV-PcrG and LcrV-LcrG. Both native and inter-genus complexes showed rigid tertiary structure, solvent-exposed hydrophobic patches, and cooperative melting behavior with high melting temperature. LcrV-PcrG and PcrV-LcrG showed nanomolar affinity of interaction, identical to PcrV-PcrG interaction, but stronger than LcrV-LcrG interaction. Calcium (a secretion blocker of T3SS) propels all the complexes towards a highly monodisperse form. Calcium and magnesium increase the helicity of the native and inter-genus complexes, and causes helix-helix stabilization. Stabilization of helices leads to a slight increase in the melting temperature by 1.5-2.0 °C. However, calcium does not alter the affinity of interaction of V-antigen and its regulator, emphasizing the effect of divalent of cations at the structural level without any regulatory implications. Therefore, the structural conservation of these inter-genus complexes could be the basis for their functional complementation.

Epigenetic Regulation of Centromere Chromatin Stability by Dietary and Environmental Factors.

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Hernández-Saavedra, Diego; Strakovsky, Rita S; Ostrosky-Wegman, Patricia; Pan, Yuan-Xiang

2017-11-01

The centromere is a genomic locus required for the segregation of the chromosomes during cell division. This chromosomal region together with pericentromeres has been found to be susceptible to damage, and thus the perturbation of the centromere could lead to the development of aneuploidic events. Metabolic abnormalities that underlie the generation of cancer include inflammation, oxidative stress, cell cycle deregulation, and numerous others. The micronucleus assay, an early clinical marker of cancer, has been shown to provide a reliable measure of genotoxic damage that may signal cancer initiation. In the current review, we will discuss the events that lead to micronucleus formation and centromeric and pericentromeric chromatin instability, as well transcripts emanating from these regions, which were previously thought to be inactive. Studies were selected in PubMed if they reported the effects of nutritional status (macro- and micronutrients) or environmental toxicant exposure on micronucleus frequency or any other chromosomal abnormality in humans, animals, or cell models. Mounting evidence from epidemiologic, environmental, and nutritional studies provides a novel perspective on the origination of aneuploidic events. Although substantial evidence exists describing the role that nutritional status and environmental toxicants have on the generation of micronuclei and other nuclear aberrations, limited information is available to describe the importance of macro- and micronutrients on centromeric and pericentromeric chromatin stability. Moving forward, studies that specifically address the direct link between nutritional status, excess, or deficiency and the epigenetic regulation of the centromere will provide much needed insight into the nutritional and environmental regulation of this chromosomal region and the initiation of aneuploidy. © 2017 American Society for Nutrition.

Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein.

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Chen, Linan; Dumelie, Jason G; Li, Xiao; Cheng, Matthew Hk; Yang, Zhiyong; Laver, John D; Siddiqui, Najeeb U; Westwood, J Timothy; Morris, Quaid; Lipshitz, Howard D; Smibert, Craig A

2014-01-07

Smaug is an RNA-binding protein that induces the degradation and represses the translation of mRNAs in the early Drosophila embryo. Smaug has two identified direct target mRNAs that it differentially regulates: nanos and Hsp83. Smaug represses the translation of nanos mRNA but has only a modest effect on its stability, whereas it destabilizes Hsp83 mRNA but has no detectable effect on Hsp83 translation. Smaug is required to destabilize more than one thousand mRNAs in the early embryo, but whether these transcripts represent direct targets of Smaug is unclear and the extent of Smaug-mediated translational repression is unknown. To gain a panoramic view of Smaug function in the early embryo, we identified mRNAs that are bound to Smaug using RNA co-immunoprecipitation followed by hybridization to DNA microarrays. We also identified mRNAs that are translationally repressed by Smaug using polysome gradients and microarrays. Comparison of the bound mRNAs to those that are translationally repressed by Smaug and those that require Smaug for their degradation suggests that a large fraction of Smaug's target mRNAs are both translationally repressed and degraded by Smaug. Smaug directly regulates components of the TRiC/CCT chaperonin, the proteasome regulatory particle and lipid droplets, as well as many metabolic enzymes, including several glycolytic enzymes. Smaug plays a direct and global role in regulating the translation and stability of a large fraction of the mRNAs in the early Drosophila embryo, and has unanticipated functions in control of protein folding and degradation, lipid droplet function and metabolism.

Regulation of human histone gene expression: transcriptional and posttranscriptional control in the coupling of histone messenger RNA stability with DNA replication

International Nuclear Information System (INIS)

Baumbach, L.L.; Stein, G.S.; Stein, J.L.

1987-01-01

The extent to which transcriptional and posttranscriptional regulation contributes to the coupling of histone gene expression and DNA replication was examined during the cell cycle in synchronized HeLa S3 cells. Rates of transcription were determined in vitro in isolated nuclei. A 3-5-fold increase in cell cycle dependent histone gene transcription was observed in early S phase, prior to the peak of DNA synthesis. This result is consistent with a previous determination of histone mRNA synthesis in intact cells. The transcription of these genes did not change appreciably after inhibition of DNA replication by hydroxyurea treatment, although Northern blot analysis indicated that cellular levels of histone mRNA decreased rapidly in the presence of the drug. Total cellular levels of histone mRNA closely parallel the rate of DNA synthesis as a function of cell cycle progression, reaching a maximal 20-fold increase as compared with non S phase levels. This DNA synthesis dependent accumulation of histone mRNA occurs predominantly in the cytoplasm and appears to be mediated primarily by control of histone mRNA stability. Changes in nuclear histone mRNA levels were less pronounced. These combined observations suggest that both transcriptional regulation and posttranscriptional regulation contribute toward control of the cell cycle dependent accumulation of histone mRNA during S phase, while the stability of histone mRNA throughout S phase and the selective turnover of histone mRNAs, either at the natural termination of S phase or following inhibition of DNA synthesis, are posttranscriptionally regulated

METHOD FOR STABILIZING KLYSTRONS

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Magnuson, D.W.; Smith, D.F.

1959-04-14

High-frequency oscillators for the generation of microwaves, particularly a system for stabilizing frequency-modulated klystron oscillators of the reflex type, are described. The system takos advantage of the fact that a change in oscillator frequency will alter the normal phase displacement between the cavity and its modulator, creating an error voltage which is utilized to regulate the frequency of the oscillator and stabilize it.

New insights into transcription fidelity: thermal stability of non-canonical structures in template DNA regulates transcriptional arrest, pause, and slippage.

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Tateishi-Karimata, Hisae; Isono, Noburu; Sugimoto, Naoki

2014-01-01

The thermal stability and topology of non-canonical structures of G-quadruplexes and hairpins in template DNA were investigated, and the effect of non-canonical structures on transcription fidelity was evaluated quantitatively. We designed ten template DNAs: A linear sequence that does not have significant higher-order structure, three sequences that form hairpin structures, and six sequences that form G-quadruplex structures with different stabilities. Templates with non-canonical structures induced the production of an arrested, a slipped, and a full-length transcript, whereas the linear sequence produced only a full-length transcript. The efficiency of production for run-off transcripts (full-length and slipped transcripts) from templates that formed the non-canonical structures was lower than that from the linear. G-quadruplex structures were more effective inhibitors of full-length product formation than were hairpin structure even when the stability of the G-quadruplex in an aqueous solution was the same as that of the hairpin. We considered that intra-polymerase conditions may differentially affect the stability of non-canonical structures. The values of transcription efficiencies of run-off or arrest transcripts were correlated with stabilities of non-canonical structures in the intra-polymerase condition mimicked by 20 wt% polyethylene glycol (PEG). Transcriptional arrest was induced when the stability of the G-quadruplex structure (-ΔG°37) in the presence of 20 wt% PEG was more than 8.2 kcal mol(-1). Thus, values of stability in the presence of 20 wt% PEG are an important indicator of transcription perturbation. Our results further our understanding of the impact of template structure on the transcription process and may guide logical design of transcription-regulating drugs.

Local chromatin structure of heterochromatin regulates repeated DNA stability, nucleolus structure, and genome integrity

Energy Technology Data Exchange (ETDEWEB)

Peng, Jamy C. [Univ. of California, Berkeley, CA (United States)

2007-01-01

Heterochromatin constitutes a significant portion of the genome in higher eukaryotes; approximately 30% in Drosophila and human. Heterochromatin contains a high repeat DNA content and a low density of protein-encoding genes. In contrast, euchromatin is composed mostly of unique sequences and contains the majority of single-copy genes. Genetic and cytological studies demonstrated that heterochromatin exhibits regulatory roles in chromosome organization, centromere function and telomere protection. As an epigenetically regulated structure, heterochromatin formation is not defined by any DNA sequence consensus. Heterochromatin is characterized by its association with nucleosomes containing methylated-lysine 9 of histone H3 (H3K9me), heterochromatin protein 1 (HP1) that binds H3K9me, and Su(var)3-9, which methylates H3K9 and binds HP1. Heterochromatin formation and functions are influenced by HP1, Su(var)3-9, and the RNA interference (RNAi) pathway. My thesis project investigates how heterochromatin formation and function impact nuclear architecture, repeated DNA organization, and genome stability in Drosophila melanogaster. H3K9me-based chromatin reduces extrachromosomal DNA formation; most likely by restricting the access of repair machineries to repeated DNAs. Reducing extrachromosomal ribosomal DNA stabilizes rDNA repeats and the nucleolus structure. H3K9me-based chromatin also inhibits DNA damage in heterochromatin. Cells with compromised heterochromatin structure, due to Su(var)3-9 or dcr-2 (a component of the RNAi pathway) mutations, display severe DNA damage in heterochromatin compared to wild type. In these mutant cells, accumulated DNA damage leads to chromosomal defects such as translocations, defective DNA repair response, and activation of the G2-M DNA repair and mitotic checkpoints that ensure cellular and animal viability. My thesis research suggests that DNA replication, repair, and recombination mechanisms in heterochromatin differ from those in

BANK STABILIZATION, SHORELINE LAND-USE, AND THE DISTRIBUTION OF LARGE WOODY DEBRIS IN A REGULATED REACH OF THE UPPER MISSOURI RIVER, NORTH DAKOTA, USA

Science.gov (United States)

Large woody debris (LWD) is an important component of ecosystem function in floodplain rivers. We examined the effects on LWD distribution of shoreline land use, bank stabilization, local channel geomorphology, and distance from the dam in the Garrison Reach, a regulated reach of...

Mdm2 Phosphorylation Regulates Its Stability and Has Contrasting Effects on Oncogene and Radiation-Induced Tumorigenesis

Directory of Open Access Journals (Sweden)

Michael I. Carr

2016-09-01

Full Text Available ATM phosphorylation of Mdm2-S394 is required for robust p53 stabilization and activation in DNA-damaged cells. We have now utilized Mdm2S394A knockin mice to determine that phosphorylation of Mdm2-S394 regulates p53 activity and the DNA damage response in lymphatic tissues in vivo by modulating Mdm2 stability. Mdm2-S394 phosphorylation delays lymphomagenesis in Eμ-myc transgenic mice, and preventing Mdm2-S394 phosphorylation obviates the need for p53 mutation in Myc-driven tumorigenesis. However, irradiated Mdm2S394A mice also have increased hematopoietic stem and progenitor cell functions, and we observed decreased lymphomagenesis in sub-lethally irradiated Mdm2S394A mice. These findings document contrasting effects of ATM-Mdm2 signaling on p53 tumor suppression and reveal that destabilizing Mdm2 by promoting its phosphorylation by ATM would be effective in treating oncogene-induced malignancies, while inhibiting Mdm2-S394 phosphorylation during radiation exposure or chemotherapy would ameliorate bone marrow failure and prevent the development of secondary hematological malignancies.

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.

Long-term Stabilization of Disturbed Slopes Resulting from Construction Operations

Science.gov (United States)

2018-01-01

Highway construction disturbs soil, which must be stabilized to prevent migration of soil particles into water bodies. Stabilization is enforced by law, regulation, and a permit system. Stabilization is most efficiently attained by reestablishment of...

Protein kinase C ϵ stabilizes β-catenin and regulates its subcellular localization in podocytes.

Science.gov (United States)

Duong, Michelle; Yu, Xuejiao; Teng, Beina; Schroder, Patricia; Haller, Hermann; Eschenburg, Susanne; Schiffer, Mario

2017-07-21

Kidney disease has been linked to dysregulated signaling via PKC in kidney cells such as podocytes. PKCα is a conventional isoform of PKC and a well-known binding partner of β-catenin, which promotes its degradation. β-Catenin is the main effector of the canonical Wnt pathway and is critical in cell adhesion. However, whether other PKC isoforms interact with β-catenin has not been studied systematically. Here we demonstrate that PKCϵ-deficient mice, which develop proteinuria and glomerulosclerosis, display lower β-catenin expression compared with PKC wild-type mice, consistent with an altered phenotype of podocytes in culture. Remarkably, β-catenin showed a reversed subcellular localization pattern: Although β-catenin exhibited a perinuclear pattern in undifferentiated wild-type cells, it predominantly localized to the nucleus in PKCϵ knockout cells. Phorbol 12-myristate 13-acetate stimulation of both cell types revealed that PKCϵ positively regulates β-catenin expression and stabilization in a glycogen synthase kinase 3β-independent manner. Further, β-catenin overexpression in PKCϵ-deficient podocytes could restore the wild-type phenotype, similar to rescue with a PKCϵ construct. This effect was mediated by up-regulation of P-cadherin and the β-catenin downstream target fascin1. Zebrafish studies indicated three PKCϵ-specific phosphorylation sites in β-catenin that are required for full β-catenin function. Co-immunoprecipitation and pulldown assays confirmed PKCϵ and β-catenin as binding partners and revealed that ablation of the three PKCϵ phosphorylation sites weakens their interaction. In summary, we identified a novel pathway for regulation of β-catenin levels and define PKCϵ as an important β-catenin interaction partner and signaling opponent of other PKC isoforms in podocytes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

USP22 acts as an oncogene by regulating the stability of cyclooxygenase-2 in non-small cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Xiao, Haibo [Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092 (China); Tian, Yue [Institute of Orthopaedics, Chinese PLA General Hospital, Beijing 100853 (China); Yang, Yang; Hu, Fengqing; Xie, Xiao; Mei, Ju [Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092 (China); Ding, Fangbao, E-mail: drnail@sina.com [Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092 (China)

2015-05-08

The histone ubiquitin hydrolase ubiquitin-specific protease 22 (USP22) is an epigenetic modifier and an oncogene that is upregulated in many types of cancer. In non-small cell lung cancer (NSCLC), aberrant expression of USP22 is a predictor of poor survival, as is high expression of cyclooxygenase-2 (COX-2). Despite its oncogenic role, few substrates of USP22 have been identified and its mechanism of action in cancer remains unclear. Here, we identified COX-2 as a direct substrate of USP22 and showed that its levels are modulated by USP22 mediated deubiquitination. Silencing of USP22 downregulated COX-2, decreased its half-life, and inhibited lung carcinoma cell proliferation by directly interacting with and modulating the stability and activity of COX-2 through the regulation of its ubiquitination status. The findings of the present study suggest a potential mechanism underlying the oncogenic role of USP22 mediated by the modulation of the stability and activity of COX-2. - Highlights: • USP22 interacts with COX-2. • USP22 deubiquitinates and stabilizes COX-2. • USP22 is required for COX-2-mediated upregulation of prostaglandin E2.

Regulation of rDNA stability by sumoylation

DEFF Research Database (Denmark)

Eckert-Boulet, Nadine; Lisby, Michael

2009-01-01

Repair of DNA lesions by homologous recombination relies on the copying of genetic information from an intact homologous sequence. However, many eukaryotic genomes contain repetitive sequences such as the ribosomal gene locus (rDNA), which poses a risk for illegitimate recombination. Therefore, t......6 complex and sumoylation of Rad52, which directs DNA double-strand breaks in the rDNA to relocalize from within the nucleolus to the nucleoplasm before association with the recombination machinery. The relocalization before repair is important for maintaining rDNA stability. The focus...

Arabidopsis SUMO protease ASP1 positively regulates flowering time partially through regulating FLC stability 

KAUST Repository

Kong, Xiangxiong; Luo, Xi; Qu, Gao Ping; Liu, Peng; Jin, Jing Bo

2016-01-01

The initiation of flowering is tightly regulated by the endogenous and environment signals, which is crucial for the reproductive success of flowering plants. It is well known that autonomous and vernalization pathways repress transcription of FLOWERING LOCUS C (FLC), a focal floral repressor, but how its protein stability is regulated remains largely unknown. Here, we found that mutations in a novel Arabidopsis SUMO protease 1 (ASP1) resulted in a strong late-flowering phenotype under long-days, but to a lesser extent under short-days. ASP1 localizes in the nucleus and exhibited a SUMO protease activity in vitro and in vivo. The conserved Cys-577 in ASP1 is critical for its enzymatic activity, as well as its physiological function in the regulation of flowering time. Genetic and gene expression analyses demonstrated that ASP1 promotes transcription of positive regulators of flowering, such as FT, SOC1 and FD, and may function in both CO-dependent photoperiod pathway and FLC-dependent pathways. Although the transcription level of FLC was not affected in the loss-of-function asp1 mutant, the protein stability of FLC was increased in the asp1 mutant. Taken together, this study identified a novel bona fide SUMO protease, ASP1, which positively regulates transition to flowering at least partly by repressing FLC protein stability.

Arabidopsis SUMO protease ASP1 positively regulates flowering time partially through regulating FLC stability 

KAUST Repository

Kong, Xiangxiong

2016-12-07

The initiation of flowering is tightly regulated by the endogenous and environment signals, which is crucial for the reproductive success of flowering plants. It is well known that autonomous and vernalization pathways repress transcription of FLOWERING LOCUS C (FLC), a focal floral repressor, but how its protein stability is regulated remains largely unknown. Here, we found that mutations in a novel Arabidopsis SUMO protease 1 (ASP1) resulted in a strong late-flowering phenotype under long-days, but to a lesser extent under short-days. ASP1 localizes in the nucleus and exhibited a SUMO protease activity in vitro and in vivo. The conserved Cys-577 in ASP1 is critical for its enzymatic activity, as well as its physiological function in the regulation of flowering time. Genetic and gene expression analyses demonstrated that ASP1 promotes transcription of positive regulators of flowering, such as FT, SOC1 and FD, and may function in both CO-dependent photoperiod pathway and FLC-dependent pathways. Although the transcription level of FLC was not affected in the loss-of-function asp1 mutant, the protein stability of FLC was increased in the asp1 mutant. Taken together, this study identified a novel bona fide SUMO protease, ASP1, which positively regulates transition to flowering at least partly by repressing FLC protein stability.

Proteasome-associated deubiquitinase ubiquitin-specific protease 14 regulates prostate cancer proliferation by deubiquitinating and stabilizing androgen receptor.

Science.gov (United States)

Liao, Yuning; Liu, Ningning; Hua, Xianliang; Cai, Jianyu; Xia, Xiaohong; Wang, Xuejun; Huang, Hongbiao; Liu, Jinbao

2017-02-02

Androgen receptor (AR) is frequently over-expressed and plays a critical role in the growth and progression of human prostate cancer. The therapy attempting to target AR signalling was established in decades ago but the treatment of prostate cancer is far from being satisfactory. The assignable cause is that our understanding of the mechanism of AR regulation and re-activation remains incomplete. Increasing evidence suggests that deubiquitinases are involved in the regulation of cancer development and progression but the specific underlying mechanism often is not elucidated. In the current study, we have identified ubiquitin-specific protease 14 (USP14) as a novel regulator of AR, inhibiting the degradation of AR via deubiquitinating this oncoprotein in the androgen-responsive prostate cancer cells. We found that (i) USP14 could bind to AR, and additionally, both genetic and pharmacological inhibition of USP14 accelerated the ubiquitination and degradation of AR; (ii) downregulation or inhibition of USP14 suppressed cell proliferation and colony formation of LNcap cells and, conversely, overexpression of USP14 promoted the proliferation; and (iii) reduction or inhibition of USP14 induced G0/G1 phase arrest in LNcap prostate cancer cells. Hence, we conclude that USP14 promotes prostate cancer progression likely through stabilization of AR, suggesting that USP14 could be a promising therapeutic target for prostate cancer.

Dispersal and metapopulation stability

Directory of Open Access Journals (Sweden)

Shaopeng Wang

2015-10-01

Full Text Available Metapopulation dynamics are jointly regulated by local and spatial factors. These factors may affect the dynamics of local populations and of the entire metapopulation differently. Previous studies have shown that dispersal can stabilize local populations; however, as dispersal also tends to increase spatial synchrony, its net effect on metapopulation stability has been controversial. Here we present a simple metapopulation model to study how dispersal, in interaction with other spatial and local processes, affects the temporal variability of metapopulations in a stochastic environment. Our results show that in homogeneous metapopulations, the local stabilizing and spatial synchronizing effects of dispersal cancel each other out, such that dispersal has no effect on metapopulation variability. This result is robust to moderate heterogeneities in local and spatial parameters. When local and spatial dynamics exhibit high heterogeneities, however, dispersal can either stabilize or destabilize metapopulation dynamics through various mechanisms. Our findings have important theoretical and practical implications. We show that dispersal functions as a form of spatial intraspecific mutualism in metapopulation dynamics and that its effect on metapopulation stability is opposite to that of interspecific competition on local community stability. Our results also suggest that conservation corridors should be designed with appreciation of spatial heterogeneities in population dynamics in order to maximize metapopulation stability.

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.

Survivin counteracts the therapeutic effect of microtubule de-stabilizers by stabilizing tubulin polymers

Directory of Open Access Journals (Sweden)

Hsieh Hsing-Pang

2009-07-01

Full Text Available Abstract Background Survivin is a dual function protein. It inhibits the apoptosis of cells by inhibiting caspases, and also promotes cell growth by stabilizing microtubules during mitosis. Over-expression of survivin has been demonstrated to induce drug-resistance to various chemo-therapeutic agents such as cisplatin (DNA damaging agent and paclitaxel (microtubule stabilizer in cancers. However, survivin-induced resistance to microtubule de-stabilizers such as Vinca alkaloids and Combretastatin A-4 (CA-4-related compounds were seldom demonstrated in the past. Furthermore, the question remains as to whether survivin plays a dominant role in processing cytokinesis or inhibiting caspases activity in cells treated with anti-mitotic compounds. The purpose of this study is to evaluate the effect of survivin on the resistance and susceptibility of human cancer cells to microtubule de-stabilizer-induced cell death. Results BPR0L075 is a CA-4 analog that induces microtubule de-polymerization and subsequent caspase-dependent apoptosis. To study the relationship between the expression of survivin and the resistance to microtubule de-stabilizers, a KB-derived BPR0L075-resistant cancer cell line, KB-L30, was generated for this study. Here, we found that survivin was over-expressed in the KB-L30 cells. Down-regulation of survivin by siRNA induced hyper-sensitivity to BPR0L075 in KB cells and partially re-stored sensitivity to BPR0L075 in KB-L30 cells. Western blot analysis revealed that down-regulation of survivin induced microtubule de-stabilization in both KB and KB-L30 cells. However, the same treatment did not enhance the down-stream caspase-3/-7 activities in BPR0L075-treated KB cells. Translocation of a caspase-independent apoptosis-related molecule, apoptosis-inducing factor (AIF, from cytoplasm to the nucleus was observed in survivin-targeted KB cells under BPR0L075 treatment. Conclusion In this study, survivin plays an important role in the

Watt steam governor stability

Science.gov (United States)

Denny, Mark

2002-05-01

The physics of the fly-ball governor, introduced to regulate the speed of steam engines, is here analysed anew. The original analysis is generalized to arbitrary governor geometry. The well-known stability criterion for the linearized system breaks down for large excursions from equilibrium; we show approximately how this criterion changes.

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.

The validity and reliability of a dynamic neuromuscular stabilization-heel sliding test for core stability.

Science.gov (United States)

Cha, Young Joo; Lee, Jae Jin; Kim, Do Hyun; You, Joshua Sung H

2017-10-23

Core stabilization plays an important role in the regulation of postural stability. To overcome shortcomings associated with pain and severe core instability during conventional core stabilization tests, we recently developed the dynamic neuromuscular stabilization-based heel sliding (DNS-HS) test. The purpose of this study was to establish the criterion validity and test-retest reliability of the novel DNS-HS test. Twenty young adults with core instability completed both the bilateral straight leg lowering test (BSLLT) and DNS-HS test for the criterion validity study and repeated the DNS-HS test for the test-retest reliability study. Criterion validity was determined by comparing hip joint angle data that were obtained from BSLLT and DNS-HS measures. The test-retest reliability was determined by comparing hip joint angle data. Criterion validity was (ICC2,3) = 0.700 (preliability was (ICC3,3) = 0.953 (pvalidity data demonstrated a good relationship between the gold standard BSLLT and DNS-HS core stability measures. Test-retest reliability data suggests that DNS-HS core stability was a reliable test for core stability. Clinically, the DNS-HS test is useful to objectively quantify core instability and allow early detection and evaluation.

Comparative profiling of sarcoplasmic phosphoproteins in ovine muscle with different color stability.

Science.gov (United States)

Li, Meng; Li, Zheng; Li, Xin; Xin, Jianzeng; Wang, Ying; Li, Guixia; Wu, Liguo; Shen, Qingwu W; Zhang, Dequan

2018-02-01

The phosphorylation of sarcoplasmic proteins in postmortem muscles was investigated in relationship to color stability in the present study. Although no difference was observed in the global phosphorylation level of sarcoplasmic proteins, difference was determined in the phosphorylation levels of individual protein bands from muscles with different color stability. Correlation analysis and liquid chromatography - tandem mass spectrometry (LC-MS/MS) identification of phosphoproteins showed that most of the color stability-related proteins were glycolytic enzymes. Interestingly, the phosphorylation level of myoglobin was inversely related to meat color stability. As the phosphorylation of myoglobin increased, color stability based on a ∗ value decreased and metMb content increased. In summary, the study revealed that protein phosphorylation might play a role in the regulation of meat color stability probably by regulating glycolysis and the redox stability of myoglobin, which might be affected by the phosphorylation of myoglobin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Financial stability in the eurozone : Where do we stand?

NARCIS (Netherlands)

Arnold, I.J.M.

2007-01-01

At the start of the EMU, concerns about fiscal and monetary stability dominated the academic debate. In contrast, financial stability issues were largely overlooked. Since then, more attention has been paid to the implications of the EMU for financial regulation and supervision and to the drawbacks

Stabilizing human regulatory T cells for tolerance inducing immunotherapy.

Science.gov (United States)

He, Xuehui; Koenen, Hans Jpm; Slaats, Jeroen Hr; Joosten, Irma

2017-08-01

Many autoimmune diseases develop as a consequence of an altered balance between autoreactive immune cells and suppressive FOXP3 + Treg. Restoring this balance through amplification of Treg represents a promising strategy to treat disease. However, FOXP3 + Treg might become unstable especially under certain inflammatory conditions, and might transform into proinflammatory cytokine-producing cells. The issue of heterogeneity and instability of Treg has caused considerable debate in the field and has important implications for Treg-based immunotherapy. In this review, we discuss how Treg stability is defined and what the molecular mechanisms underlying the maintenance of FOXP3 expression and the regulation of Treg stability are. Also, we elaborate on current strategies used to stabilize human Treg for clinical purposes. This review focuses on human Treg, but considering that cell-intrinsic mechanisms to regulate Treg stability in mice and in humans might be similar, data derived from mice studies are also discussed in this paper.

Stabilization of a nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator yields insight into disease-causing mutations.

Science.gov (United States)

Vernon, Robert M; Chong, P Andrew; Lin, Hong; Yang, Zhengrong; Zhou, Qingxian; Aleksandrov, Andrei A; Dawson, Jennifer E; Riordan, John R; Brouillette, Christie G; Thibodeau, Patrick H; Forman-Kay, Julie D

2017-08-25

Characterization of the second nucleotide-binding domain (NBD2) of the cystic fibrosis transmembrane conductance regulator (CFTR) has lagged behind research into the NBD1 domain, in part because NBD1 contains the F508del mutation, which is the dominant cause of cystic fibrosis. Research on NBD2 has also been hampered by the overall instability of the domain and the difficulty of producing reagents. Nonetheless, multiple disease-causing mutations reside in NBD2, and the domain is critical for CFTR function, because channel gating involves NBD1/NBD2 dimerization, and NBD2 contains the catalytically active ATPase site in CFTR. Recognizing the paucity of structural and biophysical data on NBD2, here we have defined a bioinformatics-based method for manually identifying stabilizing substitutions in NBD2, and we used an iterative process of screening single substitutions against thermal melting points to both produce minimally mutated stable constructs and individually characterize mutations. We present a range of stable constructs with minimal mutations to help inform further research on NBD2. We have used this stabilized background to study the effects of NBD2 mutations identified in cystic fibrosis (CF) patients, demonstrating that mutants such as N1303K and G1349D are characterized by lower stability, as shown previously for some NBD1 mutations, suggesting a potential role for NBD2 instability in the pathology of CF. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis.

Science.gov (United States)

Pushpavalli, Sreerangam N C V L; Sarkar, Arpita; Ramaiah, M Janaki; Chowdhury, Debabani Roy; Bhadra, Utpal; Pal-Bhadra, Manika

2013-01-24

In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk) is activated in the mof mutants, there by causing centrosomal inactivation suggesting its role in response to genotoxic stress. A drastic decrease in the fall out nuclei in the syncytial embryos derived from mof¹/+; mnkp⁶/+ females further confirms the role of DNA damage response gene Chk2 to ensure the removal of abnormal nuclei from the embryonic precursor pool and maintain genome stability. The fact that mof mutants undergo DNA damage has been further elucidated by the increased number of single and double stranded DNA breaks. mof mutants exhibited genomic instability as evidenced by the occurance of frequent mitotic bridges in anaphase, asynchronous nuclear divisions, disruption of cytoskeleton, inactivation of centrosomes finally leading to DNA damage. Our findings are consistent to what has been reported earlier in mammals that; reduced levels of MOF resulted in increased genomic instability while total loss resulted in lethality. The study can be further extended using Drosophila as model system and carry out the interaction of MOF

Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis

Directory of Open Access Journals (Sweden)

Pushpavalli Sreerangam NCVL

2013-01-01

Full Text Available Abstract Background In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Results Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk is activated in the mof mutants, there by causing centrosomal inactivation suggesting its role in response to genotoxic stress. A drastic decrease in the fall out nuclei in the syncytial embryos derived from mof1/+; mnkp6/+ females further confirms the role of DNA damage response gene Chk2 to ensure the removal of abnormal nuclei from the embryonic precursor pool and maintain genome stability. The fact that mof mutants undergo DNA damage has been further elucidated by the increased number of single and double stranded DNA breaks. Conclusion mof mutants exhibited genomic instability as evidenced by the occurance of frequent mitotic bridges in anaphase, asynchronous nuclear divisions, disruption of cytoskeleton, inactivation of centrosomes finally leading to DNA damage. Our findings are consistent to what has been reported earlier in mammals that; reduced levels of MOF resulted in increased genomic instability while total loss resulted in lethality. The study can be further extended using

Heat shock protein 90 positively regulates Chikungunya virus replication by stabilizing viral non-structural protein nsP2 during infection.

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Indrani Das

Full Text Available BACKGROUND: The high morbidity and socio-economic loss associated with the recent massive global outbreak of Chikungunya virus (CHIKV emphasize the need to understand the biology of the virus for developing effective antiviral therapies. METHODS AND FINDINGS: In this study, an attempt was made to understand the molecular mechanism involved in Heat shock protein 90 (Hsp90 mediated regulation of CHIKV infection in mammalian cells using CHIKV prototype strain (S 27 and Indian outbreak strain of 2006 (DRDE-06. Our results showed that Hsp90 is required at a very early stage of viral replication and Hsp90 inhibitor Geldanamycin (GA can abrogate new virus particle formation more effectively in the case of S 27 than that of DRDE-06. Further analysis revealed that CHIKV nsP2 protein level is specifically reduced by GA treatment as well as HSP90-siRNA transfection; however, viral RNA remains unaltered. Immunoprecipitation analysis showed that nsP2 interacts with Hsp90 during infection; however this interaction is reduced in the presence of GA. In addition, our analysis on Hsp90 associated PI3K/Akt/mTOR signaling pathway demonstrated that CHIKV infection stabilizes Raf1 and activates Hsp90 client protein Akt, which in turn phosphorylates mTOR. Subsequently, this phosphorylation leads to the activation of two important downstream effectors, S6K and 4EBP1, which may facilitate translation of viral as well as cellular mRNAs. Hence, the data suggests that CHIKV infection is regulated by Hsp90 associated Akt phosphorylation and DRDE-06 is more efficient than S 27 in enhancing the activation of host signaling molecules for its efficient replication and virus production. CONCLUSION: Hsp90 positively regulates Chikungunya virus replication by stabilizing CHIKV-nsP2 through its interaction during infection. The study highlights the possible molecular mechanism of GA mediated inhibition of CHIKV replication and differential effect of this drug on S 27 and DRDE-06

Cardiac Coherence, Self-Regulation, Autonomic Stability and Psychosocial Well-being

Directory of Open Access Journals (Sweden)

Rollin eMcCraty

2014-09-01

Full Text Available The ability to alter one’s emotional responses is central to overall well-being and to effectively meeting the demands of life. One of the chief symptoms of events such as trauma, that overwhelm our capacities to successfully handle and adapt to them, is a shift in our internal baseline reference such that there ensues a repetitive activation of the traumatic event. This can result in high vigilance and over-sensitivity to environmental signals which are reflected in inappropriate emotional responses and autonomic nervous system dynamics. In this article we discuss the perspective that one’s ability to self-regulate the quality of feeling and emotion of one’s moment-to-moment experience is intimately tied to our physiology, and the reciprocal interactions among physiological, cognitive and emotional systems. These interactions form the basis of information processing networks in which communication between systems occurs through the generation and transmission of rhythms and patterns of activity. Our discussion emphasizes the communication pathways between the heart and brain, as well as how these are related to cognitive and emotional function and self-regulatory capacity. We discuss the hypothesis that self-induced positive emotions increase the coherence in bodily processes, which is reflected in the pattern of the heart’s rhythm. This shift in the heart rhythm in turn plays an important role in facilitating higher cognitive functions, creating emotional stability and facilitating states of calm. Over time, this establishes a new inner-baseline reference, a type of implicit memory that organizes perception, feelings and behavior. Without establishing a new baseline reference, people are at risk of getting stuck in familiar, yet unhealthy emotional and behavioral patterns and living their lives through the automatic filters of past familiar or traumatic experience.

Chromatin dynamics in genome stability

DEFF Research Database (Denmark)

Nair, Nidhi; Shoaib, Muhammad; Sørensen, Claus Storgaard

2017-01-01

Genomic DNA is compacted into chromatin through packaging with histone and non-histone proteins. Importantly, DNA accessibility is dynamically regulated to ensure genome stability. This is exemplified in the response to DNA damage where chromatin relaxation near genomic lesions serves to promote...... access of relevant enzymes to specific DNA regions for signaling and repair. Furthermore, recent data highlight genome maintenance roles of chromatin through the regulation of endogenous DNA-templated processes including transcription and replication. Here, we review research that shows the importance...... of chromatin structure regulation in maintaining genome integrity by multiple mechanisms including facilitating DNA repair and directly suppressing endogenous DNA damage....

Improvements in X-band transmitter phase stability through Klystron body temperature regulation

Science.gov (United States)

Perez, R. M.

1992-01-01

This article describes the techniques used and experimental results obtained in improving transmitter stability by control of the klystron body temperature. Related work in the measurement of klystron phase control parameters (pushing factors) is also discussed. The contribution of wave guide temperature excursions to uplink phase stability is presented. Suggestions are made as to the direction of future work in this area.

Robust Helicopter Stabilization in the Face of Wind Disturbance

DEFF Research Database (Denmark)

A. Danapalasingam, Kumeresan; Leth, John-Josef; la Cour-Harbo, Anders

2010-01-01

When a helicopter is required to hover with minimum deviations from a desired position without measurements of an affecting persistent wind disturbance, a robustly stabilizing control action is vital. In this paper, the stabilization of the position and translational velocity of a nonlinear...... controller is then designed based on nonlinear adaptive output regulations and robust stabilization of a chain of integrators by a saturated feedback. Simulation results show the effectiveness of the control design in the stabilization of helicopter motion and the built-in robustness of the controller...

Molecular chaperone complexes with antagonizing activities regulate stability and activity of the tumor suppressor LKB1.

Science.gov (United States)

Gaude, H; Aznar, N; Delay, A; Bres, A; Buchet-Poyau, K; Caillat, C; Vigouroux, A; Rogon, C; Woods, A; Vanacker, J-M; Höhfeld, J; Perret, C; Meyer, P; Billaud, M; Forcet, C

2012-03-22

LKB1 is a tumor suppressor that is constitutionally mutated in a cancer-prone condition, called Peutz-Jeghers syndrome, as well as somatically inactivated in a sizeable fraction of lung and cervical neoplasms. The LKB1 gene encodes a serine/threonine kinase that associates with the pseudokinase STRAD (STE-20-related pseudokinase) and the scaffolding protein MO25, the formation of this heterotrimeric complex promotes allosteric activation of LKB1. We have previously reported that the molecular chaperone heat shock protein 90 (Hsp90) binds to and stabilizes LKB1. Combining pharmacological studies and RNA interference approaches, we now provide evidence that the co-chaperone Cdc37 participates to the regulation of LKB1 stability. It is known that the Hsp90-Cdc37 complex recognizes a surface within the N-terminal catalytic lobe of client protein kinases. In agreement with this finding, we found that the chaperones Hsp90 and Cdc37 interact with an LKB1 isoform that differs in the C-terminal region, but not with a novel LKB1 variant that lacks a portion of the kinase N-terminal lobe domain. Reconstitution of the two complexes LKB1-STRAD and LKB1-Hsp90-Cdc37 with recombinant proteins revealed that the former is catalytically active whereas the latter is inactive. Furthermore, consistent with a documented repressor function of Hsp90, LKB1 kinase activity was transiently stimulated upon dissociation of Hsp90. Finally, disruption of the LKB1-Hsp90 complex favors the recruitment of both Hsp/Hsc70 and the U-box dependent E3 ubiquitin ligase CHIP (carboxyl terminus of Hsc70-interacting protein) that triggers LKB1 degradation. Taken together, our results establish that the Hsp90-Cdc37 complex controls both the stability and activity of the LKB1 kinase. This study further shows that two chaperone complexes with antagonizing activities, Hsp90-Cdc37 and Hsp/Hsc70-CHIP, finely control the cellular level of LKB1 protein.

Benchmarking and Regulation

DEFF Research Database (Denmark)

Agrell, Per J.; Bogetoft, Peter

. The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

Fiscal Drag as an Automatic Stability Tool, in the Case of New Regulation with Price Criteria in Automotive Sectors Special Consumption Tax (SCT

Directory of Open Access Journals (Sweden)

Abdurrahman TARAKTAŞ

2017-12-01

Full Text Available Fiscal drag is a result of real or nominal expanding economy and progressive taxation. In general, individuals are forced to enter the upper tax bracket depending on their increased income or expenditure. More tax burden can result in less consumption. Fiscal drag, lack of spending or excessive taxation can cause the economy to slow down. Traditional view suggests that fiscal drag may serve as a natural automatic stabilizer to cool the economy. However, this view ignores the supply side and in particular the potential effects of the high tax burden on economy. This study examines the extent to which the expected automatic stabilization function can be performed and the possible side effects on economic balances and income distribution of fiscal drag in our country in the case of new regulation with price criteria in automotive sectors Special Consumption Tax (SCT.

Stabilization at almost arbitrary points for chaotic systems

International Nuclear Information System (INIS)

Huang, C.-S.; Lian, K.-Y.; Su, C.-H.; Wu, J.-W.

2008-01-01

We consider how to design a feasible control input for chaotic systems via a suitable input channel to achieve the stabilization at arbitrary points. Regarding the nonlinear systems without naturally defined input vectors, we propose a local stabilization controller which works for almost arbitrary points. Subsequently, according to topologically transitive property for chaotic systems, the feedback control force is activated only when the trajectory passes through the neighboring region of the regulated point. Hence the global stabilization is achieved whereas the control effort of the hybrid controller is extremely low

Assessing the roll stability of heavy vehicles in South Africa

CSIR Research Space (South Africa)

Benade, R

2016-07-01

Full Text Available of these crashes involve heavy vehicle rollover. The regulations in the National Road Traffic Act of South Africa that govern heavy vehicle design do not directly address the roll stability of heavy vehicles. The internationally accepted method of regulating roll...

Regulating repression: roles for the sir4 N-terminus in linker DNA protection and stabilization of epigenetic states.

Directory of Open Access Journals (Sweden)

Stephanie Kueng

Full Text Available Silent information regulator proteins Sir2, Sir3, and Sir4 form a heterotrimeric complex that represses transcription at subtelomeric regions and homothallic mating type (HM loci in budding yeast. We have performed a detailed biochemical and genetic analysis of the largest Sir protein, Sir4. The N-terminal half of Sir4 is dispensable for SIR-mediated repression of HM loci in vivo, except in strains that lack Yku70 or have weak silencer elements. For HM silencing in these cells, the C-terminal domain (Sir4C, residues 747-1,358 must be complemented with an N-terminal domain (Sir4N; residues 1-270, expressed either independently or as a fusion with Sir4C. Nonetheless, recombinant Sir4C can form a complex with Sir2 and Sir3 in vitro, is catalytically active, and has sedimentation properties similar to a full-length Sir4-containing SIR complex. Sir4C-containing SIR complexes bind nucleosomal arrays and protect linker DNA from nucleolytic digestion, but less effectively than wild-type SIR complexes. Consistently, full-length Sir4 is required for the complete repression of subtelomeric genes. Supporting the notion that the Sir4 N-terminus is a regulatory domain, we find it extensively phosphorylated on cyclin-dependent kinase consensus sites, some being hyperphosphorylated during mitosis. Mutation of two major phosphoacceptor sites (S63 and S84 derepresses natural subtelomeric genes when combined with a serendipitous mutation (P2A, which alone can enhance the stability of either the repressed or active state. The triple mutation confers resistance to rapamycin-induced stress and a loss of subtelomeric repression. We conclude that the Sir4 N-terminus plays two roles in SIR-mediated silencing: it contributes to epigenetic repression by stabilizing the SIR-mediated protection of linker DNA; and, as a target of phosphorylation, it can destabilize silencing in a regulated manner.

Translational Influence on Messenger Stability

DEFF Research Database (Denmark)

Eriksen, Mette

-termination to be a global phenomena in gene regulation. The influence of codon usage in the early coding region on messenger stability was examined, in order to establish how fast or slow the ribosome has to decode the sequence for it to protect the messenger from degradation. The experiments demonstrated that very fast...

The β-1,3-glucanosyltransferase Gas1 regulates Sir2-mediated rDNA stability in Saccharomyces cerevisiae.

Science.gov (United States)

Ha, Cheol Woong; Kim, Kwantae; Chang, Yeon Ji; Kim, Bongkeun; Huh, Won-Ki

2014-07-01

In Saccharomyces cerevisiae, the stability of highly repetitive rDNA array is maintained through transcriptional silencing. Recently, a β-1,3-glucanosyltransferase Gas1 has been shown to play a significant role in the regulation of transcriptional silencing in S. cerevisiae. Here, we show that the gas1Δ mutation increases rDNA silencing in a Sir2-dependent manner. Remarkably, the gas1Δ mutation induces nuclear localization of Msn2/4 and stimulates the expression of PNC1, a gene encoding a nicotinamidase that functions as a Sir2 activator. The lack of enzymatic activity of Gas1 or treatment with a cell wall-damaging agent, Congo red, exhibits effects similar to those of the gas1Δ mutation. Furthermore, the loss of Gas1 or Congo red treatment lowers the cAMP-dependent protein kinase (PKA) activity in a cell wall integrity MAP kinase Slt2-dependent manner. Collectively, our results suggest that the dysfunction of Gas1 plays a positive role in the maintenance of rDNA integrity by decreasing PKA activity and inducing the accumulation of Msn2/4 in the nucleus. It seems that nuclear-localized Msn2/4 stimulate the expression of Pnc1, thereby enhancing the association of Sir2 with rDNA and promoting rDNA stability. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

THE IMPORTANCE OF BANKING SUPERVISION IN ENSURING FINANCIAL STABILITY

Directory of Open Access Journals (Sweden)

CĂRUNTU GENU ALEXANDRU

2014-12-01

Full Text Available Financial stability plays a vital role in terms of the financial system and the economy as a whole. Analysis and management of risks in the banking sector in order to achieve the financial stability of the whole banking system requires the use of established methods in modern management of risk. The financial crisis has demonstrated certain limits in terms of efficient management of risk. In this respect supervisory authorities have developed a number of methods and techniques to detect, monitor and amount of risk. In the present context, to enhance the stability of the banking system and prevent systemic risk, it is proposed to revise the Basel II Agreement. It was necessary to review the existing prudential regulations defining, embodied in Basel III. This new agreement brings more clarity in the financial and banking sector, addresses a wider range of risks, providing a better regulator

Acid Stability of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Pathogenicity

Energy Technology Data Exchange (ETDEWEB)

DuBois, Rebecca M.; Zaraket, Hassan; Reddivari, Muralidhar; Heath, Richard J.; White, Stephen W.; Russell, Charles J. (Tennessee-HSC); (SJCH)

2012-12-10

Highly pathogenic avian influenza viruses of the H5N1 subtype continue to threaten agriculture and human health. Here, we use biochemistry and x-ray crystallography to reveal how amino-acid variations in the hemagglutinin (HA) protein contribute to the pathogenicity of H5N1 influenza virus in chickens. HA proteins from highly pathogenic (HP) A/chicken/Hong Kong/YU562/2001 and moderately pathogenic (MP) A/goose/Hong Kong/437-10/1999 isolates of H5N1 were found to be expressed and cleaved in similar amounts, and both proteins had similar receptor-binding properties. However, amino-acid variations at positions 104 and 115 in the vestigial esterase sub-domain of the HA1 receptor-binding domain (RBD) were found to modulate the pH of HA activation such that the HP and MP HA proteins are activated for membrane fusion at pH 5.7 and 5.3, respectively. In general, an increase in H5N1 pathogenicity in chickens was found to correlate with an increase in the pH of HA activation for mutant and chimeric HA proteins in the observed range of pH 5.2 to 6.0. We determined a crystal structure of the MP HA protein at 2.50 {angstrom} resolution and two structures of HP HA at 2.95 and 3.10 {angstrom} resolution. Residues 104 and 115 that modulate the acid stability of the HA protein are situated at the N- and C-termini of the 110-helix in the vestigial esterase sub-domain, which interacts with the B loop of the HA2 stalk domain. Interactions between the 110-helix and the stalk domain appear to be important in regulating HA protein acid stability, which in turn modulates influenza virus replication and pathogenesis. Overall, an optimal activation pH of the HA protein is found to be necessary for high pathogenicity by H5N1 influenza virus in avian species.

Complex regulation controls Neurogenin3 proteolysis

Directory of Open Access Journals (Sweden)

Ryan Roark

2012-10-01

The ubiquitin proteasome system (UPS is known to be responsible for the rapid turnover of many transcription factors, where half-life is held to be critical for regulation of transcriptional activity. However, the stability of key transcriptional regulators of development is often very poorly characterised. Neurogenin 3 (Ngn3 is a basic helix–loop–helix transcription factor that plays a central role in specification and differentiation of endocrine cells of the pancreas and gut, as well as spermatogonia and regions of the brain. Here we demonstrate that Ngn3 protein stability is regulated by the ubiquitin proteasome system and that Ngn3 can be ubiquitylated on lysines, the N-terminus and, highly unusually, on non-canonical residues including cysteines and serines/threonines. Rapid turnover of Ngn3 is regulated both by binding to its heterodimeric partner E protein and by the presence of cdk inhibitors. We show that protein half-life does appear to regulate the activity of Ngn3 in vivo, but, unlike the related transcription factor c-myc, ubiquitylation on canonical sites is not a requirement for transcriptional activity of Ngn3. Hence, we characterise an important new level of Ngn3 post-translational control, which may regulate its transcriptional activity.

The BEACH Domain Protein SPIRRIG Is Essential for Arabidopsis Salt Stress Tolerance and Functions as a Regulator of Transcript Stabilization and Localization.

Directory of Open Access Journals (Sweden)

Alexandra Steffens

2015-07-01

Full Text Available Members of the highly conserved class of BEACH domain containing proteins (BDCPs have been established as broad facilitators of protein-protein interactions and membrane dynamics in the context of human diseases like albinism, bleeding diathesis, impaired cellular immunity, cancer predisposition, and neurological dysfunctions. Also, the Arabidopsis thaliana BDCP SPIRRIG (SPI is important for membrane integrity, as spi mutants exhibit split vacuoles. In this work, we report a novel molecular function of the BDCP SPI in ribonucleoprotein particle formation. We show that SPI interacts with the P-body core component DECAPPING PROTEIN 1 (DCP1, associates to mRNA processing bodies (P-bodies, and regulates their assembly upon salt stress. The finding that spi mutants exhibit salt hypersensitivity suggests that the local function of SPI at P-bodies is of biological relevance. Transcriptome-wide analysis revealed qualitative differences in the salt stress-regulated transcriptional response of Col-0 and spi. We show that SPI regulates the salt stress-dependent post-transcriptional stabilization, cytoplasmic agglomeration, and localization to P-bodies of a subset of salt stress-regulated mRNAs. Finally, we show that the PH-BEACH domains of SPI and its human homolog FAN (Factor Associated with Neutral sphingomyelinase activation interact with DCP1 isoforms from plants, mammals, and yeast, suggesting the evolutionary conservation of an association of BDCPs and P-bodies.

Stability of Control Networks in Autonomous Homeostatic Regulation of Stem Cell Lineages.

Science.gov (United States)

Komarova, Natalia L; van den Driessche, P

2018-05-01

Design principles of biological networks have been studied extensively in the context of protein-protein interaction networks, metabolic networks, and regulatory (transcriptional) networks. Here we consider regulation networks that occur on larger scales, namely the cell-to-cell signaling networks that connect groups of cells in multicellular organisms. These are the feedback loops that orchestrate the complex dynamics of cell fate decisions and are necessary for the maintenance of homeostasis in stem cell lineages. We focus on "minimal" networks that are those that have the smallest possible numbers of controls. For such minimal networks, the number of controls must be equal to the number of compartments, and the reducibility/irreducibility of the network (whether or not it can be split into smaller independent sub-networks) is defined by a matrix comprised of the cell number increments induced by each of the controlled processes in each of the compartments. Using the formalism of digraphs, we show that in two-compartment lineages, reducible systems must contain two 1-cycles, and irreducible systems one 1-cycle and one 2-cycle; stability follows from the signs of the controls and does not require magnitude restrictions. In three-compartment systems, irreducible digraphs have a tree structure or have one 3-cycle and at least two more shorter cycles, at least one of which is a 1-cycle. With further work and proper biological validation, our results may serve as a first step toward an understanding of ways in which these networks become dysregulated in cancer.

Radiochemical stability of radiopharmaceutical preparations

International Nuclear Information System (INIS)

Martins, Patricia de A.; Silva, Jose L. da; Ramos, Marcelo P.S.; Oliveira, Ideli M. de; Felgueiras, Carlos F.; Herrerias, Rosana; Zapparoli Junior, Carlos L.; Mengatti, Jair; Fukumori, Neuza T.O.; Matsuda, Margareth M.N.

2011-01-01

The 'in vitro' stability studies of the radiopharmaceutical preparations are an essential requirement for routine practice in nuclear medicine and are an important parameter for evaluating the quality, safety and efficacy required for the sanitary registration of pharmaceutical products. Several countries have published guidelines for the evaluation of pharmaceutical stability. In Brazil, the stability studies should be conducted according to the Guide for Conducting Stability Studies published in the Resolution-RE n. 1, of 29th July 2005. There are also for radiopharmaceutical products, two specific resolutions: RDC-63 regulates the Good Manufacturing Practices for Radiopharmaceuticals and RDC-64 provides the Registration of Radiopharmaceuticals, both published on the 18th December 2009. The radiopharmaceutical stability is defined as the time during which the radioisotope can be safely used for the intended purpose. The radiochemical stability can be affected by a variety of factors, including storage temperature, amount of radioactivity, radioactive concentration, presence or absence of antioxidants or other stabilizing agents. The radiochemical stability studies must be established under controlled conditions determined by the effective use of the product. The aim of this work was to evaluate the radiochemical stability of labeled molecules with 131 I, 123 I, 153 Sm, 18 F, 51 Cr, 177 Lu and 111 In as well as 67 Ga and 201 Tl radiopharmaceuticals. Radiochemical purity was evaluated after production and in the validity period, with the maximum activity and in the recommended storage conditions. The analyses were carried out by thin-layer silica gel plate, paper chromatography and gel chromatography. The experimental results showed to be in accordance with the specified limits for all the analysed products. (author)

Robust Fuzzy Control for Fractional-Order Uncertain Hydroturbine Regulating System with Random Disturbances

OpenAIRE

Fengjiao Wu; Guitao Zhang; Zhengzhong Wang

2016-01-01

The robust fuzzy control for fractional-order hydroturbine regulating system is studied in this paper. First, the more practical fractional-order hydroturbine regulating system with uncertain parameters and random disturbances is presented. Then, on the basis of interval matrix theory and fractional-order stability theorem, a fuzzy control method is proposed for fractional-order hydroturbine regulating system, and the stability condition is expressed as a group of linear matrix inequalities. ...

75 FR 58505 - Regulation Z; Truth in Lending

Science.gov (United States)

2010-09-24

.... Reasons for the Proposed Rule Congress enacted TILA based on findings that economic stability would be... and Regulation Z Congress enacted the Truth in Lending Act (TILA) based on findings that economic stability would be enhanced and competition among consumer credit providers would be strengthened by the...

Stabilized power constant alimentation

International Nuclear Information System (INIS)

Roussel, L.

1968-06-01

The study and realization of a stabilized power alimentation variable from 5 to 100 watts are described. In order to realize a constant power drift of Lithium compensated diodes, we have searched a 1 per cent precision of regulation and a response time minus than 1 sec. Recent components like Hall multiplicator and integrated amplifiers give this possibility and it is easy to use permutable circuits. (author) [fr

Real-time transient stabilization and voltage regulation of power generators with unknown mechanical power input

International Nuclear Information System (INIS)

Kenne, Godpromesse; Goma, Raphael; Nkwawo, Homere; Lamnabhi-Lagarrigue, Francoise; Arzande, Amir; Vannier, Jean Claude

2010-01-01

A nonlinear adaptive excitation controller is proposed to enhance the transient stability and voltage regulation of synchronous generators with unknown power angle and mechanical power input. The proposed method is based on a standard third-order model of a synchronous generator which requires only information about the physical available measurements of relative angular speed, active electric power, infinite bus and generator terminal voltages. The operating conditions are computed online using the above physical available measurements, the terminal voltage reference value and the estimate of the mechanical power input. The proposed design is therefore capable of providing satisfactory voltage in the presence of unknown variations of the power system operating conditions. Using the concept of sliding mode equivalent control techniques, a robust decentralized adaptive controller which insures the exponential convergence of the outputs to the desired ones, is obtained. Real-time experimental results are reported, comparing the performance of the proposed adaptive nonlinear control scheme to one of the conventional AVR/PSS controller. The high simplicity of the overall adaptive control scheme and its robustness with respect to line impedance variation including critical unbalanced operating condition and temporary turbine fault, constitute the main positive features of the proposed approach.

Real-time transient stabilization and voltage regulation of power generators with unknown mechanical power input

Energy Technology Data Exchange (ETDEWEB)

Kenne, Godpromesse, E-mail: gokenne@yahoo.co [Laboratoire d' Automatique et d' Informatique Appliquee (LAIA), Departement de Genie Electrique, Universite de Dschang, B.P. 134 Bandjoun (Cameroon); Goma, Raphael, E-mail: raphael.goma@lss.supelec.f [Laboratoire des Signaux et Systemes (L2S), CNRS-SUPELEC, Universite Paris XI, 3 Rue Joliot Curie, 91192 Gif-sur-Yvette (France); Nkwawo, Homere, E-mail: homere.nkwawo@iutv.univ-paris13.f [Departement GEII, Universite Paris XIII, 99 Avenue Jean Baptiste Clement, 93430 Villetaneuse (France); Lamnabhi-Lagarrigue, Francoise, E-mail: lamnabhi@lss.supelec.f [Laboratoire des Signaux et Systemes (L2S), CNRS-SUPELEC, Universite Paris XI, 3 Rue Joliot Curie, 91192 Gif-sur-Yvette (France); Arzande, Amir, E-mail: Amir.arzande@supelec.f [Departement Energie, Ecole Superieure d' Electricite-SUPELEC, 3 Rue Joliot Curie, 91192 Gif-sur-Yvette (France); Vannier, Jean Claude, E-mail: Jean-claude.vannier@supelec.f [Departement Energie, Ecole Superieure d' Electricite-SUPELEC, 3 Rue Joliot Curie, 91192 Gif-sur-Yvette (France)

2010-01-15

A nonlinear adaptive excitation controller is proposed to enhance the transient stability and voltage regulation of synchronous generators with unknown power angle and mechanical power input. The proposed method is based on a standard third-order model of a synchronous generator which requires only information about the physical available measurements of relative angular speed, active electric power, infinite bus and generator terminal voltages. The operating conditions are computed online using the above physical available measurements, the terminal voltage reference value and the estimate of the mechanical power input. The proposed design is therefore capable of providing satisfactory voltage in the presence of unknown variations of the power system operating conditions. Using the concept of sliding mode equivalent control techniques, a robust decentralized adaptive controller which insures the exponential convergence of the outputs to the desired ones, is obtained. Real-time experimental results are reported, comparing the performance of the proposed adaptive nonlinear control scheme to one of the conventional AVR/PSS controller. The high simplicity of the overall adaptive control scheme and its robustness with respect to line impedance variation including critical unbalanced operating condition and temporary turbine fault, constitute the main positive features of the proposed approach.

Study on the stability of waterpower-speed control system for hydropower station with air cushion surge chamber

International Nuclear Information System (INIS)

Guo, W C; Yang, J D; Chen, J P; Teng, Y

2014-01-01

According to the fact that the effects of penstock, unit and governor on stability of water level fluctuation for hydropower station with air cushion surge chamber are neglected in previous researches, in this paper, Thoma assumption is broken through, the complete mathematical model of waterpower-speed control system for hydropower station with air cushion surge chamber is established, and the comprehensive transfer function and linear homogeneous differential equation that characterize the dynamic characteristics of system are derived. The stability domain that characterizes the good or bad of stability quantitatively is drawn by using the stability conditions. The effects of the fluid inertia in water diversion system, the air cushion surge chamber parameters, hydraulic turbine characteristics, generator characteristics, and regulation modes of governor on the stability of waterpower-speed control system are analyzed through stability domain. The main conclusions are as follows: The fluid inertia in water diversion system and hydraulic turbine characteristics have unfavorable effects on the system while generator characteristics have favorable effect. The stability keeps getting better with the increase of chamber height and basal area and the decrease of air pressure and air polytropic exponent. The stability of power regulation mode is obviously better than that of frequency regulation mode

Small Ro/Pax Vessel stability study

DEFF Research Database (Denmark)

Erichsen, Henrik; Kristensen, Hans Otto Holmegaard; Jensen, Jørgen Juncher

2015-01-01

In 2009 new damage stability requirements for passenger ships based on a probabilistic method were adopted by IMO and are now part of the current SOLAS Chapter II-1 regulations (SOLAS 2009). The mandate from IMO was to keep the same safety level as inherent in the old deterministic damage stabili...

DC microgrids providing frequency regulation in electrical power system - imperfect communication issues

DEFF Research Database (Denmark)

Bašić, Hrvoje; Dragicevic, Tomislav; Pandžić, Hrvoje

2017-01-01

This paper presents a model of multiple DC microgrids with battery energy storage systems and demand response capability, taking part in primary frequency regulation of electrical power system. Although DC microgrids can contribute to stability and efficiency of frequency regulation, these complex...... systems may cause serious stability issues due to the imperfect communication. This work presents possible scenarios of unstable primary frequency regulation in a simplified model of electrical power system with DC microgrids, which are controlled through communication network....

Modelling of the automatic stabilization system of the aircraft course by a fuzzy logic method

Science.gov (United States)

Mamonova, T.; Syryamkin, V.; Vasilyeva, T.

2016-04-01

The problem of the present paper concerns the development of a fuzzy model of the system of an aircraft course stabilization. In this work modelling of the aircraft course stabilization system with the application of fuzzy logic is specified. Thus the authors have used the data taken for an ordinary passenger plane. As a result of the study the stabilization system models were realised in the environment of Matlab package Simulink on the basis of the PID-regulator and fuzzy logic. The authors of the paper have shown that the use of the method of artificial intelligence allows reducing the time of regulation to 1, which is 50 times faster than the time when standard receptions of the management theory are used. This fact demonstrates a positive influence of the use of fuzzy regulation.

A training rule which guarantees finite-region stability for a class of closed-loop neural-network control systems.

Science.gov (United States)

Kuntanapreeda, S; Fullmer, R R

1996-01-01

A training method for a class of neural network controllers is presented which guarantees closed-loop system stability. The controllers are assumed to be nonlinear, feedforward, sampled-data, full-state regulators implemented as single hidden-layer neural networks. The controlled systems must be locally hermitian and observable. Stability of the closed-loop system is demonstrated by determining a Lyapunov function, which can be used to identify a finite stability region about the regulator point.

Stabilizing local boundary conditions for two-dimensional shallow water equations

KAUST Repository

Dia, Ben Mansour

2018-03-27

In this article, we present a sub-critical two-dimensional shallow water flow regulation. From the energy estimate of a set of one-dimensional boundary stabilization problems, we obtain a set of polynomial equations with respect to the boundary values as a requirement for the energy decrease. Using the Riemann invariant analysis, we build stabilizing local boundary conditions that guarantee the stability of the hydrodynamical state around a given steady state. Numerical results for the controller applied to the nonlinear problem demonstrate the performance of the method.

Super-paramagnetic core-shell material with tunable magnetic behavior by regulating electron transfer efficiency and structure stability of the shell

Directory of Open Access Journals (Sweden)

Wenyan Zhang

Full Text Available In this work, a spherical nano core-shell material was constructed by encapsulating Fe3O4 microsphere into conductive polymer-metal composite shell. The Fe3O4 microspheres were fabricated by assembling large amounts of Fe3O4 nano-crystals, which endowed the microspheres with super-paramagnetic property and high saturation magnetization. The polymer-metal composite shell was constructed by inserting Pt nano-particles (NPs into the conductive polymer polypyrrole (PPy. As size and dispersion of the Pt NPs has an important influence on their surface area and surface energy, it was effective to enlarge the interface area between PPy and Pt NPs, enhance the electron transfer efficiency of PPy/Pt composite shell, and reinforced the shell’s structural stability just by tuning the size and dispersion of Pt NPs. Moreover, core-shell structure of the materials made it convenient to investigate the PPy/Pt shell’s shielding effect on the Fe3O4 core’s magnetic response to external magnetic fields. It was found that the saturation magnetization of Fe3O4/PPy/Pt core-shell material could be reduced by 20.5% by regulating the conductivity of the PPy/Pt shell. Keywords: Super-paramagnetic, Conductivity, Magnetic shielding, Structural stability

Study of the power supply topology with high stability for accelerator

International Nuclear Information System (INIS)

Wu Wei; Wang Yunfang; Wang Jiewei

2005-01-01

The requirements of the power supply for accelerator are analyzed. A few of topologies of the highly stabilized power supply are discussed. The types are listed: Auto-transformers-diode rectifier-transistor regulating current. Thyristor rectifier regulating voltage -transistor regulating current, Diode rectifier -DC-chopping. Thyristor rectifier regulating voltage -two-quadrant-chopping. The advantages and disadvantages of the topologies for power supply are discussed. The notice questions of the power supply designed for accelerator are analyzed. (authors)

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.

Tipping the balance of RNA stability by 3' editing of the transcriptome.

Science.gov (United States)

Chung, Christina Z; Seidl, Lauren E; Mann, Mitchell R; Heinemann, Ilka U

2017-11-01

The regulation of active microRNAs (miRNAs) and maturation of messenger RNAs (mRNAs) that are competent for translation is a crucial point in the control of all cellular processes, with established roles in development and differentiation. Terminal nucleotidyltransferases (TNTases) are potent regulators of RNA metabolism. TNTases promote the addition of single or multiple nucleotides to an RNA transcript that can rapidly alter transcript stability. The well-known polyadenylation promotes transcript stability while the newly discovered but ubiquitious 3'-end polyuridylation marks RNA for degradation. Monoadenylation and uridylation are essential control mechanisms balancing mRNA and miRNA homeostasis. This review discusses the multiple functions of non-canonical TNTases, focusing on their substrate range, biological functions, and evolution. TNTases directly control mRNA and miRNA levels, with diverse roles in transcriptome stabilization, maturation, silencing, or degradation. We will summarize the current state of knowledge on non-canonical nucleotidyltransferases and their function in regulating miRNA and mRNA metabolism. We will review the discovery of uridylation as an RNA degradation pathway and discuss the evolution of nucleotidyltransferases along with their use in RNA labeling and future applications as therapeutic targets. The biochemically and evolutionarily highly related adenylyl- and uridylyltransferases play antagonizing roles in the cell. In general, RNA adenylation promotes stability, while uridylation marks RNA for degradation. Uridylyltransferases evolved from adenylyltransferases in multiple independent evolutionary events by the insertion of a histidine residue into the active site, altering nucleotide, but not RNA specificity. Understanding the mechanisms regulating RNA stability in the cell and controlling the transcriptome is essential for efforts aiming to influence cellular fate. Selectively enhancing or reducing RNA stability allows for

Posttranscriptional Regulation of Cyclooxygenase-2 in Rat Intestinal Epithelial Cells

Directory of Open Access Journals (Sweden)

Zhonghua Zhang

2000-01-01

Full Text Available Modulation of cyclooxygenase-2 (COX-2 mRNA stability plays an important role in the regulation of its expression by oncogenic Ras. Here, we evaluate COX-2 mRNA stability in response to treatment with two known endogenous promoters of gastrointestinal cancer, the bile acid (chenodeoxycholate; CD and ceramide. Treatment with CD and ceramide resulted in a 10-fold increase in the level of COX-2 protein and a four-fold lengthening of the half-life of COX-2 mRNA. COX-2 mRNA stability was assessed by Northern blot analysis and by evaluating the AU-rich element located in the COX-2 3′-UTR. A known inhibitor of mitogen-activated protein (MAP/extracellular signal-regulated kinase (ERK kinase (MEK, PD98059, reversed the effects of CD or ceramide to stabilize COX-2 mRNA. Overexpression of a dominant-negative ERK-1 or ERK-2 protein also led to destabilization of COX-2 mRNA. Treatment with a p38 MAPK inhibitor, PD169316, or transfection with a dominant-negative p38 MAPK construct reversed the effect of CD or ceramide to stabilize COX-2 mRNA. Expression of a dominant-negative c-Jun N-terminal kinase (JNK had no effect on COX-2 mRNA stability in cells treated with CD or ceramide. We conclude that posttranscriptional mechanisms play an important role in the regulation of COX-2 expression during carcinogenesis.

Voltage Stabilizer Based on SPWM technique Using Microcontroller

OpenAIRE

K. N. Tarchanidis; J. N. Lygouras; P. Botsaris

2013-01-01

This paper presents an application of the well known SPWM technique on a voltage stabilizer, using a microcontroller. The stabilizer is AC/DC/AC type. So, the system rectifies the input AC voltage to a suitable DC level and the intelligent control of an embedded microcontroller regulates the pulse width of the output voltage in order to produce through a filter a perfect sinusoidal AC voltage. The control program on the microcontroller has the ability to change the FET transistor ...

Mms1 is an assistant for regulating G-quadruplex DNA structures.

Science.gov (United States)

Schwindt, Eike; Paeschke, Katrin

2017-11-02

The preservation of genome stability is fundamental for every cell. Genomic integrity is constantly challenged. Among those challenges are also non-canonical nucleic acid structures. In recent years, scientists became aware of the impact of G-quadruplex (G4) structures on genome stability. It has been shown that folded G4-DNA structures cause changes in the cell, such as transcriptional up/down-regulation, replication stalling, or enhanced genome instability. Multiple helicases have been identified to regulate G4 structures and by this preserve genome stability. Interestingly, although these helicases are mostly ubiquitous expressed, they show specificity for G4 regulation in certain cellular processes (e.g., DNA replication). To this date, it is not clear how this process and target specificity of helicases are achieved. Recently, Mms1, an ubiquitin ligase complex protein, was identified as a novel G4-DNA-binding protein that supports genome stability by aiding Pif1 helicase binding to these regions. In this perspective review, we discuss the question if G4-DNA interacting proteins are fundamental for helicase function and specificity at G4-DNA structures.

Theory for the stability and regulation of epigenetic landscapes

International Nuclear Information System (INIS)

Micheelsen, Mille A; Mitarai, Namiko; Sneppen, Kim; Dodd, Ian B

2010-01-01

Cells can often choose among several stably heritable phenotypes. Examples are the expressions of genes in eukaryotic cells where long chromosomal regions can adopt persistent and heritable silenced or active states that may be associated with positive feedback in dynamic modification of nucleosomes. We generalize this mechanism in terms of bistability associated with valleys in an epigenetic landscape. A transfer matrix method was used to rigorously follow the system through the disruptive process of cell division. This combined treatment of noisy dynamics both between and during cell division provides an efficient way to calculate the stability of alternative states in a broad range of epigenetic systems

Epigenetic regulation of macrophage function

NARCIS (Netherlands)

Hoeksema, M.A.

2016-01-01

Atherosclerosis is a lipid-driven chronic inflammatory disorder with a key role for macrophages in all disease stages. Macrophages are involved as scavengers of lipids, regulate inflammation, attract other immune cells and contribute to the resolution of inflammation, fibrosis and plaque stability.

Analysis of the production stability of mixed grasslands. II. A mathematical framework for the quantification of production stability of grassland ecosystems

NARCIS (Netherlands)

Schulte, R.P.O.

2003-01-01

The analysis of the intrinsic properties and processes of ecosystems, which regulate the production stability of mixed grasslands, has been complicated by the environmental noise caused by stochastic weather fluctuations. A mathematical framework is presented to deduct the actual, the extrinsic and

Model format for a vaccine stability report and software solutions.

Science.gov (United States)

Shin, Jinho; Southern, James; Schofield, Timothy

2009-11-01

A session of the International Association for Biologicals Workshop on Stability Evaluation of Vaccine, a Life Cycle Approach was devoted to a model format for a vaccine stability report, and software solutions. Presentations highlighted the utility of a model format that will conform to regulatory requirements and the ICH common technical document. However, there need be flexibility to accommodate individual company practices. Adoption of a model format is premised upon agreement regarding content between industry and regulators, and ease of use. Software requirements will include ease of use and protections against inadvertent misspecification of stability design or misinterpretation of program output.

Financial Regulations and the Diversification of Funding Sources in Higher Education Institutions: Selected European Experiences

Science.gov (United States)

Stachowiak-Kudla, Monika; Kudla, Janusz

2017-01-01

The paper addresses the problem of the financial regulations' impact on the share of private financing in higher education institutions (HEIs). The authors postulate the trade-off between the size and stability of public financing and the regulations fostering stability of HEIs' funds. If the public sources are insufficient then the regulations…

Stability Simulation of a Vehicle with Wheel Active Steering

Directory of Open Access Journals (Sweden)

Brabec Pavel

2016-01-01

Full Text Available This paper deals with the possibility of increasing the vehicle driving stability at a higher speed. One of the ways how to achieve higher stability is using the 4WS system. Mathematical description of vehicle general movement is a very complex task. For simulation, models which are aptly simplified are used. For the first approach, so-called single-truck vehicle model (often linear is usually used. For the simulation, we have chosen to extend the model into a two-truck one, which includes the possibility to input more vehicle parameters. Considering the 4WS system, it is possible to use a number of potential regulations. In our simulation model, the regulation system with compound coupling was used. This type of regulation turns the rear wheels depending on the input parameters of the system (steering angle of the front wheels and depending on the output moving quantities of the vehicle, most frequently the yaw rate. Criterion for compensation of lateral deflection centre of gravity angle is its zero value, or more precisely the zero value of its first-order derivative. Parameters and set-up of the simulation model were done in conjunction with the dSAPACE software. Reference performances of the vehicle simulation model were made through the defined manoeuvres. But the simulation results indicate that the rear-wheels steering can have a positive effect on the vehicle movement stability, especially when changing the driving direction at high speed.

Identification of long-term containment/stabilization technology performance issues

International Nuclear Information System (INIS)

Matthern, G.E.; Nickelson, D.F.

1997-01-01

U.S. Department of Energy (DOE) faces a somewhat unique challenge when addressing in situ remedial alternatives that leave long-lived radionuclides and hazardous contaminants onsite. These contaminants will remain a potential hazard for thousands of years. However, the risks, costs, and uncertainties associated with removal and offsite disposal are leading many sites to select in situ disposal alternatives. Improvements in containment, stabilization, and monitoring technologies will enhance the viability of such alternatives for implementation. DOE's Office of Science and Technology sponsored a two day workshop designed to investigate issues associated with the long-term in situ stabilization and containment of buried, long-lived hazardous and radioactive contaminants. The workshop facilitated communication among end users representing most sites within the DOE, regulators, and technologists to define long-term performance issues for in situ stabilization and containment alternatives. Participants were divided into groups to identify issues and a strategy to address priority issues. This paper presents the results of the working groups and summarizes the conclusions. A common issue identified by the work groups is communication. Effective communication between technologists, risk assessors, end users, regulators, and other stakeholders would contribute greatly to resolution of both technical and programmatic issues

Emotion Regulation in Young Children with Autism Spectrum Disorders

Science.gov (United States)

Berkovits, Lauren; Eisenhower, Abbey; Blacher, Jan

2017-01-01

There has been little research connecting underlying emotion processes (e.g., emotion regulation) to frequent behavior problems in young children with autism spectrum disorder (ASD). This study examined the stability of emotion regulation and its relationship with other aspects of child functioning. Participants included 108 children with ASD,…

Fermilab main accelerator quadrupole transistorized regulators for improved tune stability

International Nuclear Information System (INIS)

Yarema, R.J.; Pfeffer, H.

1977-01-01

During early operation of the Fermilab Main Accelerator, tune fluctuations, caused by the SCR-controlled power supplies in the quad bus, limited the beam aperature at low energies. To correct this problem, two transistorized power supplies were built in 1975 to regulate and filter the main ring quad magnet current during injection and beam acceleration through the rf transistion region. There is one power supply in series with each quad bus. Each supply uses 320 parallel power transistors and is rated at 300A, 120V. Since the voltage and current capabilities of the transistorized supplies are limited, the supplies are turned-off at about 25GeV. A real-time computer system initiates turn-on of the SCR-controlled power supplies and regulation takeover by the SCR-controlled supplies, at the appropriate times

A digital intensity stabilization system for HeNe laser

Science.gov (United States)

Wei, Zhimeng; Lu, Guangfeng; Yang, Kaiyong; Long, Xingwu; Huang, Yun

2012-02-01

A digital intensity stabilization system for HeNe laser is developed. Based on a switching power IC to design laser power supply and a general purpose microcontroller to realize digital PID control, the system constructs a closed loop to stabilize the laser intensity by regulating its discharge current. The laser tube is made of glass ceramics and its integrated structure is steady enough to eliminate intensity fluctuations at high frequency and attenuates all intensity fluctuations, and this makes it easy to tune the control loop. The control loop between discharge current and photodiode voltage eliminates the long-term drifts. The intensity stability of the HeNe laser with this system is 0.014% over 12 h.

Current regulator for the stabilization of an electrostatic Van de Graaff generator

International Nuclear Information System (INIS)

Gabet, A.; Taieb, J.

1953-01-01

In a previous report (CEA report number 46) we described a current regulator destined to enslave the current of charge of the strap of a model of Van de Graaff. We will now describe the regulator destined to the 5 MeV Van de Graaff built in the Nuclear center of Saclay. (author) [fr

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.

Charge regulation as a stabilization mechanism for shell-like assemblies of polyoxometalates

NARCIS (Netherlands)

Verhoeff, A.A.; Kistler, M.L.; Bhatt, A.; Pigga, J.; Groenewold, J.; Klokkenburg, M.; Veen, S.J.; Roy, S.; Liu, T.; Kegel, W.K.

2007-01-01

We show that the equilibrium size of single-layer shells composed of polyoxometalate macroions is inversely proportional to the dielectric constant of the medium in which they are dispersed. This behavior is consistent with a stabilization mechanism based on Coulomb repulsion combined with charge

Robust Fuzzy Control for Fractional-Order Uncertain Hydroturbine Regulating System with Random Disturbances

Directory of Open Access Journals (Sweden)

Fengjiao Wu

2016-01-01

Full Text Available The robust fuzzy control for fractional-order hydroturbine regulating system is studied in this paper. First, the more practical fractional-order hydroturbine regulating system with uncertain parameters and random disturbances is presented. Then, on the basis of interval matrix theory and fractional-order stability theorem, a fuzzy control method is proposed for fractional-order hydroturbine regulating system, and the stability condition is expressed as a group of linear matrix inequalities. Furthermore, the proposed method has good robustness which can process external random disturbances and uncertain parameters. Finally, the validity and superiority are proved by the numerical simulations.

CENTRAL BANKS AND FINANCIAL STABILITY - Literature review

Directory of Open Access Journals (Sweden)

Adina APÃTÃCHIOAE

2013-06-01

Full Text Available Financial stability is a feature of the financial system, reflecting its ability to determine an efficient allocation of the resources and to manage financial risk by its own self-regulating mechanisms. Since the condition of financial systems changes over time, due to various shocks that components suffers, financial stability is a dynamic feature, but the system itself is constantly attempting to recover under the action of specific auto regulatory mechanisms. It is generally accepted that central banks play an important role in ensuring financial stability, there are a number of specific features that can help them achieve financial stability. Recent phenomena such as deregulation, globalization, the intensification of innovation, and so on, have supplemented the functions of central banks and at the same time, led to an intensification of links between banking and other large sectors of the financial system: insurance and financial markets.The objective of this article is to present the different views in the literature on the role of the central bank in ensuring financial stability and the new challenges that she must confront in assuming this new mandate. The role of central banks in ensuring financial stability is in the forefront and should be expanded beyond the traditional functions of stability, which determined that monetary and stability policies to converge. Moreover, due to vulnerabilities manifested by the financial markets in recent decades and that capital flows have become more intense, these vulnerabilities may spread rapidly, increasing the fragility of all markets and, for this reason, ensuring financial stability has become a key objective of public policies. Especially, since the stability of financial systems stimulates economic development and improved living standards, the competent authorities pays a particular attention to these issues

14 CFR 1310.11 - Regulations of the Office of Management and Budget.

Science.gov (United States)

2010-01-01

... Budget. (a) The regulations in this part supplement the regulations of the Office of Management and... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Regulations of the Office of Management and Budget. 1310.11 Section 1310.11 Aeronautics and Space AIR TRANSPORTATION SYSTEM STABILIZATION AIR...

Cep169, a Novel Microtubule Plus-End-Tracking Centrosomal Protein, Binds to CDK5RAP2 and Regulates Microtubule Stability.

Directory of Open Access Journals (Sweden)

Yusuke Mori

Full Text Available The centrosomal protein, CDK5RAP2, is a microcephaly protein that regulates centrosomal maturation by recruitment of a γ-tubulin ring complex (γ-TuRC onto centrosomes. In this report, we identified a novel human centrosomal protein, Cep169, as a binding partner of CDK5RAP2, a member of microtubule plus-end-tracking proteins (+TIPs. Cep169 interacts directly with CDK5RAP2 through CM1, an evolutionarily conserved domain, and colocalizes at the pericentriolar matrix (PCM around centrioles with CDK5RAP2. In addition, Cep169 interacts with EB1 through SxIP-motif responsible for EB1 binding, and colocalizes with CDK5RAP2 at the microtubule plus-end. EB1-binding-deficient Cep169 abolishes EB1 interaction and microtubule plus-end attachment, indicating Cep169 as a novel member of +TIPs. We further show that ectopic expression of either Cep169 or CDK5RAP2 induces microtubule bundling and acetylation in U2OS cells, and depletion of Cep169 induces microtubule depolymerization in HeLa cells, although Cep169 is not required for assembly of γ-tubulin onto centrosome by CDK5RAP2. These results show that Cep169 targets microtubule tips and regulates stability of microtubules with CDK5RAP2.

Improved temperature regulation of APS linac RF components

International Nuclear Information System (INIS)

Dortwegt, R.

1998-01-01

The temperature of the APS S-Band linac's high-power rf components is regulated by water from individual closed-loop deionized (DI) water systems. The rf components are all made of oxygen-free high-conductivity copper and respond quickly to temperature changes. The SLED cavities are especially temperature-sensitive and cause beam energy instabilities when the temperature is not well regulated. Temperature regulation better than ± 0.1 F is required to achieve good energy stability. Improvements in the closed-loop water systems have enabled them to achieve a regulation of ± 0.05 F over long periods. Regulation philosophy and equipment are discussed and numerical results are presented

Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration.

Science.gov (United States)

Sailland, Juliette; Tribollet, Violaine; Forcet, Christelle; Billon, Cyrielle; Barenton, Bruno; Carnesecchi, Julie; Bachmann, Alice; Gauthier, Karine Cécile; Yu, Shan; Giguère, Vincent; Chan, Franky L; Vanacker, Jean-Marc

2014-10-21

Several physiopathological processes require orientated cellular migration. This phenomenon highly depends on members of the RHO family of GTPases. Both excessive and deficient RHO activity impair directional migration. A tight control is thus exerted on these proteins through the regulation of their activation and of their stability. Here we show that the estrogen-related receptor α (ERRα) directly activates the expression of TNFAIP1, the product of which [BTB/POZ domain-containing adapter for Cullin3-mediated RhoA degradation 2 (BACURD2)] regulates RHOA protein turnover. Inactivation of the receptor leads to enhanced RHOA stability and activation. This results in cell disorientation, increased actin network, and inability to form a lamellipodium at the migration edge. As a consequence, directional migration, but not cell motility per se, is impaired in the absence of the receptor, under pathological as well as physiological conditions. Altogether, our results show that the control exerted by ERRα on RHOA stability is required for directional migration.

Epigenetic regulation of ageing: linking environmental inputs to genomic stability

Science.gov (United States)

Benayoun, Bérénice A.; Pollina, Elizabeth A.; Brunet, Anne

2016-01-01

Preface Ageing is affected by both genetic and non-genetic factors. Here, we review the chromatin-based epigenetic changes that occur during ageing, the role of chromatin modifiers in modulating lifespan and the importance of epigenetic signatures as biomarkers of ageing. We also discuss how epigenome remodeling by environmental stimuli impacts several aspects of transcription and genomic stability, with important consequences on longevity, and outline epigenetic differences between the ‘mortal soma’ and the ‘immortal germline’. Finally, we discuss the inheritance of ageing characteristics and potential chromatin-based strategies to delay or reverse hallmarks of ageing or age-related diseases. PMID:26373265

Investigation of the factors affecting the reliability of precision measurement of a liquid helium temperature under its regulation and stabilization in dynamic conditions

International Nuclear Information System (INIS)

Demishev, A.G.; Suplin, V.Z.; Khirnyj, V.F.; Ryazantsev, A.F.; Nemish, I.Yu.

1989-01-01

In the process of regulation and stabilization of liquid helium temperature at the initial stage of pressure increase the effect of advanced temperature increase, indicated by a carcass semiconductor thermometer, and its subsequent jump to the value corresponding to the temperature of liquid at the given moment is revealed. It is shown that irregular peculiarities in the indices of the carcass thermometers do not reflect the actual character of liquid temperature change, but are the consequence of processes taking place on their surfaces. A supposition is made that the peculiarities are determined by mutual effect of heat, released by measurement current in the thermometer, and the process of collapse of gas bubbles adhering to its surface

Geomorphic status of regulated rivers in the Iberian Peninsula.

Science.gov (United States)

Lobera, G; Besné, P; Vericat, D; López-Tarazón, J A; Tena, A; Aristi, I; Díez, J R; Ibisate, A; Larrañaga, A; Elosegi, A; Batalla, R J

2015-03-01

River regulation by dams modifies flow regimes, interrupts the transfer of sediment through channel networks, and alters downstream bed dynamics, altogether affecting channel form and processes. So far, most studies on the geomorphic impacts of dams are restricted to single rivers, or even single river stretches. In this paper we analyse the geomorphic status of 74 river sites distributed across four large basins in the Iberian Peninsula (i.e. 47 sites located downstream of dams). For this purpose, we combine field data with hydrological data available from water agencies, and analyse historical (1970) and current aerial photographs. In particular, we have developed a Geomorphic Status (GS) index that allows us to assess the physical structure of a given channel reach and its change through time. The GS encompasses a determination of changes in sedimentary units, sediment availability, bar stability and channel flow capacity. Sites are statistically grouped in four clusters based on contrasted physical and climate characteristics. Results emphasise that regulation changes river's flow regime with a generalized reduction of the magnitude and frequency of floods (thus flow competence). This, in addition to the decrease downstream sediment supply, results in the loss of active bars as they are encroached by vegetation, to the point that only reaches with little or no regulation maintain exposed sedimentary deposits. The GS of regulated river reaches is negatively correlated with magnitude of the impoundment (regulation). Heavily impacted reaches present channel stabilization and, in contrast to the hydrological response, the distance and number of tributaries do not reverse the geomorphic impact of the dams. Stabilization limits river dynamics and may contribute to the environmental degradation of the fluvial ecosystem. Overall, results describe the degree of geomorphological alteration experienced by representative Iberian rivers mostly because of regulation

STABILITY CONTROL OF ELEVATING-TRANSFER VEHICLES IN THE CONSTRUCTION

Directory of Open Access Journals (Sweden)

Zhadanovskiy Boris Vasil’evich

2016-05-01

Full Text Available The underground space is widely used in the construction in big cities of the Russian Federation. These works need the use of elevating-transfer vehicles. In this case the requirements of norms and regulations on operating safety should be strictly observed, because their breach often leads to emergency situations and injuries. The organizational and technological solutions when developing the design documentation and executing construction and assembly works should be primarily based on the stability of lifting facilities. The author states the requirements to installation of lifting tackles (cranes. The features of their installation in different operation conditions on construction sites are described. The crane stability depends on many different indicators, which are considered by the author. The calculation algorithms of crane stability are offered.

Lysine Deacetylases and Regulated Glycolysis in Macrophages.

Science.gov (United States)

Shakespear, Melanie R; Iyer, Abishek; Cheng, Catherine Youting; Das Gupta, Kaustav; Singhal, Amit; Fairlie, David P; Sweet, Matthew J

2018-06-01

Regulated cellular metabolism has emerged as a fundamental process controlling macrophage functions, but there is still much to uncover about the precise signaling mechanisms involved. Lysine acetylation regulates the activity, stability, and/or localization of metabolic enzymes, as well as inflammatory responses, in macrophages. Two protein families, the classical zinc-dependent histone deacetylases (HDACs) and the NAD-dependent HDACs (sirtuins, SIRTs), mediate lysine deacetylation. We describe here mechanisms by which classical HDACs and SIRTs directly regulate specific glycolytic enzymes, as well as evidence that links these protein deacetylases to the regulation of glycolysis-related genes. In these contexts, we discuss HDACs and SIRTs as key control points for regulating immunometabolism and inflammatory outputs from macrophages. Copyright © 2018 Elsevier Ltd. All rights reserved.

Stabilizing local boundary conditions for two-dimensional shallow water equations

KAUST Repository

Dia, Ben Mansour; Oppelstrup, Jesper

2018-01-01

In this article, we present a sub-critical two-dimensional shallow water flow regulation. From the energy estimate of a set of one-dimensional boundary stabilization problems, we obtain a set of polynomial equations with respect to the boundary

Tyrosine Phosphorylation of the Human Serotonin Transporter: A Role in the Transporter Stability and Function

Science.gov (United States)

Annamalai, Balasubramaniam; Mannangatti, Padmanabhan; Arapulisamy, Obulakshmi; Shippenberg, Toni S.; Jayanthi, Lankupalle D.

2012-01-01

The serotonin (5-HT) transporter (SERT) regulates serotoninergic neurotransmission by clearing 5-HT released into the synaptic space. Phosphorylation of SERT on serine and threonine mediates SERT regulation. Whether tyrosine phosphorylation regulates SERT is unknown. Here, we tested the hypothesis that tyrosine-phosphorylation of SERT regulates 5-HT transport. In support of this, alkali-resistant 32P-labeled SERT was found in rat platelets, and Src-tyrosine kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo [3,4,d]pyrimidine (PP2) decreased platelet SERT function and expression. In human placental trophoblast cells expressing SERT, PP2 reduced transporter function, expression, and stability. Although siRNA silencing of Src expression decreased SERT function and expression, coexpression of Src resulted in PP2-sensitive increases in SERT function and expression. PP2 treatment markedly decreased SERT protein stability. Compared with WT-SERT, SERT tyrosine mutants Y47F and Y142F exhibited reduced 5-HT transport despite their higher total and cell surface expression levels. Moreover, Src-coexpression increased total and cell surface expression of Y47F and Y142F SERT mutants without affecting their 5-HT transport capacity. It is noteworthy that Y47F and Y142F mutants exhibited higher protein stability compared with WT-SERT. However, similar to WT-SERT, PP2 treatment decreased the stability of Y47F and Y142F mutants. Furthermore, compared with WT-SERT, Y47F and Y142F mutants exhibited lower basal tyrosine phosphorylation and no further enhancement of tyrosine phosphorylation in response to Src coexpression. These results provide the first evidence that SERT tyrosine phosphorylation supports transporter protein stability and 5HT transport. PMID:21992875

Performance of municipal waste stabilization ponds in the Canadian Arctic

DEFF Research Database (Denmark)

Ragush, Colin M.; Schmidt, Jordan J.; Krkosek, Wendy H.

2015-01-01

The majority of small remote communities in the Canadian arctic territory of Nunavut utilize waste stabilization ponds (WSPs) for municipal wastewater treatment because of their relatively low capital and operational costs, and minimal complexity. New national effluent quality regulations have be...

Effect of impurities and ripple upon power regulation in self-sustained tokamaks

International Nuclear Information System (INIS)

Bromberg, L.; Cohn, D.R.

1981-01-01

Tokamak power reactors will likely operate in a self sustained heating mode where additional power losses are introduced to permit higher levels of alpha particle heating (and thus higher levels of total fusion power) at thermal equilibrium. Illustrative 0-dimensional calculations are made to assess requirements for power regulation of self sustained tokamak plasmas by the use of impurity radiation. Effects of impurities upon allowable fuel density and thermal stability are determined. Requirements are calculated for passive thermal stability control by temperature driven radial motion in the presence of ripple transport losses; it appears that stability might be attained over a relatively wide temperature range with a small amount of ripple transport loss. Requirements for power regulation by the use of ripple transport are also determined

USP21 regulates Hippo pathway activity by mediating MARK protein turnover

DEFF Research Database (Denmark)

Nguyen, Thanh Hung; Kugler, Jan-Michael; Loya, Anand Chainsukh

2017-01-01

observed in cancer and often correlates with worse survival. The activity and stability of Hippo pathway components, including YAP/TAZ, AMOT and LATS1/2, are regulated by ubiquitin-mediated protein degradation. Aberrant expression of ubiquitin ligase complexes that regulate the turnover of Hippo components...

The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.

Science.gov (United States)

Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C; Riedel, Christian G; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R; Riera, Celine E; Lillemeier, Bjorn F; Kemphues, Kenneth; Yates, John R; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

2015-07-07

FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants of aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response, and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3-ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity. Copyright © 2015 Elsevier Inc. All rights reserved.

ANALYSIS OF PERTURBED MOTION STABILITY OF WHEELER VEHICLES BRAKES CONTROL SYSTEM

Directory of Open Access Journals (Sweden)

V. Verbytskiyi

2011-01-01

Full Text Available The analysis of the perturbed motion stability of the brake automatic control system on the basis of Lyapunov’s second method is carried out. Using transformations of Lurie there has been ob-tained the canonical form of the system of equations of automatic control. It allowed determining the necessary and sufficient conditions of the asymptotic stability of the system irrespective of its initial condition and a definite choice of the admissible characteristic of the regulator.

Petroleum products price regulation in Nov Scotia : a six-month review

International Nuclear Information System (INIS)

2007-03-01

Gasoline pricing regulation was introduced in July 2006 in order to achieve the following 3 main objectives: (1) stabilize prices by reducing the frequency of price changes and creating more uniform pricing across the province, (2) maintain industry infrastructure by slowing or halting the decline in the dealer network, particularly in rural areas, by improving viability through regulated margins, and (3) minimize the cost to consumers since higher prices are expected to result from the actions needed to maintain price stability and the higher margins needed to maintain industry infrastructure. This report examined the extent to which these objectives were achieved and contained the findings and recommendations of a review of the first six months of gasoline price regulation in Nova Scotia. The report discussed the rationale for regulation, study objectives, approach, and warning signs. It also discussed gasoline regulation in Nova Scotia including how regulation works and implementing regulation. The Nova Scotia gasoline market was presented with reference to industry structure; pre-regulation competition and pricing; and how regulation may affect structure and competition. Last, the report discussed whether regulation was meeting the objectives and perspectives on regulation. Several recommendations were presented, such as reducing the benchmark price adjustment period from two weeks to one week; removing the price cap on full-serve gasoline; adopting a fixed and transparent formula for forward averaging and applying it at each adjustment; and considering a framework for regulatory review. 12 refs., 15 figs

INPP5E Preserves Genomic Stability through Regulation of Mitosis.

Science.gov (United States)

Sierra Potchanant, Elizabeth A; Cerabona, Donna; Sater, Zahi Abdul; He, Ying; Sun, Zejin; Gehlhausen, Jeff; Nalepa, Grzegorz

2017-03-15

The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase that is mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in nondividing cells. Here, we report that INPP5E further contributes to cellular homeostasis by regulating cell division. We found that silencing or genetic knockout of INPP5E in human and murine cells impairs the spindle assembly checkpoint, centrosome and spindle function, and maintenance of chromosomal integrity. Consistent with a cell cycle regulatory role, we found that INPP5E expression is cell cycle dependent, peaking at mitotic entry. INPP5E localizes to centrosomes, chromosomes, and kinetochores in early mitosis and shuttles to the midzone spindle at mitotic exit. Our findings identify the previously unknown, essential role of INPP5E in mitosis and prevention of aneuploidy, providing a new perspective on the function of this phosphoinositide phosphatase in health and development. Copyright © 2017 Sierra Potchanant et al.

Overexpression of Exportin-5 Overrides the Inhibitory Effect of miRNAs Regulation Control and Stabilize Proteins via Posttranslation Modifications in Prostate Cancer

Directory of Open Access Journals (Sweden)

Naseruddin Höti

2017-10-01

Full Text Available Although XPO5 has been characterized to have tumor-suppressor features in the miRNA biogenesis pathway, the impact of altered expression of XPO5 in cancers is unexplored. Here we report a novel “oncogenic” role of XPO5 in advanced prostate cancer. Using prostate cancer models, we found that excess levels of XPO5 override the inhibitory effect of the canoncial miRNA-mRNA regulation, resulting in a global increase in proteins expression. Importantly, we found that decreased expression of XPO5 could promote an increase in proteasome degradation, whereas overexpression of XPO5 leads to altered protein posttranslational modification via hyperglycosylation, resulting in cellular protein stability. We evaluated the therapeutic advantage of targeting XPO5 in prostate cancer and found that knocking down XPO5 in prostate cancer cells suppressed cellular proliferation and tumor development without significantly impacting normal fibroblast cells survival. To our knowledge, this is the first report describing the oncogenic role of XPO5 in overriding the miRNAs regulation control. Furthermore, we believe that these findings will provide an explanation as to why, in some cancers that express higher abundance of mature miRNAs, fail to suppress their potential protein targets.

A technical basis for meeting waste form stability requirements of 10 CFR 61

International Nuclear Information System (INIS)

Chang, W.Y.; Skoski, L.; Eng, R.; Tuite, P.T.

1988-01-01

To assure that solidified low level waste forms meet the stability requirements of 10 CFR 61 regulations, the US Nuclear Regulatory Commission (NRC) has published Branch Technical Positions (BTPs) and draft Regulatory Guide on waste form stability. These guidance documents describe the test procedures and acceptance criteria for six stability parameters: leachability, compressive strength, immersion effect, radiation effect, thermal stability and biodegradability. The most recent set of recommended tests and acceptance criteria are presented in the November 1986 Preliminary Draft Regulatory Guide Low Level Waste Form Stability. The objective of this study was to: (1) investigate the regulatory and technical bases for the required stability tests, (2) evaluate the relevance of these tests and acceptance criteria based on actual test results, and (3) recommended alternatives to the testing and acceptance criteria. The latter two objectives are discussed in this paper

The role of zinc in genomic stability

International Nuclear Information System (INIS)

Sharif, Razinah; Thomas, Philip; Zalewski, Peter; Fenech, Michael

2012-01-01

Zinc (Zn) is an essential trace element required for maintaining both optimal human health and genomic stability. Zn plays a critical role in the regulation of DNA repair mechanisms, cell proliferation, differentiation and apoptosis involving the action of various transcriptional factors and DNA or RNA polymerases. Zn is an essential cofactor or structural component for important antioxidant defence proteins and DNA repair enzymes such as Cu/Zn SOD, OGG1, APE and PARP and may also affect activities of enzymes such as BHMT and MTR involved in methylation reactions in the folate-methionine cycle. This review focuses on the role of Zn in the maintenance of genome integrity and the effects of deficiency or excess on genomic stability events and cell death.

Trapped particle stability for the kinetic stabilizer

Science.gov (United States)

Berk, H. L.; Pratt, J.

2011-08-01

A kinetically stabilized axially symmetric tandem mirror (KSTM) uses the momentum flux of low-energy, unconfined particles that sample only the outer end-regions of the mirror plugs, where large favourable field-line curvature exists. The window of operation is determined for achieving magnetohydrodynamic (MHD) stability with tolerable energy drain from the kinetic stabilizer. Then MHD stable systems are analysed for stability of the trapped particle mode. This mode is characterized by the detachment of the central-cell plasma from the kinetic-stabilizer region without inducing field-line bending. Stability of the trapped particle mode is sensitive to the electron connection between the stabilizer and the end plug. It is found that the stability condition for the trapped particle mode is more constraining than the stability condition for the MHD mode, and it is challenging to satisfy the required power constraint. Furthermore, a severe power drain may arise from the necessary connection of low-energy electrons in the kinetic stabilizer to the central region.

Radioactive air emissions notice of construction for the 105N Basin Stabilization

International Nuclear Information System (INIS)

Coenenberg, E.T.

1994-01-01

The 105N Basin (basin) Stabilization will place the basin in a radiologically and environmentally safe condition so that it can be decommissioned at a later date. The basin is in the 105N Building, which is located in the 100N Area. The 100N Area is located in the Northern portion of the Hanford Site approximately 35 miles northwest of the city of Richland, Washington. The basin stabilization objectives are to inspect for Special Nuclear Material (SNM) (i.e., fuel assemblies and fuel pieces), remove the water from the basin and associated pits, and stabilize the basin surface. The stabilization will involve removal of basin hardware, removal of basin sediments, draining of basin water, and cleaning and stabilizing basin surfaces to prevent resuspension of radioactive emissions to the air. These activities will be conducted in accordance with all applicable regulations

Frequency Stability Improvement of Low Inertia Systems Using Synchronous Condensers

DEFF Research Database (Denmark)

Nguyen, Ha Thi; Yang, Guangya; Nielsen, Arne Hejde

2016-01-01

of converter interfaced components (wind turbine, HVDC, and Photovoltaic) may have negative effects on the stability of the power system. These components do not have enough inertia response to control frequency excursion, so the power grid can depend on few synchronous machines for frequency regulation...... and reduce the system inertia. Consequently, the frequency stability of the system will be easily jeopardized. To address these issues, the paper studies frequency characteristics of future Western Danish renewable-based system that uses a majority of wind turbine generators. Different scenarios of wind...

Systematic analysis of stability patterns in plant primary metabolism.

Directory of Open Access Journals (Sweden)

Dorothee Girbig

Full Text Available Metabolic networks are characterized by complex interactions and regulatory mechanisms between many individual components. These interactions determine whether a steady state is stable to perturbations. Structural kinetic modeling (SKM is a framework to analyze the stability of metabolic steady states that allows the study of the system Jacobian without requiring detailed knowledge about individual rate equations. Stability criteria can be derived by generating a large number of structural kinetic models (SK-models with randomly sampled parameter sets and evaluating the resulting Jacobian matrices. Until now, SKM experiments applied univariate tests to detect the network components with the largest influence on stability. In this work, we present an extended SKM approach relying on supervised machine learning to detect patterns of enzyme-metabolite interactions that act together in an orchestrated manner to ensure stability. We demonstrate its application on a detailed SK-model of the Calvin-Benson cycle and connected pathways. The identified stability patterns are highly complex reflecting that changes in dynamic properties depend on concerted interactions between several network components. In total, we find more patterns that reliably ensure stability than patterns ensuring instability. This shows that the design of this system is strongly targeted towards maintaining stability. We also investigate the effect of allosteric regulators revealing that the tendency to stability is significantly increased by including experimentally determined regulatory mechanisms that have not yet been integrated into existing kinetic models.

Relativistic stability of interacting Fermi gas in a strong magnetic field

International Nuclear Information System (INIS)

Wang Lilin; Tian Jincheng; Men Fudian; Zhang Yipeng

2013-01-01

By means of the single particle energy spectrum of weak interaction between fermions and Poisson formula, the thermodynamic potential function of relativistic Fermi gas in a strong magnetic field is derived. Based on this, we obtained the criterion of stability for the system. The results show that the mechanics stability of a Fermi gas with weak interacting is influenced by the interacting. While the magnetic field is able to regulate the influence and the relativistic effect has almost no effect on it. (authors)

Effects of protein phosphorylation on color stability of ground meat.

Science.gov (United States)

Li, Meng; Li, Xin; Xin, Jianzeng; Li, Zheng; Li, Guixia; Zhang, Yan; Du, Manting; Shen, Qingwu W; Zhang, Dequan

2017-03-15

The influence of protein phosphorylation on meat color stability was investigated in this study. Phosphatase and protein kinase inhibitors were added to minced ovine Longissimus thoracis et lumborum (LTL) muscle to manipulate the global phosphorylation of sarcoplasmic proteins. The data obtained show that the rate and extent of pH decline, along with lactate accumulation in postmortem muscle, were related to protein phosphorylation. Analysis of meat color and the relative content of myoglobin redox forms revealed that meat color stability was inversely related to the phosphorylation of sarcoplasmic proteins. Thus, this study suggests that protein phosphorylation may be involved in meat color development by regulating glycolysis and the redox stability of myoglobin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Negative Regulation of the Stability and Tumor Suppressor Function of Fbw7 by the Pin1 Prolyl Isomerase

Science.gov (United States)

Min, Sang-Hyun; Lau, Alan W.; Lee, Tae Ho; Inuzuka, Hiroyuki; Wei, Shuo; Huang, Pengyu; Shaik, Shavali; Lee, Daniel Yenhong; Finn, Greg; Balastik, Martin; Chen, Chun-Hau; Luo, Manli; Tron, Adriana E.; DeCaprio, James A.; Zhou, Xiao Zhen; Wei, Wenyi; Lu, Kun Ping

2012-01-01

SUMMARY Fbw7 is the substrate recognition component of the SCF (Skp1-Cullin-F-box)-type E3 ligase complex and a well-characterized tumor suppressor that targets numerous oncoproteins for destruction. Genomic deletion or mutation of FBW7 has been frequently found in various types of human cancers, however, little is known about the upstream signaling pathway(s) governing Fbw7 stability and cellular functions. Here we report that Fbw7 protein destruction and tumor suppressor function are negatively regulated by the prolyl isomerase Pin1. Pin1 interacts with Fbw7 in a phoshorylation-dependent manner and promotes Fbw7 self-ubiquitination and protein degradation by disrupting Fbw7 dimerization. Consequently, over-expressing Pin1 reduces Fbw7 abundance and suppresses Fbw7’s ability to inhibit proliferation and transformation. By contrast, depletion of Pin1 in cancer cells leads to elevated Fbw7 expression, which subsequently reduces Mcl-1 abundance, sensitizing cancer cells to Taxol. Thus, Pin1-mediated inhibition of Fbw7 contributes to oncogenesis and Pin1 may be a promising drug target for anti-cancer therapy. PMID:22608923

VALIDATING A COMPUTER-BASED TECHNIQUE FOR ASSESSING STABILITY TO FAILURE STRESS

Directory of Open Access Journals (Sweden)

I. F. Arshava

2013-03-01

Full Text Available An upsurge of interest in the implicit personality assessment, currently observed both in personality psycho-diagnostics and in experimental studies of social attitudes and prejudices, signals the shifting of researchers’ attention from de?ning between-person personality taxonomy to specifying comprehensive within-person processes, the dynamics of which can be captured at the level of an individual case. This research examines the possibility of the implicit assessment of the individual’s stability vs. susceptibility to failure stress by comparing the degrees of ef?cacy in the voluntary self-regulation of a computer-simulated information-processing activity under different conditions (patent of Ukraine № 91842, issued in 2010. By exposing two groups of participants (university undergraduates to processing the information, the scope of which exceeds the human short-term memory capacity at one of the stages of the modeled activity an unexpected and unavoidable failure is elicited. The participants who retain stability of their self-regulation behavior after having been exposed to failure, i.e. who keep processing information as effectively as they did prior to failure, are claimed to retain homeostasis and thus possess emotional stability. Those, who loose homeostasis after failure and display lower standards of self-regulation behavior, are considered to be susceptible to stress. The validity of the suggested type of the implicit diagnostics was empirically tested by clustering (K-means algorithm two samples of the participants on the  properties of their self-regulation behavior and testing between-cluster differences by a set of the explicitly assessed variables: Action control ef?cacy (Kuhl, 2001, preferred strategies of Coping with Stressful Situations (Endler, Parker, 1990,  Purpose-in-Life orientation (a Russian version of the test by Crumbaugh and Maholick, modi?ed by D.Leontiev, 1992, Psychological Well-being (Ryff, 1989

Financial Regulation in an Agent Based Macroeconomic Model

OpenAIRE

Riccetti, Luca; Russo, Alberto; Mauro, Gallegati

2013-01-01

Starting from the agent-based decentralized matching macroeconomic model proposed in Riccetti et al. (2012), we explore the effects of banking regulation on macroeconomic dynamics. In particular, we study the overall credit exposure and the lending concentration towards a single counterparty, finding that the portfolio composition seems to be more relevant than the overall exposure for banking stability, even if both features are very important. We show that a too tight regulation is dangerou...

Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1.

Science.gov (United States)

Lee, Seung Baek; Kim, Jung Jin; Nam, Hyun-Ja; Gao, Bowen; Yin, Ping; Qin, Bo; Yi, Sang-Yeop; Ham, Hyoungjun; Evans, Debra; Kim, Sun-Hyun; Zhang, Jun; Deng, Min; Liu, Tongzheng; Zhang, Haoxing; Billadeau, Daniel D; Wang, Liewei; Giaime, Emilie; Shen, Jie; Pang, Yuan-Ping; Jen, Jin; van Deursen, Jan M; Lou, Zhenkun

2015-10-01

Mutations in the E3 ubiquitin ligase Parkin have been linked to familial Parkinson's disease. Parkin has also been implicated in mitosis through mechanisms that are unclear. Here we show that Parkin interacts with anaphase promoting complex/cyclosome (APC/C) coactivators Cdc20 and Cdh1 to mediate the degradation of several key mitotic regulators independent of APC/C. We demonstrate that ordered progression through mitosis is orchestrated by two distinct E3 ligases through the shared use of Cdc20 and Cdh1. Furthermore, Parkin is phosphorylated and activated by polo-like kinase 1 (Plk1) during mitosis. Parkin deficiency results in overexpression of its substrates, mitotic defects, genomic instability, and tumorigenesis. These results suggest that the Parkin-Cdc20/Cdh1 complex is an important regulator of mitosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Tonic 5nM DA stabilizes neuronal output by enabling bidirectional activity-dependent regulation of the hyperpolarization activated current via PKA and calcineurin.

Science.gov (United States)

Krenz, Wulf-Dieter C; Rodgers, Edmund W; Baro, Deborah J

2015-01-01

Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP's first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output.

Tonic 5nM DA stabilizes neuronal output by enabling bidirectional activity-dependent regulation of the hyperpolarization activated current via PKA and calcineurin.

Directory of Open Access Journals (Sweden)

Wulf-Dieter C Krenz

Full Text Available Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA at type 1 DA receptors (D1Rs are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h. In the presence but not absence of 5nM DA, I h maximal conductance (G max was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP, which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation. Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP's first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output.

MAP Kinase Cascades Regulate the Cold Response by Modulating ICE1 Protein Stability.

Science.gov (United States)

Zhao, Chunzhao; Wang, Pengcheng; Si, Tong; Hsu, Chuan-Chih; Wang, Lu; Zayed, Omar; Yu, Zheping; Zhu, Yingfang; Dong, Juan; Tao, W Andy; Zhu, Jian-Kang

2017-12-04

Mitogen-activated protein kinase cascades are important signaling modules that convert environmental stimuli into cellular responses. We show that MPK3, MPK4, and MPK6 are rapidly activated after cold treatment. The mpk3 and mpk6 mutants display increased expression of CBF genes and enhanced freezing tolerance, whereas constitutive activation of the MKK4/5-MPK3/6 cascade in plants causes reduced expression of CBF genes and hypersensitivity to freezing, suggesting that the MKK4/5-MPK3/6 cascade negatively regulates the cold response. MPK3 and MPK6 can phosphorylate ICE1, a basic-helix-loop-helix transcription factor that regulates the expression of CBF genes, and the phosphorylation promotes the degradation of ICE1. Interestingly, the MEKK1-MKK2-MPK4 pathway constitutively suppresses MPK3 and MPK6 activities and has a positive role in the cold response. Furthermore, the MAPKKK YDA and two calcium/calmodulin-regulated receptor-like kinases, CRLK1 and CRLK2, negatively modulate the cold activation of MPK3/6. Our results uncover important roles of MAPK cascades in the regulation of plant cold response. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Evaluating the cement stabilization of arsenic-bearing iron wastes from drinking water treatment.

Science.gov (United States)

Clancy, Tara M; Snyder, Kathryn V; Reddy, Raghav; Lanzirotti, Antonio; Amrose, Susan E; Raskin, Lutgarde; Hayes, Kim F

2015-12-30

Cement stabilization of arsenic-bearing wastes is recommended to limit arsenic release from wastes following disposal. Such stabilization has been demonstrated to reduce the arsenic concentration in the Toxicity Characteristic Leaching Procedure (TCLP), which regulates landfill disposal of arsenic waste. However, few studies have evaluated leaching from actual wastes under conditions similar to ultimate disposal environments. In this study, land disposal in areas where flooding is likely was simulated to test arsenic release from cement stabilized arsenic-bearing iron oxide wastes. After 406 days submersed in chemically simulated rainwater, wastes. Presenting the first characterization of cement stabilized waste using μXRF, these results revealed the majority of arsenic in cement stabilized waste remained associated with iron. This distribution of arsenic differed from previous observations of calcium-arsenic solid phases when arsenic salts were stabilized with cement, illustrating that the initial waste form influences the stabilized form. Overall, cement stabilization is effective for arsenic-bearing wastes when acidic conditions can be avoided. Copyright © 2015 Elsevier B.V. All rights reserved.

Improving power grid transient stability by plug-in electric vehicles

International Nuclear Information System (INIS)

Gajduk, Andrej; Kocarev, Ljupco; Todorovski, Mirko; Kurths, Juergen

2014-01-01

Plug-in electric vehicles (PEVs) can serve in discharge mode as distributed energy and power resources operating as vehicle-to-grid (V2G) devices and in charge mode as loads or grid-to-vehicle devices. It has been documented that PEVs serving as V2G systems can offer possible backup for renewable power sources, can provide reactive power support, active power regulation, load balancing, peak load shaving, can reduce utility operating costs and can generate revenue. Here we show that PEVs can even improve power grid transient stability, that is, stability when the power grid is subjected to large disturbances, including bus faults, generator and branch tripping, and sudden large load changes. A control strategy that regulates the power output of a fleet of PEVs based on the speed of generator turbines is proposed and tested on the New England 10-unit 39-bus power system. By regulating the power output of the PEVs we show that (1) speed and voltage fluctuations resulting from large disturbances can be significantly reduced up to five times, and (2) the critical clearing time can be extended by 20–40%. Overall, the PEVs control strategy makes the power grid more robust. (paper)

78 FR 1690 - Semiannual Agenda of Regulations

Science.gov (United States)

2013-01-08

... OTS Freedom of Information Act (``FOIA'') and Privacy Act (``PA'') regulations will not be enforced by... counterparties, and; (c) determine if any systemic risks are posed by the transfer, disaffirmance, or termination... stability of the United States, to enforce contracts of subsidiaries or affiliates of the covered financial...

A nonlinear model for myogenic regulation of blood flow to bone: equilibrium states and stability characteristics.

Science.gov (United States)

Harrigan, T P

1996-01-01

A simple compartmental model for myogenic regulation of interstitial pressure in bone is developed, and the interaction between changes in interstitial pressure and changes in arterial and venous resistance is studied. The arterial resistance is modeled by a myogenic model that depends on transmural pressure, and the venous resistance is modeled by using a vascular waterfall. Two series capacitances model blood storage in the vascular system and interstitial fluid storage in the extravascular space. The static results mimic the observed effect that vasodilators work less well in bone than do vasoconstrictors. The static results also show that the model gives constant flow rates over a limited range of arterial pressure. The dynamic model shows unstable behavior at small values of bony capacitance and at high enough myogenic gain. At low myogenic gain, only a single equilibrium state is present, but a high enough myogenic gain, two new equilibrium states appear. At additional increases in gain, one of the two new states merges with and then separates from the original state, and the original state becomes a saddle point. The appearance of the new states and the transition of the original state to a saddle point do not depend on the bony capacitance, and these results are relevant to general fluid compartments. Numerical integration of the rate equations confirms the stability calculations and shows limit cycling behavior in several situations. The relevance of this model to circulation in bone and to other compartments is discussed.

Human cytomegalovirus gH stability and trafficking are regulated by ER-associated degradation and transmembrane architecture.

Science.gov (United States)

Gardner, Thomas J; Hernandez, Rosmel E; Noriega, Vanessa M; Tortorella, Domenico

2016-03-30

The prototypic betaherpesvirus human cytomegalovirus (CMV) establishes life-long persistence within its human host. While benign in healthy individuals, CMV poses a significant threat to the immune compromised, including transplant recipients and neonates. The CMV glycoprotein complex gH/gL/gO mediates infection of fibroblasts, and together with the gH/gL/UL128/130/131 a pentameric complex permits infection of epithelial, endothethial, and myeloid cells. Given the central role of the gH/gL complex during infection, we were interested in studying cellular trafficking of the gH/gL complex through generation of human cells that stably express gH and gL. When expressed alone, CMV gH and gL were degraded through the ER-associated degradation (ERAD) pathway. However, co-expression of these proteins stabilized the polypeptides and enhanced their cell-surface expression. To further define regulatory factors involved in gH/gL trafficking, a CMV gH chimera in which the gH transmembrane and cytoplasmic tail were replaced with that of human CD4 protein permitted cell surface gH expression in absence of gL. We thus demonstrate the ability of distinct cellular processes to regulate the trafficking of viral glycoproteins. Collectively, the data provide insight into the processing and trafficking requirements of CMV envelope protein complexes and provide an example of the co-opting of cellular processes by CMV.

Stability Constrained Efficiency Optimization for Droop Controlled DC-DC Conversion System

DEFF Research Database (Denmark)

Meng, Lexuan; Dragicevic, Tomislav; Guerrero, Josep M.

2013-01-01

implementing tertiary regulation. Moreover, system dynamic is affected when shifting VRs. Therefore, the stability is considered in optimization by constraining the eigenvalues arising from dynamic state space model of the system. Genetic algorithm is used in searching for global efficiency optimum while....... As the efficiency of each converter changes with output power, virtual resistances (VRs) are set as decision variables for adjusting power sharing proportion among converters. It is noteworthy that apart from restoring the voltage deviation, secondary control plays an important role to stabilize dc bus voltage when...

Strategies for the stabilization of longitudinal forward flapping flight revealed using a dynamically-scaled robotic fly

International Nuclear Information System (INIS)

Elzinga, Michael J; Van Breugel, Floris; Dickinson, Michael H

2014-01-01

The ability to regulate forward speed is an essential requirement for flying animals. Here, we use a dynamically-scaled robot to study how flapping insects adjust their wing kinematics to regulate and stabilize forward flight. The results suggest that the steady-state lift and thrust requirements at different speeds may be accomplished with quite subtle changes in hovering kinematics, and that these adjustments act primarily by altering the pitch moment. This finding is consistent with prior hypotheses regarding the relationship between body pitch and flight speed in fruit flies. Adjusting the mean stroke position of the wings is a likely mechanism for trimming the pitch moment at all speeds, whereas changes in the mean angle of attack may be required at higher speeds. To ensure stability, the flapping system requires additional pitch damping that increases in magnitude with flight speed. A compensatory reflex driven by fast feedback of pitch rate from the halteres could provide such damping, and would automatically exhibit gain scheduling with flight speed if pitch torque was regulated via changes in stroke deviation. Such a control scheme would provide an elegant solution for stabilization across a wide range of forward flight speeds. (paper)

School readiness of maltreated preschoolers and later school achievement: The role of emotion regulation, language, and context.

Science.gov (United States)

Panlilio, Carlomagno C; Jones Harden, Brenda; Harring, Jeffrey

2018-01-01

Guided by bio-ecological theory, this study aimed to: (1) identify heterogeneity in the developmental patterns of emotion regulation for maltreated preschool-aged children; (2) examine the role of gender, language, placement instability, cognitive stimulation, and emotional support on patterns of stability and change of emotion regulation over time; and (3) elucidate the role of emotion regulation/dysregulation patterns on later academic achievement. This study utilized data from the first cohort of the National Survey of Child and Adolescent Well-Being. Results using LCA and LTA models indicated stability and change in emotionally regulated vs. emotionally dysregulated latent classes across 4, 5, and 6 ½ years of age. Placement instability significantly increased the likelihood of being classified as emotionally dysregulated at wave 1. Moreover, children classified as emotionally dysregulated by age 6 ½ scored significantly lower than children who were classified as emotionally regulated on measures of reading and math achievement by age 10. Based on these findings, placement stability at first contact with CPS should be promoted in order to prevent cascading negative effects on emotion regulation. Additionally, children who are more emotionally dysregulated by the time they transition to formal schooling should receive increased socioemotional and socioemotional learning supports. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dc microgrid stabilization through fuzzy control of interleaved, heterogeneous storage elements

Science.gov (United States)

Smith, Robert David

As microgrid power systems gain prevalence and renewable energy comprises greater and greater portions of distributed generation, energy storage becomes important to offset the higher variance of renewable energy sources and maximize their usefulness. One of the emerging techniques is to utilize a combination of lead-acid batteries and ultracapacitors to provide both short and long-term stabilization to microgrid systems. The different energy and power characteristics of batteries and ultracapacitors imply that they ought to be utilized in different ways. Traditional linear controls can use these energy storage systems to stabilize a power grid, but cannot effect more complex interactions. This research explores a fuzzy logic approach to microgrid stabilization. The ability of a fuzzy logic controller to regulate a dc bus in the presence of source and load fluctuations, in a manner comparable to traditional linear control systems, is explored and demonstrated. Furthermore, the expanded capabilities (such as storage balancing, self-protection, and battery optimization) of a fuzzy logic system over a traditional linear control system are shown. System simulation results are presented and validated through hardware-based experiments. These experiments confirm the capabilities of the fuzzy logic control system to regulate bus voltage, balance storage elements, optimize battery usage, and effect self-protection.

Plutonium inventories for stabilization and stabilized materials

Energy Technology Data Exchange (ETDEWEB)

Williams, A.K.

1996-05-01

The objective of the breakout session was to identify characteristics of materials containing plutonium, the need to stabilize these materials for storage, and plans to accomplish the stabilization activities. All current stabilization activities are driven by the Defense Nuclear Facilities Safety Board Recommendation 94-1 (May 26, 1994) and by the recently completed Plutonium ES&H Vulnerability Assessment (DOE-EH-0415). The Implementation Plan for accomplishing stabilization of plutonium-bearing residues in response to the Recommendation and the Assessment was published by DOE on February 28, 1995. This Implementation Plan (IP) commits to stabilizing problem materials within 3 years, and stabilizing all other materials within 8 years. The IP identifies approximately 20 metric tons of plutonium requiring stabilization and/or repackaging. A further breakdown shows this material to consist of 8.5 metric tons of plutonium metal and alloys, 5.5 metric tons of plutonium as oxide, and 6 metric tons of plutonium as residues. Stabilization of the metal and oxide categories containing greater than 50 weight percent plutonium is covered by DOE Standard {open_quotes}Criteria for Safe Storage of Plutonium Metals and Oxides{close_quotes} December, 1994 (DOE-STD-3013-94). This standard establishes criteria for safe storage of stabilized plutonium metals and oxides for up to 50 years. Each of the DOE sites and contractors with large plutonium inventories has either started or is preparing to start stabilization activities to meet these criteria.

Role of CAP350 in centriolar tubule stability and centriole assembly.

Directory of Open Access Journals (Sweden)

Mikael Le Clech

Full Text Available BACKGROUND: Centrioles are microtubule-based cylindrical structures composed of nine triplet tubules and are required for the formation of the centrosome, flagella and cilia. Despite theirs importance, centriole biogenesis is poorly understood. Centrosome duplication is initiated at the G1/S transition by the sequential recruitment of a set of conserved proteins under the control of the kinase Plk4. Subsequently, the procentriole is assembled by the polymerization of centriolar tubules via an unknown mechanism involving several tubulin paralogs. METHODOLOGY/PRINCIPAL FINDINGS: Here, we developed a cellular assay to study centrosome duplication and procentriole stability based on its sensitivity to the microtubule-depolymerizing drug nocodazole. By using RNA interference experiments, we show that the stability of growing procentrioles is regulated by the microtubule-stabilizing protein CAP350, independently of hSAS-6 and CPAP which initiate procentriole growth. Furthermore, our analysis reveals the critical role of centriolar tubule stability for an efficient procentriole growth. CONCLUSIONS/SIGNIFICANCE: CAP350 belongs to a new class of proteins which associate and stabilize centriolar tubules to control centriole duplication.

Within-Family Dynamics and Self-Regulation in Preschoolers

NARCIS (Netherlands)

Karreman, A.

2006-01-01

Separate research lines have stressed the importance of within-family dynamics on the one hand and self-regulation on the other hand for the development and stability of problem behavior in young children. Few empirical studies have directly addressed the relation between family processes and

Bacterial Quorum Sensing Stabilizes Cooperation by Optimizing Growth Strategies.

Science.gov (United States)

Bruger, Eric L; Waters, Christopher M

2016-11-15

Communication has been suggested as a mechanism to stabilize cooperation. In bacteria, chemical communication, termed quorum sensing (QS), has been hypothesized to fill this role, and extracellular public goods are often induced by QS at high cell densities. Here we show, with the bacterium Vibrio harveyi, that QS provides strong resistance against invasion of a QS defector strain by maximizing the cellular growth rate at low cell densities while achieving maximum productivity through protease upregulation at high cell densities. In contrast, QS mutants that act as defectors or unconditional cooperators maximize either the growth rate or the growth yield, respectively, and thus are less fit than the wild-type QS strain. Our findings provide experimental evidence that regulation mediated by microbial communication can optimize growth strategies and stabilize cooperative phenotypes by preventing defector invasion, even under well-mixed conditions. This effect is due to a combination of responsiveness to environmental conditions provided by QS, lowering of competitive costs when QS is not induced, and pleiotropic constraints imposed on defectors that do not perform QS. Cooperation is a fundamental problem for evolutionary biology to explain. Conditional participation through phenotypic plasticity driven by communication is a potential solution to this dilemma. Thus, among bacteria, QS has been proposed to be a proximate stabilizing mechanism for cooperative behaviors. Here, we empirically demonstrate that QS in V. harveyi prevents cheating and subsequent invasion by nonproducing defectors by maximizing the growth rate at low cell densities and the growth yield at high cell densities, whereas an unconditional cooperator is rapidly driven to extinction by defectors. Our findings provide experimental evidence that QS regulation prevents the invasion of cooperative populations by QS defectors even under unstructured conditions, and they strongly support the role of

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)

The Broadening of Activities in the Financial System : Implications for Financial Stability and Regulation

NARCIS (Netherlands)

Wagner, W.B.

2006-01-01

Conglomeration and consolidation in the financial system broaden the activities financial institutions are undertaking and cause them to become more homogenous.Although resulting diversification gains make each institution appear less risky, we argue that financial stability may not improve as total

Transcriptional regulation of hepatic lipogenesis.

Science.gov (United States)

Wang, Yuhui; Viscarra, Jose; Kim, Sun-Joong; Sul, Hei Sook

2015-11-01

Fatty acid and fat synthesis in the liver is a highly regulated metabolic pathway that is important for very low-density lipoprotein (VLDL) production and thus energy distribution to other tissues. Having common features at their promoter regions, lipogenic genes are coordinately regulated at the transcriptional level. Transcription factors, such as upstream stimulatory factors (USFs), sterol regulatory element-binding protein 1C (SREBP1C), liver X receptors (LXRs) and carbohydrate-responsive element-binding protein (ChREBP) have crucial roles in this process. Recently, insights have been gained into the signalling pathways that regulate these transcription factors. After feeding, high blood glucose and insulin levels activate lipogenic genes through several pathways, including the DNA-dependent protein kinase (DNA-PK), atypical protein kinase C (aPKC) and AKT-mTOR pathways. These pathways control the post-translational modifications of transcription factors and co-regulators, such as phosphorylation, acetylation or ubiquitylation, that affect their function, stability and/or localization. Dysregulation of lipogenesis can contribute to hepatosteatosis, which is associated with obesity and insulin resistance.

Stabilizing IkappaBalpha by "consensus" design.

Science.gov (United States)

Ferreiro, Diego U; Cervantes, Carla F; Truhlar, Stephanie M E; Cho, Samuel S; Wolynes, Peter G; Komives, Elizabeth A

2007-01-26

IkappaBalpha is the major regulator of transcription factor NF-kappaB function. The ankyrin repeat region of IkappaBalpha mediates specific interactions with NF-kappaB dimers, but ankyrin repeats 1, 5 and 6 display a highly dynamic character when not in complex with NF-kappaB. Using chemical denaturation, we show here that IkappaBalpha displays two folding transitions: a non-cooperative conversion under weak perturbation, and a major cooperative folding phase upon stronger insult. Taking advantage of a native Trp residue in ankyrin repeat (AR) 6 and engineered Trp residues in AR2, AR4 and AR5, we show that the cooperative transition involves AR2 and AR3, while the non-cooperative transition involves AR5 and AR6. The major structural transition can be affected by single amino acid substitutions converging to the "consensus" ankyrin repeat sequence, increasing the native state stability significantly. We further characterized the structural and dynamic properties of the native state ensemble of IkappaBalpha and the stabilized mutants by H/(2)H exchange mass spectrometry and NMR. The solution experiments were complemented with molecular dynamics simulations to elucidate the microscopic origins of the stabilizing effect of the consensus substitutions, which can be traced to the fast conformational dynamics of the folded ensemble.

SCF(KMD) controls cytokinin signaling by regulating the degradation of type-B response regulators.

Science.gov (United States)

Kim, Hyo Jung; Chiang, Yi-Hsuan; Kieber, Joseph J; Schaller, G Eric

2013-06-11

Cytokinins are plant hormones that play critical roles in growth and development. In Arabidopsis, the transcriptional response to cytokinin is regulated by action of type-B Arabidopsis response regulators (ARRs). Although central elements in the cytokinin signal transduction pathway have been identified, mechanisms controlling output remain to be elucidated. Here we demonstrate that a family of F-box proteins, called the kiss me deadly (KMD) family, targets type-B ARR proteins for degradation. KMD proteins form an S-phase kinase-associated PROTEIN1 (SKP1)/Cullin/F-box protein (SCF) E3 ubiquitin ligase complex and directly interact with type-B ARR proteins. Loss-of-function KMD mutants stabilize type-B ARRs and exhibit an enhanced cytokinin response. In contrast, plants with elevated KMD expression destabilize type-B ARR proteins leading to cytokinin insensitivity. Our results support a model in which an SCF(KMD) complex negatively regulates cytokinin responses by controlling levels of a key family of transcription factors.

Structural homeostasis in the nervous system: A balancing act for wiring plasticity and stability

Directory of Open Access Journals (Sweden)

Jun eYin

2015-01-01

Full Text Available Experience-dependent modifications of neural circuits provide the cellular basis for functional adaptation and learning, while presenting significant challenges to the stability of neural networks. The nervous system copes with these perturbations through a variety of compensatory mechanisms with distinct spatial and temporal profiles. Mounting evidence suggests that structural plasticity, through modifications of the number and structure of synapses, or changes in local and long-range connectivity, might contribute to the stabilization of network activity and serve as an important component of the homeostatic regulation of the nervous system. Conceptually similar to the homeostatic regulation of synaptic strength and efficacy, homeostatic structural plasticity has a profound and lasting impact on the intrinsic excitability of the neuron and circuit properties, yet remains largely unexplored. In this review, we examine recent reports describing structural modifications associated with functional compensation in both developing and adult nervous systems, and discuss the potential role for structural homeostasis in maintaining network stability and its implications in physiological and pathological conditions of the nervous systems.

Regulating approaches to learning: Testing learning strategy convergences across a year at university.

Science.gov (United States)

Fryer, Luke K; Vermunt, Jan D

2018-03-01

Contemporary models of student learning within higher education are often inclusive of processing and regulation strategies. Considerable research has examined their use over time and their (person-centred) convergence. The longitudinal stability/variability of learning strategy use, however, is poorly understood, but essential to supporting student learning across university experiences. Develop and test a person-centred longitudinal model of learning strategies across the first-year university experience. Japanese university students (n = 933) completed surveys (deep and surface approaches to learning; self, external, and lack of regulation) at the beginning and end of their first year. Following invariance and cross-sectional tests, latent profile transition analysis (LPTA) was undertaken. Initial difference testing supported small but significant differences for self-/external regulation. Fit indices supported a four-group model, consistent across both measurement points. These subgroups were labelled Low Quality (low deep approaches and self-regulation), Low Quantity (low strategy use generally), Average (moderate strategy use), and High Quantity (intense use of all strategies) strategies. The stability of these groups ranged from stable to variable: Average (93% stayers), Low Quality (90% stayers), High Quantity (72% stayers), and Low Quantity (40% stayers). The three largest transitions presented joint shifts in processing/regulation strategy preference across the year, from adaptive to maladaptive and vice versa. Person-centred longitudinal findings presented patterns of learning transitions that different students experience during their first year at university. Stability/variability of students' strategy use was linked to the nature of initial subgroup membership. Findings also indicated strong connections between processing and regulation strategy changes across first-year university experiences. Implications for theory and practice are discussed. �

Matrin 3 binds and stabilizes mRNA.

Directory of Open Access Journals (Sweden)

Maayan Salton

Full Text Available Matrin 3 (MATR3 is a highly conserved, inner nuclear matrix protein with two zinc finger domains and two RNA recognition motifs (RRM, whose function is largely unknown. Recently we found MATR3 to be phosphorylated by the protein kinase ATM, which activates the cellular response to double strand breaks in the DNA. Here, we show that MATR3 interacts in an RNA-dependent manner with several proteins with established roles in RNA processing, and maintains its interaction with RNA via its RRM2 domain. Deep sequencing of the bound RNA (RIP-seq identified several small noncoding RNA species. Using microarray analysis to explore MATR3's role in transcription, we identified 77 transcripts whose amounts depended on the presence of MATR3. We validated this finding with nine transcripts which were also bound to the MATR3 complex. Finally, we demonstrated the importance of MATR3 for maintaining the stability of several of these mRNA species and conclude that it has a role in mRNA stabilization. The data suggest that the cellular level of MATR3, known to be highly regulated, modulates the stability of a group of gene transcripts.

Measuring children's regulation of emotion-expressive behavior.

Science.gov (United States)

Bar-Haim, Yair; Bar-Av, Gali; Sadeh, Avi

2011-04-01

Emotion regulation has become a pivotal concept in developmental and clinical research. However, the measurement of regulatory processes has proved extremely difficult, particularly in the context of within-subject designs. Here, we describe a formal conceptualization and a new experimental procedure, the Balloons Game, to measure a regulatory component of emotion-expressive behavior. We present the internal consistency and stability of the indices derived from the Balloons Game in a sample of 121 kindergarten children. External validation against measures that have been associated with emotion regulation processes is also provided. The findings suggest that the Balloons Game provides a reliable tool for the study of regulation of emotion expression in young children. PsycINFO Database Record (c) 2011 APA, all rights reserved.

Surface profile gradient in amorphous Ta{sub 2}O{sub 5} semi conductive layers regulates nanoscale electric current stability

Energy Technology Data Exchange (ETDEWEB)

Cefalas, A.C., E-mail: ccefalas@eie.gr [National Hellenic Research Foundation, Theoretical and Physical Chemistry Institute, 48 Vassileos Constantinou Avenue, Athens 11635 (Greece); Kollia, Z.; Spyropoulos-Antonakakis, N.; Gavriil, V. [National Hellenic Research Foundation, Theoretical and Physical Chemistry Institute, 48 Vassileos Constantinou Avenue, Athens 11635 (Greece); Christofilos, D.; Kourouklis, G. [Physics Division, School of Technology, Aristotle University of Thessaloniki, Thessaloniki 54124 (Greece); Semashko, V.V.; Pavlov, V. [Kazan Federal University, Institute of Physics, 18 Kremljovskaja str., Kazan 420008 (Russian Federation); Sarantopoulou, E. [National Hellenic Research Foundation, Theoretical and Physical Chemistry Institute, 48 Vassileos Constantinou Avenue, Athens 11635 (Greece); Kazan Federal University, Institute of Physics, 18 Kremljovskaja str., Kazan 420008 (Russian Federation)

2017-02-28

Highlights: • The work links the surface morphology of amorphous semiconductors with both their electric-thermal properties and current stability at the nanoscale (<1 μm). • Measured high correlation value between surface morphological spatial gradient and conductive electron energy spatial gradient or thermal gradient. • Unidirectional current stability is associated with asymmetric nanodomains along nanosize conductive paths. • Bidirectional current stability is inherent with either long conductive paths or nanosize conductive paths along symmetric nanodomains. • Conclusion: Surface design improves current stability across nanoelectonic junctions. - Abstract: A link between the morphological characteristics and the electric properties of amorphous layers is established by means of atomic, conductive, electrostatic force and thermal scanning microscopy. Using amorphous Ta{sub 2}O{sub 5} (a-Ta{sub 2}O{sub 5}) semiconductive layer, it is found that surface profile gradients (morphological gradient), are highly correlated to both the electron energy gradient of trapped electrons in interactive Coulombic sites and the thermal gradient along conductive paths and thus thermal and electric properties are correlated with surface morphology at the nanoscale. Furthermore, morphological and electron energy gradients along opposite conductive paths of electrons intrinsically impose a current stability anisotropy. For either long conductive paths (L > 1 μm) or along symmetric nanodomains, current stability for both positive and negative currents i is demonstrated. On the contrary, for short conductive paths along non-symmetric nanodomains, the set of independent variables (L, i) is spanned by two current stability/intability loci. One locus specifies a stable state for negative currents, while the other locus also describes a stable state for positive currents.

Rare sugar D-allose induces specific up-regulation of TXNIP and subsequent G1 cell cycle arrest in hepatocellular carcinoma cells by stabilization of p27kip1.

Science.gov (United States)

Yamaguchi, Fuminori; Takata, Maki; Kamitori, Kazuyo; Nonaka, Machiko; Dong, Youyi; Sui, Li; Tokuda, Masaaki

2008-02-01

'Rare sugars' are defined as monosaccharides that exist in nature but are only present in limited quantities. The development of mass production method of rare sugars revealed some interesting physiological effects of these on animal cells, but the mechanisms have not been well studied. We examined the effect of D-allose on the proliferation of cancer cells and the underlying molecular mechanism of the action. The HuH-7 hepatocellular carcinoma cells were treated with various monosaccharides for 48 h and D-allose was shown to inhibit cell growth by 40% in a dose-dependent manner. D-allose induced G1 cell cycle arrest but not apoptosis. The microarray analysis revealed that D-allose significantly up-regulated thioredoxin interacting protein (TXNIP) gene expression, which is often suppressed in tumor cells and western blot analysis confirmed its increase at protein level. The overexpression of TXNIP also induced G1 cell cycle arrest. Analysis of cell cycle regulatory genes showed p27kip1, a key regulator of G1/S cell cycle transition, to be increased at the protein but not the transcriptional level. Protein interaction between TXNIP and jab1, and p27kip1 and jab1, was observed, suggesting stabilization of p27kip1 protein by the competitive inhibition of jab1-mediated nuclear export of p27kip1 by TXNIP. In addition, increased interaction and nuclear localization of TXNIP and p27kip1 were apparent after D-allose treatment. Our findings surprisingly suggest that D-allose, a simple monosaccharide, may act as a novel anticancer agent via unique TXNIP induction and p27kip1 protein stabilization.

Accidents protection of the de-Qing regulator

International Nuclear Information System (INIS)

Feng Wenquan; Yang Fangxin; Zhu Genfa; Chen Zhenhua

1992-01-01

The de-Qing circuit is widely used in regulating and stabilizing HV pulse voltage in radar and electron linac. however its malfunction may cause damage to the microwave tube and pulse generator. Thus it is necessary to set up a protection circuit. The principle and problems for design are presented. Two examples employed successfully in electron linac are provided

Power system stabilizers based on distributed energy resources for damping of inter-area oscillations

Directory of Open Access Journals (Sweden)

Stefanov Predrag Č.

2014-01-01

Full Text Available This paper deals with inter-area power oscillations damping enhancement by distributed energy resources contained in typical micro grid. Main idea behind this work is to use distributed generation and distributed storage, such as battery energy storage to mimic conventional power system stabilizer, but with regulating active power output, rather than reactive power, as in standard power system stabilizer realization. The analysis of the small signal stability is established for four-machine, two-area system, with inverter based micro grids in each area. Dynamic simulation results are included in this work and they show that proposed controller provides additional damping effect to this test system.

Developing a stability assessment method for power electronics-based microgrids

Science.gov (United States)

Austin, Peter M.

Modern microgrids with microsources and energy storage are dependent on power electronics for control and regulation. Under certain circumstances power electronics can be destabilizing to the system due to an effect called negative incremental impedance. A careful review of the theory and literature on the subject is presented. This includes stability criteria for both AC and DC systems, as well as a discussion on the limitations posed by the analysis. A method to integrate stability assessment with higher-level microgrid architectural design is proposed. Crucial to this is impedance characterization of individual components, which was accomplished through simulation. DC and AC impedance measurement blocks were created in Matlab simulink to automate the process. A detailed switching-level model of a DC microgrid was implemented in simulink, including wind turbine microsource, battery storage, and three phase inverter. Maximum power point tracking (MPPT) was included to maximize the efficiency of the turbine and was implemented through three rectifier alternatives and control schemes. The stability characteristics of each was compared in the final analysis. Impedance data was collected individually from the components and used to assess stability in the system as a whole. The results included the assessment of stability, margin, and unstable operating points to demonstrate the feasibility of the proposed approach.

Association of Stability Parameters and Yield Stability of Sesame ...

African Journals Online (AJOL)

Association of Stability Parameters and Yield Stability of Sesame ( Sesamum ... Information on phenotypic stability is useful for the selection of crop varieties as well as for ... as an alternative to parametric stability measurements is important.

Financial Sector Regulation and Reforms in Emerging Markets: An Overview

OpenAIRE

Eswar S. Prasad

2010-01-01

This paper provides an overview of the complex conceptual and practical challenges that emerging market economies face as they attempt to reform their frameworks for financial regulation. These economies are striving to balance the quest for financial stability with the imperatives of financial development and broader financial inclusion. I argue that these objectives can in fact reinforce one another. I also discuss aspects of macroeconomic policies and cross-border regulation that have impl...

Phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins

KAUST Repository

Bigeard, Jean; Rayapuram, Naganand; Pflieger, Delphine; Hirt, Heribert

2014-01-01

In eukaryotes, most of the DNA is located in the nucleus where it is organized with histone proteins in a higher order structure as chromatin. Chromatin and chromatin-associated proteins contribute to DNA-related processes such as replication and transcription as well as epigenetic regulation. Protein functions are often regulated by PTMs among which phosphorylation is one of the most abundant PTM. Phosphorylation of proteins affects important properties, such as enzyme activity, protein stability, or subcellular localization. We here describe the main specificities of protein phosphorylation in plants and review the current knowledge on phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins. We also outline some future challenges to further elucidate protein phosphorylation and chromatin regulation.

Phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins

KAUST Repository

Bigeard, Jean

2014-07-10

In eukaryotes, most of the DNA is located in the nucleus where it is organized with histone proteins in a higher order structure as chromatin. Chromatin and chromatin-associated proteins contribute to DNA-related processes such as replication and transcription as well as epigenetic regulation. Protein functions are often regulated by PTMs among which phosphorylation is one of the most abundant PTM. Phosphorylation of proteins affects important properties, such as enzyme activity, protein stability, or subcellular localization. We here describe the main specificities of protein phosphorylation in plants and review the current knowledge on phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins. We also outline some future challenges to further elucidate protein phosphorylation and chromatin regulation.

Hypoxia inducible factor-1 alpha stabilization for regenerative therapy in traumatic brain injury

Directory of Open Access Journals (Sweden)

Mushfiquddin Khan

2017-01-01

Full Text Available Mild traumatic brain injury (TBI, also called concussion, initiates sequelae leading to motor deficits, cognitive impairments and subtly compromised neurobehaviors. While the acute phase of TBI is associated with neuroinflammation and nitroxidative burst, the chronic phase shows a lack of stimulation of the neurorepair process and regeneration. The deficiency of nitric oxide (NO, the consequent disturbed NO metabolome, and imbalanced mechanisms of S-nitrosylation are implicated in blocking the mechanisms of neurorepair processes and functional recovery in the both phases. Hypoxia inducible factor-1 alpha (HIF-1α, a master regulator of hypoxia/ischemia, stimulates the process of neurorepair and thus aids in functional recovery after brain trauma. The activity of HIF-1α is regulated by NO via the mechanism of S-nitrosylation of HIF-1α. S-nitrosylation is dynamically regulated by NO metabolites such as S-nitrosoglutathione (GSNO and peroxynitrite. GSNO stabilizes, and peroxynitrite destabilizes HIF-1α. Exogenously administered GSNO was found not only to stabilize HIF-1α and to induce HIF-1α-dependent genes but also to stimulate the regeneration process and to aid in functional recovery in TBI animals.

Effect of Cavity Size of Mesoporous Silica on Short DNA Duplex Stability.

Science.gov (United States)

Masuda, Tsubasa; Shibuya, Yuuta; Arai, Shota; Kobayashi, Sayaka; Suzuki, Sotaro; Kijima, Jun; Itoh, Tetsuji; Sato, Yusuke; Nishizawa, Seiichi; Yamaguchi, Akira

2018-05-15

We studied the stabilities of short (4- and 3-bp) DNA duplexes within silica mesopores modified with a positively charged trimethyl aminopropyl (TMAP) monolayer (BJH pore diameter 1.6-7.4 nm). The DNA fragments with fluorescent dye were introduced into the pores, and their fluorescence resonance energy transfer (FRET) response was measured to estimate the structuring energies of the short DNA duplexes under cryogenic conditions (temperature 233-323 K). The results confirmed the enthalpic stability gain of the duplex within size-matched pores (1.6 and 2.3 nm). The hybridization equilibrium constants found for the size-matched pores were 2 orders of magnitude larger than those for large pores (≥3.5 nm), and this size-matching effect for the enhanced duplex stability was explained by a tight electrostatic interaction between the duplex and the surface TMAP groups. These results indicate the requirement of the precise regulation of mesopore size to ensure the stabilization of hydrogen-bonded supramolecular assemblies.

Causes and effects of morphological changes of the regulated channel of the river Toplica

Directory of Open Access Journals (Sweden)

Đeković Vojislav

2005-01-01

Full Text Available The regulation of small torrential watercourses outside the urbanized areas is often based on the so-called field type of regulation. In the selection of this concept, after the regulation works, the new channel is left to the natural process of the morphological formation of the water cross-section taking care not to disturb the general stability of the regulated channel. We present the process of morphological development of the regulated channel of the river Toplica, tributary of the river Kolubara, in the period 1982-2004 i.e. from immediately after the regulation works to the present day.

The C. elegans Ortholog of USP7 controls DAF-16 stability in Insulin/IGF-1-like signaling.

Science.gov (United States)

Heimbucher, Thomas; Hunter, Tony

2015-01-01

FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and are regulated by posttranslational modification and coregulators, including components of the ubiquitin-proteasome system (UPS). Cofactors promoting DAF-16/FOXO protein stability and function in IIS have not been described yet. In a recent study, we have identified the deubiquitylating enzyme MATH-33, the ortholog of mammalian USP7/HAUSP, as an essential DAF-16 coregulator. We found that MATH-33 actively stabilizes DAF-16 protein levels when IIS is downregulated. Here we discuss how DAF-16/FOXO transcription factors are regulated by the UPS, in particular by the interplay of E3-ubiquitin ligases and deubiquitylating enzymes, which is critical for balancing DAF-16/FOXO activity and degradation. Recent findings raise the intriguing possibility that regulated oscillations in DAF-16/FOXO steady state levels play an integral role in mechanisms controlling healthspan and lifespan extension.

RNA-Mediated cis Regulation in Acinetobacter baumannii Modulates Stress-Induced Phenotypic Variation.

Science.gov (United States)

Ching, Carly; Gozzi, Kevin; Heinemann, Björn; Chai, Yunrong; Godoy, Veronica G

2017-06-01

In the nosocomial opportunistic pathogen Acinetobacter baumannii , RecA-dependent mutagenesis, which causes antibiotic resistance acquisition, is linked to the DNA damage response (DDR). Notably, unlike the Escherichia coli paradigm, recA and DDR gene expression in A. baumannii is bimodal. Namely, there is phenotypic variation upon DNA damage, which may provide a bet-hedging strategy for survival. Thus, understanding recA gene regulation is key to elucidate the yet unknown DDR regulation in A. baumannii Here, we identify a structured 5' untranslated region (UTR) in the recA transcript which serves as a cis -regulatory element. We show that a predicted stem-loop structure in this 5' UTR affects mRNA half-life and underlies bimodal gene expression and thus phenotypic variation in response to ciprofloxacin treatment. We furthermore show that the stem-loop structure of the recA 5' UTR influences intracellular RecA protein levels and, in vivo , impairing the formation of the stem-loop structure of the recA 5' UTR lowers cell survival of UV treatment and decreases rifampin resistance acquisition from DNA damage-induced mutagenesis. We hypothesize that the 5' UTR allows for stable recA transcripts during stress, including antibiotic treatment, enabling cells to maintain suitable RecA levels for survival. This innovative strategy to regulate the DDR in A. baumannii may contribute to its success as a pathogen. IMPORTANCE Acinetobacter baumannii is an opportunistic pathogen quickly gaining antibiotic resistances. Mutagenesis and antibiotic resistance acquisition are linked to the DNA damage response (DDR). However, how the DDR is regulated in A. baumannii remains unknown, since unlike most bacteria, A. baumannii does not follow the regulation of the Escherichia coli paradigm. In this study, we have started to uncover the mechanisms regulating the novel A. baumannii DDR. We have found that a cis -acting 5' UTR regulates recA transcript stability, RecA protein levels, and DNA

Prostacyclin synthase expression and epigenetic regulation in nonsmall cell lung cancer.

LENUS (Irish Health Repository)

Cathcart, Mary-Clare

2012-02-01

BACKGROUND: Prostacyclin synthase (PGIS) metabolizes prostaglandin H(2), into prostacyclin. This study aimed to determine the expression profile of PGIS in nonsmall cell lung cancer (NSCLC) and examine potential mechanisms involved in PGIS regulation. METHODS: PGIS expression was examined in human NSCLC and matched controls by reverse transcriptase polymerase chain reaction (RT-PCR), Western analysis, and immunohistochemistry. A 204-patient NSCLC tissue microarray was stained for PGIS and cyclooxygenase 2 (COX2) expression. Staining intensity was correlated with clinical parameters. Epigenetic mechanisms underpinning PGIS promoter expression were examined using RT-PCR, methylation-specific PCR, and chromatin immunoprecipitation analysis. RESULTS: PGIS expression was reduced\\/absent in human NSCLC protein samples (P < .0001), but not mRNA relative to matched controls. PGIS tissue expression was higher in squamous cell carcinoma (P = .004) and in male patients (P < .05). No significant correlation of PGIS or COX2 expression with overall patient survival was observed, although COX2 was prognostic for short-term (2-year) survival (P < .001). PGIS mRNA expression was regulated by DNA CpG methylation and histone acetylation in NSCLC cell lines, with chromatin remodeling taking place directly at the PGIS gene. PGIS mRNA expression was increased by both demethylation agents and histone deacetylase inhibitors. Protein levels were unaffected by demethylation agents, whereas PGIS protein stability was negatively affected by histone deacetylase inhibitors. CONCLUSIONS: PGIS protein expression is reduced in NSCLC, and does not correlate with overall patient survival. PGIS expression is regulated through epigenetic mechanisms. Differences in expression patterns between mRNA and protein levels suggest that PGIS expression and protein stability are regulated post-translationally. PGIS protein stability may have an important therapeutic role in NSCLC.

Genetic algorithm–based varying parameter linear quadratic regulator control for four-wheel independent steering vehicle

Directory of Open Access Journals (Sweden)

Linlin Gao

2015-11-01

Full Text Available From the perspective of vehicle dynamics, the four-wheel independent steering vehicle dynamics stability control method is studied, and a four-wheel independent steering varying parameter linear quadratic regulator control system is proposed with the help of expert control method. In the article, a four-wheel independent steering linear quadratic regulator controller for model following purpose is designed first. Then, by analyzing the four-wheel independent steering vehicle dynamic characteristics and the influence of linear quadratic regulator control parameters on control performance, a linear quadratic regulator control parameter adjustment strategy based on vehicle steering state is proposed to achieve the adaptive adjustment of linear quadratic regulator control parameters. In addition, to further improve the control performance, the proposed varying parameter linear quadratic regulator control system is optimized by genetic algorithm. Finally, simulation studies have been conducted by applying the proposed control system to the 8-degree-of-freedom four-wheel independent steering vehicle dynamics model. The simulation results indicate that the proposed control system has better performance and robustness and can effectively improve the stability and steering safety of the four-wheel independent steering vehicle.

A mutation of the fission yeast EB1 overcomes negative regulation by phosphorylation and stabilizes microtubules

International Nuclear Information System (INIS)

Iimori, Makoto; Ozaki, Kanako; Chikashige, Yuji; Habu, Toshiyuki; Hiraoka, Yasushi; Maki, Takahisa; Hayashi, Ikuko; Obuse, Chikashi; Matsumoto, Tomohiro

2012-01-01

Mal3 is a fission yeast homolog of EB1, a plus-end tracking protein (+ TIP). We have generated a mutation (89R) replacing glutamine with arginine in the calponin homology (CH) domain of Mal3. Analysis of the 89R mutant in vitro has revealed that the mutation confers a higher affinity to microtubules and enhances the intrinsic activity to promote the microtubule-assembly. The mutant Mal3 is no longer a + TIP, but binds strongly the microtubule lattice. Live cell imaging has revealed that while the wild type Mal3 proteins dissociate from the tip of the growing microtubules before the onset of shrinkage, the mutant Mal3 proteins persist on microtubules and reduces a rate of shrinkage after a longer pausing period. Consequently, the mutant Mal3 proteins cause abnormal elongation of microtubules composing the spindle and aster. Mal3 is phosphorylated at a cluster of serine/threonine residues in the linker connecting the CH and EB1-like C-terminal motif domains. The phosphorylation occurs in a microtubule-dependent manner and reduces the affinity of Mal3 to microtubules. We propose that because the 89R mutation is resistant to the effect of phosphorylation, it can associate persistently with microtubules and confers a stronger stability of microtubules likely by reinforcing the cylindrical structure. -- Highlights: ► We characterize a mutation (mal3-89R) in fission yeast homolog of EB1. ► The mutation enhances the activity to assemble microtubules. ► Mal3 is phosphorylated in a microtubule-dependent manner. ► The phosphorylation negatively regulates the Mal3 activity.

A mutation of the fission yeast EB1 overcomes negative regulation by phosphorylation and stabilizes microtubules

Energy Technology Data Exchange (ETDEWEB)

Iimori, Makoto; Ozaki, Kanako [Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake cho, Sakyo ku, Kyoto, 606-8502 (Japan); Chikashige, Yuji [Kobe Advanced ICT Research Center, National Institute of Information and Communications Technology, Kobe, 651-2492 (Japan); Habu, Toshiyuki [Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake cho, Sakyo ku, Kyoto, 606-8502 (Japan); Radiation Biology Center, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto, 606-8501 (Japan); Hiraoka, Yasushi [Kobe Advanced ICT Research Center, National Institute of Information and Communications Technology, Kobe, 651-2492 (Japan); Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, 565-0871 (Japan); Maki, Takahisa; Hayashi, Ikuko [Graduate School of Nanobioscience, Yokohama City University, Tsurumi, Yokohama, 230-0045 (Japan); Obuse, Chikashi [Graduate School of Life Science, Hokkaido University, Sapporo 001-0021 (Japan); Matsumoto, Tomohiro, E-mail: tmatsumo@house.rbc.kyoto-u.ac.jp [Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake cho, Sakyo ku, Kyoto, 606-8502 (Japan); Radiation Biology Center, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto, 606-8501 (Japan)

2012-02-01

Mal3 is a fission yeast homolog of EB1, a plus-end tracking protein (+ TIP). We have generated a mutation (89R) replacing glutamine with arginine in the calponin homology (CH) domain of Mal3. Analysis of the 89R mutant in vitro has revealed that the mutation confers a higher affinity to microtubules and enhances the intrinsic activity to promote the microtubule-assembly. The mutant Mal3 is no longer a + TIP, but binds strongly the microtubule lattice. Live cell imaging has revealed that while the wild type Mal3 proteins dissociate from the tip of the growing microtubules before the onset of shrinkage, the mutant Mal3 proteins persist on microtubules and reduces a rate of shrinkage after a longer pausing period. Consequently, the mutant Mal3 proteins cause abnormal elongation of microtubules composing the spindle and aster. Mal3 is phosphorylated at a cluster of serine/threonine residues in the linker connecting the CH and EB1-like C-terminal motif domains. The phosphorylation occurs in a microtubule-dependent manner and reduces the affinity of Mal3 to microtubules. We propose that because the 89R mutation is resistant to the effect of phosphorylation, it can associate persistently with microtubules and confers a stronger stability of microtubules likely by reinforcing the cylindrical structure. -- Highlights: Black-Right-Pointing-Pointer We characterize a mutation (mal3-89R) in fission yeast homolog of EB1. Black-Right-Pointing-Pointer The mutation enhances the activity to assemble microtubules. Black-Right-Pointing-Pointer Mal3 is phosphorylated in a microtubule-dependent manner. Black-Right-Pointing-Pointer The phosphorylation negatively regulates the Mal3 activity.

Vorinostat enhances protein stability of p27 and p21 through negative regulation of Skp2 and Cks1 in human breast cancer cells.

Science.gov (United States)

Uehara, Norihisa; Yoshizawa, Katsuhiko; Tsubura, Airo

2012-07-01

Vorinostat is a histone deacetylase inhibitor that blocks cancer cell proliferation through the regulation of cyclin-dependent kinase inhibitors. We, herein, examined the involvement of S-phase kinase-associated protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1), the components of the SCFSkp2-Cks1 (Skp1/Cul1/F-box protein) ubiquitin ligase complex, in the regulation of p27 and p21 during vorinostat-induced growth arrest of MDA-MB-231 and MCF-7 human breast cancer cells. Vorinostat significantly reduced BrdU incorporation in MDA-MB-231 and MCF-7 cells, which was associated with increased p27 and p21 protein levels without concomitant induction of p27 mRNA. Vorinostat-induced accumulation of p27 and p21 proteins was inversely correlated with the mRNA and protein levels of Skp2 and Cks1. Cycloheximide chase analysis revealed that vorinostat increased the half-life of p27 and p21 proteins. The accumulation of p27 and p21 proteins was attenuated by forced expression of Skp2 and Cks1, which conferred resistance to the vorinostat-induced S-phase reduction. These results suggest that vorinostat-induced growth arrest may be in part due to the enhanced protein stability of p27 and p21 through the downregulation of Skp2 and Cks1.

CONSIDERATIONS REGARDING FINANCIAL STABILITY

Directory of Open Access Journals (Sweden)

MERCEA PATRICIA AMALIA

2018-02-01

target digital coin concepts, use in distributed real-time payment systems of blockchain technologology, artificial intelligence, and information security. However, a large number of economists admit that the current crisis has emphasized the overcoming of the limits of (mainstream economics and its implications in the field of financial regulation and the sphere of monetary policy that should focus not only on price stability, but also on financial stability. In other words, the banks, the financial institutions must be obliged to hold a minimal countercyclical capital and mandatory reserves that should be large enough to cope with the turmoil generated by the decrease of the asset prices and the liquidity risk. In macroprudential policy, the “shadow banking system” (investment banks, hedge funds, private equity funds must also be included.Last but not least, the central banks have to cooperate with the other categories of systemic risk managers: Financial Stability Oversight Council-FSOC (USA, European Systemic Risk Board-ESRB (EU, Financial Policy Committee-FPC (Great Britain, National Committee for Financial Stability-CNSF (Romania.

Danish Working Environment Regulation. How reflexive - how political? -a Scandinavian case

DEFF Research Database (Denmark)

Koch, Christian

an understanding of the directions of the reforms made in this period. The paper operate with two analytical perspectives: The reflexive regulation perspective and the political process perspective. Danish working environment regulation is discussed through the general political initiatives taken, and through four...... specific regulation topics: The Occupational Health Services (OHS), regulation of the psychological working environment, the 'Monotonous Repeated Work'-plan and the workers' compensation. Taking the last twenty years' development as a whole the main developments in the regulation is a further shift...... in balance between material and reflexive regulation elements to the benefit of the latter. But although the reflexive elements seem to stabilize, they are vulnerable to a loss of legitimacy and changes in the political pattern.The impact on enterprise power patterns is summed up in a polarization thesis...

PID position regulation in one-degree-of-freedom Euler-Lagrange systems actuated by a PMSM

Science.gov (United States)

Verastegui-Galván, J.; Hernández-Guzmán, V. M.; Orrante-Sakanassi, J.

2018-02-01

This paper is concerned with position regulation in one-degree-of-freedom Euler-Lagrange Systems. We consider that the mechanical subsystem is actuated by a permanent magnet synchronous motor (PMSM). Our proposal consists of a Proportional-Integral-Derivative (PID) controller for the mechanical subsystem and a slight variation of field oriented control for the PMSM. We take into account the motor electric dynamics during the stability analysis. We present, for the first time, a global asymptotic stability proof for such a control scheme without requiring the mechanical subsystem to naturally possess viscous friction. Finally, as a corollary of our main result we prove global asymptotic stability for output feedback PID regulation of one-degree-of-freedom Euler-Lagrange systems when generated torque is considered as the system input, i.e. when the electric dynamics of PMSM's is not taken into account.

Conservation of Oxidative Protein Stabilization in an Insect Homologue of Parkinsonism-Associated Protein DJ-1

Energy Technology Data Exchange (ETDEWEB)

Lin, Jiusheng; Prahlad, Janani; Wilson, Mark A. (UNL)

2012-08-21

DJ-1 is a conserved, disease-associated protein that protects against oxidative stress and mitochondrial damage in multiple organisms. Human DJ-1 contains a functionally essential cysteine residue (Cys106) whose oxidation is important for regulating protein function by an unknown mechanism. This residue is well-conserved in other DJ-1 homologues, including two (DJ-1{alpha} and DJ-1{beta}) in Drosophila melanogaster. Because D. melanogaster is a powerful model system for studying DJ-1 function, we have determined the crystal structure and impact of cysteine oxidation on Drosophila DJ-1{beta}. The structure of D. melanogaster DJ-1{beta} is similar to that of human DJ-1, although two important residues in the human protein, Met26 and His126, are not conserved in DJ-1{beta}. His126 in human DJ-1 is substituted with a tyrosine in DJ-1{beta}, and this residue is not able to compose a putative catalytic dyad with Cys106 that was proposed to be important in the human protein. The reactive cysteine in DJ-1 is oxidized readily to the cysteine-sulfinic acid in both flies and humans, and this may regulate the cytoprotective function of the protein. We show that the oxidation of this conserved cysteine residue to its sulfinate form (Cys-SO{sub 2{sup -}}) results in considerable thermal stabilization of both Drosophila DJ-1{beta} and human DJ-1. Therefore, protein stabilization is one potential mechanism by which cysteine oxidation may regulate DJ-1 function in vivo. More generally, most close DJ-1 homologues are likely stabilized by cysteine-sulfinic acid formation but destabilized by further oxidation, suggesting that they are biphasically regulated by oxidative modification.

THE BANKING SUPERVISION: CAN IT REDUCE THE RISK-TAKING AND, CONSEQUENTLY, STRENGTHEN THE STABILITY OF THE BANKING SECTOR IN MOLDOVA?

Directory of Open Access Journals (Sweden)

Elena MARGARINT

2015-12-01

Full Text Available Actuality: The empirical studies on the impact of the supervision on the stability of the banking sector are mitigated, varying depending on the particular characteristics of the bank and, in addition, the country's policy in which banks operate. This is why this study is important for the banking sector in Moldova. Purpose: The objective of this article is to studies the effects of the banking supervision on the risk-taking of banks and, consequently, the stability of the banking sector in Moldova. Methods: To order to achieve its purpose, the author applied the method of static panel data with random effect. Results: This empirical analysis reported the following results: increased restrictions on the activities of banks increases the stability of the banking sector. On the other hand, the power and independence of the supervisory authority have a negative impact on the stability of Moldovan banks. The increase of the capital level strengthens the stability of Moldovan banks and, at the same time, reduces the risk. Thus, capital regulations are an important pillar of the policy of the regulation of the banking sector of Moldova.

Cable Stability

Energy Technology Data Exchange (ETDEWEB)

Bottura, L [European Organization for Nuclear Research, Geneva (Switzerland)

2014-07-01

Superconductor stability is at the core of the design of any successful cable and magnet application. This chapter reviews the initial understanding of the stability mechanism, and reviews matters of importance for stability such as the nature and magnitude of the perturbation spectrum and the cooling mechanisms. Various stability strategies are studied, providing criteria that depend on the desired design and operating conditions.

Mechanism of Stabilization of Labile Compounds by Silk Fibroin Proteins

Science.gov (United States)

2017-04-05

saliva, or urine , and their collection and storage is critical to obtain reliable results. Without proper temperature regulation protein biomarkers in... samples for long-term ambient storage and subsequent on-demand recovery and laboratory analysis. Air dried silks provide a protective barrier that...silk in the stabilization of a range of different analytes, including entrapment, storage and recovery. Here, we successfully used silk fibroin as a

Are high oil prices a threat for the price stability?

International Nuclear Information System (INIS)

Mollerus, A.

2000-01-01

The high price for oil and the decreased value of the Euro increase the risks for the stability of prices. Still, the prospects for inflation are favorable for the Euro zone. Less favorable are the consequences for the Netherlands, while the inflation difference with the Euro zone appears to become bigger, in particular as a result of the new Tax regulations in the Netherlands

Control of locomotor stability in stabilizing and destabilizing environments.

Science.gov (United States)

Wu, Mengnan/Mary; Brown, Geoffrey; Gordon, Keith E

2017-06-01

To develop effective interventions targeting locomotor stability, it is crucial to understand how people control and modify gait in response to changes in stabilization requirements. Our purpose was to examine how individuals with and without incomplete spinal cord injury (iSCI) control lateral stability in haptic walking environments that increase or decrease stabilization demands. We hypothesized that people would adapt to walking in a predictable, stabilizing viscous force field and unpredictable destabilizing force field by increasing and decreasing feedforward control of lateral stability, respectively. Adaptations in feedforward control were measured using after-effects when fields were removed. Both groups significantly (pfeedforward adaptions to increase control of lateral stability. In contrast, in the destabilizing field, non-impaired subjects increased movement variability (p0.05). When the destabilizing field was removed, increases in movement variability persisted (pfeedforward decreases in resistance to perturbations. Published by Elsevier B.V.

Factors controlling soil organic carbon stability along a temperate forest altitudinal gradient

Science.gov (United States)

Tian, Qiuxiang; He, Hongbo; Cheng, Weixin; Bai, Zhen; Wang, Yang; Zhang, Xudong

2016-01-01

Changes in soil organic carbon (SOC) stability may alter carbon release from the soil and, consequently, atmospheric CO2 concentration. The mean annual temperature (MAT) can change the soil physico-chemical characteristics and alter the quality and quantity of litter input into the soil that regulate SOC stability. However, the relationship between climate and SOC stability remains unclear. A 500-day incubation experiment was carried out on soils from an 11 °C-gradient mountainous system on Changbai Mountain in northeast China. Soil respiration during the incubation fitted well to a three-pool (labile, intermediate and stable) SOC decomposition model. A correlation analysis revealed that the MAT only influenced the labile carbon pool size and not the SOC stability. The intermediate carbon pool contributed dominantly to cumulative carbon release. The size of the intermediate pool was strongly related to the percentage of sand particle. The decomposition rate of the intermediate pool was negatively related to soil nitrogen availability. Because both soil texture and nitrogen availability are temperature independent, the stability of SOC was not associated with the MAT, but was heavily influenced by the intrinsic processes of SOC formation and the nutrient status. PMID:26733344

Feedback attitude sliding mode regulation control of spacecraft using arm motion

Science.gov (United States)

Shi, Ye; Liang, Bin; Xu, Dong; Wang, Xueqian; Xu, Wenfu

2013-09-01

The problem of spacecraft attitude regulation based on the reaction of arm motion has attracted extensive attentions from both engineering and academic fields. Most of the solutions of the manipulator’s motion tracking problem just achieve asymptotical stabilization performance, so that these controllers cannot realize precise attitude regulation because of the existence of non-holonomic constraints. Thus, sliding mode control algorithms are adopted to stabilize the tracking error with zero transient process. Due to the switching effects of the variable structure controller, once the tracking error reaches the designed hyper-plane, it will be restricted to this plane permanently even with the existence of external disturbances. Thus, precise attitude regulation can be achieved. Furthermore, taking the non-zero initial tracking errors and chattering phenomenon into consideration, saturation functions are used to replace sign functions to smooth the control torques. The relations between the upper bounds of tracking errors and the controller parameters are derived to reveal physical characteristic of the controller. Mathematical models of free-floating space manipulator are established and simulations are conducted in the end. The results show that the spacecraft’s attitude can be regulated to the position as desired by using the proposed algorithm, the steady state error is 0.000 2 rad. In addition, the joint tracking trajectory is smooth, the joint tracking errors converges to zero quickly with a satisfactory continuous joint control input. The proposed research provides a feasible solution for spacecraft attitude regulation by using arm motion, and improves the precision of the spacecraft attitude regulation.

Differential Nanos 2 protein stability results in selective germ cell accumulation in the sea urchin.

Science.gov (United States)

Oulhen, Nathalie; Wessel, Gary M

2016-10-01

Nanos is a translational regulator required for the survival and maintenance of primordial germ cells. In the sea urchin, Strongylocentrotus purpuratus (Sp), Nanos 2 mRNA is broadly transcribed but accumulates specifically in the small micromere (sMic) lineage, in part because of the 3'UTR element GNARLE leads to turnover in somatic cells but retention in the sMics. Here we found that the Nanos 2 protein is also selectively stabilized; it is initially translated throughout the embryo but turned over in the future somatic cells and retained only in the sMics, the future germ line in this animal. This differential stability of Nanos protein is dependent on the open reading frame (ORF), and is independent of the sumoylation and ubiquitylation pathways. Manipulation of the ORF indicates that 68 amino acids in the N terminus of the Nanos protein are essential for its stability in the sMics whereas a 45 amino acid element adjacent to the zinc fingers targets its degradation. Further, this regulation of Nanos protein is cell autonomous, following formation of the germ line. These results are paradigmatic for the unique presence of Nanos in the germ line by a combination of selective RNA retention, distinctive translational control mechanisms (Oulhen et al., 2013), and now also by defined Nanos protein stability. Copyright © 2016 Elsevier Inc. All rights reserved.

Active Power Regulation based on Droop for AC Microgrid

DEFF Research Database (Denmark)

Li, Chendan; Coelho, Ernane A. A.; Firoozabadi, Mehdi Savaghebi

2015-01-01

In this paper, two different control strategies are proposed to address the active power regulation issue in AC microgrids. The principle of power regulation in the droop controller is firstly introduced. Frequency scheduling and droop gain scheduling on top of droop control is proposed...... to successfully follow the active power command. The limitation of each method is discussed in term of small signal stability and light load sharing, respectively. Discussion on the effects of power command is also given. The simulation is carried out for both the strategies to verify the active power control...

Evaluation of design variants for improved inherent regulation of advanced small modular reactors - 15325

International Nuclear Information System (INIS)

Vilim, R.B.; Passerini, S.

2015-01-01

This paper examines design variants that can improve inherent regulation in Advanced Small Modular Reactors (ASMR). It looks at the nature of unprotected upsets and then develops appropriate design measures to ensure that no upset can override a capability for safe self-regulation. This work adopts a reference sodium fast reactor (SFR) design to serve as a baseline for operational and safety performance and for comparison with variants on this design. The effect of design measures on plant stability is then examined. It is found that compared to full-power operation, the stability margin is reduced under islanded-operation. Islanded-operation is more likely for an ASMR deployed in a small regional electric grid with high penetration of renewable energy sources. The stability of core power production is a function of the inlet temperature coefficient, coolant transport times, and temperature-front attenuation in heat exchangers. The interaction of these phenomena with the control system is described

The Role of the External Auditor in UK Bank Regulation and Supervision

OpenAIRE

Ojo, Marianne

2006-01-01

ABSTRACT The role of the external auditor in the supervisory process requires standards such as independence, objectivity and integrity to be achieved. Even though the regulator and external auditor perform similar functions, namely the verification of financial statements, they serve particular interests. The regulator works towards safeguarding financial stability and investor interests. On the other hand, the external auditor serves the private interests of the shareholders of a compa...

THE EUROPEAN MECHANISM FOR FINANCIAL STABILITY AND THE EURO-PLUS PACT

Directory of Open Access Journals (Sweden)

AUGUSTIN FUEREA

2012-05-01

Full Text Available The economic crisis that has affected countries from all continents has generated, among others, also a strong financial crisis, which in turn, has caused serious imbalances in the economic and financial environment of EU Member States.Under these circumstances, the Council, being in an exceptional situation, “outside the control of Member States”, as it itself states in the Preamble to Regulation No. 407/2010, considered necessary, “the immediate establishment of a stabilization mechanism at EU level in order to maintain the financial stability in the European Union”, mechanism that “would enable the Union to respond in a coordinated, rapid and effective way to the serious difficulties undergone by a certain Member State”

Political Stability and Fianancial Crisis: What the data say for the European Union’s countries.

Directory of Open Access Journals (Sweden)

Evangelos Vasileiou

2016-01-01

Full Text Available This paper tries to examine in detail political stability in the European Union’s (EU countries during the period 2002-12. Firstly, it examines the causality relationship between political stability and economic growth, which is an issue that has puzzled scholars for decades. Using the Granger causality test the empirical findings suggest that in the case of the EU’s countries, causality is one directional, moving from political stability to economic growth. Secondly, it examines the factors that affect political stability. Using the fixed effects panel data model, we may suggest that the long term recession, the increased unemployment ratios and the high levels of inflation significantly threaten political stability. However, there are other factors that are not exclusively due to economics, such as transparency, public health care, education etc., which may significantly reduce the previously mentioned consequences.  Finally, this study suggests some reforms of the EU’s regulation according to the migration policy that may smooth social and humanitarian disparities.

Political Stability and Fianancial Crisis: What the data say for the European Union’s countries.

Directory of Open Access Journals (Sweden)

Evangelos Vasileiou

2014-03-01

Full Text Available This paper tries to examine in detail political stability in the European Union’s (EU countries during the period 2002-12. Firstly, it examines the causality relationship between political stability and economic growth, which is an issue that has puzzled scholars for decades. Using the Granger causality test the empirical findings suggest that in the case of the EU’s countries, causality is one directional, moving from political stability to economic growth. Secondly, it examines the factors that affect political stability. Using the fixed effects panel data model, we may suggest that the long term recession, the increased unemployment ratios and the high levels of inflation significantly threaten political stability. However, there are other factors that are not exclusively due to economics, such as transparency, public health care, education etc., which may significantly reduce the previously mentioned consequences.  Finally, this study suggests some reforms of the EU’s regulation according to the migration policy that may smooth social and humanitarian disparities.

Functional and structural stability of the epidermal growth factor receptor in detergent micelles and phospholipid nanodiscs

DEFF Research Database (Denmark)

Mi, Li-Zhi; Grey, Michael J; Nishida, Noritaka

2008-01-01

Cellular signaling mediated by the epidermal growth factor receptor (EGFR or ErbB) family of receptor tyrosine kinases plays an important role in regulating normal and oncogenic cellular physiology. While structures of isolated EGFR extracellular domains and intracellular protein tyrosine kinase...... differential functional stability in Triton X-100 versus dodecyl maltoside. Furthermore, the kinase activity can be significantly stabilized by reconstituting purified EGF-bound EGFR dimers in phospholipid nanodiscs or vesicles, suggesting that the environment around the hydrophobic transmembrane...

Stability Enhancement of Multi machine AC Systems by Synchronverter HVDC control

Directory of Open Access Journals (Sweden)

Raouia Aouini

2016-06-01

Full Text Available This paper investigates the impact of the Synchronverter based HVDC control on power system stability. The study considers multi machine power systems, with realistic parameters. A specific tuning method of the parameters of the regulators is used. The proposed control scheme is based on the sensitivity of the poles of the HVDC neighbor zone to the control parameters, and next, on their placement using residues. The transient stability of the HVDC neighbor zone is a priori taken into account at the design stage. The new tuning method is evaluated in comparison with the standard vector control via simulation tests. Extensive tests are performed using Matlab/Simulink implementation of the IEEE 9 bus/3 machines test system. The results prove the superiority of the proposed control to the classic vector control. The synchronverter control allows to improve not only the local performances of the HVDC link, but also the overall transient stability of the AC zone in which the HVDC is inserted. (where

Human Sarcoma growth is sensitive to small-molecule mediated AXIN stabilization.

Directory of Open Access Journals (Sweden)

Alessandra De Robertis

Full Text Available Sarcomas are mesenchymal tumors showing high molecular heterogeneity, reflected at the histological level by the existence of more than fifty different subtypes. Genetic and epigenetic evidences link aberrant activation of the Wnt signaling to growth and progression of human sarcomas. This phenomenon, mainly accomplished by autocrine loop activity, is sustained by gene amplification, over-expression of Wnt ligands and co-receptors or epigenetic silencing of endogenous Wnt antagonists. We previously showed that pharmacological inhibition of Wnt signaling mediated by Axin stabilization produced in vitro and in vivo antitumor activity in glioblastoma tumors. Here, we report that targeting different sarcoma cell lines with the Wnt inhibitor/Axin stabilizer SEN461 produces a less transformed phenotype, as supported by modulation of anchorage-independent growth in vitro. At the molecular level, SEN461 treatment enhanced the stability of the scaffold protein Axin1, a key negative regulator of the Wnt signaling with tumor suppressor function, resulting in downstream effects coherent with inhibition of canonical Wnt signaling. Genetic phenocopy of small molecule Axin stabilization, through Axin1 over-expression, coherently resulted in strong impairment of soft-agar growth. Importantly, sarcoma growth inhibition through pharmacological Axin stabilization was also observed in a xenograft model in vivo in female CD-1 nude mice. Our findings suggest the usefulness of Wnt inhibitors with Axin stabilization activity as a potentialyl clinical relevant strategy for certain types of sarcomas.

A relation between Liapunov stability, non-wanderingness and Poisson stability

International Nuclear Information System (INIS)

Ahmad, K.H.

1985-07-01

In this work, some of the relations among Liapunov stability, non-wanderingness and Poisson stability are considered. In particular it is shown that for a non-wandering point in a set, positive (resp. negative) Liapunov stability in that set implies positive (resp. negative) Poisson stability in the same set. (author)

Identification of photoperiod-regulated gene in soybean and ...

Indian Academy of Sciences (India)

2014-04-15

Apr 15, 2014 ... Flowering is a critical stage in plant reproductive growth. Regulation of ... accumulation and high CO protein stability coincide at the end of the .... by 20 min of inactivation of T4 DNA polymerase at 70. ◦. C. ... tion medium and the next day, the culture was inoculated ... 2.0 and left at room temperature for 3 h.

Proportional Load Sharing and Stability of DC Microgrid with Distributed Architecture Using SM Controller

Directory of Open Access Journals (Sweden)

Muhammad Rashad

2018-01-01

Full Text Available DC microgrids look attractive in distribution systems due to their high reliability, high efficiency, and easy integration with renewable energy sources. The key objectives of the DC microgrid include proportional load sharing and precise voltage regulation. Droop controllers are based on decentralized control architectures which are not effective in achieving these objectives simultaneously due to the voltage error and load power variation. A centralized controller can achieve these objectives using a high speed communication link. However, it loses reliability due to the single point failure. Additionally, these controllers are realized through proportional integral (PI controllers which cannot ensure load sharing and stability in all operating conditions. To address limitations, a distributed architecture using sliding mode (SM controller utilizing low bandwidth communication is proposed for DC microgrids in this paper. The main advantages are high reliability, load power sharing, and precise voltage regulation. Further, the SM controller shows high robustness, fast dynamic response, and good stability for large load variations. To analyze the stability and dynamic performance, a system model is developed and its transversality, reachability, and equivalent control conditions are verified. Furthermore, the dynamic behavior of the modeled system is investigated for underdamped and critically damped responses. Detailed simulations are carried out to show the effectiveness of the proposed controller.

DC Microgrids–Part I: A Review of Control Strategies and Stabilization Techniques

Energy Technology Data Exchange (ETDEWEB)

Dragicevic, Tomislav; Lu, Xiaonan; Vasquez, Juan; Guerrero, Josep

2015-01-01

This paper presents a review of control strategies, stability analysis, and stabilization techniques for dc microgrids (MGs). Overall control is systematically classified into local and coordinated control levels according to respective functionalities in each level. As opposed to local control, which relies only on local measurements, some line of communication between units needs to be made available in order to achieve the coordinated control. Depending on the communication method, three basic coordinated control strategies can be distinguished, i.e., decentralized, centralized, and distributed control. Decentralized control can be regarded as an extension of the local control since it is also based exclusively on local measurements. In contrast, centralized and distributed control strategies rely on digital communication technologies. A number of approaches using these three coordinated control strategies to achieve various control objectives are reviewed in this paper. Moreover, properties of dc MG dynamics and stability are discussed. This paper illustrates that tightly regulated point-of-load converters tend to reduce the stability margins of the system since they introduce negative impedances, which can potentially oscillate with lightly damped power supply input filters. It is also demonstrated that how the stability of the whole system is defined by the relationship of the source and load impedances, referred to as the minor loop gain. Several prominent specifications for the minor loop gain are reviewed. Finally, a number of active stabilization techniques are presented.

Remarks on the german regulation of crowdfunding

OpenAIRE

Tröger, Tobias

2017-01-01

Crowdfunding is a buzzword that signifies a sub-set in the new forms of finance facilitated by advances in information technology usually categorized as fintech. Concerns for financial stability, investor and consumer protection, or the prevention of money laundering or funding of terrorism hinge incrementally on including the new techniques to initiate financing relationships adequately in the regulatory framework. This paper analyzes the German regulation of crowdinvesting and finds that it...

THEORETICAL CONSIDERATIONS OF PRICE STABILITY AS PART OF THE FINANCIAL STABILITY

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Magdalena RĂDULESCU

2012-09-01

Full Text Available Currently there are many authors who consider that the only objective of the central bank should be the price stability and between the respective objective and financial stability there is incompatibility. As far we are concerned, we subscribe the idea that between price stability and financial stability there are complementarities. And a strong argument in the favour of this position is also historical. Actually, many older or newer facts show that banking crises were often caused by the unfavourable macroeconomic situation coupled with the bad macroeconomic policies carried by the authorities. But, a monetary policy that aims the price stability reduces this risk. The truth is that the central banks have a series of tools that allow them to act for achieving both the objective of price stability, and that of the stability of financial sector. Although the financial stability is not, usually, an explicit objective for the modern central bank, the systematic financial instability can cancel their performances in achieving their major final objective: the price stability. Being that, because of the need that it creates to inject additional liquidity into the banking system, a crisis of the banking sector may directly affect the monetary stability. Here the mentioned complementarities arise between price stability and financial stability, although the achievement of the first does not necessarily involve the assurance of the last.

Constitutionality Degree of Indonesia Local Regulation in Political Law Perspective

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Bambang Sutrisno

2016-06-01

Full Text Available The Politics of Law holds responsibility to give the surety of all regulations, including Local Regulation, for capable of reflecting the collective will of the public as the owner of the highest sovereignty. Politics of law is always working to bring together the ius constituendum and ius constitutum  at the encounter between realism and idealism. Local Regulation as subsystems of national law, is expected to serve as a guiding instrument and guard direction for development and continuous improvement of Local Government. Therefore the existence of local regulations holds a strategic role for legal certainty, which is a necessary to create a conducive business climate and stability of the country. How To Cite: Sutrisno, B. (2016. Constitutionality Degree of Indonesia Local Regulation in Political Law Perspective. Rechtsidee, 3(1, 41-52. doi:http://dx.doi.org/10.21070/jihr.v3i1.131

Audit Independence : Its Importance to the External Auditor's Role in Banking Regulation and Supervision

OpenAIRE

Ojo, Marianne

2006-01-01

The role of the external auditor in the supervisory process requires standards such as independence,objectivity and integrity to be achieved. Even though the regulator and external auditor perform similar functions, namely the verification of financial statements, they serve particular interests. The regulator works towards safeguarding financial stability and investor interests. On the other hand, the external auditor serves the private int...

Galactic evolution with self-regulated star formation - Stability of a simple one-zone model

International Nuclear Information System (INIS)

Parravano, A.; Rosenzweig, P.; Teran, M.

1990-01-01

In a simple one-zone model of mass exchange between three components (stars, clouds, and diffused gas), a self-regulating mechanism based on the sensitivity of the condensation of small cool clouds upon the radiation density in the 912-1100 A band is presently included. This mechanism is capable of affecting the large-scale structure of the galaxies due to the fact that it acts at a large scale in a very short time. Even in the most favorable models for the production of nonlinear oscillations, the inclusion of this mechanism of self-regulation leads, in many cases, to the progressive damping of the oscillations. 26 refs

LARP6 Meets Collagen mRNA: Specific Regulation of Type I Collagen Expression

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Yujie Zhang

2016-03-01

Full Text Available Type I collagen is the most abundant structural protein in all vertebrates, but its constitutive rate of synthesis is low due to long half-life of the protein (60–70 days. However, several hundred fold increased production of type I collagen is often seen in reparative or reactive fibrosis. The mechanism which is responsible for this dramatic upregulation is complex, including multiple levels of regulation. However, posttranscriptional regulation evidently plays a predominant role. Posttranscriptional regulation comprises processing, transport, stabilization and translation of mRNAs and is executed by RNA binding proteins. There are about 800 RNA binding proteins, but only one, La ribonucleoprotein domain family member 6 (LARP6, is specifically involved in type I collagen regulation. In the 5′untranslated region (5’UTR of mRNAs encoding for type I and type III collagens there is an evolutionally conserved stem-loop (SL structure; this structure is not found in any other mRNA, including any other collagen mRNA. LARP6 binds to the 5′SL in sequence specific manner to regulate stability of collagen mRNAs and their translatability. Here, we will review current understanding of how is LARP6 involved in posttranscriptional regulation of collagen mRNAs. We will also discuss how other proteins recruited by LARP6, including nonmuscle myosin, vimentin, serine threonine kinase receptor associated protein (STRAP, 25 kD FK506 binding protein (FKBP25 and RNA helicase A (RHA, contribute to this process.

Long-term stability of sodium caseinate-stabilized nanoemulsions.

Science.gov (United States)

Yerramilli, Manispuritha; Ghosh, Supratim

2017-01-01

Oil-in-water (5 wt%) nanoemulsions were prepared with different concentration (2.5-10 wt%) of sodium caseinate as a sole emulsifier and their long-term storage stability was investigated for 6 months. Previous studies associated with sodium caseinate looked only into nanoemulsion formation; hence the challenges with long-term stability were not addressed. All nanoemulsions displayed an average droplet size sodium caseinate-stabilized nanoemulsions.

Post-translational regulation of Oct4 transcriptional activity.

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Jonathan P Saxe

Full Text Available Oct4 is a key component of the molecular circuitry which regulates embryonic stem cell proliferation and differentiation. It is essential for maintenance of undifferentiated, pluripotent cell populations, and accomplishes these tasks by binding DNA in multiple heterodimer and homodimer configurations. Very little is known about how formation of these complexes is regulated, or the mechanisms through which Oct4 proteins respond to complex extracellular stimuli which regulate pluripotency. Here, we provide evidence for a phosphorylation-based mechanism which regulates specific Oct4 homodimer conformations. Point mutations of a putative phosphorylation site can specifically abrogate transcriptional activity of a specific homodimer assembly, with little effect on other configurations. Moreover, we performed bioinformatic predictions to identify a subset of Oct4 target genes which may be regulated by this specific assembly, and show that altering Oct4 protein levels affects transcription of Oct4 target genes which are regulated by this assembly but not others. Finally, we identified several signaling pathways which may mediate this phosphorylation and act in combination to regulate Oct4 transcriptional activity and protein stability. These results provide a mechanism for rapid and reversible alteration of Oct4 transactivation potential in response to extracellular signals.

Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP effector BerB

DEFF Research Database (Denmark)

Fazli, Mustafa; Rybtke, Morten Levin; Steiner, Elisabeth

2017-01-01

Knowledge about the molecular mechanisms that are involved in the regulation of biofilm formation is essential for the development of biofilm-control measures. It is well established that the nucleotide second messenger cyclic diguanosine monophosphate (c-di-GMP) is a positive regulator of biofilm...... formation in many bacteria, but more knowledge about c-di-GMP effectors is needed. We provide evidence that c-di-GMP, the alternative sigma factor RpoN (σ54), and the enhancer-binding protein BerB play a role in biofilm formation of Burkholderia cenocepacia by regulating the production of a biofilm......-stabilizing exopolysaccharide. Our findings suggest that BerB binds c-di-GMP, and activates RpoN-dependent transcription of the berA gene coding for a c-di-GMP-responsive transcriptional regulator. An increased level of the BerA protein in turn induces the production of biofilm-stabilizing exopolysaccharide in response to high...

BWR stability analysis at Brookhaven National Laboratory

International Nuclear Information System (INIS)

Wulff, W.; Cheng, H.S.; Mallen, A.N.; Rohatgi, U.S.

1991-01-01

Following the unexpected, but safely terminated, power and flow oscillations in the LaSalle-2 Boiling Water Reactor (BWR) on March 9, 1988, the Nuclear Regulatory Commission (NRC) Offices of Nuclear Reactor Regulation (NRR) and of Analysis and Evaluation of Operational Data (AEOD) requested that the Office of Nuclear Regulatory Research (RES) carry out BWR stability analyses, centered around fourteen specific questions. Ten of the fourteen questions address BWR stability issues in general and are dealt with in this paper. The other four questions address local, out-of-phase oscillations and matters of instrumentation; they fall outside the scope of the work reported here. It was the purpose of the work documented in this report to answer ten of the fourteen NRC-stipulated questions. Nine questions are answered by analyzing the LaSalle-2 instability and related BWR transients with the BNL Engineering Plant Analyzer (EPA) and by performing an uncertainty assessment of the EPA predictions. The tenth question is answered on the basis of first principles. The ten answers are summarized

Development of an analogue multiplexed regulation for periodic 1. order delayed processes

International Nuclear Information System (INIS)

Amblard, J.C.

1967-07-01

The present note deals with the study regulations of the sampled type, for 1. order process with simple delay. In order to obtain a good stability in such regulations, together with acceptable performances, it is interesting to use polynomial type correctors acting directly on the sampled error signals. The active elements of these correctors can be shared by all the channels to be controlled. Furthermore, the determination of the correction parameters results from an optimal study of the system. In the second part is described the construction of a multiplexed regulation for diffusion ovens. (author) [fr

Regulating vacuum pump speed with feedback control

International Nuclear Information System (INIS)

Ludington, D.C.; Aneshansley, D.J.; Pellerin, R.; Guo, F.

1992-01-01

Considerable energy is wasted by the vacuum pump/motor on dairy farms. The output capacity (m 3 /min or cfm) of the vacuum pump always exceeds the capacity needed to milk cows and wash pipelines. Vacuum pumps run at full speed and load regardless of actual need for air. Excess air is admitted through a controller. Energy can be saved from electrical demand reduced by regulating vacuum pump speed according to air based on air usage. An adjustable speed drive (ASD) on the motor and controlled based upon air usage, can reduce the energy used by the vacuum pump. However, the ASD unit tested could not maintain vacuum levels within generally accepted guidelines when air usage changed. Adding a high vacuum reserve and a dual vacuum controller between the vacuum pump and the milking pipeline brought vacuum stability within guidelines. The ASD/dual vacuum system can reduce energy consumption and demand by at least 50 percent during milking and provide better vacuum stability than conventional systems. Tests were not run during washing cycles. Using 1990 costs and only the energy saved during milking, the simple payback on investment in new equipment for a 5 hp motor, speed controller and vacuum regulator would be about 5 years

IGF-IR promotes prostate cancer growth by stabilizing α5β1 integrin protein levels.

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Aejaz Sayeed

Full Text Available Dynamic crosstalk between growth factor receptors, cell adhesion molecules and extracellular matrix is essential for cancer cell migration and invasion. Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization. They also mediate signal transduction to regulate cell proliferation and survival. The type 1 insulin-like growth factor receptor (IGF-IR mediates tumor cell growth, adhesion and inhibition of apoptosis in several types of cancer. We have previously demonstrated that β1 integrins regulate anchorage-independent growth of prostate cancer (PrCa cells by regulating IGF-IR expression and androgen receptor-mediated transcriptional functions. Furthermore, we have recently reported that IGF-IR regulates the expression of β1 integrins in PrCa cells. We have dissected the mechanism through which IGF-IR regulates β1 integrin expression in PrCa. Here we report that IGF-IR is crucial for PrCa cell growth and that β1 integrins contribute to the regulation of proliferation by IGF-IR. We demonstrate that β1 integrin regulation by IGF-IR does not occur at the mRNA level. Exogenous expression of a CD4 - β1 integrin cytoplasmic domain chimera does not interfere with such regulation and fails to stabilize β1 integrin expression in the absence of IGF-IR. This appears to be due to the lack of interaction between the β1 cytoplasmic domain and IGF-IR. We demonstrate that IGF-IR stabilizes the β1 subunit by protecting it from proteasomal degradation. The α5 subunit, one of the binding partners of β1, is also downregulated along with β1 upon IGF-IR knockdown while no change is observed in the expression of the α2, α3, α4, α6 and α7 subunits. Our results reveal a crucial mechanistic role for the α5β1 integrin, downstream of IGF-IR, in regulating cancer growth.

A comparative study of stabilizing control of a planer electromagnetic levitation using PID and LQR controllers

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Mundher H.A. Yaseen

Full Text Available Magnetic levitation is a technique to suspend an object without any mechanical support. The main objective of this study is to demonstrate stabilized closed loop control of 1-DOF Maglev experimentally using real-time control simulink feature of (SIMLAB microcontroller. Proportional Integral Derivative (PID and Linear Quadratic Regulator (LQR controllers are employed to examine the stability performance of the Maglev control system under effect of unbalanced change of load and wave signal on Maglev plane. The effect of unbalanced change of applied load on single point, line and plane are presented. Furthermore, in order to study the effect of sudden change in input signal, the input of wave signal has been applied on all points of the prototype maglev plate simultaneously. The results of pulse width modulation (PWM reveal that the control system using LQR controller provides faster response to adjust the levitated plane comparing to PID controller. Moreover, the air gap distance that controlled using PID controller is rather stable with little oscillation. Meanwhile, LQR controller provided more stability and homogeneous response. Keywords: Magnetic levitation (Maglev, Linear Quadratic Regulator (LQR, PID controller, SIMLAB Platform

Arbitrage and Competition in Global Financial Regulation

DEFF Research Database (Denmark)

Ringe, Wolf-Georg

Regulatory arbitrage in financial markets refers to a number of strategies that market participants use to avoid the reach of regulation, in particular by virtue of shifting trading abroad or else relocating activities or operations of financial institutions to other jurisdictions. Where...... institutions’ excessive risk-taking. If such risk-taking would be judged by market discipline instead of posing a risk to global financial stability, the main downside of regulatory competition could be restrained. Within the boundaries of such a system, competition could then operate and contribute...... their standards solely to attract businesses and thereby impose externalities on the worldwide financial market by undermining financial stability as a global public good. Policymakers worldwide are experimenting with remedies to respond to the phenomenon. I introduce the importance of an effective special...

Exploiting sequence and stability information for directing nanobody stability engineering.

Science.gov (United States)

Kunz, Patrick; Flock, Tilman; Soler, Nicolas; Zaiss, Moritz; Vincke, Cécile; Sterckx, Yann; Kastelic, Damjana; Muyldermans, Serge; Hoheisel, Jörg D

2017-09-01

Variable domains of camelid heavy-chain antibodies, commonly named nanobodies, have high biotechnological potential. In view of their broad range of applications in research, diagnostics and therapy, engineering their stability is of particular interest. One important aspect is the improvement of thermostability, because it can have immediate effects on conformational stability, protease resistance and aggregation propensity of the protein. We analyzed the sequences and thermostabilities of 78 purified nanobody binders. From this data, potentially stabilizing amino acid variations were identified and studied experimentally. Some mutations improved the stability of nanobodies by up to 6.1°C, with an average of 2.3°C across eight modified nanobodies. The stabilizing mechanism involves an improvement of both conformational stability and aggregation behavior, explaining the variable degree of stabilization in individual molecules. In some instances, variations predicted to be stabilizing actually led to thermal destabilization of the proteins. The reasons for this contradiction between prediction and experiment were investigated. The results reveal a mutational strategy to improve the biophysical behavior of nanobody binders and indicate a species-specificity of nanobody architecture. This study illustrates the potential and limitations of engineering nanobody thermostability by merging sequence information with stability data, an aspect that is becoming increasingly important with the recent development of high-throughput biophysical methods. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The Politics of Financial Regulation Expertise

DEFF Research Database (Denmark)

Ban, Cornel; Seabrooke, Leonard; Freitas, Sarah

Who controls global policy debates on shadow banking regulation? By looking at the policy recommendations of the Bank of International Settlements, the International Monetary Fund and the Financial Stability Board, we show how experts tied to these institutions secured control over how shadow...... banking is treated. In so doing, these technocrats reinforced each other’s expertise and excluded some potential competitors (legal scholars), coopted others (select Fed and elite academic economists). The findings have important implications for studying the relationship between IOs technocrats...

Dynamical Analysis of bantam-Regulated Drosophila Circadian Rhythm Model

Science.gov (United States)

Li, Ying; Liu, Zengrong

MicroRNAs (miRNAs) interact with 3‧untranslated region (UTR) elements of target genes to regulate mRNA stability or translation, and play a crucial role in regulating many different biological processes. bantam, a conserved miRNA, is involved in several functions, such as regulating Drosophila growth and circadian rhythm. Recently, it has been discovered that bantam plays a crucial role in the core circadian pacemaker. In this paper, based on experimental observations, a detailed dynamical model of bantam-regulated circadian clock system is developed to show the post-transcriptional behaviors in the modulation of Drosophila circadian rhythm, in which the regulation of bantam is incorporated into a classical model. The dynamical behaviors of the model are consistent with the experimental observations, which shows that bantam is an important regulator of Drosophila circadian rhythm. The sensitivity analysis of parameters demonstrates that with the regulation of bantam the system is more sensitive to perturbations, indicating that bantam regulation makes it easier for the organism to modulate its period against the environmental perturbations. The effectiveness in rescuing locomotor activity rhythms of mutated flies shows that bantam is necessary for strong and sustained rhythms. In addition, the biological mechanisms of bantam regulation are analyzed, which may help us more clearly understand Drosophila circadian rhythm regulated by other miRNAs.

Harmony as Ideology: Questioning the Diversity-Stability Hypothesis.

Science.gov (United States)

Nikisianis, Nikos; Stamou, Georgios P

2016-03-01

The representation of a complex but stable, self-regulated and, finally, harmonious nature penetrates the whole history of Ecology, thus contradicting the core of the Darwinian evolution. Originated in the pre-Darwinian Natural History, this representation defined theoretically the various schools of early ecology and, in the context of the cybernetic synthesis of the 1950s, it assumed a typical mathematical form on account of α positive correlation between species diversity and community stability. After 1960, these two aforementioned concepts and their positive correlation were proposed as environmental management tools, in the face of the ecological crisis arising at the time. In the early 1970s, and particularly after May's evolutionary arguments, the consensus around this positive correlation collapsed for a while, only to be promptly restored for the purpose of attaching an ecological value on biodiversity. In this paper, we explore the history of the diversity-stability hypothesis and we review the successive terms that have been used to express community stability. We argue that this hypothesis has been motivated by the nodal ideological presuppositions of order and harmony and that the scientific developments in this field largely correspond to external social pressures. We conclude that the conflict about the diversity-stability relationship is in fact an ideological debate, referring mostly to the way we see nature and society rather than to an autonomous scientific question. From this point of view, we may understand why Ecology's concepts and perceptions may decline and return again and again, forming a pluralistic scientific history.

Axial stability of VVER-1000 reactor with control with minimum standard deviation

International Nuclear Information System (INIS)

Afanas'ev, A.M.; Torlin, B.Z.

1980-01-01

Results are given of investigations on the stability of a reactor which has, in addition to an automatic controller, a height distribution regulator (HDR) based on an auxiliary control rod (CR) or a special shortened absorption rod (SAR). The HDR was controlled by using either a special ionization chamber (IC), generating an imbalance signal which sets the CR in motion, or two ionization chambers whose difference signal causes a displacement of the SAR. Since data from numerous pickups can be used to control the height field of the VVER-1000, it is of interest to analyze how this would affect the stability of the reactor. The analysis was carried out with the improved IRINA programs. 11 refs

Stability analysis and stabilization strategies for linear supply chains

Science.gov (United States)

Nagatani, Takashi; Helbing, Dirk

2004-04-01

Due to delays in the adaptation of production or delivery rates, supply chains can be dynamically unstable with respect to perturbations in the consumption rate, which is known as “bull-whip effect”. Here, we study several conceivable production strategies to stabilize supply chains, which is expressed by different specifications of the management function controlling the production speed in dependence of the stock levels. In particular, we will investigate, whether the reaction to stock levels of other producers or suppliers has a stabilizing effect. We will also demonstrate that the anticipation of future stock levels can stabilize the supply system, given the forecast horizon τ is long enough. To show this, we derive linear stability conditions and carry out simulations for different control strategies. The results indicate that the linear stability analysis is a helpful tool for the judgement of the stabilization effect, although unexpected deviations can occur in the non-linear regime. There are also signs of phase transitions and chaotic behavior, but this remains to be investigated more thoroughly in the future.

Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program

Science.gov (United States)

Brown, Chrysothemis C.; Esterhazy, Daria; Sarde, Aurelien; London, Mariya; Pullabhatla, Venu; Osma-Garcia, Ines; al-Bader, Raya; Ortiz, Carla; Elgueta, Raul; Arno, Matthew; de Rinaldis, Emanuele; Mucida, Daniel; Lord, Graham M.; Noelle, Randolph J.

2015-01-01

Summary CD4+ T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARα, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARα as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells. PMID:25769610

pH regulation of the kinetic stability of the lipase from Thermomyces lanuginosus.

Science.gov (United States)

Wang, H; Andersen, K K; Sehgal, P; Hagedorn, J; Westh, P; Borch, K; Otzen, D E

2013-01-08

Thermomyces lanuginosus lipase (TlL) is a kinetically stable protein, resistant toward both denaturation and refolding in the presence of the ionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant decyl maltoside (DecM). We investigate the pH dependence of this kinetic stability. At pH 8, TlL remains folded and enzymatically active at multimillimolar surfactant concentrations but fails to refold from the acid urea-denatured state at submillimolar concentrations of SDS and DecM, indicating a broad concentration range of kinetic trapping or hysteresis. At pH 8, very few SDS molecules bind to TlL. The hysteresis SDS concentration range shrinks when moving to pH 4-6; in this pH range, SDS binds as micellelike clusters. Although hysteresis can be eliminated by reducing disulfide bonds, destabilizing the native state, and lowering the unfolding activation barrier, SDS sensitivity is not directly linked to intrinsic kinetic stability [its resistance to the general chemical denaturant guanidinium chloride (GdmCl)], because TlL unfolds more slowly in GdmCl at pH 6.0 than at pH 8.0. However, the estimated net charge drops from approximately -12 to approximately -5 between pH 8 and 6. SDS denatures TlL at pH 6.0 by nucleating via a critical number of bound SDS molecules on the surface of native TlL to form clusters. These results imply that SDS sensitivity is connected to the availability of appropriately charged regions on the protein. We suggest that conformational rigidity is a necessary but not sufficient feature of SDS resistance, because this has to be combined with sufficient negative electrostatic potential to avoid extensive SDS binding.

Tet Enzymes Regulate Telomere Maintenance and Chromosomal Stability of Mouse ESCs

Directory of Open Access Journals (Sweden)

Jiao Yang

2016-05-01

Full Text Available Ten-eleven translocation (Tet family proteins convert 5-methylcytosine to 5-hydroxymethylcytosine. We show that mouse embryonic stem cells (ESCs depleted of Tet1 and/or Tet2 by RNAi exhibit short telomeres and chromosomal instability, concomitant with reduced telomere recombination. Tet1 and Tet2 double-knockout ESCs also display short telomeres but to a lesser extent. Notably, Tet1/2/3 triple-knockout ESCs show heterogeneous telomere lengths and increased frequency of telomere loss and chromosomal fusion. Mechanistically, Tets depletion or deficiency increases Dnmt3b and decreases 5hmC levels, resulting in elevated methylation levels at sub-telomeres. Consistently, knockdown of Dnmt3b or addition of 2i (MAPK and GSK3β inhibitors, which also inhibits Dnmt3b, reduces telomere shortening, partially rescuing Tet1/2 deficiency. Interestingly, Tet1/2 double or Tet1/2/3 triple knockout in ESCs consistently upregulates Zscan4, which may counteract telomere shortening. Together, Tet enzymes play important roles in telomere maintenance and chromosomal stability of ESCs by modulating sub-telomeric methylation levels.

Sensitivity to lysosome-dependent cell death is directly regulated by lysosomal cholesterol content.

Directory of Open Access Journals (Sweden)

Hanna Appelqvist

Full Text Available Alterations in lipid homeostasis are implicated in several neurodegenerative diseases, although the mechanisms responsible are poorly understood. We evaluated the impact of cholesterol accumulation, induced by U18666A, quinacrine or mutations in the cholesterol transporting Niemann-Pick disease type C1 (NPC1 protein, on lysosomal stability and sensitivity to lysosome-mediated cell death. We found that neurons with lysosomal cholesterol accumulation were protected from oxidative stress-induced apoptosis. In addition, human fibroblasts with cholesterol-loaded lysosomes showed higher lysosomal membrane stability than controls. Previous studies have shown that cholesterol accumulation is accompanied by the storage of lipids such as sphingomyelin, glycosphingolipids and sphingosine and an up regulation of lysosomal associated membrane protein-2 (LAMP-2, which may also influence lysosomal stability. However, in this study the use of myriocin and LAMP deficient fibroblasts excluded these factors as responsible for the rescuing effect and instead suggested that primarily lysosomal cholesterol content determineD the cellular sensitivity to toxic insults. Further strengthening this concept, depletion of cholesterol using methyl-β-cyclodextrin or 25-hydroxycholesterol decreased the stability of lysosomes and cells became more prone to undergo apoptosis. In conclusion, cholesterol content regulated lysosomal membrane permeabilization and thereby influenced cell death sensitivity. Our data suggests that lysosomal cholesterol modulation might be used as a therapeutic strategy for conditions associated with accelerated or repressed apoptosis.

ATM phosphorylation of Mdm2 Ser394 regulates the amplitude and duration of the DNA damage response in mice

Science.gov (United States)

Gannon, Hugh S.; Woda, Bruce A.; Jones, Stephen N.

2012-01-01

Summary DNA damage induced by ionizing radiation (IR) activates the ATM kinase, which subsequently stabilizes and activates the p53 tumor suppressor protein. Although phosphorylation of p53 by ATM was found previously to modulate p53 levels and transcriptional activities in vivo, it does not appear to be a major regulator of p53 stability. We have utilized mice bearing altered Mdm2 alleles to demonstrate that ATM phosphorylation of Mdm2 serine 394 is required for robust p53 stabilization and activation after DNA damage. In addition, we demonstrate that dephosphorylation of Mdm2 Ser394 regulates attenuation of the p53-mediated response to DNA damage. Therefore, the phosphorylation status of Mdm2 Ser394 governs p53 protein levels and functions in cells undergoing DNA damage. PMID:22624716

HANFORD PLUTONIUM FINISHG PLAN (PFP) COMPLETES PLUTONIUM STABILIZATION KEY SAFETY ISSUES CLOSED

International Nuclear Information System (INIS)

GERBER, M.S.

2004-01-01

A long and intense effort to stabilize and repackage nearly 18 metric tons (MT) of plutonium-bearing leftovers from defense production and nuclear experiments concluded successfully in February, bringing universal congratulations to the Department of Energy's Hanford Site in southeast Washington State. The victorious stabilization and packaging endeavor at the Plutonium Finishing Plant (PFP), managed and operated by prime contractor Fluor Hanford, Inc., finished ahead of all milestones in Hanford's cleanup agreement with regulators, and before deadlines set by the Defense Nuclear Facilities Safety Board (DNFSB), a part of the federal Executive Branch that oversees special nuclear materials. The PFP stabilization and packaging project also completed under budget for its four-year tenure, and has been nominated for a DOE Secretarial Award. It won the Project of the Year Award in the local chapter competition of the Project Management Institute, and is being considered for awards at the regional and national level

Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability

Directory of Open Access Journals (Sweden)

Lu Kun

2008-12-01

Full Text Available Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7% stained positive for Her2 (IHC 3+, and 54% (122/223 of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5% were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2

Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-κB signaling.

Science.gov (United States)

Cao, Yang; Wei, Wei; Zhang, Nan; Yu, Qing; Xu, Wen-Bin; Yu, Wen-Jun; Chen, Guo-Qiang; Wu, Ying-Li; Yan, Hua

2015-04-10

Retinoic acid receptor alpha (RARα) plays an essential role in the regulation of many biological processes, such as hematopoietic cell differentiation, while abnormal RARα function contributes to the pathogenesis of certain diseases including cancers, especially acute promyelocytic leukemia (APL). Recently, oridonin, a natural diterpenoid isolated from Rabdosia rubescens, was demonstrated to regulate RARα by increasing its protein level. However, the underlying molecular mechanism for this action has not been fully elucidated. In the APL cell line, NB4, the effect of oridonin on RARα protein was analyzed by western blot and real-time quantitative RT-PCR analyses. Flow cytometry was performed to detect intracellular levels of reactive oxygen species (ROS). The association between nuclear factor-kappa B (NF-κB) signaling and the effect of oridonin was assessed using specific inhibitors, shRNA gene knockdown, and immunofluorescence assays. In addition, primary leukemia cells were treated with oridonin and analyzed by western blot in this study. RARα possesses transcriptional activity in the presence of its ligand, all-trans retinoic acid (ATRA). Oridonin remarkably stabilized the RARα protein, which retained transcriptional activity. Oridonin also moderately increased intracellular ROS levels, while pretreatment with the ROS scavenger, N-acetyl-l-cysteine (NAC), dramatically abrogated RARα stabilization by oridonin. More intriguingly, direct exposure to low concentrations of H2O2 also increased RARα protein but not mRNA levels, suggesting a role for ROS in oridonin stabilization of RARα protein. Further investigations showed that NAC antagonized oridonin-induced activation of NF-κB signaling, while the NF-κB signaling inhibitor, Bay 11-7082, effectively blocked the oridonin increase in RARα protein levels. In line with this, over-expression of IκΒα (A32/36), a super-repressor form of IκΒα, or NF-κB-p65 knockdown inhibited oridonin or H2O2-induced

Optimization of a pressure control valve for high power automatic transmission considering stability

Science.gov (United States)

Jian, Hongchao; Wei, Wei; Li, Hongcai; Yan, Qingdong

2018-02-01

The pilot-operated electrohydraulic clutch-actuator system is widely utilized by high power automatic transmission because of the demand of large flowrate and the excellent pressure regulating capability. However, a self-excited vibration induced by the inherent non-linear characteristics of valve spool motion coupled with the fluid dynamics can be generated during the working state of hydraulic systems due to inappropriate system parameters, which causes sustaining instability in the system and leads to unexpected performance deterioration and hardware damage. To ensure a stable and fast response performance of the clutch actuator system, an optimal design method for the pressure control valve considering stability is proposed in this paper. A non-linear dynamic model of the clutch actuator system is established based on the motion of the valve spool and coupling fluid dynamics in the system. The stability boundary in the parameter space is obtained by numerical stability analysis. Sensitivity of the stability boundary and output pressure response time corresponding to the valve parameters are identified using design of experiment (DOE) approach. The pressure control valve is optimized using particle swarm optimization (PSO) algorithm with the stability boundary as constraint. The simulation and experimental results reveal that the optimization method proposed in this paper helps in improving the response characteristics while ensuring the stability of the clutch actuator system during the entire gear shift process.

Amyloid Precursor Protein Translation Is Regulated by a 3'UTR Guanine Quadruplex.

Directory of Open Access Journals (Sweden)

Ezekiel Crenshaw

Full Text Available A central event in Alzheimer's disease is the accumulation of amyloid β (Aβ peptides generated by the proteolytic cleavage of the amyloid precursor protein (APP. APP overexpression leads to increased Aβ generation and Alzheimer's disease in humans and altered neuronal migration and increased long term depression in mice. Conversely, reduction of APP expression results in decreased Aβ levels in mice as well as impaired learning and memory and decreased numbers of dendritic spines. Together these findings indicate that therapeutic interventions that aim to restore APP and Aβ levels must do so within an ideal range. To better understand the effects of modulating APP levels, we explored the mechanisms regulating APP expression focusing on post-transcriptional regulation. Such regulation can be mediated by RNA regulatory elements such as guanine quadruplexes (G-quadruplexes, non-canonical structured RNA motifs that affect RNA stability and translation. Via a bioinformatics approach, we identified a candidate G-quadruplex within the APP mRNA in its 3'UTR (untranslated region at residues 3008-3027 (NM_201414.2. This sequence exhibited characteristics of a parallel G-quadruplex structure as revealed by circular dichroism spectrophotometry. Further, as with other G-quadruplexes, the formation of this structure was dependent on the presence of potassium ions. This G-quadruplex has no apparent role in regulating transcription or mRNA stability as wild type and mutant constructs exhibited equivalent mRNA levels as determined by real time PCR. Instead, we demonstrate that this G-quadruplex negatively regulates APP protein expression using dual luciferase reporter and Western blot analysis. Taken together, our studies reveal post-transcriptional regulation by a 3'UTR G-quadruplex as a novel mechanism regulating APP expression.

From Crisis to Stability

DEFF Research Database (Denmark)

Ban, Cornel; Seabrooke, Leonard

governance institution, and makes a number of concrete recommendations. To make the ESM accountable, more transparency is in order, about where decisions are taken and who calls the shots. Is it the ESM, the Eurogroup, the Commission, or a coalition of Member States? Our report launch attempts to answer......The European Stability Mechanism (ESM) was created to save the euro from collapse. But the Eurozone’s bailout fund is not actually an EU institution. This has a series of knock-on effects, making it difficult to hold the ESM to EU standards as regards transparency, legal review by the CJEU......, but also access to documents regulation and accountability vis-à-vis the European Parliament, the Court of Auditors and Anti-Fraud Office. Transparency International EU’s in-depth study of the governance and accountability of the ESM provides the first comprehensive analysis of the newest European economic...

Do changes in regulation affect employment duration in temporary help agencies?

DEFF Research Database (Denmark)

Antoni, Manfred; Jahn, Elke

2009-01-01

The employment duration of workers in temporary help agencies is seen as an important indicator of their job quality. Most of the countries that regulate temporary agency employment do so to insure at least a minimal level of employment stability. Over the past three decades Germany has repeatedly...

Test results of BM109 magnet field stability during ramping

International Nuclear Information System (INIS)

Kristalinski, A.

1992-12-01

This report presents results of the measured lag between the current ramp and the following magnetic field rise in BM109 magnets. The purpose of these tests is to choose identical ramping programs for PC4AN1, PC4AN2 and PC4AN3 magnets. The lag occurs due to the large eddy currents in the magnets' solid iron cores. The experiment requires a magnetic field stability of 0.1% during beam presence. Using existing equipment and a program slope of 100 Amp/sec starting at Tl yields fields within the 0.05% of set value. Add to this 0.05% for P.S. regulation to meet the required field stability of 0.1%. This program yields annual savings of $200,000 (assuming 100% usage) . Additional savings can be made by using faster slopes, but this requires additional controls

Aircraft nonlinear stability analysis and multidimensional stability region estimation under icing conditions

Directory of Open Access Journals (Sweden)

Liang QU

2017-06-01

Full Text Available Icing is one of the crucial factors that could pose great threat to flight safety, and thus research on stability and stability region of aircraft safety under icing conditions is significant for control and flight. Nonlinear dynamical equations and models of aerodynamic coefficients of an aircraft are set up in this paper to study the stability and stability region of the aircraft under an icing condition. Firstly, the equilibrium points of the iced aircraft system are calculated and analyzed based on the theory of differential equation stability. Secondly, according to the correlation theory about equilibrium points and the stability region, this paper estimates the multidimensional stability region of the aircraft, based on which the stability regions before and after icing are compared. Finally, the results are confirmed by the time history analysis. The results can give a reference for stability analysis and envelope protection of the nonlinear system of an iced aircraft.

Regulation of Homologous Recombination by SUMOylation

DEFF Research Database (Denmark)

Pinela da Silva, Sonia Cristina

factors such as the homologous recombination (HR) machinery. HR constitutes the main DSB repair pathway in Saccharomyces cerevisiae and despite being largely considered an error-free process and essential for genome stability, uncontrolled recombination can lead to loss of heterozygosity, translocations......, deletions, and genome rearrangements that can lead to cell death or cancer in humans. The post-translational modification by SUMO (small ubiquitinlike modifier) has proven to be an important regulator of HR and genome integrity, but the molecular mechanisms responsible for these roles are still unclear....... In this study I present new insights for the role of SUMOylation in regulating HR by dissecting the role of SUMO in the interaction between the central HR-mediator protein Rad52 and its paralogue Rad59 and the outcome of recombination. This data provides evidence for the importance of SUMO in promoting protein...

GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules

Science.gov (United States)

Hur, Eun-Mi; Saijilafu; Lee, Byoung Dae; Kim, Seong-Jin; Xu, Wen-Lin; Zhou, Feng-Quan

2011-01-01

Suppression of glycogen synthase kinase 3 (GSK3) activity in neurons yields pleiotropic outcomes, causing both axon growth promotion and inhibition. Previous studies have suggested that specific GSK3 substrates, such as adenomatous polyposis coli (APC) and collapsin response mediator protein 2 (CRMP2), support axon growth by regulating the stability of axonal microtubules (MTs), but the substrate(s) and mechanisms conveying axon growth inhibition remain elusive. Here we show that CLIP (cytoplasmic linker protein)-associated protein (CLASP), originally identified as a MT plus end-binding protein, displays both plus end-binding and lattice-binding activities in nerve growth cones, and reveal that the two MT-binding activities regulate axon growth in an opposing manner: The lattice-binding activity mediates axon growth inhibition induced by suppression of GSK3 activity via preventing MT protrusion into the growth cone periphery, whereas the plus end-binding property supports axon extension via stabilizing the growing ends of axonal MTs. We propose a model in which CLASP transduces GSK3 activity levels to differentially control axon growth by coordinating the stability and configuration of growth cone MTs. PMID:21937714

Adaptive neural networks control for camera stabilization with active suspension system

Directory of Open Access Journals (Sweden)

Feng Zhao

2015-08-01

Full Text Available The camera always suffers from image instability on the moving vehicle due to unintentional vibrations caused by road roughness. This article presents an adaptive neural network approach mixed with linear quadratic regulator control for a quarter-car active suspension system to stabilize the image captured area of the camera. An active suspension system provides extra force through the actuator which allows it to suppress vertical vibration of sprung mass. First, to deal with the road disturbance and the system uncertainties, radial basis function neural network is proposed to construct the map between the state error and the compensation component, which can correct the optimal state-feedback control law. The weights matrix of radial basis function neural network is adaptively tuned online. Then, the closed-loop stability and asymptotic convergence performance is guaranteed by Lyapunov analysis. Finally, the simulation results demonstrate that the proposed controller effectively suppresses the vibration of the camera and enhances the stabilization of the entire camera, where different excitations are considered to validate the system performance.

Phase stabilities at a glance: Stability diagrams of nickel dipnictides

International Nuclear Information System (INIS)

Bachhuber, F.; Rothballer, J.; Weihrich, R.; Söhnel, T.

2013-01-01

In the course of the recent advances in chemical structure prediction, a straightforward type of diagram to evaluate phase stabilities is presented based on an expedient example. Crystal structures and energetic stabilities of dipnictides NiPn 2 (Pn = N, P, As, Sb, Bi) are systematically investigated by first principles calculations within the framework of density functional theory using the generalized gradient approximation to treat exchange and correlation. These dipnictides show remarkable polymorphism that is not yet understood systematically and offers room for the discovery of new phases. Relationships between the concerned structures including the marcasite, the pyrite, the arsenopyrite/CoSb 2 , and the NiAs 2 types are highlighted by means of common structural fragments. Electronic stabilities of experimentally known and related AB 2 structure types are presented graphically in so-called stability diagrams. Additionally, competing binary phases are taken into consideration in the diagrams to evaluate the stabilities of the title compounds with respect to decomposition. The main purpose of the stability diagrams is the introduction of an image that enables the estimation of phase stabilities at a single glance. Beyond that, some of the energetically favored structure types can be identified as potential new phases

Development of the mouse neuromuscular junction in the absence of regulated secretion

NARCIS (Netherlands)

Heeroma, J.H.; Plomp, J.J.; Roubos, E.W.; Verhage, M.

2003-01-01

To investigate the role of neurotransmitter secretion in the development and stabilization of synapses, the innervation of the diaphragm and intercostal muscles was studied in munc18-1 null mutant mice, which lack regulated secretion. We found that this mutant is completely devoid of both

Dynamic Model of Kaplan Turbine Regulating System Suitable for Power System Analysis

OpenAIRE

Zhao, Jie; Wang, Li; Liu, Dichen; Wang, Jun; Zhao, Yu; Liu, Tian; Wang, Haoyu

2015-01-01

Accurate modeling of Kaplan turbine regulating system is of great significance for grid security and stability analysis. In this paper, Kaplan turbine regulating system model is divided into the governor system model, the blade control system model, and the turbine and water diversion system model. The Kaplan turbine has its particularity, and the on-cam relationship between the wicket gate opening and the runner blade angle under a certain water head on the whole range was obtained by high-o...

Design of Current-Controller with PR-regulator for LCL-Filter Based Grid-Connected Converter

DEFF Research Database (Denmark)

Zeng, Guohong; Rasmussen, Tonny Wederberg

2010-01-01

In the application of LCL-filter based converters, the structure and parameters of current-controller is very important for the system stability and output current quality. This paper presents a filter-capacitor current feedback control scheme for grid-connected converter. The controller...... is consisted of a proportional-resonance regulator and a proportional regulator. Unlike the existing control strategy with unit capacitor current feedback, the proposed method applies the proportional regulator to the feedback path, which can decouple these two regulators, and simplify the tuning process...... of the control strategy and the proposed current controller design method are verified by the simulation results of a 50kVA grid-connected inverter....

High beta and second stability region transport and stability analysis

International Nuclear Information System (INIS)

1991-01-01

This document describes ideal and resistive MHD studies of high-beta plasmas and of the second stability region. Significant progress is reported on the resistive stability properties of high beta poloidal ''supershot'' discharges. For these studies initial profiles were taken from the TRANSP code which is used extensively to analyze experimental data. When an ad hoc method of removing the finite pressure stabilization of tearing modes is implemented it is shown that there is substantial agreement between MHD stability computation and experiment. In particular, the mode structures observed experimentally are consistent with the predictions of the resistive MHD model. We also report on resistive stability near the transition to the second region in TFTR. Tearing modes associated with a nearby infernal mode may explain the increase in MHD activity seen in high beta supershots and which impede the realization of Q∼1. We also report on a collaborative study with PPPL involving sawtooth stabilization with ICRF

Large Signal Stabilization of Hybrid AC/DC Micro-Grids Using Nonlinear Robust Controller

Directory of Open Access Journals (Sweden)

Reza Pejmanfar

2017-12-01

Full Text Available This paper presents a robust nonlinear integrated controller to improve stability of hybrid AC/DC micro-grids under islanding mode. The proposed controller includes two independent controllers where each one is responsible to control one part of the system. First controller will improve the stability of input DC/DC converter. Using this controller, the voltage of DC bus is fully stabilized such that when a large disturbance occurs, its voltage will become constant without any significant dynamic. The necessity of DC bus regulation which has not been considered in previous studies, is imminent as it not only improves voltage stability of the micro-grid but also protects consumers which are directly connected to the DC bus, against voltage variations. Frequency stability of the micro-grid is provided by the second proposed controller which is applied to output DC/AC converter of the micro-grid. Adaptive method is used to make the controllers proposed in this paper, robust. Duty cycle of converters switches are adjusted such that voltage and frequency of the micro-grid are set on the desired value in minimum possible time under transient disturbances and uncertainty of the loads as well as micro-sources characteristics.

Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling.

Science.gov (United States)

Guo, Xing; Ramirez, Alejandro; Waddell, David S; Li, Zhizhong; Liu, Xuedong; Wang, Xiao-Fan

2008-01-01

The broad range of biological responses elicited by transforming growth factor-beta (TGF-beta) in various types of tissues and cells is mainly determined by the expression level and activity of the effector proteins Smad2 and Smad3. It is not fully understood how the baseline properties of Smad3 are regulated, although this molecule is in complex with many other proteins at the steady state. Here we show that nonactivated Smad3, but not Smad2, undergoes proteasome-dependent degradation due to the concerted action of the scaffolding protein Axin and its associated kinase, glycogen synthase kinase 3-beta (GSK3-beta). Smad3 physically interacts with Axin and GSK3-beta only in the absence of TGF-beta. Reduction in the expression or activity of Axin/GSK3-beta leads to increased Smad3 stability and transcriptional activity without affecting TGF-beta receptors or Smad2, whereas overexpression of these proteins promotes Smad3 basal degradation and desensitizes cells to TGF-beta. Mechanistically, Axin facilitates GSK3-beta-mediated phosphorylation of Smad3 at Thr66, which triggers Smad3 ubiquitination and degradation. Thr66 mutants of Smad3 show altered protein stability and hence transcriptional activity. These results indicate that the steady-state stability of Smad3 is an important determinant of cellular sensitivity to TGF-beta, and suggest a new function of the Axin/GSK3-beta complex in modulating critical TGF-beta/Smad3-regulated processes during development and tumor progression.

Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels.

Directory of Open Access Journals (Sweden)

Alexander V Maltsev

2017-08-01

Full Text Available Intracellular Local Ca releases (LCRs from sarcoplasmic reticulum (SR regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup that provides a major contribution to fight-or-flight response. In our simulations the faster SR Ca pumping accelerates action potential-induced Ca transient decay and quickly clears Ca under the cell membrane in diastole, preventing premature releases. Then the SR generates an earlier, more synchronized, and stronger diastolic LCR signal activating an earlier and larger inward NCX current. LCRs at higher Pup exhibit larger amplitudes and faster propagation with more collisions to each other. The LCRs overlap with Ca transient decay, causing an elevation of the average diastolic [Ca] nadir to ~200 nM (at Pup = 24 mM/s. Background Ca (in locations lacking LCRs quickly decays to resting Ca levels (<100 nM at high Pup, but remained elevated during slower decay at low Pup. Release propagation is facilitated at higher Pup by a larger LCR amplitude, whereas at low Pup by higher background Ca. While at low Pup LCRs show smaller amplitudes, their larger durations and sizes combined with longer transient decay stabilize integrals of diastolic Ca and NCX current signals. Thus, the local interplay of SR Ca pump and release channels regulates LCRs and Ca transient decay to insure fail-safe pacemaker cell operation within a wide range of rates.

The G-quadruplex DNA stabilizing drug pyridostatin promotes DNA damage and downregulates transcription of Brca1 in neurons.

Science.gov (United States)

Moruno-Manchon, Jose F; Koellhoffer, Edward C; Gopakumar, Jayakrishnan; Hambarde, Shashank; Kim, Nayun; McCullough, Louise D; Tsvetkov, Andrey S

2017-09-12

The G-quadruplex is a non-canonical DNA secondary structure formed by four DNA strands containing multiple runs of guanines. G-quadruplexes play important roles in DNA recombination, replication, telomere maintenance, and regulation of transcription. Small molecules that stabilize the G-quadruplexes alter gene expression in cancer cells. Here, we hypothesized that the G-quadruplexes regulate transcription in neurons. We discovered that pyridostatin, a small molecule that specifically stabilizes G-quadruplex DNA complexes, induced neurotoxicity and promoted the formation of DNA double-strand breaks (DSBs) in cultured neurons. We also found that pyridostatin downregulated transcription of the Brca1 gene, a gene that is critical for DSB repair. Importantly, in an in vitro gel shift assay, we discovered that an antibody specific to the G-quadruplex structure binds to a synthetic oligonucleotide, which corresponds to the first putative G-quadruplex in the Brca1 gene promoter. Our results suggest that the G-quadruplex complexes regulate transcription in neurons. Studying the G-quadruplexes could represent a new avenue for neurodegeneration and brain aging research.

Dynamic Characteristics Analysis and Stabilization of PV-Based Multiple Microgrid Clusters

DEFF Research Database (Denmark)

Zhao, Zhuoli; Yang, Ping; Wang, Yuewu

2018-01-01

-based multiple microgrid clusters. A detailed small-signal model for PV-based microgrid clusters considering local adaptive dynamic droop control mechanism of the voltage-source PV system is developed. The complete dynamic model is then used to access and compare the dynamic characteristics of the single...... microgrid and interconnected microgrids. In order to enhance system stability of the PV microgrid clusters, a tie-line flow and stabilization strategy is proposed to suppress the introduced interarea and local oscillations. Robustly selecting of the key control parameters is transformed to a multiobjective......As the penetration of PV generation increases, there is a growing operational demand on PV systems to participate in microgrid frequency regulation. It is expected that future distribution systems will consist of multiple microgrid clusters. However, interconnecting PV microgrids may lead to system...

Autoimmune regulator is acetylated by transcription coactivator CBP/p300

Energy Technology Data Exchange (ETDEWEB)

Saare, Mario, E-mail: mario.saare@ut.ee [Molecular Pathology, Institute of General and Molecular Pathology, University of Tartu, 19th Ravila Str, Tartu (Estonia); Rebane, Ana [Molecular Pathology, Institute of General and Molecular Pathology, University of Tartu, 19th Ravila Str, Tartu (Estonia); SIAF, Swiss Institute of Allergy and Asthma Research, University of Zuerich, Davos (Switzerland); Rajashekar, Balaji; Vilo, Jaak [BIIT, Bioinformatics, Algorithmics and Data Mining group, Institute of Computer Science, University of Tartu, Tartu (Estonia); Peterson, Paert [Molecular Pathology, Institute of General and Molecular Pathology, University of Tartu, 19th Ravila Str, Tartu (Estonia)

2012-08-15

The Autoimmune Regulator (AIRE) is a regulator of transcription in the thymic medulla, where it controls the expression of a large set of peripheral-tissue specific genes. AIRE interacts with the transcriptional coactivator and acetyltransferase CBP and synergistically cooperates with it in transcriptional activation. Here, we aimed to study a possible role of AIRE acetylation in the modulation of its activity. We found that AIRE is acetylated in tissue culture cells and this acetylation is enhanced by overexpression of CBP and the CBP paralog p300. The acetylated lysines were located within nuclear localization signal and SAND domain. AIRE with mutations that mimicked acetylated K243 and K253 in the SAND domain had reduced transactivation activity and accumulated into fewer and larger nuclear bodies, whereas mutations that mimicked the unacetylated lysines were functionally similar to wild-type AIRE. Analogously to CBP, p300 localized to AIRE-containing nuclear bodies, however, the overexpression of p300 did not enhance the transcriptional activation of AIRE-regulated genes. Further studies showed that overexpression of p300 stabilized the AIRE protein. Interestingly, gene expression profiling revealed that AIRE, with mutations mimicking K243/K253 acetylation in SAND, was able to activate gene expression, although the affected genes were different and the activation level was lower from those regulated by wild-type AIRE. Our results suggest that the AIRE acetylation can influence the selection of AIRE activated genes. -- Highlights: Black-Right-Pointing-Pointer AIRE is acetylated by the acetyltransferases p300 and CBP. Black-Right-Pointing-Pointer Acetylation occurs between CARD and SAND domains and within the SAND domain. Black-Right-Pointing-Pointer Acetylation increases the size of AIRE nuclear dots. Black-Right-Pointing-Pointer Acetylation increases AIRE protein stability. Black-Right-Pointing-Pointer AIRE acetylation mimic regulates a different set of AIRE

New challenge for the Norwegian electric power market: A free market of power creates stability problems

International Nuclear Information System (INIS)

Gjengedal, T.; Rabbe, O.; Ongstad, E.; Uhlen, K.; Hauger, B.; Vormedal, L.; Lysheim, D.

1997-01-01

The article relates to problems of grid stability as a consequence of market-based power turnover. In combination with special hydrologic conditions, new approaches are formed concerning power production and transmission. Efficient counter-acting efforts must be initiated at an early stage for power system stabilization also concerning future innovations from the year of 2000. Examples on the development of systems of static magnetization and damping, problems concerning dampers, power grid testing, digital regulators, faults in high voltage 3-phase systems, and evaluation of measures of improvement are discussed. 10 figs

A NEW APPROACH TO FINANCIAL REGULATION AT THE EUROPEAN LEVEL

Directory of Open Access Journals (Sweden)

Ioana Laura VALEANU

2015-12-01

Full Text Available With the recent financial and economic crisis onset, a fragility of the financial system became apparent, under the form of a series of vulnerabilities and failures with a strong destabilizing impact on the economy. In this context, a new approach to financial stability has outlined itself, pleading for a more extensive financial regulation and macro-prudential supervision, complementary to the micro-prudential one. The objectives of this article are to highlight the context and need for a new financial regulatory framework and underline the main problems of the banking system the new European regulations addresses.

Stabilizing effect of epoxidized sunflower oil as a secondary stabilizer for Ca/Hg stabilized PVC

Directory of Open Access Journals (Sweden)

2008-01-01

Full Text Available Unsaturated triglyceride oil sunflower was epoxidized and characterized by chemical and spectroscopic methods. Epoxidized sunflower oil (ESO was used as an organic thermal co-stabilizer for rigid poly(vinyl chloride (PVC in the presence of tricalcium dicitrate (Ca3(C6H5O72 and mercury (II acetate (Hg(CH3COO2. The thermo-oxidative degradation of PVC was studied in the presence of these ternary stabilizer systems at 170, 180, 190 and 200°C in N2 atmosphere. The effects of metal carboxylate combination Ca/Hg in the absence and in the presence of epoxidized sunflower oil on static heat treatment of PVC have been studied. The formation of polyene sequences was investigated by UV-visible and FT-IR spectroscopy and by comparing viscosity data obtained in the presence and in the absence of the additives. It was found that the additives retard the rate of degradation and reduce the extent of polymer chain scission associated with the thermal degradation of poly(vinyl chloride. Synergistic effects were found when stabilizer was blended in 50:50 weight ratios with either. It was found that ESO exerted a stabilizing effect on the degradation of PVC. The activation energy for degraded PVC in absence of stabilizers was 38.6 kJ•mol–1 and in the presence of Ca/Hg and Ca/Hg/ESO were 53.3 and 64.7 kJ•mol–1 respectively. In order of compare the efficiency of the epoxidized sunflower oil with these metal soap stabilizers, thermal stabilities were evaluated on the basis of evolved hydrogen chloride determined by conductometry technique and degree of discoloration are discussed.

Phase stability in yttria-stabilized zirconia from first principles

Energy Technology Data Exchange (ETDEWEB)

Carbogno, Christian; Scheffler, Matthias [Materials Department, University of California, Santa Barbara, CA (United States); Fritz-Haber-Institut der Max-Planck-Gesellschaft, Berlin (Germany); Levi, Carlos G.; Van de Walle, Chris G. [Materials Department, University of California, Santa Barbara, CA (United States)

2012-07-01

Zirconia based ceramics are of pivotal importance for a variety of industrial technologies, e.g., for thermal barrier coatings in gas and airplane turbines. Naturally, the stability of such coatings at elevated temperatures plays a critical role in these applications. It is well known that an aliovalent doping of tetragonal ZrO{sub 2} with yttria, which induces oxygen vacancies due to charge conservation, increases its thermodynamic stability. However, the atomistic mechanisms that determine the phase stability of such yttria-stabilized Zirconia (YSZ) coatings are not yet fully understood. In this work, we use density functional theory calculations to assess the electronic structure of the different YSZ polymorphs at various levels of doping. With the help of population analysis schemes, we are able to unravel the intrinsic mechanisms that govern the interaction in YSZ and that can so explain the relative stabilities of the various polymorphs. We critically compare our results to experimental measurements and discuss the implications of our findings with respect to other oxides.

Power System Stabilizer Design Based on a Particle Swarm Optimization Multiobjective Function Implemented Under Graphical Interface

Directory of Open Access Journals (Sweden)

Ghouraf Djamel Eddine

2016-05-01

Full Text Available Power system stability considered a necessary condition for normal functioning of an electrical network. The role of regulation and control systems is to ensure that stability by determining the essential elements that influence it. This paper proposes a Particle Swarm Optimization (PSO based multiobjective function to tuning optimal parameters of Power System Stabilizer (PSS; this later is used as auxiliary to generator excitation system in order to damp electro mechanicals oscillations of the rotor and consequently improve Power system stability. The computer simulation results obtained by developed graphical user interface (GUI have proved the efficiency of PSS optimized by a Particle Swarm Optimization, in comparison with a conventional PSS, showing stable   system   responses   almost   insensitive   to   large parameter variations.Our present study was performed using a GUI realized under MATLAB in our work.

Pilocarpine-induced seizures trigger differential regulation of microRNA-stability related genes in rat hippocampal neurons

OpenAIRE

Kinjo, Erika R.; Higa, Guilherme S. V.; Santos, Bianca A.; de Sousa, Erica; Damico, Marcio V.; Walter, Lais T.; Morya, Edgard; Valle, Angela C.; Britto, Luiz R. G.; Kihara, Alexandre H.

2016-01-01

Epileptogenesis in the temporal lobe elicits regulation of gene expression and protein translation, leading to reorganization of neuronal networks. In this process, miRNAs were described as being regulated in a cell-specific manner, although mechanistics of miRNAs activity are poorly understood. The specificity of miRNAs on their target genes depends on their intracellular concentration, reflecting the balance of biosynthesis and degradation. Herein, we confirmed that pilocarpine application ...

Kindlin1 regulates microtubule function to ensure normal mitosis.

Science.gov (United States)

Patel, Hitesh; Stavrou, Ifigeneia; Shrestha, Roshan L; Draviam, Viji; Frame, Margaret C; Brunton, Valerie G

2016-08-01

Loss of Kindlin 1 (Kin1) results in the skin blistering disorder Kindler Syndrome (KS), whose symptoms also include skin atrophy and reduced keratinocyte proliferation. Kin1 binds to integrins to modulate their activation and more recently it has been shown to regulate mitotic spindles and cell survival in a Plk1-dependent manner. Here we report that short-term Kin1 deletion in mouse skin results in impaired mitosis, which is associated with reduced acetylated tubulin (ac-tub) levels and cell proliferation. In cells, impaired mitosis and reduced ac-tub levels are also accompanied by reduced microtubule stability, all of which are rescued by HDAC6 inhibition. The ability of Kin1 to regulate HDAC6-dependent cellular ac-tub levels is dependent on its phosphorylation by Plk1. Taken together, these data define a novel role for Kin1 in microtubule acetylation and stability and offer a mechanistic insight into how certain KS phenotypes, such as skin atrophy and reduced cell proliferation, arise. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.

Quantifying Stability in Complex Networks: From Linear to Basin Stability

Science.gov (United States)

Kurths, Jürgen

The human brain, power grids, arrays of coupled lasers and the Amazon rainforest are all characterized by multistability. The likelihood that these systems will remain in the most desirable of their many stable states depends on their stability against significant perturbations, particularly in a state space populated by undesirable states. Here we claim that the traditional linearization-based approach to stability is in several cases too local to adequately assess how stable a state is. Instead, we quantify it in terms of basin stability, a new measure related to the volume of the basin of attraction. Basin stability is non-local, nonlinear and easily applicable, even to high-dimensional systems. It provides a long-sought-after explanation for the surprisingly regular topologies of neural networks and power grids, which have eluded theoretical description based solely on linear stability. Specifically, we employ a component-wise version of basin stability, a nonlinear inspection scheme, to investigate how a grid's degree of stability is influenced by certain patterns in the wiring topology. Various statistics from our ensemble simulations all support one main finding: The widespread and cheapest of all connection schemes, namely dead ends and dead trees, strongly diminish stability. For the Northern European power system we demonstrate that the inverse is also true: `Healing' dead ends by addition of transmission lines substantially enhances stability. This indicates a crucial smart-design principle for tomorrow's sustainable power grids: add just a few more lines to avoid dead ends. Further, we analyse the particular function of certain network motifs to promote the stability of the system. Here we uncover the impact of so-called detour motifs on the appearance of nodes with a poor stability score and discuss the implications for power grid design. Moreover, it will be shown that basin stability enables uncovering the mechanism for explosive synchronization and

The Autism Related Protein Contactin-Associated Protein-Like 2 (CNTNAP2 Stabilizes New Spines: An In Vivo Mouse Study.

Directory of Open Access Journals (Sweden)

Amos Gdalyahu

Full Text Available The establishment and maintenance of neuronal circuits depends on tight regulation of synaptic contacts. We hypothesized that CNTNAP2, a protein associated with autism, would play a key role in this process. Indeed, we found that new dendritic spines in mice lacking CNTNAP2 were formed at normal rates, but failed to stabilize. Notably, rates of spine elimination were unaltered, suggesting a specific role for CNTNAP2 in stabilizing new synaptic circuitry.

Homological stabilizer codes

Energy Technology Data Exchange (ETDEWEB)

Anderson, Jonas T., E-mail: jonastyleranderson@gmail.com

2013-03-15

In this paper we define homological stabilizer codes on qubits which encompass codes such as Kitaev's toric code and the topological color codes. These codes are defined solely by the graphs they reside on. This feature allows us to use properties of topological graph theory to determine the graphs which are suitable as homological stabilizer codes. We then show that all toric codes are equivalent to homological stabilizer codes on 4-valent graphs. We show that the topological color codes and toric codes correspond to two distinct classes of graphs. We define the notion of label set equivalencies and show that under a small set of constraints the only homological stabilizer codes without local logical operators are equivalent to Kitaev's toric code or to the topological color codes. - Highlights: Black-Right-Pointing-Pointer We show that Kitaev's toric codes are equivalent to homological stabilizer codes on 4-valent graphs. Black-Right-Pointing-Pointer We show that toric codes and color codes correspond to homological stabilizer codes on distinct graphs. Black-Right-Pointing-Pointer We find and classify all 2D homological stabilizer codes. Black-Right-Pointing-Pointer We find optimal codes among the homological stabilizer codes.

OPERATING STABILITY OF MINERAL WOOL PRODUCTS

Directory of Open Access Journals (Sweden)

Perfilov Vladimir Aleksandrovich

2016-03-01

Full Text Available Creating an effective insulation envelope of the building is possible only using high-quality materials, preserving their characteristics both in the early stages of operation, and for the whole billing period. It is an important opportunity to assess the thermal insulation properties and predict its changes over time directly in the conditions of the construction site. The products based on mineral fibers (rock and glass wool, basalt fiber are the most widely used type of insulating materials in the domestic construction. Therefore, the operational stability valuation methods must be primarily created for this group of products. The methodology for assessing the thermal insulation properties includes two main components: testing equipment and methodology for assessing the operational stability. The authors tested the methodology of the accelerated testing and prediction of durability for mineral wool products of laminated, corrugated and volume-oriented structures. The test results give good convergence with the methods recommended by the building regulations. Application of thermal insulation materials are an effective way to form the thermal envelope of the building, reducing energy costs and increasing the durability of building structures. The material properties are determined by their structure, which is formed during the technological impacts.

Feedback stabilization initiative

International Nuclear Information System (INIS)

1997-06-01

Much progress has been made in attaining high confinement regimes in magnetic confinement devices. These operating modes tend to be transient, however, due to the onset of MHD instabilities, and their stabilization is critical for improved performance at steady state. This report describes the Feedback Stabilization Initiative (FSI), a broad-based, multi-institutional effort to develop and implement methods for raising the achievable plasma betas through active MHD feedback stabilization. A key element in this proposed effort is the Feedback Stabilization Experiment (FSX), a medium-sized, national facility that would be specifically dedicated to demonstrating beta improvement in reactor relevant plasmas by using a variety of MHD feedback stabilization schemes

Feedback stabilization initiative

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-06-01

Much progress has been made in attaining high confinement regimes in magnetic confinement devices. These operating modes tend to be transient, however, due to the onset of MHD instabilities, and their stabilization is critical for improved performance at steady state. This report describes the Feedback Stabilization Initiative (FSI), a broad-based, multi-institutional effort to develop and implement methods for raising the achievable plasma betas through active MHD feedback stabilization. A key element in this proposed effort is the Feedback Stabilization Experiment (FSX), a medium-sized, national facility that would be specifically dedicated to demonstrating beta improvement in reactor relevant plasmas by using a variety of MHD feedback stabilization schemes.

Abl N-terminal Cap stabilization of SH3 domain dynamics†

OpenAIRE

Chen, Shugui; Dumitrescu, Teodora Pene; Smithgall, Thomas E.; Engen, John R.

2008-01-01

Crystal structures and other biochemical data indicate that the N-terminal cap (NCap) region of the Abelson tyrosine kinase (c-Abl) is important for maintaining the downregulated conformation of the kinase domain. The exact contributions that NCap makes in stabilizing the various intramolecular interactions within c-Abl are less clear. While the NCap appears important for locking the SH3/SH2 domains to the back of the kinase domain, there may be other more subtle elements of regulation. Hydro...

Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton

DEFF Research Database (Denmark)

Ly, Donald L.; Waheed, Faiza; Lodyga, Monika

2013-01-01

Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated coactiv......Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin......-regulated coactivator of serum response factor, is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid, and transient translocation of MRTF from the cytosol to the nucleus...... in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF...

Analysis and design of a standardized control module for switching regulators

Science.gov (United States)

Lee, F. C.; Mahmoud, M. F.; Yu, Y.; Kolecki, J. C.

1982-07-01

Three basic switching regulators: buck, boost, and buck/boost, employing a multiloop standardized control module (SCM) were characterized by a common small signal block diagram. Employing the unified model, regulator performances such as stability, audiosusceptibility, output impedance, and step load transient are analyzed and key performance indexes are expressed in simple analytical forms. More importantly, the performance characteristics of all three regulators are shown to enjoy common properties due to the unique SCM control scheme which nullifies the positive zero and provides adaptive compensation to the moving poles of the boost and buck/boost converters. This allows a simple unified design procedure to be devised for selecting the key SCM control parameters for an arbitrarily given power stage configuration and parameter values, such that all regulator performance specifications can be met and optimized concurrently in a single design attempt.

Post-Transcriptional Regulation by the Csr Global Regulatory System in Escherichia coli

OpenAIRE

Suzuki, Kazushi; 鈴木, 一史

2007-01-01

In many species of bacteria, the Csr (carbon storage regulator) global regulatory system coordinates the expression of various genes. In Escherichia coli, the central component of this system, CsrA, is a RNA-binding protein. The CsrA is a homodimer and binds to leader segments of target mRNAs, affecting their translation and stability. CsrA activity is regulated by two small non-coding RNAs, CsrB and CsrC. These RNAs contain multiple CsrA-binding sequences and act by sequestering CsrA. In thi...

Comparative study of ageing, heat treatment and accelerated carbonation for stabilization of municipal solid waste incineration bottom ash in view of reducing regulated heavy metal/metalloid leaching.

Science.gov (United States)

Santos, Rafael M; Mertens, Gilles; Salman, Muhammad; Cizer, Özlem; Van Gerven, Tom

2013-10-15

This study compared the performance of four different approaches for stabilization of regulated heavy metal and metalloid leaching from municipal solid waste incineration bottom ash (MSWI-BA): (i) short term (three months) heap ageing, (ii) heat treatment, (iii) accelerated moist carbonation, and (iv) accelerated pressurized slurry carbonation. Two distinct types of MSWI-BA were tested in this study: one originating from a moving-grate furnace incineration operation treating exclusively household refuse (sample B), and another originating from a fluid-bed furnace incineration operation that treats a mixture of household and light industrial wastes (sample F). The most abundant elements in the ashes were Si (20-27 wt.%) and Ca (16-19 wt.%), followed by significant quantities of Fe, Al, Na, S, K, Mg, Ti, and Cl. The main crystalline substances present in the fresh ashes were Quartz, Calcite, Apatite, Anhydrite and Gehlenite, while the amorphous fraction ranged from 56 to 73 wt.%. The leaching values of all samples were compared to the Flemish (NEN 7343) and the Walloon (DIN 38414) regulations from Belgium. Batch leaching of the fresh ashes at natural pH showed that seven elements exceeded at least one regulatory limit (Ba, Cr, Cu, Mo, Pb, Se and Zn), and that both ashes had excess basicity (pH > 12). Accelerated carbonation achieved significant reduction in ash basicity (9.3-9.9); lower than ageing (10.5-12.2) and heat treatment (11.1-12.1). For sample B, there was little distinction between the leaching results of ageing and accelerated carbonation with respect to regulatory limits; however carbonation achieved comparatively lower leaching levels. Heat treatment was especially detrimental to the leaching of Cr. For sample F, ageing was ineffective and heat treatment had marginally better results, while accelerated carbonation delivered the most effective performance, with slurry carbonation meeting all DIN limits. Slurry carbonation was deemed the most

Physical stability of R-(+)-Limonene emulsions stabilized by Ulva fasciata algae polysaccharide.

Science.gov (United States)

Shao, Ping; Ma, Huiling; Qiu, Qiang; Jing, Weiping

2016-11-01

The physical stability of R-(+)-Limonene emulsions stabilized by Ulva fasciata polysaccharide (UFP) was investigated in this study. Emulsion physical stability was evaluated under different polysaccharide concentrations (1%-5%, wt/wt) and pH values (3.0-11.0). The stability of R-(+)-Limonene emulsions was demonstrated by droplet size distribution, rheological properties, zeta potential and visual phase separation. R-(+)-Limonene emulsions displayed monomodal droplet size distributions, high absolute values of zeta potential and good storage stability when 3% (wt/wt) UFP was used. The rheological properties and stability of R-(+)-Limonene emulsions appeared to be dependent on polysaccharide concentration. The emulsion stability was impacted by pH. Higher zeta potential (-52.6mV) and smaller mean droplet diameter (2.45μm) were achieved in neutral liquid environment (pH 7.0). Extreme acidity caused the flocculation of emulsions, which was manifested as phase separation, while emulsions were quite stable in an alkaline environment. Through comparing the stabilities of emulsions stabilized by different emulsifiers (i.e. UFP, GA and Gelatin), the result suggested that UFP was the best emulsifying agent among them. Copyright © 2016 Elsevier B.V. All rights reserved.

Stability of yttria-stabilized zirconia during pyroprocessing tests

Energy Technology Data Exchange (ETDEWEB)

Choi, Eun-Young, E-mail: eychoi@kaeri.re.kr; Lee, Jeong; Lee, Sung-Jai; Kim, Sung-Wook; Jeon, Sang-Chae; Cho, Soo Haeng; Oh, Seung Chul; Jeon, Min Ku; Lee, Sang Kwon; Kang, Hyun Woo; Hur, Jin-Mok

2016-07-15

In this study, the feasibility of yttria-stabilized zirconia (YSZ) was investigated for use as a ceramic material, which can be commonly used for both electrolytic reduction and electrorefining. First, the stability of YSZ in salts for electrolytic reduction and electrorefining was examined. Then, its stability was demonstrated by a series of pyroprocessing tests, such as electrolytic reduction, LiCl distillation, electrorefining, and LiCl−KCl distillation, using a single stainless steel wire mesh basket containing fuel and YSZ. A single basket was used by its transportation from one test to subsequent tests without the requirements for unloading.

Remarks on boiling water reactor stability analysis. Pt. 2. Stability monitoring

Energy Technology Data Exchange (ETDEWEB)

Lange, Carsten; Hennig, Dieter; Hurtado, Antonio [Technische Univ. Dresden (Germany). Chair of Hydrogen and Nuclear Energy; Schuster, Roland [Kernkraftwerk Brunsbuettel GmbH und Co. oHG, Brunsbuettel (Germany); Lukas, Bernard [EnBW Kernkraft GmbH, Philippsburg (Germany). Kernkraftwerk Philippsburg; Aguirre, Carlos [Kernkraftwerk Leibstadt AG, Aargau (Switzerland)

2012-12-15

In part 1 of this article we explained the partly relative complex solution manifold of the differential equations describing the stability behaviour of a BWR, in particular the coexistence of different types of solutions, such as the coexistence of unstable limit cycles and stable fixed points are of interest from the operational safety point of view. The part 2 is devoted to the surveillance of the stability behaviour. We summarize some stability monitoring methods and suggest to support stability tests by RAM-ROM analyses in order to reveal in advance the stability 'landscape' of the BWR in a parameter region high sensitive for appearing of linear unstable states. The analysis of an especial stability test, performed at NPP Leibstadt (KKL), makes it clear that the measurement results can only be interpreted by application of bifurcation analysis. (orig.)

Bank, Banking System, Macroprudential Supervision, Stability of Banking System

Directory of Open Access Journals (Sweden)

Tetiana Vasilyeva

2016-10-01

assets to short term liabilities ratio and cost to income ratio. Empirical results of the research found out that grate damage to the stability of banking system has some parameters of banking activity, that’s why the main purpose of the regulation by the National Bank of Ukraine should be strengthening of macroprudential supervision and intensification of adaptation of Basel II and Basel III requirements

DNA methylation regulates neurophysiological spatial representation in memory formation

Directory of Open Access Journals (Sweden)

Eric D. Roth

2015-04-01

Full Text Available Epigenetic mechanisms including altered DNA methylation are critical for altered gene transcription subserving synaptic plasticity and the retention of learned behavior. Here, we tested the idea that one role for activity-dependent altered DNA methylation is stabilization of cognition-associated hippocampal place cell firing in response to novel place learning. We observed that a behavioral protocol (spatial exploration of a novel environment known to induce hippocampal place cell remapping resulted in alterations of hippocampal Bdnf DNA methylation. Further studies using neurophysiological in vivo single-unit recordings revealed that pharmacological manipulations of DNA methylation decreased long-term but not short-term place field stability. Together, our data highlight a role for DNA methylation in regulating neurophysiological spatial representation and memory formation.

DNA methylation regulates neurophysiological spatial representation in memory formation.

Science.gov (United States)

Roth, Eric D; Roth, Tania L; Money, Kelli M; SenGupta, Sonda; Eason, Dawn E; Sweatt, J David

2015-04-01

Epigenetic mechanisms including altered DNA methylation are critical for altered gene transcription subserving synaptic plasticity and the retention of learned behavior. Here we tested the idea that one role for activity-dependent altered DNA methylation is stabilization of cognition-associated hippocampal place cell firing in response to novel place learning. We observed that a behavioral protocol (spatial exploration of a novel environment) known to induce hippocampal place cell remapping resulted in alterations of hippocampal Bdnf DNA methylation. Further studies using neurophysiological in vivo single unit recordings revealed that pharmacological manipulations of DNA methylation decreased long-term but not short-term place field stability. Together our data highlight a role for DNA methylation in regulating neurophysiological spatial representation and memory formation.

Surface-stabilized gold nanocatalysts

Science.gov (United States)

Dai, Sheng [Knoxville, TN; Yan, Wenfu [Oak Ridge, TN

2009-12-08

A surface-stabilized gold nanocatalyst includes a solid support having stabilizing surfaces for supporting gold nanoparticles, and a plurality of gold nanoparticles having an average particle size of less than 8 nm disposed on the stabilizing surfaces. The surface-stabilized gold nanocatalyst provides enhanced stability, such as at high temperature under oxygen containing environments. In one embodiment, the solid support is a multi-layer support comprising at least a first layer having a second layer providing the stabilizing surfaces disposed thereon, the first and second layer being chemically distinct.

Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability

International Nuclear Information System (INIS)

Zhang, Jingjie; Ouyang, Weiming; Li, Jingxia; Zhang, Dongyun; Yu, Yonghui; Wang, York; Li, Xuejun; Huang, Chuanshu

2012-01-01

Suberoylanilide hydroxamic acid (SAHA) inhibiting cancer cell growth has been associated with its downregulation of cyclin D1 protein expression at transcription level or translation level. Here, we have demonstrated that SAHA inhibited EGF-induced Cl41 cell transformation via the decrease of cyclin D1 mRNA stability and induction of G0/G1 growth arrest. We found that SAHA treatment resulted in the dramatic inhibition of EGF-induced cell transformation, cyclin D1 protein expression and induction of G0/G1 growth arrest. Further studies showed that SAHA downregulation of cyclin D1 was only observed with endogenous cyclin D1, but not with reconstitutionally expressed cyclin D1 in the same cells, excluding the possibility of SAHA regulating cyclin D1 at level of protein degradation. Moreover, SAHA inhibited EGF-induced cyclin d1 mRNA level, whereas it did not show any inhibitory effect on cyclin D1 promoter-driven luciferase reporter activity under the same experimental conditions, suggesting that SAHA may decrease cyclin D1 mRNA stability. This notion was supported by the results that treatment of cells with SAHA decreased the half-life of cyclin D1 mRNA from 6.95 h to 2.57 h. Consistent with downregulation of cyclin D1 mRNA stability, SAHA treatment also attenuated HuR expression, which has been well-characterized as a positive regulator of cyclin D1 mRNA stability. Thus, our study identifies a novel mechanism responsible for SAHA inhibiting cell transformation via decreasing cyclin D1 mRNA stability and induction of G0/G1 growth arrest in Cl41 cells. -- Highlights: ► SAHA inhibits cell transformation in Cl41 cells. ► SAHA suppresses Cyclin D1 protein expression. ► SAHA decreases cyclin D1 mRNA stability.

FINANCIAL STABILITY OF ISLAMIC AND CONVENTIONAL BANKS IN BANGLADESH: REVISITING STABILITY MEASURES AND ANALYZING STABILITY BEHAVIOR

Directory of Open Access Journals (Sweden)

Md Enayet Hossain

2018-03-01

Full Text Available This study intends to assess the relative financial stability of Islamic banks in Bangladesh using three different Z-Scores as financial stability measures, based on a sample of 29 listed commercial banks (23 conventional and 6 Islamic in Bangladesh over the period 2005-2016. Apart from the existing measure of financial stability, Z-Score, the paper contributes to the literature by developing an alternative Z-Score based on bank’s loan portfolio infection ratio. We first use pair-wise comparison and find that Islamic banks are financially more stable in two stability measures i.e. Z-Score (based on Capital Adequacy Ratio and Z-Score (based on Infection Ratio. We then perform static (random effects and dynamic (GMM panel data analysis. By controlling for bank-specific, industry-specific and macroeconomic variables in the regressions, we find that Islamic banks are financially more stable in 2 panel regressions of Z-Score (based on Infection Ratio. We also find that the presence of Islamic banks increases the stability of all banks in the system including their conventional peers.

Abl N-terminal cap stabilization of SH3 domain dynamics.

Science.gov (United States)

Chen, Shugui; Dumitrescu, Teodora Pene; Smithgall, Thomas E; Engen, John R

2008-05-27

Crystal structures and other biochemical data indicate that the N-terminal cap (NCap) region of the Abelson tyrosine kinase (c-Abl) is important for maintaining the downregulated conformation of the kinase domain. The exact contributions that the NCap makes in stabilizing the various intramolecular interactions within c-Abl are less clear. While the NCap appears to be important for locking the SH3 and SH2 domains to the back of the kinase domain, there may be other more subtle elements of regulation. Hydrogen exchange (HX) and mass spectrometry (MS) were used to determine if the NCap contributes to intramolecular interactions involving the Abl SH3 domain. Under physiological conditions, the Abl SH3 domain underwent partial unfolding and its unfolding half-life was slowed during binding to the SH2 kinase linker, providing a unique assay for testing NCap-induced stabilization of the SH3 domain in various constructs. The results showed that the NCap stabilizes the dynamics of the SH3 domain in certain constructs but does not increase the relative affinity of the SH3 domain for the native SH2 kinase linker. The stabilization effect was absent in constructs of just the NCap and SH3 but was obvious when the SH2 domain and the SH2 kinase linker were present. These results suggest that interactions between the NCap and the SH3 domain can contribute to c-Abl stabilization in constructs that contain at least the SH2 domain, an effect that may partially compensate for the absence of the negative regulatory C-terminal tail found in the related Src family of kinases.

THEORETICAL CONSIDERATIONS OF PRICE STABILITY AS PART OF THE FINANCIAL STABILITY

OpenAIRE

Magdalena RĂDULESCU; Marinela TANASCOVICI

2012-01-01

Currently there are many authors who consider that the only objective of the central bank should be the price stability and between the respective objective and financial stability there is incompatibility. As far we are concerned, we subscribe the idea that between price stability and financial stability there are complementarities. And a strong argument in the favour of this position is also historical. Actually, many older or newer facts show that banking crises were often caused by the un...

Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.

Science.gov (United States)

Brown, Chrysothemis C; Esterhazy, Daria; Sarde, Aurelien; London, Mariya; Pullabhatla, Venu; Osma-Garcia, Ines; Al-Bader, Raya; Ortiz, Carla; Elgueta, Raul; Arno, Matthew; de Rinaldis, Emanuele; Mucida, Daniel; Lord, Graham M; Noelle, Randolph J

2015-03-17

CD4(+) T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4(+) T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARα, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARα as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Voltage-regulating constant-current sources in a linear induction accelerator

International Nuclear Information System (INIS)

Zhao Juan; Cao Kefeng; Deng Jianjun; Zhu Lijun; Yang Jia; Ye Chao; Huang Bin; Cao Ningxiang; Dong Jinxuan; Zhang Jichang; Yu Zhiguo; Chen Min

2002-01-01

Constant-current Sources are one of key units in a linear induction accelerator. The requirements for the sources are to supply stable direct current of high power for the induction coil, be easy to computer-control and highly stable and reliable. Applying the technique of linear current source regulating in series, the primary voltage of the power transformer is regulated through an MJYS-JL-350A type three-phase alterative voltage-regulating module. The output current variation is 300-500 A when the load variation is 0.06-0.1 Ω and the voltage drop of the regulator tube is controlled within 8 V±2V when the variation of mains voltage is in ±10%. Both the current ripple and stability meet the technical requirements. The constant-current sources are controlled through an industrial controller. For each of the constant-current sources has a smallest system comprised of 8051 which is communication-controlled through a RS-485 interface, the sources can be controlled remotely

MATLAB Stability and Control Toolbox Trim and Static Stability Module

Science.gov (United States)

Kenny, Sean P.; Crespo, Luis

2012-01-01

MATLAB Stability and Control Toolbox (MASCOT) utilizes geometric, aerodynamic, and inertial inputs to calculate air vehicle stability in a variety of critical flight conditions. The code is based on fundamental, non-linear equations of motion and is able to translate results into a qualitative, graphical scale useful to the non-expert. MASCOT was created to provide the conceptual aircraft designer accurate predictions of air vehicle stability and control characteristics. The code takes as input mass property data in the form of an inertia tensor, aerodynamic loading data, and propulsion (i.e. thrust) loading data. Using fundamental nonlinear equations of motion, MASCOT then calculates vehicle trim and static stability data for the desired flight condition(s). Available flight conditions include six horizontal and six landing rotation conditions with varying options for engine out, crosswind, and sideslip, plus three take-off rotation conditions. Results are displayed through a unique graphical interface developed to provide the non-stability and control expert conceptual design engineer a qualitative scale indicating whether the vehicle has acceptable, marginal, or unacceptable static stability characteristics. If desired, the user can also examine the detailed, quantitative results.

Finite-Time Stability and Stabilization of Nonlinear Quadratic Systems with Jumps

Directory of Open Access Journals (Sweden)

Minsong Zhang

2014-01-01

Full Text Available This paper investigates the problems of finite-time stability and finite-time stabilization for nonlinear quadratic systems with jumps. The jump time sequences here are assumed to satisfy some given constraints. Based on Lyapunov function and a particular presentation of the quadratic terms, sufficient conditions for finite-time stability and finite-time stabilization are developed to a set containing bilinear matrix inequalities (BLIMs and linear matrix inequalities (LMIs. Numerical examples are given to illustrate the effectiveness of the proposed methodology.

On the modelling of linear-assisted DC-DC voltage regulators for photovoltaic solar energy systems

Science.gov (United States)

Martínez-García, Herminio; García-Vílchez, Encarna

2017-11-01

This paper shows the modelling of linear-assisted or hybrid (linear & switching) DC/DC voltage regulators. In this kind of regulators, an auxiliary linear regulator is used, which objective is to cancel the ripple at the output voltage and provide fast responses for load variations. On the other hand, a switching DC/DC converter, connected in parallel with the linear regulator, allows to supply almost the whole output current demanded by the load. The objective of this topology is to take advantage of the suitable regulation characteristics that series linear voltage regulators have, but almost achieving the high efficiency that switching DC/DC converters provide. Linear-assisted DC/DC regulators are feedback systems with potential instability. Therefore, their modelling is mandatory in order to obtain design guidelines and assure stability of the implemented power supply system.

A Study of Strong Stability of Distributed Systems. Ph.D. Thesis

Science.gov (United States)

Cataltepe, Tayfun

1989-01-01

The strong stability of distributed systems is studied and the problem of characterizing strongly stable semigroups of operators associated with distributed systems is addressed. Main emphasis is on contractive systems. Three different approaches to characterization of strongly stable contractive semigroups are developed. The first one is an operator theoretical approach. Using the theory of dilations, it is shown that every strongly stable contractive semigroup is related to the left shift semigroup on an L(exp 2) space. Then, a decomposition for the state space which identifies strongly stable and unstable states is introduced. Based on this decomposition, conditions for a contractive semigroup to be strongly stable are obtained. Finally, extensions of Lyapunov's equation for distributed parameter systems are investigated. Sufficient conditions for weak and strong stabilities of uniformly bounded semigroups are obtained by relaxing the equivalent norm condition on the right hand side of the Lyanupov equation. These characterizations are then applied to the problem of feedback stabilization. First, it is shown via the state space decomposition that under certain conditions a contractive system (A,B) can be strongly stabilized by the feedback -B(*). Then, application of the extensions of the Lyapunov equation results in sufficient conditions for weak, strong, and exponential stabilizations of contractive systems by the feedback -B(*). Finally, it is shown that for a contractive system, the first derivative of x with respect to time = Ax + Bu (where B is any linear bounded operator), there is a related linear quadratic regulator problem and a corresponding steady state Riccati equation which always has a bounded nonnegative solution.

[Toward a deeper understanding of motivation towards exercise: measurement of integrated regulation in the Spanish context].

Science.gov (United States)

González-Cutre, David; Sicilia, Álvaro; Fernández, Alberto

2010-11-01

The purpose of this study was to validate the Behavioural Regulation in Exercise Questionnaire in the Spanish context, including items to measure integrated regulation. Participants were 524 exercisers, mean age 29.59 years. The results revealed acceptable fit indices in the confirmatory factor analysis and good internal consistency (with a Cronbach alpha of .87 for integrated regulation). The diverse subscales also conformed to a simplex pattern and the factor structure was invariant across gender and age. Integrated regulation reflected high temporal stability over a 4-week period (ICC=.90). The criterion validity analysis of integrated regulation indicated that this variable was positively predicted by satisfaction of the needs for competence and autonomy. The results regarding the importance of measuring integrated regulation in exercise are discussed.

Heat shock protein 90β stabilizes focal adhesion kinase and enhances cell migration and invasion in breast cancer cells

International Nuclear Information System (INIS)

Xiong, Xiangyang; Wang, Yao; Liu, Chengmei; Lu, Quqin; Liu, Tao; Chen, Guoan; Rao, Hai; Luo, Shiwen

2014-01-01

Focal adhesion kinase (FAK) acts as a regulator of cellular signaling and may promote cell spreading, motility, invasion and survival in malignancy. Elevated expression and activity of FAK frequently correlate with tumor cell metastasis and poor prognosis in breast cancer. However, the mechanisms by which the turnover of FAK is regulated remain elusive. Here we report that heat shock protein 90β (HSP90β) interacts with FAK and the middle domain (amino acids 233–620) of HSP90β is mainly responsible for this interaction. Furthermore, we found that HSP90β regulates FAK stability since HSP90β inhibitor 17-AAG triggers FAK ubiquitylation and subsequent proteasome-dependent degradation. Moreover, disrupted FAK-HSP90β interaction induced by 17-AAG contributes to attenuation of tumor cell growth, migration, and invasion. Together, our results reveal how HSP90β regulates FAK stability and identifies a potential therapeutic strategy to breast cancer. - Highlights: • HSP90β protects FAK from degradation by the ubiquitin-proteasome pathway. • Inhibition of HSP90β or FAK attenuates tumorigenesis of breast cancer cells. • Genetic repression of HSP90β or FAK inhibits tumor cell migration and proliferation. • Inhibition of HSP90β or FAK interferes cell invasion and cytoskeleton

Heat shock protein 90β stabilizes focal adhesion kinase and enhances cell migration and invasion in breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Xiong, Xiangyang [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China); Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi 330006 (China); State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047 (China); Wang, Yao [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China); Liu, Chengmei [State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047 (China); Lu, Quqin [Department of Biostatistics and Epidemiology, School of Public Health, Nanchang University, Nanchang, Jiangxi 330006 (China); Liu, Tao [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China); Chen, Guoan [Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006 (China); Rao, Hai [Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78229 (United States); Luo, Shiwen, E-mail: shiwenluo@ncu.edu.cn [Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Donghu District, Nanchang, Jiangxi 330006 (China)

2014-08-01

Focal adhesion kinase (FAK) acts as a regulator of cellular signaling and may promote cell spreading, motility, invasion and survival in malignancy. Elevated expression and activity of FAK frequently correlate with tumor cell metastasis and poor prognosis in breast cancer. However, the mechanisms by which the turnover of FAK is regulated remain elusive. Here we report that heat shock protein 90β (HSP90β) interacts with FAK and the middle domain (amino acids 233–620) of HSP90β is mainly responsible for this interaction. Furthermore, we found that HSP90β regulates FAK stability since HSP90β inhibitor 17-AAG triggers FAK ubiquitylation and subsequent proteasome-dependent degradation. Moreover, disrupted FAK-HSP90β interaction induced by 17-AAG contributes to attenuation of tumor cell growth, migration, and invasion. Together, our results reveal how HSP90β regulates FAK stability and identifies a potential therapeutic strategy to breast cancer. - Highlights: • HSP90β protects FAK from degradation by the ubiquitin-proteasome pathway. • Inhibition of HSP90β or FAK attenuates tumorigenesis of breast cancer cells. • Genetic repression of HSP90β or FAK inhibits tumor cell migration and proliferation. • Inhibition of HSP90β or FAK interferes cell invasion and cytoskeleton.

Effects of Sodium and Amino Acid Substrate Availability upon the Expression and Stability of the SNAT2 (SLC38A2 Amino Acid Transporter

Directory of Open Access Journals (Sweden)

Thorsten M. Hoffmann

2018-02-01

Full Text Available The SNAT2 (SLC38A2 System A amino acid transporter mediates Na+-coupled cellular uptake of small neutral α-amino acids (AAs and is extensively regulated in response to humoral and nutritional cues. Understanding the basis of such regulation is important given that AA uptake via SNAT2 has been linked to activation of mTORC1; a major controller of many important cellular processes including, for example, mRNA translation, lipid synthesis, and autophagy and whose dysregulation has been implicated in the development of cancer and conditions such as obesity and type 2 diabetes. Extracellular AA withdrawal induces an adaptive upregulation of SNAT2 gene transcription and SNAT2 protein stability but, as yet, the sensing mechanism(s that initiate this response remain poorly understood although interactions between SNAT2 and its substrates may play a vital role. Herein, we have explored how changes in substrate (AA and Na+ availability impact upon the adaptive regulation of SNAT2 in HeLa cells. We show that while AA deprivation induces SNAT2 gene expression, this induction was not apparent if extracellular Na+ was removed during the AA withdrawal period. Furthermore, we show that the increase in SNAT2 protein stability associated with AA withdrawal is selectively repressed by provision of SNAT2 AA substrates (N-methylaminoisobutyric acid and glutamine, but not non-substrates. This stabilization and substrate-induced repression were critically dependent upon the cytoplasmic N-terminal tail of SNAT2 (containing lysyl residues which are putative targets of the ubiquitin-proteasome system, because “grafting” this tail onto SNAT5, a related SLC38 family member that does not exhibit adaptive regulation, confers substrate-induced changes in stability of the SNAT2-5 chimeric transporter. In contrast, expression of SNAT2 in which the N-terminal lysyl residues were mutated to alanine rendered the transporter stable and insensitive to substrate-induced changes

Internet Addiction: Stability and Change

Science.gov (United States)

Huang, Chiungjung

2010-01-01

This longitudinal study examined five indices of stability and change in Internet addiction: structural stability, mean-level stability, differential stability, individual-level stability, and ipsative stability. The study sample was 351 undergraduate students from end of freshman year to end of junior year. Convergent findings revealed stability…

Design and Control of a Buck–Boost Charger-Discharger for DC-Bus Regulation in Microgrids

Directory of Open Access Journals (Sweden)

Carlos Andrés Ramos-Paja

2017-11-01

Full Text Available In DC and hybrid microgrids (MG, the DC-bus regulation using Energy Storage Devices (ESD is important for the stable operation of both the generators and loads. There are multiple commercial voltage levels for both ESD and DC-bus; therefore, the ESD voltage may be higher, equal or lower than the DC-bus voltage depending on the application. Moreover, most of the ESD converter controllers are linear-based, hence they ensure stability in a limited operation range. This paper proposes a system to regulate the DC-bus voltage of an MG accounting for any voltage relation between the ESD and the DC-bus voltage. The proposed system is formed by an ESD connected to a DC-bus through a bidirectional Buck–Boost converter, which is regulated by a Sliding-Mode Controller (SMC to ensure the system stability in the entire operation range. The SMC drives the Buck–Boost charger–discharger to regulate the DC-bus voltage, at the desired reference value, by charging or discharging the ESD. This paper also provides detailed procedures to design the parameters of both the SMC and the charger–dischager. Finally, simulation and experimental results validate the proposed solution and illustrate its performance.

VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle.

Science.gov (United States)

Cantarero, Lara; Sanz-García, Marta; Vinograd-Byk, Hadar; Renbaum, Paul; Levy-Lahad, Ephrat; Lazo, Pedro A

2015-06-12

Cajal bodies (CBs) are nuclear organelles associated with ribonucleoprotein functions and RNA maturation. CBs are assembled on coilin, its main scaffold protein, in a cell cycle dependent manner. The Ser-Thr VRK1 (vaccinia-related kinase 1) kinase, whose activity is also cell cycle regulated, interacts with and phosphorylates coilin regulating assembly of CBs. Coilin phosphorylation is not necessary for its interaction with VRK1, but it occurs in mitosis and regulates coilin stability. Knockdown of VRK1 or VRK1 inactivation by serum deprivation causes a loss of coilin phosphorylation in Ser184 and of CBs formation, which are rescued with an active VRK1, but not by kinase-dead VRK1. The phosphorylation of coilin in Ser184 occurs during mitosis before assembly of CBs. Loss of coilin phosphorylation results in disintegration of CBs, and of coilin degradation that is prevented by proteasome inhibitors. After depletion of VRK1, coilin is ubiquitinated in nuclei, which is partly mediated by mdm2, but its proteasomal degradation occurs in cytosol and is prevented by blocking its nuclear export. We conclude that VRK1 is a novel regulator of CBs dynamics and stability in cell cycle by protecting coilin from ubiquitination and degradation in the proteasome, and propose a model of CB dynamics.

Chaperone-Mediated Regulation of Choline Acetyltransferase Protein Stability and Activity by HSC/HSP70, HSP90, and p97/VCP

Directory of Open Access Journals (Sweden)

Trevor M. Morey

2017-12-01

for the functional regulation of wild-type and CMS-related mutant ChAT by pro-stabilizing HSPs and the pro-degradative co-chaperone p97/VCP that may have broader implications for ChAT function during cellular stress and disease.

Stabilization of mixed waste - Rocky Flats solar ponds

International Nuclear Information System (INIS)

Bittner, T.A.; Mathew, S.A.; Henderson, W.C.

1993-01-01

Among the wastes that require disposal as part of the Department of Energy's (DOE's) Environmental Restoration Program are large amounts of contaminated sludge and inorganic wastes. Halliburton NUS Corporation was awarded a contract by EG ampersand G Rocky Flats in March 1991 to stabilize mixed waste sludge contained in five solar evaporator ponds and to reprocess billets of solidified waste called Pondcrete and Saltcrete at DOE's Rocky Flats Plant. The scope of the project consists of waste characterization and treatability studies for process development, followed by design, construction and operation of various process trains to remediate different waste forms ranging from solid Pondcrete/Saltcrete blocks to aqueous brine solutions. One of the significant advances made was the development of a durable and certifiable stabilization formulation capable of treating concentrated nitrate solution wastes. The project uses high-volume grout mixing and pumping technologies with process control techniques that accommodate the heterogeneity of the wastes. To comply with all relevant environmental regulations and to provide a safe working atmosphere for plant personnel, Halliburton NUS designed process trains such that all emissions were eliminated during the remediation process. Personnel protection equipment requirements have been downgraded due to safeguards incorporated in the design. The technical and regulatory issues that were encountered would be typical of stabilization efforts underway at other DOE sites. Thus the lessons learned and concepts developed can be expected to have widespread application

Adenosine Monophosphate Binding Stabilizes the KTN Domain of the Shewanella denitrificans Kef Potassium Efflux System.

Science.gov (United States)

Pliotas, Christos; Grayer, Samuel C; Ekkerman, Silvia; Chan, Anthony K N; Healy, Jess; Marius, Phedra; Bartlett, Wendy; Khan, Amjad; Cortopassi, Wilian A; Chandler, Shane A; Rasmussen, Tim; Benesch, Justin L P; Paton, Robert S; Claridge, Timothy D W; Miller, Samantha; Booth, Ian R; Naismith, James H; Conway, Stuart J

2017-08-15

Ligand binding is one of the most fundamental properties of proteins. Ligand functions fall into three basic types: substrates, regulatory molecules, and cofactors essential to protein stability, reactivity, or enzyme-substrate complex formation. The regulation of potassium ion movement in bacteria is predominantly under the control of regulatory ligands that gate the relevant channels and transporters, which possess subunits or domains that contain Rossmann folds (RFs). Here we demonstrate that adenosine monophosphate (AMP) is bound to both RFs of the dimeric bacterial Kef potassium efflux system (Kef), where it plays a structural role. We conclude that AMP binds with high affinity, ensuring that the site is fully occupied at all times in the cell. Loss of the ability to bind AMP, we demonstrate, causes protein, and likely dimer, instability and consequent loss of function. Kef system function is regulated via the reversible binding of comparatively low-affinity glutathione-based ligands at the interface between the dimer subunits. We propose this interfacial binding site is itself stabilized, at least in part, by AMP binding.

NHERF1 regulates actin cytoskeleton organization through modulation of α-actinin-4 stability.

Science.gov (United States)

Sun, Licui; Zheng, Junfang; Wang, Qiqi; Song, Ran; Liu, Hua; Meng, Ran; Tao, Tao; Si, Yang; Jiang, Wenguo; He, Junqi

2016-02-01

The actin cytoskeleton is composed of a highly dynamic network of filamentous proteins, yet the molecular mechanism that regulates its organization and remodeling remains elusive. In this study, Na(+)/H(+) exchanger regulatory factor (NHERF)-1 loss-of-function and gain-of-function experiments reveal that polymerized actin cytoskeleton (F-actin) in HeLa cells is disorganized by NHERF1, whereas actin protein expression levels exhibit no detectable change. To elucidate the molecular mechanism underlying actin cytoskeleton disorganization by NHERF1, a combined 2-dimensional electrophoresis-matrix-assisted laser desorption/ionization-time of flight mass spectrometry approach was used to screen for proteins regulated by NHERF1 in HeLa cells. α-Actinin-4, an actin cross-linking protein, was identified. Glutathione S-transferase pull-down and coimmunoprecipitation studies showed the α-actinin-4 carboxyl-terminal region specifically interacted with the NHERF1 postsynaptic density 95/disc-large/zona occludens-1 domain. The NHERF1/α-actinin-4 interaction increased α-actinin-4 ubiquitination and decreased its expression levels, resulting in actin cytoskeleton disassembly. Our study identified α-actinin-4 as a novel NHERF1 interaction partner and provided new insights into the regulatory mechanism of the actin cytoskeleton by NHERF1. © FASEB.

Transient stability index for online stability assessment and contingency evaluation

Energy Technology Data Exchange (ETDEWEB)

Ribbens-Pavella, M; Murthy, P G; Horward, J L; Carpentier, J L

1982-04-01

An on-line methodology is proposed for assessing the robustness of a power system from the point of view of transient stability, and a scalar expression, the transient stability index, is accordingly derived. The reliability and sensitivity of this index are tested by means of simulations for a number of power system cases. The index is shown to be appropriate for online stability assessment, contingency evaluation and preventive control. 14 refs.

Towards an understanding of miRNA regulation

DEFF Research Database (Denmark)

Jensen, Trine Ilsø

miRNAs are well-known regulators of gene expression. They function post-transcriptionally by binding to complementary sites within the 3´UTR of target mRNAs, which mediates translational repression and destabilization. However, miRNA expression itself is also subjected to regulation. Here, we...... report a new method to investigate and potentially characterize the pri-miRNA transcript. Overexpression of a transdominant Drosha mutant, which is unable to cleave its substrate, enables stabilization of the pri-miRNA transcript. Drosha mutant immunoprecipitation from the nuclear compartment...... is performed followed by high-throughput sequencing (nuclear Drosha Mt2 RIPseq). This method allows for the detection of global pri-miRNA signature and also provides a method to potentially identify new Drosha substrates. Furthermore, data on the identification of a novel endogenous circular RNA sponge (ciRS-7...

Hypoxia‐induced alterations of G2 checkpoint regulators

OpenAIRE

Hasvold, Grete; Lund-Andersen, Christin; Lando, Malin; Patzke, Sebastian; Hauge, Sissel; Suo, ZhenHe; Lyng, Heidi; Syljuåsen, Randi G.

2016-01-01

Hypoxia promotes an aggressive tumor phenotype with increased genomic instability, partially due to downregulation of DNA repair pathways. However, genome stability is also surveilled by cell cycle checkpoints. An important issue is therefore whether hypoxia also can influence the DNA damage‐induced cell cycle checkpoints. Here, we show that hypoxia (24 h 0.2% O2) alters the expression of several G2 checkpoint regulators, as examined by microarray gene expression analysis and immunoblotting o...

A study on the development of regulatory guide to stability conformation and classification criteria of low and intermediate level radioactive waste

Energy Technology Data Exchange (ETDEWEB)

Lee, Geon Jae; Paek, Min Hoon; Park, Jong Gil; Han, Byeong Seop; Cheong, Jae Hak; Lee, Hae Chan; Yang, Jin Yeong; Hong, Hei Kwan; Park, Jin Baek [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

1994-01-15

The objectives of this study are to examine basic principles and terms and to suggest and recommend definite methods and criteria necessary for the classification and stability conformation of radioactive wastes. In this study, following studies were performed : investigate the domestic regulations related with the stability conformation and classification of radioactive wastes in order to keep mutual relationship and consistency between the regulations, investigate the sources, types and characteristics of domestic radioactive wastes as a basis for this study, investigate the classification criteria and methods of others countries in a general point of view and in the view point of disposal method, select the classification criteria factors for the domestic case and general case in the both general and domestic points of view, investigate the general test items for the stability conformation of radioactive waste forms and analysis on the test items and criteria of others countries for the mined cavity disposal and shallow land disposal in the view point of disposal method, experimental leaching and immersion tests for the borate and spent resin wastes as a study on the stability conformation of waste forms, selection of acceptance criteria for the both of disposal methods in the domestic and general cases.

Stabilized power constant alimentation; Alimentation regulee a puissance constante

Energy Technology Data Exchange (ETDEWEB)

Roussel, L [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1968-06-01

The study and realization of a stabilized power alimentation variable from 5 to 100 watts are described. In order to realize a constant power drift of Lithium compensated diodes, we have searched a 1 per cent precision of regulation and a response time minus than 1 sec. Recent components like Hall multiplicator and integrated amplifiers give this possibility and it is easy to use permutable circuits. (author) [French] On decrit l'etude et la realisation d'une alimentation a puissance constante reglable dans une gamme de 5 a 100 watts. Prevue pour le drift a puissance constante des diodes compensees au lithium, l'etude a ete menee en vue d'obtenir une precision de regulation de 1 pour cent et un temps de reponse inferieur a la seconde. Des systemes recents tels que multiplicateurs a effet Hall et circuits integres ont permis d'atteindre ce but tout en facilitant l'emploi de modules interchangeables. (auteur)

Stabilized power constant alimentation; Alimentation regulee a puissance constante

Energy Technology Data Exchange (ETDEWEB)

Roussel, L. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1968-06-01

The study and realization of a stabilized power alimentation variable from 5 to 100 watts are described. In order to realize a constant power drift of Lithium compensated diodes, we have searched a 1 per cent precision of regulation and a response time minus than 1 sec. Recent components like Hall multiplicator and integrated amplifiers give this possibility and it is easy to use permutable circuits. (author) [French] On decrit l'etude et la realisation d'une alimentation a puissance constante reglable dans une gamme de 5 a 100 watts. Prevue pour le drift a puissance constante des diodes compensees au lithium, l'etude a ete menee en vue d'obtenir une precision de regulation de 1 pour cent et un temps de reponse inferieur a la seconde. Des systemes recents tels que multiplicateurs a effet Hall et circuits integres ont permis d'atteindre ce but tout en facilitant l'emploi de modules interchangeables. (auteur)

Genome-Wide RNAi Ionomics Screen Reveals New Genes and Regulation of Human Trace Element Metabolism

OpenAIRE

Malinouski, Mikalai; Hasan, Nesrin M.; Zhang, Yan; Seravalli, Javier; Lin, Jie; Avanesov, Andrei; Lutsenko, Svetlana; Gladyshev, Vadim N.

2017-01-01

Trace elements are essential for human metabolism and dysregulation of their homeostasis is associated with numerous disorders. Here we characterize mechanisms that regulate trace elements in human cells by designing and performing a genome-wide high-throughput siRNA/ionomics screen, and examining top hits in cellular and biochemical assays. The screen reveals high stability of the ionomes, especially the zinc ionome, and yields known regulators and novel candidates. We further uncover fundam...

Chk2 regulates transcription-independent p53-mediated apoptosis in response to DNA damage

International Nuclear Information System (INIS)

Chen Chen; Shimizu, Shigeomi; Tsujimoto, Yoshihide; Motoyama, Noboru

2005-01-01

The tumor suppressor protein p53 plays a central role in the induction of apoptosis in response to genotoxic stress. The protein kinase Chk2 is an important regulator of p53 function in mammalian cells exposed to ionizing radiation (IR). Cells derived from Chk2-deficient mice are resistant to the induction of apoptosis by IR, and this resistance has been thought to be a result of the defective transcriptional activation of p53 target genes. It was recently shown, however, that p53 itself and histone H1.2 translocate to mitochondria and thereby induces apoptosis in a transcription-independent manner in response to IR. We have now examined whether Chk2 also regulates the transcription-independent induction of apoptosis by p53 and histone H1.2. The reduced ability of IR to induce p53 stabilization in Chk2-deficient thymocytes was associated with a marked impairment of p53 and histone H1 translocation to mitochondria. These results suggest that Chk2 regulates the transcription-independent mechanism of p53-mediated apoptosis by inducing stabilization of p53 in response to IR

Element diameter free stability parameters for stabilized methods applied to fluids

International Nuclear Information System (INIS)

Franca, L.P.; Madureira, A.L.

1992-08-01

Stability parameters for stabilized methods in fluids are suggested. The computation of the largest eigenvalue of a generalized eigenvalue problem replaces controversial definitions of element diameters and inverse estimate constants, used heretofore to compute these stability parameters. The design is employed in the advective-diffusive model, incompressible Navier-Stokes equations and the Stokes problem. (author)

Microbiological stability of rice tart stored at ambient temperature after baking

OpenAIRE

N'guessan, Elise; Cissé, Mohamed; Niyonzima, Eugene; Sindic, Marianne

2017-01-01

Very popular in Belgium, rice tart is a hot pastry sold in bakeries. It is then consumed at home, for dessert or snack. This study is conducted to investigate the microbiological stability of this foodstuff, from the end of baking to end user by consumers. In this purpose, 108 rice tart samples were collected from each of seven bakeries in five Belgium provinces. Physico-chimical analysis in addition to microbiological analysis were carried out in accordance with the European Regulation EC 20...

RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells.

Science.gov (United States)

Pandolfini, Luca; Luzi, Ettore; Bressan, Dario; Ucciferri, Nadia; Bertacchi, Michele; Brandi, Rossella; Rocchiccioli, Silvia; D'Onofrio, Mara; Cremisi, Federico

2016-05-06

Embryonic stem cells are intrinsically unstable and differentiate spontaneously if they are not shielded from external stimuli. Although the nature of such instability is still controversial, growing evidence suggests that protein translation control may play a crucial role. We performed an integrated analysis of RNA and proteins at the transition between naïve embryonic stem cells and cells primed to differentiate. During this transition, mRNAs coding for chromatin regulators are specifically released from translational inhibition mediated by RNA-induced silencing complex (RISC). This suggests that, prior to differentiation, the propensity of embryonic stem cells to change their epigenetic status is hampered by RNA interference. The expression of these chromatin regulators is reinstated following acute inactivation of RISC and it correlates with loss of stemness markers and activation of early cell differentiation markers in treated embryonic stem cells. We propose that RISC-mediated inhibition of specific sets of chromatin regulators is a primary mechanism for preserving embryonic stem cell pluripotency while inhibiting the onset of embryonic developmental programs.

Stability of dynamical systems on the role of monotonic and non-monotonic Lyapunov functions

CERN Document Server

Michel, Anthony N; Liu, Derong

2015-01-01

The second edition of this textbook provides a single source for the analysis of system models represented by continuous-time and discrete-time, finite-dimensional and infinite-dimensional, and continuous and discontinuous dynamical systems.  For these system models, it presents results which comprise the classical Lyapunov stability theory involving monotonic Lyapunov functions, as well as corresponding contemporary stability results involving non-monotonicLyapunov functions.Specific examples from several diverse areas are given to demonstrate the applicability of the developed theory to many important classes of systems, including digital control systems, nonlinear regulator systems, pulse-width-modulated feedback control systems, and artificial neural networks.   The authors cover the following four general topics:   -          Representation and modeling of dynamical systems of the types described above -          Presentation of Lyapunov and Lagrange stability theory for dynamical sy...

Natural Rate of Education as the Factor of Stability of Political Regime. Part I

Directory of Open Access Journals (Sweden)

Владимир Геннадьевич Иванов

2011-12-01

Full Text Available The given article contains hypothesis about the increasing level of influence of the system of tertiary education on stability of political regime in many modern countries. In order to reveal the mechanism of such influence the author proposes the concept natural rate of education which reflects optimal balance between labor market and educational system from the perspective of avoidance and tackling of social protests and instability. The author supposes that the stabilizing function of the system of tertiary education is caused by its role of the specific regulator of labor market and its capability to involve millions of young males, providing them long-term occupation. Under the state policy this stabilizing function may be enormously exaggerated and even reach the point of extremum and become counterproductive. The article contains interdisciplinary approach, being on junction of political science and economics. The author uses selected methodological foundations of theory of human capital and introduces the following notions: educational pyramid, educational bubble, educational scissors and others.

Effect of speed on local dynamic stability of locomotion under different task constraints in running.

Science.gov (United States)

Mehdizadeh, Sina; Arshi, Ahmed Reza; Davids, Keith

2014-01-01

A number of studies have investigated effects of speed on local dynamic stability of walking, although this relationship has been rarely investigated under changing task constraints, such as during forward and backward running. To rectify this gap in the literature, the aim of this study was to investigate the effect of running speed on local dynamic stability of forward and backward running on a treadmill. Fifteen healthy male participants took part in this study. Participants ran in forward and backward directions at speeds of 80%, 100% and 120% of their preferred running speed. The three-dimensional motion of a C7 marker was recorded using a motion capture system. Local dynamic stability of the marker was quantified using short- and long-term largest finite-time Lyapunov exponents (LyE). Results showed that short-term largest finite-time LyE values increased with participant speed meaning that local dynamic stability decreased with increasing speed. Long-term largest finite-time LyEs, however, remained unaffected as speed increased. Results of this study indicated that, as in walking, slow running is more stable than fast running. These findings improve understanding of how stability is regulated when constraints on the speed of movements is altered. Implications for the design of rehabilitation or sport practice programmes suggest how task constraints could be manipulated to facilitate adaptations in locomotion stability during athletic training.

Apoptosis inducer NGFI-B is degraded by the proteasome and stabilized by treatment with EGF

Energy Technology Data Exchange (ETDEWEB)

Strom, Bjorn O. [Department of Pharmaceutical Biosciences, University of Oslo, P.O. Box 1068 Blindern, N-0316 Oslo (Norway); Paulsen, Ragnhild E., E-mail: r.e.paulsen@farmasi.uio.no [Department of Pharmaceutical Biosciences, University of Oslo, P.O. Box 1068 Blindern, N-0316 Oslo (Norway)

2012-01-27

Highlights: Black-Right-Pointing-Pointer NGFI-B is a molecular target for some anti-cancer drugs. Black-Right-Pointing-Pointer NGFI-B turnover may be important for their anti-cancer action. Black-Right-Pointing-Pointer NGFI-B is degraded by the proteasome. Black-Right-Pointing-Pointer NGFI-B is stabilized by treatment with EGF. Black-Right-Pointing-Pointer Mimicking the EGF-induced phosphorylation also stabilizes the protein. -- Abstract: NGFI-B is a nuclear receptor and immediate early gene that is upregulated in many different tumour cell lines. As it is involved in cell death and survival, it has been suggested as a target for anti-cancer drugs. The protein level of NGFI-B is important for its functions and may be regulated through induction or stabilization. NGFI-B protein stability was studied using the protein synthesis inhibitor cycloheximide in CV1 cells transiently transfected with NGFI-B. Inhibiting the proteasome with MG132 stabilized NGFI-B, indicating that the proteasome is responsible for break-down of NGFI-B, as it is for many nuclear receptors. In order to determine regions responsible for the break-down of NGFI-B two N-terminal regions with high PEST-scores were deleted. Deletion of amino acids 122-195 containing a PEST-sequence which includes an ERK2 phosphorylation target, gave a more stable protein. In addition, treatment of the cells with the ERK2 activator EGF increased the stability of wild type NGFI-B. We then tested whether a mutation at threonine 142 influenced the stability of NGFI-B. We found that the phosphorylation-mimicking mutant NGFI-B T142E had an increased stability, while the non-phosphorylable mutant (T142A) showed similar stability to the wild type. Thus, EGF-stimulation of cells may be a mechanism for priming the cells for effects of NGFI-B by increasing its stability.

The role of the external auditor in the regulation and supervision of the UK banking system

OpenAIRE

Ojo, Marianne

2007-01-01

ABSTRACT The role of the external auditor in the supervisory process requires standards such as independence, objectivity and integrity to be achieved. Even though the regulator and external auditor perform similar functions, namely the verification of financial statements, they serve particular interests. The regulator works towards safeguarding financial stability and investor interests. On the other hand, the external auditor serves the private interests of the shareholders of a com...

Oestradiol reduces Liver Receptor Homolog-1 mRNA transcript stability in breast cancer cell lines

International Nuclear Information System (INIS)

Lazarus, Kyren A.; Zhao, Zhe; Knower, Kevin C.; To, Sarah Q.; Chand, Ashwini L.; Clyne, Colin D.

2013-01-01

Highlights: •LRH-1 is an orphan nuclear receptor that regulates tumor proliferation. •In breast cancer, high mRNA expression is associated with ER+ status. •In ER−ve cells, despite very low mRNA, we found abundant LRH-1 protein. •Our data show distinctly different LRH-1 protein isoforms in ER− and ER+ breast cancer cells. •This is due to differences in LRH-1 mRNA and protein stability rates. -- Abstract: The expression of orphan nuclear receptor Liver Receptor Homolog-1 (LRH-1) is elevated in breast cancer and promotes proliferation, migration and invasion in vitro. LRH-1 expression is regulated by oestrogen (E 2 ), with LRH-1 mRNA transcript levels higher in oestrogen receptor α (ERα) positive (ER+) breast cancer cells compared to ER− cells. However, the presence of LRH-1 protein in ER− cells suggests discordance between mRNA transcript levels and protein expression. To understand this, we investigated the impact of mRNA and protein stability in determining LRH-1 protein levels in breast cancer cells. LRH-1 transcript levels were significantly higher in ER+ versus ER− breast cancer cells lines; however LRH-1 protein was expressed at similar levels. We found LRH-1 mRNA and protein was more stable in ER− compared to ER+ cell lines. The tumor-specific LRH-1 variant isoform, LRH-1v4, which is highly responsive to E 2 , showed increased mRNA stability in ER− versus ER+ cells. In addition, in MCF-7 and T47-D cell lines, LRH-1 total mRNA stability was reduced with E 2 treatment, this effect mediated by ERα. Our data demonstrates that in ER− cells, increased mRNA and protein stability contribute to the abundant protein expression levels. Expression and immunolocalisation of LRH-1 in ER− cells as well as ER− tumors suggests a possible role in the development of ER− tumors. The modulation of LRH-1 bioactivity may therefore be beneficial as a treatment option in both ER− and ER+ breast cancer

Oestradiol reduces Liver Receptor Homolog-1 mRNA transcript stability in breast cancer cell lines

Energy Technology Data Exchange (ETDEWEB)

Lazarus, Kyren A. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Environmental and Biotechnology Centre, Swinburne University, Hawthorn, Victoria 3122 (Australia); Zhao, Zhe; Knower, Kevin C. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); To, Sarah Q. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168 (Australia); Chand, Ashwini L. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Clyne, Colin D., E-mail: Colin.clyne@princehenrys.org [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168 (Australia)

2013-08-30

Highlights: •LRH-1 is an orphan nuclear receptor that regulates tumor proliferation. •In breast cancer, high mRNA expression is associated with ER+ status. •In ER−ve cells, despite very low mRNA, we found abundant LRH-1 protein. •Our data show distinctly different LRH-1 protein isoforms in ER− and ER+ breast cancer cells. •This is due to differences in LRH-1 mRNA and protein stability rates. -- Abstract: The expression of orphan nuclear receptor Liver Receptor Homolog-1 (LRH-1) is elevated in breast cancer and promotes proliferation, migration and invasion in vitro. LRH-1 expression is regulated by oestrogen (E{sub 2}), with LRH-1 mRNA transcript levels higher in oestrogen receptor α (ERα) positive (ER+) breast cancer cells compared to ER− cells. However, the presence of LRH-1 protein in ER− cells suggests discordance between mRNA transcript levels and protein expression. To understand this, we investigated the impact of mRNA and protein stability in determining LRH-1 protein levels in breast cancer cells. LRH-1 transcript levels were significantly higher in ER+ versus ER− breast cancer cells lines; however LRH-1 protein was expressed at similar levels. We found LRH-1 mRNA and protein was more stable in ER− compared to ER+ cell lines. The tumor-specific LRH-1 variant isoform, LRH-1v4, which is highly responsive to E{sub 2}, showed increased mRNA stability in ER− versus ER+ cells. In addition, in MCF-7 and T47-D cell lines, LRH-1 total mRNA stability was reduced with E{sub 2} treatment, this effect mediated by ERα. Our data demonstrates that in ER− cells, increased mRNA and protein stability contribute to the abundant protein expression levels. Expression and immunolocalisation of LRH-1 in ER− cells as well as ER− tumors suggests a possible role in the development of ER− tumors. The modulation of LRH-1 bioactivity may therefore be beneficial as a treatment option in both ER− and ER+ breast cancer.

Learning-induced and stathmin-dependent changes in microtubule stability are critical for memory and disrupted in ageing

Science.gov (United States)

Uchida, Shusaku; Martel, Guillaume; Pavlowsky, Alice; Takizawa, Shuichi; Hevi, Charles; Watanabe, Yoshifumi; Kandel, Eric R.; Alarcon, Juan Marcos; Shumyatsky, Gleb P.

2014-01-01

Changes in the stability of microtubules regulate many biological processes, but their role in memory remains unclear. Here we show that learning causes biphasic changes in the microtubule-associated network in the hippocampus. In the early phase, stathmin is dephosphorylated, enhancing its microtubule-destabilizing activity by promoting stathmin-tubulin binding, whereas in the late phase these processes are reversed leading to an increase in microtubule/KIF5-mediated localization of the GluA2 subunit of AMPA receptors at synaptic sites. A microtubule stabilizer paclitaxel decreases or increases memory when applied at the early or late phases, respectively. Stathmin mutations disrupt changes in microtubule stability, GluA2 localization, synaptic plasticity and memory. Aged wild-type mice show impairments in stathmin levels, changes in microtubule stability, and GluA2 localization. Blocking GluA2 endocytosis rescues memory deficits in stathmin mutant and aged wild-type mice. These findings demonstrate a role for microtubules in memory in young adult and aged individuals. PMID:25007915

Modeling, Stability Analysis and Active Stabilization of Multiple DC-Microgrids Clusters

DEFF Research Database (Denmark)

Shafiee, Qobad; Dragicevic, Tomislav; Vasquez, Juan Carlos

2014-01-01

), and more especially during interconnection with other MGs, creating dc MG clusters. This paper develops a small signal model for dc MGs from the control point of view, in order to study stability analysis and investigate effects of CPLs and line impedances between the MGs on stability of these systems....... This model can be also used to synthesis and study dynamics of control loops in dc MGs and also dc MG clusters. An active stabilization method is proposed to be implemented as a dc active power filter (APF) inside the MGs in order to not only increase damping of dc MGs at the presence of CPLs but also...... to improve their stability while connecting to the other MGs. Simulation results are provided to evaluate the developed models and demonstrate the effectiveness of proposed active stabilization technique....

[The 2,3-diphosphoglycerate shunt and stabilization of the ATP level in mammalian erythrocytes].

Science.gov (United States)

Ataullakhanov, A I; Ataullakhanov, F I; Vitvitskiĭ, V M; Zhabotinskiĭ, A M; Pichugin, A V

1985-06-01

The mechanisms of regulation of energy metabolism in erythrocytes of various mammalian species were investigated. In native erythrocytes of man, sheep, cow, dog and mouse the dependencies of the rates of glucose uptake on ATP concentration (i.e., regulatory parameters of glycolysis) were measured. These parameters plotted in normalized coordinates are not species-specific (invariant). The dependence of the rate of ATP-consuming processes on ATP concentration has been studied for the first time in intact mammalian erythrocytes. This dependence was found to be linear only in the species, in whose erythrocytes the activity of 2,3-diphosphoglycerate shunt is practically zero. In all species under study, the stabilization of ATP level is provided for mainly by the hexokinase-phosphofructokinase system. A comparison of regulatory mechanisms of energy metabolism in mammalian (sheep, cow) erythrocytes, in which the 2,3-diphosphoglycerate shunt is absent, with human and animal erythrocytes, in which this pathway is active, points to the important role of the 2,3-diphosphoglycerate shunt in regulation of energy conversion in erythrocytes. This shunt operates as an additional stabilizer protecting the cell from extremal influences.

New image-stabilizing system

Science.gov (United States)

Zhao, Yuejin

1996-06-01

In this paper, a new method for image stabilization with a three-axis image- stabilizing reflecting prism assembly is presented, and the principle of image stabilization in this prism assembly, formulae for image stabilization and working formulae with an approximation up to the third power are given in detail. In this image-stabilizing system, a single chip microcomputer is used to calculate value of compensating angles and thus to control the prism assembly. Two gyroscopes act as sensors from which information of angular perturbation is obtained, three stepping motors drive the prism assembly to compensate for the movement of image produced by angular perturbation. The image-stabilizing device so established is a multifold system which involves optics, mechanics, electronics and computer.

Main tasks of studying strong regulation of excitation of complex electrical system generators

Energy Technology Data Exchange (ETDEWEB)

Gruzdev, I.A.; Yekimova, M.M.

1982-01-01

A survey is made of the current state of studies of the damping properties of complex electricity systems. The calculation programs of stability are based on frequency methods using the method of D-division. Now, when ARV of strong effect dominates at the SG, the task of coordinating their adjustments develops. Consequently, the following questions are discussed: study of the properties of quality functional with several points of regulation in the circuits of different structure; development of the efficient procedures for coordinating the ARV adjustment of the related energy systems; and creation of resources for solving these tasks. Results are presented of coordinating the ARV adjustments of the generators of the 3-machine electricity system. As an example, nonlinear relationships are shown between the obtained degree of stability and the coefficient of stabilization.

Stability and Hopf Bifurcation Analysis on a Nonlinear Business Cycle Model

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Liming Zhao

2016-01-01

Full Text Available This study begins with the establishment of a three-dimension business cycle model based on the condition of a fixed exchange rate. Using the established model, the reported study proceeds to describe and discuss the existence of the equilibrium and stability of the economic system near the equilibrium point as a function of the speed of market regulation and the degree of capital liquidity and a stable region is defined. In addition, the condition of Hopf bifurcation is discussed and the stability of a periodic solution, which is generated by the Hopf bifurcation and the direction of the Hopf bifurcation, is provided. Finally, a numerical simulation is provided to confirm the theoretical results. This study plays an important role in theoretical understanding of business cycle models and it is crucial for decision makers in formulating macroeconomic policies as detailed in the conclusions of this report.

Environmental Regulation Impacts on Eastern Interconnection Performance

Energy Technology Data Exchange (ETDEWEB)

Markham, Penn N [ORNL; Liu, Yilu [ORNL; Young II, Marcus Aaron [ORNL

2013-07-01

In the United States, recent environmental regulations will likely result in the removal of nearly 30 GW of oil and coal-fired generation from the power grid, mostly in the Eastern Interconnection (EI). The effects of this transition on voltage stability and transmission line flows have previously not been studied from a system-wide perspective. This report discusses the results of power flow studies designed to simulate the evolution of the EI over the next few years as traditional generation sources are replaced with environmentally friendlier ones such as natural gas and wind.

Computation of stabilizing PI and PID controllers using the stability boundary locus

International Nuclear Information System (INIS)

Tan, Nusret; Kaya, Ibrahim; Yeroglu, Celaleddin; Atherton, Derek P.

2006-01-01

In this paper, a new method for the calculation of all stabilizing PI controllers is given. The proposed method is based on plotting the stability boundary locus in the (k p , k i )-plane and then computing the stabilizing values of the parameters of a PI controller. The technique presented does not require sweeping over the parameters and also does not need linear programming to solve a set of inequalities. Thus it offers several important advantages over existing results obtained in this direction. Beyond stabilization, the method is used to shift all poles to a shifted half plane that guarantees a specified settling time of response. Computation of stabilizing PI controllers which achieve user specified gain and phase margins is studied. It is shown via an example that the stabilizing region in the (k p , k i )-plane is not always a convex set. The proposed method is also used to design PID controllers. The limiting values of a PID controller which stabilize a given system are obtained in the (k p , k i )-plane (k p , k d )-plane and (k i , k d )-plane. Furthermore, the proposed method is used to compute all the parameters of a PI controller which stabilize a control system with an interval plant family. Examples are given to show the benefits of the method presented

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

Nrf2, the Master Regulator of Anti-Oxidative Responses

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Sandra Vomund

2017-12-01

Full Text Available Tight regulation of inflammation is very important to guarantee a balanced immune response without developing chronic inflammation. One of the major mediators of the resolution of inflammation is the transcription factor: the nuclear factor erythroid 2-like 2 (Nrf2. Stabilized following oxidative stress, Nrf2 induces the expression of antioxidants as well as cytoprotective genes, which provoke an anti-inflammatory expression profile, and is crucial for the initiation of healing. In view of this fundamental modulatory role, it is clear that both hyper- or hypoactivation of Nrf2 contribute to the onset of chronic diseases. Understanding the tight regulation of Nrf2 expression/activation and its interaction with signaling pathways, known to affect inflammatory processes, will facilitate development of therapeutic approaches to prevent Nrf2 dysregulation and ameliorate chronic inflammatory diseases. We discuss in this review the principle mechanisms of Nrf2 regulation with a focus on inflammation and autophagy, extending the role of dysregulated Nrf2 to chronic diseases and tumor development.

AGC kinases, mechanisms of regulation ‎and innovative drug development.

Science.gov (United States)

Leroux, Alejandro E; Schulze, Jörg O; Biondi, Ricardo M

2018-02-01

The group of AGC kinases consists of 63 evolutionarily related serine/threonine protein kinases comprising PDK1, PKB/Akt, SGK, PKC, PRK/PKN, MSK, RSK, S6K, PKA, PKG, DMPK, MRCK, ROCK, NDR, LATS, CRIK, MAST, GRK, Sgk494, and YANK, while two other families, Aurora and PLK, are the most closely related to the group. Eight of these families are physiologically activated downstream of growth factor signalling, while other AGC kinases are downstream effectors of a wide range of signals. The different AGC kinase families share aspects of their mechanisms of inhibition and activation. In the present review, we update the knowledge of the mechanisms of regulation of different AGC kinases. The conformation of the catalytic domain of many AGC kinases is regulated allosterically through the modulation of the conformation of a regulatory site on the small lobe of the kinase domain, the PIF-pocket. The PIF-pocket acts like an ON-OFF switch in AGC kinases with different modes of regulation, i.e. PDK1, PKB/Akt, LATS and Aurora kinases. In this review, we make emphasis on how the knowledge of the molecular mechanisms of regulation can guide the discovery and development of small allosteric modulators. Molecular probes stabilizing the PIF-pocket in the active conformation are activators, while compounds stabilizing the disrupted site are allosteric inhibitors. One challenge for the rational development of allosteric modulators is the lack of complete structural information of the inhibited forms of full-length AGC kinases. On the other hand, we suggest that the available information derived from molecular biology and biochemical studies can already guide screening strategies for the identification of innovative mode of action molecular probes and the development of selective allosteric drugs for the treatment of human diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

STABILIZATION OF A MIXED WASTE SLUDGE SURROGATE CONTAINING MORE THAN 260 PPM MERCURY

International Nuclear Information System (INIS)

Smith, W. J.; Feizollahi, F.; Brimley, R.

2002-01-01

In an earlier demonstration of an innovative mercury stabilization technology for the Department of Energy, ATG's full-scale process stabilized mercury in soils that initially contained more than 260 ppm of mercury of unknown speciation. The treated waste satisfied the leaching standards for mercury that qualify wastes containing less than 260 ppm for land disposal. This paper describes the extension of that work to demonstrate a full-scale process for the stabilization of a representative sludge that contained more than 260 ppm of Hg of several mercury species. RCRA (Resource Conservation and Recovery Act) regulations now require the recovery of mercury from any waste containing more than 260 ppm of mercury, usually with thermal retorts. The results of this work with a surrogate sludge, and of the previous work with an actual soil, support a proposal now before the U.S. EPA (Environmental Protection Agency) to allow such wastes to be stabilized without retorting. The full-scale demonstration with a sulfide reagent reduced the mercury concentrations in extracts of treated sludge below the relevant leaching standard, a Universal Treatment Standard (UTS) limit of 0.025 mg mercury per liter of leachate generated by the Toxicity Characteristic Leaching Procedure (TCLP). The sulfide formulation reduced the concentration to about onehalf the UTS limit

RCRA facility stabilization initiative

International Nuclear Information System (INIS)

1995-02-01

The RCRA Facility Stabilization Initiative was developed as a means of implementing the Corrective Action Program's management goals recommended by the RIS for stabilizing actual or imminent releases from solid waste management units that threaten human health and the environment. The overall goal of stabilization is to, as situations warrant, control or abate threats to human health and/or the environment from releases at RCRA facilities, and/or to prevent or minimize the further spread of contamination while long-term remedies are pursued. The Stabilization initiative is a management philosophy and should not be confused with stabilization technologies

Recent Progress in Stability and Stabilization of Systems with Time-Delays

Directory of Open Access Journals (Sweden)

Magdi S. Mahmoud

2017-01-01

Full Text Available This paper overviews the research investigations pertaining to stability and stabilization of control systems with time-delays. The prime focus is the fundamental results and recent progress in theory and applications. The overview sheds light on the contemporary development on the linear matrix inequality (LMI techniques in deriving both delay-independent and delay-dependent stability results for time-delay systems. Particular emphases will be placed on issues concerned with the conservatism and the computational complexity of the results. Key technical bounding lemmas and slack variable introduction approaches will be presented. The results will be compared and connections of certain delay-dependent stability results are also discussed.

Nolinear stability analysis of nuclear reactors : expansion methods for stability domains

International Nuclear Information System (INIS)

Yang, Chae Yong

1992-02-01

Two constructive methods for estimating asymptotic stability domains of nonlinear reactor models are developed in this study: an improved Chang and Thorp's method based on expansion of a Lyapunov function and a new method based on expansion of any positive definite function. The methods are established on the concept of stability definitions of Lyapunov itself. The first method provides a sequence of stability regions that eventually approaches the exact stability domain, but requires many expansions in order to obtain the entire stability region because the starting Lyapunov function usually corresponds to a small stability region and because most dynamic systems are stiff. The second method (new method) requires only a positive definite function and thus it is easy to come up with a starting region. From a large starting region, the entire stability region is estimated effectively after sufficient iterations. It is particularly useful for stiff systems. The methods are applied to several nonlinear reactor models known in the literature: one-temperature feedback model, two-temperature feedback model, and xenon dynamics model, and the results are compared. A reactor feedback model for a pressurized water reactor (PWR) considering fuel and moderator temperature effects is developed and the nonlinear stability regions are estimated for the various values of design parameters by using the new method. The steady-state properties of the nonlinear reactor system are analyzed via bifurcation theory. The analysis of nonlinear phenomena is carried out for the various forms of reactivity feedback coefficients that are both temperature- (or power-) independent and dependent. If one of two temperature coefficients is positive, unstable limit cycles or multiplicity of the steady-state solutions appear when the other temperature coefficient exceeds a certain critical value. As an example, even though the fuel temperature coefficient is negative, if the moderator temperature

Biophysics of filament length regulation by molecular motors

International Nuclear Information System (INIS)

Kuan, Hui-Shun; Betterton, M D

2013-01-01

Regulating physical size is an essential problem that biological organisms must solve from the subcellular to the organismal scales, but it is not well understood what physical principles and mechanisms organisms use to sense and regulate their size. Any biophysical size-regulation scheme operates in a noisy environment and must be robust to other cellular dynamics and fluctuations. This work develops theory of filament length regulation inspired by recent experiments on kinesin-8 motor proteins, which move with directional bias on microtubule filaments and alter microtubule dynamics. Purified kinesin-8 motors can depolymerize chemically-stabilized microtubules. In the length-dependent depolymerization model, the rate of depolymerization tends to increase with filament length, because long filaments accumulate more motors at their tips and therefore shorten more quickly. When balanced with a constant filament growth rate, this mechanism can lead to a fixed polymer length. However, the mechanism by which kinesin-8 motors affect the length of dynamic microtubules in cells is less clear. We study the more biologically realistic problem of microtubule dynamic instability modulated by a motor-dependent increase in the filament catastrophe frequency. This leads to a significant decrease in the mean filament length and a narrowing of the filament length distribution. The results improve our understanding of the biophysics of length regulation in cells. (paper)

Fuzzy-Based Hybrid Control Algorithm for the Stabilization of a Tri-Rotor UAV.

Science.gov (United States)

Ali, Zain Anwar; Wang, Daobo; Aamir, Muhammad

2016-05-09

In this paper, a new and novel mathematical fuzzy hybrid scheme is proposed for the stabilization of a tri-rotor unmanned aerial vehicle (UAV). The fuzzy hybrid scheme consists of a fuzzy logic controller, regulation pole-placement tracking (RST) controller with model reference adaptive control (MRAC), in which adaptive gains of the RST controller are being fine-tuned by a fuzzy logic controller. Brushless direct current (BLDC) motors are installed in the triangular frame of the tri-rotor UAV, which helps maintain control on its motion and different altitude and attitude changes, similar to rotorcrafts. MRAC-based MIT rule is proposed for system stability. Moreover, the proposed hybrid controller with nonlinear flight dynamics is shown in the presence of translational and rotational velocity components. The performance of the proposed algorithm is demonstrated via MATLAB simulations, in which the proposed fuzzy hybrid controller is compared with the existing adaptive RST controller. It shows that our proposed algorithm has better transient performance with zero steady-state error, and fast convergence towards stability.

New stability and stabilization for switched neutral control systems

International Nuclear Information System (INIS)

Xiong Lianglin; Zhong Shouming; Ye Mao; Wu Shiliang

2009-01-01

This paper concerns stability and stabilization issues for switched neutral systems and presents new classes of piecewise Lyapunov functionals and multiple Lyapunov functionals, based on which, two new switching rules are introduced to stabilize the neutral systems. One switching rule is designed from the solution of the so-called Lyapunov-Metzler linear matrix inequalities. The other is based on the determination of average dwell time computed from a new class of linear matrix inequalities (LMIs). And then, state-feedback control is derived for the switched neutral control system mainly based on the state switching rules. Finally, three examples are given to demonstrate the effectiveness of the proposed method.

Combined effect of upstream surge chamber and sloping ceiling tailrace tunnel on dynamic performance of turbine regulating system of hydroelectric power plant

International Nuclear Information System (INIS)

Guo, Wencheng; Yang, Jiandong

2017-01-01

Highlights: • Nonlinear mathematical model and Hopf bifurcation analysis of turbine regulating system are presented. • Dynamic performance of turbine regulating system under 0.5 times Thoma sectional area is analyzed and a novel dynamic performance is revealed. • Relationship between two bifurcation lines and wave superposition is studied. • Combined effect mechanisms of upstream surge chamber and sloping ceiling tailrace tunnel on stability are revealed and optimization methods are proposed. - Abstract: Based on the nonlinear mathematical model of the turbine regulating system of hydroelectric power plant with upstream surge chamber and sloping ceiling tailrace tunnel and the Hopf bifurcation theory, this paper firstly studies the dynamic performance of the turbine regulating system under 0.5 times Thoma sectional area of surge chamber, and reveals a novel dynamic performance. Then, the relationship between the two bifurcation lines and the wave superposition of upstream surge chamber and sloping ceiling tailrace tunnel is analyzed. Finally, the effect mechanisms of the wave superposition on the system stability are investigated, and the methods to improve the system stability are proposed. The results indicate that: Under the combined effect of upstream surge chamber and sloping ceiling tailrace tunnel, the dynamic performance of the turbine regulating system of hydroelectric power plant shows an obvious difference on the two sides of the critical sectional area of surge chamber. There are two bifurcation lines for the condition of 0.5 times Thoma sectional area, i.e. Bifurcation line 1 and Bifurcation line 2, which represent the stability characteristics of the flow oscillation of “penstock-sloping ceiling tailrace tunnel” and the water-level fluctuation in upstream surge chamber, respectively. The stable domain of the system is determined by Bifurcation line 2. The effect of upstream surge chamber mainly depends on its sectional area, while the

Stability of Soil Organic Matter in Alpine Ecosystems: No Relationship with Vegetation

Science.gov (United States)

Matteodo, M.; Sebag, D.; Vittoz, P.; Verrecchia, E. P.

2016-12-01

There is an emerging understanding of mechanisms governing soil organic matter (SOM) stability, which is challenging the historical view of carbon persistence1. According to this alternative vision, SOM stability is not directly regulated by the molecular structure of plant inputs (i.e. the historical view), but the biotic and abiotic conditions of the surrounding environment which play a major role and mediate the influence of compound chemistry. The persistence of SOM is thus influenced by ecological conditions, controlling the access and activity of decomposers' enzymes and being ecosystem-dependent. In this study, we investigated differences of (1) carbon content, and (2) stability of organic matter in litter and organomineral layers from the most widespread plant communities at the subalpine-alpine level of the Swiss Alps. For this purpose, 230 samples from 47 soil profiles have been analysed across seven plant communities, along a subalpine-alpine elevation gradient. Both calcareous and siliceous grasslands were studied, as well as snowbed and ridge communities. Aboveground litter and A horizons were sampled and analysed using Rock-Eval Pyrolysis, a proxy-technique commonly used for the investigation of organic matter composition and stability2,3. Results show that the litter layers of the seven plant communities are significantly different in terms of total organic carbon (TOC) content, but slightly variable in terms of stability. The situation is radically different in the organomineral horizons where the amount of organic carbon is interestingly homogeneous, as well as the SOM stability. In mineral horizons, the amount and stability of SOM are mainly driven by the geological settings, and therefore vary in the different plant communities. These results show a clear disconnection between organic, organomineral, and mineral horizons in terms of factors governing soil organic matter stability. Consistent with the recent view of the carbon balance, plant input

Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis thaliana.

Science.gov (United States)

Giuntoli, Beatrice; Shukla, Vinay; Maggiorelli, Federica; Giorgi, Federico M; Lombardi, Lara; Perata, Pierdomenico; Licausi, Francesco

2017-10-01

The Group VII Ethylene Responsive Factors (ERFs-VII) RAP2.2 and RAP2.12 have been mainly characterized with regard to their contribution as activators of fermentation in plants. However, transcriptional changes measured in conditions that stabilize these transcription factors exceed the mere activation of this biochemical pathway, implying additional roles performed by the ERF-VIIs in other processes. We evaluated gene expression in transgenic Arabidopsis lines expressing a stabilized form of RAP2.12, or hampered in ERF-VII activity, and identified genes affected by this transcriptional regulator and its homologs, including some involved in oxidative stress response, which are not universally induced under anaerobic conditions. The contribution of the ERF-VIIs in regulating this set of genes in response to chemically induced or submergence-stimulated mitochondria malfunctioning was found to depend on the plant developmental stage. A similar age-dependent mechanism also restrained ERF-VII activity upon the core-hypoxic genes, independently of the N-end rule pathway, which is accounted for the control of the anaerobic response. To conclude, this study shed new light on a dual role of ERF-VII proteins under submergence: as positive regulators of the hypoxic response and as repressors of oxidative-stress related genes, depending on the developmental stage at which plants are challenged by stress conditions. © 2017 John Wiley & Sons Ltd.

Nutlin-3 down-regulates retinoblastoma protein expression and inhibits muscle cell differentiation

Energy Technology Data Exchange (ETDEWEB)

Walsh, Erica M. [Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118 (United States); Niu, MengMeng; Bergholz, Johann [Center of Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, 610014 China (China); Jim Xiao, Zhi-Xiong, E-mail: jxiao@bu.edu [Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118 (United States); Center of Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, 610014 China (China)

2015-05-29

The p53 tumor suppressor gene plays a critical role in regulation of proliferation, cell death and differentiation. The MDM2 oncoprotein is a major negative regulator for p53 by binding to and targeting p53 for proteasome-mediated degradation. The small molecule inhibitor, nutlin-3, disrupts MDM2-p53 interaction resulting in stabilization and activation of p53 protein. We have previously shown that nutlin-3 activates p53, leading to MDM2 accumulation as concomitant of reduced retinoblastoma (Rb) protein stability. It is well known that Rb is important in muscle development and myoblast differentiation and that rhabdomyosarcoma (RMS), or cancer of the skeletal muscle, typically harbors MDM2 amplification. In this study, we show that nutlin-3 inhibited myoblast proliferation and effectively prevented myoblast differentiation, as evidenced by lack of expression of muscle differentiation markers including myogenin and myosin heavy chain (MyHC), as well as a failure to form multinucleated myotubes, which were associated with dramatic increases in MDM2 expression and decrease in Rb protein levels. These results indicate that nutlin-3 can effectively inhibit muscle cell differentiation. - Highlights: • Nutlin-3 inhibits myoblast proliferation and prevents differentiation into myotubes. • Nutlin-3 increases MDM2 expression and down-regulates Rb protein levels. • This study has implication in nutlin-3 treatment of rhabdomyosarcomas.

Self-regulated dynamical criticality in human ECoG

Directory of Open Access Journals (Sweden)

Guillermo eSolovey

2012-07-01

Full Text Available Mounting experimental and theoretical results indicate that neural systems are poised near a critical state. In human subjects, however, most evidence comes from functional MRI studies, an indirect measurement of neuronal activity with poor temporal resolution. Electrocorticography (ECoG provides a unique window into human brain activity: each electrode records, with high temporal resolution, the activity resulting from the sum of the local field potentials of sim 10^5 neurons. We show that the human brain ECoG recordings display features of self-regulated dynamical criticality: dynamical modes of activation drift around the critical stability threshold, moving in and out of the unstable region and equilibrating the global dynamical state at a very fast time scale. Moreover, the analysis also reveals differences between the resting state and a motor task, associated with increased stability of a fraction of the dynamical modes.

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

Directory of Open Access Journals (Sweden)

Mario Sarcinelli

2004-09-01

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

pH regulation of the kinetic stability of the lipase from Thermomyces lanuginosus

DEFF Research Database (Denmark)

Wang, H.; Andersen, Kell Kleiner; Sehgal, P.

2013-01-01

Thermomyces lanuginosus lipase (TlL) is a kinetically stable protein, resistant toward both denaturation and refolding in the presence of the ionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant decyl maltoside (DecM). We investigate the pH dependence of this kinetic stability....... At pH 8, TlL remains folded and enzymatically active at multimillimolar surfactant concentrations but fails to refold from the acid urea-denatured state at submillimolar concentrations of SDS and DecM, indicating a broad concentration range of kinetic trapping or hysteresis. At pH 8, very few SDS...... molecules bind to TlL. The hysteresis SDS concentration range shrinks when moving to pH 4–6; in this pH range, SDS binds as micellelike clusters. Although hysteresis can be eliminated by reducing disulfide bonds, destabilizing the native state, and lowering the unfolding activation barrier, SDS sensitivity...

International cooperation for the development of consistent and stable transportation regulations to promote and enhance safety and security

International Nuclear Information System (INIS)

Strosnider, J.

2004-01-01

International commerce of radioactive materials crosses national boundaries, linking separate regulatory institutions with a common purpose and making it necessary for these institutions to work together in order to achieve common safety goals in a manner that does not place an undue burden on industry and commerce. Widespread and increasing use of radioactive materials across the world has led to increases in the transport of radioactive materials. The demand for consistency in the oversight of international transport has also increased to prevent unnecessary delays and costs associated with incongruent or redundant regulatory requirements by the various countries through which radioactive material is transported. The International Atomic Energy Agency (IAEA) is the authority for international regulation of transportation of radioactive materials responsible for promulgation of regulations and guidance for the establishment of acceptable methods of transportation for the international community. As such, the IAEA is seen as the focal point for consensus building between its Member States to develop consistency in transportation regulations and reviews and to ensure the safe and secure transport of radioactive material. International cooperation is also needed to ensure stability in our regulatory processes. Changes to transportation regulations should be based on an anticipated safety benefit supported by risk information and insights gained from continuing experience, evaluation, and research studies. If we keep safety as the principle basis for regulatory changes, regulatory stability will be enhanced. Finally, as we endeavour to maintain consistency and stability in our international regulations, we must be mindful of the new security challenges that lay before the international community as a result of a changing terrorist environment. Terrorism is a problem of global concern that also requires international cooperation and support, as we look for ways to

High beta and second stability region transport and stability analysis

International Nuclear Information System (INIS)

Hughes, M.H.; Phillps, M.W.; Todd, A.M.M.; Krishnaswami, J.; Hartley, R.

1992-09-01

This report describes ideal and resistive studies of high-beta plasmas and of the second stability region. Emphasis is focused on ''supershot'' plasmas in TFIR where MHD instabilities are frequently observed and which spoil their confinement properties. Substantial results are described from the analysis of these high beta poloidal plasmas. During these studies, initial pressure and safety factor profiles were obtained from the TRANSP code, which is used extensively to analyze experimental data. Resistive MBD stability studies of supershot equilibria show that finite pressure stabilization of tearing modes is very strong in these high βp plasmas. This has prompted a detailed re-examination of linear tearing mode theory in which we participated in collaboration with Columbia University and General Atomics. This finite pressure effect is shown to be highly sensitive to small scale details of the pressure profile. Even when an ad hoc method of removing this stabilizing mechanism is implemented, however, it is shown that there is only superficial agreement between resistive MBD stability computation and the experimental data. While the mode structures observed experimentally can be found computationally, there is no convincing correlation with the experimental observations when the computed results are compared with a large set of supershot data. We also describe both the ideal and resistive stability properties of TFIR equilibria near the transition to the second region. It is shown that the highest β plasmas, although stable to infinite-n ideal ballooning modes, can be unstable to the so called ''infernal'' modes associated with small shear. The sensitivity of these results to the assumed pressure and current density profiles is discussed. Finally, we describe results from two collaborative studies with PPPL. The first involves exploratory studies of the role of the 1/1 mode in tokamaks and, secondly, a study of sawtooth stabilization using ICRF

A universal trend of reduced mRNA stability near the translation-initiation site in prokaryotes and eukaryotes.

Directory of Open Access Journals (Sweden)

Wanjun Gu

2010-02-01

Full Text Available Recent studies have suggested that the thermodynamic stability of mRNA secondary structure near the start codon can regulate translation efficiency in Escherichia coli, and that translation is more efficient the less stable the secondary structure. We survey the complete genomes of 340 species for signals of reduced mRNA secondary structure near the start codon. Our analysis includes bacteria, archaea, fungi, plants, insects, fishes, birds, and mammals. We find that nearly all species show evidence for reduced mRNA stability near the start codon. The reduction in stability generally increases with increasing genomic GC content. In prokaryotes, the reduction also increases with decreasing optimal growth temperature. Within genomes, there is variation in the stability among genes, and this variation correlates with gene GC content, codon bias, and gene expression level. For birds and mammals, however, we do not find a genome-wide trend of reduced mRNA stability near the start codon. Yet the most GC rich genes in these organisms do show such a signal. We conclude that reduced stability of the mRNA secondary structure near the start codon is a universal feature of all cellular life. We suggest that the origin of this reduction is selection for efficient recognition of the start codon by initiator-tRNA.

Stability of Hyperthermophilic Proteins

DEFF Research Database (Denmark)

Stiefler-Jensen, Daniel

stability by randomly generate mutants and lengthy screening processes to identify the best new mutants. However, with the increase in available genomic sequences of thermophilic or hyperthermophilic organisms a world of enzymes with intrinsic high stability are now available. As these organisms are adapted...... to life at high temperatures so are their enzymes, as a result the high stability is accompanied by low activity at moderate temperatures. Thus, much effort had been put into decoding the mechanisms behind the high stability of the thermophilic enzymes. The hope is to enable scientist to design enzymes...... in the high stability of hyperthermophilic enzymes. The thesis starts with an introduction to the field of protein and enzyme stability with special focus on the thermophilic and hyperthermophilic enzymes and proteins. After the introduction three original research manuscripts present the experimental data...

The significance of translation regulation in the stress response

Science.gov (United States)

2013-01-01

RNA stabilization and lower dilution by growth counterbalanced this effect. Conclusions We show that the contribution of translational regulation to the control of gene expression is significant in the stress response. Post-transcriptional regulation is complex and not systematically co-directional with transcription regulation. Post-transcriptional regulation is important to the understanding of gene expression control. PMID:23985063

Bacterial translational regulations: high diversity between all mRNAs and major role in gene expression

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Picard Flora

2012-10-01

Full Text Available Abstract Background In bacteria, the weak correlations at the genome scale between mRNA and protein levels suggest that not all mRNAs are translated with the same efficiency. To experimentally explore mRNA translational level regulation at the systemic level, the detailed translational status (translatome of all mRNAs was measured in the model bacterium Lactococcus lactis in exponential phase growth. Results Results demonstrated that only part of the entire population of each mRNA species was engaged in translation. For transcripts involved in translation, the polysome size reached a maximum of 18 ribosomes. The fraction of mRNA engaged in translation (ribosome occupancy and ribosome density were not constant for all genes. This high degree of variability was analyzed by bioinformatics and statistical modeling in order to identify general rules of translational regulation. For most of the genes, the ribosome density was lower than the maximum value revealing major control of translation by initiation. Gene function was a major translational regulatory determinant. Both ribosome occupancy and ribosome density were particularly high for transcriptional regulators, demonstrating the positive role of translational regulation in the coordination of transcriptional networks. mRNA stability was a negative regulatory factor of ribosome occupancy and ribosome density, suggesting antagonistic regulation of translation and mRNA stability. Furthermore, ribosome occupancy was identified as a key component of intracellular protein levels underlining the importance of translational regulation. Conclusions We have determined, for the first time in a bacterium, the detailed translational status for all mRNAs present in the cell. We have demonstrated experimentally the high diversity of translational states allowing individual gene differentiation and the importance of translation-level regulation in the complex process linking gene expression to protein

Stability investigation of total parenteral nutrition admixture prepared in a hospital pharmacy

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Mirković Dušica

2008-01-01

Full Text Available Background/Aim. In the cases when nutrition of patients can not be orally nor enterally performed, parenteral nutrition is a method of the therapy that provides more successful and rapid recovery. In that way, hospitalization can be significantly shorter, healing costs reduced and mortality minimized. Total parenteral nutrition (TPN admixtures are the most complex systems which contain amino acids, carbohydrates, lipid emulsion, macroelectrolytes (Na+, K+, Ca2+, Mg2+, Cl-, SO42-, PO43-, oligoelements, hydro- and liposoluble vitamines, heparin, insulin and water. Concerning the mentioned complexity, special attention should be payed to physicochemical and microbiological stability of a mixture, because of interactions among components, that can be very hard to analyze. The aim of this study was to investigate the problem of stability of TPN admixtures prepared in a hospital pharmacy. Methods. Admixture TPN was aseptically prepared in laminar air - flow environment on the basis of the specified order in supplementing components and additives to basic solutions. Solutions were kept in sterile multicompartment ethylene-vinyl-acetate bags. After preparation and slow homogenization, TPN admixtures were submitted to physicochemical and microbiological stability analyses in various period of time. The assessment of physical stability of TPN admixture was done on the basis of visual inspection, determination of pH value and measuring of particle size. The investigation of sterility and pyrogenic test were performed according to Ph. Yug. V regulations. Results. Physico-chemical and microbiological analyses were applied and no significant changes in visual sense, pH value and droplet size stability of the TPN admixture were observed during the period of 60 hours. The lipid droplets were smaller in size than 5 μm, that is the most common pharmacopoeia requirement. Conclusion. The results of our study confirmed that a TPN admixture prepared in a hospital

A robust nonlinear stabilizer as a controller for improving transient stability in micro-grids.

Science.gov (United States)

Azimi, Seyed Mohammad; Afsharnia, Saeed

2017-01-01

This paper proposes a parametric-Lyapunov approach to the design of a stabilizer aimed at improving the transient stability of micro-grids (MGs). This strategy is applied to electronically-interfaced distributed resources (EI-DRs) operating with a unified control configuration applicable to all operational modes (i.e. grid-connected mode, islanded mode, and mode transitions). The proposed approach employs a simple structure compared with other nonlinear controllers, allowing ready implementation of the stabilizer. A new parametric-Lyapunov function is proposed rendering the proposed stabilizer more effective in damping system transition transients. The robustness of the proposed stabilizer is also verified based on both time-domain simulations and mathematical proofs, and an ultimate bound has been derived for the frequency transition transients. The proposed stabilizer operates by deploying solely local information and there are no needs for communication links. The deteriorating effects of the primary resource delays on the transient stability are also treated analytically. Finally, the effectiveness of the proposed stabilizer is evaluated through time-domain simulations and compared with the recently-developed stabilizers performed on a multi-resource MG. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Energy storage systems impact on the short-term frequency stability of distributed autonomous microgrids, an analysis using aggregate models

DEFF Research Database (Denmark)

Serban, Ioan; Teodorescu, Remus; Marinescu, Corneliu

2013-01-01

This study analyses the integration impact of battery energy storage systems (BESSs) on the short-term frequency control in autonomous microgrids (MGs). Short-term frequency stability relates with the primary or speed control level, as defined in the regulations of the classical grids. The focus...

Dynamic postural stability in blind athletes using the biodex stability system.

Science.gov (United States)

Aydoğ, E; Aydoğ, S T; Cakci, A; Doral, M N

2006-05-01

Three systems affect the upright standing posture in humans - visual, vestibular, and somatosensory. It is well known that the visually impaired individuals have bad postural balance. On the other hand, it is a well documented fact that some sports can improve postural balance. Therefore, it is aimed in this study to evaluate the dynamic postural stability in goal-ball athletes. Twenty blind goal-ball players, 20 sighted and 20 sedentary blind controls were evaluated using the Biodex Stability System. Three adaptation trials and three test evaluations (a 20-second balance test at a platform stability of 8) were applied to the blind people, and to the sighted with eyes open and closed. Dynamic postural stability was measured on the basis of three indices: overall, anteroposterior, and mediolateral. Means of each test score were calculated. The tests results were compared for the blind athletes, sighted (with eyes open and closed) subjects, and sedentary blind people. There were significant differences between the results of the blind people and the sighted subjects with regards to all of the three indices. Although the stability of goal-ball players was better than sedentary blinds', only ML index values were statistically different (4.47 +/- 1.24 in the goal-ball players; 6.46 +/- 3.42 in the sedentary blind, p = 0.04). Dynamic postural stability was demonstrated to be affected by vision; and it was found that blind people playing goal-ball 1 - 2 days per week have higher ML stability than the sedentary sighted people.

Can the UN Stabilize Mali? Towards a UN Stabilization Doctrine?

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Arthur Boutellis

2015-06-01

Full Text Available Almost two years after the deployment of the United Nations Multidimensional Integrated Stabilization Mission in Mali (MINUSMA in July 2013, the increasing number of asymmetric terrorist attacks targeting UN peacekeepers – in the context of a drawn-out peace process – has raised a number of questions in Mali, the sub-region, and in New York, over the relevance and adequacies of MINUSMA’s mandate and capabilities. It also raises a broader issue, of whether the consent-based UN peacekeeping tool is appropriate and can be effective in carrying out stabilization mandates in such a context and what doctrine such operations should be based on. The UN is indeed under increasing pressure from host countries and some African troop-contributing countries to go on the offensive. Member States have also increasingly recognized terrorism and organized crime as a strategic threat, and while opposed to the UN directly engaging in counterterrorism (CT operations, some may wish to see the UN playing a greater stabilization role following the January 2013 French military intervention in Mali. However, little guidance and means have been given so far to UN missions for dealing with such threats and implementing effective stabilization mandates. The High-Level Panel on Peace Operations, which recently released its report, noted that the usage of the term “stabilization” by the UN requires clarification. This article analyses the complex and evolving nature of threats in northern Mali and implications for MINUSMA and describes the military and political tools – including mediation – so far available within and outside the UN. The article concludes that the UN is bound to move towards stabilization when and if deployed in contexts such as Mali’s if it wants to remain relevant. However, such a move should be based on an overarching UN stabilization doctrine and context-specific UN-wide stabilization strategies which are first and foremost political

The BWR Stability Issue

International Nuclear Information System (INIS)

D'Auria, F.

2008-01-01

The purpose of this paper is to supply general information about Boiling Water Reactor (BWR) stability. The main concerned topics are: phenomenological aspects, experimental database, modelling features and capabilities, numerical models, three-dimensional modelling, BWR system performance during stability, stability monitoring and licensing aspects.

Stability of parallel flows

CERN Document Server

Betchov, R

2012-01-01

Stability of Parallel Flows provides information pertinent to hydrodynamical stability. This book explores the stability problems that occur in various fields, including electronics, mechanics, oceanography, administration, economics, as well as naval and aeronautical engineering. Organized into two parts encompassing 10 chapters, this book starts with an overview of the general equations of a two-dimensional incompressible flow. This text then explores the stability of a laminar boundary layer and presents the equation of the inviscid approximation. Other chapters present the general equation

Prolyl hydroxylase domain enzymes: important regulators of cancer metabolism

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Yang M

2014-08-01

Full Text Available Ming Yang,1 Huizhong Su,1 Tomoyoshi Soga,2 Kamil R Kranc,3 Patrick J Pollard1 1Cancer Biology and Metabolism Group, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK; 2Institute for Advanced Biosciences, Keio University, Mizukami, Tsuruoka, Yamagata, Japan; 3MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK Abstract: The hypoxia-inducible factor (HIF prolyl hydroxylase domain enzymes (PHDs regulate the stability of HIF protein by post-translational hydroxylation of two conserved prolyl residues in its α subunit in an oxygen-dependent manner. Trans-4-prolyl hydroxylation of HIFα under normal oxygen (O2 availability enables its association with the von Hippel-Lindau (VHL tumor suppressor pVHL E3 ligase complex, leading to the degradation of HIFα via the ubiquitin-proteasome pathway. Due to the obligatory requirement of molecular O2 as a co-substrate, the activity of PHDs is inhibited under hypoxic conditions, resulting in stabilized HIFα, which dimerizes with HIFβ and, together with transcriptional co-activators CBP/p300, activates the transcription of its target genes. As a key molecular regulator of adaptive response to hypoxia, HIF plays important roles in multiple cellular processes and its overexpression has been detected in various cancers. The HIF1α isoform in particular has a strong impact on cellular metabolism, most notably by promoting anaerobic, whilst inhibiting O2-dependent, metabolism of glucose. The PHD enzymes also seem to have HIF-independent functions and are subject to regulation by factors other than O2, such as by metabolic status, oxidative stress, and abnormal levels of endogenous metabolites (oncometabolites that have been observed in some types of cancers. In this review, we aim to summarize current understandings of the function and regulation of PHDs in cancer with an emphasis on their roles in metabolism. Keywords: prolyl hydroxylase domain (PHD

Effect of core stability exercise on postural stability in children with Down syndrome

OpenAIRE

Sobhy M. Aly

2016-01-01

Down syndrome is one of the commonest causes of developmental delay in children. Postural stability problems often exist with Down syndrome. To investigate the effect of core stability exercises on postural stability in children with down syndrome. Thirty children (21 boys and 9 girls) with down syndrome, with ages ranged from 6 to 10 years were participated in this study. They were assigned randomlyinto study and control group. Study group received core stability exercises and conventional p...

Triphenylamine - a 'new' stabilizer for nitrocellulose based propellants. Pt. 1: chemical stability studies

Energy Technology Data Exchange (ETDEWEB)

Wilker, Stephan; Heeb, Gerhard [WIWEB ASt Heimerzheim, Grosses Cent, 53913 Swisttal (Germany); Vogelsanger, Beat [Nitrochemie Wimmis AG, Niesenstr. 44, 3752 Wimmis (Switzerland); Petrzilek, Jan; Skladal, Jan [Explosia a.s. - Research Institute of Industrial Chemistry (VUPCH), 532 17 Pardubice (Czech Republic)

2007-04-15

Triphenylamine (TPA) was used for the first time in France in 1937 as a stabilizer for propellants. The stability of those samples was described as 'good'. Around 1950 an American group produced TPA stabilized propellants and investigated the decomposition mechanism. Apart from one single experiment in the 1970s no further attempts were made to take TPA as a stabilizer for propellants. With the background of an increasingly critical discussion about nitrosamines in propellants and their declaration of being carcinogenic, TPA revealed a renaissance since the year 2000. To achieve the goal of nitrosamine free propellants several TPA stabilized propellants were produced. Their processability, stability and ballistic properties were investigated. This publication summarizes the most important results of stability tests on more than 30 different TPA stabilized propellants including the decomposition mechanism, the synthesis of the consecutive products and their stabilizing properties. In addition, the internal compatibility of TPA with the most important propellant ingredients is discussed and its relative decomposition rate is compared with that of other stabilizers. In summary TPA is a suitable stabilizer for propellants. It has nevertheless two disadvantages. It is relatively rapidly consumed in double base formulations (which makes it difficult to pass the criteria of AOP-48, Ed. 2) and the stabilizing activity of the two major consecutive products 4-NO{sub 2}-TPA and especially 4,4{sup '}-di-NO{sub 2}-TPA is low. (Abstract Copyright [2007], Wiley Periodicals, Inc.)

Stability of matter

International Nuclear Information System (INIS)

Thirring, W.

1985-01-01

Basing on quantum mechanics and the simple Hamiltonian consisting of kinetic energy and Coulomb potential, heuristic arguments and estimates are used to guess the essential stability properties of many-particle systems. In view of applications in astrophysics, gravitation as a second potential and thermodynamic arguments are added. The guesses thus obtained are confronted with known exact results. The connection between the stabilities against explosion and against implosion, and thermodynamic stability is considered. In systems with a particle number larger than approx= 10 54 (corresponding to the Jupiter mass) gravitational energy prevails over the electrostatic energy and determines the history of a star. Negative specific heat accompanies life and death of a star. Finally the role of stability and instability in the universe for life is outlined. (G.Q.)

Glycogen synthase kinase 3 alpha phosphorylates and regulates the osteogenic activity of Osterix.

Science.gov (United States)

Li, Hongyan; Jeong, Hyung Min; Choi, You Hee; Lee, Sung Ho; Jeong, Hye Gwang; Jeong, Tae Cheon; Lee, Kwang Youl

2013-05-10

Osteoblast-specific transcription factor Osterix is a zinc-finger transcription factor that required for osteoblast differentiation and new bone formation. The function of Osterix can be modulated by post-translational modification. Glycogen synthase kinase 3 alpha (GSK3α) is a multifunctional serine/threonine protein kinase that plays a role in the Wnt signaling pathways and is implicated in the control of several regulatory proteins and transcription factors. In the present study, we investigated how GSK3α regulates Osterix during osteoblast differentiation. Wide type GSK3α up-regulated the protein level, protein stability and transcriptional activity of Osterix. These results suggest that GSK3α regulates osteogenic activity of Osterix. Copyright © 2013 Elsevier Inc. All rights reserved.

MODERN APPROACHES TO THE IMPLEMENTATION OF MONETARY POLICY AND THE REGULATION OF FINANCIAL SYSTEMS

Directory of Open Access Journals (Sweden)

Radu CUHAL

2013-01-01

Full Text Available This study determines the modern approaches to the implementation of monetary policy and regulation of financial systems. Set of measures to prevent and overcome the financial crisis is grounded taking into consideration different areas of research and the IMF. New tasks of monetary policy in central banks are specified and they are intended to ensure the financial stability of the state (within the common fiscal policy. The main directions of elaboration and implementation of new monetary policy mechanism, which is intended to ensure the effective solution of problems in macro prudential supervision and financial stability, are examined.

Modern approaches to the implementation of monetary policy and the regulation of financial systems

Directory of Open Access Journals (Sweden)

Basistîi Nicolae

2013-01-01

Full Text Available This study determines the modern approaches to the implementation of monetary policy and regulation of financial systems. Set of measures to prevent and overcome the financial crisis is grounded taking into consideration different areas of research and the IMF.New tasks of monetary policy in central banks are specified and they are intended to ensure the financial stability of the state (within the common fiscal policy.The main directions of elaboration and implementation of new monetary policy mechanism, which is intended to ensure the effective solution of problems in macro prudential supervision and financial stability, are examined.

Stability evaluation of occlusal changes obtained with Fränkel's Function Regulator-2

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Tânia Gnecchi Tanaka

2012-12-01

Full Text Available OBJECTIVE: To analyze the stability of occlusal changes promoted by the Frankel's Functional Regulator 2 (FR-2, in a mean period of 7.16 years post treatment. METHODS: Fifty-four pairs of models were evaluated, from 18 patients treated with FR-2. All patients had Class II, division 1 malocclusion, with initial mean age of 10.77 years and were treated with FR-2 for 18 months. The models were evaluated at the beginning of treatment (T1, at the end (T2 and after 7.16 years post treatment (T3. For occlusal evaluation, the treatment priority index (TPI was applied on the three analyzed phases. The alterations that occurred between phases were verified with one another through paired Student's t test, with critical value of 0.05. RESULTS: A statistically significant reduction of TPI was verified, from the initial to the final phase of the treatment, reflecting the efficiency of treatment performed with FR-2, specially due to improvement in molar relation, overjet and overbite. Apart from this, the Class II correction remained stable over time. CONCLUSIONS: In this way, it is concluded that the FR-2 appliance showed to be efficient for the dental correction of Class II malocclusion, with stable occlusal results after 7.16 years post treatment.OBJETIVO: analisar a estabilidade das alterações oclusais promovidas pelo aparelho Regulador de Função Fränkel-2 (RF-2, num período médio de 7,16 anos pós-tratamento. MÉTODOS: foram avaliados 54 pares de modelos, provenientes de 18 pacientes tratados por meio do aparelho RF-2. Todos os pacientes possuíam má oclusão de Classe II, divisão 1, com idade inicial média de 10,77 anos e foram tratados com o RF-2 por 18 meses. Os modelos foram avaliados no início do tratamento (T1, no final do tratamento (T2 e decorridos 7,16 anos pós-tratamento ativo (T3. Para a avaliação oclusal, aplicou-se o Índice de Prioridade de Tratamento (IPT nas três fases analisadas. As alterações ocorridas entre as fases

Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock.

Science.gov (United States)

Narasimamurthy, Rajesh; Virshup, David M

2017-01-01

An approximately 24-h biological timekeeping mechanism called the circadian clock is present in virtually all light-sensitive organisms from cyanobacteria to humans. The clock system regulates our sleep-wake cycle, feeding-fasting, hormonal secretion, body temperature, and many other physiological functions. Signals from the master circadian oscillator entrain peripheral clocks using a variety of neural and hormonal signals. Even centrally controlled internal temperature fluctuations can entrain the peripheral circadian clocks. But, unlike other chemical reactions, the output of the clock system remains nearly constant with fluctuations in ambient temperature, a phenomenon known as temperature compensation. In this brief review, we focus on recent advances in our understanding of the posttranslational modifications, especially a phosphoswitch mechanism controlling the stability of PER2 and its implications for the regulation of temperature compensation.

Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock

Directory of Open Access Journals (Sweden)

David M. Virshup

2017-04-01

Full Text Available An approximately 24-h biological timekeeping mechanism called the circadian clock is present in virtually all light-sensitive organisms from cyanobacteria to humans. The clock system regulates our sleep–wake cycle, feeding–fasting, hormonal secretion, body temperature, and many other physiological functions. Signals from the master circadian oscillator entrain peripheral clocks using a variety of neural and hormonal signals. Even centrally controlled internal temperature fluctuations can entrain the peripheral circadian clocks. But, unlike other chemical reactions, the output of the clock system remains nearly constant with fluctuations in ambient temperature, a phenomenon known as temperature compensation. In this brief review, we focus on recent advances in our understanding of the posttranslational modifications, especially a phosphoswitch mechanism controlling the stability of PER2 and its implications for the regulation of temperature compensation.

Regulation of the flow rate of liquid-metal coolants on experimental stands

International Nuclear Information System (INIS)

Kozlov, F.A.; Laptev, G.I.

1988-01-01

Systems for automatic regulation of the flow rate of alkali metals, based on the series ENIV, VIN, and TsLIN three-phase electromagnetic pumps with a pumping rate of 0.5-200 m 3 per hour, were evaluated. The stability of each system was investigated by the method of undamped oscillations. The possibility of employing the analog temperature regulators VRT-2, RPA-T, and R113 was assessed. The functions performed by the most suitable automatic regulation unit, the RPA-T, were described. The limiting period of flow rate oscillations with a maximum gain of the RPA-T in alkali metal regulation systems equaled about 0.5 sec and the minimum integration time of the RPA-T was an order of magnitude longer than the optimal interval. Use of the systems on experimental stands enabled raising the quality of the studies and expanding the zone of servicing of the facilities by the same personnel

Evaluation of petroleum products pricing regulation in Nova Scotia : a 2 year review

International Nuclear Information System (INIS)

2008-11-01

Gasoline price regulation was introduced in Nova Scotia on July 1st, 2006. This report presented the findings and recommendations of a review of the first two years of the gasoline price regulation in Nova Scotia. The regulations had three main objectives. This review examined whether, and to what extent, they were achieved. The objectives were to stabilize price, maintain industry infrastructure, and minimize cost to consumers. The report described the rationale for the regulation, study objectives, and approach taken to gasoline regulation in Nova Scotia, including the objectives and technical aspects of how regulation works. The gasoline market in Nova Scotia was examined, including the market structure and competitive behaviour in an unregulated market. The report also provided some theoretical perspectives on how regulation was likely to affect industry structure and competitive behaviour. The extent to which the regulation was meeting its objectives was then assessed and perspectives on the regulation from consumers, retailers and wholesalers were offered. Last, the report provided a review of the findings in terms of the key elements of regulatory design and set out recommendations for improving the system. It was recommended that in order to improve certainty, particularly given the regulated price differences amongst grades, the regulations should be amended to include grade specifications referencing octane ratings. tabs., figs

Long non-coding RNAs as regulators of the endocrine system.

Science.gov (United States)

Knoll, Marko; Lodish, Harvey F; Sun, Lei

2015-03-01

Long non-coding RNAs (lncRNAs) are a large and diverse group of RNAs that are often lineage-specific and that regulate multiple biological functions. Many are nuclear and are essential parts of ribonucleoprotein complexes that modify chromatin segments and establish active or repressive chromatin states; others are cytosolic and regulate the stability of mRNA or act as microRNA sponges. This Review summarizes the current knowledge of lncRNAs as regulators of the endocrine system, with a focus on the identification and mode of action of several endocrine-important lncRNAs. We highlight lncRNAs that have a role in the development and function of pancreatic β cells, white and brown adipose tissue, and other endocrine organs, and discuss the involvement of these molecules in endocrine dysfunction (for example, diabetes mellitus). We also address the associations of lncRNAs with nuclear receptors involved in major hormonal signalling pathways, such as estrogen and androgen receptors, and the relevance of these associations in certain endocrine cancers.

A novel vehicle dynamics stability control algorithm based on the hierarchical strategy with constrain of nonlinear tyre forces

Science.gov (United States)

Li, Liang; Jia, Gang; Chen, Jie; Zhu, Hongjun; Cao, Dongpu; Song, Jian

2015-08-01

Direct yaw moment control (DYC), which differentially brakes the wheels to produce a yaw moment for the vehicle stability in a steering process, is an important part of electric stability control system. In this field, most control methods utilise the active brake pressure with a feedback controller to adjust the braked wheel. However, the method might lead to a control delay or overshoot because of the lack of a quantitative project relationship between target values from the upper stability controller to the lower pressure controller. Meanwhile, the stability controller usually ignores the implementing ability of the tyre forces, which might be restrained by the combined-slip dynamics of the tyre. Therefore, a novel control algorithm of DYC based on the hierarchical control strategy is brought forward in this paper. As for the upper controller, a correctional linear quadratic regulator, which not only contains feedback control but also contains feed forward control, is introduced to deduce the object of the stability yaw moment in order to guarantee the yaw rate and side-slip angle stability. As for the medium and lower controller, the quantitative relationship between the vehicle stability object and the target tyre forces of controlled wheels is proposed to achieve smooth control performance based on a combined-slip tyre model. The simulations with the hardware-in-the-loop platform validate that the proposed algorithm can improve the stability of the vehicle effectively.

Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions

Science.gov (United States)

Doyle, Andrew D.; Carvajal, Nicole; Jin, Albert; Matsumoto, Kazue; Yamada, Kenneth M.

2015-11-01

The physical properties of two-dimensional (2D) extracellular matrices (ECMs) modulate cell adhesion dynamics and motility, but little is known about the roles of local microenvironmental differences in three-dimensional (3D) ECMs. Here we generate 3D collagen gels of varying matrix microarchitectures to characterize their regulation of 3D adhesion dynamics and cell migration. ECMs containing bundled fibrils demonstrate enhanced local adhesion-scale stiffness and increased adhesion stability through balanced ECM/adhesion coupling, whereas highly pliable reticular matrices promote adhesion retraction. 3D adhesion dynamics are locally regulated by ECM rigidity together with integrin/ECM association and myosin II contractility. Unlike 2D migration, abrogating contractility stalls 3D migration regardless of ECM pore size. We find force is not required for clustering of activated integrins on 3D native collagen fibrils. We propose that efficient 3D migration requires local balancing of contractility with ECM stiffness to stabilize adhesions, which facilitates the detachment of activated integrins from ECM fibrils.

Development of an analogue multiplexed regulation for periodic 1. order delayed processes; Etude et realisation d'une regulation analogique multiplexee pour processus aperiodiques du 1. ordre avec retard pur

Energy Technology Data Exchange (ETDEWEB)

Amblard, J C [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

1967-07-15

The present note deals with the study regulations of the sampled type, for 1. order process with simple delay. In order to obtain a good stability in such regulations, together with acceptable performances, it is interesting to use polynomial type correctors acting directly on the sampled error signals. The active elements of these correctors can be shared by all the channels to be controlled. Furthermore, the determination of the correction parameters results from an optimal study of the system. In the second part is described the construction of a multiplexed regulation for diffusion ovens. (author) [French] La presente note concerne l'etude des regulations de type echantillonne, pour processus du 1. ordre avec retard pur. Pour obtenir une bonne stabilite de telles regulations, ainsi que des performances correcte il est interessant d'utiliser des correcteurs de type polynomial, agissant directement sur les signaux d'erreur echantillonnes. Les elements actifs de ces correcteurs peuvent etre pris communs a toutes les voies a controler. D'autre part, la determination des parametres de correction decoula d'une etude optimale du systeme. Dans une seconde partie on decrit la realisation d'une regulation multiplexee de fours a diffusion. (auteur)

Rescue of glaucoma-causing mutant myocilin thermal stability by chemical chaperones

Science.gov (United States)

Burns, J. Nicole; Orwig, Susan D.; Harris, Julia L.; Watkins, J. Derrick; Vollrath, Douglas; Lieberman, Raquel L.

2010-01-01

Mutations in myocilin cause an inherited form of open angle glaucoma, a prevalent neurodegenerative disorder associated with increased intraocular pressure. Myocilin forms part of the trabecular meshwork extracellular matrix presumed to regulate intraocular pressure. Missense mutations, clustered in the olfactomedin (OLF) domain of myocilin, render the protein prone to aggregation in the endoplasmic reticulum of trabecular meshwork cells, causing cell dysfunction and death. Cellular studies have demonstrated temperature-sensitive secretion of myocilin mutants, but difficulties in expression and purification have precluded biophysical characterization of wild-type (wt) myocilin and disease-causing mutants in vitro. We have overcome these limitations by purifying wt and select glaucoma-causing mutant (D380A, I477N, I477S, K423E) forms of the OLF domain (228–504) fused to maltose binding protein (MBP) from E. coli. Monomeric fusion proteins can be isolated in solution. To determine the relative stability of wt and mutant OLF domains, we developed a fluorescence thermal stability assay without removal of MBP, and provide the first direct evidence that mutated OLF is folded but less thermally stable than wt. We tested the ability of seven chemical chaperones to stabilize mutant myocilin. Only sarcosine and trimethylamine N-oxide were capable of shifting the melting temperature of all mutants tested to near that of wt OLF. Our work lays the foundation for the identification of tailored small molecules capable of stabilizing mutant myocilin and promoting secretion to the extracellular matrix, to better control intraocular pressure and ultimately delay the onset of myocilin glaucoma. PMID:20334347

Stability of heterodyne terahertz receivers

NARCIS (Netherlands)

Kooi, J.W.; Baselmans, J.J.A.; Baryshev, A.; Schieder, R.; Hajenius, M.; Gao, J.R.; Klapwijk, T.M.; Voronov, B.; Gol'tsman, G.

2006-01-01

In this paper we discuss the stability of heterodyne terahertz receivers based on small volume NbN phonon cooled hot electron bolometers (HEBs). The stability of these receivers can be broken down in two parts: the intrinsic stability of the HEB mixer and the stability of the local oscillator (LO)

Stabilization

Directory of Open Access Journals (Sweden)

Muhammad H. Al-Malack

2016-07-01

Full Text Available Fuel oil flyash (FFA produced in power and water desalination plants firing crude oils in the Kingdom of Saudi Arabia is being disposed in landfills, which increases the burden on the environment, therefore, FFA utilization must be encouraged. In the current research, the effect of adding FFA on the engineering properties of two indigenous soils, namely sand and marl, was investigated. FFA was added at concentrations of 5%, 10% and 15% to both soils with and without the addition of Portland cement. Mixtures of the stabilized soils were thoroughly evaluated using compaction, California Bearing Ratio (CBR, unconfined compressive strength (USC and durability tests. Results of these tests indicated that stabilized sand mixtures could not attain the ACI strength requirements. However, marl was found to satisfy the ACI strength requirement when only 5% of FFA was added together with 5% of cement. When the FFA was increased to 10% and 15%, the mixture’s strength was found to decrease to values below the ACI requirements. Results of the Toxicity Characteristics Leaching Procedure (TCLP, which was performed on samples that passed the ACI requirements, indicated that FFA must be cautiously used in soil stabilization.

Yield stability and relationships among stability parameters in faba bean (Vicia faba L. genotypes

Directory of Open Access Journals (Sweden)

Tamene Temesgen

2015-06-01

Full Text Available Sixteen faba bean genotypes were evaluated in 13 environments in Ethiopia during the main cropping season for three years (2009–2011. The objectives of the study were to evaluate the yield stability of the genotypes and the relative importance of different stability parameters for improving selection in faba bean. The study was conducted using a randomized complete block design with four replications. G × E interaction and yield stability were estimated using 17 different stability parameters. Pooled analysis of variance for grain yield showed that the main effects of both genotypes and environments, and the interaction effect, were highly significant (P ≤ 0.001 and (P ≤ 0.01, respectively. The environment main effect accounted for 89.27% of the total yield variation, whereas genotype and G × E interaction effects accounted for 2.12% and 3.31%, respectively. Genotypic superiority index (Pi and FT3 were found to be very informative for selecting both high-yielding and stable faba bean genotypes. Twelve of the 17 stability parameters, including CVi, RS, α, λ, S2di, bi, Si(2, Wi, σi2, EV, P59, and ASV, were influenced simultaneously by both yield and stability. They should accordingly be used as complementary criteria to select genotypes with high yield and stability. Although none of the varieties showed consistently superior performance across all environments, the genotype EK 01024-1-2 ranked in the top third of the test entries in 61.5% of the test environments and was identified as the most stable genotype, with type I stability. EK 01024-1-2 also showed a 17.0% seed size advantage over the standard varieties and was released as a new variety in 2013 for wide production and named “Gora”. Different stability parameters explained genotypic performance differently, irrespective of yield performance. It was accordingly concluded that assessment of G × E interaction and yield stability should not be based on a single or a few

Stability of heterodyne terahertz receivers

OpenAIRE

Kooi, J. W.; Baselmans, J. J. A.; Baryshev, A.; Schieder, R.; Hajenius, M.; Gao, J. R.; Klapwijk, T. M.; Voronov, B.; Gol'tsman, G.

2006-01-01

In this paper we discuss the stability of heterodyne terahertz receivers based on small volume NbN phonon cooled hot electron bolometers (HEBs). The stability of these receivers can be broken down in two parts: the intrinsic stability of the HEB mixer and the stability of the local oscillator (LO) signal injection scheme. Measurements show that the HEB mixer stability is limited by gain fluctuations with a 1/f spectral distribution. In a 60 MHz noise bandwidth this results in an Allan varian...

A capacitor-free CMOS LDO regulator with AC-boosting and active-feedback frequency compensation

Energy Technology Data Exchange (ETDEWEB)

Zhou Qianneng; Wang Yongsheng; Lai Fengchang, E-mail: qianneng@hit.edu.c [Microelectronics Center, Harbin Institute of Technology, Harbin 150001 (China)

2009-04-15

A capacitor-free CMOS low-dropout (LDO) regulator for system-on-chip (SoC) applications is presented. By adopting AC-boosting and active-feedback frequency compensation (ACB-AFFC), the proposed LDO regulator, which is independent of an off-chip capacitor, provides high closed-loop stability. Moreover, a slew rate enhancement circuit is adopted to increase the slew rate and decrease the output voltage dips when the load current is suddenly switched from low to high. The LDO regulator is designed and fabricated in a 0.6 mum CMOS process. The active silicon area is only 770 x 472 mum{sup 2}. Experimental results show that the total error of the output voltage due to line variation is less than +-0.197%. The load regulation is only 0.35 mV/mA when the load current changes from 0 to 100 mA.

The Self-esteem Stability Scale (SESS) for Cross-Sectional Direct Assessment of Self-esteem Stability

OpenAIRE

Tobias Altmann; Marcus Roth

2018-01-01

Self-esteem stability describes fluctuations in the level of self-esteem experienced by individuals over a brief period of time. In recent decades, self-esteem stability has repeatedly been shown to be an important variable affecting psychological functioning. However, measures of self-esteem stability are few and lacking in validity. In this paper, we present the Self-Esteem Stability Scale (SESS), a unidimensional and very brief scale to directly assess self-esteem stability. In four studie...

Interval stability for complex systems

Science.gov (United States)

Klinshov, Vladimir V.; Kirillov, Sergey; Kurths, Jürgen; Nekorkin, Vladimir I.

2018-04-01

Stability of dynamical systems against strong perturbations is an important problem of nonlinear dynamics relevant to many applications in various areas. Here, we develop a novel concept of interval stability, referring to the behavior of the perturbed system during a finite time interval. Based on this concept, we suggest new measures of stability, namely interval basin stability (IBS) and interval stability threshold (IST). IBS characterizes the likelihood that the perturbed system returns to the stable regime (attractor) in a given time. IST provides the minimal magnitude of the perturbation capable to disrupt the stable regime for a given interval of time. The suggested measures provide important information about the system susceptibility to external perturbations which may be useful for practical applications. Moreover, from a theoretical viewpoint the interval stability measures are shown to bridge the gap between linear and asymptotic stability. We also suggest numerical algorithms for quantification of the interval stability characteristics and demonstrate their potential for several dynamical systems of various nature, such as power grids and neural networks.

Multiple layers of posttranslational regulation refine circadian clock activity in Arabidopsis.

Science.gov (United States)

Seo, Pil Joon; Mas, Paloma

2014-01-01

The circadian clock is a cellular time-keeper mechanism that regulates biological rhythms with a period of ~24 h. The circadian rhythms in metabolism, physiology, and development are synchronized by environmental cues such as light and temperature. In plants, proper matching of the internal circadian time with the external environment confers fitness advantages on plant survival and propagation. Accordingly, plants have evolved elaborated regulatory mechanisms that precisely control the circadian oscillations. Transcriptional feedback regulation of several clock components has been well characterized over the past years. However, the importance of additional regulatory mechanisms such as chromatin remodeling, protein complexes, protein phosphorylation, and stability is only starting to emerge. The multiple layers of circadian regulation enable plants to properly synchronize with the environmental cycles and to fine-tune the circadian oscillations. This review focuses on the diverse posttranslational events that regulate circadian clock function. We discuss the mechanistic insights explaining how plants articulate a high degree of complexity in their regulatory networks to maintain circadian homeostasis and to generate highly precise waveforms of circadian expression and activity.

Legal culture as a factor of social stability

Directory of Open Access Journals (Sweden)

M M Akulich

2015-12-01

Full Text Available The article examines legal culture as a factor of stability in developing societies referring to the concepts of culture proposed by P.A. Sorokin, L.N. Kogan, M.T. Iovchuk and other famous sociologists. The authors state that in the modern sociological literature legal culture is studied mainly from the theoretical rather than empirical standpoint: the sociology has accumulated a lot of data on the legal culture, although its study in the context of agreements and conflicts, stability and destructiveness is not enough. Legal culture should be regarded as a regulator and stabilizer of social interactions and relationships in both specific countries and the global space. Thus, identifying regional and global aspects of legal culture has become an important theoretical problem of the sociological studies nowadays as well as considering legal culture in relation to moral, economic and political values and priorities. The authors argue that it is not possible to build a state of law and civil society without raising the level of legal culture, and present the results of the sociological study of the legal culture in the south of the Tyumen region conducted in 2013. This survey revealed an average level of following the law in 55% of the local population, although 90% consider themselves law-abiding citizens. At the same time, 46% believe in the possibility to manipulate the law, and 60% approve the principle of equity of the law. The authors conclude that the identified average level of legal culture among the local population is an indicator of a quite stable and successful development of the region under study.

Plants from Chernobyl zone could shed light on genome stability in radioactive environment

Science.gov (United States)

Shevchenko, Galina; Talalaiev, Oleksandr; Doonan, John

2016-07-01

For nearly 30 years, despite of chronic radiation, flora in Chernobyl zone continue to flourish, evidencing the adaptation of plants to such an environment. Keeping in mind interplanetary missions, this phenomenon is a challenge for plant space research since it highlights the possible mechanisms of genome protection and stabilization in harmful environment. Plants are sessile organisms and, contrary to animals, could not escape the external impact. Therefore, plants should evolve the robust system allowing DNA-protection against damage, which is of special interest. Our investigations show that Arabidopsis thaliana from Chernobyl zone tolerate radiomimetics and heavy metals better than control plants from non-polluted areas. Besides, its genome is less affected by such mutagens. qPCR investigations have revealed up-regulation of some genes involved in DNA damage response. In particular, expression of ATR is increased slightly and downstream expression of CycB1:1 gene is increased significantly after bleomycin treatment suggesting role of ATR-dependent pathway in genome stabilization. Several DNA repair pathways are known to exist in plants. We continue investigations on gene expression from different DNA repair pathways as well as cell cycle regulation and investigation of PCD hallmarks in order to reveal the mechanism of plant tolerance to radiation environment. Our investigations provide unique information for space researchers working on biotechnology of radiation tolerant plants.

The statistical stability phenomenon

CERN Document Server

Gorban, Igor I

2017-01-01

This monograph investigates violations of statistical stability of physical events, variables, and processes and develops a new physical-mathematical theory taking into consideration such violations – the theory of hyper-random phenomena. There are five parts. The first describes the phenomenon of statistical stability and its features, and develops methods for detecting violations of statistical stability, in particular when data is limited. The second part presents several examples of real processes of different physical nature and demonstrates the violation of statistical stability over broad observation intervals. The third part outlines the mathematical foundations of the theory of hyper-random phenomena, while the fourth develops the foundations of the mathematical analysis of divergent and many-valued functions. The fifth part contains theoretical and experimental studies of statistical laws where there is violation of statistical stability. The monograph should be of particular interest to engineers...

Nonlinear Synergetic Governor Controllers for Steam Turbine Generators to Enhance Power System Stability

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Xingbao Ju

2017-07-01

Full Text Available This paper proposes a decentralized nonlinear synergetic governor controller (NSGC for turbine generators to enhance power system stability by using synergetic control theory and the feedback linearization technique. The precise feedback linearization model of a turbine-generator with a steam valve control is obtained, at first, by using a feedback linearization technique. Then based on this model, a manifold is defined as a linear combination of the deviation of the rotor angle, speed deviation, and speed derivative. The control law of the proposed NSGC is deduced and the stability condition of the whole closed-loop system is subsequently analyzed. According to the requirement of the primary frequency regulation, an additional proportional integral (PI controller is designed to dynamically track the steady-state value of the rotor angle. Case studies are undertaken based on a single-machine infinite-bus system and the New England system, respectively. Simulation results show that the proposed NSGC can suppress the power oscillations and improve transient stability more effectively in comparison with the conventional proportional-integral-derivative (PID governor controller. Moreover, the proposed NSGC is robust to the variations of the system operating conditions.

Sleep stability and transitions in patients with idiopathic REM sleep behavior disorder and patients with Parkinson's disease

DEFF Research Database (Denmark)

Christensen, Julie Anja Engelhard; Jennum, Poul; Koch, Henriette

2016-01-01

Objective: Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) are at high risk of developing Parkinson's disease (PD). As wake/sleep-regulation is thought to involve neurons located in the brainstem and hypothalamic areas, we hypothesize that the neurodegeneration in i......RBD/PD is likely to affect wake/sleep and REM/non-REM (NREM) sleep transitions. Methods: We determined the frequency of wake/sleep and REM/NREM sleep transitions and the stability of wake (W), REM and NREM sleep as measured by polysomnography (PSG) in 27 patients with PD, 23 patients with iRBD, 25 patients...... with periodic leg movement disorder (PLMD) and 23 controls. Measures were computed based on manual scorings and data-driven labeled sleep staging. Results: Patients with PD showed significantly lower REM stability than controls and patients with PLMD. Patients with iRBD had significantly lower REM stability...

Probabilistic stability analysis: the way forward for stability analysis of sustainable power systems.

Science.gov (United States)

Milanović, Jovica V

2017-08-13

Future power systems will be significantly different compared with their present states. They will be characterized by an unprecedented mix of a wide range of electricity generation and transmission technologies, as well as responsive and highly flexible demand and storage devices with significant temporal and spatial uncertainty. The importance of probabilistic approaches towards power system stability analysis, as a subsection of power system studies routinely carried out by power system operators, has been highlighted in previous research. However, it may not be feasible (or even possible) to accurately model all of the uncertainties that exist within a power system. This paper describes for the first time an integral approach to probabilistic stability analysis of power systems, including small and large angular stability and frequency stability. It provides guidance for handling uncertainties in power system stability studies and some illustrative examples of the most recent results of probabilistic stability analysis of uncertain power systems.This article is part of the themed issue 'Energy management: flexibility, risk and optimization'. © 2017 The Author(s).

Gravity stabilizes itself

International Nuclear Information System (INIS)

Chakraborty, Sumanta; SenGupta, Soumitra

2017-01-01

We show that a possible resolution to the stabilization of an extra spatial dimension (radion) can be obtained solely in the context of gravitational dynamics itself without the necessity of introducing any external stabilizing field. In this scenario the stabilized value of the radion field gets determined in terms of the parameters appearing in the higher curvature gravitational action. Furthermore, the mass of the radion field and its coupling to the standard model fields are found to be in the weak scale implying possible signatures in the TeV scale colliders. Some resulting implications are also discussed. (orig.)

Gravity stabilizes itself

Energy Technology Data Exchange (ETDEWEB)

Chakraborty, Sumanta; SenGupta, Soumitra [Indian Association for the Cultivation of Science, Department of Theoretical Physics, Kolkata (India)

2017-08-15

We show that a possible resolution to the stabilization of an extra spatial dimension (radion) can be obtained solely in the context of gravitational dynamics itself without the necessity of introducing any external stabilizing field. In this scenario the stabilized value of the radion field gets determined in terms of the parameters appearing in the higher curvature gravitational action. Furthermore, the mass of the radion field and its coupling to the standard model fields are found to be in the weak scale implying possible signatures in the TeV scale colliders. Some resulting implications are also discussed. (orig.)

26S Proteasome regulation of Ankrd1/CARP in adult rat ventricular myocytes and human microvascular endothelial cells

International Nuclear Information System (INIS)

Samaras, Susan E.; Chen, Billy; Koch, Stephen R.; Sawyer, Douglas B.; Lim, Chee Chew; Davidson, Jeffrey M.

2012-01-01

Highlights: ► The 26S proteasome regulates Ankrd1 levels in cardiomyocytes and endothelial cells. ► Ankrd1 protein degrades 60-fold faster in endothelial cells than cardiomyocytes. ► Differential degradation appears related to nuclear vs. sarcolemmal localization. ► Endothelial cell density shows uncoupling of Ankrd1 mRNA and protein levels. -- Abstract: Ankyrin repeat domain 1 protein (Ankrd1), also known as cardiac ankyrin repeat protein (CARP), increases dramatically after tissue injury, and its overexpression improves aspects of wound healing. Reports that Ankrd1/CARP protein stability may affect cardiovascular organization, together with our findings that the protein is crucial to stability of the cardiomyocyte sarcomere and increased in wound healing, led us to compare the contribution of Ankrd1/CARP stability to its abundance. We found that the 26S proteasome is the dominant regulator of Ankrd1/CARP degradation, and that Ankrd1/CARP half-life is significantly longer in cardiomyocytes (h) than endothelial cells (min). In addition, higher endothelial cell density decreased the abundance of the protein without affecting steady state mRNA levels. Taken together, our data and that of others indicate that Ankrd1/CARP is highly regulated at multiple levels of its expression. The striking difference in protein half-life between a muscle and a non-muscle cell type suggests that post-translational proteolysis is correlated with the predominantly structural versus regulatory role of the protein in the two cell types.

Getting the right balance between regulation and governance in the non-bank financial sector

Directory of Open Access Journals (Sweden)

David G Mayes

2012-10-01

Full Text Available This paper uses the example of the collapse of the finance company sector in New Zealand in 2006-2010 to illustrate the problems with light touch regulation and a reliance on good governance to ensure financial stability. It shows two major governance failures, the first in the governance of the sector by the authorities and the second, serious failures in corporate governance by the firms involved. While a light touch may assist economic development it also increases fragility. New Zealand has now switched to a greater emphasis on regulation and to a better alignment of incentives to ensure good governance. While other countries might consider implementing aspects of its new bank resolution regime most are opting for considerably more regulation and compliance costs.

Ankyrin G expression is associated with androgen receptor stability, invasiveness, and lethal outcome in prostate cancer patients.

Science.gov (United States)

Wang, Tingting; Abou-Ouf, Hatem; Hegazy, Samar A; Alshalalfa, Mohammed; Stoletov, Konstantin; Lewis, John; Donnelly, Bryan; Bismar, Tarek A

2016-12-01

Ankyrin G (ANK3) is a member of the Ankyrin family, which functions to provide cellular stability by anchoring the cytoskeleton to the plasma membrane. Deregulation of ANK3 expression has been observed in multiple human cancers but its mechanism remains unknown. ANK3 expression in relation to disease progression and patients' outcome was investigated in two cohorts of prostate cancer (PCA). Mechanistic studies were carried out in vitro and in vivo using several PCA cell lines and the avian embryo model. Silencing ANK3 resulted in significant reduction of cell proliferation through an AR-independent mechanism. Decreased ANK3 expression delayed S phase to G2/M cell cycle transition and reduced the expression of cyclins A and B. However, cells with knocked-down ANK3 exhibited significant increase in cell invasion through an AR-dependent mechanism. Furthermore, we found that ANK3 is a regulator of AR protein stability. ANK3 knockdown also promoted cancer cell invasion and extravasations in vivo using the avian embryo model (p cancer tissues was correlated with better cancer-specific survival of PCA patients (p = 0.012). Silencing ANK3 results in significant reduction of cell proliferation through an AR-independent mechanism. ANK3 knockdown results in significant increase in cell invasion through an AR-dependent mechanism. ANK3 is a regulator of AR protein stability. ANK3 knockdown also promotes cancer cell invasion and extravasation in vivo using the avian embryo model.

Calculational-theoretical studies of the system of local automated regulators and lateral ionization chambers

International Nuclear Information System (INIS)

Aleksakov, A.N.; Emel'yanov, I.Ya.; Nikolaev, E.V.; Panin, V.M.; Podlazov, L.N.; Rogova, V.D.

1987-01-01

Methods of engineering synthesis of the systems for nuclear reactor local automated power regulation and radial-azimuthal energy distribution stabilization operating according to lateral ionization chamber signals are described. Results of calculational-theoretical investigations into the system efficiency and peculiarities of its reaction to some perturbations typical of the RBMK type reactors are considered

Cyber Deterrence and Stability

Energy Technology Data Exchange (ETDEWEB)

Goychayev, Rustam [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Carr, Geoffrey A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Weise, Rachel A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Donnelly, David A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Clements, Samuel L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Benz, Jacob M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Rodda, Kabrena E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bartholomew, Rachel A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); McKinnon, Archibald D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Andres, Richard B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2017-09-30

Throughout the 20th and early 21st centuries, deterrence and arms control have been cornerstones of strategic stability between the superpowers. However, the weaponization of the cyber realm by State actors and the multipolar nature of cyber conflict now undermines that stability. Strategic stability is the state in which nations believe that if they act aggressively to undermine U.S. national interests and the post-World War II liberal democratic order, the consequences will outweigh the benefits. The sense of lawlessness and lack of consequences in the cyber realm embolden States to be more aggressive in taking actions that undermine stability. Accordingly, this paper examines 1) the role of deterrence and arms control in securing cyber stability, and 2) the limitations and challenges associated with these traditional national security paradigms as applied to this emerging threat domain. This paper demonstrates that many 20th-century deterrence and arms control concepts are not particularly applicable in the cyber realm. However, they are not entirely irrelevant. The United States can distill lessons learned from this rich deterrence and arms control experience to develop and deploy a strategy to advance cyber stability.

Experimental and theoretical studies on stability of new stabilizers for N-methyl-P-nitroaniline derivative in CMDB propellants

Energy Technology Data Exchange (ETDEWEB)

Tang, Qiufan [Xi’an Modern Chemistry Research Institute, Xi’an 710065 (China); Fan, Xuezhong, E-mail: xuezhongfan@126.com [Xi’an Modern Chemistry Research Institute, Xi’an 710065 (China); Li, Jizhen [Xi’an Modern Chemistry Research Institute, Xi’an 710065 (China); Key Laboratory of Applied Surface and Colloid Chemistry, MOE/School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710062 (China); Bi, Fuqiang; Fu, Xiaolong; Zhai, Lianjie [Xi’an Modern Chemistry Research Institute, Xi’an 710065 (China)

2017-04-05

Highlights: • Five new stabilizers have been designed and synthesized. • The influence of the carbon chain length on the stability of propellants was studied. • Effects of temperature on the reactions of stabilizers and nitrogen oxides were explained. • The new stabilizer n-BNA was one of the most promising stabilizers. - Abstract: Although N-methyl-P-nitroaniline (MNA) was a quite effective stabilizer in composite modified double base (CMDB) propellants, it undergoes crystallization easily from nitroglycerin (NG) during storage. In order to improve its solubility in nitroglycerin (NG) and the stability in propellants, several new stabilizers including N-ethyl-p-nitroaniline (ENA), N-n-propyl-p-nitroaniline (n-PNA), N-i-propyl-p-nitroaniline (i-PNA), N-n-butyl-p-nitroaniline (n-BNA) and N-t-butyl-p-nitroaniline (t-BNA) were designed and synthesized to replace MNA by increasing the carbon chain length. The interaction between NG and different stabilizers was simulation by Materials Studio 5.5 and the stability and the high temperature stability performance of those new stabilizers in propellants were calculated by Gaussian 09. It was found that both the solubility of new stabilizers in NG and the stability and the high temperature stability performance of those in propellants were improved when the carbon chain length of substitution groups on nitrogen atom was increased. Thus, the n-BNA was a most potential stabilizer. Then all properties of the stabilizers were studied experimentally, which was agreement well with the theoretical analysis.

Nitride stabilized core/shell nanoparticles

Science.gov (United States)

Kuttiyiel, Kurian Abraham; Sasaki, Kotaro; Adzic, Radoslav R.

2018-01-30

Nitride stabilized metal nanoparticles and methods for their manufacture are disclosed. In one embodiment the metal nanoparticles have a continuous and nonporous noble metal shell with a nitride-stabilized non-noble metal core. The nitride-stabilized core provides a stabilizing effect under high oxidizing conditions suppressing the noble metal dissolution during potential cycling. The nitride stabilized nanoparticles may be fabricated by a process in which a core is coated with a shell layer that encapsulates the entire core. Introduction of nitrogen into the core by annealing produces metal nitride(s) that are less susceptible to dissolution during potential cycling under high oxidizing conditions.

Regulation of corneal stroma extracellular matrix assembly.

Science.gov (United States)

Chen, Shoujun; Mienaltowski, Michael J; Birk, David E

2015-04-01

The transparent cornea is the major refractive element of the eye. A finely controlled assembly of the stromal extracellular matrix is critical to corneal function, as well as in establishing the appropriate mechanical stability required to maintain corneal shape and curvature. In the stroma, homogeneous, small diameter collagen fibrils, regularly packed with a highly ordered hierarchical organization, are essential for function. This review focuses on corneal stroma assembly and the regulation of collagen fibrillogenesis. Corneal collagen fibrillogenesis involves multiple molecules interacting in sequential steps, as well as interactions between keratocytes and stroma matrix components. The stroma has the highest collagen V:I ratio in the body. Collagen V regulates the nucleation of protofibril assembly, thus controlling the number of fibrils and assembly of smaller diameter fibrils in the stroma. The corneal stroma is also enriched in small leucine-rich proteoglycans (SLRPs) that cooperate in a temporal and spatial manner to regulate linear and lateral collagen fibril growth. In addition, the fibril-associated collagens (FACITs) such as collagen XII and collagen XIV have roles in the regulation of fibril packing and inter-lamellar interactions. A communicating keratocyte network contributes to the overall and long-range regulation of stromal extracellular matrix assembly, by creating micro-domains where the sequential steps in stromal matrix assembly are controlled. Keratocytes control the synthesis of extracellular matrix components, which interact with the keratocytes dynamically to coordinate the regulatory steps into a cohesive process. Mutations or deficiencies in stromal regulatory molecules result in altered interactions and deficiencies in both transparency and refraction, leading to corneal stroma pathobiology such as stromal dystrophies, cornea plana and keratoconus. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dual Regulation of Voltage-Sensitive Ion Channels by PIP2

Directory of Open Access Journals (Sweden)

Aldo A Rodríguez Menchaca

2012-09-01

Full Text Available Over the past 16 years, there has been an impressive number of ion channels shown to be sensitive to the major phosphoinositide in the plasma membrane, phosphatidilinositol 4,5-bisphosphate (PIP2. Among them are voltage-gated channels, which are crucial for both neuronal and cardiac excitability. Voltage-gated calcium (Cav channels were shown to be regulated bidirectionally by PIP2. On one hand, PIP2 stabilized their activity by reducing current rundown but on the other hand it produced a voltage-dependent inhibition by shifting the activation curve to more positive voltages. For voltage-gated potassium (Kv channels PIP2 was first shown to prevent N-type inactivation. Careful examination of the effects of PIP2 on the activation mechanism of Kv1.2 has shown a similar bidirectional regulation as in the Cav channels. The two effects could be distinguished kinetically, in terms of their sensitivities to PIP2 and by distinct molecular determinants. The rightward shift of the Kv1.2 voltage dependence implicated basic residues in the S4-S5 linker and was consistent with stabilization of the inactive state of the voltage sensor. A third type of a voltage-gated ion channel modulated by PIP2 is the hyperpolarization-activated cyclic nucleotide-gated (HCN channel. PIP2 has been shown to enhance the opening of HCN channels by shifting their voltage-dependent activation toward depolarized potentials. The sea urchin HCN channel, SpIH, showed again a PIP2-mediated bidirectional effect but in reverse order than the depolarization-activated Cav and Kv channels: a voltage-dependent potentiation, like the mammalian HCN channels, but also an inhibition of the cGMP-induced current activation. Just like the Kv1.2 channels, distinct molecular determinants underlied the PIP2 dual effects on SpIH channels. The dual regulation of these very different ion channels, all of which are voltage dependent, points to conserved mechanisms of regulation of these channels by PIP2.

Biological stability of drinking water: controlling factors, methods and challenges

Directory of Open Access Journals (Sweden)

Emmanuelle ePrest

2016-02-01

Full Text Available Biological stability of drinking water refers to the concept of providing consumers with drinking water of same microbial quality at the tap as produced at the water treatment facility. However, uncontrolled growth of bacteria can occur during distribution in water mains and premise plumbing, and can lead to hygienic (e.g. development of opportunistic pathogens, aesthetic (e.g. deterioration of taste, odour, colour or operational (e.g. fouling or biocorrosion of pipes problems. Drinking water contains diverse microorganisms competing for limited available nutrients for growth. Bacterial growth and interactions are regulated by factors such as (i type and concentration of available organic and inorganic nutrients, (ii type and concentration of residual disinfectant, (iii presence of predators such as protozoa and invertebrates, (iv environmental conditions such as water temperature, and (v spatial location of microorganisms (bulk water, sediment or biofilm. Water treatment and distribution conditions in water mains and premise plumbing affect each of these factors and shape bacterial community characteristics (abundance, composition, viability in distribution systems. Improved understanding of bacterial interactions in distribution systems and of environmental conditions impact is needed for better control of bacterial communities during drinking water production and distribution. This article reviews (i existing knowledge on biological stability controlling factors and (ii how these factors are affected by drinking water production and distribution conditions. In addition, (iii the concept of biological stability is discussed in light of experience with well-established and new analytical methods, enabling high throughput analysis and in-depth characterization of bacterial communities in drinking water. We discuss how knowledge gained from novel techniques will improve design and monitoring of water treatment and distribution systems in order to

Biological Stability of Drinking Water: Controlling Factors, Methods, and Challenges

Science.gov (United States)

Prest, Emmanuelle I.; Hammes, Frederik; van Loosdrecht, Mark C. M.; Vrouwenvelder, Johannes S.

2016-01-01

Biological stability of drinking water refers to the concept of providing consumers with drinking water of same microbial quality at the tap as produced at the water treatment facility. However, uncontrolled growth of bacteria can occur during distribution in water mains and premise plumbing, and can lead to hygienic (e.g., development of opportunistic pathogens), aesthetic (e.g., deterioration of taste, odor, color) or operational (e.g., fouling or biocorrosion of pipes) problems. Drinking water contains diverse microorganisms competing for limited available nutrients for growth. Bacterial growth and interactions are regulated by factors, such as (i) type and concentration of available organic and inorganic nutrients, (ii) type and concentration of residual disinfectant, (iii) presence of predators, such as protozoa and invertebrates, (iv) environmental conditions, such as water temperature, and (v) spatial location of microorganisms (bulk water, sediment, or biofilm). Water treatment and distribution conditions in water mains and premise plumbing affect each of these factors and shape bacterial community characteristics (abundance, composition, viability) in distribution systems. Improved understanding of bacterial interactions in distribution systems and of environmental conditions impact is needed for better control of bacterial communities during drinking water production and distribution. This article reviews (i) existing knowledge on biological stability controlling factors and (ii) how these factors are affected by drinking water production and distribution conditions. In addition, (iii) the concept of biological stability is discussed in light of experience with well-established and new analytical methods, enabling high throughput analysis and in-depth characterization of bacterial communities in drinking water. We discussed, how knowledge gained from novel techniques will improve design and monitoring of water treatment and distribution systems in order

Biological Stability of Drinking Water: Controlling Factors, Methods, and Challenges

KAUST Repository

Prest, Emmanuelle I.

2016-02-01

Biological stability of drinking water refers to the concept of providing consumers with drinking water of same microbial quality at the tap as produced at the water treatment facility. However, uncontrolled growth of bacteria can occur during distribution in water mains and premise plumbing, and can lead to hygienic (e.g., development of opportunistic pathogens), aesthetic (e.g., deterioration of taste, odor, color) or operational (e.g., fouling or biocorrosion of pipes) problems. Drinking water contains diverse microorganisms competing for limited available nutrients for growth. Bacterial growth and interactions are regulated by factors, such as (i) type and concentration of available organic and inorganic nutrients, (ii) type and concentration of residual disinfectant, (iii) presence of predators, such as protozoa and invertebrates, (iv) environmental conditions, such as water temperature, and (v) spatial location of microorganisms (bulk water, sediment, or biofilm). Water treatment and distribution conditions in water mains and premise plumbing affect each of these factors and shape bacterial community characteristics (abundance, composition, viability) in distribution systems. Improved understanding of bacterial interactions in distribution systems and of environmental conditions impact is needed for better control of bacterial communities during drinking water production and distribution. This article reviews (i) existing knowledge on biological stability controlling factors and (ii) how these factors are affected by drinking water production and distribution conditions. In addition, (iii) the concept of biological stability is discussed in light of experience with well-established and new analytical methods, enabling high throughput analysis and in-depth characterization of bacterial communities in drinking water. We discussed, how knowledge gained from novel techniques will improve design and monitoring of water treatment and distribution systems in order

Improved two-loop beam energy stabilizer for an FN tandem accelerator

International Nuclear Information System (INIS)

Trainor, T.A.

1981-01-01

A detailed analysis of the properties of various elements in a two-loop voltage regulator for a tandem accelerator enabled design of an optimum system which reduces effective accelerating voltage noise below 100 V. Essential features of the new system are high-quality slit preamplifiers, careful attention to removal of extraneous noise sources, and proper shaping of frequency responses to maximize stable gains and ensure compatibility of the two control loops. The resultant beam energy stabilizer system is easy to operate, has well defined indicators for proper adjustment of operating parameters, and recovers reliably from beam interruptions

Life raft stabilizer

Science.gov (United States)

Radnofsky, M. I.; Barnett, J. H., Jr.; Harrison, F. L.; Marak, R. J. (Inventor)

1973-01-01

An improved life raft stabilizer for reducing rocking and substantially precluding capsizing is discussed. The stabilizer may be removably attached to the raft and is defined by flexible side walls which extend a considerable depth downwardly to one another in the water. The side walls, in conjunction with the floor of the raft, form a ballast enclosure. A weight is placed in the bottom of the enclosure and water port means are provided in the walls. Placement of the stabilizer in the water allows the weighted bottom to sink, producing submerged deployment thereof and permitting water to enter the enclosure through the port means, thus forming a ballast for the raft.

Casein kinase 1 regulates sterol regulatory element-binding protein (SREBP) to control sterol homeostasis.

Science.gov (United States)

Brookheart, Rita T; Lee, Chih-Yung S; Espenshade, Peter J

2014-01-31

Sterol homeostasis is tightly controlled by the sterol regulatory element-binding protein (SREBP) transcription factor that is highly conserved from fungi to mammals. In fission yeast, SREBP functions in an oxygen-sensing pathway to promote adaptation to decreased oxygen supply that limits oxygen-dependent sterol synthesis. Low oxygen stimulates proteolytic cleavage of the SREBP homolog Sre1, generating the active transcription factor Sre1N that drives expression of sterol biosynthetic enzymes. In addition, low oxygen increases the stability and DNA binding activity of Sre1N. To identify additional signals controlling Sre1 activity, we conducted a genetic overexpression screen. Here, we describe our isolation and characterization of the casein kinase 1 family member Hhp2 as a novel regulator of Sre1N. Deletion of Hhp2 increases Sre1N protein stability and ergosterol levels in the presence of oxygen. Hhp2-dependent Sre1N degradation by the proteasome requires Hhp2 kinase activity, and Hhp2 binds and phosphorylates Sre1N at specific residues. Our results describe a role for casein kinase 1 as a direct regulator of sterol homeostasis. Given the role of mammalian Hhp2 homologs, casein kinase 1δ and 1ε, in regulation of the circadian clock, these findings may provide a mechanism for coordinating circadian rhythm and lipid metabolism.

Long term stability of power systems

Energy Technology Data Exchange (ETDEWEB)

Kundur, P; Gao, B [Powertech Labs. Inc., Surrey, BC (Canada)

1994-12-31

Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

Landfill stabilization focus area: Technology summary

International Nuclear Information System (INIS)

1995-06-01

Landfills within the DOE Complex as of 1990 are estimated to contain 3 million cubic meters of buried waste. The DOE facilities where the waste is predominantly located are at Hanford, the Savannah River Site (SRS), the Idaho National Engineering Laboratory (INEL), the Los Alamos National Laboratory (LANL), the Oak Ridge Reservation (ORR), the Nevada Test Site (NTS), and the Rocky Flats Plant (RFP). Landfills include buried waste, whether on pads or in trenches, sumps, ponds, pits, cribs, heaps and piles, auger holes, caissons, and sanitary landfills. Approximately half of all DOE buried waste was disposed of before 1970. Disposal regulations at that time permitted the commingling of various types of waste (i.e., transuranic, low-level radioactive, hazardous). As a result, much of the buried waste throughout the DOE Complex is presently believed to be contaminated with both hazardous and radioactive materials. DOE buried waste typically includes transuranic-contaminated radioactive waste (TRU), low-level radioactive waste (LLW), hazardous waste per 40 CFR 26 1, greater-than-class-C waste per CFR 61 55 (GTCC), mixed TRU waste, and mixed LLW. The mission of the Landfill Stabilization Focus Area is to develop, demonstrate, and deliver safer,more cost-effective and efficient technologies which satisfy DOE site needs for the remediation and management of landfills. The LSFA is structured into five technology areas to meet the landfill remediation and management needs across the DOE complex. These technology areas are: assessment, retrieval, treatment, containment, and stabilization. Technical tasks in each of these areas are reviewed

Landfill stabilization focus area: Technology summary

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-06-01

Landfills within the DOE Complex as of 1990 are estimated to contain 3 million cubic meters of buried waste. The DOE facilities where the waste is predominantly located are at Hanford, the Savannah River Site (SRS), the Idaho National Engineering Laboratory (INEL), the Los Alamos National Laboratory (LANL), the Oak Ridge Reservation (ORR), the Nevada Test Site (NTS), and the Rocky Flats Plant (RFP). Landfills include buried waste, whether on pads or in trenches, sumps, ponds, pits, cribs, heaps and piles, auger holes, caissons, and sanitary landfills. Approximately half of all DOE buried waste was disposed of before 1970. Disposal regulations at that time permitted the commingling of various types of waste (i.e., transuranic, low-level radioactive, hazardous). As a result, much of the buried waste throughout the DOE Complex is presently believed to be contaminated with both hazardous and radioactive materials. DOE buried waste typically includes transuranic-contaminated radioactive waste (TRU), low-level radioactive waste (LLW), hazardous waste per 40 CFR 26 1, greater-than-class-C waste per CFR 61 55 (GTCC), mixed TRU waste, and mixed LLW. The mission of the Landfill Stabilization Focus Area is to develop, demonstrate, and deliver safer,more cost-effective and efficient technologies which satisfy DOE site needs for the remediation and management of landfills. The LSFA is structured into five technology areas to meet the landfill remediation and management needs across the DOE complex. These technology areas are: assessment, retrieval, treatment, containment, and stabilization. Technical tasks in each of these areas are reviewed.

Monetary Policy and Financial (InStability

Directory of Open Access Journals (Sweden)

Adam Koronowski

2010-06-01

Full Text Available This paper presents how monetary policy, restricted only by price stability, may easily become propitious to asset inflation and – eventually – to a financial crisis. This risk is particularly high when the financial system lacks proper regulation and effective supervision. Hasty liberalization, negligence of official oversight and „Greenspan doctrine” which refuted any activist policy promoting financial stability characterized Fed’s monetary policy under the former Fed’s governor. The paper also analyses another aspect of the linkages between monetary policy and financial crises – monetary policy reaction to financial crises. It is not surprising that it consists of cutting interest rates and bail-out of insolvent, systemically important financial institutions. Such policy, especially when run too long and changed too abruptly, not only creates moral hazards but it also sets the stage for another „search for yield” and build-up of another speculative bubble. As a result, monetary policy becomes asymmetric and pro-cyclical. Fed’s reaction to the recent crisis seems to be very much in line with this pattern typical of Fed’s policy in the past. However, this time the scale of flooding the economy with liquidity and – as a consequence – the risks of future major imbalances in the financial system are unprecedented. A general conclusion of the paper says that there can’t be a sound financial and economic system unless money itself is a scarce resource. However trivial this statement is, monetary policy of some central banks seems to miss the point.

Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation

DEFF Research Database (Denmark)

Chen, C Y; Gherzi, R; Andersen, Jens S.

2000-01-01

Regulated mRNA turnover is a highly important process, but its mechanism is poorly understood. Using interleukin-2 (IL-2) mRNA as a model, we described a role for the JNK-signaling pathway in stabilization of IL-2 mRNA during T-cell activation, acting via a JNK response element (JRE) in the 5' un...

Kinetic and Thermodynamic Aspects of Cellular Thiol-Disulfide Redox Regulation

DEFF Research Database (Denmark)

Jensen, Kristine Steen; Hansen, Rosa Erritzøe; Winther, Jakob R

2009-01-01

. In the cytosol regulatory disulfide bonds are typically formed in spite of the prevailing reducing conditions and may thereby function as redox switches. Such disulfide bonds are protected from enzymatic reduction by kinetic barriers and are thus allowed to exist long enough to elicit the signal. Factors......Regulation of intracellular thiol-disulfide redox status is an essential part of cellular homeostasis. This involves the regulation of both oxidative and reductive pathways, production of oxidant scavengers and, importantly, the ability of cells to respond to changes in the redox environment...... that affect the rate of thiol-disulfide exchange and stability of disulfide bonds are discussed within the framework of the underlying chemical foundations. This includes the effect of thiol acidity (pKa), the local electrostatic environment, molecular strain and entropy. Even though a thiol-disulfide...

Protein stability: a crystallographer’s perspective

International Nuclear Information System (INIS)

Deller, Marc C.; Kong, Leopold; Rupp, Bernhard

2016-01-01

An understanding of protein stability is essential for optimizing the expression, purification and crystallization of proteins. In this review, discussion will focus on factors affecting protein stability on a somewhat practical level, particularly from the view of a protein crystallographer. Protein stability is a topic of major interest for the biotechnology, pharmaceutical and food industries, in addition to being a daily consideration for academic researchers studying proteins. An understanding of protein stability is essential for optimizing the expression, purification, formulation, storage and structural studies of proteins. In this review, discussion will focus on factors affecting protein stability, on a somewhat practical level, particularly from the view of a protein crystallographer. The differences between protein conformational stability and protein compositional stability will be discussed, along with a brief introduction to key methods useful for analyzing protein stability. Finally, tactics for addressing protein-stability issues during protein expression, purification and crystallization will be discussed

Protein stability: a crystallographer’s perspective

Energy Technology Data Exchange (ETDEWEB)

Deller, Marc C., E-mail: mdeller@stanford.edu [Stanford University, Shriram Center, 443 Via Ortega, Room 097, MC5082, Stanford, CA 94305-4125 (United States); Kong, Leopold [National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Building 8, Room 1A03, 8 Center Drive, Bethesda, MD 20814 (United States); Rupp, Bernhard [k.-k. Hofkristallamt, 91 Audrey Place, Vista, CA 92084 (United States); Medical University of Innsbruck, Schöpfstrasse 41, A-6020 Innsbruck (Austria)

2016-01-26

An understanding of protein stability is essential for optimizing the expression, purification and crystallization of proteins. In this review, discussion will focus on factors affecting protein stability on a somewhat practical level, particularly from the view of a protein crystallographer. Protein stability is a topic of major interest for the biotechnology, pharmaceutical and food industries, in addition to being a daily consideration for academic researchers studying proteins. An understanding of protein stability is essential for optimizing the expression, purification, formulation, storage and structural studies of proteins. In this review, discussion will focus on factors affecting protein stability, on a somewhat practical level, particularly from the view of a protein crystallographer. The differences between protein conformational stability and protein compositional stability will be discussed, along with a brief introduction to key methods useful for analyzing protein stability. Finally, tactics for addressing protein-stability issues during protein expression, purification and crystallization will be discussed.

Stability of injectable pharmaceutical Compvit-B

International Nuclear Information System (INIS)

Gonzalez Gay, Olivia Teresa; Sordo Martinez, Liset; Canal Reyes, Luis Javier

2011-01-01

Compvit-B is a lyophilized injectable polypharmaceutical made up of 100 mg of B 1 , 100 mg of B 6 and 5 000 μg of B 1 2. It is prescribed to treat all types of neuropathies and neurodegenerative diseases. The objective of this paper was the technological development of a stable formulation. For the evaluation of the quality of this drug, three pilot batches were scaled up and were subjected to physical, chemical and microbiological tests; the results were all satisfactory. The stability studies of lyophilized Compvit-B were performed at room temperature. They showed that the pharmaceutical was stable for 3 years and the formulation was regenerated for 72 hours. This drug is registered at the Cuban regulating body called State Center for Drug Control and has been included in the Basic Group of Drugs in Cuba. It has been put on the market by the national drug industry. It is also widely used in the hospital services in Cuba

An experimental and numerical study of the atmospheric stability impact on wind turbine wakes

DEFF Research Database (Denmark)

Machefaux, Ewan; Larsen, Gunner Chr.; Koblitz, Tilman

2016-01-01

campus test site. Wake measurements are averaged within a mean wind speed bin of 1 m s1 and classified according to atmospheric stability using three different metrics: the Obukhov length, the Bulk–Richardson number and the Froude number. Three test cases are subsequently defined covering various...... atmospheric conditions. Simulations are carried out using large eddy simulation and actuator disk rotor modeling. The turbulence properties of the incoming wind are adapted to the thermal stratification using a newly developed spectral tensor model that includes buoyancy effects. Discrepancies are discussed......In this paper, the impact of atmospheric stability on a wind turbine wake is studied experimentally and numerically. The experimental approach is based on full-scale (nacelle based) pulsed lidar measurements of the wake flow field of a stall-regulated 500 kW turbine at the DTU Wind Energy, Risø...

Nucleolin is regulated both at the level of transcription and translation

International Nuclear Information System (INIS)

Bicknell, Katrina; Brooks, Gavin; Kaiser, Pete; Chen Hongying; Dove, Brian K.; Hiscox, Julian A.

2005-01-01

Nucleolin is a multi-functional protein that is located to the nucleolus. In tissue culture cells, the stability of nucleolin is related to the proliferation status of the cell. During development, rat cardiomyocytes proliferate actively with increases in the mass of the heart being due to both hyperplasia and hypertrophy. The timing of this shift in the phenotype of the myocyte from one capable of undergoing hyperplasia to one that can grow only by hypertrophy occurs within 4 days of post-natal development. Thus, cardiomyocytes are an ideal model system in which to study the regulation of nucleolin during growth in vivo. Using Western blot and quantitative RT-PCR (TaqMan) we found that the amount of nucleolin is regulated both at the level of transcription and translation during the development of the cardiomyocyte. However, in cells which had exited the cell cycle and were subsequently given a hypertrophic stimulus, nucleolin was regulated post-transcriptionally

T box riboswitches in Actinobacteria: Translational regulation via novel tRNA interactions

Science.gov (United States)

Sherwood, Anna V.; Grundy, Frank J.; Henkin, Tina M.

2015-01-01

The T box riboswitch regulates many amino acid-related genes in Gram-positive bacteria. T box riboswitch-mediated gene regulation was shown previously to occur at the level of transcription attenuation via structural rearrangements in the 5′ untranslated (leader) region of the mRNA in response to binding of a specific uncharged tRNA. In this study, a novel group of isoleucyl-tRNA synthetase gene (ileS) T box leader sequences found in organisms of the phylum Actinobacteria was investigated. The Stem I domains of these RNAs lack several highly conserved elements that are essential for interaction with the tRNA ligand in other T box RNAs. Many of these RNAs were predicted to regulate gene expression at the level of translation initiation through tRNA-dependent stabilization of a helix that sequesters a sequence complementary to the Shine–Dalgarno (SD) sequence, thus freeing the SD sequence for ribosome binding and translation initiation. We demonstrated specific binding to the cognate tRNAIle and tRNAIle-dependent structural rearrangements consistent with regulation at the level of translation initiation, providing the first biochemical demonstration, to our knowledge, of translational regulation in a T box riboswitch. PMID:25583497

The role of auxin in temperature regulated hypocotyl elongation

Energy Technology Data Exchange (ETDEWEB)

Estelle, Mark [Univ. of California, San Diego, CA (United States)

2015-10-02

The major goal of this project was to determine how auxin mediates the response of Arabidopsis seedlings to increased ambient temperature. Previous studies have shown that the response is due, in part, to increased auxin biosynthesis via the IPA auxin biosynthetic pathway. This effect is related to increased transcription of genes that encode enzymes in this pathway. However, during the last year we have shown that transcription of key auxin regulated genes increases within minutes of a shift to elevated temperature. This response is probably to rapid to be explained by changes in the levels of auxin biosynthetic enzymes. Interestingly, we have recently discovered that temperature shift is associated with a rapid increase in the level of the auxin co-receptor TIR1. This change appears is the result of increased stability of the protein. At the same time, we have discovered that stability of TIR1 is dependent on the chaperone HSP9o and its co-chaperone SGT1. By using the specific HSP90 inhibitor GDA, we show that HSP90 is required for the temperature dependent change in TIR1 levels. We have also shown that HSP90 and SGT1 interact directly with TIR1. Our results also lead us to propose a new model in which the plant responds rapidly to changes in ambient temperature by directly regulating the TIR1/AFB receptor system, thus modulating the auxin signaling pathway.

The future of international banking regulations in response to the financial crisis of 2007/2009: After Basel iii then what next?

Directory of Open Access Journals (Sweden)

Joseph E. Isebor

2014-06-01

Full Text Available The financial crisis 2007-2009 will not be forgotten in a hurry because of its impact on the global financial system almost replicating the Great Depression. Major and causal factors contributed to the financial crisis, and this prompted the establishment of Basel III to contain the crisis. Basel III introduced improved capital and liquidity rules, but still could not contain the crisis. This leaves regulators with questions of how to prevent another financial crisis in the future. Evidences suggest that the financial market is evolving because of its complex and changing nature, and so are the international banking regulations (Basel I, Basel II and Basel III that support the system in terms of maintaining economic and financial stability. It is clear that Basel III will not stop the next financial crisis even though the Basel accords continue to evolve in response to maintaining economic and financial stability, with the core purpose of preventing another financial crisis. Uncertainties lies ahead, and regulators cannot be sure of what will likely cause the next crisis, but indications suggest that the financial markets and international banking regulations in the form of Basel accords will continue to evolve