Poly(ADP-ribose polymerase (PARP-1 is not involved in DNA double-strand break recovery

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Fernet Marie

2003-07-01

Full Text Available Abstract Background The cytotoxicity and the rejoining of DNA double-strand breaks induced by γ-rays, H2O2 and neocarzinostatin, were investigated in normal and PARP-1 knockout mouse 3T3 fibroblasts to determine the role of poly(ADP-ribose polymerase (PARP-1 in DNA double-strand break repair. Results PARP-1-/- were considerably more sensitive than PARP-1+/+ 3T3s to induced cell kill by γ-rays and H2O2. However, the two cell lines did not show any significant difference in the susceptibility to neocarzinostatin below 1.5 nM drug. Restoration of PARP-1 expression in PARP-1-/- 3T3s by retroviral transfection of the full PARP-1 cDNA did not induce any change in neocarzinostatin response. Moreover the incidence and the rejoining kinetics of neocarzinostatin-induced DNA double-strand breaks were identical in PARP-1+/+ and PARP-1-/- 3T3s. Poly(ADP-ribose synthesis following γ-rays and H2O2 was observed in PARP-1-proficient cells only. In contrast neocarzinostatin, even at supra-lethal concentration, was unable to initiate PARP-1 activation yet it induced H2AX histone phosphorylation in both PARP1+/+ and PARP-1-/- 3T3s as efficiently as γ-rays and H2O2. Conclusions The results show that PARP-1 is not a major determinant of DNA double-strand break recovery with either strand break rejoining or cell survival as an endpoint. Even though both PARP-1 and ATM activation are major determinants of the cell response to γ-rays and H2O2, data suggest that PARP-1-dependent poly(ADP-ribose synthesis and ATM-dependent H2AX phosphorylation, are not inter-related in the repair pathway of neocarzinostatin-induced DNA double-strand breaks.

Structure/function analysis of PARP-1 in oxidative and nitrosative stress-induced monomeric ADPR formation.

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Ben Buelow

2009-07-01

Full Text Available Poly adenosine diphosphate-ribose polymerase-1 (PARP-1 is a multifunctional enzyme that is involved in two major cellular responses to oxidative and nitrosative (O/N stress: detection and response to DNA damage via formation of protein-bound poly adenosine diphosphate-ribose (PAR, and formation of the soluble 2(nd messenger monomeric adenosine diphosphate-ribose (mADPR. Previous studies have delineated specific roles for several of PARP-1's structural domains in the context of its involvement in a DNA damage response. However, little is known about the relationship between the mechanisms through which PARP-1 participates in DNA damage detection/response and those involved in the generation of monomeric ADPR. To better understand the relationship between these events, we undertook a structure/function analysis of PARP-1 via reconstitution of PARP-1 deficient DT40 cells with PARP-1 variants deficient in catalysis, DNA binding, auto-PARylation, and PARP-1's BRCT protein interaction domain. Analysis of responses of the respective reconstituted cells to a model O/N stressor indicated that PARP-1 catalytic activity, DNA binding, and auto-PARylation are required for PARP-dependent mADPR formation, but that BRCT-mediated interactions are dispensable. As the BRCT domain is required for PARP-dependent recruitment of XRCC1 to sites of DNA damage, these results suggest that DNA repair and monomeric ADPR 2(nd messenger generation are parallel mechanisms through which PARP-1 modulates cellular responses to O/N stress.

Parp-1 genetic ablation in Ela-myc mice unveils novel roles for Parp-1 in pancreatic cancer.

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Martínez-Bosch, Neus; Iglesias, Mar; Munné-Collado, Jessica; Martínez-Cáceres, Carlos; Moreno, Mireia; Guerra, Carmen; Yélamos, Jose; Navarro, Pilar

2014-10-01

Pancreatic cancer has a dismal prognosis and is currently the fourth leading cause of cancer-related death in developed countries. The inhibition of poly(ADP-ribose) polymerase-1 (Parp-1), the major protein responsible for poly(ADP-ribosy)lation in response to DNA damage, has emerged as a promising treatment for several tumour types. Here we aimed to elucidate the involvement of Parp-1 in pancreatic tumour progression. We assessed Parp-1 protein expression in normal, preneoplastic and pancreatic tumour samples from humans and from K-Ras- and c-myc-driven mouse models of pancreatic cancer. Parp-1 was highly expressed in acinar cells in normal and cancer tissues. In contrast, ductal cells expressed very low or undetectable levels of this protein, both in a normal and in a tumour context. The Parp-1 expression pattern was similar in human and mouse samples, thereby validating the use of animal models for further studies. To determine the in vivo effects of Parp-1 depletion on pancreatic cancer progression, Ela-myc-driven pancreatic tumour development was analysed in a Parp-1 knock-out background. Loss of Parp-1 resulted in increased tumour necrosis and decreased proliferation, apoptosis and angiogenesis. Interestingly, Ela-myc:Parp-1(-/-) mice displayed fewer ductal tumours than their Ela-myc:Parp-1(+/+) counterparts, suggesting that Parp-1 participates in promoting acinar-to-ductal metaplasia, a key event in pancreatic cancer initiation. Moreover, impaired macrophage recruitment can be responsible for the ADM blockade found in the Ela-myc:Parp-1(-/-) mice. Finally, molecular analysis revealed that Parp-1 modulates ADM downstream of the Stat3-MMP7 axis and is also involved in transcriptional up-regulation of the MDM2, VEGFR1 and MMP28 cancer-related genes. In conclusion, the expression pattern of Parp-1 in normal and cancer tissue and the in vivo functional effects of Parp-1 depletion point to a novel role for this protein in pancreatic carcinogenesis and shed light

Regulation of FOXO1-mediated transcription and cell proliferation by PARP-1

Energy Technology Data Exchange (ETDEWEB)

Sakamaki, Jun-ichi; Daitoku, Hiroaki; Yoshimochi, Kenji [Center for Tsukuba Advanced Research Alliance, Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577 (Japan); Miwa, Masanao [Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829 (Japan); Fukamizu, Akiyoshi, E-mail: akif@tara.tsukuba.ac.jp [Center for Tsukuba Advanced Research Alliance, Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577 (Japan)

2009-05-08

Forkhead box O (FOXO) transcription factors play an important role in a wide range of biological processes, including cell cycle control, apoptosis, detoxification of reactive oxygen species, and gluconeogenesis through regulation of gene expression. In this study, we demonstrated that PARP-1 functions as a negative regulator of FOXO1. We showed that PARP-1 directly binds to and poly(ADP-ribosyl)ates FOXO1 protein. PARP-1 represses FOXO1-mediated expression of cell cycle inhibitor p27{sup Kip1} gene. Notably, poly(ADP-ribosyl)ation activity was not required for the repressive effect of PARP-1 on FOXO1 function. Furthermore, knockdown of PARP-1 led to a decrease in cell proliferation in a manner dependent on FOXO1 function. Chromatin immunoprecipitation experiments confirmed that PARP-1 is recruited to the p27{sup Kip1} gene promoter through a binding to FOXO1. These results suggest that PARP-1 acts as a corepressor for FOXO1, which could play an important role in proper cell proliferation by regulating p27{sup Kip1} gene expression.

International Cooperation and Energy/Environment crisis

International Nuclear Information System (INIS)

Clo, A.

2009-01-01

A combination of old and new tensions led to a new energy crisis. This crisis is very difficult to solve due to the multiple interests and the global and sovranational nature of its interdependent dimensions (economic, political and environmental). In a deep global economic crisis context, the challenges posed to the modern world by energy and the environment have to be faced with the international cooperation and dialogue, as it was in the past. [it

PARP inhibition versus PARP-1 silencing: different outcomes in terms of single-strand break repair and radiation susceptibility

International Nuclear Information System (INIS)

Godon, C.; Cordelieres, F.P.; Giocanti, N.; Megnin-Chanet, F.; Hall, J.; Favaudon, V.; Godon, C.; Giocanti, N.; Megnin-Chanet, F.; Hall, J.; Favaudon, V.; Cordelieres, F.P.; Cordelieres, F.P.; Biard, D.

2008-01-01

The consequences of PARP-1 disruption or inhibition on DNA single-strand break repair (SSBR) and radio-induced lethality were determined in synchronized, iso-genic HeLa cells stably silenced or not for poly(ADP-ribose) polymerase-1 (PARP-1) (PARP-1(KD)) or XRCC1 (XRCC1(KD)). PARP-1 inhibition prevented XRCC1-YFP recruitment at sites of 405 nm laser micro irradiation, slowed SSBR 10-fold and triggered the accumulation of large persistent foci of GFP-PARP-1 and GFP-PCNA at photo damaged sites. These aggregates are presumed to hinder the recruitment of other effectors of the base excision repair (BER) pathway.PARP-1 silencing also prevented XRCC1-YFP recruitment but did not lengthen the lifetime of GFP-PCNA foci. Moreover, PARP-1(KD) and XRCC1(KD) cells in S phase completed SSBR as rapidly as controls, while SSBR was delayed in G1. Taken together, the data demonstrate that a PARP-1- and XRCC1-independent SSBR pathway operates when the short patch repair branch of the BER is deficient. Long patch repair is the likely mechanism, as GFP-PCNA recruitment at photo-damaged sites was normal in PARP-1(KD) cells. PARP-1 silencing elicited hyper-radiosensitivity, while radiosensitization by a PARP inhibitor reportedly occurs only in those cells treated in S phase. PARP-1 inhibition and deletion thus have different outcomes in terms of SSBR and radiosensitivity. (authors)

Structural Implications for Selective Targeting of PARPs.

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Steffen, Jamin D; Brody, Jonathan R; Armen, Roger S; Pascal, John M

2013-12-20

Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that use NAD(+) as a substrate to synthesize polymers of ADP-ribose (PAR) as post-translational modifications of proteins. PARPs have important cellular roles that include preserving genomic integrity, telomere maintenance, transcriptional regulation, and cell fate determination. The diverse biological roles of PARPs have made them attractive therapeutic targets, which have fueled the pursuit of small molecule PARP inhibitors. The design of PARP inhibitors has matured over the past several years resulting in several lead candidates in clinical trials. PARP inhibitors are mainly used in clinical trials to treat cancer, particularly as sensitizing agents in combination with traditional chemotherapy to reduce side effects. An exciting aspect of PARP inhibitors is that they are also used to selectivity kill tumors with deficiencies in DNA repair proteins (e.g., BRCA1/2) through an approach termed "synthetic lethality." In the midst of the tremendous efforts that have brought PARP inhibitors to the forefront of modern chemotherapy, most clinically used PARP inhibitors bind to conserved regions that permits cross-selectivity with other PARPs containing homologous catalytic domains. Thus, the differences between therapeutic effects and adverse effects stemming from pan-PARP inhibition compared to selective inhibition are not well understood. In this review, we discuss current literature that has found ways to gain selectivity for one PARP over another. We furthermore provide insights into targeting other domains that make up PARPs, and how new classes of drugs that target these domains could provide a high degree of selectivity by affecting specific cellular functions. A clear understanding of the inhibition profiles of PARP inhibitors will not only enhance our understanding of the biology of individual PARPs, but may provide improved therapeutic options for patients.

PARP-1 and PARP-2 activity in cancer-induced cachexia: potential therapeutic implications.

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Barreiro, Esther; Gea, Joaquim

2018-01-26

Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia. Genetic inhibition of PARP activity attenuated the deleterious effects seen on depleted muscles in mouse models of oncologic cachexia. In the present minireview the mechanisms whereby PARP activity inhibition may improve muscle mass and performance in models of cancer-induced cachexia are discussed. Specifically, the beneficial effects of inhibition of PARP activity on attenuation of increased oxidative stress, protein catabolism, poor muscle anabolism and mitochondrial content and epigenetic modulation of muscle phenotype are reviewed in this article. Finally, the potential therapeutic strategies of pharmacological PARP activity inhibition for the treatment of cancer-induced cachexia are also being described in this review.

Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade.

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Fenqing Shang

Full Text Available Hyperglycemia and hypertension impair endothelial function in part through oxidative stress-activated poly (ADP-ribose polymerase 1 (PARP1. Biguanides and angiotensin II receptor blockers (ARBs such as metformin and telmisartan have a vascular protective effect. We used cultured vascular endothelial cells (ECs, diabetic and hypertensive rodent models, and AMPKα2-knockout mice to investigate whether metformin and telmisartan have a beneficial effect on the endothelium via AMP-activated protein kinase (AMPK phosphorylation of PARP1 and thus inhibition of PARP1 activity. The results showed that metformin and telmisartan, but not glipizide and metoprolol, activated AMPK, which phosphorylated PARP1 Ser-177 in cultured ECs and the vascular wall of rodent models. Experiments using phosphorylated/de-phosphorylated PARP1 mutants show that AMPK phosphorylation of PARP1 leads to decreased PARP1 activity and attenuated protein poly(ADP-ribosylation (PARylation, but increased endothelial nitric oxide synthase (eNOS activity and silent mating type information regulation 2 homolog 1 (SIRT1 expression. Taken together, the data presented here suggest biguanides and ARBs have a beneficial effect on the vasculature by the cascade of AMPK phosphorylation of PARP1 to inhibit PARP1 activity and protein PARylation in ECs, thereby mitigating endothelial dysfunction.

Unfolding of core nucleosomes by PARP-1 revealed by spFRET microscopy

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Daniel Sultanov

2017-01-01

Full Text Available DNA accessibility to various protein complexes is essential for various processes in the cell and is affected by nucleosome structure and dynamics. Protein factor PARP-1 (poly(ADP-ribose polymerase 1 increases the accessibility of DNA in chromatin to repair proteins and transcriptional machinery, but the mechanism and extent of this chromatin reorganization are unknown. Here we report on the effects of PARP-1 on single nucleosomes revealed by spFRET (single-particle Förster Resonance Energy Transfer microscopy. PARP-1 binding to a double-strand break in the vicinity of a nucleosome results in a significant increase of the distance between the adjacent gyres of nucleosomal DNA. This partial uncoiling of the entire nucleosomal DNA occurs without apparent loss of histones and is reversed after poly(ADP-ribosylation of PARP-1. Thus PARP-1-nucleosome interactions result in reversible, partial uncoiling of the entire nucleosomal DNA.

Feedback-regulated poly(ADP-ribosyl)ation by PARP-1 is required for rapid response to DNA damage in living cells

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Mortusewicz, Oliver; Amé, Jean-Christophe; Leonhardt, Heinrich

2007-01-01

Genome integrity is constantly threatened by DNA lesions arising from numerous exogenous and endogenous sources. Survival depends on immediate recognition of these lesions and rapid recruitment of repair factors. Using laser microirradiation and live cell microscopy we found that the DNA-damage dependent poly(ADP-ribose) polymerases (PARP) PARP-1 and PARP-2 are recruited to DNA damage sites, however, with different kinetics and roles. With specific PARP inhibitors and mutations, we could show that the initial recruitment of PARP-1 is mediated by the DNA-binding domain. PARP-1 activation and localized poly(ADP-ribose) synthesis then generates binding sites for a second wave of PARP-1 recruitment and for the rapid accumulation of the loading platform XRCC1 at repair sites. Further PARP-1 poly(ADP-ribosyl)ation eventually initiates the release of PARP-1. We conclude that feedback regulated recruitment of PARP-1 and concomitant local poly(ADP-ribosyl)ation at DNA lesions amplifies a signal for rapid recruitment of repair factors enabling efficient restoration of genome integrity. PMID:17982172

Effects of niacin restriction on sirtuin and PARP responses to photodamage in human skin.

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Claudia A Benavente

Full Text Available Sirtuins (SIRTs and poly(ADP-ribose polymerases (PARPs, NAD(+-dependent enzymes, link cellular energy status with responses to environmental stresses. Skin is frequently exposed to the DNA damaging effects of UV irradiation, a known etiology in skin cancer. Thus, understanding the defense mechanisms in response to UV, including the role of SIRTs and PARPs, may be important in developing skin cancer prevention strategies. Here, we report expression of the seven SIRT family members in human skin. SIRTs gene expressions are progressively upregulated in A431 epidermoid carcinoma cells (SIRTs1 and 3, actinic keratoses (SIRTs 2, 3, 5, 6, and 7 and squamous cell carcinoma (SIRTs 1-7. Photodamage induces dynamic changes in SIRT expression with upregulation of both SIRT1 and SIRT4 mRNAs. Specific losses of SIRT proteins occur early after photodamage followed by accumulation later, especially for SIRT4. Niacin restriction, which decreases NAD(+, the sirtuin substrate, results in an increase in acetylated proteins, upregulation of SIRTs 2 and 4, increased inherent DNA damage, alterations in SIRT responses to photodamage, abrogation of PARP activation following photodamage, and increased sensitivity to photodamage that is completely reversed by repleting niacin. These data support the hypothesis that SIRTs and PARPs play important roles in resistance to photodamage and identify specific SIRTs that respond to photodamage and may be targets for skin cancer prevention.

Vasoactivity of rucaparib, a PARP-1 inhibitor, is a complex process that involves myosin light chain kinase, P2 receptors, and PARP itself.

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Cian M McCrudden

Full Text Available Therapeutic inhibition of poly(ADP-ribose polymerase (PARP, as monotherapy or to supplement the potencies of other agents, is a promising strategy in cancer treatment. We previously reported that the first PARP inhibitor to enter clinical trial, rucaparib (AG014699, induced vasodilation in vivo in xenografts, potentiating response to temozolomide. We now report that rucaparib inhibits the activity of the muscle contraction mediator myosin light chain kinase (MLCK 10-fold more potently than its commercially available inhibitor ML-9. Moreover, rucaparib produces additive relaxation above the maximal degree achievable with ML-9, suggesting that MLCK inhibition is not solely responsible for dilation. Inhibition of nitric oxide synthesis using L-NMMA also failed to impact rucaparib's activity. Rucaparib contains the nicotinamide pharmacophore, suggesting it may inhibit other NAD+-dependent processes. NAD+ exerts P2 purinergic receptor-dependent inhibition of smooth muscle contraction. Indiscriminate blockade of the P2 purinergic receptors with suramin abrogated rucaparib-induced vasodilation in rat arterial tissue without affecting ML-9-evoked dilation, although the specific receptor subtypes responsible have not been unequivocally identified. Furthermore, dorsal window chamber and real time tumor vessel perfusion analyses in PARP-1-/- mice indicate a potential role for PARP in dilation of tumor-recruited vessels. Finally, rucaparib provoked relaxation in 70% of patient-derived tumor-associated vessels. These data provide tantalising evidence of the complexity of the mechanism underlying rucaparib-mediated vasodilation.

PARP1 Val762Ala polymorphism reduces enzymatic activity

International Nuclear Information System (INIS)

Wang Xiaogan; Wang Zhaoqi; Tong Weimin; Shen Yan

2007-01-01

Poly(ADP-ribose) polymerase 1 (PARP1) modifies a variety of nuclear proteins by poly(ADP-ribosyl)ation, and plays diverse roles in molecular and cellular processes. A common PARP1 single nucleotide polymorphism (SNP) at codon 762, resulting in the substitution of alanine (Ala) for valine (Val) in the catalytic domain has been implicated in susceptibility to cancer. To characterize the functional effect of this polymorphism on PARP1, we performed in vitro enzymatic analysis on PARP1-Ala762 and PARP1-Val762. We found that PARP1-Ala762 displayed 57.2% of the activity of PARP1-Val762 for auto-poly(ADP-ribosyl)ation and 61.9% of the activity of PARP1-Val762 for trans-poly(ADP-ribosyl)ation of histone H1. The kinetic characterization revealed that the K m of PARP1-Ala762 was increased to a 1.2-fold of the K m of PARP1-Val762 for trans-poly(ADP-ribosyl)ation. Thus, the PARP1 Val762Ala polymorphism reduces the enzymatic activity of PARP1 by increasing K m . This finding suggests that different levels of poly(ADP-ribosyl)ation by PARP1 might aid in understanding Cancer risk of carriers of the PARP1 Val762Ala polymorphism

Effects of PARP-1 Deficiency on Th1 and Th2 Cell Differentiation

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M. Sambucci

2013-01-01

Full Text Available T cell differentiation to effector Th cells such as Th1 and Th2 requires the integration of multiple synergic and antagonist signals. Poly(ADP-ribosylation is a posttranslational modification of proteins catalyzed by Poly(ADP-ribose polymerases (PARPs. Recently, many reports showed that PARP-1, the prototypical member of the PARP family, plays a role in immune/inflammatory responses. Consistently, its enzymatic inhibition confers protection in several models of immune-mediated diseases, mainly through an inhibitory effect on NF-κB (and NFAT activation. PARP-1 regulates cell functions in many types of immune cells, including dendritic cells, macrophages, and T and B lymphocytes. Our results show that PARP-1KO cells displayed a reduced ability to differentiate in Th2 cells. Under both nonskewing and Th2-polarizing conditions, naïve CD4 cells from PARP-1KO mice generated a reduced frequency of IL-4+ cells, produced less IL-5, and expressed GATA-3 at lower levels compared with cells from wild type mice. Conversely, PARP-1 deficiency did not substantially affect differentiation to Th1 cells. Indeed, the frequency of IFN-γ+ cells as well as IFN-γ production, in nonskewing and Th1-polarizing conditions, was not affected by PARP-1 gene ablation. These findings demonstrate that PARP-1 plays a relevant role in Th2 cell differentiation and it might be a target to be exploited for the modulation of Th2-dependent immune-mediated diseases.

Understanding the importance of an energy crisis

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Mechtenberg, Abigail Reid

Human development and energy, in general, and electrical energy, specifically, co-exist seamlessly in high HDI countries where reliability and availability is greater than 99%. In numerous low HDI countries, there is 2-50% electric grid availability with reliability at or below 50% due to load shedding and faults. In Africa, solar, wind, biomass and hydroelectric energy production are cited to meet growing demand and increase reliability and availability; however, the capital costs are greater than the ability-to-pay for wide scale implementation. Since the 1970s, the United States has continued to argue over the new sustainable energy infrastructure solution(s); thus resulting in no new infrastructure being built for wide scale implementation. Together the world is facing the daunting task of averting an energy crisis in developed countries and facing energy crises in developing countries. This thesis explores the importance of energy crises: from the past, current, and future. The first part entails arguing that the United States is not on a pathway to prevent an energy crisis based on an analysis of 1986 and 2004 niche and status-quo manufacturing of light-duty vehicles. The second part answers the question of what an energy crisis looks like by exploring and investigating current electrical energy crises in Fort Portal, Uganda. This part used both anthropological and physics education empowerment research to co-design and build for various energy crisis situations in hospitals, schools, and businesses all from locally available materials and expertise. Finally, looking into the US light-duty vehicle's future, I design a new hybrid vehicle powertrain (called transition mode hybrid). This third part describes my new patent as a way to avert an energy crisis in the light-duty transportation sector.

Importin alpha binding and nuclear localization of PARP-2 is dependent on lysine 36, which is located within a predicted classical NLS

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Valovka Taras

2008-07-01

Full Text Available Abstract Background The enzymes responsible for the synthesis of poly-ADP-ribose are named poly-ADP-ribose polymerases (PARP. PARP-2 is a nuclear protein, which regulates a variety of cellular functions that are mainly controlled by protein-protein interactions. A previously described non-conventional bipartite nuclear localization sequence (NLS lies in the amino-terminal DNA binding domain of PARP-2 between amino acids 1–69; however, this targeting sequence has not been experimentally examined or validated. Results Using a site-directed mutagenesis approach, we found that lysines 19 and 20, located within a previously described bipartite NLS, are not required for nuclear localization of PARP-2. In contrast, lysine 36, which is located within a predicted classical monopartite NLS, was required for PARP-2 nuclear localization. While wild type PARP-2 interacted with importin α3 and to a very weak extent with importin α1 and importin α5, the mutant PARP-2 (K36R did not interact with importin α3, providing a molecular explanation why PARP-2 (K36R is not targeted to the nucleus. Conclusion Our results provide strong evidence that lysine 36 of PARP-2 is a critical residue for proper nuclear targeting of PARP-2 and consequently for the execution of its biological functions.

Upregulation of PEDF expression by PARP inhibition contributes to the decrease in hyperglycemia-induced apoptosis in HUVECs

International Nuclear Information System (INIS)

Chen Haibing; Jia Weiping; Xu Xun; Fan Ying; Zhu Dongqing; Wu Haixiang; Xie Zhenggao; Zheng Zhi

2008-01-01

Poly(ADP-ribose)polymerase (PARP) inhibitors decrease angiogenesis through reducing vascular endothelium growth factor (VEGF) induced proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). In contrast to VEGF, pigment epithelium-derived factor (PEDF) has been demonstrated to act as a strong endogenous inhibitor of angiogenesis. Here, we show that PARP inhibition with a specific inhibitor PJ-34 or specific PARP antisense oligonucleotide upregulates hyperglycemia-induced PEDF expression in HUVECs in a dose-dependent manner. This results in the retard of activation of p38 MAP kinase and the concomitant decrease in cell apoptosis. These results give the first direct demonstration that PEDF might represent a target for PARP inhibition treatment and the effects of PEDF on endothelial cells growth are context dependent

Analyzing structure–function relationships of artificial and cancer-associated PARP1 variants by reconstituting TALEN-generated HeLa PARP1 knock-out cells

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Rank, Lisa; Veith, Sebastian; Gwosch, Eva C.; Demgenski, Janine; Ganz, Magdalena; Jongmans, Marjolijn C.; Vogel, Christopher; Fischbach, Arthur; Buerger, Stefanie; Fischer, Jan M.F.; Zubel, Tabea; Stier, Anna; Renner, Christina; Schmalz, Michael; Beneke, Sascha; Groettrup, Marcus; Kuiper, Roland P.; Bürkle, Alexander; Ferrando-May, Elisa; Mangerich, Aswin

2016-01-01

Genotoxic stress activates PARP1, resulting in the post-translational modification of proteins with poly(ADP-ribose) (PAR). We genetically deleted PARP1 in one of the most widely used human cell systems, i.e. HeLa cells, via TALEN-mediated gene targeting. After comprehensive characterization of these cells during genotoxic stress, we analyzed structure–function relationships of PARP1 by reconstituting PARP1 KO cells with a series of PARP1 variants. Firstly, we verified that the PARP1\\E988K mutant exhibits mono-ADP-ribosylation activity and we demonstrate that the PARP1\\L713F mutant is constitutively active in cells. Secondly, both mutants exhibit distinct recruitment kinetics to sites of laser-induced DNA damage, which can potentially be attributed to non-covalent PARP1–PAR interaction via several PAR binding motifs. Thirdly, both mutants had distinct functional consequences in cellular patho-physiology, i.e. PARP1\\L713F expression triggered apoptosis, whereas PARP1\\E988K reconstitution caused a DNA-damage-induced G2 arrest. Importantly, both effects could be rescued by PARP inhibitor treatment, indicating distinct cellular consequences of constitutive PARylation and mono(ADP-ribosyl)ation. Finally, we demonstrate that the cancer-associated PARP1 SNP variant (V762A) as well as a newly identified inherited PARP1 mutation (F304L\\V762A) present in a patient with pediatric colorectal carcinoma exhibit altered biochemical and cellular properties, thereby potentially supporting human carcinogenesis. Together, we establish a novel cellular model for PARylation research, by revealing strong structure–function relationships of natural and artificial PARP1 variants. PMID:27694308

The impact on chinese economic growth and energy consumption of the Global Financial Crisis: An input-output analysis

International Nuclear Information System (INIS)

Yuan, Chaoqing; Liu, Sifeng; Xie, Naiming

2010-01-01

The dependence on foreign trade increased sharply in China, and therefore Chinese economy is obviously export-oriented. The Global Financial Crisis will impact the Chinese economic growth violently. Chinese government has recently adopted some effective measures to fight against the Global Financial Crisis. The most important measure is the 4 trillion Yuan ($586 billion) stimulus plan which was announced on November 9, 2008. This paper discusses the influence on energy consumption and economic growth of Global Financial Crisis and the stimulus plan against it by input-output analysis. The results show that the fall of exports caused by the Global Financial Crisis will lead to a decrease of 7.33% in GDP (Gross Domestic Production) and a reduction of 9.21% in energy consumption; the stimulus plan against the Global Financial Crisis will lead to an increase of 4.43% in economic growth and an increase of 1.83% in energy consumption; In the Global Financial Crisis, energy consumption per unit GDP will fall in China. (author)

Hyperactivation of PARP triggers nonhomologous end-joining in repair-deficient mouse fibroblasts.

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Natalie R Gassman

Full Text Available Regulation of poly(ADP-ribose (PAR synthesis and turnover is critical to determining cell fate after genotoxic stress. Hyperactivation of PAR synthesis by poly(ADP-ribose polymerase-1 (PARP-1 occurs when cells deficient in DNA repair are exposed to genotoxic agents; however, the function of this hyperactivation has not been adequately explained. Here, we examine PAR synthesis in mouse fibroblasts deficient in the base excision repair enzyme DNA polymerase β (pol β. The extent and duration of PARP-1 activation was measured after exposure to either the DNA alkylating agent, methyl methanesulfonate (MMS, or to low energy laser-induced DNA damage. There was strong DNA damage-induced hyperactivation of PARP-1 in pol β nullcells, but not in wild-type cells. In the case of MMS treatment, PAR synthesis did not lead to cell death in the pol β null cells, but instead resulted in increased PARylation of the nonhomologous end-joining (NHEJ protein Ku70 and increased association of Ku70 with PARP-1. Inhibition of the NHEJ factor DNA-PK, under conditions of MMS-induced PARP-1 hyperactivation, enhanced necrotic cell death. These data suggest that PARP-1 hyperactivation is a protective mechanism triggering the classical-NHEJ DNA repair pathway when the primary alkylated base damage repair pathway is compromised.

Trial watch – inhibiting PARP enzymes for anticancer therapy

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Sistigu, Antonella; Manic, Gwenola; Obrist, Florine; Vitale, Ilio

2016-01-01

ABSTRACT Poly(ADP-ribose) polymerases (PARPs) are a members of family of enzymes that catalyze poly(ADP-ribosyl)ation (PARylation) and/or mono(ADP-ribosyl)ation (MARylation), two post-translational protein modifications involved in crucial cellular processes including (but not limited to) the DNA damage response (DDR). PARP1, the most abundant family member, is a nuclear protein that is activated upon sensing distinct types of DNA damage and contributes to their resolution by PARylating multiple DDR players. Recent evidence suggests that, along with DDR, activated PARP1 mediates a series of prosurvival and proapoptotic processes aimed at preserving genomic stability. Despite this potential oncosuppressive role, upregulation and/or overactivation of PARP1 or other PARP enzymes has been reported in a variety of human neoplasms. Over the last few decades, several pharmacologic inhibitors of PARP1 and PARP2 have been assessed in preclinical and clinical studies showing potent antineoplastic activity, particularly against homologous recombination (HR)-deficient ovarian and breast cancers. In this Trial Watch, we describe the impact of PARP enzymes and PARylation in cancer, discuss the mechanism of cancer cell killing by PARP1 inactivation, and summarize the results of recent clinical studies aimed at evaluating the safety and therapeutic profile of PARP inhibitors in cancer patients. PMID:27308587

PARP-1 Interaction with and Activation by Histones and Nucleosomes.

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Thomas, Colin; Kotova, Elena; Tulin, Alexei V

2017-01-01

Poly(ADP-ribose) Polymerase 1 (PARP-1) is an abundant chromatin associated protein, typical for most eukaryotic nuclei. The localization of PARP-1 in chromatin and its enzymatic activation involves multiple interactions of PARP-1 with nucleosomal histones, other proteins, and DNA. We report a set of methods designed to reconstitute PARP-1 regulation in vitro. These methods involve the expression of PARP-1 and PARP-1-regulating proteins using bacterial and eukaryotic systems, purification of these proteins using chromatography, testing of individual interactions in vitro, assembly of active complexes, and reconstitution of PARP-1 regulating reactions in vitro.

Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue.

Science.gov (United States)

Ding, Xiaofeng; Zhou, Xixi; Cooper, Karen L; Huestis, Juliana; Hudson, Laurie G; Liu, Ke Jian

2017-09-15

Arsenite directly binds to the zinc finger domains of the DNA repair protein poly (ADP ribose) polymerase (PARP)-1, and inhibits PARP-1 activity in the base excision repair (BER) pathway. PARP inhibition by arsenite enhances ultraviolet radiation (UVR)-induced DNA damage in keratinocytes, and the increase in DNA damage is reduced by zinc supplementation. However, little is known about the effects of arsenite and zinc on the zinc finger nucleotide excision repair (NER) protein xeroderma pigmentosum group A (XPA). In this study, we investigated the difference in response to arsenite exposure between XPA and PARP-1, and the differential effectiveness of zinc supplementation in restoring protein DNA binding and DNA damage repair. Arsenite targeted both XPA and PARP-1 in human keratinocytes, resulting in zinc loss from each protein and a pronounced decrease in XPA and PARP-1 binding to chromatin as demonstrated by Chip-on-Western assays. Zinc effectively restored DNA binding of PARP-1 and XPA to chromatin when zinc concentrations were equal to those of arsenite. In contrast, zinc was more effective in rescuing arsenite-augmented direct UVR-induced DNA damage than oxidative DNA damage. Taken together, our findings indicate that arsenite interferes with PARP-1 and XPA binding to chromatin, and that zinc supplementation fully restores DNA binding activity to both proteins in the cellular context. Interestingly, rescue of arsenite-inhibited DNA damage repair by supplemental zinc was more sensitive for DNA damage repaired by the XPA-associated NER pathway than for the PARP-1-dependent BER pathway. This study expands our understanding of arsenite's role in DNA repair inhibition and co-carcinogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism

International Nuclear Information System (INIS)

Lakatos, Petra; Hegedűs, Csaba; Salazar Ayestarán, Nerea; Juarranz, Ángeles; Kövér, Katalin E.; Szabó, Éva; Virág, László

2016-01-01

Highlights: • PARP-1 is not a key regulator of photochemotherapy. • The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism. • Photosensitization by PJ-34 is associated with increased ROS production and DNA damage. • Cells sensitized by PJ-34 undergo caspase-mediated apoptosis. - Abstract: A combination of a photosensitizer with light of matching wavelength is a common treatment modality in various diseases including psoriasis, atopic dermatitis and tumors. DNA damage and production of reactive oxygen intermediates may impact pathological cellular functions and viability. Here we set out to investigate the role of the nuclear DNA nick sensor enzyme poly(ADP-ribose) polymerase 1 in photochemical treatment (PCT)-induced tumor cell killing. We found that silencing PARP-1 or inhibition of its enzymatic activity with Veliparib had no significant effect on the viability of A431 cells exposed to 8-methoxypsoralen (8-MOP) and UVA (2.5 J/cm"2) indicating that PARP-1 is not likely to be a key player in either cell survival or cell death of PCT-exposed cells. Interestingly, however, another commonly used PARP inhibitor PJ-34 proved to be a photosensitizer with potency equal to 8-MOP. Irradiation of PJ-34 with UVA caused changes both in the UV absorption and in the 1H NMR spectra of the compound with the latter suggesting UVA-induced formation of tautomeric forms of the compound. Characterization of the photosensitizing effect revealed that PJ–34 + UVA triggers overproduction of reactive oxygen species, induces DNA damage, activation of caspase 3 and caspase 8 and internucleosomal DNA fragmentation. Cell death in this model could not be prevented by antioxidants (ascorbic acid, trolox, glutathione, gallotannin or cell permeable superoxide dismutase or catalase) but could be suppressed by inhibitors of caspase-3 and −8. In conclusion, PJ-34 is a photosensitizer and PJ–34 + UVA causes DNA damage and caspase

The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism

Energy Technology Data Exchange (ETDEWEB)

Lakatos, Petra; Hegedűs, Csaba [Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen (Hungary); Salazar Ayestarán, Nerea; Juarranz, Ángeles [Department of Biology, Faculty of Sciences, Universidad Autónoma of Madrid, 28049-Madrid (Spain); Kövér, Katalin E. [Department of Inorganic and Analytical Chemistry, Faculty of Sciences, University of Debrecen, Debrecen (Hungary); Szabó, Éva [Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen (Hungary); Virág, László, E-mail: lvirag@med.unideb.hu [Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen (Hungary); MTA-DE Cell Biology and Signaling Research Group, Debrecen (Hungary)

2016-08-15

Highlights: • PARP-1 is not a key regulator of photochemotherapy. • The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism. • Photosensitization by PJ-34 is associated with increased ROS production and DNA damage. • Cells sensitized by PJ-34 undergo caspase-mediated apoptosis. - Abstract: A combination of a photosensitizer with light of matching wavelength is a common treatment modality in various diseases including psoriasis, atopic dermatitis and tumors. DNA damage and production of reactive oxygen intermediates may impact pathological cellular functions and viability. Here we set out to investigate the role of the nuclear DNA nick sensor enzyme poly(ADP-ribose) polymerase 1 in photochemical treatment (PCT)-induced tumor cell killing. We found that silencing PARP-1 or inhibition of its enzymatic activity with Veliparib had no significant effect on the viability of A431 cells exposed to 8-methoxypsoralen (8-MOP) and UVA (2.5 J/cm{sup 2}) indicating that PARP-1 is not likely to be a key player in either cell survival or cell death of PCT-exposed cells. Interestingly, however, another commonly used PARP inhibitor PJ-34 proved to be a photosensitizer with potency equal to 8-MOP. Irradiation of PJ-34 with UVA caused changes both in the UV absorption and in the 1H NMR spectra of the compound with the latter suggesting UVA-induced formation of tautomeric forms of the compound. Characterization of the photosensitizing effect revealed that PJ–34 + UVA triggers overproduction of reactive oxygen species, induces DNA damage, activation of caspase 3 and caspase 8 and internucleosomal DNA fragmentation. Cell death in this model could not be prevented by antioxidants (ascorbic acid, trolox, glutathione, gallotannin or cell permeable superoxide dismutase or catalase) but could be suppressed by inhibitors of caspase-3 and −8. In conclusion, PJ-34 is a photosensitizer and PJ–34 + UVA causes DNA damage and caspase

PARP Inhibition Prevents Ethanol-Induced Neuroinflammatory Signaling and Neurodegeneration in Rat Adult-Age Brain Slice Cultures

Science.gov (United States)

Tajuddin, Nuzhath; Kim, Hee-Yong

2018-01-01

Using rat adult-age hippocampal-entorhinal cortical (HEC) slice cultures, we examined the role of poly [ADP-ribose] polymerase (PARP) in binge ethanol’s brain inflammatory and neurodegenerative mechanisms. Activated by DNA strand breaks, PARP (principally PARP1 in the brain) promotes DNA repair via poly [ADP-ribose] (PAR) products, but PARP overactivation triggers regulated neuronal necrosis (e.g., parthanatos). Previously, we found that brain PARP1 levels were upregulated by neurotoxic ethanol binges in adult rats and HEC slices, and PARP inhibitor PJ34 abrogated slice neurodegeneration. Binged HEC slices also exhibited increased Ca+2-dependent phospholipase A2 (PLA2) isoenzymes (cPLA2 IVA and sPLA2 IIA) that mobilize proinflammatory ω6 arachidonic acid (ARA). We now find in 4-day–binged HEC slice cultures (100 mM ethanol) that PARP1 elevations after two overnight binges precede PAR, cPLA2, and sPLA2 enhancements by 1 day and high-mobility group box-1 (HMGB1), an ethanol-responsive alarmin that augments proinflammatory cytokines via toll-like receptor-4 (TLR4), by 2 days. After verifying that PJ34 effectively blocks PARP activity (↑PAR), we demonstrated that, like PJ34, three other PARP inhibitors—olaparib, veliparib, and 4-aminobenzamide—provided neuroprotection from ethanol. Importantly, PJ34 and olaparib also prevented ethanol’s amplification of the PLA2 isoenzymes, and two PLA2 inhibitors were neuroprotective—thus coupling PARP to PLA2, with PLA2 activity promoting neurodegeneration. Also, PJ34 and olaparib blocked ethanol-induced HMGB1 elevations, linking brain PARP induction to TLR4 activation. The results provide evidence in adult brains that induction of PARP1 may mediate dual neuroinflammatory pathways (PLA2→phospholipid→ARA and HMGB1→TLR4→proinflammatory cytokines) that are complicit in binge ethanol-induced neurodegeneration. PMID:29339456

Solar architecture and energy policies in France: from the oil crisis to the solar crisis

International Nuclear Information System (INIS)

Chauvin-Michel, Marion

2013-01-01

In 1973, the oil crisis creates a focus on energy efficiency policy. Public institutions implement studies on solar architecture and launch experiments and training campaigns to promote the solar equipment. But the presidential election of 1981 leads to a change in energy policy, plunging the solar sector in crisis, causing the disappearance of solar architecture

The role of hnRPUL1 involved in DNA damage response is related to PARP1.

Directory of Open Access Journals (Sweden)

Zehui Hong

Full Text Available Heterogeneous nuclear ribonucleoprotein U-like 1 (hnRPUL1 -also known as adenovirus early region 1B-associated proteins 5 (E1B-AP5 - plays a role in RNA metabolism. Recently, hnRPUL1 has also been shown to be involved in DNA damage response, but the function of hnRPUL1 in response to DNA damage remains unclear. Here, we have demonstrated that hnRPUL1 is associated with PARP1 and recruited to DNA double-strand breaks (DSBs sites in a PARP1-mediated poly (ADP-ribosyl ation dependent manner. In turn, hnRPUL1 knockdown enhances the recruitment of PARP1 to DSBs sites. Specifically, we showed that hnRPUL1 is also implicated in the transcriptional regulation of PARP1 gene. Thus, we propose hnRPUL1 as a new component related to PARP1 in DNA damage response and repair.

Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

Energy Technology Data Exchange (ETDEWEB)

Sun, Xi; Zhou, Xixi [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Du, Libo [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Liu, Wenlan [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Yang [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Hudson, Laurie G. [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Ke Jian, E-mail: kliu@salud.unm.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

2014-01-15

Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of zinc finger

Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

International Nuclear Information System (INIS)

Sun, Xi; Zhou, Xixi; Du, Libo; Liu, Wenlan; Liu, Yang; Hudson, Laurie G.; Liu, Ke Jian

2014-01-01

Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of zinc finger

The NAD+/PARP1/SIRT1 Axis in Aging.

Science.gov (United States)

Mendelsohn, Andrew R; Larrick, James W

2017-06-01

NAD+ levels decline with age in diverse animals from Caenorhabditis elegans to mice. Raising NAD+ levels by dietary supplementation with NAD+ precursors, nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), improves mitochondrial function and muscle and neural and melanocyte stem cell function in mice, as well as increases murine life span. Decreased NAD+ levels with age reduce SIRT1 function and reduce the mitochondrial unfolded protein response, which can be overcome by NR supplementation. Decreased NAD+ levels cause NAD+-binding protein DBC1 to form a complex with PARP1, inhibiting poly(adenosine diphosphate-ribose) polymerase (PARP) catalytic activity. Old mice have increased amounts of DBC1-PARP1 complexes, lower PARP activity, increased DNA damage, and reduced nonhomologous end joining and homologous recombination repair. DBC1-PARP1 complexes in old mice can be broken by increasing NAD+ levels through treatment with NMN, reducing DNA damage and restoring PARP activity to youthful levels. The mechanism of declining NAD+ levels and its fundamental importance to aging are yet to be elucidated. There is a correlation of PARP activity with mammalian life span that suggests that NAD+/SIRT1/PARP1 may be more significant than the modest effects on life span observed for NR supplementation in old mice. The NAD+/PARP1/SIRT1 axis may link NAD+ levels and DNA damage with the apparent epigenomic DNA methylation clocks that have been described.

Crisis and Policy Reformcraft: Advocacy Coalitions and Crisis-induced Change in Swedish Nuclear Energy Policy

Energy Technology Data Exchange (ETDEWEB)

Nohrstedt, Daniel

2007-04-15

This dissertation consists of three interrelated essays examining the role of crisis events in Swedish nuclear energy policymaking. The study takes stock of the idea of 'crisis exceptionalism' raised in the literature, which postulates that crisis events provide openings for major policy change. In an effort to explain crisis-induced outcomes in Swedish nuclear energy policy, each essay explores and develops theoretical assumptions derived from the Advocacy Coalition Framework (ACF). The introduction discusses the ACF and other theoretical perspectives accentuating the role of crisis in policymaking and identifies three explanations for crisis-induced policy outcomes: minority coalition mobilization, learning, and strategic action. Essay 1 analyzes the nature and development of the Swedish nuclear energy subsystem. The results contradict the ACF assumption that corporatist systems nurture narrow subsystems and small advocacy coalitions, but corroborate the assumption that advocacy coalitions remain stable over time. While this analysis identifies temporary openings in policymaking venues and in the advocacy coalition structure, it is argued that these developments did not affect crisis policymaking. Essay 2 seeks to explain the decision to initiate a referendum on nuclear power following the 1979 Three Mile Island accident. Internal government documents and other historical records indicate that strategic considerations superseded learning as the primary explanation in this case. Essay 3 conducts an in-depth examination of Swedish policymaking in the aftermath of the 1986 Chernobyl accident in an effort to explain the government's decision not to accelerate the nuclear power phaseout. Recently disclosed government documents show that minority coalition mobilization was insufficient to explain this decision. In this case, rational learning and strategic action provided a better explanation. The main theoretical contribution derived from the three

Crisis and Policy Reformcraft: Advocacy Coalitions and Crisis-induced Change in Swedish Nuclear Energy Policy

International Nuclear Information System (INIS)

Nohrstedt, Daniel

2007-04-01

This dissertation consists of three interrelated essays examining the role of crisis events in Swedish nuclear energy policymaking. The study takes stock of the idea of 'crisis exceptionalism' raised in the literature, which postulates that crisis events provide openings for major policy change. In an effort to explain crisis-induced outcomes in Swedish nuclear energy policy, each essay explores and develops theoretical assumptions derived from the Advocacy Coalition Framework (ACF). The introduction discusses the ACF and other theoretical perspectives accentuating the role of crisis in policymaking and identifies three explanations for crisis-induced policy outcomes: minority coalition mobilization, learning, and strategic action. Essay 1 analyzes the nature and development of the Swedish nuclear energy subsystem. The results contradict the ACF assumption that corporatist systems nurture narrow subsystems and small advocacy coalitions, but corroborate the assumption that advocacy coalitions remain stable over time. While this analysis identifies temporary openings in policymaking venues and in the advocacy coalition structure, it is argued that these developments did not affect crisis policymaking. Essay 2 seeks to explain the decision to initiate a referendum on nuclear power following the 1979 Three Mile Island accident. Internal government documents and other historical records indicate that strategic considerations superseded learning as the primary explanation in this case. Essay 3 conducts an in-depth examination of Swedish policymaking in the aftermath of the 1986 Chernobyl accident in an effort to explain the government's decision not to accelerate the nuclear power phaseout. Recently disclosed government documents show that minority coalition mobilization was insufficient to explain this decision. In this case, rational learning and strategic action provided a better explanation. The main theoretical contribution derived from the three essays is to posit

Aag DNA glycosylase promotes alkylation-induced tissue damage mediated by Parp1.

Science.gov (United States)

Calvo, Jennifer A; Moroski-Erkul, Catherine A; Lake, Annabelle; Eichinger, Lindsey W; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick T; Christiani, David C; Meira, Lisiane B; Samson, Leona D

2013-04-01

Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag⁻/⁻ mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.

Aag DNA glycosylase promotes alkylation-induced tissue damage mediated by Parp1.

Directory of Open Access Journals (Sweden)

Jennifer A Calvo

2013-04-01

Full Text Available Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag⁻/⁻ mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.

PARP-1 expression is increased in colon adenoma and carcinoma and correlates with OGG1.

Directory of Open Access Journals (Sweden)

Tomasz Dziaman

Full Text Available The ethiology of colon cancer is largely dependent on inflammation driven oxidative stress. The analysis of 8-oxodeoxyguanosine (8-oxodGuo level in leukocyte DNA of healthy controls (138 individuals, patients with benign adenomas (AD, 137 individuals and with malignant carcinomas (CRC, 169 individuals revealed a significant increase in the level of 8-oxodGuo in leukocyte DNA of AD and CRC patients in comparison to controls. The counteracting mechanism is base excision repair, in which OGG1 and PARP-1 play a key role. We investigated the level of PARP-1 and OGG1 mRNA and protein in diseased and marginal, normal tissues taken from AD and CRC patients and in leukocytes taken from the patients as well as from healthy subjects. In colon tumors the PARP-1 mRNA level was higher than in unaffected colon tissue and in polyp tissues. A high positive correlation was found between PARP-1 and OGG1 mRNA levels in all investigated tissues. This suggests reciprocal influence of PARP-1 and OGG1 on their expression and stability, and may contribute to progression of colon cancer. PARP-1 and OGG1 proteins level was several fold higher in polyps and CRC in comparison to normal colon tissues. Individuals bearing the Cys326Cys genotype of OGG1 were characterized by higher PARP-1 protein level in diseased tissues than the Ser326Cys and Ser326Ser genotypes. Aforementioned result may suggest that the diseased cells with polymorphic OGG1 recruit more PARP protein, which is necessary to remove 8-oxodGuo. Thus, patients with decreased activity of OGG1/polymorphism of the OGG1 gene and higher 8-oxodGuo level may be more susceptible to treatment with PARP-1 inhibitors.

Energy crisis and uranium energy resources

International Nuclear Information System (INIS)

Koryakin, Yu.I.

1975-01-01

Problems of ensuring a supply of nuclear power with fuel are reviewed. It is probable that by the year 2000 fuel requirements for nuclear power will be determined by the heat variant of its development since the fraction of fast breeders will then be very insignificant. In connection with the energy process, in western countries there has arisen the economic possibility of using more expensive uranium (more than $22 per kg U 3 O 8 ). Now there is the point of view that, in the new post-crisis conditions, nuclear power plants with light-water reactors will be competitive. It is expected that the energy crisis will give additional impetus to development of nuclear power. In some countries work is being done on extraction of uranium from sea water. In this case, in order for uranium supplies to meet nuclear energy needs for 8, 10, or 12 years, new supplies of uranium must be sought every year. For each kilogram of U 3 O 8 , supplies of uranium will cost $11-17.6 more. Annual inflation will move the recovery costs into the higher cost category. There is good reason to consider that a significant increase in the cost of nuclear power plants and a sharp rise in credit will lead to a more concrete prediction of the total nuclear power in 2000 A.D. of 2700-3200 million kW. With exhaustion of cheap supplies, uranium will be classified by politico-economic considerations. In this case the presentation concerning the competitiveness of nuclear power and conventional energy sources may change

Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells

NARCIS (Netherlands)

Verhagen, Caroline V. M.; de Haan, Rosemarie; Hageman, Floor; Oostendorp, Tim P. D.; Carli, Annalisa L. E.; O'Connor, Mark J.; Jonkers, Jos; Verheij, Marcel; van den Brekel, Michiel W.; Vens, Conchita

2015-01-01

The PARP inhibitor olaparib is currently tested in clinical phase 1 trials to define safe dose levels in combination with RT. However, certain clinically relevant insights are still lacking. Here we test, while comparing to single agent activity, the olaparib dose and genetic background dependence

Cells deficient in PARP-1 show an accelerated accumulation of DNA single strand breaks, but not AP sites, over the PARP-1-proficient cells exposed to MMS.

Science.gov (United States)

Pachkowski, Brian F; Tano, Keizo; Afonin, Valeriy; Elder, Rhoderick H; Takeda, Shunichi; Watanabe, Masami; Swenberg, James A; Nakamura, Jun

2009-12-01

Poly(ADP-ribose) polymerase-1 (PARP-1) is a base excision repair (BER) protein that binds to DNA single strand breaks (SSBs) and subsequently synthesizes and transfers poly(ADP-ribose) polymers to various nuclear proteins. Numerous biochemical studies have implicated PARP-1 as a modulator of BER; however, the role of PARP-1 in BER in living cells remains unclear partly due to lack of accurate quantitation of BER intermediates existing in cells. Since DT40 cells, chicken B lymphocytes, naturally lack PARP-2, DT40 cells allow for the investigation of the PARP-1 null phenotype without confounding by PARP-2. To test the hypothesis that PARP-1 is necessary for efficient BER during methylmethane sulfonate (MMS) exposure in vertebrate cells, intact DT40 cells and their isogenic PARP-1 null counterparts were challenged with different exposure scenarios for phenotypic characterization. With chronic exposure, PARP-1 null cells exhibited sensitivity to MMS but with an acute exposure did not accumulate base lesions or AP sites to a greater extent than wild-type cells. However, an increase in SSB content in PARP-1 null cell DNA, as indicated by glyoxal gel electrophoresis under neutral conditions, suggested the presence of BER intermediates. These data suggest that during exposure, PARP-1 impacts the stage of BER after excision of the deoxyribosephosphate moiety from the 5' end of DNA strand breaks by polymerase beta.

Imidazoquinolinone, imidazopyridine, and isoquinolindione derivatives as novel and potent inhibitors of the poly(ADP-ribose) polymerase (PARP): a comparison with standard PARP inhibitors.

Science.gov (United States)

Eltze, Tobias; Boer, Rainer; Wagner, Thomas; Weinbrenner, Steffen; McDonald, Michelle C; Thiemermann, Christoph; Bürkle, Alexander; Klein, Thomas

2008-12-01

We have identified three novel structures for inhibitors of the poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA and implicated in DNA repair, apoptosis, organ dysfunction or necrosis. 2-[4-(5-Methyl-1H-imidazol-4-yl)-piperidin-1-yl]-4,5-dihydro-imidazo[4,5,1-i,j]quinolin-6-one (BYK49187), 2-(4-pyridin-2-yl-phenyl)-4,5-dihydro-imidazo[4,5,1-i,j]quinolin-6-one (BYK236864), 6-chloro-8-hydroxy-2,3-dimethyl-imidazo-[1,2-alpha]-pyridine (BYK20370), and 4-(1-methyl-1H-pyrrol-2-ylmethylene)-4H-isoquinolin-1,3-dione (BYK204165) inhibited cell-free recombinant human PARP-1 with pIC(50) values of 8.36, 7.81, 6.40, and 7.35 (pK(i) 7.97, 7.43, 5.90, and 7.05), and murine PARP-2 with pIC(50) values of 7.50, 7.55, 5.71, and 5.38, respectively. BYK49187, BYK236864, and BYK20370 displayed no selectivity for PARP-1/2, whereas BYK204165 displayed 100-fold selectivity for PARP-1. The IC(50) values for inhibition of poly(ADP-ribose) synthesis in human lung epithelial A549 and cervical carcinoma C4I cells as well in rat cardiac myoblast H9c2 cells after PARP activation by H(2)O(2) were highly significantly correlated with those at cell-free PARP-1 (r(2) = 0.89-0.96, P < 0.001) but less with those at PARP-2 (r(2) = 0.78-0.84, P < 0.01). The infarct size caused by coronary artery occlusion and reperfusion in the anesthetized rat was reduced by 22% (P < 0.05) by treatment with BYK49187 (3 mg/kg i.v. bolus and 3 mg/kg/h i.v. during 2-h reperfusion), whereas the weaker PARP inhibitors, BYK236864 and BYK20370, were not cardioprotective. In conclusion, the imidazoquinolinone BYK49187 is a potent inhibitor of human PARP-1 activity in cell-free and cellular assays in vitro and reduces myocardial infarct size in vivo. The isoquinolindione BYK204165 was found to be 100-fold more selective for PARP-1. Thus, both compounds might be novel and valuable tools for investigating PARP-1-mediated effects.

PARP-1 inhibition alleviates diabetic cardiac complications in experimental animals.

Science.gov (United States)

Zakaria, Esraa M; El-Bassossy, Hany M; El-Maraghy, Nabila N; Ahmed, Ahmed F; Ali, Abdelmoneim A

2016-11-15

Cardiovascular complications are the major causes of mortality among diabetic population. Poly(ADP-ribose) polymerase-1 enzyme (PARP-1) is activated by oxidative stress leading to cellular damage. We investigated the implication of PARP-1 in diabetic cardiac complications. Type 2 diabetes was induced in rats by high fructose-high fat diet and low streptozotocin dose. PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for ten weeks after diabetes induction. At the end of study, surface ECG, blood pressure and vascular reactivity were studied. PARP-1 activity, reduced glutathione (GSH) and nitrite contents were assessed in heart muscle. Fasting glucose, fructosamine, insulin, and tumor necrosis factor alpha (TNF-α) levels were measured in serum. Finally, histological examination and collagen deposition detection in rat ventricular and aortic sections were carried out. Hearts isolated from diabetic animals showed increased PARP-1 enzyme activity compared to control animals while significantly reduced by 4-AB administration. PARP-1 inhibition by 4-AB alleviated cardiac ischemia in diabetic animals as indicated by ECG changes. PARP-1 inhibition also reduced cardiac inflammation in diabetic animals as evidenced by histopathological changes. In addition, 4-AB administration improved the elevated blood pressure and the associated exaggerated vascular contractility, endothelial destruction and vascular inflammation seen in diabetic animals. Moreover, PARP-1 inhibition decreased serum levels of TNF-α and cardiac nitrite but increased cardiac GSH contents in diabetic animals. However, PARP-1 inhibition did not significantly affect the developed hyperglycemia. Our findings prove that PARP-1 enzyme plays an important role in diabetic cardiac complications through combining inflammation, oxidative stress, and fibrosis mechanisms. Copyright © 2016. Published by Elsevier B.V.

Cells deficient in PARP-1 show an accelerated accumulation of DNA single strand breaks, but not AP sites, over the PARP-1-proficient cells exposed to MMS

Energy Technology Data Exchange (ETDEWEB)

Pachkowski, Brian F. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (United States); Tano, Keizo [Research Reactor Institute, Kyoto University, Kumatori (Japan); Afonin, Valeriy [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (United States); Elder, Rhoderick H. [School of Environment and Life Sciences, University of Salford, Greater Manchester (United Kingdom); Takeda, Shunichi [Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto (Japan); Watanabe, Masami [Research Reactor Institute, Kyoto University, Kumatori (Japan); Swenberg, James A. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (United States); Nakamura, Jun, E-mail: ynakamur@email.unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (United States)

2009-12-01

Poly(ADP-ribose) polymerase-1 (PARP-1) is a base excision repair (BER) protein that binds to DNA single strand breaks (SSBs) and subsequently synthesizes and transfers poly(ADP-ribose) polymers to various nuclear proteins. Numerous biochemical studies have implicated PARP-1 as a modulator of BER; however, the role of PARP-1 in BER in living cells remains unclear partly due to lack of accurate quantitation of BER intermediates existing in cells. Since DT40 cells, chicken B lymphocytes, naturally lack PARP-2, DT40 cells allow for the investigation of the PARP-1 null phenotype without confounding by PARP-2. To test the hypothesis that PARP-1 is necessary for efficient BER during methylmethane sulfonate (MMS) exposure in vertebrate cells, intact DT40 cells and their isogenic PARP-1 null counterparts were challenged with different exposure scenarios for phenotypic characterization. With chronic exposure, PARP-1 null cells exhibited sensitivity to MMS but with an acute exposure did not accumulate base lesions or AP sites to a greater extent than wild-type cells. However, an increase in SSB content in PARP-1 null cell DNA, as indicated by glyoxal gel electrophoresis under neutral conditions, suggested the presence of BER intermediates. These data suggest that during exposure, PARP-1 impacts the stage of BER after excision of the deoxyribosephosphate moiety from the 5' end of DNA strand breaks by polymerase {beta}.

Telomere shortening is associated to TRF1 and PARP1 overexpression in Duchenne muscular dystrophy.

Science.gov (United States)

Aguennouz, M'Hammed; Vita, Gian Luca; Messina, Sonia; Cama, Annamaria; Lanzano, Natalia; Ciranni, Annamaria; Rodolico, Carmelo; Di Giorgio, Rosa Maria; Vita, Giuseppe

2011-12-01

Telomere shortening is thought to contribute to premature senescence of satellite cells in Duchenne muscular dystrophy (DMD) muscle. Telomeric repeat binding factor-1 (TRF1) and poly (ADP-ribose) polymerase-1 (PARP1) are proteins known to modulate telomerase reverse transcriptase (TERT) activity, which controls telomere elongation. Here we show that an age-dependent telomere shortening occurs in DMD muscles and is associated to overexpression of mRNA and protein levels of TRF1 and PARP1. TERT expression and activity are detectable in normal control muscles and they slightly increase in DMD. This is the first demonstration of TRF1 and PARP1 overexpression in DMD muscles. They can be directly involved in replicative senescence of satellite cells and/or in the pathogenetic cascade through a cross-talk with oxidative stress and inflammatory response. Modulation of these events by TRF1 or PARP1 inhibition might represent a novel strategy for treatment of DMD and other muscular dystrophies. Copyright © 2010 Elsevier Inc. All rights reserved.

PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration

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Alexander Jonathan S

2010-12-01

Full Text Available Abstract The normal function of poly (ADP-ribose polymerase-1 (PARP-1 is the routine repair of DNA damage by adding poly (ADP ribose polymers in response to a variety of cellular stresses. Recently, it has become widely appreciated that PARP-1 also participates in diverse physiological and pathological functions from cell survival to several forms of cell death and has been implicated in gene transcription, immune responses, inflammation, learning, memory, synaptic functions, angiogenesis and aging. In the CNS, PARP inhibition attenuates injury in pathologies like cerebral ischemia, trauma and excitotoxicity demonstrating a central role of PARP-1 in these pathologies. PARP-1 is also a preferred substrate for several 'suicidal' proteases and the proteolytic action of suicidal proteases (caspases, calpains, cathepsins, granzymes and matrix metalloproteinases (MMPs on PARP-1 produces several specific proteolytic cleavage fragments with different molecular weights. These PARP-1 signature fragments are recognized biomarkers for specific patterns of protease activity in unique cell death programs. This review focuses on specific suicidal proteases active towards PARP-1 to generate signature PARP-1 fragments that can identify key proteases and particular forms of cell death involved in pathophysiology. The roles played by some of the PARP-1 fragments and their associated binding partners in the control of different forms of cell death are also discussed.

An energy crisis in Armenia

International Nuclear Information System (INIS)

Koutaniemi, P.

1994-01-01

The energy crisis in Armenia is reviewed in the article. Most of the energy generating plants in the country have come to a standstill. The only nuclear power plant in the country has been out of use since the earthquake in 1988, and power generation by the Sevan hydro power plant is limited because the level of Lake Sevan has fallen too low. At moment Armenia needs foreign aid to overcome the energy shortage. For example, the country does not have enough resources or expertise to restart the nuclear power plant

Climatic threat, energy crisis, and illusions of a nuclear revival

International Nuclear Information System (INIS)

2008-10-01

While considering the example of the French nuclear reactor fleet, and while indicating various data concerning energy savings, CO 2 emissions, energy consumption in France and in other European countries, and also the occurrence of incidents in nuclear plants, this publication discusses the context of a climatic crisis, energy crisis, and of a possible nuclear revival boosted by the decreasing use of fossil energies to comply with the objective of reduction of greenhouse gases. It discusses the relationship a nuclear revival would have with climate change, with energy safety and with energy transition

The energy crisis and Bonn's atomic energy programme

International Nuclear Information System (INIS)

Steinhaus, K.; Heimbrecht, J.

1979-01-01

What are the background and causes of the energy crisis. In whose interest and on whose back is energy policy made in our country. Will the lights go out without nuclear power. Which are the real goals and dangers of Bonn's atomic energy programme. Is coal a real alternative to nuclear power in the Federal Republic of Germany. What possibilities and requirements are there for a national and democratic energy policy in the Federal Republic of Germany. Which are the central problems of the protest movement against the government's atomic energy programme. These questions, which are still in the centre of political discussion, are investigated by the authors. (orig.) [de

China's energy consumption under the global economic crisis: Decomposition and sectoral analysis

International Nuclear Information System (INIS)

Li, Fangyi; Song, Zhouying; Liu, Weidong

2014-01-01

It is now widely recognized that there is a strong relationship between energy consumption and economic growth. Most countries′ energy demands declined during the economic depression of 2008–2009 when a worldwide economic crisis occurred. As an export-oriented economy, China suffered a serious exports decline in the course of the crisis. However, it was found that energy consumption continued to increase. Against such a background, this paper aims to assess and explain the factors causing the growth of energy consumption in China. First, we will explain the impact of domestic final use and international trade on energy consumption by using decomposition analysis. Second, embodied energy and its variation across sectors are quantified to identify the key sectors contributing to the growth. Lastly, the policy implications for long-term energy conservation are discussed. The results show that the decline in exports was one of the driving forces for energy consumption reduction in the crisis, but that the growth of domestic demand in manufacturing and construction, largely stimulated by economic stimulus plans, had the opposite effect on energy consumption. International trade contributed to decreasing energy consumption of China during and after the crisis because the structure of exports and imports changed in this period. - Highlights: • We analyze the reasons for China's energy consumption change under the global economic crisis during 2007–2010. • Domestic final use growth, especially in construction and manufacturing of machinery and equipment, resulted in energy consumption increase. • International trade is identified as a driver of energy consumption reduction during and after the crisis. • Increasing China's share of consumption or reducing its share of investment in the GDP can reduce national energy intensity

Energy shortage - a produced crisis

International Nuclear Information System (INIS)

Anon.

1979-01-01

Five articles of the central organ of the KPD/ML, the 'Roter Morgen', and a declaration of the central committee of th KPD/ML are published here. The articles deal with: raw materials-utilization and deposits; the oil-multis - the world's greatest financial power; the energy industry of the FRG; nuclear power - the new trick of the old bosses; resisting the bulling of oil prices, securing energy supply on the basis of coal. The articles are clearly combative and against capitalism, energy concerns and oil-multis. The energy crisis is declared to be a problem of capitalism which can only be solved by abolishing the capitalist system and its laws of profit. (HSCH) [de

Increased oxidative stress mediates the antitumor effect of PARP inhibition in ovarian cancer

Directory of Open Access Journals (Sweden)

Dong Hou

2018-07-01

Full Text Available PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful. Because PARP primarily functions in sensing and repairing DNA strand breaks, the therapeutic effect of PARP inhibition is generally believed to be attributed to impaired DNA repair. We here report that oxidative stress is also increased by PARP inhibition and mediates the antitumor effect. We showed that PARP1 is highly expressed in specimens of high grade serous ovarian carcinoma and its activity is required for unperturbed proliferation of ovarian cancer cells. Inhibition or depletion of PARP leads to not only an increase in DNA damage, but also an elevation in the levels of reactive oxygen species (ROS. Importantly, antioxidant N-acetylcysteine (NAC significantly attenuated the induction of DNA damage and the perturbation of proliferation by PARP inhibition or depletion. We further showed that NADPH oxidases 1 and 4 were significantly upregulated by PARP inhibition and were partially responsible for the induction of oxidative stress. Depletion of NOX1 and NOX4 partially rescued the growth inhibition of PARP1-deficient tumor xenografts. Our findings suggest that in addition to compromising the repair of DNA damage, PARP inhibition or depletion may exert extra antitumor effect by elevating oxidative stress in ovarian cancer cells. Keywords: PARP1, Oxidative stress, NADPH oxidases, Ovarian cancer

It's easy to blame industry. [Question/answer sessions on energy crisis

Energy Technology Data Exchange (ETDEWEB)

Blatz, L

1977-01-01

The energy crisis did abound before the Arab oil embargo, so says Leo Blatz, but that action did bring the crisis to the fore. This action further brought about a change in attitudes. In this interview, Mr. Blatz commented on the reasons for the crisis, wastefulness in energy consumption; cost to the U.S. to import oil; reinstatement of coal usage; renewable energy source development and the time lag in this area; reasons for the lack of understanding; profits in industry; ways to solve problems between lifestyle and energy consumption; reserving petroleum supplies for much needed petrochemicals; environmental impacts; and where the responsibility lies. He says industry is tagged as the polluter, but ''industry is nothing but a collection of human beings.'' (MCW)

Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.

Science.gov (United States)

Thorsell, Ann-Gerd; Ekblad, Torun; Karlberg, Tobias; Löw, Mirjam; Pinto, Ana Filipa; Trésaugues, Lionel; Moche, Martin; Cohen, Michael S; Schüler, Herwig

2017-02-23

Selective inhibitors could help unveil the mechanisms by which inhibition of poly(ADP-ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 clinical PARP inhibitors and commonly used research tools for their inhibition of multiple PARP enzymes. We also determined crystal structures of these compounds bound to PARP1 or PARP2. Veliparib and niraparib are selective inhibitors of PARP1 and PARP2; olaparib, rucaparib, and talazoparib are more potent inhibitors of PARP1 but are less selective. PJ34 and UPF1069 are broad PARP inhibitors; PJ34 inserts a flexible moiety into hydrophobic subpockets in various ADP-ribosyltransferases. XAV939 is a promiscuous tankyrase inhibitor and a potent inhibitor of PARP1 in vitro and in cells, whereas IWR1 and AZ-6102 are tankyrase selective. Our biochemical and structural analysis of PARP inhibitor potencies establishes a molecular basis for either selectivity or promiscuity and provides a benchmark for experimental design in assessment of PARP inhibitor effects.

Characterization of Novel Cytoplasmic PARP in the Brain of Octopus vulgaris

Science.gov (United States)

DE LISA, EMILIA; DE MAIO, ANNA; MOROZ, LEONID L.; MOCCIA, FRANCESCO; MENNELLA, MARIA ROSARIA FARAONE; DI COSMO, ANNA

2014-01-01

Recent investigation has focused on the participation of the poly (ADP-ribose) polymerase (PARP) reaction in the invertebrate central nervous system (CNS) during the process of long-term memory (LTM). In this paper, we characterize, localize, and assign a possible role to a cytoplasmic PARP in the brain of Octopus vulgaris. PARP activity was assayed in optic lobes, supraesophageal mass, and optic nerves. The highest levels of enzyme were found in the cytoplasmic fraction. Hyper-activation of the enzyme was detected in Octopus brain after visual discrimination training. Finally, cytoplasmic PARP was found to inhibit Octopus vulgaris actin polymerization. We propose that the cytoplasmic PARP plays a role in vivo to induce the cytoskeletonal reorganization that occurs during learning-induced neuronal plasticity. PMID:22815366

Carbon ion beam triggers both caspase-dependent and caspase-independent pathway of apoptosis in HeLa and status of PARP-1 controls intensity of apoptosis.

Science.gov (United States)

Ghorai, Atanu; Sarma, Asitikantha; Bhattacharyya, Nitai P; Ghosh, Utpal

2015-04-01

High linear energy transfer (LET) carbon ion beam (CIB) is becoming very promising tool for various cancer treatments and is more efficient than conventional low LET gamma or X-rays to kill malignant or radio-resistant cells, although detailed mechanism of cell death is still unknown. Poly (ADP-ribose) polymerase-1 (PARP-1) is a key player in DNA repair and its inhibitors are well-known as radio-sensitizer for low LET radiation. The objective of our study was to find mechanism(s) of induction of apoptosis by CIB and role of PARP-1 in CIB-induced apoptosis. We observed overall higher apoptosis in PARP-1 knocked down HeLa cells (HsiI) compared with negative control H-vector cells after irradiation with CIB (0-4 Gy). CIB activated both intrinsic and extrinsic pathways of apoptosis via caspase-9 and caspase-8 activation respectively, followed by caspase-3 activation, apoptotic body, nucleosomal ladder formation and sub-G1 accumulation. Apoptosis inducing factor translocation into nucleus in H-vector but not in HsiI cells after CIB irradiation contributed caspase-independent apoptosis. Higher p53 expression was observed in HsiI cells compared with H-vector after exposure with CIB. Notably, we observed about 37 % fall of mitochondrial membrane potential, activation of caspase-9 and caspase-3 and mild activation of caspase-8 without any detectable apoptotic body formation in un-irradiated HsiI cells. We conclude that reduction of PARP-1 expression activates apoptotic signals via intrinsic and extrinsic pathways in un-irradiated cells. CIB irradiation further intensified both intrinsic and extrinsic pathways of apoptosis synergistically along with up-regulation of p53 in HsiI cells resulting overall higher apoptosis in HsiI than H-vector.

Resources of Greenland and the possibilities of a joint Danish/Greenland exploitation of specially the energy resources in a period of economic crisis

International Nuclear Information System (INIS)

Taagholt, J.

1983-01-01

As Greenland is very dependent on imported articles and fuels, mainly petroleum, economic crisis or just an energy crisis will affect Greenland very much. To evaluate Greenlands situation in a crisis an account is given of the climatic conditions, of the present economic situation, and of planned development projects, The Greenland Area has Denmarks largest potential energy reserves of known coal deposits, of partially surveyed uranium deposits, of partially surveyed potential hydroelectric power reserves, and of petroleum and natural gas deposits not yet pointed out. An analysis is made of the utilization of the Greenland energy resources today, and the plans of future extended utilization. (LN)

Leading the Way to the Third Industrial Revolution. Addressing the Triple Threat of the Global Financial Crisis, Energy Crisis, and Climate Change

International Nuclear Information System (INIS)

Rifkin, J.; Da Graca Carvalho, M.; Consoli, A.; Bonifacio, M.

2008-01-01

We are at a precarious point in history. We are facing the real prospect of an economic meltdown on the scale of the Great Depression. The credit crisis is compounded by the global energy crisis and the climate change crisis, creating a potential cataclysm for civilization. There is a way out: we need to radically overhaul the way we use energy in our society

Leading the Way to the Third Industrial Revolution. Addressing the Triple Threat of the Global Financial Crisis, Energy Crisis, and Climate Change

Energy Technology Data Exchange (ETDEWEB)

Rifkin, J.; Da Graca Carvalho, M.; Consoli, A.; Bonifacio, M.

2008-12-15

We are at a precarious point in history. We are facing the real prospect of an economic meltdown on the scale of the Great Depression. The credit crisis is compounded by the global energy crisis and the climate change crisis, creating a potential cataclysm for civilization. There is a way out: we need to radically overhaul the way we use energy in our society.

Escape from Telomere-Driven Crisis Is DNA Ligase III Dependent

Directory of Open Access Journals (Sweden)

Rhiannon E. Jones

2014-08-01

Full Text Available Short dysfunctional telomeres are capable of fusion, generating dicentric chromosomes and initiating breakage-fusion-bridge cycles. Cells that escape the ensuing cellular crisis exhibit large-scale genomic rearrangements that drive clonal evolution and malignant progression. We demonstrate that there is an absolute requirement for fully functional DNA ligase III (LIG3, but not ligase IV (LIG4, to facilitate the escape from a telomere-driven crisis. LIG3- and LIG4-dependent alternative (A and classical (C nonhomologous end-joining (NHEJ pathways were capable of mediating the fusion of short dysfunctional telomeres, both displaying characteristic patterns of microhomology and deletion. Cells that failed to escape crisis exhibited increased proportions of C-NHEJ-mediated interchromosomal fusions, whereas those that escaped displayed increased proportions of intrachromosomal fusions. We propose that the balance between inter- and intrachromosomal telomere fusions dictates the ability of human cells to escape crisis and is influenced by the relative activities of A- and C-NHEJ at short dysfunctional telomeres.

Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy.

Science.gov (United States)

Nitta, Masayuki; Kozono, David; Kennedy, Richard; Stommel, Jayne; Ng, Kimberly; Zinn, Pascal O; Kushwaha, Deepa; Kesari, Santosh; Inda, Maria-del-Mar; Wykosky, Jill; Furnari, Frank; Hoadley, Katherine A; Chin, Lynda; DePinho, Ronald A; Cavenee, Webster K; D'Andrea, Alan; Chen, Clark C

2010-05-24

Despite the critical role of Epidermal Growth Factor Receptor (EGFR) in glioblastoma pathogenesis, EGFR targeted therapies have achieved limited clinical efficacy. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction. A directed RNAi screen revealed that glioblastoma cells over-expressing EGFRvIII, an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER) genes required for the repair of Reactive Oxygen Species (ROS)-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1). Subsequent studies revealed that EGFRvIII over-expression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyper-activation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy.

Directory of Open Access Journals (Sweden)

Masayuki Nitta

Full Text Available Despite the critical role of Epidermal Growth Factor Receptor (EGFR in glioblastoma pathogenesis, EGFR targeted therapies have achieved limited clinical efficacy. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction. A directed RNAi screen revealed that glioblastoma cells over-expressing EGFRvIII, an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER genes required for the repair of Reactive Oxygen Species (ROS-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1. Subsequent studies revealed that EGFRvIII over-expression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyper-activation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

Functional characterisation of an Arabidopsis gene strongly induced by ionising radiation: the gene coding the poly(ADP-ribose)polymerase-1 (AthPARP-1)

International Nuclear Information System (INIS)

Doucet-Chabeaud, G.

2000-01-01

Arabidopsis thaliana, the model-system in plant genetics, has been used to study the responses to DNA damage, experimentally introduced by γ-irradiation. We have characterised a radiation-induced gene coding a 111 kDa protein, AthPARP-1, homologous to the human poly(ADP-ribose)polymerase-1 (hPARP-1). As hPARP-1 is composed by three functional domain with characteristic motifs, AthPARP-1 binds to DNA bearing single-strand breaks and shows DNA damage-dependent poly(ADP-ribosyl)ation. The preferential expression of AthPARP-1 in mitotically active tissues is in agreement with a potential role in the maintenance of genome integrity during DNA replication, as proposed for its human counterpart. Transcriptional gene activation by ionising radiation of AthPARP-1 and AthPARP-2 genes is to date plant specific activation. Our expression analyses after exposure to various stress indicate that 1) AthPARP-1 and AthPARP-2 play an important role in the response to DNA lesions, particularly they are activated by genotoxic agents implicating the BER DNA repair pathway 2) AthPARP-2 gene seems to play an additional role in the signal transduction induced by oxidative stress 3) the observed expression profile of AthPARP-1 is in favour of the regulation of AthPARP-1 gene expression at the level of transcription and translation. This mode of regulation of AthPARP-1 protein biosynthesis, clearly distinct from that observed in animals, needs the implication of a so far unidentified transcription factor that is activated by the presence of DNA lesions. The major outcome of this work resides in the isolation and characterisation of such new transcription factor, which will provide new insight on the regulation of plant gene expression by genotoxic stress. (author) [fr

Autoimmune response to PARP and BRCA1/BRCA2 in cancer

Science.gov (United States)

Zhu, Qing; Han, Su-Xia; Zhou, Cong-Ya; Cai, Meng-Jiao; Dai, Li-Ping; Zhang, Jian-Ying

2015-01-01

Purpose To determine the role of autoantibodies to PARP1 and BRCA1/BRCA2 which were involved in the synthetic lethal interaction in cancer. Methods Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect autoantibodies to PARP1 and BRCA1/BRCA2 in 618 serum samples including 131 from breast cancer, 94 from lung cancer, 34 from ovarian cancer, 107 from prostate cancer, 76 from liver cancer, 41 from pancreatic cancer and 135 from normal individuals. The positive sera with ELISA were confirmed by Western blot. Immunohistochemistry was used to examine the expression of PARP1 and BRCA1/BRCA2 in breast cancer. Results Autoantibody frequency to PARP1, BRCA1, and BRCA2 in cancer varied from 0% to 50%. When the sera from cancer patients were tested for the presence of autoantibodies to PARP1 and BRCA1/BRCA2, the autoantibody responses slightly decreased and the positive autoantibody reactions varied from 0% to 50.0%. This was significantly higher autoantibody responses to PARP1 and BRCA1/BRCA2 (especially to PARP1 and BRCA1) in ovarian cancer and breast cancer compared to normal control sera (P cancer was different (P cancers have different profiles of autoantibodies. The autoantibodies to proteins involving the synthetic lethal interactions would be novel serological biomarker in some selective cancers. PMID:25865228

PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?

Energy Technology Data Exchange (ETDEWEB)

Swindall, Amanda F.; Stanley, Jennifer A. [Department of Radiation Oncology Comprehensive Cancer Center, University of Alabama at Birmingham School of Medicine, 176F HSROC Suite 2232B, 1700 6th Avenue South, Birmingham, AL 35249 (United States); Yang, Eddy S., E-mail: eyang@uab.edu [Department of Radiation Oncology Comprehensive Cancer Center, University of Alabama at Birmingham School of Medicine, 176F HSROC Suite 2232B, 1700 6th Avenue South, Birmingham, AL 35249 (United States); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35249 (United States); Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35249 (United States)

2013-07-26

Oxidative stress induced by reactive oxygen species can result in DNA damage within cells and subsequently increase risk for carcinogenesis. This may be averted by repair of DNA damage through the base or nucleotide excision repair (BER/NER) pathways. PARP, a BER protein, is known for its role in DNA-repair. However, multiple lesions can occur within a small range of DNA, known as oxidative clustered DNA lesions (OCDLs), which are difficult to repair and may lead to the more severe DNA double-strand break (DSB). Inefficient DSB repair can then result in increased mutagenesis and neoplastic transformation. OCDLs occur more frequently within a variety of tumor tissues. Interestingly, PARP is highly expressed in several human cancers. Additionally, chronic inflammation may contribute to tumorigenesis through ROS-induced DNA damage. Furthermore, PARP can modulate inflammation through interaction with NFκB and regulating the expression of inflammatory signaling molecules. Thus, the upregulation of PARP may present a double-edged sword. PARP is needed to repair ROS-induced DNA lesions, but PARP expression may lead to increased inflammation via upregulation of NFκB signaling. Here, we discuss the role of PARP in the repair of oxidative damage versus the formation of OCDLs and speculate on the feasibility of PARP inhibition for the treatment and prevention of cancers by exploiting its role in inflammation.

PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?

International Nuclear Information System (INIS)

Swindall, Amanda F.; Stanley, Jennifer A.; Yang, Eddy S.

2013-01-01

Oxidative stress induced by reactive oxygen species can result in DNA damage within cells and subsequently increase risk for carcinogenesis. This may be averted by repair of DNA damage through the base or nucleotide excision repair (BER/NER) pathways. PARP, a BER protein, is known for its role in DNA-repair. However, multiple lesions can occur within a small range of DNA, known as oxidative clustered DNA lesions (OCDLs), which are difficult to repair and may lead to the more severe DNA double-strand break (DSB). Inefficient DSB repair can then result in increased mutagenesis and neoplastic transformation. OCDLs occur more frequently within a variety of tumor tissues. Interestingly, PARP is highly expressed in several human cancers. Additionally, chronic inflammation may contribute to tumorigenesis through ROS-induced DNA damage. Furthermore, PARP can modulate inflammation through interaction with NFκB and regulating the expression of inflammatory signaling molecules. Thus, the upregulation of PARP may present a double-edged sword. PARP is needed to repair ROS-induced DNA lesions, but PARP expression may lead to increased inflammation via upregulation of NFκB signaling. Here, we discuss the role of PARP in the repair of oxidative damage versus the formation of OCDLs and speculate on the feasibility of PARP inhibition for the treatment and prevention of cancers by exploiting its role in inflammation

Research progress of PARP-1 inhibitors in antitumor drugs and radionuclide markers

International Nuclear Information System (INIS)

Zhao Lingzhou; Zhang Huabei

2011-01-01

Poly(ADP-ribose)polymerase (PARP) is a new target in the cancer treatment nowadays. PARP not only can repair DNA damage, regulate and control transcription, maintain the stability of intracellular environment and genome, regulate the process of cell survival and death, but also is the main transcription factor in the development of inflammation and the process of cancer. To inhibit PARP activity can reduce the DNA repair function in tumor cells, and increase the sensibility to DNA damage agents, so as to improve the efficacy of radiation therapy and chemotherapy for tumor. A number of studies have suggested that, whether used alone or combination with other chemotherapy drugs, PARP inhibitors show the potential in the anti-tumor therapeutic areas. In this paper, PARP-1 inhibitors were reviewed in antitumor research progress. According to the stage of development , PARP-1 inhibitors are classified. Several representative PARP-1 inhibitors, in clinical trials, with potential clinical value were introduced. Positron emission tomography (PET), uses the main short half-life elementary in human body as tracer, and at the molecular level, achieve the no wound, quantitative and dynamic observation about the different changes of metabolites or drugs in the body. PET is the most advanced contemporary video diagnostic technology, and this paper simply introduce the research progress of PARP-1 inhibitors labeled with radioactive nuclides. (authors)

Residential consumer behavior during and after an energy crisis

Energy Technology Data Exchange (ETDEWEB)

Aragao Neto, Raymundo [International Institute for Energy Conservation, Rio de Janeiro, RJ (Brazil)]. E-mail: raragao@iiec.org; Javaroni, Mario Cesar [ECOLUZ Consultores Associados, Rio de Janeiro, RJ (Brazil)]. E-mail: javaroni@ecoluz.com.br

2004-07-01

Brazil faced a severe energy crisis during 2001 and 2002 that reflected in all sectors including residential, and obliged to reduce in 20 per cent consumption, considering 2000 basis. New products were largely used, and domestic customs changed. This paper evaluates how residential behaviour has changed during the crisis period, and one year later what initiatives (habits, appliances) remained, considering a survey with 240 consumers. (author)

Energy crisis management: ways to cope with disruption in oil supply

Energy Technology Data Exchange (ETDEWEB)

Kanoh, T

1981-03-10

The causes and impacts of past oil-supply disruptions are examined in terms of the effectiveness of management strategies used to deal with the crisis. Progress is noted in the recent decline of US imports, augmented oil stockpiles, a turnaway from the spot market, oil self-sufficiency for Britain, conservation programs in France, price decontrol in Canada, and alternative energy projects in Japan. The International Energy Agency (IEA) plans to develop an emergency scheme that first seeks to minimize the chance of a crisis arising and then to minimize adverse impacts should one occur. The first part of the strategy incorporates demand management, increased energy production, cooperation between producing and consuming countries, and political stability. The emergency measures for dealing with an actual crisis will emphasize life and safety. 15 references. (DCK)

miR-520 promotes DNA-damage-induced trophoblast cell apoptosis by targeting PARP1 in recurrent spontaneous abortion (RSA).

Science.gov (United States)

Dong, Xiujuan; Yang, Long; Wang, Hui

2017-04-01

The establishment and maintenance of successful pregnancy mainly depends on trophoblast cells. Their dysfunction has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy. However, the underlying mechanisms of trophoblasts dysfunction remain unclear. DNA-damage-induced cell apoptosis has been reported to play a vital role in cell death. In this study, we identified a novel microRNA (miR-520) in RSA progression via regulating trophoblast cell apoptosis. Microarray analysis showed that miR-520 was highly expressed in villus of RSA patients. By using flow cytometry analysis, we observed miR-520 expression was correlated with human trophoblast cell apoptosis in vitro, along with decreased poly (ADP-ribose) polymerase-1 (PARP1) expression. With the analysis of clinic samples, we observed that miR-520 level was negatively correlated with PARP1 level in RSA villus. In addition, overexpression of PARP1 restored the miR-520-induced trophoblast cell apoptosis in vitro. The status of chromosome in trophoblast implied that miR-520-promoted DNA-damage-induced cell apoptosis to regulate RSA progression. These results indicated that the level of miR-520 might associate with RSA by prompting trophoblast cell apoptosis via PARP1 dependent DNA-damage pathway.

The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism.

Science.gov (United States)

Lakatos, Petra; Hegedűs, Csaba; Salazar Ayestarán, Nerea; Juarranz, Ángeles; Kövér, Katalin E; Szabó, Éva; Virág, László

2016-08-01

A combination of a photosensitizer with light of matching wavelength is a common treatment modality in various diseases including psoriasis, atopic dermatitis and tumors. DNA damage and production of reactive oxygen intermediates may impact pathological cellular functions and viability. Here we set out to investigate the role of the nuclear DNA nick sensor enzyme poly(ADP-ribose) polymerase 1 in photochemical treatment (PCT)-induced tumor cell killing. We found that silencing PARP-1 or inhibition of its enzymatic activity with Veliparib had no significant effect on the viability of A431 cells exposed to 8-methoxypsoralen (8-MOP) and UVA (2.5J/cm(2)) indicating that PARP-1 is not likely to be a key player in either cell survival or cell death of PCT-exposed cells. Interestingly, however, another commonly used PARP inhibitor PJ-34 proved to be a photosensitizer with potency equal to 8-MOP. Irradiation of PJ-34 with UVA caused changes both in the UV absorption and in the 1H NMR spectra of the compound with the latter suggesting UVA-induced formation of tautomeric forms of the compound. Characterization of the photosensitizing effect revealed that PJ-34+UVA triggers overproduction of reactive oxygen species, induces DNA damage, activation of caspase 3 and caspase 8 and internucleosomal DNA fragmentation. Cell death in this model could not be prevented by antioxidants (ascorbic acid, trolox, glutathione, gallotannin or cell permeable superoxide dismutase or catalase) but could be suppressed by inhibitors of caspase-3 and -8. In conclusion, PJ-34 is a photosensitizer and PJ-34+UVA causes DNA damage and caspase-mediated cell death independently of PARP-1 inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

Studies of the expression of human poly(ADP-ribose) polymerase-1 in Saccharomyces cerevisiae and identification of PARP-1 substrates by yeast proteome microarray screening.

Science.gov (United States)

Tao, Zhihua; Gao, Peng; Liu, Hung-Wen

2009-12-15

Poly(ADP-ribosyl)ation of various nuclear proteins catalyzed by a family of NAD(+)-dependent enzymes, poly(ADP-ribose) polymerases (PARPs), is an important posttranslational modification reaction. PARP activity has been demonstrated in all types of eukaryotic cells with the exception of yeast, in which the expression of human PARP-1 was shown to lead to retarded cell growth. We investigated the yeast growth inhibition caused by human PARP-1 expression in Saccharomyces cerevisiae. Flow cytometry analysis reveals that PARP-1-expressing yeast cells accumulate in the G(2)/M stage of the cell cycle. Confocal microscopy analysis shows that human PARP-1 is distributed throughout the nucleus of yeast cells but is enriched in the nucleolus. Utilizing yeast proteome microarray screening, we identified 33 putative PARP-1 substrates, six of which are known to be involved in ribosome biogenesis. The poly(ADP-ribosyl)ation of three of these yeast proteins, together with two human homologues, was confirmed by an in vitro PARP-1 assay. Finally, a polysome profile analysis using sucrose gradient ultracentrifugation demonstrated that the ribosome levels in yeast cells expressing PARP-1 are lower than those in control yeast cells. Overall, our data suggest that human PARP-1 may affect ribosome biogenesis by modifying certain nucleolar proteins in yeast. The artificial PARP-1 pathway in yeast may be used as a simple platform to identify substrates and verify function of this important enzyme.

BET Bromodomain Inhibition Synergizes with PARP Inhibitor in Epithelial Ovarian Cancer

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Sergey Karakashev

2017-12-01

Full Text Available PARP inhibition is known to be an effective clinical strategy in BRCA mutant cancers, but PARP inhibition has not been applied to BRCA-proficient tumors. Here, we show the synergy of BET bromodomain inhibition with PARP inhibition in BRCA-proficient ovarian cancers due to mitotic catastrophe. Treatment of BRCA-proficient ovarian cancer cells with the BET inhibitor JQ1 downregulated the G2-M cell-cycle checkpoint regulator WEE1 and the DNA-damage response factor TOPBP1. Combining PARP inhibitor Olaparib with the BET inhibitor, we observed a synergistic increase in DNA damage and checkpoint defects, which allowed cells to enter mitosis despite the accumulation of DNA damage, ultimately causing mitotic catastrophe. Moreover, JQ1 and Olaparib showed synergistic suppression of growth of BRCA-proficient cancer in vivo in a xenograft ovarian cancer mouse model. Our findings indicate that a combination of BET inhibitor and PARP inhibitor represents a potential therapeutic strategy for BRCA-proficient cancers.

PARP2 Is the Predominant Poly(ADP-Ribose Polymerase in Arabidopsis DNA Damage and Immune Responses.

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Junqi Song

2015-05-01

Full Text Available Poly (ADP-ribose polymerases (PARPs catalyze the transfer of multiple poly(ADP-ribose units onto target proteins. Poly(ADP-ribosylation plays a crucial role in a variety of cellular processes including, most prominently, auto-activation of PARP at sites of DNA breaks to activate DNA repair processes. In humans, PARP1 (the founding and most characterized member of the PARP family accounts for more than 90% of overall cellular PARP activity in response to DNA damage. We have found that, in contrast with animals, in Arabidopsis thaliana PARP2 (At4g02390, rather than PARP1 (At2g31320, makes the greatest contribution to PARP activity and organismal viability in response to genotoxic stresses caused by bleomycin, mitomycin C or gamma-radiation. Plant PARP2 proteins carry SAP DNA binding motifs rather than the zinc finger domains common in plant and animal PARP1 proteins. PARP2 also makes stronger contributions than PARP1 to plant immune responses including restriction of pathogenic Pseudomonas syringae pv. tomato growth and reduction of infection-associated DNA double-strand break abundance. For poly(ADP-ribose glycohydrolase (PARG enzymes, we find that Arabidopsis PARG1 and not PARG2 is the major contributor to poly(ADP-ribose removal from acceptor proteins. The activity or abundance of PARP2 is influenced by PARP1 and PARG1. PARP2 and PARP1 physically interact with each other, and with PARG1 and PARG2, suggesting relatively direct regulatory interactions among these mediators of the balance of poly(ADP-ribosylation. As with plant PARP2, plant PARG proteins are also structurally distinct from their animal counterparts. Hence core aspects of plant poly(ADP-ribosylation are mediated by substantially different enzymes than in animals, suggesting the likelihood of substantial differences in regulation.

Novel targeted therapeutics: inhibitors of MDM2, ALK and PARP

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Hsueh Chung-Tsen

2011-04-01

Full Text Available Abstract We reviewed preclinical data and clinical development of MDM2 (murine double minute 2, ALK (anaplastic lymphoma kinase and PARP (poly [ADP-ribose] polymerase inhibitors. MDM2 binds to p53, and promotes degradation of p53 through ubiquitin-proteasome degradation. JNJ-26854165 and RO5045337 are 2 small-molecule inhibitors of MDM2 in clinical development. ALK is a transmembrane protein and a member of the insulin receptor tyrosine kinases. EML4-ALK fusion gene is identified in approximately 3-13% of non-small cell lung cancer (NSCLC. Early-phase clinical studies with Crizotinib, an ALK inhibitor, in NSCLC harboring EML4-ALK have demonstrated promising activity with high response rate and prolonged progression-free survival. PARPs are a family of nuclear enzymes that regulates the repair of DNA single-strand breaks through the base excision repair pathway. Randomized phase II study has shown adding PARP-1 inhibitor BSI-201 to cytotoxic chemotherapy improves clinical outcome in patients with triple-negative breast cancer. Olaparib, another oral small-molecule PARP inhibitor, demonstrated encouraging single-agent activity in patients with advanced breast or ovarian cancer. There are 5 other PARP inhibitors currently under active clinical investigation.

Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1

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Daniëlle M. P. H. J. Boesten

2013-01-01

Full Text Available Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence. Research has shown that poly(ADP-ribose polymerase-1 (PARP-1 and subtelomeric methylation play a role in telomere stability. We hypothesized that PARP-1 plays a role in accelerated aging in chronic inflammatory diseases due to its role as coactivator of NF-κb and AP-1. Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline in human fibroblasts (HF cultured under normal conditions and under conditions of chronic oxidative stress, induced by tert-butyl hydroperoxide (t-BHP. Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions.

Challenge - oil crisis

International Nuclear Information System (INIS)

Vogler, O.

1981-01-01

After a short survey on recent developments of energy supply the risks of future energy supply and its effects are discussed. The parameters of dependence on oil-producing countries are studied and an evaluation is given on the measures which have to be taken by the Western industrialized countries in response to the dependence on oil. Further subjects are: mechanism of oil distribution in case of crisis, long-term cooperation of producer countries, measures on international level in the USA and Japan, and the energy-importing countries in the conflict area between OPEC- and industrialized countries. (UA) [de

MicroRNAs Modulate Oxidative Stress in Hypertension through PARP-1 Regulation

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Douglas F. Dluzen

2017-01-01

Full Text Available Oxidative stress is thought to contribute to aging and age-related diseases, such as cardiovascular and neurodegenerative diseases, and is a risk factor for systemic arterial hypertension. Previously, we reported differential mRNA and microRNA (miRNA expression between African American (AA and white women with hypertension. Here, we found that the poly-(ADP-ribose polymerase 1 (PARP-1, a DNA damage sensor protein involved in DNA repair and other cellular processes, is upregulated in AA women with hypertension. To explore this mechanism, we identified two miRNAs, miR-103a-2-5p and miR-585-5p, that are differentially expressed with hypertension and were predicted to target PARP1. Through overexpression of each miRNA-downregulated PARP-1 mRNA and protein levels and using heterologous luciferase reporter assays, we demonstrate that miR-103a-2-5p and miR-585-5p regulate PARP1 through binding within the coding region. Given the important role of PARP-1 in DNA repair, we assessed whether overexpression of miR-103a-2-5p or miR-585-5p affected DNA damage and cell survival. Overexpression of these miRNAs enhanced DNA damage and decreased both cell survival and colony formation. These findings highlight the role for PARP-1 in regulating oxidative DNA damage in hypertension and identify important new miRNA regulators of PARP-1 expression. These insights may provide additional avenues to understand hypertension health disparities.

Financial Crisis and Energy Efficiency. Information paper

Energy Technology Data Exchange (ETDEWEB)

de T' Serclaes, Philippine; Gasc, Emilien; Saussay, Aurelien

2009-10-15

Governments have understood the importance of financing energy efficiency now. This realisation is exemplified through the central role occupied by energy efficiency in most stimulus packages. The purpose of this memo is to identify the impact of the financial and economic crisis on the evolution of public sector investments, energy efficiency policy development, and private sector investments. The paper will first identify trends which have emerged from the implementation of IEA government stimulus packages. Most relevant case studies are then provided along with lessons and challenges.

Targeted Radiosensitization of ETS Fusion-Positive Prostate Cancer through PARP1 Inhibition

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Sumin Han

2013-10-01

Full Text Available ETS gene fusions, which result in overexpression of an ETS transcription factor, are considered driving mutations in approximately half of all prostate cancers. Dysregulation of ETS transcription factors is also known to exist in Ewing's sarcoma, breast cancer, and acute lymphoblastic leukemia. We previously discovered that ERG, the predominant ETS family member in prostate cancer, interacts with the DNA damage response protein poly (ADP-ribose polymerase 1 (PARP1 in human prostate cancer specimens. Therefore, we hypothesized that the ERG-PARP1 interaction may confer radiation resistance by increasing DNA repair efficiency and that this radio-resistance could be reversed through PARP1 inhibition. Using lentiviral approaches, we established isogenic models of ERG overexpression in PC3 and DU145 prostate cancer cell lines. In both cell lines, ERG overexpression increased clonogenic survival following radiation by 1.25 (±0.07 fold (mean ± SEM and also resulted in increased PARP1 activity. PARP1 inhibition with olaparib preferentially radiosensitized ERG-positive cells by a factor of 1.52 (±0.03 relative to ERG-negative cells (P < .05. Neutral and alkaline COMET assays and immunofluorescence microscopy assessing γ-H2AX foci showed increased short- and long-term efficiencies of DNA repair, respectively, following radiation that was preferentially reversed by PARP1 inhibition. These findings were verified in an in vivo xenograft model. Our findings demonstrate that ERG overexpression confers radiation resistance through increased efficiency of DNA repair following radiation that can be reversed through inhibition of PARP1. These results motivate the use of PARP1 inhibitors as radiosensitizers in patients with localized ETS fusion-positive cancers.

Melatonin regulates PARP1 to control the senescence-associated secretory phenotype (SASP) in human fetal lung fibroblast cells.

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Yu, Songtao; Wang, Xiaojiao; Geng, Peiliang; Tang, Xudong; Xiang, Lisha; Lu, Xin; Li, Jianjun; Ruan, Zhihua; Chen, Jianfang; Xie, Ganfeng; Wang, Zhe; Ou, Juanjuan; Peng, Yuan; Luo, Xi; Zhang, Xuan; Dong, Yan; Pang, Xueli; Miao, Hongming; Chen, Hongshan; Liang, Houjie

2017-08-01

Cellular senescence is an important tumor-suppressive mechanism. However, acquisition of a senescence-associated secretory phenotype (SASP) in senescent cells has deleterious effects on the tissue microenvironment and, paradoxically, promotes tumor progression. In a drug screen, we identified melatonin as a novel SASP suppressor in human cells. Strikingly, melatonin blunts global SASP gene expression upon oncogene-induced senescence (OIS). Moreover, poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage, was identified as a new melatonin-dependent regulator of SASP gene induction upon OIS. Here, we report two different but potentially coherent epigenetic strategies for melatonin regulation of SASP. The interaction between the telomeric repeat-containing RNA (TERRA) and PARP-1 stimulates the SASP, which was attenuated by 67.9% (illustrated by the case of IL8) by treatment with melatonin. Through binding to macroH2A1.1, PARP-1 recruits CREB-binding protein (CBP) to mediate acetylation of H2BK120, which positively regulates the expression of target SASP genes, and this process is interrupted by melatonin. Consequently, the findings provide novel insight into melatonin's epigenetic role via modulating PARP-1 in suppression of SASP gene expression in OIS-induced senescent cells. Our studies identify melatonin as a novel anti-SASP molecule, define PARP-1 as a new target by which melatonin regulates SASP, and establish a new epigenetic paradigm for a pharmacological mechanism by which melatonin interrupts PARP-1 interaction with the telomeric long noncoding RNA(lncRNA) or chromatin. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Combination strategy of PARP inhibitor with antioxidant prevent bioenergetic deficits and inflammatory changes in CCI-induced neuropathy.

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Komirishetty, Prashanth; Areti, Aparna; Gogoi, Ranadeep; Sistla, Ramakrishna; Kumar, Ashutosh

2017-02-01

Neuropathic pain, a debilitating pain condition and the underlying pathogenic mechanisms are complex and interwoven amongst each other and still there is scant information available regarding therapies which promise to treat the condition. Evidence indicate that oxidative/nitrosative stress induced poly (ADP-ribose) polymerase (PARP) overactivation initiate neuroinflammation and bioenergetic crisis culminating into neurodegenerative changes following nerve injury. Hence, we investigated the therapeutic effect of combining an antioxidant, quercetin and a PARP inhibitor, 4-amino 1, 8-naphthalimide (4-ANI) on the hallmark deficits induced by chronic constriction injury (CCI) of sciatic nerve in rats. Quercetin (25 mg/kg, p.o.) and 4-ANI (3 mg/kg, p.o.) were administered either alone or in combination for 14 days to examine sciatic functional index, allodynia and hyperalgesia using walking track analysis, Von Frey, acetone spray and hot plate tests respectively. Malondialdehyde, nitrite and glutathione levels were estimated to detect oxidative/nitrosative stress; mitochondrial membrane potential and cytochrome c oxidase activity to assess mitochondrial function; NAD & ATP levels to examine the bioenergetic status and levels of inflammatory markers were evaluated in ipsilateral sciatic nerve. Quercetin and 4-ANI alone improved the pain behaviour and biochemical alterations but the combination therapy demonstrated an appreciable reversal of CCI-induced changes. Nitrotyrosine and Poly ADP-Ribose (PAR) immunopositivity was decreased and nuclear factor erythroid 2-related factor (Nrf-2) levels were increased significantly in micro-sections of the sciatic nerve and dorsal root ganglion (DRG) of treatment group. These results suggest that simultaneous inhibition of oxidative stress-PARP activation cascade may potentially be useful strategies for management of trauma induced neuropathic pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

PARP-1 como regulador del ciclo celular

OpenAIRE

Iglesias Vázquez, Pablo

2015-01-01

En el presente estudio hemos querido investigar las implicaciones biológicas de la interacción PARP-1/E2F-1 en escenarios en los que el factor de transcripción E2F-1 resulta de gran importancia como son el desarrollo embrionario y la oncogénesis. En este respecto, hemos demostrado que tanto PJ34, inhibidor de la actividad enzimática de PARP, como gosipol, inhibidor de las interacciones proteína-proteína, son capaces de reducir la actividad transcripcional de E2F-1 y la proli...

Impact of global financial crisis on stylized facts between energy markets and stock markets

Science.gov (United States)

Leng, Tan Kim; Cheong, Chin Wen; Hooi, Tan Siow

2014-06-01

Understanding the stylized facts is extremely important and has becomes a hot issue nowadays. However, recent global financial crisis that started from United States had spread all over the world and adversely affected the commodities and financial sectors of both developed and developing countries. This paper tends to examine the impact of crisis on stylized facts between energy and stock markets using ARCH-family models based on the experience over 2008 global financial crisis. Empirical results denote that there is long lasting, persists and positively significant the autocorrelation function of absolute returns and their squares in both markets for before and during crisis. Besides that, leverage effects are found in stock markets whereby bad news has a greater impact on volatility than good news for both before and during crisis. However, crisis does not indicate any impact on risk-return tradeoff for both energy and stock markets. For forecasting evaluations, GARCH model and FIAPARCH model indicate superior out of sample forecasts for before and during crisis respectively.

A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells

Science.gov (United States)

Nüske, Stefan; Scholz, Armin M.; Bogner, Jacqueline; Ruf, Benjamin; Zolghadr, Kourosh; Drexler, Sophie E.; Drexler, Guido A.; Girst, Stefanie; Greubel, Christoph; Reindl, Judith; Siebenwirth, Christian; Romer, Tina; Friedl, Anna A.; Rothbauer, Ulrich

2016-01-01

Poly(ADP-ribose) polymerase 1 (PARP1) is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa), termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair. PMID:26950694

A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells.

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Andrea Buchfellner

Full Text Available Poly(ADP-ribose polymerase 1 (PARP1 is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa, termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair.

A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells.

Science.gov (United States)

Buchfellner, Andrea; Yurlova, Larisa; Nüske, Stefan; Scholz, Armin M; Bogner, Jacqueline; Ruf, Benjamin; Zolghadr, Kourosh; Drexler, Sophie E; Drexler, Guido A; Girst, Stefanie; Greubel, Christoph; Reindl, Judith; Siebenwirth, Christian; Romer, Tina; Friedl, Anna A; Rothbauer, Ulrich

2016-01-01

Poly(ADP-ribose) polymerase 1 (PARP1) is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa), termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair.

Overcoming energy injustice? Bulgaria’s renewable energy transition in times of crisis

OpenAIRE

Andreas, Jan-Justus; Burns, Charlotte Jennie; Touza-Montero, Julia Maria

2018-01-01

The effects of renewable energy transitions on energy costs and economic growth have led to cost concerns and a prioritisation of economic issues during the economic crisis. Bulgaria, the EU's poorest state has nevertheless already achieved its 2020 renewable energy targets. This achievement seems to challenge the widely held as- sumption that poorer countries struggle to meet environmental objectives. This paper analyses the drivers and implications of Bulgaria's renewables expansion in orde...

PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia

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Raimundo M. G. del Moral

2013-01-01

Full Text Available We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN and other renal lesions related to prolonged cold ischemia/reperfusion (IR in kidneys preserved at 4°C in University of Wisconsin (UW solution. Material and Methods. We used 30 male Parp1+/+ wild-type and 15 male Parp10/0 knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinylbutoxyl]-1(2H-isoquinolinone (DPQ at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ. We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp10/0 knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

The role of nuclear energy against the background of the worldwide energy crisis

International Nuclear Information System (INIS)

Roux, A.J.A.

1980-01-01

The availability, consumption and conservation of energy sources like oil, coal, natural gas and uranium and the distribution of these sources are discussed. The article also discusses the possible solution to the energy crisis in the future on the short, medium and long term and the position of South Africa in this regard

Radiosensitization by PARP inhibition to proton beam irradiation in cancer cells

Energy Technology Data Exchange (ETDEWEB)

Hirai, Takahisa [Department of Radiation Oncology, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo (Japan); Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Saito, Soichiro; Fujimori, Hiroaki [Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Matsushita, Keiichiro; Nishio, Teiji [Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima-shi, Hiroshima (Japan); Okayasu, Ryuichi [International Open Laboratory, National Institute of Radiological Science, Chiba-shi, Chiba (Japan); Masutani, Mitsuko, E-mail: mmasutan@nagasaki-u.ac.jp [Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (Japan)

2016-09-09

The poly(ADP-ribose) polymerase (PARP)-1 regulates DNA damage responses and promotes base excision repair. PARP inhibitors have been shown to enhance the cytotoxicity of ionizing radiation in various cancer cells and animal models. We have demonstrated that the PARP inhibitor (PARPi) AZD2281 is also an effective radiosensitizer for carbon-ion radiation; thus, we speculated that the PARPi could be applied to a wide therapeutic range of linear energy transfer (LET) radiation as a radiosensitizer. Institutes for biological experiments using proton beam are limited worldwide. This study was performed as a cooperative research at heavy ion medical accelerator in Chiba (HIMAC) in National Institute of Radiological Sciences. HIMAC can generate various ion beams; this enabled us to compare the radiosensitization effect of the PARPi on cells subjected to proton and carbon-ion beams from the same beam line. After physical optimization of proton beam irradiation, the radiosensitization effect of the PARPi was assessed in the human lung cancer cell line, A549, and the pancreatic cancer cell line, MIA PaCa-2. The effect of the PARPi, AZD2281, on radiosensitization to Bragg peak was more significant than that to entrance region. The PARPi increased the number of phosphorylated H2AX (γ-H2AX) foci and enhanced G2/M arrest after proton beam irradiation. This result supports our hypothesis that a PARPi could be applied to a wide therapeutic range of LET radiation by blocking the DNA repair response. - Highlights: • Effective radiosensitizers for particle radiation therapy have not been reported. • PARP inhibitor treatment radiosensitized after proton beam irradiation. • The sensitization at Bragg peak was greater than that at entrance region. • DSB induction and G2/M arrest is involved in the sensitization mechanism.

Edaravone abrogates LPS-induced behavioral anomalies, neuroinflammation and PARP-1.

Science.gov (United States)

Sriram, Chandra Shaker; Jangra, Ashok; Gurjar, Satendra Singh; Mohan, Pritam; Bezbaruah, Babul Kumar

2016-02-01

Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA nick-sensor enzyme that functions at the center of cellular stress response and affects the immune system at several key points, and thus modulates inflammatory diseases. Our previous study demonstrated that lipopolysaccharide (LPS)-induced depressive-like behavior in mice can be ameliorated by 3-aminobenzamide, which is a PARP-1 inhibitor. In the present study we've examined the effect of a free radical scavenger, edaravone pretreatment against LPS-induced anxiety and depressive-like behavior as well as various hippocampal biochemical parameters including PARP-1. Male Swiss albino mice were treated with edaravone (3 & 10mg/kgi.p.) once daily for 14days. On the 14th day 30min after edaravone treatment mice were challenged with LPS (1mg/kgi.p.). After 3h and 24h of LPS administration we've tested mice for anxiety and depressive-like behaviors respectively. Western blotting analysis of PARP-1 in hippocampus was carried out after 12h of LPS administration. Moreover, after 24h of LPS administration serum corticosterone, hippocampal BDNF, oxido-nitrosative stress and pro-inflammatory cytokines were estimated by ELISA. Results showed that pretreatment of edaravone (10mg/kg) ameliorates LPS-induced anxiety and depressive-like behavior. Western blotting analysis showed that LPS-induced anomalous expression of PARP-1 significantly reverses by the pretreatment of edaravone (10mg/kg). Biochemical analyses revealed that LPS significantly diminishes BDNF, increases pro-inflammatory cytokines and oxido-nitrosative stress in the hippocampus. However, pretreatment with edaravone (10mg/kg) prominently reversed all these biochemical alterations. Our study emphasized that edaravone pretreatment prevents LPS-induced anxiety and depressive-like behavior, mainly by impeding the inflammation, oxido-nitrosative stress and PARP-1 overexpression. Copyright © 2015. Published by Elsevier Inc.

PARP activity and inhibition in fetal and adult oligodendrocyte precursor cells: Effect on cell survival and differentiation.

Science.gov (United States)

Baldassarro, Vito A; Marchesini, Alessandra; Giardino, Luciana; Calzà, Laura

2017-07-01

Poly (ADP-ribose) polymerase (PARP) family members are ubiquitously expressed and play a key role in cellular processes, including DNA repair and cell death/survival balance. Accordingly, PARP inhibition is an emerging pharmacological strategy for cancer and neurodegenerative diseases. Consistent evidences support the critical involvement of PARP family members in cell differentiation and phenotype maturation. In this study we used an oligodendrocyte precursor cells (OPCs) enriched system derived from fetal and adult brain to investigate the role of PARP in OPCs proliferation, survival, and differentiation. The PARP inhibitors PJ34, TIQ-A and Olaparib were used as pharmacological tools. The main results of the study are: (i) PARP mRNA expression and PARP activity are much higher in fetal than in adult-derived OPCs; (ii) the culture treatment with PARP inhibitors is cytotoxic for OPCs derived from fetal, but not from adult, brain; (iii) PARP inhibition reduces cell number, according to the inhibitory potency of the compounds; (iv) PARP inhibition effect on fetal OPCs is a slow process; (v) PARP inhibition impairs OPCs maturation into myelinating OL in fetal, but not in adult cultures, according to the inhibitory potency of the compounds. These results have implications for PARP-inhibition therapies for diseases and lesions of the central nervous system, in particular for neonatal hypoxic/ischemic encephalopathy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

PARP-1 serves as a novel molecular marker for hepatocellular carcinoma in a Southern Chinese Zhuang population.

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Li, Jiatong; Dou, Dongwei; Li, Ping; Luo, Wenqi; Lv, Wenxin; Zhang, Chengdong; Song, Xiaowei; Yang, Yuan; Zhang, Yuening; Xu, Yanzhen; Xiao, Feifan; Wei, Yan; Qin, Jian; Li, Hongtao; Yang, Xiaoli

2017-07-01

PARP-1 (poly(ADP-ribose) polymerase-1) plays an important role in tumorigenesis. Since its effects on different populations are varied, this study investigated the impact of PARP-1 on primary hepatocellular carcinoma in a Southern Chinese Zhuang population. We assessed the global PARP-1 messenger RNA expression in patients with hepatocellular carcinoma using The Cancer Genome Atlas dataset. Increased PARP-1 expression, related to alpha-fetoprotein level, was observed. The area under the receiver operating characteristic curve value was 0.833. Kaplan-Meier survival curves indicated that higher PARP-1 expression was not correlated with poorer overall survival and recurrence-free survival. In a Zhuang population, PARP-1 messenger RNA and protein levels were increased in the hepatocellular carcinoma tissue and its adjacent liver tissues as assessed by quantitative polymerase chain reaction, immunohistochemistry, and western blotting. Higher PARP-1 level was associated with a higher tumor stage (p  0.05). Further analysis suggested that H2AX, a PARP-1 protein interaction partner, was coordinated with PARP-1 in hepatocellular carcinoma tumorigenesis. Overall, some new characteristics of PARP-1 expression were noted in the Zhuang population. PARP-1 is a novel promising diagnostic marker for hepatocellular carcinoma in the Southern Chinese Zhuang population.

Deficiency in Poly(ADP-ribose Polymerase-1 (PARP-1 Accelerates Aging and Spontaneous Carcinogenesis in Mice

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Tatiana S. Piskunova

2008-01-01

Full Text Available Genetic and biochemical studies have shown that PARP-1 and poly(ADP-ribosylation play an important role in DNA repair, genomic stability, cell death, inflammation, telomere maintenance, and suppressing tumorigenesis, suggesting that the homeostasis of poly(ADP-ribosylation and PARP-1 may also play an important role in aging. Here we show that PARP-1−/− mice exhibit a reduction of life span and a significant increase of population aging rate. Analysis of noninvasive parameters, including body weight gain, body temperature, estrous function, behavior, and a number of biochemical indices suggests the acceleration of biological aging in PARP-1−/− mice. The incidence of spontaneous tumors in both PARP-1−/− and PARP-1+/+ groups is similar; however, malignant tumors including uterine tumors, lung adenocarcinomas and hepatocellular carcinomas, develop at a significantly higher frequency in PARP-1−/− mice than PARP-1+/+ mice (72% and 49%, resp.; < .05. In addition, spontaneous tumors appear earlier in PARP-1−/− mice compared to the wild type group. Histopathological studies revealed a wide spectrum of tumors in uterus, ovaries, liver, lungs, mammary gland, soft tissues, and lymphoid organs in both groups of the mice. These results demonstrate that inactivation of DNA repair gene PARP-1 in mice leads to acceleration of aging, shortened life span, and increased spontaneous carcinogenesis.

PARP-2 regulates cell cycle-related genes through histone deacetylation and methylation independently of poly(ADP-ribosyl)ation

International Nuclear Information System (INIS)

Liang, Ya-Chen; Hsu, Chiao-Yu; Yao, Ya-Li; Yang, Wen-Ming

2013-01-01

Highlights: ► PARP-2 acts as a transcription co-repressor independently of PARylation activity. ► PARP-2 recruits HDAC5, 7, and G9a and generates repressive chromatin. ► PARP-2 is recruited to the c-MYC promoter by DNA-binding factor YY1. ► PARP-2 represses cell cycle-related genes and alters cell cycle progression. -- Abstract: Poly(ADP-ribose) polymerase-2 (PARP-2) catalyzes poly(ADP-ribosyl)ation (PARylation) and regulates numerous nuclear processes, including transcription. Depletion of PARP-2 alters the activity of transcription factors and global gene expression. However, the molecular action of how PARP-2 controls the transcription of target promoters remains unclear. Here we report that PARP-2 possesses transcriptional repression activity independently of its enzymatic activity. PARP-2 interacts and recruits histone deacetylases HDAC5 and HDAC7, and histone methyltransferase G9a to the promoters of cell cycle-related genes, generating repressive chromatin signatures. Our findings propose a novel mechanism of PARP-2 in transcriptional regulation involving specific protein–protein interactions and highlight the importance of PARP-2 in the regulation of cell cycle progression

The Brazilian energy crisis and a study to support building efficiency legislation

Energy Technology Data Exchange (ETDEWEB)

Rosa, L.P. [Federal University of Rio de Janeiro (Brazil). School of Engineering; Lomardo, L.L.B. [Fluminense Federal University and Researcher of COPPE, Rio de Janeiro (Brazil). Dept. of Architecture

2004-02-01

Brazil has gone through an important electricity generation crisis in 2001, but the country does not have as yet a legislation to improve building energy efficiency. The energy efficiency of Brazilian buildings can well be improved, as it was shown during the energy-rationing period in 2001. This efficiency increase could usher in gains in quality for indoor environments, as well as lower investments in power generation facilities, including the emission of gases into the atmosphere, flooding arable land for reservoirs, etc. The current work briefly demonstrates the lack of planning that caused the electricity crisis, some results of multi-building studies and simulations of an existing office building of Rio de Janeiro. In this parametric case-study, we have simulated variations of the window-wall ratio (WWR) with different glasses and interior shade, using the natural light, aspects deemed to be of the utmost importance for a future Brazilian building energy efficiency legislation. The need of such legislation has been much increased as a result of the energy generation crisis and its consequences. To take advantage of the problems, in order to improve the quality of the Brazilians buildings, is one of our objectives. (author)

Menadione triggers cell death through ROS-dependent mechanisms involving PARP activation without requiring apoptosis.

Science.gov (United States)

Loor, Gabriel; Kondapalli, Jyothisri; Schriewer, Jacqueline M; Chandel, Navdeep S; Vanden Hoek, Terry L; Schumacker, Paul T

2010-12-15

Low levels of reactive oxygen species (ROS) can function as redox-active signaling messengers, whereas high levels of ROS induce cellular damage. Menadione generates ROS through redox cycling, and high concentrations trigger cell death. Previous work suggests that menadione triggers cytochrome c release from mitochondria, whereas other studies implicate the activation of the mitochondrial permeability transition pore as the mediator of cell death. We investigated menadione-induced cell death in genetically modified cells lacking specific death-associated proteins. In cardiomyocytes, oxidant stress was assessed using the redox sensor RoGFP, expressed in the cytosol or the mitochondrial matrix. Menadione elicited rapid oxidation in both compartments, whereas it decreased mitochondrial potential and triggered cytochrome c redistribution to the cytosol. Cell death was attenuated by N-acetylcysteine and exogenous glutathione or by overexpression of cytosolic or mitochondria-targeted catalase. By contrast, no protection was observed in cells overexpressing Cu,Zn-SOD or Mn-SOD. Overexpression of antiapoptotic Bcl-X(L) protected against staurosporine-induced cell death, but it failed to confer protection against menadione. Genetic deletion of Bax and Bak, cytochrome c, cyclophilin D, or caspase-9 conferred no protection against menadione-induced cell death. However, cells lacking PARP-1 showed a significant decrease in menadione-induced cell death. Thus, menadione induces cell death through the generation of oxidant stress in multiple subcellular compartments, yet cytochrome c, Bax/Bak, caspase-9, and cyclophilin D are dispensable for cell death in this model. These studies suggest that multiple redundant cell death pathways are activated by menadione, but that PARP plays an essential role in mediating each of them. Copyright © 2010 Elsevier Inc. All rights reserved.

Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment

DEFF Research Database (Denmark)

Oplustilova, L.; Wolanin, K.; Bartkova, J.

2012-01-01

combinations with camptothecin or ionizing radiation. Furthermore, monitoring pARsylation and Rad51 foci formation as surrogate markers for PARP activity and HR, respectively, supported their candidacy for biomarkers of PARP-1i responses. As to resistance mechanisms, we confrmed the role of the multidrug......(ADp-ribose) polymerase-1 (PARP-1), an enzyme critical for repair pathways alternative to HR. While promising, treatment with PARP-1 inhibitors (PARP-1i) faces some hurdles, including (1) acquired resistance, (2) search for other sensitizing, non-BRCA1/2 cancer defects and (3) lack of biomarkers to predict response...

Effects of Financial Crises on the Long Memory Volatility Dependency of Foreign Exchange Rates: the Asian Crisis vs. the Global Crisis

Directory of Open Access Journals (Sweden)

Young Wook Han

2014-03-01

Full Text Available This paper examines the effects of financial crises on the long memory volatility dependency of daily exchange returns focusing on the Asian crisis in 97-98 and the Global crisis in 08-09. By using the daily KRW-USD and JPY-USD exchange rates which have different trading regions and volumes, this paper first applies both the parametric FIGARCH model and the semi-parametric Local Whittle method to estimate the long memory volatility dependency of the daily returns and the temporally aggregated returns of the two exchange rates. Then it compares the effects of the two financial crises on the long memory volatility dependency of the daily returns. The estimation results reflect that the long memory volatility dependency of the KRW-USD is generally greater than that of the JPY-USD returns and the long memory dependency of the two returns appears to be invariant to temporal aggregation. And, the two financial crises appear to affect the volatility dynamics of all the returns by inducing greater long memory dependency in the volatility process of the exchange returns, but the degree of the effects of the two crises seems to be different on the exchange rates.

Human mass balance study and metabolite profiling of 14C-niraparib, a novel poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor, in patients with advanced cancer

NARCIS (Netherlands)

van Andel, Lotte; Zhang, Z; Lu, S.; Kansra, V; Agarwal, S.; Hughes, L.; Tibben, M.; Gebretensae, A.; Lucas, L.; Hillebrand, Michel J X; Rosing, H.; Schellens, J H M|info:eu-repo/dai/nl/073926272; Beijnen, J H|info:eu-repo/dai/nl/071919570

2017-01-01

Niraparib is an investigational oral, once daily, selective poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor. In the pivotal Phase 3 NOVA/ENGOT/OV16 study, niraparib met its primary endpoint of improving progression-free survival (PFS) for adult patients with recurrent, platinum sensitive,

Rucaparib: a novel PARP inhibitor for BRCA advanced ovarian cancer

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Colombo I

2018-03-01

Full Text Available Ilaria Colombo, Stephanie Lheureux, Amit Manulal Oza Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada Abstract: Rucaparib is a potent small-molecule inhibitor of poly (ADP-ribose polymerase (PARP proteins (PARP-1, PARP-2 and PARP-3 that play an important role in repairing DNA damage and maintaining genomic stability. Tumors with mutations in BRCA1/2 or other homologous recombination deficiency (HRD genes are particularly sensitive to PARP inhibitors because of “synthetic lethality”, whereby a therapeutic agent can take advantage of an intrinsic weakness in DNA repair. Rucaparib has been investigated in several preclinical and clinical studies showing promising activity in BRCA-mutant and BRCA–wild-type epithelial ovarian cancers (EOCs. Dose-escalation Phase I studies have established the recommended Phase II dose to be 600 mg twice a day for oral rucaparib. Phase II and III studies have defined its role as treatment for BRCA-mutant recurrent high-grade EOC and as maintenance treatment for platinum-sensitive relapsed EOC following response to platinum-based chemotherapy. Genomic loss of heterozygosity has also been investigated as a potential signature of HRD and as a potential predictive biomarker of response. Treatment-induced adverse events (AEs have been observed in almost all patients treated with rucaparib, but mainly lower grade; with the most common being nausea, vomiting, asthenia/fatigue, anemia and transient transaminitis. The majority of AEs occurred early in treatment, were transient and have been easily managed with supportive treatment, dose interruption or discontinuation. This review will analyze the results of clinical trials investigating efficacy and safety of rucaparib in patients with ovarian cancer. Keywords: rucaparib, ovarian cancer, BRCA mutations, homologous recombination deficiency, maintenance treatment, PARP inhibitor

Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications

Science.gov (United States)

Yoon, Sarah; Jo, Yuna; Kwon, So Mee; Kim, Kyoung Min; Kwon, Keun Sang; Kim, Chan Young; Woo, Hyun Goo

2015-01-01

Poly (ADP-ribose) polymerase1 (PARP1) has been reported as a possible target for chemotherapy in many cancer types. However, its action mechanisms and clinical implications for gastric cancer survival are not yet fully understood. Here, we investigated the effect of PARP1 inhibition in the growth of gastric cancer cells. PARP1 inhibition by Olaparib or PARP1 siRNA could significantly attenuate growth and colony formation of gastric cancer cells, and which were mediated through induction of G2/M cell cycle arrest but not apoptosis. FOXO3A expression was induced by PARP1 inhibition, suggesting that FOXO3A might be one of downstream target of the PARP1 effect on gastric cancer cell growth. In addition, by performing tissue microarrays on the 166 cases of gastric cancer patients, we could observe that the expression status of PARP1 and FOXO3A were significantly associated with overall survival (OS) and relapse-free survival (RFS). Strikingly, combined expression status of PARP1 and FOXO3A showed better prediction for patient's clinical outcomes. The patient group with PARP1+/FOXO3A− expression had the worst prognosis while the patient group with PARP1−/FOXO3A+ had the most favorable prognosis (OS: P = 6.0 × 10−9, RFS: P = 2.2 × 10−8). In conclusion, we suggest that PARP1 and FOXO3A play critical roles in gastric cancer progression, and might have therapeutic and/or diagnostic potential in clinic. PMID:26540566

Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor Sensitivity in Fanconi Anemia Head and Neck Cancers.

Science.gov (United States)

Lombardi, Anne J; Hoskins, Elizabeth E; Foglesong, Grant D; Wikenheiser-Brokamp, Kathryn A; Wiesmüller, Lisa; Hanenberg, Helmut; Andreassen, Paul R; Jacobs, Allison J; Olson, Susan B; Keeble, Winifred W; Hays, Laura E; Wells, Susanne I

2015-04-15

Fanconi anemia is an inherited disorder associated with a constitutional defect in the Fanconi anemia DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with Fanconi anemia are predisposed to formation of head and neck squamous cell carcinomas (HNSCC) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease. Using HNSCC cell lines derived from the tumors of patients with Fanconi anemia, and murine HNSCC cell lines derived from the tumors of wild-type and Fancc(-/-) mice, we sought to define Fanconi anemia-dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of Fanconi anemia HNSCC cells for non-homologous end joining (NHEJ). Surprisingly, interstrand crosslinker (ICL) sensitivity was not necessarily Fanconi anemia-dependent in human or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in Fanconi anemia cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by PARP in Fanconi anemia-deficient cells. Moreover, human and murine Fanconi anemia HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by Fanconi anemia gene complementation. The observed reliance upon PARP-mediated mechanisms reveals a means by which Fanconi anemia HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual. ©2015 American Association for Cancer Research.

New approaches of PARP-1 inhibitors in human lung cancer cells and cancer stem-like cells by some selected anthraquinone-derived small molecules.

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Yu-Ru Lee

Full Text Available Poly (ADP-ribose polymerase-1 (PARP-1 and telomerase, as well as DNA damage response pathways are targets for anticancer drug development, and specific inhibitors are currently under clinical investigation. The purpose of this work is to evaluate anticancer activities of anthraquinone-derived tricyclic and tetracyclic small molecules and their structure-activity relationships with PARP-1 inhibition in non-small cell lung cancer (NSCLC and NSCLC-overexpressing Oct4 and Nanog clone, which show high-expression of PARP-1 and more resistance to anticancer drug. We applied our library selected compounds to NCI's 60 human cancer cell-lines (NCI-60 in order to generate systematic profiling data. Based on our analysis, it is hypothesized that these drugs might be, directly and indirectly, target components to induce mitochondrial permeability transition and the release of pro-apoptotic factors as potential anti-NSCLC or PARP inhibitor candidates. Altogether, the most active NSC747854 showed its cytotoxicity and dose-dependent PARP inhibitory manner, thus it emerges as a promising structure for anti-cancer therapy with no significant negative influence on normal cells. Our studies present evidence that telomere maintenance should be taken into consideration in efforts not only to overcome drug resistance, but also to optimize the use of telomere-based therapeutics. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and telomerase inhibitors, in particular. Together, the data presented here expand our insight into the PARP inhibitors and support the resource-demanding lead optimization of structurally related small molecules for human cancer therapy.

New Approaches of PARP-1 Inhibitors in Human Lung Cancer Cells and Cancer Stem-Like Cells by Some Selected Anthraquinone-Derived Small Molecules

Science.gov (United States)

Yu, Dah-Shyong; Huang, Kuo-Feng; Chou, Shih-Jie; Chen, Tsung-Chih; Lee, Chia-Chung; Chen, Chun-Liang; Chiou, Shih-Hwa; Huang, Hsu-Shan

2013-01-01

Poly (ADP-ribose) polymerase-1 (PARP-1) and telomerase, as well as DNA damage response pathways are targets for anticancer drug development, and specific inhibitors are currently under clinical investigation. The purpose of this work is to evaluate anticancer activities of anthraquinone-derived tricyclic and tetracyclic small molecules and their structure-activity relationships with PARP-1 inhibition in non-small cell lung cancer (NSCLC) and NSCLC-overexpressing Oct4 and Nanog clone, which show high-expression of PARP-1 and more resistance to anticancer drug. We applied our library selected compounds to NCI's 60 human cancer cell-lines (NCI-60) in order to generate systematic profiling data. Based on our analysis, it is hypothesized that these drugs might be, directly and indirectly, target components to induce mitochondrial permeability transition and the release of pro-apoptotic factors as potential anti-NSCLC or PARP inhibitor candidates. Altogether, the most active NSC747854 showed its cytotoxicity and dose-dependent PARP inhibitory manner, thus it emerges as a promising structure for anti-cancer therapy with no significant negative influence on normal cells. Our studies present evidence that telomere maintenance should be taken into consideration in efforts not only to overcome drug resistance, but also to optimize the use of telomere-based therapeutics. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and telomerase inhibitors, in particular. Together, the data presented here expand our insight into the PARP inhibitors and support the resource-demanding lead optimization of structurally related small molecules for human cancer therapy. PMID:23451039

Mechanistic Links Between PARP, NAD, and Brain Inflammation After TBI

Science.gov (United States)

2015-10-01

1 AWARD NUMBER: W81XWH-13-2-0091 TITLE: Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI PRINCIPAL INVESTIGATOR...COVERED 25 Sep 2014 - 24 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI 5b. GRANT...efficacy of veliparib and NAD as agents for suppressing inflammation and improving outcomes after traumatic brain injury. The animal models include

From oil crisis to climate crisis

International Nuclear Information System (INIS)

Langseth, Bjarne

2000-01-01

The oil crisis in the 1970s led to the shift from oil to hydro- and nuclear power. An almost similar shift might soon come as a ''climate crisis''. A climate crisis may imply a renaissance for hydropower and nuclear power and natural gas will be used on a large scale. In Europe, natural gas is currently considered environmentally friendly. Although there is at present growing opposition to nuclear power in Sweden and Germany, this attitude may change as the result of increased focus on the costs of the alternatives. A forced phase-out of nuclear power in Europe simultaneously with a climate crisis with reduced energy production from fossil fuels is likely to entail significantly increased prices of electricity. In Norway, 98% of the country's electric power production is based on hydro power, which means that much more heating can be based on electricity than in countries in which electricity is produced by combustion of fossil fuels. Much research is in progress to find technologies that will make it possible to shift from fossil fuel energy to energy from renewable sources like solar, water, wind, biomass and geothermal energy

PARPi-FL - a Fluorescent PARP1 Inhibitor for Glioblastoma Imaging

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Christopher P. Irwin

2014-05-01

Full Text Available New intravital optical imaging technologies have revolutionized our understanding of mammalian biology and continue to evolve rapidly. However, there are only a limited number of imaging probes available to date. In this study, we investigated in mouse models of glioblastoma whether a fluorescent small molecule inhibitor of the DNA repair enzyme PARP1, PARPi-FL, can be used as an imaging agent to detect glioblastomas in vivo. We demonstrated that PARPi-FL has appropriate biophysical properties, low toxicity at concentrations used for imaging, high stability in vivo, and accumulates selectively in glioblastomas due to high PARP1 expression. Importantly, subcutaneous and orthotopic glioblastoma xenografts were imaged with high contrast clearly defining tumor tissue from normal surrounding tissue. This research represents a step toward exploring and developing PARPi-FL as an optical intraoperative imaging agent for PARP1 in the clinic.

PARP inhibitor rucaparib induces changes in NAD levels in cells and liver tissues as assessed by MRS.

Science.gov (United States)

Almeida, Gilberto S; Bawn, Carlo M; Galler, Martin; Wilson, Ian; Thomas, Huw D; Kyle, Suzanne; Curtin, Nicola J; Newell, David R; Maxwell, Ross J

2017-09-01

Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy ( 1 H-MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD + ) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response. SW620 (colorectal) and A2780 (ovarian) cancer cell lines, and PARP1 wild-type (WT) and PARP1 knock-out (KO) mice, were treated with rucaparib, temozolomide (methylating agent) or a combination of both drugs. 1 H-MRS spectra were obtained from perchloric acid extracts of tumour cells and mouse liver. Both cell lines showed an increase in NAD + levels following PARP inhibitor treatment in comparison with temozolomide treatment. Liver extracts from PARP1 WT mice showed a significant increase in NAD + levels after rucaparib treatment compared with untreated mouse liver, and a significant decrease in NAD + levels in the temozolomide-treated group. The combination of rucaparib and temozolomide did not prevent the NAD + depletion caused by temozolomide treatment. The 1 H-MRS results show that NAD + levels can be used as a biomarker of PARP inhibitor and methylating agent treatments, and suggest that in vivo measurement of NAD + would be valuable. Copyright © 2017 John Wiley & Sons, Ltd.

Towards a Continental Energy Market: From the Energy Crisis to the Free Trade Agreement, 1970-88.

Science.gov (United States)

Bennett, Paul W.

1989-01-01

Discusses the impact the 1973 oil embargo and resulting energy crisis had on Canadian energy policies, which eventually led in 1987 to the enactment of the Free Trade Agreement between Canada and the United States. Includes excerpts of three documents which reveal much about the shift in Canadian policy toward a continental energy market. (LS)

Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA.

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Simon Gemble

2015-07-01

Full Text Available Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at "difficult-to-replicate" sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS, a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3'-5' DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.

ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy

DEFF Research Database (Denmark)

Rodríguez-Vargas, José Manuel; Ruiz-Magaña, María José; Ruiz-Ruiz, Carmen

2012-01-01

, leading to ATP depletion (an early event after nutrient deprivation). The absence of PARP-1 blunted AMPK activation and prevented the complete loss of mTOR activity, leading to a delay in autophagy. PARP-1 depletion favors apoptosis in starved cells, suggesting a pro-survival role of autophagy and PARP-1...

Distinct spatio temporal patterns and PARP dependence of XRCC1 recruitment to single-strand break and base excision repair

International Nuclear Information System (INIS)

Campalans, Anna; Kortulewski, Thierry; Amouroux, Rachel; Radicella, J. Pablo; Menoni, Herve; Vermeulen, Wim

2013-01-01

Single-strand break repair (SSBR) and base excision repair (BER) of modified bases and abasic sites share several players. Among them is XRCC1, an essential scaffold protein with no enzymatic activity, required for the coordination of both pathways. XRCC1 is recruited to SSBR by PARP-1, responsible for the initial recognition of the break. The recruitment of XRCC1 to BER is still poorly understood. Here we show by using both local and global induction of oxidative DNA base damage that XRCC1 participation in BER complexes can be distinguished from that in SSBR by several criteria. We show first that XRCC1 recruitment to BER is independent of PARP. Second, unlike SSBR complexes that are assembled within minutes after global damage induction, XRCC1 is detected later in BER patches, with kinetics consistent with the repair of oxidized bases. Third, while XRCC1-containing foci associated with SSBR are formed both in eu- and heterochromatin domains, BER complexes are assembled in patches that are essentially excluded from heterochromatin and where the oxidized bases are detected. (authors)

Effect of MRE11 loss on PARP-inhibitor sensitivity in endometrial cancer in vitro.

Directory of Open Access Journals (Sweden)

Romana Koppensteiner

Full Text Available To evaluate the frequency of MRE11/RAD50/NBS1 (MRN-complex loss of protein expression in endometrial cancers (EC and to determine whether loss of MRE11 renders the cancer cells sensitive to Poly(ADP-ribose polymerase (PARP-inhibitory treatment.MRN expression was examined in 521 samples of endometrial carcinomas and in 10 cancer cell lines. A putative mutation hotspot in the form of an intronic poly(T allele in MRE11 was sequenced in selected cases (n = 26. Sensitivity to the PARP-inhibitor, BMN673 was tested in colony formation assays before and after MRE11 silencing using siRNA. Homologous recombination (HR DNA repair was evaluated by RAD51-foci formation assay upon irradiation and drug treatment.Loss of MRE11 protein was found in 30.7% of EC tumours and significantly associated with loss of RAD50, NBS1 and mismatch repair protein expression. One endometrial cell line showed a markedly reduced MRE11 expression due to a homozygous poly(T mutation of MRE11, thereby exhibiting an increased sensitivity to BMN673. MRE11 depletion sensitizes MRE11 expressing EC cell lines to the treatment with BMN673. The increased sensitivity to PARP-inhibition correlates with reduced RAD51 foci formation upon ionizing radiation in MRE11-depleted cells.Loss of the MRE11 protein predicts sensitivity to PARP-inhibitor sensitivity in vitro, defining it as an additional synthetic lethal gene with PARP. The high incidence of MRE11 loss in ECs can be potentially exploited for PARP-inhibitor therapy. Furthermore, MRE11 protein expression using immunohistochemistry could be investigated as a predictive biomarker for PARP-inhibitor treatment.

Biodiesel and bioethanol production: A sustainable alternative for the energy crisis?

Directory of Open Access Journals (Sweden)

Claudia Castro Martínez

2012-09-01

Full Text Available The present contribution intends to give an overview of the current -status of the energy crisis and suggest some sustainable alternatives for energy production. In first place, a brief summary of the history about resources for energy production is presented. The high dependency of fossil combustibles it is well known and has been estimated that more than 90% of the used energy comes from non-renewable resources such as oil, gas and carbon. In the same way, here, it is described that oil is, by far, the main source of energy used to date and as a consequence, this resource is, unavoidably,coming to an end and at the same time is causing and increasing environmental pollution problems. Later in this work, it is suggested that in order to achieve the energetic sustainability, the development of alternative sources that will allow the reduction of toxic greenhouse gas (GHG emissions as well as a decrease of water usage along with a decrease in the energy production costs are needed. One of the alternatives that have been proposed is the production of biofuels, such as biodiesel and bioethanol. Here, some of the main properties at the level of the employed raw materials and production systems are cited. Finally, this work suggests some solutions that are under development worldwide in order to face thiscurrent energy situation.

Impacts of the financial crisis on climate and energy policy. Memo

International Nuclear Information System (INIS)

2009-01-01

By request of the Dutch Ministry of Housing, Spatial Planning and the Environment, the Netherlands Bureau for Economic Policy Analysis (CPB) and the Environmental Assessment Agency (PBL) have mapped the main effects of the credit crisis on Dutch climate and energy policy. This memo describes the effects of the credit crisis on the economy (question 1) and more particularly the effect on realizing the Dutch targets for 2020 for climate and energy policy as established in the policy program 'Clean and Efficient' (question 2). A distinction should be made between the short term effects (during the recession) and the longer term effects (the years after)(question 5). Moreover, the realization of the Kyoto target for 2008-2012 is addressed (question 3) as well as the question if the Dutch government can incentivise investments in climate and energy that can contribute to economic recovery in the short term (question 4) [mk] [nl

Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo

Directory of Open Access Journals (Sweden)

Masaaki Yasukawa

2016-02-01

Full Text Available Cisplatin is a commonly used chemotherapeutic drug for treatment of oral carcinoma, and combinatorial effects are expected to exert greater therapeutic efficacy compared with monotherapy. Poly(ADP-ribosylation is reported to be involved in a variety of cellular processes, such as DNA repair, cell death, telomere regulation, and genomic stability. Based on these properties, poly(ADP-ribose polymerase (PARP inhibitors are used for treatment of cancers, such as BRCA1/2 mutated breast and ovarian cancers, or certain solid cancers in combination with anti-cancer drugs. However, the effects on oral cancer have not been fully evaluated. In this study, we examined the effects of PARP inhibitor on the survival of human oral cancer cells in vitro and xenografted tumors derived from human oral cancer cells in vivo. In vitro effects were assessed by microculture tetrazolium and survival assays. The PARP inhibitor AZD2281 (olaparib showed synergetic effects with cisplatin in a dose-dependent manner. Combinatorial treatment with cisplatin and AZD2281 significantly inhibited xenografted tumor growth compared with single treatment of cisplatin or AZD2281. Histopathological analysis revealed that cisplatin and AZD2281 increased TUNEL-positive cells and decreased Ki67- and CD31-positive cells. These results suggest that PARP inhibitors have the potential to improve therapeutic strategies for oral cancer.

Pathway-Enriched Gene Signature Associated with 53BP1 Response to PARP Inhibition in Triple-Negative Breast Cancer.

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Hassan, Saima; Esch, Amanda; Liby, Tiera; Gray, Joe W; Heiser, Laura M

2017-12-01

Effective treatment of patients with triple-negative (ER-negative, PR-negative, HER2-negative) breast cancer remains a challenge. Although PARP inhibitors are being evaluated in clinical trials, biomarkers are needed to identify patients who will most benefit from anti-PARP therapy. We determined the responses of three PARP inhibitors (veliparib, olaparib, and talazoparib) in a panel of eight triple-negative breast cancer cell lines. Therapeutic responses and cellular phenotypes were elucidated using high-content imaging and quantitative immunofluorescence to assess markers of DNA damage (53BP1) and apoptosis (cleaved PARP). We determined the pharmacodynamic changes as percentage of cells positive for 53BP1, mean number of 53BP1 foci per cell, and percentage of cells positive for cleaved PARP. Inspired by traditional dose-response measures of cell viability, an EC 50 value was calculated for each cellular phenotype and each PARP inhibitor. The EC 50 values for both 53BP1 metrics strongly correlated with IC 50 values for each PARP inhibitor. Pathway enrichment analysis identified a set of DNA repair and cell cycle-associated genes that were associated with 53BP1 response following PARP inhibition. The overall accuracy of our 63 gene set in predicting response to olaparib in seven breast cancer patient-derived xenograft tumors was 86%. In triple-negative breast cancer patients who had not received anti-PARP therapy, the predicted response rate of our gene signature was 45%. These results indicate that 53BP1 is a biomarker of response to anti-PARP therapy in the laboratory, and our DNA damage response gene signature may be used to identify patients who are most likely to respond to PARP inhibition. Mol Cancer Ther; 16(12); 2892-901. ©2017 AACR . ©2017 American Association for Cancer Research.

Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype.

Science.gov (United States)

Chacon-Cabrera, Alba; Mateu-Jimenez, Mercè; Langohr, Klaus; Fermoselle, Clara; García-Arumí, Elena; Andreu, Antoni L; Yelamos, Jose; Barreiro, Esther

2017-12-01

Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1 -/- ) and Parp-2 -/- mice. In diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing mice (wild type, Parp-1 -/- , and Parp-2 -/- ), PARP activity (ADP-ribose polymers, pADPr), redox balance, muscle fiber phenotype, apoptotic nuclei, tyrosine release, protein ubiquitination, muscle-specific E3 ligases, NF-κB signaling pathway, markers of muscle anabolism (Akt, mTOR, p70S6K, and mitochondrial DNA) were evaluated along with body and muscle weights, and limb muscle force. Compared to wild type cachectic animals, in both respiratory and limb muscles of Parp-1 -/- and Parp-2 -/- cachectic mice: cancer induced-muscle wasting characterized by increased PARP activity, protein oxidation, tyrosine release, and ubiquitin-proteasome system (total protein ubiquitination, atrogin-1, and 20S proteasome C8 subunit) were blunted, the reduction in contractile myosin and atrophy of the fibers was attenuated, while no effects were seen in other structural features (inflammatory cells, internal or apoptotic nuclei), and markers of muscle anabolism partly improved. Activation of either PARP-1 or -2 is likely to play a role in muscle protein catabolism via oxidative stress, NF-κB signaling, and enhanced proteasomal degradation in cancer-induced cachexia. Therapeutic potential of PARP activity inhibition deserves attention. © 2017 Wiley Periodicals, Inc.

PARP1 inhibitors: contemporary attempts at their use in anticancer therapy and future perspective

Directory of Open Access Journals (Sweden)

Ewelina Wiśnik

2016-04-01

Full Text Available Current cancer therapies are based mainly on the use of compounds that cause DNA damage. Unfortunately, even the combination therapies do not give rewarding effects, due to the high efficiency of DNA damage repair mechanisms in tumor cells. Therefore, the present studies should be focused on proteins that are involved in DNA repair systems. Poly(ADP-ribose polymerase-1 is an example of a protein commonly known as an enzyme that plays a role in the detection of DNA damage and repair. Activation of PARP1 in response to DNA damage leads to poly-ADP-ribosylation of proteins contributing to DNA repair systems, therefore facilitating the maintenance of genome stability. On the other hand, inhibition of PARP1 enzyme results in the accumulation of DNA damage, which in turn contributes to cell death. Studies on inhibitors of PARP1 are still ongoing, and some of them are currently in the third phase of clinical trials. To date, only one representative of the PARP1 inhibitors, called olaparib, has been approved for anti-cancer therapy in the EU and the USA. Moreover, a growing body of evidence indicates a role of this protein in various intracellular processes such as bioenergetics, proliferation, regulation of gene expression, cell death as well as immunoregulation. A number of different intracellular processes regulated by PARP1 give rise to potential wider use of PARP1 inhibitors in treatment of other diseases, including immune or autoimmune disorders.

Considering Time-Dependency of Social Vulnerability in Crisis Modeling and Management

Science.gov (United States)

Aubrecht, C.; Steinnocher, K.; Freire, S.; Loibl, W.; Peters-Anders, J.; Ungar, J.

2012-04-01

Crisis and disaster management is much more than the immediate first-response actions following an incident. In many projects the main focus has been on the phase starting at the point when an unwanted event happens and lasting until the activities return to normal routines (i.e., ad hoc reaction rather than proactive mitigation). There has been less emphasis on the other phases of the disaster management cycle such as prevention, preparedness, recovery and reconstruction, even though those phases have a strong influence on the general status of a society and its citizens. Especially the potential of a crisis to escalate into a large-scale disaster is heavily dependent on the overall level of preparedness as well as on the planning of mitigation and response actions and their timely execution. There is a need for improved decision-making support that enables modeling of different crisis scenarios and their impacts according to chosen prevention and response actions. Vulnerability describing the status of a society with respect to an imposed hazard or potential impact is considered a strongly multidisciplinary concept. A central objective of vulnerability assessment is to provide indications where and how people - and more specifically, what kind of people - might be affected by a certain impact. Results should provide decision- and policy-makers with supporting information to target response and mitigation actions adequately. For assessment of the social dimension of vulnerability, population exposure mapping is usually considered the starting point. Integration of social structure and varying aspects of resilience further differentiate situation-specific vulnerability patterns on a local scale. In a disaster risk management context, assessment of human vulnerability has generally been lagging behind hazard analysis efforts. Accurately estimating population exposure is a key component of catastrophe loss modeling, one element of effective integrated risk analysis

The impact of the crisis on the energy demand and energy intensity in Central and Eastern European countries

Directory of Open Access Journals (Sweden)

Attila HUGYECZ

2011-12-01

Full Text Available The purpose of our paper is to analyze the impact of the recent crisis on the oil and electricity demand and the energy intensity of different Central and Eastern European countries, namely the Czech Republic, Hungary, Poland and Slovakia. Furthermore, we would like to reveal whether there is a lag in the adjustment of energy consumption. In analyzing energy intensity, we use motor gasoline, diesel oil and electricity consumption data and ignore coal and natural gas data. By so doing, we avoid failures arising from changing coal/gas consumption due to changing weather conditions. Our results show that the crisis did impact energy consumption and reveal that the improvement of energy intensity halted in 2009, implying that the economic players did not immediately adjust their energy consumption according to their economic activity. The gasoline and diesel intensity, however, deteriorated (increased only in the Czech Republic and in Hungary. In Slovakia and Poland there were no significant changes.

PARP-1 Inhibition Is Neuroprotective in the R6/2 Mouse Model of Huntington's Disease.

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Antonella Cardinale

Full Text Available Poly (ADP-ribose polymerase 1 (PARP-1 is a nuclear enzyme that is involved in physiological processes as DNA repair, genomic stability, and apoptosis. Moreover, published studies demonstrated that PARP-1 mediates necrotic cell death in response to excessive DNA damage under certain pathological conditions. In Huntington's disease brains, PARP immunoreactivity was described in neurons and in glial cells, thereby suggesting the involvement of apoptosis in HD. In this study, we sought to determine if the PARP-1 inhibitor exerts a neuroprotective effect in R6/2 mutant mice, which recapitulates, in many aspects, human HD. Transgenic mice were treated with the PARP-1 inhibitor INO-1001 mg/Kg daily starting from 4 weeks of age. After transcardial perfusion, histological and immunohistochemical studies were performed. We found that INO 1001-treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the vehicle treated ones. Primary outcome measures such as striatal atrophy, morphology of striatal neurons, neuronal intranuclear inclusions and microglial reaction confirmed a neuroprotective effect of the compound. INO-1001 was effective in significantly increasing activated CREB and BDNF in the striatal spiny neurons, which might account for the beneficial effects observed in this model. Our findings show that PARP-1 inhibition could be considered as a valid therapeutic approach for HD.

Energy shortage: a produced crisis. Energieknappheit - die gemachte Krise

Energy Technology Data Exchange (ETDEWEB)

1979-01-01

Five articles of the central organ of the KPD/ML, the Roter Morgen, and a declaration of the central committee of th KPD/ML are published here. The articles deal with: raw materials-utilization and deposits; the oil-multis - the world's greatest financial power; the energy industry of the FRG; nuclear power - the new trick of the old bosses; resisting the bulling of oil prices, securing energy supply on the basis of coal. The articles are clearly combative and against capitalism, energy concerns, and oil-multis. The energy crisis is declared to be a problem of capitalism which can only be solved by abolishing the capitalist system and its laws of profit.

Energy shortage: a produced crisis. Energieknappheit - die gemachte Krise

Energy Technology Data Exchange (ETDEWEB)

1979-01-01

Five articles of the central organ of the KPD/ML, the Roter Morgen, and a declaration of the central committee of th KPD/ML are published here. The articles deal with: raw materials-utilization and deposits; the oil-multis - the world's greatest financial power; the energy industry of the FRG; nuclear power - the new trick of the old bosses; resisting the bulling of oil prices, securing energy supply on the basis of coal. The articles are clearly combative and against capitalism, energy concerns, and oil-multis. The energy crisis is declared to be a problem of capitalism which can only be solved by abolishing the capitalist system and its laws of profit.

Energy Strategy of Russia in the Conditions of Economic Crisis

Directory of Open Access Journals (Sweden)

Kashulin Danila A.

2016-10-01

Full Text Available The article is devoted to the transformation of the energy strategy of Russia in the conditions of the current economic crisis. The special attention is paid to current trends in the sphere of international relations having a decisive influence on the formation of Russia’s energy strategy. The authors point to the crisis of the modern world, the deepening of interstate contradictions, the expansion of confrontation, the revision of the uniform principles of trade, established by the World Trade Organization, the changes in the global financial system. The authors investigate the possibility of political arrangements between the leading suppliers of oil on the destabilization of the oil market in order to achieve geopolitical goals. In the article special attention is also paid to the issue of political motivation of anti-Russian sanctions directed at impeding Russia’s development and its Fuel & Energy Complex, in particular. Today, against the background of the current political situation, the energy strategy of Russia is exposed to adjustment. The country has the important task of ensuring technological independence of the energy sector on the basis of import substitution of the equipment, diversification of the directions of export of energy resources, preservation of leading positions in the world market of peaceful nuclear energy, etc. The authors conclude that the energy strategy of Russia is important part of foreign policy strategy of the country, and it is focused on practical cooperation with all countries and is aimed at protecting interests of the state.

A phenanthrene derived PARP inhibitor is an extra-centrosomes de-clustering agent exclusively eradicating human cancer cells

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Izraeli Shai

2011-09-01

Full Text Available Abstract Background Cells of most human cancers have supernumerary centrosomes. To enable an accurate chromosome segregation and cell division, these cells developed a yet unresolved molecular mechanism, clustering their extra centrosomes at two poles, thereby mimicking mitosis in normal cells. Failure of this bipolar centrosome clustering causes multipolar spindle structures and aberrant chromosomes segregation that prevent normal cell division and lead to 'mitotic catastrophe cell death'. Methods We used cell biology and biochemical methods, including flow cytometry, immunocytochemistry and live confocal imaging. Results We identified a phenanthrene derived PARP inhibitor, known for its activity in neuroprotection under stress conditions, which exclusively eradicated multi-centrosomal human cancer cells (mammary, colon, lung, pancreas, ovarian while acting as extra-centrosomes de-clustering agent in mitosis. Normal human proliferating cells (endothelial, epithelial and mesenchymal cells were not impaired. Despite acting as PARP inhibitor, the cytotoxic activity of this molecule in cancer cells was not attributed to PARP inhibition alone. Conclusion We identified a water soluble phenanthridine that exclusively targets the unique dependence of most human cancer cells on their supernumerary centrosomes bi-polar clustering for their survival. This paves the way for a new selective cancer-targeting therapy, efficient in a wide range of human cancers.

California's crisis: An exploratory analysis of lifestyle, energy use, and conservation

Science.gov (United States)

Gossard, Marcia Hill

Electricity is one of the most serious issues of the 21st century. Modern human societies have become completely dependent upon energy to power modern life---resulting in unwanted environmental effects. Although electricity itself is invisible, many of the most conspicuous household items consume the most electricity. The 2001 energy crisis in California provides a unique opportunity to study how people negotiated their lives during a time of perceived resource scarcity, increased electricity prices, and threats of blackouts. Combining cultural and environmental literatures, I argued that changes in resource availability (perceived or real) led to unsettled lives in which beliefs, rituals and ways of behaving began to be questioned---resulting in new patterns of action organized around lifestyle. As a conceptual framework, lifestyle can be useful for understanding the patterns of people's everyday lives, the objects they consume, and the degrees to which those lifestyles affect the environment. Using data from the California Residential Electricity Conservation Study (CRECS), this research explores the ways households navigated and used different conservation strategies during the summers of 2001 and 2002. Analysis of Behavioral Conservation Strategies (BCS) that require ongoing effort and attention by household residents in order to achieve successful conservation outcomes (e.g., turning off lights or regulating indoor temperature), and Consumer Investment Strategies (CIS) that are one-time purchases improving efficiency (e.g., purchase of an appliance or fixture) reveal different strategies of action over the two years. Wealth indicators and time constraints were less important for predicting conservation, while cultural differences and household composition were better predictors of conservation efforts. In addition, despite assumptions that people are unwilling to change their lifestyle in order to conserve electricity, households employed more strategies that

Microglial activation induced by brain trauma is suppressed by post-injury treatment with a PARP inhibitor

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d'Avila Joana C

2012-02-01

Full Text Available Abstract Background Traumatic brain injury (TBI induces activation of microglia. Activated microglia can in turn increase secondary injury and impair recovery. This innate immune response requires hours to days to become fully manifest, thus providing a clinically relevant window of opportunity for therapeutic intervention. Microglial activation is regulated in part by poly(ADP-ribose polymerase-1 (PARP-1. Inhibition of PARP-1 activity suppresses NF-kB-dependent gene transcription and thereby blocks several aspects of microglial activation. Here we evaluated the efficacy of a PARP inhibitor, INO-1001, in suppressing microglial activation after cortical impact in the rat. Methods Rats were subjected to controlled cortical impact and subsequently treated with 10 mg/kg of INO-1001 (or vehicle alone beginning 20 - 24 hours after the TBI. Brains were harvested at several time points for histological evaluation of inflammation and neuronal survival, using markers for microglial activation (morphology and CD11b expression, astrocyte activation (GFAP, and neuronal survival (NeuN. Rats were also evaluated at 8 weeks after TBI using measures of forelimb dexterity: the sticky tape test, cylinder test, and vermicelli test. Results Peak microglial and astrocyte activation was observed 5 to 7 days after this injury. INO-1001 significantly reduced microglial activation in the peri-lesion cortex and ipsilateral hippocampus. No rebound inflammation was observed in rats that were treated with INO-1001 or vehicle for 12 days followed by 4 days without drug. The reduced inflammation was associated with increased neuronal survival in the peri-lesion cortex and improved performance on tests of forelimb dexterity conducted 8 weeks after TBI. Conclusions Treatment with a PARP inhibitor for 12 days after TBI, with the first dose given as long as 20 hours after injury, can reduce inflammation and improve histological and functional outcomes.

The economic and financial crisis: impacts on energy balances and prices

International Nuclear Information System (INIS)

Hyafil, Antoine

2009-01-01

The current economic crisis finds its origin in the existence of a global market for human capital, without unified prices: the development of a debt economy in Western countries can be regarded as an attempt to maintain economic growth in spite of the resulting pressure on labor wages. While the sub-prime crisis has shown the limits of such an attempt, the author believes that debt driven economic growth will continue to prevail in Western countries until price imbalances on the global market for human capital are resolved. This probably implies a substitution of public to private debt, and of private consumption to public investment with the resulting implications on public deficits, supply and demand, and relative prices. Energy prices will be sensitive to public spending's both mechanical impact on economic growth and qualitative impact on energy efficiency

Elements of an Alternative to Nuclear Power as a Response to the Energy-Environment Crisis in India: Development as Freedom and a Sustainable Energy Utility

Science.gov (United States)

Mathai, Manu V.

2009-01-01

Even as the conventional energy system is fundamentally challenged by the "energy-environment crisis," its adherents have presented the prospect of "abundant" and purportedly "green" nuclear power as part of a strategy to address the crisis. Surveying the development of nuclear power in India, this article finds that…

A study on the role of nuclear energy in overcoming environment and resource crisis -For the establishment of sustainable energy policy-

International Nuclear Information System (INIS)

Han, Pil Soon; Choi, Yung Myung; Ham, Chul Hoon; Cho, Il Hoon; Jung, Heum Soo; Lee, Tae Joon; Lee, Duk Sun

1995-04-01

This study is mainly composed of the analyses of the current circumstances and the future views on the global warming and the exhaustion of energy resources related to the use of energy, and the suggestion on the role of nuclear energy as the most prospective countermeasure on energy crisis. The effects of the problems of global warming and energy crisis on the 21st century are look upon and the strategies of each countries to their crises are analyzed in this study. In energy source and the characteristics of nuclear energy resource, and the necessity of the sustainable development of nuclear energy was emphasized. We suggested the enlargement of the development of nuclear energy in the aspects of the international trends, the national economic options and the deficiency of energy resources, and proposed the detail of the short - and long - term strategies on these matters. 22 figs, 39 tabs, 45 refs. (Author)

Sigma-2 ligands and PARP inhibitors synergistically trigger cell death in breast cancer cells

International Nuclear Information System (INIS)

McDonald, Elizabeth S.; Mankoff, Julia; Makvandi, Mehran; Chu, Wenhua; Chu, Yunxiang; Mach, Robert H.; Zeng, Chenbo

2017-01-01

The sigma-2 receptor is overexpressed in proliferating cells compared to quiescent cells and has been used as a target for imaging solid tumors by positron emission tomography. Recent work has suggested that the sigma-2 receptor may also be an effective therapeutic target for cancer therapy. Poly (ADP-ribose) polymerase (PARP) is a family of enzymes involved in DNA damage response. In this study, we looked for potential synergy of cytotoxicity between PARP inhibitors and sigma-2 receptor ligands in breast cancer cell lines. We showed that the PARP inhibitor, YUN3-6, sensitized mouse breast cancer cell line, EMT6, to sigma-2 receptor ligand (SV119, WC-26, and RHM-138) induced cell death determined by cell viability assay and colony forming assay. The PARP inhibitor, olaparib, sensitized tumor cells to a different sigma-2 receptor ligand SW43-induced apoptosis and cell death in human triple negative cell line, MDA-MB-231. Olaparib inhibited PARP activity and cell proliferation, and arrested cells in G2/M phase of the cell cycle in MDA-MB-231 cells. Subsequently cells became sensitized to SW43 induced cell death. In conclusion, the combination of sigma-2 receptor ligands and PARP inhibitors appears to hold promise for synergistically triggering cell death in certain types of breast cancer cells and merits further investigation. - Highlights: • PARPi, YUN3-6 and olaparib, and σ2 ligands, SV119 and SW43, were evaluated. • Mouse and human breast cancer cells, EMT6 and MDA-MB-231 respectively, were used. • YUN3-6 and SV119 synergistically triggered cell death in EMT6 cells. • Olaparib and SW43 additively triggered cell death in MDA-MB-231 cells. • Olaparib arrested cells in G2/M in MDA-MB-231 cells.

US business and the energy crisis: a survey of managers

Energy Technology Data Exchange (ETDEWEB)

Kefalas, A G [Univ. of Georgia, Athens; Mehra, S

1979-09-01

Although there seems to be an uncomfortably clear consensus among academic and other researchers that energy availability, accessibility, and affordability can no longer be taken for granted, most governments seem to have great difficulty in devising an energy policy that will solve the energy crisis or at least clarify the energy confusion. In 1974, barely a year after the 1973 oil embargo, a survey was conducted of US executives, asking them to comment about the severity of the energy situation and its impact upon their organizations. The results were published in the September 1976 issue of Energy Policy. Last November, five years since the 1973 experience, the survey was repeated, with production and inventory control personnel. This article presents a comparison of the two surveys.

Influence of the financial crisis on SMEs in the energy area

International Nuclear Information System (INIS)

Grass, M.; Schoder, T.; Scheller, E.

2009-05-01

This final report for the Swiss Federal Office of Energy (SFOE) presents and discusses the results of an opinion survey made among small and medium-scale enterprises (SME) in Switzerland concerning the influence of the financial crisis. The methods and questionnaires used are briefly described and the enterprises questioned are characterised. Innovation activities and research and development activities are reviewed. The effects of the financial crisis on business in 2008 are reported on and present and future developments are discussed. The general framework for long-term development is discussed, as are commercial, institutional and governmental general conditions. The report is concluded with a literature list

Renewable Energy Project Financing: Impacts of the Financial Crisis and Federal Legislation

Energy Technology Data Exchange (ETDEWEB)

Schwabe, P.; Cory, K.; Newcomb, J.

2009-07-01

Extraordinary financial market conditions have disrupted the flows of equity and debt investment into U.S. renewable energy (RE) projects since the fourth quarter of 2008. The pace and structure of renewable energy project finance has been reshaped by a combination of forces, including the financial crisis, global economic recession, and major changes in federal legislation affecting renewable energy finance. This report explores the impacts of these key market events on renewable energy project financing and development.

High resolution respirometry analysis of polyethylenimine-mediated mitochondrial energy crisis and cellular stress

DEFF Research Database (Denmark)

Hall, Arnaldur; Larsen, Anna Karina; Parhamifar, Ladan

2013-01-01

and spectrophotometry analysis of cytochrome c oxidase activity we were able to identify complex IV (cytochrome c oxidase) as a likely specific site of PEI mediated inhibition within the electron transport system. Unraveling the mechanisms of PEI-mediated mitochondrial energy crisis is central for combinatorial design...... of PEI-mediated plasma membrane damage and subsequent ATP leakage to the extracellular medium. Studies with freshly isolated mouse liver mitochondria corroborated with bioenergetic findings and demonstrated parallel polycation concentration- and time-dependent changes in state 2 and state 4o oxygen flux...... as well as lowered ADP phosphorylation (state 3) and mitochondrial ATP synthesis. Polycation-mediated reduction of electron transport system activity was further demonstrated in 'broken mitochondria' (freeze-thawed mitochondrial preparations). Moreover, by using both high-resolution respirometry...

Challenge - oil crisis. Herausforderung Oelkrise. Risiken - Vorsorge - Alternativen

Energy Technology Data Exchange (ETDEWEB)

Vogler, O

1981-01-01

After a short survey on recent developments of energy supply the risks of future energy supply and its effects are discussed. The parameters of dependence on oil-producing countries are studied and an evaluation is given on the measures which have to be taken by the Western industrialized countries in response to the dependence on oil. Further subjects are: mechanism of oil distribution in case of crisis, long-term cooperation of producer countries, measures on international level in the USA and Japan, and the energy-importing countries in the conflict area between OPEC- and industrialized countries.

Energy and environment: the risks and the challenges of a predicted crisis

International Nuclear Information System (INIS)

Durand, B.

2007-01-01

The human development is closely correlated to the energies use. And the energy consumption is correlated to the environmental pollution. This book allows to understand the nature of the difficulties and their importance, and to identify actions to fight against the crisis. Bringing many data, it provides information on the different energies sources, the primary, final and use energy, the reserves, the potential of the renewable energies, the risks for the health and the environment, the constraints and the 21 century perspectives. (A.L.B.)

Activity-based assay for human mono-ADP-ribosyltransferases ARTD7/PARP15 and ARTD10/PARP10 aimed at screening and profiling inhibitors.

Science.gov (United States)

Venkannagari, Harikanth; Fallarero, Adyary; Feijs, Karla L H; Lüscher, Bernhard; Lehtiö, Lari

2013-05-13

Poly(ADP-ribose) polymerases (PARPs) or diphtheria toxin like ADP-ribosyl transferases (ARTDs) are enzymes that catalyze the covalent modification of proteins by attachment of ADP-ribose units to the target amino acid residues or to the growing chain of ADP-ribose. A subclass of the ARTD superfamily consists of mono-ADP-ribosyl transferases that are thought to modify themselves and other substrate proteins by covalently adding only a single ADP-ribose moiety to the target. Many of the ARTD enzymes are either established or potential drug targets and a functional activity assay for them will be a valuable tool to identify selective inhibitors for each enzyme. Existing assays are not directly applicable for screening of inhibitors due to the different nature of the reaction and different target molecules. We modified and applied a fluorescence-based assay previously described for PARP1/ARTD1 and tankyrase/ARTD5 for screening of PARP10/ARTD10 and PARP15/ARTD7 inhibitors. The assay measures the amount of NAD(+) present after chemically converting it to a fluorescent analog. We demonstrate that by using an excess of a recombinant acceptor protein the performance of the activity-based assay is excellent for screening of compound libraries. The assay is homogenous and cost effective, making it possible to test relatively large compound libraries. This method can be used to screen inhibitors of mono-ARTDs and profile inhibitors of the enzyme class. The assay was optimized for ARTD10 and ARTD7, but it can be directly applied to other mono-ARTDs of the ARTD superfamily. Profiling of known ARTD inhibitors against ARTD10 and ARTD7 in a validatory screening identified the best inhibitors with submicromolar potencies. Only few of the tested ARTD inhibitors were potent, implicating that there is a need to screen new compound scaffolds. This is needed to create small molecules that could serve as biological probes and potential starting points for drug discovery projects against

The nuclear protein Poly(ADP-ribose) polymerase 3 (AtPARP3) is required for seed storability in Arabidopsis thaliana.

Science.gov (United States)

Rissel, D; Losch, J; Peiter, E

2014-11-01

The deterioration of seeds during prolonged storage results in a reduction of viability and germination rate. DNA damage is one of the major cellular defects associated with seed deterioration. It is provoked by the formation of reactive oxygen species (ROS) even in the quiescent state of the desiccated seed. In contrast to other stages of seed life, DNA repair during storage is hindered through the low seed water content; thereby DNA lesions can accumulate. To allow subsequent seedling development, DNA repair has thus to be initiated immediately upon imbibition. Poly(ADP-ribose) polymerases (PARPs) are important components in the DNA damage response in humans. Arabidopsis thaliana contains three homologues to the human HsPARP1 protein. Of these three, only AtPARP3 was very highly expressed in seeds. Histochemical GUS staining of embryos and endosperm layers revealed strong promoter activity of AtPARP3 during all steps of germination. This coincided with high ROS activity and indicated a role of the nuclear-localised AtPARP3 in DNA repair during germination. Accordingly, stored parp3-1 mutant seeds lacking AtPARP3 expression displayed a delay in germination as compared to Col-0 wild-type seeds. A controlled deterioration test showed that the mutant seeds were hypersensitive to unfavourable storage conditions. The results demonstrate that AtPARP3 is an important component of seed storability and viability. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Is energy crisis a chance for the future?

International Nuclear Information System (INIS)

Beigbeder, Ch.

2008-01-01

The explosion of fossil fuel prices is considered as a threat for our industries, for employment and for our economic growth. But why would not it be finally a formidable opportunity to create a new growth, sustainable, respectful to the environment and to future generations? We have been frantically consuming energy for 150 years now, considering that our resources are unexhaustible. However, another way to stimulate growth, consume energy, and manage to combine security of supplies and fight against global warming as well is possible. Energy efficiency techniques, development of renewable energy sources and electric-powered vehicles, CO 2 capture and sequestration are some of the components of this new deal. Accelerated by the present day situation and stimulated by competition, each can contribute to generate growth and employment. The present day crisis leads us to count even more on inventiveness and research and to intelligently change our behaviours without diminishing our comfort. (J.S.)

Hyperthermia and PARP1-inhibition for sensitization of radiation and cisplatin treatment of cervical carcinoma cells

International Nuclear Information System (INIS)

Franken, Nicolaas; Oei, Arlene; Leeuwen, Caspar van; Stalpers, Lukas; Rodermond, Hans; Bel, Arjan; Kok, Petra; Crezee, Hans

2014-01-01

Ionizing radiation causes single and double strand breaks (SSBs and DSBs). DSBs are among the most critical DNA lesions and can be repaired via either non-homologous end joining (NHEJ) in which PARP1, Ku70 and DNA-PKcs are important, or homologous recombination (HR), where BRCA2 and Rad51 are essential. Hyperthermia disturbs HR by temporary inactivation of BRCA2. Cisplatin disrupts NHEJ and PARP1-inhibitor blocks Poly-(ADP-ribose)polymerase- 1, which is important in SSB repair, NHEJ and backup-NHEJ. Our goal was to investigate the additional effectiveness of hyperthermia and PARP1-inhibition on radiation and/or cisplatin treatment. Cervical carcinoma cells (SiHa) were treated at different temperature levels levels (41.0-43.0℃, PARP1-inhibitor (100 μM; NU1025), gamma-irradiation doses (0-8 Gy) or cisplatin (1'R for 1 h). Clonogenic assays were carried out to measure survival and γH2AX staining was used to visualize DSBs. To elucidate mechanisms of action expression levels of DNA repair proteins BRCA2 and DNA-PKcs were investigated after 42.0℃ (1 h) using western blot. Combined hyperthermia and radiation resulted in an increased number of γH2AX foci as compared to radiation alone. Hyperthermia treatment in combination with cisplatin and PARP1 inhibitor and with radiation and PARP1 inhibitor significantly decreased cell survival. Western blot demonstrated a decreased expression of BRCA2 protein at 30 min after hyperthermia treatment. Adding PARP1-inhibitor significantly improves the effectiveness of combined hyperthermia radiotherapy and combined hyperthermia-cisplatin treatment on cervical carcinoma cells. Hyperthermia affects DNA-DSB repair as is indicated by increased γH2AX foci numbers and decreased BRCA2 expression. (author)

Continued growth expected for wood energy despite turbulence of the economic crisis : wood energy markets, 2008-2009

Science.gov (United States)

Rens Hartkamp; Bengt Hillring; Warren Mabee; Olle Olsson; Kenneth Skog; Henry Spelter; Johan Vinterback; Antje Wahl

2009-01-01

The economic crisis has not reduced the demand for wood energy, which is expected to continue to grow. The downturn in sawmill production caused a shortage of raw material supply for wood pellet producers. With decreased demand for pulpwood-quality roundwood for wood and paper products in 2009, some pulpwood is being converted into wood energy. Economies of scale are...

The struggle for energy. How the growing need for oil and gas will cause a world crisis

International Nuclear Information System (INIS)

Op het Veld, R.

2008-07-01

Due to the rapid and continued economic growth of China and India, energy demand is increasing rapidly. At the same time, the Western world is facing decreasing oil and gas reserves. As a result, it becomes increasingly dependent on the Middle East and countries such as Russia and Venezuela. Shell and ExxonMobil, who were once dominant oil giants, are losing territory to state energy companies such as Saudi Aramco and Gazprom. The author analyses all these developments, also based on a series of interviews with various experts from trade and industry and the government in the Netherlands and abroad. The author states that the only solution for the energy issue and the climate issue is the development of alternative energy sources. However, for the present this will not suffice to meet growing demand. The battle for energy ultimately paints a picture that is not rosy, involving a crisis and an increasing international rat race for energy. [mk] [nl

P2X7 receptor-mediated PARP1 activity regulates astroglial death in the rat hippocampus following status epilepticus

Directory of Open Access Journals (Sweden)

Ji Yang eKim

2015-09-01

Full Text Available Poly(ADP-ribose polymerase-1 (PARP1 plays a regulatory role in apoptosis, necrosis, and other cellular processes after injury. Recently, we revealed that PARP1 regulates the differential neuronal/astroglial responses to pilocarpine-induced status epilepticus (SE in the distinct brain regions. In addition, P2X7 receptor (P2X7R, an ATP-gated ion channel, activation accelerates astroglial apoptosis, while it attenuates clasmatodendrosis (lysosome-derived autophagic astroglial death. Therefore, we investigated whether P2X7R regulates regional specific astroglial PARP1 expression/activation in response to SE. In the present study, P2X7R activation exacerbates SE-induced astroglial apoptosis, while P2X7R inhibition attenuates it accompanied by increasing PARP1 activity in the molecular layer of the dentate gyrus following SE. In the CA1 region, however, P2X7R inhibition deteriorates SE-induced clasmatodendrosis via PARP1 activation following SE. Taken together, our findings suggest that P2X7R function may affect SE-induced astroglial death by regulating PARP1 activation/expression in regional-specific manner. Therefore, the selective modulation of P2X7R-mediated PARP1 functions may be a considerable strategy for controls in various types of cell deaths.

Fossil fuels, uranium, and the energy crisis

Energy Technology Data Exchange (ETDEWEB)

Playford, P E

1977-01-01

Relevant data on the world energy picture are presented to indicate present energy sources and resources, especially fossil fuels and the role of uranium in energy production, with some predictions for the future. World energy is presently being derived from petroleum (some 62%), coal (31%), hydropower (6%), and nuclear (1%). The fundamental cause of the present world energy crisis is attributed to the increase in consumption of petroleum over the past 20 yr, compared with the relatively small size and unequal distribution of the world's remaining reserves. The reserves/production ratio for petroleum has fallen steadily from a general level of 60 to 80 yr from 1920 to 1955, to about 31 yr today. New oil is becoming harder and more expensive to find and produce, the size of discoveries is declining. There is no reason to believe that this trend will be substantially altered, and production is expected to begin to decline between 1985 and 1990. Gas resources also are expected to fall short after the mid-1980s. Coal reserves are enormous, but their full utilization is doubtful because of economic and environmental problems. Tar sands and oil shale resources are potentially major sources of oil, and they are expected to become more competitive with petroleum as higher oil prices occur.

Inter-dependence not Over-dependence: Reducing Urban Transport Energy Dependence

Energy Technology Data Exchange (ETDEWEB)

Saunders, Michael James; Rodrigues da Silva, Antonio Nelson

2007-07-01

A major issue of concern in today's world is urban transport energy dependence and energy supply security. In an energy inter-dependent world, energy over-dependence brings risks to urban transport systems. Many urban areas are over-dependent on finite petroleum resources for transport. New technology and the development and integration of renewable resources into transport energy systems may reduce some of the current transport energy dependence of urban areas. However, the most effective means of reducing energy dependence is to first design urban areas for this condition. An urban policy framework is proposed that requires transport energy dependence to be measured and controlled in the urban development process. A new tool has been created for this purpose, the Transport Energy Specification (TES), which measures transport energy dependence of urban areas. This creates the possibility for cities to regulate urban development with respect to energy dependence. Trial assessments were performed in Germany, New Zealand and Brazil; initial analysis by transport and government professionals shows promise of this tool being included into urban policy. The TES combined with a regulatory framework has the potential to significantly reduce transport energy consumption and dependence in urban areas in the future. (auth)

Will Britain go the way of the Incas. [Suggestions for alleviating energy crisis

Energy Technology Data Exchange (ETDEWEB)

Clancy, J.

The author states that the rise in oil prices at the end of 1973 was presented to the British public by the Government as a temporary crisis solvable by political means, if the people would restrain their use of energy temporarily until the balance of payments could be righted and North Sea oil arrived. Instead, it is a real crisis, and a type of crisis not encountered before, because fossil fuels (petroleum and natural gas) will be exhausted in the not-too-distant future. It is recommended that the Government be honest in presenting the problem by re-examining the direction society is taking, fostering conservation, instituting long-term planning, making information available on energy-using goods, etc. Otherwise, it is predicted that more oil-type and other material crises will develop and unless people have been prepared, unrest and social chaos--certainly unemployment--will develop. But so far, neither the Government nor industry exhibits a real commitment to conservation (in Britain fuel industries continue in open competition with each other and all but one are State undertakings). Examples are given of what government should be planning and fostering. A question is raised about overconfidence in nuclear energy (which may lead to corner cutting and lower safety) and lack of funding in other areas (geothermal, winds, tides, fusion). (LTN)

PARP Inhibitors in Ovarian Cancer.

Science.gov (United States)

Mittica, Gloria; Ghisoni, Eleonora; Giannone, Gaia; Genta, Sofia; Aglietta, Massimo; Sapino, Anna; Valabrega, Giorgio

2018-03-05

Treatment of Epithelial Ovarian Cancer (EOC), historically based on surgery and platinum doublet chemotherapy, is associated with high risk of relapse and poor prognosis for recurrent disease. In this landscape, the innovative treatment with PARP inhibitors (PARPis) demonstrated an outstanding activity in EOC, and is currently changing clinical practice in BRCA mutant patients. To highlight the mechanism of action, pharmacokinetics, clinical activity, indications and current strategies of development of Olaparib, Niraparib, Rucaparib, Talazoparib and Veliparib, the 5 most relevant PARPis. We performed a review on Pubmed using 'ovarian cancer' and the name of each PARPi (PARP inhibitor) discussed in the review as Medical Subject Headings (MeSH) keywords. The same search was performed on "clinicaltrial.gov" to identify ongoing clinical trials and on "google.com/patents" and "uspto.gov" for recent patents exploring PARPIs in ovarian cancer. Olaparib, Niraparib and Rucaparib are already approved for treatment of recurrent EOC and their indications are partially overlapping. Talazoparib and Veliparib are promising PARPis, but currently under investigation in early phase trials. Several studies are evaluating PARPis in monotherapy or in associations, in a wide range of settings (i.e. first line, neoadjuvant, platinum-sensitive and resistant disease). PARPis are valuable options in patients with recurrent ovarian cancer with promising activity in different stages of this disease. Further studies are required to better define optimal clinical settings, predictors of response beyond BRCA mutations and strategies to overcome secondary resistance of PARPis therapy in EOC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Modified crisis intervention for personality disorder.

Science.gov (United States)

Rudnick, A

1998-01-01

This study proposes that the goal of crisis intervention for persons with personality disorders should be to return them to their pre-crisis level of functioning, even though this is maladaptive. This is contrasted with standard crisis intervention, which aims to return normal or neurotic persons to their pre-crisis normal or neurotic functioning, usually by means of few and short-term therapeutic encounters. The modification proposed costs more time and resources in persons with personality disorders in crisis and fits the intervention to the personality type. This is illustrated by the case of Eve, a patient in crisis, whose pre-crisis functioning was maladaptive because of a dependent personality disorder. The goal of (modified) crisis intervention in this case was to return the patient to her dependent lifestyle, by means of pharmacotherapy combined with intensive supportive psychotherapy during 3-4 months of partial (day) hospitalization. The special nature of crisis in personality disorders is discussed.

PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells.

Directory of Open Access Journals (Sweden)

Jelena Marković

Full Text Available Despite significant progress, the molecular mechanisms responsible for pancreatic beta cell depletion and development of diabetes remain poorly defined. At present, there is no preventive measure against diabetes. The positive impact of CXCL12 expression on the pancreatic beta cell prosurvival phenotype initiated this study. Our aim was to provide novel insight into the regulation of rat CXCL12 gene (Cxcl12 transcription. The roles of poly(ADP-ribose polymerase-1 (PARP-1 and transcription factor Yin Yang 1 (YY1 in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation. The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression. Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription. Streptozotocin (STZ-induced general toxicity in pancreatic beta cells was followed by changes in Cxcl12 promoter regulation. PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression. During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding. These interactions were accompanied by Cxcl12 downregulation. In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1. These interactions resulted in higher Cxcl12 expression. The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the

Chaos and Crisis: Propositions for a General Theory of Crisis Communication.

Science.gov (United States)

Seeger, Matthew W.

2002-01-01

Presents key concepts of chaos theory (CT) as a general framework for describing organizational crisis and crisis communication. Discusses principles of predictability, sensitive dependence on initial conditions, bifurcation as system breakdown, emergent self-organization, and fractals and strange attractors as principles of organization. Explores…

The Prognostic Value of BRCA1 and PARP Expression in Epithelial Ovarian Carcinoma

DEFF Research Database (Denmark)

Hjortkjær, Mette; Waldstrøm, Marianne; Jakobsen, Anders

2017-01-01

BRCA1/2 mutation status in epithelial ovarian cancer (EOC) presently relies on genetic testing which is resource consuming. Immunohistochemistry is cheap, fairly reproducible, and may identify gene product alterations due to both germline and somatic mutations and other defects along the BRCA gene...... tissue from 170 patients with EOC was stained immunohistochemically with BRCA1 and PARP antibodies. Semiquantitative analyses were performed to determine loss of, equivocal, and retained BRCA1 and high versus low PARP protein expression. These parameters were analyzed for relation with patient...

PARP-1 depletion in combination with carbon ion exposure significantly reduces MMPs activity and overall increases TIMPs expression in cultured HeLa cells

International Nuclear Information System (INIS)

Ghorai, Atanu; Sarma, Asitikantha; Chowdhury, Priyanka; Ghosh, Utpal

2016-01-01

Hadron therapy is an innovative technique where cancer cells are precisely killed leaving surrounding healthy cells least affected by high linear energy transfer (LET) radiation like carbon ion beam. Anti-metastatic effect of carbon ion exposure attracts investigators into the field of hadron biology, although details remain poor. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are well-known radiosensitizer and several PARP-1 inhibitors are in clinical trial. Our previous studies showed that PARP-1 depletion makes the cells more radiosensitive towards carbon ion than gamma. The purpose of the present study was to investigate combining effects of PARP-1 inhibition with carbon ion exposure to control metastatic properties in HeLa cells. Activities of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) were measured using the gelatin zymography after 85 MeV carbon ion exposure or gamma irradiation (0- 4 Gy) to compare metastatic potential between PARP-1 knock down (HsiI) and control cells (H-vector - HeLa transfected with vector without shRNA construct). Expression of MMP-2, MMP-9, tissue inhibitor of MMPs such as TIMP-1, TIMP-2 and TIMP-3 were checked by immunofluorescence and western blot. Cell death by trypan blue, apoptosis and autophagy induction were studied after carbon ion exposure in each cell-type. The data was analyzed using one way ANOVA and 2-tailed paired-samples T-test. PARP-1 silencing significantly reduced MMP-2 and MMP-9 activities and carbon ion exposure further diminished their activities to less than 3 % of control H-vector. On the contrary, gamma radiation enhanced both MMP-2 and MMP-9 activities in H-vector but not in HsiI cells. The expression of MMP-2 and MMP-9 in H-vector and HsiI showed different pattern after carbon ion exposure. All three TIMPs were increased in HsiI, whereas only TIMP-1 was up-regulated in H-vector after irradiation. Notably, the expressions of all TIMPs were significantly higher in HsiI than H-vector at 4 Gy. Apoptosis was

Concurrent targeting of nitrosative stress-PARP pathway corrects functional, behavioral and biochemical deficits in experimental diabetic neuropathy

Energy Technology Data Exchange (ETDEWEB)

Negi, Geeta; Kumar, Ashutosh [Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062 (India); Sharma, Shyam S., E-mail: sssharma@niper.ac.in [Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062 (India)

2010-01-01

Peroxynitrite mediated nitrosative stress, an indisputable initiator of DNA damage and overactivation of poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated after sensing DNA damage, are two crucial pathogenetic mechanisms in diabetic neuropathy. The intent of the present study was to investigate the effect of combination of a peroxynitrite decomposition catalyst (PDC), FeTMPyP and a PARP inhibitor, 4-ANI against diabetic peripheral neuropathy. The end points of evaluation of the study included motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) for evaluating nerve functions; thermal hyperalgesia and mechanical allodynia for assessing nociceptive alterations, malondialdehyde and peroxynitrite levels to detect oxidative stress-nitrosative stress; NAD concentration in sciatic nerve to assess overactivation of PARP. Additionally immunohistochemical studies for nitrotyrosine and Poly(ADP-ribose) (PAR) was also performed. Treatment with the combination of FeTMPyP and 4-ANI led to significant improvement in nerve functions and pain parameters and also attenuated the oxidative-nitrosative stress markers. Further, the combination also reduced the overactivation of PARP as evident from increased NAD levels and decreased PAR immunopositivity in sciatic nerve microsections. Thus, it can be concluded that treatment with the combination of a PDC and PARP inhibitor attenuates alteration in peripheral nerves in diabetic neuropathy (DN).

Energy crisis and rationing: a comparison between the argentinian and brazilian programs; Crisis energetica y racionamiento: los programas de Argentina y Brasil, una comparacion

Energy Technology Data Exchange (ETDEWEB)

Urbiztondo, Santiago; Navajas, Fernando [Fundacion de Investigaciones Economicas Latinoamericanas (FIEL)(Argentina)

2006-01-15

Although they have been equitable compared, the energy policies taken by Brazil and Argentina as a solution to the energy crisis lived by each one of these countries in years 2001 and 2002, they have enormous differences in terms of the real problem and nature of the established measures. Firstly the central aspects of the demand rationing mechanism adopted by Brazil for the electrical crisis of 2001 are presented. Afterwards the measures adopted in Argentina during the 2004 crisis in the electricity and natural gas rationing are discussed. From this exhibition of facts, comparisons are made and conclusions extracted looking forward to clarify the important differences separating both cases, differences that as the study reveals meant for the Argentine scheme the breach of the expected objectives. In the last section the changes implemented in the Argentine scheme are reflected during year 2005 to counteract the bad results obtained, nevertheless this modifications attacked only in a partial way the original program weaknesses. [Spanish] Si bien han sido comparadas equitativamente, las politicas energeticas tomadas por Brasil y Argentina como solucion a las crisis energeticas vividas por cada uno en el 2001 y 2004 presentan enormes diferencias a nivel de problema real y naturaleza de las medidas establecidas. Primeramente son presentados los aspectos centrales del mecanismo de racionamiento de la demanda adoptados por Brasil en la crisis electrica de 2001. Luego se comentan las medidas adoptadas en Argentina durante su crisis en el ano 2004 en el racionamiento de electricidad y gas natural. A partir de esta exposicion de hechos se realizan comparaciones y se extraen conclusiones que buscan clarificar las importantes diferencias que separan a ambos casos, diferencias que, como revela el estudio, significaron para el esquema argentino el incumplimiento de los objetivos esperados. En la ultima seccion se reflejan los cambios implementados en el esquema argentino

Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction

DEFF Research Database (Denmark)

Fang, Evandro Fei; Scheibye-Knudsen, Morten; Brace, Lear E

2014-01-01

with excessive cleavage of PINK1 and increased mitochondrial membrane potential. The mitochondrial abnormalities appear to be caused by decreased activation of the NAD(+)-SIRT1-PGC-1α axis triggered by hyperactivation of the DNA damage sensor PARP-1. This phenotype is rescued by PARP-1 inhibition...... or by supplementation with NAD(+) precursors that also rescue the lifespan defect in xpa-1 nematodes. Importantly, this pathogenesis appears common to ataxia-telangiectasia and Cockayne syndrome, two other DNA repair disorders with neurodegeneration, but absent in XPC, a DNA repair disorder without neurodegeneration...

BZLF1 Expression of EBV is correlated with PARP1 Regulation on Nasopharyngeal Carcinoma Tissues

Directory of Open Access Journals (Sweden)

Wahyu nur laili fajri, Ahmad Rofi'i, Fatchiyah Fatchiyah

2013-04-01

Full Text Available Nasopharyngeal carcinomas (NPC is a cancer that arises in the epithelial tissue that covers the inside of the nasopharyngeal mucosa and nasopharynx. Infected Epstein Barr Virus (EBV cell in a latent infection associated with the expression of nine latent proteins. Latent Membrane Protein 1 (LMP1 is one of latent proteins, and mayor EBV oncoprotein, with functions including virus growth, and to activate BamHI-Z Leftward Reading Frame 1 (BZLF1-EBV, which can inhibit p53 to induce apoptotic resistance, metastasis, and immune modulation. The body will respond to the expansion of EBV infection with activation of Poly(ADP-ribosePolymerase-1 (PARP1. The objective of study is to observe the expression of BZLF1 and determine PARP1 regulation in nasopharyngeal tissues. NPC-T2, NPC-T3 and polyp tissues slides are from Ulin Hospital, Banjarmasin. To characterize the necrotic cells such as pyknosis, karyorrhexsis, and karyolysis, histological slides were stained by HE that the necrotic cells measured by using a BX-53 microscope (Olympus with CellSens Standard software. Tissues slides were stained by using immunofluorohistochemistry with EBV-BZLF1 antibody-Mouse anti-EBV monoclonal antibody against Goat anti-mouse IgG-FITC and anti-PARP1 antibody (MC-10 against Goat anti-mouse IgG labeled Rhodamin. The expression intensities were measured by Confocal Laser Scanning Microscope (Olympus. The percentage number of necrotic cells and BZLF1 and PARP1 expression intensity were analyzed using SPSS 16.0 by one-way ANOVA test with α = 0.05, beside that we use correlate and regression analyze. The research showed that the amount of karryorhexis higher than pyknosis and karyolysis in both tissues. BZLF1 expression 1.79 INT/sel (in polyp, 2.76 INT/sel (NPC Type 2 and 4.36 INT/sel (NPC Type 3, PARP1 expression 2.25 INT/sel (in polyp, 3.31 INT/sel (NPC Type 2, dan 5.93 INT/sel (NPC Type 3.The high of intensity of expression BZLF1 induced the increasing of PARP1 expression

Poly(ADP-ribose polymerase 1 (PARP1 overexpression in human breast cancer stem cells and resistance to olaparib.

Directory of Open Access Journals (Sweden)

Marine Gilabert

Full Text Available BACKGROUND: Breast cancer stem cells (BCSCs have been recognized as playing a major role in various aspects of breast cancer biology. To identify specific biomarkers of BCSCs, we have performed comparative proteomics of BCSC-enriched and mature cancer cell populations from the human breast cancer cell line (BCL, BrCA-MZ-01. METHODS: ALDEFLUOR assay was used to sort BCSC-enriched (ALDH+ and mature cancer (ALDH- cell populations. Total proteins were extracted from both fractions and subjected to 2-Dimensional Difference In-Gel Electrophoresis (2-D DIGE. Differentially-expressed spots were excised and proteins were gel-extracted, digested and identified using MALDI-TOF MS. RESULTS: 2-D DIGE identified poly(ADP-ribose polymerase 1 (PARP1 as overexpressed in ALDH+ cells from BrCA-MZ-01. This observation was confirmed by western blot and extended to four additional human BCLs. ALDH+ cells from BRCA1-mutated HCC1937, which had the highest level of PARP1 overexpression, displayed resistance to olaparib, a specific PARP1 inhibitor. CONCLUSION: An unbiased proteomic approach identified PARP1 as upregulated in ALDH+, BCSC-enriched cells from various human BCLs, which may contribute to clinical resistance to PARP inhibitors.

Gas crisis in Europe

International Nuclear Information System (INIS)

2002-01-01

The gas crisis in Europe is getting more evident. Basing his discussion on BP's annual statistical review of world energy, 2002, the author concludes that an increasing number of the major European consumers of natural gas may acquire a supply- and safety problem and become more dependent on imported gas for operating power stations. This is going to be most dramatic for France, Germany and Italy. Great Britain have gas reserves that will last for about seven years. Spain is an interesting ''phenomenon'' in the European gas market; they have trebled their gas consumption during the last decade. Europe's dependence on a high production rate on the Norwegian Shelf has become stronger from year to year

2030 the ecological crisis

International Nuclear Information System (INIS)

Ferone, G.

2008-01-01

The ecological crisis will happen on 2030. A combination of climatic change, energy problems, increase in population, will mix up. The author debates about true questions on the economy: how to get quickly towards renewable energies use, how much will it cost, must we generalize the carbon tax, what about economic giant as India and China, what about the technology development to solve the crisis? (A.L.B.)

Electric energy production and environmental licensing: citizenship in Brazil in time of ecological crisis

International Nuclear Information System (INIS)

Bettencourt, Marcia Pires da Luz

2017-01-01

The choices of energy sources gain relevance in the face of the ecological crisis which has a central questioning on the modes of production and consumption and that stems from a system which changes everything into merchandise. On one hand, brazilian electricity generation has the advantage of using clean energy in great part of its composition, at least in discourse. On the other hand, though, there are high social and environmental costs, especially for communities living near the regions where projects for the electricity sector are built. This research aimed to identify and analyse different modes society takes part in the process of choosing energy sources for electricity generation in Brazil. It discusses the links between the ecological crisis and the production of electrical energy; how the institutional mechanisms for social participation on issues related to the production of electric power in Brazil work; and, how civil society participates in environmental licensing in the National Environment Council (CONAMA). A set of related approaches to the nature of the ecological crisis and the forms of social participation was adopted in the theoretical framework and an analysis of the electric sector panorama in Brazil has been drawn up. In order to investigate the forms society participates in issues related to the composition of the brazilian electricity matrix, the methodology comprised a documentary analysis and a case study. They included three categories of actors: (1) CONAMA's councilors, (2) experts from the Field; and (3) actors involved in the diagnosis study, planning and management of the electricity sector. The research identified inconsistencies, ambiguities and other relevant issues about the participation of society in the production of electrical energy. Such issues are related to: deficiencies in the mechanisms for information access; lack of transparency and patterns in internal documents; lack of social participation in the elaboration of

Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1 alpha axis

DEFF Research Database (Denmark)

Fakouri, Nima Borhan; Durhuus, Jon Ambaek; Regnell, Christine Elisabeth

2017-01-01

(ADP) ribose polymerase 1 (PARP1) activity, low endogenous NAD+, low expression of SIRT1 and PGC1α and low adenosine monophosphate (AMP)-activated kinase (AMPK) activity. We conclude that replication stress via Rev1-deficiency contributes to metabolic stress caused by compromized mitochondrial function via...... the PARP-NAD+-SIRT1-PGC1α axis....

PARPs database: A LIMS systems for protein-protein interaction data mining or laboratory information management system

Directory of Open Access Journals (Sweden)

Picard-Cloutier Aude

2007-12-01

Full Text Available Abstract Background In the "post-genome" era, mass spectrometry (MS has become an important method for the analysis of proteins and the rapid advancement of this technique, in combination with other proteomics methods, results in an increasing amount of proteome data. This data must be archived and analysed using specialized bioinformatics tools. Description We herein describe "PARPs database," a data analysis and management pipeline for liquid chromatography tandem mass spectrometry (LC-MS/MS proteomics. PARPs database is a web-based tool whose features include experiment annotation, protein database searching, protein sequence management, as well as data-mining of the peptides and proteins identified. Conclusion Using this pipeline, we have successfully identified several interactions of biological significance between PARP-1 and other proteins, namely RFC-1, 2, 3, 4 and 5.

Recurrent hypoinsulinemic hyperglycemia in neonatal rats increases PARP-1 and NF-κB expression and leads to microglial activation in the cerebral cortex.

Science.gov (United States)

Gisslen, Tate; Ennis, Kathleen; Bhandari, Vineet; Rao, Raghavendra

2015-11-01

Hyperglycemia is a common metabolic problem in extremely low-birth-weight preterm infants. Neonatal hyperglycemia is associated with increased mortality and brain injury. Glucose-mediated oxidative injury may be responsible. Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in DNA repair and cell survival. However, PARP-1 overactivation leads to cell death. NF-κB is coactivated with PARP-1 and regulates microglial activation. The effects of recurrent hyperglycemia on PARP-1/NF-κB expression and microglial activation are not well understood. Rat pups were subjected to recurrent hypoinsulinemic hyperglycemia of 2 h duration twice daily from postnatal (P) day 3-P12 and killed on P13. mRNA and protein expression of PARP-1/NF-κB and their downstream effectors were determined in the cerebral cortex. Microgliosis was determined using CD11 immunohistochemistry. Recurrent hyperglycemia increased PARP-1 expression confined to the nucleus and without causing PARP-1 overactivation and cell death. NF-κB mRNA expression was increased, while IκB mRNA expression was decreased. inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) mRNA expressions were decreased. Hyperglycemia significantly increased the number of microglia. Recurrent hyperglycemia in neonatal rats is associated with upregulation of PARP-1 and NF-κB expression and subsequent microgliosis but not neuronal cell death in the cerebral cortex.

Thailand: Post-Crisis Rebalancing

OpenAIRE

Chalongphob Sussangkarn; Deunden Nikomborirak

2012-01-01

Since the Asian financial crisis in 1997, Thailand has become highly dependent on exports as the main engine of economic growth. In 2008, the ratio of export to GDP was about 76.5 percent. The global economic crisis triggered by the sub-prime loans debacle in the United States has prompted Thailand to rethink its high dependence on export. This paper examines the options for external and internal economic rebalancing strategies for Thailand. External rebalancing will require Thailand to rely ...

Differential expression of PARP1 mRNA in leucocytes of patients ...

Indian Academy of Sciences (India)

P. 2011 Differential expression of PARP1 mRNA in leucocytes of patients with Down's syndrome. J. Genet. ... of Alzheimer disease at an earlier age than subjects with- ... family and personal informed consent. .... In effect, they report that.

A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors

Science.gov (United States)

2017-02-01

affecting the function of Fanconi Anemia (FA) genes ( FANCA /B/C/D2/E/F/G/I/J/L/M, PALB2) or DNA damage response genes involved in HR 5 (ATM, ATR...Award Number: W81XWH-10-1-0585 TITLE: A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors...To) 15 July 2010 – 2 Nov.2016 4. TITLE AND SUBTITLE A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP

Answers to energy crisis: energy efficiency, rational use of energy and renewable sources; Respostas para crise de energia eletrica: eficiencia energetica, uso racional de energia e fontes renovaveis

Energy Technology Data Exchange (ETDEWEB)

Naturesa, Jim Silva; Mariotoni, Carlos Alberto [Universidade Estadual de Campinas (FEC/UNICAMP), SP (Brazil). Fac. de Engenharia Civil, Arquitetura e Urbanismo; Menezes, Taciana de V.; Perrone, Fernando Pinto Dias; Lepetitgaland, Karla Kwiatkowski [Centrais Eletricas Brasileiras S.A (ELETROBRAS), Rio de Janeiro, RJ (Brazil)

2008-07-01

This article presents the main advances in energy efficiency of Brazil, the results of the electrical energy alternatives sources incentive program until May of 2007, and examples of using energy in a reasonable way. In our point of view, these three initiatives are essentials in any energetic planning and must be considered with seriousness, mainly at moments of energy crisis. (author)

RECOVERY OF amiRNA3-PARP1 TRANSGENIC MAIZE PLANTS ...

African Journals Online (AJOL)

ACSS

Positive plant selectable marker genes are commonly used in plant transformation because they not only enhance the frequency of generation transgenic tissues but are considered biosafe, unlike antibiotic or herbicide resistance genes. In this study, the binary vector pNOV2819-ubiamiRNA3PARP1, harbouring the ...

Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells

NARCIS (Netherlands)

Verhagen, C.V.M.; Haan, R. den; Hageman, F.; Oostendorp, T.P.; Carli, A.L.; O'Connor, M.J.; Jonkers, J.; Verheij, M.; Brekel, M.W. van den; Vens, C.

2015-01-01

BACKGROUND AND PURPOSE: The PARP inhibitor olaparib is currently tested in clinical phase 1 trials to define safe dose levels in combination with RT. However, certain clinically relevant insights are still lacking. Here we test, while comparing to single agent activity, the olaparib dose and genetic

Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells

NARCIS (Netherlands)

Verhagen, C.V.M.; de Haan, R.; Hageman, F.; Oostendorp, T.P.D.; Carli, A.L.E.; O'Connor, M.J.; Jonkers, J.; Verheij, M.; van den Brekel, M.W.; Vens, C.

2015-01-01

Background and purpose The PARP inhibitor olaparib is currently tested in clinical phase 1 trials to define safe dose levels in combination with RT. However, certain clinically relevant insights are still lacking. Here we test, while comparing to single agent activity, the olaparib dose and genetic

ATM-Deficient Colorectal Cancer Cells Are Sensitive to the PARP Inhibitor Olaparib.

Science.gov (United States)

Wang, Chen; Jette, Nicholas; Moussienko, Daniel; Bebb, D Gwyn; Lees-Miller, Susan P

2017-04-01

The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), and we previously showed that MCL cell lines with loss of ATM are sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Next-generation sequencing of patient tumors has revealed that ATM is altered in many human cancers including colorectal, lung, prostate, and breast. Here, we show that the colorectal cancer cell line SK-CO-1 lacks detectable ATM protein expression and is sensitive to the PARP inhibitor olaparib. Similarly, HCT116 colorectal cancer cells with shRNA depletion of ATM are sensitive to olaparib, and depletion of p53 enhances this sensitivity. Moreover, HCT116 cells are sensitive to olaparib in combination with the ATM inhibitor KU55933, and sensitivity is enhanced by deletion of p53. Together our studies suggest that PARP inhibitors may have potential for treating colorectal cancer with ATM dysfunction and/or colorectal cancer with mutation of p53 when combined with an ATM kinase inhibitor. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Poly(ADP-ribose) polymerase-1 and its cleavage products differentially modulate cellular protection through NF-kB-dependent signaling

Science.gov (United States)

Castri, Paola; Lee, Yang-ja; Ponzio, Todd; Maric, Dragan; Spatz, Maria; Bembry, Joliet; Hallenbeck, John

2014-01-01

Poly(ADP-ribose) polymerase-1 (PARP-1) and its cleavage products regulate cell viability and NF-kB activity when expressed in neurons. PARP-1 cleavage generates a 24kDa (PARP-124) and an 89kDa fragment (PARP-189). Compared to WT (PARP-1WT), the expression of an uncleavable PARP-1 (PARP-1UNCL) or of PARP-124 conferred protection from oxygen/glucose deprivation (OGD) or OGD/restoration of oxygen and glucose (ROG) damage in vitro, whereas expression of PARP-189 was cytotoxic. Viability experiments were performed in SH-SY5Y, a human neuroblastoma cell line, as well as in rat primary cortical neurons. Following OGD, the higher viability in the presence of PARP-1UNCL or PARP-124 was not accompanied with decreased formation of poly(ADP-riboses) or higher NAD levels. PARP-1 is a known cofactor for NF-kB, hence we investigated whether PARP-1 cleavage influences the inflammatory response. All PARP-1 constructs mimicked PARP-1WT in regards to induction of NF-kB translocation into the nucleus and its increased activation during ischemic challenge. However, expression of PARP-189 construct induced significantly higher NF-kB activity than PARP-1WT; and the same was true for NF-kB-dependent iNOS promoter binding activity. At a protein level, PARP-1UNCL and PARP-124 decreased iNOS (and lower levels of iNOS transcript) and COX-2, and increased Bcl-xL. The increased levels of NF-kB and iNOS transcriptional activities, seen with cytotoxic PARP-189, were accompanied by higher protein expression of COX-2 and iNOS (and higher levels of iNOS transcript) and lower protein expression of Bcl-xL. Taken together, these findings suggest that PARP-1 cleavage products may regulate cellular viability and inflammatory responses in opposing ways during in vitro models of “ischemia”. PMID:24333653

SU-E-T-245: MR Guided Focused Ultrasound Increased PARP Related Apoptosis On Prostate Cancer in Vivo

International Nuclear Information System (INIS)

Chen, L; Chen, X; Cvetkovic, D; Gupta, R; Yang, D; Ma, C

2014-01-01

Purpose: Our previous study demonstrated that significant tumor growth delay was observed in the mice treated with pulsed high intensity focused ultrasound (pHIFU). The purpose of this study is to understand the cell killing mechanisms of pHIFU. Methods: Prostate cancer cells (LNCaP), were grown orthotopically in 17 nude mice. Tumor-bearing mice were treated using pHIFU with an acoustic power of 25W, pulse width 100msec and 300 pulses in one sonication under MR guidance. Mutiple sonications were used to cover the whole tumor volume. Temperature (less than 40 degree centigrade in the focal spot) was monitored using MR thermometry. Animals were euthanized at pre-determined time points (n=2) after treatment: 0 hours; 6 hrs; 24 hrs; 48 hrs; 4 days and 7 days. Two tumorbearing mice were used as control. Three tumor-bearing mice were treated with radiation (RT, 2 Gy) using 6 MV photon beams. RT treated mice were euthanized at 0 hr, 6 hrs and 24 hrs. The tumors were processed for immunohistochemical (IHC) staining for PARP (a surrogate of apoptosis). A multispectral imaging analysis system was used to quantify the expression of PARP staining. Cell apoptosis was calculated based on the PARP expression level, which is the intensity of the DAB reaction. Results: Our data showed that PARP related apoptosis peaked at 48 hrs and 7 days in pHIFU treated mice, which is comparable to that for the RT group at 24 hrs. The preliminary results from this study were consistent with our previous study on tumor growth delay using pHIFU. Conclusion: Our results demonstrated that non-thermal pHIFU increased apoptotic tumor cell death through the PARP related pathway. MR guided pHIFU may have a great potential as a safe, noninvasive treatment modality for cancer therapy. This treatment modality might be able to synergize with PARP inhibitors to achieve better result

PARP-1 is a key player in controlling apoptosis induced by high LET carbon ion beam and low LET gamma radiation in HeLa cells

International Nuclear Information System (INIS)

Ghorai, Atanu; Ghosh, Utpal; Bhattacharyya, Nitai P.; Sarma, Asitikantha

2014-01-01

PARP-1 inhibitors have long been used as chemo-sensitizer or radio-sensitizer and specific PARP-1 inhibitors are also in clinical trial for the treatment of various cancers. PARP-1 is not only involved in DNA repair but also plays very complex role in induction of apoptosis in postirradiation condition. Our objective is to investigate role of PARP-1 in apoptosis triggered by high LET carbon ion beam (CIB) and low LET gamma. We have treated HeLa and PARP-1 knock down HeLa (Hsil) cells with various doses of CIB and gamma. We measured DNA damage by comet assay and various apoptotic parameters such as nuclear fragmentation, activation of caspase-3,8,9, AIF translocation etc. We observed higher DNA breaks and also higher apoptosis in HsiI cells compared with HeLa cells. Both CIB and gamma treatment results G2/M arrest but unlike gamma CIB makes S-phase delay, implicating that gamma and CIB triggers different pathway after DNA damage. Cell death by CIB or by gamma increased up on knocking down of PARP-1 but increase is higher for high LET CIB compared with low LET gamma. Furthermore, expression level of PARP-1 controls the intensity of overall apoptosis in cells in post-irradiation condition. So, combination of PARP-1 inhibition with high LET CIB could be a promising tool to combat cancer. (author)

The Little-Known Crisis

Science.gov (United States)

Eckholm, Erik P.

1975-01-01

For one-third of the world's people, the energy crisis means the daily scramble to find the wood they need to cook. The accelerating destruction of forests throughout Africa, Asia and Latin America and the utilization of manure as a firewood substitute may produce the most profound ecological crisis of this century. (BT)

The dual action of poly(ADP-ribose polymerase -1 (PARP-1 inhibition in HIV-1 infection: HIV-1 LTR inhibition and diminution in Rho GTPase activity

Directory of Open Access Journals (Sweden)

Slava eRom

2015-08-01

Full Text Available The transcription of HIV-1 (HIV is regulated by complex mechanisms involving various cellular factors and virus-encoded transactivators. Poly(ADP-ribose polymerase 1 (PARP-1 inhibition has emerged recently as a potent anti-inflammatory tool, since PARP-1 is involved in the regulation of some genes through its interaction with various transcription factors. We propose a novel approach to diminish HIV replication via PARP-1 inhibition using human primary monocyte-derived macrophages (MDM as an in vitro model system. PARP-1 inhibitors were able to reduce HIV replication in MDM by 60-80% after 7 days infection. Long Terminal Repeat (LTR acts as a switch in virus replication and can be triggered by several agents such as: Tat, tumor necrosis factor α (TNFα, and phorbol 12-myristate 13-acetate (PMA. Overexpression of Tat in MDM transfected with an LTR reporter plasmid led to a 4.2-fold increase in LTR activation; PARP inhibition resulted in 70% reduction of LTR activity. LTR activity, which increased 3-fold after PMA or TNFα treatment, was reduced by PARP inhibition (by 85-95%. MDM treated with PARP inhibitors showed 90% reduction in NFκB activity (known to mediate PMA- and TNFα-induced HIV LTR activation. Cytoskeleton rearrangements are important in effective HIV-1 infection. PARP inactivation reduced actin cytoskeleton rearrangements by affecting Rho GTPase machinery. These findings suggest that HIV replication in MDM could be suppressed by PARP inhibition via NFκB suppression, diminution of LTR activation and its effects on the cytoskeleton. PARP appears to be essential for HIV replication and its inhibition may provide a potent approach to treatment of HIV infection.

Increased transcript level of poly(ADP-ribose) polymerase (PARP-1) in human tricuspid compared with bicuspid aortic valves correlates with the stenosis severity

International Nuclear Information System (INIS)

Nagy, Edit; Caidahl, Kenneth; Franco-Cereceda, Anders; Bäck, Magnus

2012-01-01

Highlights: ► Oxidative stress has been implicated in the pathomechanism of calcific aortic valve stenosis. ► We assessed the transcript levels for PARP-1 (poly(ADP-ribose) polymerase), acts as a DNA damage nick sensor in stenotic valves. ► Early stage of diseased tricuspid valves exhibited higher mRNA levels for PARP-1 compared to bicuspid valves. ► The mRNA levels for PARP-1 inversely correlated with the clinical stenosis severity in tricuspid valves. ► Our data demonstrated that DNA damage pathways might be associated with stenosis severity only in tricuspid valves. -- Abstract: Oxidative stress may contribute to the hemodynamic progression of aortic valve stenosis, and is associated with activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) 1. The aim of the present study was to assess the transcriptional profile and the topological distribution of PARP-1 in human aortic valves, and its relation to the stenosis severity. Human stenotic aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery and used for mRNA extraction followed by quantitative real-time PCR to correlate the PARP-1 expression levels with the non invasive hemodynamic parameters quantifying the stenosis severity. Primary isolated valvular interstitial cells (VICs) were used to explore the effects of cytokines and leukotriene C 4 (LTC 4 ) on valvular PARP-1 expression. The thickened areas of stenotic valves with tricuspid morphology expressed significantly higher levels of PARP-1 mRNA compared with the corresponding part of bicuspid valves (0.501 vs 0.243, P = 0.01). Furthermore, the quantitative gene expression levels of PARP-1 were inversely correlated with the aortic valve area (AVA) (r = −0.46, P = 0.0469) and AVA indexed for body surface area (BSA) (r = −0.498; P = 0.0298) only in tricuspid aortic valves. LTC 4 (1 nM) significantly elevated the mRNA levels of PARP-1 by 2.38-fold in VICs. Taken together, these data suggest that

The Venezuelan oil crisis; La crisis del petroleo venezolano

Energy Technology Data Exchange (ETDEWEB)

Billig, Michelle [Council on Foreign Relations (United States)

2004-10-15

The last year, Washington was taken aback by the crisis in Caracas. Such crisis caused the crude oil prices were shot up and it exposed the United States' weak points with regard to both the forecast and the management of the possible threats to their energy supply. Both the government and the industry should do better for the next time. [Spanish] Washington fue tomado por sorpresa cuando se desato la crisis del ano pasado en Caracas, hecho que causo que se dispararan los precios del petroleo y expuso las fallas en la capacidad de Estados Unidos de pronosticar y poder manejar las amenazas a su suministro energetico. Tanto el gobierno como la industria deben hacerlo mejor la proxima vez.

Cuba - energy management in crisis. Kuba - Energiewirtschaft in der Krise

Energy Technology Data Exchange (ETDEWEB)

Lechuga Vilarino, R. (Hochschule fuer Technik, Wirtschaft und Sozialwesen (HTWS), Zittau/Goerlitz F-H (Germany)); Riesner, W. (Hochschule fuer Technik, Wirtschaft und Sozialwesen (HTWS), Zittau/Goerlitz F-H (Germany))

1994-10-01

In 1993, the drastic decline of the Cuban economy resulted in a partial revelation of socialistic economic principles. A crisis in energy supply brings big parts of agriculture and industry to a standstill caused by a lack of foreign exchange. Collapses in public traffic, daily power cut lasting hours show that the vulnerable spot of the island is exposed with the energy supply. Despite increasing own crude oil extraction (1993: 1.1 mio. t), lack in energy is drastic through dropped subsidies of the former Soviet Union as well as wanting crude oil supplies from this region (decrease of crude oil imports from previously 13 mio. t/a to 13 up to 4 mio. t/a). On the other hand, this critical situation has forced to save energy to better use national owned reserves. It is also planned to continue a nuclear power station concept blocked in 1992. In lack of an own fossil basis of ressources, the utilization of regeneration energy sources is increasingly considered with this bagasse in the centre. Nevertheless it is clear that the gap in energy coverage cannot be managed with this alone. (orig./UA)

The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines

International Nuclear Information System (INIS)

Güster, Julian David; Weissleder, Stephanie Valerie; Busch, Chia-Jung; Kriegs, Malte; Petersen, Cordula; Knecht, Rainald; Dikomey, Ekkehard; Rieckmann, Thorsten

2014-01-01

Background and purpose: HPV-negative and HPV-positive HNSCC comprise distinct tumor entities with different biological characteristics. Specific regimens for the comparably well curable HPV-positive entity that reduce side effects without compromising outcome have yet to be established. Therefore, we tested here whether the inhibition of EGFR or PARP may be used to specifically enhance the radiosensitivity of HPV-positive HNSCC cells. Materials and methods: Experiments were performed with five HPV/p16-positive HNSCC cell lines. Inhibitors used were cetuximab, olaparib and PF-00477736. The respective inhibition of EGFR, PARP and Chk1 was evaluated by Western blot, immunofluorescence analysis and assessment of cell cycle distribution. Cell survival was assessed by colony formation assay. Results: Inhibition of EGFR by cetuximab failed to radiosensitize any of the HPV-positive HNSCC cell lines tested. In contrast, PARP-inhibition resulted in a substantial radiosensitization of all strains, with the sensitization being further enhanced by the additional inhibition of Chk1. Conclusions: PARP-inhibition effectively radiosensitizes HPV-positive HNSCC cells and may therefore represent a viable alternative to chemotherapy possibly even allowing for a reduction in radiation dose. For the latter, PARP-inhibition may be combined with the inhibition of Chk1. In contrast, the inhibition of EGFR cannot be expected to radiosensitize HPV-positive HNSCC through the modulation of cellular radiosensitivity

Xeroderma Pigmentosum Group A Promotes Autophagy to Facilitate Cisplatin Resistance in Melanoma Cells through the Activation of PARP1.

Science.gov (United States)

Ge, Rui; Liu, Lin; Dai, Wei; Zhang, Weigang; Yang, Yuqi; Wang, Huina; Shi, Qiong; Guo, Sen; Yi, Xiuli; Wang, Gang; Gao, Tianwen; Luan, Qi; Li, Chunying

2016-06-01

Xeroderma pigmentosum group A (XPA), a key protein in the nucleotide excision repair pathway, has been shown to promote the resistance of tumor cells to chemotherapeutic drugs by facilitating the DNA repair process. However, the role of XPA in the resistance of melanoma to platinum-based drugs like cisplatin is largely unknown. In this study, we initially found that XPA was expressed at higher levels in cisplatin-resistant melanoma cells than in cisplatin-sensitive ones. Furthermore, the knockdown of XPA not only increased cellular apoptosis but also inhibited cisplatin-induced autophagy, which rendered the melanoma cells more sensitive to cisplatin. Moreover, we discovered that the increased XPA in resistant melanoma cells promoted poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) activation and that the inhibition of PARP1 could attenuate the cisplatin-induced autophagy. Finally, we proved that the inhibition of PARP1 and the autophagy process made resistant melanoma cells more susceptible to cisplatin treatment. Our study shows that XPA can promote cell-protective autophagy in a DNA repair-independent manner by enhancing the activation of PARP1 in melanoma cells resistant to cisplatin and that the XPA-PARP1-mediated autophagy process can be targeted to overcome cisplatin resistance in melanoma chemotherapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Biowaste energy potential in Kenya

NARCIS (Netherlands)

Nzila, C.; DeWulf, J.; Spanjers, H.; Kiriamiti, H.; Langenhove, H.

2010-01-01

Energy affects all aspects of national development. Hence the current global energy crisis demands greater attention to new initiatives on alternative energy sources that are renewable, economically feasible and sustainable. The agriculture-dependent developing countries in Africa can mitigate the

Exploratory study of a crisis commander’s perspectives on the role and value of public relations in crisis management

OpenAIRE

Mat Tazin Saidathul Nizah; Kaur Kiranjit

2017-01-01

This is an exploratory study into understanding the dominant coalition perspectives on role and values of public relations in crisis management in an energy company in Malaysia. In this study, the senior public relations of the energy company reports directly to the crisis commander (CC) in times of crisis thus, the CC was chosen as a sample where an in-depth interview was conducted. Notably, the CC perceptions represents the dominant coalition with the power to shape organisation policies an...

Targeting Sentinel Proteins and Extrasynaptic Glutamate Receptors: a Therapeutic Strategy for Preventing the Effects Elicited by Perinatal Asphyxia?

Science.gov (United States)

Herrera-Marschitz, Mario; Perez-Lobos, Ronald; Lespay-Rebolledo, Carolyne; Tapia-Bustos, Andrea; Casanova-Ortiz, Emmanuel; Morales, Paola; Valdes, Jose-Luis; Bustamante, Diego; Cassels, Bruce K

2018-02-01

Perinatal asphyxia (PA) is a relevant cause of death at the time of labour, and when survival is stabilised, associated with short- and long-term developmental disabilities, requiring inordinate care by health systems and families. Its prevalence is high (1 to 10/1000 live births) worldwide. At present, there are few therapeutic options, apart from hypothermia, that regrettably provides only limited protection if applied shortly after the insult.PA implies a primary and a secondary insult. The primary insult relates to the lack of oxygen, and the secondary one to the oxidative stress triggered by re-oxygenation, formation of reactive oxygen (ROS) and reactive nitrogen (RNS) species, and overactivation of glutamate receptors and mitochondrial deficiencies. PA induces overactivation of a number of sentinel proteins, including hypoxia-induced factor-1α (HIF-1α) and the genome-protecting poly(ADP-ribose) polymerase-1 (PARP-1). Upon activation, PARP-1 consumes high amounts of ATP at a time when this metabolite is scarce, worsening in turn the energy crisis elicited by asphyxia. The energy crisis also impairs ATP-dependent transport, including glutamate re-uptake by astroglia. Nicotinamide, a PARP-1 inhibitor, protects against the metabolic cascade elicited by the primary stage, avoiding NAD + exhaustion and the energetic crisis. Upon re-oxygenation, however, oxidative stress leads to nuclear translocation of the NF-κB subunit p65, overexpression of the pro-inflammatory cytokines IL-1β and TNF-α, and glutamate-excitotoxicity, due to impairment of glial-glutamate transport, extracellular glutamate overflow, and overactivation of NMDA receptors, mainly of the extrasynaptic type. This leads to calcium influx, mitochondrial impairment, and inactivation of antioxidant enzymes, increasing further the activity of pro-oxidant enzymes, thereby making the surviving neonate vulnerable to recurrent metabolic insults whenever oxidative stress is involved. Here, we discuss

Chaos in power: Pakistan's electricity crisis

International Nuclear Information System (INIS)

Kessides, Ioannis N.

2013-01-01

Pakistan is facing a severe electricity crisis due to a persistent and widening gap between demand and available system generating capacity. The worsening of power shortages has become a major political issue, reflecting the hardships for individuals and businesses. It threatens to undermine the credibility and legitimacy of government and to further stress the social fabric of the country. The power crisis did not emerge suddenly. It is the direct result of imprudent and reckless energy policies over the last three decades. These policies have impeded the development of cheap and abundant domestic energy sources. They have also resulted in very inefficient fuel-mix choices, compromising energy and economic security. Pakistan's energy bankruptcy is ultimately due to massive institutional and governance failure. This paper analyzes the problems confronting Pakistan's electricity sector and identifies the key elements of a potential policy response to address the country's severe power crisis. - Highlights: ► We analyze the structure, conduct, and performance of Pakistan's electricity sector. ► The causes and economic impacts of Pakistan's electricity shortages are analyzed. ► We identify the potential policy response to the power crisis

Uncertainties and risks in transitions to sustainable energy, and the part 'trust' might play in managing them: a comparison with the current pension crisis

International Nuclear Information System (INIS)

Bellaby, Paul

2010-01-01

Transition to a sustainable energy future carries uncertainties for all stakeholders, including those who research it. History does not repeat itself in detail, yet comparison with analogous processes already completed or in train could give shape to how we project the future. The author focuses not on the technical change required, but rather on the institutional and cultural changes that would be necessary to generate the political will and the consumer demand that would drive technical change and its widespread adoption. He examines a current crisis for most developed countries-that of old age pension provision, which - though lacking a link with new technology - might have similar social dynamics to an impending crisis in energy. In the analysis of the pensions crisis, the focus is upon both how risk has been encountered and also the part played by trust/mistrust in engendering and prospectively resolving crisis: between citizens and state, between regulator and providers and between consumers and providers. Analogies are drawn from in a similar way for the impending energy crisis. A refrain throughout is the dialectic between 'market' and 'plan'. It is concluded that both the actual and the impending crisis have to be reviewed in a context of relations between states as well as relations within them.

A small-world methodology of analysis of interchange energy-networks: The European behaviour in the economical crisis

International Nuclear Information System (INIS)

Dassisti, M.; Carnimeo, L.

2013-01-01

European energy policy pursues the objective of a sustainable, competitive and reliable supply of energy. In 2007, the European Commission adopted a proper energy policy for Europe supported by several documents and included an action plan to meet the major energy challenges Europe has to face. A farsighted diversified yearly mix of energies was suggested to countries, aiming at increasing security of supply and efficiency, but a wide and systemic view of energy interchanges between states was missing. In this paper, a Small-World methodology of analysis of Interchange Energy-Networks (IENs) is presented, with the aim of providing a useful tool for planning sustainable energy policies. A proof case is presented to validate the methodology by considering the European IEN behaviour in the period of economical crisis. This network is approached as a Small World Net from a modelling point of view, by supposing that connections between States are characterised by a probability value depending on economic/political relations between countries. - Highlights: • Different view of the imports and exports of electric energy flows between European for potential use in ruling exchanges. • Panel data from 1996 to 2010 as part of a network of exchanges was considered from Eurostat official database. • The European import/export energy flows modelled as a network with Small World phenomena, interpreting the evolution over the years. • Interesting systemic tool for ruling and governing energy flows between countries

Nicotinamide Inhibits Ethanol-Induced Caspase-3 and PARP-1 Over-activation and Subsequent Neurodegeneration in the Developing Mouse Cerebellum.

Science.gov (United States)

Ieraci, Alessandro; Herrera, Daniel G

2018-06-01

Fetal alcohol spectrum disorder (FASD) is the principal preventable cause of mental retardation in the western countries resulting from alcohol exposure during pregnancy. Ethanol-induced massive neuronal cell death occurs mainly in immature neurons during the brain growth spurt period. The cerebellum is one of the brain areas that are most sensitive to ethanol neurotoxicity. Currently, there is no effective treatment that targets the causes of these disorders and efficient treatments to counteract or reverse FASD are desirable. In this study, we investigated the effects of nicotinamide on ethanol-induced neuronal cell death in the developing cerebellum. Subcutaneous administration of ethanol in postnatal 4-day-old mice induced an over-activation of caspase-3 and PARP-1 followed by a massive neurodegeneration in the developing cerebellum. Interestingly, treatment with nicotinamide, immediately or 2 h after ethanol exposure, diminished caspase-3 and PARP-1 over-activation and reduced ethanol-induced neurodegeneration. Conversely, treatment with 3-aminobenzadine, a specific PARP-1 inhibitor, was able to completely block PARP-1 activation, but not caspase-3 activation or ethanol-induced neurodegeneration in the developing cerebellum. Our results showed that nicotinamide reduces ethanol-induced neuronal cell death and inhibits both caspase-3 and PARP-1 alcohol-induced activation in the developing cerebellum, suggesting that nicotinamide might be a promising and safe neuroprotective agent for treating FASD and other neurodegenerative disorders in the developing brain that shares similar cell death pathways.

Medium Btu gas from coal: a possible solution to the U. S. energy crisis

Energy Technology Data Exchange (ETDEWEB)

Taffe, P

1978-03-03

The future of coal gasification in the US, and in particular the potential of the Winkler process, are discussed. The economics and the efficiency of the Winkler process are considered. It is believed that medium Btu gas from coal is a better solution to the US energy crisis than is SNG made from coal.

Regulation of HFE expression by poly(ADP-ribose) polymerase-1 (PARP1) through an inverted repeat DNA sequence in the distal promoter.

Science.gov (United States)

Pelham, Christopher; Jimenez, Tamara; Rodova, Marianna; Rudolph, Angela; Chipps, Elizabeth; Islam, M Rafiq

2013-12-01

Hereditary hemochromatosis (HH) is a common autosomal recessive disorder of iron overload among Caucasians of northern European descent. Over 85% of all cases with HH are due to mutations in the hemochromatosis protein (HFE) involved in iron metabolism. Although the importance in iron homeostasis is well recognized, the mechanism of sensing and regulating iron absorption by HFE, especially in the absence of iron response element in its gene, is not fully understood. In this report, we have identified an inverted repeat sequence (ATGGTcttACCTA) within 1700bp (-1675/+35) of the HFE promoter capable to form cruciform structure that binds PARP1 and strongly represses HFE promoter. Knockdown of PARP1 increases HFE mRNA and protein. Similarly, hemin or FeCl3 treatments resulted in increase in HFE expression by reducing nuclear PARP1 pool via its apoptosis induced cleavage, leading to upregulation of the iron regulatory hormone hepcidin mRNA. Thus, PARP1 binding to the inverted repeat sequence on the HFE promoter may serve as a novel iron sensing mechanism as increased iron level can trigger PARP1 cleavage and relief of HFE transcriptional repression. © 2013.

Ensuring green growth in a time of economic crisis: the role of energy technology

Energy Technology Data Exchange (ETDEWEB)

NONE

2009-07-01

Despite the severity of the current financial and economic crisis, it cannot be allowed to distract us from addressing critical and strategic climate change and energy challenges. The energy sector produces 60% of global greenhouse gas emissions and so it must also be a key part of any strategy to reduce them. This paper describes the most promising low-carbon technologies, their current status and the policy framework that will be necessary to achieve their widespread deployment. It also highlights what immediate steps can be taken as part of a Clean Energy New Deal. 4 figs., 2 tabs., 1 app.

Exploratory study of a crisis commander’s perspectives on the role and value of public relations in crisis management

Directory of Open Access Journals (Sweden)

Mat Tazin Saidathul Nizah

2017-01-01

Full Text Available This is an exploratory study into understanding the dominant coalition perspectives on role and values of public relations in crisis management in an energy company in Malaysia. In this study, the senior public relations of the energy company reports directly to the crisis commander (CC in times of crisis thus, the CC was chosen as a sample where an in-depth interview was conducted. Notably, the CC perceptions represents the dominant coalition with the power to shape organisation policies and provide directions to public relations practice in managing media and communication in crisis management. Theory of excellence within the outlook of public relations empowerment was examined. The findings of this study have significantly confirmed that the patterns of the CC perceptions on role and values of public relations in crisis management are similar to other dominant coalition literature across the globe. This phenomenon needs changes to drive public relations to strive harder to be a problem solver and a strategic thinker in crisis management. This study is a significant attempt to understand the perception of the dominant coalition on public relations in crisis management and can be replicated in other sectors in Malaysia.

Substantiation of Strategic Problem Concept in Anti-Crisis Management

OpenAIRE

Inna Irtyshcheva; Svitlana Minakova

2014-01-01

The article is devoted to the definition of the essence, objectives and characteristics of strategic crisis management. The interrelation of rank anti-crisis strategy in the hierarchy of the company strategies, depending on the identity of the company local, systemic or strategic crisis is analysed. The anti-crisis strategies are defined on the grounds of common characteristics. The types of tactics in crisis management are defined.

The role of crisis in family crisis intervention: do crisis experience and crisis change matter?

NARCIS (Netherlands)

Al, C.M.W.; Stams, G.J.J.M.; van der Laan, P.H.; Asscher, J.J.

2011-01-01

Evaluation studies of crisis intervention have focused on prevention of out-of-home placement of children or family functioning, but largely neglected the aspect of crisis. The present study examined crisis in 183 families receiving Family Crisis Intervention (FCI), addressing crisis characteristics

Linear Energy Transfer-Dependent Change in Rice Gene Expression Profile after Heavy-Ion Beam Irradiation.

Science.gov (United States)

Ishii, Kotaro; Kazama, Yusuke; Morita, Ryouhei; Hirano, Tomonari; Ikeda, Tokihiro; Usuda, Sachiko; Hayashi, Yoriko; Ohbu, Sumie; Motoyama, Ritsuko; Nagamura, Yoshiaki; Abe, Tomoko

2016-01-01

A heavy-ion beam has been recognized as an effective mutagen for plant breeding and applied to the many kinds of crops including rice. In contrast with X-ray or γ-ray, the heavy-ion beam is characterized by a high linear energy transfer (LET). LET is an important factor affecting several aspects of the irradiation effect, e.g. cell survival and mutation frequency, making the heavy-ion beam an effective mutagen. To study the mechanisms behind LET-dependent effects, expression profiling was performed after heavy-ion beam irradiation of imbibed rice seeds. Array-based experiments at three time points (0.5, 1, 2 h after the irradiation) revealed that the number of up- or down-regulated genes was highest 2 h after irradiation. Array-based experiments with four different LETs at 2 h after irradiation identified LET-independent regulated genes that were up/down-regulated regardless of the value of LET; LET-dependent regulated genes, whose expression level increased with the rise of LET value, were also identified. Gene ontology (GO) analysis of LET-independent up-regulated genes showed that some GO terms were commonly enriched, both 2 hours and 3 weeks after irradiation. GO terms enriched in LET-dependent regulated genes implied that some factor regulates genes that have kinase activity or DNA-binding activity in cooperation with the ATM gene. Of the LET-dependent up-regulated genes, OsPARP3 and OsPCNA were identified, which are involved in DNA repair pathways. This indicates that the Ku-independent alternative non-homologous end-joining pathway may contribute to repairing complex DNA legions induced by high-LET irradiation. These findings may clarify various LET-dependent responses in rice.

The Energy Crisis

Science.gov (United States)

Hoefflinger, Bernd

Chip-based electronics in 2010 consumed about 10% of the world's total electric power of ˜2 TW. We have seen throughout the book that all segments, processing, memory and communication, are expected to increase their performance or bandwidth by three orders of magnitude in the decade until 2020. If this progress would be realized, the world semiconductor revenue could grow by 50-100%, and the ICT industry by 43-66% in this decade (Fig. 6.1). Progress sustained at these levels certainly depends on investments and qualified manpower, but energy has become another roadblock almost overnight. In this chapter, we touch upon the life-cycle energy of chips by assessing the energy of Si wafer manufacturing, needed to bring the chips to life, and the power efficiencies in their respective operations. An outstanding segment of power-hungry chip operations is that of operating data centers, often called server farms. Their total operating power was ˜36 GW in 2010, and we look at their evolution under the prospect of a 1,000× growth in performance by 2020. One feasible scenario is that we succeed in improving the power efficiency of Processing 1,000×, Memory 1,000×, Communication 100×, within a decade. In this case, the total required power for the world's data centers would still increase 4× to 144 GW by 2020, equivalent to 40% of the total electrical power available in all of Europe. The power prospects for mobile/wireless as well as long-line cable/radio/satellite are equally serious. Any progression by less than the factors listed above will lead to economic growth smaller than the projections given above. This demands clearly that sustainable nanoelectronics must be minimum-energy (femtojoule) electronics.

Exactly solvable energy-dependent potentials

International Nuclear Information System (INIS)

Garcia-Martinez, J.; Garcia-Ravelo, J.; Pena, J.J.; Schulze-Halberg, A.

2009-01-01

We introduce a method for constructing exactly-solvable Schroedinger equations with energy-dependent potentials. Our method is based on converting a general linear differential equation of second order into a Schroedinger equation with energy-dependent potential. Particular examples presented here include harmonic oscillator, Coulomb and Morse potentials with various types of energy dependence.

Neer Award 2016: reduced muscle degeneration and decreased fatty infiltration after rotator cuff tear in a poly(ADP-ribose) polymerase 1 (PARP-1) knock-out mouse model.

Science.gov (United States)

Kuenzler, Michael B; Nuss, Katja; Karol, Agnieszka; Schär, Michael O; Hottiger, Michael; Raniga, Sumit; Kenkel, David; von Rechenberg, Brigitte; Zumstein, Matthias A

2017-05-01

Disturbed muscular architecture, atrophy, and fatty infiltration remain irreversible in chronic rotator cuff tears even after repair. Poly (adenosine 5'-diphosphate-ribose) polymerase 1 (PARP-1) is a key regulator of inflammation, apoptosis, muscle atrophy, muscle regeneration, and adipocyte development. We hypothesized that the absence of PARP-1 would lead to a reduction in damage to the muscle subsequent to combined tenotomy and neurectomy in a PARP-1 knockout (KO) mouse model. PARP-1 KO and wild-type C57BL/6 (WT group) mice were analyzed at 1, 6, and 12 weeks (total n = 84). In all mice, the supraspinatus and infraspinatus muscles of the left shoulder were detached and denervated. Macroscopic analysis, magnetic resonance imaging, gene expression analysis, immunohistochemistry, and histology were used to assess the differences in PARP-1 KO and WT mice. The muscles in the PARP-1 KO group had significantly less retraction, atrophy, and fatty infiltration after 12 weeks than in the WT group. Gene expression of inflammatory, apoptotic, adipogenic, and muscular atrophy genes was significantly decreased in PARP-1 KO mice in the first 6 weeks. Absence of PARP-1 leads to a reduction in muscular architectural damage, early inflammation, apoptosis, atrophy, and fatty infiltration after combined tenotomy and neurectomy of the rotator cuff muscle. Although the macroscopic reaction to injury is similar in the first 6 weeks, the ability of the muscles to regenerate was much greater in the PARP-1 KO group, leading to a near-normalization of the muscle after 12 weeks. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Civil–military cooperation in crisis management in Africa

DEFF Research Database (Denmark)

Olsen, Gorm Rye

2011-01-01

Cooperation between civilian and military actors has become a catchphrase in international crisis management and development policy in the 21st century. This paper examines the crisis management policies adopted in Africa by the United States and the European Union (EU), respectively....... It is hypothesised that both actors’ crisis management policies are likely to be path dependent, despite recent significant changes in policy preferences. It is shown that the priority combining civilian and military resources in American crisis management is only implemented to a limited degree. It is consistent...... with the persistent predominance of the Pentagon and of the military instruments in US Africa policy. It illustrates the conspicuous institutional path dependency of US Africa policy, which by some is described as ‘militarised’. The EU has been able to apply both civilian and military instruments in crisis management...

Anti-Crisis Solutions for Regional Energy Sector

Directory of Open Access Journals (Sweden)

Leonid Davidovich Gitelman

2015-09-01

Full Text Available The paper considers anti-crisis solutions for the electricity sector that fall into the category of strategic ones. Their primary purpose is to ensure the flexibility and adaptability of the system and prevent emergencies in the future. The authors explain the need for a holistic approach to taking anti-crisis decisions in power engineering and propose ways to improve the economic mechanism of cost reduction based upon international practice and placed in the Russian context. The benefits of demand-side management in ensuring the reliability of power supplies amid crisis are shown. The paper looks at various implementation modalities for demandside management programmes and explores development prospects for distributed generation in Russia and stand-alone power supply options for manufacturing companies. Factors are assessed that affect the cost effectiveness of going off the grid. A general scheme of cost management aimed at reaching the strategic goals of the regional electricity sector is presented. The authors reveal possible applications and advantages of using predictive analytics for effective cost management. Ways of improving asset management are considered as well as the possibility of their employment in the Russian context. The key barriers to their implementations and ways of overcoming them are identified

Energy 2010: behind the effects of the crisis, the new world map is taking shape

International Nuclear Information System (INIS)

Martin-Amouroux, J.M.

2010-01-01

We now know the worldwide energy balance for 2009. For the first time in a quarter of a century, primary consumption fell (1.1 %) under the effect of a contraction of all the big sources of primary energy, except coal. The effects of the economic crisis were o course involved, but behind them, the changes are more of a long term nature. The movement of the centre of gravity for energy has been, since 2000, coming from the acceleration of the importance of Asia, and from the one of coal, its fuel of choice. (author)

PARP-1 Variant Rs1136410 Confers Protection against Coronary Artery Disease in a Chinese Han Population: A Two-Stage Case-Control Study Involving 5643 Subjects

Directory of Open Access Journals (Sweden)

Xue-bin Wang

2017-11-01

Full Text Available Inhibition of poly(ADP-ribose polymerase (PARP may protect against coronary artery disease (CAD in animal models, and rs1136410, a non-synonymous single nucleotide polymorphism (SNP in PARP-1, has a potential impact on PARP activities in vitro. This two-stage case-control study, involving 2803 CAD patients and 2840 controls, aimed to investigate the associations of PARP-1 rs1136410 with CAD development, lipid levels, PARP activities, 8-hydroxy-2′-dexyguanosine (8-OHdG, and interleukin (IL-6 levels in a Chinese Han population. Assuming a recessive model, the variant genotype GG of SNP rs1136410 showed a significantly inverse association with CAD risk (adjusted odds ratio (OR = 0.73, P < 0.001, left main coronary artery (LMCA lesions (P = 0.003, vessel scores (P = 0.003, and modified Gensini scores (P < 0.001. There were significant correlations of SNP rs1136410 with higher levels of total cholesterol (TC and lower levels of high-density lipoprotein cholesterol (HDL-c. In gene-environment interaction analyses, participants with the variant genotype GG, but without smoking habit, type 2 diabetes mellitus, and hyperlipidemia, conferred an 84% (P < 0.001 decreased risk of CAD. The genotype-phenotype correlation analyses further supported the functional roles of SNP rs1136410 in decreasing PARP activities and 8-OHdG levels. Taken together, our data suggest that SNP rs1136410 may confer protection against CAD through modulation of PARP activities and gene-environment interactions in a Chinese Han population.

The change from fossil fuel dependence to sustainable energy sources in Nigeria

International Nuclear Information System (INIS)

Chukwu, C.; Ajedegba, J.

2006-01-01

Nigeria faces a serious energy crisis due to declining electricity generation from domestic power plants. Although the country is highly dependent on fossil fuel resources, Nigeria has a range of unexploited biomass and hydro power resources, as well as extensive solar energy potential. This paper presented a current energy balance of Nigeria and examined ways of reaching an environmentally sustainable energy balance through the use of a mix of renewable resources. Supply and consumption details of domestic, industrial and transportation sectors as well as electricity production statistics were presented. Total hydropower potential based on the country's river system was estimated to be 10,000 MW. It was estimated that Nigeria has an average of 1.804 x 10 15 of incident solar energy annually, which is 27 times the nation's total conventional energy resources in energy units. It was noted that Nigeria also possesses a significant amount of biomass resources from several large forests that may be used to supply domestic cooking and heating needs as well as for ethanol production. It was noted that wind energy may not be a viable alternative for large scale electricity production in Nigeria. Recommendations to promote the use of renewable resources in the national energy mix included encouraging the decentralization of energy supplies; discouraging the use of wood as fuel; promoting efficient methods in the use of biomass energy resources; private sector participation; and global partnerships. 15 refs., 7 tabs

Energy crisis

International Nuclear Information System (INIS)

1977-01-01

From energy policy to the problem of public acceptance of nuclear power, problems like energy supply, energy strategies, the race of industrial countries for the short energy reserves, the West German energy demand until the year 2.000, energy conservation, and the controversy over increased use of nuclear energy are reviewed. (GL) [de

Research on crisis communication of nuclear and radiation safety

International Nuclear Information System (INIS)

Cao Yali; Zhang Ying

2013-01-01

Insufficient public cognition of nuclear and radiation safety and absence of effective method to handle crisis lead to common crisis events of nuclear and radiation safety, which brings about unfavorable impact on the sound development of nuclear energy exploring and application of nuclear technology. This paper, based on crisis communication theory, analyzed the effect of current situation on nuclear and radiation safety crisis, discussed how to handle crisis, and tried to explore the effective strategies for nuclear and radiation safety crisis handling. (authors)

The Nature of Crisis in Enterprise Activities

Directory of Open Access Journals (Sweden)

Kozachenko Ganna V.

2017-09-01

Full Text Available It is shown that the concept of enterprise anti-crisis management and its components should be based on the nature of crisis in enterprise activities, the idea of which is the fundamental basis of enterprise anti-crisis management and determines its object, subject, tasks, main guidelines and vectors. Examples of defining the concept “crisis in enterprise activities”, which testify to the lack of unity of views on its content, are given. There revealed the attributive nature of crisis in enterprise activities, according to which a crisis, being an attribute of the system “enterprise”, begins intensifying under the influence of driving forces and individual factors, which is identified by presence of disruptions in the performance by the enterprise of its functions. There substantiated the expediency of singling out manifestations of crisis in enterprise activities (crisis phenomena, crisis situation and crisis state depending on the level of disruptions in the performance by the enterprise of its functions, which is of great importance for determining the tasks of enterprise anti-crisis management. The crisis cycle in enterprise activities in any of its manifestations is analysed, features of the cycle are considered.

Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients

Directory of Open Access Journals (Sweden)

See-Hyoung Park

2015-08-01

Full Text Available BACKGROUND: Poly(ADP-ribose polymerase 1 (PARP1, γH2AX, BRCA1, and BRCA2 are conventional molecular indicators of DNA damage in cells and are often overexpressed in various cancers. In this study, we aimed, using immunohistochemical detection, whether the co-expression of PARP1, γH2AX, BRCA1, and BRCA2 in breast carcinoma (BCA tissue can provide more reliable prediction of survival of BCA patients. MATERIALS AND METHODS: We investigated immunohistochemical expression and prognostic significance of the expression of PARP1, γH2AX, BRCA1, and BRCA2 in 192 cases of BCAs. RESULTS: The expression of these four molecules predicted earlier distant metastatic relapse, shorter overall survival (OS, and relapse-free survival (RFS by univariate analysis. Multivariate analysis revealed the expression of PARP1, γH2AX, and BRCA2 as independent poor prognostic indicators of OS and RFS. In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph was an additional independent prognostic predictor for OS (P < .001 and RFS (P < .001. The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1 subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4 subgroup. CONCLUSION: This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents.

REV7 counteracts DNA double-strand break resection and affects PARP inhibition

NARCIS (Netherlands)

Xu, Guotai; Chapman, J. Ross; Brandsma, Inger; Yuan, Jingsong; Mistrik, Martin; Bouwman, Peter; Bartkova, Jirina; Gogola, Ewa; Warmerdam, Daniël; Barazas, Marco; Jaspers, Janneke E.; Watanabe, Kenji; Pieterse, Mark; Kersbergen, Ariena; Sol, Wendy; Celie, Patrick H. N.; Schouten, Philip C.; van den Broek, Bram; Salman, Ahmed; Nieuwland, Marja; de Rink, Iris; de Ronde, Jorma; Jalink, Kees; Boulton, Simon J.; Chen, Junjie; van Gent, Dik C.; Bartek, Jiri; Jonkers, Jos; Borst, Piet; Rottenberg, Sven

2015-01-01

Error-free repair of DNA double-strand breaks (DSBs) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway(1). In the absence of BRCA1-mediated HR, the administration of PARP inhibitors induces synthetic lethality of tumour cells of patients with

Uncertainties and risks in transitions to sustainable energy, and the part 'trust' might play in managing them. A comparison with the current pension crisis

Energy Technology Data Exchange (ETDEWEB)

Bellaby, Paul [Institute for Social, Cultural and Policy Research, University of Salford, Salford, Greater Manchester M5 4WT (United Kingdom)

2010-06-15

Transition to a sustainable energy future carries uncertainties for all stakeholders, including those who research it. History does not repeat itself in detail, yet comparison with analogous processes already completed or in train could give shape to how we project the future. The author focuses not on the technical change required, but rather on the institutional and cultural changes that would be necessary to generate the political will and the consumer demand that would drive technical change and its widespread adoption. He examines a current crisis for most developed countries - that of old age pension provision, which - though lacking a link with new technology - might have similar social dynamics to an impending crisis in energy. In the analysis of the pensions crisis, the focus is upon both how risk has been encountered and also the part played by trust/mistrust in engendering and prospectively resolving crisis: between citizens and state, between regulator and providers and between consumers and providers. Analogies are drawn from in a similar way for the impending energy crisis. A refrain throughout is the dialectic between 'market' and 'plan'. It is concluded that both the actual and the impending crisis have to be reviewed in a context of relations between states as well as relations within them. (author)

Uncertainties and risks in transitions to sustainable energy, and the part 'trust' might play in managing them: a comparison with the current pension crisis

Energy Technology Data Exchange (ETDEWEB)

Bellaby, Paul, E-mail: p.bellaby@salford.ac.u [Institute for Social, Cultural and Policy Research, University of Salford, Salford, Greater Manchester M5 4WT (United Kingdom)

2010-06-15

Transition to a sustainable energy future carries uncertainties for all stakeholders, including those who research it. History does not repeat itself in detail, yet comparison with analogous processes already completed or in train could give shape to how we project the future. The author focuses not on the technical change required, but rather on the institutional and cultural changes that would be necessary to generate the political will and the consumer demand that would drive technical change and its widespread adoption. He examines a current crisis for most developed countries-that of old age pension provision, which - though lacking a link with new technology - might have similar social dynamics to an impending crisis in energy. In the analysis of the pensions crisis, the focus is upon both how risk has been encountered and also the part played by trust/mistrust in engendering and prospectively resolving crisis: between citizens and state, between regulator and providers and between consumers and providers. Analogies are drawn from in a similar way for the impending energy crisis. A refrain throughout is the dialectic between 'market' and 'plan'. It is concluded that both the actual and the impending crisis have to be reviewed in a context of relations between states as well as relations within them.

IDH1/2 Mutations Sensitize Acute Myeloid Leukemia to PARP Inhibition and This Is Reversed by IDH1/2-Mutant Inhibitors.

Science.gov (United States)

Molenaar, Remco J; Radivoyevitch, Tomas; Nagata, Yasunobu; Khurshed, Mohammed; Przychodzen, Bartolomiej; Makishima, Hideki; Xu, Mingjiang; Bleeker, Fonnet E; Wilmink, Johanna W; Carraway, Hetty E; Mukherjee, Sudipto; Sekeres, Mikkael A; van Noorden, Cornelis J F; Maciejewski, Jaroslaw P

2018-04-01

Purpose: Somatic mutations in IDH1/2 occur in approximately 20% of patients with myeloid neoplasms, including acute myeloid leukemia (AML). IDH1/2 MUT enzymes produce D -2-hydroxyglutarate ( D 2HG), which associates with increased DNA damage and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor cells. Whether this also holds true for IDH1/2 MUT AML is not known. Experimental Design: Well-characterized primary IDH1 MUT , IDH2 MUT , and IDH1/2 WT AML cells were analyzed for DNA damage and responses to daunorubicin, ionizing radiation, and PARP inhibitors. Results: IDH1/2 MUT caused increased DNA damage and sensitization to daunorubicin, irradiation, and the PARP inhibitors olaparib and talazoparib in AML cells. IDH1/2 MUT inhibitors protected against these treatments. Combined treatment with a PARP inhibitor and daunorubicin had an additive effect on the killing of IDH1/2 MUT AML cells. We provide evidence that the therapy sensitivity of IDH1/2 MUT cells was caused by D 2HG-mediated downregulation of expression of the DNA damage response gene ATM and not by altered redox responses due to metabolic alterations in IDH1/2 MUT cells. Conclusions: IDH1/2 MUT AML cells are sensitive to PARP inhibitors as monotherapy but especially when combined with a DNA-damaging agent, such as daunorubicin, whereas concomitant administration of IDH1/2 MUT inhibitors during cytotoxic therapy decrease the efficacy of both agents in IDH1/2 MUT AML. These results advocate in favor of clinical trials of PARP inhibitors either or not in combination with daunorubicin in IDH1/2 MUT AML. Clin Cancer Res; 24(7); 1705-15. ©2018 AACR . ©2018 American Association for Cancer Research.

Suppression of Homologous Recombination by insulin-like growth factor-1 inhibition sensitizes cancer cells to PARP inhibitors

International Nuclear Information System (INIS)

Amin, Oreekha; Beauchamp, Marie-Claude; Nader, Paul Abou; Laskov, Ido; Iqbal, Sanaa; Philip, Charles-André; Yasmeen, Amber; Gotlieb, Walter H.

2015-01-01

Impairment of homologous recombination (HR) is found in close to 50 % of ovarian and breast cancer. Tumors with BRCA1 mutations show increased expression of the Insulin-like growth factor type 1 receptor (IGF-1R). We previously have shown that inhibition of IGF-1R results in growth inhibition and apoptosis of ovarian tumor cells. In the current study, we aimed to investigate the correlation between HR and sensitivity to IGF-1R inhibition. Further, we hypothesized that IGF-1R inhibition might sensitize HR proficient cancers to Poly ADP ribose polymerase (PARP) inhibitors. Using ovarian and breast cancer cellular models with known BRCA1 status, we evaluated their HR functionality by RAD51 foci formation assay. The 50 % lethal concentration (LC50) of Insulin-like growth factor type 1 receptor kinase inhibitor (IGF-1Rki) in these cells was assessed, and western immunoblotting was performed to determine the expression of proteins involved in the IGF-1R pathway. Moreover, IGF-1R inhibitors were added on HR proficient cell lines to assess mRNA and protein expression of RAD51 by qPCR and western blot. Also, we explored the interaction between RAD51 and Insulin receptor substance 1 (IRS-1) by immunoprecipitation. Next, combination effect of IGF-1R and PARP inhibitors was evaluated by clonogenic assay. Cells with mutated/methylated BRCA1 showed an impaired HR function, and had an overactivation of the IGF-1R pathway. These cells were more sensitive to IGF-1R inhibition compared to HR proficient cells. In addition, the IGF-IR inhibitor reduced RAD51 expression at mRNA and protein levels in HR proficient cells, and sensitized these cells to PARP inhibitor. Targeting IGF-1R might lead to improved personalized therapeutic approaches in cancer patients with HR deficiency. Targeting both PARP and IGF-1R might increase the clinical efficacy in HR deficient patients and increase the population of patients who may benefit from PARP inhibitors

On the energy crisis in noncommutative CP(1) model

International Nuclear Information System (INIS)

Sourrouille, Lucas

2010-01-01

We study the CP(1) system in (2+1)-dimensional noncommutative space with and without Chern-Simons term. Using the Seiberg-Witten map we convert the noncommutative CP(1) system to an action written in terms of the commutative fields. We find that this system presents the same infinite size instanton solution as the commutative Chern-Simons-CP(1) model without a potential term. Based on this result we argue that the BPS equations are compatible with the full variational equations of motion, rejecting the hypothesis of an 'energy crisis'. In addition we examine the noncommutative CP(1) system with a Chern-Simons interaction. In this case we find that when the theory is transformed by the Seiberg-Witten map it also presents the same instanton solution as the commutative Chern-Simons-CP(1) model.

Economic crisis and oil market balances

International Nuclear Information System (INIS)

Duquesnoy, S.; Rozenberg, J.; Hourcade, J.Ch.

2011-01-01

One might intuitively think that an economic crisis would at least relieve the pressure on oil supply since it slows energy demand. From the model of the oil market DYSMO, we show that an economic crisis may on the contrary increase tension, as it postpones investment in oil supply. (authors)

Linear Energy Transfer-Dependent Change in Rice Gene Expression Profile after Heavy-Ion Beam Irradiation.

Directory of Open Access Journals (Sweden)

Kotaro Ishii

Full Text Available A heavy-ion beam has been recognized as an effective mutagen for plant breeding and applied to the many kinds of crops including rice. In contrast with X-ray or γ-ray, the heavy-ion beam is characterized by a high linear energy transfer (LET. LET is an important factor affecting several aspects of the irradiation effect, e.g. cell survival and mutation frequency, making the heavy-ion beam an effective mutagen. To study the mechanisms behind LET-dependent effects, expression profiling was performed after heavy-ion beam irradiation of imbibed rice seeds. Array-based experiments at three time points (0.5, 1, 2 h after the irradiation revealed that the number of up- or down-regulated genes was highest 2 h after irradiation. Array-based experiments with four different LETs at 2 h after irradiation identified LET-independent regulated genes that were up/down-regulated regardless of the value of LET; LET-dependent regulated genes, whose expression level increased with the rise of LET value, were also identified. Gene ontology (GO analysis of LET-independent up-regulated genes showed that some GO terms were commonly enriched, both 2 hours and 3 weeks after irradiation. GO terms enriched in LET-dependent regulated genes implied that some factor regulates genes that have kinase activity or DNA-binding activity in cooperation with the ATM gene. Of the LET-dependent up-regulated genes, OsPARP3 and OsPCNA were identified, which are involved in DNA repair pathways. This indicates that the Ku-independent alternative non-homologous end-joining pathway may contribute to repairing complex DNA legions induced by high-LET irradiation. These findings may clarify various LET-dependent responses in rice.

Energy Crisis in Europe. Report of a researcher on his duty in Paris

Energy Technology Data Exchange (ETDEWEB)

NONE

1990-12-01

On December 6 and 7, 1990, at Brussels in Belgium, a conference was held on changes brought into Europe's energy environment by the Persian Gulf crisis and on the future prospects. The plenary session was attended by officials in charge of energy matters with the governments of the 12 EC (European Community) member countries and employees of electric power companies and gas suppliers of these countries. EC members' reports involved efforts to stabilize energy supply in the EC region, improvement on energy efficiency, promotion of energy conservation and alternative energy development, proposition for a comprehensive program SAVE (Specific Actions for Vigorous Energy Efficiency) for energy efficiency improvement, stable supply of energy, crude oil evaluation and consideration of taxation from the viewpoint of environmental protection, and suppression of energy consumption and planned consumption of stockpile (in coordination with International Energy Agency) in case of emergency, etc. Concerning the development of alternative energy and energy conservation technology, it was agreed that both long-term development efforts and accelerated development of environmentally-friendly technologies would be necessary in principle. Furthermore, discussion was made on supporting East Europe countries including Russia. (NEDO)

Energy Crisis in Europe. Report of a researcher on his duty in Paris

Energy Technology Data Exchange (ETDEWEB)

NONE

1990-12-01

On December 6 and 7, 1990, at Brussels in Belgium, a conference was held on changes brought into Europe's energy environment by the Persian Gulf crisis and on the future prospects. The plenary session was attended by officials in charge of energy matters with the governments of the 12 EC (European Community) member countries and employees of electric power companies and gas suppliers of these countries. EC members' reports involved efforts to stabilize energy supply in the EC region, improvement on energy efficiency, promotion of energy conservation and alternative energy development, proposition for a comprehensive program SAVE (Specific Actions for Vigorous Energy Efficiency) for energy efficiency improvement, stable supply of energy, crude oil evaluation and consideration of taxation from the viewpoint of environmental protection, and suppression of energy consumption and planned consumption of stockpile (in coordination with International Energy Agency) in case of emergency, etc. Concerning the development of alternative energy and energy conservation technology, it was agreed that both long-term development efforts and accelerated development of environmentally-friendly technologies would be necessary in principle. Furthermore, discussion was made on supporting East Europe countries including Russia. (NEDO)

Peeling the Energy Pickle: Expert Perceptions on Overcoming Nepal’s Electricity Crisis

DEFF Research Database (Denmark)

Sovacool, Benjamin; Dhakal, Saroj; Gippner, Olivia

2013-01-01

Underinvestment, low levels of electricity access, natural disasters, topography and hydrology make Nepal’s electricity crisis akin to ‘peeling a pickle’: difficult to pin down and hard to manage. Based primarily on the perceptions of a sample of experts, this article lays out a roadmap for how......; political instability resulting from the aftermath of the Maoist insurgency; poverty and corruption; lack of financing and investment; constrained technological and human resources; and, finally, aid dependency and political manoeuvring. We conclude by calling on Nepali policymakers to invest in distributed...

Protective Effects of Chlorella-Derived Peptide Against UVC-Induced Cytotoxicity through Inhibition of Caspase-3 Activity and Reduction of the Expression of Phosphorylated FADD and Cleaved PARP-1 in Skin Fibroblasts

Directory of Open Access Journals (Sweden)

Jong Yuh Cherng

2012-08-01

Full Text Available UVC irradiation induces oxidative stress and leads to cell death through an apoptotic pathway. This apoptosis is caused by activation of caspase-3 and formation of poly(ADP-ribose polymerase-1 (PARP-1. In this study, the underlying mechanisms of Chlorella derived peptide (CDP activity against UVC-induced cytotoxicity were investigated. Human skin fibroblasts were treated with CDP, vitamin C, or vitamin E after UVC irradiation for a total energy of 15 J/cm². After the UVC exposure, cell proliferation and caspase-3 activity were measured at 12, 24, 48, and 72 h later. Expression of phosphorylated FADD and cleaved PARP-1 were measured 16 h later. DNA damage (expressed as pyrimidine (6-4 pyrimidone photoproducts DNA concentration and fragmentation assay were performed 24 h after the UVC exposure. Results showed that UVC irradiation induced cytotoxicity in all groups except those treated with CDP. The caspase-3 activity in CDP-treated cells was inhibited from 12 h onward. Expression of phosphorylated FADD and cleaved PARP-1 were also reduced in CDP-treated cells. Moreover, UVC-induced DNA damage and fragmentation were also prevented by the CDP treatment. This study shows that treatment of CDP provides protective effects against UVC-induced cytotoxicity through the inhibition of caspase-3 activity and the reduction of phosphorylated FADD and cleaved PARP-1 expression.

Good to the last drop : the first petroleum crisis sent researchers on a trail in search of new energy solutions

International Nuclear Information System (INIS)

Nadeau, J.B.

2008-01-01

The energy crisis of the 1970s provided an incentive to look for alternative energy sources. At the time, the Organization of Petroleum Exporting Countries (OPEC) declared that the era of cheap oil was over. In addition to quadrupling oil prices, OPEC reduced production and placed total embargoes on some countries. With high oil demand and limited supply, lifestyles and habits that were founded on the oil market began to change. The energy crisis was also a catalyst to develop innovative conservation measures. Progressive trendsetters back in 1975 turned to solar and wind energy for their power needs. The author argued that had it not been for the energy crisis, developments such as the Athabasca oil sands, Hydro-Quebec's high-head electric power plants or nuclear power may never have occurred. This article then presented a brief history of the petroleum industry. Drilling technology in 1859 permitted drilling to a level of only 23 metres. In 1928 only 7 companies in the United States controlled the world oil market, notably, Exxon, Texaco, British Petroleum, Shell, Gulf, Standard Oil and Mobil Oil. OPEC was created in 1960, and by 1970 it controlled 40 per cent of the world oil market. According to the Association for the Study of Peak Oil, 1970 also marked the year when oil production began to decline. This article also summarized offshore operations in Atlantic Canada and the advent of enhanced recovery techniques, including the development of carbon sequestration. 6 figs

The Ukrainian energetic system under the light of the crisis: beyond gas transit, a governance challenge

International Nuclear Information System (INIS)

Boulanger, Quentin

2014-01-01

The objective of this report is to address and describe the problematic of the Ukrainian gas transit within a wider inner context and under the light of the current gas crisis. Beyond the European security of supply, maintaining the gas transit is a major domestic issue for Ukraine, from an economic as well as political point of view. This means that, in order to avoid a new gas crisis, Ukraine must significantly reform its energy sector in order to reduce its dependency and to re-balance its energy mix. In a first part, the author discusses gas price and transit network management as the main stakes of the gas crisis: recall of traditional dispute about gas between Russia and Ukraine, ageing and corruption as characteristics of a collapsing gas corridor, the Ukrainian law of September 2014 as a first step for a reform of energy governance. In a second part, the author discusses the future of the Ukrainian gas sector and the issue of stability of the national energy system. This should be based on short term options to strengthen the resilience of the gas sector in front of Russian supply disruption, a priority for a gas independence, and necessary review of the energy mix

Energy. The countdown

International Nuclear Information System (INIS)

Montbrial, T. de.

1979-01-01

The subject is treated under the following heads: the past -the politics of energy - the oil and nuclear power crisis (the great oil adventure; the oil crisis and international relations since October 1973; the nuclear energy crisis (why the opposition to nuclear energy, the proliferation of nuclear weapons); geopolitics and energy policy); the future - the energy crisis (the nature of the energy problem; global energy demand; toward an imbalanced oil market; natural gas, coal, nuclear and other energy sources; anticipating the second energy crisis to try to avoid it; future evolution of the price of energy; the economic effects of a massive increase in the price of oil. (UK)

Energy prices and the post oil/energy crisis Brazilian inflation: an input-output study

Energy Technology Data Exchange (ETDEWEB)

Lara-Resende, M.deM.

1982-01-01

This study is an attempt to understand the implications of the OPEC-induced severalfold increase in the international price of oil for average and sectoral domestic prices in Brazil, a large oil-importing open developing economy. Rather than using a Keynesian model (focusing on the universal characteristics of an economy), the study makes use of an open-price input-output model (capturing the structural characteristics of the Brazilian economy). The first three chapters, descriptive in nature, place in perspective the following three, which detail the model and the empirical results. The main conclusion is that, despite the significant increase observed in the post-crisis period, the relative percentage contribution of primary energy to wholesale inflation in Brazil is still relatively minor. A conservative estimate suggests that, in the years of substantial acceleration (1974 and 1979), approximately 15% of the wholesale inflation was due to energy (basically crude oil and oil derivatives). Though such low estimates are partly due to the limitations and assumptions underlying input-output analysis, it seems that the acceleration of inflation is related to more than cost increases originating in energy prices. It also seems to be related to agricultural and labor prices, as well as to the government's decision to abruptly and inopportunely raise several important product prices.

L’Italia: una crisi nella crisi.(Italy: A Crisis within the Crisis

Directory of Open Access Journals (Sweden)

Carlo D'ippoliti

2011-10-01

Full Text Available The article synthesises the large and extending literature on the financial and economic crisis from a Post-Keynesian point of view. The authors take on the position that the international and internal real imbalances are serious and worrying, but yet they are not the cause of the crisis or of its tremendous dimension. The flawed and insufficient regulation of finance is the prime cause of the crisis, as well as it is one of the main hindrances to expansionary macroeconomic policies that may less painfully drive developed countries out of the crisis. It then examines the most recent developments in the euro-area, claiming that we are not facing a sovereign debt crisis but rather a speculative attack on the euro. Finally, the article considers specifically the situation of Italy, currently at the hearth of such an attack, and suggests that the country was already facing critical developments before the 2007/2008 crisis. Thus, the policy measures so far suggested to exit the current stressful situation, in so far as they ignore this fact, seriously run the risk of proving insufficient or altogether noxious.JEL: B50; E12; G01  

Crisis, What Crisis? The Media: Business and Journalism in Times of Crisis

Directory of Open Access Journals (Sweden)

Rosario de Mateo

2010-08-01

Full Text Available The global financial and economic crisis is often used to justify a crisis of media and journalism: lower advertising, collapses in the share price, falls in consumption, more unemployment. But is this just a business crisis, or is it also a crisis in journalism and its role in democratic societies? In this case, is the journalism crisis attributable to the economic crisis or, rather, was it forged during the years of high profitability and high salaries in the mass media? These two sides of the crisis, in media industry and in journalism, are addressed in this article, which explores the evolution of mainly Spanish media in the years before the crisis. However, in order to understand how they reached the current situation, political and economic transformations in what has been called the Information Society and neoliberal globalization must be addressed.

Agro-energy - A solution for climate or a crisis exit for capital?

International Nuclear Information System (INIS)

Houtart, F.

2009-01-01

Intensive advertisement has presented agro-energy as a solution to the global warming and to the energy crisis. But how will it be possible to replace fossil fuels? It would be surprising that an economic system like capitalism does not try to supply some remedies to a situation that paralyzes it and threatens its own survivor-ship. But are these measures favorable to humanity and susceptible to warrant the future of the Earth? Are we trying to save the mankind and its vital capacities or to preserve capitalism? This book examines the role of energy in the development of humanity and then the degradation of climate and the way that capitalism has treated the problem. It deals with the real conditions of biofuels development, reveals the ecological and social conditions of their production, and denounces the social and natural catastrophes they are leading to. The book ends with a thinking about the economical function of biofuels and on the solutions offered by renewable energy sources. It proposes some changes that reveal the core of the problem: changing our development model. (J.S.)

Energy India 'dependence

International Nuclear Information System (INIS)

Cygler, C.

2007-01-01

India has an economic growth between 8 to 10 % by year. To become a great country of the twenty first century and to stop poverty it is necessary to keep this growth but the growth of India is dependant of its ability to supply electric power necessary to increase the industrial production. The country has to multiply by four its energy production. The electric production comes from thermal power plants for 65%, 26% from hydroelectric power plants, 6% from renewable energy sources and 3% from nuclear energy. Between solar energy ( India has three hundred solar days by years) and nuclear energy using thorium that can be increased India has to choose an energy policy to answer its energy demand and independence need. (N.C.)

Coping with the energy crisis: Impact assessment and potentials of non-traditional renewable energy in rural Kyrgyzstan

International Nuclear Information System (INIS)

Liu, Melisande F.M.; Pistorius, Till

2012-01-01

The Kyrgyz energy sector is characterised by a dramatic energy crisis that has deprived a substantial part of the population from access to energy. Non-traditional renewable energy sources have emerged as a promising alternative in providing basic energy services to the rural poor. Based on qualitative interview data from local households and project planners, this study sets out to assess impacts, limitations and barriers of non-traditional renewable energy projects in rural areas in Kyrgyzstan. This study argues that recent renewable energy efforts from multilateral international agencies, the private sector, and nongovernmental organisations exhibit great potential in creating tangible benefits and improving basic energy services, but have so far been inefficient in establishing and replicating sustainable and long-term energy solutions. Existing practices need to be improved by attaching greater importance to the capacities and real needs of the rural poor. The guidance of integrated programmes and policies along with alternative financing schemes and awareness-raising are urgently needed to leverage local success stories and to facilitate a sustainable energy development in rural Kyrgyzstan. - Highlights: ► We examine 11 rural households and 5 project planners in rural Kyrgyzstan. ► We assess impacts of non-traditional renewable energies compared with conventional fuels. ► Renewable energies exhibit a range of tangible benefits for rural users. ► Limitations concern performance, durability, repair, acceptance, finance and policy. ► Renewable energy is a promising alternative for rural households in Kyrgyzstan.

The United States facing their petroleum dependence; Les Etats-Unis face a leur dependance petroliere

Energy Technology Data Exchange (ETDEWEB)

Noel, P. [Institut francais des Relations Internationals, 75 - Paris (France); Universite Pierre Mendes-France-IEPE-CNRS, 38 - Grenoble (France)

2002-06-01

In the framework of ''the energy crisis of 2000-2001'', the Cheney report and the petroleum dependence, this study presents a critical examination of the United States petroleum situation, its perception in the american political milieu and the public policies implementing during the last ten years. The first section is devoted to the petroleum supply. In the second section, the american petroleum policy and the energy safety are studied. (A.L.B.)

Effects of 3-AB on PARP expression of Hela cells and apoptosis and cell cycle progression of Hela cells after X-rays irradiation

International Nuclear Information System (INIS)

Du Xiang; Zhao Hongguang; Guo Wei; Gong Shouliang; Wang Wen

2007-01-01

Objective: To study the changes of apoptosis and cell cycle progression of Hela cells after the poly (ADP- ribose) polymerase (PARP) was inhibited by its inhibitor 3-aminobenzamid (3-AB) and the mechanisms of PARP interaction with Hela cells damaged by irradiation. Methods: Hela cell line was used. Flow cytometry (FCM) was used to examine the PARP expression of control and 3 AB groups at 0, 2, 4, 8, 12 h alter administration with 5 mmol·L -1 3-AB. The percentage of apoptotic cells and cell cycle progression ol control, irradiation, 3-AB plus irradiation groups were measured with FCM at 2, 8, 12, 24 h after exposure to 2 Gy irradiation following administration with 5 mmol·L -1 3-AB. Results: The percentage of Hela cells with positive expression of PARP protein decreased after administration with 3-AB and there was significant difference between 3-AB plus irradiation group and control group (P 2 cells in the 3-AB plus irradiation group were lower than those in the irradiation group (P 2 arrest induced by irradiation. (authors)

A study on energy security and nuclear energy role

International Nuclear Information System (INIS)

Ujita, Hiroshi

2011-01-01

Energy security was a major concern for OECD governments in the early 1970s. Since then, successive oil crises, volatility of hydrocarbon prices, as well as terrorist risks and natural disasters, have brought the issue back to the centre stage of policy agendas. Here, an energy security concept has been proposed, which is defined by time frame and space frame as well. Wide-meaning energy security is divided broadly into two categories. One is short-term (∼10 y) energy crisis, which is narrow-meaning energy security. Short-term energy crisis is further divided into contingent crisis, such as energy supply chain (sealane) interruption due to conflict, accident, terrorism, etc., and structural crisis, such as price fluctuations, supply shortage, energy demand increase in Asia, technology development stagnation, etc. The other is long-term (∼100 y) energy crisis and global energy problems, such as fossil fuel exhaustion and global warming. (author)

UPP mediated Diabetic Retinopathy via ROS/PARP and NF-κB inflammatory factor pathways.

Science.gov (United States)

Luo, D-W; Zheng, Z; Wang, H; Fan, Y; Chen, F; Sun, Y; Wang, W-J; Sun, T; Xu, X

2015-01-01

Diabetic retinopathy (DR) is a leading cause of blindness in adults at working age. Human diabetic retinopathy is characterized by the basement membrane thick, pericytes loss, microaneurysms formation, retina neovascularization and vitreous hemorrhage. To investigate whether UPP activated ROS/PARP and NF-κB inflammatory factor pathways in Diabetic Retinopathy, human retinal endothelial cells (HRECs) and rats with streptozotocin-induced diabetes were used to determine the effect of UPP on ROS generation, cell apoptosis, mitochondrial membrane potential (ΔΨm) and inflammatory factor protein expression, through flow cytometry assay, immunohistochemistry, Real-time PCR, Western blot analysis and ELISA. The levels of ROS and apoptosis and the expressions of UPP (Ub and E3) and inflammatory factor protein were increased in high glucose-induced HRECs and retina of diabetic rats, while ΔΨm was decreased. The UPP inhibitor and UbshRNA could attenuate these effects through inhibiting the pathway of ROS/PARP and the expression of NF-κB inflammatory factors, and the increased UPP was a result of high glucose-induced increase of ROS generation and NF-κBp65 expression, accompanied with the decrease of ΔΨm. Clinical study showed the overexpression of UPP and detachment of epiretinal membranes in proliferative DR (PDR) patients. It has been indicated that the pathogenic effect of UPP on DR was involved in the increase of ROS generation and NF-κB expression, which associated with the ROS/PARP and NF-κB inflammatory factor pathways. Our study supports a new insight for further application of UPP inhibitor in DR treatment.

The impact of cyclin-dependent kinase 5 depletion on poly(ADP-ribose) polymerase activity and responses to radiation

International Nuclear Information System (INIS)

Bolin, Celeste; Boudra, Mohammed-Tayyib; Fernet, Marie; Vaslin, Laurence; Pennaneach, Vincent; Zaremba, Tomasz; Favaudon, Vincent; Megnin-Chanet, Frederique; Hall, Janet; Biard, Denis; Cordelieres, Fabrice P.

2012-01-01

Cyclin-dependent kinase 5 (Cdk5) has been identified as a determinant of sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Here, the consequences of its depletion on cell survival, PARP activity, the recruitment of base excision repair (BER) proteins to DNA damage sites, and overall DNA single-strand break (SSB) repair were investigated using isogenic HeLa stably depleted (KD) and Control cell lines. Synthetic lethality achieved by disrupting PARP activity in Cdk5-deficient cells was confirmed, and the Cdk5KD cells were also found to be sensitive to the killing effects of ionizing radiation (IR) but not methyl methanesulfonate or neocarzinostatin. The recruitment profiles of GFP-PARP-1 and XRCC1-YFP to sites of micro irradiated Cdk5KD cells were slower and reached lower maximum values, while the profile of GFP-PCNA recruitment was faster and attained higher maximum values compared to Control cells. Higher basal, IR, and hydrogen peroxide-induced polymer levels were observed in Cdk5KD compared to Control cells. Recruitment of GFP-PARP-1 in which serines 782, 785, and 786, potential Cdk5 phosphorylation targets, were mutated to alanines in micro-irradiated Control cells was also reduced. We hypothesize that Cdk5- dependent PARP-1 phosphorylation on one or more of these serines results in an attenuation of its ribosylating activity facilitating persistence at DNA damage sites. Despite these deficiencies, Cdk5KD cells are able to effectively repair SSBs probably via the long patch BER pathway, suggesting that the enhanced radiation sensitivity of Cdk5KD cells is due to a role of Cdk5 in other pathways or the altered polymer levels. (authors)

The Dutch Crisis and Recovery Act: Economic Recovery and Legal Crisis?

Directory of Open Access Journals (Sweden)

J Verschuuren

2010-12-01

Full Text Available In the Netherlands, the 2010 Crisis and Recovery Act aims at speeding up decisionmaking on a wide variety of activities, hoping that after the financial and economic crisis has passed, development projects can immediately be carried out without any delay caused by legal procedures in court or elsewhere. The Act meets great criticism for many reasons: it allegedly curtails citizen's procedural rights because it focuses almost exclusively on environmental standards as "obstructing" standards that need to be removed, and it infringes international and European Union law. In this note, the legal critique on the Act is analysed. The conclusion is that the sense of urgency surrounding the design of legal measures to address the economic crisis enables the legislature to implement innovations and long-time pending amendments to existing legislation. Most issues have however not been fully or properly considered. Many legal questions will arise when implementing the Act, which will retard rather than expedite projects. It is difficult to predict whether the positive effects of the Crisis and Recovery Act would outweigh the negative aspects. Much depends on the manner in which the authorities will actually apply the Act. Should they implement the Act to its full potential, the effect of the Act in sum will be negative. In that case, the Act may help the economy to recover, but it will bring about a crisis in the legal system. It will, in all probability, also not contribute to sustainable development.

ARTD1/PARP1 Negatively Regulates Glycolysis by Inhibiting Hexokinase 1 Independent of NAD+ Depletion

Directory of Open Access Journals (Sweden)

Elise Fouquerel

2014-09-01

Full Text Available ARTD1 (PARP1 is a key enzyme involved in DNA repair through the synthesis of poly(ADP-ribose (PAR in response to strand breaks, and it plays an important role in cell death following excessive DNA damage. ARTD1-induced cell death is associated with NAD+ depletion and ATP loss; however, the molecular mechanism of ARTD1-mediated energy collapse remains elusive. Using real-time metabolic measurements, we compared the effects of ARTD1 activation and direct NAD+ depletion. We found that ARTD1-mediated PAR synthesis, but not direct NAD+ depletion, resulted in a block to glycolysis and ATP loss. We then established a proteomics-based PAR interactome after DNA damage and identified hexokinase 1 (HK1 as a PAR binding protein. HK1 activity is suppressed following nuclear ARTD1 activation and binding by PAR. These findings help explain how prolonged activation of ARTD1 triggers energy collapse and cell death, revealing insight into the importance of nucleus-to-mitochondria communication via ARTD1 activation.

Energy education - a multidisciplinary approach

International Nuclear Information System (INIS)

Nezhad, H.G.

1993-01-01

One of the major global issues of the 1990s will be how to best use our scarce energy resources while maintaining a high economic growth rate and improving environmental quality. In fact, the survival of our civilization depends very much on the wise use of conventional energy sources and the development of renewable resources. Although securing our future energy needs requires joint efforts by governments, the public, and industry, the most crucial role is that of energy educators who are needed to train manpower and educate the public. In the past, education has played mainly a reactive role in crisis situations. We must become proactive now. I strongly believe that through appropriate energy education at all levels of our society, we can prevent future energy and environmental crisis and at the same rime provide our people with a safe environment and an adequate supply of energy

The prevention of an electricity crisis by smart action

International Nuclear Information System (INIS)

De Jong, C.; Steenbeek, O.W.

2001-01-01

Because of large variations in energy prices risk management is very important in a liberalized market. A sound trade of energy contracts can help to prevent an energy crisis. In this article it is highlighted how the Dutch energy market differs from other (financial) markets, and what lessons can be learned from the recent energy crisis in California, USA. The possibility to introduce the so-called Value-at-Risk standard is discussed. Also other tools which are available for parties to manage and control old and new risks in a liberalized market for electricity are outlined. 3 refs

US oil dependency and energy security

International Nuclear Information System (INIS)

Noel, P.

2002-01-01

The three papers of this document were written in the framework of a seminar organized the 30 may 2002 by the IFRI in the framework of its program Energy and Climatic Change. The first presentation deals with the american oil policy since 1980 (relation between the oil dependence and the energy security, the Reagan oil policy, the new oil policy facing the increase of the dependence). The second one deals with the US energy security (oil security, domestic energy security, policy implications). The last presentation is devoted to the US oil dependence in a global context and the problems and policies of international energy security. (A.L.B.)

Poly(ADP-ribosyl)ation links the chromatin remodeler SMARCA5/SNF2H to RNF168-dependent DNA damage signaling

DEFF Research Database (Denmark)

Smeenk, G.; Wiegant, W.W.; Luijsterburg, M.S.

2013-01-01

Ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) arising in native chromatin elicit an RNF8/RNF168-dependent ubiquitylation response, which triggers the recruitment of various repair factors. Precisely how this response is regulated in the context of chromatin remains largely...... unexplored. Here, we show that SMARCA5/SNF2H, the catalytic subunit of ISWI chromatin remodeling complexes, is recruited to DSBs in a poly(ADP-ribose) polymerase 1 (PARP1)-dependent manner. Remarkably, PARP activity, although dispensable for the efficient spreading of νH2AX into damaged chromatin......, selectively promotes spreading of SMARCA5, the E3 ubiquitin ligase RNF168, ubiquitin conjugates and the ubiquitin-binding factors RAD18 and the RAP80-BRCA1 complex throughout DSB-flanking chromatin. This suggests that PARP regulates the spatial organization of the RNF168-driven ubiquitin response to DNA...

The safety of antiangiogenic agents and PARP inhibitors in platinum-sensitive recurrent ovarian cancer.

Science.gov (United States)

Lorusso, Domenica; Fontanella, Caterina; Maltese, Giuseppa; Lepori, Stefano; Tripodi, Elisa; Bogani, Giorgio; Raspagliesi, Francesco

2017-06-01

Recurrence is a common event in endothelial ovarian cancer (EOC) patients, and the choice of the most appropriate treatment is driven by the platinum-free interval, molecular characteristics of the disease such as BRCA mutational status, previous treatments and toxicity. Areas covered: This review focuses on the main hematologic and non-hematologic toxicities correlated with the use of licensed antiangiogenic agents and PARP inhibitors in recurrent platinum-sensitive EOC, providing recommendations for their management. Expert opinion: The clinical research over the next years will be focused on a more precise characterization of molecular pathways underlying tumorigenesis of the five ovarian tumors, to improve the decision-making process in these rare diseases. For this purpose, new study designs and international collaborations will become mandatory. Immunotherapy, antiangiogenic agents and PARP inhibitors will be combined to build a treatment strategy algorithm which will allow patients to receive all the available treatment option, in the more appropriate sequence.

Political crisis poses problems for nuclear industry

Energy Technology Data Exchange (ETDEWEB)

Mitev, Lubomir [NucNet, Brussels (Belgium)

2014-11-15

The political crisis in Ukraine has given rise to several problematic issues for the nuclear industry, including the country's obvious dependence on Russia for nuclear fuel supplies and the transport of nuclear material. A 2013 report by the Polish Institute of International Affairs (PIIA) concluded that Ukraine will lean towards the development of ''intensive cooperation'' with Western nuclear regulators and companies as it seeks to increase its control over the sector and reduce its dependency on Russia. The PIIA report said the gas crises of 2006 and 2009, and especially the current destabilisation of the country, have highlighted Ukraine's ''excessive and problematic dependence'' on energy supply from Russia. The 'Energy Strategy of Ukraine Until 2030' assumes that the share of nuclear energy will remain the same in 2030 as it was in 2005 - about 50 % of the energy mix. To achieve its goals, Ukraine's strategy envisages several priority actions. Firstly, work should begin on identification of three or four sites for new nuclear stations. Secondly, the plan says that Khmelnistki-3 and -4 should be completed by 2016. Thirdly, the plan envisages six gigawatts of new nuclear capacity becoming operational between 2019 and 2021. Finally, lifetime extensions are planned for South Ukraine units 1 to 3, Zaporozhye units 1 to 6, Rovno units 2 and 3 and Khmelnitski-1.

Present Scenario of Renewable Energy in Bangladesh and a Proposed Hybrid System to Minimize Power Crisis in Remote Areas

OpenAIRE

Chowdhury, Nahid -UR-Rahman; Reza, Syed Enam; Nitol, Tofaeel Ahamed; Mahabub, Abd-Al-Fattah IBNE

2016-01-01

Abstract- Bangladesh is a densely populated country located at the South-East corner of Asia. Only 48.5% of people here have access to the grid electricity. This paper provides a comprehensive study of the contemporary renewable energy scenario in Bangladesh in terms of distribution, research and infrastructural development in the country. Renewable energy is the smartest solution of increasing energy crisis caused by using fossil fuels. But sometimes it faces question of reliability which ca...

A Parsimonious Bootstrap Method to Model Natural Inflow Energy Series

Directory of Open Access Journals (Sweden)

Fernando Luiz Cyrino Oliveira

2014-01-01

Full Text Available The Brazilian energy generation and transmission system is quite peculiar in its dimension and characteristics. As such, it can be considered unique in the world. It is a high dimension hydrothermal system with huge participation of hydro plants. Such strong dependency on hydrological regimes implies uncertainties related to the energetic planning, requiring adequate modeling of the hydrological time series. This is carried out via stochastic simulations of monthly inflow series using the family of Periodic Autoregressive models, PAR(p, one for each period (month of the year. In this paper it is shown the problems in fitting these models by the current system, particularly the identification of the autoregressive order “p” and the corresponding parameter estimation. It is followed by a proposal of a new approach to set both the model order and the parameters estimation of the PAR(p models, using a nonparametric computational technique, known as Bootstrap. This technique allows the estimation of reliable confidence intervals for the model parameters. The obtained results using the Parsimonious Bootstrap Method of Moments (PBMOM produced not only more parsimonious model orders but also adherent stochastic scenarios and, in the long range, lead to a better use of water resources in the energy operation planning.

The United States facing their petroleum dependence

International Nuclear Information System (INIS)

Noel, P.

2002-06-01

In the framework of ''the energy crisis of 2000-2001'', the Cheney report and the petroleum dependence, this study presents a critical examination of the United States petroleum situation, its perception in the american political milieu and the public policies implementing during the last ten years. The first section is devoted to the petroleum supply. In the second section, the american petroleum policy and the energy safety are studied. (A.L.B.)

We don't have an energy crisis - we have an energy currency crisis

International Nuclear Information System (INIS)

Scott, D.S.

2009-01-01

'Full text': Contrary to what almost everyone believes, we do not need to find new, non-carbon energy sources. We have plenty, including hydraulic, wind, solar, geothermal, tidal sources - and, most important, nuclear power. The latter holds the most promise for a substantial positive impact world-wide - but it is held back by the deeply imbedded, flawed mythology that nuclear power is dangerous and unsustainable. In order to deploy non-carbon sources at the level they are needed globally, we must build new nuclear plants and refurbish old ones. At the same time, we must, whenever reasonable, install other non-carbon sources, typically renewables like hydraulic and wind, whose attractiveness depends on venue. We will use the graphic of the energy system's architecture, shown above, as a platform to explain why our critical need is for a universal non-carbon energy currency that can allow non-carbon sources to escape the electricity ghetto and move into transportation fuels and chemical commodities. Today's proposals for deflecting climate disruption are not solutions. At best, they are band-aids. Any comprehensive solution must lead to zero CO 2 emissions from our energy system - not just reduced emissions. This requires not only non-carbon sources but also non-carbon currencies. We already have the non-carbon currency - electricity. But electricity can not fly airplanes, or push ships, and is a poor currency for road or rail. For these services, we will need the non-carbon - and renewable - currency, hydrogen. Only hydrogen can allow the energy from non-carbon sources like hydraulic, nuclear, sunlight or wind, to fly airplanes - to fly them further, safer, with larger payloads and without (in principle) the system emitting a drop of CO 2 . In short, hydrogen is the single, non-carbon fuel that can substitute for today's gasoline, diesel and jet-A. On the way to the Hydrogen Age, 'tether' hydrogen must play a vital role in harvesting Canada's heavy oil reserves

The Economic Crisis and Several Effects on Global Economy

Directory of Open Access Journals (Sweden)

Florina BRAN

2011-01-01

Full Text Available The main mechanism of profit making is not production according to the outcomes of several analyses of the current economic crisis. This mechanism is circulation and exchange. Starting with this observation the paper goes through a number of aspects regarding the relation between crisis and economy at global level. These aspects consist in the recent financial turmoil; who pays for the crisis; stabilizing the financial sector; recession and the financial crisis; the internationalization of the crisis; commodities and the ecological crisis; an end to neo-liberalism; what should socialists demand. We notice and comment on how important current development in the wake of the banking crisis is for the transmission of that crisis to the rest of the economy and its interaction with the more general economic crisis now emerging. It was concluded that there are good chances that the current economic order to be broken. The future shape of the order will depend more on vision of managers than on the influence of the so called objective factors.

The Energy Union

International Nuclear Information System (INIS)

Auverlot, Dominique; Beeeker, Etienne; Hossie, Gaelle; Bettzuege, Marc Oliver; Helm, Dieter; Roques, Fabien

2015-08-01

A synthesis of contributions is firstly proposed in this collective publication. In this synthesis, the authors describes the crisis faced by European energy (economic crisis, closure of some thermal power plants due to a lack of profitability, increase of electricity prices, low CO 2 quota prices resulting in a greater use of coal, an ageing refinery system, dependence on the Russian gas for some countries), identify four principles which could be used as guidelines for the European policy (responsibility, solidarity, economic rationality, resilience), define seven recommendations as objectives of a European energy policy. Then, the contributions address the following topics: security of electricity supply, security of European Union's gas supply called into question again, reforming the ETS market to strengthen the credibility of the European climate policy, a necessary evolution of the European energy and climate policy, the issue of a definition of a European energy policy as a dogma or a strategy, the challenge for building up a sustainable and consistent European energy and climate policy

Learning Crisis Unit through Post-Crisis: Characteristics and Mechanisms

Science.gov (United States)

Chebbi, Hela; Pündrich, Aline Pereira

2015-01-01

Purpose: This paper aims to identify the characteristics that a crisis unit should have to achieve effective learning after crisis. Literature has identified many relations between learning organizations and crisis; yet, there is a dearth of research on specific studies about crisis units and their post-crisis learning features. Thus, this paper…

What Perspectives for Crisis Resolution? Europe Challenged by the Iranian Crisis

International Nuclear Information System (INIS)

Cirera, Daniel

2008-01-01

There are major stakes involved in the Iranian nuclear crisis, such as regional stability, risks of new military clashes, the proliferation threat, and the energy issue. In this context, the European ability to elaborate a European policy constitutes a great challenge. Since 2003, Europeans have been trying to avoid military clashes. Their changing positions are somewhat coherent, but no single European policy has been really elaborated. To do so, Europe should set itself apart from the American strategy. The autonomization of Europe is not an ideological choice, but it falls in line with the logic of the union. Whatever the Atlanticist convictions of European rulers may be in this crisis, this ability to be autonomous constitutes the necessary condition to play a role

Crisis and Crisis Scenarios

DEFF Research Database (Denmark)

Larsen, Øjvind

2016-01-01

This special issue of Nordicum-Mediterraneum contains select proceedings from the third meeting of the Nordic Summer University research circle called “Crisis and Crisis Scenarios: Normativity, Possibilities and Dilemmas”, held April 9th — 12th, 2015 at the Lysebu Conference Centre in Oslo, Norway....... The circle’s research program runs from 2014 to 2016 and is aimed at examining the concept of crisis as it is used today in academia and public discussion. In this collection of papers from the symposium we present some of the different ways in which the topic of the study group was addressed....

On the Epistemological Crisis in Genomics

Science.gov (United States)

Dougherty, Edward R

2008-01-01

There is an epistemological crisis in genomics. At issue is what constitutes scientific knowledge in genomic science, or systems biology in general. Does this crisis require a new perspective on knowledge heretofore absent from science or is it merely a matter of interpreting new scientific developments in an existing epistemological framework? This paper discusses the manner in which the experimental method, as developed and understood over recent centuries, leads naturally to a scientific epistemology grounded in an experimental-mathematical duality. It places genomics into this epistemological framework and examines the current situation in genomics. Meaning and the constitution of scientific knowledge are key concerns for genomics, and the nature of the epistemological crisis in genomics depends on how these are understood. PMID:19440447

Crisis Communication Online

DEFF Research Database (Denmark)

Utz, Sonja; Schultz, Friederike; Glocka, Sandra

2013-01-01

Social media play in today's societies a fundamental role for the negotiation and dynamics of crises. However, classical crisis communication theories neglect the role of the medium and focus mainly on the interplay between crisis type and crisis communication strategy. Building on the recently...... developed “networked crisis communication model” we contrast effects of medium (Facebook vs. Twitter vs. online newspaper) and crisis type (intentional vs. victim) in an online experiment. Using the Fukushima Daiichi nuclear disaster as crisis scenario, we show that medium effects are stronger than...... the effects of crisis type. Crisis communication via social media resulted in a higher reputation and less secondary crisis reactions such as boycotting the company than crisis communication in the newspaper. However, secondary crisis communication, e.g. talking about the crisis communication, was higher...

US oil dependency and energy security; Dependance petroliere et securite energetique americaine

Energy Technology Data Exchange (ETDEWEB)

Noel, P [Institut francais des Relations Internationals, 75 - Paris (France); [Universite Pierre Mendes-France-IEPE-CNRS, 38 - Grenoble (France)

2002-07-01

The three papers of this document were written in the framework of a seminar organized the 30 may 2002 by the IFRI in the framework of its program Energy and Climatic Change. The first presentation deals with the american oil policy since 1980 (relation between the oil dependence and the energy security, the Reagan oil policy, the new oil policy facing the increase of the dependence). The second one deals with the US energy security (oil security, domestic energy security, policy implications). The last presentation is devoted to the US oil dependence in a global context and the problems and policies of international energy security. (A.L.B.)

Role of renewable energy policies in energy dependency in Finland: System dynamics approach

International Nuclear Information System (INIS)

Aslani, Alireza; Helo, Petri; Naaranoja, Marja

2014-01-01

Highlights: • A system dynamics model for evaluating renewable energy policies on dependency is proposed. • The model considers the role of diversification on dependency and security of energy supply in Finland. • Dependency on imported sources will decrease depends on the defined scenarios in Finland. - Abstract: Objective: We discuss the role of diversification on dependency and security of energy supply. A system dynamics model with especial focus on the role of renewable energy resources (as a portfolio) on Finland’s energy dependency is developed. The purpose is also to cover a part of research gap exists in the system dynamics modeling of energy security investigations. Methods: A causal loops diagram and a system dynamics model evaluate Finnish scenarios of renewable energy policies. The analysis describes the relationship between dynamic factors such as RE encouragement packages, dependency, and energy demand. Results: A causal loops diagram and a system dynamics model evaluate three different Finnish scenarios of renewable energy policies by 2020. Conclusion: Analysis shows that despite 7% electricity/heat consumption growth by 2020 in Finland, dependency on imported sources will decrease between 1% and 7% depend on the defined scenarios. Practice Implications: The proposed model not only helps decision makers to test their scenarios related to renewable energy polices, it can be implemented by other countries

Energy dependence of polymer gels in the orthovoltage energy range

Directory of Open Access Journals (Sweden)

Yvonne Roed

2014-03-01

Full Text Available Purpose: Ortho-voltage energies are often used for treatment of patients’ superficial lesions, and also for small- animal irradiations. Polymer-Gel dosimeters such as MAGAT (Methacrylic acid Gel and THPC are finding increasing use for 3-dimensional verification of radiation doses in a given treatment geometry. For mega-voltage beams, energy dependence of MAGAT has been quoted as nearly energy-independent. In the kilo-voltage range, there is hardly any literature to shade light on its energy dependence.Methods: MAGAT was used to measure depth-dose for 250 kVp beam. Comparison with ion-chamber data showed a discrepancy increasing significantly with depth. An over-response as much as 25% was observed at a depth of 6 cm.Results and Conclusion: Investigation concluded that 6 cm water in the beam resulted in a half-value-layer (HVL change from 1.05 to 1.32 mm Cu. This amounts to an effective-energy change from 81.3 to 89.5 keV. Response measurements of MAGAT at these two energies explained the observed discrepancy in depth-dose measurements. Dose-calibration curves of MAGAT for (i 250 kVp beam, and (ii 250 kVp beam through 6 cm of water column are presented showing significant energy dependence.-------------------Cite this article as: Roed Y, Tailor R, Pinksy L, Ibbott G. Energy dependence of polymer gels in the orthovoltage energy range. Int J Cancer Ther Oncol 2014; 2(2:020232. DOI: 10.14319/ijcto.0202.32 

Differential transactivation by orphan nuclear receptor NOR1 and its fusion gene product EWS/NOR1: possible involvement of poly(ADP-ribose) polymerase I, PARP-1.

Science.gov (United States)

Ohkura, Naganari; Nagamura, Yuko; Tsukada, Toshihiko

2008-10-15

In extraskeletal myxoid chondrosarcoma, a chromosomal translocation creates a gene fusion between EWS and an orphan nuclear receptor, NOR1. The resulting fusion protein EWS/NOR1 has been believed to lead to malignant transformation by functioning as a transactivator for NOR1-target genes. By comparing the gene expression profiles of NOR1- and EWS/NOR1-overexpressing cells, we found that they largely shared up-regulated genes, but no significant correlation was observed with respect to the transactivation levels of each gene. In addition, the proteins associated with NOR1 and EWS/NOR1 were mostly the same in these cells. The results suggest that these proteins differentially transactivate overlapping target genes through a similar transcriptional machinery. To clarify the mechanisms underlying the transcriptional divergence between NOR1 and EWS/NOR1, we searched for alternatively associated proteins, and identified poly(ADP-ribose) polymerase I (PARP-1) as an NOR1-specific binding protein. Consistent with its binding properties, PARP-1 acted as a transcriptional repressor of NOR1, but not EWS/NOR1, in a luciferase reporter assay employing PARP-1(-/-) fibroblasts. Interestingly, suppressive activity of PARP-1 was observed in a DNA response element-specific manner, and in a subtype-specific manner toward the NR4A family (Nur77, Nurr1, and NOR1), suggesting that PARP-1 plays a role in the diversity of transcriptional regulation mediated by the NR4A family in normal cells. Altogether, our findings suggest that NOR1 and EWS/NOR1 regulate overlapping target genes differently by utilizing associated proteins, including PARP-1; and that EWS/NOR1 may acquire oncogenic activities by avoiding (or gaining) transcription factor-specific modulation by the associated proteins. (c) 2008 Wiley-Liss, Inc.

Effectiveness of Blog Response Strategies to Minimize Crisis Effects

Science.gov (United States)

Tomsic, Louis P.

2010-01-01

This study examined the effects of four post-crisis responses on five different variables using a blog tool. The four post-crisis responses are information only, compensation, apology, and sympathy. The five dependent variables are reputation, anger (negative emotion), negative word-of-mouth, account acceptance and state of the publics based on…

L’Italia: una crisi nella crisi

Directory of Open Access Journals (Sweden)

Alessandro Roncaglia

2011-01-01

Full Text Available The article synthesises the large and extending literature on the financial and economic crisis from a Post-Keynesian point of view. The authors take on the position that the international and internal real imbalances are serious and worrying, but yet they are not the cause of the crisis or of its tremendous dimension. The flawed and insufficient regulation of finance is the prime cause of the crisis, as well as it is one of the main hindrances to expansionary macroeconomic policies that may less painfully drive developed countries out of the crisis. It then examines the most recent developments in the euro-area, claiming that we are not facing a sovereign debt crisis but rather a speculative attack on the euro. Finally, the article considers specifically the situation of Italy, currently at the hearth of such an attack, and suggests that the country was already facing critical developments before the 2007/2008 crisis. Thus, the policy measures so far suggested to exit the current stressful situation, in so far as they ignore this fact, seriously run the risk of proving insufficient or altogether noxious.

The energy crisis: some political considerations; La crisis energetica: algunas consideraciones politicas

Energy Technology Data Exchange (ETDEWEB)

Riechmann, J.

2009-07-01

Trends like global warming and peak oil (the end of the cheap fossil fuel age) embody an enormous potential of natural catastrophe and socio-economic upheaval. Are our affluent societies ready for the forthcoming conflicts around scarcity, when expansionist human systems collide with the biophysical limits of our finite planet? Unfortunately, we cannot exclude a revival of anti-humanist and anti-democratic political movements in XXIst century. With the global socio-ecological crisis as a background, it is worth considering the idea of Hitler as a forerunner. (Author) 34 refs.

Fuelwood: The energy crisis that won't go away. Braende - en vedvarende energikrise

Energy Technology Data Exchange (ETDEWEB)

Eckholm, E; Foley, G; Barnard, G; Timberlake, L

1987-01-01

The fuelwood crisis has seriously increased in gravity since the 1979s. In many developing countries firewood contributes to 90% of the total energy consumption. By the year 2000, 2.4 milliard people will be using firewood more quickly than the trees can grow to supply it. It is people stricken with poverty that will suffer most under this situation. Although since 1978-80, 500 million US dollars have been spent on community forest projects, many of them have not been succesful, and it is only recently that connections between the firewood crisis and deforestation, between supply and demand, have become clear. In most countries the forests disappear because the people need arable land to grow food from. Different methods of supporting tree planting projects are described, as well as ways of helping communal forestry to function satisfacorily. Ovens where much less fuel wood is needed to produce the correct heat temperatures, have been introduced in Africa, Asia and Latin America. Yet many of these ovens break down. When planning for the future, village tree plantations, the possibility of planting more trees on private gorunds, the more rationalised use of manure and farm wastes as fertilizers for trees, stricter price control and social reform, should all be kept in mind. (SM).

Energy crisis and changes in the structure of the chemical industry

Energy Technology Data Exchange (ETDEWEB)

Dedov, A G

1980-01-01

The effect of the energy crisis together with higher prices and inflation on the chemical industry is reviewed. One effect has been the search for more energy-efficient processes and more widely available raw materials. Measures taken by the industry have included the control of expenses and losses, utilization of secondary materials and energy resources and the development of new technological growth of the industry and has shifted emphasis to small-scale rather than large-scale chemical production. Capital has also been used more for modernizing existing equipment and facilities than for new construction, and industrialized countries have invested more heavily in developing countries. Trade relations between socialist and western countries have also improved. Improvements have been made in the production of aromatic hydrocarbons by extraction with the use of more efficient solvents, in catalytic and thermic hydrodealkylation of toluene, in the chlorine and nitrogen industries, in phosphorus and phosphoric acid production and in benzene and butadiene production. A new scheme for hydroxylamine production and a new technology for styrene and methanol production have been developed. Direct hydration of propylene has been introduced into the production of isopropanol and propylene ammonolysis has been used to obtain acrylonitrile. Changes in the chemical industry have reduced energy consumption per production unit by 14.2% in the U.S.A. in 1977 in comparison with 1972 and by 14.0% in Common Market countries during 1970-1976.

Efficiency and cross-correlation in equity market during global financial crisis: Evidence from China

Science.gov (United States)

Ma, Pengcheng; Li, Daye; Li, Shuo

2016-02-01

Using one minute high-frequency data of the Shanghai Composite Index (SHCI) and the Shenzhen Composite Index (SZCI) (2007-2008), we employ the detrended fluctuation analysis (DFA) and the detrended cross correlation analysis (DCCA) with rolling window approach to observe the evolution of market efficiency and cross-correlation in pre-crisis and crisis period. Considering the fat-tail distribution of return time series, statistical test based on shuffling method is conducted to verify the null hypothesis of no long-term dependence. Our empirical research displays three main findings. First Shanghai equity market efficiency deteriorated while Shenzhen equity market efficiency improved with the advent of financial crisis. Second the highly positive dependence between SHCI and SZCI varies with time scale. Third financial crisis saw a significant increase of dependence between SHCI and SZCI at shorter time scales but a lack of significant change at longer time scales, providing evidence of contagion and absence of interdependence during crisis.

'TeV Gamma-ray Crisis' and an Anisotropic Space Model

OpenAIRE

Cho, Gi-Chol; Kamoshita, Jun-ichi; Matsunaga, Mariko; Sugamoto, Akio; Watanabe, Isamu

2004-01-01

To solve the `TeV gamma crisis', we examine a model whose one spatial direction is discretized at a high energy scale. Assuming the standard extra-galactic IR photon distribution, we evaluate the mean free-path of a energetic photon which acquires an effective mass in the model. For a wide range of the value of the lattice energy scale between a few TeV and around $10^{10}$ GeV, the mean free-path of a TeV energy photon can be enlarged enough to solve the `crisis'. Taking into account the eff...

Nuclear three-body problem and energy-dependent potentials

International Nuclear Information System (INIS)

Abdurakhmanov, A.; Akhmadkhodzhaev, B.; Zubarev, A.L.; Irgaziev, B.F.

1985-01-01

Energy-dependent potentials in the three-body problem are being considered. Three-particle equations for the case of pairing energy-dependent potentials are generalized and the problems related to this ambiguous generalization are investigated. In terms of the equations obtained the tritium binding energy and vertex coupling constants (Tdn) and (Tdν) are evaluated. The binding energy and, especially, coupling constants are shown to be sensitive to a shape of the energy-dependent potential

Effects of PARP-1 inhibitors AG-014699 and AZD2281 on proliferation and apoptosis of human hepatoma cell line HepG2

Directory of Open Access Journals (Sweden)

DU Senrong

2015-06-01

Full Text Available ObjectiveTo observe the inhibitory and pro-apoptotic effects of two poly(ADP-ribose polymerase (PARP-1 inhibitors, AG-014699 and AZD2281, on human hepatoma HepG2 cells and preliminarily explore the mechanism by which AG-014699 induces HepG2 cell apoptosis, and to provide a new therapeutic target for hepatoma. MethodsThe effects of different concentrations of AG-014699 and AZD2281 on HepG2 cell proliferation were determined by MTT assay. The cell apoptosis rate was measured by flow cytometry. The expression levels of caspase-3 and caspase-8 were measured by Western Blot. Inter-group comparison was made by t test. ResultsBoth AG-014699 and AZD2281 suppressed HepG2 cell proliferation in a time- and dose-dependent manner. However, the sensitivity of HepG2 cells to the two PARP-1 inhibitors was different. The half-maximal inhibitory concentrations of AG-014699 and AZD2281 at 48 h determined by MTT assay were about 20 μmol/L and 400 μmol/L, respectively. Flow cytometry and Western blot were not used to evaluate the apoptosis of HepG2 cells exposed to AZD2281 to which these cells were not sensitive. HepG2 cell apoptosis could be induced by 10, 30, and 50 μmol/L AG-014699, and the highest apoptosis rate at 48 h was significantly higher than that of the control group (3100%±2.13% vs 09%±0013%, P＜0.01. Compared with those in the control group, the protein levels of caspase-3 and caspase-8 in HepG2 cells after 48-h exposure to 30, and 50 μmol/L AG-014699 increased. ConclusionThe two PARP-1 inhibitors AG-014699 and AZD2281 can inhibit the proliferation of HepG2 cells, which showed different sensitivities to the two inhibitors. AG-014699 can induce HepG2 cell apoptosis by up-regulating the protein expression of caspase-3 and caspase-8.

Equivalence between deep energy-dependent and shallow angular momentum dependent potentials

International Nuclear Information System (INIS)

Fiedeldey, H.; Sofianos, S.A.; Papastylianos, A.; Amos, K.A.; Allen, L.J.

1989-01-01

Recently Baye showed that supersymmetry can be applied to determine a shallow l-dependent potential phase equivalent to a deep potential, assumed to be energy-independent and have Panli forbidden states (PFS), for α-α scattering. The PFS are eliminated by this procedure. Such deep potentials are generated as equivalent local potentials (ELP) to the Resonating Group Model (RGM) and are generally energy-dependent. To eliminate this E-dependence as required for the application of Baye's method, l-dependent, but E-independent, deep local potentials were generated by the exact inversion method of Marchenko. Subsequently, the supersymmetric method was used to eliminate the PFS, ensuring that the generalized Levinson theorem is satisfied. As an example, the method was applied to the simple model of two dineutrons scattering in the RGM, where the deep ELP of Horiuchi has a substantial energy-dependence and one PFS only for l=O. 16 refs., 5 figs

Energy independence of the EU and the role of France

International Nuclear Information System (INIS)

2014-03-01

After having outlined that the Ukrainian crisis has revealed the challenge of the EU energy independence and the issue of its dependence, and also indicated the evolutions of gas imports for some European countries between 1995 and 2011, this publication discusses the level of this energy dependence as it appears through the evolution of energy resources, and through the evolution of the final energy mix. It also briefly comments the position of member states. Then, it analyses the influence of French choices on this dependence level (contribution of France to a lower dependence, evolution of energy dependence rates of European countries), and defines the potential role France could play and actions France could implement for a positive evolution of EU energy independence

TYPES OF EXPERIENCING THE CRISIS OF TRANSITION TO ADULTHOOD

Directory of Open Access Journals (Sweden)

Nadejda Valeryevna Sivrikova

2013-09-01

Full Text Available The research presents a typology of living through the crisis of transition to adulthood. On the basis of cluster analysis of data, received by means of normative crisis symptoms checklist , semantic differential, PIL test (by D.A.Leontiev, the questionnaire of terminal valuesand “Life satisfaction” method (by N.N.Melnikov, three types of living through the normative crisis of transition to adulthood were distinguished: optimal, anxiodepressive and defensive. The analysis of research’s results allows to set out the ways of psychological follow-up of a person in the crisis of transition to adulthood depending on individual peculiarities.DOI: http://dx.doi.org/10.12731/2218-7405-2013-8-9

The Global Financial Crisis and the Arab World

DEFF Research Database (Denmark)

Brach, Juliane; Loewe, Markus

2010-01-01

Much has been written on the impact of the global financial crisis on Europe, Asia and the Americas but only little on the Arab states. This article makes an early attempt to take stock of recent developments in the Arab world and offers a systematic approach to disentangle the various inter......-linkages and effects of the crisis on the region. It argues that most Arab countries might be lucky and get off lightly, especially the energy-importing Arab countries which have proved not to be very vulnerable because they are only weakly integrated into global trade and capital markets. The energy exporters have...

Fricke xylenol gel energy dependence

International Nuclear Information System (INIS)

Costa, Rosangela T.; Moreira, Marcos V.; Almeida, Adelaide de

2009-01-01

The advancement of technology has increasingly use the of ionizing radiation mainly in the areas of medicine, industry and research. The development of instruments and methods for an effective performance for detection and measurement of each radiation area was crucial. The literature have demonstrated the effectiveness of the Fricke Xylenol Gel (FXG) as an adequate chemical sensor to be used for dosimetry, once its effective atomic number and density are near to those of the soft tissue. The use of photon beams for therapeutic purpose requires knowledge of their characteristics that can vary for each equipment. Therefore, is important to know all parameters involved for the patient irradiation as the total geometry involved, type of radiation, target material composition and beam energy, that have to be taken into account in the beam dosimetry for the treatment success being the energy parameter is one of the most important. This work was developed to study the energetic dependence of the FXG dosimeter. This chemical solution is made with gelatine 300 Bloom, ferrous ammonium sulfate, xylenol orange, sulfuric acid and Milli-Q water and is based on the Fe +2 oxidation to Fe +3 , due to the ionizing radiation leading to the xylenol orange - ferric complex formation, that is linear depend on the absorbed dose. The FXG samples were irradiated with photons of different energies and the absorbance measurements were done with the spectrophotometric technique at the 585 nm, FXG highest absorption peak. The energetic dependence results presented a stronger dependence for low energies and almost independence for high energies, as expected by the interaction of radiation with matter. (author)

Are stock market crises contagious? The role of crisis definitions

NARCIS (Netherlands)

Mierau, Jochen O.; Mink, Mark

2013-01-01

Financial contagion studies generally examine whether co-movement between markets increases during a crisis. We use a flexible co-movement measure to examine how conclusions of such analyses depend on the sample chosen as the 'crisis'. To this end, we analyse stock market co-movement during the 1997

CRISIS-DIAGNOSTICS IN ANTI-CRISIS MANAGEMENT

Directory of Open Access Journals (Sweden)

Gavrylenko Valentina

2018-01-01

Full Text Available Introduction. In today’s conditions of a changing market environment, uncertainty and risk, one of the main tasks of management is the timely detection of crisis symptoms and the development of measures aimed at preventing their negative impact on the activities of the enterprise. The purpose of this article is to determine the accounting and analytical information for the development of the model KRIZІS-diagnostics and ensure the effectiveness of its functioning in anti-crisis management. Results. The analysis of definition of the concept «KRIZІS-diagnostics» in the scientific literature is carried out. Multi-factor models for assessing the financial status and the diagnostics of enterprises bankruptcy for different countries are presented. The specified classification of management KRIZІS-diagnostics is specified. The stages and tasks of KRIZІS-diagnostics are determined. The sources of information, which are determinants of the early symptoms of the crisis and necessary for KRIZІS-diagnostics are indicated and the characteristic is also given. Qualitative and quantitative indicators that characterize the business processes of the enterprise and can be used to analyze the state of the enterprise in a changing environment for preventing the crisis are determined. Conclusions. This approach of identifying crisis symptoms in business processes is the basis for managing an enterprise to make strategic management decisions in order to prevent a crisis at its early stages. The development of KRIZІS-diagnostics as an information provision for anti-crisis management is the direction of further research.

Financial crisis and crisis management in Sweden: Lessons for today

OpenAIRE

Jonung, Lars

2009-01-01

This paper gives an account of the Swedish financial crisis covering the period 1985-2000, dealing with financial deregulation and the boom in the late 1980s, the bust and the financial crisis in the early 1990s, the recovery from the crisis and the bank resolution policy adopted during the crisis. The paper focuses on three issues: the causes and consequences of the financial crisis, the policy response concerning bank resolution, and the applicability of the Swedish model of bank crisis man...

Crisis management for software development and knowledge transfer

CERN Document Server

Zykov, Sergey V

2016-01-01

This well structured book discusses lifecycle optimization of software projects for crisis management by means of software engineering methods and tools. Its outcomes are based on lessons learned from the software engineering crisis which started in the 1960s. The book presents a systematic approach to overcome the crisis in software engineering depends which not only depends on technology-related but also on human-related factors. It proposes an adaptive methodology for software product development, which optimizes the software product lifecycle in order to avoid “local” crises of software production. The general lifecycle pattern and its stages are discussed, and their impact on the time and budget of the software product development is analyzed. The book identifies key advantages and disadvantages for various models selected and concludes that there is no “silver bullet”, or universal model, which suits all software products equally well. It approaches software architecture in terms of process, dat...

Effect of APE1 T2197G (Asp148Glu Polymorphism on APE1, XRCC1, PARP1 and OGG1 Expression in Patients with Colorectal Cancer

Directory of Open Access Journals (Sweden)

Juliana C. Santos

2014-09-01

Full Text Available It has been hypothesized that genetic variation in base excision repair (BER might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a downregulation of OGG1 and an upregulation of XRCC1 expression in tumor tissue. Regarding the anatomical location of APE1, OGG1 and PARP-1, a decrease in gene expression was observed among patients with cancer in the rectum. In patients with or without some degree of tumor invasion, a significant downregulation in OGG1 was observed in tumor tissue. Interestingly, when taking into account the tumor stage, patients with more advanced grades (III and IV showed a significant repression for APE1, OGG1 and PARP-1. XRCC1 expression levels were significantly enhanced in tumor samples and were correlated with all clinical and histopathological data. Concerning the polymorphism T2197G, GG genotype carriers exhibited a significantly reduced expression of genes of the BER repair system (APE1, XRCC1 and PARP1. In summary, our data show that patients with colorectal cancer present expression changes in several BER genes, suggesting a role for APE1, XRCC1, PARP1 and OGG1 and APE1 polymorphism in colorectal carcinogenesis.

We don't have an energy crisis - we have an energy currency crisis

Energy Technology Data Exchange (ETDEWEB)

Scott, D.S. [International Association for Hydrogen Energy, Inst. for Integrated Energy Systems, Univ. of Victoria, Victoria, British Columbia (Canada)

2009-07-01

'Full text': Contrary to what almost everyone believes, we do not need to find new, non-carbon energy sources. We have plenty, including hydraulic, wind, solar, geothermal, tidal sources - and, most important, nuclear power. The latter holds the most promise for a substantial positive impact world-wide - but it is held back by the deeply imbedded, flawed mythology that nuclear power is dangerous and unsustainable. In order to deploy non-carbon sources at the level they are needed globally, we must build new nuclear plants and refurbish old ones. At the same time, we must, whenever reasonable, install other non-carbon sources, typically renewables like hydraulic and wind, whose attractiveness depends on venue. We will use the graphic of the energy system's architecture, shown above, as a platform to explain why our critical need is for a universal non-carbon energy currency that can allow non-carbon sources to escape the electricity ghetto and move into transportation fuels and chemical commodities. Today's proposals for deflecting climate disruption are not solutions. At best, they are band-aids. Any comprehensive solution must lead to zero CO{sub 2} emissions from our energy system - not just reduced emissions. This requires not only non-carbon sources but also non-carbon currencies. We already have the non-carbon currency - electricity. But electricity can not fly airplanes, or push ships, and is a poor currency for road or rail. For these services, we will need the non-carbon - and renewable - currency, hydrogen. Only hydrogen can allow the energy from non-carbon sources like hydraulic, nuclear, sunlight or wind, to fly airplanes - to fly them further, safer, with larger payloads and without (in principle) the system emitting a drop of CO{sub 2}. In short, hydrogen is the single, non-carbon fuel that can substitute for today's gasoline, diesel and jet-A. On the way to the Hydrogen Age, 'tether' hydrogen must play a vital role

Crisis Communication and Management: Surviving a Public Relations Crisis

Science.gov (United States)

Eramo, Eric M.

2009-01-01

Crisis management, or crisis communication, is never a good thing for a business to experience. It is, however, a public relations' professional moment to shine and put their honed skills to good use. A good crisis management plan is not only action during the crisis but preparation and reflection. Hiring a PR firm that deals with crisis…

Capitalist Crisis, Communication, & Culture – Introduction to the Special Issue of tripleC

OpenAIRE

Christian Fuchs; Matthias Schafranek; David Hakken; Marcus Breen

2010-01-01

The worldwide economic downturn is indicative for a new large crisis of capitalism. The future of capitalism is in this situation not determined, but depends on collective human agency. This introduction to the special issue of tripleC on “Capitalist Crisis, Communication & Culture” presents general arguments about the crisis, a general model of the political economy of capitalist communication, and a systematic typology of literature about capitalist crisis & communication. The introduced mo...

Genetic variants in PARP1 (rs3219090) and IRF4 (rs12203592) genes associated with melanoma susceptibility in a Spanish population

International Nuclear Information System (INIS)

Peña-Chilet, Maria; Ribas, Gloria; Blanquer-Maceiras, Maite; Ibarrola-Villava, Maider; Martinez-Cadenas, Conrado; Martin-Gonzalez, Manuel; Gomez-Fernandez, Cristina; Mayor, Matias; Aviles, Juan Antonio; Lluch, Ana

2013-01-01

Few high penetrance genes are known in Malignant Melanoma (MM), however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP, SLC45A2 and TYR has been observed. Lately, genome-wide association studies (GWAS) have been the ideal strategy to identify new common, low-penetrance susceptibility loci. In this case–control study, we try to validate in our population nine melanoma associated markers selected from published GWAS in melanoma predisposition. We genotyped the 9 markers corresponding to 8 genes (PARP1, MX2, ATM, CCND1, NADSYN1, CASP8, IRF4 and CYP2R1) in 566 cases and 347 controls from a Spanish population using KASPar probes. Genotypes were analyzed by logistic regression and adjusted by phenotypic characteristics. We confirm the protective role in MM of the rs3219090 located on the PARP1 gene (p-value 0.027). Additionally, this SNP was also associated with eye color (p-value 0.002). A second polymorphism, rs12203592, located on the IRF4 gene was associated with protection to develop MM for the dominant model (p-value 0.037). We have also observed an association of this SNP with both lentigines (p-value 0.014) and light eye color (p-value 3.76 × 10 -4 ). Furthermore, we detected a novel association with rs1485993, located on the CCND1 gene, and dark eye color (p-value 4.96 × 10 -4 ). Finally, rs1801516, located on the ATM gene, showed a trend towards a protective role in MM similar to the one firstly described in a GWAS study. To our knowledge, this is the first time that these SNPs have been associated with MM in a Spanish population. We confirmed the proposed role of rs3219090, located on the PARP1 gene, and rs12203592, located on the IRF4 gene, as protective to MM along the same lines as have previous genome-wide associated works. Finally, we have seen associations between IRF4, PARP1, and CCND1 and phenotypic characteristics, confirming previous results for the IRF4 gene and presenting novel data for the last two, suggesting that

Oil and the world energy crisis

Energy Technology Data Exchange (ETDEWEB)

1981-01-01

Almost half of the needs for primary in the world are covered by oil. The rapid growth in oil prices because of the 1973 oil crisis caused a growth in prices for other source of energy as well, primarily coal and natural gas. The sale price of 1 m/sup 3/ of oil in 1973 equalled--$18.87, and later $31.45. In recent years, the cost of 1 m/sup 3/ of oil reached $188.69, and by the end of the century, according to forecasts, should reach $628.98. The cost of extracting 1 m/sup 3/ of oil in the Near East equals $1.57, and in the North Sea $44.03-75.48. The cost of producing 1 m/sup 3/ of synthetic oil from bitumenous sands equals $94.35-157.25, and from fuel shales $94.35-122.14. The explored oil reserves at the end of 1979 were, in million T: in the OPEC countries 58, 265, including 22, 261 in Saudi Arabia, and 25, 539 in the rest of the world. Oil extraction in 1979 was, in million T: in the OPEC countries 1574 (100%), including 510 (32.4%) in Saudi Arabia, 175 ((11.1%) in Iraq, 145 (9.2%) in Iran, 130 (8.2%) in Kuwait, 125 (7.9%) in Venezuela, 114 (7.2%) in Nigeria, 101 (6.4%) in Libya, 88 (5.6%) in the United Arab Emirates, other OPEC countries 186 (11.8%), in the other countries of the world 1550 (100%), including the United States 479 (30.9%), 108 (7.0%) in The Chinese People's Republic, 86 (5.5%) in Canada, 80 (5.2%) in Mexico, 79 (5.1%) in Great Britain, 28 (1.8%) in Arab Republic of Egypt, 18 (1.2%) in Norway, and 86 (5.5%) in other countries.

Energy problems and nuclear power in Japan

International Nuclear Information System (INIS)

Shirasawa, T.

1980-01-01

International petroleum situation maintains the balance between demand and supply for the time being, but hereafter, it seems to be more serious and uncertain. Japanese economy tided over the first oil crisis with difficulty, and moreover, responded to the second oil crisis after the Iranian revolution somehow or other. But oil price has continued to rise, and the acceleration of inflation, the serious depression of businesses and electric power crisis are feared. In Japan where the dependence on imported petroleum is as high as 75%, it is necessary to establish the long term energy policy making energy saving and the development of substitute energy as its mainstay. In August, 1979, the report concerning the interim prospect of long term energy demand and supply was made. Largest efforts will be exerted to reduce the oil import. Then the total demand of energy in 1985 will be 582 million kl calculated in terms of petroleum. The law concerning energy saving was enacted in June, 1979. As the substitute energy, imported coal, LNG and nuclear power generation should be adopted. However, in order to put these energies in practical use, many problems to be solved remain. 21 nuclear power plants of 14.9 million kW capacity are in operation, and provide with 12% of total power generation installations. 30 million kW of nuclear power generation will be attained by 1985. (Kako, I.)

The World Economy in the Times of Financial Crisis and its Impact on European Energy Policy

OpenAIRE

Peter Baláž; Juraj Bayer

2015-01-01

Since 2007, globalization of the world economy has led to the expansion of the financial crisis. It affects the long-term international negative positions of EU members. They reacted to the new situation by carrying out structural reforms and by support of new adaptation programs. An important element of this process was the preparing of the convergence of the national energy policies in the framework of the Europe 20-20-20 program, which should remain one of the determining elements of their...

Influence of the financial crisis on SMEs in the energy area; Einfluss der Finanzkrise auf KMU im Energiebereich: Ergebnisse einer Unternehmensbefragung

Energy Technology Data Exchange (ETDEWEB)

Grass, M.; Schoder, T.; Scheller, E.

2009-05-15

This final report for the Swiss Federal Office of Energy (SFOE) presents and discusses the results of an opinion survey made among small and medium-scale enterprises (SME) in Switzerland concerning the influence of the financial crisis. The methods and questionnaires used are briefly described and the enterprises questioned are characterised. Innovation activities and research and development activities are reviewed. The effects of the financial crisis on business in 2008 are reported on and present and future developments are discussed. The general framework for long-term development is discussed, as are commercial, institutional and governmental general conditions. The report is concluded with a literature list

Incident energy dependence of pt correlations at relativistic energies

CERN Document Server

Adams, J; Ahammed, Z; Amonett, J; Anderson, B D; Arkhipkin, D; Averichev, G S; Badyal, S K; Bai, Y; Balewski, J; Barannikova, O; Barnby, L S; Baudot, J; Bekele, S; Belaga, V V; Bellingeri-Laurikainen, A; Bellwied, R; Berger, J; Bezverkhny, B I; Bharadwaj, S; Bhasin, A; Bhati, A K; Bhatia, V S; Bichsel, H; Bielcik, J; Bielcikova, J; Billmeier, A; Bland, L C; Blyth, C O; Bonner, B E; Botje, M; Boucham, A; Bouchet, J; Brandin, A V; Bravar, A; Bystersky, M; Cadman, R V; Cai, X Z; Caines, H; Calderón de la Barca-Sanchez, M; Castillo, J; Catu, O; Cebra, D; Chajecki, Z; Chaloupka, P; Chattopadhyay, S; Chen, H F; Chen, Y; Cheng, J; Cherney, M; Chikanian, A; Christie, W; Coffin, J P; Cormier, T M; Cramer, J G; Crawford, H J; Das, D; Das, S; Daugherity, M; De Moura, M M; Dedovich, T G; Derevshchikov, A A; Didenko, L; Dietel, T; Dogra, S M; Dong, W J; Dong, X; Draper, J E; Du, F; Dubey, A K; Dunin, V B; Dunlop, J C; Dutta, M R; Mazumdar; Eckardt, V; Edwards, W R; Efimov, L G; Emelianov, V; Engelage, J; Eppley, G; Erazmus, B; Estienne, M; Fachini, P; Faivre, J; Fatemi, R; Fedorisin, J; Filimonov, K; Filip, P; Finch, E; Fine, V; Fisyak, Yu; Fu, J; Gagliardi, C A; Gaillard, L; Gans, J; Ganti, M S; Geurts, F; Ghazikhanian, V; Ghosh, P; González, J E; Gos, H; Grachov, O; Grebenyuk, O; Grosnick, D P; Guertin, S M; Guo, Y; Sen-Gupta, A; Gutíerrez, T D; Hallman, T J; Hamed, A; Hardtke, D; Harris, J W; Heinz, M; Henry, T W; Hepplemann, S; Hippolyte, B; Hirsch, A; Hjort, E; Hoffmann, G W; Huang, H Z; Huang, S L; Hughes, E W; Humanic, T J; Igo, G; Ishihara, A; Jacobs, P; Jacobs, W W; Jedynak, M; Jiang, H; Jones, P G; Judd, E G; Kabana, S; Kang, K; Kaplan, M; Keane, D; Kechechyan, A; Khodyrev, V Yu; Kiryluk, J; Kisiel, A; Kislov, E M; Klay, J; Klein, S R; Koetke, D D; Kollegger, T; Kopytine, M; Kotchenda, L; Kowalik, K L; Krämer, M; Kravtsov, P; Kravtsov, V I; Krüger, K; Kuhn, C; Kulikov, A I; Kumar, A; Kutuev, R K; Kuznetsov, A A; Lamont, M A C; Landgraf, J M; Lange, S; Laue, F; Lauret, J; Lebedev, A; Lednicky, R; Lehocka, S; Le Vine, M J; Li, C; Li, Q; Li, Y; Lin, G; Lindenbaum, S J; Lisa, M A; Liu, F; Liu, H; Liu, L; Liu, Q J; Liu, Z; Ljubicic, T; Llope, W J; Long, H; Longacre, R S; López-Noriega, M; Love, W A; Lu, Y; Ludlam, T; Lynn, D; Ma, G L; Ma, J G; Ma, Y G; Magestro, D; Mahajan, S; Mahapatra, D P; Majka, R; Mangotra, L K; Manweiler, R; Margetis, S; Markert, C; Martin, L; Marx, J N; Matis, H S; Matulenko, Yu A; McClain, C J; McShane, T S; Meissner, F; Melnik, Yu M; Meschanin, A; Miller, M L; Minaev, N G; Mironov, C; Mischke, A; Mishra, D K; Mitchell, J; Mohanty, B; Molnár, L; Moore, C F; Morozov, D A; Munhoz, M G; Nandi, B K; Nayak, S K; Nayak, T K; Nelson, J M; Netrakanti, P K; Nikitin, V A; Nogach, L V; Nurushev, S B; Odyniec, Grazyna Janina; Ogawa, A; Okorokov, V; Oldenburg, M; Olson, D; Pal, S K; Panebratsev, Yu A; Panitkin, S Y; Pavlinov, A I; Pawlak, T; Peitzmann, T; Perevozchikov, V; Perkins, C; Peryt, W; Petrov, V A; Phatak, S C; Picha, R; Planinic, M; Pluta, J; Porile, N; Porter, J; Poskanzer, A M; Potekhin, M V; Potrebenikova, E V; Potukuchi, B V K S; Prindle, D; Pruneau, C A; Putschke, J; Rakness, G; Raniwala, R; Raniwala, S; Ravel, O; Ray, R L; Razin, S V; Reichhold, D M; Reid, J G; Reinnarth, J; Renault, G; Retière, F; Ridiger, A; Ritter, H G; Roberts, J B; Rogachevski, O V; Romero, J L; Rose, A; Roy, C; Ruan, L; Russcher, M; Sahoo, R; Sakrejda, I; Salur, S; Sandweiss, J; Sarsour, M; Savin, I; Sazhin, P S; Schambach, J; Scharenberg, R P; Schmitz, N; Schweda, K; Seger, J; Seyboth, P; Shahaliev, E; Shao, M; Shao, W; Sharma, M; Shen, W Q; Shestermanov, K E; Shimansky, S S; Sichtermann, E P; Simon, F; Singaraju, R N; Smirnov, N; Snellings, R; Sood, G; Sørensen, P; Sowinski, J; Speltz, J; Spinka, H M; Srivastava, B; Stadnik, A; Stanislaus, T D S; Stock, R; Stolpovsky, A; Strikhanov, M N; Stringfellow, B C; Suaide, A A P; Sugarbaker, E R; Suire, C; Sumbera, M; Surrow, B; Swanger, M; Symons, T J M; Szanto de Toledo, A; Tai, A; Takahashi, J; Tang, A H; Tarnowsky, T J; Thein, D; Thomas, J H; Timoshenko, S; Tokarev, M; Trentalange, S; Tribble, R E; Tsai, O D; Ulery, J; Ullrich, T; Underwood, D G; Van Buren, G; Van Leeuwen, M; Van der Molen, A M; Varma, R; Vasilevski, I M; Vasilev, A N; Vernet, R; Vigdor, S E; Viyogi, Y P; Vokal, S; Voloshin, S A; Waggoner, W T; Wang, F; Wang, G; Wang, X L; Wang, Y; Wang, Z M; Ward, H; Watson, J W; Webb, J C; Westfall, G D; Wetzler, A; Whitten, C; Wieman, H; Wissink, S W; Witt, R; Wood, J; Wu, J; Xu, N; Xu, Z; Xu, Z Z; Yamamoto, E; Yepes, P; Yurevich, V I; Zborovský, I; Zhang, H; Zhang, W M; Zhang, Y; Zhang, Z P; Zoulkarneev, R; Zoulkarneeva, Y; Zubarev, A N

2005-01-01

We present results for two-particle transverse momentum correlations, , as a function of event centrality for Au+Au collisions at sqrt(sNN) = 20, 62, 130, and 200 GeV at the Relativistic Heavy Ion Collider. We observe correlations decreasing with centrality that are similar at all four incident energies. The correlations multiplied by the multiplicity density increase with incident energy and the centrality dependence may show evidence of processes such as thermalization, minijet production, or the saturation of transverse flow. The square root of the correlations divided by the event-wise average transverse momentum per event shows little or no beam energy dependence and generally agrees with previous measurements at the Super Proton Synchrotron.

Energy policy of North Korea

International Nuclear Information System (INIS)

Rueth, G.

2006-01-01

Since the year 1990, North Korea suffers internal-policy problems as well as foreign-political problems. The gross domestic investment decreased by 3.8% yearly between the years 1990 and 1998. Many actual problems of North Korea correspond with the energy crisis in this land affecting nearly all sectors of economy and society. This energy crisis was released by the fact, that the former Soviet Union has stopped the supply of primary energy in the year 1991. In the contribution under consideration, the author reports on the energy policy of North Korea. The main themes of this contribution are: (a) Development and characteristics of the energy sector; (b) Crisis of the energy sector; (c) Consequences of the energy crisis in North Korea; (d) Possibilities of the solution of the energy crisis. For the U.S.A. and the international community, the energy crisis offers the possibility to turn North Korea to negotiations by means of remedial measures in the energy sector. In response, North Korea should drop its nuclear energy program. Apart from such positive incentives, the threat of sanctions is conceivable. North Korea imports nearly 70 % of its oil demand from the People's Republic of China. Therefore, China has an great influence on North Korea. The energy crisis of North Korea shows the fatal consequences of a falsely performed energy policy with respect to the population of this land and with respect to the stability and disposing capacity of the political leadership

Proton energy dependence of slow neutron intensity

International Nuclear Information System (INIS)

Teshigawara, Makoto; Harada, Masahide; Watanabe, Noboru; Kai, Tetsuya; Sakata, Hideaki; Ikeda, Yujiro

2001-01-01

The choice of the proton energy is an important issue for the design of an intense-pulsed-spallation source. The optimal proton beam energy is rather unique from a viewpoint of the leakage neutron intensity but no yet clear from the slow-neutron intensity view point. It also depends on an accelerator type. Since it is also important to know the proton energy dependence of slow-neutrons from the moderators in a realistic target-moderator-reflector assembly (TMRA). We studied on the TMRA proposed for Japan Spallation Neutron Source. The slow-neutron intensities from the moderators per unit proton beam power (MW) exhibit the maximum at about 1-2 GeV. At higher proton energies the intensity per MW goes down; at 3 and 50 GeV about 0.91 and 0.47 times as low as that at 1 GeV. The proton energy dependence of slow-neutron intensities was found to be almost the same as that of total neutron yield (leakage neutrons) from the same bare target. It was also found that proton energy dependence was almost the same for the coupled and decoupled moderators, regardless the different moderator type, geometry and coupling scheme. (author)

Risk of severe hematologic toxicities in cancer patients treated with PARP inhibitors: results of monotherapy and combination therapy trials

Directory of Open Access Journals (Sweden)

Alecu I

2018-02-01

Full Text Available Iulian Alecu, Tsveta Milenkova, Simon R Turner Research and Development, AstraZeneca UK Limited, Cambridge, UKThe tolerability profile of PARP inhibitors often includes hematologic toxicities, and the characterization of these adverse events is important to allow effective management by clinicians. Zhou et al1 recently carried out a meta-analysis of the incidence and relative risks of severe neutropenia, thrombocytopenia, and anemia events in 12 randomized controlled trials of PARP inhibitors, either as monotherapy or in combination with chemotherapy or radiotherapy. The authors concluded that olaparib resulted in a higher incidence of severe (common terminology criteria for adverse events [CTCAE] grade $3 neutropenia when compared with niraparib and veliparib; however, these conclusions are based on inappropriate and incomplete comparisons of hematologic toxicity with olaparib or veliparib in combination with myelotoxic chemotherapy versus niraparib monotherapy. While both monotherapy and combination therapy olaparib studies are discussed in the paper, the neutropenia analysis is based on olaparib data solely from studies in combination with paclitaxel or paclitaxel plus carboplatin. In order to inform the practicing clinician of the relative risk of hematologic toxicity associated with different PARP inhibitors, direct comparison needs to be conducted based on monotherapy, where applicable, as per the approved drug indication, otherwise the reader is given misleading information.View the original paper by Zhou et al.

LENR/"Cold Fusion" and Modern Physics: A Crisis Within a Crisis

Science.gov (United States)

Mallove, Eugene F. E.

2004-03-01

The primary theorists in the field of Cold Fusion/LENR have generally assumed that the excess heat phenomena is commensurate with nuclear ash (such as helium), whether already identified or presumed to be present but not yet found, and moreover that it can be explained by hydrided metal lattice structures acting coherently. Though this was an excellent initial hypothesis, the commensurate nuclear ash hypothesis has not been proved, and appears to be approximately correct in only a few experiments. At the same time, compelling evidence has also emerged for other microphysical sources of energy that were unexpected by accepted physics. The exemplars have been the work Dr. Randell Mills and his colleagues at BlackLight Power Corporation and Dr. Paulo and Alexandra Correa in Canada.This has led to a crisis within a crisis: Neither "cold fusion" nor "Modern Physics" will be able to explain the full range of experimental data now available---not even the data within "mainstream" cold fusion/LENR per se--- by insisting that the fundamental paradigms of Modern Physics are without significant flaw. The present crisis is of magnitude comparable to the Copernican Revolution. Neither Modern Physics nor Cold Fusion/LENR will survive in their present forms when this long delayed revolution has run its course.

Heavy rare earths, permanent magnets, and renewable energies: An imminent crisis

International Nuclear Information System (INIS)

Smith Stegen, Karen

2015-01-01

This article sounds the alarm that a significant build-out of efficient lighting and renewable energy technologies may be endangered by shortages of rare earths and rare earth permanent magnets. At the moment, China is the predominant supplier of both and its recent rare earth industrial policies combined with its own growing demand for rare earths have caused widespread concern. To diversify supplies, new mining—outside of China—is needed. But what many observers of the “rare earth problem” overlook is that China also dominates in (1) the processing of rare earths, particularly the less abundant heavy rare earths, and (2) the supply chains for permanent magnets. Heavy rare earths and permanent magnets are critical for many renewable energy technologies, and it will require decades to develop new non-Chinese deposits, processing capacity, and supply chains. This article clarifies several misconceptions, evaluates frequently proposed solutions, and urges policy makers outside of China to undertake measures to avert a crisis, such as greater support for research and development and for the cultivation of intellectual capital. - Highlights: • Rare earths are needed for many efficient lighting and renewable energy technologies. • The industries for rare earths and permanent magnets are dominated by China. • China's reliability is compromised, necessitating non-Chinese mining and processing. • Recycling, substitution and reducing rare earth content are long-term solutions only. • Policy makers should support development of supply chains and intellectual capital

A fat fractal crisis in a quasi-dissipative system

International Nuclear Information System (INIS)

Shen, Ying; Dai, Jun; Jiang, Yumei; He, Yue; He, Da-Ren

2006-01-01

A crisis, induced by a sudden change of a fat strange set to a transit, is observed in a system, which is a two-dimensional discontinuous and noninvertible map and displays a dissipation sowing linear time dependence. It is shown analytically and numerically that, in this crisis, the characteristic scaling exponent takes a large value of 1.72; this is in agreement with the observed superlong transients

Good neighborhood in a crisis? Germans and French in search of a common energy policy (1973 - 1980); Stoerfall fuer die gute Nachbarschaft? Deutsche und Franzosen auf der Suche nach einer gemeinsamen Energiepolitik (1973-1980)

Energy Technology Data Exchange (ETDEWEB)

Tauer, Sandra

2012-11-01

The oil crisis of autumn 1973 was a turning point of the seventies. Citizens of industrialized countries were brought to realize their dependence on Arab imported oil the hard way. Using the example of German-French relations, the author investigates if there were instances of cooperation in energy policy, and in what concrete manner. Using historical primary energy sources, she starts by investigating the actions and political strategies of the German and French governments and also describes the search for multilateral solutions. Examples are presented to show how civil society is affected. This first systematic analysis of German-French relations shows that energy policy had great importance for the bilateral relation even though results of German-French cooperation were few and far between.

Crisis? What crisis? How European professionals handle crises and crisis communication

NARCIS (Netherlands)

Verhoeven, P.; Tench, R.; Zerfass, A.; Moreno, A.; Verčič, D.

2014-01-01

A broad study in 43 European countries shows that 70% of communication professionals encounter at least one crisis a year, mostly institutional, related to the performance of the organization or a crisis in management or leadership. Organizational response and image restoration approaches are mainly

Crisis?: What crisis?: currency vs. banking in the financial crisis of 1931

OpenAIRE

Albrecht Ritschl; Samad Salferaz

2010-01-01

This paper examines the role of currency and banking in the German financial crisis of 1931 for both Germany and the U.S. We specify a structural dynamic factor model to identify financial and monetary factors separately for each of the two economies. We find that monetary transmission through the Gold Standard played only a minor role in causing and propagating the crisis, while financial distress was important. We also find evidence of crisis propagation from Germany to the U.S. via the ban...

Crisis Thought

OpenAIRE

Morris, Edwin Kent

2016-01-01

Crisis thought is an idea that gives a name to and accounts for some of the problematics of the sign crisis in political, social, cultural, and economic discourse. Specifically, crisis thought is a discursive formation, a concept used loosely here to refer to an assemblage of signs such as anxiety or fear that evoke or invoke similar, but inaccurate connotations as crisis in political and everyday usage. The general question this study grapples with is why political, social, cultural, and eco...

An impending platinum crisis and its implications for the future of the automobile

International Nuclear Information System (INIS)

Yang, C.-J.

2009-01-01

The global demand for platinum has consistently outgrown supply in the past decade. This trend likely will continue and the imbalance may possibly escalate into a crisis. Platinum plays pivotal roles in both conventional automobile emissions control and the envisioned hydrogen economy. A platinum crisis would have profound implications on energy and environment. On the one hand, inadequate platinum supply will prevent widespread commercialization of hydrogen fuel-cell vehicles. On the other hand, expensive platinum may enhance the competitiveness of hybrid, plug-in hybrid, and battery-powered electric cars. Policymakers should weigh the potential impacts of a platinum crisis in energy policy.

vPARP Adjusts MVP Expression in Drug-resistant Cell Lines in Conjunction with MDR Proteins.

Science.gov (United States)

Wojtowicz, Karolina; Januchowski, Radoslaw; Nowicki, Michal; Zabel, Maciej

2017-06-01

The definition of vault (ribonucleoprotein particles) function remains highly complex. Vaults may cooperate with multidrug resistance (MDR) proteins, supporting their role in drug resistance. This topic is the main theme of this publication. The cell viability was determined by an MTT assay. The protein expression was detected by western blot analysis. The proteins were knocked-down using siRNA. No major vault protein (MVP) in the LoVo/Dx and W1PR cell lines after tunicamycin treatment was shown. In W1PR cells with knocked-down MVP, a statistically significant decrease in cell viability was noted. In LoVo/Dx, W1TR and A2780TR cells were vault poly-ADP-ribose polymerase (vPARP) was knockdown, a decrease in cell viability was shown. Also, MVP silencing induced an increase in glycoprotein P (Pgp) expression in LoVo/Dx cells. MVP is important for the drug resistance of cancer cells, but it probably requires the presence of vPARP for full activation. Some correlations between MDR proteins and vaults exist. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Energy dependence of nonlocal optical potentials

Science.gov (United States)

Lovell, A. E.; Bacq, P.-L.; Capel, P.; Nunes, F. M.; Titus, L. J.

2017-11-01

Recently, a variety of studies have shown the importance of including nonlocality in the description of reactions. The goal of this work is to revisit the phenomenological approach to determining nonlocal optical potentials from elastic scattering. We perform a χ2 analysis of neutron elastic scattering data off 40Ca, 90Zr, and 208Pb at energies E ≈5 -40 MeV, assuming a Perey and Buck [Nucl. Phys. 32, 353 (1962), 10.1016/0029-5582(62)90345-0] or Tian et al. [Int. J. Mod. Phys. E 24, 1550006 (2015), 10.1142/S0218301315500068] nonlocal form for the optical potential. We introduce energy and asymmetry dependencies in the imaginary part of the potential and refit the data to obtain a global parametrization. Independently of the starting point in the minimization procedure, an energy dependence in the imaginary depth is required for a good description of the data across the included energy range. We present two parametrizations, both of which represent an improvement over the original potentials for the fitted nuclei as well as for other nuclei not included in our fit. Our results show that, even when including the standard Gaussian nonlocality in optical potentials, a significant energy dependence is required to describe elastic-scattering data.

Stability and crisis in social and political development

Directory of Open Access Journals (Sweden)

S. V. Stavchenko

2015-03-01

Determined that the balance and stability on the one hand, and the crisis loss of balance of power between the main actors, leading to instability of institutions, on the other hand, forming two potential «poles» that cause and «energy» of the political process, the vectors of its changes. This process affects the type of the country and its institutional organization. In general, the political crisis dysfunction manifested in political institutions, and is characterized by loss of legitimacy of institutional and substantive elements of the political system. Legitimacy can become leaders, political leaders, political leaders and even the basic law of the country (in the case of revolution, for example. The indicators serve as the political crisis of the political system parameters responsible for the restoration of the political system. Violations of system­parameters mean that in the looming crisis.

Sectoral energy demand studies: Application of the end-use approach to Asian countries

International Nuclear Information System (INIS)

1991-01-01

Events since August 1990 have shown that the world is still dependent on oil despite efforts to decrease that dependency since the oil crisis of 1973 and 1979. Thirteen countries participated in the REDP (UNDP-funded Regional Energy Development Programme) energy planning activities called ''Sectoral energy demand studies'' in which country teams benefited from training in energy data analysis, sectoral accounting of energy demand, and forecasting with the use of MEDEE-S model. This publication documents the training materials on sectoral energy demand series. It includes eight chapters which were indexed separately. Refs, figs, tabs

The World Economy in the Times of Financial Crisis and its Impact on European Energy Policy

Directory of Open Access Journals (Sweden)

Peter Baláž

2015-03-01

Full Text Available Since 2007, globalization of the world economy has led to the expansion of the financial crisis. It affects the long-term international negative positions of EU members. They reacted to the new situation by carrying out structural reforms and by support of new adaptation programs. An important element of this process was the preparing of the convergence of the national energy policies in the framework of the Europe 20-20-20 program, which should remain one of the determining elements of their success in support of the international competitiveness of the EU.

Ramses 2010 - World crisis and global governance

International Nuclear Information System (INIS)

Moreau Defarges, Ph.; Montbrial, Th. de

2009-01-01

2009: the world has changed and is learning to live with the crisis. Not only it is expected to last long but also it impacts the overall social life and in particular the political systems (through governments, elections..). The Ramses 2010 book presents the world through two main axes, crisis and governance, and analyses its geopolitical situation in 8 parts dealing with: world economy, energy and climate, USA, Europe, Middle-East/Maghreb, Asia, Africa, and Latin America. It comprises 53 entries by country and/or topic with maps and key data (150 countries). (J.S.)

Effect of 3-aminobenzamide, PARP inhibitor, on matrix metalloproteinase-9 level in plasma and brain of ischemic stroke model

International Nuclear Information System (INIS)

Koh, Seong-Ho; Chang, Dae-Il; Kim, Hee-Tae; Kim, Juhan; Kim, Myung-Ho; Kim, Kyung Suk; Bae, Inhee; Kim, Haekwon; Kim, Dong Won; Kim, Seung Hyun

2005-01-01

We investigated the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the levels of plasma and brain matrix metalloproteinase-9 (MMP-9) and the expression of nuclear factor kappa B (NF-κB) during experimental focal cerebral ischemia. The 3-aminobenzamide (3-AB), a PARP inhibitor, and saline were administered to 80 Sprague-Dawley rats [3-AB group; 5 rats for plasma sampling, 35 for brain sampling, and 40 for TTC staining] and to 85 rats (10, 35, and 40, respectively), respectively, 10 min before the occlusion of the left middle cerebral artery (MCAo) for 2 h. Infarct volume was measured by TTC staining, the serial levels of plasma and brain MMP-9 were measured by zymography just before and 2, 4, 8, 24, 48, and 72 h after MCAo, brain NF-κB activity was determined by Western blotting, and neutrophil infiltration was evaluated by assessing myeloperoxidase activity. Compared with control group, the levels of plasma and brain MMP-9, brain NF-κB, and MPO activities were significantly reduced in 3-AB group at each time point (p < 0.05). Plasma MMP-9 increased maximally at 4 h and then decreased rapidly, brain MMP-9 increased maximally at 24 h and persisted until 72 h, and NF-κB increased maximally at 24 h and then decreased slowly in both groups. Therefore, the PARP inhibitor reduces the expression of MMP-9 and NF-κB and the infiltration of neutrophils in ischemic stroke

Was the 2007 crisis really a global banking crisis?

NARCIS (Netherlands)

Shehzad, Choudhry Tanveer; De Haan, Jakob

We argue that the 2007 crisis was not a global banking crisis. Stock prices of banks in emerging countries faced a temporary shock but quickly recovered, while stock prices of banks located in industrial countries remained much lower than before the 2007 crisis. Our results also suggest that stock

Summary address by Dr. Ulf Lantzke, Executive Director of the International Energy Agency, to a meeting of the Nikkei Center, Tokyo on 10th April, 1978. [Will there be an energy crisis in 1985

Energy Technology Data Exchange (ETDEWEB)

Lantzke, Ulf

1978-05-01

Five key points were made: (1) Energy is a major element underlying current problems besetting the world economy. Uncertainty about energy policy is contributing to trade problems, persistent inflation, and lagging economic activity. Stronger energy policies are needed in all of the industrial countries. (2) The current oil market surplus is only a temporary phenomenon and should not be a cause for slackening efforts to strengthen energy policies immediately. Current slack conditions in the world oil market do not alter the underlying long-term trend of rising oil consumption which still threatens to bring about a major energy crisis. Because of growing lead times for energy policy action to take effect, the necessary policies need to be set in place immediately. (3) Oil is not the only problem in energy policy. The lack of energy consciousness among the public is a major obstacle to conservation efforts. Lengthy judicial and regulatory procedures are hampering efforts to expand nuclear power. Large-scale substitution of oil by coal will require major investments in mining, transportation infrastructure and coal-burning facilities. (4) Existing policy efforts of IEA Member countries will be inadequate to achieve the objective of holding IEA oil imports to 26m b/d by 1985. It would be a mistake to assume that another energy crisis or large real price increases in energy is inevitable. (DLC)

Low energy neutron scattering for energy dependent cross sections. General considerations

Energy Technology Data Exchange (ETDEWEB)

Rothenstein, W; Dagan, R [Technion-Israel Inst. of Tech., Haifa (Israel). Dept. of Mechanical Engineering

1996-12-01

We consider in this paper some aspects related to neutron scattering at low energies by nuclei which are subject to thermal agitation. The scattering is determined by a temperature dependent joint scattering kernel, or the corresponding joint probability density, which is a function of two variables, the neutron energy after scattering, and the cosine of the angle of scattering, for a specified energy and direction of motion of the neutron, before the interaction takes place. This joint probability density is easy to calculate, when the nucleus which causes the scattering of the neutron is at rest. It can be expressed by a delta function, since there is a one to one correspondence between the neutron energy change, and the cosine of the scattering angle. If the thermal motion of the target nucleus is taken into account, the calculation is rather more complicated. The delta function relation between the cosine of the angle of scattering and the neutron energy change is now averaged over the spectrum of velocities of the target nucleus, and becomes a joint kernel depending on both these variables. This function has a simple form, if the target nucleus behaves as an ideal gas, which has a scattering cross section independent of energy. An energy dependent scattering cross section complicates the treatment further. An analytic expression is no longer obtained for the ideal gas temperature dependent joint scattering kernel as a function of the neutron energy after the interaction and the cosine of the scattering angle. Instead the kernel is expressed by an inverse Fourier Transform of a complex integrand, which is averaged over the velocity spectrum of the target nucleus. (Abstract Truncated)

Normalization of energy-dependent gamma survey data.

Science.gov (United States)

Whicker, Randy; Chambers, Douglas

2015-05-01

Instruments and methods for normalization of energy-dependent gamma radiation survey data to a less energy-dependent basis of measurement are evaluated based on relevant field data collected at 15 different sites across the western United States along with a site in Mongolia. Normalization performance is assessed relative to measurements with a high-pressure ionization chamber (HPIC) due to its "flat" energy response and accurate measurement of the true exposure rate from both cosmic and terrestrial radiation. While analytically ideal for normalization applications, cost and practicality disadvantages have increased demand for alternatives to the HPIC. Regression analysis on paired measurements between energy-dependent sodium iodide (NaI) scintillation detectors (5-cm by 5-cm crystal dimensions) and the HPIC revealed highly consistent relationships among sites not previously impacted by radiological contamination (natural sites). A resulting generalized data normalization factor based on the average sensitivity of NaI detectors to naturally occurring terrestrial radiation (0.56 nGy hHPIC per nGy hNaI), combined with the calculated site-specific estimate of cosmic radiation, produced reasonably accurate predictions of HPIC readings at natural sites. Normalization against two to potential alternative instruments (a tissue-equivalent plastic scintillator and energy-compensated NaI detector) did not perform better than the sensitivity adjustment approach at natural sites. Each approach produced unreliable estimates of HPIC readings at radiologically impacted sites, though normalization against the plastic scintillator or energy-compensated NaI detector can address incompatibilities between different energy-dependent instruments with respect to estimation of soil radionuclide levels. The appropriate data normalization method depends on the nature of the site, expected duration of the project, survey objectives, and considerations of cost and practicality.

Preference shares of the Equipment Agency for the energy mastership. Contribution to the national debate on the energy; Actions prioritaires du Ministere de l'Equipement pour la maitrise de l'energie. Contribution au debat national sur l'energie

Energy Technology Data Exchange (ETDEWEB)

NONE

2003-02-01

The transport and building sectors are responsible of 2/3 or the energy consumption in France and near 50% of the greenhouse gases emission. The transports are very dependent of the hydrocarbons and constitute the more vulnerable sector of a resources crisis. Today the geographical and political risks are the more important concerning the energy supply. In this context this report brings information and preference shares to decrease the energy demand in the transports and the building sectors. (A.L.B.)

Nuclear symmetry energy in density dependent hadronic models

International Nuclear Information System (INIS)

Haddad, S.

2008-12-01

The density dependence of the symmetry energy and the correlation between parameters of the symmetry energy and the neutron skin thickness in the nucleus 208 Pb are investigated in relativistic Hadronic models. The dependency of the symmetry energy on density is linear around saturation density. Correlation exists between the neutron skin thickness in the nucleus 208 Pb and the value of the nuclear symmetry energy at saturation density, but not with the slope of the symmetry energy at saturation density. (author)

School Crisis Management: A Model of Dynamic Responsiveness to Crisis Life Cycle

Science.gov (United States)

Liou, Yi-Hwa

2015-01-01

Purpose: This study aims to analyze a school's crisis management and explore emerging aspects of its response to a school crisis. Traditional linear modes of analysis often fail to address complex crisis situations. The present study applied a dynamic crisis life cycle model that draws on chaos and complexity theory to a crisis management case,…

Bio-fuels: energies between decline and revival; Les biocombustibles: des energies entre declin et renouveau

Energy Technology Data Exchange (ETDEWEB)

Mathieu, A.

1999-12-01

The development of bio-fuels is highly dependent of the variations of the prices of major energies, of the agriculture prices and of the situation of the environmental concerns. Thus at the crossroad of various sectors of activity one can question the relevance of the use of bio-fuels, today marginalized. Their development is always taken into consideration during crisis periods (agriculture, energy and pollution). However, once the crisis is gone, it remains the question of the economical viability and sustainability of the infatuation for these non-conventional energies. This paper presents some modalities of valorization of bio-fuels in France and in foreign countries: 1 - the renewable energy sources in France and in the European Union; 2 - the development of bio-fuels at the service of foresters and agriculturists: present day situation and perspectives of wood fuel in France (individual and collective uses), perspectives of biomass energy after the common agricultural policy reform, the objectives of the European Union; 3 - the energy valorization of biomass at the service of environment: forestry exploitation (land planning, pollution abatement), management of public dumps and water processing plants (incineration of household wastes, biogas generation); 4 - the bio-fuels competitiveness. (J.S.)

Density and starting-energy dependent effective interaction

International Nuclear Information System (INIS)

Yamaguchi, Norio; Nagata, Sinobu; Kasuga, Teruo

1979-01-01

A new effective potential constructed from the reaction matrix calculation of nuclear matters is proposed, taking three-body effects into account. Starting from the two-body scattering equation for nuclear matters, an equation with averaged momentum is introduced as the definition of effective interaction. The parameters in the equation are the Fermi momentum and the starting energy. The nuclear density dependence and the starting energy dependence are independently treated in the potential. The effective interactions including three-body effects were calculated. The dependence on the starting energy is large. The effective interaction is more attractive in the triplet E state, and assures overall saturation without any artificial renormalization. The reaction matrix calculation can be well reproduced by the calculation with this effective potential. The results of calculation for the binding energy of He-4 and O-16 and the shell model matrix elements of O-16 are represented. (Kato, T.)

Implementing the EU climate and energy package with the economic crisis

International Nuclear Information System (INIS)

Kerebel, C.

2009-01-01

In March 2007, the European heads of state and government agreed at their European Council upon a 20% greenhouse gas (GHG) emission reduction target compared to 1990-levels and a 20% share of renewable energies in EU's final energy consumption by 2020. To implement these commitments, the European Commission prepared a set of legislative proposals - the so-called 'Climate and Energy Package' - which was jointly endorsed by the European Parliament and the European Council in Dec. 2008 and formally adopted in April 2009. This new policy will run from 2013 to 2020. Hence, the reinforcement of European Union's energy and climate policy in the decade to come was decided and prepared in 2007-2008. But in the meantime, the economic conditions worldwide and in Europe more particularly have radically changed compared to what they were in 2007-2008 when the package was designed. The European Commission has drafted its proposals for the Climate and Energy Package following the outcomes of an impact assessment based on several modeling tools. These modeling tools were not used for determining the 20-20 in 2020 targets or checking their feasibility - those were political targets decided by the European Council in March 2007. The models served to assess the effects and costs of different allocation methodologies. In its drafting proposals, the Commission projected an annual Gross Domestic Product (GDP) growth of 2.2% on average until 2010 in the EU and a 2.4% growth between 2010 and 2020. But because of the economic crisis, the European Union has on the contrary seen a sharp fall of its GDP in 2009: according to the latest forecast by the International Monetary Fund (IMF), which is quite similar with forecasts from other organizations, such as the European Commission or the OECD, the EU-27 should see its GDP decrease by 4.2% in 2009. Opinions are divided when it comes to the question of when and how fast the economy recovers. The IMF has predicted a rather flat GDP growth in 2010

Implementing the EU climate and energy package with the economic crisis

Energy Technology Data Exchange (ETDEWEB)

Kerebel, C.

2009-07-01

In March 2007, the European heads of state and government agreed at their European Council upon a 20% greenhouse gas (GHG) emission reduction target compared to 1990-levels and a 20% share of renewable energies in EU's final energy consumption by 2020. To implement these commitments, the European Commission prepared a set of legislative proposals - the so-called 'Climate and Energy Package' - which was jointly endorsed by the European Parliament and the European Council in Dec. 2008 and formally adopted in April 2009. This new policy will run from 2013 to 2020. Hence, the reinforcement of European Union's energy and climate policy in the decade to come was decided and prepared in 2007-2008. But in the meantime, the economic conditions worldwide and in Europe more particularly have radically changed compared to what they were in 2007-2008 when the package was designed. The European Commission has drafted its proposals for the Climate and Energy Package following the outcomes of an impact assessment based on several modeling tools. These modeling tools were not used for determining the 20-20 in 2020 targets or checking their feasibility - those were political targets decided by the European Council in March 2007. The models served to assess the effects and costs of different allocation methodologies. In its drafting proposals, the Commission projected an annual Gross Domestic Product (GDP) growth of 2.2% on average until 2010 in the EU and a 2.4% growth between 2010 and 2020. But because of the economic crisis, the European Union has on the contrary seen a sharp fall of its GDP in 2009: according to the latest forecast by the International Monetary Fund (IMF), which is quite similar with forecasts from other organizations, such as the European Commission or the OECD, the EU-27 should see its GDP decrease by 4.2% in 2009. Opinions are divided when it comes to the question of when and how fast the economy recovers. The IMF has predicted a rather

Fulfilling the Kyoto protocol in Spain: A matter of economic crisis or environmental policies?

International Nuclear Information System (INIS)

Zafrilla, Jorge Enrique; López, Luis Antonio; Cadarso, María Ángeles; Dejuán, Óscar

2012-01-01

In 2008, Spain exceeded by 20.9% the CO 2 emissions allowed by the Kyoto Protocol for 2012. The financial and economic crisis has transformed these figures: as production fell so did energy demand and with it CO 2 emissions. Will the Spanish economic crisis allow Spain to fulfill its commitments? With this in mind, we have developed an extended input–output model able to forecast energy demand and compute CO 2 emissions linked to the consumption of energy goods: petroleum products, gas and coal. The results show that the crisis, and in particularly, the stagnation of the construction industry, is only one of the pillars which help to contain these emissions at −6.81%. The possibility of incorporating environmental policies, new technologies and increases in the price of crude oil in these simulations, means an even greater reduction of emissions than the impact of the crisis (−9.76%). The final result of our most pessimistic/realistic scenario is that, in 2012, Spain will exceed its CO 2 emissions, linked to the combustion of energy goods, by only 0.9%. - Highlights: ► We use an extended input–output model to forecast the evolution of CO 2 emissions. We evaluate the economic crisis impact on emissions figures (2008–2012). ► The environmental policies are introduced by considering structural trends. ► In our reference scenario, Spain exceeds Kyoto commitments only by 0.9% in 2012. ► The 16.6% emissions reduction is explained by trends (−9.8%) and crisis (−6,8%).

Crisis Communication of Nuclear Regulatory Organisations: Towards global thinking

International Nuclear Information System (INIS)

Martell, Meritxell; Menendez, Susan; Calvo, Marina

2013-01-01

The OECD Nuclear Energy Agency (NEA) Committee on Nuclear Regulatory Activities (CNRA) Working Group on Public Communication of Nuclear Regulatory Organisations (WGPC) organised the workshop 'Crisis communication: facing the challenges' on 9-10 May 2012 in Madrid to address the international dimension of the communicative responses to crises by assessing the experience of Nuclear Regulatory Organisations of the NEA member countries and their stakeholders. The CNRA/WGPC also prepared in 2011, before the Fukushima-Daiichi nuclear accident occurred, a Road Map for Crisis Communication of Nuclear Regulatory Organisations which focused only on national aspects. This 'road map' had not considered the international dimension. CNRA mandated the WGPC to expand the Road Map so as to conclude the follow-up activity on crisis communication. The objective of the present document is to firstly, identify the key messages which can be extracted from three surveys carried out among the WGPC members after Fukushima-Daiichi's accident (Appendices II, III and IV), and incorporate them into the Road Map for Crisis Communication. Secondly, the good practices on public communication of NROs, which were presented during the OECD/NEA Workshop on Crisis Communication: Facing the Challenges, are reported. Following the structure of the road map for public communication responses during crisis included in the NEA report entitled 'Road Map for Crisis Communication of Nuclear Regulatory Organisations - National aspects', the good practices on communication before, during and after a crisis are provided. Overall, the emphasis of this report is on the international aspects of crisis communication, rather than the national dimension. (authors)

Crisis management of State Office for Nuclear Safety of Czech Republic

International Nuclear Information System (INIS)

Koldus, F.; Starostova, V.

2005-01-01

tate Office for Nuclear Safety is a regulatory body responsible for governmental administration and supervision in the fields, of uses of nuclear energy and of radiation protection. firstly and secondly which establish a workplace for the crisis management and Crisis Staff and compile a Crisis Plan because of to be prepared to solve the emergency situations at the field of its own activities. At the beginning of the contribution the basic information about activities of Emergency Response Center of State Office for Nuclear Safety as a workplace of Crisis Staff of State Office for Nuclear Safety , which provide technical and organizational support to Crisis Staff of State Office for Nuclear Safety , is presented. State Office for Nuclear Safety has its own elaborated and approved Crisis Plan as a general document to plan measures and procedures in case of emergency situations and which is compile according to law No. 240/2000 Coll., on Crisis management of the Czech Republic, and according to Governmental Order No. 462/2000 Coll. (authors)

Presentation of the CEA's crisis national organization: coordination centre in case of crisis, crisis technical teams, intervention means, and so on

International Nuclear Information System (INIS)

Pectorin, X.

2010-01-01

After having briefly recalled the existence of a legal framework for crisis management organisation, this report briefly describes how the CEA plans the crisis management. This management is based on the definition of critical scenarios, on the building up of a crisis management team, and on the elaboration of crisis management operational documents. It evokes the alert organisation and the triggering of crisis management. Then, it describes the CEA's national crisis organisation with its main crisis management structures, the role and the operation of the Crisis Coordination Centre (CCC, the decision body), the role and operation of the Central Crisis Technical Teams (ETC-C, Equipes Techniques de Crise Centrales), the role of field interveners (various rescue, protection, health care and technical teams) and of other additional intervention actors. It evokes the objectives of the various exercises which are organised every year at the internal, national or international level

Study of energy dependence of a extrapolation chamber in low energy X-rays beams

International Nuclear Information System (INIS)

Bastos, Fernanda M.; Silva, Teogenes A. da

2014-01-01

This work was with the main objective to study the energy dependence of extrapolation chamber in low energy X-rays to determine the value of the uncertainty associated with the variation of the incident radiation energy in the measures in which it is used. For studying the dependence of energy, were conducted comparative ionization current measurements between the extrapolation chamber and two ionization chambers: a chamber mammography, RC6M model, Radcal with energy dependence less than 5% and a 2575 model radioprotection chamber NE Technology; both chambers have very thin windows, allowing its application in low power beams. Measurements were made at four different depths of 1.0 to 4.0 mm extrapolation chamber, 1.0 mm interval, for each reference radiation. The study showed that there is a variable energy dependence on the volume of the extrapolation chamber. In other analysis, it is concluded that the energy dependence of extrapolation chamber becomes smaller when using the slope of the ionization current versus depth for the different radiation reference; this shows that the extrapolation technique, used for the absorbed dose calculation, reduces the uncertainty associated with the influence of the response variation with energy radiation

Dependability of wind energy generators with short-term energy storage.

Science.gov (United States)

Sørensen, B

1976-11-26

Power fluctuations and power duration curves for wind energy generators, including energy storage facilities of a certain capacity, are compared to those of typical nuclear reactors. A storage system capable of delivering the yearly average power output for about 10 hours already makes the dependability of the wind energy system comparable to that of a typical nuclear plant.

Italy's recurrent energy dependency dilemma

International Nuclear Information System (INIS)

Ippolito, F.

1993-01-01

This paper first critically assesses the objectives of Italy's 1988 National Energy Plan which, in light of the moratorium on nuclear energy, called for moderate but steady reductions in imported energy supplies through the implementation of energy conservation programs and the development of available domestic conventional and renewable energy sources. The economics and energy analyses evidence that, in view this nation's current troubled economic situation, the Energy Plan's target for the year 2000 of a 76% dependency on foreign oil is just not good enough and not in line with stricter European environmental normatives limiting carbon dioxide emissions. It is argued that in order to effectively reduce the nation's excessively high energy costs, keep pace with other industrialized countries in a highly competitive market (Italy's energy tariffs are almost 55% greater than those of Germany and France), and to respect new European anti-pollution laws, Italy must restart its nuclear program and take advantage of the recent advances being made in passive reactor safety systems

Energy-dependent point interactions in one dimension

International Nuclear Information System (INIS)

Coutinho, F A B; Nogami, Y; Tomio, Lauro; Toyama, F M

2005-01-01

We consider a new type of point interaction in one-dimensional quantum mechanics. It is characterized by a boundary condition at the origin that involves the second and/or higher order derivatives of the wavefunction. The interaction is effectively energy dependent. It leads to a unitary S-matrix for the transmission-reflection problem. The energy dependence of the interaction can be chosen such that any given unitary S-matrix (or the transmission and reflection coefficients) can be reproduced at all energies. Generalization of the results to coupled-channel cases is discussed

World energy use in 2010: over 5% growth. Energy markets have combined crisis recovery and strong industry dynamism. Enerdata analyses the trends in energy demand, based on its 2010 data for G20 countries. May 5, 2011

International Nuclear Information System (INIS)

2011-01-01

Energy markets have combined crisis recovery and strong industry dynamism. Analysis of the energy consumption in 2010 of major countries by Enerdata, based on our global energy database. Energy consumption in the G20 soared by more than 5% in 2010, after the slight decrease of 2009. This strong increase is the result of two converging trends. On the one-hand, industrialized countries, which experienced sharp decreases in energy demand in 2009, recovered firmly in 2010, almost coming back to historical trends. Oil, gas, coal, and electricity markets followed the same trend. On the other hand, China and India, which showed no signs of slowing down in 2009, continued their intense demand for all forms of energy. (authors)

Molecular docking and 3D-QSAR studies on inhibitors of DNA damage signaling enzyme human PARP-1.

Science.gov (United States)

Fatima, Sabiha; Bathini, Raju; Sivan, Sree Kanth; Manga, Vijjulatha

2012-08-01

Poly (ADP-ribose) polymerase-1 (PARP-1) operates in a DNA damage signaling network. Molecular docking and three dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed on human PARP-1 inhibitors. Docked conformation obtained for each molecule was used as such for 3D-QSAR analysis. Molecules were divided into a training set and a test set randomly in four different ways, partial least square analysis was performed to obtain QSAR models using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Derived models showed good statistical reliability that is evident from their r², q²(loo) and r²(pred) values. To obtain a consensus for predictive ability from all the models, average regression coefficient r²(avg) was calculated. CoMFA and CoMSIA models showed a value of 0.930 and 0.936, respectively. Information obtained from the best 3D-QSAR model was applied for optimization of lead molecule and design of novel potential inhibitors.

Expression profiles of vault components MVP, TEP1 and vPARP and their correlation to other multidrug resistance proteins in ovarian cancer.

Science.gov (United States)

Szaflarski, Witold; Sujka-Kordowska, Patrycja; Pula, Bartosz; Jaszczyńska-Nowinka, Karolina; Andrzejewska, Małgorzata; Zawierucha, Piotr; Dziegiel, Piotr; Nowicki, Michał; Ivanov, Pavel; Zabel, Maciej

2013-08-01

Vaults are cytoplasmic ribonucleoprotein particles composed of three proteins (MVP, TEP1, vPARP) and vault‑associated RNAs (vRNAs). Although the cellular functions of vaults remain unclear, vaults are strongly linked to the development of multidrug resistance (MDR), the major obstacle to the efficient treatment of cancers. Available published data suggest that vaults and their components are frequently upregulated in broad variety of multidrug-resistant cancer cell lines and tumors of different histological origin. Here, we provide detailed analysis of vault protein expression in post-surgery ovarian cancer samples from patients that were not exposed to chemotherapy. Our analysis suggests that vault proteins are expressed in the ovaries of healthy individuals but their expression in cancer patients is changed. Specifically, MVP, TEP1 and vPARP mRNA levels are significantly decreased in cancer samples with tendency of lower expression in higher-grade tumors. The pattern of vault protein mRNA expression is strongly correlated with the expression of other MDR-associated proteins such as MDR1, MRP1 and BCRP. Surprisingly, the protein levels of MVP, TEP1 and vPARP are actually increased in the higher‑grade tumors suggesting existence of post-transcriptional regulation of vault component production.

Spirituality, Crisis, and Illusions

Directory of Open Access Journals (Sweden)

LOSONCZ, Alpar

2016-03-01

Full Text Available This article deals with the structural interpretations of the ongoing crisis. The author considers the approaches of Joseph Alois Schumpeter and Tibor Scitovsky that thematize the long-run destiny of capitalism. The viewpoint is constituted as the relation between the structural socio-economic tendencies and existential constellations. What is addressed by the crisis is capitalism as a dependent system. The author emphasizes that capitalism cannot survive without the outside sphere, reciprocal interactions, economics of community, eco-system and complex eco-social moments. This can be applied to the frequently mentioned embeddedness which is related to Polanyi and other researchers who are influenced by Polanyi’s concepts. Embeddedness can be analyzed through the holon, from the inside perspective. Only comprehensive perspective enables to see the entire horizon, since capitalism cannot summarize the eco-system, not even with the most sophisticated techniques that recognize monetary expressions.

Behaviour of Lyapunov exponents near crisis points in the dissipative standard map

Science.gov (United States)

Pompe, B.; Leven, R. W.

1988-11-01

We numerically study the behaviour of the largest Lyapunov characteristic exponent λ1 in dependence on a control parameter in the 2D standard map with dissipation. In order to investigate the system's motion in parameter intervals slightly above crisis points we introduce "partial" Lyapunov exponents which characterize the average exponential divergence of nearby orbits on a semi-attractor at a boundary crisis and on distinct parts of a "large" chaotic attractor near an interior crisis. In the former case we find no significant difference between λ1 in the pre-crisis regime and the partial Lyapunov exponent describing transient chaotic motions slightly above the crisis. For the latter case we give a quantitative description of the drastic increase of λ1. Moreover, a formula which connects the critical exponent of a chaotic transient above a boundary crisis with a pointwise dimension is derived.

Perspective of long term demand and supply of energy and general inspection of energy policy

International Nuclear Information System (INIS)

1983-01-01

Since the oil crisis, Japanese energy policy was promoted to get rid of the excess dependence on petroleum and to attain energy security, but energy situation largely changed during the past ten years, and it has become necessary to make general inspection on the long term demand and supply of energy and the energy policy. After the second oil crisis, the worldwide demand of petroleum decreased drastically due to the rapid price rise, and the base price of crude oil was lowered for the first time. It is necessary to positively endeavor to reduce energy cost with new idea. The points of the general inspection are the correspondence of the energy policy to the large structural change of energy, the most desirable system for attaining the optimum structure of energy demand and supply and the utilization of market mechanism as far as possible. This report is the results of discussion held eight times since April, 1983. The change of energy situation in Japan and abroad and the perspective, the new problems in energy countermeasures and the trend of response, the preferential and effective promotion of general energy countermeasures and so on are reported. This report shows the fundamental direction of energy countermeasures hereafter, and the concrete and special examination must be made on many remaining problems. (Kako, I.)

Disrupting gatekeeping practices: Journalists’ source selection in times of crisis

Science.gov (United States)

van der Meer, Toni G.L.A.; Verhoeven, Piet; Beentjes, Johannes W.J.; Vliegenthart, Rens

2016-01-01

As gatekeepers, journalists have the power to select the sources that get a voice in crisis coverage. The aim of this study is to find out how journalists select sources during a crisis. In a survey, journalists were asked how they assess the following sources during an organizational crisis: news agencies, an organization undergoing a crisis, and the general public. The sample consisted of 214 Dutch experienced journalists who at least once covered a crisis. Using structural equation modeling, sources’ likelihood of being included in the news was predicted using five source characteristics: credibility, knowledge, willingness, timeliness, and the relationship with the journalist. Findings indicated that during a crisis, news agencies are most likely to be included in the news, followed by the public, and finally the organization. The significance of the five source characteristics is dependent on source type. For example, to be used in the news, news agencies and organizations should be mainly evaluated as knowledgeable, whereas information from the public should be both credible and timely. In addition, organizations should not be seen as too willing or too eager to communicate. The findings imply that, during a crisis, journalists remain critical gatekeepers; however, they rely mainly on familiar sources. PMID:29278263

Disrupting gatekeeping practices: Journalists' source selection in times of crisis.

Science.gov (United States)

van der Meer, Toni G L A; Verhoeven, Piet; Beentjes, Johannes W J; Vliegenthart, Rens

2017-10-01

As gatekeepers, journalists have the power to select the sources that get a voice in crisis coverage. The aim of this study is to find out how journalists select sources during a crisis. In a survey, journalists were asked how they assess the following sources during an organizational crisis: news agencies, an organization undergoing a crisis, and the general public. The sample consisted of 214 Dutch experienced journalists who at least once covered a crisis. Using structural equation modeling, sources' likelihood of being included in the news was predicted using five source characteristics: credibility, knowledge, willingness, timeliness, and the relationship with the journalist. Findings indicated that during a crisis, news agencies are most likely to be included in the news, followed by the public, and finally the organization. The significance of the five source characteristics is dependent on source type. For example, to be used in the news, news agencies and organizations should be mainly evaluated as knowledgeable, whereas information from the public should be both credible and timely. In addition, organizations should not be seen as too willing or too eager to communicate. The findings imply that, during a crisis, journalists remain critical gatekeepers; however, they rely mainly on familiar sources.

Chinese Crisis Management

National Research Council Canada - National Science Library

Gudgel, Andy

2004-01-01

.... China's crisis management strategy is geared towards obtaining the maximum political advantage for China, as opposed to resolving the crisis. China tries to define the crisis on its terms in order to shape the resolution favorably.

Energy dependence corrections to MOSFET dosimetric sensitivity

International Nuclear Information System (INIS)

Cheung, T.; Yu, P.K.N.; Butson, M.J.; Illawarra Cancer Care Centre, Crown St, Wollongong

2009-01-01

Metal Oxide Semiconductor Field Effect Transistors (MOSFET's) are dosimeters which are now frequently utilized in radiotherapy treatment applications. An improved MOSFET, clinical semiconductor dosimetry system (CSDS) which utilizes improved packaging for the MOSFET device has been studied for energy dependence of sensitivity to x-ray radiation measurement. Energy dependence from 50 kVp to 10 MV x-rays has been studied and found to vary by up to a factor of 3.2 with 75 kVp producing the highest sensitivity response. The detectors average life span in high sensitivity mode is energy related and ranges from approximately 100 Gy for 75 kVp x-rays to approximately 300 Gy at 6MV x-ray energy. The MOSFET detector has also been studied for sensitivity variations with integrated dose history. It was found to become less sensitive to radiation with age and the magnitude of this effect is dependant on radiation energy with lower energies producing a larger sensitivity reduction with integrated dose. The reduction in sensitivity is however approximated reproducibly by a slightly non linear, second order polynomial function allowing corrections to be made to reading to account for this effect to provide more accurate dose assessments both in phantom and in-vivo.

Energy dependence corrections to MOSFET dosimetric sensitivity.

Science.gov (United States)

Cheung, T; Butson, M J; Yu, P K N

2009-03-01

Metal Oxide Semiconductor Field Effect Transistors (MOSFET's) are dosimeters which are now frequently utilized in radiotherapy treatment applications. An improved MOSFET, clinical semiconductor dosimetry system (CSDS) which utilizes improved packaging for the MOSFET device has been studied for energy dependence of sensitivity to x-ray radiation measurement. Energy dependence from 50 kVp to 10 MV x-rays has been studied and found to vary by up to a factor of 3.2 with 75 kVp producing the highest sensitivity response. The detectors average life span in high sensitivity mode is energy related and ranges from approximately 100 Gy for 75 kVp x-rays to approximately 300 Gy at 6 MV x-ray energy. The MOSFET detector has also been studied for sensitivity variations with integrated dose history. It was found to become less sensitive to radiation with age and the magnitude of this effect is dependant on radiation energy with lower energies producing a larger sensitivity reduction with integrated dose. The reduction in sensitivity is however approximated reproducibly by a slightly non linear, second order polynomial function allowing corrections to be made to readings to account for this effect to provide more accurate dose assessments both in phantom and in-vivo.

Energy crisis: policy response

Energy Technology Data Exchange (ETDEWEB)

Nemetz, P N [ed.

1981-01-01

Resource-management techniques must be applied to assess the risks, benefits, priorities, and potentials of the different energy options as prospective slowdowns in the flow of crude oil threaten recurring energy crises. The 23 contributors to this book use various managerial approaches in the formulation of energy policies. There is little agreement among the remedies put forth as to which policies will best achieve a balanced energy system. While some experts argue that Canadian energy policy should emphasize intensive development of coal, others claim that it ought to strive for greater reliance on electricity, and still others contend that the transition to soft energy paths is a preferable policy approach. The essays offer a broad range of policy responses, examining not only technical and economic possibilities, but political and institutional alternatives as well. 147 references, 18 figures, 30 tables.

Constraints on cosmological birefringence energy dependence from CMB polarization data

International Nuclear Information System (INIS)

Gubitosi, G.; Paci, F.

2013-01-01

We study the possibility of constraining the energy dependence of cosmological birefringence by using CMB polarization data. We consider four possible behaviors, characteristic of different theoretical scenarios: energy-independent birefringence motivated by Chern-Simons interactions of the electromagnetic field, linear energy dependence motivated by a 'Weyl' interaction of the electromagnetic field, quadratic energy dependence, motivated by quantum gravity modifications of low-energy electrodynamics, and inverse quadratic dependence, motivated by Faraday rotation generated by primordial magnetic fields. We constrain the parameters associated to each kind of dependence and use our results to give constraints on the models mentioned. We forecast the sensitivity that Planck data will be able to achieve in this respect

Crisis as a Factor of the Sustainability Violation in the Economic Systems

Directory of Open Access Journals (Sweden)

Dzhereliuk Iuliia O.

2017-01-01

Full Text Available The article substantiates that crisis is a factor of violation of the enterprise’s sustainability as economic system, crisis can occur at all stages of the life cycle of enterprise, act as a brake against the further development of enterprise and its movement to the next stage of development. On the basis of theoretical generalization, the author’s own approach to the definition of concept of «crisis» is presented. Causes of occurrence of crisis were generalized depending on certain stage of the life cycle of enterprise. It has been specified that crisis poses a threat to the sustainability of enterprise, but, despite this, it is the regularity and necessity of development, which in all its manifestations and consequences will be overcome by anti-crisis. The theoretical approaches by different scientists as to interpretation of the concept of «anti-crisis sustainability» were considered that allowed to substantiate the author’s own approach to the interpretation of this concept. Prospects for further research in this directions will be systematization of the factors to ensure the anti-crisis sustainability of enterprise in a competitive environment.

Managing crisis

OpenAIRE

Bakacsi, Gyula

2010-01-01

The traditional approach to crisis management suggest autocratic leadership, that has risks anyway (leader is the bottle-neck of problem solving, single-loop learning, crisis management is a matter of efficiency). However, managing nowadays crisis is rather effectiveness issue, and requires double-loop learning (second-order change) and leadership role in the sense of Kotter’s theory. Paper discusses the top-management’s leadership responsibilities, and their special tasks in the problem solv...

Crisis Response Strategy and Crisis Types Suitability: A Preliminary Study on MH370

Directory of Open Access Journals (Sweden)

Mohamad Ashari Noratikah

2017-01-01

Full Text Available In time of crisis, the organisation’s tactic in responding to the crisis according to its type/s may significantly affect the organisation’s effort to survive its reputational damages. The study of crisis response strategy (CRS requires further exploration within the Malaysian context, moreso with the greater and apparent use of social media as a platform for the organisation in crisis to reach out to its stakeholders. This preliminary paper studies the MH370 crisis in light of Coombs [1] Situational Crisis Communication Theory (SCCT. It aims to discuss the suitability of the CRS applied by Malaysia Airlines System (MAS with the crisis type/s that was/were experienced by the organisation. Hence, the need for this paper to investigate the crisis type/s of MH370 and examines the CRS applied by MAS by content analysing media statements that were disseminated directly to the organisation’s stakeholders on Facebook during the first day of the crisis. Results ultimately show an interesting analysis to the crisis type of MH370, and the suitability of the CRS applied by MAS for that matter.

Energy and Economic Crisis

International Nuclear Information System (INIS)

2000-01-01

The relationship between the economy and the energy is much more complex of what looks. However, they are continued making, in some cases, absolute statements that used to listen in the past as dogmas, among those that are highly correlated in energy consumption and the Gross National Product GNP and that the countries follow the same development pattern more or less, mainly in connection with the energy consumption. Such statements are not completely misses, neither completely correct and they have behind many simplifications. Of a part, of the historical evolution analysis of several countries or groups of countries on long periods, it confirms the fact that the economic growth, induces an increment in general in the total consumption of energy and vice versa: Energy available with more speed and to smaller price it favors the economic development. Other important factors that impact in the growth of the energy consumption, besides the economic development, are, among, the population's increment, the state of technological development and the cultural customs of use

BANKING INTERMEDIATION AND CONSEQUENCES OF FINANCIAL CRISIS

Directory of Open Access Journals (Sweden)

Medar Lucian-Ion

2012-12-01

Full Text Available The financial intermediation of bank institutions, has an essential role in mobilising of the available funds and their distribution in various products and services, for economic growth. The extent that banking system is in distress or passing through a period of crisis, then, everything turns into a general crisis, especially that, in some states, natural and legal persons have been learned ,,to live’’ on the credits.The effectiveness of banking intermediation activity in Romania depends on how fast the market is enabled under the influence of the new European regulations. The Romanian market in all its forms is the second largest in the EU, and the banking system is almost entirely made up of banks with foreign capital. The romanian banking market has not suffered so much because of the financial crisis. To the extent that banking institutions provide the necessary funds, Romania has important resources for the transition to a new economic cycle based on sustainable development.

Hemolytic crisis

Science.gov (United States)

... page: //medlineplus.gov/ency/article/003270.htm Hemolytic crisis To use the sharing features on this page, please enable JavaScript. Hemolytic crisis occurs when large numbers of red blood cells ...

the dutch crisis and recovery act: economic recovery and legal crisis

African Journals Online (AJOL)

Jonathan

THE DUTCH CRISIS AND RECOVERY ACT: ECONOMIC RECOVERY AND. LEGAL CRISIS? J Verschuuren. 1 Introduction. Throughout the world, governments are responding to the financial and economic crisis. Such responses vary from supporting the banking system to adopting economic stimulus packages. The latter ...

Dalla crisi finanziaria alla crisi reale. ( Financial and real crisis

Directory of Open Access Journals (Sweden)

Carlo D'Adda

2010-03-01

Full Text Available  The financial crisis of 2008 is put in relation with two bubbles, financial and housing. Easy credit is at the origin of both bubbles. Risky bonds were issued to mobilize mortgages originated in the housing market, and bad bonds entered a fantastic number of institutional and private portfolios all over the world without any perception of the their risk. Unfortunately, bank credit to speculators was abundant and fed the final growth of the bubbles. When fears started to spread, the fall was immediate and expectations impaired very rapidly. The main aggregate demand components were severely curtailed and production fell as well. This is the crisis of the real economy. Fortunately, as opposed to what happened in 1929, the interventions of central banks and governments have been of an unprecedented size. The bail out of insolvent banks in particular has been providential. The exit from the current crisis, however, will surely be slow.  JEL: E44, G01, G10

If there is dissipation the particle can gain energy

International Nuclear Information System (INIS)

De Carvalho, R Egydio

2015-01-01

In this work, we summarize two different mechanisms to gain energy from the presence of dissipation in a time-dependent non-linear system. The particles can gain energy, in the average, from two different scenarios: i) for very week dissipation with the creation of an attractor with high velocity, and ii) in the opposite limit, for very strong dissipation, the particles can also gain energy from a boundary crisis. From the thermodynamic viewpoint both results are totally acceptable. (paper)

Are oil and gas stocks from the Australian market riskier than coal and uranium stocks? Dependence risk analysis and portfolio optimization

International Nuclear Information System (INIS)

Arreola Hernandez, Jose

2014-01-01

This article models the dependence risk and resource allocation characteristics of two 20-stock coal–uranium and oil–gas sector portfolios from the Australian market in the context of the global financial crisis of 2008–2009. The modeling framework implemented consists of pair vine copulas and, linear and nonlinear portfolio optimization methods with respect to five risk measures. The paper's objectives are to find out if the oil and gas stocks are riskier than the coal and uranium stocks, to identify the optimization method and risk measure that produce the best risk-return trade-off, to recognize the stocks in which the optimal weight allocations converge on average, and to acknowledge the vine copula model that best accounts for the overall dependence of the energy portfolios. The research findings indicate that the oil stocks have higher dependence risk than the coal, uranium and gas stocks in financial crisis periods. The higher risk of the oil stocks is confirmed by the larger concentration of symmetric and asymmetric dependence they have in the negative tail. The canonical vine (c-vine) copula model is observed to better capture the overall dependence of the energy portfolios. The combination of a pair c-vine copula and nonlinear portfolio optimization produces the highest return relative to risk. The optimal weight allocations converge on average in some stocks. - Highlights: • Vine copula dependence modeling of coal, uranium, oil and gas stocks • Oil stocks are riskier than coal, uranium and gas stocks in financial crisis periods. • The c-vine model better captures the overall dependence of the energy portfolios. • Vine copulas and nonlinear optimization combined produce the best results. • The optimal weight allocations converge on average in some stocks

Energy-dependent inversion of p+16O scattering data

International Nuclear Information System (INIS)

Cooper, S.G.

1997-01-01

A fast iterative procedure is developed to determine potentials by inversion from elastic cross section, analysing powers and reaction cross-section measurements covering a wide energy range. The procedure incorporates both energy and parity dependence. The method is applied to extensive p+ 16 O scattering data for an energy range from 27.3 to 46.1 MeV, giving a solution which simultaneously reproduces the data at all energies. The wide angle data is well reproduced by including parity dependence and a linear energy dependence is established for the real potential, including the parity-dependent component. The real terms agree qualitatively with potentials derived from the single channel RGM, but the central and spin-orbit imaginary components have distinct features strongly suggestive of further non-local contributions, possibly arising from channel coupling. The large data set is found essential to reduce the potential ambiguities present when fitting scattering data. (orig.)

Current Studies on Crisis Response Communication:Focus on Crisis Communication Theories in the United States

OpenAIRE

平澤 敦

2017-01-01

Researchers have shown an increased interest in crisis communication as well as crisis management. Crisis communication became an established corporate discipline in the last 20 years. Because of the recent rash of corporate (organizational) scandals, natural disasters and so on, importance of crisis communication (management) attracts much more attention than the past.Crisis communication is used to help governments and companies organizations to respond to and recover from a crisis. Crisis ...

Conceptual Framework of Crisis Negotiation Competency Development in Managers of Internal Affairs Bodies

Directory of Open Access Journals (Sweden)

Vakhnina V.V.

2017-11-01

Full Text Available In this article the authors examine the psychological features of the development of an integral psychological concept of crisis negotiation activities from the perspective of system-situational and reflexive approaches.This research forms the basis of a new scientific direction in legal psychology, the psychology of crisis negotiation activities of employees of internal affairs bodies, as a system of coping with and preventing crisis in negotiations.The data was collected and analysed in several stages from 1995 to 2014 and included a survey of managers of internal affairs bodies as well as a systematic analysis of the data pool of 1705 crisis situations.Basing on the analysis the authors propose a matrix of negotiations which identifies priority strategies and possible crisis zones at various stages of the negotiation process depending on the characteristics of the situation, thus helping to carry out crisis negotiations effectively.

Crisis communication: an inequalities perspective on the 2010 Boston water crisis.

Science.gov (United States)

Galarce, Ezequiel M; Viswanath, K

2012-12-01

Although the field of crisis risk communication has generated substantial research, the interaction between social determinants, communication processes, and behavioral compliance has been less well studied. With the goal of better understanding these interactions, this report examines how social determinants influenced communications and behavioral compliance during the 2010 Boston, Massachusetts, water crisis. An online survey was conducted to assess Boston residents' knowledge, beliefs, attitudes, mass and interpersonal communication, and preventive behaviors on emergency preparedness topics dealing with the water crisis. Of a total sample of 726 respondents, approximately one-third (n = 267) reported having been affected by the water crisis. Only data from affected participants were analyzed. Following an order to boil water, 87.5% of respondents refrained from drinking unboiled tap water. These behaviors and other cognitive and attitudinal factors, however, were not uniform across population subgroups. All communication and behavioral compliance variables varied across sociodemographic factors. Crisis communication, in conjunction with other public health preparedness fields, is central to reducing the negative impact of sudden hazards. Emergency scenarios such as the Boston water crisis serve as unique opportunities to understand how effectively crisis messages are conveyed to and received by different segments of the population.

Talking about a Crisis - Italian Bloggers' Perceptions of Alitalia's Crisis Responses

DEFF Research Database (Denmark)

Valentini, Chiara; Romenti, Stefania

In this study we intend to examine the way in which bloggers and blog readers framed a company performance during a crisis, but looking at the most discussed crisis's themes, at the sources of their statements and at their evaluations. To facilitate that, we focused on a specific crisis case......, the Alitalia's one, as this case shows some specificities that have influenced the contents of the communicative discourses among bloggers and blog readers on the organization's response to its crisis....

Hypertensive Crisis

Science.gov (United States)

... Artery Disease Venous Thromboembolism Aortic Aneurysm More Hypertensive Crisis: When You Should Call 9-1-1 for ... Nov 13,2017 A hypertensive ( high blood pressure ) crisis is when blood pressure rises quickly and severely ...

About Crisis. A Short and Joyless Description

Directory of Open Access Journals (Sweden)

Ion Pohoata

2009-05-01

Full Text Available Crisis clearly distinguishes itself from the large mass of economic phenomena through its provocative force, which fuels theoretical discourse. The more harmful, the more generous the energies it deploys and consumes for explanatory and obstacle overcoming purposes. The result is that every crisis teaches us a lesson. What interests us is who writes and who learns from this lesson, and if they do. Then we try to find why serious crises, like the current one, occur once or twice in a century. What is the role that big world market players have in crisis "preparation", onset and resorption? Do solutions originate in the state's support or in the market? Does globalization erase national borders in such situations? How and to what extent real economy may penalize a guilty party that constantly comes from nominal economy? What are the problems raised by such an outcome for the strategy to follow and for economic sciences in general, etc.?

[Expression of PARP/NF-κB and intervention effect of 5-AIQ/PDTC in SAP rats with adrenal damage].

Science.gov (United States)

Yang, Bo; Guo, Wen-Yi; Yu, Jia; Zhao, Kai-liang; Shi, Qiao; Zuo, Teng; Wang, Wei-xing

2013-10-15

To explore the expression of poly (ADP-ribose) polymerase/nuclear factor-κB (PARP/NF-κB) and intervention effect of 5-aminoisoquinolinone/pyrrolidine dithiocarbamate (5-AIQ/PDTC) in severe acute pancreatitis (SAP) rats with adrenal damage. The primarily cultured adrenocortical cells were quantitatively divided into control group (SO), pancreatitis group (SAP), PDTC drug control group (SO+PDTC), PDTC intervention group (SAP+PDTC), 5-AIQ drug control group (SO+ 5-AIQ) and 5-AIQ intervention group (SAP+5-AIQ). The SAP and 2 intervention groups were stimulated with the sera of SAP rats. Then corresponding drugs were added and culture continued for 12 hours. The corticosterone levels and PARP/NF-κB expression were observed for each group. Adrenal cells in vitro cultured were round or oval, had secretory granules and could be stained by 3β-hydroxysteroid dehydrogenase antibody. The adherence rate was 60% after 48-hour culturing. The corticosterone level of SAP group was significantly lower than that of SO group [ (216.4 ± 15.7) vs (294.8 ± 16.3) µg/L, P SAP group (P SAP and PDTC intervention groups were higher than SO group while 5-AIQ intervention group was significantly lower than SAP and PDTC intervention groups, but higher than SO and drug control groups. The expression of NF-κB in SAP group was higher than that in SO group. Two intervention groups were lower than SAP group, but higher than SO and drug control groups. The pathway of PARP/NF-κB participates in adrenal damage of SAP rats. To a certain extent, the uses of 5-AIQ and PDTC may alleviate adrenal damage.

Energy and markets: a dangerous liaison

International Nuclear Information System (INIS)

Pauron, M.

2008-01-01

At the occasion of a colloquium organised by the Paris-Dauphine university, several economists have discussed the possible impacts that the world financial crisis would have on the energy. The energy crisis and the financial crisis are distinct crises with strong interactions, like the rise of the oil barrel price which follows the dollar drop, but no simple answer can be drawn since no consensus exists on the ins and outs of the crisis

NATIONAL SYSTEM OF CRISIS MANAGEMENT AS A TACTICAL AND STRATEGIC DIRECTION OF THE RUSSIAN ECONOMY

Directory of Open Access Journals (Sweden)

I. V. Gladkov

2014-01-01

Full Text Available Depending on the origin, nature and extent of the crisis, measures of state intervention and direction must be different. In this regard, it seems appropriate to talk about the need to form a national crisis management system.

Why there is no crisis of the "spin crisis"

CERN Document Server

Bradamante, F

2016-01-01

In a recent eprint [1] it is argued that the experimental determinations of the spin-dependent structure function g1 have been done incorrectly and that a reanalysis of those data suggests that the original motivation to argue fora "spin crisis", namely the small contribution of quark spins to the nucleon spin, is invalid. In a subsequent note [2] the theoretical understanding, as it has evolved from almost 30 years of theoretical and experimental scrutiny, has been shortly summarised. In this short note, arguments are presented that the line of reasoning in Ref. [1] does not apply, at least not for the Compass data.

Study on energy demand function of korea considering replacement among energy sources and the structural changes of demand behavior

Energy Technology Data Exchange (ETDEWEB)

Moon, C.K. [Korea Energy Economics Institute, Euiwang (Korea, Republic of)

1997-08-01

If the necessity of careful study on energy function is mentioned, it should be stressed that energy investment not only needs a long gestation period but also, acts as the bottleneck in the production capacity of an economy when investment is not enough. Thereby, the adverse effect of an energy supply shortage is very big. Especially, the replacement/supplemental relationship between energy and capital which corresponds to the movement on the iso-quanta curve is believed to have a direct relation with the answer as to whether long-term economic development would be possible under an energy crisis and its influence on technology selection. Furthermore, the advantages of technological advances which correspond to the movement on the iso-quanta curve has a direct relation with the question whether long-term economic development would be possible under an energy crisis depending on whether its direction is toward energy-saving or energy-consuming. This study tackles the main issues and outlines of the quantitative approach method based on the accounting approach method for modeling energy demand, quantitative economics approach method, and production model. In order to model energy demand of the Korean manufacturing industry, related data was established and a positive analytical model is completed and presented based on these. 122 refs., 10 tabs.

Package models and the information crisis of prebiotic evolution.

Science.gov (United States)

Silvestre, Daniel A M M; Fontanari, José F

2008-05-21

The coexistence between different types of templates has been the choice solution to the information crisis of prebiotic evolution, triggered by the finding that a single RNA-like template cannot carry enough information to code for any useful replicase. In principle, confining d distinct templates of length L in a package or protocell, whose survival depends on the coexistence of the templates it holds in, could resolve this crisis provided that d is made sufficiently large. Here we review the prototypical package model of Niesert et al. [1981. Origin of life between Scylla and Charybdis. J. Mol. Evol. 17, 348-353] which guarantees the greatest possible region of viability of the protocell population, and show that this model, and hence the entire package approach, does not resolve the information crisis. In particular, we show that the total information stored in a viable protocell (Ld) tends to a constant value that depends only on the spontaneous error rate per nucleotide of the template replication mechanism. As a result, an increase of d must be followed by a decrease of L, so that the net information gain is null.

Crisis Response Strategy and Crisis Types Suitability: A Preliminary Study on MH370

OpenAIRE

Mohamad Ashari Noratikah; Abang Ahmad Dayang Aizza Maisha; Samani Mus Chairil

2017-01-01

In time of crisis, the organisation’s tactic in responding to the crisis according to its type/s may significantly affect the organisation’s effort to survive its reputational damages. The study of crisis response strategy (CRS) requires further exploration within the Malaysian context, moreso with the greater and apparent use of social media as a platform for the organisation in crisis to reach out to its stakeholders. This preliminary paper studies the MH370 crisis in light of Coombs [1] Si...

[Economic crisis and mental health. SESPAS report 2014].

Science.gov (United States)

Gili, Margalida; García Campayo, Javier; Roca, Miquel

2014-06-01

Studies published before the financial crisis of 2008 suggest that economic difficulties contribute to poorer mental health. The IMPACT study conducted in primary health care centers in Spain found a significant increase in common mental disorders. Between 2006 and 2010, mood disorders increased by 19%, anxiety disorders by 8% and alcohol abuse disorders by 5%. There were also gender differences, with increased alcohol dependence in women during the crisis period. The most important risk factor for this increase was unemployment. In parallel, antidepressant consumption has increased in recent years, although there has not been a significant inrease in the number of suicides. Finally, the study offers some proposals to reduce the impact of the crisis on mental health: increased community services, employment activation measures, and active policies to reduce alcohol consumption and prevent suicidal behavior, particularly among young people. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

The Euro crisis. Causes and Symptoms

Directory of Open Access Journals (Sweden)

Christoph S. Weber

2015-06-01

Full Text Available The Euro crisis is mainly a consequence of the international financial crisis of 2008. Thereby, the term Euro crisis is misleading as there is no currency crisis. First, the article shows some of the birth defects of the Euro. Second, it shows that the increase in public debt was caused by rescue measures for banks and anti-cyclical fiscal policy. Third, we argue that the Euro crisis is not just one crisis (a sovereign debt crisis but it is a combination of several macroeconomic crises including a growth crisis, a labour market crisis, a public debt crisis, and a current account crisis.

The impact of crisis response strategy, crisis type, and corporate social responsibility on post-crisis consumer trust and purchase intention

NARCIS (Netherlands)

Hegner, Sabrina M.; Beldad, Ardion D.; Kraesgenberg, Anne Lotte

2016-01-01

Organisational crises can have deleterious consequences for organisational reputation and sales. Hence, one exigent question pertains to the effects of a company's action prior to the crisis and its crisis response on customers' post-crisis attitude and behavioural intention. To address that

THE CURRENCY CRISIS TRIGGER OF THE ROMANIAN FINANCIAL CRISIS OF 2008

Directory of Open Access Journals (Sweden)

Radu SOVIANI

2014-07-01

Full Text Available This paper analyses the ways the financial crisis started to manifest into the Romanian Financial System, through the exchange rate channel. The focus of this Paper is on how the Romanian decision makers contributed in triggering the financial crisis (that would have been triggered anyway. The paper will determine the trigger (the first obvious event for the Romanian Financial Crisis (the debut and it will prove that the consequences of this trigger could have been anticipated - it is in line with similar triggers for the debut in other currency crises. Therefore, one of the main conclusions of this paper is that while a global crisis starts to manifest the local economy should limit the exuberance of the decision makers in order to smooth the effects of the crisis.

Crisis Communication

OpenAIRE

Anca Jarmila Guţă

2006-01-01

The paper presents the manner in which the crisis of different types can disturb the normal activity of an organization and also the modalities by which the communication in this situation can solve or attenuate the negative effects of a crisis.

Effects of symmetry energy and momentum dependent interaction on low-energy reaction mechanisms

Directory of Open Access Journals (Sweden)

Zheng H.

2016-01-01

Full Text Available We study the dipole response associated with the Pygmy Dipole Resonance (PDR and the Isovector Giant Dipole Resonance (IVGDR, in connection with specific properties of the nuclear effective interaction (symmetry energy and momentum dependence, in the neutron-rich systems 68Ni, 132Sn and 208Pb. We perform our investigation within a microscopic transport model based on the Landau-Vlasov kinetic equation.We observe that the peak energies of PDR and IVGDR are shifted to higher values when employing momentum dependent interactions, with respect to the results obtained neglecting momentum dependence. The calculated energies are close to the experimental values and similar to the results obtained in Hartree-Fock (HF with Random Phase Approximation (RPA calculations.

The US Financial Crisis

DEFF Research Database (Denmark)

Campbell, John L.

2011-01-01

Many comparative political economists hold that market performance depends on the presence of institutional complementarities. Some argue that when institutions reinforce similar incentives markets work best. Others disagree and argue that for markets to function well institutions must compensate...... for each other's shortcomings rather than reinforce each other's incentives. This paper uses evidence from the US financial crisis of 2008 to adjudicate this debate. It argues that different types of institutional complementarities are necessary in combination to ensure market stability and successful...

Collisional energy dependence of molecular ionization by metastable rare gas atoms

International Nuclear Information System (INIS)

Martin, R.M.; Parr, T.P.

1979-01-01

The collisional energy dependence of several molecular total ionization cross sections by metastable rare gas atoms was studied over the thermal energy region using the crossed molecular beam time-of-flight method. Results are reported for the collision systems He, Ne, and Ar ionizing the geometric isomers cis- and trans-dichloroethylene and ortho- and para-dichlorobenzene. The He ionization cross sections oscillate about an energy dependence of E/sup -1/2/ over the energy range 0.004--1.0 eV, and the Ar*+para-dichlorobenzene cross section oscillates about an energy dependence of E/sup -2/5/ over the energy range 0.011--0.64 eV. The remaining systems are characterized by ''bent'' E/sup -m/ dependences with m values of 0.56--0.70 at low energies changing to 0.07--0.29 at higher energies. Comparison with the slopes of the He* systems and the Ar*+para-dichlorobenzene system shows that the ''bent'' and ''oscillating'' energy dependences are similar except for the form of the cross section functions at the lowest energies. No systematic differences are found between the cross section energy dependences for ionization of different geometric isomers or for ionization by the different metastable rare gas atoms

Poly(ADP-ribose polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain

Directory of Open Access Journals (Sweden)

Prashanth Komirishetty

2016-01-01

Full Text Available Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose polymerase (PARP upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neuronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the involvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.

Poly(ADP-ribose) polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain.

Science.gov (United States)

Komirishetty, Prashanth; Areti, Aparna; Gogoi, Ranadeep; Sistla, Ramakrishna; Kumar, Ashutosh

2016-10-01

Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose) polymerase (PARP) upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neuronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the involvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.

Long Memory Models to Generate Synthetic Hydrological Series

Directory of Open Access Journals (Sweden)

Guilherme Armando de Almeida Pereira

2014-01-01

Full Text Available In Brazil, much of the energy production comes from hydroelectric plants whose planning is not trivial due to the strong dependence on rainfall regimes. This planning is accomplished through optimization models that use inputs such as synthetic hydrologic series generated from the statistical model PAR(p (periodic autoregressive. Recently, Brazil began the search for alternative models able to capture the effects that the traditional model PAR(p does not incorporate, such as long memory effects. Long memory in a time series can be defined as a significant dependence between lags separated by a long period of time. Thus, this research develops a study of the effects of long dependence in the series of streamflow natural energy in the South subsystem, in order to estimate a long memory model capable of generating synthetic hydrologic series.

Possibilities and tools of business crisis management during the natural crisis

OpenAIRE

Bosáková, Renáta

2009-01-01

This work analyses disposable tools of business crisis management to manage crisis which are induced by natural threats and it considers possibilities of these methods using. On basis of performed analysis then in the practical part it uses the acceptable methods and tools to look for threats and risks of the firm and suggests optimal structure of crisis plan.

Dutch guideline for the management of hypertensive crisis -- 2010 revision.

Science.gov (United States)

van den Born, B J H; Beutler, J J; Gaillard, C A J M; de Gooijer, A; van den Meiracker, A H; Kroon, A A

2011-05-01

Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hypertensive crisis with retinopathy under hypertensive emergencies instead of urgencies. With regard to the treatment of hypertensive emergencies, nicardipine instead of nitroprusside or labetalol is favoured for the management of perioperative hypertension, whereas labetalol has become the drug of choice for the treatment of hypertension associated with pre-eclampsia. For the treatment of hypertensive urgencies, oral administration of nifedipine retard instead of captopril is recommended as first-line therapy. In addition, a section on the management of hypertensive emergencies according to the type of target organ involved has been added. Efforts to increase the awareness and treatment of hypertension in the population at large may lower the incidence of hypertensive crisis and its complications.

LA ACTUACIÓN DE LAS AUTORIDADES ESPAÑOLAS FRENTE A LA CRISIS FINANCIERA

Directory of Open Access Journals (Sweden)

Antoni Garrido Torres

2013-01-01

Full Text Available The direct impact of the financial crisis on the Spanish banking system has been small, thanks mainly to the existing securitization model in Spain, far from the so-called originate and distribute that generated most of the financial turmoil. However, the indirect impact of the crisis has been considerable, due to the fact that Spanish banks highly depended on external financing. In the following pages, we analyze the main measures taken by the Spanish authorities to face the crisis in the banking system, with particular attention to the restructuring of savings banks.

Detection unit with corrected energy dependence

International Nuclear Information System (INIS)

Viererbl, L.

1989-01-01

The detection unit consists of a plastic scintillator with a layer of a powder semicrystalline scintillator deposited on its surface. An inorgaic monocrystalline scintillator is placed inside the plastic scintillator and surrounded with an absorption layer, except for the window. The advantage of the detection unit is a reduced energy dependence of response, especially in the energy range 100 to 400 keV. (E.J.). 3 figs

Communication in the state of crisis

OpenAIRE

Senić Vladimir; Senić Radoslav

2015-01-01

Due to diversity of research related to crisis it is rather important to present definitions of various key terms related to crisis, crisis management and crisis communication, in order to establish tangible boundaries among them. Those three are mutually intertwined and should be considered starting from the first symptoms of crisis to crisis management and finally crisis communication. In the state of crisis, conventional management practice is often not adequate, while types of reaction ar...

Dalla crisi finanziaria alla crisi reale

Directory of Open Access Journals (Sweden)

CARLO D’ADDA

2010-01-01

Full Text Available The financial crisis of 2008 is put in relation with two bubbles, financial and housing. Easy credit is at the origin of both bubbles. Risky bonds were issued to mobilize mortgages originated in the housing market, and bad bonds entered a fantastic number of institutional and private portfolios all over the world without any perception of the their risk. Unfortunately, bank credit to speculators was abundant and fed the final growth of the bubbles. When fears started to spread, the fall was immediate and expectations impaired very rapidly. The main aggregate demand components were severely curtailed and production fell as well. This is the crisis of the real economy. Fortunately, as opposed to what happened in 1929, the interventions of central banks and governments have been of an unprecedented size. The bail out of insolvent banks in particular has been providential. The exit from the current crisis, however, will surely be slow.

THE ROLE AND IMPORTANCE OF COMPANY CRISIS DIAGNOSIS IN ANTI-CRISIS MANAGEMENT

OpenAIRE

Klodane, Alona

2016-01-01

Nowadays, under a free market, crises at companies are a frequent phenomenon; however, anti-crisis management and related aspects are currently a little researched problem in Latvia. The research aim is to examine the nature of company crisis diagnosis and its role and importance in the anti-crisis management system. The research general tasks are: to describe the nature of company crisis diagnosis and review the scope, purpose and tasks of performing a diagnosis; to examine the role and impo...

Generalized Energy-Dependent Q Values for Fission

Energy Technology Data Exchange (ETDEWEB)

Vogt, R

2010-03-31

We extend Madland's parameterization of the energy release in fission to obtain the dependence of the fission Q value for major and minor actinides on the incident neutron energies in the range 0 {le} E{sub n} {le} 20 MeV. Our parameterization is based on the actinide evaluations recommended for the ENDF/B-VII.1 release. This paper describes the calculation of energydependent fission Q values based on the calculation of the prompt energy release in fission by Madland. This calculation was adopted for use in the LLNL ENDL database and then generalized to obtain the prompt fission energy release for all actinides. Here the calculation is further generalized to the total energy release in fission. There are several stages in a fission event, depending on the time scale. Neutrons and gammas may be emitted at any time during the fission event.While our discussion here is focussed on compound nucleus creation by an incident neutron, similar parameterizations could be obtained for incident gammas or spontaneous fission.

Water and Energy Services in Times of War _ The Political Crisis of Yemen, 2011 - 2016

Science.gov (United States)

Aklan, Musaed; de Fraiture, Charlotte; Hayde, Laszlo

2017-04-01

The current war in Yemen affects the lives of Yemenis, their properties, and basic needs. It has damaged many parts of fuel, electricity, water and sanitation systems. This paper investigates how this war has affected the main sources of energy and water, their availability and prices. Beside literature review and different documents collected from different related governmental sectors, a rapid assessment through field interviews was conducted to collect the primary data. The prices of petroleum products keep unstable and have increased by more than 10 times of pre-crisis costs. The water has become three to four times more expensive. The majority of families relied on the public electricity grids before the war was unleashed. At present, the public electricity and water systems serve less than 20% of urban and rural families. Solar energy has become the first energy source, whereas generators are considered to be the second main power supply. Additionally, rainwater started to be collected as a secondary water source. Many people are willing to continue using this new sources. The study verifies the importance renewable resources transition to achieve secure sustainable water and energy management. Not only in Yemen but also this lessons can be applied to other similar conditions countries in the Middle East, where Decision makers and researchers should give more attention.

Competitiveness of Slovakia and the Economic Crisis

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Silvia Ručinská

2009-12-01

Full Text Available The impacts of financial crisis in the beginning of this year have also been felt by the Slovak economy. It could be argued that the competitiveness of Slovakia is under the influence of the world economic crisis, as it is a small, open and pro-export oriented economy, hence influenced by foreign markets. Because of limited extent of domestic market, the foreign demand plays a key role in economic growth, a role that depends on the development of international economic affairs. As the biggest Slovak trade partners are in a deep recession, it induces a slowdown in the domestic economy as well. Financial problems of numerous banks in these countries, in combination with the growing lack of trust in the performance of the economies have resulted in a decline in demand and consumption, which had its effects on Slovakia as well. Based on our analysis of the manifestations and consequences of the financial crisis we show the effects on competitiveness of Slovakia, as well as on public policy.

Crisis Diagnosis in Anti-Crisis Management Process in a Company

OpenAIRE

Ruta Meiste; Sandra Jakstiene

2015-01-01

Crisis concept links up to its appearance area. Some different kinds and levels of crises have been found: we face with global, mainly nature cataclysm crises, state economic crises, corporate crises and individual or psychological crises. The research area of this paper is micro level, i.e. corporate crises or crisis in a company. However, it is emphasized that company is a sociotechnical system, performing in a complex environment, therefore crisis in a company is closely related to global ...

Emergent collaboration infrastructures technology design for inter-organizational crisis management

CERN Document Server

Reuter, Christian

2015-01-01

​Using the domain of crisis management, Christian Reuter explores challenges and opportunities for technology design in emergent environments. He therefore empirically analyzes collaborative work in inter-organizational crisis - such as the police, fire departments, energy network operators and citizens - in order to identify collaboration practices that reveal work infrastructure limitations. He also designs, implements and evaluates novel concepts and ICT artifacts towards the support of emergent collaboration. Besides the discovery of potential organizational effects on the ability to deal

Challenging the Woodfuel Crisis in West African Woodlands

DEFF Research Database (Denmark)

Hansfort, Sofie Louise; Mertz, Ole

2011-01-01

Fear of an upcoming woodfuel crisis caused by increasing woodfuel consumption in Bamako has had great influence on forestry policies aiming to reduce the impacts of urban woodfuel consumption. During the last 20 years, energy gap analyses—the relationship between supply and demand of woodfuels......—have been produced by the government of Mali to prove the impacts of woodfuel consumption in Bamako on surrounding woodlands. This study evaluates the methodology and data used to describe this woodfuel crisis through a comparison with regional and historical data. The results of the energy gap analyses...... are challenged by using different estimates of woody resource availability and woodfuel consumption to create best and worst case scenarios. These show either high surpluses or high deficits with a difference of 2.7 million tons/yr. The woodfuel system of Bamako is highly dynamic and it is very difficult...

Energy drink consumption and increased risk for alcohol dependence.

Science.gov (United States)

Arria, Amelia M; Caldeira, Kimberly M; Kasperski, Sarah J; Vincent, Kathryn B; Griffiths, Roland R; O'Grady, Kevin E

2011-02-01

Energy drinks are highly caffeinated beverages that are increasingly consumed by young adults. Prior research has established associations between energy drink use and heavier drinking and alcohol-related problems among college students. This study investigated the extent to which energy drink use might pose additional risk for alcohol dependence over and above that from known risk factors. Data were collected via personal interview from 1,097 fourth-year college students sampled from 1 large public university as part of an ongoing longitudinal study. Alcohol dependence was assessed according to DSM-IV criteria. After adjustment for the sampling design, 51.3%(wt) of students were classified as "low-frequency" energy drink users (1 to 51 days in the past year) and 10.1%(wt) as "high-frequency" users (≥52 days). Typical caffeine consumption varied widely depending on the brand consumed. Compared to the low-frequency group, high-frequency users drank alcohol more frequently (141.6 vs. 103.1 days) and in higher quantities (6.15 vs. 4.64 drinks/typical drinking day). High-frequency users were at significantly greater risk for alcohol dependence relative to both nonusers (AOR = 2.40, 95% CI = 1.27 to 4.56, p = 0.007) and low-frequency users (AOR = 1.86, 95% CI = 1.10, 3.14, p = 0.020), even after holding constant demographics, typical alcohol consumption, fraternity/sorority involvement, depressive symptoms, parental history of alcohol/drug problems, and childhood conduct problems. Low-frequency energy drink users did not differ from nonusers on their risk for alcohol dependence. Weekly or daily energy drink consumption is strongly associated with alcohol dependence. Further research is warranted to understand the possible mechanisms underlying this association. College students who frequently consume energy drinks represent an important target population for alcohol prevention. Copyright © 2010 by the Research Society on Alcoholism.

Narratives of crisis: identity crisis or crisis of meaning?!

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Roseli Araújo Barros Costa

2006-06-01

Full Text Available This article is about a review of a broader research on the understanding of the professional development of Mathematics teachers, especially the results of the analysis of one of the selected categories, the projectors and the crisis narratives. This analysis was theoretically supported by Larrosa (2002. To carry out the research, we adopted the qualitative research, with a narrative focus, based on semi-structured interviews about the life history of a teacher who teaches mathematics in Basic Education. Based on a concept of professional development taken from a continuous perspective, idealized in a broader context of teaching work, permeating crises and conflicts, the analysis shows that the teacher's crisis reports are related to factors such as: low salaries, conflicts in her current institution Lack of social prestige and insecurity. His reports reveal that initial training did nothing to address the "new" changes in education. It shows that their lack of enthusiasm is associated with the emptying of the useful meaning of their formation, which results from the overvaluation of their exchange value. However, a crisis narrative can construct the present as a critical moment in the double sense of the word as a decisive moment and, at the same time, as a moment in which the subject critically recovers his own history, appropriates himself critically To find out where it is and to decide its own movement (LARRROSA, 2002. The individual, by critically restoring his history, can rethink the past, think the present, and (reconstruct his own future. The teacher, in her crisis narratives, shows that, by critically recovering her story, by putting out all her "revolt", she opens a "door" that will possibly show a new path to be taken. This seeks new challenges for their professional development

Reforming Romanian energy policy

International Nuclear Information System (INIS)

Perkins, S.

1993-01-01

Success in reforming energy sector depends on the implementation of the programme of economic reform agreed in February 1993. The difficulty of the negotiations between the International Monetary Fund and the Romanian government reflects the wider difficulties faced by the economy as a whole. They can be blamed in part on the legacy of uneconomic and inflexible industrial development and in part on opposition from interest groups which stand to lose from reform. Nonetheless, in spite of hesitant approach, the government does appear committed to the economic reform necessary to establish a market-oriented economy. But as the danger of a financial crisis engendered by the inadequately supported short-term borrowing of foreign exchange becomes urgent, the question is whether economic reform can be now implemented fast enough to protect economic enterprises and saving from a debt crisis. The scope for further delay in implementing the 1993 economic reform programme is fast disappearing. Procrastination should not be allowed to threaten the success of the reforms achieved in the energy and other sectors of the economy. 8 refs., 2 figs

Political pragmatism and principles in times of crisis : the role of pragmatist political crisis management during the U.S. financial crisis

NARCIS (Netherlands)

Bartenberger, M.

2017-01-01

Based on philosophical pragmatism, this study builds a model of pragmatist crisis management at the political-strategic level and contrasts it with a principle-guided approach towards political crisis management. It identifies four cornerstons of pragmatist political crisis management and builds a

Sickle Cell Crisis (For Teens)

Science.gov (United States)

... Safe Videos for Educators Search English Español Sickle Cell Crisis (Pain Crisis) KidsHealth / For Teens / Sickle Cell ... drepanocíticas (Crisis de dolor) What Is a Sickle Cell Crisis? Sickle cell disease changes the shape of ...

Companies’ management during economic crisis

OpenAIRE

Kumpikaitė, Vilmantė; Grybauskas, Andrius; Juodelis, Mantas; Strumyla, Dovydas

2011-01-01

Lots of companies faced recent economic crisis. It was generated by global markets deregulation and it triggered relevant situation to emerge other types of crisis. Many scientists all over the world analyses how crisis affected global economy and changed companies’ management actions. Scientists exclude these types of crisis: economic, informational, physical, human resource, reputational, psychopathic acts production and financial. This paper examines economic crisis generated negative effe...

Prospect for the oil market as a consequence of the financial crisis

International Nuclear Information System (INIS)

Koppelaar, R.

2008-11-01

The Peak Oil Netherlands Foundation shines its light on the consequences of the financial crisis for the global oil market and the relation between oil prices and the credit crisis; short term supply and demand on the oil market; supply and demand of petroleum up to 2015; the volatility of the oil price and the meaning of volatility for the energy transition [mk] [nl

The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin

DEFF Research Database (Denmark)

Wang, Yifan; Bernhardy, Andrea J; Cruz, Cristina

2016-01-01

Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and...

Waiting for a Crisis: Case Studies of Crisis Leaders in Higher Education

Science.gov (United States)

Muffet-Willett, Stacy L.

2010-01-01

This study examines the system of crisis leadership in higher education. Using case study methods, five crisis leadership participants were interviewed to develop a deep understanding of how they perceive their university crisis leadership system. Two participants were from a private institution, and three were from a public institution. Higher…