Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.

Science.gov (United States)

Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H; Pirvola, Ulla

2011-01-01

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27(Kip1) and p21(Cip1) expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells.

Cyclin D1 overexpression, cell cycle progression and radiosensitivity in MBP cells

International Nuclear Information System (INIS)

Wu Lijun; Yu Zengliang

2000-11-01

Clones that exhibited a minimum of 7-8 fold cyclin D1 level above the parent cell lines or the vector control were obtained after transfected with the entire coding sequence of human 1.1 kb cyclin D1 cDNA. Studies showed that there was no significant difference in Radiosensitivity between over-expressing cyclin D1 and control cultures from either mouse or human origin. Using flow cytometry to access cell cycle distribution in the exponentially growth cultures of MCF10F-D1-21 and MCF10F-V-3, it was found that there was a 50 percent increase in the proportion of G2/M phase cells and 5.3 percent decrease in the proportion of G0/G1 phase cells in MCF10F-D1-21 comparing with MCF10F-V-3, though they were with the same proportion of cells in S phase

Long-term hormonal contraceptive use is associated with a reversible suppression of antral follicle count and a break from hormonal contraception may improve oocyte yield.

Science.gov (United States)

Letourneau, Joseph M; Cakmak, Hakan; Quinn, Molly; Sinha, Nikita; I Cedars, Marcelle; Rosen, Mitchell P

2017-09-01

Unlike infertility, patients presenting for fertility preservation (FP) are often using combined hormonal contraceptives (CHC). We studied whether long-term (≥6 months) CHC use is associated with reversible suppression of antral follicle count (AFC). This is a longitudinal study of FP cycles from 2012 to 2016. We studied three groups: those without CHC exposure (NO CHC), those with CHC usage with a CHC break (BREAK), and without a break (NO BREAK) prior to ovarian stimulation. We assessed ovarian reserve by AFC at initial consultation and discussed the possibility of CHC suppression of AFC. Patients chose between ovarian stimulation with no CHC break versus ovarian stimulation after a CHC break. AFC was measured serially in the BREAK group. We assessed whether AFC suppression was reversed in the BREAK group. Total oocyte yield was compared among the NO CHC, BREAK, and NO BREAK groups. T tests, ANOVA, and linear/logistic regressions were used. Seven hundred forty-three women underwent FP. Twenty-one percent (n = 154) were taking long-term CHC (≥6 months). AFC suppression was more likely with CHC use (OR 1.6, 95% CI 1.1-2.4, P = 0.011). The BREAK group (n = 79) stopped CHC for an average of 4 months. AFC improvement started at 1 month and plateaued at approximately 6- to 7-month break. The BREAK group had approximately twice as many oocytes per initial AFC as NO BREAK (2.8 ± 3.8 vs. 1.4 ± 0.9, P women present for FP on CHC, AFC may be suppressed. A CHC break of several months is associated with an increase in AFC and a potential improvement in overall egg yield.

Glycogen synthase kinase 3 has a limited role in cell cycle regulation of cyclin D1 levels.

Science.gov (United States)

Yang, Ke; Guo, Yang; Stacey, William C; Harwalkar, Jyoti; Fretthold, Jonathan; Hitomi, Masahiro; Stacey, Dennis W

2006-08-30

The expression level of cyclin D1 plays a vital role in the control of proliferation. This protein is reported to be degraded following phosphorylation by glycogen synthase kinase 3 (GSK3) on Thr-286. We recently showed that phosphorylation of Thr-286 is responsible for a decline in cyclin D1 levels during S phase, an event required for efficient DNA synthesis. These studies were undertaken to test the possibility that phosphorylation by GSK3 is responsible for the S phase specific decline in cyclin D1 levels, and that this event is regulated by the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway which controls GSK3. We found, however, that neither PI3K, AKT, GSK3, nor proliferative signaling activity in general is responsible for the S phase decline in cyclin D1 levels. In fact, the activity of these signaling kinases does not vary through the cell cycle of proliferating cells. Moreover, we found that GSK3 activity has little influence over cyclin D1 expression levels during any cell cycle phase. Inhibition of GSK3 activity by siRNA, LiCl, or other chemical inhibitors failed to influence cyclin D1 phosphorylation on Thr-286, even though LiCl efficiently blocked phosphorylation of beta-catenin, a known substrate of GSK3. Likewise, the expression of a constitutively active GSK3 mutant protein failed to influence cyclin D1 phosphorylation or total protein expression level. Because we were unable to identify any proliferative signaling molecule or pathway which is regulated through the cell cycle, or which is able to influence cyclin D1 levels, we conclude that the suppression of cyclin D1 levels during S phase is regulated by cell cycle position rather than signaling activity. We propose that this mechanism guarantees the decline in cyclin D1 levels during each S phase; and that in so doing it reduces the likelihood that simple over expression of cyclin D1 can lead to uncontrolled cell growth.

Bimetallic Ag–Ni/C particles as cathode catalyst in AFCs (alkaline fuel cells)

International Nuclear Information System (INIS)

Song, Xingjuan; Zhang, Dongming

2014-01-01

AFCs (alkaline fuel cells) is one of the promising fuel cells, due to their low working temperature and less corrosive environment. However, decreasing the catalyst cost and improving its performance are still the challenges in its application. Transition metal as the catalyst for AFCs not only can reduce its cost, but also has great electro-catalytic efficiency. In this paper, Carbon supported Ag–Ni bimetallic catalysts with differential Ag/Ni atomic ratios were prepared by chemically reducing silver and nickel salts. Ag 3 Ni/C shows the relatively higher ORR (oxygen reduction reaction) activity among the differential Ag/Ni bimetallic particles. In order to improve the activity and stability, the catalysts were heat-treated at the temperature of 500 °C. The results indicate that the limiting current density has been improved greatly for Ag 3 Ni/C-500 °C, which is as high as 2.5× that of Ag/C. The microstructure investigation show that the non-equilibrium state of Ag–Ni alloy by heat treatment is confirmed by HRTEM (high-resolution transmission electron microscopy) images, and Ag(111) surfaces are decreased in XRD pattern, which results in the ORR activity improved and overpotential decreased. Heat treatment also has contributed to Ag–Ni/C electrochemistry stability in some degree. - Highlights: • Ag–Ni/C is applied as cathode catalyst for AFCs (alkaline fuel cells). • Ag 3 Ni/C-500 °C shows the best performance. • Non-equilibrium state of Ag–Ni alloy by heat treatment is observed. • The decreased Ag(111) surfaces are favor to improve the catalyst activity

Advanced nuclear fuel cycles activities in IAEA

International Nuclear Information System (INIS)

Nawada, H.P.; Ganguly, C.

2007-01-01

Full text of publication follows. Of late several developments in reprocessing areas along with advances in fuel design and robotics have led to immense interest in partitioning and transmutation (P and T). The R and D efforts in the P and T area are being paid increased attention as potential answers to ever-growing issues threatening sustainability, environmental protection and non-proliferation. Any fuel cycle studies that integrate partitioning and transmutation are also known as ''advanced fuel cycles'' (AFC), that could incinerate plutonium and minor actinide (MA) elements (namely Am, Np, Cm, etc.) which are the main contributors to long-term radiotoxicity. The R and D efforts in developing these innovative fuel cycles as well as reactors are being co-ordinated by international initiatives such as Innovative Nuclear Power Reactors and Fuel Cycles (INPRO), the Generation IV International Forum (GIF) and the Global Nuclear Energy Partnership (GENP). For these advanced nuclear fuel cycle schemes to take shape, the development of liquid-metal-cooled reactor fuel cycles would be the most essential step for implementation of P and T. Some member states are also evaluating other concepts involving the use of thorium fuel cycle or inert-matrix fuel or coated particle fuel. Advanced fuel cycle involving novel partitioning methods such as pyrochemical separation methods to recover the transuranic elements are being developed by some member states which would form a critical stage of P and T. However, methods that can achieve a very high reduction (>99.5%) of MA and long-lived fission products in the waste streams after partitioning must be achieved to realize the goal of an improved protection of the environment. In addition, the development of MA-based fuel is also an essential and crucial step for transmutation of these transuranic elements. The presentation intends to describe progress of the IAEA activities encompassing the following subject-areas: minimization of

Measurement of antral follicle count in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey.

Science.gov (United States)

Christianson, Mindy S; Shoham, Gon; Tobler, Kyle J; Zhao, Yulian; Cordeiro, Christina N; Leong, Milton; Shoham, Zeev

2015-10-01

The purpose of the present study was to identify trends in the therapeutic approaches used to measure antral follicle count (AFC) in patients undergoing in vitro fertilization (IVF) treatment worldwide. A retrospective evaluation utilizing the results of a web-based survey, IVF-Worldwide ( www.IVF-Worldwide.com ), was performed. Responses from 796 centers representing 593,200 cycles were evaluated. The majority of respondents (71.2 %) considered antral follicle count as a mandatory part of their practice with most (69.0 %) measuring AFC in the follicular phase. Most respondents (89.7 %) reported that they would modify the IVF stimulation protocol based on the AFC. There was considerable variation regarding a limit for the number of antral follicles required to initiate an IVF cycle with 46.1 % designating three antral follicles as their limit, 39.9 % selecting either four or five follicles as their limit, and 14.0 % reporting a higher cutoff criteria. With respect to antral follicle size, 61.5 % included follicles ranging between 2 and 10 mm in the AFC. When asked to identify the best predictor of ovarian hyper-response during IVF cycles, AFC was selected most frequently (49.4 %), followed by anti-Mullerian hormone level (42.7 %). Age was selected as the best predictor of ongoing pregnancy rate in 81.7 % of respondents. While a large proportion of respondents utilized AFC as part of their daily practice and modified IVF protocol based on the measurement, the majority did not consider AFC as the best predictor of ongoing pregnancy rate.

Creeping of hysteresis cycles; Reptation des cycles d'hysteresis

Energy Technology Data Exchange (ETDEWEB)

Neel, L [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Faculte des Sciences de Grenoble, 38 (France)

1959-07-01

Creeping consists of a kind of progressive translation of dissymmetric ferromagnetic hysteresis cycles as a function of the order number of the cycle. It is interpreted here by means of a probable coupling field, the existence of which is connected to a statistical conception of the distribution of the elementary regions. (author) [French] La reptation consiste en une sorte de translation progressive des cycles d'hysteresis ferromagnetiques dissymetriques en fonction du numero d'ordre du cycle. L'auteur l'interprete au moyen d'un champ aleatoire de couplage dont l'existence est liee a une conception statistique de la distribution des domaines elementaires. (auteur)

Initial and transition cycle development for KALIMER uranium fueled core

International Nuclear Information System (INIS)

Kim, Sang Ji; Kim, Young In; Kim, Young Jin; Park, Chang Kue

1998-01-01

An economic and safe equilibrium Uranium metallic fuelled core having been established, strategic loading schemes for initial and transition cycles to early reach target equilibrium cycles are suggested for U-U and U-Pu transition cycles. An iterative method to find initial core enrichment splits is developed. With non-uniform feed enrichments at the initial core adopted, this iterative method shows KALIMER can reach Uranium equilibrium cycles just after 4 reloads, keeping feed enrichment unchanged from cycle 2. Recycling of self-generated Pu is not sufficient to make KALIMER a pure Pu equilibrium core even after 56 reloads. equilibrium cycles are suggested for U-U and U-Pu transition cycles. An iterative method to find initial core enrichment splits is developed. With non-uniform feed enrichments at the initial core adopted, this iterative method shows KALIMER can reach Uranium equilibrium cycles just after 4 reloads, keeping feed enrichment unchanged from cycle 2. Recycling of self-generated Pu is not sufficient to make KALIMER a pure Pu equilibrium core even after 56 reloads

Individualization of the FSH starting dose in IVF/ICSI cycles using the antral follicle count

Directory of Open Access Journals (Sweden)

La Marca Antonio

2013-02-01

Full Text Available Abstract Background The FSH starting dose is usually chosen according to women’s age, anamnesis, clinical criteria and markers of ovarian reserve. Currently used markers include antral follicle count (AFC, which is considered to have a very high performance in predicting ovarian response to FSH. The objective of the present study to elaborate a nomogram based on AFC for the calculation of the appropriate FSH starting dose in IVF cycles. Methods This is a retrospective study performed at the Mother-Infant Department of Modena University Hospital. IVF patients (n=505 were subjected to blood sampling and transvaginal ultrasound for measurement of serum day3 FSH, estradiol and AFC. The variables predictive of the number of retrieved oocytes were assessed by backwards stepwise multiple regression. The variables reaching the statistical significance were then used in the calculation for the final predictive model. Results A model based on age, AFC and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting dose lower than 225 IU in 50.2% and 18.1% of patients younger and older than 35 years, respectively. Conclusions The daily FSH dose may be calculated on the basis of age and two markers of ovarian reserve, namely AFC and FSH, with the last two variables being the most significant predictors. The nomogram seems easily applicable during the daily clinical practice.

Acquired radioresistance of cancer and the AKT/GSK3β/cyclin D1 overexpression cycle

International Nuclear Information System (INIS)

Shimura, Tsutomu

2011-01-01

Fractionated radiotherapy (RT) is widely used in cancer therapy for its advantages in the preservation of normal tissues. However, repopulation of surviving tumor cells during fractionated RT limits the efficacy of RT. In fact, repopulating tumors often acquire radioresistance and this is the major cause of failure of RT. We have recently demonstrated that human tumor cells acquire radioresistance when exposed to fractionated radiation (FR) of X-rays every 12 hours for 1 month. The acquired radioresistance was associated with overexpression of cyclin D1, a result of a series of molecular changes; constitutive activation of DNA-PK and AKT with concomitant down-regulation of glycogen synthase kinase-3β (GSK3β) which results in suppression of cyclin D1 proteolysis. Aberrant cyclin D1 overexpression in S-phase induced DNA double strand breaks which activated DNA-PK and established the vicious cycle of cycling D1 overexpression. This overexpression of cyclin D1 is responsible for the radioresistance phenotype of long-term FR cells, since this phenotype was completely abrogated by treatment of FR cells by the AKT/PKB signaling inhibitor (API-2), an AKT inhibitor or by a Cdk4 inhibitor. Thus, targeting the AKT/GSK3β/cyclin D1/Cdk4 pathway can be an efficient modality to suppress acquired radioresistance of tumor cells. In this article, I overview the newly discovered molecular mechanisms underlying acquired radioresistance of tumor cells induced by FR, and propose a strategy for eradication of tumors using fractionated RT by overcoming tumor radioresistance. (author)

A novel role for the cell cycle regulatory complex cyclin D1-CDK4 in gluconeogenesis

OpenAIRE

Hosooka, Tetsuya; Ogawa, Wataru

2016-01-01

Dysregulation of gluconeogenesis is a key pathological feature of type 2 diabetes. However, the molecular mechanisms underlying the regulation of gluconeogenesis remain unclear. Bhalla et?al. recently reported that cyclin D1 suppresses hepatic gluconeogenesis through CDK4?dependent phosphorylation of PGC1alpha and consequent inhibition of its activity. The cyclin D1?CDK4 might thus serve as an important link between the cell cycle and control of energy metabolism through modulation of PGC1alp...

Core Follow Calculation for Palo Verde Unit 1 in Cycles 1 through 4 using DeCART2D/MASTER4.0 Code System

International Nuclear Information System (INIS)

Jeong, Hee Jeong; Choi, Yonghee; Kim, Sungmin; Lee, Kyunghoon

2017-01-01

To verify and validate the DeCART2D/MASTER4.0 design system, core follow calculations of Palo Verde Unit 1(PV-1) in cycles 1 through 4 are performed. The calculation results are compared with the measured data and will be used in the generation of bias and uncertainty factors in the DeCART2D/MASTER4.0 design system. The DeCART2D/MASTER codes system has been developed in KAERI for the PWR (Pressurized water reactors) core design including SMRs (Small Modular Reactors). Core follow calculations of Pale Verde Unit 1 in Cycles 1 through 4 have been performed. Reactivities, assembly powers and startup parameters such as EPC, RW, ITC and IBW are compared with the measured data. This work will be used in the generation of bias and uncertainty factors in DeCART2D/MASTER4.0 design system.

Establishment and cell cycle distribution pattern of a radioresistant subline from human lung cancer D6 cell line

International Nuclear Information System (INIS)

Wei Qichun; Zheng Shu

2003-01-01

Objective: To establish a radioresistant cell subline from a human D6 lung cancer cell line and investigate the mechanism of radioresistance. Methods: D6 human NSCLC cells were exposed to X-rays generated by a linear accelerator(650 cGy per fraction). After a total exposure dose of 5200 cGy, a monoclone was obtained. The radiosensitivity and cell cycle distribution of this clone, together with its parent D6 cells, were measured by clonogenic assay and flow cytometry. Results: The new clone, namely D 6 -R subline, had a higher D 0 (D 0 =2.08 Gy) and a broader initial shoulder(Dq=1.64 Gy, N=2.20) than those of the parent D6 cell line (D 0 =1.84 Gy, Dq=0.34 Gy, N=1.20), being 1.65-fold increase in radioresistance as regards to the SF 2 . The D6-R subline also showed higher percentage of cells in S phase(53.4% vs 37.8%), but lower percentages in G 1 (44.1% vs 57.2%) and G 2 /M(2.5% vs 5%) phases. Conclusion: The new subline D6-R is more radioresistant as compare to its parent D6 cell line, and has a different cell cycle distribution

25-Hydroxyvitamin D and Long Menstrual Cycles in a Prospective Cohort Study.

Science.gov (United States)

Jukic, Anne Marie Z; Wilcox, Allen J; McConnaughey, D Robert; Weinberg, Clarice R; Steiner, Anne Z

2018-05-01

Vitamin D insufficiency is associated with subfertility and prolonged estrus cycles in animals, but humans have not been well studied. A prospective time-to-pregnancy study, Time to Conceive (2010-2015), collected up to 4 months of daily diary data. Participants were healthy, late reproductive-aged women in North Carolina who were attempting pregnancy. We examined menstrual cycle length as a continuous variable and in categories: long (35+ days) and short (≤25 days). Follicular phase length and luteal phase length were categorized as long (18+ days) or short (≤10 days). We estimated associations between those lengths and serum 25-hydroxyvitamin D (25[OH]D) using linear mixed models and marginal models. There were 1,278 menstrual cycles from 446 women of whom 5% were vitamin D deficient (25[OH]D, <20 ng/ml), 69% were between 20 and 39 ng/ml, and 26% were 40 ng/ml or higher. There was a dose-response association between vitamin D levels and cycle length. Compared with the highest 25(OH)D level (≥40 ng/ml), 25(OH)D deficiency was associated with almost three times the odds of long cycles (adjusted odds ratio [aOR] = 2.8 [95% confidence interval (CI) = 1.0, 7.5]). The aOR was 1.9 (1.1, 3.5) for 20 to <30 ng/ml. The probability of a long follicular phase and the probability of a short luteal phase both increased with decreasing 25(OH)D. Lower levels of 25(OH)D are associated with longer follicular phase and an overall longer menstrual cycle. Our results are consistent with other evidence supporting vitamin D's role in the reproductive axis, which may have broader implications for reproductive success.

SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

International Nuclear Information System (INIS)

Bonifati, Serena; Daly, Michele B.; St Gelais, Corine; Kim, Sun Hee; Hollenbaugh, Joseph A.; Shepard, Caitlin; Kennedy, Edward M.; Kim, Dong-Hyun; Schinazi, Raymond F.; Kim, Baek; Wu, Li

2016-01-01

SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G_1/G_0 phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.

SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

Energy Technology Data Exchange (ETDEWEB)

Bonifati, Serena [Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH (United States); Daly, Michele B. [Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States); St Gelais, Corine; Kim, Sun Hee [Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH (United States); Hollenbaugh, Joseph A.; Shepard, Caitlin [Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States); Kennedy, Edward M. [Department of Molecular Genetics and Microbiology, Duke University, Durham, NC (United States); Kim, Dong-Hyun [Department of Pharmacy, School of Pharmacy, Kyung-Hee University, Seoul (Korea, Republic of); Schinazi, Raymond F. [Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States); Kim, Baek, E-mail: baek.kim@emory.edu [Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States); Department of Pharmacy, School of Pharmacy, Kyung-Hee University, Seoul (Korea, Republic of); Wu, Li, E-mail: wu.840@osu.edu [Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH (United States)

2016-08-15

SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G{sub 1}/G{sub 0} phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.

A new MCM modification cycle regulates DNA replication initiation.

Science.gov (United States)

Wei, Lei; Zhao, Xiaolan

2016-03-01

The MCM DNA helicase is a central regulatory target during genome replication. MCM is kept inactive during G1, and it initiates replication after being activated in S phase. During this transition, the only known chemical change to MCM is the gain of multisite phosphorylation that promotes cofactor recruitment. Because replication initiation is intimately linked to multiple biological cues, additional changes to MCM can provide further regulatory points. Here, we describe a yeast MCM SUMOylation cycle that regulates replication. MCM subunits undergo SUMOylation upon loading at origins in G1 before MCM phosphorylation. MCM SUMOylation levels then decline as MCM phosphorylation levels rise, thus suggesting an inhibitory role of MCM SUMOylation during replication. Indeed, increasing MCM SUMOylation impairs replication initiation, partly through promoting the recruitment of a phosphatase that decreases MCM phosphorylation and activation. We propose that MCM SUMOylation counterbalances kinase-based regulation, thus ensuring accurate control of replication initiation.

E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation.

Science.gov (United States)

Carcagno, Abel L; Marazita, Mariela C; Ogara, María F; Ceruti, Julieta M; Sonzogni, Silvina V; Scassa, María E; Giono, Luciana E; Cánepa, Eduardo T

2011-01-01

A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell cycle and provides an additional mechanism to limit E2F activity.

E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation.

Directory of Open Access Journals (Sweden)

Abel L Carcagno

Full Text Available BACKGROUND: A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. CONCLUSIONS/SIGNIFICANCE: The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell

BISON Investigation of the Effect of the Fuel- Cladding Contact Irregularities on the Peak Cladding Temperature and FCCI Observed in AFC-3A Rodlet 4

Energy Technology Data Exchange (ETDEWEB)

Medvedev, Pavel G. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-09-01

The primary objective of this report is to document results of BISON analyses supporting Fuel Cycle Research and Development (FCRD) activities. Specifically, the present report seeks to provide explanation for the microstructural features observed during post irradiation examination of the helium-bonded annular U-10Zr fuel irradiated during the AFC-3A experiment. Post irradiation examination of the AFC-3A rodlet revealed microstructural features indicative of the fuel-cladding chemical interaction (FCCI) at the fuel-cladding interface. Presence of large voids was also observed in the same locations. BISON analyses were performed to examine stress and temperature profiles and to investigate possible correlation between the voids and FCCI. It was found that presence of the large voids lead to a formation of circumferential temperature gradients in the fuel that may have redirected migrating lanthanides to the locations where fuel and cladding are in contact. Resulting localized increase of lanthanide concentration is expected to accelerate FCCI. The results of this work provide important guidance to the post irradiation examination studies. Specifically, the hypothesis of lanthanides being redirected from the voids to the locations where the fuel and the cladding are in contact should be verified by conducting quantitative electron microscopy or Electron Probe Micro-Analyzer (EPMA). The results also highlight the need for computer models capable of simulating lanthanide diffusion in metallic fuel and establish a basis for validation of such models.

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

Science.gov (United States)

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

2008-02-01

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

Initial-state-radiation production of D{sub s} Mesons and high precision measurements of D{sub s}1(2536) at Babar

Energy Technology Data Exchange (ETDEWEB)

Roney, Michael [Stanford Linear Accelerator Center - SLAC, National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025-7015 (United States); Izen, Joseph Michael [University of Texas at Dallas, Department of Physics, EC 36, 800 West Campbell Road, Richardson, Texas 75080-3021 (United States)

2010-07-01

A search for charmonium and other new states is performed in a study of exclusive initial-state-radiation production of D{sub s}{sup +}D{sub s}{sup -}, D{sub s}{sup *+}D{sub s}{sup -}, and D{sub s}{sup *+}D{sub s}{sup *-} events from electron-positron annihilations at a center-of-mass energy of 10.58 GeV. The data sample corresponds to an integrated luminosity of 525 fb{sup -1} recorded by the BaBar experiment at the PEP-II storage ring. We also study the decay width and the mass of the D{sub s}1(2536) meson with high precision via the decay channel D{sub s}1(2536){yields}D{sup +*} K{sup 0}{sub s} using 384 fb{sup -1} of data recorded by the BABAR experiment. (author)

Toward commercialization of FBR cycle (1). Promotion of R and D on technologies maintaining sustainable society

International Nuclear Information System (INIS)

Nagaoki, Yoshihiro; Nagura, Fuminori; Sakaguchi, Tomoyoshi; Kawasaki, Hirotsugu; Kikuchi, Shin

2008-01-01

The FBR cycle is a key technology maintaining a sustainable society through efficient utilization of limited uranium resources and conformance to global environmental protection. The domestic and overseas R and D of the FBR cycle entered on a new phase aiming at its commercialization and JAEA started the Fast Reactor Cycle Technology Development (FaCT) project. The FaCT project targeted at international standardization of the FBR fuel cycle and promoting the advanced R and D on the innovative technologies to increase cost-efficiency and reliability for the commercialization under international competition and cooperation. The combination of a sodium cooled FBR and advanced fuel cycle system with advanced aqueous reprocessing and simplified pelletizing fuel fabrication was selected a major concept. (T. Tanaka)

Splitting Travel Time Based on AFC Data: Estimating Walking, Waiting, Transfer, and In-Vehicle Travel Times in Metro System

Directory of Open Access Journals (Sweden)

Yong-Sheng Zhang

2015-01-01

Full Text Available The walking, waiting, transfer, and delayed in-vehicle travel times mainly contribute to route’s travel time reliability in the metro system. The automatic fare collection (AFC system provides huge amounts of smart card records which can be used to estimate all these times distributions. A new estimation model based on Bayesian inference formulation is proposed in this paper by integrating the probability measurement of the OD pair with only one effective route, in which all kinds of times follow the truncated normal distributions. Then, Markov Chain Monte Carlo method is designed to estimate all parameters endogenously. Finally, based on AFC data in Guangzhou Metro, the estimations show that all parameters can be estimated endogenously and identifiably. Meanwhile, the truncated property of the travel time is significant and the threshold tested by the surveyed data is reliable. Furthermore, the superiority of the proposed model over the existing model in estimation and forecasting accuracy is also demonstrated.

Report on the workshop "Decay spectroscopy at CARIBU: advanced fuel cycle applications, nuclear structure and astrophysics". 14-16 April 2011, Argonne National Laboratory, USA.

Energy Technology Data Exchange (ETDEWEB)

Kondev, F.; Carpenter, M.P.; Chowdhury, P.; Clark, J.A.; Lister, C.J.; Nichols, A.L.; Swewryniak, D. (Nuclear Engineering Division); (Univ. of Massachusetts); (Univ. of Surrey)

2011-10-06

A workshop on 'Decay Spectroscopy at CARIBU: Advanced Fuel Cycle Applications, Nuclear Structure and Astrophysics' will be held at Argonne National Laboratory on April 14-16, 2011. The aim of the workshop is to discuss opportunities for decay studies at the Californium Rare Isotope Breeder Upgrade (CARIBU) of the ATLAS facility with emphasis on advanced fuel cycle (AFC) applications, nuclear structure and astrophysics research. The workshop will consist of review and contributed talks. Presentations by members of the local groups, outlining the status of relevant in-house projects and availabile equipment, will also be organized. time will also be set aside to discuss and develop working collaborations for future decay studies at CARIBU. Topics of interest include: (1) Decay data of relevance to AFC applications with emphasis on reactor decay heat; (2) Discrete high-resolution gamma-ray spectroscopy following radioactive decya and related topics; (3) Calorimetric studies of neutron-rich fission framgents using Total ABsorption Gamma-Ray Spectrometry (TAGS) technique; (4) Beta-delayed neutron emissions and related topics; and (5) Decay data needs for nuclear astrophysics.

Insight from a Critical Review on the Safety Analysis of Nuclear Fuel Cycle Facility for Domestic Regulatory System

International Nuclear Information System (INIS)

Hong, Soon Joon; Chung, Young Wook; Jeong, Seung Young

2010-01-01

Korea has 20 nuclear power plants in operation, and 10,761 ton of spent fuel deposited in plant sites. The capacity of reservoir for spent fuel in plant sites is to begin to be full in 2016. The light water reactors of 16 units generate around 320 ton/year and the heavy water reactors of 4 units around 380 ton/year in Korea. And the electricity generated by nuclear power plants is planned to increase up to 59% share by 2030. Spent fuel classified as high level radioactive waste in law is characterized by high level radiation, high heat generation, and high radiological toxicity. In the contrary, it is also a very useful domestic energy source. Thus, the safe management of spent fuel is very important confronting job in nuclear industry. Advanced fuel cycle (AFC) using pyro-process is an innovative technology, by which environmental load is drastically relieved because the extracted long-lived fission products are burn in fast breeder reactors. Domestic nuclear industry also has a perspective road map for the construction of AFC facilities. However, there is not a sufficiently detailed licensing regulatory system yet. Moreover, there is no systematic frame for the safety evaluation. This paper reviews the safety analysis system of foreign fuel cycle facilities. Critical review leads to the insight for setting-up safety analysis system of domestic AFC facilities

Vacuum type D initial data

Science.gov (United States)

García-Parrado Gómez-Lobo, Alfonso

2016-09-01

A vacuum type D initial data set is a vacuum initial data set of the Einstein field equations whose data development contains a region where the space–time is of Petrov type D. In this paper we give a systematic characterisation of a vacuum type D initial data set. By systematic we mean that the only quantities involved are those appearing in the vacuum constraints, namely the first fundamental form (Riemannian metric) and the second fundamental form. Our characterisation is a set of conditions consisting of the vacuum constraints and some additional differential equations for the first and second fundamental forms These conditions can be regarded as a system of partial differential equations on a Riemannian manifold and the solutions of the system contain all possible regular vacuum type D initial data sets. As an application we particularise our conditions for the case of vacuum data whose data development is a subset of the Kerr solution. This has applications in the formulation of the nonlinear stability problem of the Kerr black hole.

Serum dehydroepiandrosterone sulphate concentration is not a predictive factor in IVF outcomes before the first cycle of GnRH agonist administration in women with normal ovarian reserve.

Directory of Open Access Journals (Sweden)

Michał Kunicki

Full Text Available The aim of our study was to determine whether serum dehydroepiandrosterone sulphate (DHEAS concentration and the models incorporating it could help clinicians to predict IVF outcomes in women with normal ovarian reserve undergoing their first long protocol.We performed a retrospective analysis of 459 women undergoing cycles of intracytoplasmic sperm injection (ICSI for the first time in a long GnRH agonist protocol.Embryo transfer was performed in 407 women (88.7%. The fertilisation rate was 78.6%. The clinical pregnancy rate was 44.8% per started cycle and 50.6% per embryo transfer. Our univariate model revealed that the best predictors of clinical pregnancy were the number of mature oocytes, the number of embryos transferred and the number of good quality embryos, account for the clinical parameters that reflect ovarian reserve the best being AMH level and AFC. DHEAS did not predict clinical pregnancy (OR 1.001, 95% CI, 0.999-1.004. After adjusting for the number of embryos transferred and class of embryos in a multivariate model, the best predictors were age (OR 0.918, 95% CI, 0.867-0.972 and AFC (OR 1.022, 95% CI, 0.992-1.053. Serum DHEAS levels were positively correlated with AFC (r = 0.098, P<0.039 and testosterone levels (r = 0.371, P<0.001, as well as the number of mature oocytes (r = 0.109, P<0.019; serum DHEAS levels were negatively correlated with age (r = -0.220, P<0.001, follicle-stimulating hormone (FSH, (r = -0.116, P<0.015 and sex hormone-binding globulin (SHBG, (r = -0.193, P<0.001.DHEAS concentration (in addition to the known factors of ovarian reserve does not predict clinical pregnancy in women with normal ovarian reserve who are undergoing ICSI.

Geometrically nonlinear transient vibrations of actively damped anti-symmetric angle ply laminated composite shallow shell using active fibre composite (AFC) actuators

Science.gov (United States)

Ashok, M. H.; Shivakumar, J.; Nandurkar, Santosh; Khadakbhavi, Vishwanath; Pujari, Sanjay

2018-02-01

In present work, the thin laminated composite shallow shell as smart structure with AFC material’s ACLD treatment is analyzed for geometrically nonlinear transient vibrations. The AFC material is used to make the constraining layer of the ACLD treatment. Golla-Hughes-McTavish (GHM) is used to model the constrained viscoelastic layer of the ACLD treatment in time domain. Along with a simple first-order shear deformation theory the Von Kármán type non-linear strain displacement relations are used for deriving this electromechanical coupled problem. A 3-dimensional finite element model of smart composite panels integrated with the ACLD treated patches has been modelled to reveal the performance of ACLD treated patches on improving the damping properties of slender anti-symmetric angle-ply laminated shallow shell, in controlling the transient vibrations which are geometrically nonlinear. The mathematical results explain that the ACLD treated patches considerably enhance the damping properties of anti-symmetric angle-ply panels undergoing geometrically nonlinear transient vibrations.

Association between antral follicle count and reproductive measures in New Zealand lactating dairy cows maintained in a pasture-based production system.

Science.gov (United States)

Martinez, Marcelo F; Sanderson, Neil; Quirke, Laurel D; Lawrence, Stephen B; Juengel, Jennifer L

2016-02-01

The antral follicle count (AFC) in cattle is consistent throughout the estrous cycle of individual cows, and cows with a lower AFC have lower fertility. We assessed the AFC at random stages of the estrous cycle, examined the correlation between AFC classifications, and determined the relationship between the most rapid and practical laboratory-based AFC classification (AFC of follicles of ≥ 2 mm in diameter) and fertility measures in New Zealand lactating dairy cows. Cows detected in estrus (n = 202) or not (n = 239) during the first 4 weeks of the breeding season were subjected to ultrasonography and classified as having a high, medium, or low AFC at the time of scanning (on-site classification). Images from ultrasound scanning were recorded onto video for accurate follicle counting in an imaging laboratory. A strong association (P Cows with a high AFC had a shorter (P cows with a low AFC. The AFC was positively associated (P cows (7.6 ± 0.3 ng/mL) than in low-AFC cows (6.5 ± 0.3 ng/mL), whether these were pregnant (7.7 ± 0.3 ng/mL) or not (6.3 ± 0.2 ng/mL). A rapid on-site scoring system determined that cows classified as having a high AFC had a shorter (P cows with a low on-site AFC. Collectively, we have confirmed an association between AFC2 and fertility, and these results support the hypothesis that cows with a greater number of antral follicles are more fertile than cows with a lesser number of follicles. Although the on-site classification was related to resumption of estrous cycles after calving, associations with other fertility measurements could not be observed, highlighting a need for further refinement of the on-site classification system for rapid phenotyping of the AFC. Copyright © 2016 Elsevier Inc. All rights reserved.

East Asian Financial Cycles: Asian vs. Global Financial Crises

OpenAIRE

Akira Kohsaka; Jun-ichi Shinkai

2014-01-01

We examine the role of financial shocks in business cycles in general and in financial crises in particular in East Asia (Indonesia, Korea, Malaysia and Thailand) since the 1990s. Estimating a Financial Conditions Index, we found that financial shocks explain most of business downturns in all the economies in the Asian Financial Crisis (AFC) in 1997-98, but that the effects of financial shocks are diverse across economies in the Global Financial Crisis (GFC) in 2008-09. In the GFC, the financ...

Prediction value of anti-Mullerian hormone (AMH) serum levels and antral follicle count (AFC) in hormonal contraceptive (HC) users and non-HC users undergoing IVF-PGD treatment.

Science.gov (United States)

Bas-Lando, Maayan; Rabinowitz, Ron; Farkash, Rivka; Algur, Nurit; Rubinstein, Esther; Schonberger, Oshrat; Eldar-Geva, Talia

2017-10-01

Use of hormone contraceptives (HC) is very popular in the reproductive age and, therefore, evaluation of ovarian reserve would be a useful tool to accurately evaluate the reproductive potential in HC users. We conducted a retrospective cohort study of 41 HC users compared to 57 non-HC users undergoing IVF-preimplantation genetic diagnosis (PGD) aiming to evaluate the effect of HC on the levels of anti-Mullerian hormone (AMH), small (2-5 mm), large (6-10 mm) and total antral follicle count (AFC) and the ability of these markers to predict IVF outcome. Significant differences in large AFC (p = 0.04) and ovarian volume (p users (p users these correlations were weaker. In HC users, the significant predictors of achieving 18 oocytes were AFC (ROC-AUC; 0.958, p = 0.001 and 0.883, p = 0.001) and AMH (ROC-AUC-0.858, p = 0.01 and 0.878, p = 0.001), respectively. The predictive values were less significant in non-HC users. These findings are important in women treated for PGD, in ovum donors and for assessing the fertility prognosis in women using HC and wishing to postpone pregnancy.

Anti-D Antibodies in Pregnant D Variant Antigen Carriers Initially Typed as RhD.

Science.gov (United States)

Lukacevic Krstic, Jelena; Dajak, Slavica; Bingulac-Popovic, Jasna; Dogic, Vesna; Mratinovic-Mikulandra, Jela

2016-11-01

To evaluate the incidence, the consequences, and the prevention strategy of anti-D alloimmunizations of D variant carriers in the obstetric population of Split-Dalmatia County, Croatia. RhD immunization events were evaluated retrospectively for the period between 1993 and 2012. Women were tested for RhD antigen and irregular antibodies. Those with anti-D antibody who were not serologically D- were genotyped for RHD. They were evaluated for their obstetric and transfusion history and their titer of anti-D. The neonates were evaluated for RhD status, direct antiglobulin test (DAT), hemoglobin and bilirubin levels, transfusion therapy as well as phototherapy and outcome. Out of 104,884 live births 102,982 women were tested for RhD antigen. Anti-D immunization occurred in 184 women which accounts for 0.9% of individuals at risk of anti-D formation. 181 cases occurred in women serologically typed as D-. Three women were partial D carriers (DVa n = 2, DNB n = 1), initially typed RhD+, and recognized as D variant carriers after the immunization occurred. Anti-D titer varied from 1:1 to 1:16. Six children were RhD+, four had positive DAT, and two underwent phototherapy. Anti-D immunization occurred in pregnant partial D carriers (DVa, DNB). RhD+ children had serologic markers of hemolytic disease of the fetus and newborn (HDFN), with no cases of severe HDFN.

Influence of the crystalline orientations on microcrack initiation in low-cycle fatigue

Energy Technology Data Exchange (ETDEWEB)

Mu, P. [Univ Lille Nord de France, F-59000 Lille (France); ECLille, LML, F-59650 Villeneuve d’Ascq (France); CNRS, UMR 8107, UMR 8579 (France); Aubin, V., E-mail: veronique.aubin@ecp.fr [ECP, MSSMat, F-92295 Châtenay-Malabry (France); CNRS, UMR 8107, UMR 8579 (France); Alvarez-Armas, I.; Armas, A. [IFIR, CONICET, Universidad Nacional de Rosario (Argentina)

2013-06-20

Present study aims at analyzing the crack initiation in an austenitic stainless steel in low-cycle fatigue. A fatigue test was carried out using a polished specimen. The surface of the specimen was observed in situ during the fatigue test, in order to establish the time of slip activity or crack initiation. After a number of cycles sufficient to initiate small cracks, the test was stopped and the surface observed by scanning electron microscopy. The electron backscattered diffraction technique (EBSD) was used to identify the orientations of surface grains in the central zone of the fatigue specimen. Crack-initiation sites and slip systems associated to the initiated microcracks were identified. The criterion of the maximum Schmid factor explains two-thirds of the cracks initiated in slip systems; however if the favorably oriented slip band with respect to this criterion makes an angle of around 45° to the loading direction, a crack may initiate in another slip system.

Investigating the 3-D Subduction Initiation Processes at Transform Faults and Passive Margins

Science.gov (United States)

Peng, H.; Leng, W.

2017-12-01

Studying the processes of subduction initiation is a key for understanding the Wilson cycle and improving the theory of plate tectonics. Previous studies investigated subduction initiation with geological synthesis and geodynamic modeling methods, discovering that subduction intends to initiate at the transform faults close to oceanic arcs, and that its evolutionary processes and surface volcanic expressions are controlled by plate strength. However, these studies are mainly conducted with 2-D models, which cannot deal with lateral heterogeneities of crustal thickness and strength along the plate interfaces. Here we extend the 2-D model to a 3-D parallel subduction model with high computational efficiency. With the new model, we study the dynamic controlling factors, morphology evolutionary processes and surface expressions for subduction initiation with lateral heterogeneities of material properties along transform faults and passive margins. We find that lateral lithospheric heterogeneities control the starting point of the subduction initiation along the newly formed trenches and the propagation speed for the trench formation. New subduction tends to firstly initiate at the property changing point along the transform faults or passive margins. Such finds may be applied to explain the formation process of the Izu-Bonin-Mariana (IBM) subduction zone in the western Pacific and the Scotia subduction zone at the south end of the South America. Our results enhance our understanding for the formation of new trenches and help to provide geodynamic modeling explanations for the observed remnant slabs in the upper mantle and the surface volcanic expressions.

Software Platform Evaluation - Verifiable Fuel Cycle Simulation (VISION) Model

International Nuclear Information System (INIS)

J. J. Jacobson; D. E. Shropshire; W. B. West

2005-01-01

The purpose of this Software Platform Evaluation (SPE) is to document the top-level evaluation of potential software platforms on which to construct a simulation model that satisfies the requirements for a Verifiable Fuel Cycle Simulation Model (VISION) of the Advanced Fuel Cycle (AFC). See the Software Requirements Specification for Verifiable Fuel Cycle Simulation (VISION) Model (INEEL/EXT-05-02643, Rev. 0) for a discussion of the objective and scope of the VISION model. VISION is intended to serve as a broad systems analysis and study tool applicable to work conducted as part of the AFCI (including costs estimates) and Generation IV reactor development studies. This document will serve as a guide for selecting the most appropriate software platform for VISION. This is a ''living document'' that will be modified over the course of the execution of this work

Advanced Fuels Campaign FY 2014 Accomplishments Report

Energy Technology Data Exchange (ETDEWEB)

Braase, Lori [Idaho National Lab. (INL), Idaho Falls, ID (United States). INL Systems Analyses; May, W. Edgar [Idaho National Lab. (INL), Idaho Falls, ID (United States). INL Systems Analyses

2014-10-01

The mission of the Advanced Fuels Campaign (AFC) is to perform Research, Development, and Demonstration (RD&D) activities for advanced fuel forms (including cladding) to enhance the performance and safety of the nation’s current and future reactors; enhance proliferation resistance of nuclear fuel; effectively utilize nuclear energy resources; and address the longer-term waste management challenges. This includes development of a state-of-the art Research and Development (R&D) infrastructure to support the use of a “goal-oriented science-based approach.” In support of the Fuel Cycle Research and Development (FCRD) program, AFC is responsible for developing advanced fuels technologies to support the various fuel cycle options defined in the Department of Energy (DOE) Nuclear Energy Research and Development Roadmap, Report to Congress, April 2010. AFC uses a “goal-oriented, science-based approach” aimed at a fundamental understanding of fuel and cladding fabrication methods and performance under irradiation, enabling the pursuit of multiple fuel forms for future fuel cycle options. This approach includes fundamental experiments, theory, and advanced modeling and simulation. The modeling and simulation activities for fuel performance are carried out under the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, which is closely coordinated with AFC. In this report, the word “fuel” is used generically to include fuels, targets, and their associated cladding materials. R&D of light water reactor (LWR) fuels with enhanced accident tolerance is also conducted by AFC. These fuel systems are designed to achieve significantly higher fuel and plant performance to allow operation to significantly higher burnup, and to provide enhanced safety during design basis and beyond design basis accident conditions. The overarching goal is to develop advanced nuclear fuels and materials that are robust, have high performance capability, and are more tolerant to

First measurements of dtμ-cycle characteristics in liquid H/D/T mixture

International Nuclear Information System (INIS)

Averin, Yu.P.; Balin, D.V.; Bom, V.R.

1998-01-01

The muon catalyzed fusion in dense triple mixture of hydrogen isotopes has been investigated for the first time. The experimental method is based on the registration of neutrons from dtμ fusions by a full absorption detectors in 4π geometry. The measurements have been performed in H/D/T mixture at T = 22 K and φ ≅ 1.1 LHD at four sets of isotope concentrations. The basic parameters of dtμ cycle (neutron yield, cycling rate and total sticking) in H/D/T mixtures are presented and discussed

Value of digit ratio 2D:4D, a biomarker of prenatal hormone exposure, is stable across the menstrual cycle.

Science.gov (United States)

Klimek, Magdalena; Marcinkowska, Urszula M; Jasienska, Grazyna

2017-07-01

Digit ratio (2D:4D) is used as a marker of prenatal hormone exposure and, consequently, as a predictor of many characteristics throughout a woman's lifespan. A previous study has suggested that values of 2D:4D vary across menstrual cycles and further questioned the reliability of a single measurement of 2D:4D among cycling women, while another study failed to confirm these results. However, these studies estimated the timing of cycle phases based on a date of menstruation reported by participants and also had small sample sizes. For our study, we evaluated potential changes in 2D:4D values across a menstrual cycle in a group of women among whom the phases of the menstrual cycle were determined by hormonal (luteinizing hormone based) ovulation tests. We studied 32 naturally cycling women aged 22-37 from rural Poland. Lengths of second and fourth digits were measured based on scans of both hands taken three times (i.e. in the follicular phase, peri-ovulatory phase and luteal phase of the cycle) for each participant. No differences in 2D:4D value across the menstrual cycle were detected either when right-hand, left-hand, and mean 2D:4D for both hands were analysed, nor when difference in the 2D:4D value between hands (D left-right ) was evaluated. We documented that 2D:4D is independent of the phase of the menstrual cycle and these findings suggest that among naturally cycling women, a value of 2D:4D can be reliably obtained from measurements taken during any day of the menstrual cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

A Human Long Non-Coding RNA ALT1 Controls the Cell Cycle of Vascular Endothelial Cells Via ACE2 and Cyclin D1 Pathway

Directory of Open Access Journals (Sweden)

Wen Li

2017-10-01

Full Text Available Background/Aims: ALT1 is a novel long non-coding RNA derived from the alternatively spliced transcript of the deleted in lymphocytic leukemia 2 (DLEU2. To date, ALT1 biological roles in human vascular endothelial cells have not been reported. Methods: ALT1 was knocked down by siRNAs. Cell proliferation was analyzed by cck-8. The existence and sequence of human ALT1 were identified by 3’ rapid amplification of cDNA ends. The interaction between lncRNA and proteins was analyzed by RNA-Protein pull down assay, RNA immunoprecipitation, and mass spectrometry analysis. Results: ALT1 was expressed in human umbilical vein endothelial cells (HUVECs. The expression of ALT1 was significantly downregulated in contact-inhibited HUVECs and in hypoxia-induced, growth-arrested HUVECs. Knocking down of ALT1 inhibited the proliferation of HUVECs by G0/G1 cell cycle arrest. We observed that angiotensin converting enzyme Ⅱ(ACE2 was a direct target gene of ALT1. Knocking-down of ALT1 or its target gene ACE2 could efficiently decrease the expression of cyclin D1 via the enhanced ubiquitination and degradation, in which HIF-1α and protein von Hippel-Lindau (pVHL might be involved. Conclusion: The results suggested the human long non-coding RNA ALT1 is a novel regulator for cell cycle of HUVECs via ACE2 and cyclin D1 pathway.

Predicting 2D target velocity cannot help 2D motion integration for smooth pursuit initiation.

Science.gov (United States)

Montagnini, Anna; Spering, Miriam; Masson, Guillaume S

2006-12-01

Smooth pursuit eye movements reflect the temporal dynamics of bidimensional (2D) visual motion integration. When tracking a single, tilted line, initial pursuit direction is biased toward unidimensional (1D) edge motion signals, which are orthogonal to the line orientation. Over 200 ms, tracking direction is slowly corrected to finally match the 2D object motion during steady-state pursuit. We now show that repetition of line orientation and/or motion direction does not eliminate the transient tracking direction error nor change the time course of pursuit correction. Nonetheless, multiple successive presentations of a single orientation/direction condition elicit robust anticipatory pursuit eye movements that always go in the 2D object motion direction not the 1D edge motion direction. These results demonstrate that predictive signals about target motion cannot be used for an efficient integration of ambiguous velocity signals at pursuit initiation.

A probability-based multi-cycle sorting method for 4D-MRI: A simulation study.

Science.gov (United States)

Liang, Xiao; Yin, Fang-Fang; Liu, Yilin; Cai, Jing

2016-12-01

To develop a novel probability-based sorting method capable of generating multiple breathing cycles of 4D-MRI images and to evaluate performance of this new method by comparing with conventional phase-based methods in terms of image quality and tumor motion measurement. Based on previous findings that breathing motion probability density function (PDF) of a single breathing cycle is dramatically different from true stabilized PDF that resulted from many breathing cycles, it is expected that a probability-based sorting method capable of generating multiple breathing cycles of 4D images may capture breathing variation information missing from conventional single-cycle sorting methods. The overall idea is to identify a few main breathing cycles (and their corresponding weightings) that can best represent the main breathing patterns of the patient and then reconstruct a set of 4D images for each of the identified main breathing cycles. This method is implemented in three steps: (1) The breathing signal is decomposed into individual breathing cycles, characterized by amplitude, and period; (2) individual breathing cycles are grouped based on amplitude and period to determine the main breathing cycles. If a group contains more than 10% of all breathing cycles in a breathing signal, it is determined as a main breathing pattern group and is represented by the average of individual breathing cycles in the group; (3) for each main breathing cycle, a set of 4D images is reconstructed using a result-driven sorting method adapted from our previous study. The probability-based sorting method was first tested on 26 patients' breathing signals to evaluate its feasibility of improving target motion PDF. The new method was subsequently tested for a sequential image acquisition scheme on the 4D digital extended cardiac torso (XCAT) phantom. Performance of the probability-based and conventional sorting methods was evaluated in terms of target volume precision and accuracy as measured

JAEA key facilities for global advanced fuel cycle R and D

Energy Technology Data Exchange (ETDEWEB)

Nomura, Shigeo; Yamamoto, Ryuichi [Nuclear Fuel Cycle Engineering Labos, JAEA, 4-33 Tokai-mura, Ibaraki, 319-1194 (Japan)

2008-07-01

Advanced fuel cycle will be realized with the mid and long term R and D during the long-term transition period from LWR cycle to advanced reactor fuel cycle. Most of JAEA facilities have been utilized to establish the current LWR and FBR (Fast Breeder Reactor) fuel cycle by implementing evolutionary R and D. An assessment of today's state experimental facilities concerning the following research issues: reprocessing, Mox fuel fabrication, irradiation and post-irradiation examination, waste management and nuclear data measurement, is made. The revolutionary R and D requests new issues to be studied: the TRU multi-recycling, minor actinide recycling, the assessment of proliferation resistance and the assessment of cost reduction. To implement the revolutionary R and D for advanced fuel cycle, however, these facilities should be refurbished to install new machines and process equipment to provide more flexible testing parameters.

Analysis of fatigue crack initiation in cycled austempered ductile cast irons

Czech Academy of Sciences Publication Activity Database

Petrenec, Martin; Beran, Přemysl; Dluhoš, J.; Zouhar, Michal; Ševčík, Martin

2010-01-01

Roč. 2, č. 1 (2010), s. 2337-2346 E-ISSN 1877-7058. [ Fatigue 2010. Praha, 06.06.2010-11.06.2010] R&D Projects: GA ČR GAP108/10/2371; GA ČR GD106/09/H035 Institutional research plan: CEZ:AV0Z20410507; CEZ:AV0Z10480505 Keywords : Low cycle fatigue * ADI * Finite element modelling * Neutron diffraction Subject RIV: JL - Materials Fatigue , Friction Mechanics

Digit ratio (2D:4D) and circulating testosterone, oestradiol, and progesterone levels across the menstrual cycle.

Science.gov (United States)

Richards, Gareth; Klimek, Magdalena; Jasienska, Grazyna; Marcinkowska, Urszula M

2018-02-01

Digit ratio (2D:4D) is used by researchers as an indicator of prenatal sex hormone exposure. Two previous studies have examined associations between 2D:4D and circulating sex steroid concentrations across the menstrual cycle in adult females. One reported that digit ratio correlated positively with oestradiol levels, whereas the other found no such effect; neither observed significant associations with progesterone. To examine associations between 2D:4D, as well as asymmetry (i.e. right minus left 2D:4D), and circulating sex steroids across the menstrual cycle. Correlational. 32 naturally cycling adult females from rural southern Poland. Salivary oestradiol, progesterone, testosterone, and testosterone to oestradiol ratio (T:O) measured during the follicular, peri-ovulatory, and luteal phases. Average levels across the cycle were also examined. Asymmetry in digit ratio correlated positively with oestradiol at each phase, as well as with average levels across the cycle. Each association, other than that relating to average levels, remained statistically significant after a range of covariates had been controlled for. No other significant correlations were observed between digit ratio variables and circulating hormone levels. Our results might suggest that low exposure to androgens and/or high exposure to oestrogens during gestation is a predictor of high oestradiol levels in naturally cycling females of reproductive age. However, considering that it was asymmetry in digit ratio, and not either right or left 2D:4D, that was a significant predictor, it is also possible that these effects reflect more general associations between bilateral asymmetry and circulating oestradiol levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles.

Science.gov (United States)

de Wit, R.; van den Berg, H.; Burghouts, J.; Nortier, J.; Slee, P.; Rodenburg, C.; Keizer, J.; Fonteyn, M.; Verweij, J.; Wils, J.

1998-01-01

We have reported previously that the anti-emetic efficacy of single agent 5HT3 antagonists is not maintained when analysed with the measurement of cumulative probabilities. Presently, the most effective anti-emetic regimen is a combination of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment of efficacy of such a combination in 125 patients, scheduled to receive cisplatin > or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs. Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg of dexamethasone and 1 mg of granisetron twice daily by oral administration. Protection was assessed during all cycles and calculated based on cumulative probability analyses using the method of Kaplan-Meier and a model for transitional probabilities. Irrespective of the type of analysis used, the anti-emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial complete acute emesis protection rate of 66% decreased to 30% according to the method of Kaplan-Meier and to 39% using the model for transitional probabilities. For delayed emesis, the initial complete protection rate of 52% decreased to 21% (Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed that protection failure in the delayed emesis period adversely influenced the acute emesis protection in the next cycle. We conclude that the anti-emetic efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple cycles of highly emetogenic chemotherapy, and that the acute emesis protection is adversely influenced by protection failure in the delayed emesis phase. PMID:9652766

A user-operated audiometry method based on the maximum likelihood principle and the two-alternative forced-choice paradigm

DEFF Research Database (Denmark)

Schmidt, Jesper Hvass; Brandt, Christian; Pedersen, Ellen Raben

2014-01-01

with standard deviation of differences from 3.9 dB to 5.2 dB in the frequency range of 250-8000 Hz. User-operated 2AFC audiometrygave thresholds 1-2 dB lower at most frequencies compared to traditional audiometry. Conclusions: User-operated 2AFC audiometry does not require specific operating skills...

New techniques for designing the initial and reload cores with constant long cycle lengths

International Nuclear Information System (INIS)

Shi, Jun; Levine, Samuel; Ivanov, Kostadin

2017-01-01

Highlights: • New techniques for designing the initial and reload cores with constant long cycle lengths are developed. • Core loading pattern (LP) calculations and comparisons have been made on two different designs. • Results show that significant savings in fuel costs can be accrued if a non-low leakage LP design strategy is enacted. - Abstract: Several utilities have increased the output power of their nuclear power plant to increase their income and profit. Thus, the utility increases the power density of the reactor, which has other consequences. One consequence is to increase the depletion of the fuel assemblies (FAs) and reduce the end-of-cycle (EOC) sum of fissionable nuclides in each FA, ∑_E_O_C. The power density and the ∑_E_O_C remaining in the FAs at EOC must be sufficiently large in many FAs when designing the loading pattern, LP, for the first and reload cycles to maintain constant cycle lengths at minimum fuel cost. Also of importance is the cycle length as well as several other factors. In fact, the most important result of this study is to understand that the ∑_E_O_Cs in the FAs must be such that in the next cycle they can sustain the energy during depletion to prevent too much power shifting to the fresh FAs and, thus, sending the maximum peak pin power, PPP_m_a_x, above its constraint. This paper presents new methods for designing the LPs for the initial and follow on cycles to minimize the fuel costs. Studsvik’s CMS code system provides a 1000 MWe LP design in their sample inputs, which is applied in this study. The first 3 cycles of this core are analyzed to minimize fuel costs, and all three cycles have the same cycle length of ∼650 days. Cycle 1 is designed to allow many used FAs to be loaded into cycles 2 and 3 to reduce their fuel costs. This could not be achieved if cycle 1 was a low leakage LP (Shi et al., 2015). Significant fuel cost savings are achieved when the new designs are applied to the higher leakage LP designs

Interactive initialization of 2D/3D rigid registration

Energy Technology Data Exchange (ETDEWEB)

Gong, Ren Hui; Güler, Özgür [The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children' s National Medical Center, Washington, DC 20010 (United States); Kürklüoglu, Mustafa [Department of Cardiac Surgery, Children' s National Medical Center, Washington, DC 20010 (United States); Lovejoy, John [Department of Orthopaedic Surgery and Sports Medicine, Children' s National Medical Center, Washington, DC 20010 (United States); Yaniv, Ziv, E-mail: ZYaniv@childrensnational.org [The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children' s National Medical Center, Washington, DC 20010 and Departments of Pediatrics and Radiology, George Washington University, Washington, DC 20037 (United States)

2013-12-15

Purpose: Registration is one of the key technical components in an image-guided navigation system. A large number of 2D/3D registration algorithms have been previously proposed, but have not been able to transition into clinical practice. The authors identify the primary reason for the lack of adoption with the prerequisite for a sufficiently accurate initial transformation, mean target registration error of about 10 mm or less. In this paper, the authors present two interactive initialization approaches that provide the desired accuracy for x-ray/MR and x-ray/CT registration in the operating room setting. Methods: The authors have developed two interactive registration methods based on visual alignment of a preoperative image, MR, or CT to intraoperative x-rays. In the first approach, the operator uses a gesture based interface to align a volume rendering of the preoperative image to multiple x-rays. The second approach uses a tracked tool available as part of a navigation system. Preoperatively, a virtual replica of the tool is positioned next to the anatomical structures visible in the volumetric data. Intraoperatively, the physical tool is positioned in a similar manner and subsequently used to align a volume rendering to the x-ray images using an augmented reality (AR) approach. Both methods were assessed using three publicly available reference data sets for 2D/3D registration evaluation. Results: In the authors' experiments, the authors show that for x-ray/MR registration, the gesture based method resulted in a mean target registration error (mTRE) of 9.3 ± 5.0 mm with an average interaction time of 146.3 ± 73.0 s, and the AR-based method had mTREs of 7.2 ± 3.2 mm with interaction times of 44 ± 32 s. For x-ray/CT registration, the gesture based method resulted in a mTRE of 7.4 ± 5.0 mm with an average interaction time of 132.1 ± 66.4 s, and the AR-based method had mTREs of 8.3 ± 5.0 mm with interaction times of 58 ± 52 s. Conclusions: Based on

Interactive initialization of 2D/3D rigid registration

International Nuclear Information System (INIS)

Gong, Ren Hui; Güler, Özgür; Kürklüoglu, Mustafa; Lovejoy, John; Yaniv, Ziv

2013-01-01

Purpose: Registration is one of the key technical components in an image-guided navigation system. A large number of 2D/3D registration algorithms have been previously proposed, but have not been able to transition into clinical practice. The authors identify the primary reason for the lack of adoption with the prerequisite for a sufficiently accurate initial transformation, mean target registration error of about 10 mm or less. In this paper, the authors present two interactive initialization approaches that provide the desired accuracy for x-ray/MR and x-ray/CT registration in the operating room setting. Methods: The authors have developed two interactive registration methods based on visual alignment of a preoperative image, MR, or CT to intraoperative x-rays. In the first approach, the operator uses a gesture based interface to align a volume rendering of the preoperative image to multiple x-rays. The second approach uses a tracked tool available as part of a navigation system. Preoperatively, a virtual replica of the tool is positioned next to the anatomical structures visible in the volumetric data. Intraoperatively, the physical tool is positioned in a similar manner and subsequently used to align a volume rendering to the x-ray images using an augmented reality (AR) approach. Both methods were assessed using three publicly available reference data sets for 2D/3D registration evaluation. Results: In the authors' experiments, the authors show that for x-ray/MR registration, the gesture based method resulted in a mean target registration error (mTRE) of 9.3 ± 5.0 mm with an average interaction time of 146.3 ± 73.0 s, and the AR-based method had mTREs of 7.2 ± 3.2 mm with interaction times of 44 ± 32 s. For x-ray/CT registration, the gesture based method resulted in a mTRE of 7.4 ± 5.0 mm with an average interaction time of 132.1 ± 66.4 s, and the AR-based method had mTREs of 8.3 ± 5.0 mm with interaction times of 58 ± 52 s. Conclusions: Based on the

Measured Thermal and Fast Neutron Fluence Rates for ATF-1 Holders During ATR Cycle 157D

Energy Technology Data Exchange (ETDEWEB)

Smith, Larry Don [Idaho National Lab. (INL), Idaho Falls, ID (United States); Miller, David Torbet [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-03-01

This report contains the thermal (2200 m/s) and fast (E>1MeV) neutron fluence rate data for the ATF-1 holders located in core for ATR Cycle 157D which were measured by the Radiation Measurements Laboratory (RML) as requested by the Power Reactor Programs (ATR Experiments) Radiation Measurements Work Order. This report contains measurements of the fluence rates corresponding to the particular elevations relative to the 80-ft. core elevation. The data in this report consist of (1) a table of the ATR power history and distribution, (2) a hard copy listing of all thermal and fast neutron fluence rates, and (3) plots of both the thermal and fast neutron fluence rates. The fluence rates reported are for the average power levels given in the table of power history and distribution.

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 1: The predicted poor responder.

Science.gov (United States)

van Tilborg, Theodora C; Torrance, Helen L; Oudshoorn, Simone C; Eijkemans, Marinus J C; Koks, Carolien A M; Verhoeve, Harold R; Nap, Annemiek W; Scheffer, Gabrielle J; Manger, A Petra; Schoot, Benedictus C; Sluijmer, Alexander V; Verhoeff, Arie; Groen, Henk; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M

2017-12-01

Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? In women with a predicted poor ovarian response (AFC IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. In total, 511 women were randomized, 234 with an AFC ≤ 7 and 277 with an AFC 8-10. The cumulative live birth rate for increased versus standard dosing was 42.4% (106/250) versus 44.8% (117/261), respectively [relative risk (RR): 0.95 (95%CI, 0.78-1.15), P = 0.58]. As an increased dose strategy was more expensive [delta costs/woman: €1099 (95%CI, 562-1591)], standard FSH dosing was the dominant strategy in our economic analysis. Despite our training programme, the AFC might have suffered from inter-observer variation. As this open study permitted small dose adjustments between cycles, potential selective cancelling of cycles in women treated with 150 IU could have influenced the cumulative results. However, since first cycle live birth rates point in the same direction we consider it unlikely that the open design masked a potential benefit for the individualized strategy. Since an increased dose in women scheduled for IVF/ICSI with a predicted poor response (AFC < 11) does not improve live birth rates and is more expensive, we recommend using a standard dose of 150 IU/day in these women. This

Tumor suppressor BLU inhibits proliferation of nasopharyngeal carcinoma cells by regulation of cell cycle, c-Jun N-terminal kinase and the cyclin D1 promoter

International Nuclear Information System (INIS)

Zhang, Xiangning; Liu, Hui; Li, Binbin; Huang, Peichun; Shao, Jianyong; He, Zhiwei

2012-01-01

Tumor suppressor genes function to regulate and block tumor cell proliferation. To explore the mechanisms underlying the tumor suppression of BLU/ZMYND10 gene on a frequently lost human chromosomal region, an adenoviral vector with BLU cDNA insert was constructed. BLU was re-expressed in nasopharyngeal carcinoma cells by transfection or viral infection. Clonogenic growth was assayed; cell cycle was analyzed by flow cytometry-based DNA content detection; c-Jun N-terminal kinase (JNK) and cyclin D1 promoter activities were measured by reporter gene assay, and phosphorylation was measured by immunoblotting. The data for each pair of groups were compared with Student t tests. BLU inhibits clonogenic growth of nasopharyngeal carcinoma cells, arrests cell cycle at G1 phase, downregulates JNK and cyclin D1 promoter activities, and inhibits phosphorylation of c-Jun. BLU inhibits growth of nasopharyngeal carcinoma cells by regulation of the JNK-cyclin D1 axis to exert tumor suppression

DMPD: CSF-1 and cell cycle control in macrophages. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 8981359 CSF-1 and cell cycle control in macrophages. Hamilton JA. Mol Reprod Dev. 1...997 Jan;46(1):19-23. (.png) (.svg) (.html) (.csml) Show CSF-1 and cell cycle control in macrophages. PubmedI...D 8981359 Title CSF-1 and cell cycle control in macrophages. Authors Hamilton JA. Publication Mol Reprod Dev

Changes in CO2 during Ocean Anoxic Event 1d indicate similarities to other carbon cycle perturbations

Science.gov (United States)

Richey, Jon D.; Upchurch, Garland R.; Montañez, Isabel P.; Lomax, Barry H.; Suarez, Marina B.; Crout, Neil M. J.; Joeckel, R. M.; Ludvigson, Greg A.; Smith, Jon J.

2018-06-01

Past greenhouse intervals of the Mesozoic were repeatedly punctuated by Ocean Anoxic Events (OAEs), major perturbations to the global carbon cycle and abrupt climate changes that may serve as relevant analogs for Earth's greenhouse gas-forced climate future. The key to better understanding these transient climate disruptions and possible CO2-forced tipping-points resides in high-resolution, precise, and accurate estimates of atmospheric CO2 for individual OAEs. Here we present a high-temporal resolution, multi-proxy pCO2 reconstruction for the onset of mid-Cretaceous (Albian-Cenomanian Boundary) OAE1d. Coupling of pCO2 estimates with carbon isotopic compositions (δ13C) of charcoal, vitrain, and cuticle from the Rose Creek Pit (RCP), Nebraska, reveals complex phasing, including a lag between the well-documented negative δ13C excursion defining the onset of OAE1d and the CO2 increase. This lag indicates that increased CO2 or other C-based greenhouse gases may not have been the primary cause of the negative excursion. Our study reveals a pCO2 increase within the interval of the negative δ13C excursion, reaching a maximum of up to ∼840 ppm (95% confidence interval -307 ppm/+167 ppm) toward its end. The reconstructed magnitude of CO2 increase (∼357 ppm) is similar to that of Late Cretaceous OAE2 but of smaller magnitude than that of other major carbon cycle perturbations of the Mesozoic assessed via stomatal methods (e.g., the Toarcian OAE [TOAE], Triassic-Jurassic boundary event, Cretaceous-Paleogene Boundary event). Furthermore, our results indicate a possible shared causal or developmental mechanism with OAE1a and the TOAE.

Advanced fuels campaign 2013 accomplishments

Energy Technology Data Exchange (ETDEWEB)

Braase, Lori [Idaho National Lab. (INL), Idaho Falls, ID (United States); Hamelin, Doug [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2013-10-01

The mission of the Advanced Fuels Campaign (AFC) is to perform Research, Development, and Demonstration (RD&D) activities for advanced fuel forms (including cladding) to enhance the performance and safety of the nation’s current and future reactors; enhance proliferation resistance of nuclear fuel; effectively utilize nuclear energy resources; and address the longer-term waste management challenges. This includes development of a state-of-the art Research and Development (R&D) infrastructure to support the use of “goal-oriented science-based approach.” In support of the Fuel Cycle Research and Development (FCRD) program, AFC is responsible for developing advanced fuels technologies to support the various fuel cycle options defined in the Department of Energy (DOE) Nuclear Energy Research and Development Roadmap, Report to Congress, April 2010. Accomplishments made during fiscal year (FY) 2013 are highlighted in this report, which focuses on completed work and results. The process details leading up to the results are not included; however, the technical contact is provided for each section.

Advanced Fuels Campaign Execution Plan

Energy Technology Data Exchange (ETDEWEB)

Kemal Pasamehmetoglu

2010-10-01

The purpose of the Advanced Fuels Campaign (AFC) Execution Plan is to communicate the structure and management of research, development, and demonstration (RD&D) activities within the Fuel Cycle Research and Development (FCRD) program. Included in this document is an overview of the FCRD program, a description of the difference between revolutionary and evolutionary approaches to nuclear fuel development, the meaning of science-based development of nuclear fuels, and the “Grand Challenge” for the AFC that would, if achieved, provide a transformational technology to the nuclear industry in the form of a high performance, high reliability nuclear fuel system. The activities that will be conducted by the AFC to achieve success towards this grand challenge are described and the goals and milestones over the next 20 to 40 year period of research and development are established.

Advanced Fuels Campaign Execution Plan

Energy Technology Data Exchange (ETDEWEB)

Kemal Pasamehmetoglu

2011-09-01

The purpose of the Advanced Fuels Campaign (AFC) Execution Plan is to communicate the structure and management of research, development, and demonstration (RD&D) activities within the Fuel Cycle Research and Development (FCRD) program. Included in this document is an overview of the FCRD program, a description of the difference between revolutionary and evolutionary approaches to nuclear fuel development, the meaning of science-based development of nuclear fuels, and the 'Grand Challenge' for the AFC that would, if achieved, provide a transformational technology to the nuclear industry in the form of a high performance, high reliability nuclear fuel system. The activities that will be conducted by the AFC to achieve success towards this grand challenge are described and the goals and milestones over the next 20 to 40 year period of research and development are established.

Ovarian morphology in polycystic ovary syndrome

DEFF Research Database (Denmark)

Nylander, Malin; Frøssing, Signe; Bjerre, Anne H.

2017-01-01

in estimates of ovarian volume and antral follicle count (AFC) from two-dimensional (2D) and 3D transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI). Material and Methods A cross-sectional study on 66 overweight women with polycystic ovary syndrome (PCOS) according to Rotterdam criteria. Ovarian...... between AMH and AFC from 2D TVUS, 3D TVUS, and MRI were 0.67, 0.78, and 0.70, respectively (P PCOS population, 2D TVUS underestimated ovarian volume and AFC as compared with 3D TVUS and MRI. Serum AMH correlated best with AFC from 3D TVUS, followed by MRI...... and 2D TVUS. The advantage of 3D TVUS might be of minor clinical importance when diagnosing PCOS, but useful when the actual AFC are of interest, e.g. in fertility counseling and research....

Associations between age at first calving, rearing average daily weight gain, herd milk yield and dairy herd production, reproduction, and profitability.

Science.gov (United States)

Krpálková, L; Cabrera, V E; Kvapilík, J; Burdych, J; Crump, P

2014-10-01

The objective of this study was to evaluate the associations of variable intensity in rearing dairy heifers on 33 commercial dairy herds, including 23,008 cows and 18,139 heifers, with age at first calving (AFC), average daily weight gain (ADG), and milk yield (MY) level on reproduction traits and profitability. Milk yield during the production period was analyzed relative to reproduction and economic parameters. Data were collected during a 1-yr period (2011). The farms were located in 12 regions in the Czech Republic. The results show that those herds with more intensive rearing periods had lower conception rates among heifers at first and overall services. The differences in those conception rates between the group with the greatest ADG (≥0.800 kg/d) and the group with the least ADG (≤0.699 kg/d) were approximately 10 percentage points in favor of the least ADG. All the evaluated reproduction traits differed between AFC groups. Conception at first and overall services (cows) was greatest in herds with AFC ≥800 d. The shortest days open (105 d) and calving interval (396 d) were found in the middle AFC group (799 to 750 d). The highest number of completed lactations (2.67) was observed in the group with latest AFC (≥800 d). The earliest AFC group (≤749 d) was characterized by the highest depreciation costs per cow at 8,275 Czech crowns (US$414), and the highest culling rate for cows of 41%. The most profitable rearing approach was reflected in the middle AFC (799 to 750 d) and middle ADG (0.799 to 0.700 kg) groups. The highest MY (≥8,500 kg) occurred with the earliest AFC of 780 d. Higher MY led to lower conception rates in cows, but the highest MY group also had the shortest days open (106 d) and a calving interval of 386 d. The same MY group had the highest cow depreciation costs, net profit, and profitability without subsidies of 2.67%. We conclude that achieving low AFC will not always be the most profitable approach, which will depend upon farm

Blastocyst transfer does not improve cycle outcome as compared to D3 transfer in antagonist cycles with an elevated progesterone level on the day of hCG.

Science.gov (United States)

Demirel, Cem; Aydoğdu, Serkan; Özdemir, Arzu İlknur; Keskin, Gülşah; Baştu, Ercan; Buyru, Faruk

2017-09-01

To evaluate the association between progesterone elevation on the day of human chorionic gonadotropin (hCG) administration and clinical pregnancy rates of gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles with the transfer of embryos at different developmental stages (day-3 versus day-5 ETs). This is a retrospective analysis of fresh IVF/ICSI; 194 cycles out of 2676 conducted in a single center. A total of 2676 cycles were analyzed, of which 386 had no progesterone measurements available. Two hundred eighteen cycles had progesterone elevation (p>1.5 ng/mL) giving an overall incidence of 9.5%. Twenty-four cycles were excluded from further analysis. Of the remaining 194 cycles, 151 had day-3 transfers and 43 had blastocyst transfers. There was no statistically significant difference in pregnancy and clinical pregnancy rates per transfer between the D3-ET and D5-ET groups (46% vs. 49%, and 39% vs. 35%, respectively). The results of this study suggest that blastocyst transfer does not improve cycle outcomes compared with D3 transfer in GnRH antagonist cycles with an elevated progesterone level on the day of hCG.

Ovarian response and cumulative live birth rate of women undergoing in-vitro fertilisation who had discordant anti-Mullerian hormone and antral follicle count measurements: a retrospective study.

Directory of Open Access Journals (Sweden)

Hang Wun Raymond Li

Full Text Available OBJECTIVE: To evaluate ovarian response and cumulative live birth rate of women undergoing in-vitro fertilization (IVF treatment who had discordant baseline serum anti-Mullerian hormone (AMH level and antral follicle count (AFC. METHODS: This is a retrospective cohort study on 1,046 women undergoing the first IVF cycle in Queen Mary Hospital, Hong Kong. Subjects receiving standard IVF treatment with the GnRH agonist long protocol were classified according to their quartiles of baseline AMH and AFC measurements after GnRH agonist down-regulation and before commencing ovarian stimulation. The number of retrieved oocytes, ovarian sensitivity index (OSI and cumulative live-birth rate for each classification category were compared. RESULTS: Among our studied subjects, 32.2% were discordant in their AMH and AFC quartiles. Among them, those having higher AMH within the same AFC quartile had higher number of retrieved oocytes and cumulative live-birth rate. Subjects discordant in AMH and AFC had intermediate OSI which differed significantly compared to those concordant in AMH and AFC on either end. OSI of those discordant in AMH and AFC did not differ significantly whether either AMH or AFC quartile was higher than the other. CONCLUSIONS: When AMH and AFC are discordant, the ovarian responsiveness is intermediate between that when both are concordant on either end. Women having higher AMH within the same AFC quartile had higher number of retrieved oocytes and cumulative live-birth rate.

Microstructural characterization of the cycling behavior of electrodeposited manganese oxide supercapacitors using 3D electron tomography

Science.gov (United States)

Dalili, N.; Clark, M. P.; Davari, E.; Ivey, D. G.

2016-10-01

Manganese oxide has been investigated extensively as an electrochemical capacitor or supercapacitor electrode material. Manganese oxide is inexpensive to fabricate and exhibits relatively high capacitance values, i.e., in excess of 200 F g-1 in many cases; the actual value depends very much on the fabrication method and test conditions. The cycling behavior of Mn oxide, fabricated using anodic electrodeposition, is investigated using slice and view techniques, via a dual scanning electron microscope (SEM) and focused ion beam (FIB) instrument to generate three-dimensional (3D) images, coupled with electrochemical characterization. The initial as-fabricated electrode has a rod-like appearance, with a fine-scale, sheet-like morphology within the rods. The rod-like structure remains after cycling, but there are significant morphological changes. These include partial dissolution of Mn oxide followed by redeposition of Mn oxide in regions close to the substrate. The redeposited material has a finer morphology than the original as-fabricated Mn oxide. The Mn oxide coverage is also better near the substrate. These effects result in an increase in the specific capacitance.

Correlation of normal-range FMR1 repeat length or genotypes and reproductive parameters.

Science.gov (United States)

Maslow, Bat-Sheva L; Davis, Stephanie; Engmann, Lawrence; Nulsen, John C; Benadiva, Claudio A

2016-09-01

This study aims to ascertain whether the length of normal-ranged CGG repeats on the FMR1 gene correlates with abnormal reproductive parameters. We performed a retrospective, cross-sectional study of all FMR1 carrier screening performed as part of routine care at a large university-based fertility center from January 2011 to March 2014. Correlations were performed between normal-range FMR1 length and baseline serum anti-Müllerian hormone (AMH), cycle day 3 follicle stimulating hormone (FSH), ovarian volumes (OV), antral follicle counts (AFC), and incidence of diminished ovarian reserve (DOR), while controlling for the effect of age. Six hundred three FMR1 screening results were collected. One subject was found to be a pre-mutation carrier and was excluded from the study. Baseline serum AMH, cycle day 3 FSH, OV, and AFC data were collected for the 602 subjects with normal-ranged CGG repeats. No significant difference in median age was noted amongst any of the FMR1 repeat genotypes. No significant correlation or association was found between any allele length or genotype, with any of the reproductive parameters or with incidence of DOR at any age (p > 0.05). However, subjects who were less than 35 years old with low/low genotype were significantly more likely to have below average AMH levels compared to those with normal/normal genotype (RR 3.82; 95 % CI 1.38-10.56). This large study did not demonstrate any substantial association between normal-range FMR1 repeat lengths and reproductive parameters.

Performance analysis and optimization for generalized quantum Stirling refrigeration cycle with working substance of a particle confined in a general 1D potential

Science.gov (United States)

Yin, Yong; Chen, Lingen; Wu, Feng

2018-03-01

A generalized irreversible quantum Stirling refrigeration cycle (GIQSRC) is proposed. The working substance of the GIQSRC is a particle confined in a general 1D potential which energy spectrum can be expressed as εn = ℏωnσ . Heat leakage and non-ideal regeneration loss are taken into account. The expressions of coefficient of performance (COP) and dimensionless cooling load are obtained. The different practical cases of the energy spectrum are analyzed. The results of this paper are meaningful to understand the quantum thermodynamics cycles with a particle confined in different potential as working substance.

Hepatitis C Virus core+1/ARF Protein Modulates the Cyclin D1/pRb Pathway and Promotes Carcinogenesis.

Science.gov (United States)

Moustafa, Savvina; Karakasiliotis, Ioannis; Mavromara, Penelope

2018-05-01

Viruses often encompass overlapping reading frames and unconventional translation mechanisms in order to maximize the output from a minimum genome and to orchestrate their timely gene expression. Hepatitis C virus (HCV) possesses such an unconventional open reading frame (ORF) within the core-coding region, encoding an additional protein, initially designated ARFP, F, or core+1. Two predominant isoforms of core+1/ARFP have been reported, core+1/L, initiating from codon 26, and core+1/S, initiating from codons 85/87 of the polyprotein coding region. The biological significance of core+1/ARFP expression remains elusive. The aim of the present study was to gain insight into the functional and pathological properties of core+1/ARFP through its interaction with the host cell, combining in vitro and in vivo approaches. Our data provide strong evidence that the core+1/ARFP of HCV-1a stimulates cell proliferation in Huh7-based cell lines expressing either core+1/S or core+1/L isoforms and in transgenic liver disease mouse models expressing core+1/S protein in a liver-specific manner. Both isoforms of core+1/ARFP increase the levels of cyclin D1 and phosphorylated Rb, thus promoting the cell cycle. In addition, core+1/S was found to enhance liver regeneration and oncogenesis in transgenic mice. The induction of the cell cycle together with increased mRNA levels of cell proliferation-related oncogenes in cells expressing the core+1/ARFP proteins argue for an oncogenic potential of these proteins and an important role in HCV-associated pathogenesis. IMPORTANCE This study sheds light on the biological importance of a unique HCV protein. We show here that core+1/ARFP of HCV-1a interacts with the host machinery, leading to acceleration of the cell cycle and enhancement of liver carcinogenesis. This pathological mechanism(s) may complement the action of other viral proteins with oncogenic properties, leading to the development of hepatocellular carcinoma. In addition, given that

Antimüllerian hormone levels and antral follicle count as prognostic indicators in a personalized prediction model of live birth.

Science.gov (United States)

Nelson, Scott M; Fleming, Richard; Gaudoin, Marco; Choi, Bokyung; Santo-Domingo, Kenny; Yao, Mylene

2015-08-01

To compare antimüllerian hormone (AMH) and antral follicle count (AFC) separately and in combination with clinical characteristics for the prediction of live birth after controlled ovarian stimulation. Retrospective development and temporal external validation of prediction model. Outpatient IVF clinic. We applied the boosted tree method to develop three prediction models incorporating clinical characteristics plus AMH or AFC or the combination on 2,124 linked IVF cycles from 2006 to 2010 and temporally externally validated predicted live-birth probabilities with an independent data set comprising 1,121 cycles from 2011 to 2012. None. Predictive power (posterior log of odds ratio compared to age, or PLORA), reclassification, receiver operator characteristic analysis, calibration, dynamic range. Predictive power, was highest for the AMH model (PLORA = 29.1), followed by the AMH-AFC model (PLORA = 28.3) and AFC model (PLORA = 22.5). The prediction errors were 1% to models, except for the predicted live-birth probabilities of model, where the prediction error was 8%. The improvement in predictive power was highest for the AMH model: 76.2% improvement over age alone relative to 59% improvement for AFC and 73.3% for the combined model. Receiver operating characteristic analysis demonstrated that the AMH and the combined model had comparable discrimination (area under the curve = 0.716) and similar prediction error for high and low strata of live-birth prediction, with an improvement of 6.3% over age alone. The validated prediction model confirmed that AMH when combined with clinical characteristics can accurately identify the likelihood of live birth with a low prediction error. AFC provided no added predictive value beyond AMH. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Utilização da contagem de folículos antrais para predição do padrão de resposta em ciclos de hiperestimulação controlada com antagonista de GnRH Use of antral follicle count to predict the response pattern in controlled ovarian hyperstimulation cycles with GnRH antagonist

Directory of Open Access Journals (Sweden)

Maria do Carmo Borges de Souza

2008-01-01

Full Text Available OBJETIVO: verificar se existe relação preditiva entre a contagem de folículos antrais (CFA no segundo dia do ciclo com o padrão de resposta em ciclos de hiperestimulação ovariana controlada para injeção intracitoplasmática de espermatozóide (ICSI. MÉTODOS: estudo prospectivo, desenvolvido de maio de 2004 a maio de 2005, no qual 51 pacientes com idade 15 mm no dia do desencadeamento da ovulação, número total e em metáfase II de oócitos captados, número de embriões de boa qualidade transferidos e taxa de gestação. A análise estatística foi realizada pelos testes t de Student e de Mann-Whitney, com significância estatística de 5% (pPURPOSE: to establish whether there is a predictive relationship between the antral follicle count (AFC on the second day of the cycle and the response pattern in controlled ovarian hyperstimulation cycles for intracytoplasmic sperm injection (ICSI. METHODS: a prospective study developed from May 2004 to May 2005, in which 51 patients aged 15 mm on the day of ovulation triggering, the total number of oocytes retrieved and in metaphases II, the number of good quality embryos transferred and pregnancy rate. The statistical analysis was performed by the t-Student test and the Mann-Whitney test, with statistical significance of 5% (p15 mm on the day of ovulation triggering (p=0.0001, the total number of oocytes retrieved (p=0.0001 and those in metaphases II (p=0.0001. Such correlation between AFC and pregnancy was not observed (p=0.43. There was no significant correlation between AFC and the number of good quality embryos transferred (p=0.081. CONCLUSIONS: AFC on the second day of the stimulated cycle can be used to predict the quality of ovarian stimulation, the number of oocytes retrieved and the number of mature oocytes in in vitro fertilization cycles using GnRH antagonist.

1D Ni-Co oxide and sulfide nanoarray/carbon aerogel hybrid nanostructures for asymmetric supercapacitors with high energy density and excellent cycling stability.

Science.gov (United States)

Hao, Pin; Tian, Jian; Sang, Yuanhua; Tuan, Chia-Chi; Cui, Guanwei; Shi, Xifeng; Wong, C P; Tang, Bo; Liu, Hong

2016-09-15

The fabrication of supercapacitor electrodes with high energy density and excellent cycling stability is still a great challenge. A carbon aerogel, possessing a hierarchical porous structure, high specific surface area and electrical conductivity, is an ideal backbone to support transition metal oxides and bring hope to prepare electrodes with high energy density and excellent cycling stability. Therefore, NiCo 2 S 4 nanotube array/carbon aerogel and NiCo 2 O 4 nanoneedle array/carbon aerogel hybrid supercapacitor electrode materials were synthesized by assembling Ni-Co precursor needle arrays on the surface of the channel walls of hierarchical porous carbon aerogels derived from chitosan in this study. The 1D nanostructures grow on the channel surface of the carbon aerogel vertically and tightly, contributing to the enhanced electrochemical performance with ultrahigh energy density. The energy density of NiCo 2 S 4 nanotube array/carbon aerogel and NiCo 2 O 4 nanoneedle array/carbon aerogel hybrid asymmetric supercapacitors can reach up to 55.3 Wh kg -1 and 47.5 Wh kg -1 at a power density of 400 W kg -1 , respectively. These asymmetric devices also displayed excellent cycling stability with a capacitance retention of about 96.6% and 92% over 5000 cycles.

1,25(OH)2D3 disrupts glucose metabolism in prostate cancer cells leading to a truncation of the TCA cycle and inhibition of TXNIP expression.

Science.gov (United States)

Abu El Maaty, Mohamed A; Alborzinia, Hamed; Khan, Shehryar J; Büttner, Michael; Wölfl, Stefan

2017-10-01

Prostate cell metabolism exhibits distinct profiles pre- and post-malignancy. The malignant metabolic shift converts prostate cells from "citrate-producing" to "citrate-oxidizing" cells, thereby enhancing glucose metabolism, a phenotype that contrasts classical tumoral Warburg metabolism. An on-line biosensor chip system (BIONAS 2500) was used to monitor metabolic changes (glycolysis and respiration) in response to the putative anti-cancer nutraceutical 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ], in different prostate cancer (PCa) cell lines (LNCaP, VCaP, DU145 and PC3). LNCaP cells exhibited profound metabolic responsiveness to the treatment and thus extensive analysis of metabolism-modulating effects of 1,25(OH) 2 D 3 were performed, including mRNA expression analysis of key metabolic genes (e.g. GLUT1 and PDHK1), analysis of TCA cycle metabolites, glucose uptake/consumption measurements, ATP production, and mitochondrial biogenesis/activity. Altogether, data demonstrate a vivid disruption of glucose metabolism by 1,25(OH) 2 D 3 , illustrated by a decreased glucose uptake and an accumulation of citrate/isocitrate due to TCA cycle truncation. Depletion of glycolytic intermediates led to a consistent decrease in TXNIP expression in response to 1,25(OH) 2 D 3 , an effect that coincided with the activation of AMPK signaling and a reduction in c-MYC expression. Reduction in TXNIP levels in response to 1,25(OH) 2 D 3 was rescued by an AMPK signaling inhibitor and mimicked by a MYC inhibitor highlighting the possible involvement of both pathways in mediating 1,25(OH) 2 D 3 's metabolic effects in PCa cells. Furthermore, pharmacological and genetic modulation of the androgen receptor showed similar and disparate effects on metabolic parameters compared to 1,25(OH) 2 D 3 treatment, highlighting the AR-independent nature of 1,25(OH) 2 D 3 's metabolism-modulating effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of vitamin D on cell cycle, apoptosis, and some apoptosis related molecules in systemic lupus erythematosus

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Nafise Tabasi

2015-11-01

Full Text Available Objective(s:Genetic and environmental factors are involved in the pathogenesis of systemic lupus erythematosus (SLE. Autoreactive lymphocytes are cleared through apoptosis and any disturbance in the apoptosis or clearance of apoptotic cells may disturb tolerance and lead to autoimmunity. Vitamin D has anti-proliferative effects and controls cell cycle progression. In this study we investigated the effects of vitamin D on cell cycle and apoptosis induction in lupus patients. Materials and Methods:Isolated peripheral blood mononuclear cells (PBMCs from 25 SLE patients were cultured in the presence of 50 nM of 1,25(OH2D3; then one part of the cells were stained with FITC labeled Annexin V and PI and were analyzed for apoptosis determination. For gene expression assessment of FasL, Bcl-2 and Bax, RNA was extracted from one another part of the cells, cDNA was synthesized and gene expression analysis was performed using Real time PCR. An additional part of the cells were treated with PI and the cell cycle was analyzed using flowcytometer. Results: The mean number of early apoptotic cells in vitamin D treated cells decreased significantly (18.48±7.9% compared to untreated cells (22.02±9.4% (P=0.008. Cell cycle analysis showed a significant increase in G1 phase in vitamin D treated cells (67.33±5.2% compared to non treated ones (60.77±5.7% (P =0.02. Vitamin D up-regulated the expression levels of Bcl-2 by (18.87 fold increase, and down-regulated expression of Bax (23% and FasL (25%. Conclusion:Vitamin D has regulatory effects on cell cycle progression, apoptosis and apoptosis related molecules in lupus patients.

Synthesizing Porous NaTi2(PO4)3 Nanoparticles Embedded in 3D Graphene Networks for High-Rate and Long Cycle-Life Sodium Electrodes.

Science.gov (United States)

Wu, Chao; Kopold, Peter; Ding, Yuan-Li; van Aken, Peter A; Maier, Joachim; Yu, Yan

2015-06-23

Sodium ion batteries attract increasing attention for large-scale energy storage as a promising alternative to the lithium counterparts in view of low cost and abundant sodium source. However, the large ion radius of Na brings about a series of challenging thermodynamic and kinetic difficulties to the electrodes for sodium-storage, including low reversible capacity and low ion transport, as well as large volume change. To mitigate or even overcome the kinetic problems, we develop a self-assembly route to a novel architecture consisting of nanosized porous NASICON-type NaTi2(PO4)3 particles embedded in microsized 3D graphene network. Such architecture synergistically combines the advantages of a 3D graphene network and of 0D porous nanoparticles. It greatly increases the electron/ion transport kinetics and assures the electrode structure integrity, leading to attractive electrochemical performance as reflected by a high rate-capability (112 mAh g(-1) at 1C, 105 mAh g(-1) at 5C, 96 mAh g(-1) at 10C, 67 mAh g(-1) at 50C), a long cycle-life (capacity retention of 80% after 1000 cycles at 10C), and a high initial Coulombic efficiency (>79%). This nanostructure design provides a promising pathway for developing high performance NASICON-type materials for sodium storage.

The DnaA Cycle in Escherichia coli: Activation, Function and Inactivation of the Initiator Protein

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Tsutomu Katayama

2017-12-01

Full Text Available This review summarizes the mechanisms of the initiator protein DnaA in replication initiation and its regulation in Escherichia coli. The chromosomal origin (oriC DNA is unwound by the replication initiation complex to allow loading of DnaB helicases and replisome formation. The initiation complex consists of the DnaA protein, DnaA-initiator-associating protein DiaA, integration host factor (IHF, and oriC, which contains a duplex-unwinding element (DUE and a DnaA-oligomerization region (DOR containing DnaA-binding sites (DnaA boxes and a single IHF-binding site that induces sharp DNA bending. DiaA binds to DnaA and stimulates DnaA assembly at the DOR. DnaA binds tightly to ATP and ADP. ATP-DnaA constructs functionally different sub-complexes at DOR, and the DUE-proximal DnaA sub-complex contains IHF and promotes DUE unwinding. The first part of this review presents the structures and mechanisms of oriC-DnaA complexes involved in the regulation of replication initiation. During the cell cycle, the level of ATP-DnaA level, the active form for initiation, is strictly regulated by multiple systems, resulting in timely replication initiation. After initiation, regulatory inactivation of DnaA (RIDA intervenes to reduce ATP-DnaA level by hydrolyzing the DnaA-bound ATP to ADP to yield ADP-DnaA, the inactive form. RIDA involves the binding of the DNA polymerase clamp on newly synthesized DNA to the DnaA-inactivator Hda protein. In datA-dependent DnaA-ATP hydrolysis (DDAH, binding of IHF at the chromosomal locus datA, which contains a cluster of DnaA boxes, results in further hydrolysis of DnaA-bound ATP. SeqA protein inhibits untimely initiation at oriC by binding to newly synthesized oriC DNA and represses dnaA transcription in a cell cycle dependent manner. To reinitiate DNA replication, ADP-DnaA forms oligomers at DnaA-reactivating sequences (DARS1 and DARS2, resulting in the dissociation of ADP and the release of nucleotide-free apo-DnaA, which then

Advanced Fuels Campaign 2012 Accomplishments

Energy Technology Data Exchange (ETDEWEB)

Not Listed

2012-11-01

The Advanced Fuels Campaign (AFC) under the Fuel Cycle Research and Development (FCRD) program is responsible for developing fuels technologies to support the various fuel cycle options defined in the DOE Nuclear Energy Research and Development Roadmap, Report to Congress, April 2010. The fiscal year 2012 (FY 2012) accomplishments are highlighted below. Kemal Pasamehmetoglu is the National Technical Director for AFC.

Muon cycling rate in D/T mixture including doubly muonic molecule formation

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M. R. Eskandari

2002-06-01

Full Text Available   In the present work, the fundamental behavior of four body molecule formations of pt μμ , pd μμ , dt μμ , tt μμ , and pp μμ in a D/T fusion are considered. Their higher fusion rate, specially the available data for dt μμ , encouraged us to study the muon cycling rate in D/T fusion in the temperature range of (100-1400 K, density and deuterium-tritium concentration ratio. For this purpose, various values for the doubly muonic molecule formation are chosen and with the comparison to the experimental results, the doubly muonic formation rate of 109 s-1 is predicted theoretically. Our calculated cycling rate has shown that having not considered the doubly muonic formation in previous calculations had made no serious changes in the previously calculated values.

Advanced Fuel Cycle Economic Tools, Algorithms, and Methodologies

Energy Technology Data Exchange (ETDEWEB)

David E. Shropshire

2009-05-01

The Advanced Fuel Cycle Initiative (AFCI) Systems Analysis supports engineering economic analyses and trade-studies, and requires a requisite reference cost basis to support adequate analysis rigor. In this regard, the AFCI program has created a reference set of economic documentation. The documentation consists of the “Advanced Fuel Cycle (AFC) Cost Basis” report (Shropshire, et al. 2007), “AFCI Economic Analysis” report, and the “AFCI Economic Tools, Algorithms, and Methodologies Report.” Together, these documents provide the reference cost basis, cost modeling basis, and methodologies needed to support AFCI economic analysis. The application of the reference cost data in the cost and econometric systems analysis models will be supported by this report. These methodologies include: the energy/environment/economic evaluation of nuclear technology penetration in the energy market—domestic and internationally—and impacts on AFCI facility deployment, uranium resource modeling to inform the front-end fuel cycle costs, facility first-of-a-kind to nth-of-a-kind learning with application to deployment of AFCI facilities, cost tradeoffs to meet nuclear non-proliferation requirements, and international nuclear facility supply/demand analysis. The economic analysis will be performed using two cost models. VISION.ECON will be used to evaluate and compare costs under dynamic conditions, consistent with the cases and analysis performed by the AFCI Systems Analysis team. Generation IV Excel Calculations of Nuclear Systems (G4-ECONS) will provide static (snapshot-in-time) cost analysis and will provide a check on the dynamic results. In future analysis, additional AFCI measures may be developed to show the value of AFCI in closing the fuel cycle. Comparisons can show AFCI in terms of reduced global proliferation (e.g., reduction in enrichment), greater sustainability through preservation of a natural resource (e.g., reduction in uranium ore depletion), value from

Coexisting cycles in a class of 3-D discrete maps

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Agliari Anna

2012-08-01

Full Text Available In this paper we consider the class of three-dimensional discrete maps M (x, y, z = [φ(y, φ(z, φ(x], where φ : ℝ → ℝ is an endomorphism. We show that all the cycles of the 3-D map M can be obtained by those of φ(x, as well as their local bifurcations. In particular we obtain that any local bifurcation is of co-dimension 3, that is three eigenvalues cross simultaneously the unit circle. As the map M exhibits coexistence of cycles when φ(x has a cycle of period n ≥ 2, making use of the Myrberg map as endomorphism, we describe the structure of the basins of attraction of the attractors of M and we study the effect of the flip bifurcation of a fixed point. Dans ce papier nous considérons la classe des applications trois-dimensionnelles discrètes M (x, y, z = [φ(y, φ(z, φ(x], où φ : ℝ → ℝ est un endomorphisme. Nous montrons que tous les cycles de l’application 3-D M peuvent être obtenus par ceux de φ(x, ainsi que leurs bifurcations locales. En particulier, nous obtenons que toute bifurcation locale est de co-dimension 3, c’est-à-dire que trois valeurs propres franchissent simultanément le cercle unité. Comme l’application M exhibe une coexistence de cycles lorsque φ(x a un cycle de période n ≥ 2, en utilisant l’application de Myrberg comme endomorphisme, nous décrivons la structure des bassins d’attraction des attracteurs de M et nous étudions les effets d’une bifurcation de doublement de période d’un point fixe.

48 CFR 315.606-1 - Receipt and initial review.

Science.gov (United States)

2010-10-01

... CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Unsolicited Proposals 315.606-1 Receipt and initial review. (d) OPDIVs shall not refuse consideration of an unsolicited proposal because an organization initially submitted it as a grant application. However, OPDIVs shall not award contracts based on...

Low-cycle fatigue of welded joints: coupled initiation propagation model

International Nuclear Information System (INIS)

Madi, Yazid; Recho, Naman; Matheron, Philippe

2004-01-01

This paper deals with the low-cycle fatigue (LC) design of welded structures, the aim being the critical analysis of the rule used in the RCC-MR [Design and construction rules for mechanical components of FBR nuclear islands, AFCEN, 1993], for the design and construction of fast breeder reactors. The study takes into account the evolution of the material behavior laws and damage accumulation during the fatigue loading. The adopted model consists of analyzing separately the behavior and the damage evolutions. It allows us to determine the damage ratio corresponding to initiation and propagation of a significant crack in order to determine the life duration. This model suggests the existence of a threshold level of loading, above which micro-cracks initiate. The initiation fatigue life can then be neglected below the threshold level. This work shows also that the RCC-MR rules are valid below this threshold load level

Engineering aspects of a D-D commercial tokamak reactor

International Nuclear Information System (INIS)

Evans, K. Jr.; Baker, C.C.; Brooks, J.N.

1981-01-01

This paper presents some of the engineering aspects of WILDCAT, a conceptual design of a D-D tokamak, fusion reactor. This conceptual design has evolved from initial studies of D-D tokamak reactors, and is intended to be a study of a later-model, commerical fusion reactor in the same sense that STARFIRE was such a study for D-T fuel cycle. The major guidelines of the study have been to utilize as fully as possible the advantages of the D-D fuel cycle but to avoid unnecessary extrapolations of parameters from existing D-T designs, in particular STARFIRE. The paper consists of an overview of the reference design, a description of each of the major engineering systems (rf current drive, burn cycle, impurity control, first wall, blanket/shield, TF magnets, and tritium system, and a summary of conclusions)

File list: NoD.Emb.05.AllAg.Mitotic_cycle_12-14 [Chip-atlas[Archive

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Speeding through cell cycle roadblocks: Nuclear cyclin D1-dependent kinase and neoplastic transformation

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Diehl J Alan

2008-09-01

Full Text Available Abstract Mitogenic induction of cyclin D1, the allosteric regulator of CDK4/6, is a key regulatory event contributing to G1 phase progression. Following the G1/S transition, cyclin D1 activation is antagonized by GSK3β-dependent threonine-286 (Thr-286 phosphorylation, triggering nuclear export and subsequent cytoplasmic degradation mediated by the SCFFbx4-αBcrystallin E3 ubiquitin ligase. Although cyclin D1 overexpression occurs in numerous malignancies, overexpression of cyclin D1 alone is insufficient to drive transformation. In contrast, cyclin D1 mutants refractory to phosphorylation-dependent nuclear export and degradation are acutely transforming. This raises the question of whether overexpression of cyclin D1 is a significant contributor to tumorigenesis or an effect of neoplastic transformation. Significantly, recent work strongly supports a model wherein nuclear accumulation of cyclin D1-dependent kinase during S-phase is a critical event with regard to transformation. The identification of mutations within SCFFbx4-αBcrystallin ligase in primary tumors provides mechanistic insight into cyclin D1 accumulation in human cancer. Furthermore, analysis of mouse models expressing cyclin D1 mutants refractory to degradation indicate that nuclear cyclin D1/CDK4 kinase triggers DNA re-replication and genomic instability. Collectively, these new findings provide a mechanism whereby aberrations in post-translational regulation of cyclin D1 establish a cellular environment conducive to mutations that favor neoplastic growth.

Transcription of ribosomal RNA genes is initiated in the third cell cycle of bovine embryos

DEFF Research Database (Denmark)

Jakobsen, Anne Sørig; Avery, Birthe; Dieleman, Steph J.

2006-01-01

Transcription from the embryos own ribosomal genes is initiated in most species at the same time as the maternal-embryonic transition. Recently data have indicated that a minor activation may take place during the third embryonic cell cycle in the bovine, one cell cycle before the major activation...

Correlation between a 2D channelized Hotelling observer and human observers in a low-contrast detection task with multislice reading in CT.

Science.gov (United States)

Yu, Lifeng; Chen, Baiyu; Kofler, James M; Favazza, Christopher P; Leng, Shuai; Kupinski, Matthew A; McCollough, Cynthia H

2017-08-01

Model observers have been successfully developed and used to assess the quality of static 2D CT images. However, radiologists typically read images by paging through multiple 2D slices (i.e., multislice reading). The purpose of this study was to correlate human and model observer performance in a low-contrast detection task performed using both 2D and multislice reading, and to determine if the 2D model observer still correlate well with human observer performance in multislice reading. A phantom containing 18 low-contrast spheres (6 sizes × 3 contrast levels) was scanned on a 192-slice CT scanner at five dose levels (CTDI vol = 27, 13.5, 6.8, 3.4, and 1.7 mGy), each repeated 100 times. Images were reconstructed using both filtered-backprojection (FBP) and an iterative reconstruction (IR) method (ADMIRE, Siemens). A 3D volume of interest (VOI) around each sphere was extracted and placed side-by-side with a signal-absent VOI to create a 2-alternative forced choice (2AFC) trial. Sixteen 2AFC studies were generated, each with 100 trials, to evaluate the impact of radiation dose, lesion size and contrast, and reconstruction methods on object detection. In total, 1600 trials were presented to both model and human observers. Three medical physicists acted as human observers and were allowed to page through the 3D volumes to make a decision for each 2AFC trial. The human observer performance was compared with the performance of a multislice channelized Hotelling observer (CHO_MS), which integrates multislice image data, and with the performance of previously validated CHO, which operates on static 2D images (CHO_2D). For comparison, the same 16 2AFC studies were also performed in a 2D viewing mode by the human observers and compared with the multislice viewing performance and the two CHO models. Human observer performance was well correlated with the CHO_2D performance in the 2D viewing mode [Pearson product-moment correlation coefficient R = 0.972, 95% confidence

Advanced Fuels Campaign FY 2011 Accomplishments Report

Energy Technology Data Exchange (ETDEWEB)

Not Listed

2011-11-01

One of the major research and development (R&D) areas under the Fuel Cycle Research and Development (FCRD) program is advanced fuels development. The Advanced Fuels Campaign (AFC) has the responsibility to develop advanced fuel technologies for the Department of Energy (DOE) using a science-based approach focusing on developing a microstructural understanding of nuclear fuels and materials. Accomplishments made during fiscal year (FY 20) 2011 are highlighted in this report, which focuses on completed work and results. The process details leading up to the results are not included; however, the technical contact is provided for each section. The order of the accomplishments in this report is consistent with the AFC work breakdown structure (WBS).

The Correlations of Anti-Mullerian Hormone, Follicle-Stimulating Hormone and Antral Follicle Count in Different Age Groups of Infertile Women

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Ludmila Barbakadze

2015-02-01

Full Text Available Background: The objective of our study was to identify the correlations between the tests currently used in ovarian reserve assessment: anti-Mullerian hormone (AMH, follicle stimulating hormone (FSH and antral follicle count (AFC and to distinguish the most reliable markers for ovarian reserve in order to select an adequate strategy for the initial stages of infertility treatment. Materials and Methods: In this prospective study, 112 infertile women were assessed. Subjects were divided into three age groups: group I <35 years (n=39, group II 35-40 years (n=31, and group III 41-46 years (n=42. AMH, FSH and AFC were determined on days 2-3 of the patients’ menstrual cycles. Results: There was a significantly elevated negative correlation between age and AMH level (rs =-0.67, p<0.0001 and AFC (rs =-0.55, p<0.0001. We observed a significantly positive correlation between age and FSH (rs =0.38, p<0.0001. AMH negatively correlated with FSH (rs =-0.48, p<0.0001 and positively with AFC (r=- 0.71, p=0.0001. There was a moderate negative relation between FSH and AFC (r=-0.41, p=0.0001 and moderate positive relation between age and FSH (rs =0.38, p<0.0001. The correlation analysis performed in separate groups showed that AMH and AFC showed a statistically significant positive correlation for group I (r=0.57, p<0.0001, group II (r=0.69, p<0.0001 and group III (r=0.47, p<0.002. A statistically significant correlation between FSH and AMH was detected only in groups I (r=-0.41, p<0.02 and II (r=-0.55, p<0.0001. A statistically significant correlation existed between FSH and AFC only in group III (r=-0.42, p<0.006, as well as between age and AFC only in group I (r=-0.35, p<0.03. Conclusion: Currently, AMH should be considered as the more reliable of the ovarian reserve assessments tests compared to FSH. There is a strong positive correlation between serum AMH level and AFC. The use of AMH combined with AFC may improve ovarian reserve evaluation.

Phage T4 endonuclease SegD that is similar to group I intron endonucleases does not initiate homing of its own gene.

Science.gov (United States)

Sokolov, Andrey S; Latypov, Oleg R; Kolosov, Peter M; Shlyapnikov, Michael G; Bezlepkina, Tamara A; Kholod, Natalia S; Kadyrov, Farid A; Granovsky, Igor E

2018-02-01

Homing endonucleases are a group of site-specific endonucleases that initiate homing, a nonreciprocal transfer of its own gene into a new allele lacking this gene. This work describes a novel phage T4 endonuclease, SegD, which is homologous to the GIY-YIG family of homing endonucleases. Like other T4 homing endonucleases SegD recognizes an extended, 16bp long, site, cleaves it asymmetrically to form 3'-protruding ends and digests both unmodified DNA and modified T-even phage DNA with similar efficiencies. Surprisingly, we revealed that SegD cleavage site was identical in the genomes of segD - and segD + phages. We found that segD gene was expressed during the T4 developmental cycle. Nevertheless, endonuclease SegD was not able to initiate homing of its own gene as well as genetic recombination between phages in its site inserted into the rII locus. Copyright © 2018 Elsevier Inc. All rights reserved.

Genetic and clinical predictors of ovarian response in assisted reproductive technology

Science.gov (United States)

Wiweko, B.; Damayanti, I.; Suryandari, D.; Natadisastra, M.; Pratama, G.; Sumapraja, K.; Meutia, K.; Iffanolia, P.; Harzief, A. K.; Hestiantoro, A.

2017-08-01

Several factors are known to influence ovarian response to rFSH stimulation such as age, antral follicle count (AFC), and basal FSH level, Mutation of allele Ser680Asn in FSHR gene was responsible to ovarian resistance toward exogenous FSH. The aim of this study is to develop a prediction model of ovarian response to COS in IVF. This study was a prospective cohort study. One hundred and thirteen women undergoing their first cycle of IVF in Yasmin IVF Clinic Jakarta were recruited to this study. Clinical datas included were age, BMI, and AFC. Basal FSH and E2 as well as serum AMH was measured from peripheral blood taken at second day of cycle. Bsr-1 enzyme is used to identify the polymorphism in exon 10 position 680 with RFLP technique. Three genotype polymorphism, Asn/Asn (255 bp ribbon), Asn/Ser (97 bp and 158 bp), and Ser/Ser (97 bp, 158 bp, and 255 bp). AFC has the highest predictor for ovarian response with AUC 0.922 (CI 95% 0.833-1.000). AMH also showed high predicting value (AUC 0.843 CI 95% 0.663-1.000). The multivariate analysis revealed combination of AFC, AMH, age, and basal FSH is a good model for ovarian response prediction (AUC=0.97). No significant relation between Asn/Asn, Asn/Ser, or Ser/Ser genotype FSHR polymorphism with ovarian response (p = 0.866) and total dose of rRSH (p = 0.08). This study showed that model combination of AFC, AMH, patient’s age and basal FSH are very good to predict number of mature oocytes.

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity.

Science.gov (United States)

Gorman, Shelley; Buckley, Alysia G; Ling, Kak-Ming; Berry, Luke J; Fear, Vanessa S; Stick, Stephen M; Larcombe, Alexander N; Kicic, Anthony; Hart, Prue H

2017-08-01

In disease settings, vitamin D may be important for maintaining optimal lung epithelial integrity and suppressing inflammation, but less is known of its effects prior to disease onset. Female BALB/c dams were fed a vitamin D 3 -supplemented (2280 IU/kg, VitD + ) or nonsupplemented (0 IU/kg, VitD - ) diet from 3 weeks of age, and mated at 8 weeks of age. Male offspring were fed the same diet as their mother. Some offspring initially fed the VitD - diet were switched to a VitD + diet from 8 weeks of age (VitD -/+ ). At 12 weeks of age, signs of low-level inflammation were observed in the bronchoalveolar lavage fluid (BALF) of VitD - mice (more macrophages and neutrophils), which were suppressed by subsequent supplementation with vitamin D 3 There was no difference in the level of expression of the tight junction proteins occludin or claudin-1 in lung epithelial cells of VitD + mice compared to VitD - mice; however, claudin-1 levels were reduced when initially vitamin D-deficient mice were fed the vitamin D 3 -containing diet (VitD -/+ ). Reduced total IgM levels were detected in BALF and serum of VitD -/+ mice compared to VitD + mice. Lung mRNA levels of the vitamin D receptor (VDR) were greatest in VitD -/+ mice. Total IgG levels in BALF were greater in mice fed the vitamin D 3 -containing diet, which may be explained by increased activation of B cells in airway-draining lymph nodes. These findings suggest that supplementation of initially vitamin D-deficient mice with vitamin D 3 suppresses signs of lung inflammation but has limited effects on the epithelial integrity of the lungs. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

The potential role of ribosomal protein S5 on cell cycle arrest and initiation of murine erythroleukemia cell differentiation.

Science.gov (United States)

Matragkou, Christina N; Papachristou, Eleni T; Tezias, Sotirios S; Tsiftsoglou, Asterios S; Choli-Papadopoulou, Theodora; Vizirianakis, Ioannis S

2008-07-01

Evidence now exists to indicate that some ribosomal proteins besides being structural components of the ribosomal subunits are involved in the regulation of cell differentiation and apoptosis. As we have shown earlier, initiation of erythroid differentiation of murine erythroleukemia (MEL) cells is associated with transcriptional inactivation of genes encoding ribosomal RNAs and ribosomal proteins S5 (RPS5) and L35a. In this study, we extended these observations and investigated whether transfection of MEL cells with RPS5 cDNA affects the onset of initiation of erythroid maturation and their entrance in cell cycle arrest. Stably transfected MEL cloned cells (MEL-C14 and MEL-C56) were established and assessed for their capacity to produce RPS5 RNA transcript and its translated product. The impact of RPS5 cDNA transfection on the RPS5 gene expression patterns and the accumulation of RPS5 protein in inducible transfected MEL cells were correlated with their ability to: (a) initiate differentiation, (b) enter cell cycle arrest at G(1)/G(0) phase, and (c) modulate the level of cyclin-dependent kinases CDK2, CDK4, and CDK6. The data presented indicate that deregulation of RPS5 gene expression (constitutive expression) affects RPS5 protein level and delays both the onset of initiation of erythroid maturation and entrance in cell cycle arrest in inducer-treated MEL cells. 2008 Wiley-Liss, Inc.

The hype cycle in 3D displays: inherent limits of autostereoscopy

Science.gov (United States)

Grasnick, Armin

2013-06-01

Since a couple of years, a renaissance of 3dimensional cinema can be observed. Even though the stereoscopy was quite popular within the last 150 years, the 3d cinema has disappeared and re-established itself several times. The first boom in the late 19th century stagnated and vanished after a few years of success, the same happened again in 50's and 80's of the 20th century. With the commercial success of the 3d blockbuster "Avatar" in 2009, at the latest, it is obvious that the 3d cinema is having a comeback. How long will it last this time? There are already some signs of a declining interest in 3d movies, as the discrepancy between expectations and the results delivered becomes more evident. From the former hypes it is known: After an initial phase of curiosity (high expectations and excessive fault tolerance), a phase of frustration and saturation (critical analysis and subsequent disappointment) will follow. This phenomenon is known as "Hype Cycle" The everyday experienced evolution of technology has conditioned the consumers. The expectation "any technical improvement will preserve all previous properties" cannot be fulfilled with present 3d technologies. This is an inherent problem of stereoscopy and autostereoscopy: The presentation of an additional dimension caused concessions in relevant characteristics (i.e. resolution, brightness, frequency, viewing area) or leads to undesirable physical side effects (i.e. subjective discomfort, eye strain, spatial disorientation, feeling of nausea). It will be verified that the 3d apparatus (3d glasses or 3d display) is also the source for these restrictions and a reason for decreasing fascination. The limitations of present autostereoscopic technologies will be explained.

L3.PHI.CTF.P10.02-rev2 Coupling of Subchannel T/H (CTF) and CRUD Chemistry (MAMBA1D)

Energy Technology Data Exchange (ETDEWEB)

Salko, Robert K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Palmtag, Scott [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Collins, Benjamin S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kendrick, Brian [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Seker, Jeffrey [Westinghouse Electric Company LLC, Cranberry Township, PA (United States)

2015-05-15

The purpose of this milestone is to create a preliminary capability for modeling light water reactor (LWR) thermal-hydraulic (T/H) and CRUD growth using the CTF subchannel code and the subgrid version of the MAMBA CRUD chemistry code, MAMBA1D. In part, this is a follow-on to Milestone L3.PHI.VCS.P9.01, which is documented in Report CASL-U-2014-0188-000, titled "Development of CTF Capability for Modeling Reactor Operating Cycles with Crud Growth". As the title suggests, the previous milestone set up a framework for modeling reactor operation cycles with CTF. The framework also facilitated coupling to a CRUD chemistry capability for modeling CRUD growth throughout the reactor operating cycle. To demonstrate the capability, a simple CRUD \\surrogate" tool was developed and coupled to CTF; however, it was noted that CRUD growth predictions by the surrogate were not considered realistic. This milestone builds on L3.PHI.VCS.P9.01 by replacing this simple surrogate tool with the more advanced MAMBA1D CRUD chemistry code. Completing this task involves addressing unresolved tasks from Milestone L3.PHI.VCS.P9.01, setting up an interface to MAMBA1D, and extracting new T/H information from CTF that was not previously required in the simple surrogate tool. Speci c challenges encountered during this milestone include (1) treatment of the CRUD erosion model, which requires local turbulent kinetic energy (TKE) (a value that CTF does not calculate) and (2) treatment of the MAMBA1D CRUD chimney boiling model in the CTF rod heat transfer solution. To demonstrate this new T/H, CRUD modeling capability, two sets of simulations were performed: (1) an 18 month cycle simulation of a quarter symmetry model of Watts Bar and (2) a simulation of Assemblies G69 and G70 from Seabrook Cycle 5. The Watts Bar simulation is merely a demonstration of the capability. The simulation of the Seabrook cycle, which had experienced CRUD-related fuel rod failures, had actual CRUD-scrape data to compare with

Microstructure evolution during high cycle fatigue in Mg–6Zn–1Mn alloy

Energy Technology Data Exchange (ETDEWEB)

Yu, Daliang [College of Materials Science and Engineering, Chongqing University, Chongqing 400045 (China); National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China); Zhang, Dingfei, E-mail: zhangdingfei@cqu.edu.cn [College of Materials Science and Engineering, Chongqing University, Chongqing 400045 (China); National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China); Luo, Yuanxin [College of Mechanical Engineering, Chongqing University, Chongqing 400030 (China); Sun, Jing; Xu, Junyao [College of Materials Science and Engineering, Chongqing University, Chongqing 400045 (China); National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China); Pan, Fusheng [National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China); Chongqing Academy of Science and Technology, Chongqing 401123 (China)

2016-03-21

Microstructure evolution during high cycle fatigue in extruded Mg–6Zn–1Mn alloy was investigated by servo-hydraulic fatigue testing machine with pull–push sinusoidal loading. The results show that in high stress cycles (cyclic stress≥129 MPa) high cycle fatigue tests promote deformation; however, in low stress cycles (cyclic stress≤125 MPa) high cycle fatigue tests make a contribution to room temperature recrystallization in Mg–6Zn–1Mn alloy. The grain refinement increased with increasing cycles. Electron Back-Scattered Diffraction (EBSD) analyses showed that dynamic recrystallization (DRX) has occurred in post-fatigued alloys, accompanied by the presence of a high number density of low-angle grain boundaries (LAGBs). LAGBs generated in the vicinity of initiation grain boundaries and subdivided coarse grains. In the specimens that subjected to higher cycles, the fraction of LAGBs decreased and high-angle grain boundaries (HAGBs) gradually increased. With the cyclic number increasing the texture intensity was significantly weakened. The DRX in post-fatigued specimens was related to Continuous DRX (CDRX) mechanism.

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

International Nuclear Information System (INIS)

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

2000-01-01

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

SHP1-mediated cell cycle redistribution inhibits radiosensitivity of non-small cell lung cancer

International Nuclear Information System (INIS)

Cao, Rubo; Ding, Qian; Li, Pindong; Xue, Jun; Zou, Zhenwei; Huang, Jing; Peng, Gang

2013-01-01

Radioresistance is the common cause for radiotherapy failure in non-small cell lung cancer (NSCLC), and the degree of radiosensitivity of tumor cells is different during different cell cycle phases. The objective of the present study was to investigate the effects of cell cycle redistribution in the establishment of radioresistance in NSCLC, as well as the signaling pathway of SH2 containing Tyrosine Phosphatase (SHP1). A NSCLC subtype cell line, radioresistant A549 (A549S1), was induced by high-dose hypofractionated ionizing radiations. Radiosensitivity-related parameters, cell cycle distribution and expression of cell cycle-related proteins and SHP1 were investigated. siRNA was designed to down-regulate SHP1expression. Compared with native A549 cells, the proportion of cells in the S phase was increased, and cells in the G0/G1 phase were consequently decreased, however, the proportion of cells in the G2/M phase did not change in A549S1 cells. Moreover, the expression of SHP1, CDK4 and CylinD1 were significantly increased, while p16 was significantly down-regulated in A549S1 cells compared with native A549 cells. Furthermore, inhibition of SHP1 by siRNA increased the radiosensitivity of A549S1 cells, induced a G0/G1 phase arrest, down-regulated CDK4 and CylinD1expressions, and up-regulated p16 expression. SHP1 decreases the radiosensitivity of NSCLC cells through affecting cell cycle distribution. This finding could unravel the molecular mechanism involved in NSCLC radioresistance

Effect of prepubertal and postpubertal growth and age at first calving on production and reproduction traits during the first 3 lactations in Holstein dairy cattle.

Science.gov (United States)

Krpálková, L; Cabrera, V E; Vacek, M; Stípková, M; Stádník, L; Crump, P

2014-05-01

The objective of this study was to evaluate the effect of body condition score (BCS), body weight (BW), average daily weight gain (ADG), and age at first calving (AFC) of Holstein heifers on production and reproduction parameters in the 3 subsequent lactations. The data set consisted of 780 Holstein heifers calved at 2 dairy farms in the Czech Republic from 2007 to 2011. Their BW and BCS were measured at monthly intervals during the rearing period (5 to 18 mo of age), and the milk production and reproduction data of the first 3 lactations were collected over an 8-yr period (2005 to 2012). The highest milk yield in the first lactation was found in the group with medium ADG (5 to 14 mo of age; 0.949 to 0.850 kg of ADG). The highest average milk yield over lifetime performance was detected in heifers with the highest total ADG (≥ 0.950 kg/d). The difference in milk yield between the evaluated groups of highest ADG (in total and postpubertal growth ≥ 0.950 kg/d and in prepubertal growth ≥ 0.970 kg/d) and the lowest ADG (≤ 0.849 kg/d) was approximately 1,000 kg/305 d per cow. The highest milk yield in the first lactation was found in the group with the highest AFC ≥ 751 d, for which fat and protein content in the milk was not reduced. Postpubertal growth (11 to 14 mo of age) had the greatest effect on AFC. The group with lowest AFC ≤ 699 d showed a negative effect on milk yield but only in the first 100 d of the first parity. The highest ADG was detrimental to reproduction parameters in the first lactation. The highest BW at 14 mo (≥ 420 kg) led to lower AFC. Groups according to BCS at 14 mo showed no differences in AFC or milk yield in the first lactation or lifetime average production per lactation. We concluded that low AFC ≤ 699 d did not show a negative effect on subsequent production and reproduction parameters. Therefore, a shorter rearing period is recommended for dairy herds with suitable management. Copyright © 2014 American Dairy Science

Amounts of artificial food dyes and added sugars in foods and sweets commonly consumed by children.

Science.gov (United States)

Stevens, Laura J; Burgess, John R; Stochelski, Mateusz A; Kuczek, Thomas

2015-04-01

Artificial food colors (AFCs) are used to color many beverages, foods, and sweets in the United States and throughout the world. In the United States, the Food and Drug Administration (FDA) limits the AFCs allowed in the diet to 9 different colors. The FDA certifies each batch of manufactured AFCs to guarantee purity and safety. The amount certified has risen from 12 mg/capita/d in 1950 to 62 mg/capita/d in 2010. Previously, we reported the amounts of AFCs in commonly consumed beverages. In this article, the amounts of AFCs in commonly consumed foods and sweets are reported. In addition, the amount of sugars in each product is included. Amounts of AFCs reported here along with the beverage data show that many children could be consuming far more dyes than previously thought. Clinical guidance is given to help caregivers avoid AFCs and reduce the amount of sugars in children's diets. © The Author(s) 2014.

ZENK expression in the auditory pathway of black-capped chickadees (Poecile atricapillus) as a function of D note number and duty cycle of chick-a-dee calls.

Science.gov (United States)

Scully, Erin N; Schuldhaus, Brenna C; Congdon, Jenna V; Hahn, Allison H; Campbell, Kimberley A; Wilson, David R; Sturdy, Christopher B

2018-06-08

Black-capped chickadees (Poecile atricapillus) use their namesake chick-a-dee call for multiple functions, altering the features of the call depending on context. For example, duty cycle (the proportion of time filled by vocalizations) and fine structure traits (e.g., number of D notes) can encode contextual factors, such as predator size and food quality. Wilson and Mennill [1] found that chickadees show stronger behavioral responses to playback of chick-a-dee calls with higher duty cycles, but not to the number of D notes. That is, independent of the number of D notes in a call, but dependent on the overall proportion of time filled with vocalization, birds responded more to higher duty cycle playback compared to lower duty cycle playback. Here we presented chickadees with chick-a-dee calls that contained either two D (referred to hereafter as 2 D) notes with a low duty cycle, 2 D notes with a high duty cycle, 10 D notes with a high duty cycle, or 2 D notes with a high duty cycle but played in reverse (a non-signaling control). We then measured ZENK expression in the auditory nuclei where perceptual discrimination is thought to occur. Based on the behavioral results of Wilson and Mennill [1], we predicted we would observe the highest ZENK expression in response to forward-playing calls with high duty cycles; we predicted we would observe no significant difference in ZENK expression between forward-playing high duty cycle playbacks (2 D or 10 D). We found no significant difference between forward-playing 2 D and 10 D high duty cycle playbacks. However, contrary to our predictions, we did not find any effects of altering the duty cycle or note number presented. Copyright © 2018 Elsevier B.V. All rights reserved.

Outsourcing Innovation in Product Cycles

OpenAIRE

Chu, Hsiao-Lei

2012-01-01

In this quality-ladder product-cycles model, a southern firm can undertake innovation by collaborating with a northern firm through R&D outsourcing. Generally, I find that the initial steady-state scale of R&D outsourcing and the fraction of innovative tasks undertaken by southern labor through R&D outsourcing critically affect the results of comparative statics. Particularly, the friendly policy to promote R&D outsourcing may be beneficial for both of the North and the South only if the scal...

Extracellular matrix-dependent myosin dynamics during G1-S phase cell cycle progression in hepatocytes

International Nuclear Information System (INIS)

Bhadriraju, Kiran; Hansen, Linda K.

2004-01-01

Cell spreading and proliferation are tightly coupled in anchorage-dependent cells. While adhesion-dependent proliferation signals require an intact actin cytoskeleton, and some of these signals such as ERK activation have been characterized, the role of myosin in spreading and cell cycle progression under different extracellular matrix (ECM) conditions is not known. Studies presented here examine changes in myosin activity in freshly isolated hepatocytes under ECM conditions that promote either proliferation (high fibronectin density) or growth arrest (low fibronectin density). Three different measures were obtained and related to both spreading and cell cycle progression: myosin protein levels and association with cytoskeleton, myosin light chain phosphorylation, and its ATPase activity. During the first 48 h in culture, corresponding with transit through G1 phase, there was a six-fold increase in both myosin protein levels and myosin association with actin cytoskeleton. There was also a steady increase in myosin light chain phosphorylation and ATPase activity with spreading, which did not occur in non-spread, growth-arrested cells on low density of fibronectin. Myosin-inhibiting drugs blocked ERK activation, cyclin D1 expression, and S phase entry. Overexpression of the cell cycle protein cyclin D1 overcame both ECM-dependent and actomyosin-dependent inhibition of DNA synthesis, suggesting that cyclin D1 is a key event downstream of myosin-dependent cell cycle regulation

miR-340 inhibits glioblastoma cell proliferation by suppressing CDK6, cyclin-D1 and cyclin-D2

International Nuclear Information System (INIS)

Li, Xuesong; Gong, Xuhai; Chen, Jing; Zhang, Jinghui; Sun, Jiahang; Guo, Mian

2015-01-01

Glioblastoma development is often associated with alteration in the activity and expression of cell cycle regulators, such as cyclin-dependent kinases (CKDs) and cyclins, resulting in aberrant cell proliferation. Recent studies have highlighted the pivotal roles of miRNAs in controlling the development and growth of glioblastoma. Here, we provide evidence for a function of miR-340 in the inhibition of glioblastoma cell proliferation. We found that miR-340 is downregulated in human glioblastoma tissue samples and several established glioblastoma cell lines. Proliferation and neurosphere formation assays revealed that miR-340 plays an oncosuppressive role in glioblastoma, and that its ectopic expression causes significant defect in glioblastoma cell growth. Further, using bioinformatics, luciferase assay and western blot, we found that miR-340 specifically targets the 3′UTRs of CDK6, cyclin-D1 and cyclin-D2, leading to the arrest of glioblastoma cells in the G0/G1 cell cycle phase. Confirming these results, we found that re-introducing CDK6, cyclin-D1 or cyclin-D2 expression partially, but significantly, rescues cells from the suppression of cell proliferation and cell cycle arrest mediated by miR-340. Collectively, our results demonstrate that miR-340 plays a tumor-suppressive role in glioblastoma and may be useful as a diagnostic biomarker and/or a therapeutic avenue for glioblastoma. - Highlights: • miR-340 is downregulated in glioblastoma samples and cell lines. • miR-340 inhibits glioblastoma cell proliferation. • miR-340 directly targets CDK6, cyclin-D1, and cyclin-D2. • miR-340 regulates glioblastoma cell proliferation via CDK6, cyclin-D1 and cyclin-D2

miR-340 inhibits glioblastoma cell proliferation by suppressing CDK6, cyclin-D1 and cyclin-D2

Energy Technology Data Exchange (ETDEWEB)

Li, Xuesong; Gong, Xuhai [Department of Neurology, Daqing Oilfield General Hospital, Daqing, Heilongjiang 163001 (China); Chen, Jing [Department of Neurology, Daqing Longnan Hospital, Daqing, Heilongjiang, 163001 China (China); Zhang, Jinghui [Department of Cardiology, The Fourth Hospital of Harbin City, Harbin, Heilongjiang 150026 (China); Sun, Jiahang [Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086 (China); Guo, Mian, E-mail: guomian_hyd@163.com [Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086 (China)

2015-05-08

Glioblastoma development is often associated with alteration in the activity and expression of cell cycle regulators, such as cyclin-dependent kinases (CKDs) and cyclins, resulting in aberrant cell proliferation. Recent studies have highlighted the pivotal roles of miRNAs in controlling the development and growth of glioblastoma. Here, we provide evidence for a function of miR-340 in the inhibition of glioblastoma cell proliferation. We found that miR-340 is downregulated in human glioblastoma tissue samples and several established glioblastoma cell lines. Proliferation and neurosphere formation assays revealed that miR-340 plays an oncosuppressive role in glioblastoma, and that its ectopic expression causes significant defect in glioblastoma cell growth. Further, using bioinformatics, luciferase assay and western blot, we found that miR-340 specifically targets the 3′UTRs of CDK6, cyclin-D1 and cyclin-D2, leading to the arrest of glioblastoma cells in the G0/G1 cell cycle phase. Confirming these results, we found that re-introducing CDK6, cyclin-D1 or cyclin-D2 expression partially, but significantly, rescues cells from the suppression of cell proliferation and cell cycle arrest mediated by miR-340. Collectively, our results demonstrate that miR-340 plays a tumor-suppressive role in glioblastoma and may be useful as a diagnostic biomarker and/or a therapeutic avenue for glioblastoma. - Highlights: • miR-340 is downregulated in glioblastoma samples and cell lines. • miR-340 inhibits glioblastoma cell proliferation. • miR-340 directly targets CDK6, cyclin-D1, and cyclin-D2. • miR-340 regulates glioblastoma cell proliferation via CDK6, cyclin-D1 and cyclin-D2.

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

Directory of Open Access Journals (Sweden)

Nicolas Moniaux

2009-09-01

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

CRISPR-mediated control of the bacterial initiation of replication.

Science.gov (United States)

Wiktor, Jakub; Lesterlin, Christian; Sherratt, David J; Dekker, Cees

2016-05-05

Programmable control of the cell cycle has been shown to be a powerful tool in cell-biology studies. Here, we develop a novel system for controlling the bacterial cell cycle, based on binding of CRISPR/dCas9 to the origin-of-replication locus. Initiation of replication of bacterial chromosomes is accurately regulated by the DnaA protein, which promotes the unwinding of DNA at oriC We demonstrate that the binding of CRISPR/dCas9 to any position within origin or replication blocks the initiation of replication. Serial-dilution plating, single-cell fluorescence microscopy, and flow-cytometry experiments show that ongoing rounds of chromosome replication are finished upon CRISPR/dCas9 binding, but no new rounds are initiated. Upon arrest, cells stay metabolically active and accumulate cell mass. We find that elevating the temperature from 37 to 42°C releases the CRISR/dCas9 replication inhibition, and we use this feature to recover cells from the arrest. Our simple and robust method of controlling the bacterial cell cycle is a useful asset for synthetic biology and DNA-replication studies in particular. The inactivation of CRISPR/dCas9 binding at elevated temperatures may furthermore be of wide interest for CRISPR/Cas9 applications in genomic engineering. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cell cycle regulation by the Wee1 Inhibitor PD0166285, Pyrido [2,3-d] pyimidine, in the B16 mouse melanoma cell line

International Nuclear Information System (INIS)

Hashimoto, Osamu; Shinkawa, Masako; Torimura, Takuji; Nakamura, Toru; Selvendiran, Karuppaiyah; Sakamoto, Masaharu; Koga, Hironori; Ueno, Takato; Sata, Michio

2006-01-01

Wee1 kinase plays a critical role in maintaining G2 arrest through its inhibitory phosphorylation of cdc2. In previous reports, a pyridopyrimidine molecule PD0166285 was identified to inhibit Wee1 activity at nanomolar concentrations. This G2 checkpoint abrogation by PD0166285 was demonstrated to kill cancer cells, there at a toxic highest dose of 0.5 μM in some cell lines for exposure periods of no longer than 6 hours. The deregulated cell cycle progression may have ultimately damaged the cancer cells. We herein report one of the mechanism by which PD0166285 leads to cell death in the B16 mouse melanoma cell line. Tumor cell proliferation was determined by counting cell numbers. Cell cycle distribution was determined by flow cytometry. Morphogenesis analysis such as microtubule stabilization, Wee1 distribution, and cyclin B location were observed by immunofluorescence confocal microscopy. An immunoblot analysis of cdc2-Tyr15, cyclin D, E, p16, 21, 27, and Rb. A real-time PCR of the mRNA of cyclin D were completed. In our experiment, B16 cells also dramatically abrogated the G2 checkpoint and were found to arrest in the early G1 phase by treatment with 0.5 μM for 4 hours observed by flow cytometry. Cyclin D mRNA decreased within 4 hours observed by Real-time PCR. Rb was dephosphrylated for 24 hours. However, B16 cells did not undergo cell death after 0.5 μM treatment for 24 hours. Immnofluoscence microscopy showed that the cells become round and small in the morphogenesis. More interesting phenomena were that microtubule stabilization was blocked, and Wee1 distribution was restricted after treatment for 4 hours. We analyzed the effect of Wee1 inhibitor PD0166285 described first by Wang in the G2 transition in the B16 melanoma cell line. The inhibitor PD0166285 abrogated G2/M checkpoint inducing early cell division. Moreover, we found that the treatment of cells with the inhibitor is related to microtubule stabilization and decrease in cyclin D transcription

Active flow control insight gained from a modified integral boundary layer equation

Science.gov (United States)

Seifert, Avraham

2016-11-01

Active Flow Control (AFC) can alter the development of boundary layers with applications (e.g., reducing drag by separation delay or separating the boundary layers and enhancing vortex shedding to increase drag). Historically, significant effects of steady AFC methods were observed. Unsteady actuation is significantly more efficient than steady. Full-scale AFC tests were conducted with varying levels of success. While clearly relevant to industry, AFC implementation relies on expert knowledge with proven intuition and or costly and lengthy computational efforts. This situation hinders the use of AFC while simple, quick and reliable design method is absent. An updated form of the unsteady integral boundary layer (UIBL) equations, that include AFC terms (unsteady wall transpiration and body forces) can be used to assist in AFC analysis and design. With these equations and given a family of suitable velocity profiles, the momentum thickness can be calculated and matched with an outer, potential flow solution in 2D and 3D manner to create an AFC design tool, parallel to proven tools for airfoil design. Limiting cases of the UIBL equation can be used to analyze candidate AFC concepts in terms of their capability to modify the boundary layers development and system performance.

A life cycle analysis approach to D and D decision-making

International Nuclear Information System (INIS)

Yuracko, K.L.; Gresalfi, M.; Yerace, P.; Krstich, M.; Gerrick, D.

1998-05-01

This paper describes a life cycle analysis (LCA) approach that makes decontamination and decommissioning (D and D) of US Department of Energy facilities more efficient and more responsive to the concerns of the society. With the considerable complexity of D and D projects and their attendant environmental and health consequences, projects can no longer be designed based on engineering and economic criteria alone. Using the LCA D and D approach, the evaluation of material disposition alternatives explicitly includes environmental impacts, health and safety impacts, socioeconomic impacts, and stakeholder attitudes -- in addition to engineering and economic criteria. Multi-attribute decision analysis is used to take into consideration the uncertainties and value judgments that are an important part of all material disposition decisions. Use of the LCA D and D approach should lead to more appropriate selections of material disposition pathways and a decision-making process that is both understandable and defensible. The methodology and procedures of the LCA D and D approach are outlined and illustrated by an application of the approach at the Department of Energy's West Valley Demonstration Project. Specifically, LCA was used to aid decisions on disposition of soil and concrete from the Tank Pad D and D Project. A decision tree and the Pollution Prevention/Waste Minimization Users Guide for Environmental Restoration Projects were used to identify possible alternatives for disposition of the soil and concrete. Eight alternatives encompassing source reduction, segregation, treatment, and disposal were defined for disposition of the soil; two alternatives were identified for disposition of the concrete. Preliminary results suggest that segregation and treatment are advantageous in the disposition of both the soil and the concrete. This and other recent applications illustrate the strength and ease of application of the LCA D and D approach

Correlation between a 2D Channelized Hotelling Observer and Human Observers in a Low-contrast Detection Task with Multi-slice Reading in CT

Science.gov (United States)

Yu, Lifeng; Chen, Baiyu; Kofler, James M.; Favazza, Christopher P.; Leng, Shuai; Kupinski, Matthew A.; McCollough, Cynthia H.

2017-01-01

Purpose Model observers have been successfully developed and used to assess the quality of static 2D CT images. However, radiologists typically read images by paging through multiple 2D slices (i.e. multi-slice reading). The purpose of this study was to correlate human and model observer performance in a low-contrast detection task performed using both 2D and multi-slice reading, and to determine if the 2D model observer still correlate well with human observer performance in multi-slice reading. Methods A phantom containing 18 low-contrast spheres (6 sizes × 3 contrast levels) was scanned on a 192-slice CT scanner at 5 dose levels (CTDIvol = 27, 13.5, 6.8, 3.4, and 1.7 mGy), each repeated 100 times. Images were reconstructed using both filtered-backprojection (FBP) and an iterative reconstruction (IR) method (ADMIRE, Siemens). A 3D volume of interest (VOI) around each sphere was extracted and placed side-by-side with a signal-absent VOI to create a 2-alternative forced choice (2AFC) trial. Sixteen 2AFC studies were generated, each with 100 trials, to evaluate the impact of radiation dose, lesion size and contrast, and reconstruction methods on object detection. In total, 1600 trials were presented to both model and human observers. Three medical physicists acted as human observers and were allowed to page through the 3D volumes to make a decision for each 2AFC trial. The human observer performance was compared with the performance of a multi-slice channelized Hotelling observer (CHO_MS), which integrates multi-slice image data, and with the performance of previously validated CHO, which operates on static 2D images (CHO_2D). For comparison, the same 16 2AFC studies were also performed in a 2D viewing mode by the human observers and compared with the multi-slice viewing performance and the two CHO models. Results Human observer performance was well correlated with the CHO_2D performance in the 2D viewing mode (Pearson product-moment correlation coefficient R=0

Paired related homeobox 1 transactivates dopamine D2 receptor to maintain propagation and tumorigenicity of glioma-initiating cells

Institute of Scientific and Technical Information of China (English)

Yamu Li; Ying Liu; Shu Li; Xiaobing Jiang; Guangwei Du; Yan Zhou; Wen Wang; Fangyu Wang; Qiushuang Wu; Wei Li; Xiaoling Zhong; Kuan Tian; Tao Zeng; Liang Gao

2017-01-01

Glioblastoma multiforme (GBM) is a highly invasive brain tumor with limited therapeutic means and poor prognosis.Recent studies indicate that glioma-initiating cells/glioma stem cells (GICs/GSCs) may be responsible for tumor initiation,infiltration,and recurrence.GlCs could aberrantly employ molecular machinery balancing self-renewal and differentiation of embryonic neural precursors.Here,we find that paired related homeobox 1 (PRRX1),a homeodomain transcription factor that was previously reported to control skeletal development,is expressed in cortical neural progenitors and is required for their self-renewal and proper differentiation.Further,PRRX1 is overrepresented in glioma samples and labels GlCs.Glioma cells and GlCs depleted with PRRX1 could not propagate in vitro or form tumors in the xenograft mouse model.The GIC self-renewal function regulated by PRRX1 is mediated by dopamine D2 receptor (DRD2).PRRX1 directly binds to the DRD2 promoter and transactivates its expression in GlCs.Blockage of the DRD2 signaling hampers GIC self-renewal,whereas its overexpression restores the propagating and tumorigenic potential of PRRX1-depleted GlCs.Finally,PRRX1 potentiates GlCs via DRD2-mediated extracellular signal-related kinase (ERK) and AKT activation.Thus,our study suggests that therapeutic targeting the PRRX1-DRD2-ERK/AKT axis in GlCs is a promising strategy for treating GBMs.

Risk charts to identify low and excessive responders among first-cycle IVF/ICSI standard patients

DEFF Research Database (Denmark)

la Cour Freiesleben, N; Gerds, Thomas Alexander; Forman, Julie Lyng

2011-01-01

Ovarian stimulation carries a risk of either low or excessive ovarian response. The aim was to develop prognostic models for identification of standard (ovulatory and normal basal FSH) patients’ risks of low and excessive response to conventional stimulation for IVF/intracytoplasmic sperm injection....... Prospectively collected data on 276 first-cycle patients treated with 150 IU recombinant FSH (rFSH)/day in a long agonist protocol were analysed. Logistic regression analysis was applied to the outcome variables:low (seven or less follicles) and excessive (20 or more follicles) response. Variables were woman......’s age, menstrual cycle length, weight or body mass index, ovarian volume, antral follicle count (AFC) and basal FSH. The predictive performance of the models was evaluated from the prediction error (Brier score, %) where zero corresponds to a perfect prediction. Model stability was assessed using 1000...

Synergistic fuel cycles of the future

International Nuclear Information System (INIS)

Meneley, D.A.; Dastur, A.R.

1997-01-01

Good neutron economy is the basis of the fuel cycle flexibility in the CANDU reactor. This paper describes the fuel cycle options available to the CANDU owner with special emphasis on resource conservation and waste management. CANDU fuel cycles with low initial fissile content operate with relatively high conversion ratio. The natural uranium cycle provides over 55 % of energy from the plutonium that is created during fuel life. Resource utilization is over 7 MWd/kg NU. This can be improved by slight enrichment (between 0.9 and 1.2 wt % U235) of the fuel. Resource utilization increases to 11 MWd/kg NU with the Slightly Enriched Uranium cycle. Thorium based cycles in CANDU operate at near-breeder efficiency. Obey provide attractive options when used with natural uranium or separated (reactor grade and weapons grade) plutonium as driver fuels. In the latter case, the energy from the U233 plus the initial plutonium content amounts to 3.4 GW(th).d/kg Pu-fissile. The same utilization is expected from the use of FBR plutonium in a CANDU thorium cycle. Extension of natural resource is achieved by the use of spent fuels in CANDU. The LWR/CANDU Tandem cycle leads to an additional 77 % of energy through the use of reprocessed LWR fuel (which has a fissile content of 1.6 wt %) in CANDU. Dry reprocessing of LWR fuel with the OREOX process (a more safeguardable alternative to the PUREX process) provides an additional 50 % energy. Uranium recovered (RU) from separation of plutonium contained in spent LWR fuel provides an additional 15 MWd/kg RU. CANDU's low fissile requirement provides the possibility, through the use of non-fertile targets, of extracting energy from the minor actinides contained in spent fuel. In addition to the resource utilization advantage described above, there is a corresponding reduction in waste arisings with such cycles. This is especially significant when separated plutonium is available as a fissile resource. (author)

Targeting CPS1 in the treatment of Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea cycle disorder.

Science.gov (United States)

Diez-Fernandez, Carmen; Häberle, Johannes

2017-04-01

Carbamoyl phosphate synthetase 1 (CPS1) deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder (UCD), which can lead to life-threatening hyperammonemia. Unless promptly treated, it can result in encephalopathy, coma and death, or intellectual disability in surviving patients. Over recent decades, therapies for CPS1D have barely improved leaving the management of these patients largely unchanged. Additionally, in many cases, current management (protein-restriction and supplementation with citrulline and/or arginine and ammonia scavengers) is insufficient for achieving metabolic stability, highlighting the importance of developing alternative therapeutic approaches. Areas covered: After describing UCDs and CPS1D, we give an overview of the structure- function of CPS1. We then describe current management and potential novel treatments including N-carbamoyl-L-glutamate (NCG), pharmacological chaperones, and gene therapy to treat hyperammonemia. Expert opinion: Probably, the first novel CPS1D therapies to reach the clinics will be the already commercial substance NCG, which is the standard treatment for N-acetylglutamate synthase deficiency and has been proven to rescue specific CPS1D mutations. Pharmacological chaperones and gene therapy are under development too, but these two technologies still have key challenges to be overcome. In addition, current experimental therapies will hopefully add further treatment options.

Cyclin D1 and p22ack1 play opposite roles in plant growth and development

International Nuclear Information System (INIS)

Cho, Jeong Woo; Park, Sun Chung; Shin, Eun Ah; Kim, Chong Ki; Han, Woong; Sohn, Soo-In; Song, Pill Soon; Wang, Myeong Hyeon

2004-01-01

The plant cell division cycle, a highly coordinated process, is continually regulated during the growth and development of plants. In this report, we demonstrate how two cell-cycle regulators act together to control cell proliferation in transgenic Arabidopsis. To identify potential cyclin dependent kinase regulators from Arabidopsis, we employed an two-hybrid screening system to isolate genes encoding G1 specific cyclin-interacting proteins. One of these, p22 ack1 , which encodes a novel 22 kDa protein, binds to cyclin D1. Overexpression of p22 ack1 in transgenic Arabidopsis resulted in growth retardation due to a strong inhibition of cell division in the leaf primordial and meristematic tissue. The leaf shape of p22 ack1 transgenic Arabidopsis was altered from oval in wild-type to dentate. Wild-type phenotype was successfully restored in F1 hybrids by cross-hybridizing the p22 ackl Arabidopsis mutants with cyclin D1. Taken together, these results suggest that p22 ack1 and cyclin D1, which act antagonistically, are major rate-limiting factors for cell division in the leaf meristem

Cycle d'Information/Formation sur l'Environnement d'Automatisme SCHNEIDER - French version only

CERN Multimedia

2003-01-01

Pour poursuivre notre connaissance sur l'Environnement d'Automatisme SCHNEIDER afin d'intégrer d'une manière optimale leur gamme d'automates industriels (PLCs) dans notre système de contrôle du LHC, le GUAPI( Groupe des Utilisateurs d'Automates Programmables Industriels du CERN) organise un cycle d'information/formation gratuite dédié aux utilisateurs actuels et potentiels du CERN. Les dates retenues sont les suivantes : Mercredi 26 Mars de 9h à 12h : Contrôleur Logique MICRO-PLC Gamme ZELIO Gamme Nano, Gamme PLC TWIDO. Nota : Cette formation aura lieu au bâtiment 593 /Salle 17 de l'enseignement technique. Elle sera essentiellement assurée par Xavier BONNAUD, Marc DUFFOURNET et Médéric JET de SCHNEIDER qui assurent le support technique et commercial pour le CERN. Le nombre de places étant limité (20), il est demandé aux participants de s'inscrire à l'avance (E-Mail : Raymond.Brun@cern.ch ou tel 76946). Mercredi 9 Avril de 9h à 12h : Solutions redondantes Hot et Warm Standby Mardi 13 Ma...

Cycle d'Information/Formation sur l'Environnement d'Automatisme SCHNEIDER - French version only

CERN Multimedia

2003-01-01

Pour poursuivre notre connaissance sur l'Environnement d'Automatisme SCHNEIDER afin d'intégrer d'une manière optimale leur gamme d'automates industriels (PLCs) dans notre système de contrôle du LHC, le GUAPI( Groupe des Utilisateurs d'Automates Programmables Industriels du CERN) organise un cycle d'information/formation gratuite dédié aux utilisateurs actuels et potentiels du CERN. Les dates retenues sont les suivantes : Mercredi 26 Mars de 9h à 12h : Contrôleur Logique MICRO-PLC Gamme ZELIO Gamme Nano, Gamme PLC TWIDO. Nota : Cette formation aura lieu au bâtiment 593 /Salle 17 de l'enseignement technique. Elle sera essentiellement assurée par Xavier BONNAUD, Marc DUFFOURNET et Médéric JET de SCHNEIDER qui assurent le support technique et commercial pour le CERN. Le nombre de places étant limité (20), il est demandé aux participants de s'inscrire à l'avance (E-Mail : Raymond.Brun@cern.ch ou tel 76946). Mercredi 9 Avril de 9h à 12h : Solutions redondantes Hot et Warm Standby Mardi 13...

2D discontinuous piecewise linear map: Emergence of fashion cycles.

Science.gov (United States)

Gardini, L; Sushko, I; Matsuyama, K

2018-05-01

We consider a discrete-time version of the continuous-time fashion cycle model introduced in Matsuyama, 1992. Its dynamics are defined by a 2D discontinuous piecewise linear map depending on three parameters. In the parameter space of the map periodicity, regions associated with attracting cycles of different periods are organized in the period adding and period incrementing bifurcation structures. The boundaries of all the periodicity regions related to border collision bifurcations are obtained analytically in explicit form. We show the existence of several partially overlapping period incrementing structures, that is, a novelty for the considered class of maps. Moreover, we show that if the time-delay in the discrete time formulation of the model shrinks to zero, the number of period incrementing structures tends to infinity and the dynamics of the discrete time fashion cycle model converges to those of continuous-time fashion cycle model.

3D characterization and modeling of low cycle fatigue damage mechanisms at high temperature in a cast aluminum alloy

International Nuclear Information System (INIS)

Dezecot, Sebastien; Maurel, Vincent; Buffiere, Jean-Yves; Szmytka, Fabien; Koster, Alain

2017-01-01

Synchrotron X-ray tomography was used to monitor damage evolution in three dimensions during in situ Low Cycle Fatigue (LCF) tests at high temperature (250 °C) for an industrial material. The studied material is an AlSi7Cu3Mg aluminum alloy (close to ASTM A319) produced by Lost Foam Casting (LFC), a process which generates coarse microstructures but is nevertheless used for engine parts by the automotive industry. The volume analysis (3D images) has shown that cracks are extremely sensitive to microstructural features: coarse pores and hard particles of the eutectic regions are critical regarding respectively the main crack initiation and the crack growth. Finite Elements (FE) simulations, performed on meshes directly generated from 3D volumes and containing only pores, have revealed that mechanical fields also play a major role on the crack behavior. Initiation sites corresponded to areas of maximum inelastic strain while the crack path was globally correlated to high stress triaxiality and inelastic strain fields.

Irradiation of UO{sub 2} sheathed in thick tubes effect of initial gap; Irradiation d'oxyde d'uranium en gaine resistante effet du jeu diametral initial sur le comportement global (programme CC-7: 1. et 2. tranches)

Energy Technology Data Exchange (ETDEWEB)

Janvier, J C; De Bernardy de Sigoyer, B.; Delmas, R [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

1967-07-01

Sixteen fuel elements made of thick zircaloy tubes containing sintered UO{sub 2}, were irradiated to burn-ups of 3000 resp. 6000 MWd/t. The specific power was continuously measured for each element. The initial diametral clearance was either 0.31 mm (free thermal expansion) or 0.12 mm (thermal expansion stress). The examinations of irradiated fuel elements suggest that : - when the initial gap is high, the fuel expands until it comes in close contact to the sheath; the thermal resistance between fuel and sheath is higher than in the case the fuel is stressed. - a central hole and lenticular voids in movement toward the center by evaporation - condensation can be seen only in specimens having the highest initial gap. - some fission products are concentrated at a certain distance from the center, corresponding to bright rings {beta} autoradiography pictures; that event occurs only in large gap specimens. - fission gas release does not seem to be influenced by mechanical stresses applied to the fuel; the fraction released is coherent, in every, case, with the probable temperature distribution. (authors) [French] Seize cartouches d'oxyde d'uranium fritte a gaines tres epaisses de zircaloy ont ete irradiees dans des conditions de puissance calorifique mesurees continument. Pour huit de ces cartouches le jeu diametral initial entre UO{sub 2} et gaine etait de 0,31 mm et le combustible etait libre de se dilater; pour les huit autres 3 soumises aux memes conditions d'irradiation, le jeu initial etait de 0,12 mm, de sorte que le combustible se trouvait comprime par dilatation differentielle. Les taux de combustion etaient soit de 3000, soit de 6000 MWj/t. Les examens post-irradiatoires suggerent que; - lorsque la jeu initial est eleve, l'UO{sub 2} se dilate jusqu'a venir pratiquement en contact avec la gaine; la resistance thermique a l'interface est alors nettement plus grande que lorsqu'il y a compression mecanique. - la presence d'une cheminee centrale et l'existence de

Atmospheric Carbon Dioxide and its Relation to Carbon Cycle Perturbations During Ocean Anoxic Event 1d: A High Resolution Record From Dispersed Plant Cuticle

Science.gov (United States)

Richey, J. D.; Upchurch, G. R.; Joeckel, R.; Smith, J. J.; Ludvigson, G. A.; Lomax, B. H.

2013-12-01

Past geological greenhouse intervals are associated with Ocean Anoxic Events (OAEs), which result from an increase in marine primary productivity and/or an increase in the preservation of organic matter. The end point is widespread black shale deposition combined with a long-term atmospheric positive δ13C excursion and an increase in the burial of 12C. Some OAEs show a negative δ13C excursion preceding the positive excursion, indicating a perturbation in the global carbon cycle prior to the initiation of these events. The Rose Creek (RCP) locality, southeastern Nebraska, is the only known terrestrial section that preserves OAE1d (Cretaceous, Albian-Cenomanian Boundary) and has abundant charcoal and plant cuticle. These features allow for a combined carbon isotope and stomatal index (SI) analysis to determine both changes in the cycling between carbon pools (C isotope analysis) and changes in paleo-CO2 via changes in SI. Preliminary (and ongoing) SI data analysis using dispersed cuticle of Pandemophyllum kvacekii (an extinct Laurel) collected at 30 cm intervals indicate changes in SI consistent with changes in CO2. Fitting our samples to a published RCP δ13C profile, pre-excursion CO2 concentrations are high. CO2 decreases to lower concentrations in the basal 1.2 m of the RCP section, where δ13Cbulk shows a negative excursion and δ13Ccharcoal remains at pre-excursion values. CO2 concentrations become higher toward the top of the negative δ13C excursion, where δ13Cbulk and δ13Ccharcoal are at their most negative values, and drop as the negative carbon excursion terminates. Using published transfer functions, we estimate that pre-excursion CO2 concentrations were a maximum of 900 ppm. In the basal 1.2 m of RCP, CO2 drops to a maximum of 480 ppm, and rises to a maximum of 710 ppm near the top of the negative excursion. As δ13C values rise towards pre-excursion values, CO2 declines to a maximum of 400 ppm. The trend in SI is comparable to the trend in δ13

Kenya AIDS Vaccine Initiative (KAVI) : un centre d'excellence en ...

International Development Research Centre (IDRC) Digital Library (Canada)

Ce projet est une initiative conjointe de l'Université de Nairobi, au Kenya, et des universités du Manitoba et de Toronto, au Canada. L'objectif : faire de la Kenya AIDS Vaccine Initiative (KAVI) un centre d'excellence pour la formation aux essais de vaccins contre le VIH et à d'autres essais en matière de prévention à ...

Fatigue crack initiation and propagation in steels exposed to inert and corrosive environments. Final report, May 1, 1977--December 31, 1977

Energy Technology Data Exchange (ETDEWEB)

Youseffi, K.; Finnie, I.

1978-02-01

The fatigue crack initiation life of AISI 1018 steel was investigated using compact tension specimens having sharp notch root radii. The data were analyzed using two methods for predicting initiation in strain cycling experiments. Also, another approach in which initiation is related to the stress intensity factor was developed. The next phase, that of propagation, was studied using AISI 1018 steel and a new high strength steel HY-180. The crack propagation data obtained for both steels tested in air can be described accurately by the power law first suggested by Paris, da/dN = C(..delta..K)/sup n/, where a is the crack length, N the number of cycles, and C and n are material constants. However, the exponent n was found to be two times larger for AISI 1018 steel than HY-180 steel.

Fatigue crack initiation and propagation in steels exposed to inert and corrosive environments. Final report, May 1, 1977--December 31, 1977

International Nuclear Information System (INIS)

Youseffi, K.; Finnie, I.

1978-02-01

The fatigue crack initiation life of AISI 1018 steel was investigated using compact tension specimens having sharp notch root radii. The data were analyzed using two methods for predicting initiation in strain cycling experiments. Also, another approach in which initiation is related to the stress intensity factor was developed. The next phase, that of propagation, was studied using AISI 1018 steel and a new high strength steel HY-180. The crack propagation data obtained for both steels tested in air can be described accurately by the power law first suggested by Paris, da/dN = C(ΔK)/sup n/, where a is the crack length, N the number of cycles, and C and n are material constants. However, the exponent n was found to be two times larger for AISI 1018 steel than HY-180 steel

Design for life-cycle profit with simultaneous consideration of initial manufacturing and end-of-life remanufacturing

Science.gov (United States)

Kwak, Minjung; Kim, Harrison

2015-01-01

Remanufacturing is emerging as a promising solution for achieving green, profitable businesses. This article considers a manufacturer that produces new products and also remanufactured versions of the new products that become available at the end of their life cycle. For such a manufacturer, design decisions at the initial design stage determine both the current profit from manufacturing and future profit from remanufacturing. To maximize the total profit, design decisions must carefully consider both ends of product life cycle, i.e. manufacturing and end-of-life stages. This article proposes a decision-support model for the life-cycle design using mixed-integer nonlinear programming. With an aim to maximize the total life-cycle profit, the proposed model searches for an (at least locally) optimal product design (i.e. design specifications and the selling price) for the new and remanufactured products. It optimizes both the initial design and design upgrades at the end-of-life stage and also provides corresponding production strategies, including production quantities and take-back rate. The model is extended to a multi-objective model that maximizes both economic profit and environmental-impact saving. To illustrate, the developed model is demonstrated with an example of a desktop computer.

Znhit1 causes cell cycle arrest and down-regulates CDK6 expression

International Nuclear Information System (INIS)

Yang, Zhengmin; Cao, Yonghao; Zhu, Xiaoyan; Huang, Ying; Ding, Yuqiang; Liu, Xiaolong

2009-01-01

Cyclin-dependent kinase 6 (CDK6) is the key element of the D-type cyclin holoenzymes which has been found to function in the regulation of G1-phase of the cell cycle and is presumed to play important roles in T cell function. In this study, Znhit1, a member of a new zinc finger protein family defined by a conserved Zf-HIT domain, induced arrest in the G1-phase of the cell cycle in NIH/3T3 cells. Of the G1 cell cycle factors examined, the expression of CDK6 was found to be strongly down-regulated by Znhit1 via transcriptional repression. This effect may have correlations with the decreased acetylation level of histone H4 in the CDK6 promoter region. In addition, considering that CDK6 expression predominates in T cells, the negative regulatory role of Znhit1 in TCR-induced T cell proliferation was validated using transgenic mice. These findings identified Znhit1 as a CDK6 regulator that plays an important role in cell proliferation.

ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT - REMOVAL OF PRECURSORS TO DISINFECTION BY-PRODUCTS IN DRINKING WATER, PCI MEMBRANE SYSTEMS FYNE PROCESS MODEL ROP 1434 WITH AFC-30 NANOFILTRATON AT BARROW, AK - NSF 00/19/EPADW395

Science.gov (United States)

Equipment testing and verification of PCI Membrane Systems Inc. Fyne Process nanofiltraton systems Model ROP 1434 equipped with a C10 module containing AFC-30 tubular membranes was conducted from 3/16-5/11/2000 in Barrow, AS. The source water was a moderate alkalinity, moderately...

Cost-benefit analysis on FBR cycle R and D for the world

International Nuclear Information System (INIS)

Kawasaki, Hirotsugu

2006-01-01

This analysis was estimated on the assumption that the nuclear power generation will be changed by FBR and both LWR and FBR indicate same nuclear power generation cost and the environmental load. The cost-benefit analysis results on FBR cycle R and D in the world showed that increase of power generation cost with increase of uranium fuel cost will be avoided and decrease of power generation cost by introducing FBR. The cost-benefit analysis results on FBR cycle R and D in Japan showed that about 9 billions yen will be obtained by the above two economic effects. Cost-benefit effects by introducing FBR, economic estimation method of cost-benefit effect, range and contents of cost-benefit effect on FBR R and D, preconditions of evaluation, and evaluation results are explained. (S.Y.)

VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells.

Science.gov (United States)

Bindra, Ranjit S; Vasselli, James R; Stearman, Robert; Linehan, W Marston; Klausner, Richard D

2002-06-01

Renal cell carcinoma is associated with mutation of the von Hippel-Lindau (VHL) tumor suppressor gene. Cell lines derived from these tumors cannot exit the cell cycle when deprived of growth factors, and the ability to exit the cell cycle can be restored by the reintroduction of wild-type protein VHL (pVHL). Here, we report that cyclin D1 is overexpressed and remains inappropriately high in during contact inhibition in pVHL-deficient cell lines. In addition, hypoxia increased the expression of cyclin D1 specifically in pVHL-negative cell lines into which pVHL expression was restored. Hypoxic-induction of cyclin D1 was not observed in other pVHL-positive cell lines. This suggests a model whereby in some kidney cell types, pVHL may regulate a proliferative response to hypoxia, whereas the loss of pVHL leads to constitutively elevated cyclin D1 and abnormal proliferation under normal growth conditions.

Msx homeobox genes inhibit differentiation through upregulation of cyclin D1.

Science.gov (United States)

Hu, G; Lee, H; Price, S M; Shen, M M; Abate-Shen, C

2001-06-01

During development, patterning and morphogenesis of tissues are intimately coordinated through control of cellular proliferation and differentiation. We describe a mechanism by which vertebrate Msx homeobox genes inhibit cellular differentiation by regulation of the cell cycle. We show that misexpression of Msx1 via retroviral gene transfer inhibits differentiation of multiple mesenchymal and epithelial progenitor cell types in culture. This activity of Msx1 is associated with its ability to upregulate cyclin D1 expression and Cdk4 activity, while Msx1 has minimal effects on cellular proliferation. Transgenic mice that express Msx1 under the control of the mouse mammary tumor virus long terminal repeat (MMTV LTR) display impaired differentiation of the mammary epithelium during pregnancy, which is accompanied by elevated levels of cyclin D1 expression. We propose that Msx1 gene expression maintains cyclin D1 expression and prevents exit from the cell cycle, thereby inhibiting terminal differentiation of progenitor cells. Our model provides a framework for reconciling the mutant phenotypes of Msx and other homeobox genes with their functions as regulators of cellular proliferation and differentiation during embryogenesis.

Very High Cycle Fatigue Crack Initiation Mechanism in Nugget Zone of AA 7075 Friction Stir Welded Joint

Directory of Open Access Journals (Sweden)

Chao He

2017-01-01

Full Text Available Very high cycle fatigue behavior of nugget zone in AA 7075 friction stir welded joint was experimentally investigated using ultrasonic fatigue testing system (20 kHz to clarify the crack initiation mechanism. It was found that the fatigue strength of nugget zone decreased continuously even beyond 107 cycles with no traditional fatigue limits. Fatigue cracks initiated from the welding defects located at the bottom side of the friction stir weld. Moreover, a special semicircular zone could be characterized around the crack initiation site, of which the stress intensity factor approximately equaled the threshold of fatigue crack propagation rate. Finally, a simplified model was proposed to estimate the fatigue life by correlating the welding defect size and applied stress. The predicted results are in good agreement with the experimental results.

Prognostic value of jaundice in patients with gallbladder cancer by the AFC-GBC-2009 study group.

Science.gov (United States)

Regimbeau, J M; Fuks, D; Bachellier, P; Le Treut, Y P; Pruvot, F R; Navarro, F; Chiche, L; Farges, O

2011-06-01

Jaundice is frequent in patients with gallbladder cancer (GBC) and indicates advanced disease and, according to some teams, precludes routine operative exploration. The present study was designed to re-assess the prognostic value of jaundice in patients with GBC. Patients with GBC operated from 1998 to 2008 were included in a retrospective multicenter study (AFC). The main outcome measured was the prognostic value of jaundice in patients with GBC focusing on morbidity, mortality and survival. A total of 110 of 429 patients with GBC presented with jaundice, with a median age of 66 years (range: 31-88). The resectability rate was 45% (n=50) and the postoperative mortality and morbidity rates were 16% and 62%, respectively; 71% had R0 resection and 46% had lymph node involvement. Overall 1- and 3-year survivals of the 110 jaundiced patients were 41% and 15%, respectively. For the 50 resected patients, 1- and 3-year survivals were 48% and 19%, respectively (real 5-year survivors n=4) which were significantly higher than that of the 60 non-resected patients (31%, 0%, p=0.001). Among the resected jaundiced patients, T-stage, N and M status were found to have a significant impact on survival. R0 resection did not increase the overall survival in all resected patients, but R0 increased median survival in the subgroup of N0 patients (20 months versus 6 months, p=0.01). This series confirms that jaundice is a poor prognostic factor. However, the presence of jaundice does not preclude resection, especially in highly selected patients (N0). Copyright © 2011 Elsevier Ltd. All rights reserved.

CRISPR-mediated control of the bacterial initiation of replication

NARCIS (Netherlands)

Wiktor, J.M.; Lesterlin, Christian; Sherratt, David J.; Dekker, C.

2016-01-01

Programmable control of the cell cycle has been shown to be a powerful tool in cell-biology studies. Here, we develop a novel system for controlling the bacterial cell cycle, based on binding of CRISPR/dCas9 to the origin-of-replication locus. Initiation of replication of bacterial chromosomes is

Advanced Fuels Campaign FY 2010 Accomplishments Report

Energy Technology Data Exchange (ETDEWEB)

Lori Braase

2010-12-01

The Fuel Cycle Research and Development (FCRD) Advanced Fuels Campaign (AFC) Accomplishment Report documents the high-level research and development results achieved in fiscal year 2010. The AFC program has been given responsibility to develop advanced fuel technologies for the Department of Energy (DOE) using a science-based approach focusing on developing a microstructural understanding of nuclear fuels and materials. The science-based approach combines theory, experiments, and multi-scale modeling and simulation aimed at a fundamental understanding of the fuel fabrication processes and fuel and clad performance under irradiation. The scope of the AFC includes evaluation and development of multiple fuel forms to support the three fuel cycle options described in the Sustainable Fuel Cycle Implementation Plan4: Once-Through Cycle, Modified-Open Cycle, and Continuous Recycle. The word “fuel” is used generically to include fuels, targets, and their associated cladding materials. This document includes a brief overview of the management and integration activities; but is primarily focused on the technical accomplishments for FY-10. Each technical section provides a high level overview of the activity, results, technical points of contact, and applicable references.

D-amino acids inhibit initial bacterial adhesion: thermodynamic evidence.

Science.gov (United States)

Xing, Su-Fang; Sun, Xue-Fei; Taylor, Alicia A; Walker, Sharon L; Wang, Yi-Fu; Wang, Shu-Guang

2015-04-01

Bacterial biofilms are structured communities of cells enclosed in a self-produced hydrated polymeric matrix that can adhere to inert or living surfaces. D-Amino acids were previously identified as self-produced compounds that mediate biofilm disassembly by causing the release of the protein component of the polymeric matrix. However, whether exogenous D-amino acids could inhibit initial bacterial adhesion is still unknown. Here, the effect of the exogenous amino acid D-tyrosine on initial bacterial adhesion was determined by combined use of chemical analysis, force spectroscopic measurement, and theoretical predictions. The surface thermodynamic theory demonstrated that the total interaction energy increased with more D-tyrosine, and the contribution of Lewis acid-base interactions relative to the change in the total interaction energy was much greater than the overall nonspecific interactions. Finally, atomic force microscopy analysis implied that the hydrogen bond numbers and adhesion forces decreased with the increase in D-tyrosine concentrations. D-Tyrosine contributed to the repulsive nature of the cell and ultimately led to the inhibition of bacterial adhesion. This study provides a new way to regulate biofilm formation by manipulating the contents of D-amino acids in natural or engineered systems. © 2014 Wiley Periodicals, Inc.

Obatoclax, a Pan-BCL-2 Inhibitor, Targets Cyclin D1 for Degradation to Induce Antiproliferation in Human Colorectal Carcinoma Cells.

Science.gov (United States)

Or, Chi-Hung R; Chang, Yachu; Lin, Wei-Cheng; Lee, Wee-Chyan; Su, Hong-Lin; Cheung, Muk-Wing; Huang, Chang-Po; Ho, Cheesang; Chang, Chia-Che

2016-12-27

Colorectal cancer is the third most common cancer worldwide. Aberrant overexpression of antiapoptotic BCL-2 (B-cell lymphoma 2) family proteins is closely linked to tumorigenesis and poor prognosis in colorectal cancer. Obatoclax is an inhibitor targeting all antiapoptotic BCL-2 proteins. A previous study has described the antiproliferative action of obatoclax in one human colorectal cancer cell line without elucidating the underlying mechanisms. We herein reported that, in a panel of human colorectal cancer cell lines, obatoclax inhibits cell proliferation, suppresses clonogenicity, and induces G₁-phase cell cycle arrest, along with cyclin D1 downregulation. Notably, ectopic cyclin D1 overexpression abrogated clonogenicity suppression but also G₁-phase arrest elicited by obatoclax. Mechanistically, pre-treatment with the proteasome inhibitor MG-132 restored cyclin D1 levels in all obatoclax-treated cell lines. Cycloheximide chase analyses further revealed an evident reduction in the half-life of cyclin D1 protein by obatoclax, confirming that obatoclax downregulates cyclin D1 through induction of cyclin D1 proteasomal degradation. Lastly, threonine 286 phosphorylation of cyclin D1, which is essential for initiating cyclin D1 proteasomal degradation, was induced by obatoclax in one cell line but not others. Collectively, we reveal a novel anticancer mechanism of obatoclax by validating that obatoclax targets cyclin D1 for proteasomal degradation to downregulate cyclin D1 for inducing antiproliferation.

Study of crack initiation in low-cycle fatigue of an austenitic stainless steel

International Nuclear Information System (INIS)

Mu, P.

2011-03-01

The material studied is an austenitic stainless steel, that is widely used in nuclear equipment for its very high corrosion resistance combined to good mechanical properties. Although crack initiation is proved to play an important role in fatigue, its mechanisms have not been fully understood. Some crack initiation criteria based on physical mechanisms of plastic deformation have been defined. However, these criteria are not easy to use and valid, as they need local variables at the grain scale. The present study aims at establishing a crack initiation criterion in low-cycle fatigue, which should be usable under variable amplitude loading conditions. Tension-compression fatigue tests were first carried out to characterize the mechanical behavior of the stainless steel AISI 316L. The mechanical behavior was simulated using a self-consistent model using a crystalline plastic law based on dislocation densities. The evolution of surface damage was observed during a fatigue test using an in situ optical microscopic device. Cracks were analyzed after 2000 cycles and their crystallographic characteristics calculated. As surface grains exhibit larger strain because they are less constraint by neighbor grains, a specific numerical frame is necessary to determine stress state in surface grains. A localization law specific to surface grains under cyclic loading was identified from finite element simulations. The proposed form needs an intergranular accommodation variable, on the pattern of the localization law of Cailletaud-Pilvin. Stress-strain state in surface grains was simulated. Potential indicators for crack initiation were then compared on a same experimental data base. Indicators based on the equivalent plastic strain were found to be suitable indicators of fatigue damage. (author)

Advanced Reactor Fuels Irradiation Experiment Design Objectives

Energy Technology Data Exchange (ETDEWEB)

Chichester, Heather Jean MacLean [Idaho National Lab. (INL), Idaho Falls, ID (United States); Hayes, Steven Lowe [Idaho National Lab. (INL), Idaho Falls, ID (United States); Dempsey, Douglas [Idaho National Lab. (INL), Idaho Falls, ID (United States); Harp, Jason Michael [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-09-01

This report summarizes the objectives of the current irradiation testing activities being undertaken by the Advanced Fuels Campaign relative to supporting the development and demonstration of innovative design features for metallic fuels in order to realize reliable performance to ultra-high burnups. The AFC-3 and AFC-4 test series are nearing completion; the experiments in this test series that have been completed or are in progress are reviewed and the objectives and test matrices for the final experiments in these two series are defined. The objectives, testing strategy, and test parameters associated with a future AFC test series, AFC-5, are documented. Finally, the future intersections and/or synergies of the AFC irradiation testing program with those of the TREAT transient testing program, emerging needs of proposed Versatile Test Reactor concepts, and the Joint Fuel Cycle Study program’s Integrated Recycle Test are discussed.

Advanced Reactor Fuels Irradiation Experiment Design Objectives

International Nuclear Information System (INIS)

Chichester, Heather Jean MacLean; Hayes, Steven Lowe; Dempsey, Douglas; Harp, Jason Michael

2016-01-01

This report summarizes the objectives of the current irradiation testing activities being undertaken by the Advanced Fuels Campaign relative to supporting the development and demonstration of innovative design features for metallic fuels in order to realize reliable performance to ultra-high burnups. The AFC-3 and AFC-4 test series are nearing completion; the experiments in this test series that have been completed or are in progress are reviewed and the objectives and test matrices for the final experiments in these two series are defined. The objectives, testing strategy, and test parameters associated with a future AFC test series, AFC-5, are documented. Finally, the future intersections and/or synergies of the AFC irradiation testing program with those of the TREAT transient testing program, emerging needs of proposed Versatile Test Reactor concepts, and the Joint Fuel Cycle Study program’s Integrated Recycle Test are discussed.

Cyclin D1 Expression and Its Correlation with Histopathological Differentiation in Oral Squamous Cell Carcinoma

Directory of Open Access Journals (Sweden)

Swati Saawarn

2012-01-01

Full Text Available Background. Cyclin D1 regulates the G1 to S transition of cell cycle. Its deregulation or overexpression may lead to disturbance in the normal cell cycle control and tumour formation. Overexpression of cyclin D1 has been reported in various tumors of diverse histogenesis. This case control retrospective study was carried out to study the immunohistochemical reactivity and expression of cyclin D1 and its association with site, clinical staging, and histopathological differentiation of oral squamous cell carcinoma (OSCC. Methods. Forty formalin-fixed paraffin-embedded tissue blocks of biopsy specimens of oral squamous cell carcinoma were immunohistochemically evaluated for expression of cyclin D1. Results. Cyclin D1 expression was seen in 45% cases of OSCC. It did not correlate with site and clinical staging. Highest expression was seen in well-differentiated, followed by moderately differentiated, and poorly differentiated squamous cell carcinomas, with a statistically significant correlation. Conclusion. Cyclin D1 expression significantly increases with increase in differentiation.

Systematic Standardized and Individualized Assessment of Masticatory Cycles Using Electromagnetic 3D Articulography and Computer Scripts

Directory of Open Access Journals (Sweden)

Ramón Fuentes

2017-01-01

Full Text Available Masticatory movements are studied for decades in odontology; a better understanding of them could improve dental treatments. The aim of this study was to describe an innovative, accurate, and systematic method of analyzing masticatory cycles, generating comparable quantitative data. The masticatory cycles of 5 volunteers (Class I, 19 ± 1.7 years without articular or dental occlusion problems were evaluated using 3D electromagnetic articulography supported by MATLAB software. The method allows the trajectory morphology of the set of chewing cycles to be analyzed from different views and angles. It was also possible to individualize the trajectory of each cycle providing accurate quantitative data, such as number of cycles, cycle areas in frontal view, and the ratio between each cycle area and the frontal mandibular border movement area. There was a moderate negative correlation (−0.61 between the area and the number of cycles: the greater the cycle area, the smaller the number of repetitions. Finally it was possible to evaluate the area of the cycles through time, which did not reveal a standardized behavior. The proposed method provided reproducible, intelligible, and accurate quantitative and graphical data, suggesting that it is promising and may be applied in different clinical situations and treatments.

Vibrating sample magnetometer 2D and 3D magnetization effects associated with different initial magnetization states

Directory of Open Access Journals (Sweden)

Ronald E. Lukins

2017-05-01

Full Text Available Differences in VSM magnetization vector rotation associated with various initial magnetization states were demonstrated. Procedures and criteria were developed to select sample orientation and initial magnetization states to allow for the combination of two different 2D measurements runs (with the same field profiles to generate a dataset that can be representative of actual 3D magnetization rotation. Nickel, cast iron, and low moment magnetic tape media were used to demonstrate these effects using hysteresis and remanent magnetization test sequences. These results can be used to generate 2D and 3D magnetic properties to better characterize magnetic phenomena which are inherently three dimensional. Example applications are magnetic tape-head orientation sensitivity, reinterpretation of 3D coercivity and other standard magnetic properties, and multi-dimensional shielding effectiveness.

Cyclin d1 expression in odontogenic cysts.

Science.gov (United States)

Taghavi, Nasim; Modabbernia, Shirin; Akbarzadeh, Alireza; Sajjadi, Samad

2013-01-01

In the present study expression of cyclin D1 in the epithelial lining of odontogenic keratocyst, radicular cyst, dentigerous cyst and glandular odontogenic cyst was investigated to compare proliferative activity in these lesions. Immunohistochemical staining of cyclin D1 on formalin-fixed, paraffin-embedded tissue sections of odontogenic keratocysts (n=23), dentigerous cysts (n=20), radicular cysts (n=20) and glandular odontogenic cysts (n=5) was performed by standard EnVision method. Then, slides were studied to evaluate the following parameters in epithelial lining of cysts: expression, expression pattern, staining intensity and localization of expression. The data analysis showed statistically significant difference in cyclin D1 expression in studied groups (p keratocysts, but difference was not statistically significant among groups respectively (p=0.204, 0.469). Considering expression localization, cyclin D1 positive cells in odontogenic keratocysts and dentigerous cysts were frequently confined in parabasal layer, different from radicular cysts and glandular odontogenic cysts. The difference was statistically significant (p keratocyst and the entire cystic epithelium of glandular odontogenic cysts comparing to dentigerous cysts and radicular cysts, implying the possible role of G1-S cell cycle phase disturbances in the aggressiveness of odontogenic keratocyst and glandular odontogenic cyst.

DUPIC fuel cycle economics assessment (1)

International Nuclear Information System (INIS)

Choi, H. B.; Roh, G. H.; Kim, D. H.

1999-04-01

This is a state-of-art report that describes the current status of the DUPIC fuel cycle economics analysis conducted by the DUPIC fuel compatibility assessment group of the DUPIC fuel development project. For the DUPIC fuel cycle economics analysis, the DUPIC fuel compatibility assessment group has organized the 1st technical meeting composed of 8 domestic specialists from government, academy, industry, etc. and a foreign specialist of hot-cell design from TRI on July 16, 1998. This report contains the presentation material of the 1st technical meeting, published date used for the economics analysis and opinions of participants, which could be utilized for further DUPIC fuel cycle and back-end fuel cycle economics analyses. (author). 11 refs., 7 charts

Engineering, installation, testing, and initial operation of the DIII-D Advanced Divertor

International Nuclear Information System (INIS)

Andersen, P.M.; Baxi, C.B.; Reis, E.E.; Schaffer, M.J.; Smith, J.P.

1990-09-01

The Advanced Divertor (AD) for General Atomics tokamak, DIII-D, was installed in the summer of 1990. The AD has enabled two classes of physics experiments to be run: divertor biasing and divertor baffling. Both are new experiments for DIII-D. The AD has two principal components: (1) a continuous ring electrode; and (2) a toroidally symmetric baffle. The tokamak can be run in bias baffle or standard DIII-D divertor modes by accurate positioning of the outer divertor strike point through the use of the DIII-D control system. The paper covers design, analysis, fabrication, installation, instrumentation, testing, initial operation, and future plans for the Advanced Divertor from an engineering viewpoint. 2 refs., 5 figs

Titan 2D: Understanding Titan’s Seasonal Atmospheric Cycles

Science.gov (United States)

Wong, Michael; Zhang, X.; Li, C.; Hu, R.; Shia, R.; Newman, C.; Müller-Wodarg, I.; Yung, Y.

2013-10-01

In this study, we present results from a novel two-dimensional (2D) model that simulates the physics and chemistry of Titan’s atmosphere. Despite being an icy moon of Saturn, Titan is the only Solar System object aside from Earth that is sheathed by a thick nitrogen-dominated atmosphere. This vulnerable gaseous envelope—an embodiment of a delicate coupling between photochemistry, radiation, and dynamics—is Nature’s laboratory for the synthesis of complex organic molecules. Titan’s large obliquity generates pronounced seasonal cycles in its atmosphere, and the Cassini spacecraft has been observing these variations since 2004. In particular, Cassini measurements show that the latitudinal distribution of Titan’s rich mélange of hydrocarbon species follows seasonal patterns. The mixing ratios of hydrocarbons increase with latitude towards the winter pole, suggesting a pole-to-pole circulation that reverses after equinox. Using a one-dimensional photochemical model of Titan’s atmosphere, we show that photochemistry alone cannot produce the observed meridional hydrocarbon distribution. This necessitates the employment of a 2D chemistry-transport model that includes meridional circulation as well as diffusive processes and photochemistry. Of additional concern, no previous 2D model of Titan extends beyond 500 km altitude—a critical limitation since the peak of methane photolysis is at 800 km. Our 2D model is the first to include Titan’s stratosphere, mesosphere, and thermosphere. The meridional circulation in our 2D model is derived from the outputs of two general circulation models (GCMs): the TitanWRF GCM (Newman et al. 2011) covering the troposphere, stratosphere, and lower mesosphere, and a thermosphere general circulation model (TGCM) covering the remainder of the atmosphere through the thermosphere (Müller-Wodarg et al. 2003; 2008). This presentation will focus on the utilization of these advances applied to the 2D Caltech/JPL KINETICS model to

The alpha-fetoprotein (AFP) third domain: a search for AFP interaction sites of cell cycle proteins.

Science.gov (United States)

Mizejewski, G J

2016-09-01

The carboxy-terminal third domain of alpha-fetoprotein (AFP-3D) is known to harbor binding and/or interaction sites for hydrophobic ligands, receptors, and binding proteins. Such reports have established that AFP-3D consists of amino acid (AA) sequence stretches on the AFP polypeptide that engages in protein-to-protein interactions with various ligands and receptors. Using a computer software program specifically designed for such interactions, the present report identified AA sequence fragments on AFP-3D that could potentially interact with a variety of cell cycle proteins. The cell cycle proteins identified were (1) cyclins, (2) cyclin-dependent kinases, (3) cell cycle-associated proteins (inhibitors, checkpoints, initiators), and (4) ubiquitin ligases. Following detection of the AFP-3D to cell cycle protein interaction sites, the computer-derived AFP localization AA sequences were compared and aligned with previously reported hydrophobic ligand and receptor interaction sites on AFP-3D. A literature survey of the association of cell cycle proteins with AFP showed both positive relationships and correlations. Previous reports of experimental AFP-derived peptides effects on various cell cycle proteins served to confirm and verify the present computer cell cycle protein identifications. Cell cycle protein interactions with AFP-CD peptides have been reported in cultured MCF-7 breast cancer cells subjected to mRNA microarray analysis. After 7 days in culture with MCF-7 cells, the AFP-derived peptides were shown to downregulate cyclin E, SKP2, checkpoint suppressors, cyclin-dependent kinases, and ubiquitin ligases that modulate cyclin E/CdK2 transition from the G1 to the S-phase of the cell cycle. Thus, the experimental data on AFP-CD interaction with cell cycle proteins were consistent with the "in silico" findings.

Initial investment to 3D printing technologies in a construction company

OpenAIRE

Cernohorsky, Zdenek; Matejka, Petr

2017-01-01

This article deals with an initial investment to 3D printing technologies in a construction company. The investment refers to the use of building information models and their integration with 3D printing technology within a construction company. In the first part, there will be discussed an introduction of 3D printing scheme in a construction company from a lifecycle perspective in general. As a part of this scheme, the ideal variant of an initial investment will be considered a.k.a a pilot p...

The impact of UV irradiation on the radical initiating capacity of dissolved dyes

International Nuclear Information System (INIS)

Vig, A.; Czilik, M.; Rusznak, I.

2002-01-01

Complete text of publication follows. Kinetics of photodecomposition of three model dyes dissolved in isopropanol-water mixture has been determined after exposure to UV radiation in the range from 360 through 400 nm and from 220 through 400 nm, respectively. It has been disclosed earlier that photodecomposition of the dissolved dyes was decelerated initially by the presence of the dissolved oxygen in the system. The presence of a radical initiator, AIBN was indispensable for arriving at the decomposition of the irradiated dye solution in the range from 360 through 400 nm. The equation of W i D = [O 2 ]/τ D was used for the calculation of radical initiating rate of the irradiated dye molecule on the isopropanol (W i D (mol/l x s)), where [O 2 ] (mol/l) is the dissolved oxygen concentration in the system and τ D (s) is duration of the induction period of the photodestruction of the dissolved dye. The equation is valid only for photodecomposition which are not chain reaction. The photodegradation of dissolved dyes was also other then chain reaction, consequently the above equation could be applied in the study too. The average radical initiating rate of the dyes applied in this study was in the order of magnitude equal to that of AIBN. The number of cycles between the first radical formation and the last regeneration of the dye molecule could be calculated in bath systems (in the presence and absence of oxygen, respectively): K = W i D /W D , where K is the number of cycles, W D (mol/l x s) is the initial rate of the decomposition of the dissolved dyed. The number of cycles in the oxygen containing systems significantly exceeded those obtained in the oxygen systems because W D was markedly higher in the latter system than in the former one

Human T-cell leukemia virus type 1 Tax and cell cycle progression: role of cyclin D-cdk and p110Rb.

Science.gov (United States)

Neuveut, C; Low, K G; Maldarelli, F; Schmitt, I; Majone, F; Grassmann, R; Jeang, K T

1998-06-01

Human T-cell leukemia virus type 1 is etiologically linked to the development of adult T-cell leukemia and various human neuropathies. The Tax protein of human T-cell leukemia virus type I has been implicated in cellular transformation. Like other oncoproteins, such as Myc, Jun, and Fos, Tax is a transcriptional activator. How it mechanistically dysregulates the cell cycle is unclear. Previously, it was suggested that Tax affects cell-phase transition by forming a direct protein-protein complex with p16(INK4a), thereby inactivating an inhibitor of G1-to-S-phase progression. Here we show that, in T cells deleted for p16(INK4a), Tax can compel an egress of cells from G0/G1 into S despite the absence of serum. We also show that in undifferentiated myocytes, expression of Tax represses cellular differentiation. In both settings, Tax expression was found to increase cyclin D-cdk activity and to enhance pRb phosphorylation. In T cells, a Tax-associated increase in steady-state E2F2 protein was also documented. In searching for a molecular explanation for these observations, we found that Tax forms a protein-protein complex with cyclin D3, whereas a point-mutated and transcriptionally inert Tax mutant failed to form such a complex. Interestingly, expression of wild-type Tax protein in cells was also correlated with the induction of a novel hyperphosphorylated cyclin D3 protein. Taken together, these findings suggest that Tax might directly influence cyclin D-cdk activity and function, perhaps by a route independent of cdk inhibitors such as p16(INK4a).

Standalone BISON Fuel Performance Results for Watts Bar Unit 1, Cycles 1-3

Energy Technology Data Exchange (ETDEWEB)

Clarno, Kevin T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Pawlowski, Roger [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Stimpson, Shane [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Powers, Jeffrey [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2016-03-07

The Consortium for Advanced Simulation of Light Water Reactors (CASL) is moving forward with more complex multiphysics simulations and increased focus on incorporating fuel performance analysis methods. The coupled neutronics/thermal-hydraulics capabilities within the Virtual Environment for Reactor Applications Core Simulator (VERA-CS) have become relatively stable, and major advances have been made in analysis efforts, including the simulation of twelve cycles of Watts Bar Nuclear Unit 1 (WBN1) operation. While this is a major achievement, the VERA-CS approaches for treating fuel pin heat transfer have well-known limitations that could be eliminated through better integration with the BISON fuel performance code. Several approaches are being implemented to consider fuel performance, including a more direct multiway coupling with Tiamat, as well as a more loosely coupled one-way approach with standalone BISON cases. Fuel performance typically undergoes an independent analysis using a standalone fuel performance code with manually specified input defined from an independent core simulator solution or set of assumptions. This report summarizes the improvements made since the initial milestone to execute BISON from VERA-CS output. Many of these improvements were prompted through tighter collaboration with the BISON development team at Idaho National Laboratory (INL). A brief description of WBN1 and some of the VERA-CS data used to simulate it are presented. Data from a small mesh sensitivity study are shown, which helps justify the mesh parameters used in this work. The multi-cycle results are presented, followed by the results for the first three cycles of WBN1 operation, particularly the parameters of interest to pellet-clad interaction (PCI) screening (fuel-clad gap closure, maximum centerline fuel temperature, maximum/minimum clad hoop stress, and cumulative damage index). Once the mechanics of this capability are functioning, future work will target cycles with

Experimental investigation of crack initiation in face-centered cubic materials in the high and very high cycle fatigue regime

Energy Technology Data Exchange (ETDEWEB)

Straub, Thomas

2016-07-01

Materials in many modern small-scale applications are under complex cyclic stress states and undergo up to 10{sup 9} cycles. Fatigue mechanisms limit their lifetime and lead to failure. Therefore, the Very High Cycle Fatigue (VHCF) regime needs to be studied. This thesis investigates the fatigue mechanisms and crack initiation of nickel, aluminum and copper on a small-scale in the VHCF regime by means of innovative fatigue experimentation. Firstly, the development and implementation of a novel custom-built resonant fatigue setup showed that the resonant frequency of bending micro-samples changes with increasing cycle number due to the accumulating fatigue damage. Then, additional insights on early damage formation have been explored. Mechanisms, prior to crack initiation, such as slip band formation at a state where it appears in only a few grains, have been observed. Cyclic hardening, vacancy formation and oxidation formation may be considered as possible explanations for early fatigue mechanisms. In addition, the new experimental setup can be used to define parameters needed for crack initiation models. Finally, these crack initiation processes have been experimentally examined for pure aluminum and pure copper.

Strain localization and fatigue crack initiation in ultrafine-grained copper in high- and giga-cycle region

Czech Academy of Sciences Publication Activity Database

Kunz, Ludvík; Lukáš, Petr; Navrátilová, L.

2014-01-01

Roč. 58, JAN (2014), s. 202-208 ISSN 0142-1123 R&D Projects: GA ČR GAP108/10/2001; GA MŠk(CZ) ED1.1.00/02.0068 Institutional support: RVO:68081723 Keywords : Fatigue crack initiation * Strain localization * Stability of ultrafine-grained structure * UFG Cu Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.275, year: 2014

Enhanced cycling stability of Li-rich nanotube cathodes by 3D graphene hierarchical architectures for Li-ion batteries

International Nuclear Information System (INIS)

Ma, Dingtao; Li, Yongliang; Wu, Maosheng; Deng, Libo; Ren, Xiangzhong; Zhang, Peixin

2016-01-01

A hybrid composite of Li 1.2 Mn 0.54 Ni 0.13 Co 0.13 O 2 nanotubes (LMNCO NTs) wrapped with reduced graphene oxide (RGO) nanosheets (LMNCO@RGO) was prepared as cathode for lithium-ion batteries. The discharge capacity of the LMNCO@RGO composite is only reducing 3.5% after 100 cycles at 1 C. Such composite which simultaneously combines a high surface area of LMNCO NTs with shorten ionic diffusion pathway and high conductivity of 3D graphene hierarchical architectures as well as structural protection layers, displaying a good cycling stability.

The two chromosomes of Vibrio cholerae are initiated at different time points in the cell cycle

DEFF Research Database (Denmark)

Rasmussen, Tue; Jensen, Rasmus Bugge; Skovgaard, Ole

2007-01-01

for analysing flow cytometry data and marker frequency analysis, we show that the small chromosome II is replicated late in the C period of the cell cycle, where most of chromosome I has been replicated. Owing to the delay in initiation of chromosome II, the two chromosomes terminate replication...... at approximately the same time and the average number of replication origins per cell is higher for chromosome I than for chromosome II. Analysis of cell-cycle parameters shows that chromosome replication and segregation is exceptionally fast in V. cholerae. The divided genome and delayed replication of chromosome...... II may reduce the metabolic burden and complexity of chromosome replication by postponing DNA synthesis to the last part of the cell cycle and reducing the need for overlapping replication cycles during rapid proliferation...

The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells

Science.gov (United States)

Badia, Roger; Pujantell, Maria; Riveira-Muñoz, Eva; Puig, Teresa; Torres-Torronteras, Javier; Martí, Ramón; Clotet, Bonaventura; Ampudia, Rosa M.; Ballana, Ester

2016-01-01

Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases (CDK). Here, we have used primary human monocyte-derived macrophages differentiated through different stimuli to evaluate macrophage heterogeneity on cell activation and proliferation and susceptibility to HIV-1 infection. Stimulation of monocytes with GM-CSF induces a non-proliferating macrophage population highly restrictive to HIV-1 infection, characterized by the upregulation of the G1/S-specific cyclin D2, known to control early steps of cell cycle progression. Knockdown of cyclin D2, enhances HIV-1 replication in GM-CSF macrophages through inactivation of SAMHD1 restriction factor by phosphorylation. Co-immunoprecipitation experiments show that cyclin D2 forms a complex with CDK4 and p21, a factor known to restrict HIV-1 replication by affecting the function of the downstream cascade that leads to SAMHD1 deactivation. Thus, we demonstrate that cyclin D2 acts as regulator of cell cycle proteins affecting SAMHD1-mediated HIV-1 restriction in non-proliferating macrophages. PMID:27541004

Phenotypic variation in anti-Mullerian hormone (AMH) production per follicle in women with polycystic ovary syndrome (PCOS) and isolated polycystic ovarian morphology (PCOM): an observational cross-sectional study.

Science.gov (United States)

Bhide, Priya; Kulkarni, Abhijit; Dilgil, Merve; Dhir, Puja; Shah, Amit; Gudi, Anil; Homburg, Roy

2017-10-01

This observational study compares the ratio of serum anti-Mullerian hormone (AMH) to the total antral follicle count (AFC) (as a marker of AMH production per follicle) in the various phenotypes of women with polycystic ovary syndrome (PCOS) and isolated polycystic ovarian morphology (PCOM). Two hundred and sixty-two women were recruited. Women with PCOS were divided into four phenotypes based on the diagnostic inclusion criteria of oligo-anovulation (OA), hyperandrogenism (HA) and polycystic ovarian morphology (PCOM). These included Group A (OA + HA + PCOM), Group B (OA + HA), Group C (HA + PCOM) and Group D (OA + PCOM). A ratio of serum AMH to total AFC was calculated and expressed as the AMH/AFC ratio which was compared in the phenotypes of PCOS and isolated PCOM. The median AMH/AFC ratios in PCOS-A, PCOS-D, PCOS-C and PCOM were 1.5, 1.6, 1.2 and 1.1, respectively. There were significant differences in the groups compared [F(3, 238) = 6.14, p = 0.000)]. The ratios were significantly higher in the oligo-anovulatory phenotypes PCOS-A and PCOS-D than the PCOM (p = 0.004 and 0.002, respectively). There was no significant difference in the ratio between ovulatory phenotype PCOS-C and PCOM (p = 0.59). The role of androgens and LH in per-follicle AMH production remains limited. The findings support the hypothesis of a key role for AMH in the mechanism of anovulation in PCOS.

Initial investment to 3D printing technologies in a construction company

Directory of Open Access Journals (Sweden)

Cernohorsky, Zdenek

2017-06-01

Full Text Available This article deals with an initial investment to 3D printing technologies in a construction company. The investment refers to the use of building information models and their integration with 3D printing technology within a construction company. In the first part, there will be discussed an introduction of 3D printing scheme in a construction company from a lifecycle perspective in general. As a part of this scheme, the ideal variant of an initial investment will be considered a.k.a a pilot project. In the second part, there will be a more detailed discussion of the pilot project, more about each activities which should be its parts and which should analyze cost categories. These categories will be about particular lifecycle stages of the pilot project. In the third part, a summary is done. This article could be a handout for a construction company in a term of an initial investment to 3D printing.

Antral follicle counts are strongly associated with live-birth rates after assisted reproduction, with superior treatment outcome in women with polycystic ovaries.

Science.gov (United States)

Holte, Jan; Brodin, Thomas; Berglund, Lars; Hadziosmanovic, Nermin; Olovsson, Matts; Bergh, Torbjörn

2011-09-01

To evaluate the association of antral follicle count (AFC) with in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) outcome in a large unselected cohort of patients covering the entire range of AFC. Prospective observational study. University-affiliated private infertility center. 2,092 women undergoing 4,308 IVF-ICSI cycles. AFC analyzed for associations with treatment outcome and statistically adjusted for repeated treatments and age. Pregnancy rate, live-birth rate, and stimulation outcome parameters. The AFC was log-normally distributed. Pregnancy rates and live-birth rates were positively associated with AFC in a log-linear way, leveling out above AFC ∼30. Treatment outcome was superior among women with polycystic ovaries, independent from ovulatory status. The findings were significant also after adjustment for age and number of oocytes retrieved. Pregnancy and live-birth rates are log-linearly related to AFC. Polycystic ovaries, most often excluded from studies on ovarian reserve, fit as one extreme in the spectrum of AFC; a low count constitutes the other extreme, with the lowest ovarian reserve and poor treatment outcome. The findings remained statistically significant also after adjustment for the number of oocytes retrieved, suggesting this measure of ovarian reserve comprises information on oocyte quality and not only quantity. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Circulating basal anti-Müllerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization.

Science.gov (United States)

Nardo, Luciano G; Gelbaya, Tarek A; Wilkinson, Hannah; Roberts, Stephen A; Yates, Allen; Pemberton, Phil; Laing, Ian

2009-11-01

To evaluate the clinical value of basal anti-Müllerian hormone (AMH) measurements compared with other available determinants, apart from chronologic age, in the prediction of ovarian response to gonadotrophin stimulation. Prospective cohort study. Tertiary referral center for reproductive medicine and an IVF unit. Women undergoing their first cycle of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Basal levels of FSH and AMH as well as antral follicle count (AFC) were measured in 165 subjects. All patients were followed prospectively and their cycle outcomes recorded. Predictive value of FSH, AMH, and AFC for extremes of ovarian response to stimulation. Out of the 165 women, 134 were defined as normal responders, 15 as poor responders, and 16 as high responders. Subjects in the poor response group were significantly older then those in the other two groups. Anti-Müllerian hormone levels and AFC were markedly raised in the high responders and decreased in the poor responders. Compared with FSH and AFC, AMH performed better in the prediction of excessive response to ovarian stimulation-AMH area under receiver operating characteristic curve (ROC(AUC)) 0.81, FSH ROC(AUC) 0.66, AFC ROC(AUC) 0.69. For poor response, AMH (ROC(AUC) 0.88) was a significantly better predictor than FSH (ROC(AUC) 0.63) but not AFC (ROC(AUC) 0.81). AMH prediction of ovarian response was independent of age and PCOS. Anti-Müllerian hormone cutoffs of >3.75 ng/mL and stimulation with exogenous gonadotrophins. Overall, this biomarker is superior to basal FSH and AFC, and has the potential to be incorporated in to work-up protocols to predict patient's ovarian response to treatment and to individualize strategies aiming at reducing the cancellation rate and the iatrogenic complications of COH.

Brayton Cycle Numerical Modeling using the RELAP5-3D code, version 4.3.4

Energy Technology Data Exchange (ETDEWEB)

Longhini, Eduardo P.; Lobo, Paulo D.C.; Guimarães, Lamartine N.F.; Filho, Francisco A.B.; Ribeiro, Guilherme B., E-mail: edu_longhini@yahoo.com.br [Instituto de Estudos Avançados (IEAv), São José dos Campos, SP (Brazil). Divisão de Energia Nuclear

2017-07-01

This work contributes to enable and develop technologies to mount fast micro reactors, to generate heat and electric energy, for the purpose to warm and to supply electrically spacecraft equipment and, also, the production of nuclear space propulsion effect. So, for this purpose, the Brayton Cycle demonstrates to be an optimum approach for space nuclear power. The Brayton thermal cycle gas has as characteristic to be a closed cycle, with two adiabatic processes and two isobaric processes. The components performing the cycle's processes are compressor, turbine, heat source, cold source and recuperator. Therefore, the working fluid's mass flow runs the thermal cycle that converts thermal energy into electrical energy, able to use in spaces and land devices. The objective is numerically to model the Brayton thermal cycle gas on nominal operation with one turbomachine composed for a radial-inflow compressor and turbine of a 40.8 kWe Brayton Rotating Unit (BRU). The Brayton cycle numerical modeling is being performed with the program RELAP5-3D, version 4.3.4. The nominal operation uses as working fluid a mixture 40 g/mole He-Xe with a flow rate of 1.85 kg/s, shaft rotational speed of 45 krpm, compressor and turbine inlet temperature of 400 K and 1149 K, respectively, and compressor exit pressure 0.931 MPa. Then, the aim is to get physical corresponding data to operate each cycle component and the general cycle on this nominal operation. (author)

Brayton Cycle Numerical Modeling using the RELAP5-3D code, version 4.3.4

International Nuclear Information System (INIS)

Longhini, Eduardo P.; Lobo, Paulo D.C.; Guimarães, Lamartine N.F.; Filho, Francisco A.B.; Ribeiro, Guilherme B.

2017-01-01

This work contributes to enable and develop technologies to mount fast micro reactors, to generate heat and electric energy, for the purpose to warm and to supply electrically spacecraft equipment and, also, the production of nuclear space propulsion effect. So, for this purpose, the Brayton Cycle demonstrates to be an optimum approach for space nuclear power. The Brayton thermal cycle gas has as characteristic to be a closed cycle, with two adiabatic processes and two isobaric processes. The components performing the cycle's processes are compressor, turbine, heat source, cold source and recuperator. Therefore, the working fluid's mass flow runs the thermal cycle that converts thermal energy into electrical energy, able to use in spaces and land devices. The objective is numerically to model the Brayton thermal cycle gas on nominal operation with one turbomachine composed for a radial-inflow compressor and turbine of a 40.8 kWe Brayton Rotating Unit (BRU). The Brayton cycle numerical modeling is being performed with the program RELAP5-3D, version 4.3.4. The nominal operation uses as working fluid a mixture 40 g/mole He-Xe with a flow rate of 1.85 kg/s, shaft rotational speed of 45 krpm, compressor and turbine inlet temperature of 400 K and 1149 K, respectively, and compressor exit pressure 0.931 MPa. Then, the aim is to get physical corresponding data to operate each cycle component and the general cycle on this nominal operation. (author)

Cell Cycle Dependent Expression of Plk1 in Synchronized Porcine Fetal Fibroblasts

Czech Academy of Sciences Publication Activity Database

Anger, Martin; Kues, W. A.; Klíma, Jiří; Mielenz, M.; Kubelka, Michal; Motlík, Jan; Ešner, M.; Dvořák, P.; Carnwath, J. W.; Niemann, H.

2003-01-01

Roč. 65, č. 3 (2003), s. 245-253 ISSN 1040-452X R&D Projects: GA MŠk LN00A065 Grant - others:FIRCA(XX) R03-TW-05530-01 Institutional research plan: CEZ:AV0Z5045916 Keywords : Plk1 * serum deprivation * cell cycle Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.543, year: 2003

HIV-1 reverse transcription initiation: a potential target for novel antivirals?

NARCIS (Netherlands)

Abbink, Truus E. M.; Berkhout, Ben

2008-01-01

Reverse transcription is an essential step in the retroviral life cycle, as it converts the genomic RNA into DNA. In this review, we describe recent developments concerning the initiation step of this complex, multi-step reaction. During initiation of reverse transcription, a cellular tRNA primer is

Physics of fusion-fuel cycles

International Nuclear Information System (INIS)

McNally, J.R. Jr.

1981-01-01

The evaluation of nuclear fusion fuels for a magnetic fusion economy must take into account the various technological impacts of the various fusion fuel cycles as well as the relative reactivity and the required β's and temperatures necessary for economic steady-state burns. This paper will review some of the physics of the various fusion fuel cycles (D-T, catalyzed D-D, D- 3 He, D- 6 Li, and the exotic fuels: 3 He 3 He and the proton-based fuels such as P- 6 Li, P- 9 Be, and P- 11 B) including such items as: (1) tritium inventory, burnup, and recycle, (2) neutrons, (3) condensable fuels and ashes, (4) direct electrical recovery prospects, (5) fissile breeding, etc. The advantages as well as the disadvantages of the different fusion fuel cycles will be discussed. The optimum fuel cycle from an overall standpoint of viability and potential technological considerations appears to be catalyzed D-D, which could also support smaller relatively clean, lean-D, rich- 3 He satellite reactors as well as fission reactors

Visibility of microcalcification clusters and masses in breast tomosynthesis image volumes and digital mammography: A 4AFC human observer study

International Nuclear Information System (INIS)

Timberg, P.; Baath, M.; Andersson, I.; Mattsson, S.; Tingberg, A.; Ruschin, M.

2012-01-01

Purpose: To investigate the visibility of simulated lesions in digital breast tomosynthesis (BT) image volumes compared with 2D digital mammography (DM). Methods: Simulated lesions (masses and microcalcifications) were added to images of the same women acquired on a DM system (Mammomat Novation, Siemens) and a BT prototype. The same beam quality was used for the DM and BT acquisitions. The total absorbed dose resulting from a 25-projection BT acquisition and reconstruction (BT 25 ) was approximately twice that of a single DM view. By excluding every other projection image from the reconstruction (BT 13 ), approximately the same dose as in DM was effected. Simulated microcalcifications were digitally added with varying contrast to the DM and BT images. Simulated masses with 8 mm diameter were also added to BT images. A series of 4-alternative forced choice (4AFC) human observer experiments were conducted. Four medical physicists participated in all experiments, each consisting of 60 trials per experimental condition. The observers interpreted the BT image volumes in cine-mode at a fixed image sequence speed. The required threshold contrast (S t ) to achieve a detectability index (d') of 2.5 (i.e., 92.5% correct decisions) was determined. Results: The S t for mass detection in DM was approximately a factor of 2 higher than required in BT indicating that the detection of masses was improved under BT conditions compared to DM. S t for microcalcification detection was higher for BT than for DM at both BT dose levels (BT 25 and BT 13 ), with a statistically significant difference in S t between DM and BT 13 . These results indicate a dose-dependent decrease in detection performance in BT for detection of microcalcifications. Conclusions: In agreement with previous investigations, masses of size 8 mm can be detected with less contrast in BT than in DM indicating improved detection performance for BT. However, for the investigated microcalcifications, the results of this

Timing of initiation of macronuclear DNA synthesis is set during the preceding cell cycle in Paramecium tetraurelia: analysis of the effects of abrupt changes in nutrient level

International Nuclear Information System (INIS)

Ching, A.S.L.; Berger, J.D.

1986-01-01

In many eukaryotic organisms, initiation of DNA synthesis is associated with a major control point within the cell cycle and reflects the commitment of the cell to the DNA replication-division portion of the cell cycle. In paramecium, the timing of DNA synthesis initiation is established prior to fission during the preceding cell cycle. DNA synthesis normally starts at 0.25 in the cell cycle. When dividing cells are subjected to abrupt nutrient shift-up by transfer from a chemostat culture to medium with excess food, or shift-down from a well-fed culture to exhausted medium, DNA synthesis initiation in the post-shift cell cycle occurs at 0.25 of the parental cell cycle and not at either 0.25 in the post-shift cell cycle or at 0.25 in the equilibrium cell cycle produced under the post-shift conditions. The long delay prior to initiation of DNA synthesis following nutritional shift-up is not a consequence of continued slow growth because the rate of protein synthesis increases rapidly to the normal level after shift-up. Analysis of the relation between increase in cell mass and initiation of DNA synthesis following nutritional shifts indicates that increase in cell mass, per se, is neither a necessary nor a sufficient condition for initiation of DNA synthesis, in spite of the strong association between accumulation of cell mass and initiation of DNA synthesis in cells growing under steady-state conditions

Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R.

Science.gov (United States)

Li, Ge; Park, Hyeon U; Liang, Dong; Zhao, Richard Y

2010-07-07

Cell cycle G2 arrest induced by HIV-1 Vpr is thought to benefit viral proliferation by providing an optimized cellular environment for viral replication and by skipping host immune responses. Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive. To examine this initiation event, we measured the Vpr effect over a single cell cycle. We found that even though Vpr stops the cell cycle at the G2/M phase, but the initiation event actually occurs in the S phase of the cell cycle. Specifically, Vpr triggers activation of Chk1 through Ser345 phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser345 phosphorylation by Vpr was confirmed by siRNA gene silencing and site-directed mutagenesis. Moreover, downregulation of DNA replication licensing factors Cdt1 by siRNA significantly reduced Vpr-induced Chk1-Ser345 phosphorylation and G2 arrest. Even though hydroxyurea (HU) and ultraviolet light (UV) also induce Chk1-Ser345 phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas vpr-expressing cells completed S phase and stopped at the G2/M boundary. Furthermore, unlike HU/UV, Vpr promotes Chk1- and proteasome-mediated protein degradations of Cdc25B/C for G2 induction; in contrast, Vpr had little or no effect on Cdc25A protein degradation normally mediated by HU/UV. These data suggest that Vpr induces cell cycle G2 arrest through a unique molecular mechanism that regulates host cell cycle regulation in an S-phase dependent fashion.

Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R

Directory of Open Access Journals (Sweden)

Liang Dong

2010-07-01

Full Text Available Abstract Background Cell cycle G2 arrest induced by HIV-1 Vpr is thought to benefit viral proliferation by providing an optimized cellular environment for viral replication and by skipping host immune responses. Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive. Results To examine this initiation event, we measured the Vpr effect over a single cell cycle. We found that even though Vpr stops the cell cycle at the G2/M phase, but the initiation event actually occurs in the S phase of the cell cycle. Specifically, Vpr triggers activation of Chk1 through Ser345 phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser345 phosphorylation by Vpr was confirmed by siRNA gene silencing and site-directed mutagenesis. Moreover, downregulation of DNA replication licensing factors Cdt1 by siRNA significantly reduced Vpr-induced Chk1-Ser345 phosphorylation and G2 arrest. Even though hydroxyurea (HU and ultraviolet light (UV also induce Chk1-Ser345 phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas vpr-expressing cells completed S phase and stopped at the G2/M boundary. Furthermore, unlike HU/UV, Vpr promotes Chk1- and proteasome-mediated protein degradations of Cdc25B/C for G2 induction; in contrast, Vpr had little or no effect on Cdc25A protein degradation normally mediated by HU/UV. Conclusions These data suggest that Vpr induces cell cycle G2 arrest through a unique molecular mechanism that regulates host cell cycle regulation in an S-phase dependent fashion.

The 3D Elevation Program initiative: a call for action

Science.gov (United States)

Sugarbaker, Larry J.; Constance, Eric W.; Heidemann, Hans Karl; Jason, Allyson L.; Lukas, Vicki; Saghy, David L.; Stoker, Jason M.

2014-01-01

The 3D Elevation Program (3DEP) initiative is accelerating the rate of three-dimensional (3D) elevation data collection in response to a call for action to address a wide range of urgent needs nationwide. It began in 2012 with the recommendation to collect (1) high-quality light detection and ranging (lidar) data for the conterminous United States (CONUS), Hawaii, and the U.S. territories and (2) interferometric synthetic aperture radar (ifsar) data for Alaska. Specifications were created for collecting 3D elevation data, and the data management and delivery systems are being modernized. The National Elevation Dataset (NED) will be completely refreshed with new elevation data products and services. The call for action requires broad support from a large partnership community committed to the achievement of national 3D elevation data coverage. The initiative is being led by the U.S. Geological Survey (USGS) and includes many partners—Federal agencies and State, Tribal, and local governments—who will work together to build on existing programs to complete the national collection of 3D elevation data in 8 years. Private sector firms, under contract to the Government, will continue to collect the data and provide essential technology solutions for the Government to manage and deliver these data and services. The 3DEP governance structure includes (1) an executive forum established in May 2013 to have oversight functions and (2) a multiagency coordinating committee based upon the committee structure already in place under the National Digital Elevation Program (NDEP). The 3DEP initiative is based on the results of the National Enhanced Elevation Assessment (NEEA) that was funded by NDEP agencies and completed in 2011. The study, led by the USGS, identified more than 600 requirements for enhanced (3D) elevation data to address mission-critical information requirements of 34 Federal agencies, all 50 States, and a sample of private sector companies and Tribal and local

Cyclin D1, Id1 and EMT in breast cancer

International Nuclear Information System (INIS)

Tobin, Nicholas P; Sims, Andrew H; Lundgren, Katja L; Lehn, Sophie; Landberg, Göran

2011-01-01

Cyclin D1 is a well-characterised cell cycle regulator with established oncogenic capabilities. Despite these properties, studies report contrasting links to tumour aggressiveness. It has previously been shown that silencing cyclin D1 increases the migratory capacity of MDA-MB-231 breast cancer cells with concomitant increase in 'inhibitor of differentiation 1' (ID1) gene expression. Id1 is known to be associated with more invasive features of cancer and with the epithelial-mesenchymal transition (EMT). Here, we sought to determine if the increase in cell motility following cyclin D1 silencing was mediated by Id1 and enhanced EMT-features. To further substantiate these findings we aimed to delineate the link between CCND1, ID1 and EMT, as well as clinical properties in primary breast cancer. Protein and gene expression of ID1, CCND1 and EMT markers were determined in MDA-MB-231 and ZR75 cells by western blot and qPCR. Cell migration and promoter occupancy were monitored by transwell and ChIP assays, respectively. Gene expression was analysed from publicly available datasets. The increase in cell migration following cyclin D1 silencing in MDA-MB-231 cells was abolished by Id1 siRNA treatment and we observed cyclin D1 occupancy of the Id1 promoter region. Moreover, ID1 and SNAI2 gene expression was increased following cyclin D1 knock-down, an effect reversed with Id1 siRNA treatment. Similar migratory and SNAI2 increases were noted for the ER-positive ZR75-1 cell line, but in an Id1-independent manner. In a meta-analysis of 1107 breast cancer samples, CCND1 low /ID1 high tumours displayed increased expression of EMT markers and were associated with reduced recurrence free survival. Finally, a greater percentage of CCND1 low /ID1 high tumours were found in the EMT-like 'claudin-low' subtype of breast cancer than in other subtypes. These results indicate that increased migration of MDA-MB-231 cells following cyclin D1 silencing can be mediated by Id

Progressive damage during thermal shock cycling of D-gun sprayed thermal barrier coatings with hollow spherical ZrO{sub 2}-8Y{sub 2}O{sub 3}

Energy Technology Data Exchange (ETDEWEB)

Ke, P.L. [State Key Lab for Corrosion and Protection, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China) and School of Metallurgy and Materials, University of Birmingham, Birmingham B15 2TT (United Kingdom)]. E-mail: csun@imr.ac.cn; Wang, Q.M. [State Key Lab for Corrosion and Protection, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Gong, J. [State Key Lab for Corrosion and Protection, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Sun, C. [State Key Lab for Corrosion and Protection, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Zhou, Y.C. [State Key Lab for Corrosion and Protection, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China)

2006-11-05

Thermal shock cycling behaviors of D-gun sprayed TBCs with a hollow spherical ZrO{sub 2}-8Y{sub 2}O{sub 3} (HSP-YSZ) top coat and NiCrAlY bond coat on directionally solidified Ni-base superalloys DZ125 were investigated at high temperature (1100 deg. C) {r_reversible} room temperature (RT) repeatedly by water quenching. Scanning electron microscopy (SEM) was used to characterize the coating microstructure and failure morphology. The results showed that failure of the D-gun sprayed TBC starts with crack initiation along the splats boundary in the ceramic top coat and the non-alumina oxides. The cracks propagate and coalesce with the increasing thermal cycling. The extensive cracking of the rapidly formed non-alumina oxides, resulting from the depletion of aluminum in the bond coat, aids to delamination of the outer ceramic layer. The stress distributions in TGO layer at different thermal shock cycles was measured by luminescence spectroscopy to investigate the failure mechanism of TBC system.

Sonic Hedgehog Initiates Cochlear Hair Cell Regeneration through Downregulation of Retinoblastoma Protein

Science.gov (United States)

Lu, Na; Chen, Yan; Wang, Zhengmin; Chen, Guoling; Lin, Qin; Chen, Zheng-Yi; Li, Huawei

2013-01-01

Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration. PMID:23211596

E2F1-Mediated Upregulation of p19INK4d Determines Its Periodic Expression during Cell Cycle and Regulates Cellular Proliferation

OpenAIRE

Carcagno, Abel L.; Marazita, Mariela C.; Ogara, María F.; Ceruti, Julieta M.; Sonzogni, Silvina V.; Scassa, María E.; Giono, Luciana E.; Cánepa, Eduardo T.

2011-01-01

Background: A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality o...

Simultaneous Multiple MS Binding Assays Addressing D1 and D2 Dopamine Receptors.

Science.gov (United States)

Schuller, Marion; Höfner, Georg; Wanner, Klaus T

2017-10-09

MS Binding Assays are a label-free alternative to radioligand binding assays. They provide basically the same capabilities as the latter, but use a non-labeled reporter ligand instead of a radioligand. In contrast to radioligand binding assays, MS Binding Assays offer-owing to the selectivity of mass spectrometric detection-the opportunity to monitor the binding of different reporter ligands at different targets simultaneously. The present study shows a proof of concept for this strategy as exemplified for MS Binding Assays selectively addressing D 1 and D 2 dopamine receptors in a single binding experiment. A highly sensitive, rapid and robust LC-ESI-MS/MS quantification method capable of quantifying both SCH23390 and raclopride, selectively addressing D 1 and D 2 receptors, respectively, was established and validated for this purpose. Based thereon, simultaneous saturation and competition experiments with SCH23390 and raclopride in the presence of both D 1 and D 2 receptors were performed and analyzed by LC-MS/MS within a single chromatographic cycle. The present study thus demonstrates the feasibility of this strategy and the high versatility of MS Binding Assays that appears to surpass that common for conventional radioligand binding assays. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

ROLE OF PI3K-AKT-mTOR AND Wnt SIGNALING PATHWAYS IN G1-S TRANSITION OF CELL CYCLE IN CANCER CELLS

Directory of Open Access Journals (Sweden)

LAKSHMIPATHI eVADLAKONDA

2013-04-01

Full Text Available The PI3K–Akt pathway together with one of its downstream targets, the mechanistic target of rapamycin (mTOR is a highly deregulated pathway in cancers. There is a reciprocal relation between the Akt phosphorylation and mTOR complexes. Akt phosphorylated at T308 activates mTORC1 by inhibition of the tuberous sclerosis complex (TSC1/2, where as mTORC2 is recognized as the kinase that phosphorylates Akt at S473. Recent developments in the research on regulatory mechanisms of autophagy places mTORC1 mediated inhibition of autophagy at the central position in activation of proliferation and survival pathways in cells. Autophagy is a negative regulator of Wnt signaling pathway and the downstream effectors of Wnt signaling pathway, cyclin D1 and the c-Myc, are the key players in initiation of cell cycle and regulation of the G1-S transition in cancer cells. Production of reaction oxygen species (ROS, a common feature of a cancer cell metabolism, activates several downstream targets like the transcription factors FoxO, which play key roles in promoting the progression of cell cycle. A model is presented on the role of PI3K -Akt - mTOR and Wnt pathways in regulation of the progression of cell cycle through Go-G1-and S phases.

Space exploration initiative (SEI) logistics support lessons from the DoD

Science.gov (United States)

Cox, John R.; McCoy, Walbert G.; Jenkins, Terence

Proven and innovative logistics management approaches and techniques used for developing and supporting DoD and Strategic Defense Initiative Office (SDIO) systems are described on the basis of input from DoD to the SEI Synthesis Group; SDIO-developed logistics initiatives, innovative tools, and methodologies; and logistics planning support provided to the NASA/Johnson Planet Surface System Office. The approach is tailored for lunar/Martian surface operations, and provides guidelines for the development and management of a crucial element of the SEI logistics support program. A case study is presented which shows how incorporation of DoD's proven and innovative logistics management approach, tools, and techniques can substantially benefit early logistics planning for SEI, while also implementing many of DoD's recommendations for SEI.

6-Nitro-2-(3-hydroxypropyl-1H-benz[de]isoquinoline-1,3-dione, a potent antitumor agent, induces cell cycle arrest and apoptosis

Directory of Open Access Journals (Sweden)

Singh Shashank K

2010-12-01

Full Text Available Abstract Background Anticancer activities of several substituted naphthalimides (1H-benz[de]isoquinoline-1,3-diones are well documented. Some of them have undergone Phase I-II clinical trials. Presently a series of ten N-(hydroxyalkyl naphthalimides (compounds 1a-j were evaluated as antitumor agents. Methods Compounds 1a-j were initially screened in MOLT-4, HL-60 and U-937 human tumor cell lines and results were compared with established clinical drugs. Cytotoxicities of compounds 1d and 1i were further evaluated in a battery of human tumor cell lines and in normal human peripheral blood mononuclear cells. Cell cycle analysis of compound 1i treated MOLT-4 cells was studied by flow cytometry. Its apoptosis inducing effect was carried out in MOLT-4 and HL-60 cells by flow cytometry using annexin V-FITC/PI double staining method. The activities of caspase-3 and caspase-6 in MOLT-4 cells following incubation with compound 1i were measured at different time intervals. Morphology of the MOLT-4 cells after treatment with 1i was examined under light microscope and transmission electron microscope. 3H-Thymidine and 3H-uridine incorporation in S-180 cells in vitro following treatment with 8 μM concentration of compounds 1d and 1i were studied. Results 6-Nitro-2-(3-hydroxypropyl-1H-benz[de]isoquinoline-1,3-dione (compound 1i, has exhibited maximum activity as it induced significant cytotoxicity in 8 out of 13 cell lines employed. Interestingly it did not show any cytotoxicity against human PBMC (IC50 value 273 μM. Cell cycle analysis of compound 1i treated MOLT-4 cells demonstrated rise in sub-G1 fraction and concomitant accumulation of cells in S and G2/M phases, indicating up-regulation of apoptosis along with mitotic arrest and/or delay in exit of daughter cells from mitotic cycle respectively. Its apoptosis inducing effect was confirmed in flow cytometric study in MOLT-4 and the action was mediated by activation of both caspase 3 and 6. Light and

Sizewell B cycle 5 core design with Framatome ANP's CASCADE-3D and British Energy's PANTHER

International Nuclear Information System (INIS)

Attale, F.; Koegl, J.; Knight, M.; Bryce, P.

2001-01-01

Sizewell B Cycle 5 is the first cycle, after 4 cycles with BNFL fuel, with a reload consisting of Framatome ANP HTP (high thermal performance) fuel assemblies. The impact of this fuel vendor change on the Nuclear Design area is that, according to British energy's (BE) practice, the Framatome ANP's nuclear design code system CASCADE-3D is used for the majority of the cycle specific safety case calculations. However, other parts of the safety submission (e.g. 3D transient analyses) are made by using the BE code PANTHER. Before using in parallel two different code systems for reload core licensing extensive comparisons of applied methodologies and obtained results were required to ensure an acceptable level of agreement. (orig.)

Characterisation of cyclists’ willingness to pay for green initiatives at Africa’s largest cycle tour

Directory of Open Access Journals (Sweden)

Melville Saayman

2016-08-01

Full Text Available The Cape Argus Pick n Pay Cycle Tour is a major event on the road cycling calendar. The majority of cyclists travel significant distances and participation produces a substantial carbon footprint. This paper examines participants’ willingness to pay to offset their carbon footprint. The purpose of this paper is to make a contribution to the literature by linking willingness to pay to attitudes towards or beliefs (green views about the initiatives in place, to ensure a greener cycle tour. Factor analysis is used to identify different types of cyclists, based on their green views: those with green money, those who prefer green products and the “re-cyclers”. The results of the regression analysis reveal that socio-demographic variables and the right attitude towards the environment are significant predictors of stated willingness to pay for climate change mitigation.

DNA Amplification by Breakage/Fusion/Bridge Cycles Initiated by Spontaneous Telomere Loss in a Human Cancer Cell Line

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Anthony W.l. Lo

2002-01-01

Full Text Available The development of genomic instability is an important step in generatingthe multiple genetic changes required for cancer. One consequence of genomic instability is the overexpression of oncogenes due to gene amplification. One mechanism for gene amplification is the breakagelfusionlbridge (B/F/Bcyclethatinvolvesthe repeated fusion and breakage of chromosomes following the loss of a telomere. B/F/B cycles have been associated with low-copy gene amplification in human cancer cells, and have been proposed to be an initiating event in high-copy gene amplification. We have found that spontaneous telomere loss on a marker chromosome 16 in a human tumor cell line results in sister chromatid fusion and prolonged periods of chromosome instability. The high rate of anaphase bridges involving chromosome 16 demonstrates that this instability results from B/F/B cycles. The amplification of subtelomeric DNA on the marker chromosome provides conclusive evidence that B/F/B cycles initiated by spontaneous telomere loss are a mechanism for gene amplification in human cancer cells.

The performance of integrated active fiber composites in carbon fiber laminates

International Nuclear Information System (INIS)

Melnykowycz, M; Brunner, A J

2011-01-01

Piezoelectric elements integrated into fiber-reinforced polymer-matrix laminates can provide various functions in the resulting adaptive or smart composite. Active fiber composites (AFC) composed of lead zirconate titanate (PZT) fibers can be used as a component in a smart material system, and can be easily integrated into woven composites. However, the impact of integration on the device and its functionality has not been fully investigated. The current work focuses on the integration and performance of AFC integrated into carbon-fiber-reinforced plastic (CFRP) laminates, focusing on the strain sensor performance of the AFC–CFRP laminate under tensile loading conditions. AFC were integrated into cross-ply CFRP laminates using simple insertion and interlacing of the CFRP plies, with the AFC always placed in the 90° ply cutout area. Test specimens were strained to different strain levels and then cycled with a 0.01% strain amplitude, and the resulting signal from the AFC was monitored. Acoustic emission monitoring was performed during tensile testing to provide insight to the failure characteristics of the PZT fibers. The results were compared to those from past studies on AFC integration; the strain signal of AFC integrated into CFRP was much lower than that for AFC integrated into woven glass fiber laminates. However, the profiles of the degradations of the AFC signal resulting from the strain were nearly identical, showing that the PZT fibers fragmented in a similar manner for a given global strain. The sensor performance recovered upon unloading, which is attributed to the closure of cracks between PZT fiber fragments

Technology development for nuclear fuel cycle waste treatment - Decontamination, decommissioning and environmental restoration (1)

International Nuclear Information System (INIS)

Lee, Byung Jik; Won, Hui Jun; Yoon, Ji Sup and others

1997-12-01

Through the project of D econtamination, decommissioning and environmental restoration technology development , the following were studied. 1. Development of decontamination and repair technology for nuclear fuel cycle facilities 2. Development of dismantling technology 3. Environmental remediation technology development. (author). 95 refs., 45 tabs., 163 figs

SU-D-207A-07: The Effects of Inter-Cycle Respiratory Motion Variation On Dose Accumulation in Single Fraction MR-Guided SBRT Treatment of Renal Cell Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Stemkens, B; Glitzner, M; Kontaxis, C; Prins, F; Crijns, SPM; Kerkmeijer, L; Lagendijk, J; Berg, CAT van den; Tijssen, RHN [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Denis de Senneville, B [Imaging Division, University Medical Center Utrecht, Utrecht (Netherlands); IMB, UMR 5251 CNRS/University of Bordeaux (France)

2016-06-15

Purpose: To assess the dose deposition in simulated single-fraction MR-Linac treatments of renal cell carcinoma, when inter-cycle respiratory motion variation is taken into account using online MRI. Methods: Three motion characterization methods, with increasing complexity, were compared to evaluate the effect of inter-cycle motion variation and drifts on the accumulated dose for an SBRT kidney MR-Linac treatment: 1) STATIC, in which static anatomy was assumed, 2) AVG-RESP, in which 4D-MRI phase-volumes were time-weighted, based on the respiratory phase and 3) PCA, in which 3D volumes were generated using a PCA-model, enabling the detection of inter-cycle variations and drifts. An experimental ITV-based kidney treatment was simulated in a 1.5T magnetic field on three volunteer datasets. For each volunteer a retrospectively sorted 4D-MRI (ten respiratory phases) and fast 2D cine-MR images (temporal resolution = 476ms) were acquired to simulate MR-imaging during radiation. For each method, the high spatio-temporal resolution 3D volumes were non-rigidly registered to obtain deformation vector fields (DVFs). Using the DVFs, pseudo-CTs (generated from the 4D-MRI) were deformed and the dose was accumulated for the entire treatment. The accuracies of all methods were independently determined using an additional, orthogonal 2D-MRI slice. Results: Motion was most accurately estimated using the PCA method, which correctly estimated drifts and inter-cycle variations (RMSE=3.2, 2.2, 1.1mm on average for STATIC, AVG-RESP and PCA, compared to the 2DMRI slice). Dose-volume parameters on the ITV showed moderate changes (D99=35.2, 32.5, 33.8Gy for STATIC, AVG-RESP and PCA). AVG-RESP showed distinct hot/cold spots outside the ITV margin, which were more distributed for the PCA scenario, since inter-cycle variations were not modeled by the AVG-RESP method. Conclusion: Dose differences were observed when inter-cycle variations were taken into account. The increased inter-cycle

BRCA1-IRIS regulates cyclin D1 expression in breast cancer cells

International Nuclear Information System (INIS)

Nakuci, Enkeleda; Mahner, Sven; DiRenzo, James; ElShamy, Wael M.

2006-01-01

The regulator of cell cycle progression, cyclin D1, is up-regulated in breast cancer cells; its expression is, in part, dependent on ERα signaling. However, many ERα-negative tumors and tumor cell lines (e.g., SKBR3) also show over-expression of cyclin D1. This suggests that, in addition to ERα signaling, cyclin D1 expression is under the control of other signaling pathways; these pathways may even be over-expressed in the ERα-negative cells. We previously noticed that both ERα-positive and -negative cell lines over-express BRCA1-IRIS mRNA and protein. Furthermore, the level of over-expression of BRCA1-IRIS in ERα-negative cell lines even exceeded its over-expression level in ERα-positive cell lines. In this study, we show that: (1) BRCA1-IRIS forms complex with two of the nuclear receptor co-activators, namely, SRC1 and SRC3 (AIB1) in an ERα-independent manner. (2) BRCA1-IRIS alone, or in connection with co-activators, is recruited to the cyclin D1 promoter through its binding to c-Jun/AP1 complex; this binding activates the cyclin D1 expression. (3) Over-expression of BRCA1-IRIS in breast cells over-activates JNK/c-Jun; this leads to the induction of cyclin D1 expression and cellular proliferation. (4) BRCA1-IRIS activation of JNK/c-Jun/AP1 appears to account for this, because in cells that were depleted from BRCA1-IRIS, JNK remained inactive. However, depletion of SRC1 or SRC3 instead reduced c-Jun expression. Our data suggest that this novel signaling pathway links BRCA1-IRIS to cellular proliferation through c-Jun/AP1 nuclear pathway; finally, this culminates in the increased expression of the cyclin D1 gene

The N=1 effective actions of D-branes in Type IIA and IIB orientifolds

International Nuclear Information System (INIS)

Grimm, Thomas W.; Vieira Lopes, Daniel

2012-01-01

We discuss the four-dimensional N=1 effective actions of single space-time filling Dp-branes in general Type IIA and Type IIB Calabi-Yau orientifold compactifications. The effective actions depend on an infinite number of normal deformations and gauge connection modes. For D6-branes the N=1 Kähler potential, the gauge-coupling function, the superpotential and the D-terms are determined as functions of these fields. They can be expressed as integrals over chains which end on the D-brane cycle and a reference cycle. The infinite deformation space will reduce to a finite dimensional moduli space of special Lagrangian submanifolds upon imposing F- and D-term supersymmetry conditions. We show that the Type IIA moduli space geometry is captured by three real functionals encoding the deformations of special Lagrangian submanifolds, holomorphic three-forms and Kähler two-forms of Calabi-Yau manifolds. These elegantly combine in the N=1 Kähler potential, which reduces after applying mirror symmetry to the results previously determined for space-time filling D3-, D5- and D7-branes. We also propose general chain integral expressions for the Kähler potentials of Type IIB D-branes.

Inhibition of Rac1 activity induces G1/S phase arrest through the GSK3/cyclin D1 pathway in human cancer cells.

Science.gov (United States)

Liu, Linna; Zhang, Hongmei; Shi, Lei; Zhang, Wenjuan; Yuan, Juanli; Chen, Xiang; Liu, Juanjuan; Zhang, Yan; Wang, Zhipeng

2014-10-01

Rac1 has been shown to regulate the cell cycle in cancer cells. Yet, the related mechanism remains unclear. Thus, the present study aimed to investigate the mechanism involved in the regulation of G1/S phase transition by Rac1 in cancer cells. Inhibition of Rac1 by inhibitor NSC23766 induced G1/S phase arrest and inhibited the proliferation of A431, SW480 and U2-OS cells. Suppression of GSK3 by shRNA partially rescued G1/S phase arrest and inhibition of proliferation. Incubation of cells with NSC23766 reduced p-AKT and inactivated p-GSK3α and p-GSK3β, increased p-cyclin D1 expression and decreased the level of cyclin D1 protein. Consequently, cyclin D1 targeting transcriptional factor E2F1 expression, which promotes G1 to S phase transition, was also reduced. In contrast, constitutive active Rac1 resulted in increased p-AKT and inactivated p-GSK3α and p-GSK3β, decreased p-cyclin D1 expression and enhanced levels of cyclin D1 and E2F1 expression. Moreover, suppression of GSK3 did not alter p-AKT or Rac1 activity, but decreased p-cyclin D1 and increased total cyclin D1 protein. However, neither Rac1 nor GSK3 inhibition altered cyclin D1 at the RNA level. Moreover, after inhibition of Rac1 or GSK3 following proteasome inhibitor MG132 treatment, cyclin D1 expression at the protein level remained constant, indicating that Rac1 and GSK3 may regulate cyclin D1 turnover through phosphorylation and degradation. Therefore, our findings suggest that inhibition of Rac1 induces cell cycle G1/S arrest in cancer cells by regulation of the GSK3/cyclin D1 pathway.

Flexible fuel cycle initiative for the transition period from current reactors to next generation reactors

International Nuclear Information System (INIS)

Yamashita, Junichi; Fukasawa, Tetsuo; Hoshino, Kuniyoshi; Kawamura, Fumio; Shiina, Kouji; Sasahira, Akira

2005-01-01

A sustainable electricity supply by fast breeder reactors (FBRs) is essential to ensure energy security and prevent global warming. Transition from light water reactors (LWRs) to FBRs and establishment of an FBR cycle are indispensable, which requires plutonium (Pu) for the introduction of FBRs. The authors propose advanced system called 'Flexible Fuel Cycle Initiative (FFCI)' which can respond flexibly the future expected technical and social uncertainties, can hold no surplus Pu, and can achieve an economical FBR cycle. In the new concept of FFCI, 2nd LWR reprocessing which would succeed Rokkasho Reprocessing Plant is a simple facility to carry out only uranium (U) removal and residual 'recycle material' is stored or utilized. According to FBRs introduction status, recycle material is immediately treated in an FBR reprocessing to fabricate FBR fuel or temporarily stored for the utilization in FBRs at necessary timing. FFCI has high flexibility by having several options for future uncertainties by the introduction of recycle material as a buffer material between LWR and FBR cycles. (author)

Perturbative expansion and the initial value problem of the K.d.V. equations

International Nuclear Information System (INIS)

Turchetti, G.

1980-01-01

For the potential K.d.V. equation is considered a perturbation expansion in which the initial condition is imposed on the zeroth order term. The N soliton solutions turn out to be rational functions in the expansion parameter so that the perturbation series can be exactly summed by the [N-1/N] Pade approximants; moreover the [n-1/n] and [n/n] Pade approximants for n [pt

Fuel cycle and waste newsletter. Vol. 3, No. 2, July 2007

International Nuclear Information System (INIS)

2007-07-01

The top stories in this issue of the Fuel Cycle and Waste Newsletter highlight some important activities of the Division to reduce the nuclear threats worldwide. It involves conditioning and possible repatriation spent sealed radioactive sources, conversion of research reactors from high enriched uranium fuel to low enriched uranium and return of the fuel to the USA and to the Russian Federation. These activities have great technical challenges and are connected with important legal and administrative work. Topics covered are mobile hot cell (SHARS) for conditioning of spent high-activity sealed radioactive sources and support of global efforts to remove highly enriched uranium from international commerce. The activities of the waste technology section (WTS), and of the nuclear fuel cycle and materials section (NFC and MS) are presented as well as the launch of the IAEA's international decommissioning network. Further discussions include the development and implementation of radioactive waste management policies and strategies, the national reporting tool upgrade of the Net -Enabled Waste Management Data Base (NEWMBD), spent fuel assessment and research, spent fuel treatment options, FUMEX (FUel Modelling at EXtende Burnup), FUWAC (Fuel and Water Chemistry), the International Nuclear Fuel Cycle Information System (INFCIS), research reactor availability and reliability, research reactor coalitions and upcoming training course on research reactor water quality management as well as ongoing activities related to Advanced Fuel Cycles (AFC). Recent publications and meetings in 2007 are listed

Localization of ORC1 During the Cell Cycle in Human Leukemia Cells

Directory of Open Access Journals (Sweden)

Frederick D. Coffman

2011-01-01

Full Text Available The interaction of the origin recognition complex (ORC with replication origins is a critical parameter in eukaryotic replication initiation. In mammals the ORC remains bound except during mitosis, thus the localization of ORC complexes allows localization of origins. A monoclonal antibody that recognizes human ORC1 was used to localize ORC complexes in populations of human MOLT-4 cells separated by cell cycle position using centrifugal elutriation. ORC1 staining in cells in early G1 is diffuse and primarily peripheral. As the cells traverse G1, ORC1 accumulates and becomes more localized towards the center of the nucleus, however around the G1/S boundary the staining pattern changes and ORC1 appears peripheral. By mid to late S phase ORC1 immunofluorescence is again concentrated at the nuclear center. During anaphase, ORC1 staining is localized mainly in the pericentriolar regions. These findings suggest that concerted movements of origin DNA sequences in addition to the previously documented assembly and disassembly of protein complexes are an important aspect of replication initiation loci in eukaryotes.

Six1 promotes proliferation of pancreatic cancer cells via upregulation of cyclin D1 expression.

Directory of Open Access Journals (Sweden)

Zhaoming Li

Full Text Available Six1 is one of the transcription factors that act as master regulators of development and are frequently dysregulated in cancers. However, the role of Six1 in pancreatic cancer is not clear. Here we show that the relative expression of Six1 mRNA is increased in pancreatic cancer and correlated with advanced tumor stage. In vitro functional assays demonstrate that forced overexpression of Six1 significantly enhances the growth rate and proliferation ability of pancreatic cancer cells. Knockdown of endogenous Six1 decreases the proliferation of these cells dramatically. Furthermore, Six1 promotes the growth of pancreatic cancer cells in a xenograft assay. We also show that the gene encoding cyclin D1 is a direct transcriptional target of Six1 in pancreatic cancer cells. Overexpression of Six1 upregulates cyclin D1 mRNA and protein, and significantly enhances the activity of the cyclin D1 promoter in PANC-1 cells. We demonstrate that Six1 promotes cell cycle progression and proliferation by upregulation of cyclin D1. These data suggest that Six1 is overexpressed in pancreatic cancer and may contribute to the increased cell proliferation through upregulation of cyclin D1.

Benefits of high gradient solidification for creep and low cycle fatigue of AM1 single crystal superalloy

Energy Technology Data Exchange (ETDEWEB)

Steuer, S., E-mail: Susanne.Steuer@ensma.fr [Institut Pprime, CNRS – ENSMA – Université de Poitiers, UPR CNRS 3346, Department of Physics and Mechanics of Materials, ENSMA – Téléport 2, 1 avenue Clément Ader, BP 40109, 86961 Futuroscope Chasseneuil Cedex (France); Villechaise, P. [Institut Pprime, CNRS – ENSMA – Université de Poitiers, UPR CNRS 3346, Department of Physics and Mechanics of Materials, ENSMA – Téléport 2, 1 avenue Clément Ader, BP 40109, 86961 Futuroscope Chasseneuil Cedex (France); Pollock, T.M. [Materials Department, University of California Santa Barbara, Santa Barbara, CA 93106-5050 (United States); Cormier, J. [Institut Pprime, CNRS – ENSMA – Université de Poitiers, UPR CNRS 3346, Department of Physics and Mechanics of Materials, ENSMA – Téléport 2, 1 avenue Clément Ader, BP 40109, 86961 Futuroscope Chasseneuil Cedex (France)

2015-10-01

The influence of high thermal gradient processing on the creep and low cycle fatigue properties of the AM1 Ni-based single crystal superalloy has been studied. Isothermal creep (from 750 °C up to 1200 °C) and low cycle fatigue (750 °C and 950 °C) experiments were performed for AM1 alloy solidified with a conventional radiation cooled (Bridgman) and higher thermal gradient liquid-metal cooled (LMC) casting process to produce coarse and finer-scaled dendritic structures, respectively. There was no significant effect of the casting technique on creep properties, due to the very similar microstructures (γ′-size and γ-channel width) established after full heat treatment of both Bridgman and LMC samples. For low cycle fatigue properties, the benefit of the higher gradient LMC process was dependent on the testing temperature. At 750 °C, cracks primarily initiated at pores created by solidification shrinkage in both Bridgman and LMC samples. Samples produced by the LMC technique demonstrated fatigue lives up to 4 times longer, compared to the Bridgman samples, due to refined porosity. At 950 °C the low cycle fatigue properties of the LMC and conventionally solidified material were not distinguishable due to a shift of crack initiation sites from internal pores to oxidized surface layers or near-surface pores. The benefit of the LMC approach was, however, apparent in fatigue at 950 °C when testing in a vacuum environment. Based on these results, a crack initiation model based on the local slip activity close to casting defect is proposed.

R and D for fast reactor fuel cycle technologies in JNC

International Nuclear Information System (INIS)

Kiyoto, Aizawa

2001-01-01

Research and development on innovative FR cycle systems including P and T of TRU and LLFP is being performed at JNC in Japan. The commercialization of FR cycle system can be expected to contribute greatly to security of energy resource and preservation of global environment in the world. As a result of the Phase I of the Feasibility Study on Commercialized FR Cycle Systems (Feasibility Study), a few promising FR plant concepts and these related several promising fuel cycle concepts to be able to achieve the goals for commercialization have emerged, and a road-map related to these concepts is under preparation. A concept of innovative recycle system that can efficiently reprocess and fabricate TRU, and burn them in the FR is studied in the first step. Studies on partitioning and transmutation for long-lived fission products will be performed as the long-term R and D including isotope separation. Economic competitiveness is especially a key issue to establish the isotope separation technology. JNC will actively promote international collaboration from the viewpoint of the most effective use of available resources. (author)

HFR1 Sequesters PIF1 to Govern the Transcriptional Network Underlying Light-Initiated Seed Germination in Arabidopsis[C][W][OPEN

Science.gov (United States)

Shi, Hui; Zhong, Shangwei; Mo, Xiaorong; Liu, Na; Nezames, Cynthia D.; Deng, Xing Wang

2013-01-01

Seed germination is the first step for seed plants to initiate a new life cycle. Light plays a predominant role in promoting seed germination, where the initial phase is mediated by photoreceptor phytochrome B (phyB). Previous studies showed that PHYTOCHROME-INTERACTING FACTOR1 (PIF1) represses seed germination downstream of phyB. Here, we identify a positive regulator of phyB-dependent seed germination, LONG HYPOCOTYL IN FAR-RED1 (HFR1). HFR1 blocks PIF1 transcriptional activity by forming a heterodimer with PIF1 that prevents PIF1 from binding to DNA. Our whole-genomic analysis shows that HFR1 and PIF1 oppositely mediate the light-regulated transcriptome in imbibed seeds. Through the HFR1–PIF1 module, light regulates expression of numerous genes involved in cell wall loosening, cell division, and hormone pathways to initiate seed germination. The functionally antagonistic HFR1–PIF1 pair constructs a fail-safe mechanism for fine-tuning seed germination during low-level illumination, ensuring a rapid response to favorable environmental changes. This study identifies the HFR1–PIF1 pair as a central module directing the whole genomic transcriptional network to rapidly initiate light-induced seed germination. PMID:24179122

Northern peatland initiation lagged abrupt increases in deglacial atmospheric CH4.

Science.gov (United States)

Reyes, Alberto V; Cooke, Colin A

2011-03-22

Peatlands are a key component of the global carbon cycle. Chronologies of peatland initiation are typically based on compiled basal peat radiocarbon (14C) dates and frequency histograms of binned calibrated age ranges. However, such compilations are problematic because poor quality 14C dates are commonly included and because frequency histograms of binned age ranges introduce chronological artefacts that bias the record of peatland initiation. Using a published compilation of 274 basal 14C dates from Alaska as a case study, we show that nearly half the 14C dates are inappropriate for reconstructing peatland initiation, and that the temporal structure of peatland initiation is sensitive to sampling biases and treatment of calibrated 14C dates. We present revised chronologies of peatland initiation for Alaska and the circumpolar Arctic based on summed probability distributions of calibrated 14C dates. These revised chronologies reveal that northern peatland initiation lagged abrupt increases in atmospheric CH4 concentration at the start of the Bølling-Allerød interstadial (Termination 1A) and the end of the Younger Dryas chronozone (Termination 1B), suggesting that northern peatlands were not the primary drivers of the rapid increases in atmospheric CH4. Our results demonstrate that subtle methodological changes in the synthesis of basal 14C ages lead to substantially different interpretations of temporal trends in peatland initiation, with direct implications for the role of peatlands in the global carbon cycle.

Enhancing signal detection and completely eliminating scattering using quasi-phase-cycling in 2D IR experiments.

Science.gov (United States)

Bloem, Robbert; Garrett-Roe, Sean; Strzalka, Halina; Hamm, Peter; Donaldson, Paul

2010-12-20

We demonstrate how quasi-phase-cycling achieved by sub-cycle delay modulation can be used to replace optical chopping in a box-CARS 2D IR experiment in order to enhance the signal size, and, at the same time, completely eliminate any scattering contamination. Two optical devices are described that can be used for this purpose, a wobbling Brewster window and a photoelastic modulator. They are simple to construct, easy to incorporate into any existing 2D IR setup, and have attractive features such as a high optical throughput and a fast modulation frequency needed to phase cycle on a shot-to-shot basis.

1D Nano materials 2012

International Nuclear Information System (INIS)

Yanqiu Zhu, Y.; Ma, R.; Whitby, R.; Acquah, S.

2013-01-01

We witnessed an initial hyped period and enthusiasm on carbon nano tubes in the 1990s later went through a significant expansion into nano tubes of other materials (metal di chalcogenides, boron nitride, etc.) as well as various nano wires and nano rods. While much of the hype might have gone, the research on one-dimensional (1D) nano materials has matured as one of the most active research areas within the nano science and nano technology community, flourishing with ample, exciting, and new research opportunities. Just like any other research frontier, researchers working in the 1D nano materials field are constantly striving to develop new fundamental science as well as potential applications. It remains a common belief that versatility and tunability of 1D nano materials would challenge many new rising tasks coming from our resource and energy demanding modern society. The traditional semiconductor industry has produced so many devices and systems from transistors, sensors, lasers, and LEDs to more sophisticated solar panels, which are now part of our daily lives. By down sizing the core components or parts to 1D form, one might wonder how fundamentally the dimensionality and morphology would impact the device performance, this is, as always, requiring us to fully understand the structure-property relationship in 1D nano materials. It may be equally crucial in connecting discovery-driven fundamental science to market-driven technology industry concerning potentially relevant findings derived from these novel materials. The importance of a platform that allows active researchers in this field to present their new development in a timely and efficient manner is therefore self-evident. Following the success of two early special issues devoted to 1D nano materials, this is the third one in a row organized by the same group of guest editors, attesting that such a platform has been well received by the readers

Galerkin FEM for Fractional Order Parabolic Equations with Initial Data in H − s , 0 ≤ s ≤ 1

KAUST Repository

Jin, Bangti; Lazarov, Raytcho; Pasciak, Joseph; Zhou, Zhi

2013-01-01

We investigate semi-discrete numerical schemes based on the standard Galerkin and lumped mass Galerkin finite element methods for an initial-boundary value problem for homogeneous fractional diffusion problems with non-smooth initial data. We assume that Ω ⊂ ℝd , d = 1,2,3 is a convex polygonal (polyhedral) domain. We theoretically justify optimal order error estimates in L2- and H1-norms for initial data in H-s (Ω), 0 ≤ s ≤ 1. We confirm our theoretical findings with a number of numerical tests that include initial data v being a Dirac δ-function supported on a (d-1)-dimensional manifold. © 2013 Springer-Verlag.

Classification of Dansgaard-Oeschger climatic cycles by the application of similitude signal processing

Energy Technology Data Exchange (ETDEWEB)

Sole, Jordi [Department of Physics, Universitat Autonoma de Barcelona, Campus de la UAB 08193 Bellaterra (Cerdanyola del Valles), Catalunya (Spain) and Institut de Ciencies del Mar (CSIC), 08003 Barcelona, Catalunya (Spain)]. E-mail: jsole@icm.csic.es; Turiel, Antonio [Institut de Ciencies del Mar (CSIC), 08003 Barcelona, Catalunya (Spain); Llebot, Josep Enric [Department of Physics, Universitat Autonoma de Barcelona, Campus de la UAB 08193 Bellaterra (Cerdanyola del Valles), Catalunya (Spain)

2007-06-25

In this work we have performed a detailed analysis, using signal processing tools, to study time series of data (temperature proxy) extracted from the GRIP ice-core records and we relate it with the evolution of atmospheric CO{sub 2} within the last glacial period. Our method is based in considering the warm periods known as Dansgaard-Oeschger (D/O) events and posterior returns to the cold stage as a climatic cycle. After the warming phase, D/O events relax to the initial cold state in three different ways, what gives rise to three classes of cycles. Also, the Younger/Dryas-Bolling/Allerod (Y/D-B/A) cycle corresponds to one of the classes obtained. We have found that all cycles start with identical warming phases which seem completely unrelated to variations in CO{sub 2} concentration. We discuss on the consequences for global climatology of such steady pattern of cycles.

Final Hazard Categorization and Auditable Safety Analysis for the Remediation of the 118-D-1, 118-D-2, 118-D-3, 118-H-1, 118-H-2 and 118-H-3 Solid Waste Burial Grounds

Energy Technology Data Exchange (ETDEWEB)

T. J. Rodovsky

2006-03-01

This report presents the initial hazard categorization, final hazard categorization and auditable safety analysis for the remediation of the 118-D-1, 118-D-2, and 118-D-3 Burial Grounds located within the 100-D/DR Area of the Hanford Site and the 118-H-1, 118-H-2, and 118-H-3 Burial Grounds located within the 100-H Area of the Hanford Site.

Dataset on the effects of CYB5D2 on the distribution of HeLa cervical cancer cell cycle

Directory of Open Access Journals (Sweden)

Yanyun Xie

2016-03-01

Full Text Available We have recently reported that CYB5D2 plays a role in suppression of cervical cancer tumorigenesis, “CYB5D2 displays tumor suppression activities towards cervical cancer” [1]. We provide the accompany data here describing the effects of CYB5D2 overexpression and addition of recombinant CYB5D2 on HeLa cell cycle distribution. Furthermore, we will present the conditions used to specifically determine CYB5D2 expression in primary cervical and cervical cancer tissues using immunohistochemistry (IHC and the patient cohort involved in assessing the CYB5D2 protein levels in primary cervical and cervical cancer tissues.

Sleep-wake cycle of adolescents in Côte d'Ivoire: influence of age, gender, religion and occupation.

Science.gov (United States)

Borchers, Claudia; Randler, Christoph

2012-12-01

The human sleep-wake cycle is characterized by significant individual differences. Those differences in the sleep-wake cycle are partially heritable but are also influenced by environmental factors like the light/dark cycle or social habits. In this study we analyse for the first time the sleep-wake rhythm of adolescent pupils and working adolescents in a less industrialised country in West Africa near the equator. The aim of this study was to explore the sleep wake cycle in this geographical region, using Côte d'Ivoire as an example. Data collection took place between 2nd of March and 10th of June 2009. 588 adolescents (338 girls, 250 boys) between 10 and 15 years (mean ± SD: 12.72 ± 1.63) participated in this study. We collected data on the religion of the participants (Christian (N = 159), Muslim (N = 352), other/no religion (N = 77)) and their occupation. Participants were either pupils attending school (N = 336) or adolescents that were already working (N = 252) and not attending school. The interviewer filled in the questionnaire. We found significant effects of age (p gender (p religion (p < 0.001) and region (p < 0.001). The midpoint of sleep was on average 1:26 (SD: 00:30) on weekdays and 1:37 (SD: 00:42) on weekend days. There are significant differences between weekdays and weekend days, but these were only small. Sleep duration suggests that adolescents in Côte d'Ivoire may gain sufficient sleep during week and weekend days, and thus, may live more in accordance with their own biological clock than adolescents in the northern hemisphere. In contrast, the data can be interpreted that adolescents live in a permanent 'jetlag'. Factors may be the more continuous light/dark cycle in the tropics, low amount of ambient light and less electricity.

Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI : A multicentre trial and cost-effectiveness analysis

NARCIS (Netherlands)

van Tilborg, Theodora C.; Oudshoorn, Simone C.; Eijkemans, Marinus J. C.; Mochtar, Monique H.; van Golde, Ron J. T.; Hoek, Annemieke; Kuchenbecker, Walter K. H.; Fleischer, Kathrin; de Bruin, Jan Peter; Groen, Henk; van Wely, Madelon; Lambalk, Cornelis B.; Laven, Joop S. E.; Mol, Ben Willem J.; Broekmans, Frank J. M.; Torrance, Helen L.

2017-01-01

STUDY QUESTION: Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment? SUMMARY ANSWER: In women initiating IVF/ICSI, AFC-based individualized FSH dosing

Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI: a multicentre trial and cost-effectiveness analysis

NARCIS (Netherlands)

van Tilborg, Theodora C.; Oudshoorn, Simone C.; Eijkemans, Marinus J. C.; Mochtar, Monique H.; van Golde, Ron J. T.; Hoek, Annemieke; Kuchenbecker, Walter K. H.; Fleischer, Kathrin; de Bruin, Jan Peter; Groen, Henk; van Wely, Madelon; Lambalk, Cornelis B.; Laven, Joop S. E.; Mol, Ben Willem J.; Broekmans, Frank J. M.; Torrance, Helen L.

2017-01-01

STUDY QUESTION: Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment? SUMMARY ANSWER: In women initiating IVF/ICSI, AFC-based individualized FSH dosing

Imaging- and Flow Cytometry-based Analysis of Cell Position and the Cell Cycle in 3D Melanoma Spheroids

Science.gov (United States)

Beaumont, Kimberley A.; Anfosso, Andrea; Ahmed, Farzana

2015-01-01

Three-dimensional (3D) tumor spheroids are utilized in cancer research as a more accurate model of the in vivo tumor microenvironment, compared to traditional two-dimensional (2D) cell culture. The spheroid model is able to mimic the effects of cell-cell interaction, hypoxia and nutrient deprivation, and drug penetration. One characteristic of this model is the development of a necrotic core, surrounded by a ring of G1 arrested cells, with proliferating cells on the outer layers of the spheroid. Of interest in the cancer field is how different regions of the spheroid respond to drug therapies as well as genetic or environmental manipulation. We describe here the use of the fluorescence ubiquitination cell cycle indicator (FUCCI) system along with cytometry and image analysis using commercial software to characterize the cell cycle status of cells with respect to their position inside melanoma spheroids. These methods may be used to track changes in cell cycle status, gene/protein expression or cell viability in different sub-regions of tumor spheroids over time and under different conditions. PMID:26779761

Cycle to Cycle Variation Study in a Dual Fuel Operated Engine

KAUST Repository

Pasunurthi, Shyamsundar

2017-03-28

The standard capability of engine experimental studies is that ensemble averaged quantities like in-cylinder pressure from multiple cycles and emissions are reported and the cycle to cycle variation (CCV) of indicated mean effective pressure (IMEP) is captured from many consecutive combustion cycles for each test condition. However, obtaining 3D spatial distribution of all the relevant quantities such as fuel-air mixing, temperature, turbulence levels and emissions from such experiments is a challenging task. Computational Fluid Dynamics (CFD) simulations of engine flow and combustion can be used effectively to visualize such 3D spatial distributions. A dual fuel engine is considered in the current study, with manifold injected natural gas (NG) and direct injected diesel pilot for ignition. Multiple engine cycles in 3D are simulated in series like in the experiments to investigate the potential of high fidelity RANS simulations coupled with detailed chemistry, to accurately predict the CCV. Cycle to cycle variation (CCV) is expected to be due to variabilities in operating and boundary conditions, in-cylinder stratification of diesel and natural gas fuels, variation in in-cylinder turbulence levels and velocity flow-fields. In a previous publication by the authors [1], variabilities in operating and boundary conditions are incorporated into several closed cycle simulations performed in parallel. Stochastic variations/stratifications of fuel-air mixture, turbulence levels, temperature and internal combustion residuals cannot be considered in such closed cycle simulations. In this study, open cycle simulations with port injection of natural gas predicted the combined effect of the stratifications on the CCV of in-cylinder pressure. The predicted Coefficient of Variation (COV) of cylinder pressure is improved compared to the one captured by closed cycle simulations in parallel.

A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression.

Science.gov (United States)

Mir, Riyaz A; Bele, Aditya; Mirza, Sameer; Srivastava, Shashank; Olou, Appolinaire A; Ammons, Shalis A; Kim, Jun Hyun; Gurumurthy, Channabasavaiah B; Qiu, Fang; Band, Hamid; Band, Vimla

2015-12-28

Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest, which is rescued by exogenous ECD, demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here, we demonstrate that ECD protein levels and subcellular localization are invariant during cell cycle progression, suggesting a potential role of posttranslational modifications or protein-protein interactions. Since phosphorylated ECD was recently shown to interact with the PIH1D1 adaptor component of the R2TP cochaperone complex, we examined the requirement of ECD phosphorylation in cell cycle progression. Notably, phosphorylation-deficient ECD mutants that failed to bind to PIH1D1 in vitro fully retained the ability to interact with the R2TP complex and yet exhibited a reduced ability to rescue Ecd-deficient cells from cell cycle arrest. Biochemical analyses demonstrated an additional phosphorylation-independent interaction of ECD with the RUVBL1 component of the R2TP complex, and this interaction is essential for ECD's cell cycle progression function. These studies demonstrate that interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Development of FR fuel cycle in japan (1) development scope of fuel cycle technology

International Nuclear Information System (INIS)

Nakamura, H.; Funasaka, H.; Namekawa, T.

2008-01-01

A fast reactor (FR) cycle has a potential to realize a sustainable energy supply system that is harmonized with environment by fully recycling both uranium (U) and transuranium (TRU) elements. In Japan, a Feasibility Study on Commercialized FR Cycle Systems (FS) was launched in July 1999, and through two different study phases, a final report was presented in 2006. As a result of FS, a combined system of sodium-cooled FR with mixed-oxide (MOX) fuel, advanced aqueous reprocessing and simplified pelletizing fuel fabrication was considered to be most promising for commercialization. The advanced aqueous reprocessing system, which is called the New Extraction system for TRU recovery (NEXT), consists of a U crystallization process for the bulk of U recovery, a simplified solvent extraction process for residual U, plutonium (Pu) and neptunium (Np) without Pu partitioning and purification, and a process for recovering americium (Am) and curium (Cm) from the raffinate. The ratio of Pu/U concentration in the mother solution after crystallization is adequate for MOX fuel fabrication, and thus complicated powder mixing processes for adjusting Pu content in MOX fuel can be eliminated in the subsequent simplified fuel fabrication system. In this system, lubricant-mixing process can also be eliminated by adopting the advanced technology in which lubricant is coated on the inner surface of a die before fuel powder supply. Such a simplification could help us overcoming the difficulty to treat MA bearing fuel powders in a hot cell. Ministry of Education, Culture, Sports, Science and Technology (MEXT) reviewed these results of FS in 2006 and identified the most promising FR cycle concept proposed in the FS phase II study as a mainline choice for commercialization. According to such a governmental assessment, R and D activities of FR cycle systems were decided to be concentrated mainly to the innovative technology development for the mainline concept. The stage of R and D project was

Initial concepts on energetics and mass releases during nonnuclear explosive events in fuel cycle facilities

International Nuclear Information System (INIS)

Halverson, M.A.; Mishima, J.

1986-09-01

Non-nuclear explosions are one of the initiating events (accidents) considered in the US Nuclear Regulatory Commission study of formal methods for estimating the airborne release of radionuclides from fuel cycle facilities. Methods currently available to estimate the energetics and mass airborne release from the four types of non-nuclear explosive events (fast and slow physical explosions and fast and slow chemical explosions) are reviewed. The likelihood that fast physical explosions will occur in fuel cycle facilities appears to be remote and this type of explosion is not considered. Methods to estimate the consequences of slow physical and fast chemical explosions are available. Methods to estimate the consequences of slow chemical explosions are less well defined

Economic Effect on the Plutonium Cycle of Employing {sup 235}U in Fast Reactor Start-Up; Incidence Economique du Demarrage des Reacteurs Rapides a l'Aide d'Uranium-235 sur le Cycle du Plutonium

Energy Technology Data Exchange (ETDEWEB)

Van Dievoet, J.; Egleme, M.; Hermans, L. [BELGONUCLEAIRE, Bruxelles (Belgium)

1967-09-15

factors, inventory factors) from one cycle to another, with a comparative study of the use of {sup 235}U in thermal and fast reactors, variations in the discounted fuel cycle costs from one cycle to another, and weight and characteristics of the recycled fuel, of the additional fuel required and of excess fuel. (author) [French] Le memoire presente les premiers resultats d'une etude entreprise dans le cadre d'un contrat d'association Euratom-Belgique et destinee a evaluer l'interet de l'alimentation de reacteurs rapides en uranium-235. Plusieurs possibilites se presentent pour le demarrage d'un reacteur rapide a l'aide d'uranium-235. 1. Le reacteur peut etre alimente en permanence avec de l'uranium enrichi, le plutonium produit servant a demarrer et a alimenter d'autres reacteurs; dans ce cas, l'uranium est recycle dans le reacteur en y ajoutant de l'uranium enrichi. 2. Le plutonium produit dans le reacteur peut etre partiellement recycle dans celui-ci, ainsi que l'uranium; dans ce cas, le reacteur se transforme progressivement en un reacteur au plutonium. Ces deux cas peuvent etre combines pour un reacteur a plusieurs zones d'enrichissement, ou l'on peut appliquer simultanement les deux politiques a des zones differentes, c'est-a-dire: alimenter, par exemple, la zone interne en uranium enrichi et recycler le plutonium dans la zone externe. Le mode de traitement du combustible irradie rend egalement le probleme complexe, selon que l'on traite ensemble ou separement le coeur et les couvertures axiales; de meme, pour un reacteur a plusieurs zones d'enrichissement, celles-ci peuvent etre traitees ensemble ou separement. Les calculs sont effectues a l'aide d'un code de calcul utilisant, pour lavpartie relative aux caracteristiques des reacteurs successifs, les coefficients d'equivalence definis par Baker and Ross et, pour la partie economique, la methode du cout actualise du cycle du combustible. Dans la premiere phase des travaux, une analyse approcheedu phenomene a ete

Homogeneous Thorium Fuel Cycles in Candu Reactors

Energy Technology Data Exchange (ETDEWEB)

Hyland, B.; Dyck, G.R.; Edwards, G.W.R.; Magill, M. [Chalk River Laboratories, Atomic Energy of Canada Limited (Canada)

2009-06-15

The CANDU{sup R} reactor has an unsurpassed degree of fuel-cycle flexibility, as a consequence of its fuel-channel design, excellent neutron economy, on-power refueling, and simple fuel bundle [1]. These features facilitate the introduction and full exploitation of thorium fuel cycles in Candu reactors in an evolutionary fashion. Because thorium itself does not contain a fissile isotope, neutrons must be provided by adding a fissile material, either within or outside of the thorium-based fuel. Those same Candu features that provide fuel-cycle flexibility also make possible many thorium fuel-cycle options. Various thorium fuel cycles can be categorized by the type and geometry of the added fissile material. The simplest of these fuel cycles are based on homogeneous thorium fuel designs, where the fissile material is mixed uniformly with the fertile thorium. These fuel cycles can be competitive in resource utilization with the best uranium-based fuel cycles, while building up a 'mine' of U-233 in the spent fuel, for possible recycle in thermal reactors. When U-233 is recycled from the spent fuel, thorium-based fuel cycles in Candu reactors can provide substantial improvements in the efficiency of energy production from existing fissile resources. The fissile component driving the initial fuel could be enriched uranium, plutonium, or uranium-233. Many different thorium fuel cycle options have been studied at AECL [2,3]. This paper presents the results of recent homogeneous thorium fuel cycle calculations using plutonium and enriched uranium as driver fuels, with and without U-233 recycle. High and low burnup cases have been investigated for both the once-through and U-233 recycle cases. CANDU{sup R} is a registered trademark of Atomic Energy of Canada Limited (AECL). 1. Boczar, P.G. 'Candu Fuel-Cycle Vision', Presented at IAEA Technical Committee Meeting on 'Fuel Cycle Options for LWRs and HWRs', 1998 April 28 - May 01, also Atomic Energy

The partition dimension of cycle books graph

Science.gov (United States)

Santoso, Jaya; Darmaji

2018-03-01

Let G be a nontrivial and connected graph with vertex set V(G), edge set E(G) and S ⊆ V(G) with v ∈ V(G), the distance between v and S is d(v,S) = min{d(v,x)|x ∈ S}. For an ordered partition ∏ = {S 1, S 2, S 3,…, Sk } of V(G), the representation of v with respect to ∏ is defined by r(v|∏) = (d(v, S 1), d(v, S 2),…, d(v, Sk )). The partition ∏ is called a resolving partition of G if all representations of vertices are distinct. The partition dimension pd(G) is the smallest integer k such that G has a resolving partition set with k members. In this research, we will determine the partition dimension of Cycle Books {B}{Cr,m}. Cycle books graph {B}{Cr,m} is a graph consisting of m copies cycle Cr with the common path P 2. It is shown that the partition dimension of cycle books graph, pd({B}{C3,m}) is 3 for m = 2, 3, and m for m ≥ 4. pd({B}{C4,m}) is 3 + 2k for m = 3k + 2, 4 + 2(k ‑ 1) for m = 3k + 1, and 3 + 2(k ‑ 1) for m = 3k. pd({B}{C5,m}) is m + 1.

Chromatin association of UHRF1 during the cell cycle

KAUST Repository

Al-Gashgari, Bothayna

2017-05-01

Ubiquitin-like with PHD and RING Finger domains 1 (UHRF1) is a nuclear protein that associates with chromatin. Regardless of the various functions of UHRF1 in the cell, one of its more important functions is its role in the maintenance of DNA methylation patterns by the recruitment of DNMT1. Studies on UHRF1 based on this function have revealed the importance of UHRF1 during the cell cycle. Moreover, based on different studies various factors were described to be involved in the regulation of UHRF1 with different functionalities that can control its binding affinity to different targets on chromatin. These factors are regulated differently in a cell cycle specific manner. In light of this, we propose that UHRF1 has different binding behaviors during the cell cycle in regard to its association with chromatin. In this project, we first analyzed the binding behavior of endogenous UHRF1 from different unsynchronized cell systems in pull-down assays with peptides and oligonucleotides. Moreover, to analyze UHRF1 binding behavior during the cell cycle, we used two different approaches. First we sorted Jurkat and HT1080 cells based on their cell cycle stage using FACS analysis. Additionally, we synchronized HeLa cells to different stages of the cell cycle by chemical treatments, and used extracts from cellsorting and cell synchronization experiments for pull-down assays. We observed that UHRF1 in different cell systems has different preferences in regard to its binding to H3 unmodified and H3K9me3. Moreover, we detected that UHRF1, in general, displays different patterns between different stages of cell cycle; however, we cannot draw a final model for UHRF1 binding pattern during cell cycle.

Phenotypes and functions of persistent Sendai virus-induced antibody forming cells and CD8+ T cells in diffuse nasal-associated lymphoid tissue typify lymphocyte responses of the gut.

Science.gov (United States)

Rudraraju, Rajeev; Surman, Sherri; Jones, Bart; Sealy, Robert; Woodland, David L; Hurwitz, Julia L

2011-02-20

Lymphocytes of the diffuse nasal-associated lymphoid tissue (d-NALT) are uniquely positioned to tackle respiratory pathogens at their point-of-entry, yet are rarely examined after intranasal (i.n.) vaccinations or infections. Here we evaluate an i.n. inoculation with Sendai virus (SeV) for elicitation of virus-specific antibody forming cells (AFCs) and CD8(+) T cells in the d-NALT. Virus-specific AFCs and CD8(+) T cells each appeared by day 7 after SeV inoculation and persisted for 8 months, explaining the long-sustained protection against respiratory virus challenge conferred by this vaccine. AFCs produced IgM, IgG1, IgG2a, IgG2b and IgA, while CD8+ T cells were cytolytic and produced low levels of cytokines. Phenotypic analyses of virus-specific T cells revealed striking similarities with pathogen-specific immune responses in the intestine, highlighting some key features of adaptive immunity at a mucosal site. Copyright © 2010 Elsevier Inc. All rights reserved.

Escape of O(3P), O(1D), and O(1S) from the Martian atmosphere

Science.gov (United States)

Fox, Jane L.; Hać, Aleksander B.

2018-01-01

We have computed here the escape probabilities, fluxes and rates for hot O atoms that are initially produced in the ground state and the first two excited metastable states, O(1D)and O(1S), in the Martian thermosphere by dissociative recombination of O2+. In order to compare our results with those of our previous calculations and with those of others, we have employed here the pre-MAVEN models that we have used previously. To compute the escape probabilities, we have employed the Monte Carlo escape code that has been described previously, but we here use for the first time energy-dependent elastic cross sections for collisions of the energetic O atoms with each of the twelve background species in our model. We also incorporate three mechanisms that interchange identities of the O(3P) and O(1D) atoms, including collisional excitation of O(3P) to O(1D), quenching of O(1D) to O(3P), and excitation exchange of O(1D) with O(3P). We find that the escape probabilities of O atoms that are produced initially as O(1D) are reduced compared to those in which these processes are not included, but the escape probabilities of O atoms that are initially produced as O(3P) are not significantly reduced. As a guide for our future research and those of other investigators, we review here what is known about the interactions of O atoms with other species in which the energies of the O atoms are altered, and several other sources of hot and escaping O, many of which have been suggested by other investigators. We will incorporate these data in a future MAVEN-like model.

Effect of main inclusions on crack initiation in bearing steel in the very high cycle fatigue regime

Science.gov (United States)

Gu, Chao; Bao, Yan-ping; Gan, Peng; Wang, Min; He, Jin-shan

2018-06-01

This work aims to investigate the effect of main inclusions on crack initiation in bearing steel in the very high cycle fatigue (VHCF) regime. The size and type of inclusions in the steel were quantitatively analyzed, and VHCF tests were performed. Some fatigue cracks were found to be initiated in the gaps between inclusions (Al2O3, MgO-Al2O3) and the matrix, while other cracks originated from the interior of inclusions (TiN, MnS). To explain the related mechanism, the tessellated stresses between inclusions and the matrix were calculated and compared with the yield stress of the matrix. Results revealed that the inclusions could be classified into two types under VHCF; of these two, only one type could be regarded as holes. Findings in this research provide a better understanding of how inclusions affect the high cycle fatigue properties of bearing steel.

1 | Page PROSPECTUS INITIATIVE DES CONSEILS ...

International Development Research Centre (IDRC) Digital Library (Canada)

khaled fourati

INITIATIVE DES CONSEILS SUBVENTIONNAIRES DE LA RECHERCHE ... années environ ont créé un contexte dans lequel la science, la technologie et .... précis. La nature de cette collaboration transfrontalière sera déterminée et appuyée.

Dopamine D/sub 2/ and D/sub 1/ receptors: biochemical characterization

Energy Technology Data Exchange (ETDEWEB)

Niznik, H B

1986-01-01

In order to label dopamine D/sub 2/ receptors reversibly and selectively the potent substituted benzamide neuroleptic, YM-09151-2, was tritium labeled and its binding characteristics to striatal homogenates investigated. (/sup 3/H) YM-09151-2 bound to D/sub 2/ receptors with high affinity in a specific, saturable, reversible and sodium dependent fashion, displaying an appropriate pharmacological D/sub 2/ receptor profile. (/sup 3/H) YM-09151-2 appears to be the ligand of choice for labeling D/sub 2/ receptors since it displays approximately 20-fold lower affinity for serotonergic S/sub 2/ receptors than does (/sup 3/H) spiperone. As an initial step towards the molecular identification of the ligand binding subunit of the striatal D/sub 2/ receptor, photolabile analogues of the substituted benzamide clebopride were synthesized and their reversible and irreversible binding interactions to D/sub 2/ receptors characterized. D/sub 2/ receptor photoinactivation was prevented in a concentration and stereoselective manner by dopaminergic agonists and antagonists. In vivo biodistribution studies with (/sup 125/I) iodoazidoclebopride confirmed the ligand's ability to bind to D/sub 2/ receptor-rich regions and as such, may become a useful tool for the molecular characterization of D/sub 2/ receptor proteins. Digitonin solubilized striatal dopamine D/sub 2/ and D/sub 1/ receptors can be completely separated with full retention of biological activity by steric exclusion High Pressure Liquid Chromatography (HPLC) with corresponding Stokes radii of 7.1 and 5.6 nm.

HIV-1 Vif's Capacity To Manipulate the Cell Cycle Is Species Specific.

Science.gov (United States)

Evans, Edward L; Becker, Jordan T; Fricke, Stephanie L; Patel, Kishan; Sherer, Nathan M

2018-04-01

Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion production, reflecting species-specific incompatibilities between viral Tat and Rev proteins and essential host factors cyclin T1 (CCNT1) and exportin-1 (XPO1, also known as CRM1), respectively. To determine if mouse cell blocks other than CCNT1 and XPO1 affect HIV's postintegration stages, we studied HIV-1 NL4-3 gene expression in mouse NIH 3T3 cells modified to constitutively express HIV-1-compatible versions of CCNT1 and XPO1 (3T3.CX cells). 3T3.CX cells supported both Rev-independent and Rev-dependent viral gene expression and produced relatively robust levels of virus particles, confirming that CCNT1 and XPO1 represent the predominant blocks to these stages. Unexpectedly, however, 3T3.CX cells were remarkably resistant to virus-induced cytopathic effects observed in human cell lines, which we mapped to the viral protein Vif and its apparent species-specific capacity to induce G 2 /M cell cycle arrest. Vif was able to mediate rapid degradation of human APOBEC3G and the PPP2R5D regulatory B56 subunit of the PP2A phosphatase holoenzyme in mouse cells, thus demonstrating that Vif NL4-3 's modulation of the cell cycle can be functionally uncoupled from some of its other defined roles in CUL5-dependent protein degradation. Vif was also unable to induce G 2 /M cell cycle arrest in other nonhuman cell types, including cells derived from nonhuman primates, leading us to propose that one or more human-specific cofactors underpin Vif's ability to modulate the cell cycle. IMPORTANCE Cells derived from mice and other rodents exhibit profound blocks to HIV-1 replication, thus hindering the development of a low-cost small-animal model for studying HIV/AIDS. Here, we engineered otherwise-nonpermissive mouse cells to express HIV-1-compatible versions of two species-specific host dependency factors, cyclin T1 (CCNT1) and exportin-1 (XPO1) (3T3.CX cells). We show that 3T3.CX cells rescue HIV-1

Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers

Science.gov (United States)

Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi

2013-01-01

Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

Initial Sea Trails of the DEXA D05 Wave Energy Converter

DEFF Research Database (Denmark)

Lavelle, John; Kofoed, Jens Peter

This report presents an analysis of sensors data leading to an initial assessment of the power performance from sea trails of the DEXA D05 Wave Energy Converter (WEC). The sea trails where performed approx. 1 nautical mile offshore from Hanstholm, Denmark during 2011. The converter was 1:5 scale....... The DEXA D05 WEC was built, deployed and operated by the client DEXAWAVE ApS and the analysis of the sensor data, given here, has been carried out by John Lavelle under supervision by Jens Peter Kofoed in the Wave Energy Research Group at the department of Civil Engineering, Aalborg University (AAU)....... model of the planned full scale DEXA WEC with a hydraulic Power Take Off (PTO). The converter had sensors to measure mooring forces, motions, as well as pressure and displacement sensors in the PTOs. The report gives the calculated power production efficiency and an analysis of the mooring forces...

The Chinese initial public offering market : underpricing, duration to listing and hot issue cycles

OpenAIRE

Guo, Haifeng

2017-01-01

This thesis conducts three empirical studies on the Chinese A-share initial public offering (IPO) market, specifically, underpricing and short-run underperformance, duration from offering to listing and hot and cold issuing cycles. Before the empirical analysis, the literature is reviewed associated with these three topics. In addition, this thesis presents an overview of the Chinese IPO market which is found to undergo an experiment period from 1984 to 1990, a transition period from 1991 to ...

The D5-brane effective action and superpotential in N=1 compactifications

International Nuclear Information System (INIS)

Grimm, Thomas W.; Ha, Tae-Won; Klemm, Albrecht; Klevers, Denis

2009-01-01

The four-dimensional effective action for D5-branes in generic compact Calabi-Yau orientifolds is computed by performing a Kaluza-Klein reduction. The N=1 Kaehler potential, the superpotential, the gauge-kinetic coupling function and the D-terms are derived in terms of the geometric data of the internal space and of the two-cycle wrapped by the D5-brane. In particular, we obtain the D5-brane and flux superpotential by integrating out four-dimensional three-forms which couple via the Chern-Simons action. Also the infinitesimal complex structure deformations of the two-cycle induced by the deformations of the ambient space contribute to the F-terms. The superpotential can be expressed in terms of relative periods depending on both the open and closed moduli. To analyze this dependence we blow up along the two-cycle and obtain a rigid divisor in an auxiliary compact threefold with negative first Chern class. The variation of the mixed Hodge structure on this blown-up geometry is equivalent to the original deformation problem and can be analyzed by Picard-Fuchs equations. We exemplify the blow-up procedure for a non-compact Calabi-Yau threefold given by the canonical bundle over del Pezzo surfaces.

EU contribution to ITER CTA fuel cycle design and R and D

International Nuclear Information System (INIS)

Murdoch, D.; Bekris, N.; Boissin, J.-C.; Day, C.; Gilroy, J.; Glugla, M.; Laesser, R.; Mack, A.

2003-01-01

Design and supporting R and D are being carried out in the EU in preparation for the construction of International Thermonuclear Experimental Reactor (ITER). As the Fuel Cycle systems are located in 'time-critical' buildings the detailed design of piping, ducting, cabling and services is being done to ensure compatibility with the building. R and D is focussed on improvements to the reference designs for ITER, extension of parametric studies to cover all operating modes and long term experiments to test component reliability. In addition emphasis is being placed on design and R and D for the Water Detritiation System, an important barrier against routine release of tritium

Nuclear characteristics of D-D fusion reactor blankets, (1)

International Nuclear Information System (INIS)

Nakashima, Hideki; Ohta, Masao; Seki, Yasushi.

1977-01-01

Fusion reactors operating on the deuterium (D-D) cycle are considered promising for their freedom from tritium breeding in the blanket. In this paper, neutronic and photonic calculations are undertaken covering several blanket models of the D-D fusion reactor, using presently available data, with a view to comparing the nuclear characteristics of these models, in particular, the nuclear heating rates and their spatial distributions. Nine models are taken up for the study, embodying various combinations of coolant, blanket, structural and reflector materials. About 10 MeV is found to be a typical value for the total nuclear energy deposition per source neutron in the models considered here. The realization of high energy gain is contingent upon finding a favorable combination of blanket composition and configuration. The resulting implications on the thermal design aspect are briefly discussed. (auth.)

Initiating insulin therapy in children and adolescents with type 1 diabetes mellitus

Directory of Open Access Journals (Sweden)

Subhash Kumar Wangnoo

2015-01-01

Full Text Available The primary clinical goals to be achieved with insulin initiation are elimination of ketosis and hyperglycemia with prevention of chronic complications. Insulin therapy is the mainstay in management of type 1 diabetes, which should be aimed at achieving good glycemic control, with achievement of hemoglobin A1c (HbA1c <7.5%, pre-meal self-monitored blood glucose (SMBG of 90-130 mg/dL, bed time SMBG of 100-140 mg/dL, mean blood glucose level of 120-160 mg/dL and no ketonuria. Two classes of insulin are available for use in T1DM viz. bolus/prandial insulins (rapid-acting insulins and short-acting insulins and basal insulins (intermediate-acting insulin and long-acting insulin. Insulin glargine and glulisine can be used in children above 6 years, lispro in children above 3 years and detemir and aspart in children above 2 years. The caution for hypoglycemia should be exercised while prescribing them. Degludec is currently not approved for pediatric use. The initial insulin regimen should comprise of ≥2 daily bolus and ≥1 basal insulin injections. Insulin intensification would be required if the initial regimen fails, which can be achieved by increasing frequency of long and rapid acting insulin analogues. The American Diabetes Association guidelines recommend HbA1c targets of <8.0% for children <6 years of age, ≤7.5% for children 6 to 12 years of age, and ≤7.0% for adolescents, 12-18 years of age. However, the evidence is now in favor of a single target HbA1c of ≤7.5% for all children and adolescents <19 years of age.

About a case of prostate lymphomatous injury: initial evaluation and early therapy evaluation by PET/T.D.M. with {sup 18}F-F.D.G; A propos d'un cas d'atteinte lymphomateuse prostatique: bilan initial et evaluation therapeutique precoce par TEPTDM au F-18 FDG

Energy Technology Data Exchange (ETDEWEB)

Cimarelli, S.; Mognetti, T.; Desuzinges, C. [Service de medecine nucleaire, centre Leon-Berard, (France); Lachenal, F.; Sebban, C. [departement de medecine, centre Leon-Berard, (France); Chassagne Clement, C. [departement d' anatomo-pathologie, centre Leon-Berard, Lyon, (France)

2009-05-15

The non Hodgkin lymphomas can grow up on organs without any lymphoid tissue. A prostate infiltration occurs in 0.002-1% of the whole ( of non Hodgkin lymphomas). The interest of the positron computed tomography/computed tomography (PET/T.D.M.) with {sup 18}F-fluorodeoxyglucose (F.D.G.) for the initial and post therapy evaluation of aggressive non Hodgkin lymphomas was the object of a recent international consensus. For the early evaluation, its use is still to precise. We report the case of forty four years old man with an aggressive non Hodgkin lymphoma, at an advanced stage with initially a an muscular, ganglion, osteo-medullar prostate overgrowth. We discuss of the interest of the metabolic imaging in this rare clinical form of non Hodgkin lymphoma. (N.C.)

Studies on muon cycling rates in muon catalyzed D-T fusion system with possible four-body muonic molecules formation

International Nuclear Information System (INIS)

Eskandri, M.R.; Hosini Motlagh, N.; Hataf, A.

2000-01-01

In recent studies, it is shown that the fusion rate for four-body molecules of ppμμ, ddμμ, ptμμ, pdμμ, dtμμ, ttμμ, is considerably larger than that of similar three-body molecules of ppμμ, ddμμ, ptμμ, pdμμ, dtμμ, ttμμ. It is shown that for dtμμ, fusion rate is R f (dt) ≅ 3 * 10 13 - 6 * * 10 13 S -1 which is 40 times higher than fusion rate of dtμμ molecule. In this paper we have looked for the effect of these molecules formation in muon catalyzed D-T fusion. The required data for all possible branches do not exist, so the main dtμμ branch are considered here. By choosing a variable value for dtμμ molecule formation rate and comparing obtained cycling rates with existing experimental values, the order of this parameter is evaluated to be ≅ 10 9 S -1 . Using obtained data in different conditions of D-T muon cycling rate calculations have shown that considering of four-body molecule formations in existing muon injection intensities do not make considerable change in three-body muonic molecule cycling rate

Neutronic analysis of the 1D and 1E banks reflux detection system

Energy Technology Data Exchange (ETDEWEB)

Blanchard, A.

1999-12-21

Two H Canyon neutron monitoring systems for early detection of postulated abnormal reflux conditions in the Second Uranium Cycle 1E and 1D Mixer-Settle Banks have been designed and built. Monte Carlo neutron transport simulations using the general purpose, general geometry, n-particle MCNP code have been performed to model expected response of the monitoring systems to varying conditions.The confirmatory studies documented herein conclude that the 1E and 1D neutron monitoring systems are able to achieve adequate neutron count rates for various neutron source and detector configurations, thereby eliminating excessive integration count time. Neutron count rate sensitivity studies are also performed. Conversely, the transport studies concluded that the neutron count rates are statistically insensitive to nitric acid content in the aqueous region and to the transition region length. These studies conclude that the 1E and 1D neutron monitoring systems are able to predict the postulated reflux conditions for all examined perturbations in the neutron source and detector configurations. In the cases examined, the relative change in the neutron count rates due to postulated transitions from normal {sup 235}U concentration levels to reflux levels remain satisfactory detectable.

Neutronic analysis of the 1D and 1E banks reflux detection system

International Nuclear Information System (INIS)

Blanchard, A.

1999-01-01

Two H Canyon neutron monitoring systems for early detection of postulated abnormal reflux conditions in the Second Uranium Cycle 1E and 1D Mixer-Settle Banks have been designed and built. Monte Carlo neutron transport simulations using the general purpose, general geometry, n-particle MCNP code have been performed to model expected response of the monitoring systems to varying conditions.The confirmatory studies documented herein conclude that the 1E and 1D neutron monitoring systems are able to achieve adequate neutron count rates for various neutron source and detector configurations, thereby eliminating excessive integration count time. Neutron count rate sensitivity studies are also performed. Conversely, the transport studies concluded that the neutron count rates are statistically insensitive to nitric acid content in the aqueous region and to the transition region length. These studies conclude that the 1E and 1D neutron monitoring systems are able to predict the postulated reflux conditions for all examined perturbations in the neutron source and detector configurations. In the cases examined, the relative change in the neutron count rates due to postulated transitions from normal 235 U concentration levels to reflux levels remain satisfactory detectable

Mid-Ocean Ridge Melt Supply and Glacial Cycles: A 3D EPR Study of Crustal Thickness, Layer 2A, and Bathymetry

Science.gov (United States)

Boulahanis, B.; Aghaei, O.; Carbotte, S. M.; Huybers, P. J.; Langmuir, C. H.; Nedimovic, M. R.; Carton, H. D.; Canales, J. P.

2017-12-01

Recent studies suggest that eustatic sea level fluctuations induced by glacial cycles in the Pleistocene may influence mantle-melting and volcanic eruptions at mid-ocean ridges (MOR), with models predicting variation in oceanic crustal thickness linked to sea level change. Previous analyses of seafloor bathymetry as a proxy for crustal thickness show significant spectral energy at frequencies linked to Milankovitch cycles of 1/23, 1/41, and 1/100 ky-1, however the effects of faulting in seafloor relief and its spectral characteristics are difficult to separate from climatic signals. Here we investigate the hypothesis of climate driven periodicity in MOR magmatism through spectral analysis, time series comparisons, and statistical characterization of bathymetry data, seismic layer 2A thickness (as a proxy for extrusive volcanism), and seafloor-to-Moho thickness (as a proxy for total magma production). We utilize information from a three-dimensional multichannel seismic study of the East Pacific Rise and its flanks from 9°36`N to 9°57`N. We compare these datasets to the paleoclimate "LR04" benthic δ18O stack. The seismic dataset covers 770 km2 and provides resolution of Moho for 92% of the imaged region. This is the only existing high-resolution 3-D image across oceanic crust, making it ideal for assessing the possibility that glacial cycles modulate magma supply at fast spreading MORs. The layer 2A grid extends 9 km (170 ky) from the ridge axis, while Moho imaging extends to a maximum of 16 km (310 ky). Initial results from the East Pacific Rise show a relationship between sea level and both crustal thickness and sea floor depth, consistent with the hypothesis that magma supply to MORs may be modulated by glacial cycles. Analysis of crustal thickness and bathymetry data reveals spectral peaks at Milankovitch frequencies of 1/100 ky-1 and 1/41 ky-1 where datasets extend sufficiently far from the ridge. The layer 2A grid does not extend sufficiently far from the

Effect of Repeated Freeze-Thaw Cycles on Beef Quality and Safety

Science.gov (United States)

Rahman, Mohammad Hafizur; Hossain, Mohammad Mujaffar; Rahman, Syed Mohammad Ehsanur; Hashem, Mohammad Abul

2014-01-01

The objectives of this study were to know the effect of repeated freeze-thaw cycles of beef on the sensory, physicochemical quality and microbiological assessment. The effects of three successive freeze-thaw cycles on beef forelimb were investigated comparing with unfrozen fresh beef for 75 d by keeping at −20±1℃. The freeze-thaw cycles were subjected to three thawing methods and carried out to know the best one. As the number of freeze-thaw cycles increased color and odor declined significantly before cook within the cycles and tenderness, overall acceptability also declined among the cycles after cook by thawing methods. The thawing loss increased and dripping loss decreased significantly (pcycles and then decreased. Cooking loss increased in cycle 1 and 3, but decreased in cycle 2. pH decreased significantly (pcycles. Moreover, drip loss, cooking loss and WHC were affected (pcycles. 2-Thiobarbituric acid (TBARS) value increased (pcycles and among the cycles by thawing methods. Total viable bacteria, total coliform and total yeast-mould count decreased significantly (pcycles in comparison to the initial count in repeated freeze-thaw cycles. As a result, repeated freeze-thaw cycles affected the sensory, physicochemical and microbiological qua- lity of beef, causing the deterioration of beef quality, but improved the microbiological quality. Although repeated freeze-thaw cycles did not affect much on beef quality and safety but it may be concluded that repeated freeze and thaw should be minimized in terms of beef color for commercial value and WHC and tenderness/juiciness for eating quality. PMID:26761286

A Framework for Evaluating R&D Impacts and Supply Chain Dynamics Early in a Product Life Cycle. Looking inside the black box of innovation

Energy Technology Data Exchange (ETDEWEB)

Jordan, Gretchen [360 Innovation LLC (United States); Mote, Jonathan [George Washington Univ., Washington, DC (United States); Ruegg, Rosalie [TIA Consulting Inc. (United States); Choi, Thomas [Arizona State Univ., Tempe, AZ (United States); Becker-Dippmann, Angela [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2014-06-01

This report provides a framework for evaluation of R&D investments aimed at speeding up the pace of innovation and strengthening domestic manufacturing and supply chains, which make up a portion of the investments of the U.S. Department of Energy's (DOEs) Office of Energy Efficiency and Renewable Energy (EERE). These investments focus on early phases of the product life cycle, characterized as extending from pre-product, late stage R&D, to initial product introduction and through to early market growth. The investments aim to provide support for additional technology, supply-chain, manufacturing, and early market development to enhance or create markets for clean energy technologies and strengthen the U.S. industry base.

H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication.

Science.gov (United States)

Wu, Rentian; Wang, Zhiquan; Zhang, Honglian; Gan, Haiyun; Zhang, Zhiguo

2017-01-09

DNA replication is tightly regulated to occur once and only once per cell cycle. How chromatin, the physiological substrate of DNA replication machinery, regulates DNA replication remains largely unknown. Here we show that histone H3 lysine 9 demethylase Kdm4d regulates DNA replication in eukaryotic cells. Depletion of Kdm4d results in defects in DNA replication, which can be rescued by the expression of H3K9M, a histone H3 mutant transgene that reverses the effect of Kdm4d on H3K9 methylation. Kdm4d interacts with replication proteins, and its recruitment to DNA replication origins depends on the two pre-replicative complex components (origin recognition complex [ORC] and minichromosome maintenance [MCM] complex). Depletion of Kdm4d impairs the recruitment of Cdc45, proliferating cell nuclear antigen (PCNA), and polymerase δ, but not ORC and MCM proteins. These results demonstrate a novel mechanism by which Kdm4d regulates DNA replication by reducing the H3K9me3 level to facilitate formation of pre-initiative complex. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Piperine causes G1 phase cell cycle arrest and apoptosis in melanoma cells through checkpoint kinase-1 activation.

Directory of Open Access Journals (Sweden)

Neel M Fofaria

Full Text Available In this study, we determined the cytotoxic effects of piperine, a major constituent of black and long pepper in melanoma cells. Piperine treatment inhibited the growth of SK MEL 28 and B16 F0 cells in a dose and time-dependent manner. The growth inhibitory effects of piperine were mediated by cell cycle arrest of both the cell lines in G1 phase. The G1 arrest by piperine correlated with the down-regulation of cyclin D1 and induction of p21. Furthermore, this growth arrest by piperine treatment was associated with DNA damage as indicated by phosphorylation of H2AX at Ser139, activation of ataxia telangiectasia and rad3-related protein (ATR and checkpoint kinase 1 (Chk1. Pretreatment with AZD 7762, a Chk1 inhibitor not only abrogated the activation of Chk1 but also piperine mediated G1 arrest. Similarly, transfection of cells with Chk1 siRNA completely protected the cells from G1 arrest induced by piperine. Piperine treatment caused down-regulation of E2F1 and phosphorylation of retinoblastoma protein (Rb. Apoptosis induced by piperine was associated with down-regulation of XIAP, Bid (full length and cleavage of Caspase-3 and PARP. Furthermore, our results showed that piperine treatment generated ROS in melanoma cells. Blocking ROS by tiron protected the cells from piperine mediated cell cycle arrest and apoptosis. These results suggest that piperine mediated ROS played a critical role in inducing DNA damage and activation of Chk1 leading to G1 cell cycle arrest and apoptosis.

Fuel Cells and Other Emerging Manportable Power Technologies for the NATO Warfighter. Part 1: Power Sources for Manportable/Manwearable Applications (Piles a combustible et autres technologies portatives d’alimentation en energie pour les combattants de l’OTAN - Partie 1: Sources d’alimentation pour les applications transportables/portables par l’homme)

Science.gov (United States)

2014-10-01

combinations the open circuit voltage is between 1 and 1.2 V, whereas the on load voltage is typically 0.4 – 0.5 V for DMFC, 0.65 – 0.7 V for PEMFC and...contrast to AFC it was shown the AEM is not irreversibly destroyed by CO2. As with PEMFC , AEMFC also offers the possibility to be directly fuelled with...ppm for the LT PEM FC. For HT PEMFC the catalysts must be resistant to support corrosion (nanoparticles detachment) and to fast degradation processes

Damage study of an austenitic stainless steel in high cycle multiaxial fatigue regime;Etude de l'endommagement d'un acier inoxydable austenitique par fatigue multiaxiale a grand nombre de cycles

Energy Technology Data Exchange (ETDEWEB)

Poncelet, M. [CEA Saclay, DEN, SRMA, 91 - Gif-sur-Yvette (France); Barbier, G.; Raka, B.; Vincent, L.; Desmorat, R. [LMT Cachan, ENS Cachan/CNRS/UPMC/PRES Univ. Sud Paris, 94 - Cachan (France); Barbier, G. [EDF R and D / LaMSID, 92 - Clamart (France)

2010-02-15

Biaxial fatigue tests are performed up to 1 000 000 cycles at room temperature. Cross specimens of 304L steel thinned in their centre to initiate crack, are loaded by a biaxial testing machine. The strain at the centre of the sample is measured during loading using a stroboscopic Digital Image Correlation (DIC) technique, and crack initiation on the whole gauge zone is early detected by a second DIC-based measurement. A special optical assembly is designed to allow for simultaneous measurements. Three types of loadings are performed: equi-biaxial with a loading ratio R = 0.1, equi-biaxial with loading ratio R = -1, pseudo uniaxial (cyclic loading at R 0.1 in one direction and constant loading in the other). First results are commented. (authors)

Implementing the 4D cycle of appreciative inquiry in health care: a methodological review.

Science.gov (United States)

Trajkovski, Suza; Schmied, Virginia; Vickers, Margaret; Jackson, Debra

2013-06-01

To examine and critique how the phases of the 4D cycle (Discovery, Dream, Design, and Destiny) of appreciative inquiry are implemented in a healthcare context. Appreciative inquiry is a theoretical research perspective, an emerging research methodology and a world view that builds on action research, organizational learning, and organizational change. Increasing numbers of articles published provide insights and learning into its theoretical and philosophical underpinnings. Many articles describe appreciative inquiry and the outcomes of their studies; however, there is a gap in the literature examining the approaches commonly used to implement the 4D cycle in a healthcare context. A methodological review following systematic principles. A methodological review was conducted including articles from the inception of appreciative inquiry in 1986 to the time of writing this review in November, 2011. Key database searches included CINAHL, Emerald, MEDLINE, PubMed, PsycINFO, and Scopus. A methodological review following systematic principles was undertaken. Studies were included if they described in detail the methods used to implement the 4D cycle of appreciative inquiry in a healthcare context. Nine qualitative studies met the inclusion criteria. Results highlighted that appreciative inquiry application is unique and varied between studies. The 4D phases were not rigid steps and were adapted to the setting and participants. Overall, participant enthusiasm and commitment were highlighted suggesting appreciative inquiry was mostly positively perceived by participants. Appreciative inquiry provides a positive way forward shifting from problems to solutions offering a new way of practicing in health care and health research. © 2012 Blackwell Publishing Ltd.

AIB1 regulates the ovarian cancer cell cycle through TUG1.

Science.gov (United States)

Li, L; Gan, Z-H; Qin, L; Jiao, S-H; Shi, Y

2017-12-01

To explore the mechanism of amplified in breast cancer 1 (AIB1) to promote ovarian cancer progress. Cor correlation analysis was performed to obtain the top 100 lncRNAs that were positively correlated with AIB1. The relationship of taurine upregulated gene 1 (TUG1) and clinicopathological characteristics. Moreover, Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were performed to predict the biological process where TUG1 may be involved in. At last, Cell Counting Kit-8 (CCK-8), colon formation and flow cytometry were conducted to explore the biological process that TUG1 may influence. Meanwhile, Western blot was performed to explore the mechanism of TUG1. In this study, it was found that P73 antisense RNA 1T (TP73-AS1), LINC00654 and TUG1 had the tumor-promoting effect in the top 100 lncRNAs that were positively correlated with AIB1. The expression level of TUG1 was significantly decreased after intervention of AIB1. Then, the clinical data were analyzed and the results showed that TUG1 was related to the tumor residue, tumor staging, tumor grade and lymph node metastasis. Moreover, the bioinformatics analysis revealed that TUG1 was mainly involved in the regulation of cell cycle. After intervention in TUG1, it was found that the cell proliferation capacity was significantly decreased, and the cell cycle was arrested in G1 phase. Finally, Western blot revealed that the expressions of G1 phase-related proteins were significantly changed. This study indicated that AIB1 regulates the cycle of ovarian cancer cells through TUG1. This study proved that AIB1 can regulate the cell cycle through regulating TUG1.

Development of a new concept automatic frequency controller for an ultrasmall C-band linear accelerator guide

International Nuclear Information System (INIS)

Kamino, Yuichiro; Tsukuda, Kazuhiro; Kokubo, Masaki; Miura, Sadao; Hirai, Etsuro; Hiraoka, Masahiro; Ishikawa, Junzo

2007-01-01

We are developing a four-dimensional, image-guided radiotherapy system with a gimbaled x-ray head. The system has pursuing irradiation capability in addition to precise irradiation capability, owing to its agile x-ray head. The moving x-ray head requires a very small C-band accelerator guide. The heat intensity of the accelerator guide is much higher than that of conventional S-band medical linear accelerators. The resonance frequency varies over almost 1.0 MHz with a thermal time constant of about 30 s. An automatic frequency controller (AFC) is employed to compensate for this variation in resonance frequency. Furthermore, we noted that fast AFC response is important for step-and-shoot intensity modulation radiotherapy (IMRT), in which the beam is turned on and off frequently. Therefore, we invented a digital AFC, based on a new concept, to provide effective compensation for the thermal characteristics of the accelerator guide and to ensure stable and optimized x-ray treatment. An important aspect of the performance of the AFC is the capture-frequency range over which the AFC can seek, lock on to, and track the resonance frequency. The conventional, analog AFC used in S-band medical linear accelerators would have a capture-frequency range of about 0.9 MHz, if applied to our accelerator guide, and would be inappropriate. Conversely, our new AFC has a capture-frequency range of 24 MHz, which is well suited to our accelerator guide. The design concept behind this new AFC has been developed and verified. A full prototype system was constructed and tested on an existing accelerator guide at the rated x-ray output (500 cGy/min) of our radiotherapy system, with a pulse-repetition frequency of 300 Hz. The AFC acquired the resonance frequency of the accelerator guide within 0.15 s after beam-on, and provided stable tracking and adjustment of the frequency of the microwave source to the resonance frequency of the accelerator guide. With a planned improvement of the

The effect of calcium and vitamin D supplementation on menstrual cycle, body mass index and hyperandrogenism state of women with poly cystic ovarian syndrome

Directory of Open Access Journals (Sweden)

Hatav Ghasemi Tehrani

2014-01-01

Full Text Available Background: Poly cystic ovary syndrome (PCOS is considered one of the most common endocrine disorders of women in reproductive age. The aim of this study was evaluating the efficacy of calcium and Vitamin D supplementation on the regularity of menstrual cycles, body mass index (BMI and hyper androgenism state of women with PCOS. Materials and Methods: In this clinical trial, 80 women with PCOS were evaluated. They randomly located in four groups receiving metformin (group 1, metformin plus calcium and Vitamin D (group 2, calcium and Vitamin D (group 3 and placebo (group 4 for 4 months. BMI, regularity of menstrual cycles, hyperandrogenism (hirsutism and acne and serum calcium and Vitamin D levels were compared in four studying groups at baseline and 4 months after the trial. Results: All studied subjects were similar at baseline (P > 0.05. After trial, the frequency of hirsutism and acne were not different among groups. Frequency regular menstrual cycle and dominant follicle were significantly higher in group 1 and 2 than others (P < 0.05. After trial, there was no significant difference with respect to BMI among groups. Conclusion: Vitamin D and calcium supplementation in addition to metformin therapy in women with PCOS could result in a better outcome in a variety of PCOS symptoms including menstrual regularity, and ovulation.

Alteronol induces cell cycle arrest and apoptosis via increased reactive oxygen species production in human breast cancer T47D cells.

Science.gov (United States)

Ren, Boxue; Li, Defang; Si, Lingling; Ding, Yangfang; Han, Jichun; Chen, Xiaoyu; Zheng, Qiusheng

2018-04-01

Emerging evidence showed that alteronol has a potential antitumour effect in several tumour cells. However, the antitumour effect of alteronol on breast cancer has not been reported. This study investigated the mechanisms of alteronol-induced cell proliferation inhibition in human breast cancer T47D cells. After treatment with alteronol, T47D cell proliferation was examined by MTT assay. The cell cycle distribution, cell apoptosis, reactive oxygen species level and mitochondrial membrane potential were evaluated via flow cytometry. Next, the protein levels of cyclin B1, cdc2, p21, p-cyclin B1, p-cdc2, p53, Bax, Bcl-2 and cytochrome c were analysed using Western blot analysis. Meanwhile, the mRNA levels of cyclin B1, cdc2, p21 and p53 were examined by qRT-PCR. Our data showed that alteronol inhibited the proliferation of T47D cells via inducing G2-phase arrest and cell apoptosis. Compared with control group, alteronol significantly increased ROS level and triggered mitochondrial dysfunction in alteronol-treated T47D cells. Further studies showed that the mRNA and protein levels of cdc2 and cyclin B1 were downregulated, while the mRNA and protein levels of p21, p53, p-cyclin B1, p-cdc2 and cytochrome c were upregulated. In addition, the expression level of Bax was increased, and the expression level of Bcl-2 was decreased. Alteronol induced T47D cell cycle arrest and cell apoptosis through increasing ROS production and triggering mitochondrial dysfunction, and subsequently inhibiting T47D cell proliferation. © 2018 Royal Pharmaceutical Society.

One-loop transition amplitudes in the D1D5 CFT

Energy Technology Data Exchange (ETDEWEB)

Carson, Zaq; Hampton, Shaun; Mathur, Samir D. [Department of Physics, The Ohio State University,191 West Woodruff Ave, Columbus, OH 43210 (United States)

2017-01-02

We consider the issue of thermalization in the D1D5 CFT. Thermalization is expected to correspond to the formation of a black hole in the dual gravity theory. We start from the orbifold point, where the theory is essentially free, and does not thermalize. In earlier work it was noted that there was no clear thermalization effect when the theory was deformed off the orbifold point to first order in the relevant twist perturbation. In this paper we consider the deformation to second order in the twist, where we do find effects that can cause thermalization of an initial perturbation. We consider a 1-loop process where two untwisted copies of the CFT are twisted to one copy and then again untwisted to two copies. We start with a single oscillator excitation on the initial CFT, and compute the effect of the two twists on this state. We find simple approximate expressions for the Bogoliubov coefficients and the behavior of the single oscillator excitation in the continuum limit, where the mode numbers involved are taken to be much larger than unity. We also prove a number of useful relationships valid for processes with an arbitrary number of twist insertions.

One-loop transition amplitudes in the D1D5 CFT

Science.gov (United States)

Carson, Zaq; Hampton, Shaun; Mathur, Samir D.

2017-01-01

We consider the issue of thermalization in the D1D5 CFT. Thermalization is expected to correspond to the formation of a black hole in the dual gravity theory. We start from the orbifold point, where the theory is essentially free, and does not thermalize. In earlier work it was noted that there was no clear thermalization effect when the theory was deformed off the orbifold point to first order in the relevant twist perturbation. In this paper we consider the deformation to second order in the twist, where we do find effects that can cause thermalization of an initial perturbation. We consider a 1-loop process where two untwisted copies of the CFT are twisted to one copy and then again untwisted to two copies. We start with a single oscillator excitation on the initial CFT, and compute the effect of the two twists on this state. We find simple approximate expressions for the Bogoliubov coefficients and the behavior of the single oscillator excitation in the continuum limit, where the mode numbers involved are taken to be much larger than unity. We also prove a number of useful relationships valid for processes with an arbitrary number of twist insertions.

Quantum-Carnot engine for particle confined to 2D symmetric potential well

International Nuclear Information System (INIS)

Belfaqih, Idrus Husin; Sutantyo, Trengginas Eka Putra; Prayitno, T. B.; Sulaksono, Anto

2015-01-01

Carnot model of heat engine is the most efficient cycle consisting of isothermal and adiabatic processes which are reversible. Although ideal gas usually used as a working fluid in the Carnot engine, Bender used quantum particle confined in 1D potential well as a working fluid. In this paper, by following Bender we generalize the situation to 2D symmetric potential well. The efficiency is express as the ratio of the initial length of the system to the final length of the compressed system. The result then is shown that for the same ratio, 2D potential well is more efficient than 1D potential well

Quantum-Carnot engine for particle confined to 2D symmetric potential well

Energy Technology Data Exchange (ETDEWEB)

Belfaqih, Idrus Husin, E-mail: idrushusin21@gmail.com; Sutantyo, Trengginas Eka Putra, E-mail: trengginas.eka@gmail.com; Prayitno, T. B., E-mail: teguh-budi@unj.ac.id [Department of Physics, Universitas Negeri Jakarta, Jl. Pemuda Rawamangun, Jakarta Timur, 13220 (Indonesia); Sulaksono, Anto, E-mail: anto.sulaksono@sci.ui.ac.id [Department of Physics, Universitas Indonesia, Depok, Jawa Barat, 164242 (Indonesia)

2015-09-30

Carnot model of heat engine is the most efficient cycle consisting of isothermal and adiabatic processes which are reversible. Although ideal gas usually used as a working fluid in the Carnot engine, Bender used quantum particle confined in 1D potential well as a working fluid. In this paper, by following Bender we generalize the situation to 2D symmetric potential well. The efficiency is express as the ratio of the initial length of the system to the final length of the compressed system. The result then is shown that for the same ratio, 2D potential well is more efficient than 1D potential well.

Impaired TCA cycle flux in mitochondria in skeletal muscle from type 2 diabetic subjects

DEFF Research Database (Denmark)

Gaster, Michael; Nehlin, Jan O; Minet, Ariane D

2012-01-01

The diabetic phenotype is complex, requiring elucidation of key initiating defects. Recent research has shown that diabetic myotubes express a primary reduced tricarboxylic acid (TCA) cycle flux. A reduced TCA cycle flux has also been shown both in insulin resistant offspring of T2D patients...... and exercising T2D patients in vivo. This review will discuss the latest advances in the understanding of the molecular mechanisms regulating the TCA cycle with focus on possible underlying mechanism which could explain the impaired TCA flux in insulin resistant human skeletal muscle in type 2 diabetes....... A reduced TCA is both a marker and a maker of the diabetic phenotype....

Toward "Age-Friendly Slums"? Health Challenges of Older Slum Dwellers in Nairobi and the Applicability of the Age-Friendly City Approach.

Science.gov (United States)

Aboderin, Isabella; Kano, Megumi; Owii, Hilda Akinyi

2017-10-20

A majority of urban residents in sub-Saharan Africa (SSA) and other developing regions live in informal settlements, or slums. Much of the discourse on slum health centres on younger generations, while an intensifying agenda on healthy ageing as yet lacks a systematic focus on slums. Similarly, the global age-friendly cities (AFC) movement does not, thus far, extend to slums. This paper examines the particular challenges that a slum-focused age-friendly initiative in SSA may need to address, and the relevance of present AFC indicators and domains for initiatives to advance the health and well-being of older slum dwellers. The analysis builds on the case of two slum communities in Nairobi, Kenya. It analyzes two bodies of relevant evidence from these settlements, namely on the health and social circumstances of older residents, and on the local application and measurement of AFC indicators. The findings point to a set of unsurprising, but also less obvious, core health and social adversities that an age-friendly initiative in such settlements would need to consider. The findings show, further, that the current AFC domains and indicators framework only partly capture these adversities, but that there is potential for adapting the framework to be meaningful for slum settings. The paper concludes by underscoring the need for, and opportunities inherent in, the pursuit of an "age-friendly slums" initiative going forward.

Toward “Age-Friendly Slums”? Health Challenges of Older Slum Dwellers in Nairobi and the Applicability of the Age-Friendly City Approach

Science.gov (United States)

Aboderin, Isabella; Owii, Hilda Akinyi

2017-01-01

A majority of urban residents in sub-Saharan Africa (SSA) and other developing regions live in informal settlements, or slums. Much of the discourse on slum health centres on younger generations, while an intensifying agenda on healthy ageing as yet lacks a systematic focus on slums. Similarly, the global age-friendly cities (AFC) movement does not, thus far, extend to slums. This paper examines the particular challenges that a slum-focused age-friendly initiative in SSA may need to address, and the relevance of present AFC indicators and domains for initiatives to advance the health and well-being of older slum dwellers. The analysis builds on the case of two slum communities in Nairobi, Kenya. It analyzes two bodies of relevant evidence from these settlements, namely on the health and social circumstances of older residents, and on the local application and measurement of AFC indicators. The findings point to a set of unsurprising, but also less obvious, core health and social adversities that an age-friendly initiative in such settlements would need to consider. The findings show, further, that the current AFC domains and indicators framework only partly capture these adversities, but that there is potential for adapting the framework to be meaningful for slum settings. The paper concludes by underscoring the need for, and opportunities inherent in, the pursuit of an “age-friendly slums” initiative going forward. PMID:29053576

Systems Analysis of an Advanced Nuclear Fuel Cycle Based on a Modified UREX+3c Process

International Nuclear Information System (INIS)

Johnson, E.R.; Best, R.E.

2009-01-01

The research described in this report was performed under a grant from the U.S. Department of Energy (DOE) to describe and compare the merits of two advanced alternative nuclear fuel cycles -- named by this study as the 'UREX+3c fuel cycle' and the 'Alternative Fuel Cycle' (AFC). Both fuel cycles were assumed to support 100 1,000 MWe light water reactor (LWR) nuclear power plants operating over the period 2020 through 2100, and the fast reactors (FRs) necessary to burn the plutonium and minor actinides generated by the LWRs. Reprocessing in both fuel cycles is assumed to be based on the UREX+3c process reported in earlier work by the DOE. Conceptually, the UREX+3c process provides nearly complete separation of the various components of spent nuclear fuel in order to enable recycle of reusable nuclear materials, and the storage, conversion, transmutation and/or disposal of other recovered components. Output of the process contains substantially all of the plutonium, which is recovered as a 5:1 uranium/plutonium mixture, in order to discourage plutonium diversion. Mixed oxide (MOX) fuel for recycle in LWRs is made using this 5:1 U/Pu mixture plus appropriate makeup uranium. A second process output contains all of the recovered uranium except the uranium in the 5:1 U/Pu mixture. The several other process outputs are various waste streams, including a stream of minor actinides that are stored until they are consumed in future FRs. For this study, the UREX+3c fuel cycle is assumed to recycle only the 5:1 U/Pu mixture to be used in LWR MOX fuel and to use depleted uranium (tails) for the makeup uranium. This fuel cycle is assumed not to use the recovered uranium output stream but to discard it instead. On the other hand, the AFC is assumed to recycle both the 5:1 U/Pu mixture and all of the recovered uranium. In this case, the recovered uranium is reenriched with the level of enrichment being determined by the amount of recovered plutonium and the combined amount of the

The phenotypic spectrum of organic acidurias and urea cycle disorders Part 1: the initial presentation

NARCIS (Netherlands)

Kölker, Stefan; Garcia-Cazorla, Angeles; Cazorla, Angeles Garcia; Valayannopoulos, Vassili; Lund, Allan M.; Burlina, Alberto B.; Sykut-Cegielska, Jolanta; Wijburg, Frits A.; Teles, Elisa Leão; Zeman, Jiri; Dionisi-Vici, Carlo; Barić, Ivo; Karall, Daniela; Augoustides-Savvopoulou, Persephone; Aksglaede, Lise; Arnoux, Jean-Baptiste; Avram, Paula; Baumgartner, Matthias R.; Blasco-Alonso, Javier; Chabrol, Brigitte; Chakrapani, Anupam; Chapman, Kimberly; I Saladelafont, Elisenda Cortès; Couce, Maria L.; de Meirleir, Linda; Dobbelaere, Dries; Dvorakova, Veronika; Furlan, Francesca; Gleich, Florian; Gradowska, Wanda; Grünewald, Stephanie; Jalan, Anil; Häberle, Johannes; Haege, Gisela; Lachmann, Robin; Laemmle, Alexander; Langereis, Eveline; de Lonlay, Pascale; Martinelli, Diego; Matsumoto, Shirou; Mühlhausen, Chris; de Baulny, Hélène Ogier; Ortez, Carlos; Peña-Quintana, Luis; Ramadža, Danijela Petković; Rodrigues, Esmeralda; Scholl-Bürgi, Sabine; Sokal, Etienne; Staufner, Christian; Summar, Marshall L.; Thompson, Nicholas; Vara, Roshni; Pinera, Inmaculada Vives; Walter, John H.; Williams, Monique; Burgard, Peter

2015-01-01

Background The clinical presentation of patients with organic acidurias (OAD) and urea cycle disorders (UCD) is variable; symptoms are often non-specific. Aims/methods To improve the knowledge about OAD and UCD the E-IMD consortium established a web-based patient registry. Results We registered 795

Expression, processing, and localization of PmpD of Chlamydia trachomatis Serovar L2 during the chlamydial developmental cycle.

Directory of Open Access Journals (Sweden)

Andrey O Kiselev

Full Text Available BACKGROUND: While families of polymorphic membrane protein (pmp genes have been identified in several Chlamydia species, their function remains mostly unknown. These proteins are of great interest, however, because of their location in the outer membrane and possible role in chlamydial virulence. METHODOLOGY/PRINCIPAL FINDING: We analyzed the relative transcription of the pmpD gene, a member of the pmp gene family in C. trachomatis serovar L2, and its protein product translation and processing during the chlamydial developmental cycle. By real-time reverse transcription polymerase chain reaction, the pmpD gene was found to be upregulated at 16 to 24 four hours after infection. Using polyclonal antibodies generated against the predicted passenger domain of PmpD, we demonstrated that it is initially localized on the surface of reticulate bodies, followed by its secretion outside Chlamydia starting at 24 hours after infection. In elementary bodies, we found a approximately 157 kDa PmpD only inside the cell. Both events, the upregulation of pmpD gene transcription and PmpD protein processing and secretion, are coincidental with the period of replication and differentiation of RBs into EBs. We also demonstrated that, in the presence of penicillin, the cleavage and secretion of the putative passenger domain was suppressed. CONCLUSION/SIGNIFICANCE: Our results are in agreement with the general concept that PmpD is an autotransporter protein which is post-translationally processed and secreted in the form of the putative passenger domain outside Chlamydia at mid- to- late point after infection, coinciding with the development of RBs into EBs.

Cyclin K and cyclin D1b are oncogenic in myeloma cells

Directory of Open Access Journals (Sweden)

Renoir Jack-Michel

2010-05-01

Full Text Available Abstract Background Aberrant expression of cyclin D1 is a common feature in multiple myeloma (MM and always associated with mantle cell lymphoma (MCL. CCND1 gene is alternatively spliced to produce two cyclin D1 mRNA isoforms which are translated in two proteins: cyclin D1a and cyclin D1b. Both isoforms are present in MM cell lines and primary cells but their relative role in the tumorigenic process is still elusive. Results To test the tumorigenic potential of cyclin D1b in vivo, we generated cell clones derived from the non-CCND1 expressing MM LP-1 cell line, synthesizing either cyclin D1b or cyclin K, a structural homolog and viral oncogenic form of cyclin D1a. Immunocompromised mice injected s.c. with LP-1K or LP-1D1b cells develop tumors at the site of injection. Genome-wide analysis of LP-1-derived cells indicated that several cellular processes were altered by cyclin D1b and/or cyclin K expression such as cell metabolism, signal transduction, regulation of transcription and translation. Importantly, cyclin K and cyclin D1b have no major action on cell cycle or apoptosis regulatory genes. Moreover, they impact differently cell functions. Cyclin K-expressing cells have lost their migration properties and display enhanced clonogenic capacities. Cyclin D1b promotes tumorigenesis through the stimulation of angiogenesis. Conclusions Our study indicates that cyclin D1b participates into MM pathogenesis via previously unrevealed actions.

Initial Screening of Thermochemical Water-Splitting Cycles for High Efficiency Generation of Hydrogen Fuels Using Nuclear Power

International Nuclear Information System (INIS)

Brown, L.C.; Funk, J.F.; Showalter, S.K.

1999-01-01

OAK B188 Initial Screening of Thermochemical Water-Splitting Cycles for High Efficiency Generation of Hydrogen Fuels Using Nuclear Power There is currently no large scale, cost-effective, environmentally attractive hydrogen production process, nor is such a process available for commercialization. Hydrogen is a promising energy carrier, which potentially could replace the fossil fuels used in the transportation sector of our economy. Fossil fuels are polluting and carbon dioxide emissions from their combustion are thought to be responsible for global warming. The purpose of this work is to determine the potential for efficient, cost-effective, large-scale production of hydrogen utilizing high temperature heat from an advanced nuclear power station. Almost 800 literature references were located which pertain to thermochemical production of hydrogen from water and over 100 thermochemical watersplitting cycles were examined. Using defined criteria and quantifiable metrics, 25 cycles have been selected for more detailed study

The prevalence of polycystic ovary syndrome in a normal population according to the Rotterdam criteria versus revised criteria including anti-Mullerian hormone.

Science.gov (United States)

Lauritsen, M P; Bentzen, J G; Pinborg, A; Loft, A; Forman, J L; Thuesen, L L; Cohen, A; Hougaard, D M; Nyboe Andersen, A

2014-04-01

What is the prevalence in a normal population of polycystic ovary syndrome (PCOS) according to the Rotterdam criteria versus revised criteria including anti-Müllerian hormone (AMH)? The prevalence of PCOS was 16.6% according to the Rotterdam criteria. When replacing the criterion for polycystic ovaries by antral follicle count (AFC) > 19 or AMH > 35 pmol/l, the prevalence of PCOS was 6.3 and 8.5%, respectively. WHAT IS KNOWN ALREADY?: The Rotterdam criteria state that two out of the following three criteria should be present in the diagnosis of PCOS: oligo-anovulation, clinical and/or biochemical hyperandrogenism and polycystic ovaries (AFC ≥ 12 and/or ovarian volume >10 ml). However, with the advances in sonography, the relevance of the AFC threshold in the definition of polycystic ovaries has been challenged, and AMH has been proposed as a marker of polycystic ovaries in PCOS. From 2008 to 2010, a prospective, cross-sectional study was performed including 863 women aged 20-40 years and employed at Copenhagen University Hospital, Rigshospitalet, Denmark. We studied a subgroup of 447 women with a mean (±SD) age of 33.5 (±4.0) years who were all non-users of hormonal contraception. Data on menstrual cycle disorder and the presence of hirsutism were obtained. On cycle Days 2-5, or on a random day in the case of oligo- or amenorrhoea, sonographic and endocrine parameters were measured. The prevalence of PCOS was 16.6% according to the Rotterdam criteria. PCOS prevalence significantly decreased with age from 33.3% in women polycystic ovaries with a significant age-related decrease from 69.0% in women polycystic ovaries in women with PCOS according to the Rotterdam criteria [area under the curve (AUC) 0.994; 95% confidence interval (CI): 0.990-0.999] and AUC 0.992 (95% CI: 0.987-0.998), respectively], and an AMH cut-off value of 18 pmol/l and AMH Z-score of -0.2 showed the best compromise between sensitivity (91.8 and 90.4%, respectively) and specificity (98.1 and

Activation of mammalian target of rapamycin signaling promotes cell cycle progression and protects cells from apoptosis in mantle cell lymphoma.

Science.gov (United States)

Peponi, Evangelia; Drakos, Elias; Reyes, Guadalupe; Leventaki, Vasiliki; Rassidakis, George Z; Medeiros, L Jeffrey

2006-12-01

Mantle cell lymphoma (MCL) is characterized by the t(11;14) and cyclin D1 overexpression. However, additional molecular events are most likely required for oncogenesis, possibly through cell cycle and apoptosis deregulation. We hypothesized that mammalian target of rapamycin (mTOR) is activated in MCL and contributes to tumor proliferation and survival. In MCL cell lines, pharmacological inhibition of the phosphoinositide 3-kinase/AKT pathway was associated with decreased phosphorylation (activation) of mTOR and its downstream targets phosphorylated (p)-4E-BP1, p-p70S6 kinase, and p-ribosomal protein S6, resulting in apoptosis and cell cycle arrest. These changes were associated with down-regulation of cyclin D1 and the anti-apoptotic proteins cFLIP, BCL-XL, and MCL-1. Furthermore, silencing of mTOR expression using mTOR-specific short interfering RNA decreased phosphorylation of mTOR signaling proteins and induced cell cycle arrest and apoptosis. Silencing of eukaryotic initiation factor (eIF4E), a downstream effector of mTOR, recapitulated these results. We also assessed mTOR signaling in MCL tumors using immunohistochemical methods and a tissue microarray: 10 of 30 (33%) expressed Ser473p-AKT, 13 of 21 (62%) Ser2448p-mTOR, 22 of 22 (100%) p-p70S6K, and 5 of 20 (25%) p-ribosomal protein S6. Total eIF4E binding protein 1 and eukaryotic initiation factor 4E were expressed in 13 of 14 (93%) and 16 of 29 (55%) MCL tumors, respectively. These findings suggest that the mTOR signaling pathway is activated and may contribute to cell cycle progression and tumor cell survival in MCL.

[Circadian rhythm variation of the clock genes Per1 and cell cycle related genes in different stages of carcinogenesis of buccal mucosa in animal model].

Science.gov (United States)

Tan, Xuemei; Ye, Hua; Yang, Kai; Chen, Dan; Tang, Hong

2015-07-01

To investigate the expression and circadian rhythm variation of biological clock gene Per1 and cell cycle genes p53, CyclinD1, cyclin-dependent kinases (CDK1), CyclinB1 in different stages of carcinogenesis in buccal mucosa and its relationship with the development of buccal mucosa carcinoma. Ninety golden hamsters were housed under 12 hours light-12 hours dark cycles, and the model of buccal squamous cell carcinoma was established by using the dimethylbenzanthracene (DMBA) to smear the golden hamster buccal mucosa. Before the DMBA was used and after DMBA was used 6 weeks and 14 weeks respectively, the golden hamsters were sacrificed at 6 different time points (5 rats per time point) within 24 hour, including 4, 8, 12, 16, 20 and 24 hour after lights onset (HALO), and the normal buccal mucosa, precancerous lesions and cancer tissue were obtained, respectively. HE stained sections were prepared to observe the canceration of each tissue. Real time RT-PCR was used to detect the mRNA expression of Per1, p53, CyclinD1, CDK1 and CyclinB1, and a cosine analysis method was applied to determine the circadian rhythm variation of Per1, p53, CyclinD1, CDK1 and CyclinB1 mRNA expression, which were characterized by median, amplitude and acrophase. The expression of Per1, p53, CDK1 and CyclinD1 mRNA in 6 different time points within 24 hours in the tissues of three different stages of carcinogenesis had circadian rhythm, respectively. However, the CyclinB1 mRNA was expressed with circadian rhythm just in normal and cancer tissue (P circadian rhythm was in disorder (P > 0.05). As the development of carcinoma, the median of Per1 and p53 mRNA expression were significantly decreased (P circadian rhythm of clock gene Per1 and cell cycle genes p53, CyclinD1, CDK1, CyclinB1 expression remarkably varied with the occurrence and development of carcinoma. Further research into the interaction between circadian and cell cycle of two cycle activity and relationship with the carcinogenesis may

[Biodegradation characteristics of o-chlorophenol with photosynthetic bacteria PSB-1D].

Science.gov (United States)

Hu, Xiao-min; Dong, Yi-hu; Li, Liang; Lu, Juan; He, Ying-dian; Gao, Yang

2010-07-01

A strain of photosynthetic bacteria named PSB-1D with degradation of o-chlorophenol (2-CP) was isolated and screened from the shallow substrate sludge in downstream side of the sewage outfall of an insecticide factory. The PSB-1D is identified preliminarily as Rhodopseudomonas sp. according to its colony and cell morphological properties, physiological biochemical characteristics and absorption spectrum analysis of living cells. The experiments results of relationship between PSB-1D growth and o-chlorophenol degradation showed that the degradation rate of o-chlorophenol was up to 57.26% after 7 days cultural time. The main environmental factors including way of illumination and oxygen, initial pH, cultural temperature, illumination intensity had distinctly influenced on the o-chlorophenol degradation with PSB-1D. The results showed that the optimum conditions were as following: an anaerobic light, pH 7.0, temperature 30 degrees C, illumination intensity 4000 lx,initial o-chlorophenol concentration 50 mg/L. Under that cultural condition, the degradation rate of o-chlorophenol could reach to 62.08%. The degradation kinetic data fitted the Andrews model well. In addition, the biodegradation process of o-chlorophenol can be well described by enzymatic reaction of high concentration inhibition, with the maximum substrate utilization rate 0.309 d(-1), Michaelis-Menten constant 2.733 mg/L, inhibitory constant 230.15 mg/L respectively.

Coupling of Nod1D and HOTCHANNEL: static case; Acoplamiento de Nod1D y HOTCHANNEL: caso estatico

Energy Technology Data Exchange (ETDEWEB)

Gomez T, A.M. [IPN-ESFM, 07738 Mexico D.F. (Mexico); Ovando C, R. [IIE-Gcia. de Energia Nuclear, Cuernavaca, Morelos (Mexico)]. e-mail: rovando@iie.org.mx

2003-07-01

In this work the joining of the programs Nod1D and HOTCHANNEL, developed in the National Polytechnic Institute (IPN) and in the Electrical Research Institute (IIE) respectively is described. The first one allows to study the neutronic of a nuclear reactor and the second one allows to carry out the analysis of hot channel of a Boiling Water Reactor (BWR). Nod1 D is a program that it solves by nodal methods type finite element those diffusion equations in multigroup, and it is the static part of Nod Kin that it solves the diffusion equation in their time dependent part. For another side HOTCHANNEL is based on a mathematical model constituted by four conservation equations (two of mass conservation, one of motion quantity and one of energy), which are solved applying one discretization in implicit finite differences. Both programs have been verified in independent form using diverse test problems. In this work the modifications that were necessary to carry out to both for obtaining a coupled program that it provides the axial distribution of the neutron flux, the power, the burnup and the void fraction, among others parameters as much as neutronic as thermal hydraulics are described. Those are also mentioned limitations, advantages and disadvantages of the final product to which has been designated Nod1 D-HotChn. Diverse results for the Cycle 1 of the Laguna Verde Unit 1 reactor of the Nucleo electric central comparing them with those obtained directly with the CoreMasterPresto code are provided. (Author)

Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation

Energy Technology Data Exchange (ETDEWEB)

Cheng, Ya-Hsin, E-mail: yhcheng@mail.cmu.edu.tw [Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China); Li, Lih-Ann; Lin, Pinpin; Cheng, Li-Chuan [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan, ROC (China); Hung, Chein-Hui [Graduate Institute of Clinical Medicine Sciences, Chang Gung University, Puizi City, Chiayi 613, Taiwan, ROC (China); Chang, Nai Wen [Department of Biochemistry, School of Medicine, China Medical University, Taichung, Taiwan, ROC (China); Lin, Chingju [Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China)

2012-09-15

Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation. -- Highlights: ► Baicalein causes the G1 phase arrest by decreasing Rb phosphorylation. ► Baicalein modulates AhR-mediated cell proliferation. ► Both AhR activation and cyclin D1 degradation results in hypophosphorylation of Rb. ► Baicalein facilitates cyclin D1 degradation by signalling the GSK-3β pathway.

Radiosynthesis, rodent biodistribution, and metabolism of 1-deoxy-1-[18F]fluoro-d-fructose

International Nuclear Information System (INIS)

Haradahira, Terushi; Tanaka, Akihiro; Maeda, Minoru; Kanazawa, Yoko; Ichiya, Yu-Ichi; Masuda, Kouji

1995-01-01

Fluorine-18 labeled analog of d-fructose, 1-deoxy-1-[ 18 F]fluoro-d-fructose (1-[ 18 F]FDFrc), was synthesized by nucleophilic substitution of [ 18 F]fluoride ion and the effect of the fluorine substitution on its in vivo metabolism was investigated. The tissue distributions of 1-[ 18 F]FDFrc in rats and tumor bearing mice showed initial high uptake and subsequent rapid washout of the radioactivity in the principal sites of d-fructose metabolism (kidneys, liver and small intestine). The uptakes in the brain and tumor (fibrosarcoma) were the lowest and moderate, respectively, but tended to increase with time. The in vivo metabolic studies of 1-[ 18 F]FDFrc and nonradiactive 1-FDFrc in mouse brain and tumor showed that the fluorinated analog remained unmetabolized in these tissues, indicating that the substitution of fluorine at the C-1 position produces a nonmetabolizable analog of d-fructose. Thus, 1-[ 18 F]FDFrc had no features of a metabolic trapping tracer without showing any appreciable organ or tumor specific localization

Life Cycle Characterization of Sulfolobus Monocaudavirus 1, an Extremophilic Spindle-Shaped Virus with Extracellular Tail Development.

Science.gov (United States)

Uldahl, Kristine B; Jensen, Signe B; Bhoobalan-Chitty, Yuvaraj; Martínez-Álvarez, Laura; Papathanasiou, Pavlos; Peng, Xu

2016-06-15

We provide here, for the first time, insights into the initial infection stages of a large spindle-shaped archaeal virus and explore the following life cycle events. Our observations suggest that Sulfolobus monocaudavirus 1 (SMV1) exhibits a high adsorption rate and that virions adsorb to the host cells via three distinct attachment modes: nosecone association, body association, and body/tail association. In the body/tail association mode, the entire virion, including the tail(s), aligns to the host cell surface and the main body is greatly flattened, suggesting a possible fusion entry mechanism. Upon infection, the intracellular replication cycle lasts about 8 h, at which point the virions are released as spindle-shaped tailless particles. Replication of the virus retarded host growth but did not cause lysis of the host cells. Once released from the host and at temperatures resembling that of its natural habitat, SMV1 starts developing one or two tails. This exceptional property of undergoing a major morphological development outside, and independently of, the host cell has been reported only once before for the related Acidianus two-tailed virus. Here, we show that SMV1 can develop tails of more than 900 nm in length, more than quadrupling the total virion length. Very little is known about the initial life cycle stages of viruses infecting hosts of the third domain of life, Archaea This work describes the first example of an archaeal virus employing three distinct association modes. The virus under study, Sulfolobus monocaudavirus 1, is a representative of the large spindle-shaped viruses that are frequently found in acidic hot springs. The results described here will add valuable knowledge about Archaea, the least studied domain in the virology field. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Cytokinins Are Initial Targets of Light in the Control of Bud Outgrowth(1[OPEN])

Czech Academy of Sciences Publication Activity Database

Roman, H.; Girault, T.; Barbier, F.; Peron, T.; Brouard, N.; Pěnčík, Aleš; Novák, Ondřej; Vian, A.; Sakr, S.; Lothier, J.; Le Gourrierec, J.; Leduc, N.

2016-01-01

Roč. 172, č. 1 (2016), s. 489-509 ISSN 0032-0889 R&D Projects: GA MŠk(CZ) LO1204; GA MŠk LK21306 Institutional support: RVO:61389030 Keywords : cell-cycle regulation * pea axillary buds * oryza-sativa l. * apical dominance * rosa sp * arabidopsis-thaliana * lateral buds * meristem activity * plant-responses * acts downstream Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.456, year: 2016

Continuation of connecting orbits in 3d-ODEs. (ii) cycle-to-cycle connections.

NARCIS (Netherlands)

Doedel, E.J.; Kooi, B.W.; van Voorn, G.A.K.; Kuznetzov, Y.A.

2009-01-01

In Part I of this paper we have discussed new methods for the numerical continuation of point-to-cycle connecting orbits in three-dimensional autonomous ODE's using projection boundary conditions. In this second part we extend the method to the numerical continuation of cycle-to-cycle connecting

17-AAG mediated targeting of Hsp90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry.

Science.gov (United States)

Chaklader, M; Das, P; Pereira, J A; Law, A; Chattopadhyay, S; Chatterjee, R; Mondal, A; Law, S

2012-07-01

Peritoneal or retro-peritoneal sarcomatosis related malignant ascites formation is a rare but serious consequence of the locoregional metastatic event. The present work aimed to study the effect of the Hsp90 inhibitor (17-AAG), an ansamycin analog, on cell cycle and DNA replication specific chaperone-clients interaction in the event of peritoneal sarcoma related malignant ascites formation in mouse model at the late stage of malignant growth. We administered 17-AAG, an Hsp90 inhibitor, divided doses (330 μg/kg b.w./day for first five days then next ten days with166 μg/kg b.w./day) through intra-peritoneal route of inbred Swiss albino mice bearing full grown peritoneal malignant ascites of sarcoma-180. Our study was evaluated by peripheral blood hemogram analysis, malignant ascitic cytology, cell viability test, survival time and mitotic indexing. Furthermore, flowcytometric HSP90, TERT, CyclinD1, PCNA and GM-CSF expression analysis has been considered for special objective of the study. Our experimental efforts reduced the aggressive proliferation of malignant ascites by drastic downregulation of TERT and cyclin D1 on the verge of cell cycle entry along with DNA replication processivity factor PCNA by directly modulating their folding machinery - heat shock protein 90. Consequently, we observed that malignant ascitic cells became error prone during the event of karyokinesis and produced micronucleus containing malignant cells with low viability. Peripheral neutrophilia due to over-expression of GM-CSF by the peritoneal malignant ascites were also controlled by the treatment with 17-AAG and overall, the treatment modality improved the median survival time. Finally we can conclude that 17AAG administration might serve as a prospective pharmacological agent for the management of peritoneal sarcoma related malignant ascites and throws light towards prolonged survival of the patients concerned.

Life-cycle cost analysis of adsorption cycles for desalination

KAUST Repository

Thu, Kyaw

2010-08-01

This paper presents the thermo-economic analysis of the adsorption desalination (AD) cycle that is driven by low-temperature waste heat from exhaust of industrial processes or renewable sources. The AD cycle uses an adsorbent such as the silica gel to desalt the sea or brackish water. Based on an experimental prototype AD plant, the life-cycle cost analysis of AD plants of assorted water production capacities has been simulated and these predictions are translated into unit cost of water production. Our results show that the specific energy consumption of the AD cycle is 1.38 kWh/m3 which is the lowest ever reported. For a plant capacity of 1000 m3/d, the AD cycle offers a unit cost of $0.457/m3 as compared to more than $0.9 for the average RO plants. Besides being cost-effective, the AD cycle is also environment-friendly as it emits less CO2 emission per m3 generated, typically 85% less, by comparison to an RO process. © 2010 Desalination Publications.

Accurate expressions for the power efficiency of a class-D power amplifier in a limit-cycle transmitter configuration

NARCIS (Netherlands)

Sarkeshi, M.; Mahmoudi, R.; Roermund, van A.H.M.

2009-01-01

Limit-cycle based, self-oscillating amplifiers are promising candidates for linear amplification of complex signals with high peak-to-average ratio, while maintaining high power efficiency. Limit-cycle transmitters employ switch class-D power amplifiers in order to achieve high Efficiency. In this

1-{beta}-D-arabinofuranosylcytosine is cytotoxic in quiescent normal lymphocytes undergoing DNA excision repair

Energy Technology Data Exchange (ETDEWEB)

Yamauchi, Takahiro; Kawai, Yasukazu; Ueda, Takanori [Fukui Medical Univ., Matsuoka (Japan)

2002-12-01

We have sought to clarify the potential activity of the S-phase-specific antileukemic agent 1-{beta}-D-arabinofuranosylcytosine (ara-C), an inhibitor of DNA synthesis, in quiescent cells that are substantially non-sensitive to nucleoside analogues. It was hypothesized that the combination of ara-C with DNA damaging agents that initiate DNA repair will expand ara-C cytotoxicity to non-cycling cells. The repair kinetics, which included incision of damaged DNA, gap-filling by DNA synthesis and rejoining by ligation, were evaluated using the single cell gel electrophoresis (Comet) assay and the thymidine incorporation assay. When normal lymphocytes were treated with ultraviolet C or with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), the processes of DNA excision repair were promptly initiated and rapidly completed. When the cells were incubated with ara-C prior to irradiation or BCNU treatment, the steps of DNA synthesis and rejoining in the repair processes were both inhibited. The ara-C-mediated inhibition of the repair processes was concentration-dependent, with the effect peaking at 10{mu}M. The combination of ara-C with these DNA repair initiators exerted subsequent cytotoxicity, which was proportional to the extent of the repair inhibition in the presence of ara-C. In conclusion, ara-C was cytotoxic in quiescent cells undergoing DNA repair. This might be attributed to unrepaired DNA damage that remained in the cells, thereby inducing lethal cytotoxicity. Alternatively, ara-C might exert its own cytotoxicity by inhibiting DNA synthesis in the repair processes. Such a strategy may be effective against a dormant subpopulation in acute leukemia that survives chemotherapy. (author)

1-β-D-arabinofuranosylcytosine is cytotoxic in quiescent normal lymphocytes undergoing DNA excision repair

International Nuclear Information System (INIS)

Yamauchi, Takahiro; Kawai, Yasukazu; Ueda, Takanori

2002-01-01

We have sought to clarify the potential activity of the S-phase-specific antileukemic agent 1-β-D-arabinofuranosylcytosine (ara-C), an inhibitor of DNA synthesis, in quiescent cells that are substantially non-sensitive to nucleoside analogues. It was hypothesized that the combination of ara-C with DNA damaging agents that initiate DNA repair will expand ara-C cytotoxicity to non-cycling cells. The repair kinetics, which included incision of damaged DNA, gap-filling by DNA synthesis and rejoining by ligation, were evaluated using the single cell gel electrophoresis (Comet) assay and the thymidine incorporation assay. When normal lymphocytes were treated with ultraviolet C or with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), the processes of DNA excision repair were promptly initiated and rapidly completed. When the cells were incubated with ara-C prior to irradiation or BCNU treatment, the steps of DNA synthesis and rejoining in the repair processes were both inhibited. The ara-C-mediated inhibition of the repair processes was concentration-dependent, with the effect peaking at 10μM. The combination of ara-C with these DNA repair initiators exerted subsequent cytotoxicity, which was proportional to the extent of the repair inhibition in the presence of ara-C. In conclusion, ara-C was cytotoxic in quiescent cells undergoing DNA repair. This might be attributed to unrepaired DNA damage that remained in the cells, thereby inducing lethal cytotoxicity. Alternatively, ara-C might exert its own cytotoxicity by inhibiting DNA synthesis in the repair processes. Such a strategy may be effective against a dormant subpopulation in acute leukemia that survives chemotherapy. (author)

Effect of berberine on cell cycle arrest and cell survival during cerebral ischemia and reperfusion and correlations with p53/cyclin D1 and PI3K/Akt.

Science.gov (United States)

Chai, Yu-Shuang; Hu, Jun; Lei, Fan; Wang, Yu-Gang; Yuan, Zhi-Yi; Lu, Xi; Wang, Xin-Pei; Du, Feng; Zhang, Dong; Xing, Dong-Ming; Du, Li-Jun

2013-05-15

Berberine acted as a natural medicine with multiple pharmacological activities. In the present study, we examined the effect of berberine against cerebral ischemia damage from cell cycle arrest and cell survival. Oxygen-glucose deprivation of PC12 cells and primary neurons, and carotid artery ligation in mice were used as in vitro and in vivo cerebral ischemia models. We found that the effect of berberine on cell cycle arrest during ischemia was mediated by decreased p53 and cyclin D1, increased phosphorylation of Bad (higher expression of p-Bad and higher ratio of p-Bad to Bad) and decreased cleavage of caspase 3. Meanwhile, berberine activated the PI3K/Akt pathway during the reperfusion, especially the phosphor-activation of Akt, to promote the cell survival. The neural protective effect of berberine was remained in the presence of inhibitor of mitogen-activated protein/extracellular signal-regulated kinase (MEK), but was suppressed by the inhibitors of PI3K and Akt. We demonstrated that berberine induced cell cycle arrest and cell survival to resist cerebral ischemia injury. Copyright © 2013 Elsevier B.V. All rights reserved.

Initial results of H-mode edge pedestal turbulence evolution with quadrature reflectometer measurements on DIII-D

Energy Technology Data Exchange (ETDEWEB)

Wang, G. [University of California, Los Angeles, CA 90095 (United States)]. E-mail: wangg@fusion.gat.com; Peebles, W.A. [University of California, Los Angeles, CA 90095 (United States); Doyle, E.J. [University of California, Los Angeles, CA 90095 (United States); Rhodes, T.L. [University of California, Los Angeles, CA 90095 (United States); Zeng, L. [University of California, Los Angeles, CA 90095 (United States); Nguyen, X. [University of California, Los Angeles, CA 90095 (United States); Osborne, T.H. [General Atomics, San Diego, CA 92186-5608 (United States); Snyder, P.B. [General Atomics, San Diego, CA 92186-5608 (United States); Kramer, G.J. [Princeton Plasma Physics Laboratory, Princeton, NJ 08543 (United States); Nazikian, R. [Princeton Plasma Physics Laboratory, Princeton, NJ 08543 (United States); Groebner, R.J. [General Atomics, San Diego, CA 92186-5608 (United States); Burrell, K.H. [General Atomics, San Diego, CA 92186-5608 (United States); Leonard, A.W. [General Atomics, San Diego, CA 92186-5608 (United States); Fenstermacher, M.E. [Lawrence Livermore National Laboratory, Livermore, CA 94550 (United States); Strait, E.J. [General Atomics, San Diego, CA 92186-5608 (United States)

2007-06-15

High-resolution quadrature reflectometer measurements of density fluctuation levels have been obtained on DIII-D for H-mode edge pedestal studies. Initial results are presented from the L-H transition to the first ELM for two cases: (i) a low pedestal beta discharge, in which density turbulence in the pedestal has little change during the ELM-free phase, and (ii) a high pedestal beta discharge in which both density and magnetic turbulence are observed to increase before the first ELM. These high beta data are consistent with the existence of electromagnetic turbulence suggested by some transport models. During Type-I ELM cycles, when little magnetic turbulence can be observed, pedestal turbulence increases just after an ELM crash and then decreases before next ELM strikes, in contrast to a drop after ELM crash and then it re-grows when strong magnetic turbulence shows similar behavior. Clear ELM precursors are observed on {<=}20% of Type-I ELMs observed to date.

Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition.

Science.gov (United States)

Allen, Jodi C; Seidel, Petra; Schlosser, Tobias; Ramsay, Emma E; Ge, Qi; Ammit, Alaina J

2012-01-01

Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G(1) cell cycle progression-cyclin D1-in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

Closed cycle construction: an integrated process for the separation and reuse of C&D waste.

Science.gov (United States)

Mulder, Evert; de Jong, Tako P R; Feenstra, Lourens

2007-01-01

In The Netherlands, construction and demolition (C&D) waste is already to a large extent being reused, especially the stony fraction, which is crushed and reused as a road base material. In order to increase the percentage of reuse of the total C&D waste flow to even higher levels, a new concept has been developed. In this concept, called 'Closed Cycle Construction', the processed materials are being reused at a higher quality level and the quantity of waste that has to be disposed of is minimised. For concrete and masonry, the new concept implies that the material cycle will be completely closed, and the original constituents (clay bricks, gravel, sand, cement stone) are recovered in thermal processes. The mixed C&D waste streams are separated and decontaminated. For this purpose several dry separation techniques are being developed. The quality of the stony fraction is improved so much, that this fraction can be reused as an aggregate in concrete. The new concept has several benefits from a sustainability point of view, namely less energy consumption, less carbon dioxide emission, less waste production and less land use (for excavation and disposal sites). One of the most remarkable benefits of the new concept is that the thermal process steps are fuelled with the combustible fraction of the C&D waste itself. Economically the new process is more or less comparable with the current way of processing C&D waste. On the basis of the positive results of a feasibility study, currently a pilot and demonstration project is being carried out. The aim is to optimise the different process steps of the Closed Cycle Construction process on a laboratory scale, and then to verify them on a large scale. The results of the project are promising, so far.

Crack initiation and propagation in welded joints of turbine and boiler steels during low cycle fatigue

International Nuclear Information System (INIS)

Lindblom, J.; Sandstroem, R.; Linde, L.; Henderson, P.

1990-01-01

Low cycle fatigue (LCF) tests have been performed at 300 and 565 degrees C on welded joints and on microstructures to be found in or near welded joints in a low alloy ferritic steel 0.5 Cr, 0.5 Mo, 0.25 V. The difference in lifetimes between the 300 degrees C and 565 degrees C tests was small comparing the same microstructures and strain ranges, although the stress amplitude was greater at 300 degrees C. Under constant stress conditions the fatigue life depended on the fatigue life of the parent metal but under constant strain conditions the lifetime was governed by that of the bainitic structures. Strain controlled LCF tests have been performed at 750 degrees C on welded joints in the austenitic steel AISI 316 and on different parent and weld metals used in these joints. In continuously cycled samples all cracks were transgranular and initiated at the surface; hold-time samples displayed internally initiated intergranular cracking in the weld metal. Under constant strain conditions the 316 parent and weld metals exhibited similar lifetimes. When considering a constant stress situation the strength of the microsturctures decreased in the following order: Sanicro weld metal, cold deformed parent metal, undeformed parent metal and weld metal (K.A.E.)

Les dépenses militaires : la fin des cycles ?

Directory of Open Access Journals (Sweden)

Aude Fleurant

2010-12-01

Full Text Available Cet article retrace le cheminement du plus récent cycle des dépenses militaires mondiales (1989-2010 et met en évidence les phénomènes économiques et industriels qui l’ont caractérisé. Il se penche également sur la période contemporaine d’où émane un processus d’investissement plus soutenu à l’échelle internationale qui pourrait bien mettre fin à cette évolution cyclique des dépenses militaires. Au delà de cette question, le texte fait le point sur de nombreux sujets essentiels à la compréhension de l’économie militaire contemporaine tels l’émergence d’un nouveau paradigme sécuritaire, le tracé technologique qui l’a accompagné et la mutation au sein de la base industrielle de défense qui en a résulté.This article traces the progression of the most recent cycle of world military spending (1989-2010, highlighting both economic and industrial phenomena that made it distinct. It also examines the current period, in which there is a sustained military investment process on an international scale, a trend that could well put an end to the cyclical profile defence spending has shown since the end of World War 2. Beyond this issue, the text provides an update on a number of subjects essential to a better understanding of the current defence economy such as the adoption of a new security paradigm, the evolution of military technology that occurred with it, and the defence industry transformation that was a consequence of it.

Quadratic reactivity fuel cycle model

International Nuclear Information System (INIS)

Lewins, J.D.

1985-01-01

For educational purposes it is highly desirable to provide simple yet realistic models for fuel cycle and fuel economy. In particular, a lumped model without recourse to detailed spatial calculations would be very helpful in providing the student with a proper understanding of the purposes of fuel cycle calculations. A teaching model for fuel cycle studies based on a lumped model assuming the summability of partial reactivities with a linear dependence of reactivity usefully illustrates fuel utilization concepts. The linear burnup model does not satisfactorily represent natural enrichment reactors. A better model, showing the trend of initial plutonium production before subsequent fuel burnup and fission product generation, is a quadratic fit. The study of M-batch cycles, reloading 1/Mth of the core at end of cycle, is now complicated by nonlinear equations. A complete account of the asymptotic cycle for any order of M-batch refueling can be given and compared with the linear model. A complete account of the transient cycle can be obtained readily in the two-batch model and this exact solution would be useful in verifying numerical marching models. It is convenient to treat the parabolic fit rho = 1 - tau 2 as a special case of the general quadratic fit rho = 1 - C/sub tau/ - (1 - C)tau 2 in suitably normalized reactivity and cycle time units. The parabolic results are given in this paper

How search in science impacts on the value of inventions at early and late stages in the R&D cycle

DEFF Research Database (Denmark)

Beukel, Karin; Valentin, Finn; Lund Jensen, Rasmus

. The patents filed on these inventions offer, through their citations to prior art, a fine-grained view of the role of science along the R&D cycle. Applying a unique text-mining algorithm we categorize a set of 1,058 patens from Scandinavian drug discovery firms into six types of drug-related inventions. Tests...

Systems Analysis of an Advanced Nuclear Fuel Cycle Based on a Modified UREX+3c Process

Energy Technology Data Exchange (ETDEWEB)

E. R. Johnson; R. E. Best

2009-12-28

The research described in this report was performed under a grant from the U.S. Department of Energy (DOE) to describe and compare the merits of two advanced alternative nuclear fuel cycles -- named by this study as the “UREX+3c fuel cycle” and the “Alternative Fuel Cycle” (AFC). Both fuel cycles were assumed to support 100 1,000 MWe light water reactor (LWR) nuclear power plants operating over the period 2020 through 2100, and the fast reactors (FRs) necessary to burn the plutonium and minor actinides generated by the LWRs. Reprocessing in both fuel cycles is assumed to be based on the UREX+3c process reported in earlier work by the DOE. Conceptually, the UREX+3c process provides nearly complete separation of the various components of spent nuclear fuel in order to enable recycle of reusable nuclear materials, and the storage, conversion, transmutation and/or disposal of other recovered components. Output of the process contains substantially all of the plutonium, which is recovered as a 5:1 uranium/plutonium mixture, in order to discourage plutonium diversion. Mixed oxide (MOX) fuel for recycle in LWRs is made using this 5:1 U/Pu mixture plus appropriate makeup uranium. A second process output contains all of the recovered uranium except the uranium in the 5:1 U/Pu mixture. The several other process outputs are various waste streams, including a stream of minor actinides that are stored until they are consumed in future FRs. For this study, the UREX+3c fuel cycle is assumed to recycle only the 5:1 U/Pu mixture to be used in LWR MOX fuel and to use depleted uranium (tails) for the makeup uranium. This fuel cycle is assumed not to use the recovered uranium output stream but to discard it instead. On the other hand, the AFC is assumed to recycle both the 5:1 U/Pu mixture and all of the recovered uranium. In this case, the recovered uranium is reenriched with the level of enrichment being determined by the amount of recovered plutonium and the combined amount

Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI: a multicentre trial and cost-effectiveness analysis.

Science.gov (United States)

van Tilborg, Theodora C; Oudshoorn, Simone C; Eijkemans, Marinus J C; Mochtar, Monique H; van Golde, Ron J T; Hoek, Annemieke; Kuchenbecker, Walter K H; Fleischer, Kathrin; de Bruin, Jan Peter; Groen, Henk; van Wely, Madelon; Lambalk, Cornelis B; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M; Torrance, Helen L

2017-12-01

Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment? In women initiating IVF/ICSI, AFC-based individualized FSH dosing does not improve live birth rates or reduce costs as compared to a standard FSH dose. In IVF or ICSI, ovarian reserve testing is often used to adjust the FSH dose in order to normalize ovarian response and optimize live birth rates. However, no robust evidence for the (cost-)effectiveness of this practice exists. Between May 2011 and May 2014 we performed a multicentre prospective cohort study with two embedded RCTs in women scheduled for IVF/ICSI. Based on the AFC, women entered into one of the two RCTs (RCT1: AFC 15) or the cohort (AFC 11-15). The primary outcome was ongoing pregnancy achieved within 18 months after randomization resulting in a live birth (delivery of at least one live foetus after 24 weeks of gestation). Data from the cohort with weight 0.5 were combined with both RCTs in order to conduct a strategy analysis. Potential half-integer numbers were rounded up. Differences in costs and effects between the two treatment strategies were compared by bootstrapping. In both RCTs women were randomized to an individualized (RCT1:450/225 IU, RCT2:100 IU) or standard FSH dose (150 IU). Women in the cohort all received the standard dose (150 IU). Anti-Müllerian hormone (AMH) was measured to assess AMH post-hoc as a biomarker to individualize treatment. For RCT1 dose adjustment was allowed in subsequent cycles based on pre-specified criteria in the standard group only. For RCT2 dose adjustment was allowed in subsequent cycles in both groups. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. We included 1515 women, of whom 483 (31.9%) entered the cohort, 511 (33.7%) RCT1 and 521 (34.4%) RCT2. Live births occurred in 420/747 (56.3%) women

The Hamburg oceanic carbon cycle circulation model. Cycle 1

International Nuclear Information System (INIS)

Maier-Reimer, E.; Heinze, C.

1992-02-01

The carbon cycle model calculates the prognostic fields of oceanic geochemical carbon cycle tracers making use of a 'frozen' velocity field provided by a run of the LSG oceanic circulation model (see the corresponding manual, LSG=Large Scale Geostrophic). The carbon cycle model includes a crude approximation of interactions between sediment and bottom layer water. A simple (meridionally diffusive) one layer atmosphere model allows to calculate the CO 2 airborne fraction resulting from the oceanic biogeochemical interactions. (orig.)

Numerical simulation of Ge solar cells using D-AMPS-1D code

Energy Technology Data Exchange (ETDEWEB)

Barrera, Marcela, E-mail: barrera@tandar.cnea.gov.ar [Comision Nacional de Energia Atomica, Avenida General Paz 1499, San Martin 1650, Buenos Aires (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) (Argentina); Rubinelli, Francisco [Instituto de Desarrollo Tecnologico para la Industria Quimica (INTEC)-CONICET, Gueemes 3450, Santa Fe 3000 (Argentina); Rey-Stolle, Ignacio [Instituto de Energia Solar, Universidad Politecnica de Madrid, Avenida Complutense 30, Madrid 28040 (Spain); Pla, Juan [Comision Nacional de Energia Atomica, Avenida General Paz 1499, San Martin 1650, Buenos Aires (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) (Argentina)

2012-08-15

A solar cell is a solid state device that converts the energy of sunlight directly into electricity by the photovoltaic effect. When light with photon energies greater than the band gap is absorbed by a semiconductor material, free electrons and free holes are generated by optical excitation in the material. The main characteristic of a photovoltaic device is the presence of internal electric field able to separate the free electrons and holes so they can pass out of the material to the external circuit before they recombine. Numerical simulation of photovoltaic devices plays a crucial role in their design, performance prediction, and comprehension of the fundamental phenomena ruling their operation. The electrical transport and the optical behavior of the solar cells discussed in this work were studied with the simulation code D-AMPS-1D. This software is an updated version of the one-dimensional (1D) simulation program Analysis of Microelectronic and Photonic Devices (AMPS) that was initially developed at The Penn State University, USA. Structures such as homojunctions, heterojunctions, multijunctions, etc., resulting from stacking layers of different materials can be studied by appropriately selecting characteristic parameters. In this work, examples of cells simulation made with D-AMPS-1D are shown. Particularly, results of Ge photovoltaic devices are presented. The role of the InGaP buffer on the device was studied. Moreover, a comparison of the simulated electrical parameters with experimental results was performed.

Numerical simulation of Ge solar cells using D-AMPS-1D code

International Nuclear Information System (INIS)

Barrera, Marcela; Rubinelli, Francisco; Rey-Stolle, Ignacio; Plá, Juan

2012-01-01

A solar cell is a solid state device that converts the energy of sunlight directly into electricity by the photovoltaic effect. When light with photon energies greater than the band gap is absorbed by a semiconductor material, free electrons and free holes are generated by optical excitation in the material. The main characteristic of a photovoltaic device is the presence of internal electric field able to separate the free electrons and holes so they can pass out of the material to the external circuit before they recombine. Numerical simulation of photovoltaic devices plays a crucial role in their design, performance prediction, and comprehension of the fundamental phenomena ruling their operation. The electrical transport and the optical behavior of the solar cells discussed in this work were studied with the simulation code D-AMPS-1D. This software is an updated version of the one-dimensional (1D) simulation program Analysis of Microelectronic and Photonic Devices (AMPS) that was initially developed at The Penn State University, USA. Structures such as homojunctions, heterojunctions, multijunctions, etc., resulting from stacking layers of different materials can be studied by appropriately selecting characteristic parameters. In this work, examples of cells simulation made with D-AMPS-1D are shown. Particularly, results of Ge photovoltaic devices are presented. The role of the InGaP buffer on the device was studied. Moreover, a comparison of the simulated electrical parameters with experimental results was performed.

Hamiltonian Cycles on Random Eulerian Triangulations

DEFF Research Database (Denmark)

Guitter, E.; Kristjansen, C.; Nielsen, Jakob Langgaard

1998-01-01

. Considering the case n -> 0, this implies that the system of random Eulerian triangulations equipped with Hamiltonian cycles describes a c=-1 matter field coupled to 2D quantum gravity as opposed to the system of usual random triangulations equipped with Hamiltonian cycles which has c=-2. Hence, in this case...

Arabidopsis EST1/SMG7-like protein is a novel regulator of meiotic cell cycle progression

Czech Academy of Sciences Publication Activity Database

Riehs, N.; Akimcheva, S.; Bulánková, P.; Idol, R.; Široký, Jiří; Shippen, D.; Schweizer, D.; Říha, K.

2007-01-01

Roč. 274, č. 1 (2007), s. 71 ISSN 1742-464X. [32nd FEBS Congress - Molecular Machines. 07.07.2007-12.07.2007, Vienna] R&D Projects: GA ČR(CZ) GA522/06/0380 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : meiosis * Arabidopsis * cell cycle Subject RIV: BO - Biophysics

Sizewell B cycle 5 core design with Framatome ANP's CASCADE-3D and British Energy's PANTHER

Energy Technology Data Exchange (ETDEWEB)

Attale, F.; Koegl, J. [Framatome ANP GmbH, Nuclear Fuel Cycle, Erlangen (Germany); Knight, M.; Bryce, P. [British Energy, Nuclear Technology Branch, Gloucester (United Kingdom)

2001-07-01

Sizewell B Cycle 5 is the first cycle, after 4 cycles with BNFL fuel, with a reload consisting of Framatome ANP HTP (high thermal performance) fuel assemblies. The impact of this fuel vendor change on the Nuclear Design area is that, according to British energy's (BE) practice, the Framatome ANP's nuclear design code system CASCADE-3D is used for the majority of the cycle specific safety case calculations. However, other parts of the safety submission (e.g. 3D transient analyses) are made by using the BE code PANTHER. Before using in parallel two different code systems for reload core licensing extensive comparisons of applied methodologies and obtained results were required to ensure an acceptable level of agreement. (orig.)

Low cycle fatigue of austempered ductile cast iron alloyed with nickel at room and at depressed temperature

Czech Academy of Sciences Publication Activity Database

Petrenec, Martin; Beran, Přemysl; Šmíd, Miroslav; Roupcová, Pavla; Tesařová, H.

2009-01-01

Roč. 16, 3a (2009), s. 1-6 ISSN 1335-0803. [Degradácia konštrukčných materiálov 2009. Tatranská Lomnica, 02.09.2009-04.09.2009] R&D Projects: GA AV ČR 1QS200410502 Institutional research plan: CEZ:AV0Z20410507; CEZ:AV0Z10480505 Keywords : Low cycle fatigue * ADI with nickel alloying * Neutron diffraction * Fatigue crack initiation * Depressed temperature Subject RIV: JL - Materials Fatigue , Friction Mechanics

Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein

International Nuclear Information System (INIS)

Lu, Na; Chen, Yan; Wang, Zhengmin; Chen, Guoling; Lin, Qin; Chen, Zheng-Yi; Li, Huawei

2013-01-01

Highlights: ► Shh activation in neonatal cochleae enhances sensory cell proliferation. ► Proliferating supporting cells can transdifferentiate into hair cells. ► Shh promotes proliferation by transiently modulating pRb activity. ► Shh inhibits pRb by inhibiting transcription and increasing phosphorylation of pRb. -- Abstract: Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.

Analysis of thorium and uranium fuel cycles in an iso-breeder lead fast reactor using extended-EQL3D procedure

International Nuclear Information System (INIS)

Fiorina, Carlo; Krepel, Jiri; Cammi, Antonio; Franceschini, Fausto; Mikityuk, Konstantin; Ricotti, Marco Enrico

2013-01-01

Highlights: ► Extension of EQL3D procedure to calculate radio-toxicity and decay heat. ► Characterization of uranium- and thorium-fueled LFR from BOL to equilibrium. ► Safety improvements for a LFR in a closed thorium cycle. ► Advantages of thorium-fueled LFR in terms of decay heat and radio-toxicity generation. ► Safety, decay heat and radio-toxicity concerns for a Th–Pu beginning-of-life core. - Abstract: Use of thorium in fast reactors has typically been considered as a secondary option, mainly thanks to a possible self-sustaining thorium cycle already in thermal reactors and due to the limited breeding capabilities compared to U–Pu in the fast neutron energy range. In recent years nuclear waste management has become more important, and the thorium option has been reconsidered for the claimed potential to burn transuranic waste and the lower build-up of hazardous isotopes in a closed cycle. To ascertain these claims and their limitations, the fuel cycle isotopic inventory, and associated waste radio-toxicity and decay heat, should be quantified and compared to the case of the uranium cycle using realistic core configurations, with complete recycle of all the actinides. Since the transition from uranium to thorium fuel cycles will likely involve a transuranic burning phase, this transition and the challenges that the evolving fuel actinide composition presents, for instance on reactor feedback parameters, should also be analyzed. In the present paper, these issues are investigated based on core physics analysis of the Lead-cooled Fast Reactor ELSY, performed with the fast reactor ERANOS code and the EQL3D procedure allowing full-core characterization of the equilibrium cycle and the transition cycles. In order to compute radio-toxicity and decay heat, EQL3D has been extended by developing a new module, which has been assessed against ORIGEN-S and is presented here. The capability of the EQL3D procedure to treat full-core 3D geometries allowed to

Interaction of environmental contaminants with zebrafish organic anion transporting polypeptide, Oatp1d1 (Slco1d1)

Energy Technology Data Exchange (ETDEWEB)

Popovic, Marta; Zaja, Roko [Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb (Croatia); Fent, Karl [University of Applied Sciences Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Swiss Federal Institute of Technology (ETH Zürich), Department of Environmental System Sciences, Institute of Biogeochemistry and Pollution Dynamics, CH-8092 Zürich (Switzerland); Smital, Tvrtko, E-mail: smital@irb.hr [Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb (Croatia)

2014-10-01

Polyspecific transporters from the organic anion transporting polypeptide (OATP/Oatp) superfamily mediate the uptake of a wide range of compounds. In zebrafish, Oatp1d1 transports conjugated steroid hormones and cortisol. It is predominantly expressed in the liver, brain and testes. In this study we have characterized the transport of xenobiotics by the zebrafish Oatp1d1 transporter. We developed a novel assay for assessing Oatp1d1 interactors using the fluorescent probe Lucifer yellow and transient transfection in HEK293 cells. Our data showed that numerous environmental contaminants interact with zebrafish Oatp1d1. Oatp1d1 mediated the transport of diclofenac with very high affinity, followed by high affinity towards perfluorooctanesulfonic acid (PFOS), nonylphenol, gemfibrozil and 17α-ethinylestradiol; moderate affinity towards carbaryl, diazinon and caffeine; and low affinity towards metolachlor. Importantly, many environmental chemicals acted as strong inhibitors of Oatp1d1. A strong inhibition of Oatp1d1 transport activity was found by perfluorooctanoic acid (PFOA), chlorpyrifos-methyl, estrone (E1) and 17β-estradiol (E2), followed by moderate to low inhibition by diethyl phthalate, bisphenol A, 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4 tetrahydronapthalene and clofibrate. In this study we identified Oatp1d1 as a first Solute Carrier (SLC) transporter involved in the transport of a wide range of xenobiotics in fish. Considering that Oatps in zebrafish have not been characterized before, our work on zebrafish Oatp1d1 offers important new insights on the understanding of uptake processes of environmental contaminants, and contributes to the better characterization of zebrafish as a model species. - Highlights: • We optimized a novel assay for determination of Oatp1d1 interactors • Oatp1d1 is the first SLC characterized fish xenobiotic transporter • PFOS, nonylphenol, diclofenac, EE2, caffeine are high affinity Oatp1d1substrates • PFOA, chlorpyrifos

Interaction of environmental contaminants with zebrafish organic anion transporting polypeptide, Oatp1d1 (Slco1d1)

International Nuclear Information System (INIS)

Popovic, Marta; Zaja, Roko; Fent, Karl; Smital, Tvrtko

2014-01-01

Polyspecific transporters from the organic anion transporting polypeptide (OATP/Oatp) superfamily mediate the uptake of a wide range of compounds. In zebrafish, Oatp1d1 transports conjugated steroid hormones and cortisol. It is predominantly expressed in the liver, brain and testes. In this study we have characterized the transport of xenobiotics by the zebrafish Oatp1d1 transporter. We developed a novel assay for assessing Oatp1d1 interactors using the fluorescent probe Lucifer yellow and transient transfection in HEK293 cells. Our data showed that numerous environmental contaminants interact with zebrafish Oatp1d1. Oatp1d1 mediated the transport of diclofenac with very high affinity, followed by high affinity towards perfluorooctanesulfonic acid (PFOS), nonylphenol, gemfibrozil and 17α-ethinylestradiol; moderate affinity towards carbaryl, diazinon and caffeine; and low affinity towards metolachlor. Importantly, many environmental chemicals acted as strong inhibitors of Oatp1d1. A strong inhibition of Oatp1d1 transport activity was found by perfluorooctanoic acid (PFOA), chlorpyrifos-methyl, estrone (E1) and 17β-estradiol (E2), followed by moderate to low inhibition by diethyl phthalate, bisphenol A, 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4 tetrahydronapthalene and clofibrate. In this study we identified Oatp1d1 as a first Solute Carrier (SLC) transporter involved in the transport of a wide range of xenobiotics in fish. Considering that Oatps in zebrafish have not been characterized before, our work on zebrafish Oatp1d1 offers important new insights on the understanding of uptake processes of environmental contaminants, and contributes to the better characterization of zebrafish as a model species. - Highlights: • We optimized a novel assay for determination of Oatp1d1 interactors • Oatp1d1 is the first SLC characterized fish xenobiotic transporter • PFOS, nonylphenol, diclofenac, EE2, caffeine are high affinity Oatp1d1substrates • PFOA, chlorpyrifos

Influence of pores on crack initiation in monotonic tensile and cyclic loadings in lost foam casting A319 alloy by using 3D in-situ analysis

International Nuclear Information System (INIS)

Wang, Long; Limodin, Nathalie; El Bartali, Ahmed; Witz, Jean-François; Seghir, Rian; Buffiere, Jean-Yves; Charkaluk, Eric

2016-01-01

Lost Foam Casting (LFC) process is replacing the conventional gravity Die Casting (DC) process in automotive industry for the purpose of geometry optimization, cost reduction and consumption control. However, due to lower cooling rate, LFC produces in a coarser microstructure that reduces fatigue life. In order to study the influence of the casting microstructure of LFC Al-Si alloy on damage micromechanisms under monotonic tensile loading and Low Cycle Fatigue (LCF) at room temperature, an experimental protocol based on the three dimensional (3D) in-situ analysis has been set up and validated. This paper focuses on the influence of pores on crack initiation in monotonic and cyclic tensile loadings. X-ray Computed Tomography (CT) allowed the microstructure of material being characterized in 3D and damage evolution being followed in-situ also in 3D. Experimental and numerical mechanical fields were obtained by using Digital Volume Correlation (DVC) technique and Finite Element Method (FEM) simulation respectively. Pores were shown to have an important influence on strain localization as large pores generate enough strain localization zones for crack initiation both in monotonic tensile and cyclic loadings.

Influence of pores on crack initiation in monotonic tensile and cyclic loadings in lost foam casting A319 alloy by using 3D in-situ analysis

Energy Technology Data Exchange (ETDEWEB)

Wang, Long, E-mail: longwang_calt@163.com [Univ. Lille, CNRS, Centrale Lille, Arts et Metiers Paris tech, FRE 3723 – LML – Laboratoire de Mecanique de Lille, F-59000 Lille (France); Limodin, Nathalie; El Bartali, Ahmed; Witz, Jean-François; Seghir, Rian [Univ. Lille, CNRS, Centrale Lille, Arts et Metiers Paris tech, FRE 3723 – LML – Laboratoire de Mecanique de Lille, F-59000 Lille (France); Buffiere, Jean-Yves [Laboratoire Matériaux, Ingénierie et Sciences (MATEIS), CNRS UMR5510, INSA-Lyon, 20 Av. Albert Einstein, 69621 Villeurbanne (France); Charkaluk, Eric [Univ. Lille, CNRS, Centrale Lille, Arts et Metiers Paris tech, FRE 3723 – LML – Laboratoire de Mecanique de Lille, F-59000 Lille (France)

2016-09-15

Lost Foam Casting (LFC) process is replacing the conventional gravity Die Casting (DC) process in automotive industry for the purpose of geometry optimization, cost reduction and consumption control. However, due to lower cooling rate, LFC produces in a coarser microstructure that reduces fatigue life. In order to study the influence of the casting microstructure of LFC Al-Si alloy on damage micromechanisms under monotonic tensile loading and Low Cycle Fatigue (LCF) at room temperature, an experimental protocol based on the three dimensional (3D) in-situ analysis has been set up and validated. This paper focuses on the influence of pores on crack initiation in monotonic and cyclic tensile loadings. X-ray Computed Tomography (CT) allowed the microstructure of material being characterized in 3D and damage evolution being followed in-situ also in 3D. Experimental and numerical mechanical fields were obtained by using Digital Volume Correlation (DVC) technique and Finite Element Method (FEM) simulation respectively. Pores were shown to have an important influence on strain localization as large pores generate enough strain localization zones for crack initiation both in monotonic tensile and cyclic loadings.

U.S. FUEL CYCLE TECHNOLOGIES R&D PROGRAM FOR NEXT GENERATION NUCLEAR MATERIALS MANAGEMENT

Directory of Open Access Journals (Sweden)

M.C. MILLER

2013-11-01

Full Text Available The U.S. Department of Energy's Fuel Cycle Technologies R&D program under the Office of Nuclear Energy is working to advance technologies to enhance both the existing and future fuel cycles. One thrust area is in developing enabling technologies for next generation nuclear materials management under the Materials Protection, Accounting and Control Technologies (MPACT Campaign where advanced instrumentation, analysis and assessment methods, and security approaches are being developed under a framework of Safeguards and Security by Design. An overview of the MPACT campaign's activities and recent accomplishments is presented along with future plans.

1,5-Anhydro-D-fructose from D-fructose

DEFF Research Database (Denmark)

Dekany, Gyula; Lundt, Inge; Niedermaier, Fabian

2007-01-01

1,5-Anhydro-D-fructose was efficiently prepared from D-fructose via regiospecific 1,5-anhydro ring formation of 2,3-O-isopropylidene-1-O-methyl(tolyl)sulfonyl-D-fructopyranose and subsequent deprotection.......1,5-Anhydro-D-fructose was efficiently prepared from D-fructose via regiospecific 1,5-anhydro ring formation of 2,3-O-isopropylidene-1-O-methyl(tolyl)sulfonyl-D-fructopyranose and subsequent deprotection....

microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2.

Science.gov (United States)

Nie, Jing; Liu, Lin; Zheng, Wei; Chen, Lin; Wu, Xin; Xu, Yingxin; Du, Xiaohui; Han, Weidong

2012-01-01

Deregulated microRNAs participate in carcinogenesis and cancer progression, but their roles in cancer development remain unclear. In this study, miR-365 expression was found to be downregulated in human colon cancer tissues as compared with that in matched non-neoplastic mucosa tissues, and its downregulation was correlated with cancer progression and poor survival in colon cancer patients. Functional studies revealed that restoration of miR-365 expression inhibited cell cycle progression, promoted 5-fluorouracil-induced apoptosis and repressed tumorigenicity in colon cancer cell lines. Furthermore, bioinformatic prediction and experimental validation were used to identify miR-365 target genes and indicated that the antitumor effects of miR-365 were probably mediated by its targeting and repression of Cyclin D1 and Bcl-2 expression, thus inhibiting cell cycle progression and promoting apoptosis. These results suggest that downregulation of miR-365 in colon cancer may have potential applications in prognosis prediction and gene therapy in colon cancer patients.

4d N=1 from 6d (1,0)

Energy Technology Data Exchange (ETDEWEB)

Razamat, Shlomo S. [Physics Department, Technion,Haifa, 32000 (Israel); Vafa, Cumrun [Jefferson Physical Laboratory, Harvard University,Cambridge, MA 02138 (United States); Zafrir, Gabi [Physics Department, Technion,Haifa, 32000 (Israel); Kavli IPMU (WPI), UTIAS, the University of Tokyo,Kashiwa, Chiba 277-8583 (Japan)

2017-04-11

We study the geometry of 4d N=1 SCFT’s arising from compactification of 6d (1,0) SCFT’s on a Riemann surface. We show that the conformal manifold of the resulting theory is characterized, in addition to moduli of complex structure of the Riemann surface, by the choice of a connection for a vector bundle on the surface arising from flavor symmetries in 6d. We exemplify this by considering the case of 4d N=1 SCFT’s arising from M5 branes probing ℤ{sub k} singularity compactified on a Riemann surface. In particular, we study in detail the four dimensional theories arising in the case of two M5 branes on ℤ{sub 2} singularity. We compute the conformal anomalies and indices of such theories in 4d and find that they are consistent with expectations based on anomaly and the moduli structure derived from the 6 dimensional perspective.

Change in serum 25-hydroxyvitamin D with antiretroviral treatment initiation and nutritional intervention in HIV-positive adults

DEFF Research Database (Denmark)

Yilma, Daniel; Kæstel, Pernille; Olsen, Mette Frahm

2016-01-01

daily allowance of vitamin D (10 μg/200 g). The level of serum 25(OH)D before nutritional intervention and ART initiation was compared with serum 25(OH)D of HIV-negative individuals. A total of 348 HIV-positive and 100 HIV-negative persons were recruited. The median baseline serum 25(OH)D level......Low vitamin D level in HIV-positive persons has been associated with disease progression. We compared the levels of serum 25-hydroxyvitamin D (25(OH)D) in HIV-positive and HIV-negative persons, and investigated the role of nutritional supplementation and antiretroviral treatment (ART) on serum 25...... was higher in HIV-positive than in HIV-negative persons (42·5 v. 35·3 nmol/l, P17 kg/m2 were randomised to either LNS supplementation (n 189) or no supplementation (n 93) during the first 3 months of ART. The supplemented group had a 4·1 (95 % CI 1·7, 6·4) nmol/l increase in serum 25(OH)D, whereas the non...

4D stress evolution models of the San Andreas Fault System: Investigating time- and depth-dependent stress thresholds over multiple earthquake cycles

Science.gov (United States)

Burkhard, L. M.; Smith-Konter, B. R.

2017-12-01

4D simulations of stress evolution provide a rare insight into earthquake cycle crustal stress variations at seismogenic depths where earthquake ruptures nucleate. Paleoseismic estimates of earthquake offset and chronology, spanning multiple earthquakes cycles, are available for many well-studied segments of the San Andreas Fault System (SAFS). Here we construct new 4D earthquake cycle time-series simulations to further study the temporally and spatially varying stress threshold conditions of the SAFS throughout the paleoseismic record. Interseismic strain accumulation, co-seismic stress drop, and postseismic viscoelastic relaxation processes are evaluated as a function of variable slip and locking depths along 42 major fault segments. Paleoseismic earthquake rupture histories provide a slip chronology dating back over 1000 years. Using GAGE Facility GPS and new Sentinel-1A InSAR data, we tune model locking depths and slip rates to compute the 4D stress accumulation within the seismogenic crust. Revised estimates of stress accumulation rate are most significant along the Imperial (2.8 MPa/100yr) and Coachella (1.2 MPa/100yr) faults, with a maximum change in stress rate along some segments of 11-17% in comparison with our previous estimates. Revised estimates of earthquake cycle stress accumulation are most significant along the Imperial (2.25 MPa), Coachella (2.9 MPa), and Carrizo (3.2 MPa) segments, with a 15-29% decrease in stress due to locking depth and slip rate updates, and also postseismic relaxation from the El Mayor-Cucapah earthquake. Because stress drops of major strike-slip earthquakes rarely exceed 10 MPa, these models may provide a lower bound on estimates of stress evolution throughout the historical era, and perhaps an upper bound on the expected recurrence interval of a particular fault segment. Furthermore, time-series stress models reveal temporally varying stress concentrations at 5-10 km depths, due to the interaction of neighboring fault

Effects of asphalt fume condensate exposure on acute pulmonary responses

Energy Technology Data Exchange (ETDEWEB)

Ma, J.Y.C.; Barger, M.W.; Castranova, V. [Health Effects Lab. Div., National Inst. for Occupational Safety and Health, Morgantown, WV (United States); Kriech, A.J. [Heritage Research Group, Indianapolis, IN (United States)

2000-10-01

The present study was carried out to characterize the effects of in vitro exposure to paving asphalt fume condensate (AFC) on alveolar macrophage (AM) functions and to monitor acute pulmonary responses to in vivo AFC exposure in rats. Methods: For in vitro studies, rat primary AM cultures were incubated with various concentrations of AFC for 24 h at 37 C. AM-conditioned medium was collected and assayed for lactate dehydrogenase (LDH) as a marker of cytotoxicity. Tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-1 (IL-1) production were assayed in AM-conditioned medium to monitor AM function. The effect of AFC on chemiluminescence (CL) generated by resting AM or AM in response to zymosan or PMA stimulation was also determined as a marker of AM activity. For in vivo studies, rats received either (1) a single intratracheal (IT) instillation of saline, or 0.1 mg or 0.5 mg AFC and were killed 1 or 3 days later; or (2) IT instillation of saline, or 0.1, 0.5, or 2 mg AFC for three consecutive days and were killed the following day. Differential counts of cells harvested by bronchoalveolar lavage were measured to monitor inflammation. Acellular LDH and protein content in the first lavage fluid were measured to monitor damage. CL generation, TNF-{alpha} and IL-1 production by AM were assayed to monitor AM function. Results: In vitro AFC exposure at <200 {mu}g/ml did not induce cytotoxicity, oxidant generation, or IL-1 production by AM, but it did cause a small but significant increase in TNF-{alpha} release from AM. In vitro exposure of AM to AFC resulted in a significant decline of CL in response to zymosan or PMA stimulation. The in vivo studies showed that AFC exposure did not induce significant neutrophil infiltration or alter LDH or protein content in acellular lavage samples. Macrophages obtained from AFC-exposed rats did not show significant differences in oxidant production or cytokine secretion at rest or in response to LPS in comparison with control

International nuclear fuel cycle fact book. Revision 6

International Nuclear Information System (INIS)

Harmon, K.M.; Lakey, L.T.; Leigh, I.W.; Jeffs, A.G.

1986-01-01

The International Fuel Cycle Fact Book has been compiled in an effort to provide (1) an overview of worldwide nuclear power and fuel cycle programs and (2) current data concerning fuel cycle and waste management facilities, R and D programs and key personnel. Additional information on each country's program is available in the International Source Book: Nuclear Fuel Cycle Research and Development, PNL-2478, Rev. 2

A metabolic nitrogen balance study for 40 d and evaluation of the menstrual cycle on protein requirement in young Nigerian women.

Science.gov (United States)

Egun, G N; Atinmo, T

1993-09-01

A long-term N balance study was carried out to determine the adequacy of an estimated protein requirement level recommended for young healthy Nigerian women and the effect of the menstrual cycle on the requirement. Eleven healthy young women, 25 (SD 2.6) years, were fed on a diet providing 0.6 g protein (N x 6.25)/kg per d and an average energy intake of 0.17 (SD 0.012) MJ/kg per d. Urine, faeces, sweat and menstrual fluids were collected for estimation of N balance. Menstrual N loss varied among individuals ranging from 46 to 124 mg N/d with an average of 89 (SD 21.8) mg N/d. Individual N balance was found to vary according to the day of the menstrual cycle. Positive N balances were recorded at about ovulation while negative balances were observed just before the onset of menstruation. The average N balance ranged from +8.49 (SD 5.64) to -430 (SD 7.84) mg N/kg per d. Nevertheless, an overall cumulative positive N balance of +5.7 (SD 6.98) mg N/kg per d which did not change significantly with time was observed for the last 5 d of two consecutive 20 d diet periods, although three subjects were in negative N balance. Blood biochemical measurements were stable except for one subject who had elevated serum aspartate aminotransferase (EC 2.6.1.1) levels. These findings suggest that our estimate of protein requirements was sufficient to achieve N balance equilibrium in a majority (70%) of young women. However, to satisfy 97.5% of the population, slight adjustments might be necessary in the energy intake since subjects who were in cumulative negative N balance also lost weight.

CARMA3 is overexpressed in colon cancer and regulates NF-κB activity and cyclin D1 expression

International Nuclear Information System (INIS)

Miao, Zhifeng; Zhao, Tingting; Wang, Zhenning; Xu, Yingying; Song, Yongxi; Wu, Jianhua; Xu, Huimian

2012-01-01

Highlights: ► CARMA3 expression is elevated in colon cancers. ► CARMA3 promotes proliferation and cell cycle progression in colon cancer cells. ► CARMA3 upregulates cyclinD1 through NF-κB activation. -- Abstract: CARMA3 was recently reported to be overexpressed in cancers and associated with the malignant behavior of cancer cells. However, the expression of CARMA3 and its biological roles in colon cancer have not been reported. In the present study, we analyzed the expression pattern of CARMA3 in colon cancer tissues and found that CARMA3 was overexpressed in 30.8% of colon cancer specimens. There was a significant association between CARMA3 overexpression and TNM stage (p = 0.0383), lymph node metastasis (p = 0.0091) and Ki67 proliferation index (p = 0.0035). Furthermore, knockdown of CARMA3 expression in HT29 and HCT116 cells with high endogenous expression decreased cell proliferation and cell cycle progression while overexpression of CARMA3 in LoVo cell line promoted cell proliferation and facilitated cell cycle transition. Further analysis showed that CARMA3 knockdown downregulated and its overexpression upregulated cyclin D1 expression and phospho-Rb levels. In addition, we found that CARMA3 depletion inhibited p-IκB levels and NF-κB activity and its overexpression increased p-IκB expression and NF-κB activity. NF-κB inhibitor BAY 11-7082 reversed the role of CARMA3 on cyclin D1 upregulation. In conclusion, our study found that CARMA3 is overexpressed in colon cancers and contributes to malignant cell growth by facilitating cell cycle progression through NF-κB mediated upregulation of cyclin D1.

Determination of a Wear Initiation Cycle by using a Contact Resistance Measurement in Nuclear Fuel Fretting

International Nuclear Information System (INIS)

Lee, Young Ho; Kim, Hyung Kyu

2008-01-01

In nuclear fuel fretting, the improving of the contact condition with a modified spring shape is a useful method for increasing the wear resistance of the nuclear fuel rod. This is because the fretting wear resistance between the fuel rod and grid spring is mainly affected by the grid spring shape rather than the environment, the contact modes, etc. In addition, the wear resistance is affected by the wear debris behavior between contact surfaces. So, it is expected that the wear initiation of each spring shape should be determined in order to evaluate a wear resistance. However, it is almost impossible to measure the wear behavior in contact surfaces on a real time basis because the contact surfaces are always hidden. Besides, the results of the worn surface observation after the fretting wear tests are restricted to archive the information on the wear debris behavior and the formation mechanism of the wear scar. In order to evaluate the wear behavior during the fretting wear tests, it is proposed that the contact resistance measurement is a useful method for examining the wear initiation cycle and modes. Generally, fretting wear damages are rapidly progressed by a localized plastic deformation between the contact surfaces, crack initiation and fracture of the deformed surface with a strain hardening difference between a surface and a subsurface and finally a detachment of wear debris. After this, wear debris is easily oxidized by frictional heat, test environment, etc. At this time, a small amount of electric current applied between the contact surfaces will be influenced by the wear debris, which could be an obstacle to an electric current flow. So, it is possible to archive the information on the wear behavior by measuring the contact resistance. In order to determine the wear initiation cycle during the fretting wear tests, in this study, fretting wear tests have been performed by applying a constant electric current in room temperature air

Edge-disjoint Hamiltonian cycles in hypertournaments

DEFF Research Database (Denmark)

Thomassen, Carsten

2006-01-01

We introduce a method for reducing k-tournament problems, for k >= 3, to ordinary tournaments, that is, 2-tournaments. It is applied to show that a k-tournament on n >= k + 1 + 24d vertices (when k >= 4) or on n >= 30d + 2 vertices (when k = 3) has d edge-disjoint Hamiltonian cycles if and only...

Anti-müllerian hormone levels are associated with live birth rates in ART, but the predictive ability of anti-müllerian hormone is modest.

Science.gov (United States)

Alson, Sara S E; Bungum, Leif J; Giwercman, Aleksander; Henic, Emir

2018-06-01

The aim was to evaluate the association between serum Anti-Müllerian Hormone (AMH) level and cumulative live birth rates (LBR) in patients undergoing their first in vitro fertilization (IVF) treatment cycle, and to compare serum AMH levels with Antral Follicle Count (AFC) and Ovarian Sensitivity Index (OSI) as predictors of live birth. A prospective cohort study of 454 patients under the age of 40 and with a regular menstrual cycle of 21-35 days, undergoing their first IVF treatment cycles between September 2010 and June 2015. Participants were divided into three groups based on their AMH level, (AMH ≤10, AMH 10-distribution between patients with or without live birth was analyzed using a Mann-Whitney-test, and live birth rates were compared between groups by a chi-squared test for linear trend. The ability of AMH, OSI and AFC as predictors of live birth was assessed by a receiver operating characteristics-analysis and the area under the curve (AUC) was calculated. Patients with live birth had a higher AMH, median (range) 26 [0-137] pmol/l, compared with patients without live birth, AMH 22 [0-154] pmol/l, p = 0.035. Mean live birth rate (SD) was 0.36 (0.48) in the total cohort, 0.26 (0.44) in AMH-group birth rates increased with 8% per AMH-group (95% CI: 0.02 -0.14, p = 0.015). The AUC for AFC was 0.56, for AMH 0.57 and for OSI 0.63, respectively. AMH concentration in serum is associated with live birth rates after IVF. Our results suggest that both AMH, AFC and OSI have an equal but modest predictive ability in relation to live birth rate. Copyright © 2018 Elsevier B.V. All rights reserved.

U. S. Fuel Cycle Technologies R and D Program for Next Generation Nuclear Materials Management

International Nuclear Information System (INIS)

Miller, M. C.; Vega, D. A.

2013-01-01

The U. S. Department of Energy's Fuel Cycle Technologies R and D program under the Office of Nuclear Energy is working to advance technologies to enhance both the existing and future fuel cycles. One thrust area is in developing enabling technologies for next generation nuclear materials management under the Materials Protection, Accounting and Control Technologies (MPACT) Campaign where advanced instrumentation, analysis and assessment methods, and security approaches are being developed under a framework of Safeguards and Security by Design. An overview of the MPACT campaign's activities and recent accomplishments is presented along with future plans

Fast isotropic banding-free bSSFP imaging using 3D dynamically phase-cycled radial bSSFP (3D DYPR-SSFP)

Energy Technology Data Exchange (ETDEWEB)

Benkert, Thomas; Blaimer, Martin; Breuer, Felix A. [Research Center Magnetic Resonance Bavaria (MRB), Wuerzburg (Germany); Ehses, Philipp [Tuebingen Univ. (Germany). Dept. of Neuroimaging; Max Planck Institute for Biological Cybernetics, Tuebingen (Germany). High-Field MR Center; Jakob, Peter M. [Research Center Magnetic Resonance Bavaria (MRB), Wuerzburg (Germany); Wuerzburg Univ. (Germany). Dept. of Experimental Physics 5

2016-05-01

Aims: Dynamically phase-cycled radial balanced steady-state free precession (DYPR-SSFP) is a method for efficient banding artifact removal in bSSFP imaging. Based on a varying radiofrequency (RF) phase-increment in combination with a radial trajectory, DYPR-SSFP allows obtaining a banding-free image out of a single acquired k-space. The purpose of this work is to present an extension of this technique, enabling fast three-dimensional isotropic banding-free bSSFP imaging. Methods: While banding artifact removal with DYPR-SSFP relies on the applied dynamic phase-cycle, this aspect can lead to artifacts, at least when the number of acquired projections lies below a certain limit. However, by using a 3D radial trajectory with quasi-random view ordering for image acquisition, this problem is intrinsically solved, enabling 3D DYPR-SSFP imaging at or even below the Nyquist criterion. The approach is validated for brain and knee imaging at 3 Tesla. Results: Volumetric, banding-free images were obtained in clinically acceptable scan times with an isotropic resolution up to 0.56 mm. Conclusion: The combination of DYPR-SSFP with a 3D radial trajectory allows banding-free isotropic volumetric bSSFP imaging with no expense of scan time. Therefore, this is a promising candidate for clinical applications such as imaging of cranial nerves or articular cartilage.

Sequence of neuron origin and neocortical laminar fate: relation to cell cycle of origin in the developing murine cerebral wall

Science.gov (United States)

Takahashi, T.; Goto, T.; Miyama, S.; Nowakowski, R. S.; Caviness, V. S. Jr

1999-01-01

Neurons destined for each region of the neocortex are known to arise approximately in an "inside-to-outside" sequence from a pseudostratified ventricular epithelium (PVE). This sequence is initiated rostrolaterally and propagates caudomedially. Moreover, independently of location in the PVE, the neuronogenetic sequence in mouse is divisible into 11 cell cycles that occur over a 6 d period. Here we use a novel "birth hour" method that identifies small cohorts of neurons born during a single 2 hr period, i.e., 10-20% of a single cell cycle, which corresponds to approximately 1.5% of the 6 d neuronogenetic period. This method shows that neurons arising with the same cycle of the 11 cycle sequence in mouse have common laminar fates even if they arise from widely separated positions on the PVE (neurons of fields 1 and 40) and therefore arise at different embryonic times. Even at this high level of temporal resolution, simultaneously arising cells occupy more than one cortical layer, and there is substantial overlap in the distributions of cells arising with successive cycles. We demonstrate additionally that the laminar representation of cells arising with a given cycle is little if at all modified over the early postnatal interval of histogenetic cell death. We infer from these findings that cell cycle is a neuronogenetic counting mechanism and that this counting mechanism is integral to subsequent processes that determine cortical laminar fate.

Nuclear-fuel-cycle education: Module 1. Nuclear fuel cycle overview

International Nuclear Information System (INIS)

Eckhoff, N.D.

1981-07-01

This educational module is an overview of the nuclear-fule-cycle. The overview covers nuclear energy resources, the present and future US nuclear industry, the industry view of nuclear power, the International Nuclear Fuel Cycle Evaluation program, the Union of Concerned Scientists view of the nuclear-fuel-cycle, an analysis of this viewpoint, resource requirements for a model light water reactor, and world nuclear power considerations

Multi-Unit Initiating Event Analysis for a Single-Unit Internal Events Level 1 PSA

Energy Technology Data Exchange (ETDEWEB)

Kim, Dong San; Park, Jin Hee; Lim, Ho Gon [KAERI, Daejeon (Korea, Republic of)

2016-05-15

The Fukushima nuclear accident in 2011 highlighted the importance of considering the risks from multi-unit accidents at a site. The ASME/ANS probabilistic risk assessment (PRA) standard also includes some requirements related to multi-unit aspects, one of which (IE-B5) is as follows: 'For multi-unit sites with shared systems, DO NOT SUBSUME multi-unit initiating events if they impact mitigation capability [1].' However, the existing single-unit PSA models do not explicitly consider multi-unit initiating events and hence systems shared by multiple units (e.g., alternate AC diesel generator) are fully credited for the single unit and ignores the need for the shared systems by other units at the same site [2]. This paper describes the results of the multi-unit initiating event (IE) analysis performed as a part of the at-power internal events Level 1 probabilistic safety assessment (PSA) for an OPR1000 single unit ('reference unit'). In this study, a multi-unit initiating event analysis for a single-unit PSA was performed, and using the results, dual-unit LOOP initiating event was added to the existing PSA model for the reference unit (OPR1000 type). Event trees were developed for dual-unit LOOP and dual-unit SBO which can be transferred from dual- unit LOOP. Moreover, CCF basic events for 5 diesel generators were modelled. In case of simultaneous SBO occurrences in both units, this study compared two different assumptions on the availability of the AAC D/G. As a result, when dual-unit LOOP initiating event was added to the existing single-unit PSA model, the total CDF increased by 1∼ 2% depending on the probability that the AAC D/G is available to a specific unit in case of simultaneous SBO in both units.

International nuclear fuel cycle fact book. Revision 6

Energy Technology Data Exchange (ETDEWEB)

Harmon, K.M.; Lakey, L.T.; Leigh, I.W.; Jeffs, A.G.

1986-01-01

The International Fuel Cycle Fact Book has been compiled in an effort to provide (1) an overview of worldwide nuclear power and fuel cycle programs and (2) current data concerning fuel cycle and waste management facilities, R and D programs and key personnel. Additional information on each country's program is available in the International Source Book: Nuclear Fuel Cycle Research and Development, PNL-2478, Rev. 2.

Non-thermal distribution of O(1D) atoms in the night-time thermosphere

Science.gov (United States)

Yee, Jeng-Hwa

1988-01-01

The 6300 A O(1D-3P) emission has been used for many years to remotely monitor the thermospheric temperature from the Doppler width of its line profile. The O(1D) atoms in the nighttime thermosphere are initially produced by the dissociative recombination of O2(+) ions with kinetic energy much greater than the thermal energy of the ambient neutrals. The validity of the technique to monitor neutral ambient temperature by measuring O(1D) 6300 A emission depends on the degree of thermalization of the O(1D) atoms. The object of this study is to calculate the velocity distribution of the O(1D) atoms and to examine the effect of nonthermal distribution on the nighttime thermospheric neutral temperature determined.

SUMO modification of Stra13 is required for repression of cyclin D1 expression and cellular growth arrest.

Directory of Open Access Journals (Sweden)

Yaju Wang

Full Text Available Stra13, a basic helix-loop-helix (bHLH transcription factor is involved in myriad biological functions including cellular growth arrest, differentiation and senescence. However, the mechanisms by which its transcriptional activity and function are regulated remain unclear. In this study, we provide evidence that post-translational modification of Stra13 by Small Ubiquitin-like Modifier (SUMO dramatically potentiates its ability to transcriptionally repress cyclin D1 and mediate G(1 cell cycle arrest in fibroblast cells. Mutation of SUMO acceptor lysines 159 and 279 located in the C-terminal repression domain has no impact on nuclear localization; however, it abrogates association with the co-repressor histone deacetylase 1 (HDAC1, attenuates repression of cyclin D1, and prevents Stra13-mediated growth suppression. HDAC1, which promotes cellular proliferation and cell cycle progression, antagonizes Stra13 sumoylation-dependent growth arrest. Our results uncover an unidentified regulatory axis between Stra13 and HDAC1 in progression through the G(1/S phase of the cell cycle, and provide new mechanistic insights into regulation of Stra13-mediated transcriptional repression by sumoylation.

Engineering 3D bicontinuous hierarchically macro-mesoporous LiFePO4/C nanocomposite for lithium storage with high rate capability and long cycle stability.

Science.gov (United States)

Zhang, Qian; Huang, Shao-Zhuan; Jin, Jun; Liu, Jing; Li, Yu; Wang, Hong-En; Chen, Li-Hua; Wang, Bin-Jie; Su, Bao-Lian

2016-05-16

A highly crystalline three dimensional (3D) bicontinuous hierarchically macro-mesoporous LiFePO4/C nanocomposite constructed by nanoparticles in the range of 50~100 nm via a rapid microwave assisted solvothermal process followed by carbon coating have been synthesized as cathode material for high performance lithium-ion batteries. The abundant 3D macropores allow better penetration of electrolyte to promote Li(+) diffusion, the mesopores provide more electrochemical reaction sites and the carbon layers outside LiFePO4 nanoparticles increase the electrical conductivity, thus ultimately facilitating reverse reaction of Fe(3+) to Fe(2+) and alleviating electrode polarization. In addition, the particle size in nanoscale can provide short diffusion lengths for the Li(+) intercalation-deintercalation. As a result, the 3D macro-mesoporous nanosized LiFePO4/C electrode exhibits excellent rate capability (129.1 mA h/g at 2 C; 110.9 mA h/g at 10 C) and cycling stability (87.2% capacity retention at 2 C after 1000 cycles, 76.3% at 5 C after 500 cycles and 87.8% at 10 C after 500 cycles, respectively), which are much better than many reported LiFePO4/C structures. Our demonstration here offers the opportunity to develop nanoscaled hierarchically porous LiFePO4/C structures for high performance lithium-ion batteries through microwave assisted solvothermal method.

A conserved cyclin-binding domain determines functional interplay between anaphase-promoting complex-Cdh1 and cyclin A-Cdk2 during cell cycle progression

DEFF Research Database (Denmark)

Lukas, C; Kramer, E R; Peters, J M

2001-01-01

Periodic activity of the anaphase-promoting complex (APC) ubiquitin ligase determines progression through multiple cell cycle transitions by targeting cell cycle regulators for destruction. At the G(1)/S transition, phosphorylation-dependent dissociation of the Cdh1-activating subunit inhibits...... the APC, allowing stabilization of proteins required for subsequent cell cycle progression. Cyclin-dependent kinases (CDKs) that initiate and maintain Cdh1 phosphorylation have been identified. However, the issue of which cyclin-CDK complexes are involved has been a matter of debate, and the mechanism...... of how cyclin-CDKs interact with APC subunits remains unresolved. Here we substantiate the evidence that mammalian cyclin A-Cdk2 prevents unscheduled APC reactivation during S phase by demonstrating its periodic interaction with Cdh1 at the level of endogenous proteins. Moreover, we identified...

Regulation of the cell cycle by irradiation

International Nuclear Information System (INIS)

Akashi, Makoto

1995-01-01

The molecular mechanism of cell proliferation is extremely complex; deregulation results in neoplastic transformation. In eukaryotes, proliferation of cells is finely regulated through the cell cycle. Studies have shown that the cell cycle is regulated by s series of enzymes known as cyclin-dependent kinases (CDKs). The activities of CDKs are controlled by their association with regulatory subunits, cyclins; the expression of cyclins and the activation of the different cyclin-CDK complexes are required for the cell to cycle. Thus, the cell cycle is regulated by activating and inhibiting phosphorylation of the CDK subunits and this program has internal check points at different stages of the cell cycle. When cells are exposed to external insults such as DNA damaging agents, negative regulation of the cell cycle occurs; arrest in either G1 or G2 stage is induced to prevent the cells from prematurely entering into the next stage before DNA is repaired. Recently, a potent inhibitor of CDKs, which inhibits the phosphorylation of retinoblastoma susceptibility (Rb) gene product by cyclin A-CDK2, cyclin E-CDK2, cyclin D1-CDK4, and cyclin D2-CDK4 complexes has been identified. This protein named WAF1, Sdi1, Cip1, or p21 (a protein of Mr 21,000) contains a p53-binding site in its promoter and studies have reported that the expression of WAF1 was directly regulated by p53; cells with loss of p53 activity due to mutational alteration were unable to induce WAF1. This chapter will be focused on the mechanisms of the cell cycle including inhibitors of CDKs, and the induction of WAF1 by irradiation through a pathway independent of p53 will be also described. (author)

Involvement of Dopamine D1/D5 and D2 Receptors in Context-Dependent Extinction Learning and Memory Reinstatement.

Science.gov (United States)

André, Marion Agnès Emma; Manahan-Vaughan, Denise

2015-01-01

Dopamine contributes to the regulation of higher order information processing and executive control. It is important for memory consolidation processes, and for the adaptation of learned responses based on experience. In line with this, under aversive learning conditions, application of dopamine receptor antagonists prior to extinction result in enhanced memory reinstatement. Here, we investigated the contribution of the dopaminergic system to extinction and memory reinstatement (renewal) of an appetitive spatial learning task in rodents. Rats were trained for 3 days in a T-maze (context "A") to associate a goal arm with a food reward, despite low reward probability (acquisition phase). On day 4, extinction learning (unrewarded) occurred, that was reinforced by a context change ("B"). On day 5, re-exposure to the (unrewarded) "A" context took place (renewal of context "A", followed by extinction of context "A"). In control animals, significant extinction occurred on day 4, that was followed by an initial memory reinstatement (renewal) on day 5, that was, in turn, succeeded by extinction of renewal. Intracerebral treatment with a D1/D5-receptor antagonist prior to the extinction trials, elicited a potent enhancement of extinction in context "B". By contrast, a D1/D5-agonist impaired renewal in context "A". Extinction in the "A" context on day 5 was unaffected by the D1/D5-ligands. Treatment with a D2-receptor antagonist prior to extinction had no overall effect on extinction in context "B" or renewal in context "A", although extinction of the renewal effect was impaired on day 5, compared to controls. Taken together, these data suggest that dopamine acting on the D1/D5-receptor modulates both acquisition and consolidation of context-dependent extinction. By contrast, the D2-receptor may contribute to context-independent aspects of this kind of extinction learning.

Characterization of soluble glycoprotein D-mediated herpes simplex virus type 1 infection

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