Safe Use of Hydrogen and Hydrogen Systems

NASA Technical Reports Server (NTRS)

Maes, Miguel

2006-01-01

This is a viewgraph presentation that is a course for teaching the safe use of hydrogen. The objectives of the course are 1. To familiarize the student with H2 safety properties 2. To enable the identification, evaluations and addressing of H2 system hazards 3. To teach: a. Safe practices for, b. Design, c. Materials selection, d. H2 system operation, e. Physical principles and empirical observations on which these safe practices are based, f. How to respond to emergency situations involving H2, g How to visualize safety concepts through in-class exercises, h. Identify numerous parameters important to H2 safety.

F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability

PubMed Central

Kang, Jingjing; Gao, Jie; Yao, Wenwu; Kang, Lin; Gao, Shan; Yang, Hao; Ji, Bin; Li, Ping; Liu, Jing; Yao, Jiahao; Xin, Wenwen; Zhao, Baohua; Wang, Jinglin

2017-01-01

ABSTRACT Epsilon toxin (ETX), a potent toxin, is produced by types B and D strains of Clostridium perfringens, which could cause severe diseases in humans and domestic animals. Mutant rETXF199E was previously demonstrated to be a good vaccine candidate. However, the mechanism concerned remains unknown. To clarify how F199E substitution reduced ETX toxicity, we performed a series of experiments. The results showed that the cell-binding and pore-forming ability of rETXF199E was almost abolished. We speculated that F199E substitution reduced toxicity by depriving the receptor binding capability of ETX, which contributed to the hypothesis that domain I of ETX is responsible for cell binding. In addition, our data suggested that ETX could cause Ca2+ release from intracellular Ca2+ stores, which may underlie an alternate pathway leading to cell death. Furthermore, ETX induced crenation of the MDCK cells was observed, with sags and crests first appearing on the surface of condensed MDCK cells, according to scanning electron microscopy. The data also demonstrated the safety and potentiality of rETXF199E as a vaccine candidate for humans. In summary, findings of this work potentially contribute to a better understanding of the pathogenic mechanism of ETX and the development of vaccine against diseases caused by ETX, using mutant proteins. PMID:28304231

Evaluation of the DoD Safety Program: DoD Guard & Reserve Safety Survey

DTIC Science & Technology

2008-12-12

Alexandria,VA,22350-1500 8 . PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S... 8 -98) Prescribed by ANSI Std Z39-18 hot line D E PA R T M E N T O F D E F E N S E To report fraud, waste, mismanagement, and abuse of authority...Results 2007 Table 1 Percentile Scores, Percent Distribution of Responses, and Average Response Scores - 8 - sse oe LP oe sse SP LP SSA sse

Multi-method laboratory user evaluation of an actionable clinical performance information system: Implications for usability and patient safety.

PubMed

Brown, Benjamin; Balatsoukas, Panos; Williams, Richard; Sperrin, Matthew; Buchan, Iain

2018-01-01

Electronic audit and feedback (e-A&F) systems are used worldwide for care quality improvement. They measure health professionals' performance against clinical guidelines, and some systems suggest improvement actions. However, little is known about optimal interface designs for e-A&F, in particular how to present suggested actions for improvement. We developed a novel theory-informed system for primary care (the Performance Improvement plaN GeneratoR; PINGR) that covers the four principal interface components: clinical performance summaries; patient lists; detailed patient-level information; and suggested actions. As far as we are aware, this is the first report of an e-A&F system with all four interface components. (1) Use a combination of quantitative and qualitative methods to evaluate the usability of PINGR with target end-users; (2) refine existing design recommendations for e-A&F systems; (3) determine the implications of these recommendations for patient safety. We recruited seven primary care physicians to perform seven tasks with PINGR, during which we measured on-screen behaviour and eye movements. Participants subsequently completed usability questionnaires, and were interviewed in-depth. Data were integrated to: gain a more complete understanding of usability issues; enhance and explain each other's findings; and triangulate results to increase validity. Participants committed a median of 10 errors (range 8-21) when using PINGR's interface, and completed a median of five out of seven tasks (range 4-7). Errors violated six usability heuristics: clear response options; perceptual grouping and data relationships; representational formats; unambiguous description; visually distinct screens for confusable items; and workflow integration. Eye movement analysis revealed the integration of components largely supported effective user workflow, although the modular design of clinical performance summaries unnecessarily increased cognitive load. Interviews and questionnaires revealed PINGR is user-friendly, and that improved information prioritisation could further promote useful user action. Comparing our results with the wider usability literature we refine a previously published set of interface design recommendations for e-A&F. The implications for patient safety are significant regarding: user engagement; actionability; and information prioritisation. Our results also support adopting multi-method approaches in usability studies to maximise issue discovery and the credibility of findings. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

E2F function in muscle growth is necessary and sufficient for viability in Drosophila

PubMed Central

Zappia, Maria Paula; Frolov, Maxim V.

2016-01-01

The E2F transcription factor is a key cell cycle regulator. However, the inactivation of the entire E2F family in Drosophila is permissive throughout most of animal development until pupation when lethality occurs. Here we show that E2F function in the adult skeletal muscle is essential for animal viability since providing E2F function in muscles rescues the lethality of the whole-body E2F-deficient animals. Muscle-specific loss of E2F results in a significant reduction in muscle mass and thinner myofibrils. We demonstrate that E2F is dispensable for proliferation of muscle progenitor cells, but is required during late myogenesis to directly control the expression of a set of muscle-specific genes. Interestingly, E2f1 provides a major contribution to the regulation of myogenic function, while E2f2 appears to be less important. These findings identify a key function of E2F in skeletal muscle required for animal viability, and illustrate how the cell cycle regulator is repurposed in post-mitotic cells. PMID:26823289

15 CFR 718.1 - Definition.

Code of Federal Regulations, 2012 CFR

2012-01-01

...(g)(1) and 304(e)(2) of the Act and other trade secrets as follows: (a) Financial data; (b) Sales and marketing data (other than shipment data); (c) Pricing data; (d) Personnel data; (e) Research data; (f) Patent data; (g) Data maintained for compliance with environmental or occupational health and safety...

15 CFR 718.1 - Definition.

Code of Federal Regulations, 2014 CFR

2014-01-01

...(g)(1) and 304(e)(2) of the Act and other trade secrets as follows: (a) Financial data; (b) Sales and marketing data (other than shipment data); (c) Pricing data; (d) Personnel data; (e) Research data; (f) Patent data; (g) Data maintained for compliance with environmental or occupational health and safety...

15 CFR 718.1 - Definition.

Code of Federal Regulations, 2011 CFR

2011-01-01

...(g)(1) and 304(e)(2) of the Act and other trade secrets as follows: (a) Financial data; (b) Sales and marketing data (other than shipment data); (c) Pricing data; (d) Personnel data; (e) Research data; (f) Patent data; (g) Data maintained for compliance with environmental or occupational health and safety...

15 CFR 718.1 - Definition.

Code of Federal Regulations, 2013 CFR

2013-01-01

...(g)(1) and 304(e)(2) of the Act and other trade secrets as follows: (a) Financial data; (b) Sales and marketing data (other than shipment data); (c) Pricing data; (d) Personnel data; (e) Research data; (f) Patent data; (g) Data maintained for compliance with environmental or occupational health and safety...

Cell cycle regulator E2F4 is essential for the development of the ventral telencephalon.

PubMed

Ruzhynsky, Vladimir A; McClellan, Kelly A; Vanderluit, Jacqueline L; Jeong, Yongsu; Furimsky, Marosh; Park, David S; Epstein, Douglas J; Wallace, Valerie A; Slack, Ruth S

2007-05-30

Early forebrain development is characterized by extensive proliferation of neural precursors coupled with complex structural transformations; however, little is known regarding the mechanisms by which these processes are integrated. Here, we show that deficiency of the cell cycle regulatory protein, E2F4, results in the loss of ventral telencephalic structures and impaired self-renewal of neural precursor cells. The mechanism underlying aberrant ventral patterning lies in a dramatic loss of Sonic hedgehog (Shh) expression specifically in this region. The E2F4-deficient phenotype can be recapitulated by interbreeding mice heterozygous for E2F4 with those lacking one allele of Shh, suggesting a genetic interaction between these pathways. Treatment of E2F4-deficient cells with a Hh agonist rescues stem cell self-renewal and cells expressing the homeodomain proteins that specify the ventral telencephalic structures. Finally, we show that E2F4 deficiency results in impaired activity of Shh forebrain-specific enhancers. In conclusion, these studies establish a novel requirement for the cell cycle regulatory protein, E2F4, in the development of the ventral telencephalon.

National Dam Safety Program. Jacksons Pond Dam (NJ00771), Arthurkill River Basin, Rahway River, Union County, New Jersey. Phase I Inspection Report.

DTIC Science & Technology

1981-08-01

previouuly mentioned, bedrock in the area consists of red shale and sandstone of Triassic age . -2 SI 1.3 Pertinent Data a. Drainage Area 40 square miles b...COyP rFEONII NowTO \\ ASCU ~T - .LA1LP1?, F NAINLPOGA FISPCINO NNFDDM ~coeiEI laic- it leF~IN Ipo l ii m8I,_ -QA I EV APPENDIX 1 CHECK LIST VISUAL...a r.f ,i 13 14 TS C910C. 41,0-1 S70~ m f"", S C~ tec,( (Caed 3 /e-a2~V ’U0 16 r67 (k~otc ,yrude iVLAOti & L1Away k I 3 eř A.A 17 19 Or(CL age

Field Demonstration for P-D-680 Solvent Replacement (Part II)

DTIC Science & Technology

1998-05-12

jo \\ Ji o < s NJ £. ° 8? Q- 3* £?. «" «< o Ö- 8" 03 O C O ~ e O 3 re *i re re w8 g 3 2> 8 = er ^ o 3 ^ fS Ni O...34 3 3. 3. n_ £ 2. O 2- e. re Z. 2 3 v! 3 oso,o,<f)( ji «s S?3re-t930.Q3^. «o.03rt3-3c"o=; 1 » < 3 -•■n O -t33^c«^3ga3 re...soWfirtH T^ skd uiEita, ox^fifk^. 4. KrflTjTS, SAFETY 0? ALTERATIVE F-D-S80 SOLVENT Have you, cr did you have knowledge of ethers

Genomic structure, expression pattern, and functional characterization of transcription factor E2F-2 from black tiger shrimp (Penaeus monodon)

PubMed Central

Zhao, Chao; Qiu, Lihua

2017-01-01

Transcription factor E2F-2 is a regulator of cell cycle. Researchers identified E2F-2 genes from yeasts to humans, but few reports investigated E2F-2 gene from black tiger shrimp. In the present study, we cloned E2F-2 gene from black tiger shrimp (Penaeus monodon). Full-length PmE2F-2 complementary DNA sequence measures 3,189 bp with an open reading frame of 1,371 bp. Complete PmE2F-2 genomic sequence (17,305 bp) of P. monodon contains nine exons, which are separated by eight introns. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that PmE2F-2 is highly expressed in hepatopancreas and ovaries of P. monodon. Highest PmE2F-2 expression levels were observed in stage III ovarian development of P. monodon. PmE2F-2 expression levels were significantly augmented in ovaries of P. monodon after 5-hydroxytryptamine injection and eyestalk ablation. RNA interference experiments were conducted to examine PmE2F-2, PmCDK2, and PmCyclin E expression profiles. PmE2F-2 was successfully knocked down in ovaries and hepatopancreas via double-stranded RNA (dsRNA)–E2F-2 injection. In the same organs, PmE2F-2 expression localization and level were investigated through in situ hybridization, which revealed consistent results with those of qRT-PCR. After dsRNA—E2F-2 injection, gonadosomatic index of shrimp was significantly lower than those following dsRNA—GFP and phosphate-buffered solution injections. Therefore, PmE2F-2 may be involved in ovarian maturation in P. monodon. PMID:28558060

Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice.

PubMed

Iglesias, Ainhoa; Murga, Matilde; Laresgoiti, Usua; Skoudy, Anouchka; Bernales, Irantzu; Fullaondo, Asier; Moreno, Bernardino; Lloreta, José; Field, Seth J; Real, Francisco X; Zubiaga, Ana M

2004-05-01

E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.

Development of Robotics Applications in a Solid Propellant Mixing Laboratory

DTIC Science & Technology

1988-06-01

implementation of robotic hardware and software into a laboratory environment requires a carefully structured series of phases which examines, in...strategy. The general methodology utilized in this project is discussed in Appendix A. The proposed laboratory robotics development program was structured ...Accessibility - Potential modifications - Safety precautions e) Robot Transport - Slider mechanisms - Linear tracks - Gantry configuration - Mobility f

E2F8 as a Novel Therapeutic Target for Lung Cancer

PubMed Central

Park, Sin-Aye; Platt, James; Lee, Jong Woo; López-Giráldez, Francesc; Herbst, Roy S.

2015-01-01

Background: The E2F members have been divided into transcription activators (E2F1-E2F3) and repressors (E2F4-E2F8). E2F8 with E2F7 has been known to play an important physiologic role in embryonic development and cell cycle regulation by repressing E2F1. However, the function of E2F8 in cancer cells is unknown. Methods: E2F8 expression was assessed by immunoblotting or immunofluorescence staining in human lung cancer (LC) cells and tissues from LC patients (n = 45). Cell proliferation, colony formation, and invasion analysis were performed to evaluate the role of E2F8 in LC. Microarray analysis was used to determine the target genes of E2F8. The regulation of E2F8 on the expression of ubiquitin-like PHD and RING domain-containing 1 (UHRF1), one of E2F8 target genes, was determined using chromatin immunoprecipitation and promoter activity assays. Human LC xenograft models were used to determine the effects of inhibiting E2F8 by siRNAs (n = 7 per group) or antisense morpholino (n = 8 per group) on tumor growth. Survival was analyzed using the Kaplan-Meier method and group differences by the Student’s t test. All statistical tests were two-sided. Results: LC tumors overexpressed E2F8 compared with normal lung tissues. Depletion of E2F8 inhibited cell proliferation and tumor growth. E2F8 knockdown statistically significantly reduced the expression of UHRF1 (~60%-70%, P < .001), and the direct binding of E2F8 on the promoter of UHRF1 was identified. Kaplan-Meier analysis with a public database showed prognostic significance of aberrant E2F8 expression in LC (HR = 1.91 95% CI = 1.21 to 3.01 in chemo-naïve patients, P = .0047). Conclusions: We demonstrated that E2F8 is overexpressed in LC and is required for the growth of LC cells. These findings implicate E2F8 as a novel therapeutic target for LC treatment. PMID:26089541

Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study.

PubMed

Anty, R; Favre, G; Coilly, A; Rossignol, E; Houssel-Debry, P; Duvoux, C; De Ledinghen, V; Di Martino, V; Leroy, V; Radenne, S; Kamar, N; Canva, V; D'Alteroche, L; Durand, F; Dumortier, J; Lebray, P; Besch, C; Tran, A; Canivet, C M; Botta-Fridlund, D; Montialoux, H; Moreno, C; Conti, F; Silvain, C; Perré, P; Habersetzer, F; Abergel, A; Debette-Gratien, M; Dharancy, S; Esnault, V L M; Fougerou-Leurent, C; Cagnot, C; Diallo, A; Veislinger, A; Danjou, H; Samuel, D; Pageaux, G-P; Duclos-Vallée, J-C

2018-06-01

In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m 2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m 2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73). The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients. © 2018 John Wiley & Sons Ltd.

Brief Report: Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs Tenofovir Disoproxil Fumarate (TDF), Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine (E/C/F) for Initial HIV-1 Treatment: Week 144 Results.

PubMed

Arribas, José R; Thompson, Melanie; Sax, Paul E; Haas, Bernhard; McDonald, Cheryl; Wohl, David A; DeJesus, Edwin; Clarke, Amanda E; Guo, Susan; Wang, Hui; Callebaut, Christian; Plummer, Andrew; Cheng, Andrew; Das, Moupali; McCallister, Scott

2017-06-01

In 2 double-blind phase 3 trials, 1733 antiretroviral-naive adults were randomized to tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), each coformulated with elvitegravir/cobicistat/emtricitabine (E/C/F). At 144 weeks, TAF was superior to TDF in virologic efficacy, with 84.2% vs 80.0% having HIV-1 RNA <50 copies/mL (difference 4.2%; 95% confidence interval: 0.6% to 7.8%). TAF had less impact than TDF on bone mineral density and renal biomarkers. No participants on TAF had renal-related discontinuations vs 12 on TDF (P < 0.001), with no cases of proximal tubulopathy for TAF vs 4 for TDF. There were greater increases in lipids with TAF vs TDF, with no difference in the total cholesterol to high-density lipoprotein ratio. For initial HIV therapy, E/C/F/TAF is superior to E/C/F/TDF in efficacy and bone and renal safety.

E2F4 is required for early eye patterning.

PubMed

Ruzhynsky, Vladimir A; Furimsky, Marosh; Park, David S; Wallace, Valerie A; Slack, Ruth S

2009-01-01

Increasingly, studies reveal novel functions for cell cycle proteins during development. Here, we investigated the role of E2F4 in eye development. E2F4-deficient mouse embryos exhibit severe early eye patterning defects, which are evident from embryonic day 11.5 and characterized by aberrant shape of the optic cup, coloboma as well as abnormal eye pigmentation. Loss of E2F4 is associated with proximal-distal patterning defects in the optic vesicle. These defects are characterized by the expansion of optic stalk marker gene expression to the optic cup and reduced expression of ventral optic cup markers. These defects are associated with a split of Shh expression domain at the ventral midline of the forebrain and expansion of the Shh activity into the ventral optic cup. Despite these patterning defects, early neuronal differentiation and Shh expression in the retina are not affected by E2F4 deletion. Overall, the results of our studies show a novel role of E2F4 in the early eye development. 2009 S. Karger AG, Basel.

National Dam Safety Program. St. James Lake Dam (Inventory Number NY 779), St. Lawrence River Basin, Jefferson County, New York. Phase I Inspection Report.

DTIC Science & Technology

1980-02-14

cifs is only 3 percent of the Probable kaximum Flood (P11F) which was coi’puted to be 13,670 cfs.’ The 1 /2 PI4F is 7,046 cfs. Therefore, the darn...calnnot pass the 1 /2 P,4F without being overtopped. The downstreami hazard is a 1 ijhtly traveled road thAt travels northe] {o the cantonment area. -g ;:p...c t of t e si l a si ad.u t o l1 1 . The discharg caact oftesiia sindqa fraf1ows in excess of 3 per cent of the Nl (siiaAaaiy=40cs.~~ e spillway is

40 CFR 721.5185 - 2-Propen-1-one, 1-(4-morpholinyl)-.

Code of Federal Regulations, 2013 CFR

2013-07-01

...), (a)(3)(ii), (a)(4), (a)(6)(v), (b) (concentration set at 1.0 percent), and (c). Safety 4/4H EVOH/PE... in accordance with the American Society for Testing Materials (ASTM) F739 method and found by EPA to.... Requirements as specified in § 721.72 (a), (b), (c), (d), (e) (concentration set at 1.0 percent), (f), (g)(1...

40 CFR 721.5185 - 2-Propen-1-one, 1-(4-morpholinyl)-.

Code of Federal Regulations, 2011 CFR

2011-07-01

...), (a)(3)(ii), (a)(4), (a)(6)(v), (b) (concentration set at 1.0 percent), and (c). Safety 4/4H EVOH/PE... in accordance with the American Society for Testing Materials (ASTM) F739 method and found by EPA to.... Requirements as specified in § 721.72 (a), (b), (c), (d), (e) (concentration set at 1.0 percent), (f), (g)(1...

40 CFR 721.5185 - 2-Propen-1-one, 1-(4-morpholinyl)-.

Code of Federal Regulations, 2012 CFR

2012-07-01

...), (a)(3)(ii), (a)(4), (a)(6)(v), (b) (concentration set at 1.0 percent), and (c). Safety 4/4H EVOH/PE... in accordance with the American Society for Testing Materials (ASTM) F739 method and found by EPA to.... Requirements as specified in § 721.72 (a), (b), (c), (d), (e) (concentration set at 1.0 percent), (f), (g)(1...

40 CFR 721.5185 - 2-Propen-1-one, 1-(4-morpholinyl)-.

Code of Federal Regulations, 2014 CFR

2014-07-01

...), (a)(3)(ii), (a)(4), (a)(6)(v), (b) (concentration set at 1.0 percent), and (c). Safety 4/4H EVOH/PE... in accordance with the American Society for Testing Materials (ASTM) F739 method and found by EPA to.... Requirements as specified in § 721.72 (a), (b), (c), (d), (e) (concentration set at 1.0 percent), (f), (g)(1...

E2F8 as a Novel Therapeutic Target for Lung Cancer.

PubMed

Park, Sin-Aye; Platt, James; Lee, Jong Woo; López-Giráldez, Francesc; Herbst, Roy S; Koo, Ja Seok

2015-09-01

The E2F members have been divided into transcription activators (E2F1-E2F3) and repressors (E2F4-E2F8). E2F8 with E2F7 has been known to play an important physiologic role in embryonic development and cell cycle regulation by repressing E2F1. However, the function of E2F8 in cancer cells is unknown. E2F8 expression was assessed by immunoblotting or immunofluorescence staining in human lung cancer (LC) cells and tissues from LC patients (n = 45). Cell proliferation, colony formation, and invasion analysis were performed to evaluate the role of E2F8 in LC. Microarray analysis was used to determine the target genes of E2F8. The regulation of E2F8 on the expression of ubiquitin-like PHD and RING domain-containing 1 (UHRF1), one of E2F8 target genes, was determined using chromatin immunoprecipitation and promoter activity assays. Human LC xenograft models were used to determine the effects of inhibiting E2F8 by siRNAs (n = 7 per group) or antisense morpholino (n = 8 per group) on tumor growth. Survival was analyzed using the Kaplan-Meier method and group differences by the Student's t test. All statistical tests were two-sided. LC tumors overexpressed E2F8 compared with normal lung tissues. Depletion of E2F8 inhibited cell proliferation and tumor growth. E2F8 knockdown statistically significantly reduced the expression of UHRF1 (~60%-70%, P < .001), and the direct binding of E2F8 on the promoter of UHRF1 was identified. Kaplan-Meier analysis with a public database showed prognostic significance of aberrant E2F8 expression in LC (HR = 1.91 95% CI = 1.21 to 3.01 in chemo-naïve patients, P = .0047). We demonstrated that E2F8 is overexpressed in LC and is required for the growth of LC cells. These findings implicate E2F8 as a novel therapeutic target for LC treatment. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Engine performance with a hydrogenated safety fuel

NASA Technical Reports Server (NTRS)

Schey, Oscar W; Young, Alfred W

1933-01-01

This report presents the results of an investigation to determine the engine performance obtained with a hydrogenated safety fuel developed to eliminate fire hazard. The tests were made on a single-cylinder universal test engine at compression ratios of 5.0, 5.5, and 6.0. Most of the tests were made with a fuel-injection system, although one set of runs was made with a carburetor when using gasoline to establish comparative performance. The tests show that the b.m.e.p. obtained with safety fuel when using a fuel-injection system is slightly higher than that obtained with gasoline when using a carburetor, although the fuel consumption with safety fuel is higher. When the fuel-injection system is used with each fuel and with normal engine temperatures the b.m.e.p. with safety fuel is from 2 to 4 percent lower than with gasoline and the fuel consumption about 25 to 30 percent higher. However, a few tests at an engine coolant temperature of 250 F have shown a specific fuel consumption approximating that obtained with gasoline with only a slight reduction in power. The idling of the test engine was satisfactory with the safety fuel. Starting was difficult with a cold engine but could be readily accomplished when the jacket water was hot. It is believed that the use of the safety fuel would practically eliminate crash fires.

Two decades of pharmacovigilance and clinical experience with highly purified rabies immunoglobulin F(ab')2 fragments.

PubMed

Reveneau, Elisa; Cottin, Pascale; Rasuli, Anvar

2017-03-01

Rabies is a worldwide zoonotic viral disease with no specific treatment once symptoms occur; manifest disease is almost always fatal. WHO recommendations for exposed individuals include immediate attention to the wound and use of rabies immunoglobulin and/or vaccine for post-exposure prophylaxis (PEP). Here, we provide an overview of the clinical experience with a highly purified preparation of F(ab') 2 fragments from equine rabies immunoglobulin (F(ab') 2 pERIG; Favirab TM ) in rabies PEP. Areas covered: Our review comprises a retrospective analysis of adverse event reports in the Sanofi Pasteur global pharmacovigilance database for F(ab') 2 pERIG, including adverse event reports from eight Sanofi Pasteur-sponsored clinical trials and post-market surveillance data collected between 1995 and 2014. The general safety profile of F(ab') 2 pERIG is discussed, as are the occurrence of rare anaphylactic reactions, and suspected intervention failure. Expert commentary: Over 20 years of clinical development and post-licensure experience has established the safety and effectiveness of F(ab') 2 pERIG (Favirab TM ) in rabies PEP.

47 CFR 25.143 - Licensing provisions for the 1.6/2.4 GHz Mobile-Satellite Service and 2 GHz Mobile-Satellite...

Code of Federal Regulations, 2014 CFR

2014-10-01

... space stations authorized by the Commission. (d)-(e) [Reserved] (f) Safety and distress communications... 47 Telecommunication 2 2014-10-01 2014-10-01 false Licensing provisions for the 1.6/2.4 GHz Mobile... COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Applications and Licenses...

A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting

PubMed Central

Lindeman, Geoffrey J.; Dagnino, Lina; Gaubatz, Stefan; Xu, Yuhui; Bronson, Roderick T.; Warren, Henry B.; Livingston, David M.

1998-01-01

Homozygous E2F-5 knockout embryos and mice have been generated. Although embryonic development appeared normal, newborn mice developed nonobstructive hydrocephalus, suggesting excessive cerebrospinal fluid (CSF) production. Although the CSF-producing choroid plexus displayed normal cellular organization, it contained abundant electron-lucent epithelial cells, consistent with excessive CSF secretory activity. Moreover, E2F-5 CNS expression in normal animals was largely confined to the choroid plexus. Cell cycle kinetics were not perturbed in homozygous knockout embryo fibroblasts. Thus, E2F-5 is not essential for cell proliferation. Rather, it affects the secretory behavior of a differentiated neural tissue. PMID:9553039

Review of Electromagnetic Frequency (EMF) Safety Program for Homestead ARB, FL

DTIC Science & Technology

2012-11-28

using technique number MSL-7. Calibrations below I GHz were perfonned in a electrical characterist.ics of the cell and the measured net power...Altimeter ( CARA ) 1 per F-16 4 .2-4.2 GHz 100/10 0 .8 2 .4 482 AMXS/MXAAS AN/APG68 Fire Control Radar (FCR) 1 per F-1 6 Classified Classified Classified...A. MPE fot· Upper T ier Electric Magnetic field Powet· Averaging Fr equency Field - nns strength - n ns Density - nns (S) time R ange (t) (E

A Randomized, Blinded, Controlled, Dose-Ranging Study of a Respiratory Syncytial Virus Recombinant Fusion (F) Nanoparticle Vaccine in Healthy Women of Childbearing Age.

PubMed

Glenn, Gregory M; Fries, Louis F; Thomas, D Nigel; Smith, Gale; Kpamegan, Eloi; Lu, Hanxin; Flyer, David; Jani, Dewal; Hickman, Somia P; Piedra, Pedro A

2016-02-01

Respiratory syncytial virus (RSV) is a leading cause of infant morbidity and mortality. A recombinant RSV fusion protein nanoparticle vaccine (RSV F vaccine) candidate for maternal immunization was tested for safety and immunogenicity in women of childbearing age. Three hundred thirty women (18-35 years) were randomized to receive 1 or 2 doses of RSV F vaccine (60 or 90 µg) with or without aluminum phosphate adjuvant, or placebo at days 0 and 28. Safety was evaluated over 180 days; immunogenicity and RSV infection rates were evaluated over 112 days. All vaccine formulations were well tolerated, without vaccine-related serious adverse events. Anti-F immunoglobulin G antibodies rose 6.5-15.6-fold, with significantly higher levels in 2-dose, adjuvanted regimens at day 56. Palivizumab-competitive antibody levels were undetectable at day 0 but increased up to 325 µg/mL at day 56. A 2.7- and 3.5-fold rise in RSV/A and RSV/B microneutralization antibodies were noted at day 56. Between days 56 and 112, 21% (12/56) of placebo recipients and 11% of vaccinees (26/244) showed evidence of a recent RSV infection (P = .04). The vaccine appeared safe, immunogenic, and reduced RSV infections. Further development as a vaccine for use in maternal immunization is warranted. NCT01704365. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

LOFT L2-3 blowdown experiment safety analyses D, E, and G; LOCA analyses H, K, K1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perryman, J.L.; Keeler, C.D.; Saukkoriipi, L.O.

1978-12-01

Three calculations using conservative off-nominal conditions and evaluation model options were made using RELAP4/MOD5 for blowdown-refill and RELAP4/MOD6 for reflood for Loss-of-Fluid Test Experiment L2-3 to support the experiment safety analysis effort. The three analyses are as follows: Analysis D: Loss of commercial power during Experiment L2-3; Analysis E: Hot leg quick-opening blowdown valve (QOBV) does not open during Experiment L2-3; and Analysis G: Cold leg QOBV does not open during Experiment L2-3. In addition, the results of three LOFT loss-of-coolant accident (LOCA) analyses using a power of 56.1 MW and a primary coolant system flow rate of 3.6 millionmore » 1bm/hr are presented: Analysis H: Intact loop 200% hot leg break; emergency core cooling (ECC) system B unavailable; Analysis K: Pressurizer relief valve stuck in open position; ECC system B unavailable; and Analysis K1: Same as analysis K, but using a primary coolant system flow rate of 1.92 million 1bm/hr (L2-4 pre-LOCE flow rate). For analysis D, the maximum cladding temperature reached was 1762/sup 0/F, 22 sec into reflood. In analyses E and G, the blowdowns were slower due to one of the QOBVs not functioning. The maximum cladding temperature reached in analysis E was 1700/sup 0/F, 64.7 sec into reflood; for analysis G, it was 1300/sup 0/F at the start of reflood. For analysis H, the maximum cladding temperature reached was 1825/sup 0/F, 0.01 sec into reflood. Analysis K was a very slow blowdown, and the cladding temperatures followed the saturation temperature of the system. The results of analysis K1 was nearly identical to analysis K; system depressurization was not affected by the primary coolant system flow rate.« less

Development of Flight Safety Prediction Methodology for U. S. Naval Safety Center. Revision 1

DTIC Science & Technology

1970-02-01

Safety Center. The methodology develoned encompassed functional analysis of the F-4J aircraft, assessment of the importance of safety- sensitive ... Sensitivity ... ....... . 4-8 V 4.5 Model Implementation ........ ......... . 4-10 4.5.1 Functional Analysis ..... ........... . 4-11 4. 5. 2 Major...Function Sensitivity Assignment ........ ... 4-13 i 4.5.3 Link Dependency Assignment ... ......... . 4-14 4.5.4 Computer Program for Sensitivity

Enzyme- and label-free electrochemical aptasensor for kanamycin detection based on double stir bar-assisted toehold-mediated strand displacement reaction for dual-signal amplification.

PubMed

Hong, Feng; Chen, Xixue; Cao, Yuting; Dong, Youren; Wu, Dazhen; Hu, Futao; Gan, Ning

2018-07-30

It is critically important to detect antibiotic residues for monitoring food safety. In this study, an enzyme- and label-free electrochemical aptasensor for antibiotics, with kanamycin (Kana) as a typical analyte, was developed based on a double stir bar-assisted toehold-mediated strand displacement reaction (dSB-TMSDR) for dual-signal amplification. First, we modified two gold electrodes (E-1 and E-2) with different DNA probes (S1/S2 hybrid probe in E-1 and DNA fuel strand S3 in E-2). In the presence of Kana, an S1/S2 probe can be disassembled from E-1 to form an S2/Kana complex in supernatant. The S2/Kana could react with S3 on E-2 to form S2/S3 hybrid and release Kana through TMSDR. After then, the target recycling was triggered. Subsequently, the formed S2/S3 hybrid can also trigger a hybridization chain reaction (HCR). Consequently, the dual-signal amplification strategy was established, which resulted in many long dsDNA chains on E-2. The chains can associate with methylene blue (MB) as redox probes to produce a current response for the quantification of Kana. The assay exhibited high sensitivity and specificity with a detection limit at 16 fM Kana due to the dual-signal amplification. The double stir bars system can both increase phase separation and prevent leakage of DNA fuel to reduce background interference. Moreover, it allows flexible sequence design of the TMSDR probes. The assay was successfully employed to detect Kana residues in food and showed potential application value in food safety detection. Copyright © 2018 Elsevier B.V. All rights reserved.

An Optimized Protocol for Electrophoretic Mobility Shift Assay Using Infrared Fluorescent Dye-labeled Oligonucleotides.

PubMed

Hsieh, Yi-Wen; Alqadah, Amel; Chuang, Chiou-Fen

2016-11-29

Electrophoretic Mobility Shift Assays (EMSA) are an instrumental tool to characterize the interactions between proteins and their target DNA sequences. Radioactivity has been the predominant method of DNA labeling in EMSAs. However, recent advances in fluorescent dyes and scanning methods have prompted the use of fluorescent tagging of DNA as an alternative to radioactivity for the advantages of easy handling, saving time, reducing cost, and improving safety. We have recently used fluorescent EMSA (fEMSA) to successfully address an important biological question. Our fEMSA analysis provides mechanistic insight into the effect of a missense mutation, G73E, in the highly conserved HMG transcription factor SOX-2 on olfactory neuron type diversification. We found that mutant SOX-2 G73E protein alters specific DNA binding activity, thereby causing olfactory neuron identity transformation. Here, we present an optimized and cost-effective step-by-step protocol for fEMSA using infrared fluorescent dye-labeled oligonucleotides containing the LIM-4/SOX-2 adjacent target sites and purified SOX-2 proteins (WT and mutant SOX-2 G73E proteins) as a biological example.

Interface design recommendations for computerised clinical audit and feedback: Hybrid usability evidence from a research-led system.

PubMed

Brown, Benjamin; Balatsoukas, Panos; Williams, Richard; Sperrin, Matthew; Buchan, Iain

2016-10-01

Audit and Feedback (A&F) is a widely used quality improvement technique that measures clinicians' clinical performance and reports it back to them. Computerised A&F (e-A&F) system interfaces may consist of four key components: (1) Summaries of clinical performance; (2) Patient lists; (3) Patient-level data; (4) Recommended actions. There is a lack of evidence regarding how to best design e-A&F interfaces; establishing such evidence is key to maximising usability, and in turn improving patient safety. To evaluate the usability of a novel theoretically-informed and research-led e-A&F system for primary care (the Performance Improvement plaN GeneratoR: PINGR). (1) Describe PINGR's design, rationale and theoretical basis; (2) Identify usability issues with PINGR; (3) Understand how these issues may interfere with the cognitive goals of end-users; (4) Translate the issues into recommendations for the user-centred design of e-A&F systems. Eight experienced health system evaluators performed a usability inspection using an innovative hybrid approach consisting of five stages: (1) Development of representative user tasks, Goals, and Actions; (2) Combining Heuristic Evaluation and Cognitive Walkthrough methods into a single protocol to identify usability issues; (3) Consolidation of issues; (4) Severity rating of consolidated issues; (5) Analysis of issues according to usability heuristics, interface components, and Goal-Action structure. A final list of 47 issues were categorised into 8 heuristic themes. The most error-prone heuristics were 'Consistency and standards' (13 usability issues; 28% of the total) and 'Match between system and real world' (n=10, 21%). The recommended actions component of the PINGR interface had the most usability issues (n=21, 45%), followed by patient-level data (n=5, 11%), patient lists (n=4, 9%), and summaries of clinical performance (n=4, 9%). The most error-prone Actions across all user Goals were: (1) Patient selection from a list; (2) Data identification from a figure (both population-level and patient-level); (3) Disagreement with a system recommendation. By contextualising our findings within the wider literature on health information system usability, we provide recommendations for the design of e-A&F system interfaces relating to their four key components, in addition to how they may be integrated within a system. Copyright © 2016. Published by Elsevier Ireland Ltd.

Simplification to single-tablet regimen of elvitegravir, cobicistat, emtricitabine, tenofovir DF from multi-tablet ritonavir-boosted protease inhibitor plus coformulated emtricitabine and tenofovir DF regimens: week 96 results of STRATEGY-PI.

PubMed

Arribas, Jose R; DeJesus, Edwin; van Lunzen, Jan; Zurawski, Christine; Doroana, Manuela; Towner, William; Lazzarin, Adriano; Nelson, Mark; McColl, Damian; Andreatta, Kristen; Swamy, Raji; Szwarcberg, Javier; Nguyen, Thai

2017-05-01

Antiretroviral therapy (ART) simplification to a single-tablet regimen can benefit HIV-1-infected, virologically suppressed, individuals on ART composed of multiple pills. We assessed long-term efficacy and safety of switching to co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF) from multi-tablet ritonavir-boosted protease inhibitor (PI + RTV) plus F/TDF (TVD) regimens. STRATEGY-PI was a 96-week, phase 3b, randomized (2:1), open-label, non-inferiority study examining the efficacy, safety, and tolerability of switching to E/C/F/TDF from PI + RTV + TVD regimens in virologically suppressed individuals (HIV-1 RNA <50 copies/mL). Participants were randomized to switch to E/C/F/TDF (switch group) or to continue their PI + RTV + TVD regimens (no-switch group). Eligibility criteria included no resistance to F/TDF or history of virologic failure, and estimated creatinine clearance ≥70 mL/min. At week 96, 87% (252/290) of switch and 70% (97/139) of no-switch participants maintained HIV-1 RNA <50 copies/mL (difference: 17%, 95% CI 8.7-26.0%, p < 0.001). Superiority of the switch to E/C/F/TDF vs. no-switch was due to a smaller proportion of both virologic failures (switch, 1% [3/290]; no-switch, 6% [8/139]) and discontinuations for non-virologic reasons (switch, 11% [31/290]; no-switch, 24% [33/139]). No treatment-emergent resistance was observed in switch subjects with virologic failure. Discontinuation rates from adverse events were 3% in both groups (9/293, switch; 4/140, no-switch). Switching from PI + RTV + TVD to E/C/F/TDF was associated with significant improvements in patient-reported outcomes related to gastrointestinal symptoms (nausea and bloating). E/C/F/TDF is a safe, effective long-term alternative to multi-tablet PI + RTV + TVD-based regimens in virologically suppressed, HIV-1-infected adults, and improves patient-reported gastrointestinal symptoms.

Summary of Federal Aviation Administration Responses to National Transportation Safety Board Safety Recommendations.

DTIC Science & Technology

1981-04-01

out i designated restricted/warning areas or under radar surveillance in air traffic control assigned airspace. The status of this recomrnenda- tion...FEDER1. C AL AVIATI0 ACAINISTPAT 0 SASHIIGII 0 OFFICE-E F YwLL A ky OF OEkA AVATON APM I STATI RFSPONSEs 70 NAN -F (d) NON 0 A on mIhhEohhImlI El...NTSB recawendations which are still open pending FAA action (i.e., those that have not been designated as "Closed" by the NTSB as a result of acceptable

OPERATION CASTLE. Radiological Safety. Volume 2

DTIC Science & Technology

1985-09-01

d.’ That, orcopt as noted sbovo, a radiolocical safety program similar to that of CaSTIS, bo planned for future operations» e. That research and...sane manner as that for liONGEL’iT, indicated l60 nr/hr at 1830M, 3 March« The infinity dose of the UTHUK natives was computed at 58r« The decision...status of /JLUK mt pot up f o» .. consideratioa aprroxlmatoly 200CM, 2 March. This atoll ha» a reported. ^ population of 401; The infinity dose wa

23 CFR 924.9 - Planning.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., management, operation, education, enforcement, and emergency services; (D) Considers safety needs of all public roads; (E) Adopts a strategic safety goal; (F) Identifies key emphasis areas and describes a... infrastructure safety problems and opportunities on all public roads and all users, and focuses resources on...

48 CFR 22.406-8 - Investigations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... statements taken during an investigation or the employee's identity to anyone other than an authorized... Investigation Summary Sheet, is the first page of the report; and (2) The agency head must process the report as... and Safety Standards statute; (E) Corrective measures taken; and (F) Any information that may be...

Programmatic Environmental Assessment (EA) for Hazardous Materials Removal at F. E. Warren Air Force Base, Wyoming

DTIC Science & Technology

2013-05-31

ACM). The FEW Environmental Planning Function ( EPF ) conducted the analysis of this proposed action. 2. PURPOSE AND NEED FOR ACTION. The... EPF determined that the proposed action has the potential to affect Air Quality, Occupational Safety and Health, Cultural Resources and Hazardous Waste

30 CFR 77.1434 - Retirement criteria.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Personnel... corrosion; (e) Distortion of the rope structure; (f) Heat damage from any source; (g) Diameter reduction due...

Development and Application of a New Method for Specific and Sensitive Enumeration of Spores of Nonproteolytic Clostridium botulinum Types B, E, and F in Foods and Food Materials ▿

PubMed Central

Peck, Michael W.; Plowman, June; Aldus, Clare F.; Wyatt, Gary M.; Penaloza Izurieta, Walter; Stringer, Sandra C.; Barker, Gary C.

2010-01-01

The highly potent botulinum neurotoxins are responsible for botulism, a severe neuroparalytic disease. Strains of nonproteolytic Clostridium botulinum form neurotoxins of types B, E, and F and are the main hazard associated with minimally heated refrigerated foods. Recent developments in quantitative microbiological risk assessment (QMRA) and food safety objectives (FSO) have made food safety more quantitative and include, as inputs, probability distributions for the contamination of food materials and foods. A new method that combines a selective enrichment culture with multiplex PCR has been developed and validated to enumerate specifically the spores of nonproteolytic C. botulinum. Key features of this new method include the following: (i) it is specific for nonproteolytic C. botulinum (and does not detect proteolytic C. botulinum), (ii) the detection limit has been determined for each food tested (using carefully structured control samples), and (iii) a low detection limit has been achieved by the use of selective enrichment and large test samples. The method has been used to enumerate spores of nonproteolytic C. botulinum in 637 samples of 19 food materials included in pasta-based minimally heated refrigerated foods and in 7 complete foods. A total of 32 samples (5 egg pastas and 27 scallops) contained spores of nonproteolytic C. botulinum type B or F. The majority of samples contained <100 spores/kg, but one sample of scallops contained 444 spores/kg. Nonproteolytic C. botulinum type E was not detected. Importantly, for QMRA and FSO, the construction of probability distributions will enable the frequency of packs containing particular levels of contamination to be determined. PMID:20709854

Development and application of a new method for specific and sensitive enumeration of spores of nonproteolytic Clostridium botulinum types B, E, and F in foods and food materials.

PubMed

Peck, Michael W; Plowman, June; Aldus, Clare F; Wyatt, Gary M; Izurieta, Walter Penaloza; Stringer, Sandra C; Barker, Gary C

2010-10-01

The highly potent botulinum neurotoxins are responsible for botulism, a severe neuroparalytic disease. Strains of nonproteolytic Clostridium botulinum form neurotoxins of types B, E, and F and are the main hazard associated with minimally heated refrigerated foods. Recent developments in quantitative microbiological risk assessment (QMRA) and food safety objectives (FSO) have made food safety more quantitative and include, as inputs, probability distributions for the contamination of food materials and foods. A new method that combines a selective enrichment culture with multiplex PCR has been developed and validated to enumerate specifically the spores of nonproteolytic C. botulinum. Key features of this new method include the following: (i) it is specific for nonproteolytic C. botulinum (and does not detect proteolytic C. botulinum), (ii) the detection limit has been determined for each food tested (using carefully structured control samples), and (iii) a low detection limit has been achieved by the use of selective enrichment and large test samples. The method has been used to enumerate spores of nonproteolytic C. botulinum in 637 samples of 19 food materials included in pasta-based minimally heated refrigerated foods and in 7 complete foods. A total of 32 samples (5 egg pastas and 27 scallops) contained spores of nonproteolytic C. botulinum type B or F. The majority of samples contained <100 spores/kg, but one sample of scallops contained 444 spores/kg. Nonproteolytic C. botulinum type E was not detected. Importantly, for QMRA and FSO, the construction of probability distributions will enable the frequency of packs containing particular levels of contamination to be determined.

E2F transcription factors and digestive system malignancies: how much do we know?

PubMed

Xanthoulis, Athanasios; Tiniakos, Dina G

2013-06-07

E2F family of transcription factors regulates various cellular functions related to cell cycle and apoptosis. Its individual members have traditionally been classified into activators and repressors, based on in vitro studies. However their contribution in human cancer is more complicated and difficult to predict. We review current knowledge on the expression of E2Fs in digestive system malignancies and its clinical implications for patient prognosis and treatment. E2F1, the most extensively studied member and the only one with prognostic value, exhibits a tumor-suppressing activity in esophageal, gastric and colorectal adenocarcinoma, and in hepatocellular carcinoma (HCC), whereas in pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma may function as a tumor-promoter. In the latter malignancies, E2F1 immunohistochemical expression has been correlated with higher tumor grade and worse patient survival, whereas in esophageal, gastric and colorectal adenocarcinomas is a marker of increased patient survival. E2F2 has only been studied in colorectal cancer, where its role is not considered significant. E2F4's role in colorectal, gastric and hepatic carcinogenesis is tumor-promoting. E2F8 is strongly upregulated in human HCC, thus possibly contributing to hepatocarcinogenesis. Adenoviral transfer of E2F as gene therapy to sensitize pancreatic cancer cells for chemotherapeutic agents has been used in experimental studies. Other therapeutic strategies are yet to be developed, but it appears that targeted approaches using E2F-agonists or antagonists should take into account the tissue-dependent function of each E2F member. Further understanding of E2Fs' contribution in cellular functions in vivo would help clarify their role in carcinogenesis.

ns2np4 (n = 4, 5) lone pair triplets whirling in M*F2E3 (M* = Kr, Xe): Stereochemistry and ab initio analyses

NASA Astrophysics Data System (ADS)

Galy, Jean; Matar, Samir F.

2017-02-01

The stereochemistry of ns2np4 (n = 4, 5) lone pair LP characterizing noble gas Kr and Xe (labeled M*) in M*F2 difluorides is examined within coherent crystal chemistry and ab initio visualizations. M*2+ in such oxidation state brings three lone pairs (E) and difluorides are formulated M*F2E3. The analyses use electron localization function (ELF) obtained within density functional theory calculations showing the development of the LP triplets whirling {E3} quantified in the relevant chemical systems. Detailed ELF data analyses allowed showing that in α KrF2E3 and isostructural XeF2E3 difluorides the three E electronic clouds merge or hybridize into a torus and adopt a perfect gyration circle with an elliptical section, while in β KrF2 the network architecture deforms the whole torus into an ellipsoid shape. Original precise metrics are provided for the torus in the different compounds under study. In KrF2 the geometric changes upon β → α phase transition is schematized and mechanisms for the transformation with temperature or pressure are proposed. The results are further highlighted by electronic band structure calculations which show similar features of equal band gaps of 3 eV in both α and β KrF2 and a reorganization of frontier orbitals due to the different orientations of the F-Kr-F linear molecule in the two tetragonal structures.

Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis

PubMed Central

Mori, Munemasa; Hazan, Renin; Danielian, Paul S.; Mahoney, John E.; Li, Huijun; Lu, Jining; Miller, Emily S.; Zhu, Xueliang; Lees, Jacqueline A.; Cardoso, Wellington V.

2017-01-01

Abnormal development of multiciliated cells is a hallmark of a variety of human conditions associated with chronic airway diseases, hydrocephalus and infertility. Multiciliogenesis requires both activation of a specialized transcriptional program and assembly of cytoplasmic structures for large-scale centriole amplification that generates basal bodies. It remains unclear, however, what mechanism initiates formation of these multiprotein complexes in epithelial progenitors. Here we show that this is triggered by nucleocytoplasmic translocation of the transcription factor E2f4. After inducing a transcriptional program of centriole biogenesis, E2f4 forms apical cytoplasmic organizing centres for assembly and nucleation of deuterosomes. Using genetically altered mice and E2F4 mutant proteins we demonstrate that centriole amplification is crucially dependent on these organizing centres and that, without cytoplasmic E2f4, deuterosomes are not assembled, halting multiciliogenesis. Thus, E2f4 integrates nuclear and previously unsuspected cytoplasmic events of centriole amplification, providing new perspectives for the understanding of normal ciliogenesis, ciliopathies and cancer. PMID:28675157

Development of Flight-Safety Prediction Methodology for U.S. Naval Safety Center

DTIC Science & Technology

1969-06-01

i~.n~. I ShS81.ib A m, fOP i WY ii W i i A (G Wr aft sod Nabe ~reaeded by n or 6n/ai*rgtan e e *SN ONIa "N I a)M ) ) ()Function or Equipment Name...110.1 PE99. SYSTfM D1.60ANU Y 1ET 4333 Chet A 4 0 BILOWS IIL A.134 11 VEIL SY STE BlNCS 14314 121k A OVISC0$J6 OAMPIMS Cho tic 013121230 SUNS viscous...02113 PN64*0 SPOILER P841 CYL 14212 KEA6 OUTBYOARD SPOILER PWR CYL 14252 *CC@& SPOILER FOLLOW Up Roo A1S 1425 RI ~ A FOLLOW UP TORfiJ tUsk Sy 1421. CSI5

29 CFR Appendix F to Subpart R of... - Perimeter Columns: Non-Mandatory Guidelines for Complying With § 1926.756(e) To Protect the...

Code of Federal Regulations, 2012 CFR

2012-07-01

... to Subpart R of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND... Steel Erection Pt. 1926, Subpt. R, App. F Appendix F to Subpart R of Part 1926—Perimeter Columns: Non...

29 CFR Appendix F to Subpart R of... - Perimeter Columns: Non-Mandatory Guidelines for Complying With § 1926.756(e) To Protect the...

Code of Federal Regulations, 2014 CFR

2014-07-01

... to Subpart R of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND... Steel Erection Pt. 1926, Subpt. R, App. F Appendix F to Subpart R of Part 1926—Perimeter Columns: Non...

29 CFR Appendix F to Subpart R of... - Perimeter Columns: Non-Mandatory Guidelines for Complying With § 1926.756(e) To Protect the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... to Subpart R of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND... Steel Erection Pt. 1926, Subpt. R, App. F Appendix F to Subpart R of Part 1926—Perimeter Columns: Non...

29 CFR Appendix F to Subpart R of... - Perimeter Columns: Non-Mandatory Guidelines for Complying With § 1926.756(e) To Protect the...

Code of Federal Regulations, 2011 CFR

2011-07-01

... to Subpart R of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND... Steel Erection Pt. 1926, Subpt. R, App. F Appendix F to Subpart R of Part 1926—Perimeter Columns: Non...

29 CFR Appendix F to Subpart R of... - Perimeter Columns: Non-Mandatory Guidelines for Complying With § 1926.756(e) To Protect the...

Code of Federal Regulations, 2013 CFR

2013-07-01

... to Subpart R of Part 1926 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND... Steel Erection Pt. 1926, Subpt. R, App. F Appendix F to Subpart R of Part 1926—Perimeter Columns: Non...

A lentiviral vector with expression controlled by E2F-1: A potential tool for the study and treatment of proliferative diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strauss, Bryan E.; Patricio, Juliana Rotelli; Program in Biotechnology, University of Sao Paulo

2006-10-06

We have constructed a lentiviral vector with expression limited to cells presenting active E2F-1 protein, a potential advantage for gene therapy of proliferative diseases. For the FE2FLW vector, the promoter region of the human E2F-1 gene was utilized to drive expression of luciferase cDNA, included as a reporter of viral expression. Primary, immortalized, and transformed cells were transduced with the FE2FLW vector and cell cycle alterations were induced with serum starvation/replacement, contact inhibition or drug treatment, revealing cell cycle-dependent changes in reporter activity. Forced E2F-1 expression, but not E2F-2 or E2F-3, increased reporter activity, indicating a major role for thismore » factor in controlling expression from the FE2FLW virus. We show the utility of this vector as a reporter of E2F-1 and proliferation-dependent cellular alterations upon cytotoxic/cytostatic treatment, such as the introduction of tumor suppressor genes. We propose that the FE2FLW vector may be a starting point for the development of gene therapy strategies for proliferative diseases, such as cancer or restinosis.« less

An assessment of traffic safety culture related to engagement efforts to improve traffic safety : research programs.

DOT National Transportation Integrated Search

2016-12-01

The Center for Health and Safety Culture at Montana State University developed a survey to investigate the traffic safety culture related to engagement in traffic safety citizenship behaviors. The development of the survey was based on an augmented f...

Rare emergence of drug resistance in HIV-1 treatment-naïve patients after 48 weeks of treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide.

PubMed

Margot, Nicolas A; Kitrinos, Kathryn M; Fordyce, Marshall; McCallister, Scott; Miller, Michael D; Callebaut, Christian

2016-03-01

Tenofovir alafenamide (TAF), a novel prodrug of the NtRTI tenofovir (TFV), delivers TFV-diphosphate (TFV-DP) to target cells more efficiently than the current prodrug, tenofovir disoproxil fumarate (TDF), with a 90% reduction in TFV plasma exposure. TAF, within the fixed dose combination of elvitegravir /cobicistat / emtricitabine (FTC)/TAF (E/C/F/TAF), has been evaluated in one Phase 2 and two Phase 3 randomized, double-blinded studies in HIV-infected treatment-naive patients, comparing E/C/F/TAF to E/C/F/TDF. In these studies, the TAF-containing group demonstrated non-inferior efficacy to the TDF-containing comparator group with 91.9% of E/C/F/TAF patients having <50 copies/mL of HIV-1 RNA at week 48. An integrated resistance analysis across these three studies was conducted, including HIV-1 genotypic analysis at screening, and genotypic/phenotypic analysis for patients with HIV-1 RNA>400 copies/mL at virologic failure. Pre-existing primary resistance-associated mutations (RAMs) were observed at screening among the 1903 randomized and treated patients: 7.5% had NRTI-RAMs, 18.2% had NNRTI-RAMs, and 3.4% had primary PI-RAMs. Pre-treatment RAMs did not influence treatment response at Week 48. In the E/C/F/TAF group, resistance development was rare; seven patients (0.7%, 7/978) developed NRTI-RAMs, five of whom (0.5%, 5/978) also developed primary INSTI-RAMs. In the E/C/F/TDF group, resistance development was also rare; seven patients (0.8%, 7/925) developed NRTI-RAMs, four of whom (0.4%, 4/925) also developed primary INSTI-RAMs. An additional analysis by deep sequencing in virologic failures revealed minimal differences compared to population sequencing. Overall, resistance development was rare in E/C/F/TAF-treated patients, and the pattern of emergent mutations was similar to E/C/F/TDF.

NASA DFRC Practices for Prototype Qualification

NASA Technical Reports Server (NTRS)

Lokos, William A.

2009-01-01

This slide presentation reviews the practices that Dryden uses for qualification of the prototypes of aircraft. There are many views of aircraft that Dryden has worked with. Included is a discussion of basic considerations for strength, a listing of standards and references, a discussion of typical safety of flight approaches, a discussion of the prototype design, using the X-29A as an example, and requirements for new shapes (i.e., the DAST-ARW1 , F-8 Super Critical Wing, AFTI/F-111 MAW), new control laws (i.e., AAW F-18), new operating envelope (i.e., F-18 HARV), limited sope add-on or substitute structure (i.e., SR-71 LASRE, ECLIPSE, F-16XL SLFC), and extensively modified or replaced structure (i.e., SOFIA, B747SP). There is a listing of causes for the failure of the prototype.

Word Frequency Analysis. MOS: 57H. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

8217 . -4 1a’ _________ Palms 1t. FLL& T - VI;:.P - -- S LtrTZE5 I Lu" I rprz l * 4 2lE p:Zn.uAwn PLCU4LLE 14 Piz;* I P RTICULAR 4 PZR1S 7 J _________ 2...I’ I VIn 1 fIV 7 IaIIA!’I TIP 2 1-111 L LAlT P i;10! S II*,s , 11- 1 L Ii1! p UIIIc tInlG Z :𔃻 S -W (INSf4 2 IZ 1111tE~ ;l ,’I I z a5T p Oil ’(1$I1...p --G 6 RIGGING- I~ V~. 1 5EL~ .1 50:L I SF AFY~~3!.rS_7I; 7 SAFETY I----c- 7 -- ss1 ’_F T_-------- 1 HPPI 7A! I1CEUE SCP .~LaG 3 SHUTWI ~ SC’~J’!LI

Quality Control of Injection Molded Eyewear by Non-Contact Deflectometry

NASA Astrophysics Data System (ADS)

Speck, A.; Zelzer, B.; Langenbucher, A.; Eppig, T.

2014-07-01

Occupational eye wear such as safety spectacles are manufactured by injection molding techniques. Testing of the assembled safety spectacle lenses in transmission is state of the art, but there is a lack of surface measurement systems for occupational safety lenses. The purpose of this work was to validate a deflectometric setup for topography measurement, detection of defects and visualization of the polishing quality, e.g. casting indentations or impressions, for the production process of safety spectacles. The setup is based on a customized stereo phase measuring deflectometer (PMD), equipped with 3 cameras with f'1,2 = 16 mm and f'3 = 8.5 mm and a specified measurement uncertainty of ± 3 μm. Sixteen plastic lenses and 8 corresponding injection molds from 4 parallel cavities were used for validation of the deflectometer. For comparison an interferometric method and a reference standard (< λ/10 super polished) was used. The accuracy and bias with a spherical safety spectacle sample was below 1 μm, according to DIN ISO 5725-2.2002-12. The repeatability was 2.1 μm and 35.7 μm for a blind radius fit. In conclusion, the PMD technique is an appropriate tool for characterizing occupational safety spectacle and injections mold surfaces. With the presented setup we were able to quantify the surface quality. This can be useful and may optimize the quality of the end product, in addition to standardized measuring systems in transmission.

Competencies of Organizational Effectiveness Consultants in the U.S. Army

DTIC Science & Technology

1981-05-01

through OD. Management Review, 1978, 67(2), 52-56. Huse, E. F. Organization development and change. St. Paul , MN: West Publishing, 1975. Huse, E. F...11(4), 457-474. Paul , W. J., Robertson, K. B., & Herzberg, F. Job enrichment pays off. Harvard Business Review, 1969, 47, 61-78. Pedalino, E... Neubert , S. F., & Hulswit, F. T. How one R&D department increased productivity. International Journal of Research Management, 1974, 17(5), 17-22

Novel functions for the transcription factor E2F4 in development and disease

PubMed Central

Sage, Julien

2016-01-01

ABSTRACT The E2F family of transcription factors is a key determinant of cell proliferation in response to extra- and intra-cellular signals. Within this family, E2F4 is a transcriptional repressor whose activity is critical to engage and maintain cell cycle arrest in G0/G1 in conjunction with members of the retinoblastoma (RB) family. However, recent observations challenge this paradigm and indicate that E2F4 has a multitude of functions in cells besides this cell cycle regulatory role, including in embryonic and adult stem cells, during regenerative processes, and in cancer. Some of these new functions are independent of the RB family and involve direct activation of target genes. Here we review the canonical functions of E2F4 and discuss recent evidence expanding the role of this transcription factor, with a focus on cell fate decisions in tissue homeostasis and regeneration. PMID:27753528

Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study.

PubMed

Tran, Jonathan Q; Hartung, Jeffrey P; Olson, Allan D; Mendzelevski, Boaz; Timony, Gregg A; Boehm, Marcus F; Peach, Robert J; Gujrathi, Sheila; Frohna, Paul A

2018-03-01

Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. This randomized, double-blind, placebo-controlled, positive-controlled, parallel-group thorough QT study characterized the effects of ozanimod on cardiac repolarization in healthy subjects. Eligible subjects were randomized to 1 of 2 groups: ozanimod (escalated from 0.25 to 2 mg over 14 days) or placebo (for 14 days). A single dose of moxifloxacin 400 mg or placebo was administered on days 2 and 17. The primary end point was the time-matched, placebo-corrected, baseline-adjusted mean QTcF (ΔΔQTcF). A total of 113/124 (91.1%) subjects completed the study. The upper limits of the 2-sided 90% confidence intervals for ΔΔQTcF for both ozanimod 1 and 2 mg were below the 10-millisecond regulatory threshold. No QTcF >480 milliseconds or postdose change in QTcF of >60 milliseconds was observed. There was no evidence of a positive relationship between concentrations of ozanimod and its active metabolites and ΔΔQTcF. Although ozanimod blunted the observed diurnal increase in heart rate, excursions below predose heart rates were no greater than with placebo. Results demonstrate that ozanimod does not prolong the QTc interval or cause clinically significant bradycardia, supporting ozanimod's evolving favorable cardiac safety profile. © 2017 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Mining e-cigarette adverse events in social media using Bi-LSTM recurrent neural network with word embedding representation.

PubMed

Xie, Jiaheng; Liu, Xiao; Dajun Zeng, Daniel

2018-01-01

Recent years have seen increased worldwide popularity of e-cigarette use. However, the risks of e-cigarettes are underexamined. Most e-cigarette adverse event studies have achieved low detection rates due to limited subject sample sizes in the experiments and surveys. Social media provides a large data repository of consumers' e-cigarette feedback and experiences, which are useful for e-cigarette safety surveillance. However, it is difficult to automatically interpret the informal and nontechnical consumer vocabulary about e-cigarettes in social media. This issue hinders the use of social media content for e-cigarette safety surveillance. Recent developments in deep neural network methods have shown promise for named entity extraction from noisy text. Motivated by these observations, we aimed to design a deep neural network approach to extract e-cigarette safety information in social media. Our deep neural language model utilizes word embedding as the representation of text input and recognizes named entity types with the state-of-the-art Bidirectional Long Short-Term Memory (Bi-LSTM) Recurrent Neural Network. Our Bi-LSTM model achieved the best performance compared to 3 baseline models, with a precision of 94.10%, a recall of 91.80%, and an F-measure of 92.94%. We identified 1591 unique adverse events and 9930 unique e-cigarette components (ie, chemicals, flavors, and devices) from our research testbed. Although the conditional random field baseline model had slightly better precision than our approach, our Bi-LSTM model achieved much higher recall, resulting in the best F-measure. Our method can be generalized to extract medical concepts from social media for other medical applications. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis

PubMed Central

Eiring, Anna M.; Neviani, Paolo; Santhanam, Ramasamy; Oaks, Joshua J.; Chang, Ji Suk; Notari, Mario; Willis, William; Gambacorti-Passerini, Carlo; Volinia, Stefano; Marcucci, Guido; Caligiuri, Michael A.; Leone, Gustavo W.

2008-01-01

Several RNA binding proteins (RBPs) have been implicated in the progression of chronic myelogenous leukemia (CML) from the indolent chronic phase to the aggressively fatal blast crisis. In the latter phase, expression and function of specific RBPs are aberrantly regulated at transcriptional or posttranslational levels by the constitutive kinase activity of the BCR/ABL oncoprotein. As a result, altered expression/function of RBPs leads to increased resistance to apoptotic stimuli, enhanced survival, growth advantage, and differentiation arrest of CD34+ progenitors from patients in CML blast crisis. Here, we identify the mRNAs bound to the hnRNP-A1, hnRNP-E2, hnRNP-K, and La/SSB RBPs in BCR/ABLtransformed myeloid cells. Interestingly, we found that the mRNA encoding the transcription factor E2F3 associates to hnRNP-A1 through a conserved binding site located in the E2F3 3′ untranslated region (UTR). E2F3 levels were up-regulated in CML-BCCD34+ in a BCR/ABL kinase– and hnRNP-A1 shuttling–dependent manner. Moreover, by using shRNA-mediated E2F3 knock-down and BCR/ABL-transduced lineage-negative bone marrow cells from E2F3+/+ and E2F3−/− mice, we show that E2F3 expression is important for BCR/ABL clonogenic activity and in vivo leukemogenic potential. Thus, the complexity of the mRNA/RBP network, together with the discovery of E2F3 as an hnRNP-A1–regulated factor, outlines the relevant role played by RBPs in posttranscriptional regulation of CML development and progression. PMID:17925491

Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease.

PubMed

Nilsson, Eric E; Anway, Matthew D; Stanfield, Jacob; Skinner, Michael K

2008-05-01

Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1-F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8-E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1-F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1-F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states.

Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease

PubMed Central

Nilsson, Eric E; Anway, Matthew D; Stanfield, Jacob; Skinner, Michael K

2017-01-01

Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1–F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8–E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1–F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1–F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states. PMID:18304984

Transcriptional control of stem cell fate by E2Fs and pocket proteins

PubMed Central

Julian, Lisa M.; Blais, Alexandre

2015-01-01

E2F transcription factors and their regulatory partners, the pocket proteins (PPs), have emerged as essential regulators of stem cell fate control in a number of lineages. In mammals, this role extends from both pluripotent stem cells to those encompassing all embryonic germ layers, as well as extra-embryonic lineages. E2F/PP-mediated regulation of stem cell decisions is highly evolutionarily conserved, and is likely a pivotal biological mechanism underlying stem cell homeostasis. This has immense implications for organismal development, tissue maintenance, and regeneration. In this article, we discuss the roles of E2F factors and PPs in stem cell populations, focusing on mammalian systems. We discuss emerging findings that position the E2F and PP families as widespread and dynamic epigenetic regulators of cell fate decisions. Additionally, we focus on the ever expanding landscape of E2F/PP target genes, and explore the possibility that E2Fs are not simply regulators of general ‘multi-purpose’ cell fate genes but can execute tissue- and cell type-specific gene regulatory programs. PMID:25972892

Alternative Green Solvents Project

NASA Technical Reports Server (NTRS)

Maloney, Phillip R.

2012-01-01

Necessary for safe and proper functioning of equipment. Mainly halogenated solvents. Tetrachloride, Trichloroethylene (TCE), CFC-113. No longer used due to regulatory/safety concerns. Precision Cleaning at KSC: Small % of total parts. Used for liquid oxygen (LOX) systems. Dual solvent process. Vertrel MCA (decafluoropentane (DFP) and trons-dichloroethylene) HFE-7100. DFP has long term environmental concerns. Project Goals: a) Identify potential replacements. b) 22 wet chemical processes. c) 3 alternative processes. d) Develop test procedures. e) Contamination and cleaning. f) Analysis. g) Use results to recommend alternative processes. Conclusions: a) No alternative matched Vertrel in this study. b) No clear second place solvent. c) Hydrocarbons- easy; Fluorinated greases- difficult. d) Fluorinated component may be needed in replacement solvent. e) Process may need to make up for shortcoming of the solvent. f) Plasma and SCC02 warrant further testing.

MicroRNA-424/E2F6 feedback loop modulates cell invasion, migration and EMT in endometrial carcinoma

PubMed Central

Lu, Zheng; Nian, Zhou; Jingjing, Zhang; Tao, Luo; Quan, Li

2017-01-01

Our previous study explored the roles of microRNA-424 (miR-424) in the development of endometrial carcinoma (EC) and analyzed the miR-424/E2F7 axis in EC cell growth. In this study, we investigated the status of miR-424 in human endometrial cancer tissues, which were collected from a cohort of Zunyi patients. We found that the expression level of miR-424 was associated with clinical tumor stage, cell differentiation, lymph node metastasis and cell migration ability. Cell function experiments demonstrated that miR-424 overexpression suppressed the invasion and migration abilities of endometrial carcinoma cells in vitro. Bioinformatic predictions and dual-luciferase reporter assays suggested E2F6 as a possible target of miR-424. RT-PCR and western blot assays demonstrated that miR-424 transfection reduced the expression level of E2F6, while inhibiting miR-424 with ASO-miR-424 (antisense oligonucleotides of miR-424) increased the expression level of E2F6. Cell function experiments indicated that E2F6 transfection rescued the EC cell phenotype induced by miR-424. In addition, we also found that E2F6 negatively regulated miR-424 expression in EC cells. In summary, our results demonstrated that the miR-424/E2F6 feedback loop modulates cell invasion, migration and EMT in EC and that the miR-424/E2Fs regulation network may serve as a new and potentially important therapeutic target in EC. PMID:29371986

Structures and electron affinities of the di-arsenic fluorides As2Fn/As2Fn- (n=1-8).

PubMed

Kasalová, Veronika; Schaefer, Henry F

2005-04-15

Developments in the preparation of new materials for microelectronics are focusing new attention on molecular systems incorporating several arsenic atoms. A systematic investigation of the As2Fn/As2Fn- systems was carried out using Density Functional Theory methods and a DZP++ quality basis set. Global and low-lying local geometric minima and relative energies are discussed and compared. The three types of neutral-anion separations reported in this work are: the adiabatic electron affinity (EAad), the vertical electron affinity (EAvert), and the vertical detachment energy (VDE). Harmonic vibrational frequencies pertaining to the global minimum for each compound are reported. From the first four studied species (As2Fn, n=1-4), all neutral molecules and their anions are shown to be stable with respect to As-As bond breaking. The neutral As2F molecule and its anion are predicted to have Cs symmetry. We find the trans F-As-As-F isomer of C2h symmetry and a pyramidalized vinylidene-like As-As-F2- isomer of Cs symmetry to be the global minima for the As2F2 and As2F2- species, respectively. The lowest lying minima of As2F3 and As2F3- are vinyl radical-like structures F-As-As-F2 of Cs symmetry. The neutral As2F4 global minimum is a trans-bent (like Si2H4) F2-As-As-F2 isomer of C2 symmetry, while its anion is predicted to have an unusual fluorine-bridged (C(1)) structure. The global minima of the neutral As2Fn species, n=5-8, are weakly bound complexes, held together by dipole-dipole interactions. All such structures have the AsFm-AsFn form, where (m,n) is (2,3) for As2F5, (3,3) for As2F6, (4,3) for As2F7), and (5,3) for As2F8. For As2F8 the beautiful pentavalent F4As-AsF4 structure (analogous to the stable AsF5 molecule) lies about 30 kcal/mol above the AsF3 . . . AsF5 complex. The stability of AsF(5) depends crucially on the strong As-F bonds, and replacing one of these with an As-As bond (in F4As-AsF4) has a very negative impact on the molecule's stability. The anions As2Fn-, n=5-8, are shown to be stable with respect to the As-As bond breaking, and we predict that all of them have fluorine-bridged or fluorine-linked structures. The zero-point vibrational energy corrected adiabatic electron affinities are predicted to be 2.28 eV (As2F), 1.95 eV (As2F2), 2.39 eV (As2F3), 1.71 eV (As2F4), 2.72 eV (As2F5), 1.79 eV (As2F6), 5.26 eV (As2F7), and 3.40 eV (As2F8) from the BHLYP method. Vertical detachment energies are rather large, especially for species with fluorine-bridged global minima, having values up to 6.45 eV (As2F7, BHLYP).

TFDP3 was expressed in coordination with E2F1 to inhibit E2F1-mediated apoptosis in prostate cancer.

PubMed

Ma, Yueyun; Xin, Yijuan; Li, Rui; Wang, Zhe; Yue, Qiaohong; Xiao, Fengjing; Hao, Xiaoke

2014-03-10

TFDP3 has been previously identified as an inhibitor of E2F molecules. It has been shown to suppress E2F1-induced apoptosis dependent P53 and to play a potential role in carcinogenesis. However, whether it indeed helps cancer cells tolerate apoptosis stress in cancer tissues remains unknown. TFDP3 expression was assessed by RT-PCR, in situ hybridization and immunohistochemistry in normal human tissues, cancer tissues and prostate cancer tissues. The association between TFDP3 and E2F1 in prostate cancer development was analyzed in various stages. Apoptosis was evaluated with annexin-V and propidium iodide staining and flow-cytometry. The results show that, in 96 samples of normal human tissues, TFDP3 could be detected in the cerebrum, esophagus, stomach, small intestine, bronchus, breast, ovary, uterus, and skin, but seldom in the lung, muscles, prostate, and liver. In addition, TFDP3 was highly expressed in numerous cancer tissues, such as brain-keratinous, lung squamous cell carcinoma, testicular seminoma, cervical carcinoma, skin squamous cell carcinoma, gastric adenocarcinoma, liver cancer, and prostate cancer. Moreover, TFDP3 was positive in 23 (62.2%) of 37 prostate cancer samples regardless of stage. Furthermore, immunohistochemistry results show that TFDP3 was always expressed in coordination with E2F1 at equivalent expression levels in prostate cancer tissues, and was highly expressed particularly in samples of high stage. When E2F1 was extrogenously expressed in LNCap cells, TFDP3 could be induced, and the apoptosis induced by E2F1 was significantly decreased. It was demonstrated that TFDP3 was a broadly expressed protein corresponding to E2F1 in human tissues, and suggested that TFDP3 is involved in prostate cancer cell survival by suppressing apoptosis induced by E2F1. Copyright © 2013 Elsevier B.V. All rights reserved.

Copy number variations of E2F1: a new genetic risk factor for testicular cancer.

PubMed

Rocca, Maria Santa; Di Nisio, Andrea; Marchiori, Arianna; Ghezzi, Marco; Opocher, Giuseppe; Foresta, Carlo; Ferlin, Alberto

2017-03-01

Testicular germ cell tumor (TGCT) is one of the most heritable forms of cancer. In last years, many evidence suggested that constitutional genetic factors, mainly single nucleotide polymorphisms, can increase its risk. However, the possible contribution of copy number variations (CNVs) in TGCT susceptibility has not been substantially addressed. Indeed, an increasing number of studies have focused on the effect of CNVs on gene expression and on the role of these structural genetic variations as risk factors for different forms of cancer. E2F1 is a transcription factor that plays an important role in regulating cell growth, differentiation, apoptosis and response to DNA damage. Therefore, deficiency or overexpression of this protein might significantly influence fundamental biological processes involved in cancer development and progression, including TGCT. We analyzed E2F1 CNVs in 261 cases with TGCT and 165 controls. We found no CNVs in controls, but 17/261 (6.5%) cases showed duplications in E2F1 Blot analysis demonstrated higher E2F1 expression in testicular samples of TGCT cases with three copies of the gene. Furthermore, we observed higher phosphorylation of Akt and mTOR in samples with E2F1 duplication. Interestingly, normal, non-tumoral testicular tissue in patient with E2F1 duplication showed lower expression of E2F1 and lower AKT/mTOR phosphorylation with respect to adjacent tumor tissue. Furthermore, increased expression of E2F1 obtained in vitro in NTERA-2 testicular cell line induced increased AKT/mTOR phosphorylation. This study suggests for the first time an involvement of E2F1 CNVs in TGCT susceptibility and supports previous preliminary data on the importance of AKT/mTOR signaling pathway in this cancer. © 2017 Society for Endocrinology.

Automatic Barometric Updates from Ground-Based Navigational Aids

DTIC Science & Technology

1990-03-12

ro fAutomatic Barometric Updates US Department from of Transportation Ground-Based Federal Aviation Administration Navigational Aids Office of Safety...tighter vertical spacing controls , particularly for operations near Terminal Control Areas (TCAs), Airport Radar Service Areas (ARSAs), military climb and...E.F., Ruth, J.C., and Williges, B.H. (1987). Speech Controls and Displays. In Salvendy, G., E. Handbook of Human Factors/Ergonomics, New York, John

Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia (the ADvance Trial): A Two Year Follow-up Including Results of Delayed Activation.

PubMed

Leoutsakos, Jeannie-Marie S; Yan, Haijuan; Anderson, William S; Asaad, Wael F; Baltuch, Gordon; Burke, Anna; Chakravarty, M Mallar; Drake, Kristen E; Foote, Kelly D; Fosdick, Lisa; Giacobbe, Peter; Mari, Zoltan; McAndrews, Mary Pat; Munro, Cynthia A; Oh, Esther S; Okun, Michael S; Pendergrass, Jo Cara; Ponce, Francisco A; Rosenberg, Paul B; Sabbagh, Marwan N; Salloway, Stephen; Tang-Wai, David F; Targum, Steven D; Wolk, David; Lozano, Andres M; Smith, Gwenn S; Lyketsos, Constantine G

2018-06-09

Given recent challenges in developing new treatments for Alzheimer dementia (AD), it is vital to explore alternate treatment targets, such as neuromodulation for circuit dysfunction. We previously reported an exploratory Phase IIb double-blind trial of deep brain stimulation targeting the fornix (DBS-f) in mild AD (the ADvance trial). We reported safety but no clinical benefits of DBS-f versus the delayed-on (sham) treatment in 42 participants after one year. However, secondary post hoc analyses of the one-year data suggested a possible DBS-f benefit for participants≥65 years. To examine the long-term safety and clinical effects of sustained and delayed-on DBS-f treatment of mild AD after two years. 42 participants underwent implantation of DBS-f electrodes, with half randomized to active DBS-f stimulation (early on) for two years and half to delayed-on (sham) stimulation after 1 year to provide 1 year of active DBS-f stimulation (delayed on). We evaluated safety and clinical outcomes over the two years of the trial. DBS-f had a favorable safety profile with similar rates of adverse events across both trial phases (years 1 and 2) and between treatment arms. There were no differences between treatment arms on any primary clinical outcomes. However, post-hoc age group analyses suggested a possible benefit among older (>65) participants. DBS-f was safe. Additional study of mechanisms of action and methods for titrating stimulation parameters will be needed to determine if DBS has potential as an AD treatment. Future efficacy studies should focus on patients over age 65.

East Coast Air Combat Maneuvering Range (EC/ACMR) Ocean Tower Construction Completion Report.

DTIC Science & Technology

1978-03-01

c)D Sa con itionS.r n lectricaldes St rm oactlvtto ~Utost 311fa :... ea rjn d~ ,Rjon,&gj B. ADMIN a m . cu a C. OPERATIONS: O;erations at Tower F3 ...nections. D. EQUIP STATUS - NONE E. LOGISTICS - NONE F. TRAINING NONE C. SAFETY - NO ACCIDENTS H. t,.EDICAL- NO INJURIES 1. ,ORALE- Nigh ad Tower f3 ...74. .-- Y .~lile B-. driven 59 ftv/5 6 0, 060, and 040 haieers; AV B,"F - e driven 57 ft w/5 6 0 and 040 hammers; AV BPP 82 v/540. Total weather time

Cell Signaling by a Novel SH2 Domain Protein that is Overexpressed with Her2 in Breast Cancer

DTIC Science & Technology

1998-01-01

1990) Methods Enzymol. 185, 51. Wary, K. K, Mainiero, F ., Isakoff, S. J., Marcantonio , E. E., and Giancotti 527-537 F . G. (1996) Cell 87, 733-743...family of SH2 domain proteins and acts cell nonautonomously in excretory canal development. Dev. Biol. 184:150-164. 3. Pelicci, G., L. Lanfrancone, F ...Grignani, J. McGlade, F . Cavallo, G. Forni, I. Nicoletti, T. Pawson, and P. G. Pelicci. 1992. A novel transforming protein (SHC) with an SH2

E2F transcription factors and digestive system malignancies: how much do we know?

PubMed

Evangelou, Konstantinos; Havaki, Sophia; Kotsinas, Athanassios

2014-08-07

The E2F proteins comprise a family of 8 members that function as transcription factors. They are key targets of the retinoblastoma protein (RB) and were initially divided into groups of activators and repressors. Accumulating data suggest that there is no specific role for each individual E2F member. Instead, each E2F can exert a variety of cellular effects, some of which represent opposing ones. For instance, specific E2Fs can activate transcription and repression, promote or hamper cell proliferation, augment or inhibit apoptosis, all being dependent on the cellular context. This complexity reflects the importance that these transcription factors have on a cell's fate. Thus, delineating the specific role for each E2F member in specific malignancies, although not easy, is a challenging and continuously pursued task, especially in view of potential E2F targeted therapies. Therefore, several reviews are continuously trying to evaluate available data on E2F status in various malignancies. Such reviews have attempted to reach a consensus, often in the simplistic form of oncogenes or tumor suppressor genes for the E2Fs. However they frequently miss spatial and temporal alterations of these factors during tumor development, which should also be considered in conjunction with the status of the regulatory networks that these factors participate in. In the current ''Letter to the Editor'', we comment on the flaws, misinterpretations and omissions in one such review article published recently in the World Journal of Gastroenterology regarding the role of E2Fs in digestive system malignancies.

3-T MRI safety assessments of magnetic dental attachments and castable magnetic alloys

PubMed Central

Miyata, K; Abe, Y; Ishii, T; Ishigami, T; Ohtani, K; Nagai, E; Ohyama, T; Umekawa, Y; Nakabayashi, S

2015-01-01

Objectives: To assess the safety of different magnetic dental attachments during 3-T MRI according to the American Society for Testing and Materials F2182-09 and F2052-06e1 standard testing methods and to develop a method to determine MRI compatibility by measuring magnetically induced torque. Methods: The temperature elevations, magnetically induced forces and torques of a ferromagnetic stainless steel keeper, a coping comprising a keeper and a cast magnetic alloy coping were measured on MRI systems. Results: The coping comprising a keeper demonstrated the maximum temperature increase (1.42 °C) for the whole-body-averaged specific absorption rate and was calculated as 2.1 W kg−1 with the saline phantom. All deflection angles exceeded 45°. The cast magnetic alloy coping had the greatest deflection force (0.33 N) during 3-T MRI and torque (1.015 mN m) during 0.3-T MRI. Conclusions: The tested devices showed minimal radiofrequency (RF)-induced heating in a 3-T MR environment, but the cast magnetic alloy coping showed a magnetically induced deflection force and torque approximately eight times that of the keepers. For safety, magnetic dental attachments should be inspected before and after MRI and large prostheses containing cast magnetic alloy should be removed. Although magnetic dental attachments may pose no great risk of RF-induced heating or magnetically induced torque during 3-T MRI, their magnetically induced deflection forces tended to exceed acceptable limits. Therefore, the inspection of such devices before and after MRI is important for patient safety. PMID:25785821

Development of dye-sensitized solar cells composed of liquid crystal embedded, electrospun poly(vinylidene fluoride-co-hexafluoropropylene) nanofibers as polymer gel electrolytes.

PubMed

Ahn, Sung Kwang; Ban, Taewon; Sakthivel, P; Lee, Jae Wook; Gal, Yeong-Soon; Lee, Jin-Kook; Kim, Mi-Ra; Jin, Sung-Ho

2012-04-01

In order to overcome the problems associated with the use of liquid electrolytes in dye-sensitized solar cells (DSSCs), a new system composed of liquid crystal embedded, polymer electrolytes has been developed. For this purpose, three types of DSSCs have been fabricated. The cells contain electrospun poly(vinylidene fluoride-co-hexafluoropropylene) (e-PVdF-co-HFP) polymer gel electrolyte, with and without doping with the liquid crystal E7 and with a liquid electrolyte. The morphologies of the newly prepared DSSCs were explored using field emission scanning electron microscopy (FE-SEM). Analysis of the FE-SEM images indicate that the DSSC composed of E7 embedded on e-PVdF-co-HFP polymer gel electrolyte has a greatly regular morphology with an average diameter. The ionic conductivity of E7 embedded on e-PVdF-co-HFP polymer gel electrolyte was found to be 2.9 × 10(-3) S/cm at room temperature, a value that is 37% higher than that of e-PVdF-co-HFP polymer gel electrolyte. The DCCS containing the E7 embedded, e-PVdF-co-HFP polymer gel electrolyte was observed to possess a much higher power conversion efficiency (PCE = 6.82%) than that of an e-PVdF-co-HFP nanofiber (6.35%). In addition, DSSCs parameters of the E7 embedded, e-PVdF-co-HFP polymer gel electrolyte (V(oc) = 0.72 V, J(sc) = 14.62 mA/cm(2), FF = 64.8%, and PCE = 6.82% at 1 sun intensity) are comparable to those of a liquid electrolyte (V(oc) = 0.75 V, J(sc) = 14.71 mA/cm(2), FF = 64.9%, and PCE = 7.17%, both at a 1 sun intensity).

Cranberry extract inhibits in vitro adhesion of F4 and F18+Escherichia coli to pig intestinal epithelium and reduces in vivo excretion of pigs orally challenged with F18+ verotoxigenic E. coli.

PubMed

Coddens, Annelies; Loos, Michaela; Vanrompay, Daisy; Remon, Jean Paul; Cox, Eric

2017-04-01

F4 + E. coli and F18 + E. coli infections are an important threat for pig industry worldwide. Antibiotics are commonly used to treat infected piglets, but the emerging development of resistance against antibiotics raises major concerns. Hence, alternative therapies to prevent pigs from F4 + E. coli and F18 + E. coli infections need to be developed. Since cranberry previously showed anti-adhesive activity against uropathogenic E. coli, we aimed to investigate whether cranberry extract could also inhibit binding of F4 + E. coli and F18 + E. coli to pig intestinal epithelium. Using the in vitro villus adhesion assay, we found that low concentrations of cranberry extract (20μg or 100μg/ml) have strong inhibitory activity on F4 + E. coli (75.3%, S.D.=9.31 or 95.8%, S.D.=2.56, respectively) and F18 + E. coli adherence (100% inhibition). This effect was not due to antimicrobial activity. Moreover, cranberry extract (10mg or 100mg) could also abolish in vivo binding of F4 and F18 fimbriae to the pig intestinal epithelium in ligated loop experiments. Finally, two challenge experiments with F18 + E. coli were performed to address the efficacy of in-feed or water supplemented cranberry extract. No effect could be observed in piglets that received cranberry extract only in feed (1g/kg or 10g/kg). However, supplementation of feed (10g/kg) and drinking water (1g/L) significantly decreased excretion and diarrhea. The decreased infection resulted in a decreased serum antibody response indicating reduced exposure to F18 + E. coli. Copyright © 2017 Elsevier B.V. All rights reserved.

Common Core Curriculum for Vocational Education. Category F: Stages and Structure of Curriculum Development. F-4: Safety.

ERIC Educational Resources Information Center

Winegar, Gary

This module on safety is one of a set of four on stages and structure of curriculum development and is part of a larger series of thirty-four modules comprising a core curriculum intended for use in the professional preparation of vocational educators in the areas of agricultural, business, home economics, and industrial education. Following the…

Safety and Immunogenicity of 3 Formulations of an Investigational Respiratory Syncytial Virus Vaccine in Nonpregnant Women: Results From 2 Phase 2 Trials

PubMed Central

Beran, Jiři; Lickliter, Jason D; Schwarz, Tino F; Johnson, Casey; Chu, Laurence; Domachowske, Joseph B; Van Damme, Pierre; Withanage, Kanchanamala; Fissette, Laurence A; David, Marie-Pierre; Maleux, Koen; Schmidt, Alexander C; Picciolato, Marta; Dieussaert, Ilse

2018-01-01

Abstract Background Respiratory syncytial virus (RSV) causes bronchiolitis and pneumonia in neonates and infants. RSV vaccination during pregnancy could boost preexisting neutralizing antibody titers, providing passive protection to newborns. Methods Two observer-blinded, controlled studies (RSV F-020 [clinical trials registration NCT02360475] and RSV F-024 [NCT02753413]) evaluated immunogenicity and safety of an investigational RSV vaccine in healthy, nonpregnant 18–45-year-old women. Both studies used a licensed adult formulation of combined tetanus toxoid-diphtheria toxoid-acellular pertussis (Tdap) vaccine as a control. RSV F-020 evaluated immunogenicity and safety: participants were randomized (1:1:1:1) to receive 1 dose of RSV–prefusion F protein (PreF) vaccine containing 30 µg or 60 µg of nonadjuvanted RSV-PreF, 60 µg of aluminum-adjuvanted RSV-PreF, or Tdap. RSV F-024 evaluated safety: participants were randomized 1:1 to receive 1 dose of 60 µg of nonadjuvanted RSV-PreF or Tdap. Results Both studies showed similar reactogenicity profiles for RSV-PreF and Tdap. No serious adverse events were considered vaccine related. In RSV F-020, geometric mean ratios of RSV-A neutralizing antibody levels at day 30 versus prevaccination were 3.1–3.9 in RSV-PreF recipients and 0.9 in controls. Palivizumab-competing antibody concentrations increased >14-fold in RSV-PreF recipients on day 30. RSV antibody titers waned after day 30 but remained well above baseline through day 90. Conclusions All formulations of RSV-PreF boosted preexisting immune responses in 18–45-year old women with comparable immunogenicity. The RSV-PreF safety profile was similar to that of Tdap vaccine. PMID:29401325

Evaluation of a variable speed limit system for wet and extreme weather conditions : phase 1 report.

DOT National Transportation Integrated Search

2012-06-01

Weather presents considerable challenges to the highway system, both in terms of safety and operations. From a safety standpoint, weather (i.e. precipitation in the form of rain, snow or ice) reduces pavement friction, thus increasing the potential f...

National Dam Safety Program. Garnerville Dam (Inventory Number N.Y. 744), Hudson River Basin, Rockland County, New York. Phase I Inspection Report,

DTIC Science & Technology

1980-08-01

drain and the 8-inch pipeline are in good operating condition and appear to be well maintained. e. Reservoir Area There are neither slides, rockfalls ...Stability fOpcrc c- ,k- I p. Miscellaneous 1 1I I L Project ._Dheet___ _.. Subject ABy Gi ___ A _ A _Chk. by I 0 Q I 40 CiQI /" e6dn-r-f/aa /Ortf e / 7, 4 o

39 CFR 777.21 - General procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Selection. When acquisition of a site under consideration would likely involve displacement of a person... displacement referred to in paragraph (f) of this section. (e) Shorter Notice Period, Unusual Circumstances. An... or safety. (f) Notice of Displacement. Normally, a notice of displacement will be given at the time...

E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells.

PubMed

Castillo, Daniela S; Campalans, Anna; Belluscio, Laura M; Carcagno, Abel L; Radicella, J Pablo; Cánepa, Eduardo T; Pregi, Nicolás

2015-01-01

E2F transcription factors regulate a wide range of biological processes, including the cellular response to DNA damage. In the present study, we examined whether E2F family members are transcriptionally induced following treatment with several genotoxic agents, and have a role on the cell DNA damage response. We show a novel mechanism, conserved among diverse species, in which E2F1 and E2F2, the latter specifically in neuronal cells, are transcriptionally induced after DNA damage. This upregulation leads to increased E2F1 and E2F2 protein levels as a consequence of de novo protein synthesis. Ectopic expression of these E2Fs in neuronal cells reduces the level of DNA damage following genotoxic treatment, while ablation of E2F1 and E2F2 leads to the accumulation of DNA lesions and increased apoptotic response. Cell viability and DNA repair capability in response to DNA damage induction are also reduced by the E2F1 and E2F2 deficiencies. Finally, E2F1 and E2F2 accumulate at sites of oxidative and UV-induced DNA damage, and interact with γH2AX DNA repair factor. As previously reported for E2F1, E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase and induces histone acetylation following genotoxic insult. The results presented here unveil a new mechanism involving E2F1 and E2F2 in the maintenance of genomic stability in response to DNA damage in neuronal cells.

E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells

PubMed Central

Castillo, Daniela S; Campalans, Anna; Belluscio, Laura M; Carcagno, Abel L; Radicella, J Pablo; Cánepa, Eduardo T; Pregi, Nicolás

2015-01-01

E2F transcription factors regulate a wide range of biological processes, including the cellular response to DNA damage. In the present study, we examined whether E2F family members are transcriptionally induced following treatment with several genotoxic agents, and have a role on the cell DNA damage response. We show a novel mechanism, conserved among diverse species, in which E2F1 and E2F2, the latter specifically in neuronal cells, are transcriptionally induced after DNA damage. This upregulation leads to increased E2F1 and E2F2 protein levels as a consequence of de novo protein synthesis. Ectopic expression of these E2Fs in neuronal cells reduces the level of DNA damage following genotoxic treatment, while ablation of E2F1 and E2F2 leads to the accumulation of DNA lesions and increased apoptotic response. Cell viability and DNA repair capability in response to DNA damage induction are also reduced by the E2F1 and E2F2 deficiencies. Finally, E2F1 and E2F2 accumulate at sites of oxidative and UV-induced DNA damage, and interact with γH2AX DNA repair factor. As previously reported for E2F1, E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase and induces histone acetylation following genotoxic insult. The results presented here unveil a new mechanism involving E2F1 and E2F2 in the maintenance of genomic stability in response to DNA damage in neuronal cells. PMID:25892555

Automated cGMP-compliant radiosynthesis of [18 F]-(E)-PSS232 for brain PET imaging of metabotropic glutamate receptor subtype 5.

PubMed

Park, Jun Young; Son, Jeongmin; Yun, Mijin; Ametamey, Simon M; Chun, Joong-Hyun

2018-01-01

(E)-3-(Pyridin-2-yl ethynyl)cyclohex-2-enone O-(3-(2-[ 18 F]-fluoroethoxy)propyl) oxime ([ 18 F]-(E)-PSS232, [ 18 F]2a) is a recently developed radiotracer that can be used to visualize metabotropic glutamate receptor subtype 5 (mGlu 5 ) in vivo. The mGlu 5 has become an attractive therapeutic and diagnostic target owing to its role in many neuropsychiatric disorders. Several carbon-11-labeled and fluorine-18-labeled radiotracers have been developed to measure mGlu 5 receptor occupancy in the human brain. The radiotracer [ 18 F]2a, which is used as an analogue for [ 11 C]ABP688 ([ 11 C]1) and has a longer physical half-life, is a selective radiotracer that exhibits high binding affinity for mGlu 5 . Herein, we report the fully automated radiosynthesis of [ 18 F]2a using a commercial GE TRACERlab™ FX- FN synthesizer for routine production and distribution to nearby satellite clinics. Nucleophilic substitution of the corresponding mesylate precursor with cyclotron-produced [ 18 F]fluoride ion at 100°C in dimethyl sulfoxide (DMSO), followed by high-performance liquid chromatography (HPLC) purification and formulation, readily provided [ 18 F]2a with a radiochemical yield of 40 ± 2% (decay corrected, n = 5) at the end of synthesis. Radiochemical purity for the [ 18 F]-(E)-conformer was greater than 95%. Molar activity was determined to be 63.6 ± 9.6 GBq/μmol (n = 5), and the overall synthesis time was 70 minutes. Copyright © 2017 John Wiley & Sons, Ltd.

National Conference on Campus Safety (19th, Brown University, Providence, Rhode Island, June 26-28, 1972). Safety Monographs for Schools and Colleges, No. 32.

ERIC Educational Resources Information Center

Green, Jack N., Ed.

Most of this conference report is made up of papers presented on miscellaneous campus safety topics: two papers titled "Handicapped on Campus," by Charles Wingstrom and by Joseph F. Kuchta, Sal Mazzata, and Charles A. Cofield; "Radiation Hazards and Control" by Howard Browne; "Safety in the 70's" by Harold E. O'Shell; "OSHA (Occupational Safety…

Meat Entree Operation Guides Developed for Use in Fort Lee Interim Central Food Preparation Facility

DTIC Science & Technology

1978-11-01

ROAST L -10-2 IN G RED IEN...OPERATION.AL GUIDE FOR B A R B E U JE f) CHICKEN INGREDIENTS & BATCH SIZE L -128 S tandard S erv:ing: 8 o f 2 p cs. E st. P rep T im e: 5. 5 hours 1...8217 ( · - · - - · · - - - . - - ~ - . . , L A B E L E R ( 7 0 ) ) ~ ~ ( ~ P A L L E T I Z E , , . OPERATIONAL GUIDE FOR CHICKEN CACCIATORE L -130

36 CFR 261.53 - Special closures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... communities. (c) Objects or areas of historical, archeological, geological, or paleontological interest. (d) Scientific experiments or investigations. (e) Public health or safety. (f) Property. ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dobromir Panayotov; Andrew Grief; Brad J. Merrill

'Fusion for Energy' (F4E) develops designs and implements the European Test Blanket Systems (TBS) in ITER - Helium-Cooled Lithium-Lead (HCLL) and Helium-Cooled Pebble-Bed (HCPB). Safety demonstration is an essential element for the integration of TBS in ITER and accident analyses are one of its critical segments. A systematic approach to the accident analyses had been acquired under the F4E contract on TBS safety analyses. F4E technical requirements and AMEC and INL efforts resulted in the development of a comprehensive methodology for fusion breeding blanket accident analyses. It addresses the specificity of the breeding blankets design, materials and phenomena and atmore » the same time is consistent with the one already applied to ITER accident analyses. Methodology consists of several phases. At first the reference scenarios are selected on the base of FMEA studies. In the second place elaboration of the accident analyses specifications we use phenomena identification and ranking tables to identify the requirements to be met by the code(s) and TBS models. Thus the limitations of the codes are identified and possible solutions to be built into the models are proposed. These include among others the loose coupling of different codes or code versions in order to simulate multi-fluid flows and phenomena. The code selection and issue of the accident analyses specifications conclude this second step. Furthermore the breeding blanket and ancillary systems models are built on. In this work challenges met and solutions used in the development of both MELCOR and RELAP5 codes models of HCLL and HCPB TBSs will be shared. To continue the developed models are qualified by comparison with finite elements analyses, by code to code comparison and sensitivity studies. Finally, the qualified models are used for the execution of the accident analyses of specific scenario. When possible the methodology phases will be illustrated in the paper by limited number of tables and figures. Description of each phase and its results in detail as well the methodology applications to EU HCLL and HCPB TBSs will be published in separate papers. The developed methodology is applicable to accident analyses of other TBSs to be tested in ITER and as well to DEMO breeding blankets.« less

Recombination reactions of 5-eV O(3P) atoms on a MgF2 surface

NASA Technical Reports Server (NTRS)

Orient, O. J.; Chutjian, A.; Murad, E.

1990-01-01

A source of hyperthermal, ground-state, impurity-free, atomic oxygen of an energy variable in the range 2-100 eV has been developed. Experimental results are presented of emission spectra in the wavelength range 250-850 nm produced by collisions of 5-eV O(3P) atoms with adsorbed NO and CO molecules on a MgF2 surface.

Silencing of E2F3 suppresses tumor growth of Her2+ breast cancer cells by restricting mitosis.

PubMed

Lee, Miyoung; Oprea-Ilies, Gabriela; Saavedra, Harold I

2015-11-10

The E2F transcriptional activators E2F1, E2F2 and E2F3a regulate many important cellular processes, including DNA replication, apoptosis and centrosome duplication. Previously, we demonstrated that silencing E2F1 or E2F3 suppresses centrosome amplification (CA) and chromosome instability (CIN) in Her2+ breast cancer cells without markedly altering proliferation. However, it is unknown whether and how silencing a single E2F activator, E2F3, affects malignancy of human breast cancer cells. Thus, we injected HCC1954 Her2+ breast cancer cells silenced for E2F3 into mammary fat pads of immunodeficient mice and demonstrated that loss of E2F3 retards tumor growth. Surprisingly, silencing of E2F3 led to significant reductions in mitotic indices relative to vector controls, while the percentage of cells undergoing S phase were not affected. Nek2 is a mitotic kinase commonly upregulated in breast cancers and a critical regulator of Cdk4- or E2F-mediated CA. In this report, we found that Nek2 overexpression rescued back the CA caused by silencing of shE2F3. However, the effects of Nek2 overexpression in affecting tumor growth rates of shE2F3 and shE2F3; GFP cells were inconclusive. Taken together, our results indicate that E2F3 silencing decreases mammary tumor growth by reducing percentage of cells undergoing mitosis.

Antibodies derived from a toxoid MEFA (multiepitope fusion antigen) show neutralizing activities against heat-labile toxin (LT), heat-stable toxins (STa, STb), and Shiga toxin 2e (Stx2e) of porcine enterotoxigenic Escherichia coli (ETEC).

PubMed

Rausch, Dana; Ruan, Xiaosai; Nandre, Rahul; Duan, Qiangde; Hashish, Emad; Casey, Thomas A; Zhang, Weiping

2017-04-01

Enterotoxigenic Escherichia coli (ETEC) strains are the main cause of diarrhea in pigs. Pig diarrhea especially post-weaning diarrhea remains one of the most important swine diseases. ETEC bacterial fimbriae including K88, F18, 987P, K99 and F41 promote bacterial attachment to intestinal epithelial cells and facilitate ETEC colonization in pig small intestine. ETEC enterotoxins including heat-labile toxin (LT) and heat-stable toxins type Ia (porcine-type STa) and type II (STb) stimulate fluid hyper-secretion, leading to watery diarrhea. Blocking bacteria colonization and/or neutralizing enterotoxicity of ETEC toxins are considered effective prevention against ETEC diarrhea. In this study, we applied the MEFA (multiepitope fusion antigen) strategy to create toxoid MEFAs that carried antigenic elements of ETEC toxins, and examined for broad antitoxin immunogenicity in a murine model. By embedding STa toxoid STa P12F (NTFYCCELCCNFACAGCY), a STb epitope (KKDLCEHY), and an epitope of Stx2e A subunit (QSYVSSLN) into the A1 peptide of a monomeric LT toxoid (LT R192G ), two toxoid MEFAs, 'LT R192G -STb-Stx2e-STa P12F ' and 'LT R192G -STb-Stx2e-3xSTa P12F ' which carried three copies of STa P12F , were constructed. Mice intraperitoneally immunized with each toxoid MEFA developed IgG antibodies to all four toxins. Induced antibodies showed in vitro neutralizing activities against LT, STa, STb and Stx2e toxins. Moreover, suckling piglets born by a gilt immunized with 'LT R192G -STb-Stx2e-3xSTa P12F ' were protected when challenged with ETEC strains, whereas piglets born by a control gilt developed diarrhea. Results from this study showed that the toxoid MEFA induced broadly antitoxin antibodies, and suggested potential application of the toxoid MEFA for developing a broad-spectrum vaccine against ETEC diarrhea in pigs. Copyright © 2016 Elsevier B.V. All rights reserved.

Building a Dynamic Spectrum Access Smart Radio with Application to Public Safety Disaster Communications

DTIC Science & Technology

2009-08-13

User Interface Master C ontroller (MC ) C ompos ite XML C onfiguration & E vents Awareness Universal  R adio F ramework US R P 802.11 B luetooth E...Bluetooth Database US R P  Database Adapters to be evaluated in Network Testbed Memory Adaptability Policy C ontrol Interoperability Figure 4.2...10 15 20 25 30 10-3 10-2 10-1 100 101 102 103 time (sec) UDP Jitter Ji tte r ( m s) 802.3 Wired 802.11 Wireless Bluetooth GNU Radio/USRP Figure

Inhibition of Retinoblastoma Protein Inactivation

DTIC Science & Technology

2016-09-01

Retinoblastoma protein, E2F transcription factor, high throughput screen, drug discovery, x-ray crystallography 16. SECURITY CLASSIFICATION OF: 17...developed a method to perform fragment based screening by x-ray crystallography . 2.0 KEYWORDS Retinoblastoma (Rb) pathway, E2F transcription factor...cancer, cell-cycle inhibition, activation, modulation, inhibition, high throughput screening, fragment-based screening, x-ray crystallography

The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors

PubMed Central

Kim, So Yoon; Rane, Sushil G.

2011-01-01

Cell division and cell differentiation are intricately regulated processes vital to organ development. Cyclin-dependent kinases (Cdks) are master regulators of the cell cycle that orchestrate the cell division and differentiation programs. Cdk1 is essential to drive cell division and is required for the first embryonic divisions, whereas Cdks 2, 4 and 6 are dispensable for organogenesis but vital for tissue-specific cell development. Here, we illustrate an important role for Cdk4 in regulating early pancreas development. Pancreatic development involves extensive morphogenesis, proliferation and differentiation of the epithelium to give rise to the distinct cell lineages of the adult pancreas. The cell cycle molecules that specify lineage commitment within the early pancreas are unknown. We show that Cdk4 and its downstream transcription factor E2f1 regulate mouse pancreas development prior to and during the secondary transition. Cdk4 deficiency reduces embryonic pancreas size owing to impaired mesenchyme development and fewer Pdx1+ pancreatic progenitor cells. Expression of activated Cdk4R24C kinase leads to increased Nkx2.2+ and Nkx6.1+ cells and a rise in the number and proliferation of Ngn3+ endocrine precursors, resulting in expansion of the β cell lineage. We show that E2f1 binds and activates the Ngn3 promoter to modulate Ngn3 expression levels in the embryonic pancreas in a Cdk4-dependent manner. These results suggest that Cdk4 promotes β cell development by directing E2f1-mediated activation of Ngn3 and increasing the pool of endocrine precursors, and identify Cdk4 as an important regulator of early pancreas development that modulates the proliferation potential of pancreatic progenitors and endocrine precursors. PMID:21490060

49 CFR 575.302 - Vehicle labeling of safety rating information (compliance required for model year 2012 and later...

Code of Federal Regulations, 2012 CFR

2012-10-01

... label specified in paragraph (f) of this section. (2) The label must depict the star ratings for that...,” “Rear Seat” and where applicable, “Not Rated” or “To Be Rated,” the star graphic indicating each rating... point. All remaining text and symbols on the label (including the star graphic specified in paragraph (e...

49 CFR 575.302 - Vehicle labeling of safety rating information (compliance required for model year 2012 and later...

Code of Federal Regulations, 2013 CFR

2013-10-01

... label specified in paragraph (f) of this section. (2) The label must depict the star ratings for that...,” “Rear Seat” and where applicable, “Not Rated” or “To Be Rated,” the star graphic indicating each rating... point. All remaining text and symbols on the label (including the star graphic specified in paragraph (e...

49 CFR 575.302 - Vehicle labeling of safety rating information (compliance required for model year 2012 and later...

Code of Federal Regulations, 2014 CFR

2014-10-01

... label specified in paragraph (f) of this section. (2) The label must depict the star ratings for that...,” “Rear Seat” and where applicable, “Not Rated” or “To Be Rated,” the star graphic indicating each rating... point. All remaining text and symbols on the label (including the star graphic specified in paragraph (e...

National Dam Safety Program. Stony Brook Watershed Dam Site Number 7 (NJ00344), Raritan River Basin, Stony Brook, Mercer County, New Jersey. Phase 1 Inspection Report.

DTIC Science & Technology

1980-02-01

for Permit for Construction and Repair of Dam" filed on March 16, 1959. f. Design and Construction History Design data on file with NJDEP include: 1...LAr- Us a-2. hr’s. LA9~ WATF=R? SiQ_~~- SL- !E q VOL ( YFv - mcA>-) (Acmr-- =T.) 2o4~ 2-Ito STORCH ENGINEERS shootL... of 11. Project FmnnK Wmr=X---A-1

Galactosylated polyaspartamide copolymers for siRNA targeted delivery to hepatocellular carcinoma cells.

PubMed

Cavallaro, Gennara; Farra, Rossella; Craparo, Emanuela Fabiola; Sardo, Carla; Porsio, Barbara; Giammona, Gaetano; Perrone, Francesca; Grassi, Mario; Pozzato, Gabriele; Grassi, Gabriele; Dapas, Barbara

2017-06-20

The limited efficacy of available treatments for hepatocellular carcinoma (HCC) requires the development of novel therapeutic approaches. We synthesized a novel cationic polymer based on α,β-poly-(N-2-hydroxyethyl)-d,L-aspartamide (PHEA) for drug delivery to HCC cells. The copolymer was synthesized by subsequent derivatization of PHEA with diethylene triamine (DETA) and with a polyethylene glycol (PEG) derivative bearing galactose (GAL) molecules, obtaining the cationic derivative PHEA-DETA-PEG-GAL. PHEA-DETA-PEG-GAL has suitable chemical-physical characteristics for a potential systemic use and can effectively deliver a siRNA (siE2F1) targeted against the transcription factor E2F1, a gene product involved in HCC. The presence of GAL residues in the polyplexes allows the targeting of HCC cells that express the asialo-glycoprotein receptor (ASGP-R). In these cells, but not in ASGP-R non-expressing cells, PHEA-DETA-PEG-GAL/siE2F1 polyplexes induce the reduction of the mRNA and protein levels of E2F1 and of E2F1-regulated genes, all involved in the promotion of the G1/S phase transition. This results in a decrease of cell proliferation with a G1/G0 phase cells accumulation. Notably, removal of GAL residue almost completely abrogates the targeting capacity of the developed polyplexes. In conclusion, the generated polyplexes demonstrate the potential to effectively contributing to the development of novel anti-HCC therapeutic approaches via a siRNA-targeted delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

25 CFR 170.144 - What are eligible highway safety projects?

Code of Federal Regulations, 2010 CFR

2010-04-01

...-related deaths, injuries and accidents; (j) Impaired driver initiatives; (k) Child safety seat programs... travel on IRRs, such as guardrail construction and traffic markings; (f) Development of a safety management system; (g) Education and outreach highway safety programs, such as use of child safety seats...

Cardiac Safety of Ozanimod, a Novel Sphingosine‐1‐Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study

PubMed Central

Hartung, Jeffrey P.; Olson, Allan D.; Mendzelevski, Boaz; Timony, Gregg A.; Boehm, Marcus F.; Peach, Robert J.; Gujrathi, Sheila; Frohna, Paul A.

2017-01-01

Abstract Ozanimod is a novel, selective, oral sphingosine‐1‐phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. This randomized, double‐blind, placebo‐controlled, positive‐controlled, parallel‐group thorough QT study characterized the effects of ozanimod on cardiac repolarization in healthy subjects. Eligible subjects were randomized to 1 of 2 groups: ozanimod (escalated from 0.25 to 2 mg over 14 days) or placebo (for 14 days). A single dose of moxifloxacin 400 mg or placebo was administered on days 2 and 17. The primary end point was the time‐matched, placebo‐corrected, baseline‐adjusted mean QTcF (ΔΔQTcF). A total of 113/124 (91.1%) subjects completed the study. The upper limits of the 2‐sided 90% confidence intervals for ΔΔQTcF for both ozanimod 1 and 2 mg were below the 10‐millisecond regulatory threshold. No QTcF >480 milliseconds or postdose change in QTcF of >60 milliseconds was observed. There was no evidence of a positive relationship between concentrations of ozanimod and its active metabolites and ΔΔQTcF. Although ozanimod blunted the observed diurnal increase in heart rate, excursions below predose heart rates were no greater than with placebo. Results demonstrate that ozanimod does not prolong the QTc interval or cause clinically significant bradycardia, supporting ozanimod's evolving favorable cardiac safety profile. PMID:28783871

Validation of a Framework for Measuring Hospital Disaster Resilience Using Factor Analysis

PubMed Central

Zhong, Shuang; Clark, Michele; Hou, Xiang-Yu; Zang, Yuli; FitzGerald, Gerard

2014-01-01

Hospital disaster resilience can be defined as “the ability of hospitals to resist, absorb, and respond to the shock of disasters while maintaining and surging essential health services, and then to recover to its original state or adapt to a new one.” This article aims to provide a framework which can be used to comprehensively measure hospital disaster resilience. An evaluation framework for assessing hospital resilience was initially proposed through a systematic literature review and Modified-Delphi consultation. Eight key domains were identified: hospital safety, command, communication and cooperation system, disaster plan, resource stockpile, staff capability, disaster training and drills, emergency services and surge capability, and recovery and adaptation. The data for this study were collected from 41 tertiary hospitals in Shandong Province in China, using a specially designed questionnaire. Factor analysis was conducted to determine the underpinning structure of the framework. It identified a four-factor structure of hospital resilience, namely, emergency medical response capability (F1), disaster management mechanisms (F2), hospital infrastructural safety (F3), and disaster resources (F4). These factors displayed good internal consistency. The overall level of hospital disaster resilience (F) was calculated using the scoring model: F = 0.615F1 + 0.202F2 + 0.103F3 + 0.080F4. This validated framework provides a new way to operationalise the concept of hospital resilience, and it is also a foundation for the further development of the measurement instrument in future studies. PMID:24945190

Evaluation of Different Features for Face Recognition in Video

DTIC Science & Technology

2014-09-01

and Security Program (CSSP) which is led by Defence Research and Development Canada’s Centre for Security Science, in partnership with Public ...Minister of National Defence, 2014 © Sa Majesté la Reine (en droit du Canada), telle que représentée par le ministre de la Défense nationale, 2014...deployment of innovative technologies for public safety and security practitioners to achieve specific objectives; 4. Threats/Hazards F – Major trans-border

Radium-226 transfer factor from soils to crops and its simple estimation method using uranium and barium concentrations.

PubMed

Tagami, Keiko; Uchida, Shigeo

2009-09-01

Radium-226 ((226)Ra) should be assessed to determine the safety of geological disposal of high-level radioactive and transuranic wastes. Among the environmental transfer parameters that have been used in mathematical models for the environmental safety assessment, soil-to-plant transfer factor (F(v)) is of importance; it is defined as the plant/soil concentration ratio. Reported F(v) data for (226)Ra are still limited due to the low concentration of (226)Ra in plants in the natural environment. In this study, we collected F(v) of (226)Ra (F(v)-Ra) for crops and then applied a statistical approach to estimate F(v)-Ra instead of directly measuring the radionuclide. We found high correlations between (226)Ra and U concentrations in soils (because (226)Ra is a progeny in the (238)U series), and between (226)Ra and Ba concentrations in plants (because they are chemically similar in plant uptake). Using U in soil and Ba in plant values, we could estimate F(v)-Ra with good accuracy; the difference between estimated and measured F(v)-Ra values was a factor of 1.2 on average for crops. The method could estimate F(v)-Ra for the soil-to-plant systems where (226)Ra and Ba concentrations in soil are within the normal range, e.g. 8-100 Bq kg(-1)-dry for (226)Ra and 84-960 mg kg(-1)-dry for Ba.

The NAMPT/E2F2/SIRT1 axis promotes proliferation and inhibits p53-dependent apoptosis in human melanoma cells.

PubMed

Zhao, Hailong; Tang, Weiwei; Chen, Xiaowen; Wang, Siyu; Wang, Xianyan; Xu, Haiyan; Li, Lijuan

2017-11-04

Melanoma is the most common primary malignant neoplasm in adults, causing more deaths than any other skin cancer, necessitating the development of new target-based approaches. Current evidence suggests SIRT1, the mammalian nicotinamide adenine dinucleotide (NAD + )-dependent protein deacetylase, and nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting NAD + biosynthetic enzyme, together comprise a novel systemic regulatory network to play a pivotal role in cell proliferation and apoptosis. Nevertheless, how the regulation of this cofactor interfaces with signal transduction network remains poorly understood in melanoma. Here, we report NAMPT is highly expressed in melanomaassociated with poor overall survival in patients. Pharmacological and genetic inhibition of NAMPT decreased NAD + levels and melanoma cell proliferation capacity, and NAMPT knockdown induced apoptosis through the activity of the tumor suppressor p53. Next, we demonstrate NAMPT regulates the transcription factor E2F family member 2 (E2F2) in the apoptosis process. Downstream, E2F2 control the mRNA and protein levels of SIRT1. Finally, we find NAMPT mediates the apoptosis resistance of melanoma cells through NAMPT-E2F2-SIRT1 axis, more than NAD + -driven transcriptional program. Accordingly, our results demonstrated that NAMPT is a prognostic marker in melanoma, and the identificationofNAMPT-E2F2-SIRT1 pathway establishes another link between NAMPT and apoptosis events in melanoma, with therapeutic implications for this deadly cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Cue-reactivity in experienced electronic cigarette users: Novel stimulus videos and a pilot fMRI study

PubMed Central

Nichols, Travis T.; Foulds, Jonathan; Yingst, Jessica; Veldheer, Susan; Hrabovsky, Shari; Richie, John; Eissenberg, Thomas; Wilson, Stephen J.

2015-01-01

Some individuals who try electronic cigarettes (e-cigarettes) continue to use long-term. Previous research has investigated the safety of e-cigarettes and their potential for use in smoking cessation, but comparatively little research has explored chronic or habitual e-cigarette use. In particular, the relationship between e-cigarette cues and craving is unknown. We sought to bridge this gap by developing a novel set of e-cigarette (salient) and electronic toothbrush (neutral) videos for use in cue-reactivity paradigms. Additionally, we demonstrate the utility of this approach in a pilot fMRI study of 7 experienced e-cigarette users. Participants were scanned while viewing the cue videos before and after 10 minute use of their own e-cigarettes (producing an 11.7 ng/ml increase in plasma nicotine concentration). A significant session (pre- and post-use) by video type (salient and neutral) interaction was exhibited in many sensorimotor areas commonly activated in other cue-reactivity paradigms. We did not detect significant cue-related activity in other brain regions notable in the craving literature. Possible reasons for this discrepancy are discussed, including the importance of matching cue stimuli to participants’ experiences. PMID:26478134

Cue-reactivity in experienced electronic cigarette users: Novel stimulus videos and a pilot fMRI study.

PubMed

Nichols, Travis T; Foulds, Jonathan; Yingst, Jessica M; Veldheer, Susan; Hrabovsky, Shari; Richie, John; Eissenberg, Thomas; Wilson, Stephen J

2016-05-01

Some individuals who try electronic cigarettes (e-cigarettes) continue to use long-term. Previous research has investigated the safety of e-cigarettes and their potential for use in smoking cessation, but comparatively little research has explored chronic or habitual e-cigarette use. In particular, the relationship between e-cigarette cues and craving is unknown. We sought to bridge this gap by developing a novel set of e-cigarette (salient) and electronic toothbrush (neutral) videos for use in cue-reactivity paradigms. Additionally, we demonstrate the utility of this approach in a pilot fMRI study of 7 experienced e-cigarette users. Participants were scanned while viewing the cue videos before and after 10min use of their own e-cigarettes (producing an 11.7ng/ml increase in plasma nicotine concentration). A significant session (pre- and post-use) by video type (salient and neutral) interaction was exhibited in many sensorimotor areas commonly activated in other cue-reactivity paradigms. We did not detect significant cue-related activity in other brain regions notable in the craving literature. Possible reasons for this discrepancy are discussed, including the importance of matching cue stimuli to participants' experiences. Copyright © 2015 Elsevier Inc. All rights reserved.

Minutes of the Explosives Safety Seminar (19th) Held at Los Angeles, California, 9-10-11 September 1980. Volume 1

DTIC Science & Technology

1980-01-01

DOUBLE-BASE EXTRUSION COMPOSITIONS ................................... 89 Messrs. Craig E. Johnson and Paul F. Dendor V I GUN PROPELLANT PROPAGATION IN...Mullins and C. F. Baker RESULTS AND ANALYSIS OF STRENGTHENED STEEL BUILDING BLAST TESTS ..... 165 Messrs. Frederic E. Sock, Norval Dobbs, Paul Price and...347 Mr. J. Paul Glenn I viLR SESSION - EXPLOSION CONTAIMENT & VENTING Moderator - Mr. Irving Forsten EXPLOSION CONTAINMENT VESSELS AND M4TERIALS

Proceedings of the USAF Structural Integrity Program Conference Held in San Antonio, Texas on November 30-December 2, 1993

DTIC Science & Technology

1994-08-01

721 An Improved G-Tracking Method for Large Transport Aircraft ............................ 741 iv Naval aircraft Approach and...E. B. de la Motte Swedish Defence Materiel Administration, Stockholm, Sweden Capt F. A. Opaiski WL/FIBEC 090040930 An Aircraft Structural Integrity...M. Poole Canadian Transportation Safety Board 1400-1430 The Challenges Associated with the Operation of Loads Monitoring Equipment for Efficient

A Summary of the United States Food and Drug Administrations’ Food Safety Program for Imported Seafood; One Country’s Approach

PubMed Central

Koonse, Brett

2016-01-01

It is well known that the vast majority of seafood is captured or farmed in emerging countries and exported to developed countries. This has resulted in seafood being the number one traded food commodity in the world. Food safety is essential to this trade. Exporting countries should understand the regulatory food safety programs of the countries they ship to in order to comply with their applicable laws and regulations to avoid violations and disruptions in trade. The United States (U.S.) imports more seafood than any individual country in the world but the European Union (E.U.) countries, as a block, import significantly more. Each importing country has its own programs and systems in place to ensure the safety of imported seafood. However, most countries that export seafood have regulatory programs in place that comply with the import requirements of the E.U. The purpose of this paper is to describe the United States Food and Drug Administration’s (USFDA) imported seafood safety program. The primary audience for the information is foreign government regulators, seafood exporters, and U.S. importers. It can also give consumers confidence that f U.S. seafood is safe no matter which country it originates from. PMID:28231127

Signalling in the epidermis: the E2F cell cycle regulatory pathway in epidermal morphogenesis, regeneration and transformation.

PubMed

Ivanova, Iordanka A; D'Souza, Sudhir J A; Dagnino, Lina

2005-01-01

The epidermis is the outermost layer in the skin, and it is the first line of defence against the environment. The epidermis also provides a barrier against loss of fluids and electrolytes, which is crucial for life. Essential in the maintenance of this tissue is its ability to continually self-renew and regenerate after injury. These two characteristics are critically dependent on the ability of the principal epidermal cell type, the keratinocyte, to proliferate and to respond to differentiation cues. Indeed, the epidermis is a multilayered tissue composed of keratinocyte stem cells and their differentiated progeny. Central for the control of cell proliferation is the E2F transcription factor regulatory network. This signaling network also includes cyclins, cdk, cdk inhibitors and the retinoblastoma (pRb) family of proteins. The biological importance of the E2F/pRb pathway is emphasized by the fact that a majority of human tumours exhibit alterations that disrupt the ability of pRb proteins to inhibit E2F, leading to permanent activation of the latter. Further, E2F is essential for normal epidermal regeneration after injury. Other member of the E2F signaling pathway are also involved in epidermal development and pathophysiology. Thus, whereas the pRb family of proteins is essential for epidermal morphogenesis, abnormal regulation of cyclins and E2F proteins results in tumorgenesis in this tissue. In this review, we discuss the role of each member of this important growth regulatory network in epidermal formation, homeostasis and carcinogenesis.

Signalling In The Epidermis: The E2f Cell Cycle Regulatory Pathway In Epidermal Morphogenesis, Regeneration And Transformation

PubMed Central

2005-01-01

The epidermis is the outermost layer in the skin, and it is the first line of defence against the environment. The epidermis also provides a barrier against loss of fluids and electrolytes, which is crucial for life. Essential in the maintenance of this tissue is its ability to continually self-renew and regenerate after injury. These two characteristics are critically dependent on the ability of the principal epidermal cell type, the keratinocyte, to proliferate and to respond to differentiation cues. Indeed, the epidermis is a multilayered tissue composed of keratinocyte stem cells and their differentiated progeny. Central for the control of cell proliferation is the E2F transcription factor regulatory network. This signaling network also includes cyclins, cdk, cdk inhibitors and the retinoblastoma (pRb) family of proteins. The biological importance of the E2F/pRb pathway is emphasized by the fact that a majority of human tumours exhibit alterations that disrupt the ability of pRb proteins to inhibit E2F, leading to permanent activation of the latter. Further, E2F is essential for normal epidermal regeneration after injury. Other member of the E2F signaling pathway are also involved in epidermal development and pathophysiology. Thus, whereas the pRb family of proteins is essential for epidermal morphogenesis, abnormal regulation of cyclins and E2F proteins results in tumorgenesis in this tissue. In this review, we discuss the role of each member of this important growth regulatory network in epidermal formation, homeostasis and carcinogenesis. PMID:15951853

Development of Accelerated Fuel-Engines Qualification Procedures Methodology. Volume II. Appendices.

DTIC Science & Technology

1981-12-01

temperature test and the spot calibration, remove the clay filter. Reset the maximum fuel temperature safety device for 1900F. Continue cycling per Figure...34 -t " ;" " pum p . 1...0.,. Fuel ’ ’ ’ :’: ? Secondary ; Filter (S) -, A TVented Cap Removable Screen\\ - Tank Fu e.l ExpansSon DtVrent Pipe A n...practice, improper installation or adjustment of components *Do not remove or inspect secondary fuel filter. One of the initial production engines is

E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Zejun; Gong, Chaoju; Liu, Hong

2015-08-21

As the ribonucleotide reductase small subunit, the high expression of ribonucleotide reductase small subunit M2 (RRM2) induces cancer and contributes to tumor growth and invasion. In several colorectal cancer (CRC) cell lines, we found that the expression levels of RRM2 were closely related to the transcription factor E2F1. Mechanistic studies were conducted to determine the molecular basis. Ectopic overexpression of E2F1 promoted RRM2 transactivation while knockdown of E2F1 reduced the levels of RRM2 mRNA and protein. To further investigate the roles of RRM2 which was activated by E2F1 in CRC, CCK-8 assay and EdU incorporation assay were performed. Overexpression ofmore » E2F1 promoted cell proliferation in CRC cells, which was blocked by RRM2 knockdown attenuation. In the migration and invasion tests, overexpression of E2F1 enhanced the migration and invasion of CRC cells which was abrogated by silencing RRM2. Besides, overexpression of RRM2 reversed the effects of E2F1 knockdown partially in CRC cells. Examination of clinical CRC specimens demonstrated that both RRM2 and E2F1 were elevated in most cancer tissues compared to the paired normal tissues. Further analysis showed that the protein expression levels of E2F1 and RRM2 were parallel with each other and positively correlated with lymph node metastasis (LNM), TNM stage and distant metastasis. Consistently, the patients with low E2F1 and RRM2 levels have a better prognosis than those with high levels. Therefore, we suggest that E2F1 can promote CRC proliferation, migration, invasion and metastasis by regulating RRM2 transactivation. Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in CRC and provide a novel predictive marker for diagnosis and prognosis of the disease. - Highlights: • E2F1 promotes RRM2 transactivation in CRC cells. • E2F1 promotes the proliferation of CRC cells by activating RRM2. • E2F1 promotes the migration and invasion of CRC cells by activating RRM2. • E2F1 is upregulated in CRC tissues and positively associated with RRM2 level. • E2F1-mediated RRM2 transcription will provide a new strategy in CRC.« less

Reduced schedules of 4CMenB vaccine in infants and catch-up series in children: Immunogenicity and safety results from a randomised open-label phase 3b trial.

PubMed

Martinón-Torres, Federico; Safadi, Marco Aurelio P; Martinez, Alfonso Carmona; Marquez, Pilar Infante; Torres, Juan Carlos Tejedor; Weckx, Lily Yin; Moreira, Edson Duarte; Mensi, Ilhem; Calabresi, Marco; Toneatto, Daniela

2017-06-16

This study evaluated the immunogenicity and safety of a licensed meningococcal serogroup B vaccine (4CMenB) administered alone according to reduced schedules in infants or catch-up series in children. In this open-label, multicentre, phase 3b study (NCT01339923), infants randomised 1:1:1 received 4CMenB: 2+1 doses at 3½-5-11months or 6-8-11months of age, 3+1 doses at ages 2½-3½-5-11months. Children aged 2-10years received 2 catch-up doses administered 2months apart. Immune responses were measured by hSBA assays against 4 strains specific for vaccine components fHbp, NadA, PorA and NHBA. Sufficiency of immune responses was defined in groups with 2+1 doses schedules as a lower limit ≥70% for the 97.5% confidence interval of the percentage of infants with hSBA titres ≥4, 1month post-dose 2 for fHbp, NadA, PorA. Adverse events were collected for 7days post-vaccination; serious adverse events (SAEs) throughout the study. 754 infants and 404 children were enrolled. Post-primary vaccination, 98-100% of infants across all groups developed hSBA titres ≥4 for fHbp, NadA, PorA, and 48-77% for NHBA. Sufficiency of immune responses in infants receiving 2+1 schedules was demonstrated for fHbp, NadA, PorA after 2 doses of 4CMenB, as pre-specified criteria were met. Following receipt of 2 catch-up doses, 95-99% of children developed hSBA titres ≥4 for 4CMenB components. Similar safety profiles were observed across groups. A total of 45 SAEs were reported, 3 of which were related to vaccination. Reduced infant schedules and catch-up series in children were immunogenic and safe, having the potential to widen 4CMenB vaccine coverage. GlaxoSmithKline Biologicals SA. Copyright © 2017. Published by Elsevier Ltd.

United States Air Force F-35A Operational Basing Environmental Impact Statement. Volume 1

DTIC Science & Technology

2013-09-01

Evaluation (FDE) program and Weapons School (WS) beddown, the F-22 designator was used. Subsequent testing , development, and deployment resulted in...Initial F-35A Operational Basing EIS Final, September 2013 contract to develop the JSF ( designated the F-35 Lightning II). Since then, testing of F...of the aircraft even with system failures. Throughout the design and testing process, safety initiatives took previous best practices for single

Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes

PubMed Central

Shen, Shuijie; Li, Lei; Ding, Xinxin; Zheng, Jiang

2014-01-01

Pulmonary toxicity of styrene is initiated by cytochromes P450-dependent metabolic activation. P450 2E1 and P450 2F2 are considered to be two main cytochrome P450 (CYP) enzymes responsible for styrene metabolism in mice. The objective of the current study was to determine the correlation between the formation of styrene metabolites (i.e. styrene oxide and 4-vinylphenol) and pulmonary toxicity of styrene, using Cyp2e1- and Cyp2f2-null mouse models. Dramatic decrease in the formation of styrene glycol and 4-vinylphenol was found in Cyp2f2-null mouse lung microsomes, relative to that in the wild-type mouse lung microsomes. However, no significant difference in the production of the styrene metabolites was observed between lung microsomes obtained from Cyp2e1-null and the wild-type mice. The knock–out and wild-type mice were treated with styrene (6.0 mmol/kg, ip), and cell counts and LDH activity in bronchoalveolar lavage fluids were monitored to evaluate the pulmonary toxicity induced by styrene. Cyp2e1-null mice displayed similar susceptibility to lung toxicity of styrene as the wild-type animals. However, Cyp2f2-null mice were resistant to styrene-induced pulmonary toxicity. In conclusion, both P450 2E1 and P450 2F2 are responsible for the metabolic activation of styrene. The latter enzyme plays an important role in styrene-induced pulmonary toxicity. Both styrene oxide and 4-vinylphenol are suggested to participate in the development of lung injury induced by styrene. PMID:24320693

Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes.

PubMed

Shen, Shuijie; Li, Lei; Ding, Xinxin; Zheng, Jiang

2014-01-21

Pulmonary toxicity of styrene is initiated by cytochromes P450-dependent metabolic activation. P450 2E1 and P450 2F2 are considered to be two main cytochrome P450 enzymes responsible for styrene metabolism in mice. The objective of the current study was to determine the correlation between the formation of styrene metabolites (i.e., styrene oxide and 4-vinylphenol) and pulmonary toxicity of styrene, using Cyp2e1- and Cyp2f2-null mouse models. A dramatic decrease in the formation of styrene glycol and 4-vinylphenol was found in Cyp2f2-null mouse lung microsomes relative to that in the wild-type mouse lung microsomes; however, no significant difference in the production of the styrene metabolites was observed between lung microsomes obtained from Cyp2e1-null and the wild-type mice. The knockout and wild-type mice were treated with styrene (6.0 mmol/kg, ip), and cell counts and LDH activity in bronchoalveolar lavage fluids were monitored to evaluate the pulmonary toxicity induced by styrene. Cyp2e1-null mice displayed a susceptibility to lung toxicity of styrene similar to that of the wild-type animals; however, Cyp2f2-null mice were resistant to styrene-induced pulmonary toxicity. In conclusion, both P450 2E1 and P450 2F2 are responsible for the metabolic activation of styrene. The latter enzyme plays an important role in styrene-induced pulmonary toxicity. Both styrene oxide and 4-vinylphenol are suggested to participate in the development of lung injury induced by styrene.

Developing Treatment, Treatment Validation, and Treatment Scope in the Setting of an Autism Clinical Trial

DTIC Science & Technology

2013-06-01

neurodevelopmental disorders 3(2): 132-143. Buyske, S., T. A. Williams, A. E. Mars, E. S. Stenroos, S. X. Ming, R. Wang, M. Sreenath, M. F. Factura , C. Reddy, G. H...Gastroenterol Nutr. Williams, T. A., A. E. Mars, S. G. Buyske, E. S. Stenroos, R. Wang, M. F. Factura -Santiago, G. H. Lambert and W. G. Johnson (2007

Investigation of Fire-Vulnerability-Reduction Effectiveness of Fire-Resistant Diesel Fuel in Armored Vehicular Fuel Tanks

DTIC Science & Technology

1980-09-30

Aberdeen Proving Ground, Maryland, September 1976. 2. Weatherford, W.D., Jr., Fodor, G.E., Naegeli , D.W., Owens, E.C., Wright, B.R., and Schaekel, F.W...Weatherford, W.I)., Jr., Fodor, G.E., Naegeli , D.W., Owens, E.C., Wright, B.R., and Schaekel, F.W., "Development of Army Fire-Resistant Diesel Fuel," Interim

Effect of vitamins C and E on biomarkers of oxidative stress in nonsmokers

PubMed Central

Block, Gladys; Jensen, Christopher D.; Morrow, Jason D.; Holland, Nina; Norkus, Edward P.; Milne, Ginger L.; Hudes, Mark; Dalvi, Tapashi B.; Crawford, Patricia B.; Fung, Ellen B.; Schumacher, Laurie; Harmatz, Paul

2009-01-01

Background Oxidative stress is elevated in obesity, and may be a major mechanism for obesity-related diseases. Methods Nonsmokers (n=396) were randomized to 1000 mg/day vitamin C, 800 IU/day vitamin E, or placebo, for two months. Treatment effect was examined in multiple regression analyses using an intention-to-treat approach. Results Vitamin C (p=0.001) and vitamin E (p=0.043) reduced plasma F2-isoprostanes. In the overall sample, changes from baseline were +6.8%, −10.6%, and −3.9% for placebo, vitamin C, and vitamin E groups, respectively. However, a significant interaction with baseline F2-isoprostane was found. When baseline F2-isoprostane was > 50 μg/mL, vitamin C reduced F2-isoprostane by 22% (p=0.01). Vitamin E reduced it by 9.8% (p=0.46). Below that cut-point, neither treatment produced further reductions. F2-isoprostane > 50 μg/mL was strongly associated with obesity, and was present in 42% of the sample. Change in malondialdehyde concentration was minimal. Discussion These findings suggest a role for vitamin C in reducing lipid peroxidation. Future research on effects of vitamins C or E on plasma F2-isoprostane should limit participants to those with baseline levels > 50 μg/mL. Further studies are needed to establish whether treatment with vitamins C or E in persons with concentrations above that cut-point could slow the development of cardiovascular disease. PMID:18455517

Managing risk in healthcare: understanding your safety culture using the Manchester Patient Safety Framework (MaPSaF).

PubMed

Parker, Dianne

2009-03-01

To provide sufficient information about the Manchester Patient Safety Framework (MaPSaF) to allow healthcare professionals to assess its potential usefulness. The assessment of safety culture is an important aspect of risk management, and one in which there is increasing interest among healthcare organizations. Manchester Patient Safety Framework offers a theory-based framework for assessing safety culture, designed specifically for use in the NHS. The framework covers multiple dimensions of safety culture, and five levels of safety culture development. This allows the generation of a profile of an organization's safety culture in terms of areas of relative strength and challenge, which can be used to identify focus issues for change and improvement. Manchester Patient Safety Framework provides a useful method for engaging healthcare professionals in assessing and improving the safety culture in their organization, as part of a programme of risk management.

Imbalanced gp130 signalling in ApoE-deficient mice protects against atherosclerosis.

PubMed

Jones, Gareth W; McLeod, Louise; Kennedy, Catherine L; Bozinovski, Steven; Najdovska, Meri; Jenkins, Brendan J

2015-02-01

Interleukin (IL)-6 is a key modulator of the acute phase response (APR), and while both are implicated in atherosclerosis, the pathological role of specific IL-6 signalling cascades is ill-defined. Since IL-6 employs the cytokine receptor gp130 to primarily activate the STAT3 pathway, here we evaluate whether gp130-dependent STAT3 activation modulates atherosclerosis. High-fat diet-induced atherosclerosis was established in ApoE(-/-) mice crossed with gp130(F/F) knock-in mice displaying elevated gp130-dependent STAT3 activation and production of the APR protein, serum amyloid A (SAA). Also generated were gp130(F/F):Stat3(-/+):ApoE(-/-) mice displaying genetically-normalised STAT3 activation and SAA levels, and bone marrow chimeras involving ApoE(-/-) and gp130(F/F):ApoE(-/-) mice. At 10 weeks post high-fat diet, aortic atherosclerotic lesions, including the presence of CD68(+) macrophages, and plasma lipid and SAA profiles, were assessed. Aortic plaque development and plasma triglyceride levels in gp130(F/F):ApoE(-/-) mice were significantly reduced (3-fold, P < 0.001) compared to ApoE(-/-) littermates. By contrast, in gp130(F/F):ApoE(-/-) mice, atherosclerotic plaques contained augmented CD68(+) macrophage infiltrates, and plasma SAA levels were elevated, compared to ApoE(-/-) mice. Atherosclerotic lesion development and plasma triglyceride levels in gp130(F/F):ApoE(-/-) and gp130(F/F):Stat3(-/+):ApoE(-/-) mice were comparable, despite a significant (P < 0.05) reduction in macrophage numbers in lesions, and also plasma SAA levels, in gp130(F/F):Stat3(-/+):ApoE(-/-) mice. Aortic plaque development and plasma triglyceride levels were comparable in ApoE(-/-) mice reconstituted with gp130(F/F):ApoE(-/-) (ApoE(F/F:ApoE)) or ApoE(-/-) (ApoE(ApoE)) bone marrow cells. Deregulation of gp130/STAT3 signalling augments the APR and macrophage infiltration during atherosclerosis without impacting on the development of aortic plaques. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Circular RNA hsa_circ_0008039 promotes breast cancer cell proliferation and migration by regulating miR-432-5p/E2F3 axis.

PubMed

Liu, Yanhua; Lu, Cuntao; Zhou, Yizhou; Zhang, Zhihong; Sun, Li

2018-07-20

As the development of sequencing technology, more and more circular RNAs (circRNAs) are identified in human cancer tissues. Increasing evidences imply circRNAs are important regulators in tumor progression. Nevertheless, how circRNAs participate in breast cancer development and progression is not well understood. In the present study, we identified a novel circRNA hsa_circ_0008039 with upregulated expression level in breast cancer tissues. By functional experiments, we found that hsa_circ_0008039 depletion significantly suppressed the proliferation, arrested cell-cycle progression and reduced migration in breast cancer. Mechanistic investigations suggested that hsa_circ_0008039 served as a competing endogenous RNA (ceRNA) of miR-432-5p. Subsequently, E2F3 was identified as the functional target of miR-432-5p and overexpression of hsa_circ_0008039 elevated E2F3 expression in breast cancer. On the whole, our study indicated that hsa_circ_0008039 exerted oncogenic roles in breast cancer and suggested the hsa_circ_0008039/miR-432-5p/E2F3 axis might be a potential therapeutic target. Copyright © 2018 Elsevier Inc. All rights reserved.

Development of X-Ray Laser Media. Measurement of Gain and Development of Cavity Resonators for Wavelengths near 130 Angstroms. Volume 1.

DTIC Science & Technology

1983-02-01

A2/f ,11= 1.5 x 10- 6 (g u /g )[AU)] 2/f where r is the radius of the electron (2.82 10 A), c is the velocity of light (3 1018 A/sec), X is the...LASER-PRODUCED PLASMA, *2N , . / - . ’ . .. . . .. . .. . -" 4 A’.° 1. Recombination to Hydrogenic Plasma (i.e. one bound electron ). A. Collisional...its inverse (Auger) N(p) + e 0 N (plop2) (plP charge exchange (here one 2 N(zl)+ 0 N (z-2)+ example among many) (p) (plP 2) 3. Free electrons

First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers.

PubMed

Stevens, Misty W; Henry, Ralph L; Owens, S Michael; Schutz, Ralph; Gentry, W Brooks

2014-01-01

This first-in-human study examined the safety and pharmacokinetics of ch-mAb7F9, an anti-methamphetamine monoclonal antibody, in healthy volunteers. Single, escalating doses of ch-mAb7F9 over the range of 0.2 to 20 mg/kg were administered to 42 subjects who were followed for 147 d. Safety was measured by physical examinations, adverse events, vital signs, electrocardiograms, and clinical laboratory testing. Serum ch-mAb7F9 concentration and immunogenicity analyses were performed. There were no serious adverse reactions or discontinuations from the study due to adverse events. No trends emerged in the frequency, relatedness, or severity of adverse events with increased dose or between active and placebo treated subjects. Ch-mAb7F9 displayed expected IgG pharmacokinetic parameters, including a half-life of 17-19 d in the 3 highest dose groups and volume of distribution of 5-6 L, suggesting the antibody is confined primarily to the vascular compartment. Four (12.5%) of the 32 subjects receiving ch-mAb7F9 were confirmed to have developed a human anti-chimeric antibody response by the end of the study; however, this response did not appear to be dose related. Overall, no apparent safety or tolerability concerns were identified; a maximum tolerated dose was not reached in this Phase 1 study. Ch-mAb7F9 therefore appears safe for human administration.

CDH1 regulates E2F1 degradation in response to differentiation signals in keratinocytes

PubMed Central

Singh, Randeep K.; Dagnino, Lina

2017-01-01

The E2F1 transcription factor plays key roles in skin homeostasis. In the epidermis, E2F1 expression is essential for normal proliferation of undifferentiated keratinocytes, regeneration after injury and DNA repair following UV radiation-induced photodamage. Abnormal E2F1 expression promotes nonmelanoma skin carcinoma. In addition, E2F1 must be downregulated for proper keratinocyte differentiation, but the relevant mechanisms involved remain poorly understood. We show that differentiation signals induce a series of post-translational modifications in E2F1 that are jointly required for its downregulation. Analysis of the structural determinants that govern these processes revealed a central role for S403 and T433. In particular, substitution of these two amino acid residues with non-phosphorylatable alanine (E2F1 ST/A) interferes with E2F1 nuclear export, K11- and K48-linked polyubiquitylation and degradation in differentiated keratinocytes. In contrast, replacement of S403 and T433 with phosphomimetic aspartic acid to generate a pseudophosphorylated E2F1 mutant protein (E2F1 ST/D) generates a protein that is regulated in a manner indistinguishable from that of wild type E2F1. Cdh1 is an activating cofactor that interacts with the anaphase-promoting complex/cyclosome (APC/C) ubiquitin E3 ligase, promoting proteasomal degradation of various substrates. We found that Cdh1 associates with E2F1 in keratinocytes. Inhibition or RNAi-mediated silencing of Cdh1 prevents E2F1 degradation in response to differentiation signals. Our results reveal novel regulatory mechanisms that jointly modulate post-translational modifications and downregulation of E2F1, which are necessary for proper epidermal keratinocyte differentiation. PMID:27903963

CDH1 regulates E2F1 degradation in response to differentiation signals in keratinocytes.

PubMed

Singh, Randeep K; Dagnino, Lina

2017-01-17

The E2F1 transcription factor plays key roles in skin homeostasis. In the epidermis, E2F1 expression is essential for normal proliferation of undifferentiated keratinocytes, regeneration after injury and DNA repair following UV radiation-induced photodamage. Abnormal E2F1 expression promotes nonmelanoma skin carcinoma. In addition, E2F1 must be downregulated for proper keratinocyte differentiation, but the relevant mechanisms involved remain poorly understood. We show that differentiation signals induce a series of post-translational modifications in E2F1 that are jointly required for its downregulation. Analysis of the structural determinants that govern these processes revealed a central role for S403 and T433. In particular, substitution of these two amino acid residues with non-phosphorylatable alanine (E2F1 ST/A) interferes with E2F1 nuclear export, K11- and K48-linked polyubiquitylation and degradation in differentiated keratinocytes. In contrast, replacement of S403 and T433 with phosphomimetic aspartic acid to generate a pseudophosphorylated E2F1 mutant protein (E2F1 ST/D) generates a protein that is regulated in a manner indistinguishable from that of wild type E2F1. Cdh1 is an activating cofactor that interacts with the anaphase-promoting complex/cyclosome (APC/C) ubiquitin E3 ligase, promoting proteasomal degradation of various substrates. We found that Cdh1 associates with E2F1 in keratinocytes. Inhibition or RNAi-mediated silencing of Cdh1 prevents E2F1 degradation in response to differentiation signals. Our results reveal novel regulatory mechanisms that jointly modulate post-translational modifications and downregulation of E2F1, which are necessary for proper epidermal keratinocyte differentiation.

E2F1 transcription is induced by genotoxic stress through ATM/ATR activation.

PubMed

Carcagno, Abel L; Ogara, María F; Sonzogni, Silvina V; Marazita, Mariela C; Sirkin, Pablo F; Ceruti, Julieta M; Cánepa, Eduardo T

2009-05-01

E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress.

Synthesis and anti-tumor evaluation of panaxadiol halogen-derivatives.

PubMed

Xiao, Shengnan; Chen, Shuai; Sun, Yuanyuan; Zhou, Wuxi; Piao, Huri; Zhao, Yuqing

2017-09-01

In the current work, 13 novel panaxadiol (PD) derivatives were synthesized by reacting with chloroacetyl chloride and bromoacetyl bromide. Their in vitro antitumor activities were evaluated on three human tumor cell lines (HCT-116, BGC-823, SW-480) and three normal cells (human gastric epithelial cell line-GES-1, hair follicle dermal papilla cell line-HHDPC and rat myocardial cell line-H9C2) by MTT assay. Compared with PD, the results demonstrated that compound 1e, 2d, 2e showed significant anti-tumor activity against three tumor cell lines, the IC50 value of compound 2d against HCT-116 was the lowest (3.836μM). The anti-tumor activity of open-ring compounds are significantly better than the compounds of C-25 cyclization. Compound 1f, 2f, 2g showed the strong anti-tumor activity. The IC50 value of compound 2g against BGC-823 and SW-480 were the lowest (0.6μM and 0.1μM, respectively). Combined with cytotoxicity test, the IC50 value of compound 1e, 2d, 2e are greater than 100. the open-ring compounds (1f, 2f, 2g) showed a strong toxicity. The toxicity of 1f is lower than 2f and 2g. These compounds may be useful for the development of novel antiproliferative agents. Copyright © 2017. Published by Elsevier Ltd.

Novel factor Xa inhibitors: a patent review.

PubMed

de Candia, Modesto; Lopopolo, Gianfranco; Altomare, Cosimo

2009-11-01

New oral anticoagulants with favorable safety profiles and fixed doses are required for the management of thromboembolism and stroke prevention in patients with atrial fibrillation. Among them, fXa inhibitors (the so-called xabans) are attractive options that can overcome limitations (e.g., bleeding) of the current oral antithrombotic therapy. The rational design of small-molecule direct fXa inhibitors, whose importance is testified by the growing number of publications and patents recently registered, has been fully supported by the X-ray crystallography of enzyme-ligand complexes. Pubmed, SciFinder Scholar, ISI web of knowledge(SM), http://ep.espacenet.com/ and Google websites were used as the main sources for literature retrieving, and > 100 patents filed between 2006 and April 2009, reviewed and discussed herein, highlight the variety among the P1 and P4 moieties on suitable scaffolds. The replacement of the benzamidine P1 moiety, which characterizes the first generation, with less basic bioisosteric or nonpolar neutral P1 groups led to the disclosure of numerous fXa inhibitors with high potency, selectivity and oral bioavailability. Novel selective fXa inhibitors with stable pharmacokinetics, better therapeutic windows and ease-of-use than the existing anticoagulants are currently under advanced stage clinical trials. Available data from Phase II and Phase III studies reflect the drive towards fXa inhibitors as potentially more effective and safer antithrombotic drugs. Their development is expected to address two major needs for anticoagulation, namely safety and ease-of-use, and to significantly affect the anticoagulant market.

Inhibition of E2F1 activity and cell cycle progression by arsenic via retinoblastoma protein.

PubMed

Sheldon, Lynn A

2017-01-01

The regulation of cell cycle progression by steroid hormones and growth factors is important for maintaining normal cellular processes including development and cell proliferation. Deregulated progression through the G1/S and G2/M cell cycle transitions can lead to uncontrolled cell proliferation and cancer. The transcription factor E2F1, a key cell cycle regulator, targets genes encoding proteins that regulate cell cycle progression through the G1/S transition as well as proteins important in DNA repair and apoptosis. E2F1 expression and activity is inhibited by inorganic arsenic (iAs) that has a dual role as a cancer therapeutic and as a toxin that leads to diseases including cancer. An understanding of what underlies this dichotomy will contribute to understanding how to use iAs as a more effective therapeutic and also how to treat cancers that iAs promotes. Here, we show that quiescent breast adenocarcinoma MCF-7 cells treated with 17-β estradiol (E2) progress through the cell cycle, but few cells treated with E2 + iAs progress from G1 into S-phase due to a block in cell cycle progression. Our data support a model in which iAs inhibits the dissociation of E2F1 from the tumor suppressor, retinoblastoma protein (pRB) due to changes in pRB phosphorylation which leads to decreased E2F1 transcriptional activity. These findings present an explanation for how iAs can disrupt cell cycle progression through E2F1-pRB and has implications for how iAs acts as a cancer therapeutic as well as how it may promote tumorigenesis through decreased DNA repair.

Effects of Al content and annealing on the phases formation, lattice parameters, and magnetization of A lxF e2B2 (x =1.0 ,1.1 ,1.2 ) alloys

NASA Astrophysics Data System (ADS)

Levin, E. M.; Jensen, B. A.; Barua, R.; Lejeune, B.; Howard, A.; McCallum, R. W.; Kramer, M. J.; Lewis, L. H.

2018-03-01

AlF e2B2 is a ferromagnet with the Curie temperature around 300 K and has the potential to be an outstanding rare-earth free candidate for magnetocaloric applications. However, samples prepared from the melt contain additional phases which affect the functional response of the AlF e2B2 phase. We report on the effects of Al content in samples with the initial (nominal) composition of A lxF e2B2 , where x =1.0 , 1.1, and 1.2 prepared by arc-melting followed by suction casting and annealing. The as-cast A lxF e2B2 alloys contain AlF e2B2 as well as additional phases, including the primary solidifying FeB and A l13F e4 compounds, which are ferromagnetic and paramagnetic, respectively, at 300 K. The presence of these phases makes it difficult to extract the intrinsic magnetic properties of AlF e2B2 phase. Annealing of A lxF e2B2 alloys at 1040 °C for 3 days allows for reaction of the FeB with A l13F e4 to form the AlF e2B2 phase, significantly reduces the amount of additional phases, and results in nearly pure AlF e2B2 phase as confirmed with XRD, magnetization, scanning electron microscopy, and electronic transport. The values of the magnetization, effective magnetic moment per Fe atom, specific heat capacity, electrical resistivity, and Seebeck coefficient for the AlF e2B2 compound have been established.

The pie-crusting technique using a blade knife for medial collateral ligament release is unreliable in varus total knee arthroplasty.

PubMed

Kwak, Dai-Soon; In, Yong; Kim, Tae Kyun; Cho, Han Suk; Koh, In Jun

2016-01-01

Despite the documented clinical efficacy of the pie-crusting technique for medial collateral ligament (MCL) release in varus total knee arthroplasty, its quantitative effects on medial gaps and safety remain unclear. This study was undertaken to determine the efficacy (quantitative effect and consistency of the number of punctures) and the safety (frequency of early over-release) of the pie-crusting technique for MCL release. From ten pairs of cadaveric knees, one knee from each pair was randomly assigned to undergo pie crusting in extension (group E) or in flexion (group F). Pie crusting was performed in the superficial MCL using a blade until over-release occurred. After every puncture, the incremental medial gap increase was recorded, and the number of punctures required for 2- or 4-mm gap increases was assessed. In group E, the extension gap increased from 0.8 to 5.0 mm and the flexion gap increased from 0.8 to 3.0 mm. In group F, the extension gap increased from 1.0 to 3.0 mm and the flexion gap increased from 2.6 to 6.0 mm. However, the gap increments were inconsistent with those that followed the preceding blade punctures, and the number of punctures required to increase the gaps by 2 or 4 mm was variable. The number of punctures leading to over-release in group E and group F was 6 ± 1 and 3 ± 1 punctures, respectively. Overall, 70% of over-release occurred earlier than the average number of punctures leading to over-release. Pie crusting led to unpredictable gap increments and to frequent early over-release. Surgeons should decide carefully before using the pie-crusting technique for MCL release and should be cautious of performing throughout the procedure, especially when performing in a flexed knee. Therapeutic study, Level I.

The Use of a Higher Order Kinematic Relationship on the Analysis of Cylindrical Composite Panels

DTIC Science & Technology

1991-12-01

form: exNl All A 12 A 16 B11 B12 B16 D nl D12 D16 E11 E12 E16 F11 F12 F16 COyI A12 A22 A6 B12 B22 B 1 D 2 D22 D26 E12 E2 2 E16 F1 2 F22 F26 0 A16 A 26...2 + 2E,,)kw,, ,., " kErWly + (kE11 + B 1 1)4f.,. + 2(kE 6 B16 )*.,x,, + (kE6 6 + B 616 ) *X,yy + (kE 1 6 + B 1 6 ) *y,, + [k (E1 2 + E6 6 ) " B12...B1 6 ) *x, y " (kE1 6 + B1 6 ) 1Y~ + (kE31 2 + B12) p,y, + -R-- 1 O 2 - B16 o, x + 12 W- 16W y- kF12 W, y - Wk16 + D6 x x-a W k 12 + D1 2)4r,y, 0 auo

The evolution of multiagency partnerships for safety over the course of research engagement: experiences from the NoGAPS project

PubMed Central

Donaldson, Alex; Gabbe, Belinda J; Muhammad, Akram; Shee, Anna Wong; Lloyd, David G; Cook, Jill

2016-01-01

Objective Implementation of effective population-level injury prevention interventions requires broad multiagency partnerships. Different stakeholders address this from varying perspectives, and potential conflicts in priorities need to be addressed for such partnerships to be effective. The researcher-led National Guidance for Australian football Partnerships and Safety (NoGAPS) project involved the engagement and participation of seven non-academic partners, including government health promotion and safety agencies; peak sports professional and advocacy bodies and health insurance organisations. Design The partnership's ongoing development was assessed by each partner completing the Victorian Health Promotion Foundation Partnership Analysis Tool (VPAT) annually over 2011–2015. Changes in VPAT scores were compared through repeated measures analysis of variance. Results Overall, mean total VPAT scores increased significantly over the 5-year period (125.1–141.2; F5,30=4.61, p=0.003), showing a significant improvement in how the partnership was functioning over time. This was largely driven by significant increases in several VPAT domains: ‘determining the need for a partnership’ (F5,30=4.15, p=0.006), ‘making sure the partnership works’ (F5,30=2.59, p=0.046), ‘planning collaborative action’ (F5,30=5.13, p=0.002) and ‘minimising the barriers to the partnership’ (F5,30=6.66, p<0.001). Conclusion This is the first study to assess the functioning of a multiagency partnership to address sport injury prevention implementation. For NoGAPS, the engagement of stakeholders from the outset facilitated the development of new and/or stronger links between non-academic partners. Partners shared the common goal of ensuring the real-world uptake of interventions and research evidence-informed recommendations. Effective multiagency partnerships have the potential to influence the implementation of policies and practices beyond the life of a research project. PMID:27016461

Patients and families as teachers: a mixed methods assessment of a collaborative learning model for medical error disclosure and prevention.

PubMed

Langer, Thorsten; Martinez, William; Browning, David M; Varrin, Pamela; Sarnoff Lee, Barbara; Bell, Sigall K

2016-08-01

Despite growing interest in engaging patients and families (P/F) in patient safety education, little is known about how P/F can best contribute. We assessed the feasibility and acceptability of a patient-teacher medical error disclosure and prevention training model. We developed an educational intervention bringing together interprofessional clinicians with P/F from hospital advisory councils to discuss error disclosure and prevention. Patient focus groups and orientation sessions informed curriculum and assessment design. A pre-post survey with qualitative and quantitative questions was used to assess P/F and clinician experiences and attitudes about collaborative safety education including participant hopes, fears, perceived value of learning experience and challenges. Responses to open-ended questions were coded according to principles of content analysis. P/F and clinicians hoped to learn about each other's perspectives, communication skills and patient empowerment strategies. Before the intervention, both groups worried about power dynamics dampening effective interaction. Clinicians worried that P/F would learn about their fallibility, while P/F were concerned about clinicians' jargon and defensive posturing. Following workshops, clinicians valued patients' direct feedback, communication strategies for error disclosure and a 'real' learning experience. P/F appreciated clinicians' accountability, and insights into how medical errors affect clinicians. Half of participants found nothing challenging, the remainder clinicians cited emotions and enormity of 'culture change', while P/F commented on medical jargon and desire for more time. Patients and clinicians found the experience valuable. Recommendations about how to develop a patient-teacher programme in patient safety are provided. An educational paradigm that includes patients as teachers and collaborative learners with clinicians in patient safety is feasible, valued by clinicians and P/F and promising for P/F-centred medical error disclosure and prevention training. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Path forward: emerging issues and challenges.

PubMed

Gillen, Matt; Gittleman, Janie L

2010-06-01

The NIOSH Construction Program worked with industry stakeholders to develop a National Occupational Safety and Health Construction Agenda to target future research and activities. The Program and its partners are also cognizant that new developments can emerge over time and that research can play an important role in helping to understand and address these emerging issues. Examples of emerging issues relevant to construction safety and health are described. These include: (a) climate change and energy considerations; (b) green construction developments and opportunities; (c) new materials; (d) changes in industry structure and practice; (e) workforce developments and disparities; (f) injury underreporting and cost and risk shifting; and (g) increased interest in addressing root causes. Responding to emerging issues while maintaining a focus on fundamental longstanding issues represents an ongoing challenge for researchers and industry organizations. Additional research to understand the diffusion and adoption of research by the industry is also needed. Research accomplished to date provides a strong foundation for addressing future industry needs and trends. (c) 2010 Elsevier Ltd. All rights reserved.

[Algorithms for early mobilization in intensive care units].

PubMed

Nydahl, P; Dubb, R; Filipovic, S; Hermes, C; Jüttner, F; Kaltwasser, A; Klarmann, S; Mende, H; Nessizius, S; Rottensteiner, C

2017-03-01

Immobility of patients in intensive care units (ICU) can lead to long-lasting physical and cognitive decline. During the last few years, bundles for rehabilitation were developed, including early mobilization. The German guideline for positioning therapy and mobilization, in general, recommends the development of ICU-specific protocols. The aim of this narrative review is to provide guidance when developing a best practice protocol in one's own field of work. It is recommended to a) implement early mobilization as part of a bundle, including screening and management of patient's awareness, pain, anxiety, stress, delirium and family's presence, b) develop a traffic-light system of specific in- and exclusion criteria in an interprofessional process, c) use checklists to assess risks and preparation of mobilization, d) use the ICU Mobility Scale for targeting and documentation of mobilization, e) use relative safety criteria for hemodynamic and respiratory changes, and Borg Scale for subjective evaluation, f) document and evaluate systematically mobilization levels, barriers, unwanted safety events and other parameters.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanai, Dai; Ueda, Atsushi; Akagi, Tadayuki

Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, have a characteristic cell cycle with truncated G1 and G2 phases. Recent findings that suppression of Oct3/4 expression results in a reduced proliferation rate of ES cells suggest the involvement of Oct3/4 in the regulation of ES cell growth, although the underlying molecular mechanism remains unclear. In the present study, we identified E2F3a as a direct target gene of Oct3/4 in ES cells. Oct3/4 directly bound to the promoter region of the E2F3a gene and positively regulated expression of E2F3a in mouse ES cells. Suppression of E2F3a activitymore » by E2F6 overexpression led to the reduced proliferation in ES cells, which was relieved by co-expression of E2F3a. Furthermore, cell growth retardation caused by loss of Oct3/4 was rescued by E2F3a expression. These results suggest that Oct3/4 upregulates E2F3a expression to promote ES cell growth. - Highlights: • Oct3/4 positively regulates E2F3a expression in ES cells. • Oct3/4 binds to the promoter region of the E2F3a gene. • Overexpression of E2F6, an inhibitor of E2F3a, reduces ES cell growth. • E2F3a recovers growth retardation of ES cells caused by Oct3/4 reduction.« less

14 CFR 1216.200 - Scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... wetlands; (f) Develop an integrated process to involve the public in the floodplain and wetlands management... Management § 1216.200 Scope. This subpart 1216.2 prescribes procedures to: (a) Avoid long- and short-term... alternative; (c) Reduce the risk of flood loss; (d) Minimize the impact of floods on human health, safety and...

miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells

PubMed Central

Tian, Hang; Hou, Lei; Xiong, Yu-Mei; Huang, Jun-Xiang; Zhang, Wen-Hua; Pan, Yong-Ying; Song, Xing-Rong

2016-01-01

Accumulating evidence showed that microRNA-132 (miR-132) are involved in development and progression of several types of cancers, however, the function and underlying molecular mechanism of miR-132 in ovarian cancer remains unclear. In this study we investigated the biological roles and molecular mechanism of miR-132 in ovarian cancer. Here, we found that that the expression levels of miR-132 were dramatically decreased in ovarian cancer cell lines and clinical ovarian cancer tissue samples. Then, we found that introduction of miR-132 significantly suppressed the proliferation, colony formation, migration and invasion of ovarian cancer cells. Mechanism investigation revealed that miR-132 inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3’UTR. Moreover, the expression level of E2F5 was significantly increased in ovarian cancer tissues than in the adjacent normal tissues, and its expression was inversely correlated with miR-132 expression in clinical ovarian cancer tissues. Additionally, silencing E2F5 was able to inhibit the proliferation, colony formation, migration and invasion of ovarian cancer cells, parallel to the effect of miR-132 overexpression on the ovarian cancer cells. Meanwhile, overexpression of E2F5 reversed the inhibition effect mediated by miR-132 overexpression. These results indicate that miR-132 suppresses the cell proliferation, invasion, migration in ovarian cancer cells by targeting E2F5. PMID:27186275

miR-132 targeting E2F5 suppresses cell proliferation, invasion, migration in ovarian cancer cells.

PubMed

Tian, Hang; Hou, Lei; Xiong, Yu-Mei; Huang, Jun-Xiang; Zhang, Wen-Hua; Pan, Yong-Ying; Song, Xing-Rong

2016-01-01

Accumulating evidence showed that microRNA-132 (miR-132) are involved in development and progression of several types of cancers, however, the function and underlying molecular mechanism of miR-132 in ovarian cancer remains unclear. In this study we investigated the biological roles and molecular mechanism of miR-132 in ovarian cancer. Here, we found that that the expression levels of miR-132 were dramatically decreased in ovarian cancer cell lines and clinical ovarian cancer tissue samples. Then, we found that introduction of miR-132 significantly suppressed the proliferation, colony formation, migration and invasion of ovarian cancer cells. Mechanism investigation revealed that miR-132 inhibited the expression of transcription factor E2F5 by specifically targeting its mRNA 3'UTR. Moreover, the expression level of E2F5 was significantly increased in ovarian cancer tissues than in the adjacent normal tissues, and its expression was inversely correlated with miR-132 expression in clinical ovarian cancer tissues. Additionally, silencing E2F5 was able to inhibit the proliferation, colony formation, migration and invasion of ovarian cancer cells, parallel to the effect of miR-132 overexpression on the ovarian cancer cells. Meanwhile, overexpression of E2F5 reversed the inhibition effect mediated by miR-132 overexpression. These results indicate that miR-132 suppresses the cell proliferation, invasion, migration in ovarian cancer cells by targeting E2F5.

The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis

PubMed Central

Marlowe, Jennifer L.; Fan, Yunxia; Chang, Xiaoqing; Peng, Li; Knudsen, Erik S.; Xia, Ying

2008-01-01

Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr−/− fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, γH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of E2F1 expression. In contrast, ligand-dependent AHR activation protects these cells from etoposide-induced cell death. In cells expressing both proteins, AHR and E2F1 interact independently of the retinoblastoma protein (RB), because AHR and E2F1 coimmunoprecipitate from extracts of RB-negative cells. Additionally, chromatin immunoprecipitation assays indicate that AHR and E2F1 bind to the Apaf1 promoter at a region containing a consensus E2F1 binding site but no AHR binding sites. AHR activation represses Apaf1 and TAp73 mRNA induction by a constitutively active CHK2 expression vector. Furthermore, AHR overexpression blocks the transcriptional induction of Apaf1 and p73 and the accumulation of sub-G0/G1 cells resulting from ectopic overexpression of E2F1. These results point to a proproliferative, antiapoptotic function of the Ah receptor that likely plays a role in tumor progression. PMID:18524851

Population pharmacokinetics and exposure-response of osimertinib in patients with non-small cell lung cancer.

PubMed

Brown, Kathryn; Comisar, Craig; Witjes, Han; Maringwa, John; de Greef, Rik; Vishwanathan, Karthick; Cantarini, Mireille; Cox, Eugène

2017-06-01

To develop a population (pop) pharmacokinetic (PK) model for osimertinib (AZD9291) and its metabolite (AZ5104) and investigate the exposure-response relationships for selected efficacy and safety parameters. PK, safety and efficacy data were collected from two non-small cell lung cancer (NSCLC) patient studies (n = 748) and one healthy volunteer study (n = 32), after single or multiple once-daily dosing of 20-240 mg osimertinib. Nonlinear mixed effects modelling was used to characterise the popPK. Individual exposure values were used to investigate the relationship with response evaluation criteria in solid tumours (RECIST 1.1) efficacy parameters and key safety parameters (rash, diarrhoea, QTcF). A popPK model that adequately described osimertinib and its metabolite AZ5104 in a joint manner was developed. Body weight, serum albumin and ethnicity were identified as significant covariates on PK in the analysis, but were not found to have a clinically relevant impact on osimertinib exposure. No relationship was identified between exposure and efficacy over the dose range studied. A linear relationship was observed between exposure and the occurrence of rash or diarrhoea, and between concentration and QTcF, with a predicted mean (upper 90% confidence interval) increase of 14.2 (15.8) ms at the maximum concentration for an 80 mg once-daily dose at steady state. PopPK and exposure-response models were developed for osimertinib and AZ5104. There was no relationship between exposure and efficacy but a linear relationship between exposure and safety endpoints (rash, diarrhoea and QTcF) was observed. © 2016 The British Pharmacological Society.

Comparison of three dimeric 18F-AlF-NOTA-RGD tracers.

PubMed

Guo, Jinxia; Lang, Lixin; Hu, Shuo; Guo, Ning; Zhu, Lei; Sun, Zhongchan; Ma, Ying; Kiesewetter, Dale O; Niu, Gang; Xie, Qingguo; Chen, Xiaoyuan

2014-04-01

RGD peptide-based radiotracers are well established as integrin αvβ3 imaging probes to evaluate tumor angiogenesis or tissue remodeling after ischemia or infarction. In order to optimize the labeling process and pharmacokinetics of the imaging probes, we synthesized three dimeric RGD peptides with or without PEGylation and performed in vivo screening. Radiolabeling was achieved through the reaction of F-18 aluminum-fluoride complex with the cyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). Three imaging probes were synthesized as (18)F-AlF-NOTA-E[c(RGDfK)]2, (18)F-AlF-NOTA-PEG4-E[c(RGDfK)]2, and (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2. The receptor binding affinity was determined by competitive cell binding assay, and the stability was evaluated by mouse serum incubation. Tumor uptake and whole body distribution of the three tracers were compared through direct tissue sampling and PET quantification of U87MG tumor-bearing mice. All three compounds remained intact after 120 min incubation with mouse serum. They all had a rapid and relatively high tracer uptake in U87MG tumors with good target-to-background ratios. Compared with the other two tracers, (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2 had the highest tumor uptake and the lowest accumulation in the liver. The integrin receptor specificity was confirmed by co-injection of unlabeled dimeric RGD peptide. The rapid one-step radiolabeling strategy by the complexation of (18)F-aluminum fluoride with NOTA-peptide conjugates was successfully applied to synthesize three dimeric RGD peptides. Among the three probes developed, (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2 with relatively low liver uptake and high tumor accumulation appears to be a promising candidate for further translational research.

Transactivation of micrornA-320 by microRNA-383 regulates granulosa cell functions by targeting E2F1 and SF-1 proteins.

PubMed

Yin, Mianmian; Wang, Xiaorong; Yao, Guidong; Lü, Mingrong; Liang, Meng; Sun, Yingpu; Sun, Fei

2014-06-27

Our previous studies have shown that microRNA-320 (miR-320) is one of the most down-regulated microRNAs (miRNA) in mouse ovarian granulosa cells (GCs) after TGF-β1 treatment. However, the underlying mechanisms of miR-320 involved in GC function during follicular development remain unknown. In this study, we found that pregnant mare serum gonadotropin treatment resulted in the suppression of miR-320 expression in a time-dependent manner. miR-320 was mainly expressed in GCs and oocytes of mouse ovarian follicles in follicular development. Overexpression of miR-320 inhibited estradiol synthesis and proliferation of GCs through targeting E2F1 and SF-1. E2F1/SF-1 mediated miR-320-induced suppression of GC proliferation and of GC steroidogenesis. FSH down-regulated the expression of miR-320 and regulated the function of miR-320 in mouse GCs. miR-383 promoted the expression of miR-320 and enhanced miR-320-mediated suppression of GC proliferation. Injection of miR-320 into the ovaries of mice partially promoted the production of testosterone and progesterone but inhibited estradiol release in vivo. Moreover, the expression of miR-320 and miR-383 was up-regulated in the follicular fluid of polycystic ovarian syndrome patients, although the expression of E2F1 and SF-1 was down-regulated in GCs. These data demonstrated that miR-320 regulates the proliferation and steroid production by targeting E2F1 and SF-1 in the follicular development. Understanding the regulation of miRNA biogenesis and function in the follicular development will potentiate the usefulness of miRNA in the treatment of reproduction and some steroid-related disorders. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Randomized controlled trial of false safety behavior elimination therapy: a unified cognitive behavioral treatment for anxiety psychopathology.

PubMed

Schmidt, Norman B; Buckner, Julia D; Pusser, Andrea; Woolaway-Bickel, Kelly; Preston, Jennifer L; Norr, Aaron

2012-09-01

We tested the efficacy of a unified cognitive-behavioral therapy protocol for anxiety disorders. This group treatment protocol, termed false safety behavior elimination therapy (F-SET), is a cognitive-behavioral approach designed for use across various anxiety disorders such as panic disorder (PD), social anxiety disorder (SAD), and generalized anxiety disorder (GAD). F-SET simplifies, as well as broadens, key therapeutic elements of empirically validated treatments for anxiety disorders to allow for easier delivery to heterogeneous groups of patients with anxiety psychopathology. Patients with a primary anxiety disorder diagnosis (N=96) were randomly assigned to F-SET or a wait-list control. Data indicate that F-SET shows good efficacy and durability when delivered to mixed groups of patients with anxieties (i.e., PD, SAD, GAD) by relatively inexperienced clinicians. Findings are discussed in the context of balancing treatment efficacy and clinical utility. Copyright © 2012. Published by Elsevier Ltd.

United States Air Force F-35A Operational Basing Environmental Impact Statement. Appendix E: Comments

DTIC Science & Technology

2013-09-01

this pork -laden boondoggle down our throats? Finally, to those who accuse F-35 opponents of being unpatriotic, you should know better. Patriotism is...Vermont Air Guard base as the members bring money into the ar ea during training weekends/days for food , housing and entertainment. These monies...adults and children living in the noise zone 3. There was no crash data for FY 13 fo r the F-22 (page BR4-49/50) ’] • Since safety estimates of the F-35A

21 CFR 610.61 - Package label.

Code of Federal Regulations, 2010 CFR

2010-04-01

...; (d) The expiration date; (e) The preservative used and its concentration, or if no preservative is used and the absence of a preservative is a safety factor, the words “no preservative”; (f) The number...

29 CFR 1952.271 - Where the plan may be inspected.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., Occupational Safety and Health Administration, U.S. Department of Labor, 200 Constitution Avenue, NW, Room... Administration, U.S. Department of Labor, John F. Kennedy Federal Building, Room E-340, Boston, Massachusetts...

29 CFR 1952.271 - Where the plan may be inspected.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., Occupational Safety and Health Administration, U.S. Department of Labor, 200 Constitution Avenue, NW, Room... Administration, U.S. Department of Labor, John F. Kennedy Federal Building, Room E-340, Boston, Massachusetts...

Validation and application of Highway Safety Manual (Part D) and developing Florida CMF Manual, phase 2.

DOT National Transportation Integrated Search

2016-05-01

The Highway Safety Manual (HSM) Part D provides a comprehensive list of the effects of safety treatments : (countermeasures). These effects are quantified by crash modification factors (CMF) which are based on compilation : from past studies of the e...

E2F activators signal and maintain centrosome amplification in breast cancer cells.

PubMed

Lee, Mi-Young; Moreno, Carlos S; Saavedra, Harold I

2014-07-01

Centrosomes ensure accurate chromosome segregation by directing spindle bipolarity. Loss of centrosome regulation results in centrosome amplification, multipolar mitosis and aneuploidy. Since centrosome amplification is common in premalignant lesions and breast tumors, it is proposed to play a central role in breast tumorigenesis, a hypothesis that remains to be tested. The coordination between the cell and centrosome cycles is of paramount importance to maintain normal centrosome numbers, and the E2Fs may be responsible for regulating these cycles. However, the role of E2F activators in centrosome amplification is unclear. Because E2Fs are deregulated in Her2(+) cells displaying centrosome amplification, we addressed whether they signal this abnormal process. Knockdown of E2F1 or E2F3 in Her2(+) cells decreased centrosome amplification without significantly affecting cell cycle progression, whereas the overexpression of E2F1, E2F2, or E2F3 increased centrosome amplification in MCF10A mammary epithelial cells. Our results revealed that E2Fs affect the expression of proteins, including Nek2 and Plk4, known to influence the cell/centrosome cycles and mitosis. Downregulation of E2F3 resulted in cell death and delays/blocks in cytokinesis, which was reversed by Nek2 overexpression. Nek2 overexpression enhanced centrosome amplification in Her2(+) breast cancer cells silenced for E2F3, revealing a role for the E2F activators in maintaining centrosome amplification in part through Nek2.

Exploring the electrochemical properties of hole transport materials with spiro-cores for efficient perovskite solar cells from first-principles.

PubMed

Chi, Wei-Jie; Li, Quan-Song; Li, Ze-Sheng

2016-03-21

Perovskite solar cells (PSCs) with organic small molecules as hole transport materials (HTMs) have attracted considerable attention due to their power conversion efficiencies as high as 20%. In the present work, three new spiro-type hole transport materials with spiro-cores, i.e. Spiro-F1, Spiro-F2 and Spiro-F3, are investigated by using density functional theory combined with the Marcus theory and Einstein relation. Based on the calculated and experimental highest occupied molecular orbital (HOMO) levels of 30 reference molecules, an empirical equation, which can predict the HOMO levels of hole transport materials accurately, is proposed. Moreover, a simplified method, in which the hole transport pathways are simplified to be one-dimensional, is presented and adopted to qualitatively compare the molecular hole mobilities. The calculated results show that the perovskite solar cells with the new hole transport materials can have higher open-circuit voltages due to the lower HOMO levels of Spiro-F1 (-5.31 eV), Spiro-F2 (-5.42 eV) and Spiro-F3 (-5.10 eV) compared with that of Spiro-OMeTAD (-5.09 eV). Furthermore, the hole mobilities of Spiro-F1 (1.75 × 10(-2) cm(2) V(-1) s(-1)) and Spiro-F3 (7.59 × 10(-3) cm(2) V(-1) s(-1)) are 3.1 and 1.4 times that of Spiro-OMeTAD (5.65 × 10(-3) cm(2) V(-1) s(-1)) respectively, due to small reorganization energies and large transfer integrals. Interestingly, the stability properties of Spiro-F1 and Spiro-F2 are shown to be comparable to that of Spiro-OMeTAD, and the dimers of Spiro-F2 and Spiro-F3 possess better stability than that of Spiro-OMeTAD. Taking into consideration the appropriate HOMO level, improved hole mobility and enhanced stability, Spiro-F1 and Spiro-F3 may become the most promising alternatives to Spiro-OMeTAD. The present work offers a new design strategy and reliable calculation methods towards the development of excellent organic small molecules as HTMs for highly efficient and stable PSCs.

E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells

PubMed Central

Hatchi, Elodie; Rodier, Genevieve; Lacroix, Matthieu; Caramel, Julie; Kirsh, Olivier; Jacquet, Chantal; Schrepfer, Emilie; Lagarrigue, Sylviane; Linares, Laetitia Karine; Lledo, Gwendaline; Tondeur, Sylvie; Dubus, Pierre

2011-01-01

The multifunctional E4F1 protein was originally discovered as a target of the E1A viral oncoprotein. Growing evidence indicates that E4F1 is involved in key signaling pathways commonly deregulated during cell transformation. In this study, we investigate the influence of E4F1 on tumorigenesis. Wild-type mice injected with fetal liver cells from mice lacking CDKN2A, the gene encoding Ink4a/Arf, developed histiocytic sarcomas (HSs), a tumor originating from the monocytic/macrophagic lineage. Cre-mediated deletion of E4F1 resulted in the death of HS cells and tumor regression in vivo and extended the lifespan of recipient animals. In murine and human HS cell lines, E4F1 inactivation resulted in mitochondrial defects and increased production of reactive oxygen species (ROS) that triggered massive cell death. Notably, these defects of E4F1 depletion were observed in HS cells but not healthy primary macrophages. Short hairpin RNA–mediated depletion of E4F1 induced mitochondrial defects and ROS-mediated death in several human myeloid leukemia cell lines. E4F1 protein is overexpressed in a large subset of human acute myeloid leukemia samples. Together, these data reveal a role for E4F1 in the survival of myeloid leukemic cells and support the notion that targeting E4F1 activities might have therapeutic interest. PMID:21708927

Lethality of home-style dehydrator processes against Escherichia coli O157:H7 and salmonella serovars in the manufacture of ground-and-formed beef jerky and the potential for using a pathogen surrogate in process validation.

PubMed

Borowski, A G; Ingham, S C; Ingham, B H

2009-10-01

Ground-and-formed beef jerky can be made easily at home with ground beef and kits that include spice, cure, and jerky-forming equipment. Ground beef poses inherent risks of illness due to Escherichia coli O157:H7 and Salmonella contamination, making adequate pathogen lethality important in jerky manufacturing. We evaluated the effectiveness of drying regimes at eliminating E. coli O157:H7 and Salmonella in seasoned ground-and-formed beef jerky manufactured with three home-style dehydrators and one small commercial unit. Inoculated jerky strips were dried for up to 12 or 24 h in a home-style or the commercial unit, respectively, with target drying temperatures ranging from 51.7 degrees C (125 degrees F) to 71.1 degrees C (160 degrees F). Pathogen lethality varied with seasoning, temperature, and drying time (n = 288 samples). Lethality against E. coli O157:H7 ranged from 1.5 log CFU (Jerky Xpress, 57.2 degrees C [135 degrees F], 4 h) to 6.4 log CFU (Gardenmaster, 68.3 degrees C [155 degrees F], 12 h), and varied with seasoning. Lethality against Salmonella ranged from 1.7 log CFU (Jerky Xpress, 57.2 degrees C [135 degrees F], 4 h) to 6.0 log CFU (Gardenmaster, 68.3 degrees C [155 degrees F], 12 h), and also varied with seasoning. There was a > or =5-log CFU reduction in both pathogens in 0, 10, and 27 % of samples at 4, 8, and 12 h, respectively. Heating jerky for 10 min at 135 degrees C (275 degrees F) 4 or 6 h postdrying increased lethality, on average, 2.99 log CFU for Salmonella and 3.02 log CFU for E. coli O157:H7. The use of a lactic acid bacterium culture (Pediococcus spp.) as a pathogen surrogate accurately predicted safety in 28 % of samples containing E. coli O157:H7 and 78% of Salmonella-inoculated samples.

E2F1 transcription factor and its impact on growth factor and cytokine signaling.

PubMed

Ertosun, Mustafa Gokhan; Hapil, Fatma Zehra; Osman Nidai, Ozes

2016-10-01

E2F1 is a transcription factor involved in cell cycle regulation and apoptosis. The transactivation capacity of E2F1 is regulated by pRb. In its hypophosphorylated form, pRb binds and inactivates DNA binding and transactivating functions of E2F1. The growth factor stimulation of cells leads to activation of CDKs (cyclin dependent kinases), which in turn phosphorylate Rb and hyperphosphorylated Rb is released from E2F1 or E2F1/DP complex, and free E2F1 can induce transcription of several genes involved in cell cycle entry, induction or inhibition of apoptosis. Thus, growth factors and cytokines generally utilize E2F1 to direct cells to either fate. Furthermore, E2F1 regulates expressions of various cytokines and growth factor receptors, establishing positive or negative feedback mechanisms. This review focuses on the relationship between E2F1 transcription factor and cytokines (IL-1, IL-2, IL-3, IL-6, TGF-beta, G-CSF, LIF), growth factors (EGF, KGF, VEGF, IGF, FGF, PDGF, HGF, NGF), and interferons (IFN-α, IFN-β and IFN-γ). Copyright © 2016 Elsevier Ltd. All rights reserved.

49 CFR 1.86 - The Federal Motor Carrier Safety Administration.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., development, and technology transfer activities to promote safety of operation and equipment of motor vehicles for the motor carrier transportation program; and (f) Carrying out an effective communications and...

49 CFR 1.86 - The Federal Motor Carrier Safety Administration.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., development, and technology transfer activities to promote safety of operation and equipment of motor vehicles for the motor carrier transportation program; and (f) Carrying out an effective communications and...

49 CFR 1.86 - The Federal Motor Carrier Safety Administration.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., development, and technology transfer activities to promote safety of operation and equipment of motor vehicles for the motor carrier transportation program; and (f) Carrying out an effective communications and...

Development of a Piezoelectric Polymer Film Pressure Transducer for Low Frequency and Dynamic Pressure Measurement

DTIC Science & Technology

1990-12-01

Sample LOTUS 123 Cell Formulas for Reducing Reset Data A2: 0.0008 B2: 0.564 C2: -2.501 02: (A1-$A$1) E2: (@IF(@ABS(C2)>2,@TRUE,@FALSE)=1) F2: (@IF(E2...9 F14: (@IF( El4 =1,0,0.951*C14)) H14: (G14- 12 .492*D14) A15: 0.0034 B15: -0.248 015: 0.033 D15: (A14-$A$l) G15: @IF(El5=O, (F15+$G$1 1), (($G$1 1+Gl4...data corrected for rise rate and zero mean. I I F-4 I LOTUS 123 Cell Formulas Used to Reconstruct the Sine Data Al: 0.00324 Bi: -0.01 Cl: -0.14 D1: (Al

Binding of 2-[18F]fluoro-CP-118,954 to mouse acetylcholinesterase: microPET and ex vivo Cerenkov luminescence imaging studies.

PubMed

Kim, Dong Hyun; Choe, Yearn Seong; Choi, Joon Young; Lee, Kyung-Han; Kim, Byung-Tae

2011-05-01

Acetylcholinesterase (AChE) has been an important cholinergic factor for the diagnosis of Alzheimer's disease (AD), because of reduced AChE activity in the postmortem brains of AD patients. We previously developed 5,7-dihydro-3-(2-(1-(2-[(18)F]fluorobenzyl)-4-piperidinyl)ethyl)-6H-pyrrolo(3,2,f)-1,2-benzisoxazol-6-one (2-[(18)F]fluoro-CP-118,954) for in vivo studies of AChE in mice. In the present study, we automated the synthesis of 2-[(18)F]fluoro-CP-118,954 for the routine use and evaluated the radioligand by microPET and ex vivo Cerenkov luminescence imaging of mouse AChE. 4-[(18)F]Fluoro-donepezil, another AChE inhibitor, was used for comparison. Automated syntheses of 2-[(18)F]fluoro-CP-118,954 and 4-[(18)F]fluoro-donepezil resulted in high radiochemical yields (25-33% and 30-40%) and high specific activity (27.1-35.4 and 29.7-37.3 GBq/μmol). Brain microPET images of two ICR mice injected with 2-[(18)F]fluoro-CP-118,954 demonstrated high uptake in the striatum (ROI analysis: 5.1 %ID/g for the first 30 min and 4.1 %ID/g for another 30 min), and a blocking study with injection of CP-118,954 into one of the mice at 30 min after radioligand injection led to complete blocking of radioligand uptake in the striatum (ROI analysis: 1.9 %ID/g), whereas (18)F-labeled donepezil did not show specific uptake in the striatum. In another set of experiments, the brain tissues (striatum, parietal cortex, frontal cortex and cerebellum) were excised after brain microPET/CT imaging of mouse injected with 2-[(18)F]fluoro-CP-118,954, and a high striatal uptake was also detected in ex vivo optical and microPET images (ROI analysis: 1.4 %ID/g) and in γ-counting data (2.1 %ID/g at 50 min post-injection) of the brain tissues. Taken together, these results demonstrated that 2-[(18)F]fluoro-CP-118,954 specifically binds to AChE in mouse brains. Copyright © 2011 Elsevier Inc. All rights reserved.

Arginine methylation-dependent reader-writer interplay governs growth control by E2F-1

PubMed Central

Zheng, Shunsheng; Moehlenbrink, Jutta; Lu, Yi-Chien; Zalmas, Lykourgos-Panagiotis; Sagum, Cari A.; Carr, Simon; McGouran, Joanna F.; Alexander, Leila; Fedorov, Oleg; Munro, Shonagh; Kessler, Benedikt; Bedford, Mark T.; Yu, Qiang; La Thangue, Nicholas B.

2014-01-01

Summary The mechanisms that underlie and dictate the different biological outcomes of E2F-1 activity have yet to be elucidated. We describe the residue-specific methylation of E2F-1 by the asymmetric dimethylating protein arginine methyltransferase (PRMT) 1 and symmetric dimethylating PRMT5, and relate the marks to different functional consequences of E2F-1 activity. Methylation by PRMT1 hinders methylation by PRMT5, which augments E2F-1-dependent apoptosis, whereas PRMT5-dependent methylation favours proliferation by antagonising methylation by PRMT1. The ability of E2F-1 to prompt apoptosis in DNA damaged cells coincides with enhanced PRMT1 methylation. In contrast, cyclin A binding to E2F-1 impedes PRMT1 methylation and augments PRMT5 methylation, thus ensuring that E2F-1 is locked into its cell cycle progression mode. The Tudor domain protein p100-TSN reads the symmetric methylation mark, and binding of p100-TSN down-regulates E2F-1 apoptotic activity. Our results define an exquisite level of precision in the reader-writer interplay that governs the biological outcome of E2F-1 activity. PMID:24076217

National Dam Safety Program. Nelson Dam (Inventory Number VA 12501), James River Basin, Nelson County, Virginia. Phase I Inspection Report.

DTIC Science & Technology

1981-06-01

during tropical storm Camille. 5.4 Flood Potential: The 100-Year Flood, 1/2 PMF, and PH? were developed by use of the HEC-l computer program (Reference 2...Appendix V) and routed through the reservoir using the NWS-Dambreak computer program (Reference 3, Appendix V). Clark’s Tc and R coefficients for...AD-AO" 330 ARMY ENGINEER DISTRICT NORFOLK VA F/6 13/13 NATIONAL DAM SAFETY PROGRAM . NELSON DAM (INVENTORY NUMBER VA 12--ETC(U) JUN 81 B 0 TARANUNCL

Characterization of nanoscopic calcium fluoride films

NASA Astrophysics Data System (ADS)

Rehmer, A.; Kemnitz, E.

2016-09-01

Nano metal fluorides are appropriate materials for different applications e.g. heterogeneous catalysis, ceramic materials for laser applications and antireflective layers on glass, respectively. An easy way to synthesize such nano metal fluorides is the fluorolytic sol-gel synthesis which was developed some few years ago for HS-AlF3 [1] and MgF2.[2] CaF2 exhibits similar optical properties as MgF2, and thus, is a promising candidate for antireflective (AR) coatings. That means, CaF2 exhibits a lower refractive index (n500 = 1.44) as compared to common soda lime glass (n500 = 1.53). Hence, we present an easy synthesis approach toward nanoscaled CaF2 sols to fabricate finally AR-CaF2 films by dip coating. Irrespective of the choice of the calcium precursor, the CaF2 films are porous in comparison to thin dense CaF2 films which are generated by physical vapor deposition. The characterization of CaF2 films was performed by different analytical methods like HR-SEM, XPS, EDX, EP (ellipsometric porosimetry), DLS (dynamic light scattering) and CA (contact angle measurement). Beside the good optical and mechanical properties, we have investigated the surface properties of CaF2 films on glass and silicon wafer e.g. surface morphology with elemental composition, open porosity, zeta potentials at the surfaces as well as the free energy of interaction between water and the CaF2 film.

E2F8 is essential for polyploidization in mammalian cells.

PubMed

Pandit, Shusil K; Westendorp, Bart; Nantasanti, Sathidpak; van Liere, Elsbeth; Tooten, Peter C J; Cornelissen, Peter W A; Toussaint, Mathilda J M; Lamers, Wouter H; de Bruin, Alain

2012-11-01

Polyploidization is observed in all mammalian species and is a characteristic feature of hepatocytes, but its molecular mechanism and biological significance are unknown. Hepatocyte polyploidization in rodents occurs through incomplete cytokinesis, starts after weaning and increases with age. Here, we show in mice that atypical E2F8 is induced after weaning and required for hepatocyte binucleation and polyploidization. A deficiency in E2f8 led to an increase in the expression level of E2F target genes promoting cytokinesis and thereby preventing polyploidization. In contrast, loss of E2f1 enhanced polyploidization and suppressed the polyploidization defect of hepatocytes deficient for atypical E2Fs. In addition, E2F8 and E2F1 were found on the same subset of target promoters. Contrary to the long-standing hypothesis that polyploidization indicates terminal differentiation and senescence, we show that prevention of polyploidization through inactivation of atypical E2Fs has, surprisingly, no impact on liver differentiation, zonation, metabolism and regeneration. Together, these results identify E2F8 as a repressor and E2F1 as an activator of a transcriptional network controlling polyploidization in mammalian cells.

lncRNA-HIT promotes cell proliferation of non-small cell lung cancer by association with E2F1.

PubMed

Yu, L; Fang, F; Lu, S; Li, X; Yang, Y; Wang, Z

2017-05-01

Lung cancer is the leading cause of cancer-related death around the world. Long noncoding RNA (lncRNA) has pivotal roles in cancer occurrence and development. However, only a few lncRNAs have been functionally characterized. In the present study, we investigated the effects of lncRNA-HIT (HOXA transcript induced by TGFβ) expression on non-small cell lung cancer (NSCLC) cell phenotype with the gain-of-function and loss-of-function assays. We found that ectopic expression or knockdown of lncRNA-HIT markedly increased or decreased NSCLC cell proliferation, respectively. Moreover, we also showed that lncRNA-HIT interacted with E2F1 to regulate its target genes, such as Survivin, FOXM1, SKP2, NELL2 and DOK1. Collectively, our findings indicated that lncRNA-HIT affected the proliferation of NSCLC cells at least in part via regulating the occupancy of E2F1 in the promoter regions of its target genes. The lncRNA-HIT-E2F1 complex may be a potential target for NSCLC treatment.

E2F Activators Signal and Maintain Centrosome Amplification in Breast Cancer Cells

PubMed Central

Lee, Mi-Young; Moreno, Carlos S.

2014-01-01

Centrosomes ensure accurate chromosome segregation by directing spindle bipolarity. Loss of centrosome regulation results in centrosome amplification, multipolar mitosis and aneuploidy. Since centrosome amplification is common in premalignant lesions and breast tumors, it is proposed to play a central role in breast tumorigenesis, a hypothesis that remains to be tested. The coordination between the cell and centrosome cycles is of paramount importance to maintain normal centrosome numbers, and the E2Fs may be responsible for regulating these cycles. However, the role of E2F activators in centrosome amplification is unclear. Because E2Fs are deregulated in Her2+ cells displaying centrosome amplification, we addressed whether they signal this abnormal process. Knockdown of E2F1 or E2F3 in Her2+ cells decreased centrosome amplification without significantly affecting cell cycle progression, whereas the overexpression of E2F1, E2F2, or E2F3 increased centrosome amplification in MCF10A mammary epithelial cells. Our results revealed that E2Fs affect the expression of proteins, including Nek2 and Plk4, known to influence the cell/centrosome cycles and mitosis. Downregulation of E2F3 resulted in cell death and delays/blocks in cytokinesis, which was reversed by Nek2 overexpression. Nek2 overexpression enhanced centrosome amplification in Her2+ breast cancer cells silenced for E2F3, revealing a role for the E2F activators in maintaining centrosome amplification in part through Nek2. PMID:24797070

Launch Safety, Toxicity, and Environmental Effects of the High Performance Oxidizer ClF(5)

DTIC Science & Technology

1994-03-31

Pentafluoride," J. Phys. Chem. 74, 1183 (1970). 7. J. A. Blauer, H. G. McMath, F. C. Jaye, and V. S, Engleman, " Decomposition Kinetics of Chlorine Trifluoride ...similar. A greater concern is propellant release in the stratosphere. Fluorine atoms lead to catalytic decomposition of 03 at rates similar to chlorine ...Propulsion Meeting - Publication 550, 3, 447 (1990). 4. R. F. Sawyer, E. T. McMullen, and P. Purgalis, "The Reaction of Hydrazine and Chlorine Pentafluoride

Modulation of E2F activity in primary mouse B cells following stimulation via surface IgM and CD40 receptors.

PubMed

Lam, E W; Glassford, J; van der Sman, J; Banerji, L; Pizzey, A R; Shaun, N; Thomas, B; Klaus, G G

1999-10-01

Since signals via CD40 and the B cell receptor are known to synergize to induce B cell activation, we have analyzed the pocket protein/E2F complexes in mouse B lymphocytes following stimulation by anti-IgM, anti-CD40, alone or together. We find that E2F4 and DP1 form the predominant E2F heterodimers in the G0 and G1 phases of the cell cycle, complexed with hypophosphorylated p130. During late G1 and S phase this complex is replaced by at least three different E2F complexes, one of which is an E2F complex containing p107 or pRB as well as two "free" E2F complexes consisting of E2F4/DP1 and E2F1-3/DP1. These effects were mirrored by the levels and phosphorylation status of the three pocket proteins. We also observed an increase in electrophoretic mobility of DP1 and E2F4 as B cells progressed from G0 into early G1, resulting from their dephosphorylation. This is known to correlate with a decrease in DNA binding capacity of these proteins and could also be important for derepression of genes negatively regulated through E2F sites in their promoters. These results therefore indicate that the pRB/E2F pathway integrates proliferative signals emanating from the sIgM and CD40 receptors.

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

PubMed

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

PubMed Central

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 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 cycle and provides an additional mechanism to limit E2F activity. PMID:21765927

E2F1 and NF-κB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets.

PubMed

Huang, Yulin; Chen, Rui; Zhou, Jianwei

2016-01-01

Inflammation is the fundamental protective response; however disordered immuno-response can cause chronic human disease, including cancer. Inflammatory cells and mediators are essential to the tumor microenvironment and dissection of this complex molecular and cellular milieu may elucidate a connection between cancer and inflammation and help to identify potential novel therapeutic targets. Thus, focusing on transcription factor NF-κB and E2F1 in inflammation-associated cancer is urgent. NF-κB activation is prevalent in carcinomas, mainly driven by inflammatory cytokines in the tumor microenvironment. E2F1 is also involved in regulating immune responses. Understanding the crosstalk between the two pathways may contribute to the development of novel anti-cancer drugs.

Fuel Fraction Analysis of 500 MWth Gas Cooled Fast Reactor with Nitride (UN-PuN) Fuel without Refueling

NASA Astrophysics Data System (ADS)

Dewi Syarifah, Ratna; Su'ud, Zaki; Basar, Khairul; Irwanto, Dwi

2017-01-01

Nuclear Power Plant (NPP) is one of candidates which can support electricity demand in the world. The Generation IV NPP has fourth main objective, i.e. sustainability, economics competitiveness, safety and reliability, and proliferation and physical protection. One of Gen-IV reactor type is Gas Cooled Fast Reactor (GFR). In this study, the analysis of fuel fraction in small GFR with nitride fuel has been done. The calculation was performed by SRAC code, both Pij and CITATION calculation. SRAC2002 system is a code system applicable to analyze the neutronics of variety reactor type. And for the data library used JENDL-3.2. The step of SRAC calculation is fuel pin calculated by Pij calculation until the data homogenized, after it homogenized we calculate core reactor. The variation of fuel fraction is 40% up to 65%. The optimum design of 500MWth GFR without refueling with 10 years burn up time reach when radius F1:F2:F3 = 50cm:30cm:30cm and height F1:F2:F3 = 50cm:40cm:30cm, variation percentage Plutonium in F1:F2:F3 = 7%:10%:13%. The optimum fuel fraction is 41% with addition 2% Plutonium weapon grade mix in the fuel. The excess reactivity value in this case 1.848% and the k-eff value is 1.01883. The high burn up reached when the fuel fraction is low. In this study 41% fuel fraction produce faster fissile fuel, so it has highest burn-up level than the other fuel fraction.

Hazard Response Modeling Uncertainty (A Quantitative Method)

DTIC Science & Technology

1988-10-01

was conducted by the National Maritime Institute under contract to the United Kingdom Health and Safety Executive. Instantaneous releases of 2000...the National Maritime Institute under contract to the United Kingdom Health and Safety Executive with the sponsorship of numerous international...WORK UNIT ELEMENT NO. NO. NO. ACESSION NO. _____________________65502F I 00O ne I " 11. TITLE (incl& e Security Oauffication) Hazard Response

National Program for Inspection of Non-Federal Dams. Patch Reservoir Dam (MA 00122), Blackstone River Basin, Worcester, Massachusetts. Phase I Inspection Report.

DTIC Science & Technology

1978-08-01

ow epC, Oj f0L o 64w 6* +*’r4- {(lo.d, J*t*. M .C , f. * Stpm ". I47.,, 08%~~~ (3u~t 1 CY4 p.,4 5sf- Stc. ’ few&4. I tVC 100 ’ eX4 F:’/POCJ FIDV&4, 4Z...IESIT CiHAR1( * NATIONAL BUREAU OF S ANOAS- 1 % 3 *A N 7 o .. .. Vc " w .. BLACKSTONE RIVER BASIN LU WORCESTER, MASSACHUSETTS 3,4., 4• . PATCH...report. 19I. KEY WORDS (Coninue on reverse aide # 1 01*0064IOWuEIel 1 ~0F 6? l0eAk M111I..o) DAMS, INSPECTION, DAM SAFETY, Blackstone River Basin

Suppression of Escherichia coli O157:H7 by Dung Beetles (Coleoptera: Scarabaeidae) Using the Lowbush Blueberry Agroecosystem as a Model System

PubMed Central

Jones, Matthew S.; Tadepalli, Shravani; Bridges, David F.; Wu, Vivian C. H.; Drummond, Frank

2015-01-01

Wildlife as a source of microbial contamination is a food safety concern. Deer feces (scat) have been determined as a point source for Escherichia coli O157:H7 contamination of fresh produce. The ecological role of the scooped scarab (Onthophagus hecate (Panzer)), a generalist dung beetle species common in Maine blueberry fields, was explored as a biological control agent and alternatively as a pathogen vector between deer scat and food. A large-scale field survey of wildlife scat indicated that pathogenic E. coli O157:H7 was present, albeit at a low prevalence (1.9% of samples, n = 318), in the Maine lowbush blueberry agroecosystem. A manipulative field experiment verified that, should contact occur between deer scat and blueberry plants and fruit during the summer, contamination with E. coli O157:H7 can occur and persist for more than 72 h. For both the positive control and an experimental scat inoculation treatment, the levels of the bacterial population decreased over time, but at different rates (treatment x time interaction: F (1.9,18.8) = 358.486, P < 0.0001). The positive control inoculation, which resulted in a higher initial E. coli level on fruit, decayed at a faster rate than inoculation of fruit via scat in the experimental treatment. We conducted 2 laboratory studies to elucidate aspects of dung beetle feeding ecology as it relates to suppression of E. coli O157:H7 from deer scat to lowbush blueberry fruit. In both experiments, dung beetles buried the same amount of scat whether or not the scat was inoculated with the pathogen (F (1,6) = 0.001; P = 0.999 and (F (2,17) = 4.10, P = 0.147). Beetles feeding on E. coli inoculated deer scat were not found to vector the pathogen to fruit. In two studies, beetles lowered the amount of pathogenic E. coli persisting in soils compared to soils without beetles (F (2,9) = 7.757; P = 0.05 and F (2,17) = 8.0621, P = 0.004). Our study suggests that the dung beetle species, Onthophagus hecate, has the potential to contribute to the suppression of E. coli O157:H7 in agricultural landscapes. PMID:25849430

Suppression of Escherichia coli O157:H7 by Dung Beetles (Coleoptera: Scarabaeidae) using the lowbush blueberry agroecosystem as a model system.

PubMed

Jones, Matthew S; Tadepalli, Shravani; Bridges, David F; Wu, Vivian C H; Drummond, Frank

2015-01-01

Wildlife as a source of microbial contamination is a food safety concern. Deer feces (scat) have been determined as a point source for Escherichia coli O157:H7 contamination of fresh produce. The ecological role of the scooped scarab (Onthophagus hecate (Panzer)), a generalist dung beetle species common in Maine blueberry fields, was explored as a biological control agent and alternatively as a pathogen vector between deer scat and food. A large-scale field survey of wildlife scat indicated that pathogenic E. coli O157:H7 was present, albeit at a low prevalence (1.9% of samples, n = 318), in the Maine lowbush blueberry agroecosystem. A manipulative field experiment verified that, should contact occur between deer scat and blueberry plants and fruit during the summer, contamination with E. coli O157:H7 can occur and persist for more than 72 h. For both the positive control and an experimental scat inoculation treatment, the levels of the bacterial population decreased over time, but at different rates (treatment x time interaction: F (1.9,18.8) = 358.486, P < 0.0001). The positive control inoculation, which resulted in a higher initial E. coli level on fruit, decayed at a faster rate than inoculation of fruit via scat in the experimental treatment. We conducted 2 laboratory studies to elucidate aspects of dung beetle feeding ecology as it relates to suppression of E. coli O157:H7 from deer scat to lowbush blueberry fruit. In both experiments, dung beetles buried the same amount of scat whether or not the scat was inoculated with the pathogen (F(1,6) = 0.001; P = 0.999 and (F (2,17) = 4.10, P = 0.147). Beetles feeding on E. coli inoculated deer scat were not found to vector the pathogen to fruit. In two studies, beetles lowered the amount of pathogenic E. coli persisting in soils compared to soils without beetles (F (2,9) = 7.757; P = 0.05 and F (2,17) = 8.0621, P = 0.004). Our study suggests that the dung beetle species, Onthophagus hecate, has the potential to contribute to the suppression of E. coli O157:H7 in agricultural landscapes.

Development of a Flight Instrument Package

DTIC Science & Technology

1992-12-01

105 0 F 80 to 130°F 95 to 145-F Recommended Maximum Intermittent 180-F 180°F 180 F ISODAl P Velocity-Sensitive Compression ResistanceE-A-R ISODAMP C...PARnAMETER *Too". CONDIIONSo m 1W EAX ON ?" MAX UNIT* Input Iiaa6-iag al - 10 25 - 20 s0 iov vs-OPES ei sta fast Avoomii (NOW 1) - 0.2 - - 0.2 - b.V...to the supply pin is also importanft particularly over fast . contributing to the operational amplifier’s high temperature, since many types of

Efficacy of an herbal formulation LI10903F containing Dolichos biflorus and Piper betle extracts on weight management.

PubMed

Sengupta, Krishanu; Mishra, Atmatrana T; Rao, Manikeshwar K; Sarma, Kadainti Vs; Krishnaraju, Alluri V; Trimurtulu, Golakoti

2012-12-27

A novel herbal formulation LI10903F, alternatively known as LOWAT was developed based on its ability to inhibit adipogenesis and lipogenesis in 3T3-L1 adipocytes model. The clinical efficacy and tolerability of LI10903F were evaluated in an eight-week, randomized, double-blind, placebo-controlled, clinical trial in 50 human subjects with body mass index (BMI) between 30 and 40 kg/m² (clinical trial registration number: ISRCTN37381706). Participants were randomly assigned to either a placebo or LI10903F group. Subjects in the LI10903F group received 300 mg of herbal formulation thrice daily, while subjects in the placebo group received 300 mg of placebo capsules thrice daily. All subjects were provided a standard diet (2,000 kcal daily) and participated in a moderate exercise of 30 min walk for five days a week. Additionally, the safety of this herbal formulation was evaluated by a series of acute, sub-acute toxicity and genotoxicity studies in animals and cellular models. After eight weeks of supplementation, statistically significant net reductions in body weight (2.49 kg; p=0.00005) and BMI (0.96 kg/m²; p=0.00004) were observed in the LI10903F group versus placebo group. Additionally, significant increase in serum adiponectin concentration (p=0.0076) and significant decrease in serum ghrelin concentration (p=0.0066) were found in LI10903F group compared to placebo group. Adverse events were mild and were equally distributed between the two groups. Interestingly, LI10903F showed broad spectrum safety in a series of acute, sub-acute toxicity and genotoxicity studies. Results from the current research suggest that LI10903F or LOWAT is well-tolerated, safe and effective for weight management.

THE ROLE OF THE RETINOBLASTOMA/E2F1 TUMOR SUPPRESSOR PATHWAY IN THE LESION RECOGNITION STEP OF NUCLEOTIDE EXCISION REPAIR

PubMed Central

Lin, Patrick S.; McPherson, Lisa A.; Chen, Aubrey Y.; Sage, Julien; Ford, James M.

2009-01-01

The retinoblastoma Rb/E2F tumor suppressor pathway plays a major role in the regulation of mammalian cell cycle progression. The pRb protein, along with closely related proteins p107 and p130, exerts its anti-proliferative effects by binding to the E2F family of transcription factors known to regulate essential genes throughout the cell cycle. We sought to investigate the role of the Rb/E2F1 pathway in the lesion recognition step of nucleotide excision repair (NER) in mouse embryonic fibroblasts (MEFs). Rb−/−;p107−/−;p130−/− MEFs repaired both cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PPs) at higher efficiency than did wildtype cells following UV-C irradiation. The expression of damaged DNA binding gene DDB2 involved in the DNA lesion recognition step was elevated in the Rb family-deficient MEFs. To determine if the enhanced DNA repair in the absence of the Rb gene family is due to the derepression of E2F1, we assayed the ability of E2F1-deficient cells to repair damaged DNA and demonstrated that E2F1−/− MEFs are impaired for the removal of both CPDs and 6-4PPs. Furthermore, wildtype cells induced a higher expression of DDB2 and xeroderma pigmentosum gene XPC transcript levels than did E2F1−/− cells following UV-C irradiation. Using an E2F SiteScan algorithm, we uncovered a putative E2F-responsive element in the XPC promoter upstream of the transcription start site. We showed with chromatin immunoprecipitation assays the binding of E2F1 to the XPC promoter in a UV-dependent manner, suggesting that E2F1 is a transcriptional regulator of XPC. Our study identifies a novel E2F1 gene target and further supports the growing body of evidence that the Rb/E2F1 tumor suppressor pathway is involved in the regulation of the DNA lesion recognition step of nucleotide excision repair. PMID:19376752

Functional synergy between DP-1 and E2F-1 in the cell cycle-regulating transcription factor DRTF1/E2F.

PubMed Central

Bandara, L R; Buck, V M; Zamanian, M; Johnston, L H; La Thangue, N B

1993-01-01

It is widely believed that the cellular transcription factor DRTF1/E2F integrates cell cycle events with the transcription apparatus because during cell cycle progression in mammalian cells it interacts with molecules that are important regulators of cellular proliferation, such as the retinoblastoma tumour suppressor gene product (pRb), p107, cyclins and cyclin-dependent kinases. Thus, pRb, which negatively regulates early cell cycle progression and is frequently mutated in tumour cells, and the Rb-related protein p107, bind to and repress the transcriptional activity of DRTF1/E2F. Viral oncoproteins, such as adenovirus E1a and SV40 large T antigen, overcome such repression by sequestering pRb and p107 and in so doing are likely to activate genes regulated by DRTF1/E2F, such as cdc2, c-myc and DHFR. Two sequence-specific DNA binding proteins, E2F-1 and DP-1, which bind to the E2F site, contain a small region of similarity. The functional relationship between them has, however, been unclear. We report here that DP-1 and E2F-1 exist in a DNA binding complex in vivo and that they bind efficiently and preferentially as a heterodimer to the E2F site. Moreover, studies in yeast and Drosophila cells indicate that DP-1 and E2F-1 interact synergistically in E2F site-dependent transcriptional activation. Images PMID:8223441

Commercial Vessel Safety Economic Benefits.

DTIC Science & Technology

1980-02-01

AD-A09b 319 PRC SYSTEMS SERVICES CO MELEAN VA F/S 5/4 CMOMERCIAL VESSEL SAFET Y ECONOM IC BENEFITS (U) FEB Al C A CROOK , W R WHITTEMORE , M MARR5 DOT...N ., . . i* . .... ........ ’q m m l w ’ .. ... .... . .J F Y* •LEVEV teprt N. CB-ID-2-81 Commercial Vessel Safety Economic Benefits PRELIMINARY PRC...constitute endorsement or approval of such products. COMMERCIAL VESSEL SAFETY ECONOMIC BENEFITS PRC Systems Services Company 7600 Old Springhouse

48 CFR 401.301 - Policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

... (mission area). 4E Food Safety and Inspection Service. 4F [Reserved] 4G Forest Service. 4H [Reserved] 4I Natural Resources Conservation Service. 4J [Reserved] 4K Food and Nutrition Service. 4L Animal and Plant...

48 CFR 401.301 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

... (mission area). 4E Food Safety and Inspection Service. 4F [Reserved] 4G Forest Service. 4H [Reserved] 4I Natural Resources Conservation Service. 4J [Reserved] 4K Food and Nutrition Service. 4L Animal and Plant...

48 CFR 401.301 - Policy.

Code of Federal Regulations, 2013 CFR

2013-10-01

... (mission area). 4E Food Safety and Inspection Service. 4F [Reserved] 4G Forest Service. 4H [Reserved] 4I Natural Resources Conservation Service. 4J [Reserved] 4K Food and Nutrition Service. 4L Animal and Plant...

Differentiation and injury-repair signals modulate the interaction of E2F and pRB proteins with novel target genes in keratinocytes.

PubMed

Chang, Wing Y; Andrews, Joseph; Carter, David E; Dagnino, Lina

2006-08-01

E2F transcription factors are central to epidermal morphogenesis and regeneration after injury. The precise nature of E2F target genes involved in epidermal formation and repair has yet to be determined. Identification of these genes is essential to understand how E2F proteins regulate fundamental aspects of epidermal homeostasis and transformation. We have conducted a genome-wide screen using CpG island microarray analysis to identify novel promoters bound by E2F3 and E2F5 in human keratinocytes. We further characterized several of these genes, and determined that multiple E2F and retinoblastoma (pRb) family proteins associate with them in exponentially proliferating cells. We also assessed the effect on E2F and pRb binding to those genes in response to differentiation induced by bone morphogenetic protein-6 (BMP-6), or to activation of repair mechanisms induced by transforming growth factor-beta (TGF-beta). These studies demonstrate promoter- and cytokine-specific changes in binding profiles of E2F and/or pRb family proteins. For example, E2F1, 3, 4 and p107 were recruited to the N-myc promoter in cells treated with BMP-6, whereas E2F1, 3, 4, 5, p107 and p130 were bound to this promoter in the presence of TGF-beta. Functionally, these different interactions resulted in transcriptional repression by BMP-6 and TGF-beta of the N-myc gene, via mechanisms that involved E2F binding to the promoter and association with pRb-family proteins. Thus, multiple combinations of E2F and pRb family proteins may associate with and transcriptionally regulate a given target promoter in response to differentiation and injury-repair stimuli in epidermal keratinocytes.

E2F transcription factor-1 deficiency reduces pathophysiology in the mouse model of Duchenne muscular dystrophy through increased muscle oxidative metabolism.

PubMed

Blanchet, Emilie; Annicotte, Jean-Sébastien; Pradelli, Ludivine A; Hugon, Gérald; Matecki, Stéfan; Mornet, Dominique; Rivier, François; Fajas, Lluis

2012-09-01

E2F1 deletion leads to increased mitochondrial number and function, increased body temperature in response to cold and increased resistance to fatigue with exercise. Since E2f1-/- mice show increased muscle performance, we examined the effect of E2f1 genetic inactivation in the mdx background, a mouse model of Duchenne muscular dystrophy (DMD). E2f1-/-;mdx mice demonstrated a strong reduction of physiopathological signs of DMD, including preservation of muscle structure, decreased inflammatory profile, increased utrophin expression, resulting in better endurance and muscle contractile parameters, comparable to normal mdx mice. E2f1 deficiency in the mdx genetic background increased the oxidative metabolic gene program, mitochondrial activity and improved muscle functions. Interestingly, we observed increased E2F1 protein levels in DMD patients, suggesting that E2F1 might represent a promising target for the treatment of DMD.

Communications Processor Operating System Study. Executive Summary,

DTIC Science & Technology

1980-11-01

AD-A095 b36 ROME AIR DEVELOPMENT CENTER GRIFFISS AFB NY F/e 17/2 COMMUNICATIONS PROCESSOR OPERATING SYSTEM STUDY. EXECUTIVE SUMM—ETC(U) NOV 80 J...COMMUNICATIONS PROCESSOR OPERATING SYSTEM STUDY Julian Gitlih SPTIC ELECTE«^ FEfi 2 6 1981^ - E APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED "a O...Subtitle) EXECUTIVE^SUMMARY 0F> COMMUNICATIONS PROCESSOR OPERATING SYSTEM $t - • >X W tdLl - ’•• • 7 AUTHORf«! ! , Julian

ERBB2 Deficiency Alters an E2F-1-Dependent Adaptive Stress Response and Leads to Cardiac Dysfunction

PubMed Central

Perry, Marie-Claude; Dufour, Catherine R.; Eichner, Lillian J.; Tsang, David W. K.; Deblois, Geneviève; Muller, William J.

2014-01-01

The tyrosine kinase receptor ERBB2 is required for normal development of the heart and is a potent oncogene in breast epithelium. Trastuzumab, a monoclonal antibody targeting ERBB2, improves the survival of breast cancer patients, but cardiac dysfunction is a major side effect of the drug. The molecular mechanisms underlying how ERBB2 regulates cardiac function and why trastuzumab is cardiotoxic remain poorly understood. We show here that ERBB2 hypomorphic mice develop cardiac dysfunction that mimics the side effects observed in patients treated with trastuzumab. We demonstrate that this phenotype is related to the critical role played by ERBB2 in cardiac homeostasis and physiological hypertrophy. Importantly, genetic and therapeutic reduction of ERBB2 activity in mice, as well as ablation of ERBB2 signaling by trastuzumab or siRNAs in human cardiomyocytes, led to the identification of an impaired E2F-1-dependent genetic program critical for the cardiac adaptive stress response. These findings demonstrate the existence of a previously unknown mechanistic link between ERBB2 and E2F-1 transcriptional activity in heart physiology and trastuzumab-induced cardiac dysfunction. PMID:25246633

Elevated autophagy gene expression in adipose tissue of obese humans: A potential non-cell-cycle-dependent function of E2F1

PubMed Central

Haim, Yulia; Blüher, Matthias; Slutsky, Noa; Goldstein, Nir; Klöting, Nora; Harman-Boehm, Ilana; Kirshtein, Boris; Ginsberg, Doron; Gericke, Martin; Guiu Jurado, Esther; Kovsan, Julia; Tarnovscki, Tanya; Kachko, Leonid; Bashan, Nava; Gepner, Yiftach; Shai, Iris; Rudich, Assaf

2015-01-01

Autophagy genes' expression is upregulated in visceral fat in human obesity, associating with obesity-related cardio-metabolic risk. E2F1 (E2F transcription factor 1) was shown in cancer cells to transcriptionally regulate autophagy. We hypothesize that E2F1 regulates adipocyte autophagy in obesity, associating with endocrine/metabolic dysfunction, thereby, representing non-cell-cycle function of this transcription factor. E2F1 protein (N=69) and mRNA (N=437) were elevated in visceral fat of obese humans, correlating with increased expression of ATG5 (autophagy-related 5), MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β), but not with proliferation/cell-cycle markers. Elevated E2F1 mainly characterized the adipocyte fraction, whereas MKI67 (marker of proliferation Ki-67) was elevated in the stromal-vascular fraction of adipose tissue. In human visceral fat explants, chromatin-immunoprecipitation revealed body mass index (BMI)-correlated increase in E2F1 binding to the promoter of MAP1LC3B, but not to the classical cell cycle E2F1 target, CCND1 (cyclin D1). Clinically, omental fat E2F1 expression correlated with insulin resistance, circulating free-fatty-acids (FFA), and with decreased circulating ADIPOQ/adiponectin, associations attenuated by adjustment for autophagy genes. Overexpression of E2F1 in HEK293 cells enhanced promoter activity of several autophagy genes and autophagic flux, and sensitized to further activation of autophagy by TNF. Conversely, mouse embryonic fibroblast (MEF)-derived adipocytes from e2f1 knockout mice (e2f1−/−) exhibited lower autophagy gene expression and flux, were more insulin sensitive, and secreted more ADIPOQ. Furthermore, e2f1−/− MEF-derived adipocytes, and autophagy-deficient (by Atg7 siRNA) adipocytes were resistant to cytokines-induced decrease in ADIPOQ secretion. Jointly, upregulated E2F1 sensitizes adipose tissue autophagy to inflammatory stimuli, linking visceral obesity to adipose and systemic metabolic-endocrine dysfunction. PMID:26391754

Towards integrated hygiene and food safety management systems: the Hygieneomic approach.

PubMed

Armstrong, G D

1999-09-15

Integrated hygiene and food safety management systems in food production can give rise to exceptional improvements in food safety performance, but require high level commitment and full functional involvement. A new approach, named hygieneomics, has been developed to assist management in their introduction of hygiene and food safety systems. For an effective introduction, the management systems must be designed to fit with the current generational state of an organisation. There are, broadly speaking, four generational states of an organisation in their approach to food safety. They comprise: (i) rules setting; (ii) ensuring compliance; (iii) individual commitment; (iv) interdependent action. In order to set up an effective integrated hygiene and food safety management system a number of key managerial requirements are necessary. The most important ones are: (a) management systems must integrate the activities of key functions from research and development through to supply chain and all functions need to be involved; (b) there is a critical role for the senior executive, in communicating policy and standards; (c) responsibilities must be clearly defined, and it should be clear that food safety is a line management responsibility not to be delegated to technical or quality personnel; (d) a thorough and effective multi-level audit approach is necessary; (e) key activities in the system are HACCP and risk management, but it is stressed that these are ongoing management activities, not once-off paper generating exercises; and (f) executive management board level review is necessary of audit results, measurements, status and business benefits.

77 FR 21782 - International Conference on Harmonisation; Draft Guidance for Industry on E2C(R2) Periodic...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-11

... electronic submission of individual case safety reports to regulatory authorities, automated data mining... Safety Data Management: Periodic Safety Update Reports for Marketed Drugs'' (E2C guidance) and ``Addendum to E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs'' (addendum...

[The effectiveness of error reporting promoting strategy on nurse's attitude, patient safety culture, intention to report and reporting rate].

PubMed

Kim, Myoungsoo

2010-04-01

The purpose of this study was to examine the impact of strategies to promote reporting of errors on nurses' attitude to reporting errors, organizational culture related to patient safety, intention to report and reporting rate in hospital nurses. A nonequivalent control group non-synchronized design was used for this study. The program was developed and then administered to the experimental group for 12 weeks. Data were analyzed using descriptive analysis, X(2)-test, t-test, and ANCOVA with the SPSS 12.0 program. After the intervention, the experimental group showed significantly higher scores for nurses' attitude to reporting errors (experimental: 20.73 vs control: 20.52, F=5.483, p=.021) and reporting rate (experimental: 3.40 vs control: 1.33, F=1998.083, p<.001). There was no significant difference in some categories for organizational culture and intention to report. The study findings indicate that strategies that promote reporting of errors play an important role in producing positive attitudes to reporting errors and improving behavior of reporting. Further advanced strategies for reporting errors that can lead to improved patient safety should be developed and applied in a broad range of hospitals.

Acute Impact of Tobacco vs Electronic Cigarette Smoking on Oxidative Stress and Vascular Function.

PubMed

Carnevale, Roberto; Sciarretta, Sebastiano; Violi, Francesco; Nocella, Cristina; Loffredo, Lorenzo; Perri, Ludovica; Peruzzi, Mariangela; Marullo, Antonino G M; De Falco, Elena; Chimenti, Isotta; Valenti, Valentina; Biondi-Zoccai, Giuseppe; Frati, Giacomo

2016-09-01

The vascular safety of electronic cigarettes (e-Cigarettes) must still be clarified. We compared the impact of e-Cigarettes vs traditional tobacco cigarettes on oxidative stress and endothelial function in healthy smokers and nonsmoker adults. A crossover, single-blind study was performed in 40 healthy subjects (20 smokers and 20 nonsmokers, matched for age and sex). First, all subjects smoked traditional tobacco cigarettes. One week later, the same subjects smoked an e-Cigarette with the same nominal nicotine content. Blood samples were drawn just before and after smoking, and markers of oxidative stress, nitric oxide bioavailability, and vitamin E levels were measured. Flow-mediated dilation (FMD) was also measured. Smoking both e-Cigarettes and traditional cigarettes led to a significant increase in the levels of soluble NOX2-derived peptide and 8-iso-prostaglandin F2α and a significant decrease in nitric oxide bioavailability, vitamin E levels, and FMD. Generalized estimating equation analysis confirmed that all markers of oxidative stress and FMD were significantly affected by smoking and showed that the biologic effects of e-Cigarettes vstraditional cigarettes on vitamin E levels (P = .413) and FMD (P = .311) were not statistically different. However, e-Cigarettes seemed to have a lesser impact than traditional cigarettes on levels of soluble NOX2-derived peptide (P = .001), 8-iso-prostaglandin F2α (P = .046), and nitric oxide bioavailability (P = .001). Our study showed that both cigarettes have unfavorable effects on markers of oxidative stress and FMD after single use, although e-Cigarettes seemed to have a lesser impact. Future studies are warranted to clarify the chronic vascular effects of e-Cigarette smoking. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Safety and Interoperability Agreements on Bilateral Use of Artillery, Tank, and Mortar Ammunition during Training - Germany, the United Kingdom, Canada, the Netherlands, Belgium, France, and the United States

DTIC Science & Technology

1979-10-01

BRIEFIN-G OF CINCUSAREUR ON STATUS OF SUBJ. 2 NCV 77. 1. r£F A EXPLAINED BASIC CONCEPT PLAN FOR SUBJ INITIATIVE...TM 43-0001-2 8) Diameter Color Propellant: Composition — Grain Type --- Weight Web — - Primer M82 - TB 9-2300-303-10 PaUet: 165 -mm (6...perforated cylinder Weight 12. 9 kg (28. 51bs.) Web - — .109-mm (0.043 in.) Primer M82 Used with Cannon (Weapon) M2A2 (M2A1E1

Effect of the addition of MgF2 and NaF on the thermal, optical and magnetic properties of fluoride glasses for sensing applications

NASA Astrophysics Data System (ADS)

Wang, Yujie; Wang, Shuangbao; Deng, Saifu; Liu, Jianting; Zhang, Jiahui

2017-10-01

Optical glass was very important for the development of optical fiber sensor. In this paper, a new type fluoride glass of ZrF4-BaF2-AlF3-NaF-MgF2(ZBANM) was synthesized for sensing application which has low loss and high magneto-optical coefficient, and it was found that the glass system had at least 60% transmittance from 3.5 μm to 7 μm and smallest verdet constant of 4.628E-5/(rad A-1) at 632.8 nm. The relationship among the compositions of sample glass with its thermal property, optical absorptivity and magnetic-optical coefficients was respectively studied with Thermal Gravimetric-Differential Thermal Analyzer, Fourier Transform infrared spectroscopy and a home-made magneto optical bench. The study indicated that transmittance of fluoride glass structure had been obviously improved after moderate content of Mg2+ and Na+ was doped. Simultaneously, with the molar ratio of alkaline-earth ions Mg increased, the Verdet constant of fluoride glass was increased. And the glass structure with composition of 48%ZrF4-24%BaF2-6%AlF3-8%NaF-14%MgF2 exhibited a small molar absorptivity and the largest Verdet constant of 2.853E-4/(rad A-1).

Word Frequency Analysis. MOS: 26Q. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

L! 2 9 Ll- 236 t /G 2 Pi 2 3’,F/G z PU-332jS/l Z z *.I PjkPig5E 2 P :3 IZ/’ 2 wA I A 1i 2 QvA 1 . T ITy 2 .3il.-rss 2 RTZEIVEC Z .F, 11~ k 11:8E R 2 K...ADA0?U ARMY TRAINING DEVELOPMENTS INST FORT MONdROE VA /5/ADWORD FREQUENCY ANALYSIS. MOSI 24. SKILL LEVELS 1 6 2.1U) / MAY 81 A A LONGO UNCLASSIFIED...1qR1 ATTN: ATTG;-DOR 13. NUQBER OF PAGES 14 OIOMlGAEC AEaAOESI dilt.,,.l 1 - ContIrMA OfII..) 15. SECURITY CLASS. fo1 VdI. ftw.f) Unclassified 150

Assessing safety culture in NICU: psychometric properties of the Italian version of Safety Attitude Questionnaire and result implications.

PubMed

Zenere, Alessandra; Zanolin, M Elisabetta; Negri, Roberta; Moretti, Francesca; Grassi, Mario; Tardivo, Stefano

2016-04-01

Neonatal intensive care units (NICUs) are a high-risk setting. The Safety Attitude Questionnaire (SAQ) is a widely used tool to measure safety culture. The aims of the study are to verify the psychometric properties of the Italian version of SAQ, to evaluate safety culture in the NICUs and to identify improvement interventions. A cross-sectional study was conducted in 6 level III NICUs. The SAQ was translated into Italian and adapted to the context, a confirmatory factor analysis (CFA) was performed to validate the questionnaire. 193 questionnaires were collected. The mean response rate was 59.7% (range 44.5%-95.7%). The answers were analysed according to six factors: f1 - teamwork climate, f2 - safety climate, f3 - job satisfaction, f4 - stress recognition, f5 - perception of management, f6 - working conditions. The CFA indexes were adequate (McDonald's omega indexes varied from 0.74 to 0.94, the SRMR index was equal to 0.79 and the RMSEA index was 0.070, 95% CI = 0.063-0.078). The mean composite score was 57.6 (SD 17.9), ranging between 42.3 and 69.7 on a standardized 100-point scale. We highlighted significant differences among units and professions (P < 0.05). The Italian version of the SAQ proved to be an effective tool to evaluate and compare the safety culture in the NICUs. The obtained scores significantly varied both within and among the NICUs. The organizational and structural characteristics of the involved hospitals probably affect the safety culture perception by the staff. © 2015 John Wiley & Sons, Ltd.

Immunogenicity of an adeno-vector vaccine expressing the F protein of a respiratory syncytial virus manufactured from serum-free suspension culture.

PubMed

Shao, Hsiao-Yun; Hsu, Huai-Sheng; Yu, Shu-Ling; Wu, Shang-Rung; Hu, Kai-Chieh; Chang, Ching-Kun; Liu, Chia-Chyi; Chow, Yen-Hung

2016-06-01

We have developed an efficient cell culture process to scale up the production of a recombinant adenovirus that expresses the membrane-trunked fusion protein of respiratory syncytial virus (RSV; Ad-F0ΔTM). Adherent cells of human embryonic kidney (HEK) 293-derived cell, 293A, which supports the production of E1/E3-deleted Ad-F0ΔTM when cultured in the presence of fetal bovine serum (FBS), were adapted to suspension growth under serum-free medium. In doing so, we studied the immunogenicity of Ad-F0ΔTMsus, which propagated in a bioreactor that was cultured with serum-free suspension of 293A, in comparison with Ad-F0ΔTMadh, which was produced from parental 293A cells that were adherently cultured in medium containing FBS. The size and morphology of Ad-F0ΔTMsus and Ad-F0ΔTMadh virions were identical upon inspection with electron microscopy. The results showed that anti-F IgG and RSV-neutralizing titer were raised in the serum of both mice that were intranasally immunized twice with Ad-F0ΔTMsus or Ad-F0ΔTMadh at two-week injection intervals. Furthermore, the immune responses persisted for six months after vaccination. Activation of F protein-specific CD8(+) T cell's epitope associated IFN-ɣ and IL-4 was induced in both Ad-F0ΔTMsus- and Ad-F0ΔTMadh, but not in Ad-LacZsus, -immunized mouse splenocytes. No vaccine-enhanced lung inflammation, airway mucus occlusion or eosinophils infiltration were observed in Ad-immunized mice followed by RSV challenge; however, these symptoms were observed following immunization with formalin-inactivated RSV vaccine. These results indicate that the safety and potency of Ad-F0ΔTM produced from either adherent cells or suspension and serum-free cells are the same. Copyright © 2016 Elsevier B.V. All rights reserved.

The pulmonary mesenchymal tissue layer is defective in an in vitro recombinant model of nitrofen-induced lung hypoplasia.

PubMed

van Loenhout, Rhiannon B; Tseu, Irene; Fox, Emily K; Huang, Zhen; Tibboel, Dick; Post, Martin; Keijzer, Richard

2012-01-01

Despite modern treatments, congenital diaphragmatic hernia (CDH) remains associated with variable survival and significant morbidity. The associated pulmonary hypoplasia is a major determinant of outcome. To develop better treatments, improved comprehension of the pathogenesis of lung hypoplasia is warranted. We developed an in vitro cell recombinant model to mimic pulmonary hypoplasia and specifically to investigate epithelial-mesenchymal interactions and to decipher which tissue layer is primarily defective in nitrofen-induced CDH-associated lung hypoplasia. Epithelial cells (E) and fibroblasts (F) were isolated from E19 control ((C)) and nitrofen-induced hypoplastic rat lungs ((N)). Cells were recombined and cultured as either homotypic [(F(C))(E(C)) and (F(N))(E(N))] or heterotypic [(F(C))(E(N)) and (F(N))(E(C))] recombinants. Recombinants containing F(N) fibroblasts had a thickened fibroblast tissue layer and there were fewer organized alveolar-like epithelial structures compared with those in control (F(C))(E(C)) recombinants. These F(N) recombinants exhibited a decrease in terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved caspase-3 positive cells. Cell proliferation was arrested in recombinants containing F(N) fibroblasts, which also exhibited increased p27(Kip1) and p57(Kip2) expression. In conclusion, fibroblasts, and not epithelial cells, appear to be the defective cell type in nitrofen-induced hypoplastic lungs due to a decreased ability to undergo apoptosis and maintain overall proliferation. This may explain the characteristic pulmonary interstitial thickening and hypoplasia observed in both nitrofen-induced hypoplastic lungs as well as human hypoplastic CDH lungs. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Cancer cell specific cytotoxic gene expression mediated by ARF tumor suppressor promoter constructs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurayoshi, Kenta; Ozono, Eiko; Iwanaga, Ritsuko

Highlights: • ARF promoter showed higher responsiveness to deregulated E2F activity than the E2F1 promoter. • ARF promoter showed higher cancer cell-specificity than E2F1 promoter to drive gene expression. • HSV-TK driven by ARF promoter showed higher cancer cell-specific cytotoxicity than that driven by E2F1 promoter. - Abstract: In current cancer treatment protocols, such as radiation and chemotherapy, side effects on normal cells are major obstacles to radical therapy. To avoid these side effects, a cancer cell-specific approach is needed. One way to specifically target cancer cells is to utilize a cancer specific promoter to express a cytotoxic gene (suicidemore » gene therapy) or a viral gene required for viral replication (oncolytic virotherapy). For this purpose, the selected promoter should have minimal activity in normal cells to avoid side effects, and high activity in a wide variety of cancers to obtain optimal therapeutic efficacy. In contrast to the AFP, CEA and PSA promoters, which have high activity only in a limited spectrum of tumors, the E2F1 promoter exhibits high activity in wide variety of cancers. This is based on the mechanism of carcinogenesis. Defects in the RB pathway and activation of the transcription factor E2F, the main target of the RB pathway, are observed in almost all cancers. Consequently, the E2F1 promoter, which is mainly regulated by E2F, has high activity in wide variety of cancers. However, E2F is also activated by growth stimulation in normal growing cells, suggesting that the E2F1 promoter may also be highly active in normal growing cells. In contrast, we found that the tumor suppressor ARF promoter is activated by deregulated E2F activity, induced by forced inactivation of pRB, but does not respond to physiological E2F activity induced by growth stimulation. We also found that the deregulated E2F activity, which activates the ARF promoter, is detected only in cancer cell lines. These observations suggest that ARF promoter is activated by E2F only in cancer cells and therefore may be more cancer cell-specific than E2F1 promoter to drive gene expression. We show here that the ARF promoter has lower activity in normal growing fibroblasts and shows higher cancer cell-specificity compared to the E2F1 promoter. We also demonstrate that adenovirus expressing HSV-TK under the control of the ARF promoter shows lower cytotoxicity than that of the E2F1 promoter, in normal growing fibroblasts but has equivalent cytotoxicity in cancer cell lines. These results suggest that the ARF promoter, which is specifically activated by deregulated E2F activity, is an excellent candidate to drive therapeutic cytotoxic gene expression, specifically in cancer cells.« less

Long non-coding RNA H19 promotes glucose metabolism and cell growth in malignant melanoma via miR-106a-5p/E2F3 axis.

PubMed

Luan, Wenkang; Zhou, Zhou; Ni, Xin; Xia, Yun; Wang, Jinlong; Yan, Yulan; Xu, Bin

2018-03-01

lncRNA H19 has been considered as an oncogenic lncRNA in many human tumours. In the present study, we identify the role and molecular mechanism of lncRNA H19 in melanoma. QRT-PCR was used to detect the expression of lncRNA H19 and E2F3 was detected in melanoma tissues. Cell counting kit-8 (CCK8), representative metabolites analysis was used to explore the biological function of lncRNA H19, miR-106a-5p and E2F3 in melanoma cells. Bioinformatics, luciferase reporter assays, MS2-RIP and RNA pull-down assay was used to demonstrate the molecular mechanism of lncRNA H19 in melanoma. We further test the function of lncRNA H19 in vivo though Xenograft tumour assay. We found that lncRNA H19 was increased in melanoma tissue, and lncRNA H19 was correlated with poor prognosis of melanoma patients. miR-106a-5p acts as a tumour suppressor in melanoma by targeting E2F3. E2F3 affects the melanoma cell glucose metabolism and growth. We also demonstrated that lncRNA H19 may function as the sponge of miR-106a-5p to up-regulate E2F3 expression, and consequently promote the glucose metabolism and growth of melanoma. This result elucidates a new mechanism for lncRNA H19 in melanoma development and provides a survival indicator and potential therapeutic target for melanoma patients.

ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal stress in early response to DNA damage

PubMed Central

Jin, Ya-Qiong; An, Guo-Shun; Ni, Ju-Hua; Li, Shu-Yan; Jia, Hong-Ti

2014-01-01

The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents disrupt nucleolar structure and function, which results in the stabilization/activation of p53, inducing cell cycle arrest or apoptosis. Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage through transcriptional response and protein–protein interaction. Furthermore, E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1 displays in coordinating DNA damage and nucleolar stress is unclear. In this study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a characteristic feature of nucleolar stress in early response to DNA damage. We found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus was an ATM-dependent and a common event in p53-suficient and -deficient cells. Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which repressed E2F1-dependent rRNA transcription initiation, and was coupled with S phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an indicator for nucleolar stress and a component of ATM pathway, which presumably buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response to DNA damage. PMID:24675884

ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal stress in early response to DNA damage.

PubMed

Jin, Ya-Qiong; An, Guo-Shun; Ni, Ju-Hua; Li, Shu-Yan; Jia, Hong-Ti

2014-01-01

The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents disrupt nucleolar structure and function, which results in the stabilization/activation of p53, inducing cell cycle arrest or apoptosis. Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage through transcriptional response and protein-protein interaction. Furthermore, E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1 displays in coordinating DNA damage and nucleolar stress is unclear. In this study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a characteristic feature of nucleolar stress in early response to DNA damage. We found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus was an ATM-dependent and a common event in p53-suficient and -deficient cells. Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which repressed E2F1-dependent rRNA transcription initiation, and was coupled with S phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an indicator for nucleolar stress and a component of ATM pathway, which presumably buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response to DNA damage.

Ovarian ultrasonography correlated with fecal progestins and estradiol during the estrous cycle and early pregnancy in giraffes (Giraffa camelopardalis rothschildi).

PubMed

Lueders, Imke; Hildebrandt, Thomas B; Pootoolal, Jason; Rich, Peter; Gray, Charlie S; Niemuller, Cheryl A

2009-11-01

Fecal and urinary progestin analyses have shown that giraffes express a short reproductive cycle, averaging 15 days, compared with other large ruminants. However, actual ovarian events have not been correlated with the hormonal pattern. In this study, mature cycling female Rothschild giraffes (Giraffa camelopardalis rothschildi) were repeatedly examined by transrectal ultrasonography to correlate ovarian function with changes in fecal progestin (fP4 [n(c) = 6]) and estradiol (fE2 [n(c) = 6]) and serum progestin (n(c) = 2) as measured by enzyme immunoassay. Five females became pregnant and were monitored during early gestation. In this study, we discovered that hormone values for fP4 in cycling giraffes do not correlate with the classic profile of follicular development, ovulation, and luteogenesis. The corpus luteum (CL) and the next dominant follicle were forming simultaneously. A mean +/- SD peak in fE2 of 254.92 +/- 194.76 ng/g and subsequent ovulation occurred as early as 1 day after the fall in fP4. In pregnant giraffes, the CL reached a diameter significantly larger (mean +/- SD, 41.02 +/- 2.70 mm; P = 0.0126) than that during the cycle (33.48 +/- 2.80 mm), while follicular activity and fluctuating fE2 were still present. With this research, we demonstrated that the progesterone profile typically used to characterize the ovarian cycle does not correlate with luteal development in the ovaries of this species. Furthermore, we conclude that the giraffe could have evolved a short reproductive cycle because of the almost parallel order of ovarian events.

The model of self-compensation and pinning of the Fermi level in irradiated semiconductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brudnyi, V. N.; Kolin, N. G.; Smirnov, L. S.

2007-09-15

A model is developed to analyze numerically the electrical properties and the steady-state (limiting) position of the Fermi level (F{sub lim}) in tetrahedral semiconductors irradiated with high-energy particles. It is shown that an irradiated semiconductor represents a highly compensated material, in which F{sub lim} is identical to /2, where is the average energy gap between the conduction band and valence band within the entire Brillouin zone of the crystal. The experimental values of F{sub lim}, the calculated values of /2, and the data on the electrical properties of irradiated semiconductors are presented. The chemical trends controllingmore » the variation in the quantity F{sub lim} in groups of semiconductors with the similar types of chemical bonding are analyzed.« less

Tribal Pesticide Regulation

Science.gov Websites

:00PM Pacific Time, Mon-Fri A B C D E F G H I J K L M N O P Q R S T U V W X Y Z A-Z Index Health & ; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Pesticide Regulations EPA Pesticide Regulation Pesticides and the Environment Pesticide Health and Safety

Pesticides and Animal Health

Science.gov Websites

:00PM Pacific Time, Mon-Fri A B C D E F G H I J K L M N O P Q R S T U V W X Y Z A-Z Index Health & ; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Home Page Pesticide Health and Safety Information Pesticides and Animal Health Related Topics

Temporal remodeling of the cell cycle accompanies differentiation in the Drosophila germline.

PubMed

Hinnant, Taylor D; Alvarez, Arturo A; Ables, Elizabeth T

2017-09-01

Development of multicellular organisms relies upon the coordinated regulation of cellular differentiation and proliferation. Growing evidence suggests that some molecular regulatory pathways associated with the cell cycle machinery also dictate cell fate; however, it remains largely unclear how the cell cycle is remodeled in concert with cell differentiation. During Drosophila oogenesis, mature oocytes are created through a series of precisely controlled division and differentiation steps, originating from a single tissue-specific stem cell. Further, germline stem cells (GSCs) and their differentiating progeny remain in a predominantly linear arrangement as oogenesis proceeds. The ability to visualize the stepwise events of differentiation within the context of a single tissue make the Drosophila ovary an exceptional model for study of cell cycle remodeling. To describe how the cell cycle is remodeled in germ cells as they differentiate in situ, we used the Drosophila Fluorescence Ubiquitin-based Cell Cycle Indicator (Fly-FUCCI) system, in which degradable versions of GFP::E2f1 and RFP::CycB fluorescently label cells in each phase of the cell cycle. We found that the lengths of the G1, S, and G2 phases of the cell cycle change dramatically over the course of differentiation, and identified the 4/8-cell cyst as a key developmental transition state in which cells prepare for specialized cell cycles. Our data suggest that the transcriptional activator E2f1, which controls the transition from G1 to S phase, is a key regulator of mitotic divisions in the early germline. Our data support the model that E2f1 is necessary for proper GSC proliferation, self-renewal, and daughter cell development. In contrast, while E2f1 degradation by the Cullin 4 (Cul4)-containing ubiquitin E3 ligase (CRL4) is essential for developmental transitions in the early germline, our data do not support a role for E2f1 degradation as a mechanism to limit GSC proliferation or self-renewal. Taken together, these findings provide further insight into the regulation of cell proliferation and the acquisition of differentiated cell fate, with broad implications across developing tissues. Copyright © 2017 Elsevier Inc. All rights reserved.

A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites.

PubMed Central

Sellers, W R; Rodgers, J W; Kaelin, W G

1995-01-01

An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F and for RB to induce a G1/S block. Indirect evidence suggests that the binding of RB to E2F may, in addition to inhibiting E2F transactivation function, generate a complex capable of functioning as a transrepressor. Here we show that a chimera in which the E2F1 transactivation domain was replaced with the RB pocket could, in a DNA-binding and pocket-dependent manner, mimic the ability of RB to repress transcription and induce a cell cycle arrest. In contrast, a transdominant negative E2F1 mutant that is capable of blocking E2F-dependent transactivation did not. Fusion of the RB pocket to a heterologous DNA-binding domain unrelated to E2F likewise generated a transrepressor protein when scored against a suitable reporter. These results suggest that growth suppression by RB is due, at least in part, to transrepression mediated by the pocket domain bound to certain promoters via E2F. Images Fig. 4 Fig. 5 PMID:8524800

A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of an Adjuvanted HIV-1 Gag-Pol-Nef Fusion Protein and Adenovirus 35 Gag-RT-Int-Nef Vaccine in Healthy HIV-Uninfected African Adults

PubMed Central

Omosa-Manyonyi, Gloria; Mpendo, Juliet; Ruzagira, Eugene; Kilembe, William; Chomba, Elwyn; Roman, François; Bourguignon, Patricia; Koutsoukos, Marguerite; Collard, Alix; Voss, Gerald; Laufer, Dagna; Stevens, Gwynn; Hayes, Peter; Clark, Lorna; Cormier, Emmanuel; Dally, Len; Barin, Burc; Ackland, Jim; Syvertsen, Kristen; Zachariah, Devika; Anas, Kamaal; Sayeed, Eddy; Lombardo, Angela; Gilmour, Jill; Cox, Josephine; Fast, Patricia; Priddy, Frances

2015-01-01

Background Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN) may lead to a unique immune profile, inducing both strong T-cell and antibody responses. Methods In a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured. Results The vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-γ ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration. Conclusion Co-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses. Trial Registration ClinicalTrials.gov NCT01264445 PMID:25961283

Minutes of the Explosives Safety Seminar (16th), Held at the Diplomat Hotel, Hollywood, Florida on 24-26 September 1974. Volume 2

DTIC Science & Technology

1974-09-26

concrete structi-e at Battelle Memorial Labs are on hand. b, Photos and drawing of 10’ ID X 31’ steel test chamber 𔃻: Los Alamos . c. Tech data or, AEC... Technical Report, Draft. 3. M0TT, R.l., "A Theory of Fuauentation", Army Operational Research Group Ho., 113-AC-3642, Great Britain, 1943 . 4. GUI , R.W., "he...Kansas AAP, Parsons, KSBURCH, Austin AEC, Los Alamos , NMBURKE, E. F. Olin Corp., St. Marks, FLBURNER, M R. DCASR, N.Y., NYBURNS, N.J3. Dept of

Cooperativity of E-cadherin and Smad4 loss to promote diffuse-type gastric adenocarcinoma and metastasis.

PubMed

Park, Jun Won; Jang, Seok Hoon; Park, Dong Min; Lim, Na Jung; Deng, Chuxia; Kim, Dae Yong; Green, Jeffrey E; Kim, Hark Kyun

2014-08-01

Loss of E-cadherin (CDH1), Smad4, and p53 has been shown to play an integral role in gastric, intestinal, and breast cancer formation. Compound conditional knockout mice for Smad4, p53, and E-cadherin were generated to define and compare the roles of these genes in gastric, intestinal, and breast cancer development by crossing with Pdx-1-Cre, Villin-Cre, and MMTV-Cre transgenic mice. Interestingly, gastric adenocarcinoma was significantly more frequent in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice than in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(+/+) mice, demonstrating that Cdh1 heterozygosity accelerates the development and progression of gastric adenocarcinoma, in combination with loss of Smad4 and p53. Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice developed gastric adenocarcinomas without E-cadherin expression. However, intestinal and mammary adenocarcinomas with the same genetic background retained E-cadherin expression and were phenotypically similar to mice with both wild-type Cdh1 alleles. Lung metastases were identified in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice, but not in the other genotypes. Nuclear β-catenin accumulation was identified at the invasive tumor front of gastric adenocarcinomas arising in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice. This phenotype was less prominent in mice with intact E-cadherin or Smad4, indicating that the inhibition of β-catenin signaling by E-cadherin or Smad4 downregulates signaling pathways involved in metastases in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice. Knockdown of β-catenin significantly inhibited the migratory activity of Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) cell lines. Thus, loss of E-cadherin and Smad4 cooperates with p53 loss to promote the development and metastatic progression of gastric adenocarcinomas, with similarities to human gastric adenocarcinoma. This study demonstrates that inhibition of β-catenin is a converging node for the antimetastatic signaling pathways driven by E-cadherin and Smad4 in Pdx-1-Cre;Smad4(F/F);Trp53(F/F);Cdh1(F) (/+) mice, providing novel insights into mechanisms for gastric cancer metastasis. ©2014 American Association for Cancer Research.

47 CFR 80.205 - Bandwidths.

Code of Federal Regulations, 2010 CFR

2010-10-01

... frequency deviation for F3E or G3E emission is as follows: (1) 5 kHz in the 72.0-73.0 MHz, 75.4-76.0 MHz and... 12 16K0A2D 20.0 A3E 6K00A3E 8.0 A3N 2 2K66A3N 2.8 A3X 3 3K20A3X 25.0 F1B 4 280HF1B 0.3 F1B 5 300HF1B 0.5 F1B 6 16KOF1B 20.0 F1C 2K80F1C 3.0 F1D 12 16K0F1D 20.0 F2B 6 16KOF2B 20.0 F2C 7 16KOF2C 20.0 F2D...

16 CFR 1212.5 - Findings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR... rule, the Consumer Product Safety Act (CPSA), 15 U.S.C. 2058(f)(1), requires the Commission to consider... the risk of injury the rule is designed to eliminate or reduce; (2) The approximate number of consumer...

Development of Specialized Equipment to Measure Piezoelectric Coefficients of Polymer Piezoelectric Materials,

DTIC Science & Technology

1980-02-22

definition g.l = (Voc/t)(F/wt) = field/stress 2. C =KT K 1E w/t (parallel plate capacitdnce formula) ’. VL = Voc Cx’/CL for CL > Cx 4.v g/wF Kt Eoewlt...V = (g3 1 /w)F 2. V L =(Cg/c,.v oc 3. V =(Cg/CL)(g31/w)F 4. Vstd = "d3 3"/C std F 5. V L/ Vst d = (C /C ) (g ’)(C /"d " )Sg L 31 std 33 01. 6. R (in...34 and the second T " e’hicial Note No. 1 - Theory of the use of Channel Products (’DT (X() d., meteor to measure d31 direct.]y on Piezoelect.rlc Ceramic

Department of Defense Operation and Financial Support for Military Museums

DTIC Science & Technology

2009-01-01

t a r y M u s e u m s Service Museums DoD Appropriations Total Federal Other Sources Grand Total Operation and Maintenance Military... Operation and Maintenance Military Personnel DoD Appropriations F Y 2 0 0 9 F u n d i n g f o r M i l i t a r y M u s e u m s Service...museum operations , to include developing the museum’s operational budget, accessioning and deaccessioning artifacts,

Comparison of foE and M(3000)F2 variability at Ibadan, Singapore and Slough

NASA Astrophysics Data System (ADS)

Somoye, E. O.; Onori, E. O.; Akala, A. O.

2013-01-01

The variability, VR, of critical frequency of E-layer, foE, and ionospheric propagation factor, M(3000)F2 at Ibadan (7.4°N, 3.9°E, 6°S dip) is investigated for local time, seasonal and solar cycle variations. Latitudinal influence of these characteristics is sought by comparison with foE VR and M(3000)F2 VR of Slough ( 51.5°N, 359.4°E, 66.5°N dip) in the European sector, and Singapore (1.3°N,103.8°E, 17.6°S dip) in the Asian sector. While the pattern of foE VR is similar to those of other F2 characteristics with characteristic peaks around dawn and dusk, M(3000)F2 VR shows no clear diurnal trend.A lower bound of foE VR is usually 3% while the maximum VR ranges between 8% and13% at post-sunrise and pre-sunset hours at all the epochs, M(3000)F2 VR is however lower during MSA (about 9%) than during LSA and HSA when it is 4% to about 12-14%. Generally, daytime M(3000)F2 VR is greater than that of foE VR by between 5% and 10%. Furthermore, no latitudinal difference is observed in both characteristics during both HSA and MSA. While nighttime M(3000)F2 VR is about half that of nighttime foF2 VR (the critical frequency of F2-layer ) VR, daytime VR of both characteristics are about equal during the three epochs at Ibadan. For Slough, nighttime M(3000)F2 VR and nighttime foF2 VR as well as the daytime VR of both characteristics are about equal. This difference is most likely due to latitudinal effect.

E2F1/TS Immunophenotype and Survival of Patients with Colorectal Cancer Treated with 5FU-Based Adjuvant Therapy.

PubMed

Sulzyc-Bielicka, Violetta; Domagala, Pawel; Bielicki, Dariusz; Safranow, Krzysztof; Rogowski, Wojciech; Domagala, Wenancjusz

2016-07-01

The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone. Nuclear TS and E2F1 were detected by immunohistochemistry in tissue microarrays from 190 CRCs (Astler-Coller stage B2 or C). Multivariate analysis identified significant association of the combined E2F1+TS+ immunophenotype with worse OS (HR = 3,78, P = 0,009) and DFS (HR = 2,30, P = 0,03) of patients with colon cancer. There were significant differences between E2F1+TS+ and E2F1-TS- Kaplan-Meier survival curves in relation to DFS (P = 0.008) and OS (P = 0.01). About 37 and 31 % difference in 3-year DFS and OS respectively were seen between patients with E2F1+TS+ vs. E2F1-TS- colon cancer immunophenotype. The E2F1+TS+ immunophenotype may be a marker of poor prognosis (the worst DFS and OS) of patients with colon cancer treated with 5FU-based adjuvant therapy. A subgroup of patients with this immunophenotype may require different and perhaps more aggressive treatment than 5FU-based chemotherapy. Thus, the combined E2F1/TS immunophenotype could be a potential indicator of colon cancer sensitivity to 5FU.

Handling And Safety Aspects Of Fiber Optic Laser Beam Delivery Systems

NASA Astrophysics Data System (ADS)

Schonborn, K.-H.; Wodrich, W.

1988-06-01

Using lasers for therapeutic applications is getting more and more accepted. In ophthalmology Ar-lasers for intraocular applications are quite common. The Nd:YAG-laser is used as a high power tool in connection with silica fibers for different extracorporal and intracorporal applications. The CO2-laser is the cutting laser, one problem being the beam transmission: The state of the art in fibers is not sufficient up to now. Because of the high power used safety against laser radiation hazard is of great importance. The safety in laser use is primarily dependent on the surgeons cautiousness, e.g. using laser protection goggels, observing that the spot of the aiming beam is present etc. On the other hand the laser and fiber system has to be inherently safe by appropriate technical means as far as possible. An additional aspect adding to safety is the handling: With easier system handling less attention of the surgeon is necessary for driving the apparatus. Thus he can concentrate on the patient and on the procedure. In considering the fiber system one important point in handling and safety is the coupling of the fiber to the laser head. The development philosophy in this coupling may be divided into two groups: - one is trying to use standard connectors which were initially developed for data transmission; - the other is using special connectors. One example of the first group is the guiding of the laser beam from the Ar-laser to the slit-lamp in ophtalmology. Here the well-known F-SMA connectors together with a special fiber with adapted numerical aperture are used. The advantage of such a system is the low price of the connector. For high power lasers such as the clinical Nd:YAG lasers with 40 to 150 W those connectors are not suitable. Up to now every laser manufacturer developed his own connector system in this field.

Single Electron Delivery to Lewis Pairs: An Avenue to Anions by Small Molecule Activation.

PubMed

Liu, Liu Leo; Cao, Levy L; Shao, Yue; Stephan, Douglas W

2017-07-26

Single electron transfer (SET) reactions are effected by the combination of a Lewis acid (e.g., E(C 6 F 5 ) 3 E = B or Al) with a small molecule substrate and decamethylferrocene (Cp* 2 Fe). Initially, the corresponding reactions of (PhS) 2 and (PhTe) 2 were shown to give the species [Cp* 2 Fe][PhSB(C 6 F 5 ) 3 ] 1 and [Cp* 2 Fe][(μ-PhS)(Al(C 6 F 5 ) 3 ) 2 ] 2 and [Cp* 2 Fe][(μ-PhTe)(Al(C 6 F 5 ) 3 ) 2 ] 3, respectively. Analogous reactions with di-tert-butyl peroxide yielded [Cp* 2 Fe][(μ-HO)(B(C 6 F 5 ) 3 ) 2 ] 4 with isobutene while with benzoyl peroxide afforded [Cp* 2 Fe][PhC(O)OE(C 6 F 5 ) 3 ] (E = B 5, Al 6). Evidence for a radical pathway was provided by the reaction of Ph 3 SnH and p-quinone afforded [Cp* 2 Fe][HB(C 6 F 5 ) 3 ] 7 and [Cp* 2 Fe] 2 [(μ-O 2 C 6 H 4 )(E(C 6 F 5 ) 3 ) 2 ] (E = B 8, Al 9). In addition, the reaction of TEMPO with Lewis acid and Cp* 2 Fe afforded [Cp* 2 Fe][(C 5 H 6 Me 4 NOE(C 6 F 5 ) 3 ] (E = B 10, Al 11). Finally, reactions with O 2 , Se, Te and S 8 gave [Cp* 2 Fe] 2 [((C 6 F 5 ) 2 Al(μ-O)Al(C 6 F 5 ) 3 ) 2 ] 2 12, [Cp* 2 Fe] 2 [((C 6 F 5 ) 2 Al(μ-Se)Al(C 6 F 5 ) 3 ) 2 ] 2 13, [Cp* 2 Fe][(μ-Te) 2 (Al(C 6 F 5 ) 2 ) 3 ] 14 and [Cp* 2 Fe] 2 [(μ-S 7 )B(C 6 F 5 ) 3 ) 2 ] 15, respectively. The mechanisms of these SET reactions are discussed, and the ramifications are considered.

Involvement of atypical transcription factor E2F8 in the polyploidization during mouse and human decidualization.

PubMed

Qi, Qian-Rong; Zhao, Xu-Yu; Zuo, Ru-Juan; Wang, Tong-Song; Gu, Xiao-Wei; Liu, Ji-Long; Yang, Zeng-Ming

2015-01-01

Polyploid decidual cells are specifically differentiated cells during mouse uterine decidualization. However, little is known about the regulatory mechanism and physiological significance of polyploidization in pregnancy. Here we report a novel role of E2F8 in the polyploidization of decidual cells in mice. E2F8 is highly expressed in decidual cells and regulated by progesterone through HB-EGF/EGFR/ERK/STAT3 signaling pathway. E2F8 transcriptionally suppresses CDK1, thus triggering the polyploidization of decidual cells. E2F8-mediated polyploidization is a response to stresses which are accompanied by decidualization. Interestingly, polyploidization is not detected during human decidualization with the down-regulation of E2F8, indicating differential expression of E2F8 may lead to the difference of decidual cell polyploidization between mice and humans.

Involvement of atypical transcription factor E2F8 in the polyploidization during mouse and human decidualization

PubMed Central

Qi, Qian-Rong; Zhao, Xu-Yu; Zuo, Ru-Juan; Wang, Tong-Song; Gu, Xiao-Wei; Liu, Ji-Long; Yang, Zeng-Ming

2015-01-01

Polyploid decidual cells are specifically differentiated cells during mouse uterine decidualization. However, little is known about the regulatory mechanism and physiological significance of polyploidization in pregnancy. Here we report a novel role of E2F8 in the polyploidization of decidual cells in mice. E2F8 is highly expressed in decidual cells and regulated by progesterone through HB-EGF/EGFR/ERK/STAT3 signaling pathway. E2F8 transcriptionally suppresses CDK1, thus triggering the polyploidization of decidual cells. E2F8-mediated polyploidization is a response to stresses which are accompanied by decidualization. Interestingly, polyploidization is not detected during human decidualization with the down-regulation of E2F8, indicating differential expression of E2F8 may lead to the difference of decidual cell polyploidization between mice and humans. PMID:25892397

E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair.

PubMed

Singh, Randeep K; Dagnino, Lina

2016-05-03

Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis.

Tandem E2F Binding Sites in the Promoter of the p107 Cell Cycle Regulator Control p107 Expression and Its Cellular Functions

PubMed Central

Burkhart, Deborah L.; Wirt, Stacey E.; Zmoos, Anne-Flore; Kareta, Michael S.; Sage, Julien

2010-01-01

The retinoblastoma tumor suppressor (Rb) is a potent and ubiquitously expressed cell cycle regulator, but patients with a germline Rb mutation develop a very specific tumor spectrum. This surprising observation raises the possibility that mechanisms that compensate for loss of Rb function are present or activated in many cell types. In particular, p107, a protein related to Rb, has been shown to functionally overlap for loss of Rb in several cellular contexts. To investigate the mechanisms underlying this functional redundancy between Rb and p107 in vivo, we used gene targeting in embryonic stem cells to engineer point mutations in two consensus E2F binding sites in the endogenous p107 promoter. Analysis of normal and mutant cells by gene expression and chromatin immunoprecipitation assays showed that members of the Rb and E2F families directly bound these two sites. Furthermore, we found that these two E2F sites controlled both the repression of p107 in quiescent cells and also its activation in cycling cells, as well as in Rb mutant cells. Cell cycle assays further indicated that activation of p107 transcription during S phase through the two E2F binding sites was critical for controlled cell cycle progression, uncovering a specific role for p107 to slow proliferation in mammalian cells. Direct transcriptional repression of p107 by Rb and E2F family members provides a molecular mechanism for a critical negative feedback loop during cell cycle progression and tumorigenesis. These experiments also suggest novel therapeutic strategies to increase the p107 levels in tumor cells. PMID:20585628

Bioactive constituents from Chinese natural medicines. XXII. Absolute structures of new megastigmane glycosides, sedumosides E1, E2, E3, F1, F2, and G, from Sedum sarmentosum (Crassulaceae).

PubMed

Morikawa, Toshio; Zhang, Yi; Nakamura, Seikou; Matsuda, Hisashi; Muraoka, Osamu; Yoshikawa, Masayuki

2007-03-01

Six new megastigmane glycosides, sedumosides E1, E2, E3, F1, F2, and G, were isolated from the whole plant of Sedum sarmentosum (Crassulaceae). The structures of new constituents including the absolute configuration were elucidated on the basis of chemical and physicochemical evidence.

System design description for portable 1,000 CFM exhauster Skids POR-007/Skid E and POR-008/Skid F

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, O.D.

1998-07-25

The primary purpose of the two 1,000 CFM Exhauster Skids, POR-007-SKID E and POR-008-SKID F, is to provide backup to the waste tank primary ventilation systems for tanks 241-C-106 and 241-AY-102, and the AY-102 annulus in the event of a failure during the sluicing of tank 241-C-106 and subsequent transfer of sluiced waste to 241-AY-102. This redundancy is required since both of the tank ventilation systems have been declared as Safety Class systems.

Functional interaction of CCAAT/enhancer-binding-protein-α basic region mutants with E2F transcription factors and DNA.

PubMed

Kowenz-Leutz, Elisabeth; Schuetz, Anja; Liu, Qingbin; Knoblich, Maria; Heinemann, Udo; Leutz, Achim

2016-07-01

The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) regulates cell cycle arrest and terminal differentiation of neutrophils and adipocytes. Mutations in the basic leucine zipper domain (bZip) of C/EBPα are associated with acute myeloid leukemia. A widely used murine transforming C/EBPα basic region mutant (BRM2) entails two bZip point mutations (I294A/R297A). BRM2 has been discordantly described as defective for DNA binding or defective for interaction with E2F. We have separated the two BRM2 mutations to shed light on the intertwined reciprocity between C/EBPα-E2F-DNA interactions. Both, C/EBPα I294A and R297A retain transactivation capacity and interaction with E2F-DP. The C/EBPα R297A mutation destabilized DNA binding, whereas the C/EBPα I294A mutation enhanced binding to DNA. The C/EBPα R297A mutant, like BRM2, displayed enhanced interaction with E2F-DP but failed to repress E2F-dependent transactivation although both mutants were readily suppressed by E2F1 for transcription through C/EBP cis-regulatory sites. In contrast, the DNA binding enhanced C/EBPα I294A mutant displayed increased repression of E2F-DP mediated transactivation and resisted E2F-DP mediated repression. Thus, the efficient repression of E2F dependent S-phase genes and the activation of differentiation genes reside in the balanced DNA binding capacity of C/EBPα. Copyright © 2016 Elsevier B.V. All rights reserved.

Fisheries and aquaculture industries involvement to control product health and quality safety to satisfy consumer-driven objectives on retail markets in Europe.

PubMed

Roth, Eva; Rosenthal, Harald

2006-01-01

Over the past years the export of agricultural and fishery products from developing countries has substantially increased to markets within the OECD. Retailers and importers are expanding their international operations to meet consumer demands for year-round delivery of products. Moreover, consumers have become increasingly concerned about the safety of food, including those derived from aquatic resources [FAO/NACA/WHO Joint Study Group, 1999. Report food safety issues associated with products from aquaculture. WHO Technical Report Series No 883: VII, pp. 1-55]. Governments and leading businesses are responding by imposing new safety regulations and standards to the international food system (e.g. HACCP, EUREP-GAP), product liability and labeling [Reilly, A., Howgate, P., Käferstein, F., 1997. Safety hazards and the application of HACCP in aquaculture. In: Proceedings of the Second International Conference on Fish Inspection and Quality Control: A Global Focus, Arlington, VA, 19-24 May 1996. Technomic Publishing, Lancaster, PA, pp. 353-373]. Initial concerns for imports of aquacultural products from developing to industrialized countries focussed on bacterial contamination [Buras, N. 1993. Microbial safety of produce from wastewater-fed aquaculture. In: Pullin, R.V.C., Rosenthal, H., MacLean, J.L.(Eds.), Proceedings of ICLARM Conferences, vol. 31, pp. 285-295]. Today, if trade opportunities are to be maintained, these countries must adapt to a full array of regulations and standards. This paper describes four scenarios in aquaculture and fishing product trade between developing countries and countries in the European Union.

Potential antidiabetic activity of extracellular polysaccharides in submerged fermentation culture of Coriolus versicolor LH1.

PubMed

Yang, John Powen; Hsu, Taihao; Lin, Fangyi; Hsu, Wenkuang; Chen, Yucheng

2012-09-01

The separation and purification of extracellular polysaccharides from Coriolus versicolor LH1 were investigated along with their α-glucosidase inhibition properties. Three polysaccharide fractions (ePS-F2-1, ePS-F3-1, and ePS-F4-1) were separated from the culture medium of LH1 using a DEAE anion-exchange column and a Sephadex™ G-50 gel filtration column. Their chemical compositions was determined. On the basis of an α-glucosidase inhibition assay, the enzyme inhibition activities of ePS-F2-1, ePS-F3-1, and ePS-F4-1 were investigated. Among these, ePS-F4-1 had the highest enzyme inhibition effects on α-glucosidase. According to the results of the chemical component analysis, ePS-F3-1 and ePS-F4-1 are the polysaccharides which are combined with triterpenoides, and ePS-F2-1 is complexed with proteins and triterpenoides. Copyright © 2012 Elsevier Ltd. All rights reserved.

National Dam Safety Program. Woodward Dam (Inventory Number NY 507), Lower Hudson River Basin, Orange County, New York. Phase I Inspection Report,

DTIC Science & Technology

1981-06-30

omomrnuurI CONTENTS Location Plan Watershed Map Plate la : Field Sketch of Woodward Dam Plate Ib: Field Sketch of Greenleaf Dam Plate 2: Plan of Dam...goOFftkoww P L "mm alom+0a,0164m asm a Gooch~~A’~e mftLrrL - ol-ob o prat -n 4A ~ /e4 SojA S~tT IIV&-~ ~ i pqPiE5M 1%b, k&vs APPENDIX F...in ry flScrvice orflSi).. L I) Ip. lv.ay ConcrCLC Sp’%way Las j’ r. Joints Surfncc of S p 5.3i). y ’Mclarical Ar .Dra .o ~~~ LI:C azard Class E

MiR-205-5p and miR-342-3p cooperate in the repression of the E2F1 transcription factor in the context of anticancer chemotherapy resistance

PubMed Central

Lai, Xin; Gupta, Shailendra K; Schmitz, Ulf; Marquardt, Stephan; Knoll, Susanne; Spitschak, Alf; Wolkenhauer, Olaf; Pützer, Brigitte M; Vera, Julio

2018-01-01

High rates of lethal outcome in tumour metastasis are associated with the acquisition of invasiveness and chemoresistance. Several clinical studies indicate that E2F1 overexpression across high-grade tumours culminates in unfavourable prognosis and chemoresistance in patients. Thus, fine-tuning the expression of E2F1 could be a promising approach for treating patients showing chemoresistance. Methods: We integrated bioinformatics, structural and kinetic modelling, and experiments to study cooperative regulation of E2F1 by microRNA (miRNA) pairs in the context of anticancer chemotherapy resistance. Results: We showed that an enhanced E2F1 repression efficiency can be achieved in chemoresistant tumour cells through two cooperating miRNAs. Sequence and structural information were used to identify potential miRNA pairs that can form tertiary structures with E2F1 mRNA. We then employed molecular dynamics simulations to show that among the identified triplexes, miR-205-5p and miR-342-3p can form the most stable triplex with E2F1 mRNA. A mathematical model simulating the E2F1 regulation by the cooperative miRNAs predicted enhanced E2F1 repression, a feature that was verified by in vitro experiments. Finally, we integrated this cooperative miRNA regulation into a more comprehensive network to account for E2F1-related chemoresistance in tumour cells. The network model simulations and experimental data indicate the ability of enhanced expression of both miR-205-5p and miR-342-3p to decrease tumour chemoresistance by cooperatively repressing E2F1. Conclusions: Our results suggest that pairs of cooperating miRNAs could be used as potential RNA therapeutics to reduce E2F1-related chemoresistance. PMID:29464002

Repression of transcriptional activity of C/EBPalpha by E2F-dimerization partner complexes.

PubMed

Zaragoza, Katrin; Bégay, Valérie; Schuetz, Anja; Heinemann, Udo; Leutz, Achim

2010-05-01

The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, keratinocytes, and cells of the lung and placenta. C/EBPalpha transactivates lineage-specific differentiation genes and inhibits proliferation by repressing E2F-regulated genes. The myeloproliferative C/EBPalpha BRM2 mutant serves as a paradigm for recurrent human C-terminal bZIP C/EBPalpha mutations that are involved in acute myeloid leukemogenesis. BRM2 fails to repress E2F and to induce adipogenesis and granulopoiesis. The data presented here show that, independently of pocket proteins, C/EBPalpha interacts with the dimerization partner (DP) of E2F and that C/EBPalpha-E2F/DP interaction prevents both binding of C/EBPalpha to its cognate sites on DNA and transactivation of C/EBP target genes. The BRM2 mutant, in addition, exhibits enhanced interaction with E2F-DP and reduced affinity toward DNA and yet retains transactivation potential and differentiation competence that becomes exposed when E2F/DP levels are low. Our data suggest a tripartite balance between C/EBPalpha, E2F/DP, and pocket proteins in the control of proliferation, differentiation, and tumorigenesis.

Novel Tacrine-Based Pyrano[3',4':5,6]pyrano[2,3-b]quinolinones: Synthesis and Cholinesterase Inhibitory Activity.

PubMed

Hariri, Roshanak; Afshar, Zahra; Mahdavi, Mohammad; Safavi, Maliheh; Saeedi, Mina; Najafi, Zahra; Sabourian, Reyhaneh; Karimpour-Razkenari, Elahe; Edraki, Najmeh; Moghadam, Farshad Homayouni; Shafiee, Abbas; Khanavi, Mahnaz; Akbarzadeh, Tahmineh

2016-12-01

In order to develop effective anti-cholinesterase compounds, a novel series of pyrano[3',4':5,6]pyrano[2,3-b]quinolinones were designed, synthesized, and evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All derivatives showed very good AChE inhibitory (AChEI) activity (IC 50  = 0.37-5.62 μM) compared with rivastigmine (IC 50  = 11.07 μM). Among them, 11-amino-12-(2,3-dichlorophenyl)-3-methyl-7,8,9,10-tetrahydropyrano[3',4':5,6]pyrano[2,3-b]quinolin-1(12H)-one (6f) displayed the best inhibitory activity. However, most of the synthesized compounds showed no anti-BChE activity and compounds 6b and 6f were found to be only moderate inhibitors. The most potent anti-AChE compound 6f had low and moderate inhibitory activity and neuroprotective effects against beta-secretase (BACE1) and oxidative stress-induced cell death, respectively. Also, kinetic and molecular docking studies of binding interactions elucidated that compound 6f bound to both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel Developments in Organonitrogen Fluorine Chemistry from Carbon- Nitrogen

DTIC Science & Technology

1991-11-21

alkan- imines (R.FC-NBr, P.R CF3. C2 F5, n-C3F7, CF2CI. CCI3). Photolyuis of the perfluorinated N-bromo compounds af- fords the novel perfluoroazines...physical properties. Alternative and improved I syntheses of three compounds are also reported. The perfluorinated N-haloimines, CF 2-NX (X = F, Cl...ihenakaif e anibokn i ls eatv ncephl ndncepii sbTitutionths reactions ead toetdsrutrso a variety of novelrgni compounds . Ofseilitrsoaftedaiiie

Cross sections for electron collision with difluoroacetylene

NASA Astrophysics Data System (ADS)

Gupta, Dhanoj; Choi, Heechol; Kwon, Deuk-Chul; Yoon, Jung-Sik; Antony, Bobby; Song, Mi-Young

2017-04-01

We report a detailed calculation of total elastic, differential elastic, momentum transfer and electronic excitation for electron impact on difluoroacetylene (C2F2) molecules using the R-matrix method at low energies. After testing many target models, the final results are reported for the target model that gave the best target properties and predicted the lowest value of the shape resonance. The shape resonance is detected at 5.86 eV and 6.49 eV with the close-coupling and static exchange models due to 2Πg (2B2g, 2B3g) states. We observed that the effect of polarization becomes prominent at low energies below 4 eV, decreasing the magnitude of the elastic cross section systematically as it increases for C2F2. We have also computed elastic cross sections for C2H2, C2F4 and C2H4 with a similar model and compared with the experimental data for these molecules along with C2F2. General agreement is found in terms of the shape and nature of the cross section. Such a comparison shows the reliability of the present method for obtaining the cross section for C2F2. The calculation of elastic scattering cross section is extended to higher energies up to 5 keV using the spherical complex optical potential method. The two methods are found to be consistent, merging at around 12 eV for the elastic scattering cross section. Finally we report the total ionization cross section using the binary encounter Bethe method for C2F2. The perfluorination effect in the shape and magnitude of the elastic, momentum transfer and ionization cross sections when compared with C2H2 showed a similar trend to that in the C2H4-C2F4 and C6H6-C6F6 systems. The cross-section data reported in this article could be an important input for the development of a C2F2 plasma model for selective etching of Si/SiO2 in the semiconductor industry.

Assuring safety without animal testing: Unilever's ongoing research programme to deliver novel ways to assure consumer safety.

PubMed

Westmoreland, Carl; Carmichael, Paul; Dent, Matt; Fentem, Julia; MacKay, Cameron; Maxwell, Gavin; Pease, Camilla; Reynolds, Fiona

2010-01-01

Assuring consumer safety without the generation of new animal data is currently a considerable challenge. However, through the application of new technologies and the further development of risk-based approaches for safety assessment, we remain confident it is ultimately achievable. For many complex, multi-organ consumer safety endpoints, the development, evaluation and application of new, non-animal approaches is hampered by a lack of biological understanding of the underlying mechanistic processes involved. The enormity of this scientific challenge should not be underestimated. To tackle this challenge a substantial research programme was initiated by Unilever in 2004 to critically evaluate the feasibility of a new conceptual approach based upon the following key components: 1.Developing new, exposure-driven risk assessment approaches. 2.Developing new biological (in vitro) and computer-based (in silico) predictive models. 3.Evaluating the applicability of new technologies for generating data (e.g. "omics", informatics) and for integrating new types of data (e.g. systems approaches) for risk-based safety assessment. Our research efforts are focussed in the priority areas of skin allergy, cancer and general toxicity (including inhaled toxicity). In all of these areas, a long-term investment is essential to increase the scientific understanding of the underlying biology and molecular mechanisms that we believe will ultimately form a sound basis for novel risk assessment approaches. Our research programme in these priority areas consists of in-house research as well as Unilever-sponsored academic research, involvement in EU-funded projects (e.g. Sens-it-iv, Carcinogenomics), participation in cross-industry collaborative research (e.g. Colipa, EPAA) and ongoing involvement with other scientific initiatives on non-animal approaches to risk assessment (e.g. UK NC3Rs, US "Human Toxicology Project" consortium).

Development of infrared sensors using energy transfer/energy upconversion processes: Study of laser excited fluorescence in rare Earth ion doped crystals

NASA Technical Reports Server (NTRS)

Nash-Stevenson, S. K.; Reddy, B. R.; Venkateswarlu, P.

1994-01-01

A summary is presented of the spectroscopic study of three systems: LaF3:Ho(3+), LaF3:Er(3+) and CaF2:Nd(3+). When the D levels of Ho(3+) in LaF3 were resonantly excited with a laser beam of 640 nm, upconverted emissions were detected from J (416 nm), F (485 nm), and E (546 nm) levels. Energy upconverted emissions were also observed from F and E levels of Ho(3+) when the material was excited with an 800 nm near infrared laser. When the D levels of Er(3+) in LaF3 were resonantly excited with a laser beam of 637 nm, upconverted emissions were detected from the E (540 nm) and P (320, 400, and 468 nm) levels. Energy upconverted emissions were also observed from F, E, and D levels of Er(3+) when the material was resonantly excited with an 804 nm near infrared laser. When the D levels of Nd(3+) in CaF2 were resonantly excited with a laser beam of 577 nm, upconverted emissions were detected from the L (360 and 382 nm), K (418 nm), and I (432 nm) levels. Very weak upconverted emissions were detected when this system was irradiated with a near infrared laser. The numbers in parentheses are the wavelengths of the emissions.

Boring Information and Subsurface Data Base Package User’s Guide.

DTIC Science & Technology

1984-09-01

Army Engineer Waterways Experiment Station Computer Application in’ Ceotechnical Labor o y mue lctosi cia Geotechnical Engineering P0 Box 631...l F -3 7F - 2 1Y 1 U 3. T. 2 F1’--I F 4 -FEST- F,-1rE *~7 1 . ESTR - I -IL’’ 1 2 A. T F- E:7 * 7 T)*i ES l 2) 1-’E M 6FI- I; 2 6 𔄁.D L fO.W -ELLYV

Project Sedan, On-Site Radiological Safety Report

DTIC Science & Technology

1962-10-23

construction site between U2a & 95 U3a Complete construction area average 100 7/12/62 1530 Outside Bunker 2-300 50 7/12/62 1532 Inside Bunker 2-330 4 39...Analysis of Weather and Surface Radiation Data SC 202F Long Range Blast Propagation REECO 203F On-Site Rad-Safe AEC/ USBM 204F Structural Survey of

Defining Components of Team Leadership and Membership in Prehospital Emergency Medical Services.

PubMed

Crowe, Remle P; Wagoner, Robert L; Rodriguez, Severo A; Bentley, Melissa A; Page, David

2017-01-01

Teamwork is critical for patient and provider safety in high-stakes environments, including the setting of prehospital emergency medical services (EMS). We sought to describe the components of team leadership and team membership on a single patient call where multiple EMS providers are present. We conducted a two-day focus group with nine subject matter experts in crew resource management (CRM) and EMS using a structured nominal group technique (NGT). The specific question posed to the group was, "What are the specific components of team leadership and team membership on a single patient call where multiple EMS providers are present?" After round-robin submission of ideas and in-depth discussion of the meaning of each component, participants voted on the most important components of team leadership and team membership. Through the NGT process, we identified eight components of team leadership: a) creates an action plan; b) communicates; c) receives, processes, verifies, and prioritizes information; d) reconciles incongruent information; e) demonstrates confidence, compassion, maturity, command presence, and trustworthiness; f) takes charge; g) is accountable for team actions and outcomes; and h) assesses the situation and resources and modifies the plan. The eight essential components of team membership identified included: a) demonstrates followership, b) maintains situational awareness, c) demonstrates appreciative inquiry, d) does not freelance, e) is an active listener, f) accurately performs tasks in a timely manner, g) is safety conscious and advocates for safety at all times, and h) leaves ego and rank at the door. This study used a highly structured qualitative technique and subject matter experts to identify components of teamwork essential for prehospital EMS providers. These findings and may be used to help inform the development of future EMS training and assessment initiatives.

Insights into the Prostanoid Pathway in the Ovary Development of the Penaeid Shrimp Penaeus monodon

PubMed Central

Wimuttisuk, Wananit; Tobwor, Punsa; Deenarn, Pacharawan; Danwisetkanjana, Kannawat; Pinkaew, Decha; Kirtikara, Kanyawim; Vichai, Vanicha

2013-01-01

The prostanoid pathway converts polyunsaturated fatty acids (PUFAs) into bioactive lipid mediators, including prostaglandins, thromboxanes and prostacyclins, all of which play vital roles in the immune and reproductive systems in most animal phyla. In crustaceans, PUFAs and prostaglandins have been detected and often associated with female reproductive maturation. However, the presence of prostanoid biosynthesis genes remained in question in these species. In this study, we outlined the prostanoid pathway in the black tiger shrimp Penaeus monodon based on the amplification of nine prostanoid biosynthesis genes: cytosolic phospholipase A2, hematopoietic prostaglandin D synthase, glutathione-dependent prostaglandin D synthase, prostaglandin E synthase 1, prostaglandin E synthase 2, prostaglandin E synthase 3, prostaglandin F synthase, thromboxane A synthase and cyclooxygenase. TBLASTX analysis confirmed the identities of these genes with 51-99% sequence identities to their closest homologs. In addition, prostaglandin F2α (PGF2α), which is a product of the prostaglandin F synthase enzyme, was detected for the first time in P. monodon ovaries along with the previously identified PUFAs and prostaglandin E2 (PGE2) using RP-HPLC and mass-spectrometry. The prostaglandin synthase activity was also observed in shrimp ovary homogenates using in vitro activity assay. When prostaglandin biosynthesis was examined in different stages of shrimp ovaries, we found that the amounts of prostaglandin F synthase gene transcripts and PGF2α decreased as the ovaries matured. These findings not only indicate the presence of a functional prostanoid pathway in penaeid shrimp, but also suggest a possible role of the PGF2α biosynthesis in shrimp ovarian development. PMID:24116186

Formulation studies for mirtazapine orally disintegrating tablets.

PubMed

Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

2016-01-01

Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab). Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900 mL 0.1 N HCl medium, 900 mL pH 6.8 phosphate buffer or 900 mL pH 4.5 acetate buffer at 37 ± 0.2 °C as dissolution medium. Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media. Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles. Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.

Universal Logarithmic Law of the Wall in Turbulent Channel and Pipe Flows

NASA Astrophysics Data System (ADS)

Zanoun, E.-S.; Durst, F.; Nagib, Hassan

2003-11-01

The accuracy of obtaining parameters of velocity distribution in the inertial sub-layer of wall-bounded flows depends on evaluating the wall friction and spatial resolution of measurements. By focusing on these aspects of experiments and extending the range of available channel data by a factor of two, our work confirms the log-law over a power-law representation for Re_τ≥ 2×10^3. Measurements in a fully-developed pipe reveal that velocity instruments such as hot-wires are superior to pressure probes for several reasons including spatial resolution. No general technique for correcting Pitot probe data exists, and the MacMillan's displacement correction drastically changes the slope of the logarithmic law. Oil-film interferometry coupled with hot-wire measurements were used to demonstrate effects of channel aspect ratio on results and to reveal that initial tripping has insignificant effects on the Kármán constant in the fully developed region. Data reveal evidence on differences in the outer flow between channels and pipes. In channels, we find that the inertial sub-range may be represented by the simple approximate formula ;U^+≈e ln y^++10/e and the fully developed channel resistance by c_f=0.0624 Re_m-0.25 or √2/c_f; ≈ ; e; ln Re √c_f+10/e+e;(ln1/√2-1).

Predictive models of safety based on audit findings: Part 2: Measurement of model validity.

PubMed

Hsiao, Yu-Lin; Drury, Colin; Wu, Changxu; Paquet, Victor

2013-07-01

Part 1 of this study sequence developed a human factors/ergonomics (HF/E) based classification system (termed HFACS-MA) for safety audit findings and proved its measurement reliability. In Part 2, we used the human error categories of HFACS-MA as predictors of future safety performance. Audit records and monthly safety incident reports from two airlines submitted to their regulatory authority were available for analysis, covering over 6.5 years. Two participants derived consensus results of HF/E errors from the audit reports using HFACS-MA. We adopted Neural Network and Poisson regression methods to establish nonlinear and linear prediction models respectively. These models were tested for the validity of prediction of the safety data, and only Neural Network method resulted in substantially significant predictive ability for each airline. Alternative predictions from counting of audit findings and from time sequence of safety data produced some significant results, but of much smaller magnitude than HFACS-MA. The use of HF/E analysis of audit findings provided proactive predictors of future safety performance in the aviation maintenance field. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Identifying factors affecting the safety of mid-block bicycle lanes considering mixed 2-wheeled traffic flow.

PubMed

Bai, Lu; Chan, Ching-Yao; Liu, Pan; Xu, Chengcheng

2017-10-03

Electric bikes (e-bikes) have been one of the fastest growing trip modes in Southeast Asia over the past 2 decades. The increasing popularity of e-bikes raised some safety concerns regarding urban transport systems. The primary objective of this study was to identify whether and how the generalized linear regression model (GLM) could be used to relate cyclists' safety with various contributing factors when riding in a mid-block bike lane. The types of 2-wheeled vehicles in the study included bicycle-style electric bicycles (BSEBs), scooter-style electric bicycles (SSEBs), and regular bicycles (RBs). Traffic conflict technology was applied as a surrogate measure to evaluate the safety of 2-wheeled vehicles. The safety performance model was developed by adopting a generalized linear regression model for relating the frequency of rear-end conflicts between e-bikes and regular bikes to the operating speeds of BSEBs, SSEBs, and RBs in mid-block bike lanes. The frequency of rear-end conflicts between e-bikes and bikes increased with an increase in the operating speeds of e-bikes and the volume of e-bikes and bikes and decreased with an increase in the width of bike lanes. The large speed difference between e-bikes and bikes increased the frequency of rear-end conflicts between e-bikes and bikes in mid-block bike lanes. A 1% increase in the average operating speed of e-bikes would increase the expected number of rear-end conflicts between e-bikes and bikes by 1.48%. A 1% increase in the speed difference between e-bikes and bikes would increase the expected number of rear-end conflicts between e-bikes/bikes by 0.16%. The conflict frequency in mid-block bike lanes can be modeled using generalized linear regression models. The factors that significantly affected the frequency of rear-end conflicts included the operating speeds of e-bikes, the speed difference between e-bikes and regular bikes, the volume of e-bikes, the volume of bikes, and the width of bike lanes. The safety performance model can help better understand the causes of crash occurrences in mid-block bike lanes.

Comb-push Ultrasound Shear Elastography (CUSE) with Various Ultrasound Push Beams

PubMed Central

Song, Pengfei; Urban, Matthew W.; Manduca, Armando; Zhao, Heng; Greenleaf, James F.; Chen, Shigao

2013-01-01

Comb-push Ultrasound Shear Elastography (CUSE) has recently been shown to be a fast and accurate two-dimensional (2D) elasticity imaging technique that can provide a full field-of- view (FOV) shear wave speed map with only one rapid data acquisition. The initial version of CUSE was termed U-CUSE because unfocused ultrasound push beams were used. In this paper, we present two new versions of CUSE – Focused CUSE (F-CUSE) and Marching CUSE (M-CUSE), which use focused ultrasound push beams to improve acoustic radiation force penetration and produce stronger shear waves in deep tissues (e.g. kidney and liver). F-CUSE divides transducer elements into several subgroups which transmit multiple focused ultrasound beams simultaneously. M-CUSE uses more elements for each focused push beam and laterally marches the push beams. Both F-CUSE and M-CUSE can generate comb-shaped shear wave fields that have shear wave motion at each imaging pixel location so that a full FOV 2D shear wave speed map can be reconstructed with only one data acquisition. Homogeneous phantom experiments showed that U-CUSE, F-CUSE and M-CUSE can all produce smooth shear wave speed maps with accurate shear wave speed estimates. An inclusion phantom experiment showed that all CUSE methods could provide good contrast between the inclusion and background with sharp boundaries while F-CUSE and M-CUSE require shorter push durations to achieve shear wave speed maps with comparable SNR to U-CUSE. A more challenging inclusion phantom experiment with a very stiff and deep inclusion shows that better shear wave penetration could be gained by using F-CUSE and M-CUSE. Finally, a shallow inclusion experiment showed that good preservations of inclusion shapes could be achieved by both U-CUSE and F-CUSE in the near field. Safety measurements showed that all safety parameters are below FDA regulatory limits for all CUSE methods. These promising results suggest that, using various push beams, CUSE is capable of reconstructing a 2D full FOV shear elasticity map using only one push-detection data acquisition in a wide range of depths for soft tissue elasticity imaging. PMID:23591479

Comb-push ultrasound shear elastography (CUSE) with various ultrasound push beams.

PubMed

Song, Pengfei; Urban, Matthew W; Manduca, Armando; Zhao, Heng; Greenleaf, James F; Chen, Shigao

2013-08-01

Comb-push ultrasound shear elastography (CUSE) has recently been shown to be a fast and accurate 2-D elasticity imaging technique that can provide a full field-of-view (FOV) shear wave speed map with only one rapid data acquisition. The initial version of CUSE was termed U-CUSE because unfocused ultrasound push beams were used. In this paper, we present two new versions of CUSE-focused CUSE (F-CUSE) and marching CUSE (M-CUSE), which use focused ultrasound push beams to improve acoustic radiation force penetration and produce stronger shear waves in deep tissues (e.g., kidney and liver). F-CUSE divides transducer elements into several subgroups which transmit multiple focused ultrasound beams simultaneously. M-CUSE uses more elements for each focused push beam and laterally marches the push beams. Both F-CUSE and M-CUSE can generate comb-shaped shear wave fields that have shear wave motion at each imaging pixel location so that a full FOV 2-D shear wave speed map can be reconstructed with only one data acquisition. Homogeneous phantom experiments showed that U-CUSE, F-CUSE, and M-CUSE can all produce smooth shear wave speed maps with accurate shear wave speed estimates. An inclusion phantom experiment showed that all CUSE methods could provide good contrast between the inclusion and background with sharp boundaries while F-CUSE and M-CUSE require shorter push durations to achieve shear wave speed maps with comparable SNR to U-CUSE. A more challenging inclusion phantom experiment with a very stiff and deep inclusion shows that better shear wave penetration could be gained by using F-CUSE and M-CUSE. Finally, a shallow inclusion experiment showed that good preservations of inclusion shapes could be achieved by both U-CUSE and F-CUSE in the near field. Safety measurements showed that all safety parameters are below FDA regulatory limits for all CUSE methods. These promising results suggest that, using various push beams, CUSE is capable of reconstructing a 2-D full FOV shear elasticity map using only one push-detection data acquisition in a wide range of depths for soft tissue elasticity imaging.

Finite mixture modeling approach for developing crash modification factors in highway safety analysis.

PubMed

Park, Byung-Jung; Lord, Dominique; Wu, Lingtao

2016-10-28

This study aimed to investigate the relative performance of two models (negative binomial (NB) model and two-component finite mixture of negative binomial models (FMNB-2)) in terms of developing crash modification factors (CMFs). Crash data on rural multilane divided highways in California and Texas were modeled with the two models, and crash modification functions (CMFunctions) were derived. The resultant CMFunction estimated from the FMNB-2 model showed several good properties over that from the NB model. First, the safety effect of a covariate was better reflected by the CMFunction developed using the FMNB-2 model, since the model takes into account the differential responsiveness of crash frequency to the covariate. Second, the CMFunction derived from the FMNB-2 model is able to capture nonlinear relationships between covariate and safety. Finally, following the same concept as those for NB models, the combined CMFs of multiple treatments were estimated using the FMNB-2 model. The results indicated that they are not the simple multiplicative of single ones (i.e., their safety effects are not independent under FMNB-2 models). Adjustment Factors (AFs) were then developed. It is revealed that current Highway Safety Manual's method could over- or under-estimate the combined CMFs under particular combination of covariates. Safety analysts are encouraged to consider using the FMNB-2 models for developing CMFs and AFs. Copyright © 2016 Elsevier Ltd. All rights reserved.

30 CFR 74.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Definitions. 74.2 Section 74.2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH COAL MINE... consensus standards used worldwide. (f) Precision: the relative variability of measurements from a...

Fluoride induces endoplasmic reticulum stress and inhibits protein synthesis and secretion.

PubMed

Sharma, Ramaswamy; Tsuchiya, Masahiro; Bartlett, John D

2008-09-01

Exposure to excessive amounts of fluoride (F(-)) causes dental fluorosis in susceptible individuals; however, the mechanism of F(-)-induced toxicity is unclear. Previously, we have shown that high-dose F(-) activates the unfolded protein response (UPR) in ameloblasts that are responsible for dental enamel formation. The UPR is a signaling pathway responsible for either alleviating endoplasmic reticulum (ER) stress or for inducing apoptosis of the stressed cells. In this study we determined if low-dose F(-) causes ER stress and activates the UPR, and we also determined whether F(-) interferes with the secretion of proteins from the ER. We stably transfected the ameloblast-derived LS8 cell line with secreted alkaline phosphatase (SEAP) and determined activity and localization of SEAP and F(-)-mediated induction of UPR proteins. Also, incisors from mice given drinking water containing various concentrations of F(-) were examined for eucaryotic initiation factor-2, subunit alpha (eIF2alpha) phosphorylation. We found that F(-) decreases the extracellular secretion of SEAP in a linear, dose-dependent manner. We also found a corresponding increase in the intracellular accumulation of SEAP after exposure to F(-). These changes are associated with the induction of UPR proteins such as the molecular chaperone BiP and phosphorylation of the UPR sensor PKR-like ER kinase, and its substrate, eIF2alpha. Importantly, F(-)-induced phosphorylation of eIF2alphawas confirmed in vivo. These data suggest that F(-) initiates an ER stress response in ameloblasts that interferes with protein synthesis and secretion. Consequently, ameloblast function during enamel development may be impaired, and this may culminate in dental fluorosis.

EBP1 is a novel E2F target gene regulated by transforming growth factor-β.

PubMed

Judah, David; Chang, Wing Y; Dagnino, Lina

2010-11-10

Regulation of gene expression requires transcription factor binding to specific DNA elements, and a large body of work has focused on the identification of such sequences. However, it is becoming increasingly clear that eukaryotic transcription factors can exhibit widespread, nonfunctional binding to genomic DNA sites. Conversely, some of these proteins, such as E2F, can also modulate gene expression by binding to non-consensus elements. E2F comprises a family of transcription factors that play key roles in a wide variety of cellular functions, including survival, differentiation, activation during tissue regeneration, metabolism, and proliferation. E2F factors bind to the Erb3-binding protein 1 (EBP1) promoter in live cells. We now show that E2F binding to the EBP1 promoter occurs through two tandem DNA elements that do not conform to typical consensus E2F motifs. Exogenously expressed E2F1 activates EBP1 reporters lacking one, but not both sites, suggesting a degree of redundancy under certain conditions. E2F1 increases the levels of endogenous EBP1 mRNA in breast carcinoma and other transformed cell lines. In contrast, in non-transformed primary epidermal keratinocytes, E2F, together with the retinoblastoma family of proteins, appears to be involved in decreasing EBP1 mRNA abundance in response to growth inhibition by transforming growth factor-β1. Thus, E2F is likely a central coordinator of multiple responses that culminate in regulation of EBP1 gene expression, and which may vary depending on cell type and context.

Cardiac-specific ablation of the E3 ubiquitin ligase Mdm2 leads to oxidative stress, broad mitochondrial deficiency and early death

PubMed Central

Hauck, Ludger; Stanley-Hasnain, Shanna; Fung, Amelia; Grothe, Daniela; Rao, Vivek; Mak, Tak W.

2017-01-01

The maintenance of normal heart function requires proper control of protein turnover. The ubiquitin-proteasome system is a principal regulator of protein degradation. Mdm2 is the main E3 ubiquitin ligase for p53 in mitotic cells thereby regulating cellular growth, DNA repair, oxidative stress and apoptosis. However, which of these Mdm2-related activities are preserved in differentiated cardiomyocytes has yet to be determined. We sought to elucidate the role of Mdm2 in the control of normal heart function. We observed markedly reduced Mdm2 mRNA levels accompanied by highly elevated p53 protein expression in the hearts of wild type mice subjected to myocardial infarction or trans-aortic banding. Accordingly, we generated conditional cardiac-specific Mdm2 gene knockout (Mdm2f/f;mcm) mice. In adulthood, Mdm2f/f;mcm mice developed spontaneous cardiac hypertrophy, left ventricular dysfunction with early mortality post-tamoxifen. A decreased polyubiquitination of myocardial p53 was observed, leading to its stabilization and activation, in the absence of acute stress. In addition, transcriptomic analysis of Mdm2-deficient hearts revealed that there is an induction of E2f1 and c-Myc mRNA levels with reduced expression of the Pgc-1a/Ppara/Esrrb/g axis and Pink1. This was associated with a significant degree of cardiomyocyte apoptosis, and an inhibition of redox homeostasis and mitochondrial bioenergetics. All these processes are early, Mdm2-associated events and contribute to the development of pathological hypertrophy. Our genetic and biochemical data support a role for Mdm2 in cardiac growth control through the regulation of p53, the Pgc-1 family of transcriptional coactivators and the pivotal antioxidant Pink1. PMID:29267372

E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair

PubMed Central

Singh, Randeep K.; Dagnino, Lina

2016-01-01

Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis. PMID:27028861

78 FR 14877 - Pipeline Safety: Incident and Accident Reports

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-07

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket ID PHMSA-2013-0028] Pipeline Safety: Incident and Accident Reports AGENCY: Pipeline and Hazardous Materials... PHMSA F 7100.2--Incident Report--Natural and Other Gas Transmission and Gathering Pipeline Systems and...

Measuring fecal testosterone in females and fecal estrogens in males: comparison of RIA and LC/MS/MS methods for wild baboons (Papio cynocephalus)

PubMed Central

Gesquiere, Laurence R.; Ziegler, Toni E.; Chen, Patricia A.; Epstein, Katherine A.; Alberts, Susan C.; Altmann, Jeanne

2014-01-01

The development of non-invasive methods, particularly fecal determination, has made possible the assessment of hormone concentrations in wild animal populations. However, measuring fecal metabolites needs careful validation for each species and for each sex. We investigated whether radioimmunoassays (RIAs) previously used to measure fecal testosterone (fT) in male baboons and fecal estrogens (fE) in female baboons were well suited to measure these hormones in the opposite sex. We compared fE and fT concentrations determined by RIA to those measured by liquid chromatography combined with triple quadropole mass spectrometry (LC/MS/MS), a highly specific method. Additionally, we conducted a biological validation to assure that the measurements of fecal concentrations reflected physiological levels of the hormone of interest. Several tests produced expected results that led us to conclude that our RIAs can reliably measure fT and fE in both sexes, and that within-sex comparisons of these measures are valid: (i) fTRIA were significantly correlated to fTLC/MS/MS for both sexes; (ii) fTRIA were higher in adult than in immature males; (iii) fTRIA were higher in pregnant than non-pregnant females; (iv) fERIA were correlated with 17β-estradiol (fE2) and with estrone (fE1) determined by LC/MS/MS in pregnant females; (v) fERIA were significantly correlated with fE2 in non-pregnant females and nearly significantly correlated in males; (vi) fERIA were higher in adult males than in immature males. fERIA were higher in females than in males, as predicted, but unexpectedly, fTRIA were higher in females than in males, suggesting a difference in steroid metabolism in the two sexes; consequently, we conclude that while within-sex comparisons are valid, fTRIA should not be used for intersexual comparisons. Our results should open the field to important additional studies, as to date the roles of testosterone in females and estrogens in males have been little investigated. PMID:24798581

Impaired contextual modulation of memories in PTSD: an fMRI and psychophysiological study of extinction retention and fear renewal.

PubMed

Garfinkel, Sarah N; Abelson, James L; King, Anthony P; Sripada, Rebecca K; Wang, Xin; Gaines, Laura M; Liberzon, Israel

2014-10-01

Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression. Copyright © 2014 the authors 0270-6474/14/3413435-09$15.00/0.

Onecut 1 and Onecut 2 Are Potential Regulators of Mouse Retinal Development

PubMed Central

Wu, Fuguo; Sapkota, Darshan; Li, Renzhong; Mu, Xiuqian

2014-01-01

Our current study focuses on the expression of two members of the onecut transcription factor family, One-cut1 (Oc1) and Onecut2 (Oc2), in the developing mouse retina. By immunofluorescence staining, we found that Oc1 and Oc2 had very similar expression patterns throughout retinal development. Both factors started to be expressed in the retina at around embryonic day (E) 11.5. At early stages (E11.5 and E12.5), they were expressed in both the neuroblast layer (NBL) and ganglion cell layer (GCL). As development progressed (from E14.5 to postnatal day [P] 0), expression diminished in the retinal progenitor cells and became more restricted to the GCL. By P5, Oc1 and Oc2 were expressed at very low levels in the GCL. By co-labeling with transcription factors known to be involved in retinal ganglion cell (RGC) development, we found that Oc1 and Oc2 had extensive overlap with Math5 in the NBL, and that they completely overlapped with Pou4f2 and Isl1 in the GCL, but only partially in the NBL. Co-labeling of Oc1 with cell cycle markers confirmed that Oc1 was expressed in both proliferating retinal progenitors and postmitotic retinal cells. In addition, we demonstrated that expression of Oc1 and Oc2 did not require Math5, Isl1, or Pou4f2. Thus, Oc1 and Oc2 may regulate the formation of RGCs in a pathway independent of Math5, Pou4f2, and Isl1. Furthermore, we showed that Oc1 and Oc2 were expressed in both developing and mature horizontal cells (HCs). Therefore the two factors may also function in the genesis and maintenance of HCs. J. Comp. Neurol. 520:952–969, 2012. PMID:21830221

Analysis of E2F factors during epidermal differentiation.

PubMed

Chang, Wing Y; Dagnino, Lina

2005-01-01

The multigene E2F family of transcription factors is central in the control of cell cycle progression. The expression and activity of E2F proteins is tightly regulated transcriptionally and posttranslationally as a function of the proliferation and differentiation status of the cell. In this chapter, we review protocols designed to determine E2F mRNA abundance in tissues by in situ hybridization techniques. The ability to culture primary epidermal keratinocytes and maintain them as either undifferentiated or terminally differentiated cells allows the biochemical and molecular characterization of changes in E2F expression and activity. Thus, we also discuss in detail methods to analyze E2F protein abundance by immunoblot and their ability to bind DNA in cultured cells using electrophoretic mobility shift assays.

Erratum to: Magnetic field-induced modification of selection rules for Rb D2 line monitored by selective reflection from a vapor nanocell. Eur. Phys. J. D 71: 216 (2017), DOI: 10.1140/epjd/e2017-80291-6

NASA Astrophysics Data System (ADS)

Klinger, Emmanuel; Sargsyan, Armen; Tonoyan, Ara; Hakhumyan, Grant; Papoyan, Aram; Leroy, Claude; Sarkisyan, David

2018-01-01

The two technical points below are corrected by this erratum: 1. The publisher apologizes for a technical problem occurring in the scale numbering of Figure 2. The figure is corrected below. [Figure not available: see fulltext.] 2. Page 6, line 14 of the Conclusion section " F g = 2, m F = -3 → F e = 4, m F = -2" should be replaced by " F g = 2, m F = -2 → F e = 4, m F = -1".

Homogeneous Chaos, p-Forms, Scaling and the Feynman Integral

DTIC Science & Technology

1989-09-01

f)] = f I (f)(x)dPl(X) = 0; T oIR+) (v) EflI p(f),2j = E[ JI p)j 2 p p = p! 11f11 < p!lf11I ; (vi) E[I p(f)I p(g)] = E[I l )Ip (g)] = p! (f’g) 2 p From...p. 62]. ji is only 15 finitely additive on T but is countably additive on T for each fixed ir. (H,.%.) is called a finitely additive canonical...pilS)"’i(Sk)0i (sk + l ) ° ’ ’ ** Ji R xRkl. =1 p 1 k k+ 0i2k (S2k)* #i2k+l pSjkl)"’"#ip(Sp)J-e (s l ..... k )eJ (sk+1 .... S2k)dsl-...*dsk " ds k+l

Deviatoric Constitutive Relationship for Anisotropic Materials

DTIC Science & Technology

1987-06-01

SEFF = VMISES ICHECK (1) = 0 DEPSBP = 0. CALL XFORM (STR(I),STR(2),STR(3),STR(4),STR(5),STR(6), & SR2 ,SZ2 ,ST2 ,SZT2 ,SRT2 ,SRZ2,-TH) GO TO 310...END I F C c Yield h a s occured: D e t e r m i n e ALF, t h e f r a c t i o n of s t r a i n c t h a t is pre-y ie ld . C I F ( ICHECK ...c e l s e m u s t d e t e r m i n e e l a s t i c f r a c t i o n ( a l f ) (see V a v r i c k , J o h n s o n ) C ICHECK (1) = 1 TERM1 = 0

U.S. Strategic Nuclear Forces: Background, Developments, and Issues

DTIC Science & Technology

2013-10-22

32 Safety, Security, and Management ...by Amy F. Woolf. 2 Natural Resources Defense Council. Table of U.S. Strategic Offensive Force Loadings. Archive of Nuclear Data. http://www.nrdc.org...12000 14000 16000 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 Year N um be r Launchers Warheads Source: Natural Resources Defense Council

SNHG16 contributes to breast cancer cell migration by competitively binding miR-98 with E2F5.

PubMed

Cai, Chang; Huo, Qiang; Wang, Xiaolong; Chen, Bing; Yang, Qifeng

2017-04-01

Long noncoding RNAs (lncRNAs) have been proved to play important roles in cellular processes of cancer, including the development, proliferation, and migration of cancer cells. In the present study, we demonstrated small nucleolar RNA host gene 16 (SNHG16) as an oncogene on cell migration in breast cancer. Expression levels of SNHG16 were found to be frequently higher in breast cancer tissues than in the paired noncancerous tissues. Gain- and loss-of-function studies proved that SNHG16 significantly promoted breast cancer cell migration. We predicted SNHG16 as a competitive endogenous RNA (ceRNA) of E2F transcription factor 5 protein (E2F5) via competition for the shared miR-98 through bioinformatics analysis, and proved this regulation using relative quantitative real-time PCR (qRT-PCR), western blot, RNA immunoprecipitation (RIP) assay and luciferase reporter assay. In addition, we identified a positive correlation between SNHG16 and E2F5 in breast cancer tissues. Furthermore, we demonstrated that forced expression of miR-98 could partially abrogate SNHG16-mediated increase of breast cancer cells migration, suggesting that SNHG16 promoted cell migration in a miR-98 dependent manner. Taken together, our findings indicated that SNHG16 induces breast cancer cell migration by competitively binding miR-98 with E2F5, and SNHG16 can serve as a potential therapeutic target for breast cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

16 CFR 1203.53 - Interim safety standards.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., Protective Headgear for Bicyclists, (2) ASTM standards F 1447-93 or F 1447-94, Standard Specification for Protective Headgear Used in Bicycling, incorporating the relevant provisions of ASTM F 1446-93 or ASTM F 1446... Institute, 11 W. 42nd Street, 13th Floor, New York, NY 10036. Copies of the ASTM standards are available...

Linked Tumor-Selective Virus Replication and Transgene Expression from E3-Containing Oncolytic Adenoviruses†

PubMed Central

Zhu, Mingzhu; Bristol, J. Andrew; Xie, Yuefeng; Mina, Mervat; Ji, Hong; Forry-Schaudies, Suzanne; Ennist, David L.

2005-01-01

Historically, the adenoviral E3 region was found to be nonessential for viral replication in vitro. In addition, adenoviruses whose genome was more than approximately 105% the size of the native genome were inefficiently packaged. These profound observations were used experimentally to insert transgenes into the adenoviral backbone. More recently, however, the reintroduction of the E3 region into oncolytic adenoviruses has been found to positively influence antitumor efficacy in preclinical models and clinical trials. In the studies reported here, the granulocyte-macrophage colony-stimulating factor (GM-CSF) cDNA sequence has been substituted for the E3-gp19 gene in oncolytic adenoviruses that otherwise retained the E3 region. Five viruses that differed slightly in the method of transgene insertion were generated and compared to Ar6pAE2fGmF (E2F/GM/ΔE3), a previously described E3-deleted oncolytic adenovirus encoding GM-CSF. In all of the viruses, the human E2F-1 promoter regulated E1A expression and GM-CSF expression was under the control of the adenoviral E3 promoter and the packaging signal was relocated immediately upstream from the right terminal repeat. The E3-gp19-deleted viruses had similar cytolytic properties, as measured in vitro by cytotoxicity assays, but differed markedly in their capacity to express and secrete GM-CSF. Ar15pAE2fGmF (E2F/GM/E3b), the virus that produced the highest levels of GM-CSF and retained the native GM-CSF leader sequence, was selected for further analysis. The E2F/GM/E3b and E2F/GM/ΔE3 viruses exhibited similar cytotoxic activity and GM-CSF production in several tumor cell lines in vitro. However, when compared in vivo in nude mouse xenograft tumor models, E2F/GM/E3b spread through tumors to a greater extent, resulted in higher peak GM-CSF and total exposure levels in both tumor and serum, and was more efficacious than the E3-deleted virus. Using the matched WI-38 (parental) and WI-38-VA13 (simian virus 40 large T antigen transformed) cell pair, GM-CSF was shown to be selectively produced in cells expressing high levels of E2F, indicating that the tumor-selective E2F promoter controlled E1A and GM-CSF expression. PMID:15827160

ROS Production Is Essential for the Apoptotic Function of E2F1 in Pheochromocytoma and Neuroblastoma Cell Lines

PubMed Central

Espada, Lilia; Meo-Evoli, Nathalie; Sancho, Patricia; Real, Sebastian; Fabregat, Isabel; Ambrosio, Santiago; Tauler, Albert

2012-01-01

In this study we demonstrate that accumulation of reactive oxygen species (ROS) is essential for E2F1 mediated apoptosis in ER-E2F1 PC12 pheochromocytoma, and SH-SY5Y and SK-N-JD neuroblastoma stable cell lines. In these cells, the ER-E2F1 fusion protein is expressed in the cytosol; the addition of 4-hydroxytamoxifen (OHT) induces its translocation to the nucleus and activation of E2F1target genes. Previously we demonstrated that, in ER-E2F1 PC12 cells, OHT treatment induced apoptosis through activation of caspase-3. Here we show that caspase-8 activity did not change upon treatment with OHT. Moreover, over-expression of Bcl-xL arrested OHT-induced apoptosis; by contrast, over-expression of c-FLIP, did not have any effect on OHT-induced apoptosis. OHT addition induces BimL expression, its translocation to mitochondria and activation of Bax, which is paralleled by diminished mitochondrial enrichment of Bcl-xL. Treatment with a Bax-inhibitory peptide reduced OHT-induced apoptosis. These results point out the essential role of mitochondria on the apoptotic process driven by E2F1. ROS accumulation followed E2F1 induction and treatment with the antioxidant N-acetylcysteine, inhibited E2F1-induced Bax translocation to mitochondria and subsequent apoptosis. The role of ROS in mediating OHT-induced apoptosis was also studied in two neuroblastoma cell lines, SH-SY5Y and SK-N-JD. In SH-SY5Y cells, activation of E2F1 by the addition of OHT induced ROS production and apoptosis, whereas over-expression of E2F1 in SK-N-JD cells failed to induce either response. Transcriptional profiling revealed that many of the genes responsible for scavenging ROS were down-regulated following E2F1-induction in SH-SY5Y, but not in SK-N-JD cells. Finally, inhibition of GSK3β blocked ROS production, Bax activation and the down regulation of ROS scavenging genes. These findings provide an explanation for the apparent contradictory role of E2F1 as an apoptotic agent versus a cell cycle activator. PMID:23251571

Tunable cytotoxic aptamer-drug conjugates for the treatment of prostate cancer.

PubMed

Powell Gray, Bethany; Kelly, Linsley; Ahrens, Douglas P; Barry, Ashley P; Kratschmer, Christina; Levy, Matthew; Sullenger, Bruce A

2018-05-01

Therapies that can eliminate both local and metastatic prostate tumor lesions while sparing normal organ tissue are desperately needed. With the goal of developing an improved drug-targeting strategy, we turned to a new class of targeted anticancer therapeutics: aptamers conjugated to highly toxic chemotherapeutics. Cell selection for aptamers with prostate cancer specificity yielded the E3 aptamer, which internalizes into prostate cancer cells without targeting normal prostate cells. Chemical conjugation of E3 to the drugs monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) yields a potent cytotoxic agent that efficiently kills prostate cancer cells in vitro but does not affect normal prostate epithelial cells. Importantly, the E3 aptamer targets tumors in vivo and treatment with the MMAF-E3 conjugate significantly inhibits prostate cancer growth in mice, demonstrating the in vivo utility of aptamer-drug conjugates. Additionally, we report the use of antidotes to block E3 aptamer-drug conjugate cytotoxicity, providing a safety switch in the unexpected event of normal cell killing in vivo.

Thromboembolic Events After Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate: Exploratory Analyses of Two Randomized, Plasma-Controlled Studies.

PubMed

Milling, Truman J; Refaai, Majed A; Goldstein, Joshua N; Schneider, Astrid; Omert, Laurel; Harman, Amy; Lee, Martin L; Sarode, Ravi

2016-01-01

We evaluated thromboembolic events after vitamin K antagonist reversal in post hoc analyses of pooled data from 2 randomized trials comparing 4-factor prothrombin complex concentrate (4F-PCC) (Beriplex/Kcentra) with plasma. Unblinded investigators identified thromboembolic events, using standardized terms (such as "myocardial infarction," "deep vein thrombosis," "pulmonary embolism," and "ischemic stroke"). A blinded safety adjudication board reviewed serious thromboembolic events, as well as those referred by an independent unblinded data and safety monitoring board. We descriptively compared thromboembolic event and patient characteristics between treatment groups and included detailed patient-level outcome descriptions. We did not power the trials to assess safety. We enrolled 388 patients (4F-PCC: n=191; plasma: n=197) in the trials. Thromboembolic events occurred in 14 of 191 patients (7.3%) in the 4F-PCC group and 14 of 197 (7.1%) in the plasma group (risk difference 0.2%; 95% confidence interval -5.5% to 6.0%). Investigators reported serious thromboembolic events in 16 patients (4F-PCC: n=8; plasma: n=8); the data and safety monitoring board referred 2 additional myocardial ischemia events (plasma group) to the safety adjudication board for review. The safety adjudication board judged serious thromboembolic events in 10 patients (4F-PCC: n=4; plasma: n=6) as possibly treatment related. There were 8 vascular thromboembolic events in the 4F-PCC group versus 4 in the plasma group, and 1 versus 6 cardiac events, respectively. Among patients with thromboembolic events, 3 deaths occurred in each treatment group. All-cause mortality for the pooled population was 13 per group. We observed no relationship between thromboembolic event occurrence and factor levels transiently above the upper limit of normal; there were no notable differences in median factor or proteins C and S levels up to 24 hours postinfusion start in patients with and without thromboembolic events. The incidence of thromboembolic events after vitamin K antagonist reversal with 4F-PCC or plasma was similar and independent of coagulation factor levels; small differences in the number of thromboembolic event subtypes were observed between treatment groups. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

E2F3a gene expression has prognostic significance in childhood acute lymphoblastic leukemia.

PubMed

Wang, Kai-Ling; Mei, Yan-Yan; Cui, Lei; Zhao, Xiao-Xi; Li, Wei-Jing; Gao, Chao; Liu, Shu-Guang; Jiao, Ying; Liu, Fei-Fei; Wu, Min-Yuan; Ding, Wei; Li, Zhi-Gang

2014-10-01

To study E2F3a expression and its clinical significance in children with acute lymphoblastic leukemia (ALL). We quantified E2F3a expression at diagnosis in 148 children with ALL by real-time PCR. In the test cohort (n = 48), receiver operating characteristic (ROC) curve was used to find the best cut-off point to divide the patients into E2F3a low- and high-expression groups. The prognostic significance of E2F3a expression was investigated in the test cohort and confirmed in the validation cohort (n = 100). The correlations of E2F3a expression with the clinical features and treatment outcome of these patients were analyzed. ROC curve analysis indicated that the best cut-off point of E2F3a expression was 0.3780. In the test cohort, leukemia-free survival (LFS) and event-free survival (EFS) of the low-expression group were lower than those of the high-expression group (log rank: P = 0.026 for both). This finding was verified in the validation cohort. LFS, EFS, and overall survival were also lower in the low-expression group than in the high-expression group (log rank, P = 0.015, 0.008, and 0.002 respectively). E2F3a low expression was correlated with the existence of BCR-ABL fusion. An algorithm composed of E2F3a expression and minimal residual disease (MRD) could predict relapse or induction failure more precisely than current risk stratification. These results were still significant in the ALL patients without BCR-ABL fusion. Low expression of E2F3a was associated with inferior prognosis in childhood ALL. An algorithm composed of E2F3a expression and MRD could predict relapse or induction failure more precisely than that of the current risk stratification. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

(BNL/DoE-hyped) ``Self-Organized-Criticality'' (SOC) is Merely Newton's(1687) Third Law of Motion F = ma REdiscovery: LONG PRE-``Bak''!!!

NASA Astrophysics Data System (ADS)

Bak, P. R. E.; Newton, I.; Siegel, Edward Carl-Ludwig

2011-03-01

"Bak"/BNL/DoE "self-organized-criticality"(SOC) usual BNL/DoE media-hype P.R spin-doctoring "show-biz" "Bush-waaa-...-aaah!!!" is manifestly-demonstrated in two distinct ways to be nothing but Newton's Third Law of Motion F = ma REdiscovery!!! PHYSICS: (1687) cross-multiplied F = ma rewritten as 1/m = a/F = OUTPUT/INPUT = EFFECT/ CAUSE = inverse-mass mechanical-susceptibility = X ("w "); X ("w ") (F.-D. theorem-equivalence /proportionality) P("w ") "noise" power-spectrum; E w ; and E (any/all media upper-limiting-speeds) m. Thus: w E m; inversion yields: 1/w 1 /E 1 /m a/F = X ("w ") P("w "); hence: F = ma dual/inverse-integral-transform is "'SOC"'s" P(w) 1 / w (1) !!! ; "PURE"-MATHS: F = ma double-integral time-series s(t) = [vot + (1/2) at (2) ] inverse/dual-integral-transform formally defines power-spectrum: P (w) = S { s (t) e [ - (iORnoi) wt ] } dt = S { [ vot + (1 / 2) at 2) ] e [ - (iORnoi) wt ] } dt = voS { te [ - (iORnoi) wt ] } dt + (1 / 2) S { [ a = / = a (t) ] e [ - (iORnoi) wt) } dt = vo (d / dw) Delta (w) + (1 / 2) [ a = / = a (t) ] (d / dw) (2) Delta (w) = vo / w (0) + (1 / 2) [ a = / = a (t) ] / w 1 : ifa = 0 , then P(w) 1 / w 0 , VS . ifa = / = a (t) = / = 0 , then P(w) 1 /w; = by physics: ``SOC'' RE-expresses F = ma!!!: ``just `a tad' late/tardy'' REdiscovery of F=ma: LONG PRE-"Bak"!!!

A Functional Role of RB-Dependent Pathway in the Control of Quiescence in Adult Epidermal Stem Cells Revealed by Genomic Profiling

PubMed Central

Lorz, Corina; García-Escudero, Ramón; Segrelles, Carmen; Garín, Marina I.; Ariza, José M.; Santos, Mirentxu; Ruiz, Sergio; Lara, María F.; Martínez-Cruz, Ana B.; Costa, Clotilde; Buitrago-Pérez, Águeda; Saiz-Ladera, Cristina; Dueñas, Marta

2010-01-01

Continuous cell renewal in mouse epidermis is at the expense of a pool of pluripotent cells that lie in a well defined niche in the hair follicle known as the bulge. To identify mechanisms controlling hair follicle stem cell homeostasis, we developed a strategy to isolate adult bulge stem cells in mice and to define their transcriptional profile. We observed that a large number of transcripts are underexpressed in hair follicle stem cells when compared to non-stem cells. Importantly, the majority of these downregulated genes are involved in cell cycle. Using bioinformatics tools, we identified the E2F transcription factor family as a potential element involved in the regulation of these transcripts. To determine their functional role, we used engineered mice lacking Rb gene in epidermis, which showed increased expression of most E2F family members and increased E2F transcriptional activity. Experiments designed to analyze epidermal stem cell functionality (i.e.: hair regrowth and wound healing) imply a role of the Rb-E2F axis in the control of stem cell quiescence in epidermis. Electronic supplementary material The online version of this article (doi:10.1007/s12015-010-9139-0) contains supplementary material, which is available to authorized users. PMID:20376578

76 FR 70046 - Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, C, D, and D1; and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-10

... Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, C, D, and D1; and AS355E, F, F1, F2, N... France (Eurocopter) Model AS350B, B1, B2, B3, BA, C, D, and D1 helicopters; and Model AS355E, F, F1, F2... (AD 2003- 22-06), for Eurocopter Model AS350B, B1, B2, B3, BA, C, D, and D1; and Model AS355E, F, F1...

Performance Analysis of Polymorphous Computing Architectures

DTIC Science & Technology

2001-01-01

G H F Proc 5 : 4 : 3 11 1 Figure 3. Self-timed execution. D C B F G H E D B H EA CG...F D C B F G H E D B H EA CG F AProc 1 Proc 2 Proc 3 Proc 4 Proc 5 185 cution pattern when the application graph in Figure 2 is executed in a self...transform, a quadra- E Figure 10. Self-timed execution with first-iteration actors denoted by T. D B H E CG F D C B F G H E D B H EA CG F A 18 T T T

Utilizing Telemedicine in the Trauma Intensive Care Unit: Does It Impact Teamwork?

PubMed

Lazzara, Elizabeth H; Benishek, Lauren E; Patzer, Brady; Gregory, Megan E; Hughes, Ashley M; Heyne, Kyle; Salas, Eduardo; Kuchkarian, Fernanda; Marttos, Antonio; Schulman, Carl

2015-08-01

The aim of this study was to examine the impact of a telemedical robot on trauma intensive care unit (TICU) clinician teamwork (i.e., team attitudes, behaviors, and cognitions) during patient rounds. Thirty-two healthcare providers who conduct rounds volunteered to take surveys assessing teamwork attitudes and cognitions at three time periods: (1) the onset of the study, (2) the end of the 30-day control period, and (3) the end of the 30-day experimental period, which immediately followed the control period. Rounds were recorded throughout the 30-day control period and 30-day experimental period to observe provider behaviors. For the initial 30 days, there was no access to telemedicine. For the final 30 days, the rounding healthcare providers had access to the RP-7 robot (Intouch Health Inc., Santa Barbara, CA), a telemedical tool that can facilitate patient rounds conducted away from bedside. Using a one-tailed, one-way repeated-measures analysis of variance (ANOVA) to compare trust at Times 1, 2, and 3, there was no significant effect on trust: F(2, 14)=1.20, p=0.16. When a one-tailed, one-way repeated-measures ANOVA to compare transactive memory systems (TMS) at Times 1, 2, and 3 was conducted, there was no significant effect on TMS: F(2, 15)=1.33, p=0.15. We conducted a one-tailed, one-way repeated-measures ANOVA to compare team psychological safety at Times 1, 2, and 3, and there was no significant effect on team psychological safety: F(2,15)=1.53, p=0.12. There was a significant difference in communication between rounds with and without telemedicine [t(25)=-1.76, p<0.05], such that there was more task-based communication during telerounds. Telemedicine increased task-based communication and did not negatively impact team trust, psychological safety, or TMS during rounds. Telemedicine may offer advantages for some teamwork competencies without sacrificing the efficacy of others and may be adopted by intact rounding teams without hindering teamwork.

Assessment of Liver Fibrosis Using Real-time Shear-wave Elastography for Patients with Hepatitis B e Antigen-negative Chronic Hepatitis B and Alanine Transaminase <2 Times the Upper Limit of Normal.

PubMed

Liu, Jing-Hua; Zou, Yu; Chang, Wei; Wu, Jun; Zou, Yu; Xie, Yu-Chen; Lu, Yong-Ping; Wei, Jia

2017-01-01

We assessed liver fibrosis using real-time shear-wave elastography (SWE) combined with liver biopsy (LB) for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) and alanine transaminase < 2 times the upper limit of normal and hepatitis B virus DNA < 2000 IU/ml. A total of 107 patients met the inclusion criteria. Real- ime SWE and ultrasoundassisted liver biopsies were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic curve were performed to calculate the optimal area under the receiver operating characteristic curve for F0-F1 versus F2-F4, F0-F2 versus F3-F4, and F0-F3 versus F4 for real-time SWE. The most concurrent liver fibrosis degrees were between F1 and F2 for these HBeAg-negative CHB patients. Liver stiffness increased in parallel with the degree of liver fibrosis using SWE measurements. The area under the receiver operating characteristic curves was 0.881 (95% confidence interval [CI]: 0.704-1.000) for SWE (p = 0.004); 0.912 (95% CI: 0.836-0.987) for SWE (p = 0.000); 0.981 (95% CI: 0.956-1.000) for SWE (p = 0.000); 0.974 (95% CI: 0.936-1.000) for SWE (p = 0.000) when comparing F0 versus F1-F4, F0-F1 versus F2-F4, F0-F2 versus F3-F4, and F0-F3 versus F4, respectively. SWE has the advantage of providing an image of liver stiffness in real-time. As an alternative to LB, the development of all these noninvasive methods for dynamic evaluation of liver fibrosis will decrease the need for LB, making clinical care safer and more convenient for patients with liver diseases.

HABP2 p.G534E variant in patients with family history of thyroid and breast cancer

PubMed Central

Pinheiro, Maisa; Drigo, Sandra Aparecida; Tonhosolo, Renata; Andrade, Sonia C.S.; Marchi, Fabio Albuquerque; Jurisica, Igor; Kowalski, Luiz Paulo; Achatz, Maria Isabel; Rogatto, Silvia Regina

2017-01-01

Familial Papillary Thyroid Carcinoma (PTC) has been described as a hereditary predisposition cancer syndrome associated with mutations in candidate genes including HABP2. Two of 20 probands from families with history of PTC and breast carcinoma (BC) were evaluated by whole exome sequencing (WES) revealing HABP2 p.G534E. Sanger sequencing was used to confirm the involvement of this variant in three families (F1: 7 relatives; F2: 3 and F3: 3). The proband and his sister (with no malignant tumor so far) from F1 were homozygous for the variant whereas one relative with PTC from F2 was negative for the variant. Although the proband of the F3 with PTC was HABP2 wild type, three relatives presented the variant. Five of 170 healthy Brazilian individuals with no family history of BC or PTC and three of 50 sporadic PTC presented the p.G534E. These findings suggested no association of this variant with our familial PTC cases. Genes potentially associated with deregulation of the extracellular matrix organization pathway (CTSB, TNXB, COL4A3, COL16A1, COL24A1, COL5A2, NID1, LOXL2, MMP11, TRIM24 and MUSK) and DNA repair function (NBN and MSH2) were detected by WES, suggesting that other cancer-associated genes have pathogenic effects in the risk of familial PTC development. PMID:28402931

Bibliography of Soviet Laser Developments, Number 83, May - June 1986.

DTIC Science & Technology

1987-09-01

Polymethine ..................... 8 d. Coumarin .. .o-... . .. . e. Phthalimide ................. --- f. Cyanine ....................... . - - g. Xanthene...KVEKA, no. 6, 1986, 1155-1160. 25. Kostanyan, R.B.; Sanamyan, T.V. 0. Stucy on lifetimes of erbium levels in lutecium aluminum garnet. DANAA, no. 3, 1985...60, no. 5, 1986, 937-942. d. Coumarin e. Phthalimide f. Cyanine g. Xanthene h. POPOP 2. Inorganic Liquids C. GAS LASERS 1. Theory 60. Basov, N.G

Fatigue Management for Aerospace Expeditionary Forces Deployment and Sustained Operations

DTIC Science & Technology

2001-04-01

Aerospace Expeditionary Forces Deployment and Sustained Operations Contract Number Grant Number Program Element Number Author(s) LeClair, Michael A...3. F. Whitten Peters and Michael E. Ryan , US Air Force Posture State­ ment 2000, 30–31. 4. M. R. Rosekind et al., “From Laboratory to Flightdeck...Corporate Aviation Safety Semi­ nar, Flight Safety Foundation, St. Louis, Mo., 1994. 4. Philippa H. Gander, Mark R. Rosekind, and Kevin B. Gregory

Proceedings of the Symposium on Fluid-Solid Surface Intractions (2nd) Held at the Naval Ship Research and Development Center, Bethesda, Maryland, June 5-7, 1974,

DTIC Science & Technology

1974-11-29

6 . It is reasonable to define 0.01 < C/ 6 ( 4 ) as a boundary to the slip flow regime...stress layer. The result is 7 Z (2- aE RE 100 (42)7 2-a £1 + 7 • 1 6 aE The parameter 6 /Z is the same as that given in section 4 . Again, values below...Selective adsorption data for "He on clean NaF. After Meyers et alE., reference 30. A B 4 4 He (80K) Ho o NoFL 2wr - 6.07 -’ N = 6 . 7 K- F 1.9 2 A Kx (-) 4

Calibration of 3D ALE finite element model from experiments on friction stir welding of lap joints

NASA Astrophysics Data System (ADS)

Fourment, Lionel; Gastebois, Sabrina; Dubourg, Laurent

2016-10-01

In order to support the design of such a complex process like Friction Stir Welding (FSW) for the aeronautic industry, numerical simulation software requires (1) developing an efficient and accurate Finite Element (F.E.) formulation that allows predicting welding defects, (2) properly modeling the thermo-mechanical complexity of the FSW process and (3) calibrating the F.E. model from accurate measurements from FSW experiments. This work uses a parallel ALE formulation developed in the Forge® F.E. code to model the different possible defects (flashes and worm holes), while pin and shoulder threads are modeled by a new friction law at the tool / material interface. FSW experiments require using a complex tool with scroll on shoulder, which is instrumented for providing sensitive thermal data close to the joint. Calibration of unknown material thermal coefficients, constitutive equations parameters and friction model from measured forces, torques and temperatures is carried out using two F.E. models, Eulerian and ALE, to reach a satisfactory agreement assessed by the proper sensitivity of the simulation to process parameters.

The association of GSK3 beta with E2F1 facilitates nerve growth factor-induced neural cell differentiation.

PubMed

Zhou, Fangfang; Zhang, Long; Wang, Aijun; Song, Bo; Gong, Kai; Zhang, Lihai; Hu, Min; Zhang, Xiufang; Zhao, Nanming; Gong, Yandao

2008-05-23

It is widely acknowledged that E2F1 and GSK3beta are both involved in the process of cell differentiation. However, the relationship between E2F1 and GSK3beta in cell differentiation has yet to be discovered. Here, we provide evidence that in the differentiation of PC12 cells induced by nerve growth factor (NGF), GSK3beta was increased at both the mRNA and protein levels, whereas E2F1 at these two levels was decreased. Both wild-type GSK3beta and its kinase-defective mutant GSK3beta KM can inhibit E2F1 by promoting its ubiquitination through physical interaction. In addition, the colocalization of GSK3beta and E2F1 and their subcellular distribution, regulated by NGF, were observed in the process of PC12 differentiation. At the tissue level, GSK3beta colocalized and interacted with E2F1 in mouse hippocampus. Furthermore, GSK3beta facilitated neurite outgrowth by rescuing the promoter activities of Cdk inhibitors p21 and p15 from the inhibition caused by E2F1. To summarize, our findings suggest that GSK3beta can promote the ubiquitination of E2F1 via physical interaction and thus inhibit its transcription activity in a kinase activity independent manner, which plays an important role in the NGF-induced PC12 differentiation.

49 CFR 173.52 - Classification codes and compatibility groups of explosives.

Code of Federal Regulations, 2013 CFR

2013-10-01

... or hypergolic liquid) E 1.1E1.2E 1.4E Article containing a secondary detonating explosive substance....1E 1.1F 1.1G 1.1J 1.1L 9 1.2 1.2B 1.2C 1.2D 1.2E 1.2F 1.2G 1.2H 1.2J 1.2K 1.2L 10 1.3 1.3C 1.3F 1.3G...

77 FR 10358 - Acceptance of ASTM F963-11 as a Mandatory Consumer Product Safety Standard

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... Safety. Pursuant to section 106 of the Consumer Product Safety Improvement Act of 2008, ASTM F963-11 will... INFORMATION: On February 10, 2009, section 106(a) of the Consumer Product Safety Improvement Act of 2008... CONSUMER PRODUCT SAFETY COMMISSION 16 CFR Chapter II Acceptance of ASTM F963-11 as a Mandatory...

The Acquisition of Relative Clauses: How Do Second Language Learners of Arabic Do It?

ERIC Educational Resources Information Center

Algady, Dola

2013-01-01

The new developments in syntactic theory under Minimalism reconsiders the relation between the language faculty and general cognitive systems whereby language acquisition is accomplished by the interaction of Chomsky (2005)'s three factors: (F1) a minimally specified UG (Genetic endowment); (F2) Primary Linguistic Data (PLD), i.e., input; and (F3)…

Inhibitory effect of fermented Arctium lappa fruit extract on the IgE-mediated allergic response in RBL‑2H3 cells.

PubMed

Yoo, Jae-Myung; Yang, Ju Hye; Yang, Hye Jin; Cho, Won-Kyung; Ma, Jin Yeul

2016-02-01

Arctium lappa fruit has been used in traditional medicine, and it is known to exert beneficial effects, such as antioxidant, anti-inflammatory and anticancer effects. However, the effects of the Arctium lappa fruit on the allergic response remain unknown. In this study, we evaluated the anti-allergic effects of Arctium lappa fruit extract (AFE) and its fermented form (F-AFE) using immunoglobulin E (IgE)-activated RBL‑2H3 cells. To investigate the anti-allergic effects of AFE or F-AFE, we examined the release of β-hexosaminidase, a key biomarker of degranulation during an allergic reaction, and the production of pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) in the cells treated with or without the above-mentioned extracts. AFE weakly inhibited the release of β-hexosaminidase, whereas F-AFE significantly suppressed the release of β-hexosaminidase in a dose-dependent manner. Consistently, F-AFE suppressed the production of TNF-α and PGE2 in a dose-dependent manner. F-AFE exerted an inhibitory effect on the production of β-hexosaminidase, TNF-α and PGE2 with an IC50 value of 30.73, 46.96 and 36.27 µg/ml, respectively. Furthermore, F-AFE inhibited the phosphorylation of Lyn, Fyn and Syk, which are involved in the FcεRI signaling pathway, that of phosphoinositide phospholipase C (PLC)γ1/2 and protein kinase C (PKC)δ, which are associated with the degranulation process, as well as that of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK), p38 and Akt, which are associated with cytokine expression. In the late phase, F-AFE partially suppressed the phosphorylation of cytosolic phospholipase A2 (cPLA2), but not the expression of cyclooxygenase (COX)-2. To compare and identify the major components of the two extracts, we used high-performance liquid chromatography. The levels of arctigenin, one of the major compounds, were elevated 6-fold in F-AFE compared with AFE, whereas the levels of arctiin, an arctigenin glycoside, were decreased in F-AFE by approximately 57.40%. These results suggest that arctigenin plays an important role in the anti-allergic effects of F-AFE. Taken together, F-AFE containing anti-allergic phytochemicals, including arctigenin, inhibited the activation of the FcεRI receptor induced by the antigen‑IgE complex. Such effects may provide further information for the development of a phytomedicine for allergic diseases.

Effect and Tolerability of Agalsidase Alfa in Patients with Fabry Disease Who Were Treatment Naïve or Formerly Treated with Agalsidase Beta or Agalsidase Alfa.

PubMed

Goker-Alpan, Ozlem; Nedd, Khan; Shankar, Suma P; Lien, Yeong-Hau H; Weinreb, Neal; Wijatyk, Anna; Chang, Peter; Martin, Rick

2015-01-01

In a multicenter, open-label, treatment protocol (HGT-REP-059; NCT01031173), clinical effects and tolerability of agalsidase alfa (agalα; 0.2 mg/kg every other week) were evaluated in patients with Fabry disease who were treatment naïve or switched from agalsidase beta (switch). Over 24 months, data were collected on the safety profile; renal and cardiac parameters were assessed using estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), and midwall fractional shortening (MFS). Enrolled patients included 71 switch (median [range] age, 46.6 [5-84] years; male to female [M:F], 40:31) and 29 treatment naïve (38.7 [12-74] years; M:F, 14:15). Adverse events (AEs) were consistent with the known safety profile of agalα. Two switch patients had hospitalization due to possibly/probably drug-related serious AEs (one with transient ischemic attack, one with infusion-related AEs). One switch and two treatment-naïve patients discontinued treatment because of AEs. Three patients (one each switch, treatment naïve, and previous agalα) died; no deaths were considered drug-related. There was no significant change from baseline in LVMI or MFS in either group. Similarly, eGFR remained stable; mean ± standard error annualized change in eGFR (mL/min/1.73 m(2)) was -2.40 ± 1.04 in switch and -1.68 ± 2.21 in treatment-naïve patients. This is the largest cohort of patients with Fabry disease who were started on or switched to agalα in an FDA-accepted protocol during a worldwide supply shortage of agalsidase beta. Because this protocol was primarily designed to provide access to agalα, there were limitations, including not having stringent selection criteria and the lack of a placebo group.

Development of Methods and Facilities for Radio-Wave UHF Diagnostics of Plane-layered Dielectric Structures

DTIC Science & Technology

2010-02-05

Herzberger Yu. Introduction to interval computation. 1983 5. Gutman S . Identification of multilayered particles from scattering...66 68 70 72 74 76 -3 -2.5 -2 -1.5 -1 -0.5 0 0.5 f, GHz an gl e( V s ) , ra d 1 2 1 2 Fig. 5. Modeling of exfoliation in plate. Two plexiglass...1 10 0 |V s | 58 60 62 64 66 68 70 72 74 76 -3 -2.5 -2 -1.5 -1 -0.5 f, GHz an gl e( V s ) , ra d Fig. 7. Two plexiglass plates without a gap 58

Three-color FRET expands the ability to quantify the interactions of several proteins involved in actin filament nucleation

NASA Astrophysics Data System (ADS)

Wallrabe, Horst; Sun, Yuansheng; Fang, Xiaolan; Periasamy, Ammasi; Bloom, George

2012-03-01

With traditional 2-color Förster Resonance Energy Transfer (FRET) microscopy, valuable quantitative analyses can be conducted. Correlations of donor (D), acceptor (A) and their ratios (D:A) with energy transfer efficiency (E%) or distance (r) allows measurement of changes between control and experimental samples; also, clustered vs. random assembly of cellular components can be differentiated. Essentially, only the above three parameters D, A and D:A vs. E% are the basis for these deductions. 3-color FRET uses the same basic parameters, but exponentially expands the opportunities to quantify interrelationships among 3 cellular components. We investigated a number of questions based on the results of a triple combination (F1-F2-F3) of TFPNWASP/ Venus-IQGAP1/mCherry-Actin - all involved in the nucleation of actin - to apply the extensive analysis assay possible with 3-color FRET. How do changing N-WASP or IQGAP1 fluorescence levels affect actin fluorescence? What is the effect on E% of NWASP-actin by IQGAP1 or E% of IQGAP1-actin by N-WASP? These and other questions are explored in the context of all proteins of interest being in FRET distance vs. any two in the absence of the third. 4 cases are compared based on bleed-through corrected FRET: (1) all 3 interact, (2) only F1- F3 and F2-F3 [not F1-F2], (3) only F1-F2 and F2-F3 interact [not F1-F3], (4) only F1-F2 and F1-F3 interact [not F2-F3]. Other than describing the methodology in detail, several biologically relevant results are presented showing how E% (i.e. distance), fluorescence levels and ratios are affected in each of the cases. These correlations can only be observed in a 3-fluorophore combination. 3-color FRET will greatly expand the investigative range of quantitative analysis for the life-science researcher.

National Dam Safety Program. Lake Wanda Dam (NJ00510), Hudson River Basin, Tributary to Wawayanda Creek, Sussex County, New Jersey. Phase 1 Inspection Report.

DTIC Science & Technology

1980-03-01

8217 7rA’Al’A𔄀 /O’ 3 4 5 $-eS 7W# 55 Af1--7;72 6 10 12 - . . . . . ... . . . . . .’ . . .. 13 l 14 15 £ F6 3I f’f . 16 A6 18 19 200 _.._. . . . .. . . . 21’ 22...191, ~ C! . .. .. C.C C C L. C . C W .C . . . .C .C . . . .C .C . . . . .C . C . C C. . C . C 4 4 . . . a CC aa acca a aa aa C C

Therapeutic Strategies Against Cyclin E1 Amplified Ovarian Cancers

DTIC Science & Technology

2017-10-01

interaction will lead to enhancement of RB/E2F interaction and suppression of E2F- dependent oncogenic activity resulting in activity against CCNE1-amplified...relevant for CCNE1-amplified ovarian tumors which are dependent on hyperactive HR and are sensitive to suppression of BRCA1. 15. SUBJECT TERMS Ovarian...enhancement of RB/E2F interaction and suppression of E2F- dependent oncogenic activity resulting in activity against CCNE1-amplified cells. In the third

Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation.

PubMed

Ly, Lundi; Chan, Donovan; Aarabi, Mahmoud; Landry, Mylène; Behan, Nathalie A; MacFarlane, Amanda J; Trasler, Jacquetta

2017-07-01

Do paternal exposures to folic acid deficient (FD), and/or folic acid supplemented (FS) diets, throughout germ cell development adversely affect male germ cells and consequently offspring health outcomes? Male mice exposed over their lifetimes to both FD and FS diets showed decreased sperm counts and altered imprinted gene methylation with evidence of transmission of adverse effects to the offspring, including increased postnatal-preweaning mortality and variability in imprinted gene methylation. There is increasing evidence that disruptions in male germ cell epigenetic reprogramming are associated with offspring abnormalities and intergenerational disease. The fetal period is the critical time of DNA methylation pattern acquisition for developing male germ cells and an adequate supply of methyl donors is required. In addition, DNA methylation patterns continue to be remodeled during postnatal spermatogenesis. Previous studies have shown that lifetime (prenatal and postnatal) folic acid deficiency can alter the sperm epigenome and increase the incidence of fetal morphological abnormalities. Female BALB/c mice (F0) were placed on one of four amino-acid defined diets for 4 weeks before pregnancy and throughout pregnancy and lactation: folic acid control (Ctrl; 2 mg/kg), 7-fold folic acid deficient (7FD; 0.3 mg/kg), 10-fold high FS (10FS, 20 mg/kg) or 20-fold high FS (20FS, 40 mg/kg) diets. F1 males were weaned to their respective prenatal diets to allow for diet exposure during all windows of germline epigenetic reprogramming: the erasure, re-establishment and maintenance phases. F0 females were mated with chow-fed males to produce F1 litters whose germ cells were exposed to the diets throughout embryonic development. F1 males were subsequently mated with chow-fed female mice. Two F2 litters, unexposed to the experimental diets, were generated from each F1 male; one litter was collected at embryonic day (E)18.5 and one delivered and followed postnatally. DNA methylation at a global level and at the differentially methylated regions of imprinted genes (H19, Imprinted Maternally Expressed Transcript (Non-Protein Coding)-H19, Small Nuclear Ribonucleoprotein Polypeptide N-Snrpn, KCNQ1 Opposite Strand/Antisense Transcript 1 (Non-Protein Coding)-Kcnq1ot1, Paternally Expressed Gene 1-Peg1 and Paternally Expressed Gene 3-Peg3) was assessed by luminometric methylation analysis and bisulfite pyrosequencing, respectively, in F1 sperm, F2 E18.5 placenta and F2 E18.5 brain cortex. F1 males exhibited lower sperm counts following lifetime exposure to both folic acid deficiency and the highest dose of folic acid supplementation (20FS), (both P < 0.05). Post-implantation losses were increased amongst F2 E18.5 day litters from 20FS exposed F1 males (P < 0.05). F2 litters derived from both 7FD and 20FS exposed F1 males had significantly higher postnatal-preweaning pup death (both P < 0.05). Sperm from 10FS exposed males had increased variance in methylation across imprinted gene H19, P < 0.05; increased variance at a few sites within H19 was also found for the 7FD and 20FS groups (P < 0.05). While the 20FS diet resulted in inter-individual alterations in methylation across the imprinted genes Snrpn and Peg3 in F2 E18.5 placenta, ≥50% of individual sites tested in Peg1 and/or Peg3 were affected in the 7FD and 10FS groups. Inter-individual alterations in Peg1 methylation were found in F2 E18.5 day 10FS group brain cortex (P < 0.05). Not applicable. The cause of the increase in postnatal-preweaning mortality was not investigated post-mortem. Further studies are required to understand the mechanisms underlying the adverse effects of folic acid deficiency and supplementation on developing male germ cells. Genome-wide DNA and histone methylome studies as well as gene expression studies are required to better understand the links between folic acid exposures, an altered germ cell epigenome and offspring outcomes. The findings of this study provide further support for paternally transmitted environmental effects. The results indicate that both folic acid deficiency and high dose supplementation can be detrimental to germ cell development and reproductive fitness, in part by altering DNA methylation in sperm. This study was supported by a grant to J.M.T. from the Canadian Institutes of Health Research (CIHR #89944). The authors declare they have no conflicts of interest. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Fast disintegrating films containing anastrozole as a dosage form for dysphagia patients.

PubMed

Satyanarayana, Dixit Anil; Keshavarao, Kulkarni Parthasarathi

2012-12-01

The objective of the present research was to ensure safety during oral administration of medications to dysphagia patients, by preparing fast disintegrating films (FDF) containing anastrozole (ANS) which disintegrate rapidly when placed on the tongue. Films were prepared by solvent-casting method using various polymers such as hydroxyl propyl methyl cellulose (HPMC E5 LV), hydroxy propyl cellulose (HPC), poly vinyl alcohol (PVA) and sodium alginate (Na Alginate). Among the formulations examined, film prepared using HPMC E5 LV (F1) exhibited shorter disintegration time (15 sec) with satisfactory mechanical properties. Fourier transformer infrared (FTIR) & differential scanning calorimetry (DSC) analysis revealed no chemical incompatibility between drug and excipients used in the formulation. Surface morphology revealed even distribution of ANS in the film. Dissolution of drug from F1 formulation was rapid with more than 90% drug release in 240 sec. Pharmacokinetic parameters showed no statistical difference between F1 (test) and drug solution (control) indicating comparable plasma level-time profiles. The film showed an excellent stability for 24 weeks when stored at refrigerated temperature (2-8°C). These findings suggest that the fast disintegrating film as a promising candidate for delivery of ANS in dysphagic patients.

Secretion and translocation signals and DspB/F-binding domains in the type III effector DspA/E of Erwinia amylovora.

PubMed

Oh, Chang-Sik; Carpenter, Sara C D; Hayes, Marshall L; Beer, Steven V

2010-04-01

DspA/E is a type III effector of Erwinia amylovora, the bacterial pathogen that causes fire blight disease in roseaceous plants. This effector is indispensable for disease development, and it is translocated into plant cells. A DspA/E-specific chaperone, DspB/F, is necessary for DspA/E secretion and possibly for its translocation. In this work, DspB/F-binding sites and secretion and translocation signals in the DspA/E protein were determined. Based on yeast two-hybrid assays, DspB/F was found to bind DspA/E within the first 210 amino acids of the protein. Surprisingly, both DspB/F and OrfA, the putative chaperone of Eop1, also interacted with the C-terminal 1059 amino acids of DspA/E; this suggests another chaperone-binding site. Secretion and translocation assays using serial N-terminal lengths of DspA/E fused with the active form of AvrRpt2 revealed that at least the first 109 amino acids, including the first N-terminal chaperone-binding motif and DspB/F, were required for efficient translocation of DspA/E, although the first 35 amino acids were sufficient for its secretion and the presence of DspB/F was not required. These results indicate that secretion and translocation signals are present in the N terminus of DspA/E, and that at least one DspB/F-binding motif is required for efficient translocation into plant cells.

An on-line acoustic fluorocarbon coolant mixture analyzer for the ATLAS silicon tracker

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bates, R.; Battistin, M.; Berry, S.

2011-07-01

The ATLAS silicon tracker community foresees an upgrade from the present octafluoro-propane (C{sub 3}F{sub 8}) evaporative cooling fluid - to a composite fluid with a probable 10-20% admixture of hexafluoro-ethane (C{sub 2}F{sub 6}). Such a fluid will allow a lower evaporation temperature and will afford the tracker silicon substrates a better safety margin against leakage current-induced thermal runaway caused by cumulative radiation damage as the luminosity profile at the CERN Large Hadron Collider increases. Central to the use of this new fluid is a new custom-developed speed-of-sound instrument for continuous real-time measurement of the C{sub 3}F{sub 8}/C{sub 2}F{sub 6} mixturemore » ratio and flow. An acoustic vapour mixture analyzer/flow meter with new custom electronics allowing ultrasonic frequency transmission through gas mixtures has been developed for this application. Synchronous with the emission of an ultrasound 'chirp' from an acoustic transmitter, a fast readout clock (40 MHz) is started. The clock is stopped on receipt of an above threshold sound pulse at the receiver. Sound is alternately transmitted parallel and anti-parallel with the vapour flow for volume flow measurement from transducers that can serve as acoustic transmitters or receivers. In the development version, continuous real-time measurement of C{sub 3}F{sub 8}/C{sub 2}F{sub 6} flow and calculation of the mixture ratio is performed within a graphical user interface developed in PVSS-II, the Supervisory, Control and Data Acquisition standard chosen for LHC and its experiments at CERN. The described instrument has numerous potential applications - including refrigerant leak detection, the analysis of hydrocarbons, vapour mixtures for semiconductor manufacture and anesthetic gas mixtures. (authors)« less

An On-Line Acoustic Fluorocarbon Coolant Mixture Analyzer for the ATLAS Silicon Tracker

NASA Astrophysics Data System (ADS)

Bates, R.; Battistin, M.; Berry, S.; Bitadze, A.; Bonneau, P.; Bousson, N.; Boyd, G.; Botelho-Direito, J.; DiGirolamo, B.; Doubek, M.; Egorov, K.; Godlewski, J.; Hallewell, G.; Katunin, S.; Mathieu, M.; McMahon, S.; Nagai, K.; Perez-Rodriguez, E.; Rozanov, A.; Vacek, V.; Vitek, M.

2012-10-01

The ATLAS silicon tracker community foresees an upgrade from the present octafluoropropane (C3F8) evaporative cooling fluid to a composite fluid with a probable 10-20% admixture of hexafluoroethane (C2F6). Such a fluid will allow a lower evaporation temperature and will afford the tracker silicon substrates a better safety margin against leakage current-induced thermal runaway caused by cumulative radiation damage as the luminosity profile at the CERN Large Hadron Collider increases. Central to the use of this new fluid is a new custom-developed speed-of-sound instrument for continuous real-time measurement of the C3F8/C2F6 mixture ratio and flow. An acoustic vapour mixture analyzer/flow meter with new custom electronics allowing ultrasonic frequency transmission through gas mixtures has been developed for this application. Synchronous with the emission of an ultrasound `chirp' from an acoustic transmitter, a fast readout clock (40 MHz) is started. The clock is stopped on receipt of an above threshold sound pulse at the receiver. Sound is alternately transmitted parallel and anti-parallel with the vapour flow for volume flow measurement from transducers that can serve as acoustic transmitters or receivers. In the development version, continuous real-time measurement of C3F8/C2F6 flow and calculation of the mixture ratio is performed within a graphical user interface developed in PVSS-II, the Supervisory, Control and Data Acquisition standard chosen for LHC and its experiments at CERN. The described instrument has numerous potential applications - including refrigerant leak detection, the analysis of hydrocarbons, vapour mixtures for semi-conductor manufacture and anesthetic gas mixtures.

Change in genetic size of small-closed populations: Lessons from a domestic mammal population.

PubMed

Ghafouri-Kesbi, Farhad

2010-10-01

The aim of this study was to monitor changes in genetic size of a small-closed population of Iranian Zandi sheep, by using pedigree information from animals born between 1991 and 2005. The genetic size was assessed by using measures based on the probability of identity-by-descend of genes (coancestry, f, and effective population size, N(e) ), as well as measures based on probability of gene origin (effective number of founders, f(e) , effective number of founder genomes, f(g) , and effective number of non-founder genomes, f(ne) ). Average coancestry, or the degree of genetic similarity of individuals, increased from 0.81% to 1.44% during the period 1993 to 2005, at the same time that N(e) decreased from 263 to 93. The observed trend for f(e) was irregular throughout the experiment in a way that f(e) was 68, 87, 77, 92, and 80 in 1993, 1996, 1999, 2002, and 2005, respectively. Simultaneously, f(g) , the most informative effective number, decreased from 61 to 35. The index of genetic diversity (GD) which was obtained from estimates of f(g) , decreased about 2% throughout the period studied. In addition, a noticeable reduction was observed in the estimates of f(ne) from 595 in 1993 to 61 in 2005. The higher than 1 ratio of f(e) to f(g) indicated the presence of bottlenecks and genetic drift in the development of this population of Zandi sheep. From 1993 to 1999, f(ne) was much higher than f(e) , thereby indicating that with respect to loss of genetic diversity, the unequal contribution of founders was more important than the random genetic drift in non-founder generations. Subsequently, random genetic drift in non-founder generations was the major reason for f(e) > f(ne) . The minimization of average coancestry in new reproductive individuals was recommended as a means of preserving the population against a further loss in genetic diversity.

A week 48 randomized phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naïve HIV-1 patients.

PubMed

Eron, Joseph J; Orkin, Chloe; Gallant, Joel; Molina, Jean-Michel; Negredo, Eugenia; Antinori, Andrea; Mills, Anthony; Reynes, Jacques; Van Landuyt, Erika; Lathouwers, Erkki; Hufkens, Veerle; Jezorwski, John; Vanveggel, Simon; Opsomer, Magda

2018-04-19

To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naïve, HIV-1-infected adults. Phase-3, randomized, active-controlled, double-blind, international, multicenter, noninferiority study (NCT02431247). Seven hundred and twenty-five participants were randomized (1 : 1) to D/C/F/TAF (362) or control (363). The primary objective was to demonstrate noninferiority of D/C/F/TAF vs. control for percentage viral load less than 50 copies/ml (FDA-snapshot analysis) at 48 weeks (10% margin). At week 48, D/C/F/TAF was noninferior to control (91.4 vs. 88.4% achieved viral load <50 copies/ml, respectively; difference 2.7%; 95% CI -1.6 to 7.1; P < 0.0001), with 4.4 vs. 3.3% of patients, respectively, having viral load at least 50 copies/ml. No treatment-emergent mutations associated with darunavir or TAF/TDF resistance were observed in either group. Only one patient (D/C/F/TAF) developed M184I/V conferring resistance to emtricitabine. Incidences of grades 3 and 4 adverse events (5 vs. 6%), serious adverse events (5 vs. 6%) and adverse event-related discontinuations (2 vs. 4%) were low and similar between groups. Mean decrease in urine protein/creatinine ratio was greater with D/C/F/TAF than control (-22.42 vs. -10.34 mg/g, P = 0.033). Mean percentage change in bone mineral density with D/C/F/TAF vs. control was 0.21 vs. -2.73%, P < 0.0001 (hip), -0.68 vs. -2.38%, P = 0.004 (lumbar spine), and -0.26 vs. -2.97%, P < 0.0001 (femoral neck). Median change from baseline in total cholesterol/HDL-cholesterol ratio was 0.20 vs. 0.08, P = 0.036. D/C/F/TAF achieved a high virologic suppression rate (91.4%) and was noninferior to darunavir/cobicistat with F/TDF. D/C/F/TAF also demonstrated the bone and renal safety advantages of TAF in combination with darunavir/cobicistat.

Atypical E2f functions are critical for pancreas polyploidization

PubMed Central

Moreno, Eva; Toussaint, Mathilda J. M.; Tooten, Peter C. J.; van Essen, Saskia C.; van Liere, Elsbeth A.; Youssef, Sameh A.; Bongiovanni, Laura; de Bruin, Alain

2018-01-01

The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age. PMID:29329320

Atypical E2f functions are critical for pancreas polyploidization.

PubMed

Matondo, Ramadhan B; Moreno, Eva; Toussaint, Mathilda J M; Tooten, Peter C J; van Essen, Saskia C; van Liere, Elsbeth A; Youssef, Sameh A; Bongiovanni, Laura; de Bruin, Alain

2018-01-01

The presence of polyploid cells in the endocrine and exocrine pancreas has been reported for four decades. In rodents, pancreatic polyploidization is initiated after weaning and the number of polyploid cells increases with age. Surprisingly the molecular regulators and biological functions of polyploidization in the pancreas are still unknown. We discovered that atypical E2f activity is essential for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new-born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and E2f8. In contrast to its critical role in embryonic survival, conditional deletion of both of both atypical E2fs in newborn mice had no impact on postnatal survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone was sufficient to suppress polyploidization in the pancreas and associated with only a minor decrease in blood serum levels of glucose, insulin, amylase and lipase under 4 hours starvation condition compared to wildtype littermates. In mice with fewer pancreatic polyploid cells that were fed ad libitum, no major impact on hormones or enzymes levels was observed. In summary, we identified atypical E2fs to be essential for polyploidization in the pancreas and discovered that postnatal induced loss of both atypical E2fs in many organs is compatible with life until old age.

A General Purpose Ionospheric Ray Tracing Procedure

DTIC Science & Technology

1993-08-01

hmE-bmF2) /ymF2) al(2)=chap( .5d0,2.d09 (hmPl- bmE )/ymE) a2 (2) =1. a3(2)-chap(l.dOl .4142d09 (bm~l.-hmP2) ymP2) al(3)=chap( .5d0,2.d0*(bmF2- bmE )iymE...R.H Clarke, Radiowave Propagation 1 Libraries and Information Services Australian Government Publishing Service 1 Defence Central Library - Technical

[miR-503-5p inhibits the proliferation of T24 and EJ bladder cancer cells by interfering with the Rb/E2F signaling pathway].

PubMed

Li, Xiaohui; Han, Xingtao; Yang, Jinhui; Sun, Jiantao; Wei, Pengtao

2017-10-01

Objective To observe the effect of microRNA-503-5p (miR-503-5p) on the growth of T24 and EJ bladder cancer cells, and explore the possible molecular mechanism. Methods The miR-504-5p mimics or miR-NC was transfected into T24 and EJ cells. The target gene of miR-503-5p was predicted by bioinformatics. The expressions of E2F transcription factor 3 (E2F3) mRNA and Rb/E2F signaling pathway mRNA were detected by the real-time quantitative PCR (qPCR). The expressions of Rb/E2F signal pathway proteins E2F3, cyclin E, CDK2, Rb and p-Rb were detected by Western blotting. The cell cycle of bladder cancer cell lines was determined by flow cytometry. MTT assay and plate cloning assay were performed to observe the proliferation ability of bladder cancer cells. Results After miR-503-5p mimics transfection, the expression of miR-503-5p in bladder cancer cells significantly increased. The increased expression of miR-503-5p significantly reduced the expressions of E2F3 mRNA and Rb/E2F signaling pathway mRNA in bladder cancer cells. What's more, the expressions of Rb/E2F signal pathway proteins were down-regulated. The bladder cancer cells were arrested in G0/G1 phase, and their growth was significantly inhibited by miR-503-5p. Conclusion The miR-503-5p over-expression can inhibit the growth of bladder cancer cell lines T24 and EJ by down-regulating the expression of the Rb/E2F signaling pathway.

77 FR 35850 - Safety Zone; F/V Deep Sea, Penn Cove, WA

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

... 1625-AA00 Safety Zone; F/V Deep Sea, Penn Cove, WA AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a safety zone around the Fishing Vessel (F/V) Deep Sea... with the sunken F/V Deep Sea. B. Basis and Purpose On the evening of May 13, 2012, the F/V Deep Sea...

Comparison of Ion Chemistries in Octafluoro-2-butene (2-C4F8) and in Octfluorocyclobutane (c-C4F8)

NASA Astrophysics Data System (ADS)

Jiao, Charles; Dejoseph, Charles; Garscadden, Alan

2007-10-01

2-C4F8 is one of the promising candidates to replace c-C4F8 that has been widely used for dielectric etching but is not environmentally friendly. In this study we have investigated electron impact ionization and ion-molecule reactions of 2-C4F8 using Fourier transform mass spectrometry (FTMS), and compared the results with those of c-C4F8 we have studied previously. Electron impact ionization of 2-C4F8 produces 15 ionic species including C4F7,8^+, C3F3,5,6^+, C2F4^+ and CF1-3^+ as the major ions. The total ionization cross section of 2-C4F8 reaches a maximum of 1.8x10-15 cm^2 at 90 eV. The ionization is dominated by the channel forming the parent ion C4F8^+ from 12 to 18 eV, and by the channel forming C3F5^+ from 18 to 70 eV. After 70 eV, CF3^+ becomes the dominant product ion. Among the major ions generated from the electron impact ionization of 2-C4F8, only CF^+, CF2^+ and CF3^+ are found to react with 2-C4F8, via F^- abstraction or charge transfer mechanism. The charge transfer reaction of Ar^++2-C4F8 produces primarily C4F7^+.

Characterization of two genes encoding the Mycobacterium tuberculosis ribonucleotide reductase small subunit.

PubMed Central

Yang, F; Curran, S C; Li, L S; Avarbock, D; Graf, J D; Chua, M M; Lu, G; Salem, J; Rubin, H

1997-01-01

Two nrdF genes, nrdF1 and nrdF2, encoding the small subunit (R2) of ribonucleotide reductase (RR) from Mycobacterium tuberculosis have 71% identity at the amino acid level and are both highly homologous with Salmonella typhimurium R2F. The calculated molecular masses of R2-1 and R2-2 are 36,588 (322 amino acids [aa]) and 36,957 (324 aa) Da, respectively. Western blot analysis of crude M. tuberculosis extracts indicates that both R2s are expressed in vivo. Recombinant R2-2 is enzymatically active when assayed with pure recombinant M. tuberculosis R1 subunit. Both ATP and dATP are activators for CDP reduction up to 2 and 1 mM, respectively. The gene encoding M. tuberculosis R2-1, nrdF1, is not linked to nrdF2, nor is either gene linked to the gene encoding the large subunit, M. tuberculosis nrdE. The gene encoding MTP64 was found downstream from nrdF1, and the gene encoding alcohol dehydrogenase was found downstream from nrdF2. A nrdA(Ts) strain of E. coli (E101) could be complemented by simultaneous transformation with M. tuberculosis nrdE and nrdF2. An M. tuberculosis nrdF2 variant in which the codon for the catalytically necessary tyrosine was replaced by the phenylalanine codon did not complement E101 when cotransformed with M. tuberculosis nrdE. Similarly, M. tuberculosis nrdF1 and nrdE did not complement E101. Activity of recombinant M. tuberculosis RR was inhibited by incubating the enzyme with a peptide corresponding to the 7 C-terminal amino acid residues of the R2-2 subunit. M. tuberculosis is a species in which a nrdEF system appears to encode the biologically active species of RR and also the only bacterial species identified so far in which class I RR subunits are not arranged on an operon. PMID:9335290

A laboratory assessment of the potential effect of Cry1Ab/Cry2Aj-containing Bt maize pollen on Folsomia candida by toxicological and biochemical analyses.

PubMed

Zhang, Bing; Yang, Yan; Zhou, Xiang; Shen, Ping; Peng, Yufa; Li, Yunhe

2017-03-01

The common soil arthropod Folsomia candida can survive well when fed only maize pollen and thus may be exposed to insecticidal proteins by ingesting insect-resistant genetically engineered maize pollen containing Bacillus thuringiensis (Bt) proteins when being released into the soil. Laboratory experiments were conducted to assess the potential effects of Cry1Ab/Cry2Aj-producing transgenic Bt maize (Shuangkang 12-5) pollen on F. candida fitness. Survival, development, and the reproduction were not significantly reduced when F. candida fed on Bt maize pollen rather than on non-Bt maize pollen, but these parameters were significantly reduced when F. candida fed on non-Bt maize pollen containing the protease inhibitor E-64 at 75 μg/g pollen. The intrinsic rate of increase (r m ) was not significantly reduced when F. candida fed on Bt maize pollen but was significantly reduced when F. candida fed on non-Bt maize pollen containing E-64. The activities of antioxidant-related enzymes in F. candida were not significantly affected when F. candida fed on Bt maize pollen but were significantly increased when F. candida fed on non-Bt pollen containing E-64. The results demonstrate that consumption of Bt maize pollen containing Cry1Ab/Cry2Aj has no lethal or sublethal effects on F. candida. Copyright © 2017 Elsevier Ltd. All rights reserved.

Estimation of the fraction of absorbed photosynthetically active radiation (fPAR) in maize canopies using LiDAR data and hyperspectral imagery.

PubMed

Qin, Haiming; Wang, Cheng; Zhao, Kaiguang; Xi, Xiaohuan

2018-01-01

Accurate estimation of the fraction of absorbed photosynthetically active radiation (fPAR) for maize canopies are important for maize growth monitoring and yield estimation. The goal of this study is to explore the potential of using airborne LiDAR and hyperspectral data to better estimate maize fPAR. This study focuses on estimating maize fPAR from (1) height and coverage metrics derived from airborne LiDAR point cloud data; (2) vegetation indices derived from hyperspectral imagery; and (3) a combination of these metrics. Pearson correlation analyses were conducted to evaluate the relationships among LiDAR metrics, hyperspectral metrics, and field-measured fPAR values. Then, multiple linear regression (MLR) models were developed using these metrics. Results showed that (1) LiDAR height and coverage metrics provided good explanatory power (i.e., R2 = 0.81); (2) hyperspectral vegetation indices provided moderate interpretability (i.e., R2 = 0.50); and (3) the combination of LiDAR metrics and hyperspectral metrics improved the LiDAR model (i.e., R2 = 0.88). These results indicate that LiDAR model seems to offer a reliable method for estimating maize fPAR at a high spatial resolution and it can be used for farmland management. Combining LiDAR and hyperspectral metrics led to better performance of maize fPAR estimation than LiDAR or hyperspectral metrics alone, which means that maize fPAR retrieval can benefit from the complementary nature of LiDAR-detected canopy structure characteristics and hyperspectral-captured vegetation spectral information.

Population pharmacokinetics of lyophilized recombinant glucagon-like peptide-1 receptor agonist (recombinant exendin-4, rE-4) in Chinese patients with type 2 diabetes mellitus
.

PubMed

Zang, Yan-Nan; Zhang, Min-Jie; Wang, Yi-Tong; Wang, Chen; Wang, Qian; Zheng, Qing-Shan; Ji, Li-Nong; Guo, Wei; Fang, Yi

2017-08-01

To investigate the population pharmacokinetics of lyophilized recombinant glucagon-like peptide-1 receptor agonist (rE-4) in Chinese patients with type 2 diabetes mellitus (T2DM) for plasma concentration estimation and individualized treatment. Twelve patients with T2DM were enrolled to receive subcutaneous injections of rE-4 at 5 µg twice daily for 84 days. Administration dosage was adjusted from 5 µg to 10 µg twice daily at day 29 in case of glycated albumin (GA) ≥ 17%. The population pharmacokinetic model was developed in the nonlinear mixed-effects modeling software NONMEM. The data were best described by a two-compartment model with first-order absorption and elimination. The outcome parameters were as follows: apparent clearance (CL/F) 6.67 L/h, apparent distribution volume of central compartment (V_c/F) 19.4 L, absorption rate constant (K_a) 1.39 h^-1, apparent distribution volume of peripheral compartment (V_p/F) 22.6 L, intercompartmental clearance (Q/F) 1.28 L/h. The interindividual variabilities for CL/F, V_c/F, K_a, and Q/F were 64.4%, 57.7%, 45.5%, and 153.3%, respectively. The intra-individual variability of proportional error model was 41.7%. No covariate was screened out that showed significant influence on the model parameters. The established two-compartment model with first-order absorption and elimination successfully described the pharmacokinetic characteristics of rE-4 in Chinese patients with T2DM.
.

26 CFR 1.263A-0 - Outline of regulations under section 263A.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) In general. (ii) Pre-production costs. (iii) Post-production costs. (4) Practical capacity concept...) Taxes. (M) Insurance. (N) Utilities. (O) Repairs and maintenance. (P) Engineering and design costs. (Q... processing services. (E) Engineering and design services. (F) Safety engineering services. (v) Accounting...

78 FR 28652 - Advisory Committee on the Medical Uses of Isotopes: Call for Nominations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-15

...; (d) therapy physicist; (e) radiation safety officer; (f) nuclear pharmacist; (g) two radiation... NUCLEAR REGULATORY COMMISSION Advisory Committee on the Medical Uses of Isotopes: Call for Nominations AGENCY: U.S. Nuclear Regulatory Commission. ACTION: Call for Nominations. SUMMARY: The U.S...

77 FR 62538 - Advisory Committee on the Medical Uses of Isotopes: Call for Nominations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-15

...) nuclear medicine physicist; (d) therapy medical physicist; (e) radiation safety officer; (f) nuclear... NUCLEAR REGULATORY COMMISSION Advisory Committee on the Medical Uses of Isotopes: Call for Nominations AGENCY: U.S. Nuclear Regulatory Commission. ACTION: Call for nominations. SUMMARY: The U.S...

29 CFR 1910.212 - General requirements for all machines.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Machinery and Machine Guarding § 1910.212...) Alligator shears. (d) Power presses. (e) Milling machines. (f) Power saws. (g) Jointers. (h) Portable power...) Anchoring fixed machinery. Machines designed for a fixed location shall be securely anchored to prevent...

29 CFR 1910.212 - General requirements for all machines.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Machinery and Machine Guarding § 1910.212...) Alligator shears. (d) Power presses. (e) Milling machines. (f) Power saws. (g) Jointers. (h) Portable power...) Anchoring fixed machinery. Machines designed for a fixed location shall be securely anchored to prevent...

29 CFR 1910.212 - General requirements for all machines.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., DEPARTMENT OF LABOR OCCUPATIONAL SAFETY AND HEALTH STANDARDS Machinery and Machine Guarding § 1910.212...) Alligator shears. (d) Power presses. (e) Milling machines. (f) Power saws. (g) Jointers. (h) Portable power...) Anchoring fixed machinery. Machines designed for a fixed location shall be securely anchored to prevent...

Genetic architecture of atherosclerosis dissected by QTL analyses in three F2 intercrosses of apolipoprotein E-null mice on C57BL6/J, DBA/2J and 129S6/SvEvTac backgrounds

PubMed Central

Makhanova, Natalia; Morgan, Andrew P.; Kayashima, Yukako; Makhanov, Andrei; Hiller, Sylvia; Zhilicheva, Svetlana; Xu, Longquan; Pardo-Manuel de Villena, Fernando; Maeda, Nobuyo

2017-01-01

Quantitative trait locus (QTL) analyses of intercross populations between widely used mouse inbred strains provide a powerful approach for uncovering genetic factors that influence susceptibility to atherosclerosis. Epistatic interactions are common in complex phenotypes and depend on genetic backgrounds. To dissect genetic architecture of atherosclerosis, we analyzed F2 progeny from a cross between apolipoprotein E-null mice on DBA/2J (DBA-apoE) and C57BL/6J (B6-apoE) genetic backgrounds and compared the results with those from two previous F2 crosses of apolipoprotein E-null mice on 129S6/SvEvTac (129-apoE) and DBA-apoE backgrounds, and B6-apoE and 129-apoE backgrounds. In these round-robin crosses, in which each parental strain was crossed with two others, large-effect QTLs are expected to be detectable at least in two crosses. On the other hand, observation of QTLs in one cross only may indicate epistasis and/or absence of statistical power. For atherosclerosis at the aortic arch, Aath4 on chromosome (Chr)2:66 cM follows the first pattern, with significant QTL peaks in (DBAx129)F2 and (B6xDBA)F2 mice but not in (B6x129)F2 mice. We conclude that genetic variants unique to DBA/2J at Aath4 confer susceptibility to atherosclerosis at the aortic arch. A similar pattern was observed for Aath5 on chr10:35 cM, verifying that the variants unique to DBA/2J at this locus protect against arch plaque development. However, multiple loci, including Aath1 (Chr1:49 cM), and Aath2 (Chr1:70 cM) follow the second type of pattern, showing significant peaks in only one of the three crosses (B6-apoE x 129-apoE). As for atherosclerosis at aortic root, the majority of QTLs, including Ath29 (Chr9:33 cM), Ath44 (Chr1:68 cM) and Ath45 (Chr2:83 cM), was also inconsistent, being significant in only one of the three crosses. Only the QTL on Chr7:37 cM was consistently suggestive in two of the three crosses. Thus QTL analysis of round-robin crosses revealed the genetic architecture of atherosclerosis. PMID:28837567

Update of Aircraft Profile Data for the Integrated Noise Model Computer Program. Volume 1. Final Report

DTIC Science & Technology

1992-03-01

general aviation 53 Cop. Fleet 1985 BUSINESS JET 1i F turbojet & turbofan 55 Gates LEAR 25 CJ610-8 1 E,F 54 Gates LEAR 36 TFE731 -2 3 E,F...Cessna CI1 3 TFE731 -3-1005 3 * E,F 60 Mitsubishi MU300-10 J3I1D-4 3 E,F 58 Canadair CL600 ALFSO2L 3 E, 61 Canadair CL601 CF34-3A 3 E,F 62 Israel A/C ASIRA...1125 TFE731 -3A 3 EF S.. ... .. ... ... .. . .. ... .............. - - - - - - - - - - - - - - - --I.....- -- --- -- - - -------.-- -- - - -- - 4

78 FR 71033 - Pipeline Safety: Information Collection Activities, Revisions to Incident and Annual Reports for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-27

... Reports for Gas Pipeline Operators AGENCY: Pipeline and Hazardous Materials Safety Administration, DOT... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket No... Pipeline Systems; PHMSA F 7100.2-1 Annual Report for Calendar Year 20xx Natural and Other Gas Transmission...

Mitochondrial ribosomal protein S18-2 is highly expressed in endometrial cancers along with free E2F1

PubMed Central

Iurchenko, Natalia; Kovalevska, Larysa; Stip, Maria C; Budnikova, Daria; Andersson, Sonia; Polischuk, Ludmila; Buchynska, Lubov; Kashuba, Elena

2016-01-01

Endometrial cancer (EC) is one of the most frequent causes of cancer death among women in developed countries. Histopathological diagnosis and imaging techniques for EC are limited, thus new prognostic markers are needed to offer patients the best treatment and follow-up. In the present paper we showed that the level of mitochondrial ribosomal protein MRPS18-2 (S18-2) increased in EC compared with the normal endometrium and hyperplasia, based on a study of 42 patient biopsies. Importantly, high expression of free E2F1 in EC correlates well with high S18-2 expression. The EC cell line HEC-1-A, which overexpresses S18-2 constitutively, showed an increased proliferation capacity in vitro and in vivo (in SCID mice). Moreover, pan-keratin, beta-catenin and E-cadherin signals are diminished in these cells, compared to the parental HEC-1-A line, in contrast to vimentin signal that is increased. This may be associated with epithelial-mesenchymal cell transition (EMT). We conclude that high expression of S18-2 and free E2F1, and low pan-keratin, beta-catenin, and E-cadherin signals might be a good set of prognostic markers for EC. PMID:26959119

Training Strategies and Materials : Use of Flashing Yellow Operations to Improve Safety at Signals with Protected-Permissive Left Turn (PPLT) Operations

DOT National Transportation Integrated Search

2012-08-01

TxDOT project 0-6568 Use of Flashing Yellow Operations to Improve Safety at Signals with : Protected-Permissive Left Turn (PPLT) Operations has developed guidelines for : implementation of FYA PPLT displays including general guidelines on the F...

Macro-level safety analysis of pedestrian crashes in Shanghai, China.

PubMed

Wang, Xuesong; Yang, Junguang; Lee, Chris; Ji, Zhuoran; You, Shikai

2016-11-01

Pedestrian safety has become one of the most important issues in the field of traffic safety. This study aims at investigating the association between pedestrian crash frequency and various predictor variables including roadway, socio-economic, and land-use features. The relationships were modeled using the data from 263 Traffic Analysis Zones (TAZs) within the urban area of Shanghai - the largest city in China. Since spatial correlation exists among the zonal-level data, Bayesian Conditional Autoregressive (CAR) models with seven different spatial weight features (i.e. (a) 0-1 first order, adjacency-based, (b) common boundary-length-based, (c) geometric centroid-distance-based, (d) crash-weighted centroid-distance-based, (e) land use type, adjacency-based, (f) land use intensity, adjacency-based, and (g) geometric centroid-distance-order) were developed to characterize the spatial correlations among TAZs. Model results indicated that the geometric centroid-distance-order spatial weight feature, which was introduced in macro-level safety analysis for the first time, outperformed all the other spatial weight features. Population was used as the surrogate for pedestrian exposure, and had a positive effect on pedestrian crashes. Other significant factors included length of major arterials, length of minor arterials, road density, average intersection spacing, percentage of 3-legged intersections, and area of TAZ. Pedestrian crashes were higher in TAZs with medium land use intensity than in TAZs with low and high land use intensity. Thus, higher priority should be given to TAZs with medium land use intensity to improve pedestrian safety. Overall, these findings can help transportation planners and managers understand the characteristics of pedestrian crashes and improve pedestrian safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

Benzo[a]pyrene and Benzo[k]fluoranthene in Some Processed Fish and Fish Products

PubMed Central

Olatunji, Olatunde S.; Fatoki, Olalekan S.; Opeolu, Beatrice O.; Ximba, Bhekumusa J.

2015-01-01

In this study, the concentration levels of the probable carcinogenic PAH fractions, benzo[a]pyrene (BaP) and benzo[k]fluoranthrene (BkF) in fillets of some processed fish species were investigated. Fish species comprising Merluccius poli (hake), Tyrsites atun (snoek), Seriola lalandi (yellow-tail) and Brama brama (angel fish) were bought in fish shops at Gordon’s Bay, Western Cape, South Africa. The fish were gutted, filleted and prepared for edibility by frying, grilling and boiling. Polycyclic aromatic hydrocarbons were extracted from each homogenized fish sample, cleaned-up using solid phase extraction (SPE), and analysed for the PAH fractions, BaP and BkF using a Gas Chromatograph coupled with a Flame Ionization Detector (GC-FID). The sum of the two PAHs (∑2PAH) i.e., BaP and BkF ranged between 0.56 and 1.46 µg/kg, in all boiled, grilled and fried fish species. The fried fish extracts showed significantly higher (p < 0.05) abundance of ∑2PAH, than grilled and boiled fish. Dietary safety and PAHs toxicity was also discussed. PMID:25607603

Dark Matter signals at the LHC from a 3HDM

NASA Astrophysics Data System (ADS)

Cordero, A.; Hernandez-Sanchez, J.; Keus, V.; King, S. F.; Moretti, S.; Rojas, D.; Sokolowska, D.

2018-05-01

We analyse new signals of Dark Matter (DM) at the Large Hadron Collider (LHC) in a 3-Higgs Doublet Model (3HDM) where only one doublet acquires a Vacuum Expectation Value (VEV), preserving a parity Z 2. The other two doublets are inert and do not develop a VEV, leading to a dark scalar sector controlled by Z 2, with the lightest CP-even dark scalar H 1 being the DM candidate. This leads to the loop induced decay of the next-to-lightest scalar, {H}_2\\to {H}_1f\\overline{f}(f=u,d,c,s,b,e,μ, τ ) , mediated by both dark CP-odd and charged scalars. This is a smoking-gun signal of the 3HDM since it is not allowed in the 2HDM with one inert doublet and is expected to be important when H 2 and H 1 are close in mass. In practice, this signature can be observed in the cascade decay of the SM-like Higgs boson, h\\to {H}_1{H}_2\\to {H}_1{H}_1f\\overline{f} into two DM particles and di-leptons/di-jets, where h is produced from either gluon-gluon Fusion (ggF) or Vector Boson Fusion (VBF). However, this signal competes with the tree-level channel q\\overline{q}\\to {H}_1{H}_1{Z}^{\\ast}\\to {H}_1{H}_1f\\overline{f} . We devise some benchmarks, compliant with collider, DM and cosmological data, for which the interplay between these modes is discussed. In particular, we show that the resulting detector signature, [InlineMediaObject not available: see fulltext.], with invariant mass of f\\overline{f} much smaller than m Z , can potentially be extracted already during Run 2 and 3. For example, the H 2 → H 1 γ * and γ * → e + e - case will give a spectacular QED mono-shower signal.

Using the Smooth Receiver Operating Curve (ROC) Method for Evaluation and Decision Making in Biometric Systems

DTIC Science & Technology

2014-07-01

partnership with Public Safety Canada. Led by Canada Border Services Agency partners included : Royal Canadian Mounted Police, Defence Research...Canada, as represented by the Minister of National Defence, 2014 © Sa Majesté la Reine (en droit du Canada), telle que représentée par le ministre de la...innovative technologies for public safety and security practitioners to achieve specific objectives; 4. Threats/Hazards F – Major trans-border criminal

The Empirical Canadian High Arctic Ionospheric Model (E-CHAIM): Bottomside Parameterization

NASA Astrophysics Data System (ADS)

Themens, D. R.; Jayachandran, P. T.

2017-12-01

It is well known that the International Reference Ionosphere (IRI) suffers reduced accuracy in its representation of monthly median ionospheric electron density at high latitudes. These inaccuracies are believed to stem, at least in part, from a historical lack of data from these regions. Now, roughly thirty and forty years after the development of the original URSI and CCIR foF2 maps, respectively, there exists a much larger dataset of high latitude observations of ionospheric electron density. These new measurements come in the form of new ionosonde deployments, such as those of the Canadian High Arctic Ionospheric Network, the CHAMP, GRACE, and COSMIC radio occultation missions, and the construction of the Poker Flat, Resolute, and EISCAT Incoherent Scatter Radar systems. These new datasets afford an opportunity to revise the IRI's representation of the high latitude ionosphere. Using a spherical cap harmonic expansion to represent horizontal and diurnal variability and a Fourier expansion in day of year to represent seasonal variations, we have developed a new model of the bottomside ionosphere's electron density for the high latitude ionosphere, above 50N geomagnetic latitude. For the peak heights of the E and F1 layers (hmE and hmF1, respectively), current standards use a constant value for hmE and either use a single-parameter model for hmF1 (IRI) or scale hmF1 with the F peak (NeQuick). For E-CHAIM, we have diverged from this convention to account for the greater variability seen in these characteristics at high latitudes, opting to use a full spherical harmonic model description for each of these characteristics. For the description of the bottomside vertical electron density profile, we present a single-layer model with altitude-varying scale height. The scale height function is taken as the sum three scale height layer functions anchored to the F2 peak, hmF1, and hmE. This parameterization successfully reproduces the structure of the various bottomside layers while ensuring that the resulting electron density profile is free of strong vertical gradient artifacts and is doubly differentiable.

A novel mechanism of E2F1 regulation via nucleocytoplasmic shuttling: determinants of nuclear import and export.

PubMed

Ivanova, Iordanka A; Vespa, Alisa; Dagnino, Lina

2007-09-01

E2F1 is a transcription factor central for cell survival, proliferation, and repair following genomic insult. Depending on the cell type and conditions, E2F1 can induce apoptosis in transformed cells, behaving as a tumour suppressor, or impart growth advantages favouring tumour formation. The pleiotropic functions of E2F1 are a likely consequence of its ability to transcriptionally control a wide variety of target genes, and require tight regulation of its activity at multiple levels. Although sequestration of proteins to particular cellular compartments is a well-established regulatory mechanism, virtually nothing is known about its contribution to modulation of E2F1 target gene expression. We have examined the subcellular trafficking of E2F1 and, contrary to the widely held notion that this factor is constitutively nuclear, we now demonstrate that it is subjected to continuous nucleocytoplasmic shuttling. We have also defined two nuclear localization domains and a nuclear export region, which mediates CRM1-dependent transit out of the nucleus. The predominant subcellular location of E2F1 is likely determined by the balance between the activity of nuclear import and export domains, and can be modulated by differentiation stimuli in epidermal cells. Thus, we have identified a hitherto unrecognized mechanism to control E2F1 function through modulation of its subcellular localization.

49 CFR Appendix F to Part 236 - Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC System Safety...

Code of Federal Regulations, 2012 CFR

2012-10-01

... Third-Party Assessment of PTC System Safety Verification and Validation F Appendix F to Part 236... Safety Verification and Validation (a) This appendix provides minimum requirements for mandatory independent third-party assessment of PTC system safety verification and validation pursuant to subpart H or I...

49 CFR Appendix F to Part 236 - Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC System Safety...

Code of Federal Regulations, 2014 CFR

2014-10-01

... Third-Party Assessment of PTC System Safety Verification and Validation F Appendix F to Part 236... Safety Verification and Validation (a) This appendix provides minimum requirements for mandatory independent third-party assessment of PTC system safety verification and validation pursuant to subpart H or I...

49 CFR Appendix F to Part 236 - Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC System Safety...

Code of Federal Regulations, 2011 CFR

2011-10-01

... Third-Party Assessment of PTC System Safety Verification and Validation F Appendix F to Part 236... Safety Verification and Validation (a) This appendix provides minimum requirements for mandatory independent third-party assessment of PTC system safety verification and validation pursuant to subpart H or I...

49 CFR Appendix F to Part 236 - Minimum Requirements of FRA Directed Independent Third-Party Assessment of PTC System Safety...

Code of Federal Regulations, 2013 CFR

2013-10-01

... Third-Party Assessment of PTC System Safety Verification and Validation F Appendix F to Part 236... Safety Verification and Validation (a) This appendix provides minimum requirements for mandatory independent third-party assessment of PTC system safety verification and validation pursuant to subpart H or I...

E2F transcription factor 2 variants as predictive biomarkers for recurrence risk in patients with squamous cell carcinoma of the oropharynx.

PubMed

Li, Yuncheng; Sturgis, Erich M; Zhu, Lijun; Cao, Xiaoli; Wei, Qingyi; Zhang, Hua; Li, Guojun

2017-04-01

Because E2F transcription factor 2 (E2F2) promoter polymorphisms have been implicated in carcinogenesis and prognosis, we investigated associations between genetic variants in five E2F2 promoter polymorphisms and recurrence risk of squamous cell carcinoma of the oropharynx (SCCOP) in 1 008 patients. A log-rank test and multivariable Cox models were used to assess the associations. Compared with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123, patients with common homozygous genotypes had better disease-free survival (both log-rank, P < 0.001) and lower SCCOP recurrence risk (HR, 0.4, 95% CI, 0.3-0.6 and HR, 0.3, 95% CI, 0.2-0.5, respectively) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, those with common homozygous genotypes of E2F2-rs2742976 and E2F2-rs3218123 had better disease-free survival rates (both log-rank, P < 0.001) and lower recurrence risk (HR, 0.1, 95% CI, 0.1-0.4 and HR, 0.1, 95% CI, 0.0-0.2, respectively) than patients with variant genotypes. However, no significant differences were found for the other three polymorphisms. After combining the risk genotypes of the five polymorphisms and using the high-risk group (2-5 risk genotypes) as the reference group, we found that the low-risk groups (0 or 1 risk genotype) had significantly lower recurrence risk among all patients (HR, 0.4, 95% CI, 0.3-0.6) and among HPV16-positive patients (HR, 0.2, 95% CI, 0.1-0.5). Our findings suggest that E2F2 polymorphisms may individually or jointly modify SCCOP recurrence risk, particularly for SCCOP patients with HPV16-positive tumors. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Comparative Study of Learning Using E-Learning and Printed Materials on Independent Learning and Creativity

NASA Astrophysics Data System (ADS)

Wahyu Utami, Niken; Aziz Saefudin, Abdul

2018-01-01

This study aims to determine: 1) differences in students taking independent learning by using e-learning and the students who attend the learning by using the print instructional materials ; 2) differences in the creativity of students who follow learning with e-learning and the students who attend the learning by using the print instructional materials ; 3) differences in learning independence and creativity of students attend learning with e-learning and the students who attend lessons using printed teaching materials in the subject of Mathematics Instructional Media Development. This study was a quasi-experimental research design using only posttest control design. The study population was all students who take courses in Learning Mathematics Media Development, Academic Year 2014/2015 100 students and used a random sample (random sampling) is 60 students. To test the hypothesis used multivariate analysis of variance or multivariable analysis of variance (MANOVA) of the track. The results of this study indicate that 1) There is a difference in student learning independence following study using the e-learning and the students who attend lessons using printed teaching materials in the lecture PMPM ( F = 4.177, p = 0.046 < 0.05 ) ; 2 ) There is no difference in the creativity of the students who complete the learning by using e -learning and students to follow the learning using printed teaching materials in the lecture PMPM ( F = 0.470, p = 0.496 > 0.05) ; No difference learning independence and creativity of students attend learning by using e-learning and the students who attend the learning using printed teaching materials in the lecture PMPM (F = 2.452, p = 0.095 > 0.05). Based on these studies suggested that the learning using e -learning can be used to develop student creativity, while learning to use e -learning and teaching materials can be printed to use to develop students’ independence.

Mechanisms of Polymer Curing and Thermal Degradation

DTIC Science & Technology

1979-12-01

respectively. 29 0)- Fi . J . IR S e t u f i ( - 3 E hy y p e o y Ph n l S f n .30 z Iii 41 rI2P6i4000 3500 3000 42500 §200010 6010 2010 0 0 0 0...Polymer X Obs.6(_pm) Obs.(ppmA H 7.9,8.0 g,h 7.8 g,h 7.5 I ,e 7.5 i ,c,2 7.3 b,e 6.0-7.2 b,d,f,j,=CH 7.2 d 7.0 f,j 3.1 a HC C =- T O" 7.9 g 7.9 g 7.3 b...e 7.4 b,e 7.1 d 6.0-7.1 c,d,f,=CH 7.0 f,c 3.1 a 3.1 a aFor X 0 H, ggh, f= i b Based on first-order analysis of multiplets. 37 t TABLE 4. SUMMARY OF 13C

Estrogen metabolites and their relation to isoprostanes as a measure of oxidative stress

PubMed Central

Sowers, MaryFran; McConnell, Daniel; Jannausch, Mary L.; Randolph, John F.; Brook, Robert; Gold, Ellen B.; Crawford, Sybil; Lasley, Bill

2009-01-01

Objective: Estradiol (E2) and its metabolites [2-hydroxyestrone (2-OHE1) and 16α-hydroxyestrone (16α-OHE1)] are believed to curtail greater oxidative stress found in the development and progression of disease conditions including atherosclerosis. We related estrogen levels to F2a-isoprostane levels, a biomarker of oxidative stress. Design and Participants: Data were from 1647 women, aged 47-57 years, participating in the 5th annual follow-up of the Study of Women's Health Across the Nation (SWAN), a study of the menopausal transition. Measurements: Serum E2 and urinary 2-OHE1 and 16α-OHE1 concentrations were assayed by ELISA while urinary F2a-isoprostanes were assayed by EIA. Results: F2a-isoprostane concentrations were elevated in women who smoked, a behavior associated with increased oxidative stress, but not in stages of the natural menopause. Mean F2a-isoprostane concentrations among premenopausal and postmenopausal women who smoked were 1082 and 1064 pg/mL, respectively, values double those in premenopausal (343 pg/mL) and postmenopausal (379 pg/mL) non-smoking women. 2-OHE1 and F2a-isoprostane concentrations were positively and highly related [partial correlations ρY|X = 0.44 and ρY|X = 0.43 in premenopausal and postmenopausal women, respectively]. Likewise, 16α-OHE1 concentrations were positively and highly correlated with F2a-isoprostane concentrations [ρY|X = 0.52 and ρY|X = 0.59 in premenopausal and postmenopausal women, respectively]. E2 was significantly correlated with F2a-isoprostanes only in postmenopausal women [ρY|X = 0.20]. Associations were adjusted for age, body mass index, race/ethnicity, lipids, physical activity level, and alcohol consumption. Conclusions: This study does not support the commonly-held hypothesis that levels of endogenous estradiol or its estrone metabolites favorably modify oxidative stress by decreasing F2a-isoprostane levels. PMID:17980014

Substituent effects in a series of 1,7-C[subscript 60](R[subscript F])[subscript 2] compounds (R[subscript F] = CF[subscript 3], C[subscript 2]F[subscript 5], n-C[subscrip 3]F[subscript 7], i-C[subscript 3]F[subscript 7], n-C[subscript 4]F[subscript 9], s-C[subscript 4]F[subscript 9], n-C[subscript 8]F[subscript 17]): electron affinities, reduction potentials and E(LUMO) values are not always correlated

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuvychko, Igor V.; Whitaker, James B.; Larson, Bryon W.

2013-04-08

A series of seven structurally-similar compounds with different pairs of R{sub F} groups were prepared, characterized spectroscopically, and studied by electrochemical methods (cyclic and square-wave voltammetry), low-temperature anion photoelectron spectroscopy, and DFT calculations (five of the compounds are reported here for the first time). This is the first time that a set of seven R{sub F} groups have been compared with respect to their relative effects on E{sub 1/2}(0/-), electron affinity (EA), and the DFT-calculated LUMO energy. The compounds, 1,7-C{sub 60}(R{sub F}){sub 2} (R{sub F} = CF{sub 3}, C{sub 2}F{sub 5}, i-C{sub 3}F{sub 7}, n-C{sub 3}F{sub 7}, s-C{sub 4}F{sub 9},more » n-C{sub 4}F{sub 9} and n-C{sub 8}F{sub 21}), were found to have statistically different electron affinities (EA), at the {+-}10 meV level of uncertainty, but virtually identical first reduction potentials, at the {+-}10 mV level of uncertainty. The lack of a correlation between EA and E{sub 1/2}(0/-), and between E(LUMO) and E{sub 1/2}(0/-), for such similar compounds is unprecedented and suggests that explanations for differences in figures of merit for materials and/or devices that are based on equating easily measurable E{sub 1/2}(0/-) values with EAs or E(LUMO) values should be viewed with caution. The solubilities of the seven compounds in toluene varied by nearly a factor of six, but in an unpredictable way, with the C{sub 2}F{sub 5} and s-C{sub 4}F{sub 9} compounds being the most soluble and the i-C{sub 3}F{sub 7} compound being the least soluble. The effects of the different R{sub F} groups on EAs, E(LUMO) values, and solubilities should help fluorine chemists choose the right R{sub F} group to design new materials with improved morphological, electronic, optical, and/or magnetic properties.« less

Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing Pluronic F127 and Plasdone S630

PubMed Central

Wu, Xiaoyan; Ge, Weihong; Shao, Tengfei; Wu, Weijun; Hou, Jian; Cui, Li; Wang, Jing; Zhang, Zhenghai

2017-01-01

Biochanin A (BCA), a natural dietary isoflavone, has been reported to show anticancer activities. However, its low biological availability and poor aqueous solubility limit its usefulness as a chemotherapeutic agent. We developed BCA-loaded micelles with Pluronic F127 and Plasdone S630 (BCA-FS). The optimized, spherical-shaped BCA-FS was obtained at a ratio of 1:1 (F127:S630). The particle size was 25.17±1.2 nm, and the zeta potential was −10.9±0.24 mV. BCA solubility in water increased to 5.0 mg/mL after encapsulation, and the drug-loading efficiency was 5.88%±0.76%. In vitro release experiments showed a delayed release of BCA from the mixed micelles. Furthermore, the BCA absorption permeability across a Caco-2 cell monolayer from the apical side to the basolateral side increased by 54% in BCA-FS. A pharmacokinetics evaluation showed a 2.16-fold increase in the relative oral bioavailability of BCA-FS compared with raw BCA, indicating that the mixed micelles may promote absorption in the gastrointestinal tract. A gastrointestinal safety assay was used to assess the reliability and safety of BCA-FS. On the basis of these findings, we conclude that this simple nanomicelle system could be leveraged to deliver BCA and other hydrophobic drugs. PMID:28260893

Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing Pluronic F127 and Plasdone S630.

PubMed

Wu, Xiaoyan; Ge, Weihong; Shao, Tengfei; Wu, Weijun; Hou, Jian; Cui, Li; Wang, Jing; Zhang, Zhenghai

2017-01-01

Biochanin A (BCA), a natural dietary isoflavone, has been reported to show anticancer activities. However, its low biological availability and poor aqueous solubility limit its usefulness as a chemotherapeutic agent. We developed BCA-loaded micelles with Pluronic F127 and Plasdone S630 (BCA-FS). The optimized, spherical-shaped BCA-FS was obtained at a ratio of 1:1 (F127:S630). The particle size was 25.17±1.2 nm, and the zeta potential was -10.9±0.24 mV. BCA solubility in water increased to 5.0 mg/mL after encapsulation, and the drug-loading efficiency was 5.88%±0.76%. In vitro release experiments showed a delayed release of BCA from the mixed micelles. Furthermore, the BCA absorption permeability across a Caco-2 cell monolayer from the apical side to the basolateral side increased by 54% in BCA-FS. A pharmacokinetics evaluation showed a 2.16-fold increase in the relative oral bioavailability of BCA-FS compared with raw BCA, indicating that the mixed micelles may promote absorption in the gastrointestinal tract. A gastrointestinal safety assay was used to assess the reliability and safety of BCA-FS. On the basis of these findings, we conclude that this simple nanomicelle system could be leveraged to deliver BCA and other hydrophobic drugs.

Mechanisms for strain localization within Archaean craton: A structural study from the Bundelkhand Tectonic Zone, north-central India

NASA Astrophysics Data System (ADS)

Sarkar, Saheli; Patole, Vishal; Saha, Lopamudra; Pati, Jayanta Kumar; Nasipuri, Pritam

2015-04-01

The transformation of palaeo-continents involve breakup, dispersal and reassembly of cratonic blocks by collisional suturing that develop a network of orogenic (mobile) belts around the periphery of the stable cratons. The nature of deformation in the orogenic belt depends on the complex interaction of fracturing, plastic deformation and diffusive mass transfer. Additionally, the degree and amount of melting during regional deformation is critical as the presence of melt facilitates the rate of diffusive mass transfer and weakens the rock by reducing the effective viscosity of the deformed zone. The nature of strain localization and formation of ductile shear zones surrounding the cratonic blocks have been correlated with Proterozoic-Palaeozoic supercontinent assembly (Columbia, Rodinia and Gondwana reconstruction). Although, a pre-Columbia supercontinent termed as Kenorland has been postulated, there is no evidence that supports the notion due to lack of the presence of shear zones within the Archaean cratonic blocks. In this contribution, we present the detailed structural analysis of ductile shear zones within the Bundelkhand craton. The ductlile shear zone is termed as Bundelkhand Tectonic Zone (BTZ) that extends east-west for nearly 300 km throughout the craton with a width of two-three kilometer . In the north-central India, the Bundelkhand craton is exposed over an area of 26,000 sq. The craton is bounded by Central Indian Tectonic zone in the south, the Great Boundary fault in the west and by the rocks of Lesser Himalaya in the north. A series of tonalite-trondjhemite-granodiorite gneiss are the oldest rocks of the Bundelkhand craton that also contains a succession of metamorphosed supracrustal rocks comprising of banded iron formation, quartzite, calc-silicate and ultramafic rocks. K-feldspar bearing granites intrude the tonalite-trondjhemite-granodiorite and the supracrustal rocks during the time span of 2.1 to 2.5 Ga. The TTGs near Babina, in central part of Bundelkhand Craton are characterized by the development of at least three stages of folding. The penetrative foliation in the TTG is characterized by the parallel alignment of biotite and amphibole (S2). In the low-strain domains, the S2 foliation is axial planer to the small scale root less hinges (F2) of mafic boudins and anatectic leucosomes (S1). The presence of hook-shaped fold on the mafic and anatectic leucozomal layers indicates that co-axial nature of F1 and F2 folds. In general, the F2 axial planes (S2) are oriented in NNW-SSE direction. The F2 fold axes are generally north trending with sub-vertical plunge (550 -> 0060N). The intensity and tightness of last stage of folding is prominent in the leucocratic layers and is characterized by the development of open warps with E-W trending axial planes. However, the effect of F3 is not prominent in the mafic layers. Locally, small scale E-W displacement in the mafic bands corresponds to the E-W trending F3 axial plane in the leucosomes. In contrast to the TTGs, the supracrustal rocks are devoid of melting and compositional segregation. The supracrustal units are characterized by the development of E-W trending fabric. The development of tight to isoclinal folds in the leucosomes of TTGs indicates the F1 folding in the partially molten TTG occurred in the anatectic conditions. The presence of melt decreases the effective viscosity of the rock and promotes the development of tight to isoclinal folds in the F1 and F2 phases. It is also suggested that the segregation of the melt during the first and second phases of folding again increases the strength of the restite and is manifested by the development of small scale E-W displacements. The study demonstrated the change in the strength of a segment of Archaean crust due to the limited availabiliy of melt during deformation. The presence of three stages of deformation in the TTGs and E-W trending fabric in banded iron formation and quartzite indicate the opening of a palaeo-ocean after the F2 folding in the TTGs where the supracrustal sequences were deposited. The extensive lateral extent of BTZ and limited width indicate that the ductile shear zone may represent the contact domains of different fragments of pre-Bundelkhand craton that are amalgamated during N-S collisional orogeny. However, in the absence of radiometric dating, the exact timing of closure of palaeo-ocean remains elusive.

mTORC1 and CK2 coordinate ternary and eIF4F complex assembly

PubMed Central

Gandin, Valentina; Masvidal, Laia; Cargnello, Marie; Gyenis, Laszlo; McLaughlan, Shannon; Cai, Yutian; Tenkerian, Clara; Morita, Masahiro; Balanathan, Preetika; Jean-Jean, Olivier; Stambolic, Vuk; Trost, Matthias; Furic, Luc; Larose, Louise; Koromilas, Antonis E.; Asano, Katsura; Litchfield, David; Larsson, Ola; Topisirovic, Ivan

2016-01-01

Ternary complex (TC) and eIF4F complex assembly are the two major rate-limiting steps in translation initiation regulated by eIF2α phosphorylation and the mTOR/4E-BP pathway, respectively. How TC and eIF4F assembly are coordinated, however, remains largely unknown. We show that mTOR suppresses translation of mRNAs activated under short-term stress wherein TC recycling is attenuated by eIF2α phosphorylation. During acute nutrient or growth factor stimulation, mTORC1 induces eIF2β phosphorylation and recruitment of NCK1 to eIF2, decreases eIF2α phosphorylation and bolsters TC recycling. Accordingly, eIF2β mediates the effect of mTORC1 on protein synthesis and proliferation. In addition, we demonstrate a formerly undocumented role for CK2 in regulation of translation initiation, whereby CK2 stimulates phosphorylation of eIF2β and simultaneously bolsters eIF4F complex assembly via the mTORC1/4E-BP pathway. These findings imply a previously unrecognized mode of translation regulation, whereby mTORC1 and CK2 coordinate TC and eIF4F complex assembly to stimulate cell proliferation. PMID:27040916

76 FR 28131 - Federal Motor Vehicle Safety Standards; Motorcycle Helmets

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

..., this final rule sets a quasi-static load application rate for the helmet retention system; revises the... Analysis and Conclusion e. Quasi-Static Retention Test f. Helmet Conditioning Tolerances g. Other... it as a quasi-static test, instead of a static test. Specifying the application rate will aid...

29 CFR 1910.119 - Process safety management of highly hazardous chemicals.

Code of Federal Regulations, 2011 CFR

2011-07-01

... complexity of the process will influence the decision as to the appropriate PHA methodology to use. All PHA... process hazard analysis in sufficient detail to support the analysis. (3) Information pertaining to the...) Relief system design and design basis; (E) Ventilation system design; (F) Design codes and standards...

29 CFR 1910.119 - Process safety management of highly hazardous chemicals.

Code of Federal Regulations, 2010 CFR

2010-07-01

... complexity of the process will influence the decision as to the appropriate PHA methodology to use. All PHA... process hazard analysis in sufficient detail to support the analysis. (3) Information pertaining to the...) Relief system design and design basis; (E) Ventilation system design; (F) Design codes and standards...

50 CFR 38.4 - Authorized functions, powers, and duties.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Investigation of accidents and offenses; (e) Custody and disposal of lost or abandoned property; (f) Regulation of aircraft and boat traffic and safety; (g) Imposition of quarantines; (h) Evacuation of hazardous... person from the Midway Atoll National Wildlife Refuge for cause; (k) Regulation of vehicle traffic and...

76 FR 44963 - Advisory Committee on the Medical Uses of Isotopes: Call for Nominations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-27

... byproduct material; (d) therapy physicist; (e) radiation safety officer; (f) nuclear pharmacist; (g) two... NUCLEAR REGULATORY COMMISSION Advisory Committee on the Medical Uses of Isotopes: Call for Nominations AGENCY: U.S. Nuclear Regulatory Commission. ACTION: Call for Nominations. SUMMARY: The U.S...

Restoration of frictional characteristics on older Portland cement concrete pavement.

DOT National Transportation Integrated Search

1986-06-01

Safety is a very important aspect o f the highway program. The Iowa DOT : initiated an inventory of the friction values of all paved primary : roadways i n 1969. This inventory, with an ASTM E-274 test unit, has : continued to the present time. The t...

2012 BC Education Facts

ERIC Educational Resources Information Center

British Columbia Teachers' Federation, 2012

2012-01-01

This report presents facts and figures on British Columbia's education for 2012. It is divided into the following seven sections: (1) Schools, which covers: (a) Number of public schools; (b) Number of independent (private) schools; (c) School closures; (d) Rural schools and students; (e) School-district amalgamation; and (f) School safety: Seismic…

46 CFR 160.151-45 - Equipment required for servicing facilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

...); (d) Hot presses (if applicable); (e) Safety-type glue pots or equivalents; (f) Abrasive devices; (g..., or other pressure-measurement device or pressure gauge of equivalent accuracy and sensitivity; (j... liferafts, unless the facility services only non-davit-launched liferafts; (q) A supply of parts for all...

9 CFR 590.539 - Defrosting operations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 590.539 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG... objectionable odors and are unfit for human food (e.g., sour, musty, fermented, or decomposed odors) shall be... container. (1) Frozen eggs packed in metal or plastic containers may be placed in running tap water (70 F...

9 CFR 590.539 - Defrosting operations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 590.539 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG... objectionable odors and are unfit for human food (e.g., sour, musty, fermented, or decomposed odors) shall be... container. (1) Frozen eggs packed in metal or plastic containers may be placed in running tap water (70 F...

9 CFR 590.539 - Defrosting operations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 590.539 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG... objectionable odors and are unfit for human food (e.g., sour, musty, fermented, or decomposed odors) shall be... container. (1) Frozen eggs packed in metal or plastic containers may be placed in running tap water (70 F...

9 CFR 590.539 - Defrosting operations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 590.539 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG... objectionable odors and are unfit for human food (e.g., sour, musty, fermented, or decomposed odors) shall be... container. (1) Frozen eggs packed in metal or plastic containers may be placed in running tap water (70 F...

Development, Characterization, and In Vitro Biological Performance of Fluconazole-Loaded Microemulsions for the Topical Treatment of Cutaneous Leishmaniasis

PubMed Central

Graminha, Márcia; Cerecetto, Hugo; González, Mercedes

2015-01-01

Cutaneous leishmaniasis (CL) is a resistant form of leishmaniasis that is caused by a parasite belonging to the genus Leishmania. FLU-loaded microemulsions (MEs) were developed by phase diagram for topical administration of fluconazole (FLU) as prominent alternative to combat CL. Three MEs called F1, F2, and F3 (F1—60% 50 M phosphate buffer at pH 7.4 (PB) as aqueous phase, 10% cholesterol (CHO) as oil phase, and 30% soy phosphatidylcholine/oil polyoxyl-60 hydrogenated castor oil/sodium oleate (3/8/6) (S) as surfactant; F2—50% PB, 10% CHO, and 40% S; F3—40% PB, 10% CHO, and 50 % S) were characterized by droplet size analysis, zeta potential analysis, X-ray diffraction, continuous flow, texture profile analysis, and in vitro bioadhesion. MEs presented pseudoplastic flow and thixotropy was dependent on surfactant concentration. Droplet size was not affected by FLU. FLU-loaded MEs improved the FLU safety profile that was evaluated using red cell haemolysis and in vitro cytotoxicity assays with J-774 mouse macrophages. FLU-unloaded MEs did not exhibit leishmanicidal activity that was performed using MTT colourimetric assays; however, FLU-loaded MEs exhibited activity. Therefore, these MEs have potential to modulate FLU action, being a promising platform for drug delivery systems to treat CL. PMID:25650054

Photoemission study of CaF2- and SrF2-GaAs(110) interfaces formed at room temperature

NASA Astrophysics Data System (ADS)

Mao, D.; Young, K.; Kahn, A.; Zanoni, R.; McKinley, J.; Margaritondo, G.

1989-06-01

Interfaces formed by evaporating CaF2 or SrF2 on room-temperature GaAs(110) are studied with synchrotron-radiation photoemission spectroscopy. The fluoride films grow uniformly on the GaAs surface. The deposition of CaF2 and SrF2 induces a large initial band bending on p-type GaAs (~0.9 eV) and a small initial band bending on n-type GaAs (~0.25 eV). The valence band is dominated by the F 2p peak which shifts toward high binding energies by ~1.5 eV after the deposition of >=16 Å fluoride. This shift reflects an increase in the valence-band offset between the two materials as the film forms. The final band offsets are estimated at 7.7 and 8.0 eV for CaF2 and SrF2, respectively, and are in qualitative agreement with those expected from the fluoride-Si data. Core-level measurements indicate that no reaction or decomposition of the MF2 molecule takes place at the interface. The F 2s core-level line shape and the increase in the binding-energy separation of F 2s and Ca 3p with increasing coverage suggest the presence of an interface F component. Contrary to the CaF2/Si case, no measurable Ca-substrate bonding effect is observed. The dissociative effect of uv irradiation on the CaF2 film is also investigated.

Targeting the eIF4F translation initiation complex: a critical nexus for cancer development.

PubMed

Pelletier, Jerry; Graff, Jeremy; Ruggero, Davide; Sonenberg, Nahum

2015-01-15

Elevated protein synthesis is an important feature of many cancer cells and often arises as a consequence of increased signaling flux channeled to eukaryotic initiation factor 4F (eIF4F), the key regulator of the mRNA-ribosome recruitment phase of translation initiation. In many cellular and preclinical models of cancer, eIF4F deregulation results in changes in translational efficiency of specific mRNA classes. Importantly, many of these mRNAs code for proteins that potently regulate critical cellular processes, such as cell growth and proliferation, enhanced cell survival and cell migration that ultimately impinge on several hallmarks of cancer, including increased angiogenesis, deregulated growth control, enhanced cellular survival, epithelial-to-mesenchymal transition, invasion, and metastasis. By being positioned as the molecular nexus downstream of key oncogenic signaling pathways (e.g., Ras, PI3K/AKT/TOR, and MYC), eIF4F serves as a direct link between important steps in cancer development and translation initiation. Identification of mRNAs particularly responsive to elevated eIF4F activity that typifies tumorigenesis underscores the critical role of eIF4F in cancer and raises the exciting possibility of developing new-in-class small molecules targeting translation initiation as antineoplastic agents. ©2014 American Association for Cancer Research.

The over expression of long non-coding RNA ANRIL promotes epithelial-mesenchymal transition by activating the ATM-E2F1 signaling pathway in pancreatic cancer: An in vivo and in vitro study.

PubMed

Chen, Shi; Zhang, Jia-Qiang; Chen, Jiang-Zhi; Chen, Hui-Xing; Qiu, Fu-Nan; Yan, Mao-Lin; Chen, Yan-Ling; Peng, Cheng-Hong; Tian, Yi-Feng; Wang, Yao-Dong

2017-09-01

This study aims to investigate the roles of lncRNA ANRIL in epithelial-mesenchymal transition (EMT) by regulating the ATM-E2F1 signaling pathway in pancreatic cancer (PC). PC rat models were established and ANRIL overexpression and interference plasmids were transfected. The expression of ANRIL, EMT markers (E-cadherin, N-cadherin and Vimentin) and ATM-E2F1 signaling pathway-related proteins (ATM, E2F1, INK4A, INK4B and ARF) were detected. Small molecule drugs were applied to activate and inhibit the ATM-E2F1 signaling pathway. Transwell assay and the scratch test were adopted to detect cell invasion and migration abilities. ANRIL expression in the PC cells was higher than in normal pancreatic duct epithelial cells. In the PC rat models and PC cells, ANRIL interference promoted the expressions of INK4B, INK4A, ARF and E-cadherin, while reduced N-cadherin and Vimentin expression. Over-expressed ANRIL decreased the expression of INK4B, INK4A, ARF and E-cadherin, but raised N-cadherin and Vimentin expressions. By inhibiting the ATM-E2F1 signaling pathway in PC cells, E-cadherin expression increased but N-cadherin and Vimentin expressions decreased. After ANRIL was silenced or the ATM-E2F1 signaling pathway inhibited, PC cell migration and invasion abilities were decreased. In conclusion, over-expression of lncRNA ANRIL can promote EMT of PC cells by activating the ATM-E2F1 signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

E2 and SN2 Reactions of X(-) + CH3CH2X (X = F, Cl); an ab Initio and DFT Benchmark Study.

PubMed

Bento, A Patrícia; Solà, Miquel; Bickelhaupt, F Matthias

2008-06-01

We have computed consistent benchmark potential energy surfaces (PESs) for the anti-E2, syn-E2, and SN2 pathways of X(-) + CH3CH2X with X = F and Cl. This benchmark has been used to evaluate the performance of 31 popular density functionals, covering local-density approximation, generalized gradient approximation (GGA), meta-GGA, and hybrid density-functional theory (DFT). The ab initio benchmark has been obtained by exploring the PESs using a hierarchical series of ab initio methods [up to CCSD(T)] in combination with a hierarchical series of Gaussian-type basis sets (up to aug-cc-pVQZ). Our best CCSD(T) estimates show that the overall barriers for the various pathways increase in the order anti-E2 (X = F) < SN2 (X = F) < SN2 (X = Cl) ∼ syn-E2 (X = F) < anti-E2 (X = Cl) < syn-E2 (X = Cl). Thus, anti-E2 dominates for F(-) + CH3CH2F, and SN2 dominates for Cl(-) + CH3CH2Cl, while syn-E2 is in all cases the least favorable pathway. Best overall agreement with our ab initio benchmark is obtained by representatives from each of the three categories of functionals, GGA, meta-GGA, and hybrid DFT, with mean absolute errors in, for example, central barriers of 4.3 (OPBE), 2.2 (M06-L), and 2.0 kcal/mol (M06), respectively. Importantly, the hybrid functional BHandH and the meta-GGA M06-L yield incorrect trends and qualitative features of the PESs (in particular, an erroneous preference for SN2 over the anti-E2 in the case of F(-) + CH3CH2F) even though they are among the best functionals as measured by their small mean absolute errors of 3.3 and 2.2 kcal/mol in reaction barriers. OLYP and B3LYP have somewhat higher mean absolute errors in central barriers (5.6 and 4.8 kcal/mol, respectively), but the error distribution is somewhat more uniform, and as a consequence, the correct trends are reproduced.

On the local vertex antimagic total coloring of some families tree

NASA Astrophysics Data System (ADS)

Febriani Putri, Desi; Dafik; Hesti Agustin, Ika; Alfarisi, Ridho

2018-04-01

Let G(V, E) be a graph of vertex set V and edge set E. Local vertex antimagic total coloring developed from local edge and local vertex antimagic coloring of graph. Local vertex antimagic total coloring is defined f:V(G)\\cup E(G)\\to \\{1,2,3,\\ldots,|V(G)|+|E(G)|\\} if for any two adjacent vertices v 1 and v 2, w({v}1)\

Detection of QT prolongation using a novel electrocardiographic analysis algorithm applying intelligent automation: prospective blinded evaluation using the Cardiac Safety Research Consortium electrocardiographic database.

PubMed

Green, Cynthia L; Kligfield, Paul; George, Samuel; Gussak, Ihor; Vajdic, Branislav; Sager, Philip; Krucoff, Mitchell W

2012-03-01

The Cardiac Safety Research Consortium (CSRC) provides both "learning" and blinded "testing" digital electrocardiographic (ECG) data sets from thorough QT (TQT) studies annotated for submission to the US Food and Drug Administration (FDA) to developers of ECG analysis technologies. This article reports the first results from a blinded testing data set that examines developer reanalysis of original sponsor-reported core laboratory data. A total of 11,925 anonymized ECGs including both moxifloxacin and placebo arms of a parallel-group TQT in 181 subjects were blindly analyzed using a novel ECG analysis algorithm applying intelligent automation. Developer-measured ECG intervals were submitted to CSRC for unblinding, temporal reconstruction of the TQT exposures, and statistical comparison to core laboratory findings previously submitted to FDA by the pharmaceutical sponsor. Primary comparisons included baseline-adjusted interval measurements, baseline- and placebo-adjusted moxifloxacin QTcF changes (ddQTcF), and associated variability measures. Developer and sponsor-reported baseline-adjusted data were similar with average differences <1 ms for all intervals. Both developer- and sponsor-reported data demonstrated assay sensitivity with similar ddQTcF changes. Average within-subject SD for triplicate QTcF measurements was significantly lower for developer- than sponsor-reported data (5.4 and 7.2 ms, respectively; P < .001). The virtually automated ECG algorithm used for this analysis produced similar yet less variable TQT results compared with the sponsor-reported study, without the use of a manual core laboratory. These findings indicate that CSRC ECG data sets can be useful for evaluating novel methods and algorithms for determining drug-induced QT/QTc prolongation. Although the results should not constitute endorsement of specific algorithms by either CSRC or FDA, the value of a public domain digital ECG warehouse to provide prospective, blinded comparisons of ECG technologies applied for QT/QTc measurement is illustrated. Copyright © 2012 Mosby, Inc. All rights reserved.

Detection of QT prolongation using a novel ECG analysis algorithm applying intelligent automation: Prospective blinded evaluation using the Cardiac Safety Research Consortium ECG database

PubMed Central

Green, Cynthia L.; Kligfield, Paul; George, Samuel; Gussak, Ihor; Vajdic, Branislav; Sager, Philip; Krucoff, Mitchell W.

2013-01-01

Background The Cardiac Safety Research Consortium (CSRC) provides both “learning” and blinded “testing” digital ECG datasets from thorough QT (TQT) studies annotated for submission to the US Food and Drug Administration (FDA) to developers of ECG analysis technologies. This manuscript reports the first results from a blinded “testing” dataset that examines Developer re-analysis of original Sponsor-reported core laboratory data. Methods 11,925 anonymized ECGs including both moxifloxacin and placebo arms of a parallel-group TQT in 191 subjects were blindly analyzed using a novel ECG analysis algorithm applying intelligent automation. Developer measured ECG intervals were submitted to CSRC for unblinding, temporal reconstruction of the TQT exposures, and statistical comparison to core laboratory findings previously submitted to FDA by the pharmaceutical sponsor. Primary comparisons included baseline-adjusted interval measurements, baseline- and placebo-adjusted moxifloxacin QTcF changes (ddQTcF), and associated variability measures. Results Developer and Sponsor-reported baseline-adjusted data were similar with average differences less than 1 millisecond (ms) for all intervals. Both Developer and Sponsor-reported data demonstrated assay sensitivity with similar ddQTcF changes. Average within-subject standard deviation for triplicate QTcF measurements was significantly lower for Developer than Sponsor-reported data (5.4 ms and 7.2 ms, respectively; p<0.001). Conclusion The virtually automated ECG algorithm used for this analysis produced similar yet less variable TQT results compared to the Sponsor-reported study, without the use of a manual core laboratory. These findings indicate CSRC ECG datasets can be useful for evaluating novel methods and algorithms for determining QT/QTc prolongation by drugs. While the results should not constitute endorsement of specific algorithms by either CSRC or FDA, the value of a public domain digital ECG warehouse to provide prospective, blinded comparisons of ECG technologies applied for QT/QTc measurement is illustrated. PMID:22424006

Dependence of e31,f on polar axis texture for tetragonal Pb(Zrx,Ti1-x)O3 thin films

NASA Astrophysics Data System (ADS)

Yeager, Charles B.; Ehara, Yoshitaka; Oshima, Naoya; Funakubo, Hiroshi; Trolier-McKinstry, Susan

2014-09-01

It was shown by Ouyang et al. [Appl. Phys. Lett. 86, 152901 (2005)] that the piezoelectric e31,f coefficient is largest parallel to the spontaneous polarization in tetragonal PbZrxTi1-xO3 (PZT) films. However, the expected piezoelectric data are typically calculated from phenomenological constants derived from data on ceramic PZT. In this work, the dependence of e31,f on c-axis texture fraction, f001, for {001}PZT thin films was measured by growing films with systematically changed f001 using CaF2, MgO, SrTiO3, and Si substrates. An approximately linear increase in e31,f with f001 was observed for compositions up to 43 mol. % Zr, and 100% c-domain properties were extrapolated. It was demonstrated that c-axis PZT films can achieve e31,f exceeding -12 C/m2 for many tetragonal compositions. The energy harvesting figure of merit, e31,f2/ɛr, for c-axis PZT films surpassed 0.8 C2/m4. This is larger than the figure of merit of gradient-free PZT films grown on Si substrates by a factor of four.

Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

PubMed Central

Goodman, Andrew D; Bethoux, Francois; Brown, Theodore R; Schapiro, Randall T; Cohen, Ron; Marinucci, Lawrence N; Henney, Herbert R

2015-01-01

Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders. PMID:25583832

Sequential planning of flood protection infrastructure under limited historic flood record and climate change uncertainty

NASA Astrophysics Data System (ADS)

Dittes, Beatrice; Špačková, Olga; Straub, Daniel

2017-04-01

Flood protection is often designed to safeguard people and property following regulations and standards, which specify a target design flood protection level, such as the 100-year flood level prescribed in Germany (DWA, 2011). In practice, the magnitude of such an event is only known within a range of uncertainty, which is caused by limited historic records and uncertain climate change impacts, among other factors (Hall & Solomatine, 2008). As more observations and improved climate projections become available in the future, the design flood estimate changes and the capacity of the flood protection may be deemed insufficient at a future point in time. This problem can be mitigated by the implementation of flexible flood protection systems (that can easily be adjusted in the future) and/or by adding an additional reserve to the flood protection, i.e. by applying a safety factor to the design. But how high should such a safety factor be? And how much should the decision maker be willing to pay to make the system flexible, i.e. what is the Value of Flexibility (Špačková & Straub, 2017)? We propose a decision model that identifies cost-optimal decisions on flood protection capacity in the face of uncertainty (Dittes et al. 2017). It considers sequential adjustments of the protection system during its lifetime, taking into account its flexibility. The proposed framework is based on pre-posterior Bayesian decision analysis, using Decision Trees and Markov Decision Processes, and is fully quantitative. It can include a wide range of uncertainty components such as uncertainty associated with limited historic record or uncertain climate or socio-economic change. It is shown that since flexible systems are less costly to adjust when flood estimates are changing, they justify initially lower safety factors. Investigation on the Value of Flexibility (VoF) demonstrates that VoF depends on the type and degree of uncertainty, on the learning effect (i.e. kind and quality of information that we will gather in the future) and on the formulation of the optimization problem (risk-based vs. rule-based approach). The application of the framework is demonstrated on catchments in Germany. References: DWA (Deutsche Vereinigung für Wasserwirtschaft Abwasser und Abfall eV.) 2011. Merkblatt DWA-M 507-1: Deiche an Fließgewässern. (A. Bieberstein, Ed.). Hennef: DWA Deutsche Vereinigung für Wasserwirtschaft, Abwasser und Abfall e. V. Hall, J., & Solomatine, D. 2008. A framework for uncertainty analysis in flood risk management decisions. International Journal of River Basin Management, 6(2), 85-98. http://doi.org/10.1080/15715124.2008.9635339 Špačková, O. & Straub, D. 2017. Long-term adaption decisions via fully and partially observable Markov decision processes. Sustainable and Resilient Infrastructure. In print.

29 CFR 2520.104b-10 - Summary Annual Report.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... I-2h Line 8f. 4. Benefits paid Sch. H-2e(4) Sch. I-2e Line 8d. 5. Other expenses Sch. H-Subtract the sum of 2e(4) & 2i(5) from 2j Sch. I-2i Line 8g. 6. Total participants Form 5500-6f Same Line 5b. 7... expenses Sch. H-2i(5) Sch. I-2h Line 8f. 10. Benefits paid Sch. H-2e(4) Sch. I-2e Line 8d. 11. Other...

29 CFR 2520.104b-10 - Summary Annual Report.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... I-2h Line 8f. 4. Benefits paid Sch. H-2e(4) Sch. I-2e Line 8d. 5. Other expenses Sch. H-Subtract the sum of 2e(4) & 2i(5) from 2j Sch. I-2i Line 8g. 6. Total participants Form 5500-6f Same Line 5b. 7... expenses Sch. H-2i(5) Sch. I-2h Line 8f. 10. Benefits paid Sch. H-2e(4) Sch. I-2e Line 8d. 11. Other...

29 CFR 2520.104b-10 - Summary Annual Report.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... I-2h Line 8f. 4. Benefits paid Sch. H-2e(4) Sch. I-2e Line 8d. 5. Other expenses Sch. H-Subtract the sum of 2e(4) & 2i(5) from 2j Sch. I-2i Line 8g. 6. Total participants Form 5500-6f Same Line 5b. 7... expenses Sch. H-2i(5) Sch. I-2h Line 8f. 10. Benefits paid Sch. H-2e(4) Sch. I-2e Line 8d. 11. Other...

29 CFR 2520.104b-10 - Summary Annual Report.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... I-2h Line 8f. 4. Benefits paid Sch. H-2e(4) Sch. I-2e Line 8d. 5. Other expenses Sch. H-Subtract the sum of 2e(4) & 2i(5) from 2j Sch. I-2i Line 8g. 6. Total participants Form 5500-6f Same Line 5b. 7... expenses Sch. H-2i(5) Sch. I-2h Line 8f. 10. Benefits paid Sch. H-2e(4) Sch. I-2e Line 8d. 11. Other...

Culture medium type affects endocytosis of multi-walled carbon nanotubes in BEAS-2B cells and subsequent biological response.

PubMed

Haniu, Hisao; Saito, Naoto; Matsuda, Yoshikazu; Tsukahara, Tamotsu; Maruyama, Kayo; Usui, Yuki; Aoki, Kaoru; Takanashi, Seiji; Kobayashi, Shinsuke; Nomura, Hiroki; Okamoto, Masanori; Shimizu, Masayuki; Kato, Hiroyuki

2013-09-01

We examined the cytotoxicity of multi-walled carbon nanotubes (MWCNTs) and the resulting cytokine secretion in BEAS-2B cells or normal human bronchial epithelial cells (HBEpCs) in two types of culture media (Ham's F12 containing 10% FBS [Ham's F12] and serum-free growth medium [SFGM]). Cellular uptake of MWCNT was observed by fluorescent microscopy and analyzed using flow cytometry. Moreover, we evaluated whether MWCNT uptake was suppressed by 2 types of endocytosis inhibitors. We found that BEAS-2B cells cultured in Ham's F12 and HBEpCs cultured in SFGM showed similar biological responses, but BEAS-2B cells cultured in SFGM did not internalize MWCNTs, and the 50% inhibitory concentration value, i.e., the cytotoxicity, was increased by more than 10-fold. MWCNT uptake was suppressed by a clathrin-mediated endocytosis inhibitor and a caveolae-mediated endocytosis inhibitor in BEAS-2B cells cultured in Ham's F12 and HBEpCs cultured in SFGM. In conclusion, we suggest that BEAS-2B cells cultured in a medium containing serum should be used for the safety evaluation of nanomaterials as a model of normal human bronchial epithelial cells. However, the culture medium composition may affect the proteins that are expressed on the cytoplasmic membrane, which may influence the biological response to MWCNTs. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

System Synthesis for Polymorphous Computing Architectures

DTIC Science & Technology

2002-02-01

G H F Proc 5 : 4 : 3 11 1 Figure 3. Self-timed execution. D C B F G H E D B H EA CG F D C B F G H E D B H EA CG F AProc 1 Proc 2...first-iteration actors denoted by T. D B H E CG F D C B F G H E D B H EA CG F A 18 T T T T Proc 3 Proc 4 Proc 5 Proc 1 Proc 2 1 T⁄ T trmin30 ture-mirror...Phase1Algo( , ) = transientReduction( ) Output T G S′ S G T S′ S S′ Figure 11. Pseudocode to find

Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis.

PubMed

Anway, Matthew D; Rekow, Stephen S; Skinner, Michael K

2008-10-01

Exposure of gestating female rats to the anti-androgenic endocrine disruptor vinclozolin has been shown to induce transgenerational adult onset disease phenotypes. The current study, was designed to compare the actions of vinclozolin to the known anti-androgenic compound flutamide. The gestating female rats were exposed to intraperitoneal injections during embryonic day 8-14 (E8-E14) to 100mg/kg/day vinclozolin or flutamide at either 5mg or 20mg/kg/day. As previously observed, vinclozolin induced a transgenerational testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm number. In contrast, the flutamide exposures resulted in a testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm numbers in the F1 generation only, and not the F2 and F3 generation adult males. Interestingly, some of the low dose (5mg/kg) flutamide F2 generation offspring developed spinal agenesis and supernummery development (polymelia) of limbs. Although the actions of vinclozolin and flutamide appear similar in the F1 generation males, the transgenerational effects of vinclozolin do not appear to be acting through the same anti-androgenic mechanism as flutamide.

Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis

PubMed Central

Anway, Matthew D.; Rekow, Stephen S.; Skinner, Michael K.

2017-01-01

Exposure of gestating female rats to the anti-androgenic endocrine disruptor vinclozolin has been shown to induce transgenerational adult onset disease phenotypes. The current study, was designed to compare the actions of vinclozolin to the known anti-androgenic compound flutamide. The gestating female rats were exposed to intraperitoneal injections during embryonic day 8–14 (E8–E14) to 100 mg/kg/day vinclozolin or flutamide at either 5mg or 20 mg/kg/day. As previously observed, vinclozolin induced a transgenerational testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm number. In contrast, the flutamide exposures resulted in a testis phenotype of increased spermatogenic cell apoptosis and decreasedepididymal spermnumbers in the F1 generation only, and not the F2 and F3 generation adult males. Interestingly, some of the lowdose (5 mg/kg) flutamide F2 generation offspring developed spinal agenesis and supernummery development (polymelia) of limbs. Although the actions of vinclozolin and flutamide appear similar in the F1 generation males, the transgenerational effects of vinclozolin do not appear to be acting through the same anti-androgenic mechanism as flutamide. PMID:18762243

Evaluation of take-home exposure and risk associated with the handling of clothing contaminated with chrysotile asbestos.

PubMed

Sahmel, J; Barlow, C A; Simmons, B; Gaffney, S H; Avens, H J; Madl, A K; Henshaw, J; Lee, R J; Van Orden, D; Sanchez, M; Zock, M; Paustenbach, D J

2014-08-01

The potential for para-occupational (or take-home) exposures from contaminated clothing has been recognized for the past 60 years. To better characterize the take-home asbestos exposure pathway, a study was performed to measure the relationship between airborne chrysotile concentrations in the workplace, the contamination of work clothing, and take-home exposures and risks. The study included air sampling during two activities: (1) contamination of work clothing by airborne chrysotile (i.e., loading the clothing), and (2) handling and shaking out of the clothes. The clothes were contaminated at three different target airborne chrysotile concentrations (0-0.1 fibers per cubic centimeter [f/cc], 1-2 f/cc, and 2-4 f/cc; two events each for 31-43 minutes; six events total). Arithmetic mean concentrations for the three target loading levels were 0.01 f/cc, 1.65 f/cc, and 2.84 f/cc (National Institute of Occupational Health and Safety [NIOSH] 7402). Following the loading events, six matched 30-minute clothes-handling and shake-out events were conducted, each including 15 minutes of active handling (15-minute means; 0.014-0.097 f/cc) and 15 additional minutes of no handling (30-minute means; 0.006-0.063 f/cc). Percentages of personal clothes-handling TWAs relative to clothes-loading TWAs were calculated for event pairs to characterize exposure potential during daily versus weekly clothes-handling activity. Airborne concentrations for the clothes handler were 0.2-1.4% (eight-hour TWA or daily ratio) and 0.03-0.27% (40-hour TWA or weekly ratio) of loading TWAs. Cumulative chrysotile doses for clothes handling at airborne concentrations tested were estimated to be consistent with lifetime cumulative chrysotile doses associated with ambient air exposure (range for take-home or ambient doses: 0.00044-0.105 f/cc year). © 2014 Society for Risk Analysis.

Electrolytes with Improved Safety Characteristics for High Voltage, High Specific Energy Li-ion Cells

NASA Technical Reports Server (NTRS)

Smart, M. C.; Krause, F. C.; Hwang, C.; West, W. C.; Soler, J.; Whitcanack, L. W.; Prakash, G. K. S.; Ratnakumar, B. V.

2012-01-01

(1) NASA is actively pursuing the development of advanced electrochemical energy storage and conversion devices for future lunar and Mars missions; (2) The Exploration Technology Development Program, Energy Storage Project is sponsoring the development of advanced Li-ion batteries and PEM fuel cell and regenerative fuel cell systems for the Altair Lunar Lander, Extravehicular Activities (EVA), and rovers and as the primary energy storage system for Lunar Surface Systems; (3) At JPL, in collaboration with NASA-GRC, NASA-JSC and industry, we are actively developing advanced Li-ion batteries with improved specific energy, energy density and safety. One effort is focused upon developing Li-ion battery electrolyte with enhanced safety characteristics (i.e., low flammability); and (4) A number of commercial applications also require Li-ion batteries with enhanced safety, especially for automotive applications.

Testing of Hand-Held Mine Detection Systems

DTIC Science & Technology

2015-01-08

ITOP 04-2-5208 for guidance on software testing . Testing software is necessary to ensure that safety is designed into the software algorithm, and that...sensor verification areas or target lanes. F.2. TESTING OBJECTIVES. a. Testing objectives will impact on the test design . Some examples of...overall safety, performance, and reliability of the system. It describes activities necessary to ensure safety is designed into the system under test

OSIRIS and SOMBRERO Inertial Fusion Power Plant Designs, Volume 2: Designs, Assessments, and Comparisons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meier, W. R.; Bieri, R. L.; Monsler, M. J.

1992-03-01

This is a comprehensive design study of two Inertial Fusion Energy (IFE) electric power plants. Conceptual designs are presented for a fusion reactor (called Osiris) using an induction-linac heavy-ion beam driver, and another (called SOMBRERO) using a KrF laser driver. The designs covered all aspects of IFE power plants, including the chambers, heat transport and power conversion systems, balance-of-plant facilities, target fabrication, target injection and tracking, as well as the heavy-ion and KrF drivers. The point designs were assessed and compared in terms of their environmental & safety aspects, reliability and availability, economics, and technology development needs.

E2C(R2) Periodic Benefit-Risk Evaluation Report and E2C(R2) Periodic Benefit-Risk Evaluation Report--Questions and Answers; International Council for Harmonisation; Guidances for Industry; Availability. Notice.

PubMed

2016-07-19

The Food and Drug Administration (FDA or Agency) is announcing the availability of guidances for industry entitled ``E2C(R2) Periodic Benefit-Risk Evaluation'' (E2C(R2) guidance) and ``E2C(R2) Periodic Benefit-Risk Evaluation Report--Questions and Answers'' (E2C(R2) Q&A guidance). These guidances were prepared under the auspices of the International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. The E2C(R2) draft guidance, issued April 11, 2012, updated and combined two ICH guidances, ``E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs'' (E2C guidance) and ``Addendum to E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs'' (addendum to the E2C guidance). The E2C(R2) guidance is intended to describe the format, content, and timing of a Periodic Benefit-Risk Evaluation Report (PBRER) for an approved drug or biologic, and it finalizes the draft guidance. The E2C(R2) Q&A guidance is a supplementary guidance that is intended to clarify key issues in the E2C(R2) guidance.

The quiet and disturbed time performance of the IRI 2012 within 90°-130°E longitude sector during solar cycle 24

NASA Astrophysics Data System (ADS)

Bhuyan, Pradip; Yokoyama, Tatsuhiro; Supnithi, Pornchai; Kalita, Bitap Raj; Wang, Kehe; Komolmis, Tharadol; Yatini, Clara

2016-07-01

The performance of the IRI 2012 model is examined for the double peaked solar cycle 24 in the low latitude region of 90-130oE longitude in the context of the global longitudinal wave number four structure (WN4). The monthly mean values of the foF2 and the hmF2(if available) measurements at low and low mid-latitude stations Dibrugarh (27.5°N, 95°E), Hainan (19.2°N,109.7°E),Okinawa (26.5°N,128°E) and Cocos Island (12.2°S,96.8°E) during quiet times and Dibrugarh (27.5°N, 95°E), Chiang Mai (18.76°N,98.93°E), Chumphon (10.72°N,99.37°E), Kototabang (0.2°S,100.32°E) and Cocos Island (12.2°S,96.8°E ) during the disturbed days of a severe geomagnetic storm are investigated. These stations are located under the strongest peak of the longitudinal WN4 structure in NmF2 along 90-130°E longitudes. The IRI is quite successful in predicting the seasonal averages of NmF2 over this region except in the equinox afternoon period where IRI underestimates the NmF2 in low latitudes. When the monthly mean measured data is compared with IRI, the difference between the IRI model predictions and the measurements are found to follow a systematic pattern. The IRI-2012 with CCIR options slightly underestimates foF2 over Dibrugarh in day time and overestimates in the night time. The amount of underestimation varies from month to month and also depends on the solar activity levels. The IRI also underestimated the day time hmF2 and overestimated the night time hmF2 over Dibrugarh. In case of Hainan, the IRI overestimates the NmF2 in the equinox months and generally in the afternoon to post sunset period. The model values are closer in the solstice than in the equinox. In Okinawa, the trend reverses and the IRI overestimates the NmF2 in the day time and underestimates in the night time. The IRI overestimated the day time hmF2 and underestimated the night time hmF2 over Okinawa. In case of Cocos Island which lies almost on the EIA anomaly region of the southern hemisphere, IRI underestimates the peak day time NmF2 in most months. The measurements are closer to the model values in the forenoon period and in the low solar activity period. The striking feature across all the stations is the IRI underestimation of the post sunset enhancement of NmF2 in low latitudes. During the severe geomagnetic storm of 17-18 March, 2015, the IRI was not able to replicate the inhibition of EIA on the next day i.e. 18 March as observed in the 100°E longitude.

On Super Edge-magic Total Labeling of Modified Watermill Graph

NASA Astrophysics Data System (ADS)

Nurdin; Ungko, T. S.; Gormantara, J.; Abdullah, A.; Aulyah, S.; Nikita

2018-03-01

An edge-magic total labeling on a graph G is one-to-one map from V(G) ∪ E(G) onto the set of integers 1,2, ...,ν + e, where ν = |V(G)| and e = |E(G)|, with the property that, given any edge uv, f(u) + f(u, ν}) + f(ν) = k for every u,v ∈ V(G), and k is called magic valuation. An edge-magic total labeling f is called super edge-magic total if f(v(G)) = {1,2 ...,|V(G)|} and f(E(G)) = {|V(G)| + 1, |V(G)| + 2,... |V(G) + E(G)|}. In this paper we investigate edge-magic total labeling of a new graph called modified Watermill graph. Furthermore, the magic valuation of the modified Watermill graph WM(n) is k=\\frac{1}{2}(21n+3), for n odd, n ≥ 3.

E2fl1 is a meiosis-specific transcription factor in the protist Tetrahymena thermophila

PubMed Central

Zhang, Jing; Tian, Miao; Miao, Wei

2017-01-01

ABSTRACT Members of the E2F family of transcription factors have been reported to regulate the expression of genes involved in cell cycle control, DNA replication, and DNA repair in multicellular eukaryotes. Here, E2FL1, a meiosis-specific E2F transcription factor gene, was identified in the model ciliate Tetrahymena thermophila. Loss of this gene resulted in meiotic arrest prior to anaphase I. The cytological experiments revealed that the meiotic homologous pairing was not affected in the absence of E2FL1, but the paired homologous chromosomes did not separate and assumed a peculiar tandem arrangement. This is the first time that an E2F family member has been shown to regulate meiotic events. Moreover, BrdU incorporation showed that DSB processing during meiosis was abnormal upon the deletion of E2FL1. Transcriptome sequencing analysis revealed that E2FL1 knockout decreased the expression of genes involved in DNA replication and DNA repair in T. thermophila, suggesting that the function of E2F is highly conserved in eukaryotes. In addition, E2FL1 deletion inhibited the expression of related homologous chromosome segregation genes in T. thermophila. The result may explain the meiotic arrest phenotype at anaphase I. Finally, by searching for E2F DNA-binding motifs in the entire T. thermophila genome, we identified 714 genes containing at least one E2F DNA-binding motif; of these, 235 downregulated represent putative E2FL1 target genes. PMID:27892792

If You've Got It, Use It (Simulation, That Is...)

NASA Technical Reports Server (NTRS)

Frost, Chad; Tucker, George

2006-01-01

This viewgraph presentation reviews the Rotorcraft Aircrew Systems Concept Airborne Laboratory (RASCAL) UH-60 in-flight simulator, the use of simulation in support of safety monitor design specification development, the development of a failure/recovery (F/R) rating scale, the use of F/R Rating Scale as a common element between simulation and flight evaluation, and the expansion of the flight envelope without benefit of simulation.

78 FR 40045 - Airworthiness Directives; Eurocopter France Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-03

... directive (AD) for Eurocopter France (Eurocopter) Model AS350B, BA, B1, B2, B3, D, AS355E, F, F1, F2, and N... comments that we receive, as well as a report summarizing each substantive public contact with FAA... Eurocopter Model AS350B, BA, BB, B1, B2, B3, D, AS355 E, F, F1, F2, and N helicopters delivered before...

Terahertz Oscillations of Hot Electrons in Graphene

DTIC Science & Technology

2015-01-01

half the frequency ?F = 2?eF/~?OP , where 2?/?F is the time taken for carriers to accelerate ballistically to the optic phonon...resonance. Such resonance occurs at about half the frequency ωF = 2πeF/~ωOP , where 2π/ωF is the time taken for carriers to accelerate ballistically to the ... The current density on the plane is given by, Jx(t) = −4evF ∑ ~k f(~k, t) cos(φ), (2.16) where φ is the angle between ~k and the kx axis. Figure

Geraniol suppresses prostate cancer growth through down-regulation of E2F8.

PubMed

Lee, Sanghoon; Park, Yu Rang; Kim, Su-Hwa; Park, Eun-Jung; Kang, Min Ji; So, Insuk; Chun, Jung Nyeo; Jeon, Ju-Hong

2016-10-01

Geraniol, an acyclic dietary monoterpene, has been found to suppress cancer survival and growth. However, the molecular mechanism underlying the antitumor action of geraniol has not been investigated at the genome-wide level. In this study, we analyzed the microarray data obtained from geraniol-treated prostate cancer cells. Geraniol potently altered a gene expression profile and primarily down-regulated cell cycle-related gene signatures, compared to linalool, another structurally similar monoterpene that induces no apparent phenotypic changes. Master regulator analysis using the prostate cancer-specific regulatory interactome identified that the transcription factor E2F8 as a specific target molecule regulates geraniol-specific cell cycle signatures. Subsequent experiments confirmed that geraniol down-regulated E2F8 expression and the knockdown of E2F8 was sufficient to suppress cell growth by inducing G 2 /M arrest. Epidemiological analysis showed that E2F8 is up-regulated in metastatic prostate cancer and associated with poor prognosis. These results indicate that E2F8 is a crucial transcription regulator controlling cell cycle and survival in prostate cancer cells. Therefore, our study provides insight into the role of E2F8 in prostate cancer biology and therapeutics. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Genetic variants in the cell cycle control pathways contribute to early onset colorectal cancer in Lynch syndrome.

PubMed

Chen, Jinyun; Etzel, Carol J; Amos, Christopher I; Zhang, Qing; Viscofsky, Nancy; Lindor, Noralane M; Lynch, Patrick M; Frazier, Marsha L

2009-11-01

Lynch syndrome is an autosomal dominant syndrome of familial malignancies resulting from germ line mutations in DNA mismatch repair (MMR) genes. Our goal was to take a pathway-based approach to investigate the influence of polymorphisms in cell cycle-related genes on age of onset for Lynch syndrome using a tree model. We evaluated polymorphisms in a panel of cell cycle-related genes (AURKA, CDKN2A, TP53, E2F2, CCND1, TP73, MDM2, IGF1, and CDKN2B) in 220 MMR gene mutation carriers from 129 families. We applied a novel statistical approach, tree modeling (Classification and Regression Tree), to the analysis of data on patients with Lynch syndrome to identify individuals with a higher probability of developing colorectal cancer at an early age and explore the gene-gene interactions between polymorphisms in cell cycle genes. We found that the subgroup with CDKN2A C580T wild-type genotype, IGF1 CA-repeats >or=19, E2F2 variant genotype, AURKA wild-type genotype, and CCND1 variant genotype had the youngest age of onset, with a 45-year median onset age, while the subgroup with CDKN2A C580T wild-type genotype, IGF1 CA-repeats >or=19, E2F2 wild-type genotype, and AURKA variant genotype had the latest median age of onset, which was 70 years. Furthermore, we found evidence of a possible gene-gene interaction between E2F2 and AURKA genes related to CRC age of onset. Polymorphisms in these cell cycle-related genes work together to modify the age at the onset of CRC in patients with Lynch syndrome. These studies provide an important part of the foundation for development of a model for stratifying age of onset risk among those with Lynch syndrome.

Wave Propagation and Dynamics of Lattice Structures.

DTIC Science & Technology

1984-05-01

Progress in Solid Mechanics, North Holand Publishing Company, Amsterdam, 1960. [7) Y. K. Linn, and T. J. McDaniel, ’n)amics of Beam Type Periodic...deformation. -99- APPENDIX F FREQUENCY RESPONSE AND IMPULSE RESPONSE FUNCTIONS FOR LONGITUDINAL VIBRATION IN AN ELASTIC ROD Figure F1 shows the elastic rod to b...6 (F38) Rearranging eqn. (F38), .HE(w) = e’ 4e~3 ~e e 2 e1" +e " 6 e r (F39) Mlultiplying eqn. ( F1 =39) by 6Ŕ 6- and aragn te - . e 6 -e _ aix

Saving energy and reducing emissions of both polycyclic aromatic hydrocarbons and particulate matter by adding bio-solution to emulsified diesel.

PubMed

Lin, Yuan-Chung; Lee, Wen-Jhy; Chen, Chun-Chi; Chen, Chung-Bang

2006-09-01

Development of emulsified diesel has been driven by the need to reduce emissions from diesel engines and to save energy. Emulsification technology and bio-solution (NOE-7F) were used to produce emulsified diesel in this study. The experimental results indicated that there were no significant separation layers in W13 (13 wt % water + 87 wt % PDF), W16 (16 wt % water + 84 wt % PDF), W19 (19 wt % water + 81 wt % PDF), E13 (13 wt % NOE-7F water + 87 wt % PDF), E16 (16 wt % NOE-7F water + 83 wt % PDF), and E19 (19 wt % NOE-7F water + 81 wt % PDF) after premium diesel fuel (PDF) was emulsified for more than 30 days. In addition, there was no significant increase in damage from using these six emulsified fuels after the operation of the diesel generator for more than one year. The energy saving and reduction of particulate matter (PM) and total polycyclic aromatic hydrocarbons (PAHs) for W13, W16, W19, E13, E16 and E19, respectively, were 3.90%, 30.9%, 27.6%; 3.38%, 37.0%, 34.9%; 2.17%, 22.2%, 15.4%; 5.87%, 38.6%, 49.3%; 5.88%, 57.8%, 58.0%; and 4.75%, 31.1%, 47.3%, compared with PDF. The above results revealed that the bio-solution (NOE-7F) had a catalytic effect which elevated the combustion efficiency and decreased pollutant emissions during the combustion process. Furthermore, bio-solution (NOE-7F) can stabilize the emulsified fuels and enhance energy saving. Thus, emulsified fuels are highly suitable for use as alternative fuels. Due to the increasing price of diesel, emulsified diesel containing NOE-7F has potential for commercial application.

Method for disclosing invisible physical properties in metal-ferroelectric-insulator-semiconductor gate stacks

NASA Astrophysics Data System (ADS)

Sakai, Shigeki; Zhang, Wei; Takahashi, Mitsue

2017-04-01

In metal-ferroelectric-insulator-semiconductor gate stacks of ferroelectric-gate field effect transistors (FeFETs), it is impossible to directly obtain curves of polarization versus electric field (P f-E f) in the ferroelectric layer. The P f-E f behavior is not simple, i.e. the P f-E f curves are hysteretic and nonlinear, and the hysteresis curve width depends on the electric field scan amplitude. Unless the P f-E f relation is known, the field E f strength cannot be solved when the voltage is applied between the gate meal and the semiconductor substrate, and thus P f-E f cannot be obtained after all. In this paper, the method for disclosing the relationships among the polarization peak-to-peak amplitude (2P mm_av), the electric field peak-to-peak amplitude (2E mm_av), and the memory window (E w) in units of the electric field is presented. To get P mm_av versus E mm_av, FeFETs with different ferroelectric-layer thicknesses should be prepared. Knowing such essential physical parameters is helpful and in many cases enough to quantitatively understand the behavior of FeFETs. The method is applied to three groups. The first one consists of SrBi2Ta2O9-based FeFETs. The second and third ones consist of Ca x Sr1-x Bi2Ta2O9-based FeFETs made by two kinds of annealing. The method can clearly differentiate the characters of the three groups. By applying the method, ferroelectric relationships among P mm_av, E mm_av, and E w are well classified in the three groups according to the difference of the material kinds and the annealing conditions. The method also evaluates equivalent oxide thickness (EOT) of a dual layer of a deposited high-k insulator and a thermally-grown SiO2-like interfacial layer (IL). The IL thickness calculated by the method is consistent with cross-sectional image of the FeFETs observed by a transmission electron microscope. The method successfully discloses individual characteristics of the ferroelectric and the insulator layers hidden in the gate stack of a FeFET.

Application of Acoustic Signal Processing Techniques to Seismic Data.

DTIC Science & Technology

1977-06-30

Sr(U So 9RU FEND LOA SUNIT STA PLC3 LOA I STA OLC4 F A FORRE-C ;3f F’RARD I REC9; T9 3ET PAST T-4E E24F LIZE 2 0’ LC3 r ZE 0 PLC4 t~zs 0 FEND STZ 3AKSCN...0)0.4 E 4.1 33 Ŕ. 37.0 12-46-22.9 1?-34-07 .1 M VMiHM ,P1W LJ 31 wEST ER"’ %EDITEPRANFAN AqPA 301 ALBANIA P62 1220 F2 6P 2 2? 243990 al.0 N 20.4 E

The International C2 Journal, Volume 2 Number 1, 2008. Special Issue: Awareness. Tightly Coupling Cognition: Understanding How Communication and Awareness Drive Coordination in Teams

DTIC Science & Technology

2008-01-01

such organizational configurations are high so are the consequences for failure. From decades of research on teams and team or group problem solving...TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Office of Naval Research ,One Liberty Center,875 North Randolph...Naval Postgraduate School Ross Pigeau (CAN), Defence Research and Development Canada (DRDC) Mink Spaans (NED), TNO Defence, Security and Safety About

Curcumin Derivative Epigenetically Reactivates Nrf2 Antioxidative Stress Signaling in Mouse Prostate Cancer TRAMP C1 Cells.

PubMed

Li, Wenji; Su, Zheng-Yuan; Guo, Yue; Zhang, Chengyue; Wu, Renyi; Gao, Linbo; Zheng, Xi; Du, Zhi-Yun; Zhang, Kun; Kong, Ah-Ng

2018-02-19

The carcinogenesis of prostate cancer (PCa) in TRAMP model is highly correlated with hypermethylation in the promoter region of Nrf2 and the accompanying reduced transcription of Nrf2 and its regulated detoxifying genes. We aimed to investigate the effects of (3E,5E)-3,5-bis-(3,4,5-trimethoxybenzylidene)-tetrahydro-thiopyran-4-one (F10) and (3E,5E)-3,5-bis-(3,4,5-trimethoxy-benzylidene)-tetrahydropyran-4-one (E10), two synthetic curcumin derivatives, on restoring Nrf2 activity in TRAMP C1 cells. HepG2-C8 cells transfected with an antioxidant-response element (ARE)-luciferase vector were treated with F10, E10, curcumin, and sulforaphane (SFN) to compare their effects on Nrf2-ARE pathways. We performed real-time quantitative PCR and Western blotting to investigate the effects of F10 and E10 on Nrf2, correlated phase II detoxification genes. We also measured expression and activity of DNMTand HDAC enzymes. Enrichment of H3K27me3 on the promoter region of Nrf2 was explored with a chromatin immunoprecipitation (ChIP) assay. Methylation of the CpG region in Nrf2 promoter was doubly examined by bisulfite genomic sequencing (BGS) and methylation DNA immunoprecipitation (MeDIP). Compared with curcumin and SFN, F10 is more potent in activating Nrf2-ARE pathways. Both F10 and E10 enhanced level of Nrf2 and the correlated phase II detoxifying genes. BGS and MeDIP assays indicated that F10 but not E10 hypomethylated the Nrf2 promoter. F10 also downregulated the protein level of DNMT1, DNMT3a, DNMT3b, HDAC1, HDAC4, and HDAC7 and the activity of DNMTs and HDACs. F10 but not E10 effectively reduced the accumulation of H3k27me3 on the promoter of Nrf2. F10 and E10 can activate the Nrf2-ARE pathway and increase the level of Nrf2 and correlated phase II detoxification genes. The reactivation effect on Nrf2 by F10 in TRAMP C1 may come from demethylation, decrease of HDACs, and inhibition of H3k27me3 accumulation.

Phase I clinical and pharmacokinetic study of kahalalide F administered weekly as a 1-hour infusion to patients with advanced solid tumors.

PubMed

Pardo, Beatriz; Paz-Ares, Luis; Tabernero, Josep; Ciruelos, Eva; García, Margarita; Salazar, Ramón; López, Ana; Blanco, María; Nieto, Antonio; Jimeno, José; Izquierdo, Miguel Angel; Trigo, José Manuel

2008-02-15

A dose-escalation, phase I study evaluated the safety, pharmacokinetics, and efficacy of a weekly 1-h regimen of kahalalide F, a cyclic depsipeptide isolated from the marine mollusk Elysia rufescens, in adult patients with advanced solid tumors and no standard treatment available. Patients received an i.v. 1-h infusion of kahalalide F once weekly until disease progression or unacceptable toxicity. The starting kahalalide F dose was 266 microg/m(2), and dose escalation proceeded based on the worst toxicity found in the previous cohort. Thirty-eight patients were enrolled at three Spanish institutions and received once-weekly kahalalide F 1-h infusions at doses between 266 and 1,200 microg/m(2). Dose-limiting toxicities consisted of transient grade 3/4 increases in transaminase blood levels. The maximum tolerated dose for this kahalalide F schedule was 800 microg/m(2), and the recommended dose for phase II studies was 650 microg/m(2). No accumulated toxicity was found. One patient with malignant melanoma had unconfirmed partial response, one patient with metastatic lung adenocarcinoma had minor response, and six patients with different types of metastatic solid tumors had stable disease for 2.8 to 12.7 months. The noncompartmental pharmacokinetics of this kahalalide F schedule was linear and showed a narrow distribution and short body residence. The transaminitis associated with kahalalide F was dose dependent. The maximum tolerated dose was 800 microg/m(2). Dose-limiting toxicities with weekly kahalalide F 1-h i.v. infusions were transient grade 3/4 increases in blood transaminase levels, and 650 microg/m(2) was declared the recommended dose for phase II studies. This schedule showed a favorable safety profile and hints of antitumor activity.

Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke

PubMed Central

Azzopardi, David; Patel, Kharishma; Jaunky, Tomasz; Santopietro, Simone; Camacho, Oscar M.; McAughey, John; Gaça, Marianna

2016-01-01

Abstract Electronic cigarettes (E-cigarettes) are a potential means of addressing the harm to public health caused by tobacco smoking by offering smokers a less harmful means of receiving nicotine. As e-cigarettes are a relatively new phenomenon, there are limited scientific data on the longer-term health effects of their use. This study describes a robust in vitro method for assessing the cytotoxic response of e-cigarette aerosols that can be effectively compared with conventional cigarette smoke. This was measured using the regulatory accepted Neutral Red Uptake assay modified for air–liquid interface (ALI) exposures. An exposure system, comprising a smoking machine, traditionally used for in vitro tobacco smoke exposure assessments, was adapted for use with e-cigarettes to expose human lung epithelial cells at the ALI. Dosimetric analysis methods using real-time quartz crystal microbalances for mass, and post-exposure chemical analysis for nicotine, were employed to detect/distinguish aerosol dilutions from a reference Kentucky 3R4F cigarette and two commercially available e-cigarettes (Vype eStick and ePen). ePen aerosol induced 97%, 94% and 70% less cytotoxicity than 3R4F cigarette smoke based on matched EC50 values at different dilutions (1:5 vs. 1:153 vol:vol), mass (52.1 vs. 3.1 μg/cm2) and nicotine (0.89 vs. 0.27 μg/cm2), respectively. Test doses where cigarette smoke and e-cigarette aerosol cytotoxicity were observed are comparable with calculated daily doses in consumers. Such experiments could form the basis of a larger package of work including chemical analyses, in vitro toxicology tests and clinical studies, to help assess the safety of current and next generation nicotine and tobacco products. PMID:27690199

46 CFR 387.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PROPERTY FOR DEVELOPMENT OR OPERATION OF A PORT FACILITY § 387.2 Definitions. (a) Act means the Federal... for development or operation of a port facility. (d) Grantee means the Applicant to which surplus Federal property is conveyed. (e) Grantor means the Secretary. (f) Port Facility means any structure and...

Medical Services: Department of Defense Veterinary/Medical Laboratory Food Safety and Quality Assurance Program

DTIC Science & Technology

1995-02-01

ice (cream) milk and yogurt processing at the retail/user level (chap 5). o Revises and prescribes the use of DD Form 2385 (Microbiological Quality... yogurt , sandwiches and spreads, salad type convenience foods, and other processed/ p r e – p a c k a g e d a n d r e a d y – t o – e a t ( R T E ) f o o...dairy products to include, but not be limited to, fresh and cultured dairy products, frozen desserts, soft serve ice cream/milk and yogurt mix. (3) RTE

Deep crustal deformation by sheath folding in the Adirondack Mountains, USA

NASA Technical Reports Server (NTRS)

Mclelland, J. M.

1988-01-01

As described by McLelland and Isachsen, the southern half of the Adirondacks are underlain by major isoclinal (F sub 1) and open-upright (F sub 2) folds whose axes are parallel, trend approximately E-W, and plunge gently about the horizontal. These large structures are themselves folded by open upright folds trending NNE (F sub 3). It is pointed out that elongation lineations in these rocks are parallel to X of the finite strain ellipsoid developed during progressive rotational strain. The parallelism between F sub 1 and F sub 2 fold axes and elongation lineations led to the hypothesis that progressive rotational strain, with a west-directed tectonic transport, rotated earlier F sub 1-folds into parallelism with the evolving elongation lineation. Rotation is accomplished by ductile, passive flow of F sub 1-axes into extremely arcuate, E-W hinges. In order to test these hypotheses a number of large folds were mapped in the eastern Adirondacks. Other evidence supporting the existence of sheath folds in the Adirondacks is the presence, on a map scale, of synforms whose limbs pass through the vertical and into antiforms. This type of outcrop pattern is best explained by intersecting a horizontal plane with the double curvature of sheath folds. It is proposed that sheath folding is a common response of hot, ductile rocks to rotational strain at deep crustal levels. The recognition of sheath folds in the Adirondacks reconciles the E-W orientation of fold axes with an E-W elongation lineation.

30 CFR 18.94 - Application for field approval; contents of application.

Code of Federal Regulations, 2011 CFR

2011-07-01

... approval or certification has been issued under the provisions of Bureau of Mines Schedules 2D, 2E, 2F, or... under Bureau of Mines Schedule 2D, 2E, 2F, or 2G, photographs or a single layout drawing which clearly... certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G, a single layout drawing which clearly identifies...

30 CFR 18.94 - Application for field approval; contents of application.

Code of Federal Regulations, 2012 CFR

2012-07-01

... approval or certification has been issued under the provisions of Bureau of Mines Schedules 2D, 2E, 2F, or... under Bureau of Mines Schedule 2D, 2E, 2F, or 2G, photographs or a single layout drawing which clearly... certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G, a single layout drawing which clearly identifies...

30 CFR 18.94 - Application for field approval; contents of application.

Code of Federal Regulations, 2013 CFR

2013-07-01

... approval or certification has been issued under the provisions of Bureau of Mines Schedules 2D, 2E, 2F, or... under Bureau of Mines Schedule 2D, 2E, 2F, or 2G, photographs or a single layout drawing which clearly... certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G, a single layout drawing which clearly identifies...

30 CFR 18.94 - Application for field approval; contents of application.

Code of Federal Regulations, 2014 CFR

2014-07-01

... approval or certification has been issued under the provisions of Bureau of Mines Schedules 2D, 2E, 2F, or... under Bureau of Mines Schedule 2D, 2E, 2F, or 2G, photographs or a single layout drawing which clearly... certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G, a single layout drawing which clearly identifies...

30 CFR 18.94 - Application for field approval; contents of application.

Code of Federal Regulations, 2010 CFR

2010-07-01

... approval or certification has been issued under the provisions of Bureau of Mines Schedules 2D, 2E, 2F, or... under Bureau of Mines Schedule 2D, 2E, 2F, or 2G, photographs or a single layout drawing which clearly... certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G, a single layout drawing which clearly identifies...

E3L and F1L Gene Functions Modulate the Protective Capacity of Modified Vaccinia Virus Ankara Immunization in Murine Model of Human Smallpox.

PubMed

Volz, Asisa; Jany, Sylvia; Freudenstein, Astrid; Lantermann, Markus; Ludwig, Holger; Sutter, Gerd

2018-01-04

The highly attenuated Modified Vaccinia virus Ankara (MVA) lacks most of the known vaccinia virus (VACV) virulence and immune evasion genes. Today MVA can serve as a safety-tested next-generation smallpox vaccine. Yet, we still need to learn about regulatory gene functions preserved in the MVA genome, such as the apoptosis inhibitor genes F1L and E3L . Here, we tested MVA vaccine preparations on the basis of the deletion mutant viruses MVA-ΔF1L and MVA-ΔE3L for efficacy against ectromelia virus (ECTV) challenge infections in mice. In non-permissive human tissue culture the MVA deletion mutant viruses produced reduced levels of the VACV envelope antigen B5. Upon mousepox challenge at three weeks after vaccination, MVA-ΔF1L and MVA-ΔE3L exhibited reduced protective capacity in comparison to wildtype MVA. Surprisingly, however, all vaccines proved equally protective against a lethal ECTV infection at two days after vaccination. Accordingly, the deletion mutant MVA vaccines induced high levels of virus-specific CD8+ T cells previously shown to be essential for rapidly protective MVA vaccination. These results suggest that inactivation of the anti-apoptotic genes F1L or E3L modulates the protective capacity of MVA vaccination most likely through the induction of distinct orthopoxvirus specific immunity in the absence of these viral regulatory proteins.

78 FR 49116 - Airworthiness Directives; Eurocopter France Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-13

..., B2, B3, BA, C, D, and D1 helicopters; and Model AS355E, F, F1, F2, N, and NP helicopters. The... certain Eurocopter Model AS350B, B1, B2, B3, BA, C, D, and D1 and Model AS355E, F, F1, F2, N, and NP... pilot if certain regulatory recordkeeping requirements are met. As such, AD 2011-22-05 currently...

Statistical Inference on Optimal Points to Evaluate Multi-State Classification Systems

DTIC Science & Technology

2014-09-18

vs2+ ( dbcm3 ˆ 2 ) *vm3+( dbcs3 ˆ 2 ) * vs3 80 VETA <−VBCA+VBC EETA<−EBCA−EBC 82 W<− (EETA−TV) / s q r t ( VETA ) # T e s t p−v a l u e − t o compare t o a...event set, E = (ε1, ε2, ..., εk) to k distinct elements of a label set, L = (l1, l2, ..., lk) . These partitions may be referred to as classes. For...set of features, F = ( f1, f2, ..., fm) . These features are then used to assign the different elements from E to the respective labels, L , (A : E → F

WE-F-209-02: Radiation Safety Surveys of Linear Accelerators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, M.

2016-06-15

Over the past few years, numerous Accreditation Bodies, Regulatory Agencies, and State Regulations have implemented requirements for Radiation Safety Surveys following installation or modification to x-ray rooms. The objective of this session is to review best practices in performing radiation safety surveys for both Therapy and Diagnostic installations, as well as a review of appropriate survey instruments. This session will be appropriate for both therapy and imaging physicists who are looking to increase their working knowledge of radiation safety surveys. Learning Objectives: Identify Appropriate Survey Meters for Radiation Safety Surveys Develop best practices for Radiation Safety Surveys for Therapy unitsmore » that include common areas of concern. Develop best practices for Radiation Safety Surveys of Diagnostic and Nuclear Medicine rooms. Identify acceptable dose levels and the factors that affect the calculations associated with performing Radiation Safety Surveys.« less

A portable, stable and precise laser differential refractometer

NASA Astrophysics Data System (ADS)

Gong, Xiangjun; Ngai, To; Wu, Chi

2013-11-01

In this work, we present a portable laser differential refractometer with real-time detection and high precision based on the Snell's law and a 2f-2f optical design. The 2f-2f configuration solves a traditional position drifting problem of the laser beam and enhances the signal stability, where a small pinhole is illuminated by the laser light and imaged to the detector by lens placed in the middle between the detector and the pinhole. However, it also leads to a larger dimension of the instrument, limiting its applications and its sensitivity that is proportional to the optical path. Therefore, for a portable device on the basis of the 2f-2f design, a combination of a mirror and a lens was developed to minimize the optical path without affecting the 2f-2f design. Our simple and compact design reaches a resolution of 10-6 refractive index units (RIU). Moreover, the dimension of such a modified differential refractometer is significantly reduced to be portable. Owing to its real-time detection speed and high precision, this newly developed refractometer is particularly attractive when it is used as an independent and ultra-sensitive detector in many research and industrial applications wherein there is a time-dependent concentration change, e.g., the concentration determination, quality control, and study of kinetic processes in solution, including adsorption, sedimentation, and dissolution, to name few but not limited.

National Dam Safety Program. Willow Brook Dam (Inventory Number NY 35). Lower Hudson River Basin, Orange County, New York. Phase I Inspection Report,

DTIC Science & Technology

1981-08-14

ia danger of l~>ee of huaar. . i f e fro« .arge flowa downatrea« of the daa Therefore Willow Brook De« is considered to be in the "high" hazard...and Surveyor (the application la included in Appendix G) 2 * Of WAT IOW RECORDS The «lids gats controlling dischargea ia opened approxi...lake ahors Once the lake lsvsl dropa to apillway lsvsl. the gsts ia cloaed The owner haa no procedures ’or regular dam inspectiona or regular

Testing Properties of Boolean Functions

DTIC Science & Technology

2012-01-01

Applying the Hermite decomposition of f and linearity of expectation, E x,y [f(x)f(y) 〈x, y〉] = n∑ i=1 ∑ S,T∈Nn f̂(S)f̂(T )E x [HS(x)xi]E y [ HT (y)yi...otherwise it takes the value 0. Similarly, Ey[ HT (y)yi] = 1 iff T = ei. 38 Part I Exact Query Complexity 39 Chapter 5 Testing Juntas We begin by studying the...1− 2e− 6m /2 = 1− 2e−O( √ n). The estimate ν̃ is a U-statistic with kernel ψ∗f . This kernel satisfies ‖ψ∗f − Eψ∗f‖∞ ≤ 2‖ψ∗f‖∞ = 2 √ 4n log(4n/3

The Retinoblastoma Tumor Suppressor Regulates a Xenobiotic Detoxification Pathway

PubMed Central

Sáenz Robles, Maria Teresa; Case, Ashley; Chong, Jean-Leon; Leone, Gustavo; Pipas, James M.

2011-01-01

The retinoblastoma tumor suppressor (pRb) regulates cell cycle entry, progression and exit by controlling the activity of the E2F-family of transcription factors. During cell cycle exit pRb acts as a transcriptional repressor by associating with E2F proteins and thereby inhibiting their ability to stimulate the expression of genes required for S phase. Indeed, many tumors harbor mutations in the RB gene and the pRb-E2F pathway is compromised in nearly all types of cancers. In this report we show that both pRb and its interacting partners, the transcriptional factors E2F1-2-3, act as positive modulators of detoxification pathways important for metabolizing and clearing xenobiotics—such as toxins and drugs—from the body. Using a combination of conventional molecular biology techniques and microarray analysis of specific cell populations, we have analyzed the detoxification pathway in murine samples in the presence or absence of pRb and/or E2F1-2-3. In this report, we show that both pRb and E2F1-2-3 act as positive modulators of detoxification pathways in mice, challenging the conventional view of E2F1-2-3 as transcriptional repressors negatively regulated by pRb. These results suggest that mutations altering the pRb-E2F axis may have consequences beyond loss of cell cycle control by altering the ability of tissues to remove toxins and to properly metabolize anticancer drugs, and might help to understand the formation and progression rates of different types of cancer, as well as to better design appropriate therapies based on the particular genetic composition of the tumors. PMID:22022495

The educational impact of web-based and face-to-face patient deterioration simulation programs: An interventional trial.

PubMed

Chung, Catherine; Cooper, Simon J; Cant, Robyn P; Connell, Cliff; McKay, Angela; Kinsman, Leigh; Gazula, Swapnali; Boyle, Jayne; Cameron, Amanda; Cash, Penny; Evans, Lisa; Kim, Jeong-Ah; Masud, Rana; McInnes, Denise; Norman, Lisa; Penz, Erika; Rotter, Thomas; Tanti, Erin; Breakspear, Tom

2018-05-01

There are international concerns relating to the management of patient deterioration. The "failure to rescue" literature identifies that nursing staff miss cues of deterioration and often fail to call for assistance. Simulation-based educational approaches may improve nurses' recognition and management of patient deterioration. To investigate the educational impact of the First2Act web-based (WB) and face-to-face (F2F) simulation programs. A mixed methods interventional cohort trial with nursing staff from four Australian hospitals. Nursing staff working in four public and private hospital medical wards in the State of Victoria. In 2016, ward nursing staff (n = 74) from a public and private hospital completed three F2F laboratory-based team simulations with a patient actor in teams of three. 56 nursing staff from another public and private hospital individually completed a three-scenario WB simulation program (First2ActWeb) [A 91% participation rate]. Validated tools were used to measure knowledge (multi-choice questionnaire), competence (check-list of actions) and confidence (self-rated) before and after the intervention. Both WB and F2F participants' knowledge, competence and confidence increased significantly after training (p ≤0.001). Skill performance for the WB group increased significantly from 61% to 74% (p ≤ 0.05) and correlated significantly with post-test knowledge (p = 0.014). No change was seen in the F2F groups' performance scores. Course evaluations were positive with median ratings of 4/5 (WB) and 5/5 (F2F). The F2F program received significantly more positive evaluations than the WB program (p < 0.05), particularly with regard to quality of feedback. WB and F2F simulation are effective education strategies with both programs demonstrating positive learning outcomes. WB programs increase ease of access to training whilst F2F enable the development of tactile hands on skills and teamwork. A combined blended learning education strategy is recommended to enhance competence and patient safety. Copyright © 2018 Elsevier Ltd. All rights reserved.

Three - Dimensional Image Generation from an Aerial Photograph.

DTIC Science & Technology

1987-09-01

through 183 of the terrain model. To verify that this set of elevation points would appear like the desired reference image, a line drawing illustrated in...see iF. Fc -.:: ~e parameters PHV ~Anglea ir ratla-’s 1f: ~e2-a: :.s Ange i 8rramLiar t 7 :’aF the gec sctarg, Iar c~t-at2-s sLdstem. t" at -~2 S a C...d--ata p01nts. -a n1g .~tles -3. :a1 et ro~.tlnes -~ f.Pot-’-ie par-ameters ENCM: The dr-crn-at=7 cFf th7e aFfF --e ~.F-.rct icns perFforret Ccnst

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blackfield, Donald T.; Poole, Brian R.

N2F is a C/C++ code used to calculate the far zone electromagnetic (EM) field, given E and H near zone field data. The method used by N2F can be found in Ref. 1 and 2. N2F determines the far field E Φ and E θ in spherical coordinates for near zone data calculated in either Cartesian or Cylindrical geometry.

46 CFR 154.330 - Openings to accommodation, service, or control spaces.

Code of Federal Regulations, 2010 CFR

2010-10-01

... DANGEROUS CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design... and in the first tier of the superstructure must be a fixed type. (e) Air intakes and openings into... at not less than 207 kPa gauge (30 psig). (f) On liquefied toxic gas vessels, the closures required...

46 CFR 154.330 - Openings to accommodation, service, or control spaces.

Code of Federal Regulations, 2012 CFR

2012-10-01

... DANGEROUS CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design... and in the first tier of the superstructure must be a fixed type. (e) Air intakes and openings into... at not less than 207 kPa gauge (30 psig). (f) On liquefied toxic gas vessels, the closures required...

46 CFR 154.330 - Openings to accommodation, service, or control spaces.

Code of Federal Regulations, 2011 CFR

2011-10-01

... DANGEROUS CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design... and in the first tier of the superstructure must be a fixed type. (e) Air intakes and openings into... at not less than 207 kPa gauge (30 psig). (f) On liquefied toxic gas vessels, the closures required...

46 CFR 154.330 - Openings to accommodation, service, or control spaces.

Code of Federal Regulations, 2013 CFR

2013-10-01

... DANGEROUS CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design... and in the first tier of the superstructure must be a fixed type. (e) Air intakes and openings into... at not less than 207 kPa gauge (30 psig). (f) On liquefied toxic gas vessels, the closures required...

46 CFR 154.330 - Openings to accommodation, service, or control spaces.

Code of Federal Regulations, 2014 CFR

2014-10-01

... DANGEROUS CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design... and in the first tier of the superstructure must be a fixed type. (e) Air intakes and openings into... at not less than 207 kPa gauge (30 psig). (f) On liquefied toxic gas vessels, the closures required...

21 CFR 520.2325b - Sulfaquinoxaline drench.

Code of Federal Regulations, 2011 CFR

2011-04-01

....2325b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... commitment to undertake the human safety studies required by FDA. (e) Conditions of uses. As a 25-percent... for each 125 pounds of body weight for 3 to 5 days as a drench. (f) Limitations. For control of...

21 CFR 520.2325b - Sulfaquinoxaline drench.

Code of Federal Regulations, 2012 CFR

2012-04-01

....2325b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... commitment to undertake the human safety studies required by FDA. (e) Conditions of uses. As a 25-percent... for each 125 pounds of body weight for 3 to 5 days as a drench. (f) Limitations. For control of...

21 CFR 520.2325b - Sulfaquinoxaline drench.

Code of Federal Regulations, 2013 CFR

2013-04-01

....2325b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... commitment to undertake the human safety studies required by FDA. (e) Conditions of uses. As a 25-percent... for each 125 pounds of body weight for 3 to 5 days as a drench. (f) Limitations. For control of...

21 CFR 520.2325b - Sulfaquinoxaline drench.

Code of Federal Regulations, 2014 CFR

2014-04-01

....2325b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... commitment to undertake the human safety studies required by FDA. (e) Conditions of uses. As a 25-percent... for each 125 pounds of body weight for 3 to 5 days as a drench. (f) Limitations. For control of...

21 CFR 520.2325b - Sulfaquinoxaline drench.

Code of Federal Regulations, 2010 CFR

2010-04-01

....2325b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... commitment to undertake the human safety studies required by FDA. (e) Conditions of uses. As a 25-percent... for each 125 pounds of body weight for 3 to 5 days as a drench. (f) Limitations. For control of...

28 CFR 50.9 - Policy with regard to open judicial proceedings.

Code of Federal Regulations, 2011 CFR

2011-07-01

... safety of parties, witnesses, or other persons; or (iii) A substantial likelihood that ongoing... judicial proceedings pursuant to 18 U.S.C. 3509 (d) and (e) for the protection of child victims or child witnesses. (f) Because of the vital public interest in open judicial proceedings, the records of any...

28 CFR 50.9 - Policy with regard to open judicial proceedings.

Code of Federal Regulations, 2014 CFR

2014-07-01

... safety of parties, witnesses, or other persons; or (iii) A substantial likelihood that ongoing... judicial proceedings pursuant to 18 U.S.C. 3509 (d) and (e) for the protection of child victims or child witnesses. (f) Because of the vital public interest in open judicial proceedings, the records of any...

28 CFR 50.9 - Policy with regard to open judicial proceedings.

Code of Federal Regulations, 2012 CFR

2012-07-01

... safety of parties, witnesses, or other persons; or (iii) A substantial likelihood that ongoing... judicial proceedings pursuant to 18 U.S.C. 3509 (d) and (e) for the protection of child victims or child witnesses. (f) Because of the vital public interest in open judicial proceedings, the records of any...

28 CFR 50.9 - Policy with regard to open judicial proceedings.

Code of Federal Regulations, 2013 CFR

2013-07-01

... safety of parties, witnesses, or other persons; or (iii) A substantial likelihood that ongoing... judicial proceedings pursuant to 18 U.S.C. 3509 (d) and (e) for the protection of child victims or child witnesses. (f) Because of the vital public interest in open judicial proceedings, the records of any...

75 FR 35265 - Safety Standard for Infant Walkers: Final Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-21

... application, the maximum allowable displacement (i.e., movement) of the walker is 1.97 inches. The commenter... advocated increasing the maximum allowable displacement to 6 inches in accordance with ASTM F 2012. Response... playing with toys. The parking brake performance test should set limits on the displacement of the walker...

Draft genomic sequencing of six potential extraintestinal pathogenic Escherichia coli isolates from retail chicken meat.

USDA-ARS?s Scientific Manuscript database

Potential Extraintestinal pathogenic Escherichia coli isolates DP254, WH333, WH398, F356, FEX675 and FEX725 were isolated from retail chicken meat products. Here, we report the draft genome sequences for these six E. coli isolates, which are currently being used in food safety research....

30 CFR 18.95 - Approval of machines constructed of components approved, accepted or certified under Bureau of...

Code of Federal Regulations, 2011 CFR

2011-07-01

... approved, accepted or certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G. 18.95 Section 18.95..., accepted or certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G. Machines for which field approval... 2D, 2E, 2F, or 2G, shall be approved following a determination by the electrical representative that...

30 CFR 18.95 - Approval of machines constructed of components approved, accepted or certified under Bureau of...

Code of Federal Regulations, 2013 CFR

2013-07-01

... approved, accepted or certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G. 18.95 Section 18.95..., accepted or certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G. Machines for which field approval... 2D, 2E, 2F, or 2G, shall be approved following a determination by the electrical representative that...

30 CFR 18.95 - Approval of machines constructed of components approved, accepted or certified under Bureau of...

Code of Federal Regulations, 2010 CFR

2010-07-01

... approved, accepted or certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G. 18.95 Section 18.95..., accepted or certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G. Machines for which field approval... 2D, 2E, 2F, or 2G, shall be approved following a determination by the electrical representative that...

30 CFR 18.95 - Approval of machines constructed of components approved, accepted or certified under Bureau of...

Code of Federal Regulations, 2014 CFR

2014-07-01

... approved, accepted or certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G. 18.95 Section 18.95..., accepted or certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G. Machines for which field approval... 2D, 2E, 2F, or 2G, shall be approved following a determination by the electrical representative that...

30 CFR 18.95 - Approval of machines constructed of components approved, accepted or certified under Bureau of...

Code of Federal Regulations, 2012 CFR

2012-07-01

... approved, accepted or certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G. 18.95 Section 18.95..., accepted or certified under Bureau of Mines Schedule 2D, 2E, 2F, or 2G. Machines for which field approval... 2D, 2E, 2F, or 2G, shall be approved following a determination by the electrical representative that...

Calculation of Scattering Amplitude Without Partial Analysis. II; Inclusion of Exchange

NASA Technical Reports Server (NTRS)

Temkin, Aaron; Shertzer, J.; Fisher, Richard R. (Technical Monitor)

2002-01-01

There was a method for calculating the whole scattering amplitude, f(Omega(sub k)), directly. The idea was to calculate the complete wave function Psi numerically, and use it in an integral expression for f, which can be reduced to a 2 dimensional quadrature. The original application was for e-H scattering without exchange. There the Schrodinger reduces a 2-d partial differential equation (pde), which was solved using the finite element method (FEM). Here we extend the method to the exchange approximation. The S.E. can be reduced to a pair of coupled pde's, which are again solved by the FEM. The formal expression for f(Omega(sub k)) consists two integrals, f+/- = f(sub d) +/- f(sub e); f(sub d) is formally the same integral as the no-exchange f. We have also succeeded in reducing f(sub e) to a 2-d integral. Results will be presented at the meeting.

Collision-Induced Dissociation Study of Strong Hydrogen-Bonded Cluster Ions Y-(HF) n (Y=F, O2) Using Atmospheric Pressure Corona Discharge Ionization Mass Spectrometry Combined with a HF Generator.

PubMed

Sakamoto, Kenya; Sekimoto, Kanako; Takayama, Mitsuo

2017-01-01

Hydrogen fluoride (HF) was produced by a homemade HF generator in order to investigate the properties of strong hydrogen-bonded clusters such as (HF) n . The HF molecules were ionized in the form of complex ions associated with the negative core ions Y - produced by atmospheric pressure corona discharge ionization (APCDI). The use of APCDI in combination with the homemade HF generator led to the formation of negative-ion HF clusters Y - (HF) n (Y=F, O 2 ), where larger clusters with n ≥4 were not detected. The mechanisms for the formation of the HF, F - (HF) n , and O 2 - (HF) n species were discussed from the standpoints of the HF generator and APCDI MS. By performing energy-resolved collision-induced dissociation (CID) experiments on the cluster ions F - (HF) n ( n =1-3), the energies for the loss of HF from F - (HF) 3 , F - (HF) 2 , and F - (HF) were evaluated to be 1 eV or lower, 1 eV or higher, and 2 eV, respectively, on the basis of their center-of-mass energy ( E CM ). These E CM values were consistent with the values of 0.995, 1.308, and 2.048 eV, respectively, obtained by ab initio calculations. The stability of [O 2 (HF) n ] - ( n =1-4) was discussed on the basis of the bond lengths of O 2 H-F - (HF) n and O 2 - H-F(HF) n obtained by ab initio calculations. The calculations indicated that [O 2 (HF) 4 ] - separated into O 2 H and F - (HF) 3 .

A job safety program for construction workers designed to reduce the potential for occupational injury using tool box training sessions and computer-assisted biofeedback stress management techniques.

PubMed

Johnson, Kenneth A; Ruppe, Joan

2002-01-01

This project was conducted with a multicultural construction company in Hawaii, USA. The job duties performed included drywall and carpentry work. The following objectives were selected for this project: (a) fire prevention training and inspection of first aid equipment; (b) blood-borne pathogen training and risk evaluation; (c) ergonomic and risk evaluation intervention program; (d) electrical safety training and inspection program; (e) slips, trips, and falls safety training; (f) stress assessment and Personal Profile System; (g) safety and health program survey; (h) improving employee relations and morale by emphasizing spirituality; and (i) computer-assisted biofeedback stress management training. Results of the project indicated that observed safety hazards, reported injuries, and levels of perceived stress. were reduced for the majority of the population.

Novel Zn(II)2Cys6 transcription factor in Fusarium equiseti trichothecene gene cluster is a pathway specific and global regulator

USDA-ARS?s Scientific Manuscript database

Trichothecenes are among the mycotoxins of greatest concern to food and feed safety and are produced by at least two lineages of Fusarium: the F. sambucinum (FSAMSC) and F. incarnatum-equiseti (FIESC) species complexes. Trichothecene biosynthesis begins with the formation of a cyclic sesquiterpene f...

NON-Shock-Plasticity/Fracture Burst Acoustic-Emission(BAE) ``1''/f -``Noise'' Power-Spectrum(PS) Power-Law UNIVERSALITY is Merely F =ma Time-Series Integral-Transform, aka ``Bak'' -``SOC'' REdiscovery'' PRE(1687)-``Bak'' (1988)

NASA Astrophysics Data System (ADS)

Siegel, Edward

2015-06-01

NON-shock plasticity/fracture BAE[E.S.:MSE 8,310(71); PSS:(a)5,601/607(71); Xl.-Latt.Defects 5,277(74); Scripta Met.:6,785(72); 8,587/617(74); 3rd Tokyo AE Symp.(76); Acta Met. 5,383(77); JMMM 7,312(78)] ``1''/ ω-``noise'' power-spectrum ``pink''-Zipf(NOT ``red'' =Pareto) power-law UNIVERSALITY is manifestly-demonstrated in two distinct ways to be nothing but Newton 3rd Law of Motion F = ma REdiscovery!!! (aka ``Bak''(1988)-``SOC'':1687 <<<1988: 1988-1687 =301-years!!! PHYSICS:F =ma cross-multiplied as 1/m =a/F =OUTPUT/INPUT = EFFECT/CAUSE =inverse-mass mechanical-susceptibility = χ (`` ω'') χ(`` ω'') ~(F.-D.thm.) ~P(`` ω'') ``noise'' power-spectrum; (``Max & Al show''): E ~ ω & E ~ (upper-limiting-speeds media) ~m. Thus: ω ~ E ~m Inverting: 1/ ω ~ 1/E ~1/m ~a/F = χ (`` ω'') ~P(`` ω'') Thus: F =ma integral-transform(I-T) is ````SOC'''s'' P(ω) ~ 1/ ω!!! ; ''PURE''-MATHS: F =ma DOUBLE-integral time-series(T-S) s(t) =[v0t +(1/2)at2] I-T formally de?nes power-spectrum(PS): P(ω) ≡ ∫ s(t)e-iωtdt = ∫ [vot +(1/2)at2]e-iωtdt = vo ∫ a(t)e-iωtdt +(1/2)[a ≠a(t)] ∫t2e-iωtdt =vo(∂ / ∂ω) δ(ω) + (1/2)[a ≠a(t)](∂2/ ∂ω2) δ(ω) = vo/ω0 + (1/2)[a ≠a(t)]/ω 1 . 000 ...; uniform-velocity a =0 PS P(ω) = 1/ωo WHITE vs. uniform:-a>0a<0) PS P(ω) = 1/ω 1 . 000 ... pink/flicker/HYPERBOLICITY.

MILES Pressure/Seismic Response Engineering Development of MILES Test Fixture.

DTIC Science & Technology

1980-08-01

A t ditioti td t’,i o, ,,[ ’ or 44 : t 󈧗’) .0 4 ::: r-C Irr 419: 0,11 5 E+ I-E Mrl;A D ATA FAE’SUL 420: t’:r = I t,. 444: t =t tt1l N # ’’ f t o...3 17 T PA II C E R. TD ES T 58: 2 ;.rt . PI’ MERSUFEP! F112: A.ILE70 ,""",蘇_-244 EtIT": 113: [e 47it -𔄁 t+ 13 -.7!1 end 5’?: l+ " ’:;.,r...34calculate "TRANSPOSI TIOS distonce bet.ee 455: for C.=1 to ’ 4t tde n transposition T-2 416: test defe s = td deviation 456: if abs(L[C+ 4ts":477: if E

Spectral Deferred Corrections for Parabolic Partial Differential Equations

DTIC Science & Technology

2015-06-08

n− 1. (5.1) The inverse DFT is given by the formula fj = n−1∑ k=0 f̂` e 2πi`j/n, j = 0, . . . , n− 1 (5.2) (see, e.g., [23, 33]). The n complex...n−1 2∑ `=−n−1 2 f̂` e 2πi`j/n, j = 0, . . . , n− 1. (5.4) While the forms (5.1) and (5.2) are the standard representation for the DFT, the forms...samples on [0, 1], then (5.4) can be restated as f(xj) = n−1 2∑ `=−n−1 2 f̂` e 2πi`tj , j = 0, . . . , n− 1. (5.5) The corresponding trigonometric

Multiple-dose pharmacokinetics and safety of an ibuprofen-pseudoephedrine cold suspension in children.

PubMed

Gelotte, Cathy K; Prior, Mary Jane; Pendley, Charles; Zimmerman, Brenda; Lavins, Bernard J

2010-07-01

Two studies were conducted to characterize multiple-dose pharmacokinetics and potential drug interactions of ibuprofen and pseudoephedrine combined in a suspension and to evaluate safety of this combination in children with common cold, flu, or sinusitis. In the pharmacokinetic study, 24 healthy children aged 4-11 years were administered ibuprofen -pseudoephedrine suspension at 7.5 and 1.125 mg/kg, respectively, every 6 hours for 5 doses. Serial blood samples were drawn over 6 hours after final dose for assessment of steady-state pharmacokinetics. In the open-label, multicenter safety study, more than 100 children aged 2-11 years experiencing symptomatic rhinitis were enrolled. Ibuprofen -pseudoephedrine suspension was administered as needed at similar mg/kg doses every 6-8 hours for up to 3 days. Subjects enrolled in the pharmacokinetic study showed no accumulation of either drug; their weight-adjusted clearances were independent of age, and results were comparable with those from previous single-ingredient studies. For ibuprofen, oral clearance (Cl/F) was 77.5 + or - 16.4 mL/kg/h and volume of distribution (Vd/F) was 0.147 + or - 0.037 L/kg. For pseudoephedrine, Cl/F was 12.3 + or - 2.2 mL/kg/min and Vd/F was 2.52 + or - 0.47 L/kg. In the safety study, adverse events were reported for 18.4% of subjects; most were mild to moderate intensity. There was little difference in incidence of adverse events among different age and weight groups. In conclusion, administration of combined ibuprofen and pseudoephedrine in children demonstrated similar pharmacokinetics when compared with reports of the pharmacokinetics for the single-ingredient products, consistent with no apparent drug interactions. The combination suspension was generally well tolerated.

Safety of ultrasound-guided high-intensity focused ultrasound ablation for diffuse adenomyosis: A retrospective cohort study.

PubMed

Feng, Yujie; Hu, Liang; Chen, Wenzhi; Zhang, Rong; Wang, Xi; Chen, Jinyun

2017-05-01

To evaluate the safety of ultrasound-guided high-intensity focused ultrasound (HIFU) ablation for patients with diffuse adenomyosis. This was a retrospective cohort study. The data was collected from 417 symptomatic adenomyosis patients who underwent ultrasound-guided HIFU between January 2012 and December 2015 at 1st Affiliated Hospital of Chongqing Medical University, Chongqing, China. Among them were 260 patients with diffuse adenomyosis (Group D) and 157 patients with focal adenomyosis (Group F). All patients underwent contrast-enhanced magnetic resonance imaging (MRI) one week before and the day after HIFU treatment. Successful treatment with HIFU was measured by the non-perfused volume ratio (NPVR). Intraprocedural and postprocedural adverse effects and complications were recorded to assess the safety of the procedure. Patients were followed-up for three months post-treatment. Complications were given a grade A through F according to the SIR Standards. All patients successfully completed the procedure, non-perfused regions appeared in 415 (99.5%) patients. The non-perfused volume ratio (NPVR) of Group D was significantly lower than that of Group F (P<0.05). During the procedure, the odds ratio of skin-burning pain was 1.7 (OR=1.617, 95% CI: 1.103-2.532), when comparing Group D with Group F, while the odds ratio of inguinal pain was equal to 2.0 (OR=2.038, 95% CI: 1.161-3.580), when Group F was compared to Group D. 97 patients (23.3%) received nominal therapy due to complications ([Society of interventional radiology, SIR]-B grade), among them, there were 62 cases (23.8%) in Group D and 35 cases (22.3%) in Group F. No significant difference was found between the two groups (P>0.05) and neither of the reported complications of SIR-C-SIR-F occurred within the two groups. Based on our results, ultrasound-guided HIFU is safe for the treatment of diffuse adenomyosis, and controlling the ablation zone is crucial to ensure patients' safety. Copyright © 2016 Elsevier B.V. All rights reserved.

Safety, pharmacokinetics, metabolism and radiation dosimetry of 18F-tetrafluoroborate (18F-TFB) in healthy human subjects.

PubMed

Jiang, Huailei; Schmit, Nicholas R; Koenen, Alex R; Bansal, Aditya; Pandey, Mukesh K; Glynn, Robert B; Kemp, Bradley J; Delaney, Kera L; Dispenzieri, Angela; Bakkum-Gamez, Jamie N; Peng, Kah-Whye; Russell, Stephen J; Gunderson, Tina M; Lowe, Val J; DeGrado, Timothy R

2017-10-27

18 F-Tetrafluoroborate ( 18 F-TFB) is a promising iodide analog for PET imaging of thyroid cancer and sodium/iodide symporter (NIS) reporter activity in viral therapy applications. The aim of this study was to evaluate the safety, pharmacokinetics, biodistribution, and radiation dosimetry of high-specific activity 18 F-TFB in healthy human subjects. 18 F-TFB was synthesized with specific activity of 3.2 ± 1.3 GBq/μmol (at the end of synthesis). Dynamic and whole-body static PET/CT scans over 4 h were performed after intravenous administration of 18 F-TFB (333-407 MBq) in four female and four male healthy volunteers (35 ± 11 years old). Samples of venous blood and urine were collected over the imaging period and analyzed by ion-chromatography HPLC to determine tracer stability. Vital signs and clinical laboratory safety assays were measured to evaluate safety. 18 F-TFB administration was well tolerated with no significant findings on vital signs and no clinically meaningful changes in clinical laboratory assays. Left-ventricular blood pool time-activity curves showed a multi-phasic blood clearance of 18 F-radioactivity with the two rapid clearance phases over the first 20 min, followed by a slower clearance phase. HPLC analysis showed insignificant 18 F-labeled metabolites in the blood and urine over the length of the study (4 h). High uptakes were seen in the thyroid, stomach, salivary glands, and bladder. Urinary clearance of 18 F-TFB was prominent. Metabolic stability was evidenced by low accumulation of 18 F-radioactivity in the bone. Effective doses were 0.036 mSv/MBq in males and 0.064 mSv/MBq in females (p = 0.08, not significant). This initial study in healthy human subjects showed 18 F-TFB was safe and distributed in the human body similar to other iodide analogs. These data support further translational studies with 18 F-TFB as NIS gene reporter and imaging biomarker for thyroid cancer and other disease processes that import iodide.

Synthesis of [18F]-labelled Maltose Derivatives as PET Tracers for Imaging Bacterial Infection

PubMed Central

Namavari, Mohammad; Gowrishankar, Gayatri; Hoehne, Aileen; Jouannot, Erwan; Gambhir, Sanjiv S

2015-01-01

Purpose To develop novel positron emission tomography (PET) agents for visualization and therapy monitoring of bacterial infections. Procedures It is known that maltose and maltodextrins are energy sources for bacteria. Hence, 18F-labelled maltose derivatives could be a valuable tool for imaging bacterial infections. We have developed methods to synthesize 4-O-(α-D-glucopyranosyl)-6-deoxy-6-[18F]fluoro-D-glucopyranoside (6-[18F]fluoromaltose) and 4-O-(α-D-glucopyranosyl)-1-deoxy-1-[18F]fluoro-D-glucopyranoside (1-[18F]fluoromaltose) as bacterial infection PET imaging agents. 6-[18F]fluoromaltose was prepared from precursor 1,2,3-tri-O-acetyl-4-O-(2′,3′,-di-O-acetyl-4′,6′-benzylidene-α-D-glucopyranosyl)-6-deoxy-6-nosyl-D-glucopranoside (5). The synthesis involved the radio-fluorination of 5 followed by acidic and basic hydrolysis to give 6-[18F]fluoromaltose. In an analogous procedure, 1-[18F]fluoromaltose was synthesized from 2,3, 6-tri-O-acetyl-4-O-(2′,3′,4′,6-tetra-O-acetyl-α-D-glucopyranosyl)-1-deoxy-1-O-triflyl-D-glucopranoside (9). Stability of 6-[18F]fluoromaltose in phosphate-buffered saline (PBS) and human and mouse serum at 37 °C was determined. Escherichia coli uptake of 6-[18F]fluoromaltose was examined. Results A reliable synthesis of 1- and 6-[18F]fluoromaltose has been accomplished with 4–6 and 5–8 % radiochemical yields, respectively (decay-corrected with 95 % radiochemical purity). 6-[18F]fluoromaltose was sufficiently stable over the time span needed for PET studies (~96 % intact compound after 1-h and ~65 % after 2-h incubation in serum). Bacterial uptake experiments indicated that E. coli transports 6-[18F]fluoromaltose. Competition assays showed that the uptake of 6-[18F]fluoromaltose was completely blocked by co-incubation with 1 mM of the natural substrate maltose. Conclusion We have successfully synthesized 1- and 6-[18F]fluoromaltose via direct fluorination of appropriate protected maltose precursors. Bacterial uptake experiments in E. coli and stability studies suggest a possible application of 6-[18F]fluoromaltose as a new PET imaging agent for visualization and monitoring of bacterial infections. PMID:25277604

Simple systematization of vibrational excitation cross-section calculations for resonant electron-molecule scattering in the boomerang and impulse models.

PubMed

Sarma, Manabendra; Adhikari, S; Mishra, Manoj K

2007-01-28

Vibrational excitation (nu(f)<--nu(i)) cross-sections sigma(nu(f)<--nu(i) )(E) in resonant e-N(2) and e-H(2) scattering are calculated from transition matrix elements T(nu(f),nu(i) )(E) obtained using Fourier transform of the cross correlation function , where psi(nu(i))(R,t) approximately =e(-iH(A(2))-(R)t/h phi(nu(i))(R) with time evolution under the influence of the resonance anionic Hamiltonian H(A(2) (-))(A(2) (-)=N(2)(-)/H(2) (-)) implemented using Lanczos and fast Fourier transforms. The target (A(2)) vibrational eigenfunctions phi(nu(i))(R) and phi(nu(f))(R) are calculated using Fourier grid Hamiltonian method applied to potential energy (PE) curves of the neutral target. Application of this simple systematization to calculate vibrational structure in e-N(2) and e-H(2) scattering cross-sections provides mechanistic insights into features underlying presence/absence of structure in e-N(2) and e-H(2) scattering cross-sections. The results obtained with approximate PE curves are in reasonable agreement with experimental/calculated cross-section profiles, and cross correlation functions provide a simple demarcation between the boomerang and impulse models.

Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent--a pilot study.

PubMed

Lin, Kun-Ju; Hsu, Wen-Chuin; Hsiao, Ing-Tsung; Wey, Shiaw-Pyng; Jin, Lee-Way; Skovronsky, Daniel; Wai, Yau-Yau; Chang, Hsiu-Ping; Lo, Chuan-Wei; Yao, Cheng Hsiang; Yen, Tzu-Chen; Kung, Mei-Ping

2010-05-01

The compound (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([(18)F]AV-45) is a novel radiopharmaceutical capable of selectively binding to beta-amyloid (A beta) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [(18)F]AV-45 in human subjects. In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0+/-5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9+/-13.9 MBq of [(18)F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7+/-13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. In vitro autoradiography revealed exquisitely high specific binding of [(18)F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12+/-0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7+/-78.6 microGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [(18)F]AV-45 were 33.8+/-3.4 microSv/MBq and 19.3+/-1.3 microSv/MBq, respectively. [(18)F]AV-45 binds specifically to A beta in vitro, and is a safe PET tracer for studying A beta distribution in human brain. The dosimetry is suitable for clinical and research application. (c) 2010 Elsevier Inc. All rights reserved.

Joint Force Quarterly. Number 21, Spring 1999

DTIC Science & Technology

1999-03-01

T H E J O I N T W O R L D 113 Doctrine ■ O F F T H E S H E L F 115 Mahan’s Blindness and Brilliance: A Review Essay...er ) U . S . A ir Fo rc e (J oe B el a) 2d M ar in e D iv is io n, C om ba t C am er a (J ac ob A . F ul le r) Marines in Norway for Battle...98. 2d M ar in e D iv is

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research☆

PubMed Central

Rossi, Simone; Hallett, Mark; Rossini, Paolo M.; Pascual-Leone, Alvaro

2011-01-01

This article is based on a consensus conference, which took place in Certosa di Pontignano, Siena (Italy) on March 7–9, 2008, intended to update the previous safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings. Over the past decade the scientific and medical community has had the opportunity to evaluate the safety record of research studies and clinical applications of TMS and repetitive TMS (rTMS). In these years the number of applications of conventional TMS has grown impressively, new paradigms of stimulation have been developed (e.g., patterned repetitive TMS) and technical advances have led to new device designs and to the real-time integration of TMS with electroencephalography (EEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Thousands of healthy subjects and patients with various neurological and psychiatric diseases have undergone TMS allowing a better assessment of relative risks. The occurrence of seizures (i.e., the most serious TMS-related acute adverse effect) has been extremely rare, with most of the few new cases receiving rTMS exceeding previous guidelines, often in patients under treatment with drugs which potentially lower the seizure threshold. The present updated guidelines review issues of risk and safety of conventional TMS protocols, address the undesired effects and risks of emerging TMS interventions, the applications of TMS in patients with implanted electrodes in the central nervous system, and safety aspects of TMS in neuroimaging environments. We cover recommended limits of stimulation parameters and other important precautions, monitoring of subjects, expertise of the rTMS team, and ethical issues. While all the recommendations here are expert based, they utilize published data to the extent possible. PMID:19833552

Overexpression of E2F3 promotes proliferation of functional human β cells without induction of apoptosis

PubMed Central

Rady, Brian; Chen, Yanmei; Vaca, Pilar; Wang, Qian; Wang, Yong; Salmon, Patrick; Oberholzer, José

2013-01-01

The mechanisms that control proliferation, or lack thereof, in adult human β cells are poorly understood. Controlled induction of proliferation could dramatically expand the clinical application of islet cell transplantation and represents an important component of regenerative approaches to a functional cure of diabetes. Adult human β cells are particularly resistant to common proliferative targets and often dedifferentiate during proliferation. Here we show that expression of the transcription factor E2F3 has a role in regulating β-cell quiescence and proliferation. We found human islets have virtually no expression of the pro-proliferative G1/S transcription factors E2F1–3, but an abundance of inhibitory E2Fs 4–6. In proliferative human insulinomas, inhibitory E2Fs were absent, while E2F3 is expressed. Using this pattern as a “roadmap” for proliferation, we demonstrated that ectopic expression of nuclear E2F3 induced significant expansion of insulin-positive cells in both rat and human islets. These cells did not undergo apoptosis and retained their glucose-responsive insulin secretion, showing the ability to reverse diabetes in mice. Our results suggest that E2F4–6 may help maintain quiescence in human β cells and identify E2F3 as a novel target to induce proliferation of functional β cells. Refinement of this approach may increase the islets available for cell-based therapies and research and could provide important cues for understanding in vivo proliferation of β cells. PMID:23907129

Advanced Motor-Controller Development.

DTIC Science & Technology

1983-06-22

OUTPUTS: 16 BIT PROE:UCT IN ACCA , FiCC:B Oi:t2 -* 0011: 0172 B:7 .04E SIFY STA A MCAN:,* SF,-’E MULTIPLICAND 001t4 0175 iF CLF: A INIT RESUI_I_T AOll5...OL-:t41) 04: ELSE ACCA IS UNC:HANGED 0-142 01SF ::,A 0CI CLAMP 0’Fi A #0 TEST SIGN OF A C0It 0l91 E’E: fBM I C.LIPI EBRFNCH IF NEG 01t4 4 : : 001,15 19...ELSE S.:ET ACCA =-ACCB:1B TQJ5. 01 .’ NEG B .ESTOPE ACCE: 01155 C. l1’-9 E -9 PTI RETUR’N Al? I .9~~ _________ . .... ... | |- - - - . . rjOt :E

Role of SKP1-CUL1-F-Box-Protein (SCF) E3 Ubiquitin Ligases in Skin Cancer

PubMed Central

Xie, Chuan-Ming; Wei, Wenyi; Sun, Yi

2013-01-01

Many biological processes such as cell proliferation, differentiation, and cell death depend precisely on the timely synthesis and degradation of key regulatory proteins. While protein synthesis can be regulated at multiple levels, protein degradation is mainly controlled by the ubiquitin—proteasome system (UPS), which consists of two distinct steps: (1) ubiquitylation of targeted protein by E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and E3 ubiquitin ligase, and (2) subsequent degradation by the 26S proteasome. Among all E3 ubiquitin ligases, the SCF (SKP1-CUL1-F-box protein) E3 ligases are the largest family and are responsible for the turnover of many key regulatory proteins. Aberrant regulation of SCF E3 ligases is associated with various human diseases, such as cancers, including skin cancer. In this review, we provide a comprehensive overview of all currently published data to define a promoting role of SCF E3 ligases in the development of skin cancer. The future directions in this area of research are also discussed with an ultimate goal to develop small molecule inhibitors of SCF E3 ligases as a novel approach for the treatment of human skin cancer. Furthermore, altered components or substrates of SCF E3 ligases may also be developed as the biomarkers for early diagnosis or predicting prognosis. PMID:23522382

First somatic mutation of E2F1 in a critical DNA binding residue discovered in well-differentiated papillary mesothelioma of the peritoneum

PubMed Central

2011-01-01

Background Well differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare variant of epithelial mesothelioma of low malignancy potential, usually found in women with no history of asbestos exposure. In this study, we perform the first exome sequencing of WDPMP. Results WDPMP exome sequencing reveals the first somatic mutation of E2F1, R166H, to be identified in human cancer. The location is in the evolutionarily conserved DNA binding domain and computationally predicted to be mutated in the critical contact point between E2F1 and its DNA target. We show that the R166H mutation abrogates E2F1's DNA binding ability and is associated with reduced activation of E2F1 downstream target genes. Mutant E2F1 proteins are also observed in higher quantities when compared with wild-type E2F1 protein levels and the mutant protein's resistance to degradation was found to be the cause of its accumulation within mutant over-expressing cells. Cells over-expressing wild-type E2F1 show decreased proliferation compared to mutant over-expressing cells, but cell proliferation rates of mutant over-expressing cells were comparable to cells over-expressing the empty vector. Conclusions The R166H mutation in E2F1 is shown to have a deleterious effect on its DNA binding ability as well as increasing its stability and subsequent accumulation in R166H mutant cells. Based on the results, two compatible theories can be formed: R166H mutation appears to allow for protein over-expression while minimizing the apoptotic consequence and the R166H mutation may behave similarly to SV40 large T antigen, inhibiting tumor suppressive functions of retinoblastoma protein 1. PMID:21955916

75 FR 34062 - Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model AS355 E, F, F1, F2... AS 350 B, BA, B1, B2, B3, and D, and Model AS355 E, F, F1, F2, and N helicopters, with certain main... an unsafe condition for certain Eurocopter France Model AS 350 B, BA, BB, B1, B2, B3, and D, and...

Dover AFB Delaware. Revised Uniform Summary of Surface Weather Observations. Parts A-F

DTIC Science & Technology

1974-08-07

8217 C IN @1 iN 2,2 71 SE 5, _ I _____. ws . 2,. A,’ , S _____ __ . _____ ____Sw . , 2, - :j ih , I. I I 12 .. SSWA NABE O2 .O 1.4 a CIO.S921 0 soi 4... SY HrsOMthTprat u MMA c Pe. H. AFD573 t ) 91660R 77 0 41 0 2-408b- 0_F_32_F_67_F73_F _8__F_ 93_ _ol I’- a ii-E 29(,06 899 3*CE/MA296.C4.19 -4- -E _1

Qualification of the flight-critical AFTI/F-16 digital flight control system. [Advanced Fighter Technology Integration

NASA Technical Reports Server (NTRS)

Mackall, D. A.; Ishmael, S. D.; Regenie, V. A.

1983-01-01

Qualification considerations for assuring the safety of a life-critical digital flight control system include four major areas: systems interactions, verification, validation, and configuration control. The AFTI/F-16 design, development, and qualification illustrate these considerations. In this paper, qualification concepts, procedures, and methodologies are discussed and illustrated through specific examples.

Status of development of LCOS projection displays for F-22A, F/A-18E/F, and JSF cockpits

NASA Astrophysics Data System (ADS)

Kalmanash, Michael H.

2001-09-01

Projection display technology has been found to be an attractive alternative to direct view flat panel displays in many avionics applications. The projection approach permits compact high performance systems to be tailored to specific platform needs while using a complement of commercial off the shelf (COTS) components, including liquid crystal on silicon (LCOS) microdisplay imagers. A common projection engine used on multiple platforms enables improved performance, lower cost and shorter development cycles. This paper provides a status update for projection displays under development for the F-22A, the F/A-18E/F and the Lockheed Joint Strike Fighter (JSF) aircraft.

Integrated Systems Health Management for Space Exploration

NASA Technical Reports Server (NTRS)

Uckun, Serdar

2005-01-01

Integrated Systems Health Management (ISHM) is a system engineering discipline that addresses the design, development, operation, and lifecycle management of components, subsystems, vehicles, and other operational systems with the purpose of maintaining nominal system behavior and function and assuring mission safety and effectiveness under off-nominal conditions. NASA missions are often conducted in extreme, unfamiliar environments of space, using unique experimental spacecraft. In these environments, off-nominal conditions can develop with the potential to rapidly escalate into mission- or life-threatening situations. Further, the high visibility of NASA missions means they are always characterized by extraordinary attention to safety. ISHM is a critical element of risk mitigation, mission safety, and mission assurance for exploration. ISHM enables: In-space maintenance and repair; a) Autonomous (and automated) launch abort and crew escape capability; b) Efficient testing and checkout of ground and flight systems; c) Monitoring and trending of ground and flight system operations and performance; d) Enhanced situational awareness and control for ground personnel and crew; e) Vehicle autonomy (self-sufficiency) in responding to off-nominal conditions during long-duration and distant exploration missions; f) In-space maintenance and repair; and g) Efficient ground processing of reusable systems. ISHM concepts and technologies may be applied to any complex engineered system such as transportation systems, orbital or planetary habitats, observatories, command and control systems, life support systems, safety-critical software, and even the health of flight crews. As an overarching design and operational principle implemented at the system-of-systems level, ISHM holds substantial promise in terms of affordability, safety, reliability, and effectiveness of space exploration missions.

Fire Safety Aspects of Polymeric Materials. Volume 2. Test Methods, Specifications and Standards

DTIC Science & Technology

1979-01-01

San Francisco, California. RAYMOND R. HINDERSINN, Section Manager, Research Center, Hooker Chemi- cal Co., Niagara Falls, New York. WILLIAM C ...Administration, Washington, D. C . DANIEL F. SHEEHAN, DoT, U. S. Coast Guard, Washington, D. C . WILLIAM J. WERNER, Department of Housing and Urban Development...Executive Scientists and Director Advances Research Program Laboratory 3M Company P. 0. Box 33221 St. Paul, MIM 55133 Mr. William D. Manly

Investigation of the Brain Biodistribution of the Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitor [18F]GSK2647544 in Healthy Male Subjects.

PubMed

Huiban, Mickael; Coello, Christopher; Wu, Kai; Xu, Yanmei; Lewis, Yvonne; Brown, Andrew P; Buraglio, Mauro; Guan, Chenbing; Shabbir, Shaila; Fong, Regan; Passchier, Jan; Rabiner, Eugenii A; Lockhart, Andrew

2017-02-01

GSK2647544 is a potent and specific inhibitor of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), which was in development as a potential treatment for Alzheimer's disease (AD). In order to refine therapeutic dose predictions and confirm brain penetration, a radiolabelled form of the inhibitor, [ 18 F]GSK2647544, was manufactured for use in a positron emission tomography (PET) biodistribution study. [ 18 F]GSK2647544 was produced using a novel, copper iodide (Cu(I)) mediated, [ 18 F]trifluoromethylation methodology. Healthy male subjects (n = 4, age range 34-42) received an oral dose of unlabelled GSK2647544 (100 mg) and after 2 h an intravenous (iv) injection of [ 18 F]GSK2647544 (average injected activity and mass were 106 ± 47 MBq and 179 ± 55 μg, respectively) followed by dynamic PET scans for 120 min. Defined regions of interest (ROI) throughout the brain were used to obtain regional time-activity curves (TACs) and compartmental modelling analysis used to estimate the primary outcome measure, whole brain volume of distribution (V T ). Secondary PK and safety endpoints were also recorded. PET dynamic data were successfully obtained from all four subjects and there were no clinically significant variations of the safety endpoints. Inspection of the TACs indicated a relatively homogenous uptake of [ 18 F]GSK2647544 across all the ROIs examined. The mean whole brain V T was 0.56 (95 % CI, 0.41-0.72). Secondary PK parameters, C max (geometric mean) and T max (median), were 354 ng/ml and 1.4 h, respectively. Metabolism of GSK2647544 was relatively consistent across subjects, with 20-40 % of the parent compound [ 18 F]GSK2647544 present after 120 min. The study provides evidence that GSK2647544 is able to cross the blood brain barrier in healthy male subjects leading to a measurable brain exposure. The administered doses of GSK2647544 were well tolerated. Exploratory modelling suggested that a twice-daily dose of 102 mg, at steady state, would provide ~80 % trough inhibition of brain Lp-PLA 2 activity. Clintrials.gov: NCT01924858.

TaiWan Ionospheric Model (TWIM) prediction based on time series autoregressive analysis

NASA Astrophysics Data System (ADS)

Tsai, L. C.; Macalalad, Ernest P.; Liu, C. H.

2014-10-01

As described in a previous paper, a three-dimensional ionospheric electron density (Ne) model has been constructed from vertical Ne profiles retrieved from the FormoSat3/Constellation Observing System for Meteorology, Ionosphere, and Climate GPS radio occultation measurements and worldwide ionosonde foF2 and foE data and named the TaiWan Ionospheric Model (TWIM). The TWIM exhibits vertically fitted α-Chapman-type layers with distinct F2, F1, E, and D layers, and surface spherical harmonic approaches for the fitted layer parameters including peak density, peak density height, and scale height. To improve the TWIM into a real-time model, we have developed a time series autoregressive model to forecast short-term TWIM coefficients. The time series of TWIM coefficients are considered as realizations of stationary stochastic processes within a processing window of 30 days. These autocorrelation coefficients are used to derive the autoregressive parameters and then forecast the TWIM coefficients, based on the least squares method and Lagrange multiplier technique. The forecast root-mean-square relative TWIM coefficient errors are generally <30% for 1 day predictions. The forecast TWIM values of foE and foF2 values are also compared and evaluated using worldwide ionosonde data.

AML1 is overexpressed in patients with myeloproliferative neoplasms and mediates JAK2V617F-independent overexpression of NF-E2

PubMed Central

Wang, Wei; Schwemmers, Sven; Hexner, Elizabeth O.

2010-01-01

The transcription factor NF-E2 is overexpressed in the majority of patients with polycythemia vera (PV). Concomitantly, 95% of these patients carry the JAK2V617F mutation. Although NF-E2 levels correlate with JAK2V671F allele burden in some PV cohorts, the molecular mechanism causing aberrant NF-E2 expression has not been described. Here we show that NF-E2 expression is also increased in patients with essential thrombocythemia and primary myelofibrosis independent of the presence of the JAK2V617F mutation. Characterization of the NF-E2 promoter revealed multiple functional binding sites for AML1/RUNX-1. Chromatin immunoprecipitation demonstrated AML1 binding to the NF-E2 promoter in vivo. Moreover, AML1 binding to the NF-E2 promoter was significantly increased in granulocytes from PV patients compared with healthy controls. AML1 mRNA expression was elevated in patients with PV, essential thrombocythemia, and primary myelofibrosis both in the presence and absence of JAK2V617F. In addition, AML1 and NF-E2 expression were highly correlated. RNAi-mediated suppression of either AML1 or of its binding partner CBF-β significantly decreased NF-E2 expression. Moreover, expression of the leukemic fusion protein AML/ETO drastically decreased NF-E2 protein levels. Our data identify NF-E2 as a novel AML1 target gene and delineate a role for aberrant AML1 expression in mediating elevated NF-E2 expression in MPN patients. PMID:20339092

iConnect CKD - Virtual Medical Consulting: a web-based Chronic Kidney Disease, Hypertension and Diabetes Integrated Care Program.

PubMed

Katz, Ivor J; Pirabhahar, Saiyini; Williamson, Paula; Raghunath, Vishwas; Brennan, Frank; O'Sullivan, Anthony; Youssef, George; Lane, Cathie; Jacobson, Gary; Feldman, Peter; Kelly, John

2017-05-04

Chronic kidney disease (CKD) patients overwhelm specialist services and can potentially be managed in the primary care (PC). Opportunistic screening of high risk (HR) patients and follow-up in PC is the most sustainable model of care. A 'virtual consultation' (VC) model instead of traditional face to face (F2F) consultations was used, aiming to assess efficacy and safety of the model. Seventy patients were recruited from PC sites and hospital clinics, and followed for one year. The HR patients (eGFR < 30 ml/min/1.73 m 2 +/- albuminuria >30 mg/mmol/L) were randomised to either VC or F2F. Patients were monitored 6 monthly by a Clinical Nurse Specialist (CNS). The specialist team provided virtual or clinical support and included a Nephrologist, Endocrinologist, Cardiologist and Renal 'Palliative' Supportive Care. Sixty one (87%) patients were virtually tracked or consulted with 14 (23%) being HR. At 12 months there was no difference in outcomes between VC and F2F patients. All patients were successfully monitored. GPs reported high level of satisfaction and supported the model, but found software integration challenging. Patients found the system attractive and felt well managed. Specialist consults occurred within a week and if a second specialist opinion was required it took another two weeks. The program demonstrated safe, expedited and efficient follow up with a clinical and web based program. Support from the GPs and patients was encouraging, despite logistical issues. Ongoing evaluation of VC services will continue and feasibility to larger networks and more chronic diseases remains the long term goal. This article is protected by copyright. All rights reserved.

A Numerical Simulation of a Carbon Black Suspension Cell Via a Time-Reversed, Double Layer Compute Algorithm

DTIC Science & Technology

1999-12-01

be accounted for by conventional descriptions of the system response. To remedy this deficiency , researchers developed a theory or model of the...timex,tO, tev, tps REAL*8 uO, width, x, xx, yy, zz, zr REAL*8 FRACi, FRAC2,F0_XX,F0_YY,F0_ZZ REAL*8 TKl, TK2 ,TQl,Tq2 INTEGER I, J, JJ, K, KK, L, NUM...UU2(J+1) !KK = Layer J+i’s time counter. TK1 = TAU(J+1) TK2 = TK1 + DELTAT(KK) j LOOP MCM C: DO KQ = UU2(J+1), KSUM PLTTIME = TIME * 1E+09 DO

Robust Control of Multivariable and Large Scale Systems.

DTIC Science & Technology

1988-03-23

D, and let A E [0, 1]. We need to show that h ((1 - A)D1 + AD2 ) < (1 - A)h(D 1 ) + Ah(D 2) Define f:R-+R by f(t) := h((1 - t)D 1 + tD 2 ) = ebt...SVD -S M = 3UV * + U2E2 V2 *. (13.11) In this setting, / is any singular value of M, not necessarily &(M), but none of the singular values in E 2 should...a)f (x) -afr(y)] and let A be the largest value in [0, 1] that achieves #3. Obviously, since /3 > 0, A E (0, 1). Define tD := (1 - A)x + Ay. Hence f

Development of genetic techniques for the psychrotrophic fish pathogen Flavobacterium psychrophilum.

PubMed

Alvarez, B; Secades, P; McBride, M J; Guijarro, J A

2004-01-01

Flavobacterium psychrophilum, a member of the Cytophaga-Flavobacterium-Bacteroides group, is an important pathogen of salmonid fish. Previous attempts to develop genetic techniques for this fastidious, psychrotrophic bacterium have met with failure. Here we describe the development of techniques for the genetic manipulation of F. psychrophilum and the identification of plasmids, selectable markers, a reporter system, and a transposon that function in several isolates of this fish pathogen. The antibiotic resistance genes ermF, cfxA, and tetQ function in F. psychrophilum. Cloning vectors based on the F. psychrophilum cryptic plasmid pCP1 which carried these selectable markers were introduced by conjugation from E. coli, resulting in antibiotic-resistant colonies of F. psychrophilum. Conjugative transfer of DNA into F. psychrophilum was strain dependent. Efficient transfer was observed for two of the seven strains tested (THC02-90 and THC04-90). E. coli lacZY functioned in F. psychrophilum when expressed from a pCP1 promoter, allowing its development as a reporter for studies of gene expression. Plasmids isolated from F. psychrophilum were efficiently introduced into F. psychrophilum by electroporation, but plasmids isolated from E. coli were not suitable for transfer by this route, suggesting the presence of a restriction barrier. DNA isolated from F. psychrophilum was resistant to digestion by Sau3AI and BamHI, indicating that a Sau3AI-like restriction modification system may constitute part of this barrier. Tn4351 was introduced into F. psychrophilum from E. coli and transposed with apparent randomness, resulting in erythromycin-resistant colonies. The techniques developed in this study allow for genetic manipulation and analysis of this important fish pathogen.

On the Ground Electronic States of TiF and TiCl

NASA Astrophysics Data System (ADS)

Boldyrev, Alexander I.; Simons, Jack

1998-04-01

The low-lying electronic states of TiF and TiCl have been studied using high levelab initiotechniques. Both are found to have two low-lying excited electronic states,4Σ-(0.080 eV (TiF) and 0.236 eV (TiCl)) and2Δ (0.266 eV (TiF) and 0.348 eV (TiCl)), and4Φ ground states at the highest CCSD(T)/6-311++G(2d,2f) level of theory. Our theoretical predictions of4Φ ground electronic states for TiF and TiCl support recent experimental findings by Ram and Bernath, and our calculated bond lengths and vibrational frequencies are in reasonable agreement with their experimental data.

First observations of large-scale wave structure and equatorial spread F using CERTO radio beacon on the C/NOFS satellite

NASA Astrophysics Data System (ADS)

Thampi, Smitha V.; Yamamoto, Mamoru; Tsunoda, Roland T.; Otsuka, Yuichi; Tsugawa, Takuya; Uemoto, Jyunpei; Ishii, Mamoru

2009-09-01

First observations of large-scale wave structure (LSWS) and the subsequent development of equatorial spread F (ESF), using total electron content (TEC) derived from the ground based reception of beacon signals from the CERTO (Coherent Electromagnetic Radio Tomography) radio beacon on board C/NOFS (Communications/Navigation Outage Forecasting System) satellite, are presented. Selected examples of TEC variations, using measurements made during January 2009 from Bac Lieu, Vietnam (9.2°N, 105.6°E geographic, 1.7°N magnetic dip latitude) are presented to illustrate two key findings: (1) LSWS appears to play a more important role in the development of ESF than the post-sunset rise (PSSR) of the F-layer, and (2) LSWS can appear well before E region sunset. Other findings, that LSWS does not have significant zonal drift in the initial stages of growth, and can have zonal wavelengths of several hundred kilometers, corroborate earlier reports.

Development of male sterile Eruca sativa carrying a Raphanus sativus/Brassica oleracea cybrid cytoplasm.

PubMed

Nothnagel, Thomas; Klocke, Evelyn; Schrader, Otto; Linke, Bettina; Budahn, Holger

2016-02-01

Alloplasmic male sterile breeding lines of Eruca sativa were developed by intergeneric hybridization with CMS- Brassica oleracea, followed by recurrent backcrosses and determination of the breeding value. Male sterile breeding lines of rocket salad (Eruca sativa) were developed by intergeneric hybridization with cytoplasmic male sterile (CMS) cauliflower (Brassica oleracea) followed by recurrent backcrosses. Five amphidiploid F1 plants (2n = 2x = 20, CE), achieved by manual crosses and embryo rescue, showed an intermediate habit. The plants were completely male sterile and lacked seed set after pollination with the Eruca parent. Allotetraploid F1-hybrid plants (4n = 4x = 40, CCEE) obtained after colchicine treatment were backcrossed six times with pollen of the Eruca parent to select alloplasmic diploid E. sativa lines. The hybrid status and the nucleo-cytoplasmic constellation were continuously controlled by RAPD and Southern analysis during subsequent backcrosses. The ploidy level was investigated by flow cytometry and chromosome analysis. Premeiotic (sporophytic) and postmeiotic (pollen abortive) defects during the anther development were observed in the alloplasmic E. sativus plants in comparison to the CMS-cauliflower donor. No further incompatibilities were noticed between the CMS-inducing cybrid cytoplasm and the E. sativa nuclear genome. The final alloplasmic E. sativa lines were diploid with 2n = 2x = 22 chromosomes and revealed complete male sterility and restored female fertility. Plant vigor and yield potential of the CMS-E. sativa BC5 lines were comparable to the parental E. sativus line. In conclusion, the employed cybrid-cytoplasm has been proven as a vital source of CMS for E. sativa. The developed lines are directly applicable for hybrid breeding of rocket salad.

Worldwide U.S. Active Duty Military Deaths. Alphabetical Index by Name, 1 October 1979 Through 30 September 1994

DTIC Science & Technology

1994-09-30

DE LME NDO G E R A R D O MAR I GZA A I R F O R C E D E LMUNDO L I LY F E D E R I S NAVY D E LOACH B O B B Y D E A N A I R F ORCE D E LOGE B...YAN LAMON EAR LE JAME S ARTHUR EAR LEY KEN W EAR LEY R OB E R T WI L L IAM J R EAR LS M I CHAE L G EAR LS OMAR DALE EAR LY BE N JAMIN J R...8 9 B R OOK LYN E 0 4 2 2 F e b 8 2 KEN TON E 0 7 14 D e c 9 1 R OCKH I L L 0 0 2 1 4 J u l 8 1 T E XAS C I T Y E 0 6 24 Oc t 7 9

The impact of eHealth on the quality and safety of health care: a systematic overview.

PubMed

Black, Ashly D; Car, Josip; Pagliari, Claudia; Anandan, Chantelle; Cresswell, Kathrin; Bokun, Tomislav; McKinstry, Brian; Procter, Rob; Majeed, Azeem; Sheikh, Aziz

2011-01-18

There is considerable international interest in exploiting the potential of digital solutions to enhance the quality and safety of health care. Implementations of transformative eHealth technologies are underway globally, often at very considerable cost. In order to assess the impact of eHealth solutions on the quality and safety of health care, and to inform policy decisions on eHealth deployments, we undertook a systematic review of systematic reviews assessing the effectiveness and consequences of various eHealth technologies on the quality and safety of care. We developed novel search strategies, conceptual maps of health care quality, safety, and eHealth interventions, and then systematically identified, scrutinised, and synthesised the systematic review literature. Major biomedical databases were searched to identify systematic reviews published between 1997 and 2010. Related theoretical, methodological, and technical material was also reviewed. We identified 53 systematic reviews that focused on assessing the impact of eHealth interventions on the quality and/or safety of health care and 55 supplementary systematic reviews providing relevant supportive information. This systematic review literature was found to be generally of substandard quality with regards to methodology, reporting, and utility. We thematically categorised eHealth technologies into three main areas: (1) storing, managing, and transmission of data; (2) clinical decision support; and (3) facilitating care from a distance. We found that despite support from policymakers, there was relatively little empirical evidence to substantiate many of the claims made in relation to these technologies. Whether the success of those relatively few solutions identified to improve quality and safety would continue if these were deployed beyond the contexts in which they were originally developed, has yet to be established. Importantly, best practice guidelines in effective development and deployment strategies are lacking. There is a large gap between the postulated and empirically demonstrated benefits of eHealth technologies. In addition, there is a lack of robust research on the risks of implementing these technologies and their cost-effectiveness has yet to be demonstrated, despite being frequently promoted by policymakers and "techno-enthusiasts" as if this was a given. In the light of the paucity of evidence in relation to improvements in patient outcomes, as well as the lack of evidence on their cost-effectiveness, it is vital that future eHealth technologies are evaluated against a comprehensive set of measures, ideally throughout all stages of the technology's life cycle. Such evaluation should be characterised by careful attention to socio-technical factors to maximise the likelihood of successful implementation and adoption.

Transformation of heavy metal fractionation under changing environments: a case study of a drainage system in an e-waste dismantling community.

PubMed

Damrongsiri, Seelawut

2018-04-01

The change in environmental conditions during the transportation of contaminated soil and sediment was expected to affect the transformation of heavy metal fractionation. This study disclosed the serious contamination of copper (Cu), lead (Pb), and zinc (Zn) in the sewer sediment of an e-waste dismantling community in Thailand which may be caused by flushed contaminated soil and e-waste fragments. Two environmental conditions were simulated to observe the transformation of heavy metal fractionation. The anoxic sewer condition was induced using high substrate and sulfate in a closed container. The aeration of anoxic contaminated sediment was applied to simulate the transformation to an oxidative environment. The BCR sequential extraction was applied for heavy metal fractionation in this study. The study results exhibited that when heavy metal contaminated soil was transferred into this induced anoxic condition, fractionation was redistributed based on the chemical change of system that tends to be associated into F3 (oxidizable fraction) > F2 (reducible fraction) > F1 (acid soluble/exchangeable fraction). Cu exhibited the outstanding capability association to F3. The iron sulfide was not observed as usual due to its lower capability than Cu, Pb, and Zn. When contaminated sediment was transported to a more oxidative environment, the heavy metals fractionation would be redistributed again among those new environment media. It is noteworthy that F3 of Cu was stable even in oxic conditions. F2 of Fe was not developed by this oxic condition, possibly because its dehydration process was limited. The redistribution under an oxic environment became F1 > F2 > F3 indicating their more available form. This transformation was imperative and should be taken into account in heavy metal contaminated site management and control.

The Numerical Calculation of Traveling Wave Solutions of Nonlinear Parabolic Equations on the Line.

DTIC Science & Technology

1984-02-01

kc(i~~ +’~ which can be rewrittenw W (T is) Ic (sic) - (+ Using the convolution formulas and the expression for the inverse transform of-I (se e.g...2i 2f 1 2 c) + 4f1 1- f 3] 1 We now have: f ) (0,0,4) ; (2.17) f2 3(U) (0,0,0*) x 3 -, (0,,) . 3u ’ The inverse transform of (2.15) is given by: E

76 FR 51438 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

... Rule 17f-2(e) (17 CFR 240.17f-2(e)) under the Securities Exchange Act of 1934 (15 U.S.C. 78a et seq.). Rule 17f-2(e) requires members of national securities exchanges, brokers, dealers, registered transfer... SECURITIES AND EXCHANGE COMMISSION Submission for OMB Review; Comment Request Upon Written Request...

Combined Quarterly Technical Report Number 25. SATNET Development and Operation, Pluribus Satellite IMP Development, Remote Site Maintenance, Internet Operations and Maintenance, Mobile Access Terminal Network, TCP for the HP3000, TCP for VAX-UNIX.

DTIC Science & Technology

1982-05-01

the F-Bus. The two possible SuperSUE I Pollers, SSPE and SSPF, are on the E and F buses, respectively. P13 is the P13 Poller. A PSAT will have at... SSPE and SSPF are again the two possible SuperSUE Pollers. HPOL is an abbrevation for the HINPOL and HOUTPOL routines. -44- jReport No. 5003 Bolt...I IS I E-Bus,F-Bus I E-Bus Only I F-Bus only I s -- - - - - - - - - - - - - - - - - -- - - - - - P E-Bus ISMIE/ SSPE ISMIE/ SSPE ISMIF/SSPF IF-Bu3

Approximate Analysis of an Unreliable M/M/2 Retrial Queue

DTIC Science & Technology

2007-03-01

F ’ corresponds to p_6|i 44 F =m^2*x^2*( l +2* a +2*m+2*x)/Den; 45 46 %Stores the above probabilities into a vector 47 CondProb = [ A B C D E F ]; 48...53 LambdaHat = x*qf*B + ( l *qa+2*x*qf)* C + ( l *qa+x*qf)*D + l *qa* F ; 54 %The ’death’ rate 55 ThetaHat = theta*( A + B + E); 56 %The level of the orbit is...2 + λ + g , (4.2) where g = λ3 2 + 3λ + 2θ · F ( a + 1, b + 1, c + 1; λ 2 ) F

Peroxisome Proliferator-Activated Receptor β/δ Cross Talks with E2F and Attenuates Mitosis in HRAS-Expressing Cells

PubMed Central

Zhu, Bokai; Khozoie, Combiz; Bility, Moses T.; Ferry, Christina H.; Blazanin, Nicholas; Glick, Adam B.; Gonzalez, Frank J.

2012-01-01

The role of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) in Harvey sarcoma ras (Hras)-expressing cells was examined. Ligand activation of PPARβ/δ caused a negative selection with respect to cells expressing higher levels of the Hras oncogene by inducing a mitotic block. Mitosis-related genes that are predominantly regulated by E2F were induced to a higher level in HRAS-expressing Pparβ/δ-null keratinocytes compared to HRAS-expressing wild-type keratinocytes. Ligand-activated PPARβ/δ repressed expression of these genes by direct binding with p130/p107, facilitating nuclear translocation and increasing promoter recruitment of p130/p107. These results demonstrate a novel mechanism of PPARβ/δ cross talk with E2F signaling. Since cotreatment with a PPARβ/δ ligand and various mitosis inhibitors increases the efficacy of increasing G2/M arrest, targeting PPARβ/δ in conjunction with mitosis inhibitors could become a suitable option for development of new multitarget strategies for inhibiting RAS-dependent tumorigenesis. PMID:22473992