Municipal solid waste management in Rasht City, Iran.

PubMed

Alavi Moghadam, M R; Mokhtarani, N; Mokhtarani, B

2009-01-01

Pollution and health risks generated by improper solid waste management are important issues concerning environmental management in developing countries. In most cities, the use of open dumps is common for the disposal of wastes, resulting in soil and water resource contamination by leachate in addition to odors and fires. Solid waste management infrastructure and services in developing countries are far from achieving basic standards in terms of hygiene and efficient collection and disposal. This paper presents an overview of current municipal solid waste management in Rasht city, Gilan Province, Iran, and provides recommendations for system improvement. The collected data of different MSW functional elements were based on data from questionnaires, visual observations of the authors, available reports and several interviews and meetings with responsible persons. Due to an increase in population and changes in lifestyle, the quantity and quality of MSW in Rasht city has changed. Lack of resources, infrastructure, suitable planning, leadership, and public awareness are the main challenges of MSW management of Rasht city. However, the present situation of solid waste management in this city, which generates more than 400tons/d, has been improved since the establishment of an organization responsible only for solid waste management. Source separation of wastes and construction of a composting plant are the two main activities of the Rasht Municipality in recent years.

Occurrence of Fusarium spp. and Fumonisins in Stored Wheat Grains Marketed in Iran

PubMed Central

Chehri, Khosrow; Jahromi, Saeed Tamadoni; Reddy, Kasa R. N.; Abbasi, Saeed; Salleh, Baharuddin

2010-01-01

Wheat grains are well known to be invaded by Fusarium spp. under field and storage conditions and contaminated with fumonisins. Therefore, determining Fusarium spp. and fumonisins in wheat grains is of prime importance to develop suitable management strategies and to minimize risk. Eighty-two stored wheat samples produced in Iran were collected from various supermarkets and tested for the presence of Fusarium spp. by agar plate assay and fumonisins by HPLC. A total of 386 Fusarium strains were isolated and identified through morphological characteristics. All these strains belonged to F. culmorum, F. graminearum, F. proliferatum and F. verticillioides. Of the Fusarium species, F. graminearum was the most prevalent species, followed by F. verticillioides, F. proliferatum and then F. culmorum. Natural occurrence of fumonisin B1 (FB1) could be detected in 56 (68.2%) samples ranging from 15–155 μg/kg, fumonisin B2 (FB2) in 35 (42.6%) samples ranging from 12–86 μg/kg and fumonisin B3 (FB3) in 26 (31.7%) samples ranging from 13–64 μg/kg. The highest FB1 levels were detected in samples from Eilam (up to 155 μg/kg) and FB2 and FB3 in samples from Gilan Gharb (up to 86 μg/kg and 64 μg/kg). PMID:22069576

Municipal solid waste management in Rasht City, Iran

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

Alavi Moghadam, M.R.; Mokhtarani, N.; Mokhtarani, B.

2009-01-15

Pollution and health risks generated by improper solid waste management are important issues concerning environmental management in developing countries. In most cities, the use of open dumps is common for the disposal of wastes, resulting in soil and water resource contamination by leachate in addition to odors and fires. Solid waste management infrastructure and services in developing countries are far from achieving basic standards in terms of hygiene and efficient collection and disposal. This paper presents an overview of current municipal solid waste management in Rasht city, Gilan Province, Iran, and provides recommendations for system improvement. The collected data ofmore » different MSW functional elements were based on data from questionnaires, visual observations of the authors, available reports and several interviews and meetings with responsible persons. Due to an increase in population and changes in lifestyle, the quantity and quality of MSW in Rasht city has changed. Lack of resources, infrastructure, suitable planning, leadership, and public awareness are the main challenges of MSW management of Rasht city. However, the present situation of solid waste management in this city, which generates more than 400 tons/d, has been improved since the establishment of an organization responsible only for solid waste management. Source separation of wastes and construction of a composting plant are the two main activities of the Rasht Municipality in recent years.« less

Developing a climate-based risk map of fascioliasis outbreaks in Iran.

PubMed

Halimi, Mansour; Farajzadeh, Manuchehr; Delavari, Mahdi; Arbabi, Mohsen

2015-01-01

The strong relationship between climate and fascioliasis outbreaks enables the development of climate-based models to estimate the potential risk of fascioliasis outbreaks. This work aims to develop a climate-based risk map of fascioliasis outbreaks in Iran using Ollerenshaw's fascioliasis risk index incorporating geographical information system (GIS). Using this index, a risk map of fascioliasis outbreaks for the entire country was developed. We determined that the country can be divided into 4 fascioliasis outbreak risk categories. Class 1, in which the Mt value is less than 100, includes more than 0.91 of the country's area. The climate in this class is not conducive to fascioliasis outbreaks in any month. Dryness and low temperature in the wet season (December to April) are the key barriers against fascioliasis outbreaks in this class. The risk map developed based on climatic factors indicated that only 0.03 of the country's area, including Gilan province in the northern region of Iran, is highly suitable to fascioliasis outbreaks during September to January. The Mt value is greater than 500 in this class. Heavy rainfall in the summer and fall, especially in Rasht, Astara and Bandar Anzaly (≥ 1000 mm/year), creates more suitable breeding places for snail intermediate hosts. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Evaluating Three Insar Time-Series Methods to Assess Creep Motion, Case Study: Masouleh Landslide in North Iran

NASA Astrophysics Data System (ADS)

Mirzaee, S.; Motagh, M.; Akbari, B.; Wetzel, H. U.; Roessner, S.

2017-05-01

Masouleh is one of the ancient cities located in a high mountainous area in Gilan province of northern Iran. The region is threatened by a hazardous landslide, which was last activated in 1998, causing 32 dead and 45 injured. Significant temporal decorrelation caused by dense vegetation coverage within the landslide area makes the use of Synthetic Aperture Radar Interferometry (InSAR) for monitoring landslide movement very challenging. In this paper, we investigate the capability of three InSAR time-series techniques for evaluating creep motion on Masouleh landslide. The techniques are Persistent Scatterer Interferometry (PSI), Small BAseline Subset (SBAS) and SqueeSAR. The analysis is done using a dataset of 33 TerraSAR-X images in SpotLight (SL) mode covering a period of 15 months between June 2015 and September 2016. Results show the distinguished capability of SqueeSAR method in comparison to 2 other techniques for assessing landslide movement. The final number of scatterers in the landslide body detected by PSI and SBAS are about 70 and 120 respectively while this increases to about 345 in SqueeSAR. The coherence of interferograms improved by about 37% for SqueeSAR as compared to SBAS. The same rate of displacement was observed in those regions where all the methods were able to detect scatterers. Maximum rates of displacement detected by SqueeSAR technique in the northern edge, older and younger part of the landslide body are about -39, -65 and -22 mm/y, respectively.

Rapid Acute Dose Assessment Using MCNP6

NASA Astrophysics Data System (ADS)

Owens, Andrew Steven

Acute radiation doses due to physical contact with a high-activity radioactive source have proven to be an occupational hazard. Multiple radiation injuries have been reported due to manipulating a radioactive source with bare hands or by placing a radioactive source inside a shirt or pants pocket. An effort to reconstruct the radiation dose must be performed to properly assess and medically manage the potential biological effects from such doses. Using the reference computational phantoms defined by the International Commission on Radiological Protection (ICRP) and the Monte Carlo N-Particle transport code (MCNP6), dose rate coefficients are calculated to assess doses for common acute doses due to beta and photon radiation sources. The research investigates doses due to having a radioactive source in either a breast pocket or pants back pocket. The dose rate coefficients are calculated for discrete energies and can be used to interpolate for any given energy of photon or beta emission. The dose rate coefficients allow for quick calculation of whole-body dose, organ dose, and/or skin dose if the source, activity, and time of exposure are known. Doses are calculated with the dose rate coefficients and compared to results from the International Atomic Energy Agency (IAEA) reports from accidents that occurred in Gilan, Iran and Yanango, Peru. Skin and organ doses calculated with the dose rate coefficients appear to agree, but there is a large discrepancy when comparing whole-body doses assessed using biodosimetry and whole-body doses assessed using the dose rate coefficients.

Using drug sales data to evaluate the epidemiology of cardiometabolic risk factors and their inequality: an ecological study on atorvastatin and total cholesterol in Iran.

PubMed

Ahmadvand, Alireza; Farzadfar, Farshad; Jamshidi, Hamid Reza; Mohammadi, Naser; Holakouie-Naieni, Kourosh

2015-01-01

Statins have been effective medications in lowering serum total cholesterol (TC) concentrations across populations over time. The aim of this study was to estimate national and provincial trends in atorvastatin sales in Iran, to systematically quantify its relationship with socioeconomic indicators, and changes in TC level. In this retrospective ecological study, conducted in Iran, we examined trends in atorvastatin sales, the wealth index (WI) as a validly-available socio-economic indicator, and TC level between 2004 and 2011. The main outcome variable was mean atorvastatin sold in defined daily dose per 100,000 people per day (DPD). We analyzed the relationship between WI and DPD and between DPD and mean TC across time and space. At national level, both mean WI and mean DPD showed increasing trend over time, while we observed decreasing trend for TC. Mean WI and DPD in 2011 was nearly 5 and 50 time that of their respective figures in 2004, while the mean TC decreased for nearly 10%. Increases in both WI and DPD had happened in every province, but with different patterns. The maximum and minimum changes in DPD versus WI were seen in Gilan and North Khorasan respectively. A striking increase occurred in the sales for atorvastatin in Iran from 2004-2012 in most provinces examined. The wealthier a province became, the more sales were seen for atorvastatin. TC optimistically decreased from 2005 to 2011 and its decrease was positively correlated with increasing sales for atorvastatin.

What are the predictor variables of social well-being among the medical science students?

PubMed

Javadi-Pashaki, Nazila; Darvishpour, Azar

2018-01-01

Individuals with social well-being can cope more successfully with major problems of social roles. Due to the social nature of human life, it cannot be ignored to pay attention the social aspect of health. The purpose of this study was to identify variables that predict the social well-being of medical students. A descriptive-analytical study was conducted on 489 medical science students of Gilan Province, the North of Iran, during May to September 2016. The samples were selected using quota sampling method. Research instrument was a questionnaire consisting of two parts: demographic section and Keyes social well-being questionnaire. Data analysis was done using SPSS software version 19 and with descriptive and inferential statistics (t-test, ANOVA, and linear regression). The results showed that majority of the students had average social well-being. Furthermore, a significant relationship between the academic degree ( P = 0.009), major ( P = 0.0001), the interest and field's satisfaction ( P = 0.0001), and social well-being was seen. The results of linear regression model showed that four variables (academic degree, major, group membership, and the interest and field's satisfaction) were significantly associated with the social well-being ( P < 0.05). The findings demonstrate that the different effects of the demographic factors on social well-being and the need for further consideration of these factors are obvious. Thus, health and education authorities are advised to pay attention students' academic degree, major, group membership, and the interest and field's satisfaction to upgrade and maintain the level of their social well-being.

P53 gene codon 72 polymorphism in patients with oral squamous cell carcinoma in the population of northern Iran.

PubMed

Sina, Mahmud; Pedram, Mehrdad; Ghojazadeh, Morteza; Kochaki, Ahmad; Aghbali, Amirala

2014-11-01

Squamous cell carcinoma is the most common cancer of the oral cavity, and several etiologic factors are involved in its developing. Single nucleotide polymorphism (SNP) of the P53 gene codon 72 (P53c72) changes the structure of the protein and affects its activity. The prevalence of P53c72 different genotypes, which seems to vary with race and geographic location, has shown a strong correlation with many types of human cancers. The aim of this study was to investigate the correlation between P53c72polymorphism and risk of oral squamous cell carcinoma (OSCC) in the heavily populated Gilan Province in northern Iran. This case-control study was done on 55 paraffin-embedded samples from OSCC patients and 100 samples of non-dysplastic oral cavity lesions. The P53c72 genotypes were determined using the ARMS-PCR method. SPSS-15 software was used for statistical analysis. There were no significant statistical differences found between the prevalence of different P53c72 genotypes in the OSCC group vs. the control. However, the Pro/Pro genotype in OSCC samples showed a strong correlation with age, as 70% of such patients were below 50 years old. Interestingly, a large portion (40%) of the patients with the Pro/Pro genotype had the tumor in the lip area. Although P53c72 polymorphism does not appear to be a predisposing factor for OSCC in the population of Northern Iran, the Pro/Pro genotype could be considered as a risk factor for OSCC in adults below 50 years old and the anatomical location of the tumor.

Application of brown bear (Ursus arctos) records for retrospective assessment of mercury.

PubMed

Solgi, Eisa; Ghasempouri, Seyed Mahmoud

2015-01-01

Because mercury (Hg) is released into the atmosphere, wildlife living in habitats located far from point sources of metal may still be at risk. Mercury accumulation, previously considered a risk for aquatic ecosystems, is also found in many wildlife terrestrial species. The aim of the present study was to examine total Hg concentrations in the brown bear (Ursus arctos) by measurement of metal in hair from museum collections in Iran. Another objective of this investigation was to characterize the risk of Hg exposure in bears in several parts of Iran. Brown bear (Ursus arctos) hair samples (n = 35) were collected from 14 provinces in Iran for analysis of Hg contamination, performed using an advanced mercury analyzer (model Leco 254 AMA, USA) according to ASTM standard D-6722. Total Hg levels in Iranian bears from all areas ranged from 115.81 to 505.82 μg/kg, with a mean of 193.39 ng/g. Mercury concentrations in brown bear hair from different provinces in Iran were as follows in descending order: Khorasan Razavi > Esfahan > Khozestan > Yazd > Lorestan > Charmahalva Bakhtiari > Bushehr > Mazandaran > Markazi > Tehran > Ardebil > Gilan > East Azerbaijan. The highest content of Hg was found in the south (206.62 ± 31.95 ng/g), whereas the lowest levels were detected in the west (167.71 ± 32.97 ng/g). Overall total Hg content in bear hair was below harmful levels for this species. A decreasing trend was noted in the period 1986-2006, which may be mainly due to reduction of global Hg emissions. Data suggest that food habits and habitat are two important factors that influence Hg accumulation in bears.

A Comprehensive Molecular Investigation of α-Thalassemia in an Iranian Cohort from Different Provinces of North Iran.

PubMed

Eftekhari, Hajar; Tamaddoni, Ahmad; Mahmoudi Nesheli, Hassan; Vakili, Mohsen; Sedaghat, Sadegh; Banihashemi, Ali; Azizi, Mandana; Youssefi Kamangar, Reza; Akhavan-Niaki, Haleh

2017-01-01

α-Thalassemia (α-thal) is the most common monogenic disease that is caused by the absence or reduced expression of α-globin genes. The aim of this study was to investigate common α-globin mutations and their associated haplotypes in four northern provinces of Iran (Gilan, Mazandaran, Golestan, Khorasan). One thousand, one hundred and ninety-one persons were tested for α-thal mutations by gap-polymerase chain reaction (PCR), reverse dot-blot hybridization, restriction fragment length polymorphism (RFLP) analysis and sequencing. Of the nine different mutations found, the most frequent were -α 3.7 (rightward deletion) (45.6%), polyadenylation site (α p ° lyA2 α) (α2) (AATAAA>AATGAA; HBA2: c.*92 A>G) (15.27%), - - MED (Mediterranean deletion) (6.86%), -α 4.2 (leftward deletion), (6.17%), α CS α [Hb Constant Spring (Hb CS) (HBA2: c.427 T>C)] (4.62%), -α -5 nt (HBA2: c.95+2_95+6delTGAGG) (3.70%). All chromosomes bearing an α-globin point mutation [α p ° lyA2 α, -α -5 nt α, α CS α, α p ° lyA1 α (AATAAA> AATAAG; HBA2: c.*94 A>G)] showed only one haplotype that was present in most normal chromosomes, while the -α 3.7 deletion was associated with three distinct haplotypes. Our results indicate that α-thal mutations are heterogeneous and -α 3.7 and α p ° lyA2 α are the most prevalent mutations in this region. The presence of -α 3.7 with three different haplotypes suggests an older history for this mutation. The high prevalence of α p ° lyA2 α in Mazandaran Province, Iran compared to other parts of the country and the world, suggests a founder effect. Altogether, we here provide further data confirming the heterogeneity of the northern population of Iran. These data may contribute to the establishment of a national mutation database, more accurate genetic counseling and prenatal diagnosis (PND).

Incidence of cutaneous malignant melanoma in Iranian provinces and American states matched on ultraviolet radiation exposure: an ecologic study.

PubMed

Moslehi, Roxana; Zeinomar, Nur; Boscoe, Francis P

2018-03-01

Ultraviolet radiation (UVR), with UVB and UVA as the relevant components, is a risk factor for melanoma. Complete ascertainment and registration of melanoma in Iran was conducted in five provinces (Ardabil, Golestan, Mazandaran, Gilan and Kerman) during 1996-2000. The aim of our study was to compare population-based incidence data from these provinces with rates in the United States (US) while standardizing ambient UVR. Population-based rates representing all incident cases of melanoma (1996-2000) across the five Iranian provinces were compared to rates of melanoma among white non-Hispanics in the US. Overall age-standardized rates (ASR) for Iran and the US (per 100,000 person-years adjusted to 2000 world population) and standardized rate ratios (SRR) were calculated. We measured erythemally-weighted average solar UVR exposures (with contributions from both UVB and UVA range) of the five Iranian provinces using data from NASA's Total Ozone Mapping Spectrometer and selected five US states (Kentucky, Utah, Texas, Oklahoma, and Hawaii) with matching UVR exposure to each province. Incidence rates of melanoma during 1996-2000 in each Iranian province were compared to rates among white non-Hispanics in its UVR-matched US state. The overall male and female ASRs of melanoma were 0.60 (95%CI: 0.56-0.64) and 0.46 (95%CI: 0.42-0.49), respectively, for Iran and 22.78 (95%CI: 22.42-23.14) and 16.61 (95%CI: 16.30-16.92) for the US. SRRs of melanoma comparing US to Iran were 37.97 (95%CI: 35.78-40.29) for males and 36.11 (95%CI: 33.69-38.70) for females, indicating significantly higher incidence in the US. ASRs and age-specific rates of melanoma for both genders were significantly lower in each Iranian province compared to its UVR-matched US state. The markedly lower incidence rates of melanoma in Iranian provinces with similar UVR exposures to US states underscore the need for additional comparative studies to decipher the influence of other extrinsic and intrinsic factors on the risk of this malignancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Incidence of cutaneous malignant melanoma in Iranian provinces and American states matched on ultraviolet radiation exposure: an ecologic study☆

PubMed Central

Moslehi, Roxana; Zeinomar, Nur; Boscoe, Francis P.

2018-01-01

Objectives Ultraviolet radiation (UVR), with UVB and UVA as the relevant components, is a risk factor for melanoma. Complete ascertainment and registration of melanoma in Iran was conducted in five provinces (Ardabil, Golestan, Mazandaran, Gilan and Kerman) during 1996–2000. The aim of our study was to compare population-based incidence data from these provinces with rates in the United States (US) while standardizing ambient UVR. Methods Population-based rates representing all incident cases of melanoma (1996–2000) across the five Iranian provinces were compared to rates of melanoma among white non-Hispanics in the US. Overall age-standardized rates (ASR) for Iran and the US (per 100,000 person-years adjusted to 2000 world population) and standardized rate ratios (SRR) were calculated. We measured erythemally-weighted average solar UVR exposures (with contributions from both UVB and UVA range) of the five Iranian provinces using data from NASA's Total Ozone Mapping Spectrometer and selected five US states (Kentucky, Utah, Texas, Oklahoma, and Hawaii) with matching UVR exposure to each province. Incidence rates of melanoma during 1996–2000 in each Iranian province were compared to rates among white non-Hispanics in its UVR-matched US state. Results The overall male and female ASRs of melanoma were 0.60 (95%CI: 0.56–0.64) and 0.46 (95%CI: 0.42–0.49), respectively, for Iran and 22.78 (95%CI: 22.42–23.14) and 16.61 (95%CI: 16.30–16.92) for the US. SRRs of melanoma comparing US to Iran were 37.97 (95%CI: 35.78–40.29) for males and 36.11 (95%CI: 33.69–38.70) for females, indicating significantly higher incidence in the US. ASRs and age-specific rates of melanoma for both genders were significantly lower in each Iranian province compared to its UVR-matched US state. Conclusion The markedly lower incidence rates of melanoma in Iranian provinces with similar UVR exposures to US states underscore the need for additional comparative studies to decipher the influence of other extrinsic and intrinsic factors on the risk of this malignancy. PMID:29241156

Differential mortality in Iran.

PubMed

Khosravi, Ardeshir; Taylor, Richard; Naghavi, Mohsen; Lopez, Alan D

2007-07-28

Among the available data provided by health information systems, data on mortality are commonly used not only as health indicators but also as socioeconomic development indices. Recognizing that in Iran accurate data on causes of death were not available, the Deputy of Health in the Ministry of Health and Medical Education (MOH&ME) established a new comprehensive system for death registration which started in one province (Bushehr) as a pilot in 1997, and was subsequently expanded to include all other provinces, except Tehran province. These data can be used to investigate the nature and extent of differences in mortality in Iran. The objective of this paper is to estimate provincial differences in the level of mortality using this death registration system. Data from the death registration system for 2004 for each province were evaluated for data completeness, and life tables were created for provinces after correction for under-enumeration of death registration. For those provinces where it was not possible to adjust the data on adult deaths by using the Brass Growth Balance method, adult mortality was predicted based on adult literacy using information from provinces with reliable data. Child mortality (risk of a newborn dying before age 5, or 5q0) in 2004 varied between 47 per 1000 live births for both sexes in Sistan and Baluchistan province, and 25 per 1000 live births in Tehran and Gilan provinces. For adults, provincial differences in mortality were much greater for males than females. Adult mortality (risk of dying between ages 15 and 60, or 45q15) for females varied between 0.133 in Kerman province and 0.117 in Tehran province; for males the range was from 0.218 in Kerman to 0.149 in Tehran province. Life expectancy for females was highest in Tehran province (73.8 years) and lowest in Sistan and Baluchistan (70.9 years). For males, life expectancy ranged from 65.7 years in Sistan and Baluchistan province to 70.9 years in Tehran. Substantial differences in survival exist among the provinces of Iran. While the completeness of the death registration system operated by the Iranian MOH&ME appears to be acceptable in the majority of provinces, further efforts are needed to improve the quality of data on mortality in Iran, and to expand death registration to Tehran province.

The relationship between the spiritual attitude of the family caregivers of older patients with stroke and their burden.

PubMed

Torabi Chafjiri, Razieh; Navabi, Nasrin; Shamsalinia, Abbas; Ghaffari, Fatemeh

2017-01-01

Stroke is a chronic condition that necessitates multidimensional and overwhelming care. The caregivers of stroke patients are faced with various stressors that can threaten different aspects of their health, especially their mental health. Spiritual attitude and being spiritually oriented contribute significantly to mental health and can be used as a strategy for adapting to the stressful events that are part of the role of caregiving. This study was therefore conducted to investigate the relationship between the spiritual attitude of the family caregivers of older patients with stroke and their burden. This descriptive cross-sectional study was conducted in 2016. The study population consisted of all the family caregivers of older patients with stroke presenting to health care centers and nursing service companies of Gilan Province in Iran. The participants were selected through convenience sampling and consisted of 407 participants. Data were collected using the Spiritual Attitude Scale and the Caregiver Burden Inventory and were then analyzed in SPSS-18 using Pearson's correlation coefficient at a significance level of 0.05. The results showed that 88.9% of the caregivers were females. The mean age of the participants was 38.3±8.8 years. The duration of caregiving was <5 years in 84.4% of the participants, while its mean was 4.2±2.5 years. The mean score of spiritual attitude was 108.77±6.20. The majority of the participants (49.3%) had moderate and relatively favorable spiritual attitude (a score of 72-120), 27.8% had high or favorable spiritual attitude; 8.7% had mild burden, 54.4% had moderate burden and 37% had favorable burden. The mean score of burden was 28±12.75. A statistically significant positive relationship was observed in this study between the mean score of spiritual attitude and the total score of burden in all its dimensions, namely, time dependence, as well as the developmental, physical, social and emotional dimensions. Providing strategies for improving spirituality, such as teaching spiritual self-care, can improve their burden. Given that such strategies are psychologically approved and pose no side effects, they can be used as an effective, low-cost and risk-free approach for all caregivers, so that they can acquire the necessary spiritual support for overcoming the stress caused by caring for family members through the reinforcement of their spiritual beliefs in the ultimate effort to provide effective care to older patients while maintaining their own health and quality of life.

CFS Seasonal Climate Forecasts

Science.gov Websites

Europe Prec E1 E2 E3 E1 E2 E3 E1 E2 E3 E1 E2 E3 Europe T2m E1 E2 E3 E1 E2 E3 E1 E2 E3 E1 E2 E3 Misc (E3 E2 E3 E1 E2 E3 US SM E1 E2 E3 E1 E2 E3 E1 E2 E3 E1 E2 E3 Europe Prec E1 E2 E3 E1 E2 E3 E1 E2 E3 E1 E2 E3 Europe T2m E1 E2 E3 E1 E2 E3 E1 E2 E3 E1 E2 E3 Misc (E3) Global u200-u850 Atlantic u200-u850

40 CFR Appendix I to Part 266 - Tier I and Tier II Feed Rate and Emissions Screening Limits for Metals

Code of Federal Regulations, 2014 CFR

2014-07-01

... 60 1.2E+03 2.0E+05 3.6E+02 1.2E+03 1.2E+04 1.2E+03 65 1.5E+03 2.5E+05 4.3E+02 1.5E+03 1.5E+04 1.5E+03 70 1.7E+03 2.8E+05 5.0E+02 1.7E+03 1.7E+04 1.7E+03 75 1.9E+03 3.2E+05 5.8E+02 1.9E+03 1.9E+04 1.9E+03 80 2.2E+03 3.6E+05 6.4E+02 2.2E+03 2.2E+04 2.2E+03 85 2.5E+03 4.0E+05 7.6E+02 2.5E+03 2.5E+04 2.5E+03...

40 CFR Appendix I to Part 266 - Tier I and Tier II Feed Rate and Emissions Screening Limits for Metals

Code of Federal Regulations, 2012 CFR

2012-07-01

... 60 1.2E+03 2.0E+05 3.6E+02 1.2E+03 1.2E+04 1.2E+03 65 1.5E+03 2.5E+05 4.3E+02 1.5E+03 1.5E+04 1.5E+03 70 1.7E+03 2.8E+05 5.0E+02 1.7E+03 1.7E+04 1.7E+03 75 1.9E+03 3.2E+05 5.8E+02 1.9E+03 1.9E+04 1.9E+03 80 2.2E+03 3.6E+05 6.4E+02 2.2E+03 2.2E+04 2.2E+03 85 2.5E+03 4.0E+05 7.6E+02 2.5E+03 2.5E+04 2.5E+03...

40 CFR Appendix I to Part 266 - Tier I and Tier II Feed Rate and Emissions Screening Limits for Metals

Code of Federal Regulations, 2013 CFR

2013-07-01

... 60 1.2E+03 2.0E+05 3.6E+02 1.2E+03 1.2E+04 1.2E+03 65 1.5E+03 2.5E+05 4.3E+02 1.5E+03 1.5E+04 1.5E+03 70 1.7E+03 2.8E+05 5.0E+02 1.7E+03 1.7E+04 1.7E+03 75 1.9E+03 3.2E+05 5.8E+02 1.9E+03 1.9E+04 1.9E+03 80 2.2E+03 3.6E+05 6.4E+02 2.2E+03 2.2E+04 2.2E+03 85 2.5E+03 4.0E+05 7.6E+02 2.5E+03 2.5E+04 2.5E+03...

40 CFR Appendix I to Part 266 - Tier I and Tier II Feed Rate and Emissions Screening Limits for Metals

Code of Federal Regulations, 2010 CFR

2010-07-01

... 60 1.2E+03 2.0E+05 3.6E+02 1.2E+03 1.2E+04 1.2E+03 65 1.5E+03 2.5E+05 4.3E+02 1.5E+03 1.5E+04 1.5E+03 70 1.7E+03 2.8E+05 5.0E+02 1.7E+03 1.7E+04 1.7E+03 75 1.9E+03 3.2E+05 5.8E+02 1.9E+03 1.9E+04 1.9E+03 80 2.2E+03 3.6E+05 6.4E+02 2.2E+03 2.2E+04 2.2E+03 85 2.5E+03 4.0E+05 7.6E+02 2.5E+03 2.5E+04 2.5E+03...

40 CFR Appendix I to Part 266 - Tier I and Tier II Feed Rate and Emissions Screening Limits for Metals

Code of Federal Regulations, 2011 CFR

2011-07-01

... 60 1.2E+03 2.0E+05 3.6E+02 1.2E+03 1.2E+04 1.2E+03 65 1.5E+03 2.5E+05 4.3E+02 1.5E+03 1.5E+04 1.5E+03 70 1.7E+03 2.8E+05 5.0E+02 1.7E+03 1.7E+04 1.7E+03 75 1.9E+03 3.2E+05 5.8E+02 1.9E+03 1.9E+04 1.9E+03 80 2.2E+03 3.6E+05 6.4E+02 2.2E+03 2.2E+04 2.2E+03 85 2.5E+03 4.0E+05 7.6E+02 2.5E+03 2.5E+04 2.5E+03...

Relaxation of Shot-Peened Residual Stresses Under Creep Loading (Preprint)

DTIC Science & Technology

2008-10-01

6 1e-5 1e- 4 1e-3...22   1e-9 1e-8 1e-7 1e- 6 1e-5 1e- 4 1e-3 1e-2 1e-1 1e-3 1e-2 1e-1 -1% Prestrain 0% Prestrain +1% Prestrain +5% Prestrain To ta l S tra in R at e (/s...Prestrain. 23 1e-9 1e-8 1e-7 1e- 6 1e-5 1e- 4 1e-3 1e-2 1e-1 1e-3 1e-2 1e-1 -1% Prestrain 0% Prestrain +5% Prestrain To ta l S tra in R at e

40 CFR Appendix II to Part 266 - Tier I Feed Rate Screening Limits for Total Chlorine

Code of Federal Regulations, 2010 CFR

2010-07-01

.../hr) Rural (g/hr) Complex Terrain (g/hr) 4 8.2E+01 4.2E+01 1.9E+01 6 9.1E+01 4.8E+01 2.8E+01 8 1.0E+02 5.3E+01 4.1E+01 10 1.2E+02 6.2E+01 5.8E+01 12 1.3E+02 7.7E+01 7.2E+01 14 1.5E+02 9.1E+01 9.1E+01 16 1.7E+02 1.2E+02 1.1E+02 18 1.9E+02 1.4E+02 1.2E+02 20 2.1E+02 1.8E+02 1.3E+02 22 2.4E+02 2.3E+02 1...

40 CFR Appendix II to Part 266 - Tier I Feed Rate Screening Limits for Total Chlorine

Code of Federal Regulations, 2013 CFR

2013-07-01

.../hr) Rural (g/hr) Complex Terrain (g/hr) 4 8.2E+01 4.2E+01 1.9E+01 6 9.1E+01 4.8E+01 2.8E+01 8 1.0E+02 5.3E+01 4.1E+01 10 1.2E+02 6.2E+01 5.8E+01 12 1.3E+02 7.7E+01 7.2E+01 14 1.5E+02 9.1E+01 9.1E+01 16 1.7E+02 1.2E+02 1.1E+02 18 1.9E+02 1.4E+02 1.2E+02 20 2.1E+02 1.8E+02 1.3E+02 22 2.4E+02 2.3E+02 1...

40 CFR Appendix II to Part 266 - Tier I Feed Rate Screening Limits for Total Chlorine

Code of Federal Regulations, 2014 CFR

2014-07-01

.../hr) Rural (g/hr) Complex Terrain (g/hr) 4 8.2E+01 4.2E+01 1.9E+01 6 9.1E+01 4.8E+01 2.8E+01 8 1.0E+02 5.3E+01 4.1E+01 10 1.2E+02 6.2E+01 5.8E+01 12 1.3E+02 7.7E+01 7.2E+01 14 1.5E+02 9.1E+01 9.1E+01 16 1.7E+02 1.2E+02 1.1E+02 18 1.9E+02 1.4E+02 1.2E+02 20 2.1E+02 1.8E+02 1.3E+02 22 2.4E+02 2.3E+02 1...

40 CFR Appendix II to Part 266 - Tier I Feed Rate Screening Limits for Total Chlorine

Code of Federal Regulations, 2012 CFR

2012-07-01

.../hr) Rural (g/hr) Complex Terrain (g/hr) 4 8.2E+01 4.2E+01 1.9E+01 6 9.1E+01 4.8E+01 2.8E+01 8 1.0E+02 5.3E+01 4.1E+01 10 1.2E+02 6.2E+01 5.8E+01 12 1.3E+02 7.7E+01 7.2E+01 14 1.5E+02 9.1E+01 9.1E+01 16 1.7E+02 1.2E+02 1.1E+02 18 1.9E+02 1.4E+02 1.2E+02 20 2.1E+02 1.8E+02 1.3E+02 22 2.4E+02 2.3E+02 1...

40 CFR Appendix II to Part 266 - Tier I Feed Rate Screening Limits for Total Chlorine

Code of Federal Regulations, 2011 CFR

2011-07-01

.../hr) Rural (g/hr) Complex Terrain (g/hr) 4 8.2E+01 4.2E+01 1.9E+01 6 9.1E+01 4.8E+01 2.8E+01 8 1.0E+02 5.3E+01 4.1E+01 10 1.2E+02 6.2E+01 5.8E+01 12 1.3E+02 7.7E+01 7.2E+01 14 1.5E+02 9.1E+01 9.1E+01 16 1.7E+02 1.2E+02 1.1E+02 18 1.9E+02 1.4E+02 1.2E+02 20 2.1E+02 1.8E+02 1.3E+02 22 2.4E+02 2.3E+02 1...

CFSv2 Seasonal Climate Forecasts

Science.gov Websites

Nino3.4 Nino4 E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) Sea surface height and

A Coupled Creep-Plasticity Model for Residual Stress Relaxation of a Shot-Peened Nickel-Base Superalloy

DTIC Science & Technology

2007-05-01

4 1e+5 1e+ 6 1000MPa... 6 1e-5 1e- 4 1e-3 1e-2 1e-1 1e-1 1e+0 1e+1 1e+2 1e+3 1e+ 4 1e+5 1e+ 6 1000MPa 900MPa 800MPa C re ep R at e (/s ) Creep Time (s) 0% Prestrain, 650°C...increase in strain rate. The change in deformation response is significant even for small plastic strains. 1e-9 1e-8 1e-7 1e- 6 1e-5 1e- 4 1e-3

Space Shuttle Range Safety Command Destruct System Analysis and Verification. Phase 3. Breakup of Space Shuttle Cluster Via Range Safety Command Destruct System

DTIC Science & Technology

1981-03-01

1210 59188E.03 1.661E.08 l.b60E.ol 5o344E*11 1.070 .1801 BEGIN SONIC FLOW . 1307 5.2301.03 l.612E.08 1.724E.01 5.2271.11 1.066 .1912 ,1387 b.218E.03...1.625E+11 .607 90201 * 0428 6.582E+03 3*928E*07 8,905E+01 1.603E11 9600 *0400 .0646 6.608E+03 3.858E+07 9.103E+01 1581E+1l .593 *0600 .0870 6.635E+03 3.787E...03 39998E+07 8.715E+01 1.625E+11 .607 90201 * 0428 6.582E+03 3*928E*07 8,905E+01 1.603E11 9600 *0400 .0646 6.608E+03 3.858E+07 9.103E+01 1581E+1l .593

10 CFR Appendix C to Part 835 - Derived Air Concentration (DAC) for Workers From External Exposure During Immersion in a Cloud of...

Code of Federal Regulations, 2013 CFR

2013-01-01

...-05 6E+05 Kr-81 2.1E+05 yr 7E-04 2E+07 Kr-83m 1.83 h 7E-02 2E+09 Kr-85 10.72 yr 7E-04 2E+07 Kr-85m 4.48 h 2E-05 1E+06 Kr-87 76.3 min 4E-06 1E+05 Kr-88 2.84 h 1E-06 7E+04 Xe-120 40.0 min 1E-05 4E+05 Xe-121 40.1 min 2E-06 8E+04 Xe-122 20.1 h 8E-05 3E+06 Xe-123 2.14 h 6E-06 2E+05 Xe-125 16.8 h 1E-05 6E+05...

10 CFR Appendix C to Part 835 - Derived Air Concentration (DAC) for Workers From External Exposure During Immersion in a Cloud of...

Code of Federal Regulations, 2014 CFR

2014-01-01

...-05 6E+05 Kr-81 2.1E+05 yr 7E-04 2E+07 Kr-83m 1.83 h 7E-02 2E+09 Kr-85 10.72 yr 7E-04 2E+07 Kr-85m 4.48 h 2E-05 1E+06 Kr-87 76.3 min 4E-06 1E+05 Kr-88 2.84 h 1E-06 7E+04 Xe-120 40.0 min 1E-05 4E+05 Xe-121 40.1 min 2E-06 8E+04 Xe-122 20.1 h 8E-05 3E+06 Xe-123 2.14 h 6E-06 2E+05 Xe-125 16.8 h 1E-05 6E+05...

10 CFR Appendix E to Part 835 - Values for Establishing Sealed Radioactive Source Accountability and Radioactive Material Posting...

Code of Federal Regulations, 2012 CFR

2012-01-01

...+05 C-14 4.6E+06 Na-22 1.9E+01 Al-26 1.5E+01 Si-32 4.9E+04 S-35 2.4E+06 Cl-36 5.2E+05 K-40 2.7E+02 Ca-41 9.3E+06 Ca-45 1.1E+06 Sc-46 6.2E+01 Ti-44 1.5E+02 V-49 1.0E+08 Mn-53 7.5E+07 Mn-54 6.5E+01 Fe-55 2.9E+06 Fe-59 1.9E+02 Fe-60 8.1E+03 Co-56 3.9E+01 Co-57 2.3E+02 Co-58 1.3E+02 Co-60 1.7E+01 Ni-59 3.2E...

10 CFR Appendix E to Part 835 - Values for Establishing Sealed Radioactive Source Accountability and Radioactive Material Posting...

Code of Federal Regulations, 2013 CFR

2013-01-01

...+05 C-14 4.6E+06 Na-22 1.9E+01 Al-26 1.5E+01 Si-32 4.9E+04 S-35 2.4E+06 Cl-36 5.2E+05 K-40 2.7E+02 Ca-41 9.3E+06 Ca-45 1.1E+06 Sc-46 6.2E+01 Ti-44 1.5E+02 V-49 1.0E+08 Mn-53 7.5E+07 Mn-54 6.5E+01 Fe-55 2.9E+06 Fe-59 1.9E+02 Fe-60 8.1E+03 Co-56 3.9E+01 Co-57 2.3E+02 Co-58 1.3E+02 Co-60 1.7E+01 Ni-59 3.2E...

10 CFR Appendix E to Part 835 - Values for Establishing Sealed Radioactive Source Accountability and Radioactive Material Posting...

Code of Federal Regulations, 2014 CFR

2014-01-01

...+05 C-14 4.6E+06 Na-22 1.9E+01 Al-26 1.5E+01 Si-32 4.9E+04 S-35 2.4E+06 Cl-36 5.2E+05 K-40 2.7E+02 Ca-41 9.3E+06 Ca-45 1.1E+06 Sc-46 6.2E+01 Ti-44 1.5E+02 V-49 1.0E+08 Mn-53 7.5E+07 Mn-54 6.5E+01 Fe-55 2.9E+06 Fe-59 1.9E+02 Fe-60 8.1E+03 Co-56 3.9E+01 Co-57 2.3E+02 Co-58 1.3E+02 Co-60 1.7E+01 Ni-59 3.2E...

Apolipoprotein E genotyping in the Malay, Chinese and Indian ethnic groups in Malaysia-a study on the distribution of the different apoE alleles and genotypes.

PubMed

Seet, Wan Tai; Mary Anne, Tan Jin Ai; Yen, Tan Si

2004-02-01

Apolipoprotein E (apoE) is encoded by a polymorphic gene located on chromosome 19. The three common apoE alleles are epsilon2, epsilon3 and epsilon4. We studied the frequencies of the apoE alleles and genotypes in the three ethnic groups-Malay, Chinese and Indian-in Malaysia using DNA amplification followed by agarose gel electrophoresis. EDTA blood was collected and DNA was extracted using proteinase K-SDS digestion and purified by phenol-chloroform extraction. The apoE gene sequence was amplified using the PCR and apoE genotyping was performed by restriction enzyme digestion with HhaI. Genotyping of the apoE gene produces six genotypes-E2/E2, E2/E3, E3/E3, E2/E4, E3/E4 and E4/E4. The most common apoE genotype in the Malays, Chinese and Indians studied was E3/E3, thus the most common apoE allele was epsilon3. The three common apoE genotypes were E3/E3 followed by E3/E4 and E2/E3, except in the Indians where E2/E3 was not detected. The three apoE alleles were confirmed in the Malays, Chinese and Indians except for the epsilon2 allele which was absent in the Indians. The combined frequency of the apoE alleles in the Malays, Chinese and Indians was 0.058, 0.829 and 0.114 for epsilon2, epsilon3 and epsilon4, respectively.

Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs.

PubMed

Rong, Liwei; Livingstone, Mark; Sukarieh, Rami; Petroulakis, Emmanuel; Gingras, Anne-Claude; Crosby, Katherine; Smith, Bradley; Polakiewicz, Roberto D; Pelletier, Jerry; Ferraiuolo, Maria A; Sonenberg, Nahum

2008-07-01

Eukaryotic initiation factor (eIF) 4E, the mRNA 5'-cap-binding protein, mediates the association of eIF4F with the mRNA 5'-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported to the nucleus via its interaction with 4E-T (4E-transporter), but it is unclear how it is retained in the nucleus. Here we show that a sizable fraction (approximately 30%) of 4E-BP1 is localized to the nucleus, where it binds eIF4E. In mouse embryo fibroblasts (MEFs) subjected to serum starvation and/or rapamycin treatment, nuclear 4E-BPs sequester eIF4E in the nucleus. A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras-expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization.

Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs

PubMed Central

Rong, Liwei; Livingstone, Mark; Sukarieh, Rami; Petroulakis, Emmanuel; Gingras, Anne-Claude; Crosby, Katherine; Smith, Bradley; Polakiewicz, Roberto D.; Pelletier, Jerry; Ferraiuolo, Maria A.; Sonenberg, Nahum

2008-01-01

Eukaryotic initiation factor (eIF) 4E, the mRNA 5′-cap-binding protein, mediates the association of eIF4F with the mRNA 5′-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported to the nucleus via its interaction with 4E-T (4E-transporter), but it is unclear how it is retained in the nucleus. Here we show that a sizable fraction (∼30%) of 4E-BP1 is localized to the nucleus, where it binds eIF4E. In mouse embryo fibroblasts (MEFs) subjected to serum starvation and/or rapamycin treatment, nuclear 4E-BPs sequester eIF4E in the nucleus. A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras–expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization. PMID:18515545

Mextli proteins use both canonical bipartite and novel tripartite binding modes to form eIF4E complexes that display differential sensitivity to 4E-BP regulation

PubMed Central

Peter, Daniel; Weber, Ramona; Köne, Carolin; Chung, Min-Yi; Ebertsch, Linda; Truffault, Vincent; Weichenrieder, Oliver; Igreja, Cátia; Izaurralde, Elisa

2015-01-01

The eIF4E-binding proteins (4E-BPs) are a diverse class of translation regulators that share a canonical eIF4E-binding motif (4E-BM) with eIF4G. Consequently, they compete with eIF4G for binding to eIF4E, thereby inhibiting translation initiation. Mextli (Mxt) is an unusual 4E-BP that promotes translation by also interacting with eIF3. Here we present the crystal structures of the eIF4E-binding regions of the Drosophila melanogaster (Dm) and Caenorhabditis elegans (Ce) Mxt proteins in complex with eIF4E in the cap-bound and cap-free states. The structures reveal unexpected evolutionary plasticity in the eIF4E-binding mode, with a classical bipartite interface for Ce Mxt and a novel tripartite interface for Dm Mxt. Both interfaces comprise a canonical helix and a noncanonical helix that engage the dorsal and lateral surfaces of eIF4E, respectively. Remarkably, Dm Mxt contains a C-terminal auxiliary helix that lies anti-parallel to the canonical helix on the eIF4E dorsal surface. In contrast to the eIF4G and Ce Mxt complexes, the Dm eIF4E–Mxt complexes are resistant to competition by bipartite 4E-BPs, suggesting that Dm Mxt can bind eIF4E when eIF4G binding is inhibited. Our results uncovered unexpected diversity in the binding modes of 4E-BPs, resulting in eIF4E complexes that display differential sensitivity to 4E-BP regulation. PMID:26294658

Modeling and Optimization of GEDIT for In Situ Contaminant Destruction in the Vadose Zone

DTIC Science & Technology

2012-04-01

010.7264E+01 AP 8AP 9 10.4817E-010.5290E-010.7264E+01 AQ 8AQ 9 10.4817E-010.5290E-010.7264E+01 AR 8AR 9...010.1000E+010.3207E+001. AP 8AQ 8 30.1000E+010.1000E+010.3207E+001. AQ 8AR 8 30.1000E+010.1000E+010.3207E+001. AR

Pest risk assessment of the importation into the United States of unprocessed logs and chips of eighteen Eucalypt species from Australia.

Treesearch

John T. Kliejunas; Harold H., Jr. Burdsall; Gregg A. DeNitto; Andris Eglitis; Dennis A. Haugen; Michael I. Harverty; Jessie A. Micales; Mark R. Powell

2003-01-01

The unmitigated pest risk potential for the importation of unprocessed logs and chips of 18 species of eucalypts (Eucalyptus amygdalina, E. cloeziana, E. delegatensis, E. diversicolor, E. dunnii, E. globulus, E. grandis, E. nitens, E. obliqua, E. ovata, E. pilularis, E. regnans, E. saligna, E. sieberi, E. viminalis, Corymbia calophylla, C. citriodora, and C. maculata)...

Australian species of Elaphomyces (Elaphomycetaceae, Eurotiales, Ascomycota)

Treesearch

Michael A. Castellano; James M. Trappe; Karl Vernes

2011-01-01

The sequestrate ascomycete genus Elaphomyces is described and illustrated from Australia. The following thirteen new species are described: Elaphomyces aurantias, E. austrogranulatus, E. chlorocarpus, E. cooloolanus, E. coralloideus, E. laetiluteus, E. nothofagi, E. pedicellaris, E. queenslandicus, E. rugosisporus, E. suejoyceae, E....

Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1

DOE PAGES

Sekiyama, Naotaka; Arthanari, Haribabu; Papadopoulos, Evangelos; ...

2015-07-13

The eIF4E-binding protein (4E-BP) is a phosphorylation-dependent regulator of protein synthesis. The nonphosphorylated or minimally phosphorylated form binds translation initiation factor 4E (eIF4E), preventing binding of eIF4G and the recruitment of the small ribosomal subunit. Signaling events stimulate serial phosphorylation of 4E-BP, primarily by mammalian target of rapamycin complex 1 (mTORC1) at residues T 37/T 46, followed by T 70 and S 65. Hyperphosphorylated 4E-BP dissociates from eIF4E, allowing eIF4E to interact with eIF4G and translation initiation to resume. Because overexpression of eIF4E is linked to cellular transformation, 4E-BP is a tumor suppressor, and up-regulation of its activity is amore » goal of interest for cancer therapy. A recently discovered small molecule, eIF4E/eIF4G interaction inhibitor 1 (4EGI-1), disrupts the eIF4E/eIF4G interaction and promotes binding of 4E-BP1 to eIF4E. Structures of 14- to 16-residue 4E-BP fragments bound to eIF4E contain the eIF4E consensus binding motif, 54YXXXXLΦ 60 (motif 1) but lack known phosphorylation sites. We report in this paper a 2.1-Å crystal structure of mouse eIF4E in complex with m 7GTP and with a fragment of human 4E-BP1, extended C-terminally from the consensus-binding motif (4E-BP1 50–84). The extension, which includes a proline-turn-helix segment (motif 2) followed by a loop of irregular structure, reveals the location of two phosphorylation sites (S 65 and T 70). Our major finding is that the C-terminal extension (motif 3) is critical to 4E-BP1–mediated cell cycle arrest and that it partially overlaps with the binding site of 4EGI-1. Finally, the binding of 4E-BP1 and 4EGI-1 to eIF4E is therefore not mutually exclusive, and both ligands contribute to shift the equilibrium toward the inhibition of translation initiation.« less

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

Sekiyama, Naotaka; Arthanari, Haribabu; Papadopoulos, Evangelos

The eIF4E-binding protein (4E-BP) is a phosphorylation-dependent regulator of protein synthesis. The nonphosphorylated or minimally phosphorylated form binds translation initiation factor 4E (eIF4E), preventing binding of eIF4G and the recruitment of the small ribosomal subunit. Signaling events stimulate serial phosphorylation of 4E-BP, primarily by mammalian target of rapamycin complex 1 (mTORC1) at residues T 37/T 46, followed by T 70 and S 65. Hyperphosphorylated 4E-BP dissociates from eIF4E, allowing eIF4E to interact with eIF4G and translation initiation to resume. Because overexpression of eIF4E is linked to cellular transformation, 4E-BP is a tumor suppressor, and up-regulation of its activity is amore » goal of interest for cancer therapy. A recently discovered small molecule, eIF4E/eIF4G interaction inhibitor 1 (4EGI-1), disrupts the eIF4E/eIF4G interaction and promotes binding of 4E-BP1 to eIF4E. Structures of 14- to 16-residue 4E-BP fragments bound to eIF4E contain the eIF4E consensus binding motif, 54YXXXXLΦ 60 (motif 1) but lack known phosphorylation sites. We report in this paper a 2.1-Å crystal structure of mouse eIF4E in complex with m 7GTP and with a fragment of human 4E-BP1, extended C-terminally from the consensus-binding motif (4E-BP1 50–84). The extension, which includes a proline-turn-helix segment (motif 2) followed by a loop of irregular structure, reveals the location of two phosphorylation sites (S 65 and T 70). Our major finding is that the C-terminal extension (motif 3) is critical to 4E-BP1–mediated cell cycle arrest and that it partially overlaps with the binding site of 4EGI-1. Finally, the binding of 4E-BP1 and 4EGI-1 to eIF4E is therefore not mutually exclusive, and both ligands contribute to shift the equilibrium toward the inhibition of translation initiation.« less

Fighting the Russians in Winter: Three Case Studies (Leavenworth Papers, Number 5)

DTIC Science & Technology

1981-12-01

e z s aya elve les rther e e nth ey led ro eir ilroad itions l l- e i lery, inly 75- s ned ite ssians. ey centrated l e ops ey ld e rom...ines een aya e ad itions, ter e rning ree ttalions e oscow iment lanked e lies e rth e pted ture o - s ro e . ieutenant kovsky, e ite...cal e ents s practical, tain itional ts e paign rthern ssia a rant tention r eir nical s. t aya llied t oops lived i erted ilroad cars. he i pro

Modeling of Bacillus spores: Inactivation and Outgrowth

DTIC Science & Technology

2011-03-01

there has to be a suitable amount of repair enzymes viable to accomplish this. 34 Let ( )r eE t be the enzyme concentration for the spore population...was drawn from a Gaussian fitness distribution with mean, 0E and variance, 0 2 E , 2 0 0 2 0 0 0 0 ( 0 0 ) 2 ( , 1 ) , , 2 0. E E E E E E f e EE ...time progresses, the evolution of the distribution of ( )r eE t will approach the kill threshold. Since 0E is a random variable, ( )r eE t is also a

10 CFR Appendix E to Part 835 - Values for Establishing Sealed Radioactive Source Accountability and Radioactive Material Posting...

Code of Federal Regulations, 2010 CFR

2010-01-01

....9E+06 Fe-59 1.9E+02 Fe-60 8.1E+03 Co-56 3.9E+01 Co-57 2.3E+02 Co-58 1.3E+02 Co-60 1.7E+01 Ni-59 3.2E+06 Ni-63 1.3E+06 Zn-65 1.1E+02 Ge-68 5.6E+02 As-73 5.3E+02 Se-75 6.3E+01 Se-79 8.7E+05 Rb-83 9.1E+01...

10 CFR Appendix E to Part 835 - Values for Establishing Sealed Radioactive Source Accountability and Radioactive Material Posting...

Code of Federal Regulations, 2011 CFR

2011-01-01

....9E+06 Fe-59 1.9E+02 Fe-60 8.1E+03 Co-56 3.9E+01 Co-57 2.3E+02 Co-58 1.3E+02 Co-60 1.7E+01 Ni-59 3.2E+06 Ni-63 1.3E+06 Zn-65 1.1E+02 Ge-68 5.6E+02 As-73 5.3E+02 Se-75 6.3E+01 Se-79 8.7E+05 Rb-83 9.1E+01...

Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity

PubMed Central

Graff, Jeremy R.; Konicek, Bruce W.; Vincent, Thomas M.; Lynch, Rebecca L.; Monteith, David; Weir, Spring N.; Schwier, Phil; Capen, Andrew; Goode, Robin L.; Dowless, Michele S.; Chen, Yuefeng; Zhang, Hong; Sissons, Sean; Cox, Karen; McNulty, Ann M.; Parsons, Stephen H.; Wang, Tao; Sams, Lillian; Geeganage, Sandaruwan; Douglass, Larry E.; Neubauer, Blake Lee; Dean, Nicholas M.; Blanchard, Kerry; Shou, Jianyong; Stancato, Louis F.; Carter, Julia H.; Marcusson, Eric G.

2007-01-01

Expression of eukaryotic translation initiation factor 4E (eIF4E) is commonly elevated in human and experimental cancers, promoting angiogenesis and tumor growth. Elevated eIF4E levels selectively increase translation of growth factors important in malignancy (e.g., VEGF, cyclin D1) and is thereby an attractive anticancer therapeutic target. Yet to date, no eIF4E-specific therapy has been developed. Herein we report development of eIF4E-specific antisense oligonucleotides (ASOs) designed to have the necessary tissue stability and nuclease resistance required for systemic anticancer therapy. In mammalian cultured cells, these ASOs specifically targeted the eIF4E mRNA for destruction, repressing expression of eIF4E-regulated proteins (e.g., VEGF, cyclin D1, survivin, c-myc, Bcl-2), inducing apoptosis, and preventing endothelial cells from forming vessel-like structures. Most importantly, intravenous ASO administration selectively and significantly reduced eIF4E expression in human tumor xenografts, significantly suppressing tumor growth. Because these ASOs also target murine eIF4E, we assessed the impact of eIF4E reduction in normal tissues. Despite reducing eIF4E levels by 80% in mouse liver, eIF4E-specific ASO administration did not affect body weight, organ weight, or liver transaminase levels, thereby providing the first in vivo evidence that cancers may be more susceptible to eIF4E inhibition than normal tissues. These data have prompted eIF4E-specific ASO clinical trials for the treatment of human cancers. PMID:17786246

Burkholderia pseudomallei Data Gap Analysis

DTIC Science & Technology

2015-11-01

000 x E -10 1.013 25 x E +2 1.000 000 x E +2 1.000 000 x E -28 1.054 350 x E +3 4.184 000 4.184 000 x E -2 3.700 000 x E +1...1.745 329 x E -2 t = (t f + 459.67)/1.8 1.602 19 x E -19 1.000 000 x E -7 1.000 000 x E -7 3.048 000 x E -1 1.355 818 3.785 412 x E -3 2.540... 000 x E -2 1.000 000 x E +9 1.000 000 4.183 4.448 222 x E +3 6.894 757 x E +3 1.000 000 x E +2 1.000

Importin 8 mediates m7G cap-sensitive nuclear import of the eukaryotic translation initiation factor eIF4E

PubMed Central

Volpon, Laurent; Culjkovic-Kraljacic, Biljana; Osborne, Michael J.; Ramteke, Anup; Sun, Qingxiang; Niesman, Ashley; Chook, Yuh Min; Borden, Katherine L. B.

2016-01-01

Regulation of nuclear-cytoplasmic trafficking of oncoproteins is critical for growth homeostasis. Dysregulated trafficking contributes to malignancy, whereas understanding the process can reveal unique therapeutic opportunities. Here, we focus on eukaryotic translation initiation factor 4E (eIF4E), a prooncogenic protein highly elevated in many cancers, including acute myeloid leukemia (AML). Typically, eIF4E is localized to both the nucleus and cytoplasm, where it acts in export and translation of specific methyl 7-guanosine (m7G)–capped mRNAs, respectively. Nuclear accumulation of eIF4E in patients who have AML is correlated with increased eIF4E-dependent export of transcripts encoding oncoproteins. The subcellular localization of eIF4E closely correlates with patients’ responses. During clinical responses to the m7G-cap competitor ribavirin, eIF4E is mainly cytoplasmic. At relapse, eIF4E reaccumulates in the nucleus, leading to elevated eIF4E-dependent mRNA export. We have identified importin 8 as a factor that directly imports eIF4E into the nucleus. We found that importin 8 is highly elevated in untreated patients with AML, leading to eIF4E nuclear accumulation. Importin 8 only imports cap-free eIF4E. Cap-dependent changes to the structure of eIF4E underpin this selectivity. Indeed, m7G cap analogs or ribavirin prevents nuclear entry of eIF4E, which mirrors the trafficking phenotypes observed in patients with AML. Our studies also suggest that nuclear entry is important for the prooncogenic activity of eIF4E, at least in this context. These findings position nuclear trafficking of eIF4E as a critical step in its regulation and position the importin 8–eIF4E complex as a novel therapeutic target. PMID:27114554

Crystal structure of a minimal eIF4E–Cup complex reveals a general mechanism of eIF4E regulation in translational repression

PubMed Central

Kinkelin, Kerstin; Veith, Katharina; Grünwald, Marlene; Bono, Fulvia

2012-01-01

Cup is an eIF4E-binding protein (4E-BP) that plays a central role in translational regulation of localized mRNAs during early Drosophila development. In particular, Cup is required for repressing translation of the maternally contributed oskar, nanos, and gurken mRNAs, all of which are essential for embryonic body axis determination. Here, we present the 2.8 Å resolution crystal structure of a minimal eIF4E–Cup assembly, consisting of the interacting regions of the two proteins. In the structure, two separate segments of Cup contact two orthogonal faces of eIF4E. The eIF4E-binding consensus motif of Cup (YXXXXLΦ) binds the convex side of eIF4E similarly to the consensus of other eIF4E-binding proteins, such as 4E-BPs and eIF4G. The second, noncanonical, eIF4E-binding site of Cup binds laterally and perpendicularly to the eIF4E β-sheet. Mutations of Cup at this binding site were shown to reduce binding to eIF4E and to promote the destabilization of the associated mRNA. Comparison with the binding mode of eIF4G to eIF4E suggests that Cup and eIF4G binding would be mutually exclusive at both binding sites. This shows how a common molecular surface of eIF4E might recognize different proteins acting at different times in the same pathway. The structure provides insight into the mechanism by which Cup disrupts eIF4E–eIF4G interaction and has broader implications for understanding the role of 4E-BPs in translational regulation. PMID:22832024

Navy Career Sea Pay: Is it Still a Viable Compensating Wage Program? A Historical and Financial Analysis

DTIC Science & Technology

2007-06-01

220 | E7 5 262 | E7 5 468 | E7 6 118 | E7 6 147 | E7 6 267 | E7 7 17 | E7 7 37 | E7 7 81 | E8 1 61 | E8 1 64 | E8 1 57 | E8 2 62 | E8 2 76 | E8 2 70...5027 4923 4932 4640 E7-E9 451 405 387 445 447 462 453 454 448 441 441 489 MA E1-E3 1 1 1 2 12 22 33 108 135 137 160 189 E4-E6 429 414 407 416 444 483...20 262 12 24 970 8 4.60% 5.80% 1.33% 60.00% 1.60% 33.33% Apr-03 1593 10 342 4 42 467 15 26 1023 11 0.63% 40.00% 2.64% 35.71% 1.63% 42.31% Oct-03 1711

Study of the semileptonic charm decays D0→π-e+νe, D+→π0e+νe, D0→K-e+νe, and D+→ Kmacr 0e+νe

NASA Astrophysics Data System (ADS)

Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Ernst, J.; Severini, H.; Dytman, S. A.; Love, W.; Savinov, V.; Aquines, O.; Li, Z.; Lopez, A.; Mehrabyan, S.; Mendez, H.; Ramirez, J.; Huang, G. S.; Miller, D. H.; Pavlunin, V.; Sanghi, B.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Coan, T. E.; Gao, Y. S.; Liu, F.; Artuso, M.; Blusk, S.; Butt, J.; Li, J.; Menaa, N.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Redjimi, R.; Sia, R.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Zhang, K.; Csorna, S. E.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Asner, D. M.; Edwards, K. W.; Briere, R. A.; Brock, I.; Chen, J.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Adam, N. E.; Alexander, J. P.; Berkelman, K.; Cassel, D. G.; Duboscq, J. E.; Ecklund, K. M.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Pivarski, J.; Riley, D.; Ryd, A.; Sadoff, A. J.; Schwarthoff, H.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Weinberger, M.; Athar, S. B.; Patel, R.; Potlia, V.; Yelton, J.; Rubin, P.; Cawlfield, C.; Eisenstein, B. I.; Karliner, I.; Kim, D.; Lowrey, N.; Naik, P.; Sedlack, C.; Selen, M.; White, E. J.; Wiss, J.; Shepherd, M. R.; Besson, D.; Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Gong, D. T.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Smith, A.; Zweber, P.

2008-06-01

Using a sample of 1.8 million D Dmacr mesons collected at the ψ(3770) with the CLEO-c detector, we study the semileptonic decays D0→π-e+νe, D+→π0e+νe, D0→K-e+νe, and D+→ Kmacr 0e+νe. For the total branching fractions we find B(D0→π-e+νe)=0.299(11)(9)%, B(D+→π0e+νe)=0.373(22)(13)%, B(D0→K-e+νe)=3.56(3)(9)%, and B(D+→ Kmacr 0e+νe)=8.53(13)(23)%, where the first error is statistical and the second systematic. In addition, form factors are studied through fits to the partial branching fractions obtained in five q2 ranges. By combining our results with recent unquenched lattice calculations, we obtain |Vcd|=0.217(9)(4)(23) and |Vcs|=1.015(10)(11)(106), where the final error is theoretical.

Radiation Dose Deposition in the Active Marrow of Reference Man.

DTIC Science & Technology

1977-10-31

204 16 1.546E-10 .252 1,427E-10 .261 1,292E1o .273 17 1.530F-10 .237 10580E.10 9304 1.ooIEinl o272 18 9.490E11l .308 19494E-10 9249 1.3ASE-10 .268 19...IO ,269 2,399E-10 .198 29337E-10 .19217 8,124F-11 .288 1,310E-10 .?28 19331E-10 .244 18 9.013E-11 .292 2.403E-o0 . 204 2.002E-1O .199 q 7.s69E-i1 .Sl1...2.88SE-t0 viol 3,37bf-10 .155 16 1.379E-10 .227 ?.586E-i0 .179 2.030E-t0 . 204 17 2.23SEin10 .226 1.8O1E-10 .237 2,044E-10 .195 18 1.429E-I0 .?268 2367E-10

The E2 glycoprotein is necessary but not sufficient for the adaptation of classical swine fever virus lapinized vaccine C-strain to the rabbit.

PubMed

Li, Yongfeng; Xie, Libao; Zhang, Lingkai; Wang, Xiao; Li, Chao; Han, Yuying; Hu, Shouping; Sun, Yuan; Li, Su; Luo, Yuzi; Liu, Lihong; Munir, Muhammad; Qiu, Hua-Ji

2018-06-01

Classical swine fever virus (CSFV) C-strain was developed through hundreds of passages of a highly virulent CSFV in rabbits. To investigate the molecular basis for the adaptation of C-strain to the rabbit (ACR), a panel of chimeric viruses with the exchange of glycoproteins E rns , E1, and/or E2 between C-strain and the highly virulent Shimen strain and a number of mutant viruses with different amino acid substitutions in E2 protein were generated and evaluated in rabbits. Our results demonstrate that Shimen-based chimeras expressing E rns -E1-E2, E rns -E2 or E1-E2 but not E rns -E1, E rns , E1, or E2 of C-strain can replicate in rabbits, indicating that E2 in combination with either E rns or E1 confers the ACR. Notably, E2 and the amino acids P108 and T109 in Domain I of E2 are critical in ACR. Collectively, our data indicate that E2 is crucial in mediating the ACR, which requires synergistic contribution of E rns or E1. Copyright © 2018 Elsevier Inc. All rights reserved.

Nuclear assortment of eIF4E coincides with shut-off of host protein synthesis upon poliovirus infection.

PubMed

Sukarieh, R; Sonenberg, N; Pelletier, J

2010-05-01

Eukaryotic initiation factor (eIF) 4E is a subunit of the cap-binding protein complex, eIF4F, which recognizes the cap structure of cellular mRNAs to facilitate translation initiation. eIF4E is assembled into the eIF4F complex via its interaction with eIF4G, an event that is under Akt/mTOR regulation. The eIF4E-eIF4G interaction is regulated by the eIF4E binding partners, eIF4E-binding proteins and eIF4E-transporter. Cleavage of eIF4G occurs upon poliovirus infection and is responsible for the shut-off of host-cell protein synthesis observed early in infection. Here, we document that relocalization of eIF4E to the nucleus occurs concomitantly with cleavage of eIF4G upon poliovirus infection. This event is not dependent upon virus replication, but is dependent on eIF4G cleavage. We postulate that eIF4E nuclear relocalization may contribute to the shut-off of host protein synthesis that is a hallmark of poliovirus infection by perturbing the circular status of actively translating mRNAs.

A study on the immunological basis of the dissociation between type I-hypersensitivity skin reactions to Blomia tropicalis antigens and serum anti-B. tropicalis IgE antibodies

PubMed Central

2011-01-01

Background Two conditions are used as markers of atopy: the presence of circulating anti-allergen IgE antibodies and the presence of positive skin prick test (SPT) reactions to allergenic extracts. The correlation between these conditions is not absolute. This study aimed at investigating immunological parameters that may mediate this lack of correlation. Individuals whose sera contained anti-B. tropicalis extract IgE antibodies (α-BtE IgE) were divided into two groups, according to the presence or absence of skin reactivity to B. tropicalis extract (BtE). The following parameters were investigated: total IgE levels; α-BtE IgE levels; an arbitrary α-BtE IgE/total IgE ratio; the proportion of carbohydrate-reactive α-BtE IgE; the proportion of α-BtE IgE that reacted with Ascaris lumbricoides extract (AlE); the production of IL-10 by BtE- and AlE-stimulated peripheral blood cells (PBMC). Results Total IgE levels were similar in the two groups, but α-BtE IgE was significantly higher in the SPT-positive group (SPT+). A large overlap of α-BtE IgE levels was found in individuals of both groups, indicating that these levels alone cannot account for the differences in SPT outcome. Individuals of the two groups did not differ, statistically, in the proportion of α-BtE IgE that reacted with carbohydrate and in the production of IL-10 by BtE- and AlE-stimulated PBMC. Both groups had part of α-BtE IgE activity absorbed out by AlE, indicating the existence of cross-reactive IgE antibodies. However, the α-BtE IgE from the SPT-negative individuals (SPT-) was more absorbed with AlE than the α-BtE IgE from the SPT+ individuals. This finding may be ascribed to avidity differences of the α-BtE IgE that is present in the two groups of individuals, and could occur if at least part of the α-BtE IgE from the SPT- individuals were elicited by A. lumbricoides infection. Conclusion The present results suggest that a low ratio of specific IgE to total IgE levels (in a minority of individuals), and differences in α-BtE IgE avidities (which would have high affinities for A. lumbricoides antigens in SPT- than in SPT+ individuals) may play a role in the down-modulation of type-I hypersensitivity reaction against aeroallergens described in helminth-infected individuals. PMID:21631925

E6^E7, a Novel Splice Isoform Protein of Human Papillomavirus 16, Stabilizes Viral E6 and E7 Oncoproteins via HSP90 and GRP78

PubMed Central

Ajiro, Masahiko

2015-01-01

ABSTRACT Transcripts of human papillomavirus 16 (HPV16) E6 and E7 oncogenes undergo alternative RNA splicing to produce multiple splice isoforms. However, the importance of these splice isoforms is poorly understood. Here we report a critical role of E6^E7, a novel isoform containing the 41 N-terminal amino acid (aa) residues of E6 and the 38 C-terminal aa residues of E7, in the regulation of E6 and E7 stability. Through mass spectrometric analysis, we identified that HSP90 and GRP78, which are frequently upregulated in cervical cancer tissues, are two E6^E7-interacting proteins responsible for the stability and function of E6^E7, E6, and E7. Although GRP78 and HSP90 do not bind each other, GRP78, but not HSP90, interacts with E6 and E7. E6^E7 protein, in addition to self-binding, interacts with E6 and E7 in the presence of GRP78 and HSP90, leading to the stabilization of E6 and E7 by prolonging the half-life of each protein. Knocking down E6^E7 expression in HPV16-positive CaSki cells by a splice junction-specific small interfering RNA (siRNA) destabilizes E6 and E7 and prevents cell growth. The same is true for the cells with a GRP78 knockdown or in the presence of an HSP90 inhibitor. Moreover, mapping and alignment analyses for splicing elements in 36 alpha-HPVs (α-HPVs) suggest the possible expression of E6^E7 mostly by other oncogenic or possibly oncogenic α-HPVs (HPV18, -30, -31, -39, -42, -45, -56, -59, -70, and -73). HPV18 E6^E7 is detectable in HPV18-positive HeLa cells and HPV18-infected raft tissues. All together, our data indicate that viral E6^E7 and cellular GRP78 or HSP90 might be novel targets for cervical cancer therapy. PMID:25691589

Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside.

PubMed

Chantler, Paul D; Nussbacher, Amit; Gerstenblith, Gary; Schulman, Steven P; Becker, Lewis C; Ferrucci, Luigi; Fleg, Jerome L; Lakatta, Edward G; Najjar, Samer S

2011-05-01

The coupling between arterial elastance (E(A); net afterload) and left ventricular elastance (E(LV); pump performance), known as E(A)/E(LV), is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in E(LV) versus E(A). This normal exercise-induced reduction in E(A)/E(LV) decreases with advancing age. We hypothesized that sodium nitroprusside (SNP) can acutely ameliorate the age-associated deficits in E(A)/E(LV). At rest and during graded exercise to exhaustion, E(A) was characterized as end-systolic pressure/stroke volume and E(LV) as end-systolic pressure/end-systolic volume. Resting E(A)/E(LV) did not differ between old (70 ± 8 yr, n = 15) and young (30 ± 5 yr, n = 17) subjects because of a tandem increase in E(A) and E(LV) in older subjects. During peak exercise, a blunted increase in E(LV) in old (7.8 ± 3.1 mmHg/ml) versus young (11.4 ± 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in E(A)/E(LV) in old (0.25 ± 0.11) versus young (0.16 ± 0.05) subjects. SNP administration to older subjects lowered resting E(A)/E(LV) by 31% via a reduction in E(A) (10%) and an increase in E(LV) (47%) and lowered peak exercise E(A)/E(LV) (36%) via an increase in E(LV) (68%) without a change in E(A). Importantly, SNP attenuated the age-associated deficits in E(A)/E(LV) and E(LV) during exercise, and at peak exercise E(A)/E(LV) in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in E(A)/E(LV), E(A), and E(LV), in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction.

Genomic Characterization of KIR2DL4 in Families and Unrelated Individuals Reveals Extensive Diversity in Exon and Intron Sequences Including a Common Frameshift Variation Occurring in Several Alleles

DTIC Science & Technology

2005-01-18

r A L 1 3 3 4 1 4 ) w a s u s e d a s a re fe re n c e . D a s h e s in d ic a te id e n ti...le d th e tr a n s m e m b ra n e e xo n a s e xo n 7 in o rd e r to k e e p th e re la ti o n s h ip a m o n g K IR e xo n s in th e d if fe re n t...g e n e s c o n s is te n t. N u c le o ti d e p o s it io n s w e

Diagnosis of 25 genotypes of human papillomaviruses for their physical statuses in cervical precancerous/cancerous lesions: a comparison of E2/E6E7 ratio-based vs. multiple E1-L1/E6E7 ratio-based detection techniques.

PubMed

Zhang, Rong; He, Yi-feng; Chen, Mo; Chen, Chun-mei; Zhu, Qiu-jing; Lu, Huan; Wei, Zhen-hong; Li, Fang; Zhang, Xiao-xin; Xu, Cong-jian; Yu, Long

2014-10-02

Cervical lesions caused by integrated human papillomavirus (HPV) infection are highly dangerous because they can quickly develop into invasive cancers. However, clinicians are currently hampered by the lack of a quick, convenient and precise technique to detect integrated/mixed infections of various genotypes of HPVs in the cervix. This study aimed to develop a practical tool to determine the physical status of different HPVs and evaluate its clinical significance. The target population comprised 1162 women with an HPV infection history of > six months and an abnormal cervical cytological finding. The multiple E1-L1/E6E7 ratio analysis, a novel technique, was developed based on determining the ratios of E1/E6E7, E2/E6E7, E4E5/E6E7, L2/E6E7 and L1/E6E7 within the viral genome. Any imbalanced ratios indicate integration. Its diagnostic and predictive performances were compared with those of E2/E6E7 ratio analysis. The detection accuracy of both techniques was evaluated using the gold-standard technique "detection of integrated papillomavirus sequences" (DIPS). To realize a multigenotypic detection goal, a primer and probe library was established. The integration rate of a particular genotype of HPV was correlated with its tumorigenic potential and women with higher lesion grades often carried lower viral loads. The E1-L1/E6E7 ratio analysis achieved 92.7% sensitivity and 99.0% specificity in detecting HPV integration, while the E2/E6E7 ratio analysis showed a much lower sensitivity (75.6%) and a similar specificity (99.3%). Interference due to episomal copies was observed in both techniques, leading to false-negative results. However, some positive results of E1-L1/E6E7 ratio analysis were missed by DIPS due to its stochastic detection nature. The E1-L1/E6E7 ratio analysis is more efficient than E2/E6E7 ratio analysis and DIPS in predicting precancerous/cancerous lesions, in which both positive predictive values (36.7%-82.3%) and negative predictive values (75.9%-100%) were highest (based on the results of three rounds of biopsies). The multiple E1-L1/E6E7 ratio analysis is more sensitive and predictive than E2/E6E7 ratio analysis as a triage test for detecting HPV integration. It can effectively narrow the range of candidates for colposcopic examination and cervical biopsy, thereby lowering the expense of cervical cancer prevention.

Cooperative modulation by eIF4G of eIF4E-binding to the mRNA 5' cap in yeast involves a site partially shared by p20.

PubMed Central

Ptushkina, M; von der Haar, T; Vasilescu, S; Frank, R; Birkenhäger, R; McCarthy, J E

1998-01-01

Interaction between the mRNA 5'-cap-binding protein eIF4E and the multiadaptor protein eIF4G has been demonstrated in all eukaryotic translation assemblies examined so far. This study uses immunological, genetic and biochemical methods to map the surface amino acids on eIF4E that contribute to eIF4G binding. Cap-analogue chromatography and surface plasmon resonance (SPR) analyses demonstrate that one class of mutations in these surface regions disrupts eIF4E-eIF4G association, and thereby polysome formation and growth. The residues at these positions in wild-type eIF4E mediate positive cooperativity between the binding of eIF4G to eIF4E and the latter's cap-affinity. Moreover, two of the mutations confer temperature sensitivity in eIF4G binding to eIF4E which correlates with the formation of large numbers of inactive ribosome 80S couples in vivo and the loss of cellular protein synthesis activity. The yeast 4E-binding protein p20 is estimated by SPR to have a ten times lower binding affinity than eIF4G for eIF4E. Investigation of a second class of eIF4E mutations reveals that p20 shares only part of eIF4G's binding site on the cap-binding protein. The results presented provide a basis for understanding how cycling of eIF4E and eIF4G occurs in yeast translation and explains how p20 can act as a fine, but not as a coarse, regulator of protein synthesis. PMID:9707439

Stereochemical diversity in lignan biosynthesis of Arctium lappa L.

PubMed

Suzuki, Shiro; Umezawa, Toshiaki; Shimada, Mikio

2002-06-01

The stereochemistry of lignan biosynthesis in Arctium lappa L. is regulated organ-specifically. (+)-Secoisolariciresinol [81% enantiomeric excess (e.e.)] was isolated from A. lappa petioles. In sharp contrast, lignans whose predominant enantiomers have the opposite absolute configuration to that of (+)-secoisolariciresinol [i.e., (-)-matairesinol (>99% e.e.), (-)-arctigenin (>99% e.e.), and (-)-secoisolariciresinol (65% e.e.)] were isolated from seeds of the species. The stereochemical diversity of secoisolariciresinol was demonstrated with enzyme preparations from A. lappa petioles and seeds. Thus, a petiole enzyme preparation catalyzed the formation of (+)-pinoresinol (33% e.e.), (+)-lariciresinol (30% e.e.), and (+)-secoisolariciresinol (20% e.e.) from achiral coniferyl alcohol in the presence of NADPH and H202, whereas that from ripening seeds catalyzed the formation of (-)-pinoresinol (22% e.e.), (-)-lariciresinol (>99% e.e.), and (-)-secoisolariciresinol (38% e.e.) under the same conditions. In addition, the ripening seed enzyme preparation mediated the selective formation of the optically pure (>99% e.e.) (-)-enantiomer of matairesinol from racemic (+/-)-secoisolariciresinols in the presence of NADP. These results indicate that the stereochemical mechanism for lignan biosynthesis in A. lappa varies with organs, suggesting that multiple lignan-synthesizing isozymes are involved in the stereochemical control of lignan formation in A. lappa.

Franck-Condon Factors, R-Centroids Electronic Transition Moments, and Einstein Coefficients for Many Nitrogen and Oxygen Band Systems

DTIC Science & Technology

1992-02-01

5.21E-04 2.35E-04 1.071-04 4.93E-05 2.30E-05 1.088-05 5.06E-06 1.0615 1.0433 1.0266 1.0111 .9968 .9838 .9718 .9608 . 9505 .9406 .9304 3.03E-01 3.06E-01...3.49E-13 5.92E-16 1.23E-13 3.65E-13 .9056 1.9606 1.1888 7.9958 2.1710 . 0002 1.1879 1.0057 -1.4622 1.1520 1.0717 2.66E-01 3.32E-02 2.28E-01 9.36E-42 1.34E

Study of the decays D0-->pi{-}e{+}nu{e}, D{0}-->K{-}e{+}nu{e}, D{+}-->pi{0}e{+}nu{e}, and D{+}-->K0e{+}nu{e}.

PubMed

Cronin-Hennessy, D; Gao, K Y; Gong, D T; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Smith, A; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Ernst, J; Severini, H; Dytman, S A; Love, W; Savinov, V; Aquines, O; Li, Z; Lopez, A; Mehrabyan, S; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F; Coan, T E; Gao, Y S; Liu, F; Artuso, M; Blusk, S; Butt, J; Li, J; Menaa, N; Mountain, R; Nisar, S; Randrianarivony, K; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Asner, D M; Edwards, K W; Briere, R A; Brock, I; Chen, J; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Onyisi, P U E; Patterson, J R; Peterson, D; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Weinberger, M; Athar, S B; Patel, R; Potlia, V; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; White, E J; Wiss, J; Shepherd, M R; Besson, D; Pedlar, T K

2008-06-27

By using 1.8x10{6} DDpairs, we have measured B(D{0}-->pi{-}e{+}nu{e})=0.299(11)(9)%, B(D{+}-->pi{0}e{+}nu{e})=0.373(22)(13)%, B(D{0}-->K{-}e{+}nu{e})=3.56(3)(9)%, and B(D{+}-->K{0}e{+}nu{e})=8.53(13)(23)% and have studied the q;{2} dependence of the form factors. By combining our results with recent lattice calculations, we obtain |V{cd}|=0.217(9)(4)(23) and |V{cs}|=1.015(10)(11)(106).

[The effect of size reduction of corn silage on feed intake, milk production and milk composition of cows].

PubMed

Preissinger, W; Schwarz, F J; Kirchgessner, M

1998-01-01

In three experiments (E1, E2, E3) maize silage of different physical structure and of different stage of maturity at harvest were fed to 24 (E1), 36 (E2) or 28 (E3) dairy cows. The cows were fed individually over an experimental period of five or six weeks. The maize silages had a mean DM content of 28% (E1), 32% (E2) or 36% (E3). At the stage of harvest, the stovers and the cobs had a mean DM content of < 22% (E1, E2) or 27% (E3), 40% (E1), 46% (E2) or 57% (E3), respectively. The maize was harvested with a chopping length of 4 and 8 mm (E1, E3) and of 6 and 8 mm (E2), without corn cracking (E1) or with and without corn cracking (E2, E3). The daily feed ration consisted of ad libitum offered maize silage, 1.7 kg DM hay, soya bean meal (E2, E3) and concentrate. The different chopping length of 4 mm, 6 mm or 8 mm had no effect on the maize silage intake in E1 and E2. In E3 the daily maize silage intake increased by about 1.2 kg DM per cow at a chopping length of 4 mm in comparison to 8 mm, whereas only the treatment with the combination of 4 mm chopping length and corn cracking showed a significant increase in DMI. The corn cracking improved the milk yield significantly (E2) or in a tendency (E3) at 2.0 kg (E2) or at 1.6 kg (E2), while the variation of chopping length had no effect on milk yield. The different physical structure did not influence the milk fat content with mean values of 4.65% (E1), 4.15% (E2) and 4.10% (E3), respectively. The milk protein content decreased in E2 feeding maize silage with a chopping length of 8 mm and corn cracking; but in E1 and E3 no effect was seen on protein content with mean values of 3.66% (E1) or 3.51% (E2).

Bounding Analysis of Effects of Fractionation of Radionuclides inFallout on Estimation of Doses to Atomic Veterans

DTIC Science & Technology

2007-05-04

140 Sm-156 Y-91m Rh - 103m Cd-115 Te-129 La-141 Eu-156 Y-91 Ru-105 In-115m I-130 Ce-141 Eu-157 Sr-92 Rh -105m Sn-121 Te-131m Ce-143 Gd-159 Y-92 Rh ...Tc-99m 6.02 h R 1.09E+00n (0.886) Ru-103 39.35 d V 2.04E-07 9.65E-01 6.81E-12 Rh - 103m 56.119 m V 1.00E+00n (0.997) 1.00E+00 Ru-105 4.44 h...08 1.24E-08 9.09E-09 Rh - 103m 6.36E-09 1.34E-08 1.23E-08 9.07E-09 Ru-105 1.20E-02 5.36E-02 4.05E-02 3.22E-02 2.90E-10 1.30E-09 9.79E-10 7.78E-10

The relationship between obstructive sleep apnea syndrome and apolipoprotein E genetic variants.

PubMed

Uyrum, Ebru; Balbay, Oner; Annakkaya, Ali Nihat; Gulec Balbay, Ege; Silan, Fatma; Arbak, Peri

2015-01-01

Clinical and epidemiological studies indicate that obstructive sleep apnea syndrome (OSAS) has a strong genetic basis. To investigate the apolipoprotein E (APOE) alleles as a genetic risk factor in OSAS. A total of 73 patients (37 male) were included. All underwent full-night polysomnography and were evaluated for APOE alleles. The mean age was 51 ± 12 years. Forty-two of the patients had OSAS. The APOE3 allele was found in 97.3% (71/73) of the study population. The most common APOE genotype was E3/E3 (55/73, 75.3%). Compared to the individuals with no APOE2 alleles (E3/E3, E3/E4), the individuals with at least one APOE2 allele (E2/E3, E2/E4) had a 9.37-fold greater OSAS risk (OR = 9.37, 95% CI 1.13-77.7, p = 0.019). The individuals with APOE2 alleles (E2/E3, E2/E4) compared to the individuals with only an E3/E3 allele genotype had a 10-fold greater OSAS risk (OR = 10.3, 95% CI 1.24-86.61, p = 0.0308). Compared to the individuals with no APOE4 alleles (E2/E3, E3/E3), the individuals with APOE4 alleles (E2/E4, E3/E4) had a high but insignificant risk for OSAS (OR = 2.9, 95% CI 0.55-15.05, p = 0.286). The individuals with APOE4 alleles (E2/E4, E3/E4) compared to APOE3 alleles (E3/E3) had an increased but insignificant risk for OSAS (OR = 3.62, 95% CI 0.96-19.05, p = 0.127). Specific APOE genotypes are associated with OSAS in a high-risk population.

40 CFR 81.303 - Arizona.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., R141/2E X T1S, R15E X T2N, R13E 1 X T2N, R16E X T1N, R16E X T1S, R13E 1 X T1S, R16E X T2S, R14E 1 X T2S..., R13E; T1N, R14E; T1N, R15E; T1S, R14E; T1S, R14 1/2E; T1S, R15E 1 Excludes Indian country located in...); T1S, R14E (sections 124); T1S, R141/2E; and T1S, R15E 11/15/90 Nonattainment 11/15/90 Moderate. Gila...

Optimization of Daily Flight Training Schedules

DTIC Science & Technology

2014-03-01

iep iep ip X s e p Y i e p L i e p W...SOLO L CQ CQ | | 2 , | d d d iep iep ip p P p Pe e E e e E p P P Y L W i d i I               (3) SOLO L CQ | | 2 , | d d iep ... iep p P p Pe e E e e E Y L i d i I           (4) 1 , | , "CQ" o s sep s p p X s e e C e      (5) 0 0 | 2 , s d s sep s e C p

Mutational Analysis of Plant Cap-Binding Protein eIF4E Reveals Key Amino Acids Involved in Biochemical Functions and Potyvirus Infection▿

PubMed Central

German-Retana, Sylvie; Walter, Jocelyne; Doublet, Bénédicte; Roudet-Tavert, Geneviève; Nicaise, Valérie; Lecampion, Cécile; Houvenaghel, Marie-Christine; Robaglia, Christophe; Michon, Thierry; Le Gall, Olivier

2008-01-01

The eukaryotic translation initiation factor 4E (eIF4E) (the cap-binding protein) is involved in natural resistance against several potyviruses in plants. In lettuce, the recessive resistance genes mo11 and mo12 against Lettuce mosaic virus (LMV) are alleles coding for forms of eIF4E unable, or less effective, to support virus accumulation. A recombinant LMV expressing the eIF4E of a susceptible lettuce variety from its genome was able to produce symptoms in mo11 or mo12 varieties. In order to identify the eIF4E amino acid residues necessary for viral infection, we constructed recombinant LMV expressing eIF4E with point mutations affecting various amino acids and compared the abilities of these eIF4E mutants to complement LMV infection in resistant plants. Three types of mutations were produced in order to affect different biochemical functions of eIF4E: cap binding, eIF4G binding, and putative interaction with other virus or host proteins. Several mutations severely reduced the ability of eIF4E to complement LMV accumulation in a resistant host and impeded essential eIF4E functions in yeast. However, the ability of eIF4E to bind a cap analogue or to fully interact with eIF4G appeared unlinked to LMV infection. In addition to providing a functional mutational map of a plant eIF4E, this suggests that the role of eIF4E in the LMV cycle might be distinct from its physiological function in cellular mRNA translation. PMID:18480444

Study of the Decays D0→π-e+νe, D0→K-e+νe, D+→π0e+νe, and D+→ Kmacr 0e+νe

NASA Astrophysics Data System (ADS)

Cronin-Hennessy, D.; Gao, K. Y.; Gong, D. T.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Smith, A.; Zweber, P.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Ernst, J.; Severini, H.; Dytman, S. A.; Love, W.; Savinov, V.; Aquines, O.; Li, Z.; Lopez, A.; Mehrabyan, S.; Mendez, H.; Ramirez, J.; Huang, G. S.; Miller, D. H.; Pavlunin, V.; Sanghi, B.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Coan, T. E.; Gao, Y. S.; Liu, F.; Artuso, M.; Blusk, S.; Butt, J.; Li, J.; Menaa, N.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Redjimi, R.; Sia, R.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Zhang, K.; Csorna, S. E.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Asner, D. M.; Edwards, K. W.; Briere, R. A.; Brock, I.; Chen, J.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Adam, N. E.; Alexander, J. P.; Berkelman, K.; Cassel, D. G.; Duboscq, J. E.; Ecklund, K. M.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Pivarski, J.; Riley, D.; Ryd, A.; Sadoff, A. J.; Schwarthoff, H.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Weinberger, M.; Athar, S. B.; Patel, R.; Potlia, V.; Yelton, J.; Rubin, P.; Cawlfield, C.; Eisenstein, B. I.; Karliner, I.; Kim, D.; Lowrey, N.; Naik, P.; Sedlack, C.; Selen, M.; White, E. J.; Wiss, J.; Shepherd, M. R.; Besson, D.; Pedlar, T. K.

2008-06-01

By using 1.8×106 D Dmacr pairs, we have measured B(D0→π-e+νe)=0.299(11)(9)%, B(D+→π0e+νe)=0.373(22)(13)%, B(D0→K-e+νe)=3.56(3)(9)%, and B(D+→ Kmacr 0e+νe)=8.53(13)(23)% and have studied the q2 dependence of the form factors. By combining our results with recent lattice calculations, we obtain |Vcd|=0.217(9)(4)(23) and |Vcs|=1.015(10)(11)(106).

Morale, Welfare, and Recreation: Nonappropriated Funds Personnel Policy

DTIC Science & Technology

2002-04-01

Nonappropriated Fund Instrumentality established for the purpose of providing installation/community MWR activi- ties, including food and beverage , retail...2002 H i s t o r y . T h i s p r i n t i n g p u b l i s h e s a r e v i s i o n o f t h i s r e g u l a t i o n . B e c a u s e t h e p u b l i c...a t i o n h a s b e e n e x t e n s i v e l y r e v i s e d , t h e c h a n g e d p o r t i o n s h a v e n o t b e e n highlighted. Summary. This

40 CFR Appendix E to Part 61 - Compliance Procedures Methods for Determining Compliance With Subpart I

Code of Federal Regulations, 2014 CFR

2014-07-01

...-93 1.5E−03 1.5E+00 1.5E+03 Mo-99** 5.7E−02 5.7E+01 5.7E+04 Mo-101 8.4E−01 8.4E+02 8.4E+05 Na-22 3.2E−05 3.2E−02 3.2E+01 Na-24 2.6E−02 2.6E+01 2.6E+04 Nb-90 2.5E−02 2.5E+01 2.5E+04 Nb-93m 1.2E−02 1.2E+01...+03 Si-31 4.7E+00 4.7E+03 4.7E+06 Si-32 7.2E−04 7.2E−01 7.2E+02 Sm-147 1.4E−05 1.4E−02 1.4E+01 Sm-151...

40 CFR Appendix E to Part 61 - Compliance Procedures Methods for Determining Compliance With Subpart I

Code of Federal Regulations, 2013 CFR

2013-07-01

...-93 1.5E−03 1.5E+00 1.5E+03 Mo-99** 5.7E−02 5.7E+01 5.7E+04 Mo-101 8.4E−01 8.4E+02 8.4E+05 Na-22 3.2E−05 3.2E−02 3.2E+01 Na-24 2.6E−02 2.6E+01 2.6E+04 Nb-90 2.5E−02 2.5E+01 2.5E+04 Nb-93m 1.2E−02 1.2E+01...+03 Si-31 4.7E+00 4.7E+03 4.7E+06 Si-32 7.2E−04 7.2E−01 7.2E+02 Sm-147 1.4E−05 1.4E−02 1.4E+01 Sm-151...

40 CFR Appendix E to Part 61 - Compliance Procedures Methods for Determining Compliance With Subpart I

Code of Federal Regulations, 2012 CFR

2012-07-01

...-93 1.5E−03 1.5E+00 1.5E+03 Mo-99** 5.7E−02 5.7E+01 5.7E+04 Mo-101 8.4E−01 8.4E+02 8.4E+05 Na-22 3.2E−05 3.2E−02 3.2E+01 Na-24 2.6E−02 2.6E+01 2.6E+04 Nb-90 2.5E−02 2.5E+01 2.5E+04 Nb-93m 1.2E−02 1.2E+01...+03 Si-31 4.7E+00 4.7E+03 4.7E+06 Si-32 7.2E−04 7.2E−01 7.2E+02 Sm-147 1.4E−05 1.4E−02 1.4E+01 Sm-151...

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

Tan, Chye Ling; Gunaratne, Jayantha; Lai, Deborah

The Human Papillomavirus (HPV) E4 is known to be synthesized as an E1circumflexE4 fusion resulting from splice donor and acceptor sites conserved across HPV types. Here we demonstrate the existence of 2 HPV-18 E2circumflexE4 transcripts resulting from 2 splice donor sites in the 5 Prime part of E2, while the splice acceptor site is the one used for E1circumflexE4. Both E2circumflexE4 transcripts are up-regulated by keratinocyte differentiation in vitro and can be detected in clinical samples containing low-grade HPV-18-positive cells from Pap smears. They give rise to two fusion proteins in vitro, E2circumflexE4-S and E2circumflexE4-L. Whereas we could not differentiatemore » E2circumflexE4-S from E1circumflexE4 in vivo, E2circumflexE4-L could be formally identified as a 23 kDa protein in raft cultures in which the corresponding transcript was also found, and in a biopsy from a patient with cervical intraepithelial neoplasia stage I-II (CINI-II) associated with HPV-18, demonstrating the physiological relevance of E2circumflexE4 products.« less

Kinetics of plasma apolipoprotein E isoforms by LC-MS/MS: a pilot study.

PubMed

Blanchard, Valentin; Ramin-Mangata, Stéphane; Billon-Crossouard, Stéphanie; Aguesse, Audrey; Durand, Manon; Chemello, Kevin; Nativel, Brice; Flet, Laurent; Chétiveaux, Maud; Jacobi, David; Bard, Jean-Marie; Ouguerram, Khadija; Lambert, Gilles; Krempf, Michel; Croyal, Mikaël

2018-05-01

Human apoE exhibits three major isoforms (apoE2, apoE3, and apoE4) corresponding to polymorphism in the APOE gene. Total plasma apoE concentrations are closely related to these isoforms, but the underlying mechanisms are unknown. We aimed to describe the kinetics of apoE individual isoforms to explore the mechanisms for variable total apoE plasma concentrations. We used LC-MS/MS to discriminate between isoforms by identifying specific peptide sequences in subjects (three E2/E3, three E3/E3, and three E3/E4 phenotypes) who received a primed constant infusion of 2 H 3 -leucine for 14 h. apoE concentrations and leucine enrichments were measured hourly in plasma. Concentrations of apoE2 were higher than apoE3, and concentrations of apoE4 were lower than apoE3. There was no difference between apoE3 and apoE4 catabolic rates and between apoE2 and apoE3 production rates (PRs), but apoE2 catabolic rates and apoE4 PRs were lower. The mechanisms leading to the difference in total plasma apoE concentrations are therefore related to contrasted kinetics of the isoforms. Production or catabolic rates are differently affected according to the specific isoforms. On these grounds, studies on the regulation of the involved biochemical pathways and the impact of pathological environments are now warranted. Copyright © 2018 Blanchard et al.

LUMINEX®: a new technology for the simultaneous identification of five Entamoeba spp. commonly found in human stools

PubMed Central

2013-01-01

Background Six species of the genus Entamoeba, i.e., E. histolytica, E. dispar, E. moshkovskii, E. polecki, E. coli, and E. hartmanii can be found in human stools. Among these, only E. histolytica is considered to be pathogenic, causing intestinal and extra-intestinal disease, but it is morphologically identical to E. dispar and E. moshkovskii. In general, E. polecki, E. coli, and E. hartmanii can be differentiated morphologically from E. histolytica, but some of their diagnostic morphologic features may overlap creating issues for the differential diagnosis. Moreover, the previous inability to differentiate among Entamoeba species has limited epidemiologic information on E histolytica. The objective of this study was to develop a rapid, high-throughput screening method using Luminex technique for the simultaneous detection and differentiation of Entamoeba species. Methods PCR amplification was performed with biotinylated Entamoeba sp 18S rRNA gene primers, designed to amplify a fragment ranging from 382 to 429 bp of the Entamoeba spp studied. Regions of this fragment that could differentiate among E. histolytica, E. moshkovskii, E. dispar, E. hartmanii and E. coli were selected to design hybridization probes to link to Luminex beads. The assay was standardized with cloned DNA samples of each species and evaluated with 24 DNA extracts from samples obtained from individuals diagnosed with these amebas in their stools. Results Using this approach we were able to correctly identify E. histoltyica, E. dispar, E hartmanni, E. coli and E. moshkovskii in all specimens studied. From twenty four samples tested by microscopy, PCR/DNA Sequencing and real-time PCR, 100% agreed with PCR-Luminex assay for identification of E. dispar, E. moshkovskii, E. hartmanni, E. histolytica, and E. coli. Conclusion These results show that this method could be used in the diagnostic detection of Entamoeba spp in fecal samples. This diagnostic test was useful to clearly distinguish E histolytica from other species and also to strengthen epidemiologic data on Entamoeba spp. PMID:23497666

LUMINEX®: a new technology for the simultaneous identification of five Entamoeba spp. commonly found in human stools.

PubMed

Santos, Helena Lúcia Carneiro; Bandyopadhyay, Kakali; Bandea, Rebecca; Peralta, Regina Helena Saramago; Peralta, José Mauro; Da Silva, Alexandre Januário

2013-03-15

Six species of the genus Entamoeba, i.e., E. histolytica, E. dispar, E. moshkovskii, E. polecki, E. coli, and E. hartmanii can be found in human stools. Among these, only E. histolytica is considered to be pathogenic, causing intestinal and extra-intestinal disease, but it is morphologically identical to E. dispar and E. moshkovskii. In general, E. polecki, E. coli, and E. hartmanii can be differentiated morphologically from E. histolytica, but some of their diagnostic morphologic features may overlap creating issues for the differential diagnosis. Moreover, the previous inability to differentiate among Entamoeba species has limited epidemiologic information on E histolytica. The objective of this study was to develop a rapid, high-throughput screening method using Luminex technique for the simultaneous detection and differentiation of Entamoeba species. PCR amplification was performed with biotinylated Entamoeba sp 18S rRNA gene primers, designed to amplify a fragment ranging from 382 to 429 bp of the Entamoeba spp studied. Regions of this fragment that could differentiate among E. histolytica, E. moshkovskii, E. dispar, E. hartmanii and E. coli were selected to design hybridization probes to link to Luminex beads. The assay was standardized with cloned DNA samples of each species and evaluated with 24 DNA extracts from samples obtained from individuals diagnosed with these amebas in their stools. Using this approach we were able to correctly identify E. histoltyica, E. dispar, E hartmanni, E. coli and E. moshkovskii in all specimens studied. From twenty four samples tested by microscopy, PCR/DNA Sequencing and real-time PCR, 100% agreed with PCR-Luminex assay for identification of E. dispar, E. moshkovskii, E. hartmanni, E. histolytica, and E. coli. These results show that this method could be used in the diagnostic detection of Entamoeba spp in fecal samples. This diagnostic test was useful to clearly distinguish E histolytica from other species and also to strengthen epidemiologic data on Entamoeba spp.

United States Air Force Explosives Site Plan Report and Explosives Safety Program Support Initiatives

DTIC Science & Technology

2010-06-07

r i t y - S e r v i c e - E x c e l l e n c e 536 458 460 466 638 549 517 600 639 628 491 507 0 100 200 300 400...2008 through 1 August 2008. 4 I n t e g r i t y - S e r v i c e - E x c e l l e n c e Explosives Site Plans Received 0 200 400 600 800...measured on 1 June 2010. The current backlog is primarily ESPs awaiting MAJCOM response to review queries. 8 I n t e g r i t y - S e r v i c

Composite-Nanoparticles Thermal History Sensors

DTIC Science & Technology

2012-06-01

E -1 4. 214 011 X E - 2 1. 601 846 X E +1 1.000 000 X E - 2 2. 579 760 X E - 4 1 .000 000 x E - 8 1.459 390 x E +1 1. 333 22 X E -1 met ers...000 X E +1 1. 745 329 X E - 2 tk = (t0 f + 459.67)/1.8 1. 602 19 X E -19 1. 000 000 X E - 7 1. 000 000 X E - 7 3. 048 000 X E - 1 1. 355 818...ELEMENT NUMBER 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 8 . PERFORMING ORGANIZATION REPORT NUMBER 10. SPONSOR/MONITOR’S ACRONYM(S

Numerical Study of the Effect of the Fuel Film on Heat Transfer in a Rocket Engine Combustion Chamber

DTIC Science & Technology

2003-12-01

1.818 .1385E+06 .8015 13.072 .8440E+03 .0003 1.835 .1332E+06 .8046 13.158 .8232E+03 . 0002 1.852...1428E+06 .7857 13.245 .8026E+03 . 0002 1.869 .1554E+06 .7613 13.333 .7825E+03 .0001 1.887 .1401E+06...9468 16.260 .3642E+03 .0000 2.235 .2000E+05 . 9505 16.393 .3529E+03 .0000 2.247 .1841E+05 .9537

Revisiting the spider genus Eutichurus Simon, 1897 (Araneae, Eutichuridae): new species and complementary descriptions.

PubMed

Bonaldo, Alexandre B; Lise, Arno A; RamÍrez, MartÍn J; Saturnino, Regiane

2018-02-21

Six new species of the genus Eutichurus Simon, 1897 are described: E. murgai new species (based on male and female) and E. paredesi new species (male) from Peru; E. cumbia new species (female) and E. tequendama new species (male) from Colombia; E. yungas new species (male and female) from Bolivia, and E. nancyae new species (male and female) from Brazil. The males of E. marquesae Bonaldo, 1994, E. madre Bonaldo, 1994 and E. zarate Bonaldo, 1994 are described for the first time. Eutichurus brescoviti Bonaldo, 1994, described on males, is synonymized with E. tropicus (L. Koch, 1866), previously known only from females. New records for E. ibiuna Bonaldo, 1994, E. ravidus Simon, 1897, E. putus O. Pickard-Cambridge, 1898, E. silvae Bonaldo, 1994, E. lizeri Mello-Leitão, 1938, E. saylapampa Bonaldo, 1994, E. tropicus and E. manu Bonaldo, 1994 are presented. A key to all species of Eutichurus is provided, variation in the epigynal morphology of E. ibiuna is recorded and the fine morphology of E. marquesae is documented.

Perturbative QCD analysis of exclusive processes e+e-→V P and e+e-→T P

NASA Astrophysics Data System (ADS)

Lü, Cai-Dian; Wang, Wei; Xing, Ye; Zhang, Qi-An

2018-06-01

We study the e+e-→V P and e+e-→T P processes in the perturbative QCD approach based on kT factorization, where the P , V and T denotes a light pseudoscalar, vector, and tensor meson, respectively. We point out in the case of e+e-→T P transition due to charge conjugation invariance, only three channels are allowed: e+e-→a2±π∓ , e+e-→K2*±K∓ and the V-spin suppressed e+e-→K2*0K¯ 0+K¯2 *0K0 . Cross sections of e+e-→V P and e+e-→T P at √{s }=3.67 GeV and √{s }=10.58 GeV are calculated and the invariant mass dependence is found to favor the 1 /s4 power law. Most of our theoretical results are consistent with the available experimental data and other predictions can be tested at the ongoing BESIII and forthcoming Belle-II experiments.

Purification and immunochemical characterization of type e polysaccharide antigen of Streptococcus mutans.

PubMed

Hamada, S; Slade, H D

1976-07-01

The type-specific antigen of Streptococcus mutans strain MT703, serotype e, has been chromatographically purified and characterized. Two chromatographic fractions were obtained from saline extracts which reacted with both anti-MT703 whole-cell serum and Lancefield group E serum. The major fraction (eI) was identified as a polysaccharide composed of 37% glucose, 56% rhamnose, 5% protein, and 0.3% phosphorus, whereas the minor fraction (eII) contained 66% protein in addition to 10% glucose and 17% rhamnose. The immunological specificity of these antigens was found to be the same by immunodiffusion in agar gel. Another fraction with a negative charge (eIII) reacted with polyglycerophosphate antisera from Streptococcus mutans and Streptococcus pyogenes. For comparison, the MT703 antigen in a hot trichloroacetic acid extract (eA) and the group E antigen from a saline extract of cells of strain K129 (EI) were similarly purified by anionic ion-exchange chromatography. Although the ratio of glucose and rhamnose in eA was 1:0.9 and in eI and eII approximately 1:1.5, reactions of identity were obtained in gel diffusion against specific anti-e serum. This difference in ratio is probably a result of the extraction procedures. Both the type e and group E antisera were reactive with both eI and EI antigens. The adsorption of group E antiserum with MT703 cells removed all E antibody, whereas type e-specific antibody remained after adsorption with K129 cells. These results suggest that eI antigen possesses both e and E specificities, whereas EI possesses E only. These findings were supported by the quantitative precipitin test and immunodiffusion and/or immunoelectrophoretic patterns in agar gel. Methyl-beta-D-glucopyranoside markedly inhibited the precipitin reaction in both type e and group E sera. However, a significantly stronger inhibition by cellobiose of type e serum than of group E serum indicates that a beta-linked glucose-glucose dimer is the predominant antigenic determinant of the e specificity. The presence of both e and E specificities on a single polysaccharide molecule was demonstrated by the use of purified e antigen released from a specific e-anti-e complex. This antigen reacted with a group E-specific serum as well as a type e-specific serum. An examination of five S. mutans type e strains showed the presence of group E specificity also, whereas the I, II, and IV serotypes of group E streptococci only possessed the group E specificity.

An E/e' ratio on echocardiography predicts the existence of left atrial low-voltage areas and poor outcomes after catheter ablation for atrial fibrillation.

PubMed

Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Sunaga, Akihiro; Tsujimura, Takuya; Matsuda, Yasuhiro; Ohashi, Takuya; Uematsu, Masaaki

2018-05-01

An elevated left atrial pressure has been reported to play an important role in the development of atrial remodelling in atrial fibrillation (AF) patients. The study aimed at elucidating the association between the diastolic early transmitral flow velocity/mitral annular velocity (E/e', a non-invasive surrogate of left atrial pressure) and left atrial low-voltage-area existence, and the prognostic impact of the E/e' on procedural outcomes in patients undergoing AF ablation. Total of 215 consecutive patients were divided into 3 groups based on the estimated left atrial pressure: normal (E/e' < 8.0, n = 58), undetermined (E/e' = 8.0-14.0, n = 114), and elevated (E/e' > 14.0, n = 43). Left atrial endocardial voltage mapping was performed following pulmonary vein isolation. Patients with a high E/e' more frequently had low-voltage areas (E/e' < 8.0, 31%, E/e' = 8.0-14.0, 35%; E/e' > 14.0, 67%; P = 0.0001). After adjusting for other correlates, a high E/e' was an independent predictor of low-voltage-area existence (HR = 1.11, 95% CI = 1.02-1.21, P = 0.017). During a mean follow-up period of 12 ± 6 months, recurrent atrial tachyarrhythmias occurred in 22 (10%) patients after multiple (1.4 ± 0.5) procedures. Patients with an E/e' > 14 had more frequent recurrent atrial tachyarrhythmias after multiple ablation procedures than those with an E/e' ≤ 14 (23% vs. 7%, P = 0.001). A high E/e' obtained by pre-ablation echocardiography was associated with a left atrial arrhythmogenic substrate in patients undergoing AF ablation. Furthermore, a high E/e' predicted poor procedural outcomes after pulmonary vein isolation.

Building Sustainability into the Air Force Remediation Process

DTIC Science & Technology

2010-06-16

Phytoremediation Biobarrier  Wrap-up  Future Direction 2 I n t e g r i t y - S e r v i c e - E x c e l l e n c e AF Environmental Restoration...Bioreactor  Phytoremediation  Biobarrier I n t e g r i t y - S e r v i c e - E x c e l l e n c e GSR Demo Site: In situ Bioreactor  Battery acid... Phytoremediation 24 ’ 98 1998 Nov 1999 Nov 2000 Nov 2001 Nov 2002 Nov 2003 Nov 2004 Nov 2005 Nov 2006 Nov 2007 Nov 2008 Nov 2009 Nov ’ 10 Follow-Up

Characterization of Emissions Produced by the Open Burning/Open Detonation of Complex Munitions

DTIC Science & Technology

1996-09-01

Picoline I ,4-Naphthoquinone N-Nitrosomethylethylamnine 1.3 -Dinitrobenzene Methyl methanesulfonate Pentachi orobenzene N-Nitrosodi ethyl amine 1... Chromium Zinc Copper 3.2.6 Particulate Matter Less Than Ten Microns in Diameter (PM10) 3.2.7 Dioxins and Furans The analysis for dioxins and furans...6.24e-04 2.09e-03 Chromium 5.69e-06 4.19e-06 3.2 1e-06 4.36e-06 1.25e-06 -5.06e-06 Copper 1.74e-04 1.03e-04 7.16e-05 1. 16e-04 5.23e-05 1.95e-04 Lead

Searching for new light gauge bosons at e+e- colliders

NASA Astrophysics Data System (ADS)

Alikhanov, I.; Paschos, E. A.

2018-06-01

Neutral gauge bosons beyond the Standard Model are becoming interesting as possible mediators to explain several experimental anomalies. They have small masses, below 1 GeV, and are referred to as dark photons, U , A' or Z' bosons. Electron-positron collision experiments at the B-factories provide the most straightforward way to probe bosons of this kind. In the present article, we study production of the bosons at e+e- colliders operating at GeV center-of-mass energies. We have studied two channels: e+e-→γ Z' and e+e-→e+e-Z'. Analytic expressions for the cross sections and various observables such as the energy spectra of the produced bosons and the final electrons from the Z' decays are derived. We have also studied the transverse momentum distribution of the bosons and the spatial distribution of the Z'→e+e- decay vertices. It is shown that these distributions provide distinct signatures of the bosons in e+e-→γ Z'. The reaction e+e-→e+e-Z' becomes important at small Z' scattering angles where its contribution to the overall yield may be larger by orders of magnitude compared to e+e-→γ Z'. The standard processes e+e-→γ γ and e+e-→e+e-γ that lead to the same signal are considered. We include numerical predictions for the production rates at the energy √{s }=10.5 GeV . The case with a light scalar boson is also discussed. The calculations are performed in detail and can be useful for additional studies.

Observation of ψ(3686)→e^{+}e^{-}χ_{cJ} and χ_{cJ}→e^{+}e^{-}J/ψ.

PubMed

Ablikim, M; Achasov, M N; Ai, X C; Albayrak, O; Albrecht, M; Ambrose, D J; Amoroso, A; An, F F; An, Q; Bai, J Z; Baldini Ferroli, R; Ban, Y; Bennett, D W; Bennett, J V; Bertani, M; Bettoni, D; Bian, J M; Bianchi, F; Boger, E; Boyko, I; Briere, R A; Cai, H; Cai, X; Cakir, O; Calcaterra, A; Cao, G F; Cetin, S A; Chang, J F; Chelkov, G; Chen, G; Chen, H S; Chen, H Y; Chen, J C; Chen, M L; Chen, S; Chen, S J; Chen, X; Chen, X R; Chen, Y B; Cheng, H P; Chu, X K; Cibinetto, G; Dai, H L; Dai, J P; Dbeyssi, A; Dedovich, D; Deng, Z Y; Denig, A; Denysenko, I; Destefanis, M; De Mori, F; Ding, Y; Dong, C; Dong, J; Dong, L Y; Dong, M Y; Dou, Z L; Du, S X; Duan, P F; Fan, J Z; Fang, J; Fang, S S; Fang, X; Fang, Y; Farinelli, R; Fava, L; Fedorov, O; Feldbauer, F; Felici, G; Feng, C Q; Fioravanti, E; Fritsch, M; Fu, C D; Gao, Q; Gao, X L; Gao, X Y; Gao, Y; Gao, Z; Garzia, I; Goetzen, K; Gong, L; Gong, W X; Gradl, W; Greco, M; Gu, M H; Gu, Y T; Guan, Y H; Guo, A Q; Guo, L B; Guo, R P; Guo, Y; Guo, Y P; Haddadi, Z; Hafner, A; Han, S; Hao, X Q; Harris, F A; He, K L; Held, T; Heng, Y K; Hou, Z L; Hu, C; Hu, H M; Hu, J F; Hu, T; Hu, Y; Huang, G S; Huang, J S; Huang, X T; Huang, X Z; Huang, Y; Huang, Z L; Hussain, T; Ji, Q; Ji, Q P; Ji, X B; Ji, X L; Jiang, L W; Jiang, X S; Jiang, X Y; Jiao, J B; Jiao, Z; Jin, D P; Jin, S; Johansson, T; Julin, A; Kalantar-Nayestanaki, N; Kang, X L; Kang, X S; Kavatsyuk, M; Ke, B C; Kiese, P; Kliemt, R; Kloss, B; Kolcu, O B; Kopf, B; Kornicer, M; Kupsc, A; Kühn, W; Lange, J S; Lara, M; Larin, P; Leng, C; Li, C; Li, Cheng; Li, D M; Li, F; Li, F Y; Li, G; Li, H B; Li, H J; Li, J C; Li, Jin; Li, K; Li, K; Li, Lei; Li, P R; Li, Q Y; Li, T; Li, W D; Li, W G; Li, X L; Li, X N; Li, X Q; Li, Y B; Li, Z B; Liang, H; Liang, Y F; Liang, Y T; Liao, G R; Lin, D X; Liu, B; Liu, B J; Liu, C X; Liu, D; Liu, F H; Liu, Fang; Liu, Feng; Liu, H B; Liu, H H; Liu, H H; Liu, H M; Liu, J; Liu, J B; Liu, J P; Liu, J Y; Liu, K; Liu, K Y; Liu, L D; Liu, P L; Liu, Q; Liu, S B; Liu, X; Liu, Y B; Liu, Z A; Liu, Zhiqing; Loehner, H; Lou, X C; Lu, H J; Lu, J G; Lu, Y; Lu, Y P; Luo, C L; Luo, M X; Luo, T; Luo, X L; Lyu, X R; Ma, F C; Ma, H L; Ma, L L; Ma, M M; Ma, Q M; Ma, T; Ma, X N; Ma, X Y; Ma, Y M; Maas, F E; Maggiora, M; Mao, Y J; Mao, Z P; Marcello, S; Messchendorp, J G; Min, J; Mitchell, R E; Mo, X H; Mo, Y J; Morales Morales, C; Muchnoi, N Yu; Muramatsu, H; Nefedov, Y; Nerling, F; Nikolaev, I B; Ning, Z; Nisar, S; Niu, S L; Niu, X Y; Olsen, S L; Ouyang, Q; Pacetti, S; Pan, Y; Patteri, P; Pelizaeus, M; Peng, H P; Peters, K; Pettersson, J; Ping, J L; Ping, R G; Poling, R; Prasad, V; Qi, H R; Qi, M; Qian, S; Qiao, C F; Qin, L Q; Qin, N; Qin, X S; Qin, Z H; Qiu, J F; Rashid, K H; Redmer, C F; Ripka, M; Rong, G; Rosner, Ch; Ruan, X D; Sarantsev, A; Savrié, M; Schoenning, K; Schumann, S; Shan, W; Shao, M; Shen, C P; Shen, P X; Shen, X Y; Sheng, H Y; Shi, M; Song, W M; Song, X Y; Sosio, S; Spataro, S; Sun, G X; Sun, J F; Sun, S S; Sun, X H; Sun, Y J; Sun, Y Z; Sun, Z J; Sun, Z T; Tang, C J; Tang, X; Tapan, I; Thorndike, E H; Tiemens, M; Ullrich, M; Uman, I; Varner, G S; Wang, B; Wang, B L; Wang, D; Wang, D Y; Wang, K; Wang, L L; Wang, L S; Wang, M; Wang, P; Wang, P L; Wang, S G; Wang, W; Wang, W P; Wang, X F; Wang, Y; Wang, Y D; Wang, Y F; Wang, Y Q; Wang, Z; Wang, Z G; Wang, Z H; Wang, Z Y; Wang, Z Y; Weber, T; Wei, D H; Wei, J B; Weidenkaff, P; Wen, S P; Wiedner, U; Wolke, M; Wu, L H; Wu, L J; Wu, Z; Xia, L; Xia, L G; Xia, Y; Xiao, D; Xiao, H; Xiao, Z J; Xie, Y G; Xiu, Q L; Xu, G F; Xu, J J; Xu, L; Xu, Q J; Xu, Q N; Xu, X P; Yan, L; Yan, W B; Yan, W C; Yan, Y H; Yang, H J; Yang, H X; Yang, L; Yang, Y X; Ye, M; Ye, M H; Yin, J H; Yu, B X; Yu, C X; Yu, J S; Yuan, C Z; Yuan, W L; Yuan, Y; Yuncu, A; Zafar, A A; Zallo, A; Zeng, Y; Zeng, Z; Zhang, B X; Zhang, B Y; Zhang, C; Zhang, C C; Zhang, D H; Zhang, H H; Zhang, H Y; Zhang, J; Zhang, J J; Zhang, J L; Zhang, J Q; Zhang, J W; Zhang, J Y; Zhang, J Z; Zhang, K; Zhang, L; Zhang, S Q; Zhang, X Y; Zhang, Y; Zhang, Y H; Zhang, Y N; Zhang, Y T; Zhang, Yu; Zhang, Z H; Zhang, Z P; Zhang, Z Y; Zhao, G; Zhao, J W; Zhao, J Y; Zhao, J Z; Zhao, Lei; Zhao, Ling; Zhao, M G; Zhao, Q; Zhao, Q W; Zhao, S J; Zhao, T C; Zhao, Y B; Zhao, Z G; Zhemchugov, A; Zheng, B; Zheng, J P; Zheng, W J; Zheng, Y H; Zhong, B; Zhou, L; Zhou, X; Zhou, X K; Zhou, X R; Zhou, X Y; Zhu, K; Zhu, K J; Zhu, S; Zhu, S H; Zhu, X L; Zhu, Y C; Zhu, Y S; Zhu, Z A; Zhuang, J; Zotti, L; Zou, B S; Zou, J H

2017-06-02

Using 4.479×10^{8}  ψ(3686) events collected with the BESIII detector, we search for the decays ψ(3686)→e^{+}e^{-}χ_{cJ} and χ_{cJ}→e^{+}e^{-}J/ψ, where J=0, 1, 2. The decays ψ(3686)→e^{+}e^{-}χ_{cJ} and χ_{cJ}→e^{+}e^{-}J/ψ are observed for the first time. The measured branching fractions are B(ψ(3686)→e^{+}e^{-}χ_{cJ})=(11.7±2.5±1.0)×10^{-4}, (8.6±0.3±0.6)×10^{-4}, (6.9±0.5±0.6)×10^{-4} for J=0, 1, 2, and B(χ_{cJ}→e^{+}e^{-}J/ψ)=(1.51±0.30±0.13)×10^{-4}, (3.73±0.09±0.25)×10^{-3}, (2.48±0.08±0.16)×10^{-3} for J=0, 1, 2, respectively. The ratios of the branching fractions B(ψ(3686)→e^{+}e^{-}χ_{cJ})/B(ψ(3686)→γχ_{cJ}) and B(χ_{cJ}→e^{+}e^{-}J/ψ)/B(χ_{cJ}→γJ/ψ) are also reported. Also, the α values of helicity angular distributions of the e^{+}e^{-} pair are determined for ψ(3686)→e^{+}e^{-}χ_{c1,2} and χ_{c1,2}→e^{+}e^{-}J/ψ.

Hybrid Scenario Development Methodology and Tool: An Arctic-Oriented Scenario Example

DTIC Science & Technology

2011-07-01

T E N D S T A T E = S C E N A R I O T R I G G E R P O I N T SECURITY(INC DEFENCE) LEGAL ENVIRONMENTAL...SECURITY(INC DEFENCE) S C E N A R I O D E V E L O P M E N T E N D S T A T E = S C E N A R I O T R I G G E R P O I N T

Proceedings of Advanced Planning Briefing for Industry. Part 1

DTIC Science & Technology

1965-12-01

t h e flow o f in format ion and i d e a s must be both t o you and from you. We thus welcome t h e oppo r tun i t y o f p r e sen t i...megawatt, l i g h t wa te r moderated and c o o l e d , h i g h l y e n r i c h e d uranium , the rmal t y p e t h a t i s c o n s t a n t l y...a l s . Our c u r r e n t programs i n b e r y l l i u m and i n uranium have n o t t h e e x t e n s i v e - n e s s o f t h e e a r l i

Transannular E···E' Interactions in Neutral, Radical Cationic, and Dicationic Forms of cyclo-[E(CH2CH2CH2)2E'] (E, E' = S, Se, Te, and O) with Structural Feature: Dynamic and Static Behavior of E···E' Elucidated by QTAIM Dual Functional Analysis.

PubMed

Hayashi, Satoko; Matsuiwa, Kohei; Nishizawa, Nozomu; Nakanishi, Waro

2015-12-18

The nature of the transannular E-∗-E' interactions in neutral, radical cationic, and dicationic forms of cyclo-E(CH2CH2CH2)2E' (1) (E, E' = S, Se, Te, and O) (1, 1(•+), and 1(2+), respectively) is elucidated by applying QTAIM dual functional analysis (QTAIM-DFA). Hb(rc) are plotted versus Hb(rc) - Vb(rc)/2 for the data of E-∗-E' at BCPs in QTAIM-DFA, where ∗ emphasizes the existence of BCP. Plots for the fully optimized structures are analyzed by the polar coordinate (R, θ) representation. Those containing the perturbed structures are by (θp, κp): θp corresponds to the tangent line of the plot, and κp is the curvature. While (R, θ) describes the static nature, (θp, κp) represents the dynamic nature of interactions. The nature is well-specified by (R, θ) and (θp, κp). E-∗-E' becomes stronger in the order of 1 < 1(•+) < 1(2+), except for O-∗-O. While E-∗-E' (E, E' = S, Se, and Te) in 1(2+) are characterized as weak covalent bonds, except for S-∗-Te (MC nature through CT) and Se-∗-Te (TBP nature through CT), O-∗-E' seems more complex. The behavior of E-∗-E' in 1(2+) is very close to that of cyclo-E(CH2CH2CH2)E' (E, E' = S, Se, Te, and O), except for O-∗-O.

eIF4E and eIF4GI have distinct and differential imprints on multiple myeloma's proteome and signaling

PubMed Central

Attar-Schneider, Oshrat; Pasmanik-Chor, Metsada; Tartakover-Matalon, Shelly

2015-01-01

Accumulating data indicate translation plays a role in cancer biology, particularly its rate limiting stage of initiation. Despite this evolving recognition, the function and importance of specific translation initiation factors is unresolved. The eukaryotic translation initiation complex eIF4F consists of eIF4E and eIF4G at a 1:1 ratio. Although it is expected that they display interdependent functions, several publications suggest independent mechanisms. This study is the first to directly assess the relative contribution of eIF4F components to the expressed cellular proteome, transcription factors, microRNAs, and phenotype in a malignancy known for extensive protein synthesis-multiple myeloma (MM). Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets. Here, we demonstrated that eIF4E/eIF4GI indeed have individual influences on cell proteome. We used an objective, high throughput assay of mRNA microarrays to examine the significance of eIF4E/eIF4GI silencing to several cellular facets such as transcription factors, microRNAs and phenotype. We showed different imprints for eIF4E and eIF4GI in all assayed aspects. These results promote our understanding of the relative contribution and importance of eIF4E and eIF4GI to the malignant phenotype and shed light on their function in eIF4F translation initiation complex. PMID:25717031

E6D25E, HPV16 Asian variant shows specific proteomic pattern correlating in cells transformation and suppressive innate immune response

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

Chopjitt, Peechanika; Pientong, Chamsai; Sunthamala, Nuchsupha

HPV16 Asian variant (HPV16As) containing E6D25E oncogene, is commonly associated with cervical cancers of Asian populations. To explore a mechanism of E6D25E oncoprotein in carcinogenesis, we compared protein profiles in human keratinocytes expressing E6D25E with E6 of HPV16 prototype (E6Pro). A human cervical keratinocyte cell line, HCK1T, was transduced with retroviruses containing E6D25E or E6Pro genes. Biological properties of E6D25E or E6Pro transduced HCK1T cells were characterized. Protein profiles of the transduced HCK1T cells were analyzed using 2D-PAGE and characterized by mass spectrometry and western blotting. Reactomes of modulated proteins were analyzed by using the Reactome Knowledgebase. The E6D25E andmore » E6Pro oncoproteins were comparable for their abilities to degrade p53 and suppress the induction of p21, and induce cell proliferation. Interestingly, the protein profiles of the HCK1T cells transduced with E6D25E showed specific proteomic patterns different from those with E6Pro. Among altered proteins, more than 1.5-fold up- or down- regulation was observed in E6D25E-expressing cells for gp96 and keratin7 which involved in activation of TLR signaling and transformation of squamocolumnar junction cells, respectively. This report describes new cellular proteins specifically targeted by E6D25E oncoprotein that may contribute to impair immune response against viral infection and cell transformation associated with oncogenic property of HPV16As variant. - Highlights: • E6D25E HPV16 specifically modulates protein profile of human keratinocytes. • E6D25E HPV16 modulates protein profile which involves in TLR signalling and transformation of squamocolumnar junction cells. • E6D25E oncoprotein may correlate to impair of immune response against viral infection and cells transformation.« less

10 CFR Appendix A to Part 835 - Derived Air Concentrations (DAC) for Controlling Radiation Exposure to Workers at DOE Facilities

Code of Federal Regulations, 2014 CFR

2014-01-01

.../ET Na-22 2 E−07 - - 1 E+04 - - E// Na-24 4 E−07 - - 1 E+04 - - ET// Mg-28 3 E−07 3 E−07 - 1 E+04 1 E+04 - ET/St/ Al-26 4 E−08 4 E−08 - 1 E+03 1 E+03 - St/St/ Si-31 9 E−06 5 E−06 5 E−06 3 E+05 1 E+05 1 E+05 ET/St/St Si-32 1 E−07 5 E−08 1 E−08 5 E+03 2 E+03 3 E+02 St/St/St P-32 5 E−07 1 E−07 - 1 E+04 7 E...

10 CFR Appendix A to Part 835 - Derived Air Concentrations (DAC) for Controlling Radiation Exposure to Workers at DOE Facilities

Code of Federal Regulations, 2013 CFR

2013-01-01

.../ET Na-22 2 E−07 - - 1 E+04 - - E// Na-24 4 E−07 - - 1 E+04 - - ET// Mg-28 3 E−07 3 E−07 - 1 E+04 1 E+04 - ET/St/ Al-26 4 E−08 4 E−08 - 1 E+03 1 E+03 - St/St/ Si-31 9 E−06 5 E−06 5 E−06 3 E+05 1 E+05 1 E+05 ET/St/St Si-32 1 E−07 5 E−08 1 E−08 5 E+03 2 E+03 3 E+02 St/St/St P-32 5 E−07 1 E−07 - 1 E+04 7 E...

10 CFR Appendix A to Part 835 - Derived Air Concentrations (DAC) for Controlling Radiation Exposure to Workers at DOE Facilities

Code of Federal Regulations, 2012 CFR

2012-01-01

.../ET Na-22 2 E−07 - - 1 E+04 - - E// Na-24 4 E−07 - - 1 E+04 - - ET// Mg-28 3 E−07 3 E−07 - 1 E+04 1 E+04 - ET/St/ Al-26 4 E−08 4 E−08 - 1 E+03 1 E+03 - St/St/ Si-31 9 E−06 5 E−06 5 E−06 3 E+05 1 E+05 1 E+05 ET/St/St Si-32 1 E−07 5 E−08 1 E−08 5 E+03 2 E+03 3 E+02 St/St/St P-32 5 E−07 1 E−07 - 1 E+04 7 E...

Adsorption-induced auto-amplification of enantiomeric excess on an achiral surface

NASA Astrophysics Data System (ADS)

Yun, Yongju; Gellman, Andrew J.

2015-06-01

The homochirality of biomolecules is a signature of life on Earth and has significant implications in, for example, the production of pharmaceutical compounds. It has been suggested that biomolecular homochirality may have arisen from the amplification of a spontaneously formed small enantiomeric excess (e.e.). Many minerals exhibit naturally chiral surfaces and so adsorption has been proposed as one possible mechanism for such an amplification of e.e. Here we show that when gas-phase mixtures of D- and L-aspartic acid are exposed to an achiral Cu(111) surface, a small e.e. in the gas phase, e.e.g, leads to an amplification of the e.e. on the surface, e.e.s, under equilibrium conditions. Adsorption-induced amplification of e.e. does not require a chiral surface. The dependence of e.e.s on e.e.g has been modelled successfully using a Langmuir-like adsorption isotherm that incorporates the formation of homochiral adsorbate clusters on the surface.

Phylogenetic analysis of eIF4E-family members

PubMed Central

Joshi, Bhavesh; Lee, Kibwe; Maeder, Dennis L; Jagus, Rosemary

2005-01-01

Background Translation initiation in eukaryotes involves the recruitment of mRNA to the ribosome which is controlled by the translation factor eIF4E. eIF4E binds to the 5'-m7Gppp cap-structure of mRNA. Three dimensional structures of eIF4Es bound to cap-analogues resemble 'cupped-hands' in which the cap-structure is sandwiched between two conserved Trp residues (Trp-56 and Trp-102 of H. sapiens eIF4E). A third conserved Trp residue (Trp-166 of H. sapiens eIF4E) recognizes the 7-methyl moiety of the cap-structure. Assessment of GenBank NR and dbEST databases reveals that many organisms encode a number of proteins with homology to eIF4E. Little is understood about the relationships of these structurally related proteins to each other. Results By combining sequence data deposited in the Genbank databases, we have identified sequences encoding 411 eIF4E-family members from 230 species. These sequences have been deposited into an internet-accessible database designed for sequence comparisons of eIF4E-family members. Most members can be grouped into one of three classes. Class I members carry Trp residues equivalent to Trp-43 and Trp-56 of H. sapiens eIF4E and appear to be present in all eukaryotes. Class II members, possess Trp→Tyr/Phe/Leu and Trp→Tyr/Phe substitutions relative to Trp-43 and Trp-56 of H. sapiens eIF4E, and can be identified in Metazoa, Viridiplantae, and Fungi. Class III members possess a Trp residue equivalent to Trp-43 of H. sapiens eIF4E but carry a Trp→Cys/Tyr substitution relative to Trp-56 of H. sapiens eIF4E, and can be identified in Coelomata and Cnidaria. Some eIF4E-family members from Protista show extension or compaction relative to prototypical eIF4E-family members. Conclusion The expansion of sequenced cDNAs and genomic DNAs from all eukaryotic kingdoms has revealed a variety of proteins related in structure to eIF4E. Evolutionarily it seems that a single early eIF4E gene has undergone multiple gene duplications generating multiple structural classes, such that it is no longer possible to predict function from the primary amino acid sequence of an eIF4E-family member. The variety of eIF4E-family members provides a source of alternatives on the eIF4E structural theme that will benefit structure/function analyses and therapeutic drug design. PMID:16191198

Analysis of eIF4E and 4EBP1 mRNAs in head and neck cancer.

PubMed

Sunavala-Dossabhoy, Gulshan; Palaniyandi, Senthilnathan; Clark, Cheryl; Nathan, Cherie-Ann O; Abreo, Fleurette W; Caldito, Gloria

2011-10-01

The eukaryotic translation initiation factor 4E (eIF4E) in conjunction with its binding protein, 4EBP1, regulates the translation of cap-dependent mRNAs. An aberrant increase in eIF4E shifts the balance in favor of translation of transcripts that promote cell proliferation and malignancy. eIF4E protein is commonly elevated in head and neck squamous cell carcinomas (HNSCC), and its overexpression is associated with increased recurrence. An underlying mechanism for eIF4E overexpression is gene amplification, and we wanted to determine whether eIF4E mRNA could serve as a prognostic maker of HNSCC. Tumor specimens from 26 HNSCC patients and oral tissues from 17 control subjects were examined for eIF4E and 4EBP1 by semiquantitative RT-PCR and correlated with clinical and pathologic findings. Unlike eIF4E mRNA alone, expression of eIF4E relative to 4EBP1 was a more precise predictor of HNSCC and its progression (P < .01, Wilcoxon rank sum test). Eight of 26 patients (31%) had elevated eIF4E:4EBP1 (4E:4EBP1; >25), and 7 of these (87.5%) had recurrence. Alternately, from 18 patients with low 4E:4EBP1 (<25; 69%), only 5 patients had recurrence (30.1%). To determine the probability of no recurrence, Kaplan-Meier analysis showed significantly poor disease-free survival in patients with elevated 4E:4EBP1 than those with low ratios (P < .01, log rank test). Elevated 4E:4EBP1 significantly correlated with increased disease recurrence. Because 4EBP1 modulates eIF4E activity, our results highlight the importance of incorporating a joint analysis of eIF4E and 4EBP1 mRNAs in HNSCC patient care decisions. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

DNA Electrical Overstress - Hardness Assurance Data Volume.

DTIC Science & Technology

1980-07-28

boundaries due to its somewhat polysilicon nature. The grain boundaries and surface states increase the resistance measured for a particular structure and...1.3e0e0IE+ .go 9. 4Li,.4fE+43 1 . 𔃻L0 E - ,I E -. L , * I’ LI0O IVIE-.L"-’ j . OL )0 E It .=.. flOO ’II I . 00LIL-EI00 51 .I0.’LE*.1 I.04h.IC E’".L141...8217 .Ti0E+ :.’ 1 " aOE.C𔃻 0.00000 0 0 E ,. . Ol J.AE*0 - ?.,E-0 5 -1-6100000E-0j .- o Ei1 a.. 000e0E-00a .. ,C v3E-; Q ._*, - -4E-0N 1 4 .000E001 1.1 0aOE+OI

Measurement of initial-state–final-state radiation interference in the processes e + e – → μ + μ – γ and e + e – → π + π – γ [Measurement of ISR-FSR interference in the processes e + e – → μ + μ – γ and e + e – → π + π – γ

DOE PAGES

Lees, J. P.; Poireau, V.; Tisserand, V.; ...

2015-10-28

Charge asymmetry in the processes e +e – → μ +μ –γ and e +e – → π +π –γ is measured using 232 fb –1 of data collected with the BABAR detector at e +e – center-of-mass energies near 10.58 GeV. An observable is introduced and shown to be very robust against detector asymmetries while keeping a large sensitivity to the physical charge asymmetry that results from the interference between initial- and final-state radiation (FSR). The asymmetry is determined as a function of the invariant mass of the final-state tracks from production threshold to a few GeV/c 2. Itmore » is compared to the expectation from QED for e +e – → μ +μ –γ, and from theoretical models for e +e – → π +π –γ. A clear interference pattern is observed in e +e – → π +π –γ, particularly in the vicinity of the f 2(1270) resonance. As a result, the inferred rate of lowest-order FSR production is consistent with the QED expectation for e +e – → μ +μ –γ, and is negligibly small for e +e – → π +π –γ.« less

Measurement of initial-state–final-state radiation interference in the processes e + e – → μ + μ – γ and e + e – → π + π – γ [Measurement of ISR-FSR interference in the processes e + e – → μ + μ – γ and e + e – → π + π – γ

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

Lees, J. P.; Poireau, V.; Tisserand, V.

Charge asymmetry in the processes e +e – → μ +μ –γ and e +e – → π +π –γ is measured using 232 fb –1 of data collected with the BABAR detector at e +e – center-of-mass energies near 10.58 GeV. An observable is introduced and shown to be very robust against detector asymmetries while keeping a large sensitivity to the physical charge asymmetry that results from the interference between initial- and final-state radiation (FSR). The asymmetry is determined as a function of the invariant mass of the final-state tracks from production threshold to a few GeV/c 2. Itmore » is compared to the expectation from QED for e +e – → μ +μ –γ, and from theoretical models for e +e – → π +π –γ. A clear interference pattern is observed in e +e – → π +π –γ, particularly in the vicinity of the f 2(1270) resonance. As a result, the inferred rate of lowest-order FSR production is consistent with the QED expectation for e +e – → μ +μ –γ, and is negligibly small for e +e – → π +π –γ.« less

Co-infection of chickens with Eimeria praecox and Eimeria maxima does not prevent development of immunity to Eimeria maxima.

PubMed

Jenkins, M; Fetterer, R; Miska, K

2009-05-12

Previous studies revealed an ameliorating effect of Eimeria praecox on concurrent E. maxima infection, such that weight gain, feed conversion ratio, and intestinal lesions were nearly identical to uninfected or E. praecox-infected controls. The purpose of the present study was to determine if protective immunity against E. maxima challenge infection developed in chickens infected with both E. praecox and E. maxima. Day-old chickens were infected with 10(3)E. praecox, 10(3)E. maxima, or a mixture of 10(3)E. praecox and 10(3)E. maxima oocysts. Chickens were then challenged at 4 weeks of age with 5x10(4)E. praecox or 5x10(3)E. maxima oocysts and clinical signs of coccidiosis were assessed 7 days post-challenge. Relative to non-challenged controls, naïve chickens or chickens immunized with E. praecox displayed a 32-34% weight gain depression after challenge with 5x10(3)E. maxima oocysts. In contrast, chickens immunized with either E. maxima oocysts alone or a combination of E. praecox and E. maxima oocysts displayed complete protection against lower weight gain associated with E. maxima challenge. Also, protection against decreased feed conversion ratio and intestinal lesions was observed in single E. maxima- or dual E. maxima+E. praecox-immunized chickens. These findings indicate that co-infection of chickens with E. maxima and E. praecox does not prevent development of immunity against E. maxima or E. praecox challenge.

MATREX Simulation Architecture

DTIC Science & Technology

2008-03-10

r e S u p p o r t M i n e s , C o u n t e r m i n e s U n m a n n e d S y s t e m s L o g...i s t i c s N e t w o r k e d E f f e c t s C o m m a n d & C o n t r o l C o n s i s t e n t & H i g h - R e s M i s s i l e M o d e...l i n g C o n s i s t

Decreased eIF3e/Int6 expression causes epithelial-to-mesenchymal transition in breast epithelial cells.

PubMed

Gillis, L D; Lewis, S M

2013-08-01

eIF3e/Int6 is a component of the multi-subunit eIF3 complex, which binds directly to the 40S ribosome to facilitate ribosome recruitment to mRNA and hence protein synthesis. Reduced expression of eIF3e/Int6 has been found in up to 37% of human breast cancers, and expression of a truncated mutant version of the mouse eIF3e/Int6 protein leads to malignant transformation of normal mammary cells. These findings suggest that eIF3e/Int6 is a tumor suppressor; however, a recent study has reported that a reduction of eIF3e/Int6 expression in breast cancer cells leads to reduced translation of oncogenes, suggesting that eIF3e/Int6 may in fact have an oncogenic role in breast cancer. To gain a better understanding of the role of eIF3e/Int6 in breast cancer, we have examined the effects of decreased eIF3e/Int6 expression in an immortalized breast epithelial cell line, MCF-10A. Surprisingly, we find that decreased expression of eIF3e/Int6 causes breast epithelial cells to undergo epithelial-to-mesenchymal transition (EMT). We show that EMT induced by a decrease in eIF3e/Int6 expression imparts invasive and migratory properties to breast epithelial cells, suggesting that regulation of EMT by eIF3e/Int6 may have an important role in breast cancer metastasis. Furthermore, we show that reduced eIF3e/Int6 expression in breast epithelial cells causes a specific increase in the expression of the key EMT regulators Snail1 and Zeb2, which occurs at both the transcriptional and post-transcriptional levels. Together, our data indicate a novel role of eIF3e/Int6 in the regulation of EMT in breast epithelial cells and support a tumor suppressor role of eIF3e/Int6.

Toward the mechanism of eIF4F-mediated ribosomal attachment to mammalian capped mRNAs.

PubMed

Kumar, Parimal; Hellen, Christopher U T; Pestova, Tatyana V

2016-07-01

Ribosomal attachment to mammalian capped mRNAs is achieved through the cap-eukaryotic initiation factor 4E (eIF4E)-eIF4G-eIF3-40S chain of interactions, but the mechanism by which mRNA enters the mRNA-binding channel of the 40S subunit remains unknown. To investigate this process, we recapitulated initiation on capped mRNAs in vitro using a reconstituted translation system. Formation of initiation complexes at 5'-terminal AUGs was stimulated by the eIF4E-cap interaction and followed "the first AUG" rule, indicating that it did not occur by backward scanning. Initiation complexes formed even at the very 5' end of mRNA, implying that Met-tRNAi (Met) inspects mRNA from the first nucleotide and that initiation does not have a "blind spot." In assembled initiation complexes, the cap was no longer associated with eIF4E. Omission of eIF4A or disruption of eIF4E-eIF4G-eIF3 interactions converted eIF4E into a specific inhibitor of initiation on capped mRNAs. Taken together, these results are consistent with the model in which eIF4E-eIF4G-eIF3-40S interactions place eIF4E at the leading edge of the 40S subunit, and mRNA is threaded into the mRNA-binding channel such that Met-tRNAi (Met) can inspect it from the first nucleotide. Before entering, eIF4E likely dissociates from the cap to overcome steric hindrance. We also found that the m(7)G cap specifically interacts with eIF3l. © 2016 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

IgE-associated food allergy alters the presentation of paediatric eosinophilic esophagitis.

PubMed

Pelz, B J; Wechsler, J B; Amsden, K; Johnson, K; Singh, A M; Wershil, B K; Kagalwalla, A F; Bryce, P J

2016-11-01

Links between food allergens and eosinophilic esophagitis (EoE) have been established, but the interplay between EoE- and IgE-associated immediate hypersensitivity to foods remains unclear. We sought to determine the prevalence of IgE-associated food allergy at the time of diagnosis of EoE in children and to determine whether differences existed in presentation and disease compared to subjects with EoE alone. Eosinophilic esophagitis patients were stratified based on the diagnosis of IgE-associated immediate hypersensitivity (EoE + IH vs. EoE-IH). Clinical, histologic, pathologic, and endoscopic differences were investigated using a retrospective database. We found that 29% of the 198 EoE patients in our cohort had EoE + IH. These subjects presented at a younger age than those without IH (6.05 vs. 8.09 years, P = 0.013) and were more likely to have comorbid allergic disease. Surprisingly, the EoE + IH group presented with significantly different clinical symptoms, with increased dysphagia, gagging, cough, and poor appetite compared to their counterparts in the EoE-IH group. Male gender, allergic rhinitis, the presence of dysphagia, and younger age were independently associated with having EoE + IH. Specific IgE levels to common EoE-associated foods were higher in EoE + IH, regardless of eliciting immediate hypersensitivity symptoms. In contrast, IgE levels for specific foods triggering EoE were relatively lower in both the groups than IgE levels for immediate reactions. Immediate hypersensitivity is common in children with EoE and identifies a population of EoE patients with distinct clinical characteristics. Our study describes a subtype of EoE in which IgE-mediated food allergy may impact the presentation of paediatric EoE. © 2016 John Wiley & Sons Ltd.

E-Cigarette Marketing and Communication: How E-Cigarette Companies Market E-Cigarettes and the Public Engages with E-cigarette Information.

PubMed

Collins, Lauren; Glasser, Allison M; Abudayyeh, Haneen; Pearson, Jennifer L; Villanti, Andrea C

2018-01-05

Given the lack of regulation on marketing of electronic cigarettes (e-cigarettes) in the U.S. and the increasing exchange of e-cigarette-related information online, it is critical to understand how e-cigarette companies market e-cigarettes and how the public engages with e-cigarette information. Results are from a systematic review of peer-reviewed literature on e-cigarettes via a PubMed search through June 1, 2017. Search terms included: "e-cigarette*" OR "electronic cigarette" OR "electronic cigarettes" OR "electronic nicotine delivery" OR "vape" OR "vaping." Experimental studies, quasi-experimental studies, observational studies, qualitative studies, and mixed methods studies providing empirical findings on e-cigarette marketing and communication (i.e., non-marketing communication in the public) were included. One hundred twenty-four publications on e-cigarette marketing and communication were identified. They covered topics including e-cigarette advertisement claims/promotions and exposure/receptivity, the effect of e-cigarette advertisements on e-cigarette and cigarette use, public engagement with e-cigarette information, and the public's portrayal of e-cigarettes. Studies show increases in e-cigarette marketing expenditures and online engagement through social media over time, that e-cigarettes are often framed as an alternative to combustible cigarettes, and that e-cigarette advertisement exposure may be associated with e-cigarette trial in adolescents and young adults. Few studies examine the effects of e-cigarette marketing on perceptions and e-cigarette and cigarette use. Evidence suggests that exposure to e-cigarette advertisements affects perceptions and trial of e-cigarettes, but there is no evidence that exposure affects cigarette use. No studies examined how exposure to e-cigarette communication, particularly misleading or inaccurate information, impacts e-cigarette and tobacco use behaviors. The present article provides a comprehensive review of e-cigarette marketing and how the public engages with e-cigarette information. Studies suggest an association between exposure to e-cigarette marketing and lower harm perceptions of e-cigarettes, intention to use e-cigarettes, and e-cigarette trial, highlighting the need to for advertising regulations that support public health goals. Findings from this review also present the methodological limitations of the existing research (primarily due to cross-sectional and correlational analyses) and underscore the need for timely, rigorous research to provide an accurate understanding of e-cigarette marketing and communication and its impact on e-cigarette and tobacco product use. © The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Systems Engineering Measurement Primer

DTIC Science & Technology

1998-03-01

Schermerhorn , R ., “Determining metrics for...maintenance process. 12 S e l e c t a n d S p e c i f y M e a s u r e s a n d I n d i c a t o r s C o l l e c t D a t a C a l c u l a t e I n d i c a...t o r s A n a l y z e t h e M e a s u r e s o r I n d i c a t o r s R e p o r t a n d U s e t h e R e s u l t s Issues Goals Risks A

The eIF4E-binding proteins are modifiers of cytoplasmic eIF4E relocalization during the heat shock response.

PubMed

Sukarieh, R; Sonenberg, N; Pelletier, J

2009-05-01

Stress granules (SGs) arise as a consequence of cellular stress, contain stalled translation preinitiation complexes, and are associated with cell survival during environmental insults. SGs are dynamic entities with proteins relocating into and out of them during stress. Among the repertoire of proteins present in SGs is eukaryotic initiation factor 4E (eIF4E), a translation factor required for cap-dependent translation and that regulates a rate-limiting step for protein synthesis. Herein, we demonstrate that localization of eIF4E to SGs is dependent on the presence of a family of repressor proteins, eIF4E-binding proteins (4E-BPs). Our results demonstrate that 4E-BPs regulate the SG localization of eIF4E.

The 'A' genome donor of Eleusine coracana (L.) Gaertn. (Gramineae).

PubMed

Hiremath, S C; Salimath, S S

1992-08-01

In an attempt to discover 'A' and 'B' genome donor(s) to finger millet, Eleusine coracana, or its progenitor species, E. africana (both allotetraploid 2n=4x=36), five diploid species, E. Indica, E. Floccifolia, E. multiflora, E. tristachya and E. intermedia, were crossed to finger millet and its progenitor taxon. Crosses were successful only with E. coracana. Three combinations of triploid hybrids E. coracana x E. indica, E. coracana x E. floccifolia, and E. coracana x E. multiflora were obtained and analysed. Meiotic behaviour was perfectly normal in parental species. The regular number of 18 bivalents in E. coracana, 9 bivalents in E. indica, E. intermedia, E. tristachya and E. floccifolia and 8 bivalents in E. multiflora were invariably noticed. In E. coracana x E. indica hybrids a mean chromosome pairing of 8.84I+8.80II+0.03III+0.10IV per cell was found. About 86.5% of the cells showed the typical 9I+9II configuration, suggesting that E. indica (AA) is one of the diploid genome donors to cultivated species E. coracana. A mean chromosome pairing of 11.08I+7.63II+0.16III+0.04IV per cell was found in E. coracana x E. floccifolia hybrids. Two to ten bivalents and varying numbers of univalents were seen in 55% of the cells. About 45% of the cells showed the 9I+9II configuration. Various evidence suggests that perennial E. floccifolia is a primitive member of the 'A' genome group of Eleusine species, and it may not be a genome donor to E. coracana. In E. coracana x E. multiflora hybrids (2n=26) mean chromosome pairing of 21.45I+1.97II+0.13III+0.04IV per cell was found. About 91% of the cells were observed to have 20-26 univalents. Only a small percentage of the cells contained bivalents or multivalents. This pairing behaviour indicates that E. multiflora lacks genomic homology with the 'A' or 'B' genome of E. coracana. Genomically E. multiflora is a distinct species and a genomic symbol of 'C' is assigned to it. Identification of the 'B' genome donor species to cultivated millet. E. coracana remains elusive.

Search for the decay KL to pi0 e+ e- and study of the decay KL to e+ e- gamma gamma

NASA Astrophysics Data System (ADS)

Mikelsons, Peter L.

The particle decay KL-->p0e+e- is a probe of direct CP violation, a phenomenon previously only seen in KL-->pp decays. Understanding direct CP violation is an important part of understanding violation of CP symmetry in general. Experimentally, one of the obstacles to studying KL-->p0e+e- is the rare decay KL-->e+e- gg , which can mimic KL-->p0e+e- . A study of KL-->p0e+e- and KL-->e+e- gg was made as part of the KTeV E799 experiment. K-->p0p0Dalitz decays were used for normalization, and a KL flux of (2.65 +/- 0.18) × 1011 decays was measured. We observed 1578 KL-->e+e- gg candidate events, of which 1516.5 +/- 1.8 remain after background subtraction. These events allow measurement of the Bergström, Massó, and Singer KLgg vertex form- factor parameter, aK*=+0.015+/- 0.12stat.+/-0.03sys. , in mild disagreement with the previously fit value of -0.28 +/- 0.08. This form-factor implies a corresponding branching ratio of G(KL-->e+e- g g,E*g>5 MeV)/G(KL-->all ) = (5.82+/-0.15stat.+/-0.31 sys.+/-0.19BR)× 10-7 , in agreement with the QED prediction. The search for KL-->p0e+e- found two candidate events. However, 1.06 +/- 0.41 events were expected from background processes. Therefore, we do not claim observation of KL-->p0e+e- . Instead, with a single-event sensitivity of 1.00 × 10 -10, we set an upper limit on the KL-->p0e+e- branching ratio of 4.86 × 10-10 at the 90% confidence level.

Conformational changes induced in the eukaryotic translation initiation factor eIF4E by a clinically relevant inhibitor, ribavirin triphosphate

PubMed Central

Volpon, Laurent; Osborne, Michael J.; Zahreddine, Hiba; Romeo, Andrea A.; Borden, Katherine L.B.

2013-01-01

The eukaryotic translation initiation factor eIF4E is highly elevated in human cancers including acute myeloid leukemia (AML). A potential anticancer agent, ribavirin, targets eIF4E activity in AML patients corresponding to clinical responses. To date, ribavirin is the only direct inhibitor of eIF4E to reach clinical trials. We showed that ribavirin acts as a competitive inhibitor of the methyl 7-guanosine (m7G) cap, the natural ligand of eIF4E. Here we examine the conformational changes occurring in human eIF4E upon binding the active metabolite of ribavirin, ribavirin triphosphate (RTP). Our NMR data revealed an unexpected concentration dependence on RTP affinity for eIF4E. We observed NMR spectra characteristic of tight binding at low micromolar concentrations (2-5μM eIF4E) but much weaker affinity at more typical NMR concentrations (50-200μM). Comparison of chemical shift perturbation and line broadening suggest that the two eIF4E-RTP complexes differ in the precise positioning of RTP within the cap binding pocket, with the high affinity complex showing more extensive changes to the central β-sheet and dorsal surface of eIF4E, similar to m7G cap. The differences between high and low affinity complexes arise due to concentration dependent aggregation of eIF4E and RTP. Given the intracellular concentrations of eIF4E and RTP and the differential binding toward the W56A eIF4E mutant the high affinity complex is the most physiologically relevant. In summary, these findings demonstrate that RTP binds in the cap-binding site but also suggests new features of this pocket that should be considered in both drug design efforts and reveal new insights into ligand eIF4E recognition. PMID:23583375

Insight to the Interaction of the Dihydrolipoamide Acetyltransferase (E2) Core with the Peripheral Components in the Escherichia coli Pyruvate Dehydrogenase Complex via Multifaceted Structural Approaches*

PubMed Central

Chandrasekhar, Krishnamoorthy; Wang, Junjie; Arjunan, Palaniappa; Sax, Martin; Park, Yun-Hee; Nemeria, Natalia S.; Kumaran, Sowmini; Song, Jaeyoung; Jordan, Frank; Furey, William

2013-01-01

Multifaceted structural approaches were undertaken to investigate interaction of the E2 component with E3 and E1 components from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), as a representative of the PDHc from Gram-negative bacteria. The crystal structure of E3 at 2.5 Å resolution reveals similarity to other E3 structures and was an important starting point for understanding interaction surfaces between E3 and E2. Biochemical studies revealed that R129E-E2 and R150E-E2 substitutions in the peripheral subunit-binding domain (PSBD) of E2 greatly diminished PDHc activity, affected interactions with E3 and E1 components, and affected reductive acetylation of E2. Because crystal structures are unavailable for any complete E2-containing complexes, peptide-specific hydrogen/deuterium exchange mass spectrometry was used to identify loci of interactions between 3-lipoyl E2 and E3. Two peptides from the PSBD, including Arg-129, and three peptides from E3 displayed statistically significant reductions in deuterium uptake resulting from interaction between E3 and E2. Of the peptides identified on E3, two were from the catalytic site, and the third was from the interface domain, which for all known E3 structures is believed to interact with the PSBD. NMR clearly demonstrates that there is no change in the lipoyl domain structure on complexation with E3. This is the first instance where the entire wild-type E2 component was employed to understand interactions with E3. A model for PSBD-E3 binding was independently constructed and found to be consistent with the importance of Arg-129, as well as revealing other electrostatic interactions likely stabilizing this complex. PMID:23580650

Insight to the interaction of the dihydrolipoamide acetyltransferase (E2) core with the peripheral components in the Escherichia coli pyruvate dehydrogenase complex via multifaceted structural approaches.

PubMed

Chandrasekhar, Krishnamoorthy; Wang, Junjie; Arjunan, Palaniappa; Sax, Martin; Park, Yun-Hee; Nemeria, Natalia S; Kumaran, Sowmini; Song, Jaeyoung; Jordan, Frank; Furey, William

2013-05-24

Multifaceted structural approaches were undertaken to investigate interaction of the E2 component with E3 and E1 components from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), as a representative of the PDHc from Gram-negative bacteria. The crystal structure of E3 at 2.5 Å resolution reveals similarity to other E3 structures and was an important starting point for understanding interaction surfaces between E3 and E2. Biochemical studies revealed that R129E-E2 and R150E-E2 substitutions in the peripheral subunit-binding domain (PSBD) of E2 greatly diminished PDHc activity, affected interactions with E3 and E1 components, and affected reductive acetylation of E2. Because crystal structures are unavailable for any complete E2-containing complexes, peptide-specific hydrogen/deuterium exchange mass spectrometry was used to identify loci of interactions between 3-lipoyl E2 and E3. Two peptides from the PSBD, including Arg-129, and three peptides from E3 displayed statistically significant reductions in deuterium uptake resulting from interaction between E3 and E2. Of the peptides identified on E3, two were from the catalytic site, and the third was from the interface domain, which for all known E3 structures is believed to interact with the PSBD. NMR clearly demonstrates that there is no change in the lipoyl domain structure on complexation with E3. This is the first instance where the entire wild-type E2 component was employed to understand interactions with E3. A model for PSBD-E3 binding was independently constructed and found to be consistent with the importance of Arg-129, as well as revealing other electrostatic interactions likely stabilizing this complex.

The Eukaryotic Translation Initiation Factor 4E Controls Lettuce Susceptibility to the Potyvirus Lettuce mosaic virus1

PubMed Central

Nicaise, Valérie; German-Retana, Sylvie; Sanjuán, Raquel; Dubrana, Marie-Pierre; Mazier, Marianne; Maisonneuve, Brigitte; Candresse, Thierry; Caranta, Carole; LeGall, Olivier

2003-01-01

The eIF4E and eIF(iso)4E cDNAs from several genotypes of lettuce (Lactuca sativa) that are susceptible, tolerant, or resistant to infection by Lettuce mosaic virus (LMV; genus Potyvirus) were cloned and sequenced. Although Ls-eIF(iso)4E was monomorphic in sequence, three types of Ls-eIF4E differed by point sequence variations, and a short in-frame deletion in one of them. The amino acid variations specific to Ls-eIF4E1 and Ls-eIF4E2 were predicted to be located near the cap recognition pocket in a homology-based tridimensional protein model. In 19 lettuce genotypes, including two near-isogenic pairs, there was a strict correlation between these three allelic types and the presence or absence of the recessive LMV resistance genes mo11 and mo12. Ls-eIF4E1 and mo11 cosegregated in the progeny of two separate crosses between susceptible genotypes and an mo11 genotype. Finally, transient ectopic expression of Ls-eIF4E restored systemic accumulation of a green fluorescent protein-tagged LMV in LMV-resistant mo12 plants and a recombinant LMV expressing Ls-eIF4E° from its genome, but not Ls-eIF4E1 or Ls-eIF(iso)4E, accumulated and produced symptoms in mo11 or mo12 genotypes. Therefore, sequence correlation, tight genetic linkage, and functional complementation strongly suggest that eIF4E plays a role in the LMV cycle in lettuce and that mo11 and mo12 are alleles coding for forms of eIF4E unable or less effective to fulfill this role. More generally, the isoforms of eIF4E appear to be host factors involved in the cycle of potyviruses in plants, probably through a general mechanism yet to be clarified. PMID:12857809

Substitution of specific cysteine residues in E1 glycoprotein of classical swine fever virus strain Brescia affects formation of E1-E2 heterodimers and alters virulence in swine

USDA-ARS?s Scientific Manuscript database

E1, along with E^rns and E2, is one of the three envelope glycoproteins of Classical Swine Fever Virus (CSFV). E1 and E2 are anchored to the virus envelope at their carboxyl termini and E^rns loosely associates with the viral envelope. In infected cells, E2 forms homodimers and heterodimers with E1,...

40 CFR Appendix E to Part 61 - Compliance Procedures Methods for Determining Compliance With Subpart I

Code of Federal Regulations, 2010 CFR

2010-07-01

....1E+00 1.1E+03 1.1E+06 Ni-56 2.0E−03 2.0E+00 2.0E+03 Ni-57 2.1E−02 2.1E+01 2.1E+04 Ni-59 2.2E−02 2.2E+01 2.2E+04 Ni-63 1.4E−01 1.4E+02 1.4E+05 Ni-65 7.0E−01 7.0E+02 7.0E+05 Np-235 3.0E−02 3.0E+01 3.0E+04...-147 7.7E−12 In-117m 9.1E−11 Nd-149 7.1E−10 Ir-190 2.6E−12 Ni-56 1.7E−12 Ir-192 9.1E−13 Ni-57 1.8E−11...

40 CFR Appendix E to Part 61 - Compliance Procedures Methods for Determining Compliance With Subpart I

Code of Federal Regulations, 2011 CFR

2011-07-01

....1E+00 1.1E+03 1.1E+06 Ni-56 2.0E−03 2.0E+00 2.0E+03 Ni-57 2.1E−02 2.1E+01 2.1E+04 Ni-59 2.2E−02 2.2E+01 2.2E+04 Ni-63 1.4E−01 1.4E+02 1.4E+05 Ni-65 7.0E−01 7.0E+02 7.0E+05 Np-235 3.0E−02 3.0E+01 3.0E+04...-147 7.7E−12 In-117m 9.1E−11 Nd-149 7.1E−10 Ir-190 2.6E−12 Ni-56 1.7E−12 Ir-192 9.1E−13 Ni-57 1.8E−11...

Radiative Correction to e+e-to e+e- in the Electroweak Theory. I --Cross Sections for Hard Photon Emission--

NASA Astrophysics Data System (ADS)

Tobimatsu, K.; Shimizu, Y.

1985-09-01

Various cross sections for radiative Bhabha scattering, e+e-to e+e-γ, are calculated in the standard electroweak theory. They contain distributions on photon energy dσ/dk, acollinearity angle dσ/dzeta, acoplanarity angle dσ/dψ, photon transverse momentum dσ/dkT and invariant mass of final e-γ system dσ/dMeγ. In the calculation some realistic experimental cuts are imposed on the configuration of final particles and the energies are chosen to be 70, 93 and 150 GeV in accordance with TRISTAN, SLC and LEP. From the results we can see the effect of Z0-boson exchanged in the s- and t-channel and estimate backgrounds to such interesting processes as e+e-toνbar{ν}γ, tilde{γ}tilde{γ}γ and e+e-to e*eto e+e-γ.

Correlating Temporal Rules to Time-Series Data With Rule-Based Intuition

DTIC Science & Technology

2010-03-01

t i m e o b j e c t and r e t u r n s True ( i n r u l e ) or F a l s e ( n o t i n r u l e ) . Des ign : r u l e l i s t − an a r r a y t h...e . d a t e o b j e c t s . ””” def i n i t ( s e l f , name , days , i g n o r e y e a r =True ) : s e l f . name = name s e l f . days = days 49 s...a l . tm wday == 6 r u l e l i s t . append ( Sunday ( ) ) c l a s s J a n u a r y ( TimeRule ) : ””” I s True i f i t i s January

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

Sominsky, Sophia, E-mail: sophia.tab@gmail.com; Kuslansky, Yael, E-mail: ykuslansky@gmail.com; Shapiro, Beny, E-mail: benyshap@gmail.com

The present study investigated the roles of E6 and E6AP in the Wnt pathway. We showed that E6 levels are markedly reduced in cells in which Wnt signaling is activated. Coexpression of wild-type or mutant E6AP (C820A) in Wnt-activated cells stabilized E6 and enhanced Wnt/β-catenin/TCF transcription. Expression of E6AP alone in nonstimulated cells elevated β-catenin level, promoted its nuclear accumulation, and activated β-catenin/TCF transcription. A knockdown of E6AP lowered β-catenin levels. Coexpression with E6 intensified the activities of E6AP. Further experiments proved that E6AP/E6 stabilize β-catenin by protecting it from proteasomal degradation. This function was dependent on the catalytic activitymore » of E6AP, the kinase activity of GSK3β and the susceptibility of β-catenin to GSK3β phosphorylation. Thus, this study identified E6AP as a novel regulator of the Wnt signaling pathway, capable of cooperating with E6 in stimulating or augmenting Wnt/β-catenin signaling, thereby possibly contributing to HPV carcinogenesis. - Highlights: • The roles of E6 and E6AP in the Wnt pathway were investigated. • E6AP stabilizes E6 and enhances E6 activity in augmentation of Wnt signaling. • E6AP cooperates with E6 to stabilize β-catenin and stimulate Wnt/β-catenin signaling. • E6AP and E6 act through different mechanisms to augment or stimulate Wnt signaling.« less

Inhibition of mTOR/eIF4E by anti-viral drug ribavirin effectively enhances the effects of paclitaxel in oral tongue squamous cell carcinoma

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

Dai, Dehua; Chen, Hujie; Tang, Jing

Upregulation of eIF4E is associated with poor clinical outcome in many human cancers and represents a potential therapeutic target. However, the function of eIF4E remains unknown in oral tongue squamous cell carcinoma (OTSCC). In this work, we show that ribavirin, an anti-viral drug, effectively augments sensitivity of OTSCC cells to paclitaxel via inhibiting mTOR/eIF4E signaling pathway. Ribavirin dose-dependently inhibits proliferation and induces apoptosis in SCC-9 and CAL27 cells. Combination of ribavirin and paclitaxel are more effective in inhibiting proliferation and inducing apoptosis in OTSCC cells. Importantly, the in vivo efficacy of ribavirin and its synergism with paclitaxel is confirmed by two independentmore » OTSCC xenograft mouse models. Mechanistically, ribavirin significantly decreases mTOR/eIF4E signaling pathway in OTSCC cells via suppressing phosphorylation of Akt, mTOR, 4EBP1 and eIF4E. Overexpression of the phosphor-mimetic form of eIF4E (eIF4E S209D) but not the nonphosphorylatable form (eIF4E S209A) reverses the effects of ribavirin, confirming that eIF4E inhibition is the mechanism of action of ribavirin in OTSCC cells. In addition, eIF4E depletion significantly enhances the anti-proliferative and pro-apoptotic effects of paclitaxel, demonstrating the critical role of eIF4E in OTSCC cell response to paclitaxel. Our work is the first to demonstrate the efficacy of ribavirin as a single agent and synergism as combination with paclitaxel in OTSCC in vitro and in vivo. Our findings also demonstrate the therapeutic value of inhibiting eIF4E in OTSCC treatment. - Highlights: • Ribavirin effectively targets OTSCC in vitro and in vivo. • Ribavirin acts synergistically with paclitaxel in OTSCC cells. • Ribavirin inhibits Akt/mTOR/eIF4E signaling in OTSCC. • eIF4E inhibition sensitizes OTSCC cell response to paclitaxel.« less

The impact of tissue Doppler index E/e' ratio on instantaneous wave-free ratio.

PubMed

Arashi, Hiroyuki; Yamaguchi, Junichi; Ri, Tonre; Otsuki, Hisao; Nakao, Masashi; Kamishima, Kazuho; Jujo, Kentaro; Minami, Yuichiro; Ogawa, Hiroshi; Hagiwara, Nobuhisa

2018-03-01

The instantaneous wave-free ratio (iFR) is a vasodilator-free, invasive pressure wire index of the functional severity of coronary stenosis and is calculated under resting conditions. In a recent study, iFR was found to be more closely linked to coronary flow reserve (CFR) than fractional flow reserve (FFR). E/e' is a surrogate marker of left ventricular (LV) filling pressure and LV diastolic dysfunction. Coronary resting flow was found to be increased in patients with elevated E/e', and higher coronary resting flow was associated with lower CFR. Higher baseline coronary flow induces a greater loss of translesional pressure and may affect iFR. However, no reports have examined the impact of E/e' on iFR. The purpose of this study was to assess the relationship between iFR and E/e' compared with FFR. We retrospectively examined 103 consecutive patients (142 with stenosis) whose iFR, FFR, and E/e' were measured simultaneously. The mean age, LV mass index, and systolic blood pressure of patients with elevated E/e' were higher than those of patients with normal E/e'. Although no significant differences were observed in mean FFR values and % diameter stenosis, the mean iFR value in patients with elevated E/e' was significantly lower than that in patients with normal E/e'. The iFR was negatively correlated with E/e', while there was no correlation between FFR and E/e'. Multivariate analysis showed that E/e' and % diameter stenosis were independent determinants of iFR. E/e' ratio affects iFR values. Our results suggest that FFR mainly reflects the functional severity of the epicardial stenosis whereas iFR could potentially be influenced by not only epicardial stenosis but also other factors related to LV filling pressure or LV diastolic dysfunction. Further research is needed to understand the underlying mechanisms that influence the evaluation of iFR in patients with elevated E/e'. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

eIF4E Threshold Levels Differ in Governing Normal and Neoplastic Expansion of Mammary Stem and Luminal Progenitor cells

PubMed Central

Avdulov, Svetlana; Herrera, Jeremy; Smith, Karen; Peterson, Mark; Gomez-Garcia, Jose R.; Beadnell, Thomas C.; Schwertfeger, Kathryn L.; Benyumov, Alexey O.; Manivel, J. Carlos; Li, Shunan; Bielinsky, Anja-Katrin; Yee, Douglas; Bitterman, Peter B.; Polunovsky, Vitaly A.

2015-01-01

Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biological outputs remains unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased cell self-renewal, triggered DNA replication stress, and induced formation of pre-malignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biological output in lactating mammary glands, and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its pro-neoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer. PMID:25524901

eIF4E threshold levels differ in governing normal and neoplastic expansion of mammary stem and luminal progenitor cells.

PubMed

Avdulov, Svetlana; Herrera, Jeremy; Smith, Karen; Peterson, Mark; Gomez-Garcia, Jose R; Beadnell, Thomas C; Schwertfeger, Kathryn L; Benyumov, Alexey O; Manivel, J Carlos; Li, Shunan; Bielinsky, Anja-Katrin; Yee, Douglas; Bitterman, Peter B; Polunovsky, Vitaly A

2015-02-15

Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biologic outputs remain unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased self-renewal, triggered DNA replication stress, and induced formation of premalignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biologic output in lactating mammary glands and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its proneoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer. ©2014 American Association for Cancer Research.

Human Papillomavirus Type 16 E6 Induces Self-Ubiquitination of the E6AP Ubiquitin-Protein Ligase

PubMed Central

Kao, Wynn H.; Beaudenon, Sylvie L.; Talis, Andrea L.; Huibregtse, Jon M.; Howley, Peter M.

2000-01-01

The E6 protein of the high-risk human papillomaviruses (HPVs) and the cellular ubiquitin-protein ligase E6AP form a complex which causes the ubiquitination and degradation of p53. We show here that HPV16 E6 promotes the ubiquitination and degradation of E6AP itself. The half-life of E6AP is shorter in HPV-positive cervical cancer cells than in HPV-negative cervical cancer cells, and E6AP is stabilized in HPV-positive cancer cells when expression of the viral oncoproteins is repressed. Expression of HPV16 E6 in cells results in a threefold decrease in the half-life of transfected E6AP. E6-mediated degradation of E6AP requires (i) the binding of E6 to E6AP, (ii) the catalytic activity of E6AP, and (iii) activity of the 26S proteasome, suggesting that E6-E6AP interaction results in E6AP self-ubiquitination and degradation. In addition, both in vitro and in vivo experiments indicate that E6AP self-ubiquitination results primarily from an intramolecular transfer of ubiquitin from the active-site cysteine to one or more lysine residues; however, intermolecular transfer can also occur in the context of an E6-mediated E6AP multimer. Finally, we demonstrate that an E6 mutant that is able to immortalize human mammary epithelial cells but is unable to degrade p53 retains its ability to bind and degrade E6AP, raising the possibility that E6-mediated degradation of E6AP contributes to its ability to transform mammalian cells. PMID:10864652

The eIF4E-binding proteins are modifiers of cytoplasmic eIF4E relocalization during the heat shock response

PubMed Central

Sukarieh, R.; Sonenberg, N.; Pelletier, J.

2009-01-01

Stress granules (SGs) arise as a consequence of cellular stress, contain stalled translation preinitiation complexes, and are associated with cell survival during environmental insults. SGs are dynamic entities with proteins relocating into and out of them during stress. Among the repertoire of proteins present in SGs is eukaryotic initiation factor 4E (eIF4E), a translation factor required for cap-dependent translation and that regulates a rate-limiting step for protein synthesis. Herein, we demonstrate that localization of eIF4E to SGs is dependent on the presence of a family of repressor proteins, eIF4E-binding proteins (4E-BPs). Our results demonstrate that 4E-BPs regulate the SG localization of eIF4E. PMID:19244480

Transgenic Brassica rapa plants over-expressing eIF(iso)4E variants show broad-spectrum Turnip mosaic virus (TuMV) resistance.

PubMed

Kim, Jinhee; Kang, Won-Hee; Hwang, Jeena; Yang, Hee-Bum; Dosun, Kim; Oh, Chang-Sik; Kang, Byoung-Cheorl

2014-08-01

The protein-protein interaction between VPg (viral protein genome-linked) of potyviruses and eIF4E (eukaryotic initiation factor 4E) or eIF(iso)4E of their host plants is a critical step in determining viral virulence. In this study, we evaluated the approach of engineering broad-spectrum resistance in Chinese cabbage (Brassica rapa) to Turnip mosaic virus (TuMV), which is one of the most important potyviruses, by a systematic knowledge-based approach to interrupt the interaction between TuMV VPg and B. rapa eIF(iso)4E. The seven amino acids in the cap-binding pocket of eIF(iso)4E were selected on the basis of other previous results and comparison of protein models of cap-binding pockets, and mutated. Yeast two-hybrid assay and co-immunoprecipitation analysis demonstrated that W95L, K150L and W95L/K150E amino acid mutations of B. rapa eIF(iso)4E interrupted its interaction with TuMV VPg. All eIF(iso)4E mutants were able to complement an eIF4E-knockout yeast strain, indicating that the mutated eIF(iso)4E proteins retained their function as a translational initiation factor. To determine whether these mutations could confer resistance, eIF(iso)4E W95L, W95L/K150E and eIF(iso)4E wild-type were over-expressed in a susceptible Chinese cabbage cultivar. Evaluation of the TuMV resistance of T1 and T2 transformants demonstrated that the over-expression of the eIF(iso)4E mutant forms can confer resistance to multiple TuMV strains. These data demonstrate the utility of knowledge-based approaches for the engineering of broad-spectrum resistance in Chinese cabbage. © 2014 BSPP AND JOHN WILEY & SONS LTD.

Association of papillomavirus E6 proteins with either MAML1 or E6AP clusters E6 proteins by structure, function, and evolutionary relatedness

PubMed Central

Brimer, Nicole

2017-01-01

Papillomavirus E6 proteins bind to LXXLL peptide motifs displayed on targeted cellular proteins. Alpha genus HPV E6 proteins associate with the cellular ubiquitin ligase E6AP (UBE3A), by binding to an LXXLL peptide (ELTLQELLGEE) displayed by E6AP, thereby stimulating E6AP ubiquitin ligase activity. Beta, Gamma, and Delta genera E6 proteins bind a similar LXXLL peptide (WMSDLDDLLGS) on the cellular transcriptional co-activator MAML1 and thereby repress Notch signaling. We expressed 45 different animal and human E6 proteins from diverse papillomavirus genera to ascertain the overall preference of E6 proteins for E6AP or MAML1. E6 proteins from all HPV genera except Alpha preferentially interacted with MAML1 over E6AP. Among animal papillomaviruses, E6 proteins from certain ungulate (SsPV1 from pigs) and cetacean (porpoises and dolphins) hosts functionally resembled Alpha genus HPV by binding and targeting the degradation of E6AP. Beta genus HPV E6 proteins functionally clustered with Delta, Pi, Tau, Gamma, Chi, Mu, Lambda, Iota, Dyokappa, Rho, and Dyolambda E6 proteins to bind and repress MAML1. None of the tested E6 proteins physically and functionally interacted with both MAML1 and E6AP, indicating an evolutionary split. Further, interaction of an E6 protein was insufficient to activate degradation of E6AP, indicating that E6 proteins that target E6AP co-evolved to separately acquire both binding and triggering of ubiquitin ligase activation. E6 proteins with similar biological function clustered together in phylogenetic trees and shared structural features. This suggests that the divergence of E6 proteins from either MAML1 or E6AP binding preference is a major event in papillomavirus evolution. PMID:29281732

Epilachnini (Coleoptera: Coccinellidae)—A Revision of the World Genera

PubMed Central

Tomaszewska, Wioletta; Szawaryn, Karol

2016-01-01

Based on the recent revised generic classification of the tribe Epilachnini (Szawaryn et al. 2015), all 27 genera are re-described, diagnosed, illustrated, and included in an identification key. The following nomenclatural changes are made: Epilachna (Hypsa) Mulsant 1850, Epilachna (Cleta) Mulsant 1850, Solanophila Weise 1898, Epilachna (Aparodentata) Wang and Cao 1993, and Epilachna (Uniparodentata) Wang and Cao 1993 are removed from synonymy of Epilachna Chervolat 1837. The subgenus Cleta of Epilachna is raised to the genus level, as Cleta Mulsant 1850 stat. nov.; the subgenus Uniparodentata of Epilachna is raised to the genus level, as Uniparodentata Wang and Cao 1993 stat. nov. Chazeauiana Tomaszewska and Szawaryn 2015 (type species, Epilachna sahlbergi Mulsant 1850), and Epilachna (Hypsa) Mulsant 1850 (type species, Epilachna nigrolimbata Thomson 1875) are synonymized here under the name Cleta Mulsant 1850 (type species, Epilachna eckloni Mulsant 1850)—new synonyms; Fuerschia Tomaszewska and Szawaryn 2015 (type species, Coccinella canina Fabricius 1781) is synonymized with Solanophila Weise 1898 (type species, Epilachna gibbosa Crotch 1874)—new synonym; Ryszardia Tomaszewska and Szawaryn 2015 (type species, Epilachna decipiens Crotch 1874) and Epilachna (Aparodentata) Wang and Cao, 1993 (type species, Epilachna yongshanensis Cao and Xiao 1984) are synonymized under the name Uniparodentata Wang and Cao 1993 (type species, Epilachna paramagna Pang and Mao 1979)—new synonyms. Henosepilachna (Elateria) Fürsch 1964 (type species: Coccinella elaterii Rossi 1794) is removed from synomyms of Henosepilachna Li 1961 [type species, Coccinella sparsa Herbst 1786 (=Coccinella vigintioctopunctata Fabricius 1775)] and is synonymized here with Chnootriba Chevrolat 1837 (type species: Coccinella similis Thunberg 1781)—new synonym. Coccinella flavofasciata Laporte 1840, Epilachna aequatorialis Gordon 1975, E. bizonata Crotch 1874, E. convergens Crotch 1874, E. cruciata Mulsant 1850, E. dubia Crotch 1874, E. monovittata Gordon 1975, E. orthostriata Gordon 1975, E. paracuta Gordon 1975, E. patricia Mulsant 1850, E. satipensis Gordon 1975, and E. univittata Crotch 1874 are transferred to Toxotoma Weise 1900 (comb. nov.); Afissa chapini Dieke 1947, A. complicata Dieke 1947, A. convexa Dieke 1947, A. magna Dieke 1947, A. militaris Dieke 1947, A. quadricollis Dieke 1947, A. subacuta Dieke 1947, A. szechuana Dieke 1947, Epilachna boymi Jadwiszczak and Węgrzynowicz 2003, E. crepida Pang and Ślipiński 2012, E. decipiens Crotch 1874, E. dorotae Bielawski 1979, E. hamulifera Pang and Ślipiński 2012, E. malleforma Peng, Pang and Ren 2002, E. siphodenticulata Hoàng 1983, E. angusta Li 1961, E. bifibra Li 1961, E. chingjing Yu and Wang 1999, E. circumdata Hoàng 1978, E. circummaculata Pang and Mao 1977, E. clematicola Cao and Xiao 1984, E. exornata Bielawski 1965, E. folifera Pang and Mao 1979, E. fugongensis Cao and Xiao 1984, E. glochisifoliata Pang and Mao 1979, E. gressiti Li 1961, E. lata Li 1961, E. madanensis Zeng 2002, E. media Li 1961, E. mobliteratiae Li 1961, E. yongshanensis Cao and Xiao 1984, Solanophila acuta Weise 1900, and S. saginata Weise 1902 are transferred to Uniparodentata Wang and Cao 1993 (comb. nov.); Coccinella canina Fabricius 1781, Epilachna dregei Mulsant 1850, E. infirma Mulsant 1850, E. murrayi Crotch 1874 and E. paykullii Mulsant 1850 are transferred to Solanophila Weise 1898 (comb. nov.); Afissula antennata Bielawski 1967, A. rana Kapur 1958, A. uniformis Pang and Mao 1979, Epilachna ampliata Pang and Mao 1979, E. flavimarginalis Hoàng 1978, E. max Pang and Ślipiński 2012, E. parvula Crotch, E. plicata Weise 1889, and E. sanscrita Crotch 1874 are transferred to Afissa Dieke 1947 (comb. nov.); Epilachna papuensis Crotch 1874 and Subafissa brittoni Bielawski 1963 are transferred to Henosepilachna Li 1961 (comb. nov.); Epilachna admirabilis Crotch 1874, E. alternans Mulsant 1850, E. glochinosa Pang and Mao 1979, E. hopeiana Miyatake 1985, E. insignis Gorham 1892, E. macularis Mulsant 1850, E. parainsignis Pang and Mao 1979, and Solanophila maxima Weise 1898 are transferred to Diekeana Tomaszewska and Szawaryn 2015 (comb. nov.); Epilachna fulvohirta Weise 1895, E. nigrolimbata Thomson 1875, Henosepilachna griveaudi Chazeau 1975, H. vadoni Chazeau 1976, Solanophila consignata Weise 1909, S. coquereli Sicard 1907, and S. gyldenstolpei Weise 1924 are transferred to Cleta Mulsant 1850 (comb. nov.); Afidenta janczyki Fürsch 1986, Epilachna capicola Mulsant 1850, E. godarti Mulsant 1850, E. scitula Weise 1898, Henospeilachna acervata Chazeau 1975, and Solanophila blaesa Weise 1905 are transferred to Afidentula Kapur 1958 (com. nov.); Coccinella elaterii Rossi 1794, C. hirta Thunberg 1781, C. pavonia Olivier 1808, Epilachna annulata Kolbe 1897, E. biplagiata Kolbe 1897, E. cinerascens Weise 1907, E. connectens Weise 1912, E. erichi Weise, 1897, E. occellata Bertoloni, 1849, E. pauli Weise, 1897, E. tetracycla Gerstaecker, 1871, E. umbratilis Weise 1909, E. vulgaris Weise 1901, Henosepilachna bigemmata Fürsch 1991, Solanophila guttifera Weise 1899, S. hova Weise 1905, and S. kaffaeensis Weise 1906 are transferred to Chnootriba Chevrolat 1837 (com. nov.); Coccinella guttatopustulata Fabricius 1775, Epilachna aruensis Crotch 1874, E. biroi Weise 1902, E. buqueti Montrouzier 1861, E. fulvimana Weise 1903, E. immaculata Bielawski 1963, E. karapensis Bielawski 1963, E. orrori Bielawski 1963, E. samuelsoni Jadwiszczak 1991, and E. slipinskii Jadwiszczak 1987 are transferred to Papuaepilachna Tomaszewska and Szawaryn, 2013 (comb. nov.). The history of classification, the known aspects of the biology and distributional data of the tribe are summarized. PMID:27651424

Climate Prediction Center - Stratosphere: Stratosphere-Troposphere

Science.gov Websites

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A Non-oncogenic HPV 16 E6/E7 Vaccine Enhances Treatment of HPV Expressing Tumors

PubMed Central

Wieking, Bryant G.; Vermeer, Daniel W.; Spanos, William C.; Lee, Kimberly M.; Vermeer, Paola; Lee, Walter T.; Xu, Younong; Gabitzsch, Elizabeth S.; Balcaitis, Stephanie; Balint, Joseph P.; Jones, Frank R.; Lee, John H.

2012-01-01

Human papillomaviruses (HPVs) are the causative factor for greater than 90% of cervical cancers and 25% of head and neck cancers. The incidence of HPV positive (+) head and neck squamous cell carcinomas (HNSCCs) has greatly increased in the last 30 years. E6 and E7 are the two key viral oncoproteins that induce and propagate cellular transformation. An immune response generated during cisplatin/radiation therapy improves tumor clearance of HPV(+) cancers. Augmenting this induced response during therapy with an adenoviral HPV16 E6/E7 vaccine improves long term survival in preclinical models. Here we describe the generation of an HPV16 E6/E7 construct, which contains mutations that render E6/E7 non-oncogenic, while preserving antigenicity. These mutations do not allow E6/E7 to degrade p53, pRb, PTPN13, or activate telomerase. Non-oncogenic E6/E7 (E6Δ/E7Δ) expressed as a stable integrant, or in the [E1-, E2b-] adenovirus, lacks the ability to transform human cells while retaining the ability to induce an HPV specific immune response. Moreover, E6Δ/E7Δ plus chemotherapy/radiation statistically enhances clearance of established HPV(+) cancer in vivo. PMID:22918471

Restrained dark U (1 )d at low energies

NASA Astrophysics Data System (ADS)

Correia, Fagner C.; Fajfer, Svjetlana

2016-12-01

We investigate a spontaneously broken U (1 )d gauge symmetry with a muon-specific dark Higgs. Our first goal is to verify how the presence of a new dark Higgs, ϕ , and a dark gauge boson, V , can simultaneously face the anomalies from the muon magnetic moment and the proton charge radius. Second, by assuming that V must decay to an electron-positron pair, we explore the corresponding parameter space determined with the low-energy constraints coming from K →μ X , electron (g -2 )e, K →μ νμe+e-, K →μ νμμ+μ-, and τ →ντμ νμe+e-. We focus on the scenario where the V mass is below ˜2 mμ and the ϕ mass runs from few MeV to 250 MeV, with V -photon mixing of the order ˜O (10-3). Among weak process at low energies, we check the influence of the new light vector on kaon decays as well as on the scattering e+e-→μ+μ-e+e- and discuss the impact of the dark Higgs on e+e-→μ+μ-μ+μ-. Finally, we consider contributions of the V -photon mixing in the decays π0→γ e+e-, η →γ e+e-, ρ →π e+e-, K*→K e+e-, and ϕ (1020 )→η e+e-.

Smooth muscle cells in atherosclerosis originate from the local vessel wall and not circulating progenitor cells in ApoE knockout mice.

PubMed

Bentzon, Jacob F; Weile, Charlotte; Sondergaard, Claus S; Hindkjaer, Johnny; Kassem, Moustapha; Falk, Erling

2006-12-01

Recent studies of bone marrow (BM)-transplanted apoE knockout (apoE-/-) mice have concluded that a substantial fraction of smooth muscle cells (SMCs) in atherosclerosis arise from circulating progenitor cells of hematopoietic origin. This pathway, however, remains controversial. In the present study, we reexamined the origin of plaque SMCs in apoE-/- mice by a series of BM transplantations and in a novel model of atherosclerosis induced in surgically transferred arterial segments. We analyzed plaques in lethally irradiated apoE-/- mice reconstituted with sex-mismatched BM cells from eGFP+ apoE-/- mice, which ubiquitously express enhanced green fluorescent protein (eGFP), but did not find a single SMC of donor BM origin among approximately 10,000 SMC profiles analyzed. We then transplanted arterial segments between eGFP+ apoE-/- and apoE-/- mice (isotransplantation except for the eGFP transgene) and induced atherosclerosis focally within the graft by a recently invented collar technique. No eGFP+ SMCs were found in plaques that developed in apoE-/- artery segments grafted into eGFP+ apoE-/- mice. Concordantly, 96% of SMCs were eGFP+ in plaques induced in eGFP+ apoE-/- artery segments grafted into apoE-/- mice. These experiments show that SMCs in atherosclerotic plaques are exclusively derived from the local vessel wall in apoE-/- mice.

Genetically Programming Interfaces between Active Materials, Conductive Pathway and Current Collector in Li Ion Batteries

DTIC Science & Technology

2012-01-01

2 Recombinant M13 phages Clone ID pIII pVIII E4-A1 STIHGST EEEE E4-A2 ATFNTMT EEEE E4-S7 SSSSSSS EEEE E4- T7 TTTTTTT EEEE E4-H7 HHHHHHH EEEE...higher binding strength, with A1 and H7 motifs 0 5E+10 1E+11 1.5E+11 2E+11 E4-W E4-A1 E4- T7 E4-H7 Phage Clones ECS Transactions, 41 (41) 55-64...prepared through conventional approaches. 5 Compared to other bio-templates used, the advantages of M13 phages exist not only in their well-understood

A revision of the cleptoparasitic bee genus Epeolus Latreille for Nearctic species, north of Mexico (Hymenoptera, Apidae)

PubMed Central

Onuferko, Thomas M.

2018-01-01

Abstract Herein, the cleptoparasitic (cuckoo) bee genus Epeolus (Hymenoptera: Apidae) is revised for species occurring in North America, north of Mexico, and an updated checklist of all species known to occur in Canada and the United States of America is provided with comprehensive descriptions, diagnoses, and a single dichotomous key (using the same couplets for both sexes) to aid in their identification. To increase their recognition among North American naturalists, English common names are also proposed for all North American Epeolus. A total of 43 species is confirmed as present in the region, 15 of which are newly recognized. The following new species are proposed based on unique morphological (and in most cases also molecular) attributes: E. andriyi sp. n., E. attenboroughi sp. n., E. axillaris sp. n., E. basili sp. n., E. brumleyi sp. n., E. chamaesarachae sp. n., E. deyrupi sp. n., E. diadematus sp. n., E. ferrarii sp. n., E. gibbsi sp. n., E. inornatus sp. n., E. nebulosus sp. n., E. packeri sp. n., E. splendidus sp. n., and E. tessieris sp. n. Of the 15, six (E. axillaris, E. brumleyi, E. chamaesarachae, E. diadematus, E. splendidus, and E. tessieris) were identified as new species under different names (nomina nuda) in an M.Sc. thesis by Richard L. Brumley in 1965, but until now they have not been formally described. Detailed morphological comparisons with some evidence from DNA barcoding support the following synonymies, one of which C was first proposed by Brumley (1965): a) E. melectimimus Cockerell and Sandhouse, syn. n., under E. asperatus Cockerell; b) E. crucis Cockerell, syn. n., under E. compactus Cresson; c) E. mesillae palmarum Linsley, syn. n., under E. mesillae (Cockerell); and d) E. weemsi Mitchell, syn. n., and e) E. vernalis Mitchell, syn. n., under E. ilicis Mitchell. Only one member of the almost entirely Neotropical “Trophocleptria group” (Epeolus bifasciatus Cresson) is confirmed as occurring north of Mexico, and is widespread East of the Rocky Mountains. Known floral associations are indicated for each species, as are suspected or known host species of Colletes Latreille. Evidence is presented that suggests further investigation into the possible synonymy of Colletes wickhami Timberlake under C. scopiventer Swenk is warranted. PMID:29769836

A revision of the cleptoparasitic bee genus Epeolus Latreille for Nearctic species, north of Mexico (Hymenoptera, Apidae).

PubMed

Onuferko, Thomas M

2018-01-01

Herein, the cleptoparasitic (cuckoo) bee genus Epeolus (Hymenoptera: Apidae) is revised for species occurring in North America, north of Mexico, and an updated checklist of all species known to occur in Canada and the United States of America is provided with comprehensive descriptions, diagnoses, and a single dichotomous key (using the same couplets for both sexes) to aid in their identification. To increase their recognition among North American naturalists, English common names are also proposed for all North American Epeolus . A total of 43 species is confirmed as present in the region, 15 of which are newly recognized. The following new species are proposed based on unique morphological (and in most cases also molecular) attributes: E. andriyi sp. n. , E. attenboroughi sp. n. , E. axillaris sp. n. , E. basili sp. n. , E. brumleyi sp. n. , E. chamaesarachae sp. n. , E. deyrupi sp. n. , E. diadematus sp. n. , E. ferrarii sp. n. , E. gibbsi sp. n. , E. inornatus sp. n. , E. nebulosus sp. n. , E. packeri sp. n. , E. splendidus sp. n. , and E. tessieris sp. n. Of the 15, six ( E. axillaris , E. brumleyi , E. chamaesarachae , E. diadematus , E. splendidus , and E. tessieris ) were identified as new species under different names ( nomina nuda ) in an M.Sc. thesis by Richard L. Brumley in 1965, but until now they have not been formally described. Detailed morphological comparisons with some evidence from DNA barcoding support the following synonymies, one of which C was first proposed by Brumley (1965): a) E. melectimimus Cockerell and Sandhouse, syn . n ., under E. asperatus Cockerell; b) E. crucis Cockerell, syn . n ., under E. compactus Cresson; c) E. mesillae palmarum Linsley, syn . n ., under E. mesillae (Cockerell); and d) E. weemsi Mitchell, syn . n ., and e) E. vernalis Mitchell, syn . n ., under E. ilicis Mitchell. Only one member of the almost entirely Neotropical "Trophocleptria group" ( Epeolus bifasciatus Cresson) is confirmed as occurring north of Mexico, and is widespread East of the Rocky Mountains. Known floral associations are indicated for each species, as are suspected or known host species of Colletes Latreille. Evidence is presented that suggests further investigation into the possible synonymy of Colletes wickhami Timberlake under C. scopiventer Swenk is warranted.

New York Downtown Manhattan (Wall Street) Heliport - Operations Analysis

DTIC Science & Technology

1991-09-01

Unicorn World Coord. E,NJ Stat Police G -Union Pacific ENorl Air- A Unisys ENVI Corp. E Universal Television ENY Helicopters A US Air Force M_NY Air E US...Yonkers construction E 4Phillip Morris E Phillips Aviation E Phipps E Pioneer Valley E Pitcairn Finance U PMC U PNN Helicopter U Prime Production E PSE&G

E-Service Quality, E-Satisfaction and E-Loyalty of Online Shoppers in Business to Consumer Market; Evidence form Malaysia

NASA Astrophysics Data System (ADS)

Ting, Ong Soo; Ariff, Mohd Shoki Md; Zakuan, Norhayati; Sulaiman, Zuraidah; Zameri Mat Saman, Muhamad

2016-05-01

The growing usage of internet and online shopping in Malaysia presents a huge prospect in e-commerce market, specifically for B2C segment. As a result, electronic service quality (e-SQ), electronic satisfaction (e-Satisfaction) and electronic loyalty (e-Loyalty) become vital for online retailers to attract and retain online shoppers in this virtual environment. The association between e-SQ, e-Satisfaction and e-Loyalty should be continuously examined to cope with the advancement in information and communication technology, and the changing expectation of online shoppers. However, construct of e-SQ for online retailers in B2C market is still debatable. In this research, E-SERVQUAL was integrated with the other e-SQ scales to measure e-SQ of a prominent online retailer in Malaysia. Specifically, the e-SQ constructs are Efficiency, Privacy and Trust, Fulfilment, Responsiveness, Contact and Website Design. 390 sets of completed and usable questionnaires were gathered using online questionnaire and convenience sampling procedure. The result indicated that the five proposed dimensions of e-SQ constitute e-SQ of online retailer in B2C market. All the dimensions of e-SQ were found to have positive and significant effect on e-Satisfaction of online shoppers. Responsiveness of e-SQ had the strongest impact on e-satisfaction of online shoppers. The shoppers e-Satisfaction was positively and significantly affected their e-Loyalty towards continuous usage of online retailer's website. Managerial and theoretical implications are discussed based on the results of the study.

The E6 and E7 genes of human papillomavirus type 6 have weak immortalizing activity in human epithelial cells.

PubMed Central

Halbert, C L; Demers, G W; Galloway, D A

1992-01-01

Previous studies have shown that the E7 gene of human papillomavirus (HPV) type 16 or 18 alone was sufficient for immortalization of human foreskin epithelial cells (HFE) and that the efficiency was increased in cooperation with the respective E6 gene, whereas the HPV6 E6 or E7 gene was not active in HFE. To detect weak immortalizing activities of the HPV6 genes, cells were infected with recombinant retroviruses containing HPV genes, alone and in homologous and heterologous combinations. The HPV6 genes, alone or together (HPV6 E6 plus HPV6 E7), were not able to immortalize cells. However the HPV6 E6 gene, in concert with HPV16 E7, increased the frequency of immortalization threefold over that obtained with HPV16 E7 alone. Interestingly, 6 of 20 clones containing the HPV16 E6 gene and the HPV6 E7 gene were immortalized, whereas neither gene alone was sufficient. Thus, the HPV6 E6 and E7 genes have weak immortalizing activities which can be detected in cooperation with the more active transforming genes of HPV16. Acute expression of the HPV6 and HPV16 E6 and E7 genes revealed that only HPV16 E7 was able to stimulate the proliferation of cells in organotypic culture, resulting in increased expression of the proliferative cell nuclear antigen and the formation of a disorganized epithelial layer. Additionally, combinations of genes that immortalized HFE cells (HPV16 E6 plus HPV16 E7, HPV16 E6 plus HPV6 E7, and HPV6 E6 plus HPV16 E7) also stimulated proliferation. Images PMID:1312623

eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control

PubMed Central

Jennings, Martin D.; Kershaw, Christopher J.; White, Christopher; Hoyle, Danielle; Richardson, Jonathan P.; Costello, Joseph L.; Donaldson, Ian J.; Zhou, Yu; Pavitt, Graham D.

2016-01-01

In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates start codon selection. eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2α phosphorylation in response to diverse signals is a major point of translational control. Here we characterize a growth suppressor mutation in eIF2β that prevents eIF5 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation. By monitoring the binding of fluorescent nucleotides and initiator tRNA to purified eIF2 we show that the eIF2β mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components. Instead we show that the eIF2β mutation prevents eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2•GDP/eIF5 complexes. This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 targets in response to amino acid starvation. These findings provide support for the importance of eIF5 GDI activity in vivo and demonstrate that eIF2β acts in concert with eIF5 to prevent premature release of GDP from eIF2γ and thereby ensure tight control of protein synthesis initiation. PMID:27458202

eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control.

PubMed

Jennings, Martin D; Kershaw, Christopher J; White, Christopher; Hoyle, Danielle; Richardson, Jonathan P; Costello, Joseph L; Donaldson, Ian J; Zhou, Yu; Pavitt, Graham D

2016-11-16

In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates start codon selection. eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2α phosphorylation in response to diverse signals is a major point of translational control. Here we characterize a growth suppressor mutation in eIF2β that prevents eIF5 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation. By monitoring the binding of fluorescent nucleotides and initiator tRNA to purified eIF2 we show that the eIF2β mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components. Instead we show that the eIF2β mutation prevents eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2•GDP/eIF5 complexes. This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 targets in response to amino acid starvation. These findings provide support for the importance of eIF5 GDI activity in vivo and demonstrate that eIF2β acts in concert with eIF5 to prevent premature release of GDP from eIF2γ and thereby ensure tight control of protein synthesis initiation. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Archeological Survey and Testing in the Holy Cross Historic District, New Orleans, Louisiana. Volume 2

DTIC Science & Technology

1992-02-01

467 Table 4 Personal Items from Shovel Tests, 160R130. SURF SURF SURF N15 N5 NO NO $5 S5 1 2 3 W20 El5 E20 W10 E20 EO Bone button, Type B-5 Ceramic...Table 4 . Personal Items from Shovel Tests, 160R130. S15 S20 S20 S25 S25 S30 S30 S30 S32.5 E5 E35 E20 E50 E25 E50 E35 E20 E35 Bone button, Type B-5...1 1 1 7 1 471 Table 4 Personal Items from Shovel Tests, 160R130. S30 S34 S35 S45 S50 TOTAL El0 E35 E30 E30 E55 Bone button, Type B-5 1 1 Ceramic

E-cigarettes: Impact of E-Liquid Components and Device Characteristics on Nicotine Exposure.

PubMed

DeVito, Elise E; Krishnan-Sarin, Suchitra

2018-01-01

Electronic cigarette (e-cigarette) use has increased substantially in recent years. While e-cigarettes have been proposed as a potentially effective smoking cessation tool, dualuse in smokers is common and e-cigarettes are widely used by non-smokers, including youth and young-adult non-smokers. Nicotine, the primary addictive component in cigarettes, is present at varying levels in many e-liquids. E-cigarettes may lead to initiation of nicotine use in adult and youth non-smokers, re-initiation of nicotine dependence in ex-smokers or increased severity of nicotine dependence in dual-users of cigarettes and e-cigarettes. As such, there are important clinical and policy implications to understanding factors impacting nicotine exposure from e-cigarettes. However, the broad and rapidly changing range of e-liquid constituents and e-cigarette hardware which could impact nicotine exposure presents a challenge. Recent changes in regulatory oversight of e-cigarettes underscore the importance of synthesizing current knowledge on common factors which may impact nicotine exposure. This review focuses on factors which may impact nicotine exposure by changing e-cigarette use behavior, puff topography, altering the nicotine yield (amount of nicotine exiting the e-cigarette mouth piece including nicotine exhaled as vapor) or more directly by altering nicotine absorption and bioavailability. Topics reviewed include e-liquid components or characteristics including flavor additives (e.g., menthol), base e-liquid ingredients (propylene glycol, vegetable glycerin), components commonly used to dissolve flavorants (e.g., ethanol), and resulting properties of the e-liquid (e.g., pH), e-cigarette device characteristics (e.g., wattage, temperature, model) and user behavior (e.g., puff topography) which may impact nicotine exposure. E-liquid characteristics and components, e-cigarette hardware and settings, and user behavior can all contribute substantially to nicotine exposure from e-cigarettes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G.

PubMed

Papadopoulos, Evangelos; Jenni, Simon; Kabha, Eihab; Takrouri, Khuloud J; Yi, Tingfang; Salvi, Nicola; Luna, Rafael E; Gavathiotis, Evripidis; Mahalingam, Poornachandran; Arthanari, Haribabu; Rodriguez-Mias, Ricard; Yefidoff-Freedman, Revital; Aktas, Bertal H; Chorev, Michael; Halperin, Jose A; Wagner, Gerhard

2014-08-05

The interaction of the eukaryotic translation initiation factor eIF4E with the initiation factor eIF4G recruits the 40S ribosomal particle to the 5' end of mRNAs, facilitates scanning to the AUG start codon, and is crucial for eukaryotic translation of nearly all genes. Efficient recruitment of the 40S particle is particularly important for translation of mRNAs encoding oncoproteins and growth-promoting factors, which often harbor complex 5' UTRs and require efficient initiation. Thus, inhibiting the eIF4E/eIF4G interaction has emerged as a previously unpursued route for developing anticancer agents. Indeed, we discovered small-molecule inhibitors of this eIF4E/eIF4G interaction (4EGIs) that inhibit translation initiation both in vitro and in vivo and were used successfully in numerous cancer-biology and neurobiology studies. However, their detailed molecular mechanism of action has remained elusive. Here, we show that the eIF4E/eIF4G inhibitor 4EGI-1 acts allosterically by binding to a site on eIF4E distant from the eIF4G binding epitope. Data from NMR mapping and high-resolution crystal structures are congruent with this mechanism, where 4EGI-1 attaches to a hydrophobic pocket of eIF4E between β-sheet2 (L60-T68) and α-helix1 (E69-N77), causing localized conformational changes mainly in the H78-L85 region. It acts by unfolding a short 310-helix (S82-L85) while extending α-helix1 by one turn (H78-S82). This unusual helix rearrangement has not been seen in any previous eIF4E structure and reveals elements of an allosteric inhibition mechanism leading to the dislocation of eIF4G from eIF4E.

Search for the rare decays J /ψ →D0e+e-+c .c . and ψ (3686 )→D0e+e-+c .c .

NASA Astrophysics Data System (ADS)

Ablikim, M.; Achasov, M. N.; Ahmed, S.; Albrecht, M.; Amoroso, A.; An, F. F.; An, Q.; Bai, J. Z.; Bakina, O.; Baldini Ferroli, R.; Ban, Y.; Bennett, D. W.; Bennett, J. V.; Berger, N.; Bertani, M.; Bettoni, D.; Bian, J. M.; Bianchi, F.; Boger, E.; Boyko, I.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chai, J.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, S. J.; Chen, X. R.; Chen, Y. B.; Chu, X. K.; Cibinetto, G.; Dai, H. L.; Dai, J. P.; Dbeyssi, A.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; de Mori, F.; Ding, Y.; Dong, C.; Dong, J.; Dong, L. Y.; Dong, M. Y.; Dorjkhaidav, O.; Dou, Z. L.; Du, S. X.; Duan, P. F.; Fang, J.; Fang, S. S.; Fang, X.; Fang, Y.; Farinelli, R.; Fava, L.; Fegan, S.; Feldbauer, F.; Felici, G.; Feng, C. Q.; Fioravanti, E.; Fritsch, M.; Fu, C. D.; Gao, Q.; Gao, X. L.; Gao, Y.; Gao, Y. G.; Gao, Z.; Garzia, I.; Goetzen, K.; Gong, L.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, S.; Gu, Y. T.; Guo, A. Q.; Guo, L. B.; Guo, R. P.; Guo, Y. P.; Haddadi, Z.; Hafner, A.; Han, S.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, X. Q.; Heinsius, F. H.; Held, T.; Heng, Y. K.; Holtmann, T.; Hou, Z. L.; Hu, C.; Hu, H. M.; Hu, T.; Hu, Y.; Huang, G. S.; Huang, J. S.; Huang, X. T.; Huang, X. Z.; Huang, Z. L.; Hussain, T.; Ikegami Andersson, W.; Ji, Q.; Ji, Q. P.; Ji, X. B.; Ji, X. L.; Jiang, X. S.; Jiang, X. Y.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Johansson, T.; Julin, A.; Kalantar-Nayestanaki, N.; Kang, X. L.; Kang, X. S.; Kavatsyuk, M.; Ke, B. C.; Khan, T.; Kiese, P.; Kliemt, R.; Kloss, B.; Koch, L.; Kolcu, O. B.; Kopf, B.; Kornicer, M.; Kuemmel, M.; Kuhlmann, M.; Kupsc, A.; Kühn, W.; Lange, J. S.; Lara, M.; Larin, P.; Lavezzi, L.; Leithoff, H.; Leng, C.; Li, C.; Li, Cheng; Li, D. M.; Li, F.; Li, F. Y.; Li, G.; Li, H. B.; Li, H. J.; Li, J. C.; Li, Jin; Li, Kang; Li, Ke; Li, Lei; Li, P. L.; Li, P. R.; Li, Q. Y.; Li, T.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Lin, D. X.; Liu, B.; Liu, B. J.; Liu, C. X.; Liu, D.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H. B.; Liu, H. M.; Liu, Huanhuan; Liu, Huihui; Liu, J. B.; Liu, J. P.; Liu, J. Y.; Liu, K.; Liu, K. Y.; Liu, Ke; Liu, L. D.; Liu, P. L.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, Y. B.; Liu, Y. Y.; Liu, Z. A.; Liu, Zhiqing; Long, Y. F.; Lou, X. C.; Lu, H. J.; Lu, J. G.; Lu, Y.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lyu, X. R.; Ma, F. C.; Ma, H. L.; Ma, L. L.; Ma, M. M.; Ma, Q. M.; Ma, T.; Ma, X. N.; Ma, X. Y.; Ma, Y. M.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, Y. J.; Mao, Z. P.; Marcello, S.; Messchendorp, J. G.; Mezzadri, G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Mo, Y. J.; Morales Morales, C.; Morello, G.; Muchnoi, N. Yu.; Muramatsu, H.; Musiol, P.; Mustafa, A.; Nefedov, Y.; Nerling, F.; Nikolaev, I. B.; Ning, Z.; Nisar, S.; Niu, S. L.; Niu, X. Y.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Pan, Y.; Papenbrock, M.; Patteri, P.; Pelizaeus, M.; Pellegrino, J.; Peng, H. P.; Peters, K.; Pettersson, J.; Ping, J. L.; Ping, R. G.; Poling, R.; Prasad, V.; Qi, H. R.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, J. J.; Qin, N.; Qin, X. S.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Redmer, C. F.; Richter, M.; Ripka, M.; Rong, G.; Rosner, Ch.; Ruan, X. D.; Sarantsev, A.; Savrié, M.; Schnier, C.; Schoenning, K.; Shan, W.; Shao, M.; Shen, C. P.; Shen, P. X.; Shen, X. Y.; Sheng, H. Y.; Song, J. J.; Song, W. M.; Song, X. Y.; Sosio, S.; Sowa, C.; Spataro, S.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. H.; Sun, Y. J.; Sun, Y. K.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, G. Y.; Tang, X.; Tapan, I.; Tiemens, M.; Tsednee, B. T.; Uman, I.; Varner, G. S.; Wang, B.; Wang, B. L.; Wang, D.; Wang, D. Y.; Wang, Dan; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, W. P.; Wang, X. F.; Wang, Y.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. H.; Wang, Z. Y.; Wang, Zongyuan; Weber, T.; Wei, D. H.; Wei, J. H.; Weidenkaff, P.; Wen, S. P.; Wiedner, U.; Wolke, M.; Wu, L. H.; Wu, L. J.; Wu, Z.; Xia, L.; Xia, Y.; Xiao, D.; Xiao, H.; Xiao, Y. J.; Xiao, Z. J.; Xie, Y. G.; Xie, Y. H.; Xiong, X. A.; Xiu, Q. L.; Xu, G. F.; Xu, J. J.; Xu, L.; Xu, Q. J.; Xu, Q. N.; Xu, X. P.; Yan, L.; Yan, W. B.; Yan, W. C.; Yan, Y. H.; Yang, H. J.; Yang, H. X.; Yang, L.; Yang, Y. H.; Yang, Y. X.; Ye, M.; Ye, M. H.; Yin, J. H.; You, Z. Y.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yuan, C. Z.; Yuan, Y.; Yuncu, A.; Zafar, A. A.; Zeng, Y.; Zeng, Z.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. L.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, K.; Zhang, L.; Zhang, S. Q.; Zhang, X. Y.; Zhang, Y. H.; Zhang, Y. T.; Zhang, Yang; Zhang, Yao; Zhang, Yu; Zhang, Z. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, J. W.; Zhao, J. Y.; Zhao, J. Z.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, S. J.; Zhao, T. C.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, W. J.; Zheng, Y. H.; Zhong, B.; Zhou, L.; Zhou, X.; Zhou, X. K.; Zhou, X. R.; Zhou, X. Y.; Zhou, Y. X.; Zhu, K.; Zhu, K. J.; Zhu, S.; Zhu, S. H.; Zhu, X. L.; Zhu, Y. C.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zotti, L.; Zou, B. S.; Zou, J. H.; Besiii Collaboration

2017-12-01

Using the data samples of (1310.6 ±7.2 )×106 J /ψ events and (448.1 ±2.9 )×106 ψ (3686 ) events collected with the BESIII detector, we search for the rare decays J /ψ →D0e+e-+c .c . and ψ (3686 )→D0e+e-+c .c . No significant signals are observed and the corresponding upper limits on the branching fractions at the 90% confidence level are determined to be B (J /ψ →D0e+e-+c .c .)<8.5 ×10-8 and B (ψ (3686 )→D0e+e-+c .c .)<1.4 ×10-7 , respectively. Our limit on B (J /ψ →D0e+e-+c .c .) is more stringent by 2 orders of magnitude than the previous results, and B (ψ (3686 )→D0e+e-+c .c .) is measured for the first time.

E-government strategy of Surabaya city government through e-rt / rw to improve the quality of public service

NASA Astrophysics Data System (ADS)

Oktariyanda, T. A.; Rahaju, T.

2018-01-01

The use of information technology by Surabaya City Government has generated various innovations of public services such as “e-Sapa Warga”, e-Commerce, “e-RT/RW”, e-Budgeting, e-Project, e-Procurement, “e-Pendidikan”. Among the many innovations, e-RT/RW (Rukun Tetangga / Rukun Warga) is an innovation that is quite prominent because there are still many areas that have not implemented. This research can be classified as literature review and critical research. The aims of this research are to describe and analyze e-government strategy in Surabaya City through e-RT / RW to improve public service quality. The result of this research is e-government strategy in Surabaya City through e-RT / RW is already relevant and in accordance with Goldsmith’s theory of e-government. The positive impact of the implementation of e-RT / RW is the increasing quality of public services to bring benefits to all citizens Surabaya City.

Search for the rare decays J / ψ → D 0 e + e − + c . c . and ψ ( 3686 ) → D 0 e + e − + c . c .

DOE PAGES

Ablikim, M.; Achasov, M. N.; Ahmed, S.; ...

2017-12-01

Using the data samples of (1310.6 ± 7.2) × 10 6 J / ψ events and (448.1 ± 2.9) × 106 (3686) events collected with the BESIII detector, we search for the rare decays J / ψ → D 0e +e - + c.c. and (3686) → D 0e +e - + c.c.. No significant signals are observed and the corresponding upper limits on the branching fractions at the 90% confidence level are determined to be B( J /more » ψ → D0e+e- + c.c.) < 8.5 × 10 -8 and B( (3686) → D0e+e- + c.c.) < 1.4 × 10 -7, respectively. Our limit on B( J / ψ → D 0e +e - + c.c.) is more stringent by two orders of magnitude than the previous results, and the B( (3686) → D 0e +e - + c.c.) is measured for the first time. « less

Search for the rare decays J / ψ → D 0 e + e − + c . c . and ψ ( 3686 ) → D 0 e + e − + c . c .

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

Ablikim, M.; Achasov, M. N.; Ahmed, S.

Using the data samples of (1310.6 ± 7.2) × 10 6 J / ψ events and (448.1 ± 2.9) × 106 (3686) events collected with the BESIII detector, we search for the rare decays J / ψ → D 0e +e - + c.c. and (3686) → D 0e +e - + c.c.. No significant signals are observed and the corresponding upper limits on the branching fractions at the 90% confidence level are determined to be B( J /more » ψ → D0e+e- + c.c.) < 8.5 × 10 -8 and B( (3686) → D0e+e- + c.c.) < 1.4 × 10 -7, respectively. Our limit on B( J / ψ → D 0e +e - + c.c.) is more stringent by two orders of magnitude than the previous results, and the B( (3686) → D 0e +e - + c.c.) is measured for the first time. « less

Cooperative transformation and coexpression of bovine papillomavirus type 1 E5 and E7 proteins.

PubMed

Bohl, J; Hull, B; Vande Pol, S B

2001-01-01

Productively infected bovine fibropapillomas were examined for bovine papillomavirus type 1 (BPV-1) E7 localization. BPV-1 E7 was observed in the cytoplasm of basal and lower spinous epithelial cells, coexpressed in the cytoplasm of basal cells with the E5 oncoprotein. E7 was also observed in nucleoli throughout the basal and spinous layers but not in the granular cell layer. Ectopic expression of E7 in cultured epithelial cells gave rise to localization similar to that seen in productive fibropapillomas, with cytoplasmic and nucleolar expression observed. Consistent with the coexpression of E7 and E5 in basal keratinocytes, BPV-1 E7 cooperated with E5 as well as E6 in an anchorage independence transformation assay. While E5 is expressed in both basal and superficial differentiating keratinocytes, BPV-1 E7 is only observed in basal and lower spinous epithelial cells. Therefore, BPV-1 E7 may serve to modulate the cellular response of basal epithelial cells to E5 expression.

Dominant Role of HPV16 E7 in Anal Carcinogenesis

PubMed Central

Thomas, Marie K.; Pitot, Henry C.; Liem, Amy; Lambert, Paul F.

2011-01-01

Ninety percent of anal cancer is associated with human papilloma viruses (HPVs). Using our previously established HPV transgenic mouse model for anal cancer, we tested the role of the individual oncogenes E6 and E7. K14E6 and K14E7 transgenic mice were treated with dimethylbenz[a]anthracene (DMBA) to the anal canal and compared to matched nontransgenic and doubly transgenic K14E6/E7 mice. K14E7 and K14E6/E7 transgenic mice developed anal tumors (papillomas, atypias and carcinomas combined) at significantly higher rates (88% and 100%, respectively) than either K14E6 or NTG mice (18% and 19%, respectively). Likewise, K14E7 and K14E6/E7 transgenic mice developed frank cancer (carcinomas) at significantly higher rates (85% and 85%, respectively) than either K14E6 or NTG mice (18% and 10%, respectively). These findings indicate that E7 is the more potent oncogene in anal cancer caused by HPVs. PMID:21999991

40 CFR 81.303 - Arizona.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., R13E 1 X T1N, R14E X T1N, R15E X T1S, R14E 1 X T1S, R141/2E X T1S, R15E X T2N, R13E 1 X T2N, R16E X T1N...); T1S, R14E (sections 124); T1S, R141/2E; and T1S, R15E 11/15/90 Nonattainment 11/15/90 Moderate. Gila...

40 CFR 81.303 - Arizona.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., R13E 1 X T1N, R14E X T1N, R15E X T1S, R14E 1 X T1S, R141/2E X T1S, R15E X T2N, R13E 1 X T2N, R16E X T1N...); T1S, R14E (sections 124); T1S, R141/2E; and T1S, R15E 11/15/90 Nonattainment 11/15/90 Moderate. Gila...

40 CFR 81.303 - Arizona.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., R13E 1 X T1N, R14E X T1N, R15E X T1S, R14E 1 X T1S, R141/2E X T1S, R15E X T2N, R13E 1 X T2N, R16E X T1N...); T1S, R14E (sections 124); T1S, R141/2E; and T1S, R15E 11/15/90 Nonattainment 11/15/90 Moderate. Gila...

A Low Cost Video Display System Using the Motorola 6811 Single-Chip Microcomputer.

DTIC Science & Technology

1986-08-01

EB JSR VIDEO display data;wait for keyentry 0426 E1EB BD E2 4E JSR CLRBUFF clean out buffer 0427 EEE C601 LDAB #1 reset pointer 0428 ElFO D7 02 STAB...E768 Al 00 REGI CMPA OX 1303 E76A 27 OE BEQ REG3 1304 E76C E6 00 LDAB 0,X 1305 E76E 08 INX 1306 E76F Cl 53 CMPB #’S’ 1307 E771 26 15 BNE REGI jump if

Perspective view of Bailey and Massingill Store (4 North E ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Perspective view of Bailey and Massingill Store (4 North E Street, far right of frame), view looking north on E Street. Also visible are General Merchandise Building (8 North E Street), Ousley Furniture Store ( 12 North E Street), Millenery (18 North E Street), Thornton Drug (26 North E Street), B. Reynolds Building (102-106 North E Street), Saloon (108 North E Street), and Langslet Tailor Shop (110-112 North E Street) - Lakeview Downtown Historic District, E, F & G Streets between Second Street North & First Street South, Lakeview, Lake County, OR

The alveolate translation initiation factor 4E family reveals a custom toolkit for translational control in core dinoflagellates.

PubMed

Jones, Grant D; Williams, Ernest P; Place, Allen R; Jagus, Rosemary; Bachvaroff, Tsvetan R

2015-02-10

Dinoflagellates are eukaryotes with unusual cell biology and appear to rely on translational rather than transcriptional control of gene expression. The eukaryotic translation initiation factor 4E (eIF4E) plays an important role in regulating gene expression because eIF4E binding to the mRNA cap is a control point for translation. eIF4E is part of an extended, eukaryote-specific family with different members having specific functions, based on studies of model organisms. Dinoflagellate eIF4E diversity could provide a mechanism for dinoflagellates to regulate gene expression in a post-transcriptional manner. Accordingly, eIF4E family members from eleven core dinoflagellate transcriptomes were surveyed to determine the diversity and phylogeny of the eIF4E family in dinoflagellates and related lineages including apicomplexans, ciliates and heterokonts. The survey uncovered eight to fifteen (on average eleven) different eIF4E family members in each core dinoflagellate species. The eIF4E family members from heterokonts and dinoflagellates segregated into three clades, suggesting at least three eIF4E cognates were present in their common ancestor. However, these three clades are distinct from the three previously described eIF4E classes, reflecting diverse approaches to a central eukaryotic function. Heterokonts contain four clades, ciliates two and apicomplexans only a single recognizable eIF4E clade. In the core dinoflagellates, the three clades were further divided into nine sub-clades based on the phylogenetic analysis and species representation. Six of the sub-clades included at least one member from all eleven core dinoflagellate species, suggesting duplication in their shared ancestor. Conservation within sub-clades varied, suggesting different selection pressures. Phylogenetic analysis of eIF4E in core dinoflagellates revealed complex layering of duplication and conservation when compared to other eukaryotes. Our results suggest that the diverse eIF4E family in core dinoflagellates may provide a toolkit to enable selective translation as a strategy for controlling gene expression in these enigmatic eukaryotes.

Structure and Function of the Catalytic Domain of the Dihydrolipoyl Acetyltransferase Component in Escherichia coli Pyruvate Dehydrogenase Complex*

PubMed Central

Wang, Junjie; Nemeria, Natalia S.; Chandrasekhar, Krishnamoorthy; Kumaran, Sowmini; Arjunan, Palaniappa; Reynolds, Shelley; Calero, Guillermo; Brukh, Roman; Kakalis, Lazaros; Furey, William; Jordan, Frank

2014-01-01

The Escherichia coli pyruvate dehydrogenase complex (PDHc) catalyzing conversion of pyruvate to acetyl-CoA comprises three components: E1p, E2p, and E3. The E2p is the five-domain core component, consisting of three tandem lipoyl domains (LDs), a peripheral subunit binding domain (PSBD), and a catalytic domain (E2pCD). Herein are reported the following. 1) The x-ray structure of E2pCD revealed both intra- and intertrimer interactions, similar to those reported for other E2pCDs. 2) Reconstitution of recombinant LD and E2pCD with E1p and E3p into PDHc could maintain at least 6.4% activity (NADH production), confirming the functional competence of the E2pCD and active center coupling among E1p, LD, E2pCD, and E3 even in the absence of PSBD and of a covalent link between domains within E2p. 3) Direct acetyl transfer between LD and coenzyme A catalyzed by E2pCD was observed with a rate constant of 199 s−1, comparable with the rate of NADH production in the PDHc reaction. Hence, neither reductive acetylation of E2p nor acetyl transfer within E2p is rate-limiting. 4) An unprecedented finding is that although no interaction could be detected between E1p and E2pCD by itself, a domain-induced interaction was identified on E1p active centers upon assembly with E2p and C-terminally truncated E2p proteins by hydrogen/deuterium exchange mass spectrometry. The inclusion of each additional domain of E2p strengthened the interaction with E1p, and the interaction was strongest with intact E2p. E2p domain-induced changes at the E1p active site were also manifested by the appearance of a circular dichroism band characteristic of the canonical 4′-aminopyrimidine tautomer of bound thiamin diphosphate (AP). PMID:24742683

Structure and function of the catalytic domain of the dihydrolipoyl acetyltransferase component in Escherichia coli pyruvate dehydrogenase complex.

PubMed

Wang, Junjie; Nemeria, Natalia S; Chandrasekhar, Krishnamoorthy; Kumaran, Sowmini; Arjunan, Palaniappa; Reynolds, Shelley; Calero, Guillermo; Brukh, Roman; Kakalis, Lazaros; Furey, William; Jordan, Frank

2014-05-30

The Escherichia coli pyruvate dehydrogenase complex (PDHc) catalyzing conversion of pyruvate to acetyl-CoA comprises three components: E1p, E2p, and E3. The E2p is the five-domain core component, consisting of three tandem lipoyl domains (LDs), a peripheral subunit binding domain (PSBD), and a catalytic domain (E2pCD). Herein are reported the following. 1) The x-ray structure of E2pCD revealed both intra- and intertrimer interactions, similar to those reported for other E2pCDs. 2) Reconstitution of recombinant LD and E2pCD with E1p and E3p into PDHc could maintain at least 6.4% activity (NADH production), confirming the functional competence of the E2pCD and active center coupling among E1p, LD, E2pCD, and E3 even in the absence of PSBD and of a covalent link between domains within E2p. 3) Direct acetyl transfer between LD and coenzyme A catalyzed by E2pCD was observed with a rate constant of 199 s(-1), comparable with the rate of NADH production in the PDHc reaction. Hence, neither reductive acetylation of E2p nor acetyl transfer within E2p is rate-limiting. 4) An unprecedented finding is that although no interaction could be detected between E1p and E2pCD by itself, a domain-induced interaction was identified on E1p active centers upon assembly with E2p and C-terminally truncated E2p proteins by hydrogen/deuterium exchange mass spectrometry. The inclusion of each additional domain of E2p strengthened the interaction with E1p, and the interaction was strongest with intact E2p. E2p domain-induced changes at the E1p active site were also manifested by the appearance of a circular dichroism band characteristic of the canonical 4'-aminopyrimidine tautomer of bound thiamin diphosphate (AP). © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Occupational Survey Report AFSC 3E6X1; Operations Management

DTIC Science & Technology

2004-02-01

Lt Bryan Pickett Feb 04 Occupational Survey Report AFSC 3E6X1 Operations Management I n t e g r i t y - S e r v i c e - E x c e l l e n c e...Report AFSC 3E6X1 Operations Management 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK...Nellis AFB NV (5) • Fairchild AFB WA (5) • Hurlburt Field FL (6) • Eglin AFB FL (4) • Ramstein AB (5) Operations Management 3E6X1 February 2004 (Approved

Structure of an E3:E2~Ub Complex Reveals an Allosteric Mechanism Shared among RING/U-box Ligases

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

Pruneda, Jonathan N.; Littlefield, Peter J.; Soss, Sarah E.

2012-09-28

Despite the widespread importance of RING/U-box E3 ubiquitin ligases in ubiquitin (Ub) signaling, the mechanismby which this class of enzymes facilitates Ub transfer remains enigmatic. Here, we present a structural model for a RING/U-box E3:E2~Ub complex poised for Ub transfer. The model and additional analyses reveal that E3 binding biases dynamic E2~Ub ensembles toward closed conformations with enhanced reactivity for substrate lysines. We identify a key hydrogen bond between a highly conserved E3 side chain and an E2 backbone carbonyl, observed in all structures of active RING/ U-Box E3/E2 pairs, as the linchpin for allosteric activation of E2~Ub. The conformationalmore » biasing mechanism is generalizable across diverse E2s and RING/U-box E3s, but is not shared by HECT-type E3s. The results provide a structural model for a RING/ U-box E3:E2~Ub ligase complex and identify the long sought-after source of allostery for RING/UBox activation of E2~Ub conjugates.« less

Reevaluating αE-catenin monomer and homodimer functions by characterizing E-cadherin/αE-catenin chimeras

PubMed Central

Bianchini, Julie M.; Kitt, Khameeka N.; Gloerich, Martijn; Pokutta, Sabine; Weis, William I.

2015-01-01

As part of the E-cadherin–β-catenin–αE-catenin complex (CCC), mammalian αE-catenin binds F-actin weakly in the absence of force, whereas cytosolic αE-catenin forms a homodimer that interacts more strongly with F-actin. It has been concluded that cytosolic αE-catenin homodimer is not important for intercellular adhesion because E-cadherin/αE-catenin chimeras thought to mimic the CCC are sufficient to induce cell–cell adhesion. We show that, unlike αE-catenin in the CCC, these chimeras homodimerize, bind F-actin strongly, and inhibit the Arp2/3 complex, all of which are properties of the αE-catenin homodimer. To more accurately mimic the junctional CCC, we designed a constitutively monomeric chimera, and show that E-cadherin–dependent cell adhesion is weaker in cells expressing this chimera compared with cells in which αE-catenin homodimers are present. Our results demonstrate that E-cadherin/αE-catenin chimeras used previously do not mimic αE-catenin in the native CCC, and imply that both CCC-bound monomer and cytosolic homodimer αE-catenin are required for strong cell–cell adhesion. PMID:26416960

Structural insights into eRF3 and stop codon recognition by eRF1

PubMed Central

Cheng, Zhihong; Saito, Kazuki; Pisarev, Andrey V.; Wada, Miki; Pisareva, Vera P.; Pestova, Tatyana V.; Gajda, Michal; Round, Adam; Kong, Chunguang; Lim, Mengkiat; Nakamura, Yoshikazu; Svergun, Dmitri I.; Ito, Koichi; Song, Haiwei

2009-01-01

Eukaryotic translation termination is mediated by two interacting release factors, eRF1 and eRF3, which act cooperatively to ensure efficient stop codon recognition and fast polypeptide release. The crystal structures of human and Schizosaccharomyces pombe full-length eRF1 in complex with eRF3 lacking the GTPase domain revealed details of the interaction between these two factors and marked conformational changes in eRF1 that occur upon binding to eRF3, leading eRF1 to resemble a tRNA molecule. Small-angle X-ray scattering analysis of the eRF1/eRF3/GTP complex suggested that eRF1's M domain contacts eRF3's GTPase domain. Consistently, mutation of Arg192, which is predicted to come in close contact with the switch regions of eRF3, revealed its important role for eRF1's stimulatory effect on eRF3's GTPase activity. An ATP molecule used as a crystallization additive was bound in eRF1's putative decoding area. Mutational analysis of the ATP-binding site shed light on the mechanism of stop codon recognition by eRF1. PMID:19417105

Structure, Dynamics, and Interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 Examined by Molecular Modeling, Simulation, and Electrostatic Studies

PubMed Central

Bhutani, Isha; Loharch, Saurabh; Gupta, Pawan; Madathil, Rethi; Parkesh, Raman

2015-01-01

The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1) and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2) catalyze epimerization of decaprenylphosporyl ribose (DPR) todecaprenylphosporyl arabinose (DPA) and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA) demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269–330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95–113, 146–157, and 197–226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB) drug discovery and will facilitate drug development efforts against TB. PMID:25789990

Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies.

PubMed

Bhutani, Isha; Loharch, Saurabh; Gupta, Pawan; Madathil, Rethi; Parkesh, Raman

2015-01-01

The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1) and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2) catalyze epimerization of decaprenylphosporyl ribose (DPR) todecaprenylphosporyl arabinose (DPA) and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA) demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269-330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95-113, 146-157, and 197-226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB) drug discovery and will facilitate drug development efforts against TB.

Some novel insights on HPV16 related cervical cancer pathogenesis based on analyses of LCR methylation, viral load, E7 and E2/E4 expressions.

PubMed

Das Ghosh, Damayanti; Bhattacharjee, Bornali; Sen, Shrinka; Premi, Laikangbam; Mukhopadhyay, Indranil; Chowdhury, Rahul Roy; Roy, Sudipta; Sengupta, Sharmila

2012-01-01

This study was undertaken to decipher the interdependent roles of (i) methylation within E2 binding site I and II (E2BS-I/II) and replication origin (nt 7862) in the long control region (LCR), (ii) expression of viral oncogene E7, (iii) expression of the transcript (E7-E1/E4) that encodes E2 repressor protein and (iv) viral load, in human papillomavirus 16 (HPV16) related cervical cancer (CaCx) pathogenesis. The results revealed over-representation (p<0.001) of methylation at nucleotide 58 of E2BS-I among E2-intact CaCx cases compared to E2-disrupted cases. Bisulphite sequencing of LCR revealed overrepresentation of methylation at nucleotide 58 or other CpGs in E2BS-I/II, among E2-intact cases than E2-disrupted cases and lack of methylation at replication origin in case of both. The viral transcript (E7-E1/E4) that produces the repressor E2 was analyzed by APOT (amplification of papillomavirus oncogenic transcript)-coupled-quantitative-RT-PCR (of E7 and E4 genes) to distinguish episomal (pure or concomitant with integrated) from purely integrated viral genomes based on the ratio, E7 C(T)/E4 C(T). Relative quantification based on comparative C(T) (threshold cycle) method revealed 75.087 folds higher E7 mRNA expression in episomal cases over purely integrated cases. Viral load and E2 gene copy numbers were negatively correlated with E7 C(T) (p = 0.007) and E2 C(T) (p<0.0001), respectively, each normalized with ACTB C(T), among episomal cases only. The k-means clustering analysis considering E7 C(T) from APOT-coupled-quantitative-RT-PCR assay, in conjunction with viral load, revealed immense heterogeneity among the HPV16 positive CaCx cases portraying integrated viral genomes. The findings provide novel insights into HPV16 related CaCx pathogenesis and highlight that CaCx cases that harbour episomal HPV16 genomes with intact E2 are likely to be distinct biologically, from the purely integrated viral genomes in terms of host genes and/or pathways involved in cervical carcinogenesis.

CHRIS. Response Methods Handbook.

DTIC Science & Technology

1978-12-01

ssnrlc and a liIiqtiid porn pI to rc novc colicted material, t hereby convcert in ile wSNStcl ii ito a cOn tin iiooS proccss. Most vacuum i systemirs...cid50 PF FGE F G.E P G Forelelud40% P G.E E P Chromic: kcid Eon. P P,F C Foroalehyle G.E E C E P I Citric kid G.E E C E P C Formic kcid 10% F.C.C G.E

X-Ray Spectro-Polarimetry with Photoelectric Polarimeters

NASA Technical Reports Server (NTRS)

Strohmayer, T. E.

2017-01-01

We derive a generalization of forward fitting for X-ray spectroscopy to include linear polarization of X-ray sources, appropriate for the anticipated next generation of space-based photoelectric polarimeters. We show that the inclusion of polarization sensitivity requires joint fitting to three observed spectra, one for each of the Stokes parameters, I(E), U(E), and Q(E). The equations for StokesI (E) (the total intensity spectrum) are identical to the familiar case with no polarization sensitivity, and for which the model-predicted spectrum is obtained by a convolution of the source spectrum, F (E), with the familiar energy response function,(E) R(E,E), where (E) and R(E,E) are the effective area and energy redistribution matrix, respectively. In addition to the energy spectrum, the two new relations for U(E) and Q(E) include the source polarization fraction and position angle versus energy, a(E), and 0(E), respectively, and the model-predicted spectra for these relations are obtained by a convolution with the modulated energy response function, (E)(E) R(E,E), where(E) is the energy-dependent modulation fraction that quantifies a polarimeters angular response to 100 polarized radiation. We present results of simulations with response parameters appropriate for the proposed PRAXyS Small Explorer observatory to illustrate the procedures and methods, and we discuss some aspects of photoelectric polarimeters with relevance to understanding their calibration and operation.

Intricate Crystal Structure of Dihydrolipoamide Dehydrogenase (E3) with its Binding Protein: Multiple Copies, Dynamic and Static Disorders

NASA Technical Reports Server (NTRS)

Makal, A.; Hong, Y. S.; Potter, R.; Vettaikkorumakankauv, A. K.; Korotchkina, L. G.; Patel, M. S.; Ciszak, E.

2004-01-01

Human E3 and binding protein E3BP are two components of the pyruvate dehydrogenase complex. Crystallization of E3 with 221-amino acid fragment of E3BP (E3BPdd) led to crystals that diffracted to a resolution of 2.6 Angstroms. Structure determination involved molecular replacement using a dimer of E3 homolog as a search model and de novo building of the E3BPdd peptide. Solution was achieved by inclusion of one E3 dimer at a time, followed by refinement until five E3 dimers were located. This complete content of E3 provided electron density maps suitable for tracing nine peptide chains of E3BPdd, eight of them being identified with partial occupancies. Final content of the asymmetric unit consists of five E3 dimers, each binding one E3BPdd molecule. In four of these molecular complexes, E3BPdd is in static disorder resulting in E3BPdd binding to either one or the other monomer of the E3 dimer. However, E3BPdd of the fifth E3 dimer forms specific contacts that lock it at one monomer. In addition to this static disorder, E3BPdd reveals high mobility in the limited space of the crystal lattice. Support from NIH and NASA.

The eIF4F and eIFiso4F Complexes of Plants: An Evolutionary Perspective

PubMed Central

Patrick, Ryan M.; Browning, Karen S.

2012-01-01

Translation initiation in eukaryotes requires a number of initiation factors to recruit the assembled ribosome to mRNA. The eIF4F complex plays a key role in initiation and is a common target point for regulation of protein synthesis. Most work on the translation machinery of plants to date has focused on flowering plants, which have both the eIF4F complex (eIF4E and eIF4G) as well as the plant-specific eIFiso4F complex (eIFiso4E and eIFiso4G). The increasing availability of plant genome sequence data has made it possible to trace the evolutionary history of these two complexes in plants, leading to several interesting discoveries. eIFiso4G is conserved throughout plants, while eIFiso4E only appears with the evolution of flowering plants. The eIF4G N-terminus, which has been difficult to annotate, appears to be well conserved throughout the plant lineage and contains two motifs of unknown function. Comparison of eIFiso4G and eIF4G sequence data suggests conserved features unique to eIFiso4G and eIF4G proteins. These findings have answered some questions about the evolutionary history of the two eIF4F complexes of plants, while raising new ones. PMID:22611336

Study of the decays D + → η ( ' ) e + ν e

DOE PAGES

Ablikim, M.; Achasov, M. N.; Ahmed, S.; ...

2018-05-31

The charm semileptonic decays D + → ηe +v e and D + → η'e+v e are studied with a sample of e +e - collision data corresponding to an integrated luminosity of 2.93 fb -1 collected atmore » $$ \\sqrt{s}=3.773 $$ GeV with the BESIII detector. We measure the branching fractions for D+ → ηe+v e to be (10.74 ± 0.81 ± 0.51) x 10 -4, and for D+ → → η'e+v e to be (1.91 ± 0.51 ± 0.13) x 10 -4, where the uncertainties are statistical and systematic, respectively. In addition, we perform a measurement of the form factor in the decay D+ → ηe+v e. All the results are consistent with those obtained by the CLEO-c experiment.« less

Study of the decays D + → η ( ' ) e + ν e

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

Ablikim, M.; Achasov, M. N.; Ahmed, S.

The charm semileptonic decays D + → ηe +v e and D + → η'e+v e are studied with a sample of e +e - collision data corresponding to an integrated luminosity of 2.93 fb -1 collected atmore » $$ \\sqrt{s}=3.773 $$ GeV with the BESIII detector. We measure the branching fractions for D+ → ηe+v e to be (10.74 ± 0.81 ± 0.51) x 10 -4, and for D+ → → η'e+v e to be (1.91 ± 0.51 ± 0.13) x 10 -4, where the uncertainties are statistical and systematic, respectively. In addition, we perform a measurement of the form factor in the decay D+ → ηe+v e. All the results are consistent with those obtained by the CLEO-c experiment.« less

C33-A cells transfected with E6*I or E6*II the short forms of HPV-16 E6, displayed opposite effects on cisplatin-induced apoptosis.

PubMed

Vaisman, Carolina E; Del Moral-Hernandez, Oscar; Moreno-Campuzano, Samadhi; Aréchaga-Ocampo, Elena; Bonilla-Moreno, Raul; Garcia-Aguiar, Israel; Cedillo-Barron, Leticia; Berumen, Jaime; Nava, Porfirio; Villegas-Sepúlveda, Nicolas

2018-03-02

The HPV-16 E6/E7 bicistronic immature transcript produces 4 mature RNAs: the unspliced HPV-16 E6/E7 pre-mRNA product and 3 alternatively spliced mRNAs. The 3 spliced mRNAs encode short forms of the E6 oncoprotein, namely E6*I, E6*II and E6^E7. In this study we showed that transfection of C-33A cells with monocistronic constructs of these cDNAs fused to GFP, produced different effects on apoptosis, after the treatment with cisplatin. Transfection of C-33A cells with the full-length E6-GFP oncoprotein resulted in a 50% decrease in cell death, while the transfection with the E6*I-GFP construct showed only a 25% of diminution of cell death, compared to the control cells. Transfection with the E6^E7-GFP or E7-GFP construct had no effect on the number of the apoptotic cells, compared with control cells. Conversely, transfection with the E6*II construct resulted in higher cell death than the control cells. Taken together, these results suggested that E6*I or E6*II, the short forms of HPV-16 E6, displayed opposite effects on cisplatin-induced apoptosis, when transfected in C-33A cells. Copyright © 2018 Elsevier B.V. All rights reserved.

20-Hydroxyecdysone (20E) Primary Response Gene E93 Modulates 20E Signaling to Promote Bombyx Larval-Pupal Metamorphosis*

PubMed Central

Liu, Xi; Dai, Fangyin; Guo, Enen; Li, Kang; Ma, Li; Tian, Ling; Cao, Yang; Zhang, Guozheng; Palli, Subba R.; Li, Sheng

2015-01-01

As revealed in a previous microarray study to identify genes regulated by 20-hydroxyecdysone (20E) and juvenile hormone (JH) in the silkworm, Bombyx mori, E93 expression in the fat body was markedly low prior to the wandering stage but abundant during larval-pupal metamorphosis. Induced by 20E and suppressed by JH, E93 expression follows this developmental profile in multiple silkworm alleles. The reduction of E93 expression by RNAi disrupted 20E signaling and the 20E-induced autophagy, caspase activity, and cell dissociation in the fat body. Reducing E93 expression also decreased the expression of the 20E-induced pupal-specific cuticle protein genes and prevented growth and differentiation of the wing discs. Importantly, the two HTH domains in E93 are critical for inducing the expression of a subset of 20E response genes, including EcR, USP, E74, Br-C, and Atg1. By contrast, the LLQHLL and PLDLSAK motifs in E93 inhibit its transcriptional activity. E93 binds to the EcR-USP complex via a physical association with USP through its LLQHLL motif; and this association is enhanced by 20E-induced EcR-USP interaction, which attenuates the transcriptional activity of E93. E93 acts through the two HTH domains to bind to GAGA-containing motifs present in the Atg1 promoter region for inducing gene expression. In conclusion, E93 transcriptionally modulates 20E signaling to promote Bombyx larval-pupal metamorphosis. PMID:26378227

20-Hydroxyecdysone (20E) Primary Response Gene E93 Modulates 20E Signaling to Promote Bombyx Larval-Pupal Metamorphosis.

PubMed

Liu, Xi; Dai, Fangyin; Guo, Enen; Li, Kang; Ma, Li; Tian, Ling; Cao, Yang; Zhang, Guozheng; Palli, Subba R; Li, Sheng

2015-11-06

As revealed in a previous microarray study to identify genes regulated by 20-hydroxyecdysone (20E) and juvenile hormone (JH) in the silkworm, Bombyx mori, E93 expression in the fat body was markedly low prior to the wandering stage but abundant during larval-pupal metamorphosis. Induced by 20E and suppressed by JH, E93 expression follows this developmental profile in multiple silkworm alleles. The reduction of E93 expression by RNAi disrupted 20E signaling and the 20E-induced autophagy, caspase activity, and cell dissociation in the fat body. Reducing E93 expression also decreased the expression of the 20E-induced pupal-specific cuticle protein genes and prevented growth and differentiation of the wing discs. Importantly, the two HTH domains in E93 are critical for inducing the expression of a subset of 20E response genes, including EcR, USP, E74, Br-C, and Atg1. By contrast, the LLQHLL and PLDLSAK motifs in E93 inhibit its transcriptional activity. E93 binds to the EcR-USP complex via a physical association with USP through its LLQHLL motif; and this association is enhanced by 20E-induced EcR-USP interaction, which attenuates the transcriptional activity of E93. E93 acts through the two HTH domains to bind to GAGA-containing motifs present in the Atg1 promoter region for inducing gene expression. In conclusion, E93 transcriptionally modulates 20E signaling to promote Bombyx larval-pupal metamorphosis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Non-coding RNA derived from the region adjacent to the human HO-1 E2 enhancer selectively regulates HO-1 gene induction by modulating Pol II binding

PubMed Central

Maruyama, Atsushi; Mimura, Junsei; Itoh, Ken

2014-01-01

Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation. However, it remains unclear whether eRNAs are involved in the regulation of human heme oxygenase-1 gene (HO-1) induction. Here, we report that multiple nuclear-enriched eRNAs are transcribed from the regions adjacent to two human HO-1 enhancers (i.e. the distal E2 and proximal E1 enhancers), and some of these eRNAs are induced by the oxidative stress-causing reagent diethyl maleate (DEM). We demonstrated that the expression of one forward direction (5′ to 3′) eRNA transcribed from the human HO-1 E2 enhancer region (named human HO-1enhancer RNA E2-3; hereafter called eRNA E2-3) was induced by DEM in an NRF2-dependent manner in HeLa cells. Conversely, knockdown of BACH1, a repressor of HO-1 transcription, further increased DEM-inducible eRNA E2-3 transcription as well as HO-1 expression. In addition, we showed that knockdown of eRNA E2-3 selectively down-regulated DEM-induced HO-1 expression. Furthermore, eRNA E2-3 knockdown attenuated DEM-induced Pol II binding to the promoter and E2 enhancer regions of HO-1 without affecting NRF2 recruitment to the E2 enhancer. These findings indicate that eRNAE2-3 is functional and is required for HO-1 induction. PMID:25404134

Enhanced vector borne disease surveillance of California Culex mosquito populations reveals spatial and species-specific barriers of infection.

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

VanderNoot, Victoria A.; Curtis, Deanna Joy; Koh, Chung-Yan

Monitor i ng in f ectio n s in v ect o rs su c h as m osquit o es, s a nd fl i es, tsetse fl i es, a nd ticks to i denti f y hu m a n path o gens m a y s e r v e as a n ear l y w arn i ng det e ction system t o dir e ct loc a l g o v er n ment dise a se pr e v en t i v e m easu r e s . Onemore » major hurdle i n de t ection is the abi l i t y to scre e n l arge n u mbers of v e c t ors for h uman patho g ens w i thout t h e u s e of ge n o t y pe - s p ecific m o lecu l ar tec h nique s . N e x t genera t ion s equ e nc i ng (NG S ) pr o v i des a n unbi a sed p latfo r m capab l e of identi f y i ng k n o w n a n d unk n o w n p ath o ge n s circula t ing w i thin a v e ctor p opul a tion, but utili z ing t h is te c h nolo g y i s tim e - con s u ming a n d cos t l y for v ecto r -b o rne disease su r v e illan c e pr o gra m s. T o addr e s s this w e d e v e lop e d cos t -eff e ct i v e Ilumina(r) R NA- S eq l i bra r y p r epara t ion m e thodol o gies i n con j u n ction w i t h an automa t ed c ompu t at i onal a n a l y sis pipel i n e to ch a racter i ze t h e microbial popula t ions c ircula t i n g in Cu l e x m o squit o e s (Cul e x qui n quef a s c iatu s , C ul e x quinq u efasc i atus / pip i ens co m pl e x h y bri d s, and C u l e x ta r salis ) t hroug h out Californ i a. W e assembled 2 0 n o vel a n d w e l l -do c ume n ted a r b o v i ruses repres e nting mem b e rs of B u n y a v ir i da e , F l a v i virid a e, If a virida e , Meson i v i rida e , Nid o v iri d ae, O rtho m y x o virid a e, Pa r v o v iri d ae, Re o virid a e, R h a b d o v i rid a e, T y m o v iri d ae, a s w ell as s e v e r al u n assi g n e d v irus e s . In addit i o n, w e m app e d mRNA s pecies to d i vergent s peci e s of t r y panos o ma a nd pl a s modium eu k a r yotic parasit e s and cha r a c terized t he p r oka r yot i c microb i al c o mposit i on to i d enti f y bacteri a l tran s c r ipts der i v ed from wolba c hia, clo s tridi u m, m y c oplas m a, fusoba c terium and c am p y l o bacter bac t er i al spec i e s . W e utilized the s e mic r obial transcri p tomes pre s e nt in g e ogra p hical l y defined Cul e x po p ul a tions to defi n e spatial and m osqui t o specie s -spec i fic ba r r iers of i n fecti o n. T he v i r ome and microbi o me c o mpos i tion id e ntified in e ach mosqui t o p o ol pr o v i ded suf f icient resolut i on to dete r m i ne both the mosq u ito species and the g e o graphic regi o n in Californ i a w h e re t h e mosqui t o po o l orig i n ated. T his d a ta pr o v i des ins i ght in t o the compl e x i t y of microb i al spec i es cir c ulati n g in med i cal l y i mport a nt Culex mosqui t oes a nd t h eir potent i al im p act o n t he tran s missi o n of v ector-b o rne human / veter i na r y p a t hogens in C a liforn i a.« less

The Human Papillomavirus E6 Oncogene Dysregulates the Cell Cycle and Contributes to Cervical Carcinogenesis through Two Independent Activities

PubMed Central

Shai, Anny; Brake, Tiffany; Somoza, Chamorro; Lambert, Paul F.

2010-01-01

Cervical cancer is a leading cause of death due to cancer among women worldwide. Using transgenic mice to dissect the contributions of the human papillomavirus (HPV) 16 E6 and E7 oncogenes in cervical cancer, E7 was identified previously to be the dominant oncogene. Specifically, when treated with exogenous estrogen for 6 months, E7 transgenic mice developed cancer throughout the reproductive tract, but E6 transgenic mice did not. E6 contributed to carcinogenesis of the reproductive tract, as E6/E7 double transgenic mice treated for 6 months with estrogen developed larger cancers than E7 transgenic mice. In the current study, we investigated whether the E6 oncogene alone could cooperate with estrogen to induce cervical cancer after an extended estrogen treatment period of 9 months. We found that the E6 oncogene synergizes with estrogen to induce cervical cancer after 9 months, indicating that E6 has a weaker but detectable oncogenic potential in the reproductive tract compared with the E7 oncogene. Using transgenic mice that express mutant forms of HPV16 E6, we determined that the interactions of E6 with cellular α-helix and PDZ partners correlate with its ability to induce cervical carcinogenesis. In analyzing the tumors arising in E6 transgenic mice, we learned that E6 induces expression of the E2F-responsive genes, Mcm7 and cyclin E, in the absence of the E7 oncogene. E6 also prevented the expression of p16 in tumors of the reproductive tract through a mechanism mediated by the interaction of E6 with α-helix partners. PMID:17308103

Paradoxical effects of 137Cs irradiation on pharmacological stimulation of reactive oxygen species in hippocampal slices from apoE2 and apoE4 mice.

PubMed

Villasana, Laura E; Akinyeke, Tunde; Weber, Sydney; Raber, Jacob

2017-09-29

In humans, apoE, which plays a role in repair, is expressed in three isoforms: E2, E3, and E4. E4 is a risk factor for age-related cognitive decline (ACD) and Alzheimer's disease (AD), particularly in women. In contrast, E2 is a protective factor for ACD and AD. E2 and E4 might also differ in their response to cranial 137 Cs irradiation, a form of radiation typically used in a clinical setting for the treatment of cancer. This might be mediated by reactive oxygen species (ROS) in an-apoE isoform-dependent fashion. E2 and E4 female mice received sham-irradiation or cranial irradiation at 8 weeks of age and a standard mouse chow or a diet supplemented with the antioxidant alpha-lipoic acid (ALA) starting at 6 weeks of age. Behavioral and cognitive performance of the mice were assessed 12 weeks later. Subsequently, the generation of ROS in hippocampal slices was analyzed. Compared to sham-irradiated E4 mice, irradiated E4 mice showed enhanced spatial memory in the water maze. This was associated with increased hippocampal PMA-induction of ROS. Similar effects were not seen in E2 mice. Irradiation increased endogenous hippocampal ROS levels in E2 mice while decreasing those in E4 mice. NADPH activity and MnSOD levels were higher in sham-irradiated E2 than E4 mice. Irradiation increased NADPH activity and MnSOD levels in hemi brains of E4 mice but not in those of E2 mice. ALA did not affect behavioral and cognitive performance or hippocampal formation of ROS in either genotype. Thus, apoE isoforms modulate the radiation response.

Binding of an antibody mimetic of the human low density lipoprotein receptor to apolipoprotein E is governed through electrostatic forces. Studies using site-directed mutagenesis and molecular modeling.

PubMed

Raffaï, R; Weisgraber, K H; MacKenzie, R; Rupp, B; Rassart, E; Hirama, T; Innerarity, T L; Milne, R

2000-03-10

Monoclonal antibody 2E8 is specific for an epitope that coincides with the binding site of the low density lipoprotein receptor (LDLR) on human apoE. Its reactivity with apoE variants resembles that of the LDLR: it binds well with apoE3 and poorly with apoE2. The heavy chain complementarity-determining region (CDRH) 2 of 2E8 shows homology to the ligand-binding domain of the LDLR. To define better the structural basis of the 2E8/apoE interaction and particularly the role of electrostatic interactions, we generated and characterized a panel of 2E8 variants. Replacement of acidic residues in the 2E8 CDRHs showed that Asp(52), Glu(53), and Asp(56) are essential for high-affinity binding. Although Asp(31) (CDRH1), Glu(58) (CDRH2), and Asp(97) (CDRH3) did not appear to be critical, the Asp(97) --> Ala variant acquired reactivity with apoE2. A Thr(57) --> Glu substitution increased affinity for both apoE3 and apoE2. The affinities of wild-type 2E8 and variants for apoE varied inversely with ionic strength, suggesting that electrostatic forces contribute to both antigen binding and isoform specificity. We propose a model of the 2E8.apoE immune complex that is based on the 2E8 and apoE crystal structures and that is consistent with the apoE-binding properties of wild-type 2E8 and its variants. Given the similarity between the LDLR and 2E8 in terms of specificity, the LDLR/ligand interaction may also have an important electrostatic component.

Antibiotic drug rifabutin is effective against lung cancer cells by targeting the eIF4E-β-catenin axis

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

Li, Ji; Huang, Yijiang; Gao, Yunsuo

The essential roles of overexpression of eukaryotic translation initiation factor 4E (eIF4E) and aberrant activation of β-catenin in lung cancer development have been recently identified. However, whether there is a direct connection between eIF4E overexpression and β-catenin activation in lung cancer cells is unknown. In this study, we show that antibiotic drug rifabutin targets human lung cancer cells via inhibition of eIF4E-β-catenin axis. Rifabutin is effectively against lung cancer cells in in vitro cultured cells and in vivo xenograft mouse model through inhibiting proliferation and inducing apoptosis. Mechanistically, eIF4E regulates β-catenin activity in lung cancer cells as shown by the increased β-cateninmore » phosphorylation and activity in cells overexpressing eIF4E, and furthermore that the regulation is dependent on phosphorylation at S209. Rifabutin suppresses eIF4E phosphorylation, leads to decreased β-catenin phosphorylation and its subsequent transcriptional activities. Depletion of eIF4E abolishes the inhibitory effects of rifabutin on β-catenin activities and overexpression of β-catenin reverses the inhibitory effects of rifabutin on cell growth and survival, further confirming that rifabutin acts on lung cancer cells via targeting eIF4E- β-catenin axis. Our findings identify the eIF4E- β-catenin axis as a critical regulator of lung cancer cell growth and survival, and suggest that its pharmacological inhibition may be therapeutically useful in lung cancer. - Highlights: • Rifabutin targets EGFR-mutated lung cancer cells in vitro and in vivo. • eIF4E phosphorylation regulates β-catenin activity in lung cancer cells. • Rifabutin acts on lung cancer cells via eIF4E- β-catenin axis. • Rifabutin can be repurposed for lung cancer treatment.« less

40 CFR Figure E-2 to Subpart E of... - Product Manufacturing Checklist

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 5 2011-07-01 2011-07-01 false Product Manufacturing Checklist E Figure E-2 to Subpart E of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Equivalent Methods for PM2.5 or PM10â2.5 Pt. 53, Subpt. E, Fig. E-2 Figure E-2 to Subpart E of Part 53...

40 CFR Figure E-2 to Subpart E of... - Product Manufacturing Checklist

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Product Manufacturing Checklist E Figure E-2 to Subpart E of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Equivalent Methods for PM2.5 or PM10â2.5 Pt. 53, Subpt. E, Fig. E-2 Figure E-2 to Subpart E of Part 53...

High eIF4E, VEGF, and Microvessel Density in Stage I to III Breast Cancer

PubMed Central

Byrnes, Kerry; White, Stephen; Chu, Quyen; Meschonat, Carol; Yu, Herbert; Johnson, Lester W.; DeBenedetti, Arrigo; Abreo, Fleurette; Turnage, Richard H.; McDonald, John C.; Li, Benjamin D.

2006-01-01

Objective: In a prospective trial, to determine if eIF4E overexpression in breast cancer specimens is correlated with VEGF elevation, increased tumor microvessel density (MVD) counts, and a worse clinical outcome irrespective of nodal status. Summary and Background Data: In vitro, the overexpression of eukaryotic initiation factor 4E (eIF4E) up-regulates the translation of mRNAs with long 5′-untranslated regions (5′-UTRs). One such gene product is the vascular endothelial growth factor (VEGF). Methods: A total of 114 stage I to III breast cancer patients were prospectively accrued and followed with a standardized clinical surveillance protocol. Cancer specimens were quantified for eIF4E, VEGF, and MVD. Outcome endpoints were cancer recurrence and cancer-related death. Results: eIF4E overexpression was found in all cancer specimens (mean ± SD, 12.5 ± 7.6-fold). Increasing eIF4E overexpression correlated with increasing VEGF elevation (r = 0.24, P = 0.01, Spearman's coefficient), and increasing MVD counts (r = 0.35, P < 0.0002). Patients whose tumor had high eIF4E overexpression had shorter disease-free survival (P = 0.004, log-rank test) and higher cancer-related deaths (P = 0.002) than patients whose tumors had low eIF4E overexpression. Patients with high eIF4E had a hazard ratio for cancer recurrence and cancer-related death of 1.8 and 2.1 times that of patients with low eIF4E (respectively, P = 0.009 and P = 0.002, Cox proportional hazard model). Conclusions: In breast cancer patients, increasing eIF4E overexpression in the cancer specimens correlates with higher VEGF levels and MVD counts. Patients whose tumors had high eIF4E overexpression had a worse clinical outcome, independent of nodal status. Thus, eIF4E overexpression in breast cancer appears to predict increased tumor vascularity and perhaps cancer dissemination by hematogenous means. PMID:16633004

Availability, Price, and Packaging of Electronic Cigarettes and E-Liquids in Guatemala City Retailers.

PubMed

Chacon, Violeta; Arriaza, Astrid; Cavazos-Rehg, Patricia; Barnoya, Joaquin

2018-01-05

Electronic cigarettes (e-cigarettes) have the potential to normalize smoking and undermine tobacco control efforts. However, if well regulated, they also have a potential as smoking cessation aids. This study sought to determine the availability and types of e-cigarettes and e-liquids in Guatemala. We also assessed packaging characteristics and price. We surveyed a convenient sample of 39 Guatemala City retailers and purchased all e-cigarettes and e-liquids available. Duplicate samples (same brand, e-liquid type, flavor, nicotine content, or packaging) were purchased when prices were different between each other. Country of manufacture, flavor, expiration date, nicotine concentration, and price were recorded. We also documented package marketing strategies and warning labels. We purchased 64 e-cigarettes (53 unique and 11 duplicates) and 57 e-liquids (52 unique and 5 duplicates), mostly found on mall retailers. Most e-cigarettes (42, 66%) were first generation, followed by second (18, 28%) and third generations (4, 6%). Price of e-cigarettes differed significantly by generation. Most e-cigarettes (31, 58%) and 24 (46%) e-liquids did not include warning labels. Nicotine content was reported in 21 (39%) e-cigarettes that included e-liquids and 41 (79%) e-liquids' packages. E-cigarettes and e-liquids are available among a variety of retailers in Guatemala City and the industry is taking advantage of the fact that they are not regulated (eg, health claims, minimum sales age, and taxation). Our findings support the need for further research on e-cigarettes and e-liquids in Guatemala. To the best of our knowledge, this is the first study describing e-cigarettes and e-liquids available in retailers in a low/middle-income country like Guatemala. E-cigarettes and e-liquids were found in a variety of types, flavors, and nicotine concentrations in Guatemalan retailers. Our findings support the need for further research on e-cigarettes and e-liquids in Guatemala. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis.

PubMed

Dennis, Michael D; Jefferson, Leonard S; Kimball, Scot R

2012-12-14

Modulation of mRNA binding to the 40 S ribosomal subunit during translation initiation controls not only global rates of protein synthesis but also regulates the pattern of protein expression by allowing for selective inclusion, or exclusion, of mRNAs encoding particular proteins from polysomes. The mRNA binding step is modulated by signaling through a protein kinase known as the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 directly phosphorylates the translational repressors eIF4E binding proteins (4E-BP) 1 and 2, releasing them from the mRNA cap binding protein eIF4E, thereby promoting assembly of the eIF4E·eIF4G complex. mTORC1 also phosphorylates the 70-kDa ribosomal protein S6 kinase 1 (p70S6K1), which subsequently phosphorylates eIF4B, and programmed cell death 4 (PDCD4), which sequesters eIF4A from the eIF4E·eIF4G complex, resulting in repressed translation of mRNAs with highly structured 5'-untranslated regions. In the present study, we compared the role of the 4E-BPs in the regulation of global rates of protein synthesis to that of eIF4B and PDCD4. We found that maintenance of eIF4E interaction with eIF4G was not by itself sufficient to sustain global rates of protein synthesis in the absence of mTORC1 signaling to p70S6K1; phosphorylation of both eIF4B and PDCD4 was additionally required. We also found that the interaction of eIF4E with eIF4G was maintained in the liver of fasted rats as well as in serum-deprived mouse embryo fibroblasts lacking both 4E-BP1 and 4E-BP2, suggesting that the interaction of eIF4G with eIF4E is controlled primarily through the 4E-BPs.

Elmohardyia Rafael (Diptera, Pipunculidae) from northeastern Brazil: new records and description of new species.

PubMed

Marques, Dayse W A; Rafael, José A

2015-06-12

Eleven species of Elmohardyia are recorded for the first time in northeastern Brazil, the most arid Brazilian region. There are two new records, E. lindneri (Collin) and E. trinidadensis (Hardy), and nine new species, which are here described and illustrated: Elmohardyia cearensis sp. nov.; E. cheliformis sp. nov.; E. distincta sp. nov.; E. formosa sp. nov.; E. limeirai sp. nov.; E. martae sp. nov.; E. potiguar sp. nov.; E. quadricornis sp. nov. and E. rosalinae sp. nov.

A Lightweight TwiddleNet Portal

DTIC Science & Technology

2008-03-01

MAC PHY Media Independent Handover Function (Network)ES CS IS 802 Interface Client Station 802 Networks 3GPP 3 GPP 2 Network MIH Network...Entity ( . e g ). MIH Server Controller Media Independent Handover Function (Client) Information Service over L2 Transport Remote MIH Events over L2...Co-located with MIH MGMTMGMT E v e n t s E S C S IS E v e n t s E v e n t s E v e n t s Media Independent Handover User Media

Current Military Needs. War Gaming Department Perspectives, Connections 2008

DTIC Science & Technology

2008-03-12

competitive U 1 : E x t r e m i s m d i s e m p o w e r e d / p a s s i v e s u p e r e m p o w e r e d...Current Military Needs War Gaming Department Perspectives Connections 2008 Stephen Downes-Martin, Ph.D. Professor, Center for Naval Warfare Studies...policy of the War Gaming Department, the CNWS, the U.S. Naval War College, the U.S. Navy,

Achieving Generality over Conditions: Combining the Multitrait Multimethod Matrix and the Representative Design of Experiments.

DTIC Science & Technology

1984-08-02

We take that aim to have been achieved in principle (no one has challenged it), if not in practice. We aim therefore to build upon that achievement by...NJ + (J + C~ C + 2 C EU E E 4-)C o.C ~ ~+ (NJ + (N Er E o - ~.. ~____ U) C fl - C C C CE E le E0 I0 U.- E EEa E - Ui Ei . U (alKE E E E 2 2- 2 E Ca...RESEARCH Engineering Psychology Group • TECHNICAL REPORTS DISTRIBUTION LIST OSD Department of the Nay CAPT Paul R. Chatelier Tactical Development

Architecture of an Integrated Microelectronic Warfare System-on-a-Chip and Design of Key Components

DTIC Science & Technology

2004-12-01

N -modulus case results in 0 1 2 3 4 ( ii i i i i i i m e s s s s s s 1)−= + + + +L , (5.55) for an even modulus, and 0 1 2 3 4 ( 2) (i ii i...2 2 3 2 2 1 1 0 1 , , , , . N N N N N N N MRSS e e MRSS e e MRSS e e MRSS e e MRSS e e − − 1− − − = ⊕ = ⊕ = ⊕ = ⊕ = ⊕ M (5.58) Like the

Process Characterization of Electrical Discharge Machining of Highly Doped Silicon

DTIC Science & Technology

2012-06-01

EEE .! E# EEE @! E#EEEI! E#EEEJ! E# EE "! E# EE ".! E# EE "@! E# EE "I! E# EE "J! $L! $U! 07$(L<--B(L$B(F-O(D1$(ZL]\\(E[( GMU! GML! 64... EE ! LFE# EE ! L@F# EE ! L@E# EE ! L<F# EE ! L<E# EE ! L.F# EE ! &*6)! M! NDO! D! %A! DP! N5P! /G! G! LY > (Z B ; [( G&’=41416(D1ɟ$(H&%&C-$-%( IEFG(N.76=416(LY...roughing experiment. Surface roughness measurements ranged from just over 24

Power Analysis Tutorial for Experimental Design Software

DTIC Science & Technology

2014-11-01

I N S T I T U T E F O R D E F E N S E A N A L Y S E S IDA Document D-5205 November 2014 Power Analysis Tutorial for Experimental Design Software...16) [Jun 2013]. I N S T I T U T E F O R D E F E N S E A N A L Y S E S IDA Document D-5205 Power Analysis Tutorial for Experimental Design ...Test and Evaluation (T&E) community is increasing its employment of Design of Experiments (DOE), a rigorous methodology for planning and evaluating

A Coupled Creep Plasticity Model for Residual Stress Relaxation of a Shot Peened Nickel-Base Superalloy (Postprint)

DTIC Science & Technology

2008-09-01

titanium - and nickel-base alloys [1- 2,5- 6 ]. For applications that utilize aluminum and titanium alloys, subjected to moderate temperatures and...reaching the target stress for creep. 1e-9 1e-8 1e-7 1e- 6 1e-5 1e- 4 1e-3 1e-2 1e-1 1e-3 1e-2 1e-1 -1% Prestrain 0% Prestrain +1% Prestrain +5...was adapted to a rate-independent nonlinear isotropic-kinematic hardening model described by Dodds [30]. 10-9 10-8 10-7 10- 6 10-5 10- 4 10-3 10-2 10

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Science.gov Websites

m n _ 5 0 m _ m e t a d a t a _ f i l e s / f i l e l i s t . x m l " > < l i n k r e l = E d i t - T i m e - D a t a h r e f = " m n _ 5 0 m _ m e t a d a t a _ f i l e s / e d i t d a t a . m s o " > < ! - - [ i f ! m s o ] > < s t y l e > v \\ : * { b e h a v i o

Department of Defense Youth Poll Wave 10 - December 2005. Overview Report

DTIC Science & Technology

2006-07-01

Fishbein , M . & Ajzen , I . (1975). Belief, attitude, intention and behavior: An introduction to theory...a n d E x p e c t e d O u t c o m e s A s s o c ia t e d w it h M il i t a r y S e r v ic e I n f lu e n c e r s M i l i t a r y B e l ie...f s a n d Y o u t h M o t iv a t io n t o C o m p ly Y o u t h A t t i t u d e s N o r m s Y o u t h C o n f id e n c e in S u c c e s

An Experimental Investigation of Techniques to Suppress Edgetones from Perforated Wind Tunnel Walls

DTIC Science & Technology

1975-08-01

s e e m i t t e d by the p e r f o r a t e d wa l l s h a s b e e n u n d e r s t udy f o r s e v e r a l y e a r s at AEDC. A r e c e...ld at low supe r son i c speeds . Actual s amples of pe r fo ra t ed walls f r o m the t h ree t r a n s o n i c tunnels were t es ted...c t i o n flow and wal l angle that gave a r e a s o n a b l y f la t axia l Mach n u m b e r d i s t r i b u t i o n t h roughou t the

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

Fields, Whitney; Kielian, Margaret, E-mail: margaret.kielian@einstein.yu.edu

The alphavirus membrane protein E1 mediates low pH-triggered fusion of the viral and endosome membranes during virus entry. During virus biogenesis E1 associates as a heterodimer with the transmembrane protein p62. Late in the secretory pathway, cellular furin cleaves p62 to the mature E2 protein and a peripheral protein E3. E3 remains bound to E2 at low pH, stabilizing the heterodimer and thus protecting E1 from the acidic pH of the secretory pathway. Release of E3 at neutral pH then primes the virus for fusion during entry. Here we used site-directed mutagenesis and revertant analysis to define residues important formore » the interactions at the E3–E2 interface. Our data identified a key residue, E2 W235, which was required for E1 pH protection and alphavirus production. Our data also suggest additional residues on E3 and E2 that affect their interacting surfaces and thus influence the pH protection of E1 during alphavirus exit.« less

Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells.

PubMed

Avdulov, Svetlana; Li, Shunan; Michalek, Van; Burrichter, David; Peterson, Mark; Perlman, David M; Manivel, J Carlos; Sonenberg, Nahum; Yee, Douglas; Bitterman, Peter B; Polunovsky, Vitaly A

2004-06-01

Common human malignancies acquire derangements of the translation initiation complex, eIF4F, but their functional significance is unknown. Hypophosphorylated 4E-BP proteins negatively regulate eIF4F assembly by sequestering its mRNA cap binding component eIF4E, whereas hyperphosphorylation abrogates this function. We found that breast carcinoma cells harbor increases in the eIF4F constituent eIF4GI and hyperphosphorylation of 4E-BP1 which are two alterations that activate eIF4F assembly. Ectopic expression of eIF4E in human mammary epithelial cells enabled clonal expansion and anchorage-independent growth. Transfer of 4E-BP1 phosphorylation site mutants into breast carcinoma cells suppressed their tumorigenicity, whereas loss of these 4E-BP1 phosphorylation site mutants accompanied spontaneous reversion to a malignant phenotype. Thus, eIF4F activation is an essential component of the malignant phenotype in breast carcinoma.

Structure of the Human FANCL RING-Ube2T Complex Reveals Determinants of Cognate E3-E2 Selection

PubMed Central

Hodson, Charlotte; Purkiss, Andrew; Miles, Jennifer Anne; Walden, Helen

2014-01-01

Summary The combination of an E2 ubiquitin-conjugating enzyme with an E3 ubiquitin-ligase is essential for ubiquitin modification of a substrate. Moreover, the pairing dictates both the substrate choice and the modification type. The molecular details of generic E3-E2 interactions are well established. Nevertheless, the determinants of selective, specific E3-E2 recognition are not understood. There are ∼40 E2s and ∼600 E3s giving rise to a possible ∼24,000 E3-E2 pairs. Using the Fanconi Anemia pathway exclusive E3-E2 pair, FANCL-Ube2T, we report the atomic structure of the FANCL RING-Ube2T complex, revealing a specific and extensive network of additional electrostatic and hydrophobic interactions. Furthermore, we show that these specific interactions are required for selection of Ube2T over other E2s by FANCL. PMID:24389026

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

Educational storylines in entertainment television: audience reactions toward persuasive strategies in medical dramas.

PubMed

Asbeek Brusse, Elsbeth D; Fransen, Marieke L; Smit, Edith G

2015-04-01

Medical television drama series provide an important source of health information. This form of entertainment-education (E-E) can be used to influence knowledge, attitudes, and behaviors toward health-related issues. In the literature, E-E is generally regarded as a persuasive strategy in itself, whereas in an increasing number of E-E programs, several different persuasive strategies are used. An important question is how the audience ethically evaluates these strategies. The aim of the present study is to examine viewers' ethical judgments toward the use of three persuasive strategies in E-E: product placement, framing, and persuasion toward a controversial position. A survey among 525 viewers of 5 popular medical dramas demonstrates that viewers evaluate the use of the currently investigated attitudinal statements about potential persuasive strategies in E-E as being immoral and that viewers prefer neutral storylines. Adopting a strategy that viewers find inappropriate may interfere with the intended prosocial effects of E-E. A broader understanding of the appropriate and inappropriate uses of persuasive strategies in E-E is indispensable for effective E-E productions.

(E,E)-alpha-farnesene, an alarm pheromone of the termite Prorhinotermes canalifrons.

PubMed

Sobotník, Jan; Hanus, Robert; Kalinová, Blanka; Piskorski, Rafal; Cvacka, Josef; Bourguignon, Thomas; Roisin, Yves

2008-04-01

The behavioral and electroantennographic responses of Prorhinotermes canalifrons to its soldier frontal gland secretion, and two separated major components of the secretion, (E)-1-nitropentadec-1-ene and (E,E)-alpha-farnesene, were studied in laboratory experiments. Behavioral experiments showed that both the frontal gland secretion and (E,E)-alpha-farnesene triggered alarm reactions in P. canalifrons, whereas (E)-1-nitropentadec-1-ene did not affect the behavior of termite groups. The alarm reactions were characterized by rapid walking of activated termites and efforts to alert and activate other members of the group. Behavioral responses to alarm pheromone differed between homogeneous and mixed groups, suggesting complex interactions. Antennae of both soldiers and pseudergates were sensitive to the frontal gland secretion and to (E,E)-alpha-farnesene, but soldiers showed stronger responses. The dose responses to (E,E)-alpha-farnesene were identical for both soldiers and pseudergates, suggesting that both castes use similar receptors to perceive (E,E)-alpha-farnesene. Our data confirm (E,E)-alpha-farnesene as an alarm pheromone of P. canalifrons.

A role for HPV16 E5 in cervical carcinogenesis.

PubMed

Maufort, John P; Shai, Anny; Pitot, Henry C; Lambert, Paul F

2010-04-01

A subset of the mucosotropic human papillomaviruses (HPV), including HPV16, are etiologic agents for the vast majority of cervical cancers, other anogenital cancers, and a subset of head and neck squamous cell carcinomas. HPV16 encodes three oncogenes: E5, E6, and E7. Although E6 and E7 have been well-studied and clearly shown to be important contributors to these cancers, less is known about E5. In this study, we used E5 transgenic mice to investigate the role of E5 in cervical cancer. When treated for 6 months with estrogen, a cofactor for cervical carcinogenesis, E5 transgenic mice developed more severe neoplastic cervical disease than similarly treated nontransgenic mice, although no frank cancers were detected. In addition, E5 when combined with either E6 or E7 induced more severe neoplastic disease than seen in mice expressing only one viral oncogene. Prolonged treatment of E5 transgenic mice with exogenous estrogen uncovered an ability of E5 to cause frank cancer. These data indicate that E5 acts as an oncogene in the reproductive tracts of female mice.

Dominant role of HPV16 E7 in anal carcinogenesis.

PubMed

Thomas, Marie K; Pitot, Henry C; Liem, Amy; Lambert, Paul F

2011-12-20

Ninety percent of anal cancer is associated with human papilloma viruses (HPVs). Using our previously established HPV transgenic mouse model for anal cancer, we tested the role of the individual oncogenes E6 and E7. K14E6 and K14E7 transgenic mice were treated with dimethylbenz[a]anthracene (DMBA) to the anal canal and compared to matched nontransgenic and doubly transgenic K14E6/E7 mice. K14E7 and K14E6/E7 transgenic mice developed anal tumors (papillomas, atypias and carcinomas combined) at significantly higher rates (88% and 100%, respectively) than either K14E6 or NTG mice (18% and 19%, respectively). Likewise, K14E7 and K14E6/E7 transgenic mice developed frank cancer (carcinomas) at significantly higher rates (85% and 85%, respectively) than either K14E6 or NTG mice (18% and 10%, respectively). These findings indicate that E7 is the more potent oncogene in anal cancer caused by HPVs. Copyright © 2011 Elsevier Inc. All rights reserved.

40 CFR Table 2 to Subpart Uuuuu of... - Emission Limits for Existing EGUs

Code of Federal Regulations, 2013 CFR

2013-07-01

....5E0 lb/TBtu or 7.0E-2 lb/GWh. Selenium (Se) 2.2E+1 lb/TBtu or 3.0E-1 lb/GWh. b. Hydrogen chloride (HCl... (Pb) 8.1E0 lb/TBtu or 8.0E-2 lb/GWh. Manganese (Mn) 2.2E+1 lb/TBtu or 3.0E-1 lb/GWh. Nickel (Ni) 1.1E...

40 CFR Table 2 to Subpart Uuuuu of... - Emission Limits for Existing EGUs

Code of Federal Regulations, 2012 CFR

2012-07-01

....5E0 lb/TBtu or 7.0E-2 lb/GWh. Selenium (Se) 2.2E+1 lb/TBtu or 3.0E-1 lb/GWh. b. Hydrogen chloride (HCl... (Pb) 8.1E0 lb/TBtu or 8.0E-2 lb/GWh. Manganese (Mn) 2.2E+1 lb/TBtu or 3.0E-1 lb/GWh. Nickel (Ni) 1.1E...

40 CFR Table 2 to Subpart Uuuuu of... - Emission Limits for Existing EGUs

Code of Federal Regulations, 2014 CFR

2014-07-01

....5E0 lb/TBtu or 7.0E-2 lb/GWh. Selenium (Se) 2.2E+1 lb/TBtu or 3.0E-1 lb/GWh. b. Hydrogen chloride (HCl... (Pb) 8.1E0 lb/TBtu or 8.0E-2 lb/GWh. Manganese (Mn) 2.2E+1 lb/TBtu or 3.0E-1 lb/GWh. Nickel (Ni) 1.1E...

75 FR 33801 - Sunshine Act Meeting Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

..., Inc. E-3 ER09-1050-000, ER09-1192-000.... Southwest Power Pool, Inc. E-4 OMITTED. E-5 ER09-1063-000..., Inc. E-7 ER10-1069-000 Southwest Power Pool, Inc. E-8 OMITTED. E-9 RM10-23-000 Transmission Planning... Owners. E-16 OMITTED. E-17 ER09-1051-000 ISO New England Inc. and New England Power Pool. E-18 EL10-52...

Crystal structures of two bacterial HECT-like E3 ligases in complex with a human E2 reveal atomic details of pathogen-host interactions

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

Lin, David Yin-wei; Diao, Jianbo; Chen, Jue

2012-12-10

In eukaryotes, ubiquitination is an important posttranslational process achieved through a cascade of ubiquitin-activating (E1), conjugating (E2), and ligase (E3) enzymes. Many pathogenic bacteria deliver virulence factors into the host cell that function as E3 ligases. How these bacterial 'Trojan horses' integrate into the eukaryotic ubiquitin system has remained a mystery. Here we report crystal structures of two bacterial E3s, Salmonella SopA and Escherichia coli NleL, both in complex with human E2 UbcH7. These structures represent two distinct conformational states of the bacterial E3s, supporting the necessary structural rearrangements associated with ubiquitin transfer. The E2-interacting surface of SopA and NleLmore » has little similarity to those of eukaryotic E3s. However, both bacterial E3s bind to the canonical surface of E2 that normally interacts with eukaryotic E3s. Furthermore, we show that a glutamate residue on E3 is involved in catalyzing ubiquitin transfer from E3 to the substrate, but not from E2 to E3. Together, these results provide mechanistic insights into the ubiquitin pathway and a framework for understanding molecular mimicry in bacterial pathogenesis.« less

Search for the decays B_{(s)};{0} --> e;{+} micro;{-} and B_{(s)};{0} --> e;{+} e;{-} in CDF run II.

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzurri, P; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Beringer, J; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burke, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Calancha, C; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Chwalek, T; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cordelli, M; Cortiana, G; Cox, C A; Cox, D J; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lorenzo, G; Dell'orso, M; Deluca, C; Demortier, L; Deng, J; Deninno, M; Derwent, P F; di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Elagin, A; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Gessler, A; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Han, B-Y; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hays, C; Heck, M; Heijboer, A; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Hussein, M; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jha, M K; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, H W; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhr, T; Kulkarni, N P; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Lecompte, T; Lee, E; Lee, H S; Lee, S W; Leone, S; Lewis, J D; Lin, C-S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lucchesi, D; Luci, C; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mathis, M; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Merkel, P; Mesropian, C; Miao, T; Miladinovic, N; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moggi, N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Nett, J; Neu, C; Neubauer, M S; Neubauer, S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Osterberg, K; Griso, S Pagan; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Peiffer, T; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Renz, M; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Rutherford, B; Saarikko, H; Safonov, A; Sakumoto, W K; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sforza, F; Sfyrla, A; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shiraishi, S; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Stuart, D; Suh, J S; Sukhanov, A; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Ttito-Guzmán, P; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Tourneur, S; Trovato, M; Tsai, S-Y; Tu, Y; Turini, N; Ukegawa, F; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Wagner, P; Wagner, R G; Wagner, R L; Wagner, W; Wagner-Kuhr, J; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Weinelt, J; Wenzel, H; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Würthwein, F; Xie, S; Yagil, A; Yamamoto, K; Yamaoka, J; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zhang, X; Zheng, Y; Zucchelli, S

2009-05-22

We report results from a search for the lepton flavor violating decays B_{s};{0} --> e;{+} micro;{-} and B;{0} --> e;{+} micro;{-}, and the flavor-changing neutral-current decays B_{s};{0} --> e;{+} e;{-} and B;{0} --> e;{+} e;{-}. The analysis uses data corresponding to 2 fb;{-1} of integrated luminosity of pp[over ] collisions at sqrt[s] = 1.96 TeV collected with the upgraded Collider Detector (CDF II) at the Fermilab Tevatron. The observed number of B0 and B_{s};{0} candidates is consistent with background expectations. The resulting Bayesian upper limits on the branching ratios at 90% credibility level are B(B_{s};{0} --> e;{+} micro;{-}) < 2.0 x 10;{-7}, B(B;{0} --> e;{+} micro;{-}) < 6.4 x 10;{-8}, B(B_{s};{0} --> e;{+} e;{-}) < 2.8 x 10;{-7}, and B(B;{0} --> e;{+} e;{-}) < 8.3 x 10;{-8}. From the limits on B(B_{(s)};{0} --> e;{+} micro;{-}), the following lower bounds on the Pati-Salam leptoquark masses are also derived: M_{LQ}(B_{s};{0} --> e;{+} micro;{-}) > 47.8 TeV/c;{2}, and M_{LQ}(B;{0} --> e;{+} micro;{-}) > 59.3 TeV / c;{2}, at 90% credibility level.

Signalling to eIF4E in cancer

PubMed Central

Siddiqui, Nadeem; Sonenberg, Nahum

2015-01-01

Translational control plays a critical role in the regulation of gene expression in eukaryotes and affects many essential cellular processes, including proliferation, apoptosis and differentiation. Under most circumstances, translational control occurs at the initiation step at which the ribosome is recruited to the mRNA. The eukaryotic translation initiation factor 4E (eIF4E), as part of the eIF4F complex, interacts first with the mRNA and facilitates the recruitment of the 40S ribosomal subunit. The activity of eIF4E is regulated at many levels, most profoundly by two major signalling pathways: PI3K (phosphoinositide 3-kinase)/Akt (also known and Protein Kinase B, PKB)/mTOR (mechanistic/mammalian target of rapamycin) and Ras (rat sarcoma)/MAPK (mitogen-activated protein kinase)/Mnk (MAPK-interacting kinases). mTOR directly phosphorylates the 4E-BPs (eIF4E-binding proteins), which are inhibitors of eIF4E, to relieve translational suppression, whereas Mnk phosphorylates eIF4E to stimulate translation. Hyperactivation of these pathways occurs in the majority of cancers, which results in increased eIF4E activity. Thus, translational control via eIF4E acts as a convergence point for hyperactive signalling pathways to promote tumorigenesis. Consequently, recent works have aimed to target these pathways and ultimately the translational machinery for cancer therapy. PMID:26517881

Hepatitis C virus resistance to broadly neutralizing antibodies measured using replication-competent virus and pseudoparticles

PubMed Central

Wasilewski, Lisa N.; Ray, Stuart C.

2016-01-01

A better understanding of natural variation in neutralization resistance and fitness of diverse hepatitis C virus (HCV) envelope (E1E2) variants will be critical to guide rational development of an HCV vaccine. This work has been hindered by inadequate genetic diversity in viral panels and by a lack of standardization of HCV entry assays. Neutralization assays generally use lentiviral pseudoparticles expressing HCV envelope proteins (HCVpp) or chimeric full-length viruses that are replication competent in cell culture (HCVcc). There have been few systematic comparisons of specific infectivities of E1E2-matched HCVcc and HCVpp, and to our knowledge, neutralization of E1E2-matched HCVpp and HCVcc has never been compared using a diverse panel of human broadly neutralizing monoclonal antibodies (bNAbs) targeting distinct epitopes. Here, we describe an efficient method for introduction of naturally occurring E1E2 genes into a full-length HCV genome, producing replication-competent chimeric HCVcc. We generated diverse panels of E1E2-matched HCVcc and HCVpp and measured the entry-mediating fitness of E1E2 variants using the two systems. We also compared neutralization of E1E2-matched HCVcc and HCVpp by a diverse panel of human bNAbs targeting epitopes across E1E2. We found no correlation between specific infectivities of E1E2-matched HCVcc versus HCVpp, but found a very strong positive correlation between relative neutralization resistance of these same E1E2-matched HCVcc and HCVpp variants. These results suggest that quantitative comparisons of neutralization resistance of E1E2 variants can be made with confidence using either HCVcc or HCVpp, allowing the use of either or both systems to maximize diversity of neutralization panels. PMID:27667373

VizieR Online Data Catalog: Pisa pre-main sequence tracks and isochrones (Tognelli+, 2011)

NASA Astrophysics Data System (ADS)

Tognelli, E.; Prada Moroni, P. G.; Degl'Innocenti, S.

2011-07-01

Evolutionary tracks and Isochrones in the log L vs log Te plane, for the following chemical compositions: Z Y Y Y 2.00E-04 0.230 0.249 0.250 1.00E-03 0.232 0.251 0.254 2.00E-03 0.234 0.253 0.259 3.00E-03 0.236 0.254 0.263 4.00E-03 0.238 0.256 0.269 5.00E-03 0.240 0.258 0.273 6.00E-03 0.242 0.260 0.279 7.00E-03 0.244 0.262 0.283 8.00E-03 0.246 0.265 0.289 9.00E-03 0.248 0.267 0.294 1.00E-02 0.250 0.268 0.299 1.25E-02 0.255 0.274 0.311 1.50E-02 0.260 0.278 0.323 1.75E-02 0.265 0.284 0.336 2.00E-02 0.270 0.288 0.349 2.25E-02 0.275 0.294 0.361 2.50E-02 0.280 0.299 0.374 2.75E-02 0.285 0.304 0.386 3.00E-02 0.290 0.308 0.398 Each model is calculated with an initial Deuterium abundance XD=4.0E-05. For Z>=0.008, models with XD=2.0E-05 are available, too. Each model is calculated with three different values of the mixing length parameter alpha = 1.20, 1.68 (solar calibrated), 1.90. There is also a dataset for our Standard Solar Model parameters (Z=0.01377, Y=0.2533, alpha=1.68, XD=2.0E-05). (5 data files).

An analysis of the convergence of Newton iterations for solving elliptic Kepler's equation

NASA Astrophysics Data System (ADS)

Elipe, A.; Montijano, J. I.; Rández, L.; Calvo, M.

2017-12-01

In this note a study of the convergence properties of some starters E_0 = E_0(e,M) in the eccentricity-mean anomaly variables for solving the elliptic Kepler's equation (KE) by Newton's method is presented. By using a Wang Xinghua's theorem (Xinghua in Math Comput 68(225):169-186, 1999) on best possible error bounds in the solution of nonlinear equations by Newton's method, we obtain for each starter E_0(e,M) a set of values (e,M) \\in [0, 1) × [0, π ] that lead to the q-convergence in the sense that Newton's sequence (E_n)_{n ≥ 0} generated from E_0 = E_0(e,M) is well defined, converges to the exact solution E^* = E^*(e,M) of KE and further \\vert E_n - E^* \\vert ≤ q^{2^n -1} \\vert E_0 - E^* \\vert holds for all n ≥ 0. This study completes in some sense the results derived by Avendaño et al. (Celest Mech Dyn Astron 119:27-44, 2014) by using Smale's α -test with q=1/2. Also since in KE the convergence rate of Newton's method tends to zero as e → 0, we show that the error estimates given in the Wang Xinghua's theorem for KE can also be used to determine sets of q-convergence with q = e^k \\widetilde{q} for all e \\in [0,1) and a fixed \\widetilde{q} ≤ 1. Some remarks on the use of this theorem to derive a priori estimates of the error \\vert E_n - E^* \\vert after n Kepler's iterations are given. Finally, a posteriori bounds of this error that can be used to a dynamical estimation of the error are also obtained.

Hepatitis C virus resistance to broadly neutralizing antibodies measured using replication-competent virus and pseudoparticles.

PubMed

Wasilewski, Lisa N; Ray, Stuart C; Bailey, Justin R

2016-11-01

A better understanding of natural variation in neutralization resistance and fitness of diverse hepatitis C virus (HCV) envelope (E1E2) variants will be critical to guide rational development of an HCV vaccine. This work has been hindered by inadequate genetic diversity in viral panels and by a lack of standardization of HCV entry assays. Neutralization assays generally use lentiviral pseudoparticles expressing HCV envelope proteins (HCVpp) or chimeric full-length viruses that are replication competent in cell culture (HCVcc). There have been few systematic comparisons of specific infectivities of E1E2-matched HCVcc and HCVpp, and to our knowledge, neutralization of E1E2-matched HCVpp and HCVcc has never been compared using a diverse panel of human broadly neutralizing monoclonal antibodies (bNAbs) targeting distinct epitopes. Here, we describe an efficient method for introduction of naturally occurring E1E2 genes into a full-length HCV genome, producing replication-competent chimeric HCVcc. We generated diverse panels of E1E2-matched HCVcc and HCVpp and measured the entry-mediating fitness of E1E2 variants using the two systems. We also compared neutralization of E1E2-matched HCVcc and HCVpp by a diverse panel of human bNAbs targeting epitopes across E1E2. We found no correlation between specific infectivities of E1E2-matched HCVcc versus HCVpp, but found a very strong positive correlation between relative neutralization resistance of these same E1E2-matched HCVcc and HCVpp variants. These results suggest that quantitative comparisons of neutralization resistance of E1E2 variants can be made with confidence using either HCVcc or HCVpp, allowing the use of either or both systems to maximize diversity of neutralization panels.

The effect of conspecific removal on behavioral and physiological responses of dairy cattle.

PubMed

Walker, Jessica K; Arney, David R; Waran, Natalie K; Handel, Ian G; Phillips, Clive J C

2015-12-01

Adverse social and welfare implications of mixing dairy cows or separating calves from their mothers have been documented previously. Here we investigated the behavioral and physiological responses of individuals remaining after conspecifics were removed. We conducted a series of 4 experiments incorporating a range of types of different dairy cattle groupings [experiment 1 (E1), 126 outdoor lactating dairy cows; experiment 2 (E2), 120 housed lactating dairy cows; experiment 3 (E3), 18 housed dairy calves; and experiment 4 (E4), 22 housed dairy bulls] from which a subset of individuals were permanently removed (E1, n=7; E2, n=5; E3, n=9; E4, n=18). Associations between individuals were established using near-neighbor scores (based upon identities and distances between animals recorded before removal) in E1, E2, and E3. Behavioral recordings were taken for 3 to 5 d, before and after removal on a sample of cattle in all 4 experiments (E1, n=20; E2, n=20; E3, n=9; E4, n=4). In 2 experiments with relatively large groups of dairy cows, E1 and E2, the responses of cows that did and did not associate with the removed cows were compared. An increase in time that both nonassociates and associates spent eating was observed after conspecific removal in E1. In E2, this increase was restricted to cows that had not associated with the removed cows. A reduction in ruminating in remaining cattle was observed in E3 and eating in E4. Immunoglobulin A concentrations increased after separation in both E3 and E4 cattle, but did not differ significantly between associates and nonassociates in E2. Blood and milk cortisol concentrations were not affected by conspecific removal. These findings suggest that some animals had affected feeding behavior and IgA concentrations after removal of conspecifics. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Eukaryotic Initiation Factor eIFiso4G1 and eIFiso4G2 Are Isoforms Exhibiting Distinct Functional Differences in Supporting Translation in Arabidopsis*

PubMed Central

Gallie, Daniel R.

2016-01-01

The eukaryotic translation initiation factor (eIF) 4G is required during protein synthesis to promote the assembly of several factors involved in the recruitment of a 40S ribosomal subunit to an mRNA. Although many eukaryotes express two eIF4G isoforms that are highly similar, the eIF4G isoforms in plants, referred to as eIF4G and eIFiso4G, are highly divergent in size, sequence, and domain organization but both can interact with eIF4A, eIF4B, eIF4E isoforms, and the poly(A)-binding protein. Nevertheless, eIF4G and eIFiso4G from wheat exhibit preferences in the mRNAs they translate optimally. For example, mRNA containing the 5′-leader (called Ω) of tobacco mosaic virus preferentially uses eIF4G in wheat germ lysate. In this study, the eIF4G isoform specificity of Ω was used to examine functional differences of the eIF4G isoforms in Arabidopsis. As in wheat, Ω-mediated translation was reduced in an eif4g null mutant. Loss of the eIFiso4G1 isoform, which is similar in sequence to wheat eIFiso4G, did not substantially affect Ω-mediated translation. However, loss of the eIFiso4G2 isoform substantially reduced Ω-mediated translation. eIFiso4G2 is substantially divergent from eIFiso4G1 and is present only in the Brassicaceae, suggesting a recent evolution. eIFiso4G2 isoforms exhibit sequence-specific differences in regions representing partner protein and RNA binding sites. Loss of any eIF4G isoform also resulted in a substantial reduction in reporter transcript level. These results suggest that eIFiso4G2 appeared late in plant evolution and exhibits more functional similarity with eIF4G than with eIFiso4G1 during Ω-mediated translation. PMID:26578519

HPV16 and 18 genome amplification show different E4-dependence, with 16E4 enhancing E1 nuclear accumulation and replicative efficiency via its cell cycle arrest and kinase activation functions

PubMed Central

Jackson, Deborah; Mahmood, Radma

2017-01-01

To clarify E1^E4’s role during high-risk HPV infection, the E4 proteins of HPV16 and 18 were compared side by side using an isogenic keratinocyte differentiation model. While no effect on cell proliferation or viral genome copy number was observed during the early phase of either virus life cycle, time-course experiments showed that viral genome amplification and L1 expression were differently affected upon differentiation, with HPV16 showing a much clearer E4 dependency. Although E4 loss never completely abolished genome amplification, its more obvious contribution in HPV16 focused our efforts on 16E4. As previously suggested, in the context of the virus life cycle, 16E4s G2-arrest capability was found to contribute to both genome amplification success and L1 accumulation. Loss of 16E4 also lead to a reduced maintenance of ERK, JNK and p38MAPK activity throughout the genome amplifying cell layers, with 16E4 (but not 18E4) co-localizing precisely with activated cytoplasmic JNK in both wild type raft tissue, and HPV16-induced patient biopsy tissue. When 16E1 was co-expressed with E4, as occurs during genome amplification in vivo, the E1 replication helicase accumulated preferentially in the nucleus, and in transient replication assays, E4 stimulated viral genome amplification. Interestingly, a 16E1 mutant deficient in its regulatory phosphorylation sites no longer accumulated in the nucleus following E4 co-expression. E4-mediated stabilisation of 16E2 was also apparent, with E2 levels declining in organotypic raft culture when 16E4 was absent. These results suggest that 16E4-mediated enhancement of genome amplification involves its cell cycle inhibition and cellular kinase activation functions, with E4 modifying the activity and function of viral replication proteins including E1. These activities of 16E4, and the different kinase patterns seen here with HPV18, 31 and 45, may reflect natural differences in the biology and tropisms of these viruses, as well as differences in E4 function. PMID:28306742

E-Cigarette Users' Attitudes on the Banning of Sales of Nicotine E-Liquid, Its Implication on E-Cigarette Use Behaviours and Alternative Sources of Nicotine E-Liquid.

PubMed

Wong, Li Ping; Alias, Haridah; Agha Mohammadi, Nasrin; Ghadimi, Azadeh; Hoe, Victor Chee Wai

2017-12-01

The banning of sales of nicotine e-liquid in e-cigarette shops has been implemented in several states in Malaysia. The distribution of nicotine e-liquid can only be allowed by licensed pharmacies or registered medical practitioners. This study aimed to evaluate e-cigarette users' responses to the control policy in a cross-sectional survey of 851 e-cigarette users by utilizing a self-report questionnaire that assessed (1) attitudes on regulation policy of e-cigarette banning; (2) e-cigarette use behaviors; and (3) sources of e-liquid after the regulation policy has been implemented. Participants from the state of Selangor where the banning policy was implemented were surveyed. The majority (95.8%) opposed the banning and believed e-cigarettes should be sold to anyone aged 18 years or above as with tobacco cigarettes, only a minority believed that nicotine e-liquid should only be available for sale over the counter in pharmacy stores (14.6%) and in clinics with a doctor's prescription (11.8%). The majority (44.2%) reported that they would continue their e-cigarette use as before the banning policy, while 20% plan to completely stop e-cigarette usage without replacing it with any alternatives. The vast majority (87.9%) was still able to obtained nicotine e-liquid from e-cigarette shops in spite of the ban and the second most common source was from online purchase (63.1%). The sales of nicotine e-liquid from black-market were evidenced as many reported obtaining zero nicotine e-liquid from the black market (54.4%). Self- or home-made (30.8%) nicotine e-liquid was also reported. Majority of respondents that self-made e-liquid were from the average monthly income group (below MYR3000). Obtaining nicotine from the pharmacy was least preferred (21.4%). Provision of professional advice to nicotine e-liquid users along with the ban may lessen the likelihood of users switching to tobacco cigarettes or other nicotine alternatives. Banning of sales of nicotine e-liquid in e-cigarette shops resulted in a boom in the black market supplying nicotine e-liquid and, self- or home-made nicotine e-liquid. Enforcing regulations and monitoring black market sales is warranted. Efforts to educate e-cigarette users of the danger of sourcing nicotine e-liquid from the black market and self- or home-made nicotine e-liquid are essential.

Plasma B-esterase activities in European raptors.

PubMed

Roy, Claudie; Grolleau, Gérard; Chamoulaud, Serge; Rivière, Jean-Louis

2005-01-01

B-esterases are serine hydrolases composed of cholinesterases, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and carboxylesterase (CbE). These esterases, found in blood plasma, are inhibited by organophosphorus (OP) and carbamate (CB) insecticides and can be used as nondestructive biomarkers of exposure to anticholinesterase insecticides. Furthermore, B-esterases are involved in detoxification of these insecticides. In order to establish the level of these enzymes and to have reference values for their normal activities, total plasma cholinesterase (ChE), AChE and BChE activities, and plasma CbE activity were determined in 729 European raptors representing 20 species, four families, and two orders. The diurnal families of the Falconiforme order were represented by Accipitridae and Falconidae and the nocturnal families of the Strigiforme order by Tytonidae and Strigidae. Intraspecies differences in cholinesterase activities according to sex and/or age were investigated in buzzards (Buteo buteo), sparrowhawks (Accipiter nisus), kestrels (Falco tinnunculus), barn owls (Tyto alba), and tawny owls (Strix aluco). Sex-related differences affecting ChE and AChE activities were observed in young kestrels (2-3-mo-old) and age-related differences in kestrels (ChE and AChE), sparrowhawks (AChE), and tawny owls (ChE, AChE, and BChE). The interspecies analysis yielded a negative correlation between ChE activity and body mass taking into account the relative contribution of AChE and BChE to ChE activity, with the exception of the honey buzzard (Pernis apivorus). The lowest ChE activities were found in the two largest species, Bonelli's eagle (Hieraaetus fasciatus) and Egyptian vulture (Neophron percnopterus) belonging to the Accipitridae family. The highest ChE activities were found in the relatively small species belonging to the Tytonidae and Strigidae families and in honey buzzard of the Accipitridae family. Species of the Accipitridae, Tytonidae, and Strigidae families were characterized by a BChE contribution that dominated the total ChE activity, while in the species of the Falconidae family, AChE activity dominated. With the exception of the barn owl, CbE activity (eserine-insensitive alpha-naphthyl acetate esterase [alpha-NAE] activity) in all species was almost absent or very low. The values obtained in this study for ChE, AChE, and BChE activities and the AChE:BChE ratios for buzzard, kestrel, barn owl, and tawny owl provide a good estimate of the normal values in free-living individuals of these European species. They can be used as a baseline to evaluate the effect of anticholinesterase insecticides in the field.

Immortalization of normal human embryonic fibroblasts by introduction of either the human papillomavirus type 16 E6 or E7 gene alone.

PubMed

Yamamoto, Akito; Kumakura, Shin-ichi; Uchida, Minoru; Barrett, J Carl; Tsutsui, Takeki

2003-09-01

The ability of the human papillomavirus type 16 (HPV-16) E6 or E7 gene to induce immortalization of normal human embryonic fibroblast WHE-7 cells was examined. WHE-7 cells at 9 population doublings (PD) were infected with retrovirus vectors encoding either HPV-16 E6 or E7 alone or both E6 and E7 (E6/E7). One of 4 isolated clones carrying E6 alone became immortal and is currently at >445 PD. Four of 4 isolated clones carrying E7 alone escaped from crisis and are currently at >330 PD. Three of 5 isolated clones carrying E6/E7 were also immortalized and are currently at >268 PD. The immortal clone carrying E6 only and 2 of the 3 immortal clones carrying E6/E7 expressed a high level of E6 protein, and all the immortal clones carrying E7 alone and the other immortal clone carrying E6/E7 expressed a high level of E7 protein when compared to their mortal or precrisis clones. The immortal clones expressing a high level of E6 or E7 protein were positive for telomerase activity or an alternative mechanism of telomere maintenance, respectively, known as ALT (alternative lengthening of telomeres). All the mortal or precrisis clones were negative for both phenotypes. All the immortal clones exhibited abrogation of G1 arrest after DNA damage by X-ray irradiation. The expression of INK4a protein (p16(INK4a)) was undetectable in the E6-infected mortal and immortal clones, whereas Rb protein (pRb) was hyperphosphorylated only in the immortal clone. The p16(INK4a) protein was overexpressed in all the E7-infected immortal clones and their clones in the pre-crisis period as well as all the E6/E7-infected mortal and immortal clones, but the pRb expression was downregulated in all of these clones. These results demonstrate for the first time to our knowledge that HPV-16 E6 or E7 alone can induce immortalization of normal human embryonic fibroblasts. Inactivation of p16(INK4a)/pRb pathways in combination with activation of a telomere maintenance mechanism is suggested to be necessary for immortalization of normal human embryonic fibroblasts by these viral oncogenes. The susceptibility of human cells to immortalization may be related to the state of differentiation of the cells. Copyright 2003 Wiley-Liss, Inc.

40 CFR Table E-2 to Subpart E of... - Spectral Energy Distribution and Permitted Tolerance for Conducting Radiative Tests

Code of Federal Regulations, 2010 CFR

2010-07-01

... Permitted Tolerance for Conducting Radiative Tests E Table E-2 to Subpart E of Part 53 Protection of... Reference Methods and Class I and Class II Equivalent Methods for PM2.5 or PM10â2.5 Pt. 53, Subpt. E, Table E-2 Table E-2 to Subpart E of Part 53—Spectral Energy Distribution and Permitted Tolerance for...

Planning, Programming, and Budgeting System (PPBS)/Multi-year Programming: Reading Guide

DTIC Science & Technology

2010-09-01

51 B -4 Potter, Barry H ., and Jack Diamond. Guidelines for Public Expenditure...IS PA GE 1 9 b . TE LE P H ON E N U M B E R ( I n c l u d e A r e a C o d e ) U U U ...I N S T I T U T E F O R D E F E N S E A N A LY S E S IDA Document D-4057 Log: H 10-000982 September 2010 Planning, Programming, and Budgeting

Novel Compounds from Shark and Stingray Epidermal Mucus With Antimicrobial Activity Against Wound Infection Pathogens

DTIC Science & Technology

2013-03-01

530-E6 MSSA, MRSA, E. coli, VRE, E. faecalis, B. subtilis 530-E7 MSSA, MRSA, E. coli, VRE, E. faecalis, B. subtilis B. anthracis, Micrococcus sp...530-E10 MSSA, MRSA, E. coli, VRE, E. faecalis, B. subtilis Micrococcus sp. 530-A5 VRE 530-B12 VRE 530-C12 VRE B. anthracis 530-D12 VRE 530-E12...VRE Micrococcus sp. 530-F11 VRE Micrococcus sp. 530-F12 VRE Enterococcus. faecium Figure 9. Pathogen overlay assay plates showing

Helminth records from eleven species of Emoia (Sauria: Scincidae) from Oceania

USGS Publications Warehouse

Goldberg, S.R.; Bursey, C.R.; Fisher, R.N.

2005-01-01

As part of an ongoing study of the biogeography of helminth parasites of lizards from Oceania, 53 specimens of Emoia (11 species) were examined, as follows: E. atrocostata, E. boettgeri, E. caerulocauda, E. cyanogaster, E. cyanura, E. impar, E. nigra, E. nigromarginata, E. ponapea, E. sanfordi, E. trossula. One species of Digenea, Paradistomoides gregarium, and six species of Nematoda, Hedruris hanleyae, Maxvachonia chabaudi, Parapharyngodon maplestoni, Physalopteroides arnoensis, Spauligodon gehyrae, and Moaciria sp. indet., were found. These helminths have been reported previously from other lizard species. Seventeen new host records and eight new locality records are reported. ?? 2005 by University of Hawai'i Press All rights reserved.

Les vies de Galilée

ScienceCinema

Fiami

2018-05-21

Qu'est-ce que l'astronomie? A quoi sert-elle ? Qui était Galilée ? Une soirée avec Fiami, auteur et dessinateur autour des vies de Galilée, titre de son nouvel ouvrage. Galilée y joue le protagoniste ou le complice de grandes découvertes à différentes époques et sous divers profils : Galilée à Babylone (-568) | Galilée à Alexandrie (-197) | Galilée en Inde (499) | Galilée à Venise (1609) | Galilée et Halley (1705) | Galilée revient (2009) Dans le cadre de l'année mondiale de l'astronomie.

Extension of Plasma Source Ion Implantation to Ion Beam Enhanced Deposition

DTIC Science & Technology

1989-10-05

e - :. ee a- - e -e ’, -evew ,. , s , .’ ,.q e. 5t’nq s ata 3 t orcei er1l-a’ti 1,e-e 10 :o’e’- I" e ec!’ :In fQP ’t, 0 0e ej!,te Vr in,~ ;tne, ilr...e~r s ~ ~ NW’ ~q’v -eaaaje’ e,, ~ ’rt’’e ,: on2 b I oe’atio~s1, afoo$ ps ete’som 1. AGENCY USE ONLY ,Ledve oianK) .REPORT DATE 3. REPORT...Enhanced Deposition DAAL03-89-K-0048 AUTHOR( S ) John R. Conrad 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT

Fine Mapping of Murine Antibody Responses to Immunization with a Novel Soluble Form of Hepatitis C Virus Envelope Glycoprotein Complex

PubMed Central

Ruwona, Tinashe B.; Giang, Erick; Nieusma, Travis

2014-01-01

ABSTRACT The hepatitis C virus (HCV) envelope glycoprotein E1E2 complex is a candidate vaccine antigen. Previous immunization studies of E1E2 have yielded various results on its ability to induce virus-neutralizing antibodies in animal models and humans. The murine model has become a vital tool for HCV research owing to the development of humanized mice susceptible to HCV infection. In this study, we investigated the antibody responses of mice immunized with E1E2 and a novel soluble form of E1E2 (sE1E2) by a DNA prime and protein boost strategy. The results showed that sE1E2 elicited higher antibody titers and a greater breadth of reactivity than the wild-type cell-associated E1E2. However, immune sera elicited by either immunogen were only weakly neutralizing. In order to understand the contrasting results of binding and serum neutralizing activities, epitopes targeted by the polyclonal antibody responses were mapped and monoclonal antibodies (MAbs) were generated. The results showed that the majority of serum antibodies were directed to the E1 region 211 to 250 and the E2 regions 421 to 469, 512 to 539, 568 to 609, and 638 to 651, instead of the well-known immunodominant E2 hypervariable region 1 (HVR1). Unexpectedly, in MAb analysis, ∼12% of MAbs isolated were specific to the conserved E2 antigenic site 412 to 423, and 85% of them cross-neutralized multiple HCV isolates. The epitopes recognized by these MAbs are similar but distinct from the previously reported HCV1 and AP33 broadly neutralizing epitopes. In conclusion, E1E2 can prime B cells specific to conserved neutralizing epitopes, but the levels of serum neutralizing antibodies elicited are insufficient for effective virus neutralization. The sE1E2 constructs described in this study can be a useful template for rational antigen engineering. IMPORTANCE Hepatitis C virus infects 2 to 3% of the world's population and is a leading cause of liver failures and the need for liver transplantation. The virus envelope glycoprotein complex E1E2 produced by detergent extraction of cells overexpressing the protein was evaluated in a phase I clinical trial but failed to induce neutralizing antibodies in most subjects. In this study, we designed a novel form of E1E2 which is secreted from cells and is soluble and compared it to wild-type E1E2 by DNA immunization of mice. The results showed that this new E1E2 is more immunogenic than wild-type E1E2. Detailed mapping of the antibody responses revealed that antibodies to the conserved E2 antigenic site 412 to 423 were elicited but the serum concentrations were too low to neutralize the virus effectively. This soluble E1E2 provides a new reagent for studying HCV and for rational vaccine design. PMID:24965471

New Global Electron Density Observations from GPS-RO in the D- and E-Region Ionosphere

NASA Technical Reports Server (NTRS)

Wu, Dong L.

2017-01-01

A novel retrieval technique is developed for electron density (N(sub e)) in the D- and E-region (80-120 km) using the high-quality 50-Hz GPS radio occultation (GPS-RO) phase measurements. The new algorithm assumes a slow, linear variation in the F-region background when the GPS-RO passes through the D- and E-region, and extracts the N(sub e) profiles at 80-130 km from the phase advance signal caused by N(sub e). Unlike the conventional Abel function, the new approach produces a sharp N(sub e) weighting function in the lower ionosphere, and the N(sub e) retrievals are in good agreement with the IRI (International Reference Ionosphere) model in terms of monthly maps, zonal means and diurnal variations. The daytime GPS-RO N(sub e) profiles can be well characterized by the alpha-Chapman function of three parameters (N(sub mE), h(sub mE) and H), showing that the bottom of E-region is deepening and sharpening towards the summer pole. At high latitudes the monthly GPS-RO N(sub e) maps at 80-120 km reveal clear enhancement in the auroral zones, more prominent at night, as a result of energetic electron precipitation (EEP) from the outer radiation belt. The D-/E-region auroral N(sub e) is strongly correlated with K(sub p) on a daily basis. The new N(sub e) data allow further comprehensive analyses of the sporadic E (E(sub s)) phenomena in connection with the background N(sub e) in the E-region. The layered (2-10 km) and fluctuated (less than 2 km) E(sub s) components, namely N(sub e_Layer) than N(sub e_Pert), are extracted with respect to the background N( sub e_Region) on a profile-by-profile basis. The N(sub e_Layer) component has a strong but highly-refined peak at approximately 105 km, with an amplitude smaller than N(sub e_Region) approximately by an order of magnitude. The N(sub e_Pert) component, which was studied extensively in the past, is approximately 2 orders of magnitude weaker than N(sub e_Layer). Both N(sub e_Layer) and N(sub e_Pert) are subject to significant diurnal and semidiurnal variations, showing downward progression with local time in amplitude. The 11-year solar cycle dominates the N(sub e) interannual variations, showing larger N(sub e_Region) and N(sub e_Layer) but smaller N(sub e_Pert) amplitudes in the solar maximum years. Enhanced Ne profiles are often observed in the polar winter, showing good correlation with solar proton events (SPEs) and geomagnetic activity. The new methodology offers great potential for retrieving low N(sub e) in the D-region, where radio propagation and communication blackouts can occur due to enhanced ionization. For space weather applications it is recommended for GPSRO operations to raise the top of high-rate data acquisition to approximately 140 km in the future.

Separate analysis of human papillomavirus E6 and E7 messenger RNAs to predict cervical neoplasia progression

PubMed Central

Liu, Shuling; Lachkar, Bouchra; Zhang, Shuang; Xu, Chenyang; Tenjimbayashi, Yuri; Shikama, Ayumi; Tasaka, Nobutaka; Akiyama, Azusa; Sakurai, Manabu; Nakao, Sari; Ochi, Hiroyuki; Onuki, Mamiko; Matsumoto, Koji; Yoshikawa, Hiroyuki; Satoh, Toyomi

2018-01-01

A few studies previously suggested that human papillomavirus (HPV) E6 messenger RNA (mRNA) may exist uniformly in all grades of cervical intraepithelial neoplasia (CIN), whereas the detection rate of E7 mRNA may increase with disease progression from low-grade CIN to invasive carcinoma. The aim of this study was to clarify the different roles of E6 and E7 mRNAs in cervical carcinogenesis. The presence of each E6 and E7 mRNA was analyzed in 171 patients with pathologically-diagnosed CIN or cervical carcinoma. We utilized a RT-PCR assay based on consensus primers which could detect E6 mRNA (full-length E6/E7 transcript) and E7 mRNAs (spliced E6*/E7 transcripts) separately for various HPV types. E7 mRNAs were detected in 6% of CIN1, 12% of CIN2, 24% of CIN3, and 54% of cervical carcinoma. The presence of E7 mRNAs was significantly associated with progression from low-grade CIN to invasive carcinoma in contrast with E6 mRNA or high-risk HPV (HR-HPV) DNA (p = 0.00011, 0.80 and 0.54). The presence of both E6 and E7 mRNAs was significantly associated with HPV16/18 DNA but not with HR-HPV DNA (p = 0.0079 and 0.21), while the presence of E6 mRNA was significantly associated with HR-HPV DNA but not with HPV16/18 DNA (p = 0.036 and 0.089). The presence of both E6 and E7 mRNAs showed high specificity and low sensitivity (100% and 19%) for detecting CIN2+ by contrast with the positivity for HR-HPV DNA showing low specificity and high sensitivity (19% and 89%). The positive predictive value for detecting CIN2+ was even higher by the presence of both E6 and E7 mRNAs than by the positivity for HR-HPV DNA (100% vs. 91%). In 31 patients followed up for CIN1-2, the presence of both E6 and E7 mRNAs showed significant association with the occurrence of upgraded abnormal cytology in contrast with E6 mRNA, HR-HPV DNA, or HPV16/18 DNA (p = 0.034, 0.73, 0.53, and 0.72). Our findings support previous studies according to which E7 mRNA is more closely involved in cervical carcinogenesis than E6 mRNA. Moreover, the separate analysis of E6 and E7 mRNAs may be more useful than HR-HPV DNA test for detecting CIN2+ precisely and predicting disease progression. Further accumulation of evidence is warranted to validate our findings. PMID:29466435

Geographical gradient of the eIF4E alleles conferring resistance to potyviruses in pea (Pisum) germplasm.

PubMed

Konečná, Eva; Šafářová, Dana; Navrátil, Milan; Hanáček, Pavel; Coyne, Clarice; Flavell, Andrew; Vishnyakova, Margarita; Ambrose, Mike; Redden, Robert; Smýkal, Petr

2014-01-01

The eukaryotic translation initiation factor 4E was shown to be involved in resistance against several potyviruses in plants, including pea. We combined our knowledge of pea germplasm diversity with that of the eIF4E gene to identify novel genetic diversity. Germplasm of 2803 pea accessions was screened for eIF4E intron 3 length polymorphism, resulting in the detection of four eIF4E(A-B-C-S) variants, whose distribution was geographically structured. The eIF4E(A) variant conferring resistance to the P1 PSbMV pathotype was found in 53 accessions (1.9%), of which 15 were landraces from India, Afghanistan, Nepal, and 7 were from Ethiopia. A newly discovered variant, eIF4E(B), was present in 328 accessions (11.7%) from Ethiopia (29%), Afghanistan (23%), India (20%), Israel (25%) and China (39%). The eIF4E(C) variant was detected in 91 accessions (3.2% of total) from India (20%), Afghanistan (33%), the Iberian Peninsula (22%) and the Balkans (9.3%). The eIF4E(S) variant for susceptibility predominated as the wild type. Sequencing of 73 samples, identified 34 alleles at the whole gene, 26 at cDNA and 19 protein variants, respectively. Fifteen alleles were virologically tested and 9 alleles (eIF4E(A-1-2-3-4-5-6-7), eIF4E(B-1), eIF4E(C-2)) conferred resistance to the P1 PSbMV pathotype. This work identified novel eIF4E alleles within geographically structured pea germplasm and indicated their independent evolution from the susceptible eIF4E(S1) allele. Despite high variation present in wild Pisum accessions, none of them possessed resistance alleles, supporting a hypothesis of distinct mode of evolution of resistance in wild as opposed to crop species. The Highlands of Central Asia, the northern regions of the Indian subcontinent, Eastern Africa and China were identified as important centers of pea diversity that correspond with the diversity of the pathogen. The series of alleles identified in this study provides the basis to study the co-evolution of potyviruses and the pea host.

In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis

PubMed Central

2013-01-01

Background The APOE4 allele variant is the strongest known genetic risk factor for developing late-onset Alzheimer’s disease. The link between apolipoprotein E (apoE) and Alzheimer’s disease is likely due in large part to the impact of apoE on the metabolism of amyloid β (Aβ) within the brain. Manipulation of apoE levels and lipidation within the brain has been proposed as a therapeutic target for the treatment of Alzheimer’s disease. However, we know little about the dynamic regulation of apoE levels and lipidation within the central nervous system. We have developed an assay to measure apoE levels in the brain interstitial fluid of awake and freely moving mice using large molecular weight cut-off microdialysis probes. Results We were able to recover apoE using microdialysis from human cerebrospinal fluid (CSF) in vitro and mouse brain parenchyma in vivo. Microdialysis probes were inserted into the hippocampus of wild-type mice and interstitial fluid was collected for 36 hours. Levels of apoE within the microdialysis samples were determined by ELISA. The levels of apoE were found to be relatively stable over 36 hours. No apoE was detected in microdialysis samples from apoE KO mice. Administration of the RXR agonist bexarotene increased ISF apoE levels while ISF Aβ levels were decreased. Extrapolation to zero-flow analysis allowed us to determine the absolute recoverable concentration of apoE3 in the brain ISF of apoE3 KI mice. Furthermore, analysis of microdialysis samples by non-denaturing gel electrophoresis determined lipidated apoE particles in microdialysis samples were consistent in size with apoE particles from CSF. Finally, we found that the concentration of apoE in the brain ISF was dependent upon apoE isoform in human apoE KI mice, following the pattern apoE2>apoE3>apoE4. Conclusions We are able to collect lipidated apoE from the brain of awake and freely moving mice and monitor apoE levels over the course of several hours from a single mouse. Our technique enables assessment of brain apoE dynamics under physiological and pathophysiological conditions and in response to therapeutic interventions designed to affect apoE levels and lipidation within the brain. PMID:23601557

Elevated levels of p-Mnk1, p-eIF4E and p-p70S6K proteins are associated with tumor recurrence and poor prognosis in astrocytomas.

PubMed

Fan, Weibing; Wang, Weiyuan; Mao, Xinfa; Chu, Shuzhou; Feng, Juan; Xiao, Desheng; Zhou, Jianhua; Fan, Songqing

2017-02-01

Malignant astrocytomas are able to invade neighboring and distant areas of the normal brain. Signaling pathway alterations play important role in the development of astrocytomas. Deregulation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 directly or PI3K/mTOR/S6K pathway indirectly has a critical effect on promoting cellular proliferation, malignant transformation and metastasis. We examined and analyzed the correlation between expression of p-Mnk1, p-eIF4E and p-p70S6K proteins and clinicopathological features in 103 astrocytomas and 54 non-tumorous brain tissues. The results indicated that positive percentage of overexpression of p-Mnk1 and p-eIF4E proteins in astrocytomas were significantly higher than that of in the non-tumorous brain tissues (P < 0.05). Elevated p-Mnk1 and p-eIF4E and co-overexpressed three proteins were associated with tumor recurrence (P = 0.003, P = 0.006, P = 0.007, respectively). Overexpressed p-eIF4E significantly correlated with the tumor size (P = 0.019). In addition, overexpression of p-eIF4E and three proteins common expression were related to the WHO grade of astrocytomas (P = 0.001, P = 0.044 respectively). Spearman's rank correlation test further showed that the expression of p-Mnk1 was strongly positive correlated with the expression of p-eIF4E in astrocytomas (r = 0.294, P = 0.003). Besides, overexpression of p-eIF4E and co-expression of p-Mnk1, p-eIF4E and p-p70S6K proteins were inversely correlated with overall survival rates of astrocytomas. Multivariate Cox regression analysis further identified that the elevated p-eIF4E expression, three proteins common expression were correlated with unfavorable prognosis of astrocytomas regardless of ages and WHO grades. Taken together, overexpression of p-eIF4E and co-expression of p-Mnk1, p-eIF4E and p-p70S6K proteins could be used as novel independent poor prognostic biomarkers for patients with astrocytomas.

Cephalosporin and penicillin cross-reactivity in patients allergic to penicillins.

PubMed

Liu, X-D; Gao, N; Qiao, H-L

2011-03-01

Bata-lactam antibiotics are the most commonly used antibiotics which usually cause serious IgE-mediated allergic reactions. Of all bata-lactam antibiotics, penicillins have so far been the best-studied, but the studies of cephalosporins and their cross-reactivity with penicillins are rare. We sought to evaluate the IgE response in vitro and estimate cross-reactivity between penicillins and cephalosporins in patients allergic to penicillins. We studied 87 control subjects and 420 subjects allergic to penicillins. Radioallergosorbent test (RAST) was performed to detect eight types of specific-penicillin IgE and eleven types of specific-cephalosporin IgE. The cross-reactivity and different molecules recognition by IgE were studied with a radioallergosorbent inhibition test. Of 420 patients allergic to penicillins, 95 patients (22.62%) showed specific-cephalosporin IgE positive, 73 patients (17.38%) showed IgEs positive to both penicillins and cephalosporins. In specific-penicillin IgE positive group, the positive rate of specific-cephalosporin IgE was significantly higher than in specific-penicillin IgE negative group (27.14% vs. 14.57%, p < 0.01). In urticaria group, the positive rate of specific-cephalosporin IgE was significantly higher than in other symptoms group (30.65% vs. 8.11%, p < 0.05). The analysis of drugs which have the same or similar side-chains showed that benzylpenicillanyl-IgE (BPA-IgE), ampicillanyl-IgE (APA-IgE), amoxicillanyl-IgE (AXA-IgE) were respectively related to cephalothanyl-IgE (CLA-IgE), cephalexanyl-IgE (CEXA-IgE), cephalexanyl-IgE (CEXA-IgE)in sera of penicillin-allergic patients we studied, and compared with patients who had negative amoxicillin-IgE, the positive rates of specific-ampicillin IgE and specific-cephalexin IgE were significantly higher in patients who had positive amoxicillin-IgE (14.43% vs. 3.72%, 14.00% vs. 2.96%, p < 0.01). Radioallergosorbent test and radioallergosorbent inhibition test confirmed that both nuclear structure and R1 side-chain contribute to IgE recognition. There exists cross-reactivity between cephalosporins and penicillins; patients allergic to several penicillins are more likely to develop allergic reaction to cephalosporins; due to sensitization to the similar structural characteristics (nuclear and R1 side-chain), penicillin-allergic patients may develop cross-allergic reactions with not only first-generation but also third-generation cephalosporins.

HPV-16 E6/E7 promotes cell migration and invasion in cervical cancer via regulating cadherin switch in vitro and in vivo.

PubMed

Hu, Dongxiao; Zhou, Jiansong; Wang, Fenfen; Shi, Haiyan; Li, Yang; Li, Baohua

2015-12-01

Cadherin switch, as a key hallmark of epithelial-mesenchymal transition (EMT), is characterized by reduced E-cadherin expression and increased N-cadherin or P-cadherin expression, and has been implicated in many aggressive tumors, but the importance and regulatory mechanism of cadherin switch in cervical cancer have not been investigated. Our study aimed to explore the role of cadherin switch by regulation of HPV-16 E6/E7 in progression and metastasis of cervical cancer. The expressions of E-cadherin and P-cadherin were examined by immunohistochemical staining in 40 cases of high-grade cervical lesions with HPV-16 infection only in which HPV-16 E6 and E7 expression had been detected using qRT-PCR method. Through modulating E6 and E7 expression using HPV-16 E6/E7 promoter-targeting siRNAs or expressed vector in vitro, cell growth, migration, and invasion were separately tested by MTT, wound-healing and transwell invasion assays, as well as the expressions of these cadherins by western blot analyses. Finally, the expressions of these cadherins in cancerous tissues of BALB/c-nu mouse model inoculated with the stable HPV-16 E6/E7 gene silencing Siha and Caski cells were also measured by immunohistochemical staining. Pearson correlation coefficient analyses showed the strongly inverse correlation of E-cadherin expression and strongly positive correlation of P-cadherin expression with E6/E7 level in 40 cases of high-grade cervical lesions. Furthermore, the modulation of HPV-16 E6/E7 expression remarkably influenced cell proliferation, migration, and invasion, as well as the protein levels of E-cadherin and P-cadherin in cervical cell lines. Finally, the reduction of HPV-16 E6/E7 expression led to up-regulated expression of E-cadherin and down-regulated expression of P-cadherin in BALB/c-nu mouse model in vivo assay. Our results unraveled the possibility that HPV-16 E6/E7 could promote cell invasive potential via regulating cadherin switching, and consequently contribute to progression and metastasis of cervical cancer.

Molecular and clinical characterization of plasmid-mediated AmpC β-lactamase-producing Escherichia coli bacteraemia: a comparison with extended-spectrum β-lactamase-producing and non-resistant E. coli bacteraemia.

PubMed

Matsumura, Y; Nagao, M; Iguchi, M; Yagi, T; Komori, T; Fujita, N; Yamamoto, M; Matsushima, A; Takakura, S; Ichiyama, S

2013-02-01

Plasmid-mediated AmpC β-lactamase-producing Escherichia coli (AmpC-E) bacteraemia was characterized by comparison with bacteraemia caused by extended-spectrum β-lactamase (ESBL)-producing E. coli (ESBL-E) and non-resistant E. coli (NR-E) in the era of the worldwide spread of the CTX-M-15-producing O25b-ST131-B2 clone. Of 706 bloodstream E. coli isolates collected between 2005 and 2010 in three Japanese university hospitals, 111 ESBL screening-positive isolates were analysed for AmpC and ESBL genes by PCR. A case-control study was performed in which the cases consisted of all of the patients with AmpC-E bacteraemia. Phylogenetic groups, sequence types and O25b serotype were determined. Twenty-seven AmpC-E isolates (26 of which were of the CMY-2 type) were identified, and 54 ESBL-E and 54 NR-E isolates were selected for the controls. Nineteen AmpC-E isolates were also positive for ESBL. CTX-M-14 was the most prevalent ESBL type among both the AmpC-E and ESBL-E isolates. The O25b-ST131-B2 clone was the most prevalent among the ESBL-E isolates (26%) and the second most prevalent among the NR-E isolates (13%), but only one O25b-ST131-B2 clone was found among the AmpC-E isolates. Twenty-three different sequence types were identified among the AmpC-E isolates. When compared with bacteraemia with ESBL-E, previous isolation of multidrug-resistant bacteria and intravascular catheterization were independently associated with a lower risk for AmpC-E. When compared with NR-E bacteraemia, prior use of antibiotics was the only significant risk factor for AmpC-E. Unlike the spread of the O25b-ST131-B2 clone between ESBL-E and NR-E, the AmpC-E isolates were not dominated by any specific clone. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Fission yeast translation initiation factor 3 subunit eIF3h is not essential for global translation initiation, but deletion of eif3h+ affects spore formation.

PubMed

Ray, Anirban; Bandyopadhyay, Amitabha; Matsumoto, Tomohiro; Deng, Haiteng; Maitra, Umadas

2008-11-01

The fission yeast Schizosaccharomyces pombe homologue of the p40/eIF3h subunit of mammalian translation initiation factor eIF3 has been characterized in this study. We show that this protein physically associates with the 40S ribosomal particles as a constituent of the multimeric eIF3 protein complex, which consists of all five known eIF3 core subunits (eIF3a, eIF3b, eIF3c, eIF3g and eIF3i) as well as the five non-core subunits (eIF3d, eIF3e, eIF3f, eIF3h and eIF3m) that constitute an eIF3 holocomplex in fission yeast. However, affinity purification of eIF3 from fission yeast cells expressing TAP-tagged eIF3h suggests the presence of distinct forms of eIF3 that differ in their composition of the non-core subunits. Further characterization of eIF3h shows that strains lacking eif3h(+) (eif3hDelta) are viable and show no gross defects, either in vegetative growth or in the rate of in vivo protein synthesis. Polysome profile analysis shows no apparent defects in translation initiation. Furthermore, deletion of eif3h(+) does not affect the ability of the other eIF3 subunits to remain associated with one another in a tight protein complex similar to the situation in wild-type cells. Additionally, we show that human eIF3h can functionally substitute fission yeast eIF3h in complementing in vivo a genetic deletion of eif3h(+). Interestingly, mutant eif3hDelta cells show several prominent phenotypic properties. They are hypersensitive to caffeine and highly defective in meiosis, producing either no spores or incomplete tetrads with a very high frequency. The implications of these results in relation to the functions of eIF3h in Sz. pombe are discussed. (c) 2008 John Wiley & Sons, Ltd.

Human ApoE Isoforms Differentially Modulate Glucose and Amyloid Metabolic Pathways in Female Brain: Evidence of the Mechanism of Neuroprotection by ApoE2 and Implications for Alzheimer's Disease Prevention and Early Intervention.

PubMed

Keeney, Jeriel Thomas-Richard; Ibrahimi, Shaher; Zhao, Liqin

2015-01-01

Three major genetic isoforms of apolipoprotein E (ApoE), ApoE2, ApoE3, and ApoE4, exist in humans and lead to differences in susceptibility to Alzheimer's disease (AD). This study investigated the impact of human ApoE isoforms on brain metabolic pathways involved in glucose utilization and amyloid-β (Aβ) degradation, two major areas that are significantly perturbed in preclinical AD. Hippocampal RNA samples from middle-aged female mice with targeted human ApoE2, ApoE3, and ApoE4 gene replacement were comparatively analyzed with a qRT-PCR custom array for the expression of 85 genes involved in insulin/insulin-like growth factor (Igf) signaling. Consistent with its protective role against AD, ApoE2 brain exhibited the most metabolically robust profile among the three ApoE genotypes. When compared to ApoE2 brain, both ApoE3 and ApoE4 brains exhibited markedly reduced levels of Igf1, insulin receptor substrates (Irs), and facilitated glucose transporter 4 (Glut4), indicating reduced glucose uptake. Additionally, ApoE4 brain exhibited significantly decreased Pparg and insulin-degrading enzyme (Ide), indicating further compromised glucose metabolism and Aβ dysregulation associated with ApoE4. Protein analysis showed significantly decreased Igf1, Irs, and Glut4 in ApoE3 brain, and Igf1, Irs, Glut4, Pparg, and Ide in ApoE4 brain compared to ApoE2 brain. These data provide the first documented evidence that human ApoE isoforms differentially affect brain insulin/Igf signaling and downstream glucose and amyloid metabolic pathways, illustrating a potential mechanism for their differential risk in AD. A therapeutic strategy that enhances brain insulin/Igf1 signaling activity to a more robust ApoE2-like phenotype favoring both energy production and amyloid homeostasis holds promise for AD prevention and early intervention.

A longitudinal study of the relationship between receptivity to e-cigarette advertisements and e-cigarette use among baseline non-users of cigarettes and e-cigarettes, United States.

PubMed

Agaku, Israel T; Davis, Kevin; Patel, Deesha; Shafer, Paul; Cox, Shanna; Ridgeway, William; King, Brian A

2017-01-01

We investigated the relationship between receptivity to electronic cigarette (e-cigarette) advertisements at baseline and e-cigarette use at follow-up among adult baseline non-users of cigarettes and e-cigarettes. A nationally representative online panel was used to survey non-users of cigarettes and e-cigarettes ( n  = 2191) at baseline and 5-month follow-up. At baseline, respondents were shown an e-cigarette advertisement and asked if they were aware of it (exposure). Among those exposed, receptivity was self-rated for each ad using a validated scale of 1 to 5 for agreement with each of six items: "worth remembering," "grabbed my attention," "powerful," "informative," "meaningful," and "convincing." Logistic regression was used to measure the relationship between receptivity at baseline and e-cigarette use at follow-up. Among baseline non-users of cigarettes and e-cigarettes, 16.6% reported exposure to e-cigarette advertisements at baseline; overall mean receptivity score was 2.77. Among baseline non-users who reported exposure to e-cigarette advertisements, incidence of e-cigarette use at follow-up was 2.7%; among baseline non-users who reported not being exposed to e-cigarette advertisements, incidence of e-cigarette use at follow-up was 1.3%. The attributable risk percentage for e-cigarette initiation from e-cigarette advertisement exposure was 59.3%; the population attributable risk percentage from e-cigarette advertisement exposure was 22.6%. Receptivity at baseline was associated with e-cigarette use at follow-up (aOR = 1.57; 95% CI = 1.04-2.37). Receptivity to e-cigarette advertisements at baseline was associated with greater odds of e-cigarette use at follow-up among baseline non-users of cigarettes and e-cigarettes. Understanding the role of advertising in e-cigarette initiation could help inform public health policy.

Effect of ethanol-gasoline blends on small engine generator energy efficiency and exhaust emission.

PubMed

Lin, Wen-Yinn; Chang, Yuan-Yi; Hsieh, You-Ru

2010-02-01

This study was focused on fuel energy efficiency and pollution analysis of different ratios of ethanol-gasoline blended fuels (E0, E3, E6, and E9) under different loadings. In this research, the experimental system consisted of a small engine generator, a particulate matter measurement system, and an exhaust gas analyzer system. Different fuels, unleaded gasoline, and ethanol-gasoline blends (E0, E3, E6, and E9) were used to study their effects on the exhaust gas emission and were expressed as thermal efficiency of the small engine generator energy efficiency. The results suggested that particle number concentration increased as the engine loading increased; however, it decreased as the ethanol content in the blend increased. While using E6 as fuel, the carbon monoxide (CO) concentration was less than other fuels (E0, E3, and E9) for each engine loading. The average of CO concentration reduction by using E3, E6, and E9 is 42, 86, and 83%, respectively. Using an ethanol-gasoline blend led to a significant reduction in exhaust emissions by approximately 78.7, 97.5, and 89.46% of the mean average values of hydrocarbons (HCs) with E3, E6, and E9 fuels, respectively, for all engine loadings. Using an ethanol-gasoline blend led to a significant reduction in exhaust emissions by approximately 35, 86, and 77% of the mean average values of nitrogen oxides (NOx) with E3, E6, and E9 fuels, respectively, at each engine loading. The E6 fuel gave the best results of the exhaust emissions, and the E9 fuel gave the best results of the particle emissions and engine performance. The thermal efficiency of the small engine generator increased as the ethanol content in the blend increased and as the engine loading increased.

Novel Binding Motif and New Flexibility Revealed by Structural Analyses of a Pyruvate Dehydrogenase-Dihydrolipoyl Acetyltransferase Subcomplex from the Escherichia coli Pyruvate Dehydrogenase Multienzyme Complex*

PubMed Central

Arjunan, Palaniappa; Wang, Junjie; Nemeria, Natalia S.; Reynolds, Shelley; Brown, Ian; Chandrasekhar, Krishnamoorthy; Calero, Guillermo; Jordan, Frank; Furey, William

2014-01-01

The Escherichia coli pyruvate dehydrogenase multienzyme complex contains multiple copies of three enzymatic components, E1p, E2p, and E3, that sequentially carry out distinct steps in the overall reaction converting pyruvate to acetyl-CoA. Efficient functioning requires the enzymatic components to assemble into a large complex, the integrity of which is maintained by tethering of the displaced, peripheral E1p and E3 components to the E2p core through non-covalent binding. We here report the crystal structure of a subcomplex between E1p and an E2p didomain containing a hybrid lipoyl domain along with the peripheral subunit-binding domain responsible for tethering to the core. In the structure, a region at the N terminus of each subunit in the E1p homodimer previously unseen due to crystallographic disorder was observed, revealing a new folding motif involved in E1p-E2p didomain interactions, and an additional, unexpected, flexibility was discovered in the E1p-E2p didomain subcomplex, both of which probably have consequences in the overall multienzyme complex assembly. This represents the first structure of an E1p-E2p didomain subcomplex involving a homodimeric E1p, and the results may be applicable to a large range of complexes with homodimeric E1 components. Results of HD exchange mass spectrometric experiments using the intact, wild type 3-lipoyl E2p and E1p are consistent with the crystallographic data obtained from the E1p-E2p didomain subcomplex as well as with other biochemical and NMR data reported from our groups, confirming that our findings are applicable to the entire E1p-E2p assembly. PMID:25210042

The processed isoform of the translation termination factor eRF3 localizes to the nucleus to interact with the ARF tumor suppressor

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

Hashimoto, Yoshifumi; Kumagai, Naomichi; Hosoda, Nao

2014-03-14

Highlights: • So far, eRF3 has been thought to function exclusively in the cytoplasm. • eRF3 is a nucleo-cutoplasmic shuttling protein. • eRF3 has a leptomycin-sensitive nuclear export signal (NES). • Removal of NES by proteolytic cleavage allows eRF3 to translocate to the nucleus. • The processed eRF3 (p-eRF3) interacts with a nuclear tumor suppressor ARF. - Abstract: The eukaryotic releasing factor eRF3 is a multifunctional protein that plays pivotal roles in translation termination as well as the initiation of mRNA decay. eRF3 also functions in the regulation of apoptosis; eRF3 is cleaved at Ala73 by an as yet unidentifiedmore » protease into processed isoform of eRF3 (p-eRF3), which interacts with the inhibitors of apoptosis proteins (IAPs). The binding of p-eRF3 with IAPs leads to the release of active caspases from IAPs, which promotes apoptosis. Although full-length eRF3 is localized exclusively in the cytoplasm, p-eRF3 localizes in the nucleus as well as the cytoplasm. We here focused on the role of p-eRF3 in the nucleus. We identified leptomycin-sensitive nuclear export signal (NES) at amino acid residues 61–71 immediately upstream of the cleavage site Ala73. Thus, the proteolytic cleavage of eRF3 into p-eRF3 leads to release an amino-terminal fragment containing NES to allow the relocalization of eRF3 into the nucleus. Consistent with this, p-eRF3 more strongly interacted with the nuclear ARF tumor suppressor than full-length eRF3. These results suggest that while p-eRF3 interacts with IAPs to promote apoptosis in the cytoplasm, p-eRF3 also has some roles in regulating cell death in the nucleus.« less

Translation Initiation Factor AteIF(iso)4E Is Involved in Selective mRNA Translation in Arabidopsis Thaliana Seedlings

PubMed Central

Martínez-Silva, Ana Valeria; Aguirre-Martínez, César; Flores-Tinoco, Carlos E.; Alejandri-Ramírez, Naholi D.; Dinkova, Tzvetanka D.

2012-01-01

One of the most regulated steps of translation initiation is the recruitment of mRNA by the translation machinery. In eukaryotes, this step is mediated by the 5′end cap-binding factor eIF4E bound to the bridge protein eIF4G and forming the eIF4F complex. In plants, different isoforms of eIF4E and eIF4G form the antigenically distinct eIF4F and eIF(iso)4F complexes proposed to mediate selective translation. Using a microarray analysis of polyribosome- and non-polyribosome-purified mRNAs from 15 day-old Arabidopsis thaliana wild type [WT] and eIF(iso)4E knockout mutant [(iso)4E-1] seedlings we found 79 transcripts shifted from polyribosomes toward non-polyribosomes, and 47 mRNAs with the opposite behavior in the knockout mutant. The translationally decreased mRNAs were overrepresented in root-preferentially expressed genes and proteins from the endomembrane system, including several transporters such as the phosphate transporter PHOSPHATE1 (PHO1), Sucrose transporter 3 (SUC3), ABC transporter-like with ATPase activity (MRP11) and five electron transporters, as well as signal transduction-, protein modification- and transcription-related proteins. Under normal growth conditions, eIF(iso)4E expression under the constitutive promoter 35 S enhanced the polyribosomal recruitment of PHO1 supporting its translational preference for eIF(iso)4E. Furthermore, under phosphate deficiency, the PHO1 protein increased in the eIF(iso)4E overexpressing plants and decreased in the knockout mutant as compared to wild type. In addition, the knockout mutant had larger root, whereas the 35 S directed expression of eIF(iso)4E caused shorter root under normal growth conditions, but not under phosphate deficiency. These results indicate that selective translation mediated by eIF(iso)4E is relevant for Arabidopsis root development under normal growth conditions. PMID:22363683

Novel binding motif and new flexibility revealed by structural analyses of a pyruvate dehydrogenase-dihydrolipoyl acetyltransferase subcomplex from the Escherichia coli pyruvate dehydrogenase multienzyme complex.

PubMed

Arjunan, Palaniappa; Wang, Junjie; Nemeria, Natalia S; Reynolds, Shelley; Brown, Ian; Chandrasekhar, Krishnamoorthy; Calero, Guillermo; Jordan, Frank; Furey, William

2014-10-24

The Escherichia coli pyruvate dehydrogenase multienzyme complex contains multiple copies of three enzymatic components, E1p, E2p, and E3, that sequentially carry out distinct steps in the overall reaction converting pyruvate to acetyl-CoA. Efficient functioning requires the enzymatic components to assemble into a large complex, the integrity of which is maintained by tethering of the displaced, peripheral E1p and E3 components to the E2p core through non-covalent binding. We here report the crystal structure of a subcomplex between E1p and an E2p didomain containing a hybrid lipoyl domain along with the peripheral subunit-binding domain responsible for tethering to the core. In the structure, a region at the N terminus of each subunit in the E1p homodimer previously unseen due to crystallographic disorder was observed, revealing a new folding motif involved in E1p-E2p didomain interactions, and an additional, unexpected, flexibility was discovered in the E1p-E2p didomain subcomplex, both of which probably have consequences in the overall multienzyme complex assembly. This represents the first structure of an E1p-E2p didomain subcomplex involving a homodimeric E1p, and the results may be applicable to a large range of complexes with homodimeric E1 components. Results of HD exchange mass spectrometric experiments using the intact, wild type 3-lipoyl E2p and E1p are consistent with the crystallographic data obtained from the E1p-E2p didomain subcomplex as well as with other biochemical and NMR data reported from our groups, confirming that our findings are applicable to the entire E1p-E2p assembly. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Evaluation of anti-melanoma activities of (1S,2E,4R,6E,8R,11S,12R)-8,12-epoxy-2,6-cembradiene-4,11-diol, (1S,2E,4R,6E,8S,11R,12S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1S,4R,13S)-cembra-2E,7E,11E-trien-4,13-diol from the Red Sea soft coral Sarcophyton glaucum.

PubMed

Szymanski, Pawel T; Ahmed, Safwat A; Radwan, Mohamed M; Khalifa, Sherief I; Fahmy, Hesham

2014-08-01

Three natural cembranoids from the Red Sea soft coral Sarcophyton glaucum namely (1S,2E,4R,6E,8R,11S,12R)-8,12-epoxy-2,6-cembradiene-4,11-diol, (1S,2E,4R,6E,8S,11R,12S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1S,4R,13S)-cembra-2E,7E,11E-trien-4,13-diol were evaluated for their inhibitory effects on mouse melanoma B16F10 cell growth. Results show that all the cembranoids strongly inhibit viability of melanoma cells particularly during 48 -72 hrs treatment and also inhibit de novo DNA synthesis and PARP activity and stimulate fragmentation of DNA. (1S,2E,4R,6E,8R,11S,12R)-8,12-epoxy-2,6-cembradiene-4,11-diol was not cytotoxic to monkey kidney CV-1 cells at the concentration that produces the anti-melanoma effects which indicates that this compound may be a good candidate for further development. (1S,2E,4R,6E,8S,11R,12S)-8,11-epoxy-4,12-epoxy-2,6-cembradiene and (1S,4R,13S)-cembra-2E,7E,11E-trien-4,13-diol were found to be cytotoxic to healthy cells.

Characterization of two trpE genes encoding anthranilate synthase {alpha}-subunit in Azospirillum brasilense

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

Ge Shimei; Xie Baoen; Chen Sanfeng

2006-03-10

The previous report from our laboratory has recently identified a new trpE gene (termed trpE {sub 2}) which exists independently in Azospirillum brasilense Yu62. In this study, amplification of trpE(G) (termed trpE {sub 1}(G) here) confirmed that there are two copies of trpE gene, one trpE being fused into trpG while the other trpE existed independently. This is First report to suggest that two copies of the trpE gene exist in this bacterium. Comparison of the nucleotide sequence demonstrated that putative leader peptide, terminator, and anti-terminator were found upstream of trpE {sub 1}(G) while these sequence features did not existmore » in front of trpE {sub 2}. The {beta}-galactosidase activity of an A. brasilense strain carrying a trpE {sub 2}-lacZ fusion remained constant at different tryptophan concentrations, but the {beta}-galactosidase activity of the same strain carrying a trpE {sub 1}(G)-lacZ fusion decreased as the tryptophan concentration increased. These data suggest that the expression of trpE {sub 1}(G) is regulated at the transcriptional level by attenuation while trpE {sub 2} is constantly expressed. The anthranilate synthase assays with trpE {sub 1}(G){sup -} and trpE {sub 2} {sup -} mutants demonstrated that TrpE{sub 1}(G) fusion protein is feedback inhibited by tryptophan while TrpE{sub 2} protein is not. We also found that both trpE {sub 1}(G) and trpE {sub 2} gene products were involved in IAA synthesis.« less

Different Cholinesterase Inhibitor Effects on CSF Cholinesterases in Alzheimer Patients

PubMed Central

Nordberg, Agneta; Darreh-Shori, Taher; Peskind, Elaine; Soininen, Hilkka; Mousavi, Malahat; Eagle, Gina; Lane, Roger

2014-01-01

Background The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. Methods and Findings AD patients aged 50–85 years were randomized to open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE and BuChE activities were assayed by Ellman’s colorimetric method. Protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). Primary analyses were based on the Completer population (randomized patients who completed Week 13 assessments). 63 patients were randomized to treatment. Rivastigmine was associated with decreased AChE activity by 42.6% and decreased AChE protein levels by 9.3%, and decreased BuChE activity by 45.6% and decreased BuChE protein levels by 21.8%. Galantamine decreased AChE activity by 2.1% and BuChE activity by 0.5%, but increased AChE protein levels by 51.2% and BuChE protein levels by10.5%. Donepezil increased AChE and BuChE activities by 11.8% and 2.8%, respectively. Donepezil caused a 215.2%increase in AChE and 0.4% increase in BuChE protein levels. Changes in mean AChE-Readthrough/Synaptic ratios, which might reflect underlying neurodegenerative processes, were 1.4, 0.6, and 0.4 for rivastigmine, donepezil and galantamine, respectively. Conclusion The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation. PMID:19199870

Different cholinesterase inhibitor effects on CSF cholinesterases in Alzheimer patients.

PubMed

Nordberg, Agneta; Darreh-Shori, Taher; Peskind, Elaine; Soininen, Hilkka; Mousavi, Malahat; Eagle, Gina; Lane, Roger

2009-02-01

The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. AD patients aged 50-85 years were randomized to open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE and BuChE activities were assayed by Ellman's colorimetric method. Protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). Primary analyses were based on the Completer population (randomized patients who completed Week 13 assessments). 63 patients were randomized to treatment. Rivastigmine was associated with decreased AChE activity by 42.6% and decreased AChE protein levels by 9.3%, and decreased BuChE activity by 45.6% and decreased BuChE protein levels by 21.8%. Galantamine decreased AChE activity by 2.1% and BuChE activity by 0.5%, but increased AChE protein levels by 51.2% and BuChE protein levels by 10.5%. Donepezil increased AChE and BuChE activities by 11.8% and 2.8%, respectively. Donepezil caused a 215.2% increase in AChE and 0.4% increase in BuChE protein levels. Changes in mean AChE-Readthrough/Synaptic ratios, which might reflect underlying neurodegenerative processes, were 1.4, 0.6, and 0.4 for rivastigmine, donepezil and galantamine, respectively. The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation.

Effect of additional vitamin E and zinc supplementation on immunological changes in peripartum Sahiwal cows.

PubMed

Chandra, G; Aggarwal, A; Kumar, M; Singh, A K; Sharma, V K; Upadhyay, R C

2014-12-01

This study was conducted to exploit ameliorative effect of additional vitamin E and/or zinc supplementation on immune response of peripartum Sahiwal cows. Thirty-two pregnant dry Sahiwal cows were blocked into four treatment groups (n = 8), namely control, zinc (Zn), vitamin E (Vit E) and zinc + vitamin E (Zn + Vit E). Feeding regimen was same in all the groups except that the Sahiwal cows in the zinc-, vitamin E- and zinc + vitamin E-fed groups were additionally supplemented with 60 mg Zn/kg DM, 1000 IU vitamin E and 60 mg/kg + 1000 IU Zn + vitamin E, respectively, from day 60 pre-partum to day 90 post-partum. Blood samples were collected on days -60, -45, -30, -15, -7, -3, 0, 3, 7, 15, 30, 45, 60, 90 and 120 with respect to day of parturition and analysed for total immunoglobulin (TIG), immunoglobulin G (IgG), interleukin-2 (IL-2), vitamin E (Vit E) and zinc (Zn) status. Before calving, cows showed a decrease in plasma TIG, IgG, IL-2, Vit E and Zn levels. However, increased levels of plasma TIG, IgG, IL-2, Vit E and Zn were observed after calving. After calving, Sahiwal cows supplemented with Zn + Vit E had higher plasma TIG, IgG and IL-2 in comparison with cows of control and Zn + Vit E-fed groups. In the present study, plasma vitamin E level was higher in Vit E-fed and Zn + Vit E-fed cows; however, zinc level was higher in Zn- and Zn + Vit E-supplemented cows. In conclusion, a reduced immune response during peripartum period in Sahiwal cows was ameliorated by dietary vitamin E and zinc supplementation. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Entertainment-Education Narrative Versus Nonnarrative Interventions to Educate and Motivate Latinas to Engage in Mammography Screening.

PubMed

Borrayo, Evelinn A; Rosales, Monica; Gonzalez, Patricia

2017-06-01

The evidence is limited comparing the effects of entertainment-education (E-E) narrative versus nonnarrative interventions to educate and motivate Latinas to engage in mammography screening. This study compared an E-E narrative intervention to two nonnarrative interventions' effects among Latinas on breast cancer knowledge and motivation, as measured by changes in self-efficacy, behavioral norms, and behavioral intentions to engage in mammography screening. A sample of 141 Spanish-speaking Latinas was randomly assigned to one of three arms: an E-E narrative video, a nonnarrative educational video, and printed educational materials. Using a repeated measures design, the influence of the E-E narrative on pretest to posttest measures was assessed and compared to the influence of the other two interventions. The E-E narrative and nonnarrative interventions significantly increased Latinas' breast cancer knowledge, mammography self-efficacy, and behavioral norms from pretest to posttest. However, the E-E narrative participants' pretest to posttest difference in mammography self-efficacy was significantly higher when compared to the difference of the other two interventions. The effect of the E-E narrative intervention on self-efficacy and behavioral norms was moderated by the participants' absorption in the story and identification with the story characters. E-E narrative and nonnarrative interventions significantly educated and motivated Latinas to engage in mammography screening. The effects on mammography self-efficacy, an important precursor to behavior change, can be more strongly influenced by E-E narratives. Although E-E narrative and nonnarrative interventions were effective, the need still exists to assess if they can ultimately influence lifesaving breast cancer screening behaviors.

Carbon-hydrogen-related complexes in Si

NASA Astrophysics Data System (ADS)

Kolkovsky, Vl.; Stübner, R.; Gwozdz, K.; Weber, J.

2018-04-01

Several deep level transient spectroscopy (DLTS) peaks (E42, E65, E75, E90, E262, and H180) are observed in n- and p-type Czochralski-grown Si samples subjected to hydrogenation by a dc H plasma treatment. The concentration of the defects is found to be proportional to the carbon and hydrogen content in our samples. The analysis of the depth profiles performed in Si samples hydrogenated by wet chemically etching shows that all these defects contain a single H atom. E65 and E75 appear only in samples with a high oxygen content which shows that oxygen is a constituent of these defects. The analysis of the enhancement of the emission rate of the defects with electric field shows that E65, E75, E90, and E262 are single acceptors whereas E42 is a double acceptor. The presence of a barrier for hole capture (about 53 meV) can explain the absence of the enhancement of the emission rate of H180, which can be attributed to a single acceptor state. From a comparison with theory, we assign E90 to CH1BC, E42 (E262) to CH1AB, and H180 to CH1Td. The similarity of the electrical properties of E65 and E75 to those of E90 suggest that E65 and E75 may originate from the CH1BC defect with an oxygen atom in its nearest neighborhood. Our results on the CH-related complexes give a conclusive explanation of some previously reported controversial experimental data.

Potential of aryl-urea-benzofuranylthiazoles hybrids as multitasking agents in Alzheimer's disease.

PubMed

Kurt, Belma Zengin; Gazioglu, Isil; Basile, Livia; Sonmez, Fatih; Ginex, Tiziana; Kucukislamoglu, Mustafa; Guccione, Salvatore

2015-09-18

New benzofuranylthiazole derivatives containing the aryl-urea moiety were synthesized and evaluated in vitro as dual acetylcholinesterase (AChE)-butyrylcholinesterase (BuChE) inhibitors. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized compounds were assayed. The result showed that all the synthesized compounds exhibited inhibitory activity on both AChE and BuChE with 1-(4-(5-bromobenzofuran-2-yl)thiazol-2-yl)-3-(2-fluorophenyl)urea (e25, IC50 value of 3.85 μM) and 1-(4-iodophenyl)-3-(4-(5-nitrobenzofuran-2-yl)thiazol-2-yl)urea (e38, IC50 value of 2.03 μM) as the strongest inhibitors against AChE and BuChE, respectively. Compound e38 was 8.5-fold more potent than galanthamine. The selectivity index of e25 and e38 was 2.40 and 0.37 against AChE and BuChE, respectively. Compound e2, e4 and e11 (IC50 = 0.2, 0.5 and 1.13 μM, respectively) showed a better ABTS cation radical scavenging ability than the standard quercetin (IC50 = 1.18 μM). Best poses of compounds e38 on BuChE and e25 on AChE indicate that the thiazole ring and the amidic moiety are important sites of interaction with both ChEs. In addition, the benzofuran ring and phenyl ring are anchored to the side chains of both enzymes by π-π(pi-pi) interactions. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Fusion Protein Vaccines Targeting Two Tumor Antigens Generate Synergistic Anti-Tumor Effects

PubMed Central

Cheng, Wen-Fang; Chang, Ming-Cheng; Sun, Wei-Zen; Jen, Yu-Wei; Liao, Chao-Wei; Chen, Yun-Yuan; Chen, Chi-An

2013-01-01

Introduction Human papillomavirus (HPV) has been consistently implicated in causing several kinds of malignancies, and two HPV oncogenes, E6 and E7, represent two potential target antigens for cancer vaccines. We developed two fusion protein vaccines, PE(ΔIII)/E6 and PE(ΔIII)/E7 by targeting these two tumor antigens to test whether a combination of two fusion proteins can generate more potent anti-tumor effects than a single fusion protein. Materials and Methods In vivo antitumor effects including preventive, therapeutic, and antibody depletion experiments were performed. In vitro assays including intracellular cytokine staining and ELISA for Ab responses were also performed. Results PE(ΔIII)/E6+PE(ΔIII)/E7 generated both stronger E6 and E7-specific immunity. Only 60% of the tumor protective effect was observed in the PE(ΔIII)/E6 group compared to 100% in the PE(ΔIII)/E7 and PE(ΔIII)/E6+PE(ΔIII)/E7 groups. Mice vaccinated with the PE(ΔIII)/E6+PE(ΔIII)/E7 fusion proteins had a smaller subcutaneous tumor size than those vaccinated with PE(ΔIII)/E6 or PE(ΔIII)/E7 fusion proteins alone. Conclusion Fusion protein vaccines targeting both E6 and E7 tumor antigens generated more potent immunotherapeutic effects than E6 or E7 tumor antigens alone. This novel strategy of targeting two tumor antigens together can promote the development of cancer vaccines and immunotherapy in HPV-related malignancies. PMID:24058440

Evaluation of Tp-E Interval and Tp-E/QT Ratio in Patients with Aortic Stenosis.

PubMed

Yayla, Çağrı; Bilgin, Murat; Akboğa, Mehmet Kadri; Gayretli Yayla, Kadriye; Canpolat, Uğur; Dinç Asarcikli, Lale; Doğan, Mehmet; Turak, Osman; Çay, Serkan; Özeke, Özcan; Akyel, Ahmet; Yeter, Ekrem; Aydoğdu, Sinan

2016-05-01

The risk of syncope and sudden cardiac death due to ventricular arrhythmias increased in patients with aortic stenosis (AS). Recently, it was shown that Tp-e interval, Tp-e/QT, and Tp-e/QTc ratio can be novel indicators for prediction of ventricular arrhythmias and mortality. We aimed to investigate the association between AS and ventricular repolarization using Tp-e interval and Tp-e/QT ratio. Totally, 105 patients with AS and 60 control subjects were enrolled to this study. The severity of AS was defined by transthoracic echocardiographic examination. Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were measured from the 12-lead electrocardiogram. Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were significantly increased in parallel to the severity of AS (P < 0.001, P = 0.001, and P = 0.001, respectively). Also, it was shown that Tp-e/QTc ratio had significant positive correlation with mean aortic gradient (r = 0.192, P = 0.049). In multivariate logistic regression analysis, Tp-e/QTc ratio and left ventricular mass were found to be independent predictors of severe AS (P = 0.03 and P = 0.04, respectively). Our study showed that Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were increased in patients with severe AS. Tp-e/QTc ratio and left ventricular mass were found as independent predictors of severe AS. © 2015 Wiley Periodicals, Inc.

Implementation of Get with the Guideline Acute Myocardial Infarction Program at Johns Hopkins Hospital and Its Effect on Core Measures

DTIC Science & Technology

2007-05-25

allergy E Patient is discharged on hydralazine/nitrate therapy* E Hypotension* El Moderate or severe aortic stenosis El Worsening renal function* E...Hypotension* E Moderate or severe aortic stenosis El Worsening renal function* E Hyperkalemia* E Bilateral renal artery stenosis * E Pregnancy* E Other...Hyperkalemia* El Bilateral renal artery stenosis * E Pregnancy* El Other - must be documented in medical record Angiotension Receptor Blocker (ARB

26 CFR 1.367(e)-0 - Outline of §§ 1.367(e)-1 and 1.367(e)-2.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 4 2011-04-01 2011-04-01 false Outline of §§ 1.367(e)-1 and 1.367(e)-2. 1.367(e)-0 Section 1.367(e)-0 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Effects on Corporation § 1.367(e)-0 Outline of §§ 1.367(e)-1...

Prophylactic Administration of CN-105 Confers Neuroprotection Against Acute Brain Injury

DTIC Science & Technology

2017-10-01

105 was designed from the receptor binding face of apolipoprotein E, which is an endogenous protein that has been demonstrated to modify injury...apolipoprotein E (APOE - gene; apoE - protein ) polymorphism. There are three distinct apoE protein isoforms, designated apoE2, apoE3, and apoE4. Although there...data underscore the importance that apoE plays in mediating CNS responses to acute injury and neurodegeneration. The apoE protein was initially found

Evaluation of Unix-Based Integrated Office Automation Products.

DTIC Science & Technology

1994-04-01

recipient preferences of networked UNIX users. An e-mail directory contains the preferred applications (e.g., FrameMaker , Excel) for each user, and e...Future Not Available (B) FrameMaker (UNIX) E-Optional I/E-Standard Future* (B) Interleaf (UNIX) I/E-Optional I/E-Standard Future* (B) IslandWrite Not...Optional Future Not Available DXF I-Optional Future Not Available (B) EPSI I-Standard Not Available Future (B) FrameMaker (MIF) E-Optional I/E-Standard Not

[Profiles of cell proliferation and apoptosis in the mouse epithelial regeneration model K6b-E6/E7].

PubMed

Bonilla-Delgado, José; Rodríguez-Uribe, Genaro; Cortés-Malagón, Enoc Mariano; Sierra Martínez, Mónica; Acosta-Altamirano, Gustavo; Gariglio-Vidal, Patricio

2012-01-01

Mammals have limited epithelial regeneration capacity. The K6b-E6/E7 mice model has been described as useful for the study of epithelial regeneration. The objective of this study is to compare the expression of E6/E7 oncogenes with those of cell proliferation and apoptosis during epithelization. The hypothesis of this study is that alterations in cell proliferation and apoptosis in K6b-E6/E7 mice will only occur during epithelization. Deep 2 mm punches were performed in the middle of transgenic and control mice's ears. A biopsy was collected from the epithelization zone 72 hours and 2 weeks post-injury. Assays for cell proliferation and apoptosis were carried out by immunohistochemistry and TUNEL techniques, respectively. RT-PCR in situ was performed to compare E6/E7 expressions in the areas studied. Transgenic strain K6b-E6/E7 presented more proliferative cells and less apoptotic cells in epithelizated zones. This effect was limited to suprabasal stratum only, and correlates with E6/E7 oncogenes expression. Two weeks post-injury, cell proliferation and apoptosis were similar in both samples as the E6/E7 expression went down. K6b-E6/E7 mouse model is useful for epithelial regeneration. Its mechanisms should be considered for the treatment of deep wounds.

E2E: A Summary of the e2e Learning Framework.

ERIC Educational Resources Information Center

Learning and Skills Development Agency, London (England).

This publication is a summary of the E2E (Entry to Employment) Learning Framework that provides guidance on program implementation. (E2E is a new learning program for young people not yet ready or able to enter Modern Apprenticeship programs, a Level 2 program, or employment directly.) Section 2 highlights core values to which all involved should…

Comprehending Narratives Containing Flashbacks: Evidence for Temporally Organized Representations

ERIC Educational Resources Information Center

Claus, Berry; Kelter, Stephanie

2006-01-01

This study investigated the representations that readers construct for narratives describing a sequence of events. Participants read narratives describing 4 successive events in chronological order (Event 1, Event 2, Event 3, Event 4 [E1, E2, E3, E4] Experiment 1) or in nonchronological order with E1 being mentioned in a flashback (E2, E3, E1,…

E-learning in Saudi Arabia: 'To E or not to E, that is the question'.

PubMed

Al-Shehri, Ali M

2010-09-01

The Kingdom of Saudi Arabia (KSA) has witnessed unprecedented growth in higher education and E-learning in recent times. In the last five years, one university and five colleges have been commissioned every month; 800 scholarships have been awarded every month for overseas study; a national center for E-learning has been established; and E-units or departments have been set-up in almost every university. E-learning has become important for discussion to quote Shakespeare 'To E or not to E that is the question.' To examine current and future developments and challenges of E-learning in KSA. A qualitative approach was used to explore views of 30 senior academicians involved in E-learning during their attendance at a two-week course on the subject. All participants considered themselves as decision makers on E-learning in their units or departments. They felt that E-learning had come to stay, but acknowledged challenges in respect of resources, organization, management, and information technology. The fast development of E-learning poses many challenges. Clear vision and strategic planning with prospective E-learners in mind are essential to make E-learning programs cost effective.

[Construction and eukaryotic expression of PVAX1-hPV58mE6E7fcGB composite gene vaccine].

PubMed

Wang, He; Yu, Jiyun; Li, Li

2013-10-01

To construct and express a composite gene vaccine for human papillomavirus 58(HPV58)-associated cervical cancer, we inserted HPV58mE6E7 fusion gene into pCI-Fc-GPI eukaryotic expression vector, constructing a recombinant plasmid named pCI-sig-HPV58mE6E7-Fc-GPI. Then we further inserted fragment of sig-HPV58mE6E7Fc-GPI into the novel vaccine vector PVAX1-IRES-GM/B7, constructing PVAX1-HPV58mE6E7FcGB composite gene vaccine. PVAX1-HPV58mE6E7FcGB vaccine was successfully constructed and identified by restriction endonuclease and sequencing analysis. Eukaryotic expression of fusion antigen sig-HPV58mE6E7-Fc-GPI and molecular ad-juvant GM-CSF and B7. 1 were proved to be realized at the same time by flow cytometry and immunofluorescence. So PVAX1-HPV58mE6E7FcGB can be taken as a candidate of therapeutic vaccine for HPV58-associated tumors and their precancerous transformations.

S. pombe Uba1-Ubc15 Structure Reveals a Novel Regulatory Mechanism of Ubiquitin E2 Activity.

PubMed

Lv, Zongyang; Rickman, Kimberly A; Yuan, Lingmin; Williams, Katelyn; Selvam, Shanmugam Panneer; Woosley, Alec N; Howe, Philip H; Ogretmen, Besim; Smogorzewska, Agata; Olsen, Shaun K

2017-02-16

Ubiquitin (Ub) E1 initiates the Ub conjugation cascade by activating and transferring Ub to tens of different E2s. How Ub E1 cooperates with E2s that differ substantially in their predicted E1-interacting residues is unknown. Here, we report the structure of S. pombe Uba1 in complex with Ubc15, a Ub E2 with intrinsically low E1-E2 Ub thioester transfer activity. The structure reveals a distinct Ubc15 binding mode that substantially alters the network of interactions at the E1-E2 interface compared to the only other available Ub E1-E2 structure. Structure-function analysis reveals that the intrinsically low activity of Ubc15 largely results from the presence of an acidic residue at its N-terminal region. Notably, Ub E2 N termini are serine/threonine rich in many other Ub E2s, leading us to hypothesize that phosphorylation of these sites may serve as a novel negative regulatory mechanism of Ub E2 activity, which we demonstrate biochemically and in cell-based assays. Copyright © 2017 Elsevier Inc. All rights reserved.

Revision of Ascra with proposition of the bifida species group and description of two new species (Hemiptera: Pentatomidae: Edessinae).

PubMed

Santos, Bianca Tamires Silva Dos; Silva, Valeria Juliete Da; Fernandes, Jose Antonio Marin

2015-10-30

Edessa is comprised of six subgenera, Aceratodes, Ascra, Dorypleura, Edessa, Hypoxys and Pygoda. Ascra is here elevated to genus status based on characteristics of the male and female genitalia and the gibbous pronotum. This genus is comprised of eight species previously placed in Edessa-E. bifida, E. cordifera, E. petersii, E. abdita, E. championi, E. privata, E. conspersa and E. morbosa, as well as six new species. The genus Ascra was further divided into two groups of species bifida and privata separated by a different pattern of punctuation on body and pygophore. Here we present only the bifida species group formed by A. bifida, A. cordifera, A. petersii, A. abdita, and A. championi, as well as two new species-A. vluteum and A. flavoscutellata. Lectotypes of Aceratodes sigillatus, Edessa abdita, E. championi, E. cornuta, E. densata and E. petersii are designated. Aceratodes sigillatus, Edessa cornuta, E. densata, E. picata, and E. florida are considered junior synonyms of A. bifida. Interestingly, some species of this genus are considered edible in Mexico.

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

An Interactive Computer Program for the Preliminary Design and Analysis of Marine Reduction Gears.

DTIC Science & Technology

1982-03-01

4 E-4 c 043 04 4 E- PQ = 24 0 0 E- m 2054 4a =44 Env)2 d0 a b43 09 0 4 I6.4 44 = w. 0k2. . U)3c m 00 I= =C * 4 0 . O)U ad i 0 0~P In3 U= 4 40:M = 4 m...pa *Q4 2 c4~ .~ co N ra a9.* o H 00a = = :b4 H~ H U (3 C) U- of *4= t. E- H)40 UUO *n04 043 q N. W E-4 E-4 1.4-0 31 H 000 oi-4. H4 - M0 2I 2 04 E- HU...aO o %-c ’. %D in0 o f 3W -+V E4pa a noM pa pa pCa 0 pa H14 . pa H 1.4 pa ~00 MtH x 4 -4 U 4E4E4 0 E-4 H E ~ CaM N4 -40 0 UE- E.UE- u 0 c E4 0 9 E-4

Phase competition in a one-dimensional three-orbital Hubbard-Holstein model

NASA Astrophysics Data System (ADS)

Li, Shaozhi; Tang, Yanfei; Maier, Thomas A.; Johnston, Steven

2018-05-01

We study the interplay between the electron-phonon (e -ph) and on-site electron-electron (e-e) interactions in a three-orbital Hubbard-Holstein model on an extended one-dimensional lattice using determinant quantum Monte Carlo. For weak e-e and e -ph interactions, we observe a competition between an orbital-selective Mott phase (OSMP) and a (multicomponent) charge-density-wave (CDW) insulating phase, with an intermediate metallic phase located between them. For large e-e and e -ph couplings, the OSMP and CDW phases persist, while the metallic phase develops short-range orbital correlations and becomes insulating when both the e-e and e -ph interactions are large but comparable. Many of our conclusions are in line with those drawn from a prior dynamical mean-field theory study of the two-orbital Hubbard-Holstein model [Phys. Rev. B 95, 121112(R) (2017), 10.1103/PhysRevB.95.121112] in infinite dimension, suggesting that the competition between the e -ph and e-e interactions in multiorbital Hubbard-Holstein models leads to rich physics, regardless of the dimension of the system.

The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

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

Manzo-Merino, Joaquin; Massimi, Paola; Lizano, Marcela, E-mail: lizanosoberon@gmail.com

The HPV-16 E6 and E6{sup ⁎} proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6{sup ⁎}. Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins tomore » recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8.« less

Observation of Bs production at the Y(5S) resonance.

PubMed

Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Bornheim, A; Pappas, S P; Weinstein, A J; Asner, D M; Edwards, K W; Briere, R A; Chen, G P; Chen, J; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Crede, V; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Gibbons, L; Gittelman, B; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Meyer, T O; Onyisi, P U E; Patterson, J R; Peterson, D; Phillips, E A; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Shepherd, M R; Stroiney, S; Sun, W M; Urner, D; Wilksen, T; Weaver, K M; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Patel, R; Potlia, V; Stoeck, H; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Gollin, G D; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; White, E J; Williams, J; Wiss, J; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Gong, D T; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Li, S Z; Poling, R; Scott, A W; Smith, A; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Zweber, P; Ernst, J; Arms, K; Severini, H; Dytman, S A; Love, W; Mehrabyan, S; Mueller, J A; Savinov, V; Li, Z; Lopez, A; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Napolitano, J; He, Q; Muramatsu, H; Park, C S; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Maravin, Y; Artuso, M; Boulahouache, C; Blusk, S; Butt, J; Dorjkhaidav, O; Li, J; Menaa, N; Mountain, R; Nandakumar, R; Randrianarivony, K; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Csorna, S E

2006-01-20

Using the CLEO detector at the Cornell Electron Storage Ring, we have observed the Bs meson in e+e- annihilation at the Y(5S) resonance. We find 14 candidates consistent with Bs decays into final states with a J/psi or a Ds(*)- . The probability that we have observed a background fluctuation is less than 8 x 10(-10) . We have established that at the energy of the Y(5S) resonance Bs production proceeds predominantly through the creation of Bs*Bs* pairs. We find sigma(e+e- --> Bs*Bs*) = [0.11(-0.03))(+0.04)(stat) +/- 0.02(syst)]nb , and set the following limits: sigma(e+e- --> BsBs)/ sigma(e+ e- --> Bs*Bs*) <0.16 and [sigma(e+e- --> BsBs*) + sigma(e+e- --> Bs*Bs)]/sigma(e+e- -->Bs*Bs*) < 0.16 (90% C.L.). The mass of the Bs* meson is measured to be M(Bs*) = [5.414+/- 0.001(stat) +/- 0.003(syst)] GeV/c2 .

E-government Facilities Analysis for Public Services in Higher Education

NASA Astrophysics Data System (ADS)

Astawa, I. P. M.; Dewi, K. C.

2018-01-01

E-Government in higher education can be utilized in order to provide public services to stakeholders both internal and external. The research objectives is to analyze the e-government facilities for public services in higher education. The research began by reviewing the concept of public services and e-government, then continued by analysing e-government facilities based on the E-Government Maturity Level developed by Wirtz and Piehler. The research subject was the e-government website of three universities that ranked the top three of webometrics version (Indonesia country rank), while the research object was e-government facilities for public services. Data collection was done by observing e-government sites via online browsing. The research’s results indicated that all three e-government sites have met four e-government business model and provided e-government services in line with the fourth stage on the e-government development stage. It can concluded that the three universities have achieved e-government maturity at the fourth level.

Subbanding, Charge Transport and Related Applications in Semiconductor Devices.

DTIC Science & Technology

1977-10-01

3 1) .7., -, ŝ .2 437. 9 7 54.2 •0 373" 11 C 15 12E. 10 .G 4. Vi ? c .11,5i.. 2 - 9 t,5.5 . 1 05 11 .752;’L 10 .3󈧭)- 10 .11󈧰 4 10 .- ,:C2 9 7...1,- 4 -72. 53,* 7 3-5 71. 1u 3 o6.L13 2 .77d 333. ’.id 471. :j J 7. VI 1.8 71.793 05.566 199.991 335-027 470.315 o05 .753 .2. 1 72.560 o5. 029 199...6;7 ;20430E 2 .20430E 2 ;23430E 2 .20433E 2 .20430! 2 VI ;20430E 2 ;20430E 2 ;20430E 2 ;20433E 2 -20430! 2 9;8 ;20430E 2 ;20430E 2 ;20430E 2 .20430E 2

A new species of Eumops (Chiroptera: Molossidae) from southwestern Peru.

PubMed

Medina, César E; Gregorin, Renato; Zeballos, Horacio; Zamora, Hugo T; Moras, Ligiane M

2014-10-22

The genus Eumops is the most diverse genera of molossid bats in the Neotropics. In Peru this genus is widely distributed and represented by nine species: E. auripendulus, E. delticus, E. hansae, E. maurus, E. nanus, E. patagonicus, E. perotis, E. trumbulli, and E. wilsoni. After several years of mammalian diversity surveys in the coastal desert and western slopes of southwestern Peru, a specimen of Eumops was collected whose unique set of traits allows us to assert that deserves to be described as a new species. Based on molecular and morphological evidence, the new species is related to medium-large sized species (i.e. E. glaucinus, E. auripendulus, and E. perotis). Cytochrome b genetic divergence between the new species and the other species of the genus was high (> 12%) and it is consistent with morphological divergence presented for this new species. This new species, endemic to Peru, increases the diversity of Eumops to 16 species.

Erratum: Measurement of σ(e+e-→ψ(3770)→hadrons) at Ec.m.=3773MeV [Phys. Rev. Lett. 96, 092002 (2006)

NASA Astrophysics Data System (ADS)

Besson, D.; Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Gong, D. T.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Smith, A.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Zweber, P.; Ernst, J.; Arms, K.; Severini, H.; Dytman, S. A.; Love, W.; Mehrabyan, S.; Mueller, J. A.; Savinov, V.; Li, Z.; Lopez, A.; Mendez, H.; Ramirez, J.; Huang, G. S.; Miller, D. H.; Pavlunin, V.; Sanghi, B.; Shipsey, I. P. J.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Napolitano, J.; He, Q.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Coan, T. E.; Gao, Y. S.; Liu, F.; Artuso, M.; Boulahouache, C.; Blusk, S.; Butt, J.; Li, J.; Menaa, N.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Redjimi, R.; Sia, R.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Zhang, K.; Csorna, S. E.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Briere, R. A.; Chen, G. P.; Chen, J.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Adam, N. E.; Alexander, J. P.; Berkelman, K.; Cassel, D. G.; Duboscq, J. E.; Ecklund, K. M.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Meyer, T. O.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Phillips, E. A.; Pivarski, J.; Riley, D.; Ryd, A.; Sadoff, A. J.; Schwarthoff, H.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Weinberger, M.; Athar, S. B.; Avery, P.; Breva-Newell, L.; Patel, R.; Potlia, V.; Stoeck, H.; Yelton, J.; Rubin, P.; Cawlfield, C.; Eisenstein, B. I.; Karliner, I.; Kim, D.; Lowrey, N.; Naik, P.; Sedlack, C.; Selen, M.; White, E. J.; Wiss, J.; Shepherd, M. R.; Asner, D. M.; Edwards, K. W.

2010-04-01

We have updated our measurement of the cross section for e^+e^- -> psi(3770) -> hadrons, our publication "Measurement of sigma(e^+e^- -> psi(3770) -> hadrons) at E_{c.m.} = 3773 MeV", arXiv:hep-ex/0512038, Phys.Rev.Lett.96, 092002 (2006). Simultaneous with this arXiv update, we have published an erratum in Phys.Rev.Lett.104, 159901 (2010). There, and in this update, we have corrected a mistake in the computation of the error on the difference of the cross sections for e^+e^- -> psi(3770) -> hadrons and e^+e^- -> psi(3770) -> DDbar. We have also used a more recent CLEO measurement of cross section for e^+e^- -> psi(3770) -> DDbar. From this, we obtain an upper limit on the branching fraction for psi(3770) -> non-DDbar of 9% at 90% confidence level.

Charged lepton flavor violation in a class of radiative neutrino mass generation models

NASA Astrophysics Data System (ADS)

Chowdhury, Talal Ahmed; Nasri, Salah

2018-04-01

We investigate the charged lepton flavor violating processes μ →e γ , μ →e e e ¯, and μ -e conversion in nuclei for a class of three-loop radiative neutrino mass generation models with electroweak multiplets of increasing order. We find that, because of certain cancellations among various one-loop diagrams which give the dipole and nondipole contributions in an effective μ e γ vertex and a Z-penguin contribution in an effective μ e Z vertex, the flavor violating processes μ →e γ and μ -e conversion in nuclei become highly suppressed compared to μ →e e e ¯ process. Therefore, the observation of such a pattern in LFV processes may reveal the radiative mechanism behind neutrino mass generation.

Apolipoprotein E genotype in schizophrenia

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

Joober, R.; Lal, S.; Bloom, D.

We investigated the association between schizophrenia and the allelic polymorphism in the apolipoprotein E (Apo E) gene in 51 schizophrenic patients and 35 controls. The Apo E4 allele was equally represented in the schizophrenic group (16%) and the control group (20%) suggesting no association between schizophrenia and the Apo E4 allele. The apolipoprotein E (Apo E) is a polymorphic (E2, E3, and E4) lipoprotein involved in the transmembrane transport of cholesterol and is thought to play an important role in neuronal growth and in the central nervous system response to injury, particularly in the hippocampal region. Recent findings strongly suggestmore » that the Apo E4 allele is associated with cognitive deficits in normal and pathological aging, e.g., Alzheimer`s disease. 5 refs., 1 tab.« less

Measurement of cross sections of the interactions e+e- → ϕϕω and e+e- → ϕϕϕ at center-of-mass energies from 4.008 to 4.600 GeV

NASA Astrophysics Data System (ADS)

Ablikim, M.; Achasov, M. N.; Ahmed, S.; Ai, X. C.; Albayrak, O.; Albrecht, M.; Ambrose, D. J.; Amoroso, A.; An, F. F.; An, Q.; Bai, J. Z.; Bakina, O.; Baldini Ferroli, R.; Ban, Y.; Bennett, D. W.; Bennett, J. V.; Berger, N.; Bertani, M.; Bettoni, D.; Bian, J. M.; Bianchi, F.; Boger, E.; Boyko, I.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chai, J.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, S.; Chen, S. J.; Chen, X.; Chen, X. R.; Chen, Y. B.; Chu, X. K.; Cibinetto, G.; Dai, H. L.; Dai, J. P.; Dbeyssi, A.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; de Mori, F.; Ding, Y.; Dong, C.; Dong, J.; Dong, L. Y.; Dong, M. Y.; Dou, Z. L.; Du, S. X.; Duan, P. F.; Fan, J. Z.; Fang, J.; Fang, S. S.; Fang, X.; Fang, Y.; Farinelli, R.; Fava, L.; Feldbauer, F.; Felici, G.; Feng, C. Q.; Fioravanti, E.; Fritsch, M.; Fu, C. D.; Gao, Q.; Gao, X. L.; Gao, Y.; Gao, Z.; Garzia, I.; Goetzen, K.; Gong, L.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, R. P.; Guo, Y.; Guo, Y. P.; Haddadi, Z.; Hafner, A.; Han, S.; Hao, X. Q.; Harris, F. A.; He, K. L.; Heinsius, F. H.; Held, T.; Heng, Y. K.; Holtmann, T.; Hou, Z. L.; Hu, C.; Hu, H. M.; Hu, T.; Hu, Y.; Huang, G. S.; Huang, J. S.; Huang, X. T.; Huang, X. Z.; Huang, Z. L.; Hussain, T.; Ikegami Andersson, W.; Ji, Q.; Ji, Q. P.; Ji, X. B.; Ji, X. L.; Jiang, L. W.; Jiang, X. S.; Jiang, X. Y.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Johansson, T.; Julin, A.; Kalantar-Nayestanaki, N.; Kang, X. L.; Kang, X. S.; Kavatsyuk, M.; Ke, B. C.; Kiese, P.; Kliemt, R.; Kloss, B.; Kolcu, O. B.; Kopf, B.; Kornicer, M.; Kupsc, A.; Kühn, W.; Lange, J. S.; Lara, M.; Larin, P.; Leithoff, H.; Leng, C.; Li, C.; Li, Cheng; Li, D. M.; Li, F.; Li, F. Y.; Li, G.; Li, H. B.; Li, H. J.; Li, J. C.; Li, Jin; Li, K.; Li, K.; Li, Lei; Li, P. R.; Li, Q. Y.; Li, T.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, Y. B.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Lin, D. X.; Liu, B.; Liu, B. J.; Liu, C. X.; Liu, D.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H. B.; Liu, H. H.; Liu, H. H.; Liu, H. M.; Liu, J.; Liu, J. B.; Liu, J. P.; Liu, J. Y.; Liu, K.; Liu, K. Y.; Liu, L. D.; Liu, P. L.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, Y. B.; Liu, Y. Y.; Liu, Z. A.; Liu, Zhiqing; Loehner, H.; Long, Y. F.; Lou, X. C.; Lu, H. J.; Lu, J. G.; Lu, Y.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lyu, X. R.; Ma, F. C.; Ma, H. L.; Ma, L. L.; Ma, M. M.; Ma, Q. M.; Ma, T.; Ma, X. N.; Ma, X. Y.; Ma, Y. M.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, Y. J.; Mao, Z. P.; Marcello, S.; Messchendorp, J. G.; Mezzadri, G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Mo, Y. J.; Morales Morales, C.; Morello, G.; Muchnoi, N. Yu.; Muramatsu, H.; Musiol, P.; Nefedov, Y.; Nerling, F.; Nikolaev, I. B.; Ning, Z.; Nisar, S.; Niu, S. L.; Niu, X. Y.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Pan, Y.; Patteri, P.; Pelizaeus, M.; Peng, H. P.; Peters, K.; Pettersson, J.; Ping, J. L.; Ping, R. G.; Poling, R.; Prasad, V.; Qi, H. R.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, L. Q.; Qin, N.; Qin, X. S.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Redmer, C. F.; Ripka, M.; Rong, G.; Rosner, Ch.; Ruan, X. D.; Sarantsev, A.; Savrié, M.; Schnier, C.; Schoenning, K.; Shan, W.; Shao, M.; Shen, C. P.; Shen, P. X.; Shen, X. Y.; Sheng, H. Y.; Song, W. M.; Song, X. Y.; Sosio, S.; Spataro, S.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. H.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Tapan, I.; Thorndike, E. H.; Tiemens, M.; Uman, I.; Varner, G. S.; Wang, B.; Wang, B. L.; Wang, D.; Wang, D. Y.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, W.; Wang, W. P.; Wang, X. F.; Wang, Y.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. H.; Wang, Z. Y.; Wang, Zongyuan; Weber, T.; Wei, D. H.; Weidenkaff, P.; Wen, S. P.; Wiedner, U.; Wolke, M.; Wu, L. H.; Wu, L. J.; Wu, Z.; Xia, L.; Xia, L. G.; Xia, Y.; Xiao, D.; Xiao, H.; Xiao, Z. J.; Xie, Y. G.; Xie, Y. H.; Xiu, Q. L.; Xu, G. F.; Xu, J. J.; Xu, L.; Xu, Q. J.; Xu, Q. N.; Xu, X. P.; Yan, L.; Yan, W. B.; Yan, W. C.; Yan, Y. H.; Yang, H. J.; Yang, H. X.; Yang, L.; Yang, Y. X.; Ye, M.; Ye, M. H.; Yin, J. H.; You, Z. Y.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yuan, C. Z.; Yuan, Y.; Yuncu, A.; Zafar, A. A.; Zeng, Y.; Zeng, Z.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. J.; Zhang, J. L.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, K.; Zhang, L.; Zhang, S. Q.; Zhang, X. Y.; Zhang, Y.; Zhang, Y.; Zhang, Y. H.; Zhang, Y. N.; Zhang, Y. T.; Zhang, Yu; Zhang, Z. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, J. W.; Zhao, J. Y.; Zhao, J. Z.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, Q. W.; Zhao, S. J.; Zhao, T. C.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, W. J.; Zheng, Y. H.; Zhong, B.; Zhou, L.; Zhou, X.; Zhou, X. K.; Zhou, X. R.; Zhou, X. Y.; Zhu, K.; Zhu, K. J.; Zhu, S.; Zhu, S. H.; Zhu, X. L.; Zhu, Y. C.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zotti, L.; Zou, B. S.; Zou, J. H.; Besiii Collaboration

2017-11-01

Using data samples collected with the BESIII detector at the BEPCII collider at six center-of-mass energies between 4.008 and 4.600 GeV, we observe the processes e+e- → ϕϕω and e+e- → ϕϕϕ. The Born cross sections are measured and the ratio of the cross sections σ (e+e- → ϕϕω) / σ (e+e- → ϕϕϕ) is estimated to be 1.75 ± 0.22 ± 0.19 averaged over six energy points, where the first uncertainty is statistical and the second is systematic. The results represent first measurements of these interactions.

The E4 protein; structure, function and patterns of expression

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

Doorbar, John, E-mail: jdoorba@nimr.mrc.ac.uk

2013-10-15

The papillomavirus E4 open reading frame (ORF) is contained within the E2 ORF, with the primary E4 gene-product (E1{sup ∧}E4) being translated from a spliced mRNA that includes the E1 initiation codon and adjacent sequences. E4 is located centrally within the E2 gene, in a region that encodes the E2 protein′s flexible hinge domain. Although a number of minor E4 transcripts have been reported, it is the product of the abundant E1{sup ∧}E4 mRNA that has been most extensively analysed. During the papillomavirus life cycle, the E1{sup ∧}E4 gene products generally become detectable at the onset of vegetative viral genomemore » amplification as the late stages of infection begin. E4 contributes to genome amplification success and virus synthesis, with its high level of expression suggesting additional roles in virus release and/or transmission. In general, E4 is easily visualised in biopsy material by immunostaining, and can be detected in lesions caused by diverse papillomavirus types, including those of dogs, rabbits and cattle as well as humans. The E4 protein can serve as a biomarker of active virus infection, and in the case of high-risk human types also disease severity. In some cutaneous lesions, E4 can be expressed at higher levels than the virion coat proteins, and can account for as much as 30% of total lesional protein content. The E4 proteins of the Beta, Gamma and Mu HPV types assemble into distinctive cytoplasmic, and sometimes nuclear, inclusion granules. In general, the E4 proteins are expressed before L2 and L1, with their structure and function being modified, first by kinases as the infected cell progresses through the S and G2 cell cycle phases, but also by proteases as the cell exits the cell cycle and undergoes true terminal differentiation. The kinases that regulate E4 also affect other viral proteins simultaneously, and include protein kinase A, Cyclin-dependent kinase, members of the MAP Kinase family and protein kinase C. For HPV16 E1{sup ∧}E4, these kinases regulate one of the E1{sup ∧}E4 proteins main functions, the association with the cellular keratin network, and eventually also its cleavage by the protease calpain which allows assembly into amyloid-like fibres and reorganisation of the keratin network. Although the E4 proteins of different HPV types appear divergent at the level of their primary amino acid sequence, they share a recognisable modular organisation and pattern of expression, which may underlie conserved functions and regulation. Assembly into higher-order multimers and suppression of cell proliferation are common to all E4 proteins examined. Although not yet formally demonstrated, a role in virus release and transmission remains a likely function for E4. - Highlights: • E4 gene products have a modular structure, and are expressed from the E1{sup ∧}E4 spliced mRNA. • E4 proteins are modified during epithelial differentiation by phosphorylation and proteolysis. • The E4 proteins contribute to genome amplification-efficiency and virus synthesis. • E4 proteins are abundantly expressed and may facilitate efficient virus release and transmission. • High-risk E4 proteins are deposited as amyloid fibres and can be used as infection biomarkers.« less

Multivariate and Naive Bayes Text Classification Approach to Cost Growth Risk in Department of Defense Acquisition Programs

DTIC Science & Technology

2013-03-01

alerts 0.00011 3.26E-06 alternative 0.000161 0.000426 amp 5.25E-05 0.003127 amplifier 0.001501 0.000277 angular 0.000103 3.26E-06 anticipate 0.000755...0.000217 0.00056 amp 4.07E-05 0.004884 amplifier 0.002158 0.00043 angular 0.000109 4.48E-06 anticipation 0.000136 0.000453 aperture 0.000624...0.000215 instructed 0.00057 4.93E-05 java 0.000258 4.48E-05 refactoring 0.00019 2.69E-05 strike 0.000271 5.83E-05 touches 1.36E-05 9.86E-05

Tripolar Stability: The Future of Nuclear Relations Among the United States, Russia, and China

DTIC Science & Technology

2002-09-01

I N S T I T U T E F O R D E F E N S E A N A L Y S E S D E F E N S E T H R E A T R E D U C T I O N A G E N C Y Tripolar Stability: The Future of... Tripolar Stability: The Future of Nuclear Relations Among the United States, Russia, and China Brad Roberts PREFACE Since the creation of the...here were first sketched out in a symposium convened at IDA on July 28 on nuclear tripolarity , where thoughtful presentations were made on facets

Detection of Translational Equivalence

DTIC Science & Technology

2001-05-01

13L_6�4 1 5 68739 :;pE6 9 C:@O7365 H8735$:XF87fES>132�E6T9:> :;9`?�C:’¿ � dTÀÄE~;W9C:’> M739 E1)132x9C:@1 65$:;9;H�8;9 >ES6...Y47 @O4 HR@O739 :<JH8;-E65�7c<RAT6873eE~4ÈF> 1 5 > 73e’e?E65�9 :4C6RE~Q$H: `®�CREO;EO;’�:;9 EP@P@SH8;9 > M739 :<­�TAY736�: U873e’FR

Threshold and Other Properties of U Particle Production in e{sup +}e{sup -} Annihilation

DOE R&D Accomplishments Database

Perl, M. L.

1976-05-01

The anomalous e..mu.. events produced in e{sup +}e{sup -} annihilation, e{sup +} + e{sup -} ..-->.. e/sup + -/ + ..mu..{sup - +} + missing energy, (1) was explained as the decay products of a pair of U particles produced in the reaction e{sup +} + e{sup -} ..-->.. U{sup +} + U{sup -}. (2) New data is presented on the U particles in the energy region just above their production threshold and results of a study of the nature of the particles carrying off the missing energy in Eq. (1). While presenting these new results the present status of knowledge of the anomalous e..mu.. events and their U particle explanation is briefly reviewed. (JFP)

ErbB2 Trafficking and Signaling in Human Vestibular Schwannomas

DTIC Science & Technology

2008-10-01

E -Mail...R ho G D I A. B. C. D. E . ER K /R ho G D I ER K /R ho G D I pE R K/ ER K pE R K/ ER K pE R K/ ER K pE R K/ ER K pE R K/ ER K pE R K/ ER K pE R K/ ER...c on tr ol ) 0 20 40 60 80 100 Control I-JIP 30 μM I-JIP 100 μM SP60025 20 μM B rd U- po si tiv e V S ce lls (% c on tr ol ) B rd U- po si tiv e

NACA Conference on Turbojet-Engine Thrust-Augmentation Research - a Compilation of the Papers Presented by NACA Staff Members

DTIC Science & Technology

1948-10-28

N . E. Harvey, Lt. Col. J. A. Hartman, E. P. Hildestad, H. L. Eolbrook, G. E, Hopkins, Lt. Comdr. L. A...velocity and diffuser efficiency on augmentation. 1041A H oo \\=> K H n w E-i O 33 1.6 1.4 E-i co !=> Pi E-i § 1.0 o 1.2 .8...xutm E"H N 1 DO E-i O £3 E-i DO £) E-H o ^ 00 :=> ex E-t Co o Is i.5 i.O .5 :.0 ,5 2 - 750 40G <C < CD-1 T Q lg 3800°

Statistical Inference for Quality-Adjusted Survival Time

DTIC Science & Technology

2006-07-01

ACCA W 6 :9+ (’ &12 $ X 0,7,2 1+7$- 1w -$1(-5 &+9.5 N,& 0 17)󈨌 1. E o( +<$& 0,017 6 N1 N $33 &+9.5 +ə 07’:312 ’) 71471...W )𔄁 ’:+,$($(4 $2 X 07’%1. 1&+$2 ,+𔄁& ’) 2 1,( r Fs 6 ,(. $( *,(4 ,(. x&$,+$& T ACCA W )𔄁 2 1.$,( 71 X 471&&$’( ’) 2 1.$-,3 -’&+& E u1 N $33 -,33...E ,(. x&$,+$& 6 F E F E T ACCA W E 1.$,( d1471&&$’( N $+< @1(&󈨋. @’&+ #,+, E JRH GJ 6 e UVX e U B E @󈧣 6 * E

Real-Time Information Extraction from Big Data

DTIC Science & Technology

2015-10-01

I N S T I T U T E F O R D E F E N S E A N A L Y S E S Real-Time Information Extraction from Big Data Robert M. Rolfe...Information Extraction from Big Data Jagdeep Shah Robert M. Rolfe Francisco L. Loaiza-Lemos October 7, 2015 I N S T I T U T E F O R D E F E N S E...AN A LY S E S Abstract We are drowning under the 3 Vs (volume, velocity and variety) of big data . Real-time information extraction from big

Assessment of Accelerated Acquisition of Defense Programs

DTIC Science & Technology

2016-09-01

I N S T I T U T E F O R D E F E N S E A N A L Y S E S Assessment of Accelerated Acquisition of Defense Programs Richard H. Van Atta R. Royce...Defense for Acquisition . The views, opinions, and findings should not be construed as representing the official position of either the Department of...S T I T U T E F O R D E F E N S E A N A L Y S E S IDA Paper P-8161 Assessment of Accelerated Acquisition of Defense Programs Richard H. Van Atta

Maritime Analytics Prototype: Phase 3 Validation

DTIC Science & Technology

2014-01-01

maritim arehouse (GP ported on th sability Sca the training sks, errors m estionnaire, as assessed u the trial was t ” in the scien icant improv...which ed that MVA tools, and th ated the mo e, and becaus lot of prais essels. t - s, e s) n r e e e - e n s, e is P e st e e ii...rapport a environne en raison permet de une bonne navires d’ é ….... t documente n banc d’ess l’analyse de intérêt. Les c iel Widget A DDC) sur l ISTIP

10 CFR Appendix A to Part 835 - Derived Air Concentrations (DAC) for Controlling Radiation Exposure to Workers at DOE Facilities

Code of Federal Regulations, 2010 CFR

2010-01-01

...+05 2 E+05 /ET/ET Ni-56 (Inorg) 4 E−07 4 E−07 - 1 E+04 1 E+04 - ET/ET/ Ni-56 (Carbonyl) - 4 E−07 - - 1 E+04 - /St/ Ni-57 (Inorg) 5 E−07 5 E−07 - 2 E+04 2 E+04 - ET/ET/ Ni-57 (Carbonyl) - 7 E−07 - - 2 E+04 - /ET/ Ni-59 (Inorg) 2 E−06 5 E−06 - 9 E+04 2 E+05 - St/St/ Ni-59 (Carbonyl) - 6 E−07 - - 2 E+04...

10 CFR Appendix A to Part 835 - Derived Air Concentrations (DAC) for Controlling Radiation Exposure to Workers at DOE Facilities

Code of Federal Regulations, 2011 CFR

2011-01-01

...+05 2 E+05 /ET/ET Ni-56 (Inorg) 4 E−07 4 E−07 - 1 E+04 1 E+04 - ET/ET/ Ni-56 (Carbonyl) - 4 E−07 - - 1 E+04 - /St/ Ni-57 (Inorg) 5 E−07 5 E−07 - 2 E+04 2 E+04 - ET/ET/ Ni-57 (Carbonyl) - 7 E−07 - - 2 E+04 - /ET/ Ni-59 (Inorg) 2 E−06 5 E−06 - 9 E+04 2 E+05 - St/St/ Ni-59 (Carbonyl) - 6 E−07 - - 2 E+04...

Study of K + → π 0 e + ν e γ decay with OKA setup

NASA Astrophysics Data System (ADS)

Polyarush, A. Yu.; OKA Collaboration

2017-12-01

Results of study of the K + → π 0 e + ν e γ decay at OKA setup are presented. 13118 events of this decay have been observed. The branching ratio with cuts {E}γ * > 10 {{MeV}},0.6< {cos}{\\Theta }eγ * < 0.9 , is calculated R=\\frac{Br({K}+\\to {π }0{e}+{v}eγ )}{Br({K}+\\to {π }0{e}+{v}e)}=(0.59+/- 0.02(stat.)+/- 0.03(syst.))× {10}-2. For the asymmetry Aξ we get Aξ = -0.019±0.020(stat.)±0.027(syst.)

Sensitivity Analysis of Empirical Parameters in the Ionosphere-Plasmasphere Model

DTIC Science & Technology

2011-03-01

IFM output grid (Gardner , 2010). The longitudes have to be fit as well because the IPM flux tubes form a type of ‘ S ...n d 2 0 d a y ru n , a n d th e ri g h t p lo t is th e d iff e re n c e . A ft e r d a y fi v e , th e m o d e l o u tp u t h a s re a ch e d st e a ...lo c a ti o n s * . T h

Two loop renormalization of the magnetic coupling in hot QCD

NASA Astrophysics Data System (ADS)

Giovannangeli, P.

2004-04-01

Well above the critical temperature hot QCD is described by 3d electrostatic QCD with gauge coupling gE and Debye mass mE. We integrate out the Debye scales to two loop accuracy and find for the gauge coupling in the resulting magnetostatic action gM2=gE21-{1}/{48}{gE2N}/{πmE}-{17}/{4608}{gE2N}/{πmE}2+O{gE2N}/{πmE}3.

Resolving the Orientation of Cylinders and Cuboids from Projected Area Measurements

DTIC Science & Technology

2016-05-01

fabs ( e1 ) + Ay * fabs ( e2...Az * fabs ( e3 ) - A_xy; 90 g = Ax * fabs ( e4 ) + Ay * fabs ( e5 ) + Az * fabs ( e6 ) - A_xz; 91 h = Ax * fabs ( e7 ) + Ay * fabs ( e8 ) + Az * fabs ( e9...b23 * h; 128 del_r = b31 * f + b32 * g + b33 * h; 129 130 p -= del_p; 131 y -= del_y; 132 r -= del_r; 133 134 if ( fabs ( del_p ) < TOL && fabs (

The unique Leishmania EIF4E4 N-terminus is a target for multiple phosphorylation events and participates in critical interactions required for translation initiation.

PubMed

de Melo Neto, Osvaldo P; da Costa Lima, Tamara D C; Xavier, Camila C; Nascimento, Larissa M; Romão, Tatiany P; Assis, Ludmila A; Pereira, Mariana M C; Reis, Christian R S; Papadopoulou, Barbara

2015-01-01

The eukaryotic initiation factor 4E (eIF4E) recognizes the mRNA cap structure and, together with eIF4G and eIF4A, form the eIF4F complex that regulates translation initiation in eukaryotes. In trypanosomatids, 2 eIF4E homologues (EIF4E3 and EIF4E4) have been shown to be part of eIF4F-like complexes with presumed roles in translation initiation. Both proteins possess unique N-terminal extensions, which can be targeted for phosphorylation. Here, we provide novel insights on the Leishmania infantum EIF4E4 function and regulation. We show that EIF4E4 is constitutively expressed throughout the parasite development but is preferentially phosphorylated in exponentially grown promastigote and amastigote life stages, hence correlating with high levels of translation. Phosphorylation targets multiple serine-proline or threonine-proline residues within the N-terminal extension of EIF4E4 but does not require binding to the EIF4E4's partner, EIF4G3, or to the cap structure. We also report that EIF4E4 interacts with PABP1 through 3 conserved boxes at the EIF4E4 N-terminus and that this interaction is a prerequisite for efficient EIF4E4 phosphorylation. EIF4E4 is essential for Leishmania growth and an EIF4E4 null mutant was only obtained in the presence of an ectopically provided wild type gene. Complementation for the loss of EIF4E4 with several EIF4E4 mutant proteins affecting either phosphorylation or binding to mRNA or to EIF4E4 protein partners revealed that, in contrast to other eukaryotes, only the EIF4E4-PABP1 interaction but neither the binding to EIF4G3 nor phosphorylation is essential for translation. These studies also demonstrated that the lack of both EIF4E4 phosphorylation and EIF4G3 binding leads to a non-functional protein. Altogether, these findings further highlight the unique features of the translation initiation process in trypanosomatid protozoa.

The unique Leishmania EIF4E4 N-terminus is a target for multiple phosphorylation events and participates in critical interactions required for translation initiation

PubMed Central

de Melo Neto, Osvaldo P; da Costa Lima, Tamara D C; Xavier, Camila C; Nascimento, Larissa M; Romão, Tatiany P; Assis, Ludmila A; Pereira, Mariana M C; Reis, Christian R S; Papadopoulou, Barbara

2015-01-01

The eukaryotic initiation factor 4E (eIF4E) recognizes the mRNA cap structure and, together with eIF4G and eIF4A, form the eIF4F complex that regulates translation initiation in eukaryotes. In trypanosomatids, 2 eIF4E homologues (EIF4E3 and EIF4E4) have been shown to be part of eIF4F-like complexes with presumed roles in translation initiation. Both proteins possess unique N-terminal extensions, which can be targeted for phosphorylation. Here, we provide novel insights on the Leishmania infantum EIF4E4 function and regulation. We show that EIF4E4 is constitutively expressed throughout the parasite development but is preferentially phosphorylated in exponentially grown promastigote and amastigote life stages, hence correlating with high levels of translation. Phosphorylation targets multiple serine-proline or threonine-proline residues within the N-terminal extension of EIF4E4 but does not require binding to the EIF4E4's partner, EIF4G3, or to the cap structure. We also report that EIF4E4 interacts with PABP1 through 3 conserved boxes at the EIF4E4 N-terminus and that this interaction is a prerequisite for efficient EIF4E4 phosphorylation. EIF4E4 is essential for Leishmania growth and an EIF4E4 null mutant was only obtained in the presence of an ectopically provided wild type gene. Complementation for the loss of EIF4E4 with several EIF4E4 mutant proteins affecting either phosphorylation or binding to mRNA or to EIF4E4 protein partners revealed that, in contrast to other eukaryotes, only the EIF4E4-PABP1 interaction but neither the binding to EIF4G3 nor phosphorylation is essential for translation. These studies also demonstrated that the lack of both EIF4E4 phosphorylation and EIF4G3 binding leads to a non-functional protein. Altogether, these findings further highlight the unique features of the translation initiation process in trypanosomatid protozoa. PMID:26338184

Research on the E-Textbook and E-Schoolbag in China: Constructing an Ecosystem of E-Textbook and E-Schoolbag

ERIC Educational Resources Information Center

Wu, Yonghe; Lin, Lin; Ma, Xiaoling; Zhu, Zhiting

2013-01-01

The e-Textbook and e-Schoolbag initiatives have received wide attention and have been seen as the trend towards future education. This paper describes the framework of e-Textbook and e-Schoolbag including its conceptual model and system model. It further discusses the five interconnected categories that form the main parts of this Ecosystem…

Biochemical impact of soccer: an analysis of hormonal, muscle damage, and redox markers during the season.

PubMed

Silva, João Renato; Rebelo, António; Marques, Franklim; Pereira, Laura; Seabra, André; Ascensão, António; Magalhães, José

2014-04-01

This study aimed to analyze changes in performance, muscle function, and stress-related biochemical markers in professional soccer players (n = 14) at 4 timepoints (3 for performance and 4 for stress-related biochemical markers) during the soccer season [Formula: see text] preseason (E1), midseason (E2), end of the season (E3) [Formula: see text] and after the end of the recovery period (E4). Performance in 5- and 30-m sprints, countermovement jump, and agility, and maximal isokinetic knee extension and knee flexion strength were measured (E1 to E3). We observed increased in-season levels of myoglobin (E2 > E1 and E4; p < 0.05), a higher testosterone/cortisol ratio (T/C), and increased levels of creatine kinase (CK), C-reactive protein, superoxide dismutase (SOD), protein sulfhydryls (-SH), and malondialdehyde (E2 and E3 > E1 and E4; p < 0.05). Lower cortisol concentrations (E3 < E1 and E4; p < 0.05) and glutathione reductase activity (E3 < E2 and E4; p < 0.05) were observed at the end of the season. T/C, CK, SOD, -SH, and malondialdehyde decreased during the off-season, and cortisol and glutathione reductase increased (E3 < E4; p < 0.05). Agility increased in E2 and E3 (p < 0.01). Significant correlations were found during the season between hormonal and muscle function parameters (r = 0.56-0.86; p < 0.05). In addition, in E2, significant associations were observed between match-accumulated time (MATE2; minutes played by each player during the competition period), performance, and hormonal and redox parameters (r = 0.456-0.615; p < 0.05). In conclusion, this study shows that soccer players face significant changes in biomarkers of physiologic strain (muscle damage and oxidative stress-related markers) during the season, but values return to normal during the off-season. Additionally, MAT influences physical, hormonal, and oxidative stress-related parameters in professional soccer players.

DFT studies of hydrocarbon combustion on metal surfaces.

PubMed

Arya, Mina; Mirzaei, Ali Akbar; Davarpanah, Abdol Mahmood; Barakati, Seyed Masoud; Atashi, Hossein; Mohsenzadeh, Abas; Bolton, Kim

2018-02-02

Catalytic combustion of hydrocarbons is an important technology to produce energy. Compared to conventional flame combustion, the catalyst enables this process to operate at lower temperatures; hence, reducing the energy required for efficient combustion. The reaction and activation energies of direct combustion of hydrocarbons (CH → C + H) on a series of metal surfaces were investigated using density functional theory (DFT). The data obtained for the Ag, Au, Al, Cu, Rh, Pt, and Pd surfaces were used to investigate the validity of the Brønsted-Evans-Polanyi (BEP) and transition state scaling (TSS) relations for this reaction on these surfaces. These relations were found to be valid (R 2  = 0.94 for the BEP correlation and R 2  = 1.0 for the TSS correlation) and were therefore used to estimate the energetics of the combustion reaction on Ni, Co, and Fe surfaces. It was found that the estimated transition state and activation energies (E TS  = -69.70 eV and E a  = 1.20 eV for Ni, E TS  = -87.93 eV and E a  = 1.08 eV for Co and E TS  = -92.45 eV and E a  = 0.83 eV for Fe) are in agreement with those obtained by DFT calculations (E TS  = -69.98 eV and E a  = 1.23 eV for Ni, E TS  = -87.88 eV and E a  = 1.08 eV for Co and E TS  = -92.57 eV and E a  = 0.79 eV for Fe). Therefore, these relations can be used to predict energetics of this reaction on these surfaces without doing the time consuming transition state calculations. Also, the calculations show that the activation barrier for CH dissociation decreases in the order Ag ˃ Au ˃ Al ˃ Cu ˃ Pt ˃ Pd ˃ Ni > Co > Rh > Fe.

Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory

PubMed Central

Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D’Adamio, Luciano

2015-01-01

Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing – such as PSEN1/2 and ITM2b/BRI2 – cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16– 17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16–17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers. PMID:26528887

Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory.

PubMed

Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D'Adamio, Luciano

2015-12-01

Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16-17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16-17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers. Copyright © 2015 Elsevier Inc. All rights reserved.

Allelic Variations at Four Major Maturity E Genes and Transcriptional Abundance of the E1 Gene Are Associated with Flowering Time and Maturity of Soybean Cultivars

PubMed Central

Wang, Yueqiang; Chen, Xin; Ren, Haixiang; Yang, Jiayin; Cheng, Wen; Zong, Chunmei; Gu, Heping; Qiu, Hongmei; Wu, Hongyan; Zhang, Xingzheng; Cui, Tingting; Xia, Zhengjun

2014-01-01

The time to flowering and maturity are ecologically and agronomically important traits for soybean landrace and cultivar adaptation. As a typical short-day crop, long day conditions in the high-latitude regions require soybean cultivars with photoperiod insensitivity that can mature before frost. Although the molecular basis of four major E loci (E1 to E4) have been deciphered, it is not quite clear whether, or to what degree, genetic variation and the expression level of the four E genes are associated with the time to flowering and maturity of soybean cultivars. In this study, we genotyped 180 cultivars at E1 to E4 genes, meanwhile, the time to flowering and maturity of those cultivars were investigated at six geographic locations in China from 2011 to 2012 and further confirmed in 2013. The percentages of recessive alleles at E1, E2, E3 and E4 loci were 38.34%, 84.45%, 36.33%, and 7.20%, respectively. Statistical analysis showed that allelic variations at each of four loci had a significant effect on flowering time as well as maturity. We classified the 180 cultivars into eight genotypic groups based on allelic variations of the four major E loci. The genetic group of e1-nf representing dysfunctional alleles at the E1 locus flowered earliest in all the geographic locations. In contrast, cultivars in the E1E2E3E4 group originated from the southern areas flowered very late or did not flower before frost at high latitude locations. The transcriptional abundance of functional E1 gene was significantly associated with flowering time. However, the ranges of time to flowering and maturity were quite large within some genotypic groups, implying the presence of some other unknown genetic factors that are involved in control of flowering time or maturity. Known genes (e.g. E3 and E4) and other unknown factors may function, at least partially, through regulation of the expression of the E1 gene. PMID:24830458

Nonclassical MHC-E (Mamu-E) expression in the rhesus monkey placenta

PubMed Central

Dambaeva, Svetlana V.; Bondarenko, Gennadiy I.; Grendell, Richard L.; Kravitz, Rachel H.; Durning, Maureen; Golos, Thaddeus G.

2009-01-01

The aim of this study was to characterize the expression of the rhesus HLA-E ortholog Mamu-E, particularly at the maternal-fetal interface. Mamu-E expression was confirmed by locus-specific RT-PCR in the placenta as well as in peripheral blood mononuclear cells (PBMC) and other organs. We evaluated the utility of antibodies recognizing HLA-E (MEM-E/06 against native HLA-E, MEM-E/02 against denatured HLA-E) to detect Mamu-E by flow cytometry/immunofluorescence, Western blot, and immunohistochemistry (IHC). Western blot analysis of cells and selected transfectants confirmed the recognition of Mamu-E but not Mamu-AG by antibodies MEM-E/06 and HC10 but not MEM-E/02. Immunohistochemical staining of frozen sections of rhesus placenta with the MEM-E/06 antibody demonstrated expression in most populations of rhesus monkey trophoblast cells, including villous cytotrophoblasts (strong positive staining), apical membrane of syncytiotrophoblasts (light to moderate staining) and extravillous cytotrophoblasts (moderate to strong staining, especially endovascular trophoblasts in early pregnancy). Expression was not trophoblast cell-specific, especially at term, when endothelial cells in both the chorionic plate and placental villi showed strong staining for Mamu-E. Staining of rhesus extravillous trophoblast cells suggested the co-expression of Mamu-E and Mamu-AG (the rhesus HLA-G homolog) on these cells. MEM-E/06 was shown also to react with differentiating rhesus placental syncytiotrophoblasts in primary culture, detecting intracellular and weak surface expression of Mamu-E. We conclude that the gestation-dependent co-expression of Mamu-E with Mamu-AG in villous and extravillous trophoblast cells suggests important and perhaps complementary but distinct roles of these two nonclassical MHC class I loci in pregnancy at the maternal-fetal interface. In addition, the MEM-E/06 antibody will be useful for the detection of Mamu-E at the maternal-fetal interface in the rhesus monkey. PMID:17996936

A biochemical framework for eIF4E-dependent mRNA export and nuclear recycling of the export machinery.

PubMed

Volpon, Laurent; Culjkovic-Kraljacic, Biljana; Sohn, Hye Seon; Blanchet-Cohen, Alexis; Osborne, Michael J; Borden, Katherine L B

2017-06-01

The eukaryotic translation initiation factor eIF4E acts in the nuclear export and translation of a subset of mRNAs. Both of these functions contribute to its oncogenic potential. While the biochemical mechanisms that underlie translation are relatively well understood, the molecular basis for eIF4E's role in mRNA export remains largely unexplored. To date, over 3000 transcripts, many encoding oncoproteins, were identified as potential nuclear eIF4E export targets. These target RNAs typically contain a ∼50-nucleotide eIF4E sensitivity element (4ESE) in the 3' UTR and a 7-methylguanosine cap on the 5' end. While eIF4E associates with the cap, an unknown factor recognizes the 4ESE element. We previously identified cofactors that functionally interacted with eIF4E in mammalian cell nuclei including the leucine-rich pentatricopeptide repeat protein LRPPRC and the export receptor CRM1/XPO1. LRPPRC simultaneously interacts with both eIF4E bound to the 5' mRNA cap and the 4ESE element in the 3' UTR. In this way, LRPPRC serves as a specificity factor to recruit 4ESE-containing RNAs within the nucleus. Further, we show that CRM1 directly binds LRPPRC likely acting as the export receptor for the LRPPRC-eIF4E-4ESE RNA complex. We also found that Importin 8, the nuclear importer for cap-free eIF4E, imports RNA-free LRPPRC, potentially providing both coordinated nuclear recycling of the export machinery and an important surveillance mechanism to prevent futile export cycles. Our studies provide the first biochemical framework for the eIF4E-dependent mRNA export pathway. © 2017 Volpon et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Human Cells Cultured under Physiological Oxygen Utilize Two Cap-binding Proteins to recruit Distinct mRNAs for Translation*

PubMed Central

Timpano, Sara; Uniacke, James

2016-01-01

Translation initiation is a focal point of translational control and requires the binding of eIF4E to the 5′ cap of mRNA. Under conditions of extreme oxygen depletion (hypoxia), human cells repress eIF4E and switch to an alternative cap-dependent translation mediated by a homolog of eIF4E, eIF4E2. This homolog forms a complex with the oxygen-regulated hypoxia-inducible factor 2α and can escape translation repression. This complex mediates cap-dependent translation under cell culture conditions of 1% oxygen (to mimic tumor microenvironments), whereas eIF4E mediates cap-dependent translation at 21% oxygen (ambient air). However, emerging evidence suggests that culturing cells in ambient air, or “normoxia,” is far from physiological or “normal.” In fact, oxygen in human tissues ranges from 1–11% or “physioxia.” Here we show that two distinct modes of cap-dependent translation initiation are active during physioxia and act on separate pools of mRNAs. The oxygen-dependent activities of eIF4E and eIF4E2 are elucidated by observing their polysome association and the status of mammalian target of rapamycin complex 1 (eIF4E-dependent) or hypoxia-inducible factor 2α expression (eIF4E2-dependent). We have identified oxygen conditions where eIF4E is the dominant cap-binding protein (21% normoxia or standard cell culture conditions), where eIF4E2 is the dominant cap-binding protein (1% hypoxia or ischemic diseases and cancerous tumors), and where both cap-binding proteins act simultaneously to initiate the translation of distinct mRNAs (1–11% physioxia or during development and stem cell differentiation). These data suggest that the physioxic proteome is generated by initiating translation of mRNAs via two distinct but complementary cap-binding proteins. PMID:27002144

Anti-E1E2 antibodies status prior therapy favors direct-acting antiviral treatment efficacy.

PubMed

Virlogeux, Victor; Berthillon, Pascale; Bordes, Isabelle; Larrat, Sylvie; Crouy, Stéphanie; Scholtès, Caroline; Pradat, Pierre; Maynard, Marianne; Zoulim, Fabien; Leroy, Vincent; Chemin, Isabelle; Trépo, Christian; Petit, Marie-Anne

2018-03-15

Presence of anti-E1E2 antibodies was previously associated with spontaneous cure of hepatitis C virus (HCV) and predictive before treatment of a sustained virological response (SVR) to bi- or tri-therapy in naïve or experienced patients, regardless of HCV genotype. We investigated the impact of anti-E1E2 seroprevalence at baseline on treatment response in patients receiving direct-acting antiviral (DAA) therapy. We screened anti-E1E2 antibodies by ELISA in serum samples collected at treatment initiation for two groups of patients: 59 with SVR at the end of DAA treatment and 44 relapsers after DAA treatment. Nineteen patients received a combination of ribavirin (RBV) or PEG-interferon/ribavirin with sofosbuvir or daclatasvir and others received interferon-free treatment with DAA±RBV. HCV viral load was measured at different time points during treatment in a subgroup of patients. A significant association was observed between presence of anti-E1E2 and HCV viral load<6log10 prior treatment. Among patients with anti-E1E2 at baseline, 70% achieved SVR whereas among patients without anti-E1E2, only 45% achieved SVR. Conversely, 66% of patients experiencing DAA-failure were anti-E1E2 negative at baseline. In the multivariate analysis, presence of anti-E1E2 was significantly associated with SVR after adjustment on potential cofounders such as age, sex, fibrosis stage, prior HCV treatment and alanine aminotransferase (ALT) level. The presence of anti-E1E2 at treatment initiation is a predictive factor of SVR among patients treated with DAA and more likely among patients with low initial HCV viral load (<6log10). Absence of anti-E1E2 at baseline could predict DAA-treatment failure. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Reduced Perinatal Leptin Availability May Contribute to Adverse Metabolic Programming in a Rat Model of Uteroplacental Insufficiency.

PubMed

Nüsken, Eva; Wohlfarth, Maria; Lippach, Gregor; Rauh, Manfred; Schneider, Holm; Dötsch, Jörg; Nüsken, Kai-Dietrich

2016-05-01

Leptin availability in perinatal life critically affects metabolic programming. We tested the hypothesis that uteroplacental insufficiency and intrauterine stress affect perinatal leptin availability in rat offspring. Pregnant rats underwent bilateral uterine vessel ligation (LIG; n = 14), sham operation (SOP; n = 12), or no operation (controls, n = 14). Fetal livers (n = 180), placentas (n = 180), and maternal blood were obtained 4 hours (gestational day [E] 19), 24 hours (E20), and 72 hours (E22) after surgery. In the offspring, we took blood samples on E22 (n = 44), postnatal day (P) 1 (n = 29), P2 (n = 16), P7 (n = 30), and P12 (n = 30). Circulating leptin (ELISA) was significantly reduced in LIG (E22, P1, P2) and SOP offspring (E22). Postnatal leptin surge was delayed in LIG but was accelerated in SOP offspring. Placental leptin gene expression (quantitative RT-PCR) was reduced in LIG (E19, E20, E22) and SOP (E20, E22). Hepatic leptin receptor (Lepr-a, mediating leptin degradation) gene expression was increased in LIG fetuses (E20, E22) only. Surprisingly, hypoxia-inducible factors (Hif; Western blot) were unaltered in placentas and were reduced in the livers of LIG (Hif1a, E20; Hif2a, E19, E22) and SOP (Hif2a, E19) fetuses. Gene expression of prolyl hydroxylase 3, a factor expressed under hypoxic conditions contributing to Hif degradation, was increased in livers of LIG (E19, E20, E22) and SOP (E19) fetuses and in placentas of LIG and SOP (E19). In summary, reduced placental leptin production, increased fetal leptin degradation, and persistent perinatal hypoleptinemia are present in intrauterine growth restriction offspring, especially after uteroplacental insufficiency, and may contribute to perinatal programming of leptin resistance and adiposity in later life.

Perception of e-cigarette harm and its correlation with use among U.S. adolescents.

PubMed

Amrock, Stephen M; Zakhar, Joseph; Zhou, Sherry; Weitzman, Michael

2015-03-01

U.S. adolescents increasingly use e-cigarettes. The perceived harm of e-cigarettes has not been described, nor has the correlation between harm perception and e-cigarette use been assessed. This study examines correlates of e-cigarette harm perception and use of e-cigarettes in a national survey. We used cross-sectional nationally representative data from the 2012 National Youth Tobacco Survey (n = 24,658). Cross-tabulations and multivariate ordered probit and logistic regression models were employed to assess relative harm perception and e-cigarette use. Half of U.S. adolescents had heard of e-cigarettes. Of these, 13.2% (95% confidence interval [CI] = 11.7-14.9) and 4.0% (95% CI = 3.4-4.7) reported ever or currently using e-cigarettes, respectively. Of those aware of e-cigarettes, 34.2% (95% CI = 32.8-35.6) believed e-cigarettes were less harmful than cigarettes. Among those trying e-cigarettes, 71.8% (95% CI = 69.0-74.5) believed e-cigarettes were comparatively less harmful. Females and those ≥ 17 years old were more likely to perceive e-cigarettes as more harmful relative to cigarettes, while on average Whites, users of other tobacco products, and those with family members who used tobacco were more likely to perceive e-cigarettes as comparatively safer. Among cigarette-naive e-cigarette users, use of other tobacco products and perceived harm reduction by e-cigarettes were, respectively, on average associated with 1.6 and 4.1 percentage-point increases in e-cigarette use. Perception of e-cigarettes as less harmful than conventional cigarettes was associated with increased e-cigarette use, including among cigarette-naive e-cigarette users. These findings should prompt further scientific investigation and merit attention from regulators. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

An Insight into E-Collections

ERIC Educational Resources Information Center

Albert, Angeline Sheba; Navaraj, A. Johnson

2006-01-01

The present paper gives a brief introduction about E-collections. It discusses the e-books, e-journals, utility, features, advantages and issues for the development of e-collections. E-books will offer a rich learning experience, reinforced with audio, video, 3D animation and collaborative learning tools. E-journals on the other hand are…

The Douro estuarine plume: Detection, processes and dynamics =

NASA Astrophysics Data System (ADS)

Mendes, Renato Paulo dos Santos

O Douro e um dos maiores rios da Peninsula Iberica, constituindo a maior descarga de agua doce para o Oceano Atlântico na costa noroeste portuguesa. A sua pluma estuarina tem particular relevância na dinâmica costeira e na modulacao de fenomenos biogeoquimicos. Sao objetivos desta dissertacao contribuir para a compreensao dos processos fisicos associados a geracao e propagacao da pluma estuarina do Rio Douro no oceano, assim como para o conhecimento dos seus padroes de dispersao e da forma como estes alteram a hidrologia e a circulacao costeira, considerando os agentes forcadores tipicos deste fenomeno (caudal fluvial, vento e mare) e indices climaticos relevantes. Para concretizacao destes objetivos foram desenvolvidas e aplicadas metodologias inovadoras de processamento de dados de detecao remota, assim como novas implementacoes estuarinas e costeiras de modelos numericos. Atraves de imagens MODIS, otimizadas para o estudo de fenomenos costeiros, efetuou-se uma detecao rigorosa da pluma. Identificou-se uma relacao entre o sinal turbido nLw555 e o caudal, demonstrando-se este produto como um bom proxy para a observacao da pluma no oceano. As escalas temporais e espaciais da pluma foram caraterizadas atraves destas imagens, combinadas com dados de caudal fluvial, mare, vento e precipitacao, e tambem com indices climaticos relevantes. Para compreender a propagacao da pluma e caracterizar a sua dinâmica e impacto na circulacao costeira, foi desenvolvida uma aplicacao 3D de modelos estuarinos e costeiros com malhas aninhadas de resolucao variavel. Definiramse e analisaram-se diferentes cenarios de vento e descarga fluvial. A interacao da pluma do Rio Douro e do Minho foi ainda analisada atraves dos resultados de simulacoes baseadas num evento de inverno. Os compositos turbidos mostraram que a pluma e facilmente detetada quando o caudal e maior que 500 m3 s??1. A descarga fluvial e o vento sao os principais forcadores da sua propagacao, enquanto a mare e apenas importante na regiao proxima a embocadura do estuario. Observaram-se relacoes a uma escala interanual entre a turbidez da pluma e os indices climaticos East Atlantic e NAO, com uma correlacao maxima identificada com 1 e 3 meses de desfasamento, respetivamente. Com base nos resultados das simulacoes efetuadas, a pluma e classificada como de larga escala e de advecao superficial, apresentando caracteristicas de uma pluma prototipica. Em condicoes de caudal moderado a elevado, a descarga estuarina e suficiente para gerar uma corrente costeira para norte sem acao do vento. Em eventos de ventos leste, a propagacao da pluma e similar ao caso sem vento, com um aumento da velocidade da corrente. Uma corrente costeira para sul e unicamente identificada sob condicoes de forte vento de oeste. Ventos de norte tendem a estender a pluma para o largo, com uma inclinacao na direcao sudoeste, enquanto ventos de sul intensificam a corrente para norte, sendo a mistura das plumas do Douro e do Minho uma consequencia possivel. A analise desta interacao apontou a contribuicao do Douro como importante na estabilizacao da WIBP e nas trocas de agua entre o oceano e as Rias Baixas. A interacao da pluma do Douro com estuarios localizados a sul da sua foz e a confirmacao in situ da recirculacao observada nos resultados numericos afiguram-se como temas relevantes para investigacoes futuras. None

Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks.

PubMed

Bour, Alexandra; Grootendorst, Jeannette; Vogel, Elise; Kelche, Christian; Dodart, Jean-Cosme; Bales, Kelly; Moreau, Pierre-Henri; Sullivan, Patrick M; Mathis, Chantal

2008-11-21

Apolipoprotein (apo) E4, one of three human apoE (h-apoE) isoforms, has been identified as a major genetic risk factor for Alzheimer's disease and for cognitive deficits associated with aging. However, the biological mechanisms involving apoE in learning and memory processes are unclear. A potential isoform-dependent role of apoE in cognitive processes was studied in human apoE targeted-replacement (TR) mice. These mice express either the human apoE3 or apoE4 gene under the control of endogenous murine apoE regulatory sequences, resulting in physiological expression of h-apoE in both a temporal and spatial pattern similar to humans. Male and female apoE3-TR, apoE4-TR, apoE-knockout and C57BL/6J mice (15-18 months) were tested with spatial memory and avoidance conditioning tasks. Compared to apoE3-TR mice, spatial memory in female apoE4-TR mice was impaired based on their poor performances in; (i) the probe test of the water-maze reference memory task, (ii) the water-maze working memory task and (iii) an active avoidance Y-maze task. Retention performance on a passive avoidance task was also impaired in apoE4-TR mice, but not in other genotypes. These deficits in both spatial and avoidance memory tasks may be related to the anatomical and functional abnormalities previously reported in the hippocampus and the amygdala of apoE4-TR mice. We conclude that the apoE4-TR mice provide an excellent model for understanding the mechanisms underlying apoE4-dependent susceptibility to cognitive decline.

The prevalence of eosinophilic esophagitis in pediatric patients with IgE-mediated food allergy

PubMed Central

Hill, David A.; Dudley, Jesse W.; Spergel, Jonathan M.

2017-01-01

BACKGROUND Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that is triggered by food allergens and characterized by progressive esophageal dysfunction. Recently, EoE has been identified in patients undergoing oral immunotherapy (OIT) for IgE-mediated food allergy, suggesting an association. OBJECTIVE We sought to ascertain whether significant associations exist between IgE-mediated food allergies and EoE. METHODS Utilizing analysis of EMR data and manual chart review, we examined our sub-specialty care network of 35,528 children and adolescents to identify and characterize patients with IgE-mediated, and EoE food allergy. The most common food allergens were defined, and the prevalence of EoE in patients with IgE-mediated food allergy was determined. Logistic regression was used to measure the extent to which IgE-mediated food allergy to specific foods is associated with EoE. RESULTS The most common causes of EoE were milk, grains, meats, peanut, tree nuts, egg, and soy, an allergen pattern that is distinct from that of IgE-mediated food allergy. The prevalence of EoE in patients with IgE-mediated food allergy was higher than that reported in the general population (4.7% vs 0.04%). The distribution of IgE-mediated food allergens in patients with EoE was similar to that of the general population, and IgE-mediated allergy to egg (2.27; 1.91–2.64), milk (4.19; 3.52–4.97), or shellfish (1.55; 1.24–1.92) was significantly associated with EoE diagnosis. CONCLUSIONS Our findings support a clinical association between these conditions that has implications for the management of children with food allergy, and particular relevance to patients undergoing OIT. PMID:28042003

Assessing the Association Between E-Cigarette Use and Exposure to Social Media in College Students: A Cross-Sectional Study.

PubMed

Sawdey, Michael D; Hancock, Linda; Messner, Marcus; Prom-Wormley, Elizabeth C

2017-12-06

Social media platforms provide an indirect medium for encouraging e-cigarette use between individuals and also serve as a direct marketing tool from e-cigarette brands to potential users. E-cigarette users share information via social media that often contains product details or health-related claims. Determine whether e-cigarette use is associated with exposure to e-cigarettes on social media in college students. Data from a sample of 258 college students was obtained via a clicker-response questionnaire (90% response rate). Demographic, lifetime and current e-cigarette/cigarette use, and e-cigarette exposure via social media (peer posts or advertisements) were examined. Logistic regression was used to assess the relationship between lifetime and current e-cigarette use and viewing peer posts or advertisements on social media while adjusting for cigarette use and self-posting about e-cigarettes. Overall, 46% of participants reported lifetime e-cigarette use, 16% current e-cigarette use, and 7% were current dual users of e-cigarettes and cigarettes. There were positive and significant associations between lifetime e-cigarette use and viewing peer posts (aOR = 3.11; 95% CI = 1.25-7.76) as well as advertisements (aOR = 3.01; 95% CI = 1.19-7.65) on e-cigarettes via social media after adjusting for cigarette use. Current e-cigarette use was only significantly associated with viewing peer posts via social media (aOR = 7.58; 95% CI = 1.66-34.6) after adjusting for cigarette use. Conclusions/Importance: Almost half of college students view peer posts and advertisements on e-cigarettes via social media. This exposure is associated with individual e-cigarette use. Continued efforts to examine online e-cigarette content are needed to help future interventions decrease e-cigarette use.

Enzymatic activity necessary to restore the lethality due to Escherichia coli RNase E deficiency is distributed among bacteria lacking RNase E homologues

PubMed Central

Kageyama, Daisuke; Honda, Naoko; Fujimoto, Hirofumi; Kato, Atsushi

2017-01-01

Escherichia coli RNase E (Eco-RNase E), encoded by rne (Eco-rne), is considered the global RNA decay initiator. Although Eco-RNase E is an essential gene product in E. coli, some bacterial species, such as Bacillus subtilis, do not possess Eco-RNase E sequence homologues. B. subtilis instead possesses RNase J1/J2 (Bsu-RNase J1/J2) and RNase Y (Bsu-RNase Y) to execute RNA decay. Here we found that E. coli lacking the Eco-rne gene (Δrne E. coli) was viable conditional on M9 minimal media by introducing Bsu-RNase J1/J2 or Bsu-RNase Y. We also cloned an extremely short Eco-RNase E homologue (Wpi-RNase E) and a canonical sized Bsu-RNase J1/J2 homologue (Wpi-RNase J) from Wolbachia pipientis, an α-proteobacterial endosymbiont of arthropods. We found that Wpi-RNase J restored the colony-forming ability (CFA) of Δrne E. coli, whereas Wpi-RNase E did not. Unexpectedly, Wpi-RNase E restored defective CFA due to lack of Eco-RNase G, a paralogue of Eco-RNase E. Our results indicate that bacterial species that lack Eco-RNase E homologues or bacterial species that possess Eco-RNase E homologues which lack Eco-RNase E-like activities have a modest Eco-RNase E-like function using RNase J and/or RNase Y. These results suggest that Eco-RNase E-like activities might distribute among a wide array of bacteria and that functions of RNases may have changed dynamically during evolutionary divergence of bacterial lineages. PMID:28542621

Specific IgE for Fag e 3 Predicts Oral Buckwheat Food Challenge Test Results and Anaphylaxis: A Pilot Study.

PubMed

Yanagida, Noriyuki; Sato, Sakura; Maruyama, Nobuyuki; Takahashi, Kyohei; Nagakura, Ken-Ichi; Ogura, Kiyotake; Asaumi, Tomoyuki; Ebisawa, Motohiro

2018-01-01

Buckwheat (BW) is the source of a life-threatening allergen. Fag e 3-specific serum IgE (sIgE) is more useful than BW-sIgE for diagnosis; however, it is unknown whether Fag e 3-sIgE can predict oral food challenge (OFC) results and anaphylaxis. This study aimed to clarify the efficacy of Fag e 3-sIgE in predicting OFC results and anaphylaxis. We conducted a retrospective review of BW- and Fag e 3-sIgE data obtained using the ImmunoCAP® assay system and fluorescent enzyme-linked immunosorbent assay from children who underwent OFC using 3,072 mg of BW protein between July 2006 and March 2014 at Sagamihara National Hospital, Kanagawa, Japan. We analyzed 60 patients aged 1.9-13.4 years (median 6.0 years); 20 (33%) showed objective symptoms upon BW OFC. The patients without symptoms had significantly lower Fag e 3-sIgE than those with non-anaphylactic (p < 0.001) and anaphylactic reactions to BW (p = 0.004). Fag e 3-sIgE was the only tested factor that significantly predicted positive OFC results (odds ratio 8.93, 95% confidence interval 3.10-25.73, p < 0.001) and OFC-induced anaphylaxis (2.67, 1.12-6.35, p = 0.027). We suggest that a threshold Fag e 3-sIgE level of 18.0 kUE/L has 95% probability of provoking a positive reaction to BW. Fag e 3-sIgE predicted OFC results and OFC-induced anaphylaxis. We further emphasize paying careful attention to the risk of BW OFC-induced anaphylaxis. © 2018 The Author(s) Published by S. Karger AG, Basel.

QCD compositeness as revealed in exclusive vector boson reactions through double-photon annihilation: e +e - →γγ* → γV 0 and e +e - γ*γ* V$$0\\atop{a}$$V$$0\\atop{b}$$

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

Brodsky, Stanley J.; Lebed, Richard F.; Lyubovitskij, Valery E.

We study the exclusive double-photon annihilation processes, e +e - →γγ* → γV 0 and e +e - γ*γ* Vmore » $$0\\atop{a}$$V$$0\\atop{b}$$, where the V$$0\\atop{i}$$ is a neutral vector meson produced in the forward kinematical region: s>> -t and -t >> Λ$$2\\atop{QCD}$$. We show how the differential cross sections $$dσ\\atop{dt}$$, as predicted by QCD, have additional falloff in the momentum transfer squared t due to the QCD compositeness of the hadrons, consistent with the leading-twist fixed-θ CM scaling laws, both in terms of conventional Feynman diagrams and by using the AdS/QCD holographic model to obtain the results more transparently. However, even though they are exclusive channels and not associated with the conventional electron–positron annihilation process e +e -→γ*→ $$q\\bar{q}$$, these total cross sections σ(e +e -→γV 0)and σ(e +e -→V$$0\\atop{a}$$V$$0\\atop{b}$$), integrated over the dominant forward-and backward-θ CM angular domains, scale as 1/s, and thus contribute to the leading-twist scaling behavior of the ratio R e+e-. We generalize these results to exclusive double-electroweak vector-boson annihilation processes accompanied by the forward production of hadrons, such as e +e -→Z 0V 0and e +e -→W -ρ +. These results can also be applied to the exclusive production of exotic hadrons such as tetraquarks, where the cross-section scaling behavior can reveal their multiquark nature.« less

Adolescents' attitudes towards e-cigarette ingredients, safety, addictive properties, social norms, and regulation.

PubMed

Gorukanti, Anuradha; Delucchi, Kevin; Ling, Pamela; Fisher-Travis, Raymond; Halpern-Felsher, Bonnie

2017-01-01

E-cigarette use has dramatically increased. While studies have examined adolescents' attitudes towards smoking, few have extended this research to adolescents' attitudes towards e-cigarettes. The goal of this study was to examine adolescents' attitudes regarding e-cigarette ingredients, safety, addictive properties, social norms, accessibility, price, and regulation; and determine whether attitudes differ by past cigarette/e-cigarette use. Participants were 786 9th and 12th graders from California (63.21% females; mean age=16.10years [SD=1.6]; 26.61% White, 21.98% Asian/Pacific Islander, 29.82% Hispanic, and 21.59% other). Results indicated that 19.05% of participants believed smoke from e-cigarettes is water; 23.03% believed e-cigarettes aren't a tobacco product; 40.36% considered e-cigarettes to be for cessation, and 43.13% felt they were safer than cigarettes. Participants felt it was more acceptable to use e-cigarettes indoors and outdoors compared to cigarettes (p<0.0001), 23.13% felt raising e-cigarette taxes is a bad idea, 63.95% thought e-cigarettes were easier to get than cigarettes, 54.42% felt e-cigarettes cost too much, 64.33% felt the age for buying e-cigarettes should be raised, and 64.37% favored e-cigarette regulation. Adolescents who used e-cigarettes and/or cigarettes had significantly more favorable e-cigarette attitudes than non-users. This study indicates that adolescents are aware of some of the risks of e-cigarettes, although many harbor misperceptions and hold more favorable attitudes towards e-cigarettes than cigarettes. Of concern is the relationship between favorable e-cigarette attitudes and use. Findings suggest the need to provide adolescents with correct information about e-cigarette ingredients, risks, and the insufficient evidence of their role in cigarette cessation. Copyright © 2016 Elsevier Inc. All rights reserved.

Nicotine Concentration of E-Cigarettes Used by Adolescents

PubMed Central

Morean, Meghan E.; Kong, Grace; Cavallo, Dana A.; Camenga, Deepa R.; Krishnan-Sarin, Suchitra

2016-01-01

Objective E-cigarettes are popular among youth, but little is known about the nicotine concentrations of e-liquids used by adolescents. Materials and Method In Spring, 2014, we conducted cross-sectional surveys in four Connecticut high schools and two middle schools. Among past-30-day e-cigarette users (n = 513, 45% female, mean age 15.9 [SD=1.4]), we examined what nicotine concentration adolescents typically used in their e-cigarettes (range 0-30mg/mL and “I don’t know”). We first examined whether age, sex, smoking status, e-cigarette use frequency, and/or e-cigarette acquisition source were associated with using nicotine-free e-liquid, nicotine e-liquid, or not knowing the e-liquid nicotine concentration. Among nicotine users (n = 185), we then examined whether the aforementioned variables were associated with using higher nicotine concentrations. Results Adolescents reported using nicotine-free e-liquid (28.5%), nicotine e-liquid (37.4%), or not knowing their e-liquid nicotine concentration (34.1%). Nicotine users comprised more smokers and heavier e-cigarette users compared to nicotine-free e-liquid users and those who did not know their nicotine concentration. Nicotine users also comprised more males and were more likely to purchase e-cigarettes online or from tobacco shops compared to those who did not know their nicotine concentration. Among nicotine users, cigarette smoking, male sex, and purchasing e-cigarettes from tobacco shops predicted using higher nicotine concentrations. Conclusions Adolescents reported using e-liquids with variable nicotine concentrations. Smokers, males, and those who purchased their own e-cigarettes reported using the highest nicotine levels. Of concern, many adolescents were unaware of the nicotine concentration in their e-liquid, raising concerns about inadvertent nicotine exposure among youth. PMID:27592270

Nicotine concentration of e-cigarettes used by adolescents.

PubMed

Morean, Meghan E; Kong, Grace; Cavallo, Dana A; Camenga, Deepa R; Krishnan-Sarin, Suchitra

2016-10-01

E-cigarettes are popular among youth, but little is known about the nicotine concentrations of e-liquids used by adolescents. In Spring, 2014, we conducted cross-sectional surveys in four Connecticut high schools and two middle schools. Among past-30-day e-cigarette users (n=513, 45% female, mean age 15.9 [SD=1.4]), we examined what nicotine concentration adolescents typically used in their e-cigarettes (range 0-30mg/mL and "I don't know"). We first examined whether age, sex, smoking status, e-cigarette use frequency, and/or e-cigarette acquisition source were associated with using nicotine-free e-liquid, nicotine e-liquid, or not knowing the e-liquid nicotine concentration. Among nicotine users (n=185), we then examined whether the aforementioned variables were associated with using higher nicotine concentrations. Adolescents reported using nicotine-free e-liquid (28.5%), nicotine e-liquid (37.4%), or not knowing their e-liquid nicotine concentration (34.1%). Nicotine users comprised more smokers and heavier e-cigarette users compared to nicotine-free e-liquid users and those who did not know their nicotine concentration. Nicotine users also comprised more males and were more likely to purchase e-cigarettes online or from tobacco shops compared to those who did not know their nicotine concentration. Among nicotine users, cigarette smoking, male sex, and purchasing e-cigarettes from tobacco shops predicted using higher nicotine concentrations. Adolescents reported using e-liquids with variable nicotine concentrations. Smokers, males, and those who purchased their own e-cigarettes reported using the highest nicotine levels. Of concern, many adolescents were unaware of the nicotine concentration in their e-liquid, raising concerns about inadvertent nicotine exposure among youth. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Adolescents' Attitudes towards E-cigarette Ingredients, Safety, Addictive Properties, Social Norms, and Regulation

PubMed Central

Gorukanti, Anuradha; Delucchi, Kevin; Ling, Pamela; Fisher-Travis, Raymond; Halpern-Felsher, Bonnie

2017-01-01

E-cigarette use has dramatically increased. While studies have examined adolescents’ attitudes towards smoking, few have extended this research to adolescents’ attitudes towards e-cigarettes. The goal of this study was to examine adolescents' attitudes regarding e-cigarette ingredients, safety, addictive properties, social norms, accessibility, price, and regulation; and determine whether attitudes differ by past cigarette/e-cigarette use. Participants were 786 9th and 12th graders from California (63.21% females; mean age = 16.10 years [SD = 1.6]; 26.61% White, 21.98% Asian/Pacific Islander, 29.82% Hispanic, and 21.59% other). Results indicated that 19.05% of participants believed smoke from e-cigarettes is water; 23.03% believed e-cigarettes aren't a tobacco product; 40.36% considered e-cigarettes to be for cessation, and 43.13% felt they were safer than cigarettes. Participants felt it was more acceptable to use e-cigarettes indoors and outdoors compared to cigarettes (p < .0001), 23.13% felt raising e-cigarette taxes is a bad idea, 63.95% thought e-cigarettes were easier to get than cigarettes, 54.42% felt e-cigarettes cost too much, 64.33% felt the age for buying e-cigarettes should be raised, and 64.37% favored e-cigarette regulation. Adolescents who used e-cigarettes and/or cigarettes had significantly more favorable e-cigarette attitudes than non-users. This study indicates that adolescents are aware of some of the risks of e-cigarettes, although many harbor misperceptions and hold more favorable attitudes towards e-cigarettes than cigarettes. Of concern is the relationship between favorable e-cigarette attitudes and use. Findings suggest the need to provide adolescents with correct information about e-cigarette ingredients, risks, and the insufficient evidence of their role in cigarette cessation. PMID:27773711

QCD compositeness as revealed in exclusive vector boson reactions through double-photon annihilation: e +e - →γγ* → γV 0 and e +e - γ*γ* V$$0\\atop{a}$$V$$0\\atop{b}$$

DOE PAGES

Brodsky, Stanley J.; Lebed, Richard F.; Lyubovitskij, Valery E.

2017-01-01

We study the exclusive double-photon annihilation processes, e +e - →γγ* → γV 0 and e +e - γ*γ* Vmore » $$0\\atop{a}$$V$$0\\atop{b}$$, where the V$$0\\atop{i}$$ is a neutral vector meson produced in the forward kinematical region: s>> -t and -t >> Λ$$2\\atop{QCD}$$. We show how the differential cross sections $$dσ\\atop{dt}$$, as predicted by QCD, have additional falloff in the momentum transfer squared t due to the QCD compositeness of the hadrons, consistent with the leading-twist fixed-θ CM scaling laws, both in terms of conventional Feynman diagrams and by using the AdS/QCD holographic model to obtain the results more transparently. However, even though they are exclusive channels and not associated with the conventional electron–positron annihilation process e +e -→γ*→ $$q\\bar{q}$$, these total cross sections σ(e +e -→γV 0)and σ(e +e -→V$$0\\atop{a}$$V$$0\\atop{b}$$), integrated over the dominant forward-and backward-θ CM angular domains, scale as 1/s, and thus contribute to the leading-twist scaling behavior of the ratio R e+e-. We generalize these results to exclusive double-electroweak vector-boson annihilation processes accompanied by the forward production of hadrons, such as e +e -→Z 0V 0and e +e -→W -ρ +. These results can also be applied to the exclusive production of exotic hadrons such as tetraquarks, where the cross-section scaling behavior can reveal their multiquark nature.« less

Cigarette and e-liquid demand and substitution in e-cigarette-naïve smokers.

PubMed

Stein, Jeffrey S; Koffarnus, Mikhail N; Stepanov, Irina; Hatsukami, Dorothy K; Bickel, Warren K

2018-06-01

Behavioral economic methods allow experimental manipulation of price and examination of its effects on tobacco product purchasing. These methods may be used to examine tobacco product abuse liability and to prospectively model possible effects of price regulation. In the present study, we examined multiple measures of behavioral economic demand for cigarettes and e-liquid for use in a second-generation electronic cigarette (e-cigarette) in e-cigarette-naïve cigarette smokers. Twenty-five smokers received an e-cigarette (eGo ONE CT), sampled study e-liquid (24 mg/mL nicotine), and completed recurring sessions in which they used an experimental income to purchase real-world supplies of cigarettes and/or e-liquid. Participants also completed self-report measures of drug effects/liking. When products were available alone, we observed lower demand for e-liquid than for cigarettes. This effect was magnified when cigarettes and e-liquid were available concurrently. In additional assessments, e-liquid served as a partial substitute for cigarettes, but cigarettes did not serve as a substitute for e-liquid. Finally, participants rated e-liquid more poorly than cigarettes on several dimensions of drug effects/liking (any effects, liking, desire, and probability of continued use). We conclude that e-cigarette-naïve smokers value cigarettes more highly than e-liquid across multiple contexts and measurements. Nonetheless, participants still valued e-liquid positively and purchased it frequently, both as a substitute for cigarettes and independently of cigarettes. To understand the variables that influence transitions from exclusive smoking to either dual cigarette/e-cigarette use or exclusive e-cigarette use, future work should systematically examine the role of duration of e-liquid exposure. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Assessing nicotine dependence in adolescent E-cigarette users: The 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Nicotine Dependence Item Bank for electronic cigarettes.

PubMed

Morean, Meghan E; Krishnan-Sarin, Suchitra; S O'Malley, Stephanie

2018-04-26

Adolescent e-cigarette use (i.e., "vaping") likely confers risk for developing nicotine dependence. However, there have been no studies assessing e-cigarette nicotine dependence in youth. We evaluated the psychometric properties of the 4-item Patient-Reported Outcomes Measurement Information System Nicotine Dependence Item Bank for E-cigarettes (PROMIS-E) for assessing youth e-cigarette nicotine dependence and examined risk factors for experiencing stronger dependence symptoms. In 2017, 520 adolescent past-month e-cigarette users completed the PROMIS-E during a school-based survey (50.5% female, 84.8% White, 16.22[1.19] years old). Adolescents also reported on sex, grade, race, age at e-cigarette use onset, vaping frequency, nicotine e-liquid use, and past-month cigarette smoking. Analyses included conducting confirmatory factor analysis and examining the internal consistency of the PROMIS-E. Bivariate correlations and independent-samples t-tests were used to examine unadjusted relationships between e-cigarette nicotine dependence and the proposed risk factors. Regression models were run in which all potential risk factors were entered as simultaneous predictors of PROMIS-E scores. The single-factor structure of the PROMIS-E was confirmed and evidenced good internal consistency. Across models, larger PROMIS-E scores were associated with being in a higher grade, initiating e-cigarette use at an earlier age, vaping more frequently, using nicotine e-liquid (and higher nicotine concentrations), and smoking cigarettes. Adolescent e-cigarette users reported experiencing nicotine dependence, which was assessed using the psychometrically sound PROMIS-E. Experiencing stronger nicotine dependence symptoms was associated with characteristics that previously have been shown to confer risk for frequent vaping and tobacco cigarette dependence. Copyright © 2018 Elsevier B.V. All rights reserved.

E-cigarette- specific symptoms of nicotine dependence among Texas adolescents.

PubMed

Case, Kathleen R; Mantey, Dale S; Creamer, MeLisa R; Harrell, Melissa B; Kelder, Steven H; Perry, Cheryl L

2018-09-01

The potential of e-cigarettes to elicit symptoms of nicotine dependence has not been adequately studied, particularly in adolescent populations. The present study examined the prevalence of e-cigarette-specific symptoms of nicotine dependence ("symptoms of e-cigarette dependence") and the associations between these symptoms, e-cigarette usage group, and e-cigarette cessation-related items among Texas adolescents. This study involved a cross-sectional analysis of adolescents from Wave 4 of the Texas Adolescent Tobacco and Marketing Surveillance System (TATAMS) (n = 2891/N = 461,069). Chi-Square analyses examined differences in the prevalence of symptoms of dependence by e-cigarette usage group (exclusive versus dual users of e-cigarettes and combustible tobacco products) and demographic characteristics. Weighted multivariable logistic regression analyses examined the associations between symptoms of e-cigarette dependence, e-cigarette usage group, and e-cigarette cessation items. Exclusive e-cigarette users experienced symptoms of e-cigarette dependence, although the prevalence of most of the symptoms was higher for dual users. Adolescents who reported more symptoms of dependence were less likely to report both wanting to quit e-cigarettes and a past-year quit attempt for e-cigarettes (adjusted odds ratio "AOR" = 0.61 (95% CI = 0.41, 0.92) and AOR = 0.52 (95% CI = 0.30, 0.92), respectively). This study is the first to demonstrate that adolescent e-cigarette users are experiencing symptoms of dependence specific to e-cigarettes. In addition, symptoms of dependence may be barriers to e-cigarette cessation. Future research is needed to determine if characteristics of e-cigarette use (e.g. frequency and intensity) are associated with dependence. Copyright © 2018. Published by Elsevier Ltd.

The predictive role of E/e' on ischemic stroke and atrial fibrillation in Japanese patients without atrial fibrillation.

PubMed

Arai, Riku; Suzuki, Shinya; Semba, Hiroaki; Arita, Takuto; Yagi, Naoharu; Otsuka, Takayuki; Sagara, Koichi; Sasaki, Kenichi; Kano, Hiroto; Matsuno, Shunsuke; Kato, Yuko; Uejima, Tokuhisa; Oikawa, Yuji; Kunihara, Takashi; Yajima, Junji; Yamashita, Takeshi

2018-07-01

The predictive role of E/e' on ischemic stroke (IS) and atrial fibrillation (AF) in Japanese patients without AF are unclear. Shinken database includes all the new patients visiting the Cardiovascular Institute Hospital in Tokyo, Japan. E/e' has been routinely measured since 2007. Patients without AF for whom E/e' was measured at the initial visit between 2007 and 2014 (n=11 477, mean age 57.2 years old, men 59.5%) were divided into E/e' tertiles (<8.04, 8.04-11.00, >11.00). During the mean follow-up period of 1.8 years, 58 IS and 140 new appearances of AF were observed. High E/e' tertile was associated with more prevalence of atherothrombotic risks. The cumulative incidence of IS events and new appearance of AF at 6 years in low, middle, and high E/e' tertiles were 0.5%, 1.4%, and 3.0%/year (log-rank test, p<0.001), and 2.5%, 2.9%, and 4.2%/year (log-rank test, p=0.007), respectively. In multivariate analysis, high E/e' tertile was independently associated with IS (HR, 2.857, 95%CI 1.257-6.495, p=0.012). Although high E/e' tertile was independently associated with new appearance of AF when adjusted for coexistence of atherothrombotic risk factors (HR, 1.694, 95%CI, 1.097-2.616, p=0.017), the association was attenuated after adjustment for left atrial dimension. E/e' was significantly associated with incidence of IS and new appearance of AF in non-AF patients. Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Impaired protection against Trichinella spiralis in mice with high levels of IgE.

PubMed

Watanabe, Naohiro

2014-04-01

Helminth infection induces production of a large amount of immunoglobulin E (IgE) to nonhelminth antigens. Although such "irrelevant" IgE is a major proportion of total IgE in the host, its biological significance remains unclear. Therefore, I examined protective activity against Trichinella spiralis in mice with high levels of IgE by repeated injections of anti-dansyl IgE monoclonal antibody or Nippostrongylus brasiliensis infection. Injected anti-dansyl IgE occupied IgE receptors on mast cells in naive mice. Protective activity against T. spiralis, determined with number of muscle larvae 5weeks after infection, was impaired in mice treated with anti-dansyl IgE. The impaired protection was found in mice treated with anti-dansy IgE 7 and 14days after infection, but not 21 and 28days after infection, indicating that IgE-dependent protection operates at an early stage after infection. In the next experiments, mice were infected with N. brasiliensis 4weeks before T. spiralis infection to obtain high levels of IgE. The protective activity against T. spiralis was decreased by N. brasiliensis infection. On the other hand, protection against T. spiralis was comparable in IgE-deficient SJA/9 mice and in anti-IgE-treated BALB/c mice with or without N. brasiliensis infection, suggesting that impairment of protection is dependent on IgE. These results indicate that the high levels of irrelevant IgE are beneficial for helminths and, alternatively, that anti-helminth IgE antibodies are protective for hosts. In addition, the impaired protection was found in IgE high-responder mice but not in low-responder mice, suggesting that protection against T. spiralis is controlled by IgE responsiveness in the host. Copyright © 2013 Elsevier B.V. All rights reserved.

A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3.

PubMed Central

Méthot, N; Song, M S; Sonenberg, N

1996-01-01

The binding of mRNA to the ribosome is mediated by eukaryotic initiation factors eukaryotic initiation factor 4F (eIF4F), eIF4B, eIF4A, and eIF3, eIF4F binds to the mRNA cap structure and, in combination with eIF4B, is believed to unwind the secondary structure in the 5' untranslated region to facilitate ribosome binding. eIF3 associates with the 40S ribosomal subunit prior to mRNA binding. eIF4B copurifies with eIF3 and eIF4F through several purification steps, suggesting the involvement of a multisubunit complex during translation initiation. To understand the mechanism by which eIF4B promotes 40S ribosome binding to the mRNA, we studied its interactions with partner proteins by using a filter overlay (protein-protein [far Western]) assay and the two-hybrid system. In this report, we show that eIF4B self-associates and also interacts directly with the p170 subunit of eIF3. A region rich in aspartic acid, arginine, tyrosine, and glycine, termed the DRYG domain, is sufficient for self-association of eIF4B, both in vitro and in vivo, and for interaction with the p170 subunit of eIF3. These experiments suggest that eIF4B participates in mRNA-ribosome binding by acting as an intermediary between the mRNA and eIF3, via a direct interaction with the p170 subunit of eIF3. PMID:8816444

A molecular perspective on a complex polymorphic inversion system with cytological evidence of multiply reused breakpoints.

PubMed

Orengo, D J; Puerma, E; Papaceit, M; Segarra, C; Aguadé, M

2015-06-01

Genome sequence comparison across the Drosophila genus revealed that some fixed inversion breakpoints had been multiply reused at this long timescale. Cytological studies of Drosophila inversion polymorphism had previously shown that, also at this shorter timescale, some breakpoints had been multiply reused. The paucity of molecularly characterized polymorphic inversion breakpoints has so far precluded contrasting whether cytologically shared breakpoints of these relatively young inversions are actually reused at the molecular level. The E chromosome of Drosophila subobscura stands out because it presents several inversion complexes. This is the case of the E1+2+9+3 arrangement that originated from the ancestral Est arrangement through the sequential accumulation of four inversions (E1, E2, E9 and E3) sharing some breakpoints. We recently identified the breakpoints of inversions E1 and E2, which allowed establishing reuse at the molecular level of the cytologically shared breakpoint of these inversions. Here, we identified and sequenced the breakpoints of inversions E9 and E3, because they share breakpoints at sections 58D and 64C with those of inversions E1 and E2. This has allowed establishing that E9 and E3 originated through the staggered-break mechanism. Most importantly, sequence comparison has revealed the multiple reuse at the molecular level of the proximal breakpoint (section 58D), which would have been used at least by inversions E2, E9 and E3. In contrast, the distal breakpoint (section 64C) might have been only reused once by inversions E1 and E2, because the distal E3 breakpoint is displaced >70 kb from the other breakpoint limits.

A molecular perspective on a complex polymorphic inversion system with cytological evidence of multiply reused breakpoints

PubMed Central

Orengo, D J; Puerma, E; Papaceit, M; Segarra, C; Aguadé, M

2015-01-01

Genome sequence comparison across the Drosophila genus revealed that some fixed inversion breakpoints had been multiply reused at this long timescale. Cytological studies of Drosophila inversion polymorphism had previously shown that, also at this shorter timescale, some breakpoints had been multiply reused. The paucity of molecularly characterized polymorphic inversion breakpoints has so far precluded contrasting whether cytologically shared breakpoints of these relatively young inversions are actually reused at the molecular level. The E chromosome of Drosophila subobscura stands out because it presents several inversion complexes. This is the case of the E1+2+9+3 arrangement that originated from the ancestral Est arrangement through the sequential accumulation of four inversions (E1, E2, E9 and E3) sharing some breakpoints. We recently identified the breakpoints of inversions E1 and E2, which allowed establishing reuse at the molecular level of the cytologically shared breakpoint of these inversions. Here, we identified and sequenced the breakpoints of inversions E9 and E3, because they share breakpoints at sections 58D and 64C with those of inversions E1 and E2. This has allowed establishing that E9 and E3 originated through the staggered-break mechanism. Most importantly, sequence comparison has revealed the multiple reuse at the molecular level of the proximal breakpoint (section 58D), which would have been used at least by inversions E2, E9 and E3. In contrast, the distal breakpoint (section 64C) might have been only reused once by inversions E1 and E2, because the distal E3 breakpoint is displaced >70 kb from the other breakpoint limits. PMID:25712227

High incidence of HPV-associated head and neck cancers in FA deficient mice is associated with E7's induction of DNA damage through its inactivation of pocket proteins.

PubMed

Park, Jung Wook; Shin, Myeong-Kyun; Pitot, Henry C; Lambert, Paul F

2013-01-01

Fanconi anemia (FA) patients are highly susceptible to solid tumors at multiple anatomical sites including head and neck region. A subset of head and neck cancers (HNCs) is associated with 'high-risk' HPVs, particularly HPV16. However, the correlation between HPV oncogenes and cancers in FA patients is still unclear. We previously learned that FA deficiency in mice predisposes HPV16 E7 transgenic mice to HNCs. To address HPV16 E6's oncogenic potential under FA deficiency in HNCs, we utilized HPV16 E6-transgenic mice (K14E6) and HPV16 E6/E7-bi-transgenic mice (K14E6E7) on genetic backgrounds sufficient or deficient for one of the fanc genes, fancD2 and monitored their susceptibility to HNCs. K14E6 mice failed to develop tumor. However, E6 and fancD2-deficiency accelerated E7-driven tumor development in K14E6E7 mice. The increased tumor incidence was more correlated with E7-driven DNA damage than proliferation. We also found that deficiency of pocket proteins, pRb, p107, and p130 that are well-established targets of E7, could recapitulate E7's induction of DNA damage. Our findings support the hypothesis that E7 induces HPV-associated HNCs by promoting DNA damage through the inactivation of pocket proteins, which explains why a deficiency in DNA damage repair would increase susceptibility to E7-driven cancer. Our results further demonstrate the unexpected finding that FA deficiency does not predispose E6 transgenic mice to HNCs, indicating a specificity in the synergy between FA deficiency and HPV oncogenes in causing HNCs.

HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines

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

Calmon, Marilia Freitas; Sichero, Laura; Boccardo, Enrique

Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16more » E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.« less

Three Infectious Viral Species Lying in Wait in the Banana Genome

PubMed Central

Chabannes, Matthieu; Baurens, Franc-Christophe; Duroy, Pierre-Olivier; Bocs, Stéphanie; Vernerey, Marie-Stéphanie; Rodier-Goud, Marguerite; Barbe, Valérie; Gayral, Philippe

2013-01-01

Plant pararetroviruses integrate serendipitously into their host genomes. The banana genome harbors integrated copies of banana streak virus (BSV) named endogenous BSV (eBSV) that are able to release infectious pararetrovirus. In this investigation, we characterized integrants of three BSV species—Goldfinger (eBSGFV), Imove (eBSImV), and Obino l'Ewai (eBSOLV)—in the seedy Musa balbisiana Pisang klutuk wulung (PKW) by studying their molecular structure, genomic organization, genomic landscape, and infectious capacity. All eBSVs exhibit extensive viral genome duplications and rearrangements. eBSV segregation analysis on an F1 population of PKW combined with fluorescent in situ hybridization analysis showed that eBSImV, eBSOLV, and eBSGFV are each present at a single locus. eBSOLV and eBSGFV contain two distinct alleles, whereas eBSImV has two structurally identical alleles. Genotyping of both eBSV and viral particles expressed in the progeny demonstrated that only one allele for each species is infectious. The infectious allele of eBSImV could not be identified since the two alleles are identical. Finally, we demonstrate that eBSGFV and eBSOLV are located on chromosome 1 and eBSImV is located on chromosome 2 of the reference Musa genome published recently. The structure and evolution of eBSVs suggest sequential integration into the plant genome, and haplotype divergence analysis confirms that the three loci display differential evolution. Based on our data, we propose a model for BSV integration and eBSV evolution in the Musa balbisiana genome. The mutual benefits of this unique host-pathogen association are also discussed. PMID:23720724

Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-cyclin-dependent kinase 2 regulates its inhibition by eEF2 kinase.

PubMed

Hizli, Asli A; Chi, Yong; Swanger, Jherek; Carter, John H; Liao, Yi; Welcker, Markus; Ryazanov, Alexey G; Clurman, Bruce E

2013-02-01

Protein synthesis is highly regulated via both initiation and elongation. One mechanism that inhibits elongation is phosphorylation of eukaryotic elongation factor 2 (eEF2) on threonine 56 (T56) by eEF2 kinase (eEF2K). T56 phosphorylation inactivates eEF2 and is the only known normal eEF2 functional modification. In contrast, eEF2K undergoes extensive regulatory phosphorylations that allow diverse pathways to impact elongation. We describe a new mode of eEF2 regulation and show that its phosphorylation by cyclin A-cyclin-dependent kinase 2 (CDK2) on a novel site, serine 595 (S595), directly regulates T56 phosphorylation by eEF2K. S595 phosphorylation varies during the cell cycle and is required for efficient T56 phosphorylation in vivo. Importantly, S595 phosphorylation by cyclin A-CDK2 directly stimulates eEF2 T56 phosphorylation by eEF2K in vitro, and we suggest that S595 phosphorylation facilitates T56 phosphorylation by recruiting eEF2K to eEF2. S595 phosphorylation is thus the first known eEF2 modification that regulates its inhibition by eEF2K and provides a novel mechanism linking the cell cycle machinery to translational control. Because all known eEF2 regulation is exerted via eEF2K, S595 phosphorylation may globally couple the cell cycle machinery to regulatory pathways that impact eEF2K activity.

Phosphorylation of Eukaryotic Elongation Factor 2 (eEF2) by Cyclin A–Cyclin-Dependent Kinase 2 Regulates Its Inhibition by eEF2 Kinase

PubMed Central

Hizli, Asli A.; Chi, Yong; Swanger, Jherek; Carter, John H.; Liao, Yi; Welcker, Markus; Ryazanov, Alexey G.

2013-01-01

Protein synthesis is highly regulated via both initiation and elongation. One mechanism that inhibits elongation is phosphorylation of eukaryotic elongation factor 2 (eEF2) on threonine 56 (T56) by eEF2 kinase (eEF2K). T56 phosphorylation inactivates eEF2 and is the only known normal eEF2 functional modification. In contrast, eEF2K undergoes extensive regulatory phosphorylations that allow diverse pathways to impact elongation. We describe a new mode of eEF2 regulation and show that its phosphorylation by cyclin A–cyclin-dependent kinase 2 (CDK2) on a novel site, serine 595 (S595), directly regulates T56 phosphorylation by eEF2K. S595 phosphorylation varies during the cell cycle and is required for efficient T56 phosphorylation in vivo. Importantly, S595 phosphorylation by cyclin A-CDK2 directly stimulates eEF2 T56 phosphorylation by eEF2K in vitro, and we suggest that S595 phosphorylation facilitates T56 phosphorylation by recruiting eEF2K to eEF2. S595 phosphorylation is thus the first known eEF2 modification that regulates its inhibition by eEF2K and provides a novel mechanism linking the cell cycle machinery to translational control. Because all known eEF2 regulation is exerted via eEF2K, S595 phosphorylation may globally couple the cell cycle machinery to regulatory pathways that impact eEF2K activity. PMID:23184662

Eulepida mbala, a new species from Zambia (Coleoptera: Scarabaeidae: Melolonthinae).

PubMed

Sehnal, Richard

2018-03-22

The genus Eulepida Kolbe, 1894 (Coleoptera: Scarabaeidae: Melolonthinae: Leucopholini) was established to accommodate 10 Afrotropical species, seven new and three previously placed in Lepidiota Kirby, 1828, Proagosternus Blanchard, 1851, and Tricholepis Hampson, 1891. Lacroix (2010) designated Leucopholis lepidota Klug, 1855 as the type species of the genus Eulepida. Currently the genus contains 20 species divided into three groups based on morphological characters (Lacroix 2010, 2013): species group I includes Eulepida lepidota (Klug, 1855), E. minor Moser, 1913, E. nitidicollis Kolbe, 1894, E. nyassica Kolbe, 1894, E. sinuatifrons (Fairmaire, 1887), and E. zambiensis Lacroix, 2010; species group II includes E. anatina Brenske, 1896, E. tschindeana Péringuey, 1904, and E. werneri Lacroix, 2010; and species group III includes E. baumanni Kolbe, 1894, E. flavovestita Moser, 1913, E. gracilipes Kolbe, 1894, E. kameruna (Frey, 1972), E. kenyensis Lacroix, 2010, E. mamboiae Brenske, 1896, E. manowensis Moser, 1913, E. mashona Arrow, 1902, E. montana Kolbe, 1894, E. reichei (Thomson, 1858), and E. savagei (Hope, 1842). Examination of material recently collected in Zambia revealed an undescribed species belonging to species group II (sensu Lacroix 2010). This group is defined by the combination of the following characters: protibia bidentate; antennal club distinctly longer than antennal shaft; pygidium narrow, longer than wide, with a pronounced elongate terminal invagination; and parameres symmetrical, long, evenly curved in ventral aspect (Lacroix 2010). The purpose of this paper is to describe one new species, to add new geographic records for some Eulepida species of group II, and to update the key for this group. New faunistic records are reported for Eulepida tschindeana and Eulepida werneri from Zimbabwe.

Transforming properties of Felis catus papillomavirus type 2 E6 and E7 putative oncogenes in vitro and their transcriptional activity in feline squamous cell carcinoma in vivo

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

Altamura, Gennaro, E-mail: gennaro.altamura@unina.it; Corteggio, Annunziata, E-mail: ancorteg@unina.it; Pacini, Laura, E-mail: PaciniL@students.iarc.fr

Felis catus papillomavirus type 2 (FcaPV2) DNA is found in feline cutaneous squamous cell carcinomas (SCCs); however, its biological properties are still uncharacterized. In this study, we successfully expressed FcaPV2 E6 and E7 putative oncogenes in feline epithelial cells and demonstrated that FcaPV2 E6 binds to p53, impairing its protein level. In addition, E6 and E7 inhibited ultraviolet B (UVB)-triggered accumulation of p53, p21 and pro-apoptotic markers such as Cleaved Caspase3, Bax and Bak, suggesting a synergistic action of the virus with UV exposure in tumour pathogenesis. Furthermore, FcaPV2 E7 bound to feline pRb and impaired pRb levels, resulting inmore » upregulation of the downstream pro-proliferative genes Cyclin A and Cdc2. Importantly, we demonstrated mRNA expression of FcaPV2 E2, E6 and E7 in feline SCC samples, strengthening the hypothesis of a causative role in the development of feline SCC. - Highlights: • FcaPV2 E6 binds to and deregulates feline p53 protein. • FcaPV2 E7 binds to and deregulates feline pRb protein. • FcaPV2 oncogenes inhibit UVB-induced apoptosis. • FcaPV2 E6E7 and E7 increase the lifespan of primary cells. • FcaPV2 E2, E6 and E7 are expressed at the mRNA level in feline SCC in vivo.« less

Estimation of Glomerular Filtration Rate Based on Serum Cystatin C versus Creatinine in a Uruguayan Population

PubMed Central

Lujambio, Inés; Sottolano, Mariana; Robaina, Sebastián; Carusso, Florencia; da Rosa, Alicia; Ríos, Ana Carina; Olascoaga, Alicia; Gadola, Liliana; Noboa, Oscar; Staessen, Jan A.; Boggia, José

2014-01-01

Background. Estimation of glomerular filtration rate (eGFR) from biomarkers has evolved and multiple equations are available to estimate renal function at bedside. Methods. In a random sample of 119 Uruguayans (54.5% women; 56.2 years (mean)), we used Bland and Altman's method and Cohen's kappa statistic to assess concordance on a continuous or categorical (eGFR < 60 versus ≥60 mL/min/1.73 m2) scale between eGFRcys (reference) and eGFR derived from serum creatinine according to the Modification of Diet in Renal Disease (eGFRmdrd) or the Chronic Kidney Disease Epidemiology Collaboration equations (eGFRepi) or from both serum cystatin C and creatinine (eGFRmix). Results. In all participants, eGFRmdrd, eGFRepi, and eGFRmix were, respectively, 9.7, 11.5, and 5.6 mL/min/1.73 m2 higher (P < 0.0001) than eGFRcys. The prevalence of eGFR <60 mL/min/1.73 m2 was the highest for eGFRcys (21.8%), intermediate for eGFRmix (11.8%), and the lowest for eGFRmdrd (5.9%) and eGFRepi (3.4%). Using eGFRcys as reference, we found only fair agreement with the equations based on creatinine (Cohen's kappa statistic 0.15 to 0.23). Conclusion. Using different equations we reached clinically significant differences in the estimation of renal function. eGFRcys provides lower estimates, resulting in higher prevalence of eGFR <60 mL/min/1.73 m2. PMID:25215234

Role of ubiquitin and the HPV E6 oncoprotein in E6AP-mediated ubiquitination

PubMed Central

Mortensen, Franziska; Schneider, Daniel; Barbic, Tanja; Sladewska-Marquardt, Anna; Kühnle, Simone; Marx, Andreas; Scheffner, Martin

2015-01-01

Deregulation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with three different clinical pictures. Hijacking of E6AP by the E6 oncoprotein of distinct human papillomaviruses (HPV) contributes to the development of cervical cancer, whereas loss of E6AP expression or function is the cause of Angelman syndrome, a neurodevelopmental disorder, and increased expression of E6AP has been involved in autism spectrum disorders. Although these observations indicate that the activity of E6AP has to be tightly controlled, only little is known about how E6AP is regulated at the posttranslational level. Here, we provide evidence that the hydrophobic patch of ubiquitin comprising Leu-8 and Ile-44 is important for E6AP-mediated ubiquitination, whereas it does not affect the catalytic properties of the isolated catalytic HECT domain of E6AP. Furthermore, we show that the HPV E6 oncoprotein rescues the disability of full-length E6AP to use a respective hydrophobic patch mutant of ubiquitin for ubiquitination and that it stimulates E6AP-mediated ubiquitination of Ring1B, a known substrate of E6AP, in vitro and in cells. Based on these data, we propose that E6AP exists in at least two different states, an active and a less active or latent one, and that the activity of E6AP is controlled by noncovalent interactions with ubiquitin and allosteric activators such as the HPV E6 oncoprotein. PMID:26216987

Measurement of cross sections of the interactions e + e - → φφω and e + e - → φφφ at center-of-mass energies from 4.008 to 4.600 GeV

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

Ablikim, M.; Achasov, M. N.; Ahmed, S.

Using dmore » ata samples collected with the BESIII detector at the BEPCII collider at six center-of-mass energies between 4.008 and 4.600 GeV, we observe the processes e + e - → φ φ ω and e + e - → φ φ φ . The Born cross sections are measured and the ratio of the cross sections σ ( e + e - → φ φ ω ) / σ ( e + e - → φ φ φ ) is estimated to be 1.75 ± 0.22 ± 0.19 averaged over six energy points, where the first uncertainty is statistical and the second is systematic. The results represent first measurements of these interactions.« less

Measurement of cross sections of the interactions e + e - → φφω and e + e - → φφφ at center-of-mass energies from 4.008 to 4.600 GeV

DOE PAGES

Ablikim, M.; Achasov, M. N.; Ahmed, S.; ...

2017-09-14

Using dmore » ata samples collected with the BESIII detector at the BEPCII collider at six center-of-mass energies between 4.008 and 4.600 GeV, we observe the processes e + e - → φ φ ω and e + e - → φ φ φ . The Born cross sections are measured and the ratio of the cross sections σ ( e + e - → φ φ ω ) / σ ( e + e - → φ φ φ ) is estimated to be 1.75 ± 0.22 ± 0.19 averaged over six energy points, where the first uncertainty is statistical and the second is systematic. The results represent first measurements of these interactions.« less

Behavior of endocrine disrupting chemicals in Johkasou improved septic tank in Japan.

PubMed

Nakagawa, S; Matsuo, H; Motoyama, M; Nomiyama, K; Shinohara, R

2009-09-01

The behavior of estrogens (estrone: E1, 17beta-estradiol: E2, estriol: E3 and ethinylestradiol: EE2) and an androgen (testosterone) in the water and sludge from Johkasou in Japan was investigated. The concentrations of E1, E2, E3 and testosterone in water samples from the Johkasou were 33-500, N.D. approximately 150, N.D. approximately 6,700 and 500 ng/L, respectively. In sludge samples, the concentrations of E1, E2, E3, and testostrerone were N.D. approximately 39, N.D. approximately 6.7, N.D. approximately 60 and 0.2-9.0 ng/L, respectively. EE2 was not detected in all samples. The removal rates of E1, E2, E3 and testosterone in Johkasou were 45%-91%, 66%-100%, 90%-100%, and about 90%, respectively.

Behavior of the E-E' Bonds (E, E' = S and Se) in Glutathione Disulfide and Derivatives Elucidated by Quantum Chemical Calculations with the Quantum Theory of Atoms-in-Molecules Approach.

PubMed

Hayashi, Satoko; Tsubomoto, Yutaka; Nakanishi, Waro

2018-02-17

The nature of the E-E' bonds (E, E' = S and Se) in glutathione disulfide ( 1 ) and derivatives 2 - 3 , respectively, was elucidated by applying quantum theory of atoms-in-molecules (QTAIM) dual functional analysis (QTAIM-DFA), to clarify the basic contribution of E-E' in the biological redox process, such as the glutathione peroxidase process. Five most stable conformers a - e were obtained, after applying the Monte-Carlo method then structural optimizations. In QTAIM-DFA, total electron energy densities H b ( r c ) are plotted versus H b ( r c ) - V b ( r c )/2 at bond critical points (BCPs), where V b ( r c ) are potential energy densities at BCPs. Data from the fully optimized structures correspond to the static nature. Those containing perturbed structures around the fully optimized one in the plot represent the dynamic nature of interactions. The behavior of E-E' was examined carefully. Whereas E-E' in 1a - 3e were all predicted to have the weak covalent nature of the shared shell interactions, two different types of S-S were detected in 1 , depending on the conformational properties. Contributions from the intramolecular non-covalent interactions to stabilize the conformers were evaluated. An inverse relationship was observed between the stability of a conformer and the strength of E-E' in the conformer, of which reason was discussed.

SARS-CoV envelope protein palmitoylation or nucleocapid association is not required for promoting virus-like particle production.

PubMed

Tseng, Ying-Tzu; Wang, Shiu-Mei; Huang, Kuo-Jung; Wang, Chin-Tien

2014-04-27

Coronavirus membrane (M) proteins are capable of interacting with nucleocapsid (N) and envelope (E) proteins. Severe acute respiratory syndrome coronavirus (SARS-CoV) M co-expression with either N or E is sufficient for producing virus-like particles (VLPs), although at a lower level compared to M, N and E co-expression. Whether E can release from cells or E/N interaction exists so as to contribute to enhanced VLP production is unknown. It also remains to be determined whether E palmitoylation or disulfide bond formation plays a role in SARS-CoV virus assembly. SARS-CoV N is released from cells through an association with E protein-containing vesicles. Further analysis suggests that domains involved in E/N interaction are largely located in both carboxyl-terminal regions. Changing all three E cysteine residues to alanines did not exert negative effects on E release, E association with N, or E enhancement of VLP production, suggesting that E palmitoylation modification or disulfide bond formation is not required for SARS-CoV virus assembly. We found that removal of the last E carboxyl-terminal residue markedly affected E release, N association, and VLP incorporation, but did not significantly compromise the contribution of E to efficient VLP production. The independence of the SARS-CoV E enhancement effect on VLP production from its viral packaging capacity suggests a distinct SARS-CoV E role in virus assembly.

Crystal structure of the Agrobacterium virulence complex VirE1-VirE2 reveals a flexible protein that can accommodate different partners.

PubMed

Dym, Orly; Albeck, Shira; Unger, Tamar; Jacobovitch, Jossef; Branzburg, Anna; Michael, Yigal; Frenkiel-Krispin, Daphna; Wolf, Sharon Grayer; Elbaum, Michael

2008-08-12

Agrobacterium tumefaciens infects its plant hosts by a mechanism of horizontal gene transfer. This capability has led to its widespread use in artificial genetic transformation. In addition to DNA, the bacterium delivers an abundant ssDNA binding protein, VirE2, whose roles in the host include protection from cytoplasmic nucleases and adaptation for nuclear import. In Agrobacterium, VirE2 is bound to its acidic chaperone VirE1. When expressed in vitro in the absence of VirE1, VirE2 is prone to oligomerization and forms disordered filamentous aggregates. These filaments adopt an ordered solenoidal form in the presence of ssDNA, which was characterized previously by electron microscopy and three-dimensional image processing. VirE2 coexpressed in vitro with VirE1 forms a soluble heterodimer. VirE1 thus prevents VirE2 oligomerization and competes with its binding to ssDNA. We present here a crystal structure of VirE2 in complex with VirE1, showing that VirE2 is composed of two independent domains presenting a novel fold, joined by a flexible linker. Electrostatic interactions with VirE1 cement the two domains of VirE2 into a locked form. Comparison with the electron microscopy structure indicates that the VirE2 domains adopt different relative orientations. We suggest that the flexible linker between the domains enables VirE2 to accommodate its different binding partners.

SARS-CoV envelope protein palmitoylation or nucleocapid association is not required for promoting virus-like particle production

PubMed Central

2014-01-01

Background Coronavirus membrane (M) proteins are capable of interacting with nucleocapsid (N) and envelope (E) proteins. Severe acute respiratory syndrome coronavirus (SARS-CoV) M co-expression with either N or E is sufficient for producing virus-like particles (VLPs), although at a lower level compared to M, N and E co-expression. Whether E can release from cells or E/N interaction exists so as to contribute to enhanced VLP production is unknown. It also remains to be determined whether E palmitoylation or disulfide bond formation plays a role in SARS-CoV virus assembly. Results SARS-CoV N is released from cells through an association with E protein-containing vesicles. Further analysis suggests that domains involved in E/N interaction are largely located in both carboxyl-terminal regions. Changing all three E cysteine residues to alanines did not exert negative effects on E release, E association with N, or E enhancement of VLP production, suggesting that E palmitoylation modification or disulfide bond formation is not required for SARS-CoV virus assembly. We found that removal of the last E carboxyl-terminal residue markedly affected E release, N association, and VLP incorporation, but did not significantly compromise the contribution of E to efficient VLP production. Conclusions The independence of the SARS-CoV E enhancement effect on VLP production from its viral packaging capacity suggests a distinct SARS-CoV E role in virus assembly. PMID:24766657

The Human Papillomavirus Type 16 E6 Gene Alone Is Sufficient To Induce Carcinomas in Transgenic Animals

PubMed Central

Song, Shiyu; Pitot, Henry C.; Lambert, Paul F.

1999-01-01

High-risk human papillomaviruses (HPVs) are the causative agents of certain human cancers. HPV type 16 (HPV16) is the papillomavirus most frequently associated with cervical cancer in women. The E6 and E7 genes of HPV are expressed in cells derived from these cancers and can transform cells in tissue culture. Animal experiments have demonstrated that E6 and E7 together cause tumors. We showed previously that E6 and E7 together or E7 alone could induce skin tumors in mice when these genes were expressed in the basal epithelia of the skin. In this study, we investigated the role that the E6 gene plays in carcinogenesis. We generated K14E6 transgenic mice, in which the HPV16 E6 gene was directed in its expression by the human keratin 14 promoter (hK14) to the basal layer of the epidermis. We found that E6 induced cellular hyperproliferation and epidermal hyperplasia and caused skin tumors in adult mice. Interestingly, the tumors derived from E6 were mostly malignant, as opposed to the tumors from E7 mice, which were mostly benign. This result leads us to hypothesize that E6 may contribute differently than E7 to HPV-associated carcinogenesis; whereas E7 primarily contributes to the early stages of carcinogenesis that lead to the formation of benign tumors, E6 primarily contributes to the late stages of carcinogenesis that lead to malignancy. PMID:10364340

Human Papillomavirus E6/E7-Specific siRNA Potentiates the Effect of Radiotherapy for Cervical Cancer in Vitro and in Vivo

PubMed Central

Jung, Hun Soon; Rajasekaran, Nirmal; Song, Sang Yong; Kim, Young Deug; Hong, Sungyoul; Choi, Hyuck Jae; Kim, Young Seok; Choi, Jong-Sun; Choi, Yoon-La; Shin, Young Kee

2015-01-01

The functional inactivation of TP53 and Rb tumor suppressor proteins by the HPV-derived E6 and E7 oncoproteins is likely an important step in cervical carcinogenesis. We have previously shown siRNA technology to selectively silence both E6/E7 oncogenes and demonstrated that the synthetic siRNAs could specifically block its expression in HPV-positive cervical cancer cells. Herein, we investigated the potentiality of E6/E7 siRNA candidates as radiosensitizers of radiotherapy for the human cervical carcinomas. HeLa and SiHa cells were transfected with HPV E6/E7 siRNA; the combined cytotoxic effect of E6/E7 siRNA and radiation was assessed by using the cell viability assay, flow cytometric analysis and the senescence-associated β-galactosidase (SA-β-Gal) assay. In addition, we also investigated the effect of combined therapy with irradiation and E6/E7 siRNA intravenous injection in an in vivo xenograft model. Combination therapy with siRNA and irradiation efficiently retarded tumor growth in established tumors of human cervical cancer cell xenografted mice. In addition, the chemically-modified HPV16 and 18 E6/E7 pooled siRNA in combination with irradiation strongly inhibited the growth of cervical cancer cells. Our results indicated that simultaneous inhibition of HPV E6/E7 oncogene expression with radiotherapy can promote potent antitumor activity and radiosensitizing activity in human cervical carcinomas. PMID:26035754

New perspective of Grodzins E × B(E2) ↑ product rule

NASA Astrophysics Data System (ADS)

Gupta, J. B.; Katoch, Vikas

In the collective spectra of atomic nuclei, the level energy E(21+) varies with atomic number Z and neutron number N. Also the E2 decay-reduced transition probability B(E2, 01+ → 2 1+) is related to the energy E(21+). The product E(21+) × B(E2) ↑ is constant according to Grodzins product rule, independent of the vibration or rotational status of the nucleus. The product rule is often used for determining B(E2) from the known E(21+). However, the variation of the product with various parameters is also suggested in the literature. Hence, a detailed global study of this rule for (Z = 54‑‑78, 66 < N < 126) region is warranted. We use a novel method of displaying the linear relation of B(E2) ↑ with 1/E(21+) for the isotopes of each element (Xe-Pt), instead of their variation with N,Z or A. Through our work, we firmly establish the global validity of the Grodzins relation of B(E2), being proportional to the moment of inertia, except for the deviation in specific cases. Our B(E2) ↑ versus 1/E plots provide a transparent view of the variation of the low-energy nuclear structure. This gives a new perspective of their nuclear structure. Also the various theoretical interpretations of B(E2)s and the energy E(21+) are reviewed.

Fate of oestrogens during anaerobic blackwater treatment with micro-aerobic post-treatment.

PubMed

de Mes, T Z D; Kujawa-Roeleveld, K; Zeeman, G; Lettinga, G

2007-01-01

The fate of oestrone (E1), 17beta-oestradiol (E2) and 17alpha-ethynyloestradiol (EE2) was investigated in a concentrated blackwater treatment system consisting of an UASB septic tank, with micro-aerobic post-treatment. In UASB septic tank effluent a (natural) total concentration of 4.02 microg/L E1 and 18.69 microg/L E2, comprising the sum of conjugated (>70% for E1 and >80% for E2) and unconjugated forms, was measured. During post-treatment the unconjugated oestrogens were removed to below 1 microg/L. A percentage of 77% of the measured unconjugated E1 and 82% of E2 was associated with particles >1.2 microm in the final effluent implying high sorption affinity of both compounds. When spiking the UASB septic tank effluent with E1, E2, EE2 and the sulphate conjugate of E2, removal in the micro-aerobic post-treatment was >99% for both E2 and EE2 and 83% for E1. The lower removal value for E1 was a result of (slow) deconjugation during the treatment, and in the final effluent still 40% of E1 and 99% of E2 was present in conjugated form. The latter was the result of incomplete deconjugation of the spiked E2(3S) in the post-treatment system.

Identification, Classification, and Phylogeny of the Pathogenic Species Exophiala jeanselmei and Related Species by Mitochondrial Cytochrome b Gene Analysis

PubMed Central

Wang, Li; Yokoyama, Koji; Miyaji, Makoto; Nishimura, Kazuko

2001-01-01

We analyzed a 402-bp sequence of the mitochondrial cytochrome b gene of 34 strains of Exophiala jeanselmei and 16 strains representing 12 related species. The strains of E. jeanselmei were classified into 20 DNA types and 17 amino acid types. The differences between these strains were found in 1 to 60 nucleotides and 1 to 17 amino acids. On the basis of the identities and similarities of nucleotide and amino acid sequences, some strains were reidentified: i.e., two strains of E. jeanselmei var. hetermorpha and one strain of E. castellanii as E. dermatitidis (including the type strain), three strains of E. jeanselmei as E. jeanselmei var. lecanii-corni (including the type strain), three strains of E. jeanselmei as E. bergeri (including the type strain), seven strains of E. jeanselmei as E. pisciphila (including the type strain), seven strains of E. jeanselmei as E. jeanselmei var. jeanselmei (including the type strain), one strain of E. jeanselmei as Fonsecaea pedrosoi (including the type strain), and one strain of E. jeanselmei as E. spinifera (including the type strain). Some E. jeanselmei strains showed distinct nucleotide and amino acid sequences. The amino-acid-based UPGMA (unweighted pair group method with the arithmetic mean) tree exhibited nearly the same topology as those of the DNA-based trees obtained by neighbor joining, maximum parsimony, and maximum likelihood methods. PMID:11724862

Young adult e-cigarette users’ reasons for liking and not liking e-cigarettes: A qualitative study

PubMed Central

Herzog, Thaddeus A.; Muranaka, Nicholas; Fagan, Pebbles

2015-01-01

Objective To gain an in-depth understanding of what young adult electronic- or e-cigarette users like or dislike about e-cigarettes. We aimed to determine the reasons that may encourage young adults to use e-cigarettes or discourage them from using e-cigarettes. Design Twelve focus group discussions were conducted with 62 current daily e-cigarette users (63% men) of mean age = 25.1 years (Standard Deviation = 5.5). Data were analyzed following principles of inductive content analysis. Results Results indicated 12 categories of reasons for liking e-cigarettes (e.g., recreation, smoking cessation) and 6 categories of reasons for not liking e-cigarettes (e.g., poor product quality, poor smoking experience). Conclusions Young adults’ motives for using or not using e-cigarettes appear to be varied and their relative importance in terms of predicting e-cigarette use initiation, dependence, and cigarette/e-cigarette dual use needs to be carefully studied in population-based, empirical studies. The current findings suggest that e-cigarettes may serve social, recreational, and sensory expectancies that are unique relative to cigarettes and not dependent on nicotine. Further, successful use of e-cigarettes in smoking cessation will likely need higher standards of product quality control, better nicotine delivery efficiency and a counseling component that would teach smokers how to manage e-cigarette devices while trying to quit smoking cigarettes. PMID:26074148

Young adult e-cigarette users' reasons for liking and not liking e-cigarettes: A qualitative study.

PubMed

Pokhrel, Pallav; Herzog, Thaddeus A; Muranaka, Nicholas; Fagan, Pebbles

2015-01-01

To gain an in-depth understanding of what young adult electronic- or e-cigarette users like or dislike about e-cigarettes. We aimed to determine the reasons that may encourage young adults to use e-cigarettes or discourage them from using e-cigarettes. Twelve focus group discussions were conducted with 62 current daily e-cigarette users (63% men) of mean age = 25.1 years (standard deviation = 5.5). Data were analysed following principles of inductive content analysis. Results indicated 12 categories of reasons for liking e-cigarettes (e.g., recreation, smoking cessation) and 6 categories of reasons for not liking e-cigarettes (e.g. poor product quality, poor smoking experience). Young adults' motives for using or not using e-cigarettes appear to be varied and their relative importance in terms of predicting e-cigarette use initiation, dependence, and cigarette/e-cigarette dual use needs to be carefully studied in population-based, empirical studies. The current findings suggest that e-cigarettes may serve social, recreational, and sensory expectancies that are unique relative to cigarettes and not dependent on nicotine. Further, successful use of e-cigarettes in smoking cessation will likely need higher standards of product quality control, better nicotine delivery efficiency and a counselling component that would teach smokers how to manage e-cigarette devices while trying to quit smoking cigarettes.

25-KVA Amorphous Metal-Core Transformer Developmental Test Report

DTIC Science & Technology

1989-08-01

N-1801 August 1989 By G.V. Urata and J.O. Franchi Sponsored By Naval Facilites Engineering Command Technical Note and Office of Naval Research 25-kVA...wt’c.i,,., di.shtr tlion iswilm ihed 89 11 1.3 108 C4C E .0>. .4) C L ’TU m ’D ’s n C w o o en o’ 0. 1 0 4 = ~ E 0 0 -~CI u 0 44 E N N M Cn E E E~ E EE...REPRODUCE LEGIBLY. REPORT DOCUMENTATION PAGE OM No. o70-o , Pub €ic r o t r b e to jhm, t o ,im io n of Anf rflut,O . m e, o .e, *. du .a. e o ., nte tve

Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice.

PubMed

Dolejší, Eva; Liraz, Ori; Rudajev, Vladimír; Zimčík, Pavel; Doležal, Vladimír; Michaelson, Daniel M

2016-02-01

Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease. We utilized apoE4-targeted replacement mice (approved by the Tel Aviv University Animal Care Committee) to investigate whether cholinergic dysfunction, which increases during aging and is a hallmark of Alzheimer's disease, is accentuated by apoE4. This revealed that levels of the pre-synaptic cholinergic marker, vesicular acetylcholine transporter in the hippocampus and the corresponding electrically evoked release of acetylcholine, are similar in 4-month-old apoE4 and apolipoprotein E3 (apoE3) mice. Both parameters decrease with age. This decrease is, however, significantly more pronounced in the apoE4 mice. The levels of cholinacetyltransferase (ChAT), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) were similar in the hippocampus of young apoE4 and apoE3 mice and decreased during aging. For ChAT, this decrease was similar in the apoE4 and apoE3 mice, whereas it was more pronounced in the apoE4 mice, regarding their corresponding AChE and BuChE levels. The level of muscarinic receptors was higher in the apoE4 than in the apoE3 mice at 4 months and increased to similar levels with age. However, the relative representation of the M1 receptor subtype decreased during aging in apoE4 mice. These results demonstrate impairment of the evoked release of acetylcholine in hippocampus by apoE4 in 12-month-old mice but not in 4-month-old mice. The levels of ChAT and the extent of the M2 receptor-mediated autoregulation of ACh release were similar in the adult mice, suggesting that the apoE4-related inhibition of hippocampal ACh release in these mice is not driven by these parameters. Evoked ACh release from hippocampal and cortical slices is similar in 4-month-old apoE4 and apoE3 mice but is specifically and significantly reduced in hippocampus, but not cortex, of 12-month-old apoE4 mice. This effect is accompanied by decreased VAChT levels. These findings show that the hipocampal cholinergic nerve terminals are specifically affected by apoE4 and that this effect is age dependent. © 2015 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

Cholinesterase activity in the cup oyster Saccostrea sp. exposed to chlorpyrifos, imidacloprid, cadmium and copper.

PubMed

Moncaleano-Niño, Angela M; Luna-Acosta, Andrea; Gómez-Cubillos, Maria Camila; Villamil, Luisa; Ahrens, Michael J

2018-04-30

In the present study, the sensitivity and concentration dependence of three functionally-defined components of cholinesterase activity (total: T-ChE; eserine-sensitive: Es-ChE; and eserine-resistant: Er-ChE) were quantified in the gill, digestive gland and adductor muscle of the tropical cup oyster Saccostrea sp., following acute (96h) aqueous exposure to commercial formulations of the organophosphate (OP) insecticide chlorpyrifos and the neonicotinoid (NN) imidacloprid (concentration range: 0.1-100mg/L), as well as to dissolved cadmium and copper (concentration range: 1-1000μg/L). Oysters (1.5-5.0cm shell length), field-collected from a boating marina in Santa Marta, Colombia (Caribbean Sea) were exposed in the laboratory to each substance at five concentrations. T-ChE, Es-ChE, and Er-ChE activity were quantified in the three tissues in pools of 5 individuals (3 replicates per concentration), before and after inhibition with the total cholinesterase inhibitor eserine (physostigmine, 100µM). Oysters exposed to chlorpyrifos, imidacloprid and Cd showed reduced T-ChE and Es-ChE activity in gills at highest exposure concentrations, with Es-ChE activity being inhibited proportionally more so than T-ChE, whereas Er-ChE activity showed no significant concentration-response. Digestive gland also showed diminished T-ChE, Es-ChE and Er-ChE activity for highest chlorpyrifos and Cd concentrations relative to controls, but an increase of T-ChE and Er-ChE activity at the highest imidacloprid concentration (100mg/L). For Cu, T-ChE, Es-ChE and Er-ChE activities in gills and digestive gland were elevated relative to controls in oysters exposed to Cu concentrations > 100µg/L. In adductor muscle, T-ChE, Es-ChE and Er-ChE activity showed no apparent pattern for any of the four xenobiotics and concentration levels tested. Although this study confirms acute (96h) concentration-dependent reduction of tissue T-ChE and Es-ChE activity in gills and digestive glands of Saccostrea sp. exposed to high concentrations of chlorpyrifos (100mg/L), significant changes in T-ChE, Es-ChE and Er-ChE were also caused by exposure to Cd and Cu at concentrations > 100µg/L and by exposure to imidacloprid (100mg/L), indicating that cholinesterase activity is not a specific biomarker of organophosphate exposure in this species, but, rather, a biomarker of diverse xenobiotic exposure. Copyright © 2018 Elsevier Inc. All rights reserved.

Prototype development and demonstration for response, emergency staging, communications, uniform management, and evacuation (R.E.S.C.U.M.E.) : R.E.S.C.U.M.E. prototype system architecture.

DOT National Transportation Integrated Search

2014-01-01

This document provides the high-level system architecture for the Prototype Development and Demonstration of a R.E.S.C.U.M.E. system. The requirements addressed in this document are based upon those that can be found in previous R.E.S.C.U.M.E. report...

Aviation System Safety Risk Management Tool Analysis. Volume 2: Appendices

DTIC Science & Technology

1993-10-01

Part Number FY AMC Case Number BATERY BB433AA 81 E 810421201 E’ BATTERY BB433AA 81 E 810421181 [’ BATTERY BB433AA 81 E 810514141 [’ BATIERY BB433AA 81...830520061 [- BAT=ERY NOT REC 83 E 830514071 -l BATTERY NOT REC 82 E 811102131 El BATERY NOT REC 82 E 820715191 " BATTERY NOT REC 82 E 820902051 "- BATERY NOT

Observation of D+→ηe+νe

NASA Astrophysics Data System (ADS)

Mitchell, R. E.; Shepherd, M. R.; Besson, D.; Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Smith, A.; Zweber, P.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Ernst, J.; Ecklund, K. M.; Severini, H.; Love, W.; Savinov, V.; Aquines, O.; Lopez, A.; Mehrabyan, S.; Mendez, H.; Ramirez, J.; Huang, G. S.; Miller, D. H.; Pavlunin, V.; Sanghi, B.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Hu, D.; Moziak, B.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Artuso, M.; Blusk, S.; Butt, J.; Li, J.; Menaa, N.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Sia, R.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Zhang, K.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Asner, D. M.; Edwards, K. W.; Naik, P.; Briere, R. A.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Adam, N. E.; Alexander, J. P.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Galik, R. S.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Mohapatra, D.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Pivarski, J.; Riley, D.; Ryd, A.; Sadoff, A. J.; Schwarthoff, H.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Athar, S. B.; Patel, R.; Potlia, V.; Yelton, J.; Rubin, P.; Cawlfield, C.; Eisenstein, B. I.; Karliner, I.; Kim, D.; Lowrey, N.; Selen, M.; White, E. J.; Wiss, J.

2009-02-01

Using a 281pb-1 data sample collected at the ψ(3770) resonance with the CLEO-c detector at the Cornell Electron Storage Ring, we report the first observation of D+→ηe+νe. We also set upper limits for D+→η'e+νe and D+→ϕe+νe that are about 2 orders of magnitude more restrictive than those obtained by previous experiments.

The Operational Equations of State, 4: The Dulong-Petit Equation of State for Hydrocode

DTIC Science & Technology

2012-07-01

1 1 , 2 2 ln T T T T V S S V S V S HHC C H V V E S V C C E E P VdE E E V d e CT e d V CT...71. 9. Grinfeld, M. A. Thermodynamic Methods in the Theory of Heterogeneous Systems , Longman, New York, 1991. NO. OF COPIES ORGANIZATION

Equality of e+e- production amplitudes for scalar-vector and pseudoscalar-axial heavy meson-antimeson pairs

NASA Astrophysics Data System (ADS)

Voloshin, M. B.

2018-02-01

The production of heavy meson-antimeson pairs of the type S V and P A in e+e- annihilation is considered, with P and V being the ground-state JP=0- and JP=1- (anti)mesons from the (1 /2 )-doublet and S and A standing for the excited JP=0+ and JP=1+ (anti)mesons from the (1 /2 )+doublet. It is argued that the production amplitudes in these two channels should be equal up to a higher (than one) order in the heavy quark mass (ΛQCD/MQ ) expansion, A (e +e-→S V ¯ )=A (e+e-→A P ¯ ) , including both the S -wave and the D -wave amplitudes. Given that the S V and P A thresholds are extremely close, the production cross section in both channels should be the same to a high degree of accuracy. In practice, this behavior can be studied for the processes e+e-→Ds 0(2317 )D¯s *+c .c . and e+e-→Ds 1(2460 )D¯ s+c .c . in the charm sector and e+e-→Bs 0B¯s *+c .c . and e+e-→Bs 1B¯ s+c .c . in the B sector.

E-learning in Saudi Arabia: ‘To E or not to E, that is the question’

PubMed Central

Al-Shehri, Ali M.

2010-01-01

Background: The Kingdom of Saudi Arabia (KSA) has witnessed unprecedented growth in higher education and E-learning in recent times. In the last five years, one university and five colleges have been commissioned every month; 800 scholarships have been awarded every month for overseas study; a national center for E-learning has been established; and E-units or departments have been set-up in almost every university. E-learning has become important for discussion to quote Shakespeare ‘To E or not to E that is the question.’ Objectives: To examine current and future developments and challenges of E-learning in KSA. Materials and Methods: A qualitative approach was used to explore views of 30 senior academicians involved in E-learning during their attendance at a two-week course on the subject. Results: All participants considered themselves as decision makers on E-learning in their units or departments. They felt that E-learning had come to stay, but acknowledged challenges in respect of resources, organization, management, and information technology. Conclusion: The fast development of E-learning poses many challenges. Clear vision and strategic planning with prospective E-learners in mind are essential to make E-learning programs cost effective. PMID:21359026

The Role of Knowledge and Risk Beliefs in Adolescent E-Cigarette Use: A Pilot Study

PubMed Central

Rohde, Jacob A.; Noar, Seth M.; Horvitz, Casey; Cornacchione Ross, Jennifer; Sutfin, Erin L.

2018-01-01

The use of e-cigarettes and other vaping devices among adolescents is an urgent public health problem due to the concern about adolescent exposure to nicotine. This study examined: (1) adolescents’ knowledge and beliefs about e-cigarette risks; and (2) whether knowledge and risk beliefs were associated with e-cigarette use. N = 69 adolescents completed a cross-sectional survey about e-cigarette knowledge, attitudes (i.e., risk beliefs), and behavior (KAB). Nearly half (47%) of the sample reported ever using e-cigarettes. The majority of adolescents knew about many of the risks of e-cigarettes, with no differences between never- and ever-users. However, risk beliefs, such as worrying about health risks of using e-cigarettes, varied across groups. Compared to never-users, e-cigarette ever-users were significantly less likely to worry about e-cigarette health risks, less likely to think that e-cigarettes would cause them negative health consequences, and less likely to believe that e-cigarette use would lead to addiction. In a multivariable logistic regression, prior combustible cigarette use, mother’s education, and addiction risk beliefs about e-cigarettes emerged as significant predictors of adolescents’ e-cigarette use. This study reveals that while knowledge is not associated with adolescent e-cigarette use, risk beliefs do predict use. PMID:29690606

The Role of Knowledge and Risk Beliefs in Adolescent E-Cigarette Use: A Pilot Study.

PubMed

Rohde, Jacob A; Noar, Seth M; Horvitz, Casey; Lazard, Allison J; Cornacchione Ross, Jennifer; Sutfin, Erin L

2018-04-23

The use of e-cigarettes and other vaping devices among adolescents is an urgent public health problem due to the concern about adolescent exposure to nicotine. This study examined: (1) adolescents’ knowledge and beliefs about e-cigarette risks; and (2) whether knowledge and risk beliefs were associated with e-cigarette use. N = 69 adolescents completed a cross-sectional survey about e-cigarette knowledge, attitudes (i.e., risk beliefs), and behavior (KAB). Nearly half (47%) of the sample reported ever using e-cigarettes. The majority of adolescents knew about many of the risks of e-cigarettes, with no differences between never- and ever-users. However, risk beliefs, such as worrying about health risks of using e-cigarettes, varied across groups. Compared to never-users, e-cigarette ever-users were significantly less likely to worry about e-cigarette health risks, less likely to think that e-cigarettes would cause them negative health consequences, and less likely to believe that e-cigarette use would lead to addiction. In a multivariable logistic regression, prior combustible cigarette use, mother’s education, and addiction risk beliefs about e-cigarettes emerged as significant predictors of adolescents’ e-cigarette use. This study reveals that while knowledge is not associated with adolescent e-cigarette use, risk beliefs do predict use.

SIGIR Quarterly and Semiannual Report to the United States Congress

DTIC Science & Technology

2006-01-01

Seraji Substation Basrah $5,709 GRD-PCO Perini Corporation Central 1659 Shat Al...e R em o va l, Fi re Se rv ic e, a n d P u b lic Sa fe ty F ac ili ty a n d Eq u ip m en t R ep ai rs 27 8. 00 20 4. 00 0. 00 20 4. 00 0...th e tr ai ni ng a nd e qu ip pi ng o f th e Ira qi P ol ic e Se rv ic e (IP S) 2. E xa m in e th e ef fe ct iv en es s

Low-Voltage Hall Thruster Mode Transitions

DTIC Science & Technology

2014-06-01

cross field electron mobility μe┴ in Eq. 2. ee e m Be   (1) 21 1 r ee 2 eee e Be m Ωm e            (2) where me is the electron... ee e m Be   21 1 r ee 2 eee e Be m Ωm e            Be m m Tk r e e e e  Analysis of Bulk Electron Parameters 100V – 120V, 10-20

Hybrid Microcircuit Failure Rate Prediction

DTIC Science & Technology

1978-04-01

4.52E-2 8.31E-2 300 Test 3.11E7 4 7.39E-2 1.29)E-l 2.16E-1 350 Test 2.07E7 8 2.69E-1 3.,98E-1 5.50E-1 19 AN .5 .11 0 * .01 𔃾J .4-4 4--I 0 14 .00 1 4.1...Traeger (Ref. 2 and Ref. 3) have shown that organic die attach materials outgas harmful products which may drastically reduce the reliability of a...manufacturers using organic die attach methods must take special precautions to insure that the material used does not outgas exten! sively. Parts

Enduring Strategic Rivalries

DTIC Science & Technology

2014-08-01

I N S T I T U T E F O R D E F E N S E A N A L Y S E S August 2014 Approved for public release; distribution is unlimited. IDA Paper P-5178 Log: H...license under the clause at DFARS 252.227-7013 (a)(16) [Jun 2013] I N S T I T U T E F O R D E F E N S E A N A L Y S E S IDA Paper P-5178 Enduring...City and its Countryside (London: G. Phillip, 1987), 75-81. 9 See John S. Morrison, John F. Coates, and N . Boris Rankov, The Athenian Trireme: The

Affordability of Defense Acquisition Programs

DTIC Science & Technology

2015-02-01

I N S T I T U T E F O R D E F E N S E A N A L Y S E S IDA Paper P-5243 Redacted February 2015 Affordability of Defense Acquisition Programs...Gene H. Porter, Project Leader Kathleen M. Conley C. Vance Gordon R . Royce Kneece, Jr. Brian Q. Rieksts Alan H. Shaw David M. Tate INSTITUTE FOR DEFENSE...Kathleen M. Conley C. Vance Gordon R . Royce Kneece, Jr. Brian Q. Rieksts Alan H. Shaw David M. Tate I N S T I T U T E F O R D E F E N S E A N A L Y S E

Comparison of Measures of E-cigarette Advertising Exposure and Receptivity.

PubMed

Pokhrel, Pallav; Fagan, Pebbles; Herzog, Thaddeus A; Schmid, Simone; Kawamoto, Crissy T; Unger, Jennifer B

2017-10-01

We tested how various measures of e-cigarette advertising exposure and receptivity are related to each other and compare to each other in their associations with e-cigarette use susceptibility and behavior. Cross-sectional data were collected from young adult college students (N = 470; M age = 20.9, SD = 2.1; 65% women). Measures of e-cigarette advertising exposure/receptivity compared included a cued recall measure, measures of marketing receptivity, perceived ad exposure, liking of e-cigarette ads, and frequency of convenience store visit, which is considered a measure of point-of-sale ad exposure. The cued-recall measure was associated with e-cigarette use experimentation but not current e-cigarette use. Marketing receptivity was associated with current e-cigarette use but not e-cigarette use experimentation. Liking of e-cigarette ads was the only measure associated with e-cigarette use susceptibility. Frequency of convenience store visit was associated with current e-cigarette use but not e-cigarette use experimentation or susceptibility. Inclusion of multiple measures of marketing exposure and receptivity is recommended for regulatory research concerning e-cigarette marketing. Marketing receptivity and cued recall measures are strong correlates of current and ever e-cigarette use, respectively.

Comparison of Measures of E-cigarette Advertising Exposure and Receptivity

PubMed Central

Pokhrel, Pallav; Fagan, Pebbles; Herzog, Thaddeus A.; Schmid, Simone; Kawamoto, Crissy T.; Unger, Jennifer B.

2018-01-01

Objectives We tested how various measures of e-cigarette advertising exposure and receptivity are related to each other and compare to each other in their associations with e-cigarette use susceptibility and behavior. Methods Cross-sectional data were collected from young adult college students (N = 470; Mage = 20.9, SD = 2.1; 65% women). Measures of e-cigarette advertising exposure/receptivity compared included a cued recall measure, measures of marketing receptivity, perceived ad exposure, liking of e-cigarette ads, and frequency of convenience store visit, which is considered a measure of point-of-sale ad exposure. Results The cued-recall measure was associated with e-cigarette use experimentation but not current e-cigarette use. Marketing receptivity was associated with current e-cigarette use but not e-cigarette use experimentation. Liking of e-cigarette ads was the only measure associated with e-cigarette use susceptibility. Frequency of convenience store visit was associated with current e-cigarette use but not e-cigarette use experimentation or susceptibility. Conclusion Inclusion of multiple measures of marketing exposure and receptivity is recommended for regulatory research concerning e-cigarette marketing. Marketing receptivity and cued recall measures are strong correlates of current and ever e-cigarette use, respectively. PMID:29516028

E-Cigarette Marketing Exposure is Associated with E-cigarette Use among U.S. Youth

PubMed Central

Mantey, Dale S.; Cooper, Maria R.; Clendennen, Stephanie; Pasch, Keryn; Perry, Cheryl L.

2016-01-01

Introduction E-cigarettes are currently the most commonly used tobacco product among U.S. youth. However, unlike conventional cigarettes, e-cigarettes are not subject to marketing restrictions. This study investigates the association between exposure to e-cigarette marketing and susceptibility and use of e-cigarettes in youth. Methods Data were obtained from the 2014 National Youth Tobacco Survey. Participants were 22,007 U.S. middle and high school students. Multivariate logistic regression models assessed the relationship between e-cigarette marketing (internet, print, retail, TV/movies) and current and ever use as well as susceptibility to use e-cigarettes among never e-cigarette users. Results Exposure to each type of e-cigarette marketing was significantly associated with increased likelihood of ever and current use of e-cigarettes among middle and high school students. Exposure was also associated with susceptibility to use of e-cigarettes among current non-users. In multivariate models, as the number of channels of e-cigarette marketing exposure increased, the likelihood of use and susceptibility also increased. Conclusions Findings highlight the significant associations between e-cigarette marketing and e-cigarette use among youth, and the need for longitudinal research on these relationships. PMID:27080732

E5 can be expressed in anal cancer and leads to epidermal growth factor receptor-induced invasion in a human papillomavirus 16-transformed anal epithelial cell line.

PubMed

Wechsler, Erin Isaacson; Tugizov, Sharof; Herrera, Rossana; Da Costa, Maria; Palefsky, Joel M

2018-05-01

We detected the first human papillomavirus (HPV)-16-immortalized anal epithelial cell line, known as AKC2 cells to establish an in vitro model of HPV-16-induced anal carcinogenesis. Consistent with detection of E6, E7 and E5 expression in anal cancer biopsies, AKC2 cells expressed high levels of all three HPV oncogenes. Also, similar to findings in anal cancer biopsies, epidermal growth factor receptor (EGFR) was overexpressed in AKC2 cells. AKC2 cells exhibited a poorly differentiated and invasive phenotype in three-dimensional raft culture and inhibition of EGFR function abrogated AKC2 invasion. Reducing E5 expression using E5-targeted siRNAs in AKC2 cells led to knockdown of E5 expression, but also HPV-16 E2, E6 and E7 expression. AKC2 cells treated with E5-targeted siRNA had reduced levels of total and phosphorylated EGFR, and reduced invasion. Rescue of E6/E7 expression with simultaneous E5 knockdown confirmed that E5 plays a key role in EGFR overexpression and EGFR-induced invasion.

ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy.

PubMed

Shi, Yang; Yamada, Kaoru; Liddelow, Shane Antony; Smith, Scott T; Zhao, Lingzhi; Luo, Wenjie; Tsai, Richard M; Spina, Salvatore; Grinberg, Lea T; Rojas, Julio C; Gallardo, Gilbert; Wang, Kairuo; Roh, Joseph; Robinson, Grace; Finn, Mary Beth; Jiang, Hong; Sullivan, Patrick M; Baufeld, Caroline; Wood, Michael W; Sutphen, Courtney; McCue, Lena; Xiong, Chengjie; Del-Aguila, Jorge L; Morris, John C; Cruchaga, Carlos; Fagan, Anne M; Miller, Bruce L; Boxer, Adam L; Seeley, William W; Butovsky, Oleg; Barres, Ben A; Paul, Steven M; Holtzman, David M

2017-09-28

APOE4 is the strongest genetic risk factor for late-onset Alzheimer disease. ApoE4 increases brain amyloid-β pathology relative to other ApoE isoforms. However, whether APOE independently influences tau pathology, the other major proteinopathy of Alzheimer disease and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human ApoE knock-in (KI) or ApoE knockout (KO) background, here we show that P301S/E4 mice have significantly higher tau levels in the brain and a greater extent of somatodendritic tau redistribution by three months of age compared with P301S/E2, P301S/E3, and P301S/EKO mice. By nine months of age, P301S mice with different ApoE genotypes display distinct phosphorylated tau protein (p-tau) staining patterns. P301S/E4 mice develop markedly more brain atrophy and neuroinflammation than P301S/E2 and P301S/E3 mice, whereas P301S/EKO mice are largely protected from these changes. In vitro, E4-expressing microglia exhibit higher innate immune reactivity after lipopolysaccharide treatment. Co-culturing P301S tau-expressing neurons with E4-expressing mixed glia results in a significantly higher level of tumour-necrosis factor-α (TNF-α) secretion and markedly reduced neuronal viability compared with neuron/E2 and neuron/E3 co-cultures. Neurons co-cultured with EKO glia showed the greatest viability with the lowest level of secreted TNF-α. Treatment of P301S neurons with recombinant ApoE (E2, E3, E4) also leads to some neuronal damage and death compared with the absence of ApoE, with ApoE4 exacerbating the effect. In individuals with a sporadic primary tauopathy, the presence of an ε4 allele is associated with more severe regional neurodegeneration. In individuals who are positive for amyloid-β pathology with symptomatic Alzheimer disease who usually have tau pathology, ε4-carriers demonstrate greater rates of disease progression. Our results demonstrate that ApoE affects tau pathogenesis, neuroinflammation, and tau-mediated neurodegeneration independently of amyloid-β pathology. ApoE4 exerts a 'toxic' gain of function whereas the absence of ApoE is protective.

The Relationships of Expectancies With E-cigarette Use Among Hospitalized Smokers: A Prospective Longitudinal Study.

PubMed

Hendricks, Peter S; Thorne, Christopher B; Lappan, Sara N; Sweat, Noah W; Cheong, JeeWon; Ramachandran, Rekha; Kohler, Connie L; Bailey, William C; Harrington, Kathleen F

2018-01-05

Expectancies demonstrate cross-sectional associations with e-cigarette use, but the prospective relationships between expectancies and e-cigarette use are unknown. This study examined the longitudinal associations of expectancies with e-cigarette use among hospitalized tobacco cigarette smokers. E-cigarette expectancies (e-cigarette-specific Brief Smoking Consequences Questionnaire-Adult [BSCQ-A]), tobacco cigarette expectancies (tobacco-specific BSCQ-A), and number of days used e-cigarettes in the past 30 days were assessed at baseline hospitalization, 6-months post-hospitalization, and 12-months post-hospitalization among 978 hospitalized tobacco cigarette smokers. Expectancy difference scores (e-cigarette-specific expectancies minus tobacco-specific expectancies) were computed for each of the 10 BSCQ-A scales. Cross-lagged panel models tested the relationships between expectancy difference scores and number of days used e-cigarettes in the past 30 days for each of the 10 BSCQ-A scales. Though some models revealed partial associations between expectancies and e-cigarette use, only one yielded results consistent with hypotheses. Greater e-cigarette use at baseline predicted greater expectancies that e-cigarettes taste pleasant as compared to tobacco cigarettes at 6 months, which then predicted greater e-cigarette use at 12 months. To a lesser degree greater expectancies that e-cigarettes taste pleasant as compared to tobacco cigarettes at baseline predicted greater e-cigarette use at 6 months, which then predicted greater expectancies that e-cigarettes taste pleasant as compared to tobacco cigarettes at 12 months. Expectancies that e-cigarettes provide similar or more pleasant taste sensations as compared to tobacco cigarettes may be both a cause and consequence of e-cigarette use. Focusing on the taste experience may prove most effective in modifying e-cigarette use behavior. The current study offers the first longitudinal examination of expectancies and e-cigarette use. Results suggest expectancies that e-cigarettes provide similar or more pleasant taste sensations relative to tobacco cigarettes are both a cause and consequence of e-cigarette use. Efforts that focus on the e-cigarette taste experience may prove most effective in modifying e-cigarette use behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

17 CFR 402.2e - Appendix E-Temporary minimum requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Appendix E-Temporary minimum requirements. 402.2e Section 402.2e Commodity and Securities Exchanges DEPARTMENT OF THE TREASURY REGULATIONS UNDER SECTION 15C OF THE SECURITIES EXCHANGE ACT OF 1934 FINANCIAL RESPONSIBILITY § 402.2e Appendix E...

17 CFR 402.2e - Appendix E-Temporary minimum requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Appendix E-Temporary minimum requirements. 402.2e Section 402.2e Commodity and Securities Exchanges DEPARTMENT OF THE TREASURY REGULATIONS UNDER SECTION 15C OF THE SECURITIES EXCHANGE ACT OF 1934 FINANCIAL RESPONSIBILITY § 402.2e Appendix E...

17 CFR 402.2e - Appendix E-Temporary minimum requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Appendix E-Temporary minimum requirements. 402.2e Section 402.2e Commodity and Securities Exchanges DEPARTMENT OF THE TREASURY REGULATIONS UNDER SECTION 15C OF THE SECURITIES EXCHANGE ACT OF 1934 FINANCIAL RESPONSIBILITY § 402.2e Appendix E...

17 CFR 402.2e - Appendix E-Temporary minimum requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Appendix E-Temporary minimum requirements. 402.2e Section 402.2e Commodity and Securities Exchanges DEPARTMENT OF THE TREASURY REGULATIONS UNDER SECTION 15C OF THE SECURITIES EXCHANGE ACT OF 1934 FINANCIAL RESPONSIBILITY § 402.2e Appendix E...

17 CFR 402.2e - Appendix E-Temporary minimum requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Appendix E-Temporary minimum requirements. 402.2e Section 402.2e Commodity and Securities Exchanges DEPARTMENT OF THE TREASURY REGULATIONS UNDER SECTION 15C OF THE SECURITIES EXCHANGE ACT OF 1934 FINANCIAL RESPONSIBILITY § 402.2e Appendix E...

Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange

DOE PAGES

Pennington, Luke F.; Tarchevskaya, Svetlana; Brigger, Daniel; ...

2016-05-19

Omalizumab is a widely used therapeutic anti-IgE antibody. Here we report the crystal structure of the omalizumab–Fab in complex with an IgE-Fc fragment. This structure reveals the mechanism of omalizumab-mediated inhibition of IgE interactions with both high- and low-affinity IgE receptors, and explains why omalizumab selectively binds free IgE. The structure of the complex also provides mechanistic insight into a class of disruptive IgE inhibitors that accelerate the dissociation of the high-affinity IgE receptor from IgE. We use this structural data to generate a mutant IgE-Fc fragment that is resistant to omalizumab binding. Treatment with this omalizumab-resistant IgE-Fc fragment, inmore » combination with omalizumab, promotes the exchange of cell-bound full-length IgE with omalizumab-resistant IgE-Fc fragments on human basophils. Furthermore, this combination treatment also blocks basophil activation more efficiently than either agent alone, providing a novel approach to probe regulatory mechanisms underlying IgE hypersensitivity with implications for therapeutic interventions.« less

Quantification of different Eubacterium spp. in human fecal samples with species-specific 16S rRNA-targeted oligonucleotide probes.

PubMed

Schwiertz, A; Le Blay, G; Blaut, M

2000-01-01

Species-specific 16S rRNA-targeted, Cy3 (indocarbocyanine)-labeled oligonucleotide probes were designed and validated to quantify different Eubacterium species in human fecal samples. Probes were directed at Eubacterium barkeri, E. biforme, E. contortum, E. cylindroides (two probes), E. dolichum, E. hadrum, E. lentum, E. limosum, E. moniliforme, and E. ventriosum. The specificity of the probes was tested with the type strains and a range of common intestinal bacteria. With one exception, none of the probes showed cross-hybridization under stringent conditions. The species-specific probes were applied to fecal samples obtained from 12 healthy volunteers. E. biforme, E. cylindroides, E. hadrum, E. lentum, and E. ventriosum could be determined. All other Eubacterium species for which probes had been designed were under the detection limit of 10(7) cells g (dry weight) of feces(-1). The cell counts obtained are essentially in accordance with the literature data, which are based on colony counts. This shows that whole-cell in situ hybridization with species-specific probes is a valuable tool for the enumeration of Eubacterium species in feces.

Quantification of Different Eubacterium spp. in Human Fecal Samples with Species-Specific 16S rRNA-Targeted Oligonucleotide Probes

PubMed Central

Schwiertz, Andreas; Le Blay, Gwenaelle; Blaut, Michael

2000-01-01

Species-specific 16S rRNA-targeted, Cy3 (indocarbocyanine)-labeled oligonucleotide probes were designed and validated to quantify different Eubacterium species in human fecal samples. Probes were directed at Eubacterium barkeri, E. biforme, E. contortum, E. cylindroides (two probes), E. dolichum, E. hadrum, E. lentum, E. limosum, E. moniliforme, and E. ventriosum. The specificity of the probes was tested with the type strains and a range of common intestinal bacteria. With one exception, none of the probes showed cross-hybridization under stringent conditions. The species-specific probes were applied to fecal samples obtained from 12 healthy volunteers. E. biforme, E. cylindroides, E. hadrum, E. lentum, and E. ventriosum could be determined. All other Eubacterium species for which probes had been designed were under the detection limit of 107 cells g (dry weight) of feces−1. The cell counts obtained are essentially in accordance with the literature data, which are based on colony counts. This shows that whole-cell in situ hybridization with species-specific probes is a valuable tool for the enumeration of Eubacterium species in feces. PMID:10618251

Identification of RNA Aptamers that Internalize into HPV-16 E6/E7 Transformed Tonsillar Epithelial Cells

PubMed Central

Gourronc, Francoise A.; Rockey, William M.; Thiel, William H.; Giangrande, Paloma H.; Klingelhutz, Aloysius J.

2013-01-01

Human papillomavirus type 16 (HPV-16) associated oropharyngeal cancers are on a significant increase and better therapeutic strategies are needed. The HPV-16 oncogenes E6 and E7 are expressed in HPV-associated cancers and are able to transform human tonsillar epithelial cells (HTECs). We used cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to select for RNA aptamers that entered into HPV-16 E6/E7-HTECs. After 12 rounds of cell-SELEX, a pool of aptamers was obtained that had significantly greater internalization capacity (~5-fold) into E6/E7-HTECs as compared to primary HTECs or fibroblasts. Analysis of individual aptamers from the pool indicated variable internalization into E6/E7-HTECs (1 to 8-fold as compared to a negative control). Most of the individual aptamers internalized into E6/E7 and primary HTECs with similar efficiency, while one aptamer exhibited ~3-fold better internalization into E6/E7-HTECs. Aptamers that internalize into cells may be useful for delivering therapeutic agents to HPV-16 associated malignancies. PMID:24074596

Knowledge, attitudes and beliefs towards e-cigarettes among e-cigarette users and stop smoking advisors in South East England: a qualitative study.

PubMed

Tamimi, Nancy

2018-03-01

Aim To explore how e-cigarettes are perceived by a group of e-cigarette users and a group of Stop Smoking Advisors (SSAs), what are the risks and benefits they associate with e-cigarettes and how do these understandings shape participants' attitude towards e-cigarettes? Face-to-face and phone interviews were conducted with 15 e-cigarette users and 13 SSAs in South East England between 2014 and 2015. Transcribed data were analysed inductively through thematic analysis. Findings E-cigarettes were used as a therapeutic aid to stop or cut down smoking and as a smoking substitute. A prominent theme is the uncertainty e-cigarettes have generated. This included ambiguity of e-cigarettes' status and efficacy, and ambiguity of e-cigarettes' physical and social risks. Different attitudes towards e-cigarettes were identified. E-cigarettes' benefits and risks should be continuously evaluated, put into perspective and circulated to avoid ambiguity. Stop smoking services need to recognise the benefits that can be gained by using e-cigarettes as a harm reduction tool.

Solution structure analysis of the HPV16 E6 oncoprotein reveals a self-association mechanism required for E6-mediated degradation of p53

PubMed Central

Zanier, Katia; Sidi, Abdellahi ould M’hamed ould; Boulade-Ladame, Charlotte; Rybin, Vladimir; Chappelle, Anne; Atkinson, Andrew; Kieffer, Bruno; Travé, Gilles

2012-01-01

The viral oncoprotein E6 is an essential factor for cervical cancers induced by “high-risk” mucosal HPV. Among other oncogenic activities, E6 recruits the ubiquitin ligase E6AP to promote the ubiquitination and subsequent proteasomal degradation of p53. E6 is prone to self-association, which long precluded its structural analysis. Here we found that E6 specifically dimerizes through its N-terminal domain and that disruption of the dimer interface strongly increases E6 solubility. This allowed us to raise the first structural data covering the entire HPV16 E6 protein, including the high-resolution NMR structures of the two zinc-binding domains of E6 and a robust data-driven model structure of the N-terminal domain homodimer. Interestingly, homodimer interface mutations that disrupt E6 self-association also inactivate E6-mediated p53 degradation. These data suggest that E6 needs to self-associate via its N-terminal domain to promote the poly-ubiquitination of p53 by E6AP. PMID:22483108

An E-liquid Flavor Wheel: A Shared Vocabulary based on Systematically Reviewing E-liquid Flavor Classifications in Literature.

PubMed

Krüsemann, Erna Johanna Zegerina; Boesveldt, Sanne; de Graaf, Kees; Talhout, Reinskje

2018-05-18

E-liquids are available in a high variety of flavors. A systematic classification of e-liquid flavors is necessary to increase comparability of research results. In the food, alcohol and fragrance industry, flavors are classified using flavor wheels. We systematically reviewed literature on flavors related to e-cigarette use, to investigate how e-liquid flavors have been classified in research, and propose an e-liquid flavor wheel to classify e-liquids based on marketing descriptions. The search was conducted in May 2017 using PubMed and Embase databases. Keywords included terms associated with e-cigarettes, flavors, liking, learning, and wanting in articles. Results were independently screened and reviewed. Flavor categories used in the articles reviewed were extracted. Searches yielded 386 unique articles of which 28 were included. Forty-three main flavor categories were reported in these articles (e.g., tobacco, menthol, mint, fruit, bakery/dessert, alcohol, nuts, spice, candy, coffee/tea, beverages, chocolate, sweet flavors, vanilla, unflavored). Flavor classifications of e-liquids in literature showed similarities and differences across studies. Our proposed e-liquid flavor wheel contains 13 main categories and 90 subcategories, which summarize flavor categories from literature to find a shared vocabulary. For classification of e-liquids using our flavor wheel, marketing descriptions should be used. We have proposed a flavor wheel for classification of e-liquids. Further research is needed to test the flavor wheels' empirical value. Consistently classifying e-liquid flavors using our flavor wheel in research (e.g., experimental, marketing, or qualitative studies) minimizes interpretation differences and increases comparability of results. We reviewed e-liquid flavors and flavor categories used in research. A large variation in the naming of flavor categories was found and e-liquid flavors were not consistently classified. We developed an e-liquid flavor wheel and provided a guideline for systematic classification of e-liquids based on marketing descriptions. Our flavor wheel summarizes e-liquid flavors and categories used in literature in order to create a shared vocabulary. Applying our flavor wheel in research on e-liquids will improve data interpretation, increase comparability across studies, and support policy makers in developing rules for regulation of e-liquid flavors.

Increasing Total Serum IgE, Allergic Bronchopulmonary Aspergillosis, and Lung Function in Cystic Fibrosis.

PubMed

Gothe, Florian; Kappler, Matthias; Griese, Matthias

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disorder contributing to lung disease in cystic fibrosis (CF) and challenging to diagnose. This study analyzed the predictive value of increasing total IgE (t-IgE) levels in a CF cohort alongside with clinical and serologic data. A total of 387 children and young adults were followed from 2000 to 2006 and retrospectively classified into 6 groups. Patients with t-IgE levels < 95th percentile and without specific Aspergillus fumigatus (Af)-IgE were classified as "Naïve," those with Af-specific IgE (Af-sIgE) as "Sensitized." Patients with elevated t-IgE at entrance and Af-sIgE were labeled "Former ABPA," and those without, as "High t-IgE." Patients whose t-IgE values started normal and exceeded the 95th percentile during the study were labeled either "ABPA at risk" if Af-sIgE-positive or "Rising t-IgE" if not. Courses of t-IgE over time were divided into episodes with increasing IgE (ΔIgE) and related to pulmonary outcome. A total of 125 patients were classified Naïve (32%), 64 Sensitized (17%), 49 ABPA at risk (13%), 32 Rising t-IgE (8%), 102 Former ABPA (26%), and 15 High t-IgE (4%). A total of 874 ΔIgE episodes were accompanied by forced expiratory volume in 1 second (FEV 1 ) declines (r = -0.21, P < .0001). Steroid treatment of severest ΔIgE episodes resulted in improved long-term pulmonary outcomes (P < .01). This FEV 1 preservation effect was only detectable if t-IgE levels at least doubled within 3 months and exceeded the 95th age-specific percentile (P < .05). ΔIgE obtained from the course of t-IgE levels may be helpful in diagnosing treatment requiring ABPA and predicts the effect of systemic steroid treatment on pulmonary outcome. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

E6 and E7 Gene Polymorphisms in Human Papillomavirus Types-58 and 33 Identified in Southwest China

PubMed Central

Wen, Qiang; Wang, Tao; Mu, Xuemei; Chenzhang, Yuwei; Cao, Man

2017-01-01

Cancer of the cervix is associated with infection by certain types of human papillomavirus (HPV). The gene variants differ in immune responses and oncogenic potential. The E6 and E7 proteins encoded by high-risk HPV play a key role in cellular transformation. HPV-33 and HPV-58 types are highly prevalent among Chinese women. To study the gene intratypic variations, polymorphisms and positive selections of HPV-33 and HPV-58 E6/E7 in southwest China, HPV-33 (E6, E7: n = 216) and HPV-58 (E6, E7: n = 405) E6 and E7 genes were sequenced and compared to others submitted to GenBank. Phylogenetic trees were constructed by Maximum-likelihood and the Kimura 2-parameters methods by MEGA 6 (Molecular Evolutionary Genetics Analysis version 6.0). The diversity of secondary structure was analyzed by PSIPred software. The selection pressures acting on the E6/E7 genes were estimated by PAML 4.8 (Phylogenetic Analyses by Maximun Likelihood version4.8) software. The positive sites of HPV-33 and HPV-58 E6/E7 were contrasted by ClustalX 2.1. Among 216 HPV-33 E6 sequences, 8 single nucleotide mutations were observed with 6/8 non-synonymous and 2/8 synonymous mutations. The 216 HPV-33 E7 sequences showed 3 single nucleotide mutations that were non-synonymous. The 405 HPV-58 E6 sequences revealed 8 single nucleotide mutations with 4/8 non-synonymous and 4/8 synonymous mutations. Among 405 HPV-58 E7 sequences, 13 single nucleotide mutations were observed with 10/13 non-synonymous mutations and 3/13 synonymous mutations. The selective pressure analysis showed that all HPV-33 and 4/6 HPV-58 E6/E7 major non-synonymous mutations were sites of positive selection. All variations were observed in sites belonging to major histocompatibility complex and/or B-cell predicted epitopes. K93N and R145 (I/N) were observed in both HPV-33 and HPV-58 E6. PMID:28141822

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

Non-polio enteroviruses serotypes circulating in Nigeria.

PubMed

Oyero, O G; Adu, F D

2010-12-01

Enteroviruses is one of the most common group of human pathogens, causing a wide range of acute symptoms involving the cardiac and skeletal muscles, central nervous system, pancreas,skin and mucous membranes. In spite of the success recorded in polio eradication globally, infections with other enteroviruses remain frequent and sometimes very serious, requiring hospitalization. In this study we determined the various circulating serotypes of non-polio enteroviruses (NPEVs) with a view to providing information on the activity of these viruses among the Nigerian children, who usually are the most affected. Stool samples were obtained from hospitalized children at two major secondary community hospitals in Ibadan and acute flaccid paralysis (AFP) cases from 26 states ofNigeria. A presumptive identification of NPEVs was based on growth in RD cells. Isolates were identified by neutralization assay using sera obtained from the Institute for Public Health and the Environment, the Netherlands. The problems associated with this assay prompted the use of genotypic method developed at the Centers for Disease Control, Atlanta, USA for the final identification of isolates. Neutralization assay identified the 138 isolates into echoviruses (43.5%), coxsackie B viruses (29.7%) and untypeable isolates (26.8%). Finally genotyping identified echoviruses (E3, E6, E7, E11, E12, E13, E14, E19, E20, E21, E24, E29, E30, E33), coxsackieviruses (CVA3, CVA4, CVA6, CVA17, CVB3, CVB5, CVB6) and enteroviruses (EV69, EV71). The causal association of isolates with different diseases was also established. Majority of the isolates belonged to the human enterovirus gropup B (HEV-B) specie, followed by 4 and 1 in the HEV-A and HEV-C species respectively. This study forms the basis of molecular epidemiology of NPEVs being established for the first time in Nigeria. The implication of the presence of neurotropic serotypes (E3, E6, E7, E11, E14, E20, E24, E29, E30, EV71, CVB3 and CVB5) is that AFP may still be prevalent following polio eradication.

eIF4B stimulates translation of long mRNAs with structured 5′ UTRs and low closed-loop potential but weak dependence on eIF4G

PubMed Central

Sen, Neelam Dabas; Zhou, Fujun; Harris, Michael S.; Ingolia, Nicholas T.

2016-01-01

DEAD-box RNA helicases eukaryotic translation initiation factor 4A (eIF4A) and Ded1 promote translation by resolving mRNA secondary structures that impede preinitiation complex (PIC) attachment to mRNA or scanning. Eukaryotic translation initiation factor 4B (eIF4B) is a cofactor for eIF4A but also might function independently of eIF4A. Ribosome profiling of mutants lacking eIF4B or with impaired eIF4A or Ded1 activity revealed that eliminating eIF4B reduces the relative translational efficiencies of many more genes than does inactivation of eIF4A, despite comparable reductions in bulk translation, and few genes display unusually strong requirements for both factors. However, either eliminating eIF4B or inactivating eIF4A preferentially impacts mRNAs with longer, more structured 5′ untranslated regions (UTRs). These findings reveal an eIF4A-independent role for eIF4B in addition to its function as eIF4A cofactor in promoting PIC attachment or scanning on structured mRNAs. eIF4B, eIF4A, and Ded1 mutations also preferentially impair translation of longer mRNAs in a fashion mitigated by the ability to form closed-loop messenger ribonucleoprotein particles (mRNPs) via eIF4F–poly(A)-binding protein 1 (Pab1) association, suggesting cooperation between closed-loop assembly and eIF4B/helicase functions. Remarkably, depleting eukaryotic translation initiation factor 4G (eIF4G), the scaffold subunit of eukaryotic translation initiation factor 4F (eIF4F), preferentially impacts short mRNAs with strong closed-loop potential and unstructured 5′ UTRs, exactly the opposite features associated with hyperdependence on the eIF4B/helicases. We propose that short, highly efficient mRNAs preferentially depend on the stimulatory effects of eIF4G-dependent closed-loop assembly. PMID:27601676

Next-Generation NATO Reference Mobility Model (NRMM) Development (Developpement de la nouvella generation du modele de mobilite de reference de l’OTAN (NRMM))

DTIC Science & Technology

2018-01-01

Profile Database E-17 Attachment 2: NRMM Data Input Requirements E-25 Attachment 3: General Physics -Based Model Data Input Requirements E-28...E-15 Figure E-11 Examples of Unique Surface Types E-20 Figure E-12 Correlating Physical Testing with Simulation E-21 Figure E-13 Simplified Tire...Table 10-8 Scoring Values 10-19 Table 10-9 Accuracy – Physics -Based 10-20 Table 10-10 Accuracy – Validation Through Measurement 10-22 Table 10-11

Thin Film Thermoelectric Metal-Organic Framework with High Seebeck Coefficient and Low Thermal Conductivity. Supporting Information

DTIC Science & Technology

2015-04-28

François Léonard, Vitalie Stavila, Michael E. Foster, Catalin D. Spataru, Reese E. Jones, Brian M. Foley, Patrick E. Hopkins, Mark D. Allendorf, A. Alec...Léonard, Vitalie Stavila, Michael E. Foster, Catalin D. Spataru, Reese E. Jones, Brian M. Foley, Patrick E. Hopkins, Mark D. Allendorf, and A. Alec Talin...Kristopher J. Erickson, François Léonard, Vitalie Stavila, Michael E. Foster, Catalin D. Spataru, Reese E. Jones, Brian M. Foley, Patrick E. Hopkins, Mark D

Mechanism-Based Design for High-Temperature, High-Performance Composites. Book 3.

DTIC Science & Technology

1997-09-01

l(e-ß):(e-ß)--4(e:ß) 2 = el3 + -4(en-e33f, (77) 7 2 = 62:a-(e:a)2 = e?2 + 4, (78) where n = e2, ß = I-nn = eiei +e3e3, and the Cartesian...relation, the particles most susceptible to fracture are those at the larger size range of the population . Thus, with increasing standard deviation of...strength variability is associated exclusively with a single population of flaws. The second is based on comparisons of mean strengths of two or more

The Maritime Preposition Force Ship 2010

DTIC Science & Technology

1999-04-19

Lounge > k 5k r 7unkg F unkZ, r5 i gur: et36. M e E B...Showers 3 Showers 2 ater closets Lounge 2 Water closets2 urInalts 2 urinals 04 sinks 4 sInks L Bunks Bunks L L Bunks l Bunks L 0 0 0 e k I r e e ’ Bunks...SHOP 160.0 E 1 2.13305 PHOTOGRAPHIC DARK ROOM 433.2 E 1 2.13306 CREW LOUNGE E 0 2.14 GENERAL SANITARY FACILITIES 25.0 D 0 170.0 E 2.14001

Service Members in School: Military Veterans’ Experiences Using the Post-9/11 GI Bill and Pursuing Postsecondary Education

DTIC Science & Technology

2010-11-01

for Education, for the American Council on Education S E R V I C E M E M B E R S I N S C H O O L Military Veterans’ Experiences Using the Post...69 Appendix E : Focus Group Demographic Information Sheet . . . . . . . . . . . . . . 71 Appendix F: Interview Protocol for Non...Student Survey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 S E R V I C E M E M B E R S I N S C H O O L i i i C

A Study of Pediatric Emergency Room Utilization and Implications at Reynolds Army Community Hospital, Fort Sill, Oklahoma

DTIC Science & Technology

1983-05-01

in mouth ൕ/12 1728 02 +T Ś 1739 E7 Cold Ř 1745 E6 Lac. tongue ൝/12 1749 E7 Rabies shot Ř 1805 03 +T ൓/12 1829 E6 Cold ř 1839 E6 Poss. strep ...Cold,abd. pain ŕ 1310 E6 Diarrhea ř 1312 E8 +T,vomit Ś 1334 CW2 Cold,sore throat " 7/12 1342 03 +T Ŗ 1405 E4 Vcmit " 13/12 1405 E4 Vomit Ŝ/12 1418

e-Learning development in medical physics and engineering

PubMed Central

Tabakov, S

2008-01-01

Medical Physics and Engineering was among the first professions to develop and apply e-Learning (e-L). The profession provides excellent background for application of simulations and other e-L materials. The paper describes several layers for e-L development: Programming specific simulations; Building e-L modules; Development of e-L web-based programmes. The paper shows examples from these layers and outlines their specificities. At the end, the newest e-L development (project EMITEL) is briefly introduced and the necessity of a regularly updated list of e-L activities is emphasised. PMID:21614312

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

Weibel instability for a streaming electron, counterstreaming e-e, and e-p plasmas with intrinsic temperature anisotropy

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

Ghorbanalilu, M.; Physics Department, Azarbaijan Shahid Madani University, Tabriz; Sadegzadeh, S.

2014-05-15

The existence of Weibel instability for a streaming electron, counterstreaming electron-electron (e-e), and electron-positron (e-p) plasmas with intrinsic temperature anisotropy is investigated. The temperature anisotropy is included in the directions perpendicular and parallel to the streaming direction. It is shown that the beam mean speed changes the instability mode, for a streaming electron beam, from the classic Weibel to the Weibel-like mode. The analytical and numerical solutions approved that Weibel-like modes are excited for both counterstreaming e-e and e-p plasmas. The growth rates of the instabilities in e-e and e-p plasmas are compared. The growth rate is larger for e-pmore » plasmas if the thermal anisotropy is small and the opposite is true for large thermal anisotropies. The analytical and numerical solutions are in good agreement only in the small parallel temperature and wave number limits, when the instability growth rate increases linearly with normalized wave number kc∕ω{sub p}.« less

αE-catenin regulates actin dynamics independently of cadherin-mediated cell–cell adhesion

PubMed Central

Benjamin, Jacqueline M.; Kwiatkowski, Adam V.; Yang, Changsong; Korobova, Farida; Pokutta, Sabine; Svitkina, Tatyana

2010-01-01

αE-catenin binds the cell–cell adhesion complex of E-cadherin and β-catenin (β-cat) and regulates filamentous actin (F-actin) dynamics. In vitro, binding of αE-catenin to the E-cadherin–β-cat complex lowers αE-catenin affinity for F-actin, and αE-catenin alone can bind F-actin and inhibit Arp2/3 complex–mediated actin polymerization. In cells, to test whether αE-catenin regulates actin dynamics independently of the cadherin complex, the cytosolic αE-catenin pool was sequestered to mitochondria without affecting overall levels of αE-catenin or the cadherin–catenin complex. Sequestering cytosolic αE-catenin to mitochondria alters lamellipodia architecture and increases membrane dynamics and cell migration without affecting cell–cell adhesion. In contrast, sequestration of cytosolic αE-catenin to the plasma membrane reduces membrane dynamics. These results demonstrate that the cytosolic pool of αE-catenin regulates actin dynamics independently of cell–cell adhesion. PMID:20404114

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

Pennington, Luke F.; Tarchevskaya, Svetlana; Brigger, Daniel

Omalizumab is a widely used therapeutic anti-IgE antibody. Here we report the crystal structure of the omalizumab–Fab in complex with an IgE-Fc fragment. This structure reveals the mechanism of omalizumab-mediated inhibition of IgE interactions with both high- and low-affinity IgE receptors, and explains why omalizumab selectively binds free IgE. The structure of the complex also provides mechanistic insight into a class of disruptive IgE inhibitors that accelerate the dissociation of the high-affinity IgE receptor from IgE. We use this structural data to generate a mutant IgE-Fc fragment that is resistant to omalizumab binding. Treatment with this omalizumab-resistant IgE-Fc fragment, inmore » combination with omalizumab, promotes the exchange of cell-bound full-length IgE with omalizumab-resistant IgE-Fc fragments on human basophils. Furthermore, this combination treatment also blocks basophil activation more efficiently than either agent alone, providing a novel approach to probe regulatory mechanisms underlying IgE hypersensitivity with implications for therapeutic interventions.« less

A search for. nu. sub e appearance from stopped. pi. sup + and. mu. sup + decay at LAMPF (Los Alamos Meson Physics Facility)

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

Fujikawa, B.K.

We report on a recent search for {bar {nu}}{sub e} appearance from stopped {pi}{sup +} {yields} {mu}{sup +}{nu}{sub {mu}} and {mu}{sup +} {yields} e{sup +}{nu}{sub e}{bar {nu}}{sub {mu}} decay made by the LAMPF experiment E645. The appearance of {bar {nu}}{sub e} may occur from {bar {nu}}{sub {mu}} {yields} {bar {nu}}{sub e}, {nu}{sub e} {yields} {bar {nu}}{sub eL}, or {nu}{sub {mu}} {yields} {bar {nu}}{sub eL} oscillations. Appearance may also occur from rare {mu}{sup +} {yields} e{sup +}{bar {nu}}{sub e}{nu}{sub {mu}} decay, which is allowed by a multiplicative lepton charge conservation law. The neutrino energies range from E{sub {nu}} = 0 tomore » 52.8MeV. The neutrino detector, which is located 26.1 meters from the neutrino source, consists of a segmented liquid scintillator and proportional drift tube central detector surrounded by both active and passive shielding. The central detector detects {bar {nu}}{sub e} through the {bar {nu}}{sub e}p {yields} ne{sup +} Charge Current (CC) reaction, which is signaled by the direct detection of the final state positron and neutron. The hydrogen-rich liquid scintillators act as free proton targets for the {bar {nu}}{sub e}p CC reaction. The neutrons are detected through radiative neutron capture on gadolinium. We find no evidence for {bar {nu}}{sub e} appearance in the first year of running. New limits on the {bar {nu}}{sub {mu}},{nu}{sub e},{nu}{sub {mu}} {yields} {bar {nu}}{sub e} oscillation parameters and the rare {mu}{sup +} {yields} e{sup +}{bar {nu}}{sub e}{nu}{sub {mu}} decay branching ratio are presented. 87 refs., 45 figs., 17 tabs.« less

The influence of chronic stress on anxiety-like behavior and cognitive function in different human GFAP-ApoE transgenic adult male mice.

PubMed

Meng, Fan-Tao; Zhao, Jun; Fang, Hui; Liu, Ya-Jing

2015-01-01

The apolipoprotein E (ApoE) ɛ4 allele (ApoE4) is an important genetic risk factor for the pathogenesis of Alzheimer's disease (AD). In addition to genetic factors, environmental factors such as stress may play a critical role in AD pathogenesis. This study was designed to investigate the anxiety-like behavioral and cognitive changes in different human glial fibrillary acidic protein (GFAP)-ApoE transgenic adult male mice under chronic stress conditions. On the open field test, anxiety-like behavior was increased in the non-stressed GFAP-ApoE4 transgenic mice relative to the corresponding GFAP-ApoE3 (ApoE ɛ3 allele) mice. Anxiety-like behavior was increased in the stressed GFAP-ApoE3 mice relative to non-stressed GFAP-ApoE3 mice, but was unexpectedly decreased in the stressed GFAP-ApoE4 mice relative to non-stressed GFAP-ApoE4 mice. On the novel object recognition task, both GFAP-ApoE4 and GFAP-ApoE3 mice exhibited long-term non-spatial memory impairment after chronic stress. Interestingly, short-term non-spatial memory impairment (based on the novel object recognition task) was observed only in the stressed GFAP-ApoE4 male mice relative to non-stressed GFAP-ApoE4 transgenic mice. In addition, short-term spatial memory impairment was observed in the stressed GFAP-ApoE3 transgenic male mice relative to non-stressed GFAP-ApoE3 transgenic male mice; however, short-term spatial memory performance of GFAP-ApoE4 transgenic male mice was not reduced compared to non-stressed control mice based on the Y-maze task. In conclusion, our findings suggested that chronic stress affects anxiety-like behavior and spatial and non-spatial memory in GFAP-ApoE transgenic mice in an ApoE isoform-dependent manner.

Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53

PubMed Central

Martinez-Zapien, Denise; Ruiz, Francesc Xavier; Poirson, Juline; Mitschler, André; Ramirez-Ramos, Juan; Forster, Anne; Cousido-Siah, Alexandra; Masson, Murielle; Pol, Scott Vande; Podjarny, Alberto; Travé, Gilles; Zanier, Katia

2015-01-01

Summary The p53 pro-apoptotic tumor suppressor is mutated or functionally altered in most cancers. In epithelial tumors induced by “high-risk” mucosal Human Papillomaviruses (hrm-HPVs), including human cervical carcinoma and a growing number of head-and-neck cancers 1, p53 is degraded by the viral oncoprotein E6 2. In this process, E6 binds to a short LxxLL consensus sequence within the cellular ubiquitin ligase E6AP 3. Subsequently, the E6/E6AP heterodimer recruits and degrades p53 4. Neither E6 nor E6AP are separately able to recruit p53 3,5, and the precise mode of assembly of E6, E6AP and p53 is unknown. Here, we solved the crystal structure of a ternary complex comprising full-length HPV16 E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumor suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against HPV-mediated oncogenesis. PMID:26789255

Lopinavir Impairs Protein Synthesis and Induces eEF2 Phosphorylation via the Activation of AMP-Activated Protein Kinase

PubMed Central

Hong-Brown, Ly Q.; Brown, C. Randell; Huber, Danuta S.; Lang, Charles H.

2008-01-01

HIV anti-retroviral drugs decrease protein synthesis, although the underlying regulatory mechanisms of this process are not fully established. Therefore, we investigated the effects of the HIV protease inhibitor lopinavir (LPV) on protein metabolism. We also characterized the mechanisms that mediate the effects of this drug on elongation factor-2 (eEF2), a key component of the translational machinery. Treatment of C2C12 myocytes with LPV produced a dose-dependent inhibitory effect on protein synthesis. This effect was observed at 15 min and was maintained for at least 4 h. Mechanistically, LPV increased the phosphorylation of eEF2 and thereby decreased the activity of this protein. Increased phosphorylation of eEF2 was associated with increased activity of its upstream regulators AMP-activated protein kinase (AMPK) and eEF2 kinase (eEF2K). Both AMPK and eEF2K directly phosphorylated eEF2 in an in vitro kinase assay suggesting two distinct paths lead to eEF2 phosphorylation. To verify this connection, myocytes were treated with the AMPK inhibitor compound C. Compound C blocked eEF2K and eEF2 phosphorylation, demonstrating that LPV affects eEF2 activity via an AMPK-eEF2K dependent pathway. In contrast, incubation of myocytes with rottlerin suppressed eEF2K, but not eEF2 phosphorylation, suggesting that eEF2 can be regulated independent of eEF2K. Finally, LPV did not affect PP2A activity when either eEF2 or peptide was used as the substrate. Collectively, these results indicate that LPV decreases protein synthesis, at least in part, via inhibition of eEF2. This appears regulated by AMPK which can act directly on eEF2 or indirectly via the action of eEF2K. PMID:18712774

Molecular and Kinetic Properties of Two Acetylcholinesterases from the Western Honey Bee, Apis mellifera

PubMed Central

Kim, Young Ho; Cha, Deok Jea; Jung, Je Won; Kwon, Hyung Wook; Lee, Si Hyeock

2012-01-01

We investigated the molecular and kinetic properties of two acetylcholinesterases (AmAChE1 and AmAChE2) from the Western honey bee, Apis mellifera. Western blot analysis revealed that AmAChE2 has most of catalytic activity rather than AmAChE1, further suggesting that AmAChE2 is responsible for synaptic transmission in A. mellifera, in contrast to most other insects. AmAChE2 was predominately expressed in the ganglia and head containing the central nervous system (CNS), while AmAChE1 was abundantly observed not only in the CNS but also in the peripheral nervous system/non-neuronal tissues. Both AmAChEs exist as homodimers; the monomers are covalently connected via a disulfide bond under native conditions. However, AmAChE2 was associated with the cell membrane via the glycophosphatidylinositol anchor, while AmAChE1 was present as a soluble form. The two AmAChEs were functionally expressed with a baculovirus system. Kinetic analysis revealed that AmAChE2 has approximately 2,500-fold greater catalytic efficiency toward acetylthiocholine and butyrylthiocholine than AmAChE1, supporting the synaptic function of AmAChE2. In addition, AmAChE2 likely serves as the main target of the organophosphate (OP) and carbamate (CB) insecticides as judged by the lower IC50 values against AmAChE2 than against AmAChE1. When OP and CB insecticides were pre-incubated with a mixture of AmAChE1 and AmAChE2, a significant reduction in the inhibition of AmAChE2 was observed, suggesting a protective role of AmAChE1 against xenobiotics. Taken together, based on their tissue distribution pattern, molecular and kinetic properties, AmAChE2 plays a major role in synaptic transmission, while AmAChE1 has non-neuronal functions, including chemical defense. PMID:23144990

40 CFR 799.5087 - Chemical testing requirements for second group of high production volume chemicals (HPV2).

Code of Federal Regulations, 2011 CFR

2011-07-01

...: ASTM E 729-96 (Reapproved 2007) 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97 (Reapproved 2004) 2. Toxicity to Plants (Algae): ASTM E 1218... Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97...

40 CFR 799.5087 - Chemical testing requirements for second group of high production volume chemicals (HPV2).

Code of Federal Regulations, 2013 CFR

2013-07-01

...: ASTM E 729-96 (Reapproved 2007) 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97 (Reapproved 2004) 2. Toxicity to Plants (Algae): ASTM E 1218... Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97...

40 CFR 799.5087 - Chemical testing requirements for second group of high production volume chemicals (HPV2).

Code of Federal Regulations, 2012 CFR

2012-07-01

...: ASTM E 729-96 (Reapproved 2007) 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97 (Reapproved 2004) 2. Toxicity to Plants (Algae): ASTM E 1218... Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97...

40 CFR 799.5087 - Chemical testing requirements for second group of high production volume chemicals (HPV2).

Code of Federal Regulations, 2014 CFR

2014-07-01

...: ASTM E 729-96 (Reapproved 2007) 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97 (Reapproved 2004) 2. Toxicity to Plants (Algae): ASTM E 1218... Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97...

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

Hawkins, C.A.

Tests of QED to order ..cap alpha../sup 4/ performed with the ASP detector at PEP are presented. Measurements have been made of exclusive e/sup +/e/sup -/e/sup +/e/sup -/, e/sup +/e/sup -/..gamma gamma.. and ..gamma gamma gamma gamma.. final states with all particles above 50 milliradians with respect to the e/sup +/e/sup -/ beam line. These measurements represent a significant increase in statistics over previous measurements. All measurements agree well with theoretical predictions. 5 refs., 1 tab.

China’s Growing Military Power: Perpectives on Security, Ballistic Missiles, and Conventional Capabilities

DTIC Science & Technology

2002-09-01

Rice recently com pared th e present s y stem of agreem ents to th e geocentric concept of th e univ erse; th e future s y s tem of th e w orld to...neces sary . Norm ally , th e reserv e com m and post is staffed by th e w ar zone deputy logistics com m ander, oth er required staff officers

Authorized and Operating Purposes of Corps of Engineers Reservoirs

DTIC Science & Technology

1992-07-01

Puerto Rico CERRILLOS DAM AND RESERVOIR Jacksonville E-9O PORTUGUES DAM AND RESERVOIR Jacksonville E-92 South Carolina HARTWELL DAM AND LAKE Savannah E...LAKE Missouri Kansas City E-12 POMONA LAKE Kansas Kansas City E-12 PORTUGUES DAM AND RESERVOIR Puerto Rico Jacksonville E-92 PRADO DAM (SANTA ANA...PROJECT Florida Jacksonville E-92 PORTUGUES DAM AND RESERVOIR Puerto Rico Jacksonville E-92 RODMAN LOCK AND DAM (CROSS FLORIDA BARGE CANAL Florida

Forty-five Years of e{sup +}e{sup -} Annihilation Physics: 1956 to 2001

DOE R&D Accomplishments Database

Richter, B.

1984-08-01

The history of e{sup +}e{sup -} physics in the 1950's and 1960's is reviewed, followed by some highlights of the spectacular discoveries in e{sup +}e{sup -} annihilation made during the 1970's. The consolidation of knowledge during the last few years is summarized. Some predictions are made for the field of e{sup +}e{sup -} physics for the next decade and beyond. (LEW)

Entoloma subgenus Leptonia in boreal-temperate Eurasia: towards a phylogenetic species concept.

PubMed

Morozova, O V; Noordeloos, M E; Vila, J

2014-06-01

This study reveals the concordance, or lack thereof, between morphological and phylogenetic species concepts within Entoloma subg. Leptonia in boreal-temperate Eurasia, combining a critical morphological examination with a multigene phylogeny based on nrITS, nrLSU and mtSSU sequences. A total of 16 taxa was investigated. Emended concepts of subg. Leptonia and sect. Leptonia as well as the new sect. Dichroi are presented. Two species (Entoloma percoelestinum and E. sublaevisporum) and one variety (E. tjallingiorum var. laricinum) are described as new to science. On the basis of the morphological and phylogenetical evidence E. alnetorum is reduced to a variety of E. tjallingiorum, and E. venustum is considered a variety of E. callichroum. Accordingly, the new combinations E. tjallingiorum var. alnetorum and E. callichroum var. venustum are proposed. Entoloma lepidissimum var. pauciangulatum is now treated as a synonym of E. chytrophilum. Neotypes for E. dichroum, E. euchroum and E. lampropus are designated.

Sporulation dynamics of poultry Eimeria oocysts in Chennai.

PubMed

Venkateswara Rao, P; Raman, M; Gomathinayagam, S

2015-12-01

The infective form of Eimeria is the highly resistant oocyst, which is shed in the faeces of infected animals. Present study was carried out to understand the sporulation dynamics of six Eimeria oocysts viz. E. acervulina, E. brunetti, E. maxima, E. mitis, E. necatrix and E. tenella in Chennai. Faecal samples of poultry were collected from various poultry farms located in and around Tamil Nadu. Oocysts of various Eimeria species were examined microscopically for sporulation on a 6 h interval basis till complete sporulation is acheived. The sporulation time recorded was 168, 120, 216, 192, 96 and 96 h for E. acervulina, E. brunetti, E. maxima, E. mitis, E. necatrix and E. tenella respectively. It can be concluded on comparison with previous studies that humid weather conditions delay the sporulation time and dry weather and wet litter is the ideal condition for rapid sporulation.

Numerical Analysis of Turbulent Separated Subsonic Diffuser Flows

DTIC Science & Technology

1977-02-01

the s u b l a y e r r eg ion when one a t t e m p t s to use a un i fo rm coord ina te s y s t e m to d e s c r i b e the p r o - f i l es ...s u m e d p ro f i l e in the v ic in i ty of s e p a r a t i o n is ques t ionable . C l e a r l y , an adequate solut ion r e q u i r e s...in an 8-dell conical diffuser. 7.15 m O ,o H l 01 O1 (O AEDC-TR-76-159 1 .0 u~ O k O 4~ eS r-4 a ~4 el 0 . 8 0 . 6 0 . 4

Limits on a light Higgs boson in e+e- collisions at LEP

NASA Astrophysics Data System (ADS)

Akrawy, M. Z.; Alexander, G.; Allison, J.; Allport, P. P.; Anderson, K. J.; Armitage, J. C.; Arnison, G. T. J.; Ashton, P.; Azuelos, G.; Baines, J. T. M.; Ball, A. H.; Banks, J.; Barker, G. J.; Barlow, R. J.; Batley, J. R.; Beck, A.; Becker, J.; Behnke, T.; Bell, K. W.; Bella, G.; Bethke, S.; Biebel, O.; Binder, U.; Bloodworth, I. J.; Bock, P.; Breuker, H.; Brown, R. M.; Brun, R.; Buijs, A.; Burckhart, H. J.; Capiluppi, P.; Carnegie, R. K.; Carter, A. A.; Carter, J. R.; Chang, C. Y.; Charlton, D. G.; Chrin, J. T. M.; Clarke, P. E. L.; Cohen, I.; Collins, W. J.; Conboy, J. E.; Couch, M.; Coupland, M.; Cuffiani, M.; Dado, S.; Dallavalle, G. M.; Debu, P.; Deninno, M. M.; Dieckmann, A.; Dittmar, M.; Dixit, M. S.; Duchovni, E.; Duerdoth, I. P.; Dumas, D.; Mamouni, H. El; Elcombe, P. A.; Estabrooks, P. G.; Etzion, E.; Fabbri, F.; Farthouat, P.; Fischer, H. M.; Fong, D. G.; French, M. T.; Fukunaga, C.; Gaidot, A.; Ganel, O.; Gary, J. W.; Gascon, J.; Geddes, N. I.; Gee, C. N. P.; Geich-Gimbel, C.; Gensler, S. W.; Gentit, F. X.; Giacomelli, G.; Gibson, V.; Gibson, W. R.; Gillies, J. D.; Goldberg, J.; Goodrick, M. J.; Gorn, W.; Granite, D.; Gross, E.; Grunhaus, J.; Hagedorn, H.; Hagemann, J.; Hansroul, M.; Hargrove, C. K.; Harris, I.; Hart, J.; Hattersley, P. M.; Hauschild, M.; Hawkes, C. M.; Heflin, E.; Hemingway, R. J.; Heuer, R. D.; Hill, J. C.; Hillier, S. J.; Ho, C.; Hobbs, J. D.; Hobson, P. R.; Hochman, D.; Holl, B.; Homer, R. J.; Hou, S. R.; Howarth, C. P.; Hughes-Jones, R. E.; Humbert, R.; Igo-Kemenes, P.; Ihssen, H.; Imrie, D. C.; Janissen, J.; Jawahery, A.; Jeffreys, P. W.; Jeremie, H.; Jimack, M.; Jobes, M.; Jones, R. W. L.; Jovanovic, P.; Karlen, D.; Kawagoe, K.; Kawamoto, T.; Kellogg, R. G.; Kennedy, B. W.; Kleinwort, C.; Klem, D. E.; Knop, G.; Kobayashi, T.; Kokott, T. P.; Köpke, L.; Kowalewski, R.; Kreutzmann, H.; Kroll, J.; Kuwano, M.; Kyberd, P.; Lafferty, G. D.; Lamarche, F.; Larson, W. J.; Layter, J. G.; Du, P. Le; Leblanc, P.; Lee, A. M.; Lehto, M. H.; Lellouch, D.; Lennert, P.; Lessard, L.; Levinson, L.; Llyod, S. L.; Loebinger, F. K.; Lorah, J. M.; Lorazo, B.; Losty, M. J.; Ludwig, J.; Ma, J.; MacBeth, A. A.; Mannelli, M.; Marcellini, S.; Maringer, G.; Martin, A. J.; Martin, J. P.; Mashimo, T.; Mättig, P.; Maur, U.; McMahon, T. J.; McNutt, J. R.; Meijers, F.; Menszner, D.; Merritt, F. S.; Mes, H.; Michelini, A.; Middleton, R. P.; Mikenberg, G.; Mildenberger, J.; Miller, D. J.; Milstene, C.; Minowa, M.; Mohr, W.; Montanari, A.; Mori, T.; Moss, M. W.; Murphy, P. G.; Murray, W. J.; Nellen, B.; Nguyen, H. H.; Nozaki, M.; O'Dowd, A. J. P.; O'Neale, S. W.; O'Neill, B. P.; Oakham, F. G.; Odorici, F.; Ogg, M.; Oh, H.; Oreglia, M. J.; Orito, S.; Pansart, J. P.; Patrick, G. N.; Pawley, S. J.; Pfister, P.; Pilcher, J. E.; Pinfold, J. L.; Plane, D. E.; Poli, B.; Pouladdej, A.; Prebys, E.; Pritchard, T. W.; Quast, G.; Raab, J.; Redmond, M. W.; Rees, D. L.; Regimbald, M.; Riles, K.; Roach, C. M.; Robins, S. A.; Rollnik, A.; Roney, J. M.; Rossberg, S.; Rossi, A. M.; Routenburg, P.; Runge, K.; Runolfsson, O.; Sanghera, S.; Sansum, R. A.; Sasaki, M.; Saunders, B. J.; Schaile, A. D.; Schaile, O.; Schappert, W.; Scharff-Hansen, P.; Schreiber, S.; Schwarz, J.; Shapira, A.; Shen, B. C.; Sherwood, P.; Simon, A.; Siroli, G. P.; Skuja, A.; Smith, A. M.; Smith, T. J.; Snow, G. A.; Springer, R. W.; Sproston, M.; Stephens, K.; Stier, H. E.; Ströhmer, R.; Strom, D.; Takeda, H.; Takeshita, T.; Thackray, N. J.; Tsukamoto, T.; Turner, M. F.; Tysarczyk-Niemeyer, G.; van den Plas, D.; Vandalen, G. J.; Vasseur, G.; Virtue, C. J.; von der Schmitt, H.; von Krogh, J.; Wagner, A.; Wahl, C.; Walker, J. P.; Ward, C. P.; Ward, D. R.; Watkins, P. M.; Watson, A. T.; Watson, N. K.; Weber, M.; Weisz, S.; Wells, P. S.; Wermes, N.; Weymann, M.; Wilson, G. W.; Wilson, J. A.; Wingerter, I.; Winterer, V.-H.; Wood, N. C.; Wotton, S.; Wuensch, B.; Wyatt, T. R.; Yaari, R.; Yang, Y.; Yekutieli, G.; Yoshida, T.; Zeuner, W.; Zorn, G. T.

1990-11-01

Data from e+e- collisions collected with the OPAL detector at LEP have been used to exclude a standard model Higgs boson (H0) with mass below 2mμ. The analysis used 1.2 pb-1 of data taken at centre-of-mass energies between 88.3 and 95.0 GeV to search for the reactions e+e--->Z0H0, (Z0-->e+e- or μ+μ-, H0-->undetected), e+e--->Z0H0, (Z0-->νν, H0-->e+e- or γγ). The existence of a minimal standard model H0 with mass in the range 0<=mH<=2mμ is excluded at the 95% confidence level. The limit is also valid for standard model extensions with a large branching ratio for the decay of H0 to γγ.

Models of Distribution Computation: Behavior Characterization of Intelligent Problem Solving for an Agent Hierarchy in a Competitive (Web) Environment

DTIC Science & Technology

2002-10-04

N^] A U K�C g N hNBDC A U WA �AWL`HjBEHG�C g N E$jW�]E$] L j`1COA E UR tLCy`1COA E U AB;]N^M_GE$M k NW N^A C g N^ Mih �`Hj CON^MOA...y E$ Mih �MON^] j`$XA U KtB_E k N�A U WA �AWL`HjB w\\A C g My` U WE k N^j N k N U CyBiEHG...1COA E U hNXE k NB C g NiE$jW’]E$] L j`1COA E UR e"g N62 C U NBOBEHG"` U A U WA �AWL`Hj x X^` U N^A C g N^ Mih N�WNCON^M k A U NW�h

Novel insights into the architecture and protein interaction network of yeast eIF3.

PubMed

Khoshnevis, Sohail; Hauer, Florian; Milón, Pohl; Stark, Holger; Ficner, Ralf

2012-12-01

Translation initiation in eukaryotes is a multistep process requiring the orchestrated interaction of several eukaryotic initiation factors (eIFs). The largest of these factors, eIF3, forms the scaffold for other initiation factors, promoting their binding to the 40S ribosomal subunit. Biochemical and structural studies on eIF3 need highly pure eIF3. However, natively purified eIF3 comprise complexes containing other proteins such as eIF5. Therefore we have established in vitro reconstitution protocols for Saccharomyces cerevisiae eIF3 using its five recombinantly expressed and purified subunits. This reconstituted eIF3 complex (eIF3(rec)) exhibits the same size and activity as the natively purified eIF3 (eIF3(nat)). The homogeneity and stoichiometry of eIF3(rec) and eIF3(nat) were confirmed by analytical size exclusion chromatography, mass spectrometry, and multi-angle light scattering, demonstrating the presence of one copy of each subunit in the eIF3 complex. The reconstituted and native eIF3 complexes were compared by single-particle electron microscopy showing a high degree of structural conservation. The interaction network between eIF3 proteins was studied by means of limited proteolysis, analytical size exclusion chromatography, in vitro binding assays, and isothermal titration calorimetry, unveiling distinct protein domains and subcomplexes that are critical for the integrity of the protein network in yeast eIF3. Taken together, the data presented here provide a novel procedure to obtain highly pure yeast eIF3, suitable for biochemical and structural analysis, in addition to a detailed picture of the network of protein interactions within this complex.

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

Duplex unwinding and ATPase activities of the DEAD-box helicase eIF4A are coupled by eIF4G and eIF4B

PubMed Central

Özeş, Ali R.; Feoktistova, Kateryna; Avanzino, Brian C.; Fraser, Christopher S.

2011-01-01

Eukaryotic initiation factor 4A (eIF4A) is a DEAD-box helicase that stimulates translation initiation by unwinding mRNA secondary structure. The accessory proteins, eIF4G, eIF4B, and eIF4H enhance the duplex unwinding activity of eIF4A, but the extent to which they modulate eIF4A activity is poorly understood. Here, we use real time fluorescence assays to determine the kinetic parameters of duplex unwinding and ATP hydrolysis by these initiation factors. To ensure efficient duplex unwinding, eIF4B and eIF4G cooperatively activate the duplex unwinding activity of eIF4A. Our data reveal that eIF4H is much less efficient at stimulating eIF4A unwinding activity than eIF4B, implying that eIF4H is not able to completely substitute for eIF4B in duplex unwinding. By monitoring unwinding and ATPase assays using identical conditions, we demonstrate that eIF4B couples the ATP hydrolysis cycle of eIF4A with strand separation, thereby minimizing non-productive unwinding events. Using duplex substrates with altered GC contents, but with similar predicted thermal stabilities, we further show that the rate of formation of productive unwinding complexes is strongly influenced by the local stability per base pair in addition to the stability of the entire duplex. This finding explains how a change in the GC content of a hairpin while maintaining overall predicted thermal stability is able to influence translation initiation. PMID:21840318

Disruption of the G1/S Transition in Human Papillomavirus Type 16 E7-Expressing Human Cells Is Associated with Altered Regulation of Cyclin E

PubMed Central

Martin, Larry G.; Demers, G. William; Galloway, Denise A.

1998-01-01

The development of neoplasia frequently involves inactivation of the p53 and retinoblastoma (Rb) tumor suppressor pathways and disruption of cell cycle checkpoints that monitor the integrity of replication and cell division. The human papillomavirus type 16 (HPV-16) oncoproteins, E6 and E7, have been shown to bind p53 and Rb, respectively. To further delineate the mechanisms by which E6 and E7 affect cell cycle control, we examined various aspects of the cell cycle machinery. The low-risk HPV-6 E6 and E7 proteins did not cause any significant change in the levels of cell cycle proteins analyzed. HPV-16 E6 resulted in very low levels of p53 and p21 and globally elevated cyclin-dependent kinase (CDK) activity. In contrast, HPV-16 E7 had a profound effect on several aspects of the cell cycle machinery. A number of cyclins and CDKs were elevated, and despite the elevation of the levels of at least two CDK inhibitors, p21 and p16, CDK activity was globally increased. Most strikingly, cyclin E expression was deregulated both transcriptionally and posttranscriptionally and persisted at high levels in S and G2/M. Transit through G1 was shortened by the premature activation of cyclin E-associated kinase activity. Elevation of cyclin E levels required both the CR1 and CR2 domains of E7. These data suggest that cyclin E may be a critical target of HPV-16 E7 in the disruption of G1/S cell cycle progression and that the ability of E7 to regulate cyclin E involves activities in addition to the release of E2F. PMID:9444990

Serum apolipoprotein E concentration and polymorphism influence serum lipid levels in Chinese Shandong Han population.

PubMed

Han, ShuYi; Xu, YiHui; Gao, MeiHua; Wang, YunShan; Wang, Jun; Liu, YanYan; Wang, Min; Zhang, XiaoQian

2016-12-01

Apolipoprotein E (ApoE), which has been shown to influence serum lipid parameters, can bind to multiple types of lipids and plays an important role in the metabolism and homeostasis of lipids and lipoproteins. A previous study showed that ApoE concentration significantly affects serum lipid levels independently of ApoE polymorphism. The serum lipid levels were also closely correlated with dietary habits, and Shandong cuisine is famous for its high salt and oil contents, which widely differ among the different areas in China. Therefore, studying the effect of ApoE polymorphism on ApoE concentration and serum lipid levels in Shandong province is very important.A total of 815 subjects including 285 men and 530 women were randomly selected and studied from Jinan, Shandong province. In order to evaluate the association of ApoE polymorphism and serum level on lipid profiles, the ApoE genotypes, as well as levels of fasting serum ApoE and other lipid parameters, were detected in all subjects.The frequency of the ApoE E3 allele was highest (83.1%), while those of E2 and E4 were 9.4% and 7.5%, respectively, which are similar to those in other Asian populations. ApoE2 allele carriers showed significantly increased ApoE levels but lower levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and Apolipoprotein B (ApoB).We found that ApoE level is influenced by ApoE polymorphism in a gene-dependent manner. The ApoE polymorphism showed different influences on serum lipid parameters with increasing age and body mass index (BMI) in our Shandong Han population.

Serum apolipoprotein E concentration and polymorphism influence serum lipid levels in Chinese Shandong Han population

PubMed Central

Han, ShuYi; Xu, YiHui; Gao, MeiHua; Wang, YunShan; Wang, Jun; Liu, YanYan; Wang, Min; Zhang, XiaoQian

2016-01-01

Abstract Apolipoprotein E (ApoE), which has been shown to influence serum lipid parameters, can bind to multiple types of lipids and plays an important role in the metabolism and homeostasis of lipids and lipoproteins. A previous study showed that ApoE concentration significantly affects serum lipid levels independently of ApoE polymorphism. The serum lipid levels were also closely correlated with dietary habits, and Shandong cuisine is famous for its high salt and oil contents, which widely differ among the different areas in China. Therefore, studying the effect of ApoE polymorphism on ApoE concentration and serum lipid levels in Shandong province is very important. A total of 815 subjects including 285 men and 530 women were randomly selected and studied from Jinan, Shandong province. In order to evaluate the association of ApoE polymorphism and serum level on lipid profiles, the ApoE genotypes, as well as levels of fasting serum ApoE and other lipid parameters, were detected in all subjects. The frequency of the ApoE E3 allele was highest (83.1%), while those of E2 and E4 were 9.4% and 7.5%, respectively, which are similar to those in other Asian populations. ApoE2 allele carriers showed significantly increased ApoE levels but lower levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and Apolipoprotein B (ApoB). We found that ApoE level is influenced by ApoE polymorphism in a gene-dependent manner. The ApoE polymorphism showed different influences on serum lipid parameters with increasing age and body mass index (BMI) in our Shandong Han population. PMID:27977609

Effect of Optical Defocus on the Kinetic Perimetry in Young Myopic Participants.

PubMed

Hirasawa, Kazunori; Shoji, Nobuyuki

2015-01-01

The prospective study evaluated the effects of optical defocus on kinetic sensitivity using automated kinetic perimetry. The 17 eyes of 17 healthy young participants were evaluated. All of the participants had myopia (≥ -5.00 D) and mild to no astigmatism (<1.00 D). Automated kinetic perimetry was performed using the Octopus 900 perimeter with Goldmann stimuli III4e, I4e, I3e, I2e, and I1e, with stimuli presented at 14 predetermined meridians, and a velocity of 3°/s. Optical defocus was induced with soft contact lenses, and varied in 1 D increments between 0 and +7 D. Kinetic sensitivity at each defocus was evaluated and compared to sensitivity with no defocus. Although kinetic sensitivity with the III4e and I4e stimuli decreased slightly at the inferior nasal, total kinetic sensitivity measured with the III4e and I4e stimuli was unaffected by optical defocus. Conversely, kinetic sensitivity measured with the I3e, I2e, and I1e stimuli decreased at defocus greater than +6 D (p < 0.05), + 3 D (p < 0.01), and at a defocus greater than +1 D (p < 0.01), respectively. Kinetic sensitivity was unaffected by defocus when measured with III4e and I4e stimuli. However, measurements with I3e, I2e, and I1e stimuli were affected, in particular measurements with I2e and I1e stimuli. Therefore, we conclude that optimal refractive correction with a contact lens or a spectacle lens is required in order to obtain accurate kinetic perimetry results, particularly for lower intensity stimuli.

Media communication strategies for climate-friendly lifestyles - Addressing middle and lower class consumers for social-cultural change via Entertainment-Education

NASA Astrophysics Data System (ADS)

Lubjuhn, S.; Pratt, N.

2009-11-01

This paper argues that Entertainment-Education (E-E) is a striking communication strategy for reaching middle and lower socio-economic classes with climate-friendly lifestyle messages. On the international level (e.g. in the US and the Netherlands) E-E approaches are being theoretically grounded, whereas in Germany they are not yet. Therefore further theoretical discussion and mapping of E-E approaches is central for future research. As a first step towards providing further theoretical foundations for E-E in the field of sustainability, the authors suggest a threefold mapping of E-E approaches. The threefold mapping of E-E approaches for communicating climate-friendly lifestyles to middle and lower class consumers is based on recent results from academic research and practical developments on the media market. The commonalities among the three is that they all promote pro-sustainability messages in an affective-orientated rather than cognitive-orientated, factual manner. Differences can be found in: the sender of the sustainability message, the targeted consumer groups and the media approach in use. Based on this, the paper draws the conclusion that two new paths for further research activities in the field of Entertainment-Education can be proposed: (1) Improving the existing approaches in practice by using theoretical foundation from the E-E field. This comprises at its core (A) to do formative, process and summative effect research on the messages and (B) to use E-E theory from the field of social psychology, sociology and communication science for further improvement and (2) Generating new E-E theories by analyzing the existing practical approaches in the media to communicate climate change.

Upregulation of endothelial nitric oxide synthase (eNOS) and its upstream regulators in Opisthorchis viverrini associated cholangiocarcinoma and its clinical significance.

PubMed

Suksawat, Manida; Techasen, Anchalee; Namwat, Nisana; Yongvanit, Puangrat; Khuntikeo, Narong; Titapun, Attapon; Koonmee, Supinda; Loilome, Watcharin

2017-08-01

Endothelial nitric oxide synthase (eNOS) is an isoform of the enzyme nitric oxide synthase (NOS) which is constitutively expressed in endothelial cells and plays important roles in vasodilation. We previously reported the importance of eNOS activation in cholangiocarcinoma (CCA) tissues and cell lines. The present study aims to investigate the relative abundance of eNOS and phosphorylated eNOS (P-eNOS) and their upstream regulators VEGFR3, VEGFC, EphA3 and ephrin-A1, in the Opisthorchis viverrini (Ov)/N-nitrosodimethylamine (NDMA)-induced hamster CCA model and in human CCA by semiquantitative immunohistochemical analysis of the relevant tissues. Results from the hamster model suggested an increase in eNOS and P-eNOS and upstream regulators during CCA genesis. In human CCA, high immunohistochemical staining intensity of all investigated proteins was associated with the presence of metastasis. A pairwise analysis of the staining data for eNOS and its upstream regulators showed that a concurrent increase in eNOS/VEGFR3, eNOS/ephrin-A1, eNOS/VEGFC and eNOS/EphA3 was significantly associated with metastasis. An increase in eNOS/VEGFR3, eNOS/ephrin-A1 was also associated with non-papillary type CCA. Additionally, an increase in eNOS and P-eNOS was significantly correlated with a high micro-vessel level (P=0.04). Our results indicate that the development of CCA involves upregulation of eNOS and P-eNOS and their regulators. This may drive angiogenesis and metastasis in CCA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Naturally Occurring Genetic Variants of Human Acetylcholinesterase and Butyrylcholinesterase and Their Potential Impact on the Risk of Toxicity from Cholinesterase Inhibitors

PubMed Central

2016-01-01

Acetylcholinesterase (AChE) is the physiologically important target for organophosphorus toxicants (OP) including nerve agents and pesticides. Butyrylcholinesterase (BChE) in blood serves as a bioscavenger that protects AChE in nerve synapses from inhibition by OP. Mass spectrometry methods can detect exposure to OP by measuring adducts on the active site serine of plasma BChE. Genetic variants of human AChE and BChE do exist, but loss of function mutations have been identified only in the BCHE gene. The most common AChE variant, His353Asn (H322N), also known as the Yt blood group antigen, has normal AChE activity. The most common BChE variant, Ala567Thr (A539T) or the K-variant in honor of Werner Kalow, has 33% reduced plasma BChE activity. The genetic variant most frequently associated with prolonged response to muscle relaxants, Asp98Gly (D70G) or atypical BChE, has reduced activity and reduced enzyme concentration. Early studies in young, healthy males, performed at a time when it was legal to test nerve agents in humans, showed that individuals responded differently to the same low dose of sarin with toxic symptoms ranging in severity from minimal to moderate. Additionally, animal studies indicated that BChE protects from toxicants that have a higher reactivity with AChE than with BChE (e.g., nerve agents) but not from toxicants that have a higher reactivity with BChE than with AChE (e.g., OP pesticides). As a corollary, we hypothesize that individuals with genetic variants of BChE may be at increased risk of toxicity from nerve agents but not from OP pesticides. PMID:27551784

Naturally Occurring Genetic Variants of Human Acetylcholinesterase and Butyrylcholinesterase and Their Potential Impact on the Risk of Toxicity from Cholinesterase Inhibitors.

PubMed

Lockridge, Oksana; Norgren, Robert B; Johnson, Rudolph C; Blake, Thomas A

2016-09-19

Acetylcholinesterase (AChE) is the physiologically important target for organophosphorus toxicants (OP) including nerve agents and pesticides. Butyrylcholinesterase (BChE) in blood serves as a bioscavenger that protects AChE in nerve synapses from inhibition by OP. Mass spectrometry methods can detect exposure to OP by measuring adducts on the active site serine of plasma BChE. Genetic variants of human AChE and BChE do exist, but loss of function mutations have been identified only in the BCHE gene. The most common AChE variant, His353Asn (H322N), also known as the Yt blood group antigen, has normal AChE activity. The most common BChE variant, Ala567Thr (A539T) or the K-variant in honor of Werner Kalow, has 33% reduced plasma BChE activity. The genetic variant most frequently associated with prolonged response to muscle relaxants, Asp98Gly (D70G) or atypical BChE, has reduced activity and reduced enzyme concentration. Early studies in young, healthy males, performed at a time when it was legal to test nerve agents in humans, showed that individuals responded differently to the same low dose of sarin with toxic symptoms ranging in severity from minimal to moderate. Additionally, animal studies indicated that BChE protects from toxicants that have a higher reactivity with AChE than with BChE (e.g., nerve agents) but not from toxicants that have a higher reactivity with BChE than with AChE (e.g., OP pesticides). As a corollary, we hypothesize that individuals with genetic variants of BChE may be at increased risk of toxicity from nerve agents but not from OP pesticides.

E-smoking among students of medicine - frequency, pattern and motivations.

PubMed

Brożek, Grzegorz; Jankowski, Mateusz; Zejda, Jan; Jarosińska, Agnieszka; Idzik, Agnieszka; Bańka, Piotr

2017-01-01

E-smoking has become a public health problem. The objectives of this study were to assess the prevalence of e-cigarette and tobacco cigarette use; to compare the patterns of smoking; to assess the attitudes and motivations for e-cigarette use. All 1,700 students from Faculty of Medicine (Medical University of Silesia) were invited to questionnaire based cross-sectional study about the frequency and attitudes towards the use of traditional and electronic cigarettes. The data were obtained from 1,318 medical students (response 77.5%) aged 22.1 ± 2.2 years. Traditional tobacco smoked 18.1%, e-cigarettes 1.3% and 2.2% were dual smokers. The overall frequency of e-smokers was 4.9% among men and 2.8% among women (p = 0.05). Compared to tobacco users in e-smokers duration of smoking was shorter (p < 0.001), the intensity of smoking was larger (p = 0.01), the number of e-cigarettes smoked daily was higher (p < 0.001). Dual smokers more frequently used tobacco cigarettes than e-cigarettes (p = 0.01) but smoked more e-cigarettes daily (p = 0.003). The choice of e-liquid depended on the flavour (50.0%), nicotine concentration (21.7%) and price (7.6%). No-nicotine e-cigarettes were used by 6.5% smokers. Dual smokers more frequently chose e-liquids with high nicotine concentration (p = 0.01). Motivations leading to e-smoking were: quitting tobacco (58.7%), less harmful impact on health (43.5%) and the price (34.8%). E-smoking as safe for health was perceived by 6.0% of respondents (35.5% in e-smokers vs. 4.9% in non e-smokers; p < 0.001). Among students of medicine, e-smoking is apparently less popular than smoking tobacco cigarettes. Respondents considered e-cigarettes to be harmful and addictive.

Complete replication-competent adenovirus 11p vectors with E1 or E3 insertions show improved heat stability

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

Mei, Ya-Fang, E-mail: ya-fang.mei@umu.se

2016-10-15

Conventional adenovirus vectors harboring E1 or E3 deletions followed by the insertion of an exogenous gene show considerably reduced virion stability. Here, we report strategies to generate complete replication-competent Ad11p(RCAd11p) vectors that overcome the above disadvantage. A GFP cassette was successfully introduced either upstream of E1A or in the E3A region. The resulting vectors showed high expression levels of the hexon and E1genes and also strongly induced the cytopathic effect in targeted cells. When harboring oversized genomes, the RCAd11pE1 and RCAd11pE3 vectors showed significantly improved heat stability in comparison to Ad11pwt;of the three, RCAd11pE3 was the most tolerant to heatmore » treatment. Electron microscopy showed that RCAd11pE3, RCAd11pE1, Ad11pwt, and Ad11pE1 Delmanifested dominant, moderate, minimum, or no full virus particles after heat treatment at 47 °C for 5 h. Our results demonstrated that both genome size and the insertion site in the viral genome affect virion stability. -- Highlights: •Replicating adenovirus 11p GFP vectors at the E1 or E3 region were generated. •RCAd11pE3 and RCAd11pE1 vectors manifested significantly improved heat stability. •RCAd11pE3 and RCAd11pE1 showed more full viral particles than Ad11pwt after heating. •We demonstrated that both genome size and the insertion site affect virion stability.« less

Overexpression of acetylcholinesterase gene in rice results in enhancement of shoot gravitropism.

PubMed

Yamamoto, Kosuke; Shida, Satoshi; Honda, Yoshihiro; Shono, Mariko; Miyake, Hiroshi; Oguri, Suguru; Sakamoto, Hikaru; Momonoki, Yoshie S

2015-09-25

Acetylcholine (ACh), a known neurotransmitter in animals and acetylcholinesterase (AChE) exists widely in plants, although its role in plant signal transduction is unclear. We previously reported AChE in Zea mays L. might be related to gravitropism based on pharmacological study using an AChE inhibitor. Here we clearly demonstrate plant AChE play an important role as a positive regulator in the gravity response of plants based on a genetic study. First, the gene encoding a second component of the ACh-mediated signal transduction system, AChE was cloned from rice, Oryza sativa L. ssp. Japonica cv. Nipponbare. The rice AChE shared high homology with maize, siratro and Salicornia AChEs. Similar to animal and other plant AChEs, the rice AChE hydrolyzed acetylthiocholine and propionylthiocholine, but not butyrylthiocholine. Thus, the rice AChE might be characterized as an AChE (E.C.3.1.1.7). Similar to maize and siratro AChEs, the rice AChE exhibited low sensitivity to the AChE inhibitor, neostigmine bromide, compared with the electric eel AChE. Next, the functionality of rice AChE was proved by overexpression in rice plants. The rice AChE was localized in extracellular spaces of rice plants. Further, the rice AChE mRNA and its activity were mainly detected during early developmental stages (2 d-10 d after sowing). Finally, by comparing AChE up-regulated plants with wild-type, we found that AChE overexpression causes an enhanced gravitropic response. This result clearly suggests that the function of the rice AChE relate to positive regulation of gravitropic response in rice seedlings. Copyright © 2015 Elsevier Inc. All rights reserved.

Sites of disruption within E1 and E2 genes of HPV16 and association with cervical dysplasia.

PubMed

Tsakogiannis, D; Gortsilas, P; Kyriakopoulou, Z; Ruether, I G A; Dimitriou, T G; Orfanoudakis, G; Markoulatos, P

2015-11-01

Integration of HPV16 DNA into the host chromosome usually disrupts the E1 and/or E2 genes. The present study investigated the disruption of E1, E2 genes in a total of eighty four HPV16-positive precancerous and cervical cancer specimens derived from Greek women (seventeen paraffin-embedded cervical biopsies and sixty seven Thin Prep samples). Complete E2 and E1 genes were amplified using three and nine overlapping primer sets respectively, in order to define the sites of disruption. Extensive mapping analysis revealed that disruption/deletion events within E2 gene occurred in high grade and cervical cancer samples (x(2) test, P < 0.01), while no evidence of E2 gene disruption was documented among low grade cervical intraepithelial neoplasias. In addition, disruptions within the E1 gene occur both in high and low grade cervical intraepithelial neoplasia. This leads to the assumption that in low grade cervical intraepithelial neoplasias only E1 gene disruption was involved (Fisher's exact test, P < 0.05), while in high grade malignancies and cervical cancer cases deletions in both E1 and E2 genes occurred. Furthermore, the most prevalent site of disruption of E1 gene was located between nucleotides 1059 and 1323, while the most prevalent deleted region of the E2 gene was located between nucleotides 3172 and 3649 (E2 hinge region). Therefore, it is proposed that each population has its own profile of frequencies and sites of disruptions and extensive mapping analysis of E1 and E2 genes is mandatory in order to determine suitable markers for HPV16 DNA integration analysis in distinct populations. © 2015 Wiley Periodicals, Inc.

Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis.

PubMed

Thébaut, Alice; Nemeth, Antal; Le Mouhaër, Jeannie; Scheenstra, René; Baumann, Ulrich; Koot, Bart; Gottrand, Fredéric; Houwen, Roderick; Monard, Laure; de Micheaux, Sylvie Lafaye; Habes, Dalila; Jacquemin, Emmanuel

2016-12-01

D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cholestasis. Two hundred seventy-four children receiving Vedrop for vitamin E deficiency or for its prophylaxis were included from 7 European centers. Median age at treatment onset was 2 months and median follow-up was 11 months. Vedrop was prescribed at a daily dose of 0.34 mL/kg (25 IU/kg) of body weight. Three methods were used to determine a sufficient serum vitamin E status: vitamin E, vitamin E/(total cholesterol), vitamin E/(total cholesterol + triglycerides). Before Vedrop therapy, 51% of children had proven vitamin E deficiency, 30% had normal vitamin E status and 19% had an unknown vitamin E status. During the first months of treatment, vitamin E status was restored in the majority of children with insufficient levels at baseline (89% had a normal status at 6 months). All children with a normal baseline vitamin E status had a normal vitamin E status at 6 months. Among children with an unknown vitamin E status at baseline, 93% had a normal vitamin E status at 6 months. A sufficient vitamin E status was observed in 80% of children with significant cholestasis (serum total bilirubin >34.2 μmol/L). No serious adverse reaction was reported. Vedrop seems a safe and effective oral formulation of vitamin E that restores and/or maintains sufficient serum vitamin E level in the majority of children with cholestasis, avoiding the need for intramuscular vitamin E injections.

E-Cigarette Policies on College Campuses: Student Use Behaviors, Awareness, and Policy Support.

PubMed

Brown, Elizabeth M; Henes, Amy L; Olson, Lindsay T

2016-12-01

This study examined e-cigarette use and attitudes toward e-cigarette policies among students at colleges and universities with and without policies prohibiting e-cigarette use on campus. In April 2015, we fielded an online survey with a convenience sample of 930 students at 14 North Dakota colleges and universities. The survey included questions about e-cigarette use, observed e-cigarette use on campus, awareness of school e-cigarette policy, and support for policies prohibiting e-cigarette use on campus. Over 40 % of respondents had used e-cigarettes at least once, and most current users reported using them rarely (36 %). Nearly 29 % of respondents reported observing e-cigarette use on campus, and more than half of these reported seeing e-cigarette use indoors. More than 42 % did not know whether their school's policy prohibited e-cigarette use on campus, and students at schools with a policy were more likely to identify their campus policy correctly. Sixty-six percent of respondents were in favor of policies prohibiting e-cigarette use on campus, and those at schools with policies prohibiting e-cigarette use were more likely to support a campus e-cigarette policy. Policies prohibiting e-cigarette use on campus intend to restrict use, reduce prevalence, and shape social norms. This study indicates that support for campus e-cigarette policies is high, although awareness of whether e-cigarettes are included in college and university policies is low. These findings demonstrate the need for coordinated policy education efforts and may guide college administrators and student health services personnel as they consider how to implement and evaluate campus e-cigarette policies.

Chronic vitamin E deficiency impairs cognitive function in adult zebrafish via dysregulation of brain lipids and energy metabolism.

PubMed

McDougall, Melissa; Choi, Jaewoo; Magnusson, Kathy; Truong, Lisa; Tanguay, Robert; Traber, Maret G

2017-11-01

Zebrafish (Danio rerio) are a recognized model for studying the pathogenesis of cognitive deficits and the mechanisms underlying behavioral impairments, including the consequences of increased oxidative stress within the brain. The lipophilic antioxidant vitamin E (α-tocopherol; VitE) has an established role in neurological health and cognitive function, but the biological rationale for this action remains unknown. In the present study, we investigated behavioral perturbations due to chronic VitE deficiency in adult zebrafish fed from 45 days to 18-months of age diets that were either VitE-deficient (E-) or VitE-sufficient (E+). We hypothesized that E- zebrafish would display cognitive impairments associated with elevated lipid peroxidation and metabolic disruptions in the brain. Quantified VitE levels at 18-months in E- brains (5.7 ± 0.1 nmol/g tissue) were ~20-times lower than in E+ (122.8 ± 1.1; n = 10/group). Using assays of both associative (avoidance conditioning) and non-associative (habituation) learning, we found E- vs E+ fish were learning impaired. These functional deficits occurred concomitantly with the following observations in adult E- brains: decreased concentrations of and increased peroxidation of polyunsaturated fatty acids (especially docosahexaenoic acid, DHA), altered brain phospholipid and lysophospholipid composition, as well as perturbed energy (glucose/ketone), phosphatidylcholine and choline/methyl-donor metabolism. Collectively, these data suggest that chronic VitE deficiency leads to neurological dysfunction through multiple mechanisms that become dysregulated secondary to VitE deficiency. Apparently, the E- animals alter their metabolism to compensate for the VitE deficiency, but these compensatory mechanisms are insufficient to maintain cognitive function. Copyright © 2017 Elsevier Inc. All rights reserved.

High School Students’ Use of Electronic Cigarettes to Vaporize Cannabis

PubMed Central

Kong, Grace; Camenga, Deepa R.; Cavallo, Dana A.; Krishnan-Sarin, Suchitra

2015-01-01

BACKGROUND AND OBJECTIVES: Electronic cigarette (e-cigarette) use is increasing rapidly among high school (HS) students. Of concern, e-cigarettes can be used to vaporize cannabis, although use rates among adolescents are unknown. We evaluated lifetime rates of using e-cigarettes to vaporize cannabis among all lifetime e-cigarette users (27.9%), all lifetime cannabis users (29.2%), and lifetime users of both e-cigarettes and cannabis (18.8%); common means of vaporizing cannabis including hash oil, wax infused with Δ-9-tetrahydrocannabinol (THC), and dried cannabis; and demographic predictors of using e-cigarettes to vaporize cannabis. METHODS: In the spring of 2014, 3847 Connecticut HS students completed an anonymous survey assessing e-cigarette and cannabis use. RESULTS: Vaporizing cannabis using e-cigarettes was common among lifetime e-cigarette users, lifetime cannabis users, and lifetime dual users (e-cigarette 18.0%, cannabis 18.4%, dual users 26.5%). Students reported using e-cigarettes to vaporize hash oil (e-cigarette 15.4%, cannabis 15.5%, dual users 22.9%) and wax infused with THC (e-cigarette 10.0%, cannabis 10.2%, dual users 14.8%) and using portable electronic vaporizers to vaporize dried cannabis leaves (e-cigarette 19.6%, lifetime cannabis 23.1%, lifetime dual users 29.1%). Binary logistic regression indicated that male students (odds ratio [OR] = 2.05), younger students (OR = 0.64), lifetime e-cigarette users (OR = 5.27), and lifetime cannabis users (OR = 40.89) were most likely to vaporize cannabis using e-cigarettes. Rates also differed by HS attended. CONCLUSIONS: Rates of vaporizing cannabis using e-cigarettes were high. These findings raise concerns about the lack of e-cigarette regulations and the potential use of e-cigarettes for purposes other than vaping nicotine. PMID:26347431

Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of {sup 56}Fe Irradiation on the Brain

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

Haley, Gwendolen E.; Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR; Villasana, Laura

2012-11-01

Purpose: In humans, apolipoprotein E (apoE) is encoded by three major alleles ({epsilon}2, {epsilon}3, and {epsilon}4) and, compared to apoE3, apoE4 increases the risk of developing Alzheimer disease and cognitive impairments following various environmental challenges. Exposure to irradiation, including that of {sup 56}Fe, during space missions poses a significant risk to the central nervous system, and apoE isoform might modulate this risk. Methods and Materials: We investigated whether apoE isoform modulates hippocampus-dependent cognitive performance starting 2 weeks after {sup 56}Fe irradiation. Changes in reactive oxygen species (ROS) can affect cognition and are induced by irradiation. Therefore, after cognitive testing, wemore » assessed hippocampal ROS levels in ex vivo brain slices, using the ROS-sensitive fluorescent probe, dihydroethidium (DHE). Brain levels of 3-nitrotyrosine (3-NT), CuZn superoxide dismutase (CuZnSOD), extracellular SOD, and apoE were assessed using Western blotting analysis. Results: In the water maze, spatial memory retention was impaired by irradiation in apoE2 and apoE4 mice but enhanced by irradiation in apoE3 mice. Irradiation reduced DHE-oxidation levels in the enclosed blade of the dentate gyrus and levels of 3-NT and CuZnSOD in apoE2 but not apoE3 or apoE4 mice. Finally, irradiation increased apoE levels in apoE3 but not apoE2 or apoE4 mice. Conclusions: The short-term effects of {sup 56}Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial memory retention are apoE isoform-dependent.« less

E3Net: a system for exploring E3-mediated regulatory networks of cellular functions.

PubMed

Han, Youngwoong; Lee, Hodong; Park, Jong C; Yi, Gwan-Su

2012-04-01

Ubiquitin-protein ligase (E3) is a key enzyme targeting specific substrates in diverse cellular processes for ubiquitination and degradation. The existing findings of substrate specificity of E3 are, however, scattered over a number of resources, making it difficult to study them together with an integrative view. Here we present E3Net, a web-based system that provides a comprehensive collection of available E3-substrate specificities and a systematic framework for the analysis of E3-mediated regulatory networks of diverse cellular functions. Currently, E3Net contains 2201 E3s and 4896 substrates in 427 organisms and 1671 E3-substrate specific relations between 493 E3s and 1277 substrates in 42 organisms, extracted mainly from MEDLINE abstracts and UniProt comments with an automatic text mining method and additional manual inspection and partly from high throughput experiment data and public ubiquitination databases. The significant functions and pathways of the extracted E3-specific substrate groups were identified from a functional enrichment analysis with 12 functional category resources for molecular functions, protein families, protein complexes, pathways, cellular processes, cellular localization, and diseases. E3Net includes interactive analysis and navigation tools that make it possible to build an integrative view of E3-substrate networks and their correlated functions with graphical illustrations and summarized descriptions. As a result, E3Net provides a comprehensive resource of E3s, substrates, and their functional implications summarized from the regulatory network structures of E3-specific substrate groups and their correlated functions. This resource will facilitate further in-depth investigation of ubiquitination-dependent regulatory mechanisms. E3Net is freely available online at http://pnet.kaist.ac.kr/e3net.

Technical Performance Reduces during the Extra-Time Period of Professional Soccer Match-Play

PubMed Central

Harper, Liam D.; West, Daniel J.; Stevenson, Emma; Russell, Mark

2014-01-01

Despite the importance of extra-time in determining progression in specific soccer tournament matches, few studies have profiled the demands of 120-minutes of soccer match-play. With a specific focus on the extra-time period, and using a within-match approach, we examined the influence of prolonged durations of professional soccer match-play on markers of technical (i.e., skilled) performance. In 18 matches involving professional European teams played between 2010 and 2014, this retrospective study quantified the technical actions observed during eight 15-minute epochs (E1: 00∶00–14∶59 min, E2: 15∶00–29∶59 min, E3: 30∶00–44∶59 min, E4: 45∶00–59∶59 min, E5: 60∶00–74∶59 min, E6: 75∶00–89∶59 min, E7: 90∶00–104∶59 min, E8: 105∶00–119∶59 min). Analysis of players who completed the demands of the full 120 min of match-play revealed that the cumulative number of successful passes observed during E8 (61±23) was lower than E1–4 (E1: 88±23, P = 0.001; E2: 77±21, P = 0.005; E3: 79±18, P = 0.001; E4: 80±21, P = 0.001) and E7 (73±20, P = 0.002). Similarly, the total number of passes made in E8 (71±25) was reduced when compared to E1 (102±22, P = 0.001), E3 (91±19, P = 0.002), E4 (93±22, P≤0.0005) and E7 (84±20, P = 0.001). The cumulative number of successful dribbles reduced in E8 (9±4) when compared to E1 (14±4, P = 0.001) and E3 (12±4, P≤0.0005) and the total time the ball was in play was less in E8 (504±61 s) compared to E1 (598±70 s, P≤0.0005). These results demonstrate that match-specific factors reduced particular indices of technical performance in the second half of extra-time. Interventions that seek to maintain skilled performance throughout extra-time warrant further investigation. PMID:25343724

Cholinesterase (ChE) response and related mortality among birds fed ChE inhibitors

USGS Publications Warehouse

Ludke, J.L.; Hill, E.F.; Dieter, M.P.

1975-01-01

Patterns of mortality and inhibition of brain and plasma ChE in birds treated with ChE inhibitors were studied in an attempt to determine the validity of using ChE activity as a monitoring and diagnostic technique. Analysis of brain ChE activity proved to be reliable for diagnosing and monitoring effects of selected ChE inhibitors in birds. Brain ChE inhibition exceeding 20% indicated exposure, and inhibition greater than 50% was sufficient for diagnosing cause of death. Individuals that died from dietary exposure to parathion or carbofuran had brain ChE activities below 55% of normal; although individuals could survive with brain ChE activity lower than 50%. Problems associated with collection, storage, and analysis of tissues for ChE activity are discussed.

Synthesis of novel E-2-chlorovinyltellurium compounds based on the stereospecific anti-addition of tellurium tetrachloride to acetylene.

PubMed

Musalova, Maria V; Potapov, Vladimir A; Amosova, Svetlana V

2012-05-15

The reaction of tellurium tetrachloride with acetylene proceeds in a stereospecific anti-addition manner to afford the novel products E-2-chlorovinyltellurium trichloride and E,E-bis(2-chlorovinyl)tellurium dichloride. Reaction conditions for the selective preparation of each of these products were found. The latter was obtained in 90% yield in CHCl(3) under a pressure of acetylene of 10-15 atm, whereas the former product was formed in up to 72% yield in CCl(4) under a pressure of acetylene of 1-3 atm. Synthesis of the previously unknown E,E-bis(2-chlorovinyl) telluride, E,E-bis(2-chlorovinyl) ditelluride, E-2-chlorovinyl 1,2,2-trichloroethyl telluride and E,E-bis(2-chlorovinyl)-tellurium dibromide is described.

Receptivity to e-cigarette marketing, harm perceptions, and e-cigarette use.

PubMed

Pokhrel, Pallav; Fagan, Pebbles; Kehl, Lisa; Herzog, Thaddeus A

2015-01-01

To test whether exposure and receptivity to e-cigarette marketing are associated with recent e-cigarette use among young adults through increased beliefs that e-cigarettes are less harmful than cigarettes. Data were collected from 307 multiethnic 4- and 2-year college students; approximately equal proportions of current, never, and former cigarette smokers [mean age = 23.5 (SD = 5.5); 65% female]. Higher receptivity to e-cigarette marketing was associated with perceptions that e-cigarettes are less harmful than cigarettes, which in turn, were associated with higher recent e-cigarette use. The findings provide preliminary support to the proposition that marketing of e-cigarettes as safer alternatives to cigarettes or cessation aids is associated with increased e-cigarette use among young adults. The findings have implications for development of e-cigarette regulations.

Introduction to Some Fundamental Concepts of General Relativity and to Their Required Use in Some Modern Timekeeping Systems

DTIC Science & Technology

1981-12-01

t e d Riemann Curvature Wnsor and R i s the Curva ture ~ c 2 l ) a r . I n 1917, Karl Schwarzschi ld s o l v e d t h e s e e q u a t i o n...tu re of time a l o n e . I t is t h e Schwarzschild met r ic t h a t leads t o the famous concept n f t h e black h o l e . This is a...01 Well, it can: 2 m - I - - - - - 0 r c 2 Figure 2 4 One calls t h i s va lue of r t h e Schwarzschild b d l u s and o f t e n

Oxidative stress increases eukaryotic initiation factor 4E phosphorylation in vascular cells.

PubMed Central

Duncan, Roger F; Peterson, Hazel; Hagedorn, Curt H; Sevanian, Alex

2003-01-01

Dysregulated cell growth can be caused by increased activity of protein synthesis eukaryotic initiation factor (eIF) 4E. Dysregulated cell growth is also characteristic of atherosclerosis. It is postulated that exposure of vascular cells, such as endothelial cells, smooth muscle cells and monocytes/macrophages, to oxidants, such as oxidized low-density lipoprotein (oxLDL), leads to the elaboration of growth factors and cytokines, which in turn results in smooth muscle cell hyperproliferation. To investigate whether activation of eIF4E might play a role in this hyperproliferative response, vascular cells were treated with oxLDL, oxidized lipid components of oxLDL and several model oxidants, including H(2)O(2) and dimethyl naphthoquinone. Exposure to each of these compounds led to a dose- and time-dependent increase in eIF4E phosphorylation in all three types of vascular cells, correlated with a modest increase in overall translation rate. No changes in eIF4EBP, eIF2 or eIF4B modification state were observed. Increased eIF4E phosphorylation was paralleled by increased presence of eIF4E in high-molecular-mass protein complexes characteristic of its most active form. Anti-oxidants at concentrations typically employed to block oxidant-induced cell signalling likewise promoted eIF4E phosphorylation. The results of this study indicate that increased eIF4E activity may contribute to the pathophysiological events in early atherogenesis by increasing the expression of translationally inefficient mRNAs encoding growth-promoting proteins. PMID:12215171

Case Studies in e-RPL and e-PR

ERIC Educational Resources Information Center

Cameron, Roslyn; Miller, Allison

2014-01-01

The use of ePortfolios for recognition of prior learning (e-RPL) and for professional recognition (e-PR) is slowly gaining in popularity in the VET sector however their use is sporadic across educational sectors, disciplines, educational institutions and professions. Added to this is an array of purposes and types of e-RPL and e-PR models and…

Job Prospects for E/E Engineers.

ERIC Educational Resources Information Center

Basta, Nicholas

1986-01-01

Reviews job prospects for electrical/electronic E/E engineers, indicating that 1985 was not a banner year due to problems in the semiconductor manufacturing industries and in telecommunications. Also indicates that an upturn is expected for 1986 E/E graduates. (JN)

What Are Complex eHealth Innovations and How Do You Measure Them? Position Paper.

PubMed

Hübner, U

2015-01-01

eHealth and innovation are often regarded as synonyms - not least because eHealth technologies and applications are new to their users. This position paper challenges this view and aims at exploring the nature of eHealth innovation against the background of common definitions of innovation and facts from the biomedical and health informatics literature. A good understanding of what constitutes innovative eHealth developments allows the degree of innovation to be measured and interpreted. To this end, relevant biomedical and health informatics literature was searched mainly in Medline and ACM digital library. This paper presents seven facts about implementing and applying new eHealth developments hereby drawing on the experience published in the literature. The facts are: 1. eHealth innovation is relative. 2. Advanced clinical practice is the yardstick. 3. Only used and usable eHealth technology can give birth to eHealth innovatio. 4. One new single eHealth function does not make a complex eHealth innovation. 5. eHealth innovation is more evolution than revolution. 6. eHealth innovation is often triggered behind the scenes; and 7. There is no eHealth innovation without sociocultural change. The main conclusion of the seven facts is that eHealth innovations have many ingredients: newness, availability, advanced clinical practice with proven outcomes, use and usability, the supporting environment, other context factors and the stakeholder perspectives. Measuring eHealth innovation is thus a complex matter. To this end we propose the development of a composite score that expresses comprehensively the nature of eHealth innovation and that breaks down its complexity into the three dimensions: i) eHealth adoption, ii) partnership with advanced clinical practice, and iii) use and usability of eHealth. In order to better understand the momentum and mechanisms behind eHealth innovation the fourth dimension, iv) eHealth supporting services and means, needs to be studied. Conceptualising appropriate measurement instruments also requires eHealth innovation to be distinguished from eHealth sophistication, performance and quality, although innovation is intertwined with these concepts. The demanding effort for defining eHealth innovation and measuring it properly seem worthwhile and promise advances in creating better systems. This paper thus intends to stimulate the necessary discussion.

An Enantiomer of an Oral Small-Molecule TSH Receptor Agonist Exhibits Improved Pharmacologic Properties.

PubMed

Neumann, Susanne; Padia, Umesh; Cullen, Mary Jane; Eliseeva, Elena; Nir, Eshel A; Place, Robert F; Morgan, Sarah J; Gershengorn, Marvin C

2016-01-01

We are developing an orally available small-molecule, allosteric TSH receptor (TSHR) agonist for follow-up diagnostics of patients with thyroid cancer. The agonist C2 (NCGC00161870) that we have studied so far is a racemic mixture containing equal amounts of two enantiomers, E1 and E2. As enantiomers of many drugs exhibit different pharmacologic properties, we assessed the properties of E1 and E2. We separated the two enantiomers by chiral chromatography and determined E2 as the (S)-(+) isomer via crystal structure analysis. E1 and E2 were shown to bind differently to a homology model of the transmembrane domain of TSHR in which E2 was calculated to exhibit lower binding energy than E1 and was, therefore, predicted to be more potent than E1. In HEK293 cells expressing human TSHRs, C2, E1, and E2 were equally efficacious in stimulating cAMP production, but their potencies were different. E2 was more potent (EC50 = 18 nM) than C2 (EC50 = 46 nM), which was more potent than E1 (EC50 = 217 nM). In primary cultures of human thyrocytes, C2, E1, and E2 stimulated increases in thyroperoxidase mRNA of 92-, 55-, and 137-fold and in sodium-iodide symporter mRNA of 20-, 4-, and 121-fold above basal levels, respectively. In mice, C2 stimulated an increase in radioactive iodine uptake of 1.5-fold and E2 of 2.8-fold above basal level, whereas E1 did not have an effect. C2 stimulated an increase in serum T4 of 2.4-fold, E1 of 1.9-fold, and E2 of 5.6-fold above basal levels, and a 5-day oral dosing regimen of E2 increased serum T4 levels comparable to recombinant human TSH (rhTSH, Thyrogen(®)). Thus, E2 is more effective than either C2 or E1 in stimulating thyroid function and as efficacious as rhTSH in vivo. E2 represents the next step toward developing an oral drug for patients with thyroid cancer.

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.

Cellular Analysis of Boltzmann Most Probable Ideal Gas Statistics

NASA Astrophysics Data System (ADS)

Cahill, Michael E.

2018-04-01

Exact treatment of Boltzmann's Most Probable Statistics for an Ideal Gas of Identical Mass Particles having Translational Kinetic Energy gives a Distribution Law for Velocity Phase Space Cell j which relates the Particle Energy and the Particle Population according toB e(j) = A - Ψ(n(j) + 1)where A & B are the Lagrange Multipliers and Ψ is the Digamma Function defined byΨ(x + 1) = d/dx ln(x!)A useful sufficiently accurate approximation for Ψ is given byΨ(x +1) ≈ ln(e-γ + x)where γ is the Euler constant (≈.5772156649) & so the above distribution equation is approximatelyB e(j) = A - ln(e-γ + n(j))which can be inverted to solve for n(j) givingn(j) = (eB (eH - e(j)) - 1) e-γwhere B eH = A + γ& where B eH is a unitless particle energy which replaces the parameter A. The 2 approximate distribution equations imply that eH is the highest particle energy and the highest particle population isnH = (eB eH - 1) e-γwhich is due to the facts that population becomes negative if e(j) > eH and kinetic energy becomes negative if n(j) > nH.An explicit construction of Cells in Velocity Space which are equal in volume and homogeneous for almost all cells is shown to be useful in the analysis.Plots for sample distribution properties using e(j) as the independent variable are presented.

Characterisation of Translation Elongation Factor eEF1B Subunit Expression in Mammalian Cells and Tissues and Co-Localisation with eEF1A2

PubMed Central

Janikiewicz, Justyna; Doig, Jennifer; Abbott, Catherine M.

2014-01-01

Translation elongation is the stage of protein synthesis in which the translation factor eEF1A plays a pivotal role that is dependent on GTP exchange. In vertebrates, eEF1A can exist as two separately encoded tissue-specific isoforms, eEF1A1, which is almost ubiquitously expressed, and eEF1A2, which is confined to neurons and muscle. The GTP exchange factor for eEF1A1 is a complex called eEF1B made up of subunits eEF1Bα, eEF1Bδ and eEF1Bγ. Previous studies have cast doubt on the ability of eEF1B to interact with eEF1A2, suggesting that this isoform might use a different GTP exchange factor. We show that eEF1B subunits are all widely expressed to varying degrees in different cell lines and tissues, and at different stages of development. We show that ablation of any of the subunits in human cell lines has a small but significant impact on cell viability and cycling. Finally, we show that both eEF1A1 and eEF1A2 colocalise with all eEF1B subunits, in such close proximity that they are highly likely to be in a complex. PMID:25436608

Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers

NASA Technical Reports Server (NTRS)

Firstenberg, M. S.; Levine, B. D.; Garcia, M. J.; Greenberg, N. L.; Cardon, L.; Morehead, A. J.; Zuckerman, J.; Thomas, J. D.

2000-01-01

OBJECTIVES: We sought to determine the relationship between different echocardiographic indices and pulmonary capillary wedge pressures (PCWP) in normal volunteers. BACKGROUND: Indices based on tissue Doppler (TDE) and color M-mode (CMM) echocardiography have been proposed to reflect left (LV) ventricular filling pressures. These include the ratio of early diastolic transmitral velocity (E) to early myocardial velocity measured by TDE (E') and the ratio of E to the wave propagation velocity (Vp) measured from CMM images. These indices, however, have not been validated in normal individuals. METHODS: We studied seven volunteers during two phases of preload altering maneuvers, baseline, with two stages of lower body negative pressure, and repeat baseline with two stages of volume loading. The PCWP obtained from right heart catheterization was compared with diastolic indices using pulsed Doppler, TDE and CMM echocardiography. RESULTS: The PCWP ranged from 2.2 to 23.5 mm Hg. During preload alterations, significant changes in E and septal E' (both p < 0.05) but not lateral E' or Vp were observed. Furthermore, E, septal E' and E/Vp correlated with PCWP (all r > 0.80) but not combined E and TDE indices (both r < 0.15). Within individuals, a similar linear relationship was observed among E/Vp, E and septal E' (average r > 0.80). CONCLUSIONS: In subjects without heart disease, E, septal E' and E/Vp correlate with PCWP. Because the influence of ventricular relaxation is minimized, the ratio E/Vp may be the best overall index of LV filling pressures.

Application of Discrete Guidance and Control Theory to Future Army Modular Missiles.

DTIC Science & Technology

1980-09-30

30 April - I May, Dr. Pastrick and Dr. Seltzer-attended the 1980 Tactical Missiles Conference at Eglin Air Force Base. !7 t ’ I 9 * I. - , Ji ...1.7140E+00 P2= 9.0903E- 61 WnTm 1.8221E+00 DET=-1.8519E-03 P1= I.7093E+00 P2= 9.0568E-01 SWrT= 1.850E+00 DET=-1.8416E-03 Piz 1.7055E+00 P2= 9.0290E-01 * WrT...fl-n~-~a~ 4 - - I I I TECHNICAL REPORT T-79-64 I SAMPLED-DATA ANALYSIS IN PARAMETER SPACE S.M. Seltzer Technology Laboratory June 1979 Ji j edet•one

Thermal Relaxation of Adsorbed Atoms in an Intense Laser Field.

DTIC Science & Technology

1986-07-01

the position of the bond is E(t) = E Re[E exp(- iwLt )] , (2.8) and the coupled levels will be denoted by le> and Ig>. This excited state and ground...With the property P2 = P gg we can expand the exponentials as tiLtP ± iwLt e g W 1 - P + e P , (3.13)g g which allows us to write q(t) = + e P S + e...the dressed states and use the expression (3.14) for q(t), we obtain jA ikt - iWLt iw t qI(t) de k { + e PgS w e SP (4.5) kE where kf = "(4.6) is the

Exercise Dread Night: Using Allied Medical Publication-8(C) to Estimate Chemical, Biological, Radiological, and Nuclear (CBRN) Casualties

DTIC Science & Technology

2010-08-01

I N S T I T U T E F O R D E F E N S E A N A LY S E S IDA Document D-4130 August 2010 Exercise “Dread Night”: Using Allied Medical Publication-8(C...scientific and technical expertise, and conduct related research on other national challenges. I N S T I T U T E F O R D E F E N S E A N A LY S E...insult can be simply postulated, but it can also be calculated using the methodology described in AMedP-8(C). The latter approach was the one taken in

The stone huntsman spider genus Eusparassus (Araneae: Sparassidae): systematics and zoogeography with revision of the African and Arabian species.

PubMed

Moradmand, Majid

2013-01-01

An overview on the systematics of the stone huntsman spider genus Eusparassus Simon, 1903 and an identification key to the known species are presented. Six species-groups are proposed: the walckenaeri group (3 species, Eastern Mediterranean to Arabia and parts of North-Eastern Africa), dufouri group (8 species, Iberian Peninsula to parts of North-western Africa), vestigator group (3 species, Central to Eastern Africa and an isolated area in India), jaegeri group (4 species, Southern and South-Eastern Africa), tuckeri group (2 species, South-Western Africa) and doriae group (7 species, Middle East to Central and South Asia). Two species, E. pontii Caporiacco, 1935 and E. xerxes (Pocock, 1901) could not be placed in any of the above groups. The species from Africa and Arabia are revised. The following ten species are re-described: Eusparassus barbarus (Lucas, 1846), E. atlanticus Simon, 1909 stat. nov., E. syrticus Simon, 1909, E. oraniensis (Lucas, 1846), E. letourneuxi (Simon, 1874), E. fritschi (Koch, 1873) stat. rev., E. walckenaeri (Audouin, 1826), E. vestigator (Simon, 1897) comb. nov., E. laevatus (Simon, 1897) comb. nov. and E. tuckeri (Lawrence, 1927) comb. nov. The latter three species are transferred from Olios Walckenaer, 1837. Seven new species are described: Eusparassus arabicus spec. nov. (male, female) from Arabian Peninsula, E. educatus spec. nov. (male, female) from Namibia, E. reverentia spec. nov. (male, female) from Burkina Faso and Nigeria, E. jaegeri spec. nov. (male, female) from South Africa and Botswana, E. jocquei spec. nov. (male, female) from Zimbabwe, E. borakalalo spec. nov. (female) from South Africa and E. schoem-anae spec. nov. (male, female) from South Africa and Namibia. Three taxa, E. dufouri maximus Strand, 1906 syn. nov., E. rufobrunneus Caporiacco, 1941 syn. nov. and Olios furcatus Lawrence, 1927 syn. nov. are proposed as junior syn-onyms of E. oraniensis, E. vestigator comb. nov. and E. tuckeri comb. nov. respectively. Males of E. atlanticus stat. nov. and E. fritschi stat. rev. are described for the first time as in the female of E. vestigator comb. nov. Neotypes are desig-nated for E. barbarus, E. oraniensis and E. letourneuxi (all from Algeria). The male and female of Cercetius perezi Simon, 1902, which was known only from the immature holotype, are described here for the first time. This resulted in recogniz-ing the monotypic and little used generic name Cercetius Simon, 1902 as a synonym of the widely used name Eusparas-sus. Nearly all the species are illustrated for the first time. Eusparassus concolor Caporiacco, 1939 is transferred to Olios and the replacement name Olios quesitio is proposed because of secondary homonymy. For the majority of the species, new geographical records are presented. The systematics and zoogeography of the currently known species and species groups are discussed. A brief note on the copulation process of E. walckenaeri is presented.

Male-produced aggregation pheromone of Carpophilus sayi, a nitidulid vector of oak wilt disease, and pheromonal comparison with Carpophilus lugubris

Treesearch

Robert J. Bartelt; John F. Kyhl; Angie K. Ambourn; Jennifer Juzwik; Steven J. Seybold

2004-01-01

Carpophilus sayi, a nitidulid beetle vector of the oak wilt fungus, Ceratocystis fagacearum, was shown to have a male-produced aggregation pheromone. Six male-specific chemicals were identified from collections of volatiles. The two major compounds were (2E,4E,6E,8E)-3,5-dimethyl-7-ethyl-2,4,6,8- undecatetraene and (2E,4E,6E,8E...

Feasibility Studies of an Electrochemical Test Method for Nitrogen Tetroxide Compatibility Testing.

DTIC Science & Technology

1978-11-01

I - fl i ght Density Acid ( HDA ) type systems (N204—HNO 3) in order to achieve t r a - s - ~t i r - i h s I e d e...id rich ph a s e w i l l r e s u l t in HDA type nitric acid corrosion in localized , s i t e s ( i . - . , c r e v t s~s , s - t c . ) . E l e

Experiment E89-044 on the Quasielastic 3He(e,e'p) Reaction at Jefferson Laboratory

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

Penel-Nottaris, Emilie

The Jefferson Lab Hall A E89-044 experiment has measured the 3He(e,e'p) reaction cross-sections. The extraction of the longitudinal and transverse response functions for the two-body break-up 3He(e,e'p)d reaction in parallel kinematics allows the study of the bound proton electromagnetic properties inside the 3He nucleus and the involved nuclear mechanisms beyond plane wave approximations.

Mycotoxin producing potential of some isolates of Aspergillus flavus and Eurotium groups from meat products.

PubMed

el-Kady, I; el-Maraghy, S; Zohri, A N

1994-09-01

All strains (92) of A. flavus group proved to be positive for production of aflatoxin (45 to 1200 micrograms/50 ml medium) on potato dextrose liquid medium, while 59 strains only proved to be positive (35-310 micrograms/50 ml) on 15% NaCl potato-dextrose liquid medium. Most of the strains tested of A. flavus, A. flavus var. columnaris and A. oryzae produced aflatoxins B1, B2, G1 & G2. All positive strains of A. tamarii produced aflatoxins G1 & G2 while the tested isolate of A. zonatus produced aflatoxins B1 & G1. Of 95 strains tested of Eurotium, aflatoxins B1 & G1 were produced by one strain of each of E. chevalieri var. intermedium, E. repens and E. rubrum. Gliotoxin was detected in the extract of two strains of E. chevalieri and one strain of each of E. chevalieri var. intermedium and E. pseudoglaucum on the salt-free medium, and two strains of each of E. chevalieri, E. chevalieri var. intermedium and one of E. pseudoglaucum on 15% NaCl medium. Sterigmatocystin was produced by some strains of E. chevalieri, E. chevalieri var. intermedium, E. amstelodami, E. pseudoglaucum and E. rubrum on the two experimental media. One strain only of E. repens produced ochratoxin A while citrinin was detected in the extract of one strain of E. pseudoglaucum.

Transport and modeling of estrogenic hormones in a dairy farm effluent through undisturbed soil lysimeters.

PubMed

Steiner, Laure D; Bidwell, Vincent J; Di, Hong J; Cameron, Keith C; Northcott, Grant L

2010-04-01

The presence of endocrine-disrupting chemicals, including estrone (E1) and 17beta-estradiol (E2), in surface waters has been associated with physiological dysfunction in a number of aquatic organisms. One source of surface and groundwater contamination with E1 and E2 is the land application of animal wastes. The processes involved in the transport of these hormones in the soil, when applied with animal wastes, are still unclear. Therefore, a field-transport experiment was carried out, where a dairy farm effluent spiked with E1 and E2 was applied on large (50 cm diameter and 70 cm depth) undisturbed soil lysimeters. The concentrations of E1 and E2 in the leachate were monitored over a 3-month period, during which irrigation was applied. The experimental data suggest that E1 and E2 were transported through preferential/macropore flow pathways. The data from the experiment also show that E1 and E2 are leached earlier than the inert tracer (bromide). This observation can be explained either by the presence of antecedent concentrations in the soil or by an enhanced transport of E1 and E2 through the soil. A state-space mixing-cell model was further developed in order to describe the transport of E1 and E2 by three transport processes in parallel. The inverse modeling of the leaching data did not support the hypothesis that antecedent concentrations of estrogens could be responsible for the observed breakthrough curves but confirmed that estrogens were transported mainly via preferential/macropore flow and also via an enhanced transport. The parameter values that characterized this enhanced transport strongly suggest that this enhanced transport is mediated by colloids. For the first time, the simultaneous transport of E1 and E2 was modeled under transient conditions, taking into account the advection-dispersion, preferential/macropore flow, and colloidal-enhanced transport processes as well as E1 and E2 dissipation in the soil. These findings have major implications in terms of management practices to decrease E1 and E2 transport and water contamination.

Regulation of host translational machinery by African swine fever virus.

PubMed

Castelló, Alfredo; Quintas, Ana; Sánchez, Elena G; Sabina, Prado; Nogal, Marisa; Carrasco, Luis; Revilla, Yolanda

2009-08-01

African swine fever virus (ASFV), like other complex DNA viruses, deploys a variety of strategies to evade the host's defence systems, such as inflammatory and immune responses and cell death. Here, we analyse the modifications in the translational machinery induced by ASFV. During ASFV infection, eIF4G and eIF4E are phosphorylated (Ser1108 and Ser209, respectively), whereas 4E-BP1 is hyperphosphorylated at early times post infection and hypophosphorylated after 18 h. Indeed, a potent increase in eIF4F assembly is observed in ASFV-infected cells, which is prevented by rapamycin treatment. Phosphorylation of eIF4E, eIF4GI and 4E-BP1 is important to enhance viral protein production, but is not essential for ASFV infection as observed in rapamycin- or CGP57380-treated cells. Nevertheless, eIF4F components are indispensable for ASFV protein synthesis and virus spread, since eIF4E or eIF4G depletion in COS-7 or Vero cells strongly prevents accumulation of viral proteins and decreases virus titre. In addition, eIF4F is not only activated but also redistributed within the viral factories at early times of infection, while eIF4G and eIF4E are surrounding these areas at late times. In fact, other components of translational machinery such as eIF2alpha, eIF3b, eIF4E, eEF2 and ribosomal P protein are enriched in areas surrounding ASFV factories. Notably, the mitochondrial network is polarized in ASFV-infected cells co-localizing with ribosomes. Thus, translation and ATP synthesis seem to be coupled and compartmentalized at the periphery of viral factories. At later times after ASFV infection, polyadenylated mRNAs disappear from the cytoplasm of Vero cells, except within the viral factories. The distribution of these pools of mRNAs is similar to the localization of viral late mRNAs. Therefore, degradation of cellular polyadenylated mRNAs and recruitment of the translation machinery to viral factories may contribute to the inhibition of host protein synthesis, facilitating ASFV protein production in infected cells.

Regulation of Host Translational Machinery by African Swine Fever Virus

PubMed Central

Castelló, Alfredo; Quintas, Ana; Sánchez, Elena G.; Sabina, Prado; Nogal, Marisa; Carrasco, Luis; Revilla, Yolanda

2009-01-01

African swine fever virus (ASFV), like other complex DNA viruses, deploys a variety of strategies to evade the host's defence systems, such as inflammatory and immune responses and cell death. Here, we analyse the modifications in the translational machinery induced by ASFV. During ASFV infection, eIF4G and eIF4E are phosphorylated (Ser1108 and Ser209, respectively), whereas 4E-BP1 is hyperphosphorylated at early times post infection and hypophosphorylated after 18 h. Indeed, a potent increase in eIF4F assembly is observed in ASFV-infected cells, which is prevented by rapamycin treatment. Phosphorylation of eIF4E, eIF4GI and 4E-BP1 is important to enhance viral protein production, but is not essential for ASFV infection as observed in rapamycin- or CGP57380-treated cells. Nevertheless, eIF4F components are indispensable for ASFV protein synthesis and virus spread, since eIF4E or eIF4G depletion in COS-7 or Vero cells strongly prevents accumulation of viral proteins and decreases virus titre. In addition, eIF4F is not only activated but also redistributed within the viral factories at early times of infection, while eIF4G and eIF4E are surrounding these areas at late times. In fact, other components of translational machinery such as eIF2α, eIF3b, eIF4E, eEF2 and ribosomal P protein are enriched in areas surrounding ASFV factories. Notably, the mitochondrial network is polarized in ASFV-infected cells co-localizing with ribosomes. Thus, translation and ATP synthesis seem to be coupled and compartmentalized at the periphery of viral factories. At later times after ASFV infection, polyadenylated mRNAs disappear from the cytoplasm of Vero cells, except within the viral factories. The distribution of these pools of mRNAs is similar to the localization of viral late mRNAs. Therefore, degradation of cellular polyadenylated mRNAs and recruitment of the translation machinery to viral factories may contribute to the inhibition of host protein synthesis, facilitating ASFV protein production in infected cells. PMID:19714237

Unphosphorylated HSP27 (HSPB1) regulates the translation initiation process via a direct association with eIF4E in osteoblasts.

PubMed

Kuroyanagi, Gen; Tokuda, Haruhiko; Yamamoto, Naohiro; Matsushima-Nishiwaki, Rie; Kozawa, Osamu; Otsuka, Takanobu

2015-09-01

Heat-shock protein 27 (HSP27/HSPB1) and its phosphorylation are implicated in multiple physiological and pathophysiological cell functions. Our previous study reported that unphosphorylated HSP27 has an inhibitory role in triiodothyronine (T(3))‑induced osteocalcin (OC) synthesis in osteoblasts. However, the mechanisms behind the HSP27‑mediated effects on osteoblasts remain to be clarified. In the present study, to investigate the exact mechanism of HSP27 and its phosphorylation in osteoblasts, the molecular targets of HSP27 were explored using osteoblast‑like MC3T3‑E1 cells. The levels of OC mRNA induced by T(3) in the HSP27‑overexpressing cells did not show any significant differences compared with those in the control empty vector‑transfected cells. Therefore, the interactions between HSP27 and translational molecules were focused on, including eukaryotic translation initiation factor 4E (eIF4E), eIF4G and 4E‑binding protein 1 (4E‑BP1). The HSP27 protein in the unstimulated cells co‑immunoprecipitated with eIF4E, but not eIF4G or 4E‑BP1. In addition, the association of eIF4E with 4E‑BP1 was observed in the HSP27‑overexpressing cells, as well as in the control cells. Under T(3) stimulation, the binding of eIF4E to eIF4G was markedly attenuated in the HSP27‑overexpressing cells compared with the control cells. In addition, the binding of HSP27 to eIF4E in the unstimulated cells was diminished by the phosphorylation of HSP27. In response to T(3) stimulation, the association of eIF4E with eIF4G in the unphosphorylatable HSP27‑overexpressing cells was markedly reduced compared with the phospho‑mimic HSP27‑overexpressing cells. Taken together, these findings strongly suggest that unphosphorylated HSP27 associates with eIF4E in osteoblasts and suppresses the translation initiation process.

Distribution of human papilloma virus type 16 E6/E7 gene mutation in cervical precancer or cancer: A case control study in Guizhou Province, China.

PubMed

Yang, Yingjie; Ren, Jie; Zhang, Qizhu

2016-02-01

HPV-16 varies geographically and is correlated with cervical cancer genesis and progression. This study aimed to determine the distribution of HPV-16 E6/E7 genetic variation in patients with invasive cervical cancer or precancer in Guizhou Province, China. A case-control study was designed, and the distribution of HPV-16 E6/E7 genetic variation was compared among women with cervical cancer, precancer, and sexually active without cervical lesion. HPV infection was detected through flow-through hybridization and gene chip techniques to determine the prevalence of HPV 16 E6/E7 genetic variation. Among 90 specimens (30 cervical cancer, 30 precancer, 30 controls), 81 were subjected to HPV-16 E6/E7 gene sequencing. The rates of DNA sequence mutation and amino acid mutation were 76.5% (62/81) and 66.7% (54/81), respectively. Both E6 and E7 genes showed higher mutation rate than their prototypes. The prevalence of E6/E7 mutation significantly differed between the cervical cancer and the controls (P < 0.05) and between the cervical precancer and the controls (P < 0.05). Mutations were simultaneously detected at the E6-D32E (T96A) and E7-M28V (A82G)/L94P (T281C) sites of the amino acid sequence. The most common genetic variation was D32E/M28V/L94P, which accounted for 35.8% of the cases (29/81). D32E/M28V/L94P mutation was higher in the cervical cancer and precancer compared with the prototype. HPV-16 E6/E7 genetic variations, such as D32E/M28V/L94P, are more prevalent in cervical cancer or precancer than those in the controls. The possible correlation between genetic variation and cancerigenesis may be used to design an HPV vaccine for cervical carcinoma. © 2015 Wiley Periodicals, Inc.

Characterization of a new chimeric marker vaccine candidate with a mutated antigenic E2-epitope.

PubMed

Reimann, Ilona; Depner, Klaus; Utke, Katrin; Leifer, Immanuel; Lange, Elke; Beer, Martin

2010-04-21

A new chimeric pestivirus "CP7_E1E2alf_TLA", based on the infectious cDNA of bovine viral diarrhea virus (BVDV) strain CP7, was constructed. The substitution of BVDV E1 and E2 with the respective proteins of classical swine fever (CSF) strain Alfort 187 allows an optimal heterodimerization of E1 and E2 in the chimeric virus, which is beneficial for efficient and authentic virus assembly and growth. In addition, for implementation of E2-based marker diagnostics, the previously described antigenic CSFV-specific TAVSPTTLR epitope was exchanged with the corresponding E2-epitope of BVDV strain CP7. Recombinant virus CP7_E1E2alf_TLA displayed a growth defect, and was not reacting with monoclonal antibodies used in commercial E2 antibody blocking ELISAs. Therefore, efficacy as well as marker properties of CP7_E1E2alf_TLA were investigated in an animal experiment with both a high dose and a low dose vaccine preparation. All CP7_E1E2alf_TLA-vaccinated animals seroconverted until day 28 post-vaccination with neutralizing antibodies. Furthermore, at the day of challenge infection CP7_E1E2alf_TLA-immunized animals showed distinct lower ELISA values in a commercial CSFV E2 antibody test in comparison to the C-strain vaccinated controls. However, E2-ELISA reactivity as well as neutralizing titers were directly connected to the dosage used for vaccination, and only the low dose group had E2-ELISA values below threshold until challenge infection. Following challenge infection with highly virulent CSFV strain Koslov, all vaccinees were protected, however, short-term fever episodes and very limited CSFV genome detection with very low copy numbers could be observed. In conclusion, manipulation of the TAVSPTTLR-epitope within the tested chimeric virus resulted in an slightly reduced efficacy, but the E2 marker properties unexpectedly did not allow a clear differentiation of infected from vaccinated animals in some cases. Copyright 2009 Elsevier B.V. All rights reserved.

Molecular Structure of a 9-MDa Icosahedral Pyruvate Dehydrogenase Subcomplex Containing the E2 and E3 Enzymes Using Cryoelectron Microscopy*

PubMed Central

Milne, Jacqueline L. S.; Wu, Xiongwu; Borgnia, Mario J.; Lengyel, Jeffrey S.; Brooks, Bernard R.; Shi, Dan; Perham, Richard N.; Subramaniam, Sriram

2006-01-01

The pyruvate dehydrogenase multienzyme complexes are among the largest multifunctional catalytic machines in cells, catalyzing the production of acetyl CoA from pyruvate. We have previously reported the molecular architecture of an 11-MDa subcomplex comprising the 60-mer icosahedral dihydrolipoyl acetyltransferase (E2) decorated with 60 copies of the heterotetrameric (α2β2) 153-kDa pyruvate decarboxylase (E1) from Bacillus stearothermophilus (Milne, J. L. S., Shi, D., Rosenthal, P. B., Sunshine, J. S., Domingo, G. J., Wu, X., Brooks, B. R., Perham, R. N., Henderson, R., and Subramaniam, S. (2002) EMBO J. 21, 5587–5598). An annular gap of ~90 Å separates the acetyltransferase catalytic domains of the E2 from an outer shell formed of E1 tetramers. Using cryoelectron microscopy, we present here a three-dimensional reconstruction of the E2 core decorated with 60 copies of the homodimeric 100-kDa dihydrolipoyl dehydrogenase (E3). The E2E3 complex has a similar annular gap of ~75 Å between the inner icosahedral assembly of acetyltransferase domains and the outer shell of E3 homodimers. Automated fitting of the E3 coordinates into the map suggests excellent correspondence between the density of the outer shell map and the positions of the two best fitting orientations of E3. As in the case of E1 in the E1E2 complex, the central 2-fold axis of the E3 homodimer is roughly oriented along the periphery of the shell, making the active sites of the enzyme accessible from the annular gap between the E2 core and the outer shell. The similarities in architecture of the E1E2 and E2E3 complexes indicate fundamental similarities in the mechanism of active site coupling involved in the two key stages requiring motion of the swinging lipoyl domain across the annular gap, namely the synthesis of acetyl CoA and regeneration of the dithiolane ring of the lipoyl domain. PMID:16308322

A Randomized Trial of the Effect of Youth Appealing E-Cigarette Advertising on Susceptibility to Use E-Cigarettes Among Youth.

PubMed

Padon, Alisa A; Lochbuehler, Kirsten; Maloney, Erin K; Cappella, Joseph N

2017-07-05

Very little is known about how e-cigarette marketing is being perceived by youth, and the potential effect it will have on youth vaping and smoking behaviors. This limits the ability to identify youth-focused marketing efforts and to design effective policies for the regulation of e-cigarette marketing content and placement. A sample of 417 nonsmoking youth (mean age = 15, SD = 1.3) were randomly assigned to either view four e-cigarette ads with low youth appeal, four e-cigarette ads with high youth appeal or four control ads. After exposure, participants completed covert and overt measurements of e-cigarette and tobacco cigarette attitudes and susceptibility to use. Youth in an e-cigarette ad condition were more likely to select an e-cigarette item in a product choice task compared to control, and had more positive e-cigarette beliefs. Contrary to hypotheses, youth in the low youth appeal condition reported greater susceptibility to trying e-cigarettes and tobacco cigarettes compared to control. Exposure to any e-cigarette advertising may play a role in teens' decision to initiate e-cigarette and tobacco cigarette use. As the Food and Drug Administration now has regulatory authority over the marketing of e-cigarettes, regulations on e-cigarette advertising are suggested. Teens are increasingly being exposed to e-cigarette advertising, and many places are considering e-cigarette regulations, yet we know very little about how e-cigarette advertisements might influence youth tobacco use. This study utilized a novel dataset of e-cigarette ads coded for youth appeal and presented them to a sample of 417 nonsmoking teens in a randomized controlled design to test the effect of features on youth susceptibility to initiating e-cigarette and tobacco cigarette use. The findings inform evidence-based recommendations for regulating the marketing of e-cigarettes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

WW Physics at Future e{sup +}e{sup -} Linear Colliders

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

Barklow, Timothy L

Measurements of triple gauge boson couplings and strong electroweak symmetry breaking effects at future e{sup +}e{sup -} linear colliders are reviewed. The results expected from a future e{sup +}e{sup -} linear collider are compared with LHC expectations.

Search for rare and forbidden decays D+ --> h+/- e+/- e+.

PubMed

He, Q; Muramatsu, H; Park, C S; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Artuso, M; Boulahouache, C; Blusk, S; Butt, J; Dorjkhaidav, O; Li, J; Menaa, N; Mountain, R; Nandakumar, R; Randrianarivony, K; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; Briere, R A; Chen, G P; Chen, J; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Crede, V; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Galik, R S; Gibbons, L; Gittelman, B; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Meyer, T O; Onyisi, P U E; Patterson, J R; Peterson, D; Phillips, E A; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Shepherd, M R; Stroiney, S; Sun, W M; Urner, D; Wilksen, T; Weaver, K M; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Patel, R; Potlia, V; Stoeck, H; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Gollin, G D; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; White, E J; Williams, J; Wiss, J; Asner, D M; Edwards, K W; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Gong, D T; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Li, S Z; Poling, R; Scott, A W; Smith, A; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Zweber, P; Ernst, J; Severini, H; Dytman, S A; Love, W; Mehrabyan, S; Mueller, J A; Savinov, V; Li, Z; Lopez, A; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Adams, G S; Cravey, M; Cummings, J P; Danko, I; Napolitano, J

2005-11-25

Using 0.8 x 10(6) D+ D- pairs collected with the CLEO-c detector at the psi(3770) resonance, we have searched for flavor-changing neutral current and lepton-number-violating decays of D+ mesons to final states with dielectrons. We find no indication of either, obtaining 90% confidence level upper limits of B(D+ --> pi+ e+ e-) < 7.4 x 10(-6), B(D+ --> pi- e+ d+) < 3.6 x 10(-6), B(D+ --> K+ e+ e-) < 6.2 x 10(-6), and B(D+ --> K- e+ e+) < 4.5 x 10(-6).