Brand interactions and social media: enhancing user loyalty through social networking sites

OpenAIRE

Nisar, T.M.; Whitehead, C.

2016-01-01

This paper aims to investigate how user loyalty can be achieved and maintained through social networking sites. More specifically, we intend to test the relationships between brands, user loyalty and social media. The research thus provides insights into user-brand relationships through social media and argues how loyal customers can be through social networking websites. Although there are considerable numbers of studies about loyalty; there exists very limited work studying user loyalty thr...

Cooperative interplay of let-7 mimic and HuR with MYC RNA

OpenAIRE

Gunzburg, Menachem J; Sivakumaran, Andrew; Pendini, Nicole R; Yoon, Je-Hyun; Gorospe, Myriam; Wilce, Matthew Cj; Wilce, Jacqueline A

2015-01-01

Both RNA-binding proteins (RBP) and miRNA play important roles in the regulation of mRNA expression, often acting together to regulate a target mRNA. In some cases the RBP and miRNA have been reported to act competitively, but in other instances they function cooperatively. Here, we investigated HuR function as an enhancer of let-7-mediated translational repression of c-Myc despite the separation of their binding sites. Using an in vitro system, we determined that a let-7 mimic, consisting of...

USER PERCEPTION TOWARDS SOCIAL NETWORKING SITES - AN ANALYTICAL APPROACH

OpenAIRE

Dr. S. Shanmugapriya; A. Kokila

2017-01-01

A social networking site (SNS) or social media is an online platform that people use to build social networks or social relations with other people who share similar personal or career interests, activities, backgrounds or real-life connections. The advent of Social Networking sites and its resources have revolutionized the communication and social relation world. This paper aims to assess the user perception towards SNS like Facebook, Twitter and LinkedIn. In the study data was obtained thro...

End-user Acceptance of Online Shopping Sites in India

OpenAIRE

Bolar K; Shaw B

2015-01-01

Online shopping sites have recently gained momentum in India. Since the ecommerce industry is in infancy state, customer (end user) satisfaction with the online shopping is the prime concern because decreasing customer satisfaction leads to negative electronic word of mouth (eWOM) which is very severe for the business. Through a dataset gathered from 127 online shopping customers in with respect to online shopping sites in India, this study investigates the role of website quality, informatio...

Profiles of social networking sites users in the Netherlands

NARCIS (Netherlands)

Constantinides, Efthymios; Alarcón del Amo, Maria del Carmen; Lorenzo Romero, Carlota

2010-01-01

Online social networking has become a reality and integral part of the daily personal, social and business life. The extraordinary increase of the user numbers of Social Networking Sites (SNS) and the rampant creation of online communities presents businesses with many challenges and opportunities.

High-let radiation carcinogenesis

International Nuclear Information System (INIS)

Fry, R.J.M.; Powers-Risius, P.; Alpen, E.L.; Ainsworth, E.J.; Ullrich, R.L.

1982-01-01

Recent results for neutron radiation-induced tumors are presented to illustrate the complexities of the dose-response curves for high-LET radiation. It is suggested that in order to derive an appropriate model for dose-response curves for the induction of tumors by high-LET radiation it is necessary to take into account dose distribution, cell killing and the susceptibility of the tissue under study. Preliminary results for the induction of Harderian gland tumors in mice exposed to various heavy ion beams are presented. The results suggest that the effectiveness of the heavy ion beams increases with increasing LET. The slopes of the dose-response curves for the different high-LET radiations decrease between 20 and 40 rads and therefore comparisons of the relative effectiveness should be made from data obtained at doses below about 20 to 30 rads

Managing a User’s Vulnerability on a Social Networking Site

Science.gov (United States)

2015-05-01

aid not only the cyberbullying of teenagers but also the cyberstalking and cyberharassment of adults3. On a social networking site, an individual user...news/2011-07-23-facebook-stalker- sentenced_n.htm 3en.wikipedia.org/wiki/ Cyberbullying 1 posts and subsequent interactions. The owner of the site

Investigation of user behavior on social networking sites.

Science.gov (United States)

Waheed, Hajra; Anjum, Maria; Rehman, Mariam; Khawaja, Amina

2017-01-01

Social networking sites (SNS) are used for social and professional interaction with people. SNS popularity has encouraged researchers to analyze the relationship of activities performed on SNS with user behavior. In doing so, the term "user behavior" is rather used ambiguously with different interpretations, which makes it difficult to identify studies on user behavior in relation to SNS. This phenomenon has encouraged this thorough research on the characteristics of user behavior being discussed in the literature. Therefore, in this study, we aim to identify, analyze, and classify the characteristics associated with user behavior to answer the research questions designed to conduct this research. A mapping study (also called scoping study), which is a type of systematic literature review, is employed to identify potential studies from digital databases through a developed protocol. Thematic analysis is carried out for the classification of user behavior. We identified 116 primary studies for full analysis. This study found seven characteristics associated with behavior that have direct influence on SNS use and nine factors that have an indirect effect. All studies were conducted largely under seven areas that set the context of these studies. Findings show that the research on SNS is still in its early stage. The range of topics covered in the analyzed studies is quite expansive, although the depth in terms of number of studies under each topic is quite limited. This study reports that activities performed on SNS are either associated with user behavior or reflect personality characteristics. The findings of this study could be used by practitioners to evaluate their SNS platforms and develop more user-centered applications. These studies can also help organizations to understand better the needs of their employees.

Investigation of user behavior on social networking sites.

Directory of Open Access Journals (Sweden)

Hajra Waheed

Full Text Available Social networking sites (SNS are used for social and professional interaction with people. SNS popularity has encouraged researchers to analyze the relationship of activities performed on SNS with user behavior. In doing so, the term "user behavior" is rather used ambiguously with different interpretations, which makes it difficult to identify studies on user behavior in relation to SNS. This phenomenon has encouraged this thorough research on the characteristics of user behavior being discussed in the literature. Therefore, in this study, we aim to identify, analyze, and classify the characteristics associated with user behavior to answer the research questions designed to conduct this research. A mapping study (also called scoping study, which is a type of systematic literature review, is employed to identify potential studies from digital databases through a developed protocol. Thematic analysis is carried out for the classification of user behavior. We identified 116 primary studies for full analysis. This study found seven characteristics associated with behavior that have direct influence on SNS use and nine factors that have an indirect effect. All studies were conducted largely under seven areas that set the context of these studies. Findings show that the research on SNS is still in its early stage. The range of topics covered in the analyzed studies is quite expansive, although the depth in terms of number of studies under each topic is quite limited. This study reports that activities performed on SNS are either associated with user behavior or reflect personality characteristics. The findings of this study could be used by practitioners to evaluate their SNS platforms and develop more user-centered applications. These studies can also help organizations to understand better the needs of their employees.

MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling.

Science.gov (United States)

Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Lang, Ming-Fei; Yang, Su; Li, Wendong; Shi, Yanhong

2010-02-02

Neural stem cell self-renewal and differentiation is orchestrated by precise control of gene expression involving nuclear receptor TLX. Let-7b, a member of the let-7 microRNA family, is expressed in mammalian brains and exhibits increased expression during neural differentiation. However, the role of let-7b in neural stem cell proliferation and differentiation remains unknown. Here we show that let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1. Overexpression of let-7b led to reduced neural stem cell proliferation and increased neural differentiation, whereas antisense knockdown of let-7b resulted in enhanced proliferation of neural stem cells. Moreover, in utero electroporation of let-7b to embryonic mouse brains led to reduced cell cycle progression in neural stem cells. Introducing an expression vector of Tlx or cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both TLX and cyclin D1 are important targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b, by targeting TLX and cyclin D1, establishes an efficient strategy to control neural stem cell proliferation and differentiation.

Are the users of social networking sites homogeneous? A cross-cultural study

Science.gov (United States)

Alarcón-del-Amo, María-del-Carmen; Gómez-Borja, Miguel-Ángel; Lorenzo-Romero, Carlota

2015-01-01

The growing use of Social Networking Sites (SNS) around the world has made it necessary to understand individuals' behaviors within these sites according to different cultures. Based on a comparative study between two different European countries (The Netherlands versus Spain), a comparison of typologies of networked Internet users has been obtained through a latent segmentation approach. These typologies are based on the frequency with which users perform different activities, their socio-demographic variables, and experience in social networking and interaction patterns. The findings show new insights regarding international segmentation in order to analyse SNS user behaviors in both countries. These results are relevant for marketing strategists eager to use the communication potential of networked individuals and for marketers willing to explore the potential of online networking as a low cost and a highly efficient alternative to traditional networking approaches. For most businesses, expert users could be valuable opinion leaders and potential brand influencers. PMID:26321971

Are the users of social networking sites homogeneous? A cross-cultural study.

Science.gov (United States)

Alarcón-Del-Amo, María-Del-Carmen; Gómez-Borja, Miguel-Ángel; Lorenzo-Romero, Carlota

2015-01-01

The growing use of Social Networking Sites (SNS) around the world has made it necessary to understand individuals' behaviors within these sites according to different cultures. Based on a comparative study between two different European countries (The Netherlands versus Spain), a comparison of typologies of networked Internet users has been obtained through a latent segmentation approach. These typologies are based on the frequency with which users perform different activities, their socio-demographic variables, and experience in social networking and interaction patterns. The findings show new insights regarding international segmentation in order to analyse SNS user behaviors in both countries. These results are relevant for marketing strategists eager to use the communication potential of networked individuals and for marketers willing to explore the potential of online networking as a low cost and a highly efficient alternative to traditional networking approaches. For most businesses, expert users could be valuable opinion leaders and potential brand influencers.

Are the users of Social Networking Sites homogeneous? A cross-cultural study

Directory of Open Access Journals (Sweden)

MARÍA-DEL-CARMEN eALARCÓN-DEL-AMO

2015-08-01

Full Text Available The growing use of Social Networking Sites (SNS around the world has made it necessary to understand individuals’ behaviours within these sites according to different cultures. Based on a comparative study between two different European countries (The Netherlands versus Spain, a comparison of typologies of networked Internet users has been obtained through a latent segmentation approach. These typologies are based on the frequency with which users perform different activities, their socio-demographic variables, and experience in social networking and interaction patterns. The findings show new insights regarding international segmentation in order to analyse SNS user behaviours in both countries. These results are relevant for marketing strategists eager to use the communication potential of networked individuals and for marketers willing to explore the potential of online networking as a low cost and a highly efficient alternative to traditional networking approaches. For most businesses, expert users could be valuable opinion leaders and potential brand influencers.

RBE-LET relationships of high-LET radiations in drosophila mutations

International Nuclear Information System (INIS)

Yoshikawa, Isao; Takatsuji, Toshihiro; Nagano, Masaaki; Takada, Jun; Endo, Satoru; Hoshi, Masaharu

1999-01-01

The relative biological effectiveness (RBE) of 252 Cf neutrons and synchrotron-generated high-energy charged particles for mutation induction was evaluated as a function of linear energy transfer (LET), using the loss of heterozygosity for wing-hair mutations and the reversion of the mutant white-ivory eye-color in Drosophila melanogaster. Loss of heterozygosity for wing-hair mutations results predominantly from mitotic crossing over induced in wing anlage cells of larvae, while the reverse mutation of eye-color is due to an intragenic structural change (2.96 kb-DNA excision) in the white locus on the X-chromosome. The measurements were performed in a combined mutation assay system so that induced mutant wing-hair clones as well as revertant eye-color clone can be detected simultaneously in the same individual. Larvae were irradiated at the age of 3 days post oviposition with 252 Cf neutrons, carbon beam or neon beam. For the neutron irradiation, the RBE values for wing-hair mutations were larger than that for eye-color mutation by about 7 fold. The RBE of carbon ions for producing the wing-hair mutations increased with increase in LET. The estimated RBE values were found to be in the range 2 to 6.5 for the wing-hair. For neon beam irradiation, the RBE values for wing-hair mutations peak near 150 keV/μm and decrease with further increase in LET. On the other hand, the RBE values for the induction of the eye-color mutation are nearly unity in 252 Cf neutrons and both ions throughout the LET range irradiated. We discuss the relationships between the initial DNA damage and LET in considering the mechanism of somatic mutation induction. (author)

LET-effects in DNA

International Nuclear Information System (INIS)

Kraft, G.; Taucher-Scholz, G.; Heilmann, J.

1995-01-01

The use of heavy particles in radiobiological experiments provides a fundamental tool to study the influence of different ionization densities and to prove the physical basis of models and theories. The knowledge of the interaction of high LET radiation (LET: linear energy transfer [keV/microm]) with biological matter is of great importance for the application of neutrons, protons and heavier ions in radiotherapy. It is also essential in radioprotection to estimate the risk in case of exposure to high LET radiation. In this contribution, an introductory view on the physical properties of ions is given and the cellular response to high LET radiation is summarized. Then the measurements of strand break induction of DNA in solution and in intracellular DNA are reported and compared to cell survival. The possibility of changes in the quality of the lesions is discussed and finally the present status of model calculations in comparison to the experiments is given

Gene conversion in yeast as a function of linear energy transfer (LET) for low-LET radiation

International Nuclear Information System (INIS)

Unrau, P.; Morrison, D.P.; Johnson, J.R.

1992-05-01

The relative biological effectiveness (RBE) for low-LET radiation is known to depend on such factors as LET and dose rate. Microdosimetric calculations indicate that the biological target size could also be an important parameter, and calculations predict that the RBE for effects produced by hits in target sizes below about 100 nm should be unity for all low LET radiation. We have measured that RBE for gene conversion in yeast (a small target) for five different low LET photon sources, and the results were consistent with an RBE of unity, which agrees with microdosimetric predictions. 4 refs

Utilization Possibilities of Area Definition in User Space for User-Centric Pervasive-Adaptive Systems

Science.gov (United States)

Krejcar, Ondrej

The ability to let a mobile device determine its location in an indoor environment supports the creation of a new range of mobile information system applications. The goal of my project is to complement the data networking capabilities of RF wireless LANs with accurate user location and tracking capabilities for user needed data prebuffering. I created a location based system enhancement for locating and tracking users of indoor information system. User position is used for data prebuffering and pushing information from a server to his mobile client. All server data is saved as artifacts (together) with its indoor position information. The area definition for artifacts selecting is described for current and predicted user position along with valuating options for artifacts ranging. Future trends are also discussed.

LIN28 expression in malignant germ cell tumors down-regulates let-7 and increases oncogene levels

Science.gov (United States)

Murray, Matthew J.; Saini, Harpreet K.; Siegler, Charlotte A.; Hanning, Jennifer E.; Barker, Emily M.; van Dongen, Stijn; Ward, Dawn M.; Raby, Katie L.; Groves, Ian J.; Scarpini, Cinzia G.; Pett, Mark R.; Thornton, Claire M.; Enright, Anton J.; Nicholson, James C.; Coleman, Nicholas

2013-01-01

Despite their clinico-pathologic heterogeneity, malignant germ-cell-tumors (GCTs) share molecular abnormalities that are likely to be functionally important. In this study, we investigated the potential significance of down-regulation of the let-7 family of tumor-suppressor microRNAs in malignant-GCTs. Microarray results from pediatric and adult samples (n=45) showed that LIN28, the negative-regulator of let-7 biogenesis, was abundant in malignant-GCTs, regardless of patient age, tumor site or histologic subtype. Indeed, a strong negative-correlation existed between LIN28 and let-7 levels in specimens with matched datasets. Low let-7 levels were biologically significant, since the sequence complementary to the 2-7nt common let-7 seed ‘GAGGUA’ was enriched in the 3′untranslated regions of mRNAs up-regulated in pediatric and adult malignant-GCTs, compared with normal gonads (a mixture of germ cells and somatic cells). We identified 27 mRNA targets of let-7 that were up-regulated in malignant-GCT cells, confirming significant negative-correlations with let-7 levels. Among 16 mRNAs examined in a largely independent set of specimens by qRT-PCR, we defined negative-associations with let-7e levels for six oncogenes, including MYCN, AURKB, CCNF, RRM2, MKI67 and C12orf5 (when including normal control tissues). Importantly, LIN28 depletion in malignant-GCT cells restored let-7 levels and repressed all of these oncogenic let-7 mRNA targets, with LIN28 levels correlating with cell proliferation and MYCN levels. Conversely, ectopic expression of let-7e was sufficient to reduce proliferation and down-regulate MYCN, AURKB and LIN28, the latter via a double-negative feedback loop. We concluded that the LIN28/let-7 pathway has a critical pathobiological role in malignant-GCTs and therefore offers a promising target for therapeutic intervention. PMID:23774216

VR-Smart Home, prototyping of a user centered design system

NARCIS (Netherlands)

Heidari Jozam, M.; Allameh, E.; Vries, de B.; Timmermans, H.J.P.; Masoud, M.; Andreev, S.; Balandin, S.; Yevgeni, Koucheryavy

2012-01-01

In this paper, we propose a prototype of a user centered design system for Smart Homes which lets users: (1) configure different interactive tasks, and (2) express activity specifications and preferences during the design process. The main objective of this paper is how to create and to implement VR

Neoplastic cell transformation by high-LET radiation - Molecular mechanisms

Science.gov (United States)

Yang, Tracy Chui-Hsu; Craise, Laurie M.; Tobias, Cornelius A.; Mei, Man-Tong

1989-01-01

Quantitative data were collected on dose-response curves of cultured mouse-embryo cells (C3H10T1/2) irradiated with heavy ions of various charges and energies. Results suggests that two breaks formed on DNA within 80 A may cause cell transformation and that two DNA breaks formed within 20 A may be lethal. From results of experiments with restriction enzymes which produce DNA damages at specific sites, it was found that DNA double strand breaks are important primary lesions for radiogenic cell transformation and that blunt-ended double-strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship for high-LET radiation is similar to that for HGPRT locus mutation, chromosomal deletion, and cell transformation, indicating that common lesions may be involved in these radiation effects.

New "persona" concept helps site designers cater to target user segments' needs.

Science.gov (United States)

2004-09-01

Using the relatively new "persona" design concept, Web strategists create a set of archetypical user characters, each one representing one of their site's primary audiences. Then, as their site is constructed or upgraded, they champion the personas, arguing on their behalf and forcing the design team to take each audience's needs and wants into account.

High-LET particle exposure of Skylab astronauts

International Nuclear Information System (INIS)

Benton, E.V.; Peterson, D.D.; Bailey, J.V.; Parnell, T.

1977-01-01

High-LET particle radiation was registered in nuclear track recording plastic dosimeters worn on the wrists of Skylab astronauts and located in a heavily shielded film vault. The mission-average planar flux of high-LET particles with LET >= 100 keV/micron . tissue has been determined to be 2.7 +- 0.6 particles/cm 2 . day . 2π sr and 0.34 +- 0.4 particles/cm 2 . day . 2π sr, respectively, for the nine astronauts and for the film vault. Comparison of results representative of a wide range of shielding depths reveals that the magnitude and slope of the integral LET spectrum of high-LET particles inside spacecraft are proportional to the amount of shielding. (author)

Low LET radiation-induced telomerase catalytic subunit promoter activation is mediated by nuclear factor Kappa B

International Nuclear Information System (INIS)

Natarajan, M.; Hong, F.A.; Mohan, S.; Herman, T.S.

2003-01-01

Full text: The objective of this study is to understand whether low doses of low LET radiation induces survival advantage in normal cells. As an increase in telomerase activity is associated with longevity and cell proliferation, we examined the telomerase response following gamma-irradiation in normal aortic endothelial cells. Telomeric Repeat Amplification Protocol assay following low LET radiation showed an increase in telomerase enzyme activity as early as 8 h post irradiation and reaches its maximum at 24 h. Subsequent analysis revealed that the increased telomerse enzyme activity is due to increased synthesis resulting from an increased transcription. Examination of transcriptional activation of telomerase reverse transcriptase (TERT) promoter regulation showed an enhanced transcription of the telomerse gene following gamma-irradiation. In our previous reports we documented an increase in NF-kB DNA-binding property following low LET radiation (3). Therefore, to determine whether the activation of NF-kB-signaling is responsible for induced TERT promoter activation, cells transiently transfected with minimal promoter region of TERT containing wild type or mutant NF-kB binding site were examined following low LET radiation. TERT promoter activation was induced in wild type transfected cells whereas, in mutant kB binding site, the activation remained at the basal level similar to that of un-irradiated cells. More significantly, the gamma-ray mediated promoter activation of telomerase gene as well as induce telomerase enzyme activity was abrogated by ectopically expressing the IkBa mutant (IkBa (S32A/S36A)), which blocks NF-kB activation. The results thus suggest that exposure to low LET radiation could induce telomerase activity and the activation is at least, in part, mediated by the transcription factor NF-kB. Sustained activation of telomerase in these cells after low LET radiation may impart extended life span

Ataxia telangiectasia: LET dependence of cellular inactivation

International Nuclear Information System (INIS)

Blakely, E.A.; Tobias, C.A.

1984-01-01

Human Ataxia telangiectasia cells (AT 2SF line) have been irradiated in vitro under aerobic and hypoxic conditions with heavy-ion beams accelerated at the Berkeley Bevalac as a part of a study to characterize the radiation responses of genetically sensitive and resistant cell lines to high LET radiations. Results from track-segment exposures to neon, silicon, argon and iron ion beams accelerated to initial energies of from 225 to 670 MeV/amu provided an LET range between 30 to 1,000 KeV/μm. The data indicate: (1) The sensitivity of AT cells increases with increasing LET, similar to resistant human lines (e.g., T-1 cells). However, due to efficient repair, T-1 cells are more resistant than AT cells at LET values below 200 keV/μm; (2) Maximum cell kill occurs for both lines at 100-200 keV/μm; at higher LET the sensitivity of the two lines approach each other; (3) There is only small variation in the sensitivity of AT cells to particles of various atomic numbers at the same LET; differences are more pronounced in the LET domain between 50 and 200 keV/μm; and (4) AT cells have slightly lower OER values than T-1 cells in the range of LET studied below 200 keV/μm

Calculated LET-Spectrum of Antiprotons

DEFF Research Database (Denmark)

Bassler, Niels

-LET components resulting from the annihilation. Though, the calculations of dose-averaged LET in the entry region may suggest that the RBE of antiprotons in the plateau region could significantly differ from unity. Materials and Methods Monte Carlo simulations using FLUKA were performed for calculating...

The concept of average LET values determination

International Nuclear Information System (INIS)

Makarewicz, M.

1981-01-01

The concept of average LET (linear energy transfer) values determination, i.e. ordinary moments of LET in absorbed dose distribution vs. LET of ionizing radiation of any kind and any spectrum (even the unknown ones) has been presented. The method is based on measurement of ionization current with several values of voltage supplying an ionization chamber operating in conditions of columnar recombination of ions or ion recombination in clusters while the chamber is placed in the radiation field at the point of interest. By fitting a suitable algebraic expression to the measured current values one can obtain coefficients of the expression which can be interpreted as values of LET moments. One of the advantages of the method is its experimental and computational simplicity. It has been shown that for numerical estimation of certain effects dependent on LET of radiation it is not necessary to know the dose distribution but only a number of parameters of the distribution, i.e. the LET moments. (author)

VE-821, an ATR inhibitor, causes radiosensitization in human tumor cells irradiated with high LET radiation

International Nuclear Information System (INIS)

Fujisawa, Hiroshi; Nakajima, Nakako Izumi; Sunada, Shigeaki; Lee, Younghyun; Hirakawa, Hirokazu; Yajima, Hirohiko; Fujimori, Akira; Uesaka, Mitsuru; Okayasu, Ryuichi

2015-01-01

High linear energy transfer (LET) radiation such as carbon ion particles is successfully used for treatment of solid tumors. The reason why high LET radiation accomplishes greater tumor-killing than X-rays is still not completely understood. One factor would be the clustered or complex-type DNA damages. We previously reported that complex DNA double-strand breaks produced by high LET radiation enhanced DNA end resection, and this could lead to higher kinase activity of ATR protein recruited to RPA-coated single-stranded DNA. Although the effect of ATR inhibition on cells exposed to low LET gamma-rays has recently been reported, little is known regarding the effect of ATR inhibitor on cells treated with high LET radiation. The purpose of this study is to investigate the effects of the ATR inhibitor VE-821 in human tumor and normal cells irradiated with high LET carbon ions. HeLa, U2OS, and 1BR-hTERT (normal) cells were pre-treated with 1 μM VE-821 for 1 hour and irradiated with either high LET carbon ions or X-rays. Cell survival, cell cycle distribution, cell growth, and micronuclei formation were evaluated. VE-821 caused abrogation of G2/M checkpoint and forced irradiated cells to divide into daughter cells. We also found that carbon ions caused a higher number of multiple micronuclei than X-rays, leading to decreased cell survival in tumor cells when treated with VE-821, while the survival of irradiated normal cells were not significantly affected by this inhibitor. ATR inhibitor would be an effective tumor radiosensitizer with carbon ion irradiation. The online version of this article (doi:10.1186/s13014-015-0464-y) contains supplementary material, which is available to authorized users

Sketching user experiences the workbook

CERN Document Server

Greenberg, Saul; Marquardt, Nicolai; Buxton, Bill

2012-01-01

In Sketching User Experiences: The Workbook, you will learn, through step-by-step instructions and exercises, various sketching methods that will let you express your design ideas about user experiences across time. Collectively, these methods will be your sketching repertoire: a toolkit where you can choose the method most appropriate for developing your ideas, which will help you cultivate a culture of experience-based design and critique in your workplace. Features standalone modules detailing methods and exercises for practitioners who want to learn and develop their sketching skills E

Psychological risk factors of addiction to social networking site among Chinese smart phone users

OpenAIRE

Wu, Anise M. S.; Cheung, Vivi I.; Ku, L.; Hung, Eva P. W.

2013-01-01

Background and aims: Smartphones allow users to access social networking sites (SNSs) whenever and wherever they want. Such easy availability and accessibility may increase their vulnerability to addiction. Based on the social cognitive theory (SCT), we examined the impacts of outcome expectancies, self-efficacy, and impulsivity on young Chinese smartphone users' addictive tendencies toward SNSs. Methods: Two hundred seventy-seven Macau young smartphone users (116 males and 161 females; mean ...

Profiting from innovative user communities

DEFF Research Database (Denmark)

Jeppesen, Lars Bo

Modding - the modification of existing products by consumers - is increasingly exploited by manufacturers to enhance product development and sales. In the computer games industry modding has evolved into a development model in which users act as unpaid `complementors' to manufacturers' product pl......, a manufacturer can incorporate and commercialize the best complements found in the user communities. Keywords: innovation, modding, user communities, software platform, business model. JEL code(s): L21; L23; O31; O32...... platforms. This article explains how manufacturers can profit from their abilities to organize and facilitate a process of innovation by user communities and capture the value of the innovations produced in such communities. When managed strategically, two distinct, but not mutually exclusive business...... models appear from the production of user complements: firstly, a manufacturer can let the (free) user complements `drift' in the user communities, where they increase the value to consumers of owning the given platform and thus can be expected to generate increased platform sales, and secondly...

Adaptive User Profiles in Pervasive Advertising Environments

Science.gov (United States)

Alt, Florian; Balz, Moritz; Kristes, Stefanie; Shirazi, Alireza Sahami; Mennenöh, Julian; Schmidt, Albrecht; Schröder, Hendrik; Goedicke, Michael

Nowadays modern advertising environments try to provide more efficient ads by targeting costumers based on their interests. Various approaches exist today as to how information about the users' interests can be gathered. Users can deliberately and explicitly provide this information or user's shopping behaviors can be analyzed implicitly. We implemented an advertising platform to simulate an advertising environment and present adaptive profiles, which let users setup profiles based on a self-assessment, and enhance those profiles with information about their real shopping behavior as well as about their activity intensity. Additionally, we explain how pervasive technologies such as Bluetooth can be used to create a profile anonymously and unobtrusively.

Let-7b Regulates Myoblast Proliferation by Inhibiting IGF2BP3 Expression in Dwarf and Normal Chicken

Science.gov (United States)

Lin, Shumao; Luo, Wen; Ye, Yaqiong; Bekele, Endashaw J.; Nie, Qinghua; Li, Yugu; Zhang, Xiquan

2017-01-01

The sex-linked dwarf chicken is caused by the mutation of growth hormone receptor (GHR) gene and characterized by shorter shanks, lower body weight, smaller muscle fiber diameter and fewer muscle fiber number. However, the precise regulatory pathways that lead to the inhibition of skeletal muscle growth in dwarf chickens still remain unclear. Here we found a let-7b mediated pathway might play important role in the regulation of dwarf chicken skeletal muscle growth. Let-7b has higher expression in the skeletal muscle of dwarf chicken than in normal chicken, and the expression of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), which is a translational activator of IGF2, showed opposite expression trend to let-7b. In vitro cellular assays validated that let-7b directly inhibits IGF2BP3 expression through binding to its 3′UTR region, and the protein level but not mRNA level of IGF2 would be reduced in let-7b overexpressed chicken myoblast. Let-7b can inhibit cell proliferation and induce cell cycle arrest in chicken myoblast through let-7b-IGF2BP3-IGF2 signaling pathway. Additionally, let-7b can also regulate skeletal muscle growth through let-7b-GHR-GHR downstream genes pathway, but this pathway is non-existent in dwarf chicken because of the deletion mutation of GHR 3′UTR. Notably, as the loss binding site of GHR for let-7b, let-7b has enhanced its binding and inhibition on IGF2BP3 in dwarf myoblast, suggesting that the miRNA can balance its inhibiting effect through dynamic regulate its binding to target genes. Collectively, these results not only indicate that let-7b can inhibit skeletal muscle growth through let-7b-IGF2BP3-IGF2 signaling pathway, but also show that let-7b regulates myoblast proliferation by inhibiting IGF2BP3 expression in dwarf and normal chickens. PMID:28736533

77 FR 16566 - Submission for OMB Review, Comment Request, Proposed Collection: Let's Move Museums, Let's Move...

Science.gov (United States)

2012-03-21

..., Proposed Collection: Let's Move Museums, Let's Move Gardens AGENCY: Institute of Museum and Library..., comment request. SUMMARY: The Institute of Museum and Library Services announces that the following... functions of the agency, including whether the information will have practical utility; Evaluate the...

Appropriate User Acceptance Criteria For New Social Media Sites

OpenAIRE

Mirsat Yeşiltepe

2016-01-01

Nowadays social media sites have attracted many of users and they have become the mostly commonly used websites for public. These websites are used by individuals, small and even big organizations for various purposes, such as meeting your old friends, sharing your own experiences, sharing pictures and videos, promoting businesses, sharing knowledge etc. Their popularity is increasing at an increasing rate. User’s needs are endless so there will be some new area for creating...

User Defined Structural Searches in MediaWiki

DEFF Research Database (Denmark)

Bouvin, Niels Olof; Albertsen, Johannes

2008-01-01

Wikipedia has been the poster child of user contributed content using the space of MediaWiki as the canvas on which to write. While well suited for authoring simple hypermedia documents, MediaWiki does not lend itself easily to let the author create dynamically assembled documents, or create pages...

LET effects on normal and radiosensitive cell lines

International Nuclear Information System (INIS)

Geard, C.R.; Travisano, M.

1986-01-01

Charged particles in the track segment mode were produced by the RARAF Van de Graaff accelerator and used to irradiate two CHO cell lines, a radiosensitive hypermutable line EM9 and its normal parent AA8. Asynchronous cells were irradiated attached to 6 micrometer thick Mylar with protons, deuterons and helium-3 particles at LETs ranging from 10 to 150 keV per micrometer. A 50 kVp x-ray tube integrated into the track segment facility provided a low LET comparison. Following irradiation cells were monitored for clonogenicity, and in a separate series of experiments frequencies of sister chromatid exchanges. Up to 9 experiments were carried out at each LET, with a total of 8 radiations of different LETs being compared. The optimally effective LET for cell survival was between 80 and 120 keV per micrometer, with the 150 keV per micrometer particles indicating energy wastage. The differential between the normal and radiosensitive cell lines was maintained at all LETs

Manually Classifying User Search Queries on an Academic Library Web Site

Science.gov (United States)

Chapman, Suzanne; Desai, Shevon; Hagedorn, Kat; Varnum, Ken; Mishra, Sonali; Piacentine, Julie

2013-01-01

The University of Michigan Library wanted to learn more about the kinds of searches its users were conducting through the "one search" search box on the Library Web site. Library staff conducted two investigations. A preliminary investigation in 2011 involved the manual review of the 100 most frequently occurring queries conducted…

Design criteria for a hemispherical detector for LET measurements

International Nuclear Information System (INIS)

Schell, M.C.; DeLuca, P.M. Jr.; Pearson, D.W.; Attix, F.H.

1980-01-01

A detector for the direct measurement of the Linear Energy Transfer (LET) in cylindrical geometry was developed by Brandan and DeLuca. The detector successfully measured the LET of protons and a fraction of the heavy charged particles generated in cylindrical A150 plastic and graphite walls by 14.8 MeV neutrons. In this report, we present design tests for the hemispherical LET detector which will measure the LET of charged particles in spherical geometry and allow comparison with calculated LET spectra. The hemispherical LET detector will also provide a data base for radiobiological predictions with the Track Structure Model by Katz. A comparison of predictions of radiobiological effects by the Theory of Dual Radiation Action and the Track Structure Model by Edwards and the authors indicate that the Track Structure Model predicts cell survival as a function of dose more accurately and hence an additional motivation for the present construction of the hemispherical LET detector

Psychological risk factors of addiction to social networking sites among Chinese smartphone users.

Science.gov (United States)

Wu, Anise M S; Cheung, Vivi I; Ku, Lisbeth; Hung, Eva P W

2013-09-01

Smartphones allow users to access social networking sites (SNSs) whenever and wherever they want. Such easy availability and accessibility may increase their vulnerability to addiction. Based on the social cognitive theory (SCT), we examined the impacts of outcome expectancies, self-efficacy, and impulsivity on young Chinese smartphone users' addictive tendencies toward SNSs. Two hundred seventy-seven Macau young smartphone users (116 males and 161 females; mean age = 26.62) filled out an online Chinese questionnaire concerning their usage of social networking sites via smartphones, addiction tendencies toward SNSs, impulsivity trait, outcome expectancies toward the use, and Internet self-efficacy. The findings revealed that those who spent more time on SNSs also reported higher addictive tendencies. Addictive tendencies were positively correlated with both outcome expectancies and impulsivity, but negatively associated with Internet self-efficacy. These three psychological variables explained 23% of the variance in addictive tendencies. The findings of this study suggest that, compared to demographics, psychological factors provide a better account for addictive tendencies towards SNSs among Chinese smartphone users in Macau. The three psychological risk factors were low Internet self-efficacy, favorable outcome expectancies, and high impulsivity trait. Educational campaigns with screening procedures for high-risk groups are recommended for effective prevention and treatment.

9 CFR 130.18 - User fees for veterinary diagnostic reagents produced at NVSL or other authorized site (excluding...

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false User fees for veterinary diagnostic reagents produced at NVSL or other authorized site (excluding FADDL). 130.18 Section 130.18 Animals and... § 130.18 User fees for veterinary diagnostic reagents produced at NVSL or other authorized site...

LET calibration for CR-39 detectors in different oxygen environments

International Nuclear Information System (INIS)

Zhou, D.; Semones, E.; Weyland, M.; Benton, E.R.

2007-01-01

High LET (linear energy transfer) radiation is the main contributor to the radiation field in low Earth orbit (LEO) in terms of dose equivalent. CR-39 plastic nuclear track detectors (PNTDs) can measure the LET spectrum and charge spectrum for the complicated radiation field in space. Previous research indicated that the sensitivity of CR-39 is different for CR-39 PNTDs working in different oxygen environments. LET calibration for CR-39 detectors in different oxygen environments is needed. Almost all the previous LET calibration work was carried out for CR-39 detectors in good-oxygen condition, LET calibration work for CR-39 in poor-oxygen condition has not been conducted until our work. Systematic LET calibrations were carried out by JSC-SRAG (Space Radiation Analysis Group) for CR-39 detectors working in different oxygen environments and abundant results of LET calibrations were obtained. This paper introduces the method for CR-39 LET calibration, presents and discusses the calibration results and some applications

Gene-expression profiling of Saccharomyces cerevisiae irradiated by high-LET radiations

Data.gov (United States)

National Aeronautics and Space Administration — Ionizing radiations are categorized by linear energy transfer (LET) into low-LET and high-LET. High-LET is considered to have a higher relative biological...

Precise let-7 expression levels balance organ regeneration against tumor suppression

Science.gov (United States)

Wu, Linwei; Nguyen, Liem H; Zhou, Kejin; de Soysa, T Yvanka; Li, Lin; Miller, Jason B; Tian, Jianmin; Locker, Joseph; Zhang, Shuyuan; Shinoda, Gen; Seligson, Marc T; Zeitels, Lauren R; Acharya, Asha; Wang, Sam C; Mendell, Joshua T; He, Xiaoshun; Nishino, Jinsuke; Morrison, Sean J; Siegwart, Daniel J; Daley, George Q; Shyh-Chang, Ng; Zhu, Hao

2015-01-01

The in vivo roles for even the most intensely studied microRNAs remain poorly defined. Here, analysis of mouse models revealed that let-7, a large and ancient microRNA family, performs tumor suppressive roles at the expense of regeneration. Too little or too much let-7 resulted in compromised protection against cancer or tissue damage, respectively. Modest let-7 overexpression abrogated MYC-driven liver cancer by antagonizing multiple let-7 sensitive oncogenes. However, the same level of overexpression blocked liver regeneration, while let-7 deletion enhanced it, demonstrating that distinct let-7 levels can mediate desirable phenotypes. let-7 dependent regeneration phenotypes resulted from influences on the insulin-PI3K-mTOR pathway. We found that chronic high-dose let-7 overexpression caused liver damage and degeneration, paradoxically leading to tumorigenesis. These dose-dependent roles for let-7 in tissue repair and tumorigenesis rationalize the tight regulation of this microRNA in development, and have important implications for let-7 based therapeutics. DOI: http://dx.doi.org/10.7554/eLife.09431.001 PMID:26445246

Let's do comprehension 5-6

CERN Document Server

Brodie, Andrew

2015-01-01

Let's Do Comprehension is a brand new series of six titles in the popular 'Let's Do' range. Each book contains a rich variety of stimulating reading passages, accompanied by questions of varying difficulty. Designed to be used at home, each book includes tips and clues from Alice the Alligator as well as extra challenges in Brodie's Brain Boosters. There is a clear answer section for reference by parents and children, together with bright, colourful reward stickers.

Let's do comprehension 8-9

CERN Document Server

Brodie, Andrew

2015-01-01

Let's Do Comprehension is a brand new series of six titles in the popular 'Let's Do' range. Each book contains a rich variety of stimulating reading passages, accompanied by questions of varying difficulty. Designed to be used at home, each book includes tips and clues from Alice the Alligator as well as extra challenges in Brodie's Brain Boosters. There is a clear answer section for reference by parents and children, together with bright, colourful reward stickers.

Pri-let-7a-1 rs10739971 polymorphism is associated with gastric cancer prognosis and might affect mature let-7a expression

Directory of Open Access Journals (Sweden)

Li Y

2016-07-01

Full Text Available Ying Li, Qian Xu, Jingwei Liu, Caiyun He, Quan Yuan, Chengzhong Xing, Yuan Yuan Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University, Liaoning Provincial Education Department, Shenyang, People’s Republic of China Abstract: The relationship between the pri-let-7a-1 rs10739971 polymorphism and gastric cancer (GC risk has been reported. However, the role of this polymorphism in the prognosis of GC remains largely elusive. Sequenom MassARRAY platform method and the polymerase chain reaction (PCR-restriction fragment length polymorphism were used to investigate pri-let-7a-1 rs10739971 G→A in 334 GC patients. Real-time PCR detected expression of mature let-7a in serum and tissue. Patients with AA or GA+AA genotypes of the pri-let-7a-1 rs10739971 polymorphism demonstrated significantly longer survival time than those with the wild GG genotype. Stratified analysis indicated that survival time was significantly longer in women with AA or GA+AA genotypes and in Borrmann type I/II patients with GA heterozygote or GA+AA genotypes. AA genotype was more frequent in the lymphatic-metastasis-negative subgroup. Serum mature let-7a expression in healthy people with the GA heterozygote and the GA+AA genotype was higher than in those with the GG genotype, and the difference remained significant in the female healthy subgroup. Pri-let-7a-1 rs10739971 polymorphism might be a biomarker for GC prognosis, especially for female and Borrmann type I/II patients. The pri-let-7a-1 rs10739971 polymorphism might affect serum mature let-7a expression, and partly explain the mechanism of the relationship between the pri-let-7a-1 rs10739971 polymorphism and GC survival. Keywords: miRNA, let-7a, polymorphism, gastric cancer, prognosis, expression

The Lin28/let-7 axis regulates glucose metabolism

Science.gov (United States)

Zhu, Hao; Shyh-Chang, Ng; Segrè, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q.

2012-01-01

SUMMARY The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by blocking let-7 biogenesis. In studies of the Lin28/let-7 pathway, we discovered unexpected roles in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promoted an insulin-sensitized state that resisted high fat diet-induced diabetes, whereas muscle-specific loss of Lin28a and overexpression of let-7 resulted in insulin resistance and impaired glucose tolerance. These phenomena occurred in part through let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. The mTOR inhibitor rapamycin abrogated the enhanced glucose uptake and insulin-sensitivity conferred by Lin28a in vitro and in vivo. In addition, we found that let-7 targets were enriched for genes that contain SNPs associated with type 2 diabetes and fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. PMID:21962509

MicroRNA hsa-let-7b suppresses the odonto/osteogenic differentiation capacity of stem cells from apical papilla by targeting MMP1.

Science.gov (United States)

Wang, Yanqiu; Pang, Xiyao; Wu, Jintao; Jin, Lin; Yu, Yan; Gobin, Romila; Yu, Jinhua

2018-01-31

MicroRNA let-7 family acts as the key regulator of the differentiation of mesenchymal stem cells (MSCs). However, the influence of let-7b on biological characteristics of stem cells from apical papilla (SCAPs) is still controversial. In this study, the expression of hsa-let-7b was obviously downregulated during the osteogenic differentiation of SCAPs. SCAPs were then infected with hsa-let-7b or hsa-let-7b inhibitor lentiviruses. The proliferation ability was determined by CCK-8 and flow cytometry. The odonto/osteogenic differentiation capacity was analyzed by alkaline phosphatase (ALP) activity, alizarin red staining, Western blot assay, and real-time RT-PCR. Bioinformatics analysis was used to screen out the target of hsa-let-7b and the target relationship was confirmed by dual luciferase reporter assay. Hsa-let-7b was of no influence on the proliferation of SCAPs. Interferential expression of hsa-let-7b increased the ALP activity as well as the formation of calcified nodules of SCAPs. Moreover, the mRNA levels of osteoblastic markers (ALP, RUNX2, OSX, OPN, and OCN) were upregulated while the protein levels of DSPP, ALP, RUNX2, OSX, OPN, and OCN also increased considerably. Conversely, overexpression of hsa-let-7b inhibited the odonto/osteogenic differentiation capacity of SCAPs. Bioinformatics analysis revealed a putative binding site of hsa-let-7b in the matrix metalloproteinase 1 (MMP1) 3'-untranslated region (3'-UTR). Dual luciferase reporter assay confirmed that hsa-let-7b targets MMP1. The odonto/osteogenic differentiation ability of SCAPs ascended after repression of hsa-let-7b, which was then reversed after co-transfection with siMMP1. Together, hsa-let-7b can suppress the odonto/osteogenic differentiation capacity of SCAPs by targeting MMP1. © 2018 Wiley Periodicals, Inc.

Blood-letting in anorexia nervosa: a case study.

Science.gov (United States)

Morgan, J F; Lacey, J H

2000-05-01

Deliberate blood-letting has been characterized as an alternative to purging behavior in bulimia. We describe a female healthcare worker with an 8-year history of restrictive anorexia nervosa, who initially presented with anemia, using blood-letting, cold baths, and starvation to control her mental state. In contrast with the previous cases of bulimia, the aim of blood-letting in this case of anorexia nervosa was to achieve anemia. She compared the psychic correlates of anemia to emaciation, rather than to deliberate self-harm or purging. We note that mainstream 19th century psychiatry prescribed "baths, blood-letting and diet" as a treatment of "madness." Copyright 2000 by John Wiley & Sons, Inc.

The Lin28/let-7 Axis Regulates Glucose Metabolism

NARCIS (Netherlands)

Zhu, Hao; Shyh-Chang, Ng; Segre, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G.; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q.

2011-01-01

The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating-metabolism. When overexpressed in mice, both

Letting die: A moral defence | Adenugba | Sophia: An African ...

African Journals Online (AJOL)

This paper draws a distinction between letting die and active euthanasia. It argues that there is a moral difference between letting die and active euthanasia which strictly intends to cause death. The difference between letting die and active euthanasia lies in intention though intention in both cases can be said to be ...

Effects of organizational scheme and labeling on task performance in product-centered and user-centered retail Web sites.

Science.gov (United States)

Resnick, Marc L; Sanchez, Julian

2004-01-01

As companies increase the quantity of information they provide through their Web sites, it is critical that content is structured with an appropriate architecture. However, resource constraints often limit the ability of companies to apply all Web design principles completely. This study quantifies the effects of two major information architecture principles in a controlled study that isolates the incremental effects of organizational scheme and labeling on user performance and satisfaction. Sixty participants with a wide range of Internet and on-line shopping experience were recruited to complete a series of shopping tasks on a prototype retail shopping Web site. User-centered labels provided a significant benefit in performance and satisfaction over labels obtained through company-centered methods. User-centered organization did not result in improved performance except when the label quality was poor. Significant interactions suggest specific guidelines for allocating resources in Web site design. Applications of this research include the design of Web sites for any commercial application, particularly E-commerce.

The dependence of relative biological effectiveness from LET

International Nuclear Information System (INIS)

Savich, A.V.

1985-01-01

A dependence of radiation-chemical yields of DNA injuries on the LET value is found for two transformations - one and two-strand breaks of it. It is shown that the yield of one-strand breaks decreases with the increase of LET value, and the quantity of two-strand breaks at first increases reaching the maximum value within the LET range from 100 up to 150 eV/nm and then decreases. The considered semiempiric theories of the RBE dependences on LET permits using the experimentally determined parameters characterizing radiosensitivity, to estimate the efficiency of the effect of ionizing radiation on cells at different doses, types of radiation and levels of saturation with oxygen. The stage of the cell cycle is also taken into account

Let G be a group

DEFF Research Database (Denmark)

Lützen, Jesper

2015-01-01

I moderne formalistisk matematik er ontologi blevet erstattet med spørgsmålet om konsistens af et aksiomatisk system. I artiklen gøres der rede for hvordan denne opfattelse er blevet til og denne historie opfattes i sig selv som en slags erstatning for ontologi......I moderne formalistisk matematik er ontologi blevet erstattet med spørgsmålet om konsistens af et aksiomatisk system. I artiklen gøres der rede for hvordan denne opfattelse er blevet til og denne historie opfattes i sig selv som en slags erstatning for ontologi...

INFORMATION FOR THE USERS OF THE SELF-SERVICE STORES ON THE MEYRIN & PREVESSIN SITES

CERN Multimedia

Logistics Group

2001-01-01

In accordance with the Management Board's decision to rationalise the two self-service stores on the Meyrin and Prévessin sites, the users of these stores are hereby informed of the new arrangements. As of 2nd July 2001, the self-service stores will open on a half-time basis, i.e.: MEYRIN SITE SELF-SERVICE STORE (BUILDING 113) 9.00 a.m. to 12.00 midday PREVESSIN SITE SELF-SERVICE STORE (BUILDING 904) 2.30 p.m. to 4.30 p.m.

Identification of let-7-regulated oncofetal genes

DEFF Research Database (Denmark)

Boyerinas, Benjamin; Park, Sun-Mi; Shomron, Noam

2008-01-01

-regulated at the end of embryonic development. Let-7 is often down-regulated early during cancer development, suggesting that let-7-regulated oncofetal genes (LOG) may become reexpressed in cancer cells. Using comparative bioinformatics, we have identified 12 conserved LOGs that include HMGA2 and IMP-1/CRD-BP. IMP-1...

The future of high-let radiation in cancer therapy. Justification of the heavy-ion therapy programmes

International Nuclear Information System (INIS)

Wambersie, A.

1989-01-01

The introduction of new types of ionizing radiations to control the primary tumour is a promising approach in radiation therapy. High-LET (linear energy transfer) radiations produce different biological effects compared to conventional X-rays, leading to a potential therapeutic advantage over low-LET (e.g., protons or helium ions) beams, which only are aimed at improving the physical selectivity. Introduced historically to reduce the OER (oxygen enhancement ratio), there is evidence for a reduction in radiosensitivity differences, which implies an advantage or disadvantage depending on the tumour characteristics and the normal tissues at risk, which in turn raises the problem of patient selection. From clinical data, fast neutrons were found to be superior to photons in the treatments of salivary gland tumours, prostatic adenocarcinomas, and some carcinomas. Heavy ions combine the advantages of a high physical selectivity and the potential advantage of high-LET for some tumour types. Clinical indications for the use of heavy-ion beams are therefore those tumours that reside in problematic sites but are of a type for which high-LET radiations were already shown to be useful. This review discusses the improvement of the physical selectivity with proton and helium ion beams; the differential effect and the potential advantage of neutrons and high-LET radiations (including both the radiological considerations and the clinical data); and presents the rationale for heavy-ion therapy. 38 refs, 7 figs, 10 tabs

Distribution of sealed sources in use or stored by user on-site in Republic of Bulgaria

International Nuclear Information System (INIS)

Simeonov, G.

2001-01-01

Full text: Distribution of the sealed sources (SS) in use or stored by user on-site in Republic of Bulgaria has been determined by using the categorization system proposed by Institut National des Radioelements (IRE), Belgium. The criteria used to categorize the SS were the handling and monitoring equipment needed for dismantling, checking and treatment of spent sealed sources (SSS) before storage and/or final disposal. The categorization system was proposed as a basis for estimation of the needs of equipment for the new treatment and storage facility for SSS in the site of Novi Han radioactive waste repository. The categorization used to evaluate the distribution of SS in use or stored by user on-site is shown in Table I. Sealed sources are widely used in Bulgaria for industrial, medical, domestic and scientific purposes. Presently, the list of registered users of sealed beta-gamma and neutron SS consists of 387 industrial users, 78 research and control users and 14 medical users. In addition there are 48 registered users of Pu-239 static eliminators and an estimated number shows about 1000 users of Pu-239, Am- 241 or Kr-85 sources in smoke detectors. Wide range of activities with SS is controlled by CUEAPP, as license is required for use and/or storage by user of every single source. An electronic data base of the licenses for use of atomic energy is operated by CUAEPP. The investigation covered the sealed sources registered in the data base. The number of sources in different categories, their use and typical activity have been determined. The same approach has been used separately for sealed sources in use, as well as for spent sources stored by user on-site. Special attention has been paid to high activity gamma-sources used in teletherapy and irradiators, as their activities were corrected for radioactive decay (reference date: March 2001); the exact location and conditions of use or storage of every such source were established. As a result of the

In vitro RBE-LET dependence for multiple particle types

DEFF Research Database (Denmark)

Sørensen, Brita Singers; Overgaard, Jens; Bassler, Niels

2011-01-01

Background. In vitro RBE values for various high LET radiation types have been determined for many different cell types. Occasionally it is criticized that RBE for a given endpoint cannot be single-value dependent on LET alone, but also on particle species, due to the different dose deposition...... profiles on microscopic scale. Hence LET is not sufficient as a predictor of RBE, and this is one of the motivations for development of radiobiological models which explicitly depend on the detailed particle energy spectrum of the applied radiation field. The aim of the present study is to summarize...... the available data in the literature regarding the dependency of RBE on LET for different particles. Method. As RBE is highly dependent on cell type and endpoint, we discriminated the RBE-LET relationship for the three investigated cell lines and at the same endpoint (10% survival in colony formation). Data...

A Review: Some biological effects of high LET radiations

Science.gov (United States)

Wiley, A., Jr.

1972-01-01

There are qualitative and quantitative differences in the biological damage observed after exposure to high LET radiation as compared to that caused by low LET radiations. This review is concerned with these differences, which are ultimately reflected at the biochemical, cellular and even whole animal levels. In general, high LET radiations seem to produce biochemical damage which is more severe and possibly less repairable. Experimental data for those effects are presented in terms of biochemical RBE's with consideration of both early and late manifestations. An LET independent process by which significant biochemical damage may result from protons, neutrons and negative pion mesons is discussed.

Owning, letting and demanding second homes

DEFF Research Database (Denmark)

Bloze, Gintautas; Skak, Morten

register data and presents estimations of the probability of owning a second home, the decision to let the second home and the number of let weeks per year. Also income elasticities for primary and second housing demand are estimated. We find a conventional monotonic increase in demand elasticities...... for primary housing demand for non-owners of second homes; however, owners of second homes have the highest income elasticity in the middle income group....

The inactivation of papain by high LET radiations

International Nuclear Information System (INIS)

Bisby, R.H.; Cundall, R.B.; Sims, H.E.; Burns, W.G.

1984-01-01

The effect of varying LET over a wide range (0.2-1570 eV/nm) on the radiation-induced inactivation of the enzyme papain in dilute aqueous solution has been investigated. Measurements of total, reparable and non-reparable inactivation G values in oxygen, nitrous oxide and argon saturated solutions have allowed the contributions to inactivation from radicals and hydrogen peroxide to be evaluated. At high LET the results demonstrate an increasing component due to reaction of the superoxide radical, formed from oxygen produced in the track as a primary radiolysis product. This effect was not observed in our previous study with ribonuclease due to the insensitivity of ribonuclease to inactivation by superoxide and hydrogen peroxide. The results obtained with papain clearly demonstrate a maximum in G(H 2 O 2 ) at an LET of equivalent to 140 eV/nm. Generation of O 2 within the track as a primary radiolysis product at high LET now appears to be confirmed as an important mechanism leading to reduction in the oxygen enhancement ratio for cellular systems exposed to high LET radiations (Baverstock and Burns 1981). (author)

"Less Clicking, More Watching": Results from the User-Centered Design of a Multi-Institutional Web Site for Art and Culture.

Science.gov (United States)

Vergo, John; Karat, Clare-Marie; Karat, John; Pinhanez, Claudio; Arora, Renee; Cofino, Thomas; Riecken, Doug; Podlaseck, Mark

This paper summarizes a 10-month long research project conducted at the IBM T.J. Watson Research Center aimed at developing the design concept of a multi-institutional art and culture web site. The work followed a user-centered design (UCD) approach, where interaction with prototypes and feedback from potential users of the web site were sought…

High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

International Nuclear Information System (INIS)

Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

2012-01-01

Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

A SciCode web site: building bridges between owners and users

Energy Technology Data Exchange (ETDEWEB)

Gaver, C. [Atomic Energy of Canada Ltd., Mississauga, Ontario (Canada)

2000-07-01

Web technology is a tool that is gaining in popularity. Properly used, it is a powerful tool that has tremendous potential for providing better communication. It can also be effective as a training tool, an information-sharing tool, and as a means of simplifying work load, and facilitating compliance with Company procedures. The issue is one of communication. The challenge facing many large or geographically-distributed companies is how to communicate information to their staff and to their customers. Procedures overseeing quality-assurance programs and commitment to ensuring the quality of products need to be communicated to customers. Equally important is customer feedback. This information from users becomes the kernel for future product development. The issue is even more important when speaking of scientific analysis computer programs (SciCodes). Regular ongoing communication between Primary Holders and End Users is essential in the development and use of SciCodes. Without this communication, quality assurance is at risk. Quality assurance processes are an integral part in developing any SciCode. End Users also have a role to play. Primary Holders keep End Users informed of improvements or new releases. End Users must ensure they act on this information. Equally important, End Users must communicate problems or suggestions to the Primary Holder to remedy or incorporate in new releases. In other words, quality assurance processes become most effective when both Primary Holder and End Users are involved. This requires communication. Web technology offers AECL a means of providing regular, ongoing communication between its scientific-code (SciCode) Primary Holders-Owner Branches and the End Users of these codes within and outside the Company. Using the experience we have gained by developing the Y2K SciCode Web sites, setting up online documentation systems, and incorporating lessons learned from the Y2K project we have developed a model that is geared to

A SciCode web site: building bridges between owners and users

International Nuclear Information System (INIS)

Gaver, C.

2000-01-01

Web technology is a tool that is gaining in popularity. Properly used, it is a powerful tool that has tremendous potential for providing better communication. It can also be effective as a training tool, an information-sharing tool, and as a means of simplifying work load, and facilitating compliance with Company procedures. The issue is one of communication. The challenge facing many large or geographically-distributed companies is how to communicate information to their staff and to their customers. Procedures overseeing quality-assurance programs and commitment to ensuring the quality of products need to be communicated to customers. Equally important is customer feedback. This information from users becomes the kernel for future product development. The issue is even more important when speaking of scientific analysis computer programs (SciCodes). Regular ongoing communication between Primary Holders and End Users is essential in the development and use of SciCodes. Without this communication, quality assurance is at risk. Quality assurance processes are an integral part in developing any SciCode. End Users also have a role to play. Primary Holders keep End Users informed of improvements or new releases. End Users must ensure they act on this information. Equally important, End Users must communicate problems or suggestions to the Primary Holder to remedy or incorporate in new releases. In other words, quality assurance processes become most effective when both Primary Holder and End Users are involved. This requires communication. Web technology offers AECL a means of providing regular, ongoing communication between its scientific-code (SciCode) Primary Holders-Owner Branches and the End Users of these codes within and outside the Company. Using the experience we have gained by developing the Y2K SciCode Web sites, setting up online documentation systems, and incorporating lessons learned from the Y2K project we have developed a model that is geared to

Biomarkers specific to densely-ionising (high LET) radiations

International Nuclear Information System (INIS)

Brenner, D.J.; Okladnikova, N.; Hande, P.; Burak, L.; Geard, C.R.; Azizova, T.

2001-01-01

There have been several suggestions of biomarkers that are specific to high LET radiation. Such a biomarker could significantly increase the power of epidemiological studies of individuals exposed to densely-ionising radiations such as alpha particles (e.g. radon, plutonium workers, individuals exposed to depleted uranium) or neutrons (e.g. radiation workers, airline personnel). We discuss here a potentially powerful high LET biomarker (the H value) which is the ratio of induced inter-chromosomal aberrations to intra-arm aberrations. Both theoretical and experimental studies have suggested that this ratio should differ by a factor of about three between high LET radiation and any other likely clastogen, and will yield more discrimination than the previously suggested F value (ratio of inter-chromosomal aberrations to intra-chromosomal inter-arm aberrations). Evidence of the long-term stability of such chromosomal biomarkers has also been generated. Because these stable intra-arm and inter-chromosomal aberrations are (1) frequent and (2) measurable at long times after exposure, this H value appears to be a practical biomarker of high LET exposure, and several in vitro studies have confirmed the approach for unstable aberrations. The approach is currently being tested in a population of Russian radiation workers exposed several decades ago to high- or low LET radiation. (author)

Algorithmic and User Study of an Autocompletion Algorithm on a Large Medical Vocabulary

NARCIS (Netherlands)

Sevenster, M.; Van Ommering, R.C.; Qian, Y.

2012-01-01

Introduction: Autocompletion supports human-computer interaction in software applications that let users enter textual data. We will be inspired by the use case in which medical professionals enter ontology concepts, catering the ongoing demand for structured and standardized data in

INFORMATION FOR THE USERS OF THE SELF-SERVICES STORES ON THE MEYRIN AND PREVESSIN SITES

CERN Multimedia

Logistics Group

2001-01-01

In accordance with the Management Board's decision to rationalise the two self-service stores on the Meyrin and Prévessin sites, the users of these stores are hereby informed of the new arrangements. As of 2nd July 2001, the self-service stores will open on a half-time basis, i.e.: MEYRIN SITE SELF-SERVICE STORE (BUILDING 113) 9.00 a.m. to 12.00 midday PREVESSIN SITE SELF-SERVICE STORE (BUILDING 904) 2.30 p.m. to 4.30 p.m.

Design and Development of a User Interface for the Dynamic Model of Software Project Management.

Science.gov (United States)

1988-03-01

rectory of the user’s choice for future...the last choice selected. Let us assume for the sake of this tour that the user has selected all eight choices . ESTIMATED ACTUAL PROJECT SIZE DEFINITION...manipulation of varaibles in the * •. TJin~ca model "h ... ser Inter ace for the Dynamica model was designed b in iterative process of prototyping

Qualitative study on software application usage and user behaviour at South African Digital Doorway sites

CSIR Research Space (South Africa)

Gush, K

2011-10-01

Full Text Available -methods research approach provides a more comprehensive picture. Qualitative studies hold utility in complementing quantitative research, by providing data on the site environment, user interactions and perceptions, and stated requirements. This paper presents...

In vitro cellular transformation induced by charged particles of defined LET

International Nuclear Information System (INIS)

Hei, T.K.; Hall, E.J.; Komatsu, K.; Goldhagen, P.

1985-01-01

Cytotoxicity and neoplastic transformation were scored in the C/sub 3/H 10T1/2 cell system following irradiation with protons, deuterons and helium-3 ions of defined LET in the track segment mode. The charged particles were accelerated at the Radiological Research Accelerator Facility at the Nevis Laboratories of Columbia University and provided a range of LET values from 10 to 175 keV/μm. Exponential phase cultures of C3H 10T1/2 cells, growing on a thin mylar surface were irradiated with charged particles of various LET values and subsequently replated onto commercial plastic petri dishes. The cultures were incubated for six weeks at which time they were fixed, stained and type II and III scored as transformants. Over the range of LET values studied thus far, it was found that as the LET of the charged particles increased, the shoulder of the survival curves decreased and approached an exponential function of dose at LET values of 100 keV/μm and above. The transformation incidence, likewise, showed a direct correlation with LET over the dose ranges examined

Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

Science.gov (United States)

Powers, John T; Tsanov, Kaloyan M; Pearson, Daniel S; Roels, Frederik; Spina, Catherine S; Ebright, Richard; Seligson, Marc; de Soysa, Yvanka; Cahan, Patrick; Theiβen, Jessica; Tu, Ho-Chou; Han, Areum; Kurek, Kyle C; LaPier, Grace S; Osborne, Jihan K; Ross, Samantha J; Cesana, Marcella; Collins, James J; Berthold, Frank; Daley, George Q

2016-01-01

Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumor suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. However, here we show that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN mRNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN-amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma pathogenesis with broad implications for cancer pathogenesis. PMID:27383785

Applicability of LET to single events in microelectronic structures

Science.gov (United States)

Xapsos, Michael A.

1992-12-01

LET is often used as a single parameter to determine the energy deposited in a microelectronic structure by a single event. The accuracy of this assumption is examined for ranges of ion energies and volumes of silicon appropriate for modern microelectronics. It is shown to be accurate only under very restricted conditions. Significant differences arise because (1) LET is related to energy lost by the ion, not energy deposited in the volume; and (2) LET is an average value and does not account for statistical variations in energy deposition. Criteria are suggested for determining when factors other than LET should be considered, and new analytical approaches are presented to account for them. One implication of these results is that improvements can be made in space upset rate predictions by incorporating the new methods into currently used codes such as CREME and CRUP.

MicroRNA let-7, T cells, and patient survival in colorectal cancer

Science.gov (United States)

Dou, Ruoxu; Nishihara, Reiko; Cao, Yin; Hamada, Tsuyoshi; Mima, Kosuke; Masuda, Atsuhiro; Masugi, Yohei; Shi, Yan; Gu, Mancang; Li, Wanwan; da Silva, Annacarolina; Nosho, Katsuhiko; Zhang, Xuehong; Meyerhardt, Jeffrey A.; Giovannucci, Edward L.; Chan, Andrew T.; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, Shuji

2016-01-01

Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3+, CD8+, CD45RO (PTPRC)+, and FOXP3+ cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis. Logistic regression analysis and Cox proportional hazards regression were used to assess associations of let-7a (and let-7b) expression (quartile predictor variables) with T-cell densities (binary outcome variables) and mortality, respectively, controlling for tumor molecular features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Compared with cases in the lowest quartile of let-7a expression, those in the highest quartile were associated with lower densities of CD3+ [multivariate odds ratio (OR), 0.40; 95% confidence interval (CI), 0.23 to 0.67; Ptrend = 0.003] and CD45RO+ cells (multivariate OR, 0.31; 95% CI, 0.17 to 0.58; Ptrend = 0.0004), and higher colorectal cancer-specific mortality (multivariate hazard ratio, 1.82; 95% CI, 1.42 to 3.13; Ptrend = 0.001). In contrast, let-7b expression was not significantly associated with T-cell density or colorectal cancer prognosis. Our data support the role of let-7a in suppressing antitumor immunity in colorectal cancer, and suggest let-7a as a potential target of immunotherapy. PMID:27737877

Biological fingerprint of high LET radiation. Brenner hypothesis

International Nuclear Information System (INIS)

Kodama, Yoshiaki; Awa, Akio; Nakamura, Nori

1997-01-01

Hypothesis by Brenner et al. (1994) that in chromosome aberrations in human peripheral lymphocytes induced by radiation exposure, F value (dicentrics/rings) differs dependently on the LET and can be a biomarker of high LET radiation like neutron and α-ray was reviewed and evaluated as follows. Radiation and chromosome aberrations; in this section, unstable aberrations like dicentric and rings (r) and stable ones like translocation and pericentric inversions were described. F value. Brenner hypothesis. Bauchinger's refutation. F value determined by FISH method; here, FISH is fluorescence in situ hybridization. F value in studies by author's Radiation Effect Research Facility. Frequency of chromosome aberration in A-bomb survivors and ESR (ESR: electron spin resonance). The cause for fluctuation of F values. The Brenner hypothesis could not be supported by studies by author's facility, suggesting that the rate of inter-chromosomal and intra-chromosomal exchange abnormalities can not be distinguishable by the radiation LET. This might be derived from the difference in detection technology of r rather than in LET. (K.H.)

Special photographic emulsions for high LET dosimetry

International Nuclear Information System (INIS)

Katz, R.

1978-12-01

The purpose of these investigations into photographic emulsion dosimetry is to attempt to use the photographic emulsion to mimic the response of human tissues to high LET radiations. The program therefore requires that a systematic understanding of the response of mammalian cells to ionizing radiations be achieved. We have been concerned with differences in RBE and in radiation response to both high and LET radiations, and in the interrelationship between observations with these different radiations

Users guide for evaluating alternative fixed-site physical protection systems using ''FESEM''

International Nuclear Information System (INIS)

Chapman, L.D.; Kinemond, G.A.; Sasser, D.W.

1977-11-01

The objective of this manual is to provide a guide for evaluating physical protection systems using the Forcible Entry Safeguards Effectiveness Model (FESEM). It is intended for use by personnel involved in evaluating fixed-site security systems, or managers involved in making decisions related to the modification of existing protection systems or the implementation of new systems. This users' guide has been written for an audience which has some previous computer experience

Are you a developer? Let's talk!

CERN Multimedia

CERN. Geneva

2014-01-01

Many of us have to create software as part of our work, if you do probably you asked yourself some of the following: How other people at CERN develop? What technologies have they used? What worked and what didn't for them? Am I reinventing the wheel? What CERN services can make my life easier? What other services I miss that would be useful to have? How can I integrate my system with XXYY at CERN? Unfortunately there is little communication between us and we need to fix that, let's find initiatives to improve and share experiences between software engineers... let's talk!

The role of users group in the IFMIF project

International Nuclear Information System (INIS)

Matsui, H.; Sugimoto, M.; Mdslang, A.; Garin, R.

2007-01-01

Full text of publication follows: Experts of materials and fusion technology areas are the major 'users' of the IFMIF, the International Fusion Materials Irradiation Facility. Now that IFMIF-EVEDA (Engineering Validation and Engineering Design Activities) Project is implemented under the Broader Approach framework as an EU-JP bilateral collaboration, the Users' Group under IEA does not have a formal interface with the IFMIF-EVEDA project. This lack of interface may cause serious problems since this situation may lead to designing, and eventually, constructing an expensive facility that does not fulfill the users' requirements in an optimal manner. Direct connection of IEA Users group and IFMIF would face a serious difficulty since the participating parties are different to each other. The Broader Approach agreement foresees the creation of a Project Committee in particular to advise IFMIF-EVEDA Project Leader on its implementation. It would be recommendable to appoint fusion-materials and -technology experts from BA participating parties as Project Committee members and let them function as interface between the Users and IFMIF-EVEDA Project. Periodic exchange of opinion involving members of this Committee with Users group members would function as an interface with scientists from all over the world. Roles of users, i.e. fusion-materials and technology experts are identified as follows: - Contribute to the reviews all along the IFMIF-EVEDA progress - Recommendations for further improvement of irradiation and test conditions - Support performance assessments of IFMIF (if needed) - Exchange of information on: - reference materials to be used for IFMIF construction - test matrices, and PIE programs for mechanical testing (at IFMIF site) - advanced microstructural analysis at suitable international laboratories - Ensure the link with DEMO design criteria experts as well as breeding blanket expert group - Support establishment of 'materials design limit data' for IFMIF

LET dependence of scintillation yields in liquid argon

Energy Technology Data Exchange (ETDEWEB)

Doke, Tadayoshi; Hitachi, Akira; Kikuchi, Jun; Crawford, H J; Lindstrom, P J; Masuda, Kimiaki; Shibamura, Eido; Takahashi, Tan

1988-06-01

Scintillation yields (scintillation intensity per unit absorbed energy) in liquid argon for ionizing particles are reviewed as a function of LET for the particles. The maximum scintillation yield, which is obtained for relativistic heavy ions from Ne to La, is about 1.2 times larger than that for gamma rays in NaI(Tl) crystal. In the low LET region, the scintillation yields for relativistic electrons, protons and He ions are 10-20% lower than the maximum yield. This tendency can be explained by taking into account the existence of the electrons which have escaped from their parent ions. In the high LET region, a quenching effect due to high ionization density is observed for alpha particles, fission fragments and relativistic Au ions.

Superpose3D: a local structural comparison program that allows for user-defined structure representations.

Directory of Open Access Journals (Sweden)

Pier Federico Gherardini

Full Text Available Local structural comparison methods can be used to find structural similarities involving functional protein patches such as enzyme active sites and ligand binding sites. The outcome of such analyses is critically dependent on the representation used to describe the structure. Indeed different categories of functional sites may require the comparison program to focus on different characteristics of the protein residues. We have therefore developed superpose3D, a novel structural comparison software that lets users specify, with a powerful and flexible syntax, the structure description most suited to the requirements of their analysis. Input proteins are processed according to the user's directives and the program identifies sets of residues (or groups of atoms that have a similar 3D position in the two structures. The advantages of using such a general purpose program are demonstrated with several examples. These test cases show that no single representation is appropriate for every analysis, hence the usefulness of having a flexible program that can be tailored to different needs. Moreover we also discuss how to interpret the results of a database screening where a known structural motif is searched against a large ensemble of structures. The software is written in C++ and is released under the open source GPL license. Superpose3D does not require any external library, runs on Linux, Mac OSX, Windows and is available at http://cbm.bio.uniroma2.it/superpose3D.

"Let's Move" campaign: applying the extended parallel process model.

Science.gov (United States)

Batchelder, Alicia; Matusitz, Jonathan

2014-01-01

This article examines Michelle Obama's health campaign, "Let's Move," through the lens of the extended parallel process model (EPPM). "Let's Move" aims to reduce the childhood obesity epidemic in the United States. Developed by Kim Witte, EPPM rests on the premise that people's attitudes can be changed when fear is exploited as a factor of persuasion. Fear appeals work best (a) when a person feels a concern about the issue or situation, and (b) when he or she believes to have the capability of dealing with that issue or situation. Overall, the analysis found that "Let's Move" is based on past health campaigns that have been successful. An important element of the campaign is the use of fear appeals (as it is postulated by EPPM). For example, part of the campaign's strategies is to explain the severity of the diseases associated with obesity. By looking at the steps of EPPM, readers can also understand the strengths and weaknesses of "Let's Move."

Mutagenic action of radiation with different LET on Bacillus subtilis cells

International Nuclear Information System (INIS)

edinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" data-affiliation=" (Obedinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" >Borejko, A.V.; edinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" data-affiliation=" (Obedinennyj Inst. Yadernykh Issledovanij, Dubna (Russian Federation))" >Krasavin, E.A.

1997-01-01

The induction of the his - -> his + mutants in vegetative and spores of Bacillus subtilis wild type cells irradiated with γ-rays and helium ions (LET = 20-80 keV/μm) has been investigated. It was shown that the dose dependence of the mutation induction in vegetative cells is described by a linear-quadratic function of dose in case of both γ-rays and helium ions. RBE (LET) dependencies on the lethal and mutagenic effect of radiation have a local maximum. The maximum of RBE (LET) dependence on the mutagenic assay is shifted at the low region of LET in comparison with the lethal effect of irradiation. (author)

Consumer Products Advertised to Save Energy--Let the Buyer Beware.

Science.gov (United States)

1981-07-24

AD-AL06 653 GENERAL ACCOUNTING OFFICE WASHINGTON DC HUMAN RESOUR--ETC F/G 5/3 CONSUMER PRODUCTS ADVERTISED TO SAVE ENERGY--LET THE BUYER BEWA-ETC...COMPTROLLER GENERAL’S CONSUMER PRODUCTS ADVERTISED REPORT TO THE CONGRESS TO SAVE ENERGY- - LET THE BUYER BEWARE D IG E ST In efforts to reduce energy costs...and comparable, GAO believes that the best ad- vice for consumers is "let the buyer beware." (See p. 42.) F’TC ’S COMMENTS FTC said that GAO

Induction and disappearance of G2 chromatid breaks in lymphocytes after low doses of low LET γ - rays and high LET fast neutrons

International Nuclear Information System (INIS)

Vral, Anne; Thierens, Hubert; Baeyens, Ans; De Ridder, Leo

2001-01-01

In view of the potential importance of the G2 assay for detecting chromosomal radiosensitivity and possible predisposition to cancer the need to elucidate the mechanism underlying the formation of chromatid breaks, observed with the G2 assay after low dose irradiation, has been recognised. In this study we irradiated blood samples of 4 healthy donors with low LET γ-rays and high LET neutrons, which initially produce the same number of dsb but of a different quality. By means of the G2 assay, we determined the number of chromatid breaks induced by γ-rays and neutrons and compared the kinetics of chromatid break rejoining for radiations of different quality. In a first set of experiments a dose-response curve for the formation of chromatid breaks was carried out for γ-rays and neutrons with doses ranging between 0.1 and 0.5 Gy. In a second set of experiments the kinetics of chromatid break formation and disappearance was investigated after a dose of 0.5 Gy using post-irradiation times ranging between 0.5 h and 3.5 h. For the highest dose of 0.5 Gy the number of isochromatid breaks were also scored. No significant differences in the number of chromatid breaks were observed between low LET γ-rays and high LET neutrons for the 4 donors at any of the doses given. The dose response curves for the formation of chromatid breaks are linear for both radiation qualities and RBE values equal to one were obtained. Scoring of isochromatid breaks at the highest dose of 0.5 Gy revealed that high LET neutrons are however more effective at inducing isochromatid breaks (RBE of 6.2). The rejoining experiments further showed that the kinetics of disappearance of chromatid breaks following irradiation with low LET γ-rays or high-LET neutrons are not significantly different. T 1/2 0.92 h for γ-rays and t 1/2 = 0.84 h for neutrons were obtained. In conclusion, our results show that at low doses of radiation the induction as well as the disappearance of G2 chromatid breaks is LET

A simple theory of LET spectra of heavy ion beams

International Nuclear Information System (INIS)

Wilson, J.W.; Townsend, L.W.; Schimmerling, W.; Norbury, J.W.; Wong, M.; Badavi, F.

1985-01-01

The transition of high energy ion beams through extended matter is of considerable interest to the space program as well as radiobiology and medical therapy. The transition is defined in terms of various atomic/molecular and nuclear cross sections in a Boltzmann-like equation. One dimensional solutions are derived herein from which LET spectra are derived for secondary fragments. Such LET spectra are fundamental to the evaluation of beam quality, biological effects, and radiation shield effectiveness. Sensitivity of LET spectral distributions to uncertainty in physical parameters such as the isotopic fragmentation parameters, fragment mass, and absorption cross section is established for a number of ion beams. The main limitation in LET studies is the paucity of both elemental and isotopic fragmentation data. The elemental fragmentation data is more readily available because of its simple experimental procedures. It has been suggested by some that natural abundance ratios should be used with the elemental cross sections but this leads to an order-of-magnitude error in LET spectra in many cases. Very few examples of isotopic fragmentation measurements are available. Although major advances in nuclear fragmentation theory have been made, we must await more extensive isotopic fragmentation experiments for final validation

Let7a involves in neural stem cell differentiation relating with TLX level

Energy Technology Data Exchange (ETDEWEB)

Song, Juhyun [Department of Anatomy, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Kyoung Joo; Oh, Yumi [Department of Anatomy, Yonsei University College of Medicine, Seoul (Korea, Republic of); BK21 Plus Project for Medical Sciences, and Brain Research Institute, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Jong Eun, E-mail: jelee@yuhs.ac [Department of Anatomy, Yonsei University College of Medicine, Seoul (Korea, Republic of); BK21 Plus Project for Medical Sciences, and Brain Research Institute, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2015-07-10

Neural stem cells (NSCs) have the potential for differentiation into neurons known as a groundbreaking therapeutic solution for central nervous system (CNS) diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have focused on the study on microRNA's role in CNS. Some micro RNAs have been reported significant functions in NSC self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a) has known as the regulator of diverse cellular mechanisms including cell differentiation and proliferation. In present study, we investigated whether Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. We performed the following experiments: western blot analysis, TaqMan assay, RT-PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed that let7a play important roles in controlling NSC fate determination. Thus, manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency of NSC's neuronal differentiation for CNS disorders. - Highlights: • Let7a influences on NSC differentiation and proliferation. • Let7a involves in mainly NSC differentiation rather than proliferation. • Let7a positively regulates the TLX expression.

Let7a involves in neural stem cell differentiation relating with TLX level

International Nuclear Information System (INIS)

Song, Juhyun; Cho, Kyoung Joo; Oh, Yumi; Lee, Jong Eun

2015-01-01

Neural stem cells (NSCs) have the potential for differentiation into neurons known as a groundbreaking therapeutic solution for central nervous system (CNS) diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have focused on the study on microRNA's role in CNS. Some micro RNAs have been reported significant functions in NSC self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a) has known as the regulator of diverse cellular mechanisms including cell differentiation and proliferation. In present study, we investigated whether Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. We performed the following experiments: western blot analysis, TaqMan assay, RT-PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed that let7a play important roles in controlling NSC fate determination. Thus, manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency of NSC's neuronal differentiation for CNS disorders. - Highlights: • Let7a influences on NSC differentiation and proliferation. • Let7a involves in mainly NSC differentiation rather than proliferation. • Let7a positively regulates the TLX expression

Diffusion-kinetic theories for LET effects on the radiolysis of water

International Nuclear Information System (INIS)

Pimblott, S.M.; LaVerne, J.A.

1994-01-01

Diffusion-kinetic methods are used to investigate the effects of incident particle linear energy transfer (LET) on the radiolysis of water and aqueous solutions. Chemically realistic deterministic diffusion-kinetic calculations examining the scavenging capacity dependences of the scavenged yield of e aq - and of OH demonstrate that the scavenged yields are related to the underlying time-dependent kinetics in the absence of the scavenger by a simple Laplace transform relationship. This relationship is also shown to link the effect of an e eq - scavenger on the formation of H 2 with the time dependence of H 2 production in the absence of the scavenger. The simple Laplace relationship does not work well when applied to H 2 O 2 formation in high-LET particle tracks even though such a relationship is valid with low-LET particles. It is found that while the secondary reaction of H 2 O 2 with e aq - can be neglected in low-LET particle radiolysis, it is of considerable significance in the tracks produced by high-LET particles. The increased importance of this reaction with increasing LET is the major reason for the failure of the Laplace relationship for H 2 O 2 . 55 refs., 9 figs., 2 tabs

Models for cell survival with low LET radiation

International Nuclear Information System (INIS)

Payne, M.G.; Garrett, W.R.

1975-01-01

A model for cell survival under low LET irradiation was developed in which the cell is considered to have N 0 -independent sensitive sites, each of which can exist in either an undamaged state (state A) or one of two damaged states. Radiation can change the sensitive sites from the undamaged state to either of two damaged states. The first damaged state (state B) can either be repaired or be promoted on the second damaged state (state C), which is irreparable. The promotion from the first damaged state to the second can occur due to any of the following: (1) further radiation damage, (2) an abortive attempt to repair the site, or (3) the arrival at a part of the cell cycle where the damage is ''fixed.'' Subject to the further assumptions that radiation damage can occur either indirectly (i.e., through radiation products) or due to direct interaction, and that repair of the first damaged state is a one-step process, expressions can be derived for P(N/sub A/, N/sub B/,t) = probability that after time t a cell will have N/sub A/ sites in state A and N/sub B/ in state B. The problem of determining P(N/sub A/, N/sub B/, t) is formulated for arbitrary time dependences of the radiation field and of all rate coefficients. A large family of cell-survival models can be described by interpreting the sensitive sites in different ways and by making different choices of rate coefficients and of the combinations of numbers of sites in different states that will lead to cell death. (U.S.)

Irradiation of single cells with individual high-LET particles

International Nuclear Information System (INIS)

Nelson, J.M.; Braby, L.A.

1993-01-01

The dose-limiting normal tissue of concern when irradiating head and neck lesions is often the vascular endothelium within the treatment field. Consequently, the response of capillary endothelial cells exposed to moderate doses of high LET particles is essential for establishing exposure limits for neutron-capture therapy. In an effort to characterize the high-LET radiation biology of cultured endothelial cells, the authors are attempting to measure cellular response to single particles. The single-particle irradiation apparatus, described below, allows them to expose individual cells to known numbers of high-LET particles and follow these cells for extended periods, in order to assess the impact of individual particles on cell growth kinetics. Preliminary cell irradiation experiments have revealed complications related to the smooth and efficient operation of the equipment; these are being resolved. Therefore, the following paragraphs deal primarily with the manner by which high LET particles deposit energy, the requirements for single-cell irradiation, construction and assembly of such apparatus, and testing of experimental procedures, rather than with the radiation biology of endothelial cells

High LET radiation and mechanism of DNA damage repair

International Nuclear Information System (INIS)

Furusawa, Yoshiya

2004-01-01

Clarifying the mechanism of repair from radiation damage gives most important information on radiation effects on cells. Approximately 10% of biological experiments groups in Heavy Ion Medical Accelerator in Chiba (HIMAC) cooperative research group has performed the subject. They gave a lot of new findings on the mechanism, and solved some open questions. The reason to show the peak of relative biological effectiveness RBE at around 100-200 keV/μm causes miss-repair of DNA damage. Sub-lethal damage generated by high linear energy transfer (LET) radiation can be repaired fully. Potentially lethal damages by high-LET radiation also repaired, but the efficiency decreased with the LET, and so on. (author)

Molecular analysis of two genes between let-653 and let-56 in the unc-22(IV) region of Caenorhabditis elegans.

Science.gov (United States)

Marra, M A; Prasad, S S; Baillie, D L

1993-01-01

A previous study of genomic organization described the identification of nine potential coding regions in 150 kb of genomic DNA from the unc-22(IV) region of Caenorhabditis elegans. In this study, we focus on the genomic organization of a small interval of 0.1 map unit bordered on the right by unc-22 and on the left by the left-hand breakpoints of the deficiencies sDf9, sDf19 and sDf65. This small interval at present contains a single mutagenically defined locus, the essential gene let-56. The cosmid C11F2 has previously been used to rescue let-56. Therefore, at least some of C11F2 must reside in the interval. In this paper, we report the characterization of two coding elements that reside on C11F2. Analysis of nucleotide sequence data obtained from cDNAs and cosmid subclones revealed that one of the coding elements closely resembles aromatic amino acid decarboxylases from several species. The other of these coding elements was found to closely resemble a human growth factor activatable Na+/H+ antiporter. Paris of oligonucleotide primers, predicted from both coding elements, have been used in PCR experiments to position these coding elements between the left breakpoint of sDf19 and the left breakpoint of sDf65, between the essential genes let-653 and let-56.

Experimental and calculated LET distributions in the Cosmos-2044 biosatellite orbit

International Nuclear Information System (INIS)

Dudkin, V.E.; Karpov, O.N.; Potapov, Yu.V.; Benton, E.V.; Frank, A.L.; Watts, J.W. Jr.

1992-01-01

During the flight of the Cosmos-2044 biosatellite, joint U.S.S.R.-U.S.A. investigations of different characteristics of cosmic radiation (CR) in the near-Earth environment were carried out. The U.S. dielectric track detectors CR-39 and Soviet BYa- and BR-type nuclear photo-emulsions were used as detectors. The present work shows some results of experimental measurements of linear energy transfer (LET) spectra of CR particles obtained with the use of these detectors, which were placed both inside and outside the satellite. The LET spectra measurement with plastic detectors is composed of two parts: the measurement of galactic cosmic rays (GCR) particles, and of short-range particles. The contributions of these components to the total LET distribution at various thicknesses of the shielding were analyzed and the results of these studies are presented. Calculated LET spectra in the Cosmos-2044 orbit were compared with experimental data. On the basis of experimental and calculated values of the LET spectra, absorbed and equivalent CR doses were calculated. In the shielding range of 1-1.5 g cm -2 , outside the spacecraft, the photo-emulsions yielded 10.3 mrad d -1 and 27.5 mrem d -1 (LET ≥ 2 MeV cm -1 ) while the CR-39 yielded averages of 1.43 mrad d -1 and 13.4 mrem d -1 (LET ≥ 40 MeV cm -1 ). Inside the spacecraft (≥10 g cm -2 ) the photo-emulsions yielded 8.9 mrad d -1 and 14.5 mrem d -1 . (author)

High-LET dose-response characteristics by track structure theory of heavy charged particles

International Nuclear Information System (INIS)

Hansen, J.W.; Olsen, K.J.

1981-09-01

The track structure theory developed by Katz and co-workers ascribes the effect of high-LET radiation to the highly inhomogeneous dose distribution due to low energy Δ-rays ejected from the particle track. The theory predicts the effectiveness of high-LET radiation by using the ion parameters zsub(eff') effective charge of the ion, and β = v/c, the relative ion velocity, together with the characteristic dose D 37 derived from low-LET dose-response characteristic of the detector and the approximate size asub(0) of the sensitive element of the detector. 60 Co gamma-irradiation is used as a reference low-LET radiation, while high-LET radiation ranging from 16 MeV protons to 4 MeV/amu 16 0-ions covering an initial LET range of 30-5500 MeVcm 2 /g is obtained from a tandem Van de Graaff accelerator. A thin film (5mg/cm 2 ) radiochromic dye cyanide plastic dosemeter was used as detector with the characteristic dose of 16.8 Mrad and a sensitive element size of 10 -7 cm. Theoretical and experimental effectiveness, RBE, agreed within 10 to 25% depending on LET. (author)

Yields of clustered DNA damage induced by charged-particle radiations of similar kinetic energy per nucleon: LET dependence in different DNA microenvironments

International Nuclear Information System (INIS)

Keszenman, D.J.; Sutherland, B.M.

2010-01-01

To determine the linear energy transfer (LET) dependence of the biological effects of densely ionizing radiation in relation to changes in the ionization density along the track, we measured the yields and spectrum of clustered DNA damages induced by charged particles of different atomic number but similar kinetic energy per nucleon in different DNA microenvironments. Yeast DNA embedded in agarose in solutions of different free radical scavenging capacity was irradiated with 1 GeV protons, 1 GeV/nucleon oxygen ions, 980 MeV/nucleon titanium ions or 968 MeV/nucleon iron ions. The frequencies of double-strand breaks (DSBs), abasic sites and oxypurine clusters were quantified. The total DNA damage yields per absorbed dose induced in non-radioquenching solution decreased with LET, with minor variations in radioquenching conditions being detected. However, the total damage yields per particle fluence increased with LET in both conditions, indicating a higher efficiency per particle to induce clustered DNA damages. The yields of DSBs and non-DSB clusters as well as the damage spectra varied with LET and DNA milieu, suggesting the involvement of more than one mechanism in the formation of the different types of clustered damages.

Let the Writer Beware! - a Look at Aspects of the EU Legislation Concerning Instructional Texts

Directory of Open Access Journals (Sweden)

Peter Kastberg

2012-08-01

Full Text Available We have probably all heard the story of the person who supposedly put a wet dog into the microwave oven to let it dry or the story of the person who drank coffee from a plastic cup and got severely burned, or the one in which a jogger stumbles and falls in the too long shoe laces of his / her sneakers. Whether or not stories like these are urban legends is hard to determine with any certainty. But judging from the ever increasing volume of the instruction manuals accompanying, for instance, our household appliances and other end user products there could be some truth to them.

Let the Writer Beware! - a Look at Aspects of the EU Legislation Concerning Instructional Texts

Directory of Open Access Journals (Sweden)

Peter Kastberg

2007-03-01

Full Text Available We have probably all heard the story of the person who supposedly put a wet dog into the microwave oven to let it dry or the story of the person who drank coffee from a plastic cup and got severely burned, or the one in which a jogger stumbles and falls in the too long shoe laces of his / her sneakers. Whether or not stories like these are urban legends is hard to determine with any certainty. But judging from the ever increasing volume of the instruction manuals accompanying, for instance, our household appliances and other end user products there could be some truth to them.

Examining Users' E-Satisfaction in the Usage of Social Networking Sites; Contribution from Utilitarian and Hedonic Information Systems

Science.gov (United States)

Ariff, Mohd Shoki Md; Shan, Tay Kai; Zakuan, Norhayati; Ishak, Nawawi; Ridzuan Wahi, Mohd

2014-06-01

E-satisfaction (eSAT) is an important success factor of online service providers such as social networking sites (SNSs). The utilitarian and hedonic information systems are crucial in determining users' eSAT of SNSs, especially among young users. The utilitarian aspect of an information system is productivity-oriented which aims to enhance the users' task performance, and it is important in measuring eSAT of SNSs. In this study, the original constructs of Perceived Ease of Use (PEOU) and Perceived Usefulness (PU) of TAM of utilitarian information system was first developed in this research framework. The use of SNSs, such as Facebook, is pleasure-oriented, in which self-fulfilling values to the users are important in determining users' satisfaction towards the SNSs. Therefore, Perceived Enjoyment (PE) of hedonic information system is added to the framework. Thus, the research framework of this study includes both utilitarian (PEOU and PU) and hedonic (PE) aspects of information systems to determine Malaysian young users' eSAT in the usage of Facebook, a social networking site. In this framework, the effects of PEOU, PU and PE on eSAT in the usage of Facebook are examined among Facebook's users in the age of 18 - 24 years old. The effects of PEOU on PU and PE are also examined. Online questionnaire survey was employed and a total of 384 sets of questionnaires were gathered from users of Facebook. The results indicated that PEOU has positive effects on PU and PE in the context of Facebook. In addition, PEOU, PU and PE are also found to have positive effects on eSAT. PE of hedonic information system exerted higher effect on eSAT, compared to PEOU and PU of utilitarian information system, highlighting the importance of pleasure orientation in the usage of Facebook of SNSs. Managerial and theoretical implications of the study are discussed in term of measuring and enhancing users' eSAT in the usage of SNSs, particularly Facebook.

Dynamic User Interfaces for Service Oriented Architectures in Healthcare.

Science.gov (United States)

Schweitzer, Marco; Hoerbst, Alexander

2016-01-01

Electronic Health Records (EHRs) play a crucial role in healthcare today. Considering a data-centric view, EHRs are very advanced as they provide and share healthcare data in a cross-institutional and patient-centered way adhering to high syntactic and semantic interoperability. However, the EHR functionalities available for the end users are rare and hence often limited to basic document query functions. Future EHR use necessitates the ability to let the users define their needed data according to a certain situation and how this data should be processed. Workflow and semantic modelling approaches as well as Web services provide means to fulfil such a goal. This thesis develops concepts for dynamic interfaces between EHR end users and a service oriented eHealth infrastructure, which allow the users to design their flexible EHR needs, modeled in a dynamic and formal way. These are used to discover, compose and execute the right Semantic Web services.

77 FR 70449 - Medical Device User Fee and Modernization Act; Notice to Public of Web Site Location of Fiscal...

Science.gov (United States)

2012-11-26

... and Drug Administration (FDA) is announcing the Web site location where the Agency will post two lists... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1021] Medical Device User Fee and Modernization Act; Notice to Public of Web Site Location of Fiscal Year 2013...

76 FR 61367 - Medical Device User Fee and Modernization Act; Notice to Public of Web Site Location of Fiscal...

Science.gov (United States)

2011-10-04

.... ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the Web site location where... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-N-0270; formerly Docket No. 2007N-0357] Medical Device User Fee and Modernization Act; Notice to Public of Web Site...

78 FR 66746 - Medical Device User Fee and Modernization Act; Notice to Public of Web Site Location of Fiscal...

Science.gov (United States)

2013-11-06

... and Drug Administration (FDA or the Agency) is announcing the Web site location where the Agency will... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1021] Medical Device User Fee and Modernization Act; Notice to Public of Web Site Location of Fiscal Year 2014...

The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

Science.gov (United States)

McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

2017-07-07

The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

End User Evaluations

Science.gov (United States)

Jay, Caroline; Lunn, Darren; Michailidou, Eleni

As new technologies emerge, and Web sites become increasingly sophisticated, ensuring they remain accessible to disabled and small-screen users is a major challenge. While guidelines and automated evaluation tools are useful for informing some aspects of Web site design, numerous studies have demonstrated that they provide no guarantee that the site is genuinely accessible. The only reliable way to evaluate the accessibility of a site is to study the intended users interacting with it. This chapter outlines the processes that can be used throughout the design life cycle to ensure Web accessibility, describing their strengths and weaknesses, and discussing the practical and ethical considerations that they entail. The chapter also considers an important emerging trend in user evaluations: combining data from studies of “standard” Web use with data describing existing accessibility issues, to drive accessibility solutions forward.

The LET Procedure for Prosthetic Myocontrol: Towards Multi-DOF Control Using Single-DOF Activations.

Directory of Open Access Journals (Sweden)

Markus Nowak

Full Text Available Simultaneous and proportional myocontrol of dexterous hand prostheses is to a large extent still an open problem. With the advent of commercially and clinically available multi-fingered hand prostheses there are now more independent degrees of freedom (DOFs in prostheses than can be effectively controlled using surface electromyography (sEMG, the current standard human-machine interface for hand amputees. In particular, it is uncertain, whether several DOFs can be controlled simultaneously and proportionally by exclusively calibrating the intended activation of single DOFs. The problem is currently solved by training on all required combinations. However, as the number of available DOFs grows, this approach becomes overly long and poses a high cognitive burden on the subject. In this paper we present a novel approach to overcome this problem. Multi-DOF activations are artificially modelled from single-DOF ones using a simple linear combination of sEMG signals, which are then added to the training set. This procedure, which we named LET (Linearly Enhanced Training, provides an augmented data set to any machine-learning-based intent detection system. In two experiments involving intact subjects, one offline and one online, we trained a standard machine learning approach using the full data set containing single- and multi-DOF activations as well as using the LET-augmented data set in order to evaluate the performance of the LET procedure. The results indicate that the machine trained on the latter data set obtains worse results in the offline experiment compared to the full data set. However, the online implementation enables the user to perform multi-DOF tasks with almost the same precision as single-DOF tasks without the need of explicitly training multi-DOF activations. Moreover, the parameters involved in the system are statistically uniform across subjects.

Mutagenic action of radiation with different LET on Bacillus subtilis cells

International Nuclear Information System (INIS)

Borejko, A.V.; Krasavin, E.A.

1996-01-01

The induction of the his - →his + mutants in vegetative and spores of Bacillus subtilis wild type cells irradiated with γ-rays and helium ions (LET=20-80 keV/μm has been investigated. It was shown that the dose dependence of the mutation induction in vegetative cells is described by a linear-quadratic function of dose in case of both γ-rays and helium ions. RBE (LET) dependence on the mutagenic assay is shifted at the low region of LET. (author). 11 refs., 4 figs

Fast Neutrons - LET Distributions and the Response of Mammalian Cells

Energy Technology Data Exchange (ETDEWEB)

Bewley, D. K. [Medical Research Council Cyclotron Unit, Hammersmith Hospital, London (United Kingdom)

1968-03-15

Distributions of stopping power (LET) are given for four beams of fast neutrons, namely, neutrons of 14.6 MeV, neutrons produced by bombarding a thick beryllium target with 15 MeV deuterons, neutrons of 3 MeV, and fast neutrons produced by bombardment of a {sup 235}U converter plate with thermal neutrons. The track average LET is correlated with mean neutron energy, but the dose average is approximately constant. However, neither of these types of average is expected to have much relevance to radiobiology. Further, specification of a ''biologically effective LET'' depends on the biological test used, and is not solely a function of the radiation quality. An attempt has been made to calculate the response of T.I. kidney cells in tissue culture to these four beams of neutrons, based on their response to charged particles using the track-segment method. The calculated RBE's of the neutron beams are lower than the observed values and the calculated values of the oxygen enhancement ratio are higher. These differences seem too great to be explained by errors in dosimetry and in the calculated LET spectra. The suggestion is made that LET is not an adequate criterion of radiation quality, and that the discrepancies may be explained by more detailed consideration of the part played by delta rays and by heavy recoil tracks of short range. (author)

Keep it local (and final): Remnant preferences in "let alone" ellipsis.

Science.gov (United States)

Harris, Jesse A; Carlson, Katy

2016-01-01

The let alone construction (John can't run a mile, let alone a marathon) differs from standard coordination structures (with and or but) by requiring ellipsis of the second conjunct--for example, a marathon is the remnant of an elided clause [[see text] a marathon]. In support of an ellipsis account, a corpus study of British and American English finds that let alone exhibits a Locality bias, as the second conjunct preferentially contrasts with the nearest lexical item of the same syntactic type. Two self-paced reading studies show that the Locality bias is active during online processing, but must be reconciled with indicators of semantic contrast and discourse information. Further, a sentence-rating study shows that the Locality bias interacts with a Finality bias that favours placing the let alone phrase at the end of a clause, which sometimes necessitates a nonlocal contrast. Together, the results show how a general bias in ellipsis for local contrasts is affected by discourse demands, such as the need for scalar contrast imposed by let alone, thereby offering a window into how possibly divergent syntactic and discourse constraints impact sentence processing.

High-LET radiation carcinogenesis

International Nuclear Information System (INIS)

Fry, R.J.M.; Powers-Risius, P.; Alpen, E.L.; Ainsworth, E.J.

1985-01-01

The dose-response curves for the induction of tumors by high-LET radiation are complex and are insufficiently understood. There is no model or formulation to describe the dose-response relationship over a range 0 to 100 rad. Evidence suggests that at doses below 20 rad the response is linear, at least for life shortening and some tumor systems. Thus, limiting values of RBEs for the induction of cancer in various tissues can be determined, but it will require sufficient data obtained at low single doses or with small fractions. The results obtained from experiments with heavy ions indicate an initial linear response with a plateauing of the curve at a tumor incidence level that is dependent on the type of tissue. The RBE values for the heavy ions using 60 Co gamma rays as the reference radiation increase with the estimated LET from 4 for 4 H to about 27 for 56 Fe, 40 Ar. The dose-responses and RBEs for 56 Fe and 40 Ar are similar to those for fission neutrons. These findings suggest the possibility that the effectiveness for tumor induction reaches a maximum. 26 refs., 4 figs., 2 tabs

Apoptosis induced by high- and low-LET radiations

International Nuclear Information System (INIS)

Hendry, J.H.; Potten, C.S.; Merritt, A.

1995-01-01

Cell death after irradiation occurs by apoptosis in certain cell populations in tissues. The phenomenon also occurs after high linear energy transfer (LET) irradiation, and the relative biological effectiveness (RBE) is 3 to 4 (with respect to low-LET radiation and apoptosis in intestinal crypts) for neutrons with energies of 14 MeV and up to 600 MeV. It is thought that p53 plays a role in the phenomenon, as radiation-induced apoptosis is not observed in p53-null animals. (orig.)

Generalized concept of the LET-RBE relationship of radiation-induced chromosome aberration and cell death

International Nuclear Information System (INIS)

Takatsuji, Toshihiro; Yoshikawa, Isao; Sasaki, Masao S.

1999-01-01

The frequency of chromosome aberrations per traversal of a nucleus by a charged particle at the low dose limit increases proportionally to the square of the linear energy transfer (LET), peaks at about 100 keV/μm and then decreases with further increase of LET. This has long been interpreted as an excessive energy deposition over the necessary energy required to produce a biologically effective event. Here, we present an alternative interpretation. Cell traversed by a charged particle has certain probability to receive lethal damage leading to direct death. Such events may increase with an increase of LET and the number of charged particles traversing the cell. Assuming that the lethal damage is distributed according to a Poisson distribution, the probability that a cell has no such damage is expressed by e -cLx , where c is a constant, L is LET, and x is the number of charged particles traversing the cell. From these assumptions, the frequency of chromosome aberration in surviving cells can be described by Y=αSD+βS 2 D 2 with the empirical relation Y=αD+βD 2 in the low LET region, where S=e -cL , α is a value proportional to LET, β is a constant, and D is the absorbed dose. This model readily explains the empirically established relationship between LET and relative biological effectiveness (RBE). The model can also be applied to clonogenic survival. If cells can survive and they have neither unstable chromosome aberrations nor other lethal damage, the LET-RBE relationship for clonogenic survival forms a humped curve. The relationship between LET and inactivation cross-section becomes proportional to the square of LET in the low LET region when the frequency of a directly lethal events is sufficiently smaller than unity, and the inactivation cross-section saturates to the cell nucleus cross-sectional area with an increase in LET in the high LET region. (author)

Improvement of date palm plant lets during rooting stage by silver ion

International Nuclear Information System (INIS)

Sharaf, M.M.; Khamis, M.A.; El Bana, A.; Abd El Galeil, L.M.; Zaid, Z.E.

2012-01-01

This study aim to promote growth plant lets of date palm cv. Zaghlool by decreasing ethylene production inside the containers during rooting stage. Data obtained declared that three silver thiosulphate (STS) levels added to one half strength MS rooting medium improved significantly three rooting measurements (rooting percentage; number and length of developed root lets). However, the lightest STS level (0.25 ml/L of 4 mM STS solution) was the superior, while highest one (1.0 ml/L) was the inferior from statistical point of view. Data obtained displayed that providing MS rooting medium with silver nitrate improved 3 rooting measurements (rooting %; number of root lets and their length) for Zaghloul date palm shoot lets proliferated from somatic embryos. However, the 0.50 mg/L AgNO 3 provided MS medium was the most preferable in this concern. Plant lets were transferred to capped tubes contained 1/4 liquid MS medium through 3 weeks in the growth chamber (under aseptic condition). Ventilation was allowed gradually by punching holes in aluminum foil caps during first five days of 2 nd week. After then, the plant lets were transplanted in acclimatization green house on mixture from (peat moss + perlite + vermiculite at 1:1:1) and survival percentage was 75% after three months.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Radiation-Induced Epigenetic Alterations after Low and High LET Irradiations

Energy Technology Data Exchange (ETDEWEB)

Aypar, Umut; Morgan, William F.; Baulch, Janet E.

2011-02-01

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding the delayed, non-targeted effects of radiation including radiationinduced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET x-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. MiRNA shown to be altered in expression level after x-ray irradiation are involved in chromatin remodeling and DNA methylation. Different and higher incidence of epigenetic changes were observed after exposure to low LET x-rays than high LET Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This study also shows that the irradiated cells acquire epigenetic changes even though they are chromosomally stable suggesting that epigenetic aberrations may arise in the cell without initiating RIGI.

Potential proteins targeted by let-7f-5p in HeLa cells.

Science.gov (United States)

Wang, Yu; Chen, Xiujuan; Zhang, Yi; Song, Jiandong

2017-07-24

MicroRNAs are a class of small, endogenous, non-coding RNAs mediating posttranscriptional gene silencing. The current authors hypothesized that let-7f-5p is likely involved in cell invasion and proliferation by regulating the expression of target genes. The current study combined let-7f-5p with iTRAQ to assess its effect on gene expression in HeLa cells. Results indicated that 164 proteins were expressed at different levels in HeLa cells overexpressing let-7f-5p and negative controls and that 172 proteins were expressed at different levels in let-7f-5p-silenced HeLa cells and negative controls. Results indicated that let-7f-5p may suppress insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in HeLa cells.

Let us fish4tomorrow

OpenAIRE

J.D., Farrugia

2015-01-01

All over the world, governments and stakeholders are trying to cope with overfishing. Overfishing is when too much fish is caught which leads to an overall degradation of the marine ecosystem. It is the non-sustainable use of ocean resources. http://www.um.edu.mt/think/let-us-fish4tomorrow/

Killing, letting die and euthanasia.

Science.gov (United States)

Husak, D N

1979-12-01

Medical ethicists debate whether or not the moral assessment of cases of euthanasia should depend on whether the patient is 'killed' or 'allowed to die'. The usual presupposition is that a clear distinction between killing and letting die can be drawn so that this substantive question is not begged. I contend that the categorisation of cases of instances of killing rather than as instances of letting die depends in part on a prior moral assessment of the case. Hence is it trivially rather than substantively true that the distinction has moral significance. But even if a morally neutral (ie non-question begging) distinction could be drawn, its application to the euthanasia controversy is problematic. I illustrate the difficulties of employing this distinction to reach moral conclusions by critically discussing Philippa Foot's recent treatment of euthanasia. I conclude that even if an act of euthanasia is an instance of killing, and there exists a prima facie moral duty not to kill, and no more stringent duty overrides this duty, one still cannot determine such an act to be morally impermissible.

Killing, letting die and euthanasia.

Science.gov (United States)

Husak, D N

1979-01-01

Medical ethicists debate whether or not the moral assessment of cases of euthanasia should depend on whether the patient is 'killed' or 'allowed to die'. The usual presupposition is that a clear distinction between killing and letting die can be drawn so that this substantive question is not begged. I contend that the categorisation of cases of instances of killing rather than as instances of letting die depends in part on a prior moral assessment of the case. Hence is it trivially rather than substantively true that the distinction has moral significance. But even if a morally neutral (ie non-question begging) distinction could be drawn, its application to the euthanasia controversy is problematic. I illustrate the difficulties of employing this distinction to reach moral conclusions by critically discussing Philippa Foot's recent treatment of euthanasia. I conclude that even if an act of euthanasia is an instance of killing, and there exists a prima facie moral duty not to kill, and no more stringent duty overrides this duty, one still cannot determine such an act to be morally impermissible. PMID:541821

MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly

Energy Technology Data Exchange (ETDEWEB)

Tian, Yuan; Hao, Shaobo [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052 (China); Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government (China); Ye, Minhua [Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006 (China); Zhang, Anling [Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052 (China); Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government (China); Nan, Yang [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Wang, Guangxiu; Jia, Zhifan [Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052 (China); Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government (China); Yu, Kai; Guo, Lianmei [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Pu, Peiyu [Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052 (China); Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government (China); Huang, Qiang, E-mail: huangqiang209@163.com [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Zhong, Yue, E-mail: zhongyue2457@sina.com [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China)

2015-03-06

We demonstrated that IKBKE is overexpressed in human gliomas and that the downregulation of IKBKE markedly inhibits the proliferative and invasive abilities of glioma cells, which is consistent with the results reported by several different research groups. Therefore, IKBKE represents a promising therapeutic target for the treatment of glioma. In the present study, we verified that the microRNAs let-7b and let-7i target IKBKE through luciferase assays and found that let-7b/i mimics can knock down IKBKE and upregulate E-cadherin through western blot analysis. Moreover, the expression levels of let-7b/i were significantly lower in glioma cell lines than that in normal brain tissues, as determined by quantitative real-time PCR. Furthermore, let-7b/i inhibit the invasion and migration of glioma cells, as determined through wound healing and Transwell assays. The above-mentioned data suggest that let-7b/i inhibit the invasive ability of glioma cells by directly downregulating IKBKE and indirectly upregulating E-cadherin. - Highlights: • Let-7b and let-7i are downregulated in glioma cell lines. • IKBKE is a target gene of let-7b/i. • Let-7b/i inhibit the invasion and migration of glioma cells. • Let-7b/i upregulate E-cadherin by downregulating IKBKE.

MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly

International Nuclear Information System (INIS)

Tian, Yuan; Hao, Shaobo; Ye, Minhua; Zhang, Anling; Nan, Yang; Wang, Guangxiu; Jia, Zhifan; Yu, Kai; Guo, Lianmei; Pu, Peiyu; Huang, Qiang; Zhong, Yue

2015-01-01

We demonstrated that IKBKE is overexpressed in human gliomas and that the downregulation of IKBKE markedly inhibits the proliferative and invasive abilities of glioma cells, which is consistent with the results reported by several different research groups. Therefore, IKBKE represents a promising therapeutic target for the treatment of glioma. In the present study, we verified that the microRNAs let-7b and let-7i target IKBKE through luciferase assays and found that let-7b/i mimics can knock down IKBKE and upregulate E-cadherin through western blot analysis. Moreover, the expression levels of let-7b/i were significantly lower in glioma cell lines than that in normal brain tissues, as determined by quantitative real-time PCR. Furthermore, let-7b/i inhibit the invasion and migration of glioma cells, as determined through wound healing and Transwell assays. The above-mentioned data suggest that let-7b/i inhibit the invasive ability of glioma cells by directly downregulating IKBKE and indirectly upregulating E-cadherin. - Highlights: • Let-7b and let-7i are downregulated in glioma cell lines. • IKBKE is a target gene of let-7b/i. • Let-7b/i inhibit the invasion and migration of glioma cells. • Let-7b/i upregulate E-cadherin by downregulating IKBKE

LET-effects in DNA

International Nuclear Information System (INIS)

Kraft, G.; Taucher-Scholz, G.; Heilmann, J.

1994-11-01

In this contribution, an introductory view on the physical properties of ions is given and the cellular response to high LET radiation is summarized. Then the measurements of strand break induction of DNA in solution and in intracellular DNA are reported and compared to cell survival. The possibility of changes in the quality of the lesions is discussed and finally the present status of model calculations in comparison to the experiments is given. (orig./HSI)

14 CFR 151.47 - Performance of construction work: Letting of contracts.

Science.gov (United States)

2010-01-01

... Development Projects § 151.47 Performance of construction work: Letting of contracts. (a) Advertising required... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Performance of construction work: Letting... project, each contract for construction work on a project in the amount of more than $2,000 must be...

User-Interface Design Characteristics of Fortune 500 B2C E-Commerce Sites and Industry Differences

Science.gov (United States)

Zhao, Jensen J.; Truell, Allen D.; Alexander, Melody W.

2006-01-01

This study examined the user-interface design characteristics of 107 Fortune 500 B2C e-commerce Web sites and industry differences. Data were collected from corporate homepages, B2C product/service pages, B2C interactive shopping pages, as well as customer satisfaction of 321 online shoppers. The findings indicate that (a) to attract online…

What can we learn from the neutron clinical experience for improving ion-beam techniques and high-LET patient selection?

International Nuclear Information System (INIS)

Wambersie, A.; Jones, D.T.L.; Gueulette, J.; Gahbauer, R.; DeLuca, P.M.

2010-01-01

Historically, improvements in radiotherapy have been mainly due to improvements in physical selectivity: beam penetration, collimation, dosimetry, treatment planning; and advances in imaging. Neutrons were the first high-LET (linear energy transfer) radiation to be used clinically and showed improvement in the differential response of radiation resistant tumors and normal tissues. The benefits of fast neutrons (and other forms of high LET radiations) are due to their biological effects: a reduction of the OER, a reduction in the differential cell radiosensitivity related to their position in the mitotic cycle, and a reduction in cellular repair capacity (thus less importance of fractionation). The poor physical selectivity of the early neutron therapy beams introduced a systematic bias in comparison with the photon treatments and created a negative perception for neutron therapy. However, significant improvements in the neutron therapy equipment resulted in a physical selectivity similar to modern MV photon therapy. The tumor types or sites where the best therapeutic results were obtained included inoperable or recurrent salivary gland tumors locally extended prostatic adenocarcinomas, and slowly growing well-differentiated sarcomas. The benefit of neutrons for some other well-defined groups of patients was demonstrated in randomized trials. It was estimated that about 20 % of all radiotherapy patients could benefit from fast neutrons (if neutrons are delivered under satisfactory physical conditions). An important issue for fast neutron therapy is the selection of the types of patients who could most benefit from high-LET radiations. The same issue is raised today with other high-LET radiations (e.g., 12 C ions). It is reasonable to assume that the same types of patients would benefit from 12 C irradiation. Of course the better physical selectivity of ion beams enhances the treatment possibilities but this is true for both the high-LET and low-LET radiations (i

Don't Let Osteoporosis Slow You Down | NIH MedlinePlus the Magazine

Science.gov (United States)

... has never let anything stop her from doing what she loves, and she wasn't about to let osteoporosis keep her off the dance floor. It's that kind of spirit that led the National Osteoporosis Foundation (NOF) to ...

Keep it local (and final): Remnant preferences in ‘let alone’ ellipsis

Science.gov (United States)

Harris, Jesse A.; Carlson, Katy

2015-01-01

The let alone construction (John can't run a mile, let alone a marathon) differs from standard coordination structures (with and or but) by requiring ellipsis of the second conjunct, e.g., a marathon is the remnant of an elided clause [John run a marathon]. In support of an ellipsis account, a corpus study of British and American English finds that let alone exhibits a Locality bias, as the second conjunct preferentially contrasts with the nearest lexical item of the same syntactic type. Two self-paced reading studies show that the Locality bias is active during online processing, but must be reconciled with indicators of semantic contrast and discourse information. Further, a sentence-rating study shows that the Locality bias interacts with a Finality bias that favors placing the let alone phrase at the end of a clause, which sometimes necessitates a non-local contrast. Together, the results show how a general bias in ellipsis for local contrasts is affected by discourse demands, such as the need for scalar contrast imposed by let alone, thereby offering a window into how possibly divergent syntactic and discourse constraints impact sentence processing. PMID:26085004

Radiation-induced epigenetic alterations after low and high LET irradiations

International Nuclear Information System (INIS)

Aypar, Umut; Morgan, William F.; Baulch, Janet E.

2011-01-01

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise in the

Radiation-induced epigenetic alterations after low and high LET irradiations

Energy Technology Data Exchange (ETDEWEB)

Aypar, Umut, E-mail: uaypa001@umaryland.edu [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Morgan, William F. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Baulch, Janet E. [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

2011-02-10

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NF{kappa}B), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise

A User-Centered Approach to Adaptive Hypertext Based on an Information Relevance Model

Science.gov (United States)

Mathe, Nathalie; Chen, James

1994-01-01

Rapid and effective to information in large electronic documentation systems can be facilitated if information relevant in an individual user's content can be automatically supplied to this user. However most of this knowledge on contextual relevance is not found within the contents of documents, it is rather established incrementally by users during information access. We propose a new model for interactively learning contextual relevance during information retrieval, and incrementally adapting retrieved information to individual user profiles. The model, called a relevance network, records the relevance of references based on user feedback for specific queries and user profiles. It also generalizes such knowledge to later derive relevant references for similar queries and profiles. The relevance network lets users filter information by context of relevance. Compared to other approaches, it does not require any prior knowledge nor training. More importantly, our approach to adaptivity is user-centered. It facilitates acceptance and understanding by users by giving them shared control over the adaptation without disturbing their primary task. Users easily control when to adapt and when to use the adapted system. Lastly, the model is independent of the particular application used to access information, and supports sharing of adaptations among users.

let-7 miRNAs Can Act through Notch to Regulate Human Gliogenesis

Directory of Open Access Journals (Sweden)

M. Patterson

2014-11-01

Full Text Available It is clear that neural differentiation from human pluripotent stem cells generates cells that are developmentally immature. Here, we show that the let-7 plays a functional role in the developmental decision making of human neural progenitors, controlling whether these cells make neurons or glia. Through gain- and loss-of-function studies on both tissue and pluripotent derived cells, our data show that let-7 specifically regulates decision making in this context by regulation of a key chromatin-associated protein, HMGA2. Furthermore, we provide evidence that the let-7/HMGA2 circuit acts on HES5, a NOTCH effector and well-established node that regulates fate decisions in the nervous system. These data link the let-7 circuit to NOTCH signaling and suggest that this interaction serves to regulate human developmental progression.

LNS users primer for accessing government sites on the ARPA network. [MIT. -->. ANL, BNL, LBL, and New York Univ. Courant Inst

Energy Technology Data Exchange (ETDEWEB)

Kannel, M.

1979-06-01

This primer was developed as part of the study conducted by the Laboratory for Nuclear Science (LNS) on the feasibility of networks for computer resource sharing. The primer is an instructinal guide for the LNS user who would like to access and use computers at other government sites on the ARPA network. The format is a series of scenarios of actual recorded on-line terminal sessions' showing the novice user how to access the foreign site, obtain help documentation, run a simple program, and transfer files to and from the foreign site. Access to the ARPA network in these scenarios is via Multics or the Massachusetts Institute of Technology Terminal Interface Processor. The foreign government sites accessed are the computing facilities at Argonne National Laboratory, Brookhaven National Laboratory, Lawrence Livermore Laboratory, and New York University Courant Institute. This technique of auditing actual terminal sessions as a teaching aid can be extended to include other computing facilities as well as other networks.

Data Mining and Privacy of Social Network Sites' Users: Implications of the Data Mining Problem.

Science.gov (United States)

Al-Saggaf, Yeslam; Islam, Md Zahidul

2015-08-01

This paper explores the potential of data mining as a technique that could be used by malicious data miners to threaten the privacy of social network sites (SNS) users. It applies a data mining algorithm to a real dataset to provide empirically-based evidence of the ease with which characteristics about the SNS users can be discovered and used in a way that could invade their privacy. One major contribution of this article is the use of the decision forest data mining algorithm (SysFor) to the context of SNS, which does not only build a decision tree but rather a forest allowing the exploration of more logic rules from a dataset. One logic rule that SysFor built in this study, for example, revealed that anyone having a profile picture showing just the face or a picture showing a family is less likely to be lonely. Another contribution of this article is the discussion of the implications of the data mining problem for governments, businesses, developers and the SNS users themselves.

Communication and Consumer Activities of Social Networking Sites Users: Cases from Germany, Poland and Russia

Directory of Open Access Journals (Sweden)

Malgorzata Bartosik-Purgat

2017-12-01

Full Text Available The growth of the Internet heavily influences people’s lives every day, especially by the development of Social Networking Sites (SNS, which since their first appearance have been constantly recording a growing number of users. The main purpose of this paper is to identify the significance of SNS in relation to two activities of individual users: communication and consumer behaviour. The study focuses on the three most popular SNS in three neighbouring countries (Germany, Poland, and Russia namely, FACEBOOK, VKONTAKTE, and YOUTUBE. The methodological approach is twofold: firstly, the authors developed a theoretical background of the areas of using SNS and formulated research questions; secondly, they applied the PAPI and CAWI methods for the data analysis. Regarding the researched activities, it should be noted that SNS users use these platforms more often for communication than consumer actions. The most useful here is FACEBOOK in comparison to YOUTUBE. This study provides results, which can be useful in the management of the enterprises that use SNS for their marketing communication in Germany, Poland, and Russia.

Factors determinating the shape of survival curves of Escherichia coli cells irradiated by ionizing radiation with different LET. The dependence of the shape of survival curve on LET

International Nuclear Information System (INIS)

Kozubek, S.; Krasavin, E.A.; Fajsi, Ch.

1984-01-01

The dependence of the shape of bacterial sUrvival curve in the case of Escherichia coli Wild type, rec - and pol - mutants on linear energy transfer is considered. When increasing LET of the radiation the shouldered survival curves are transformed to exponential ones. In the case of sensitive mutants the transformation is observed for smaller values of LET. The dependence of cell sensitivity on LET calculated on the basis of Landau-Vavilov distribution is compared with earlier calculations. The comparison showed a good agreement between two methods of calculation for ions with 4 MeV per nucleon energy

Radiosensitivity of yeast cells as a function of radiation LET

International Nuclear Information System (INIS)

Lobachevskij, P.N.; Krasavin, E.A.

1988-01-01

A model is proposed for interpreting the radiosensitivity of yeast cells as a function of linear energy transfer (LET) of ionizing radiation. The model takes into account the role of repair processes in sensitivity of yeast cells to ionizing radiation of different LET. Two types of repair are discussed: (1) a nonspecific repair (characteristic of both haploid and diploid cells), and (2) a diploid - soecific repair (characteristic of diploid cells only)

LET spectrometry with track etch detectors-Use in high-energy radiation fields

International Nuclear Information System (INIS)

Jadrnickova, I.; Spurny, F.

2008-01-01

For assessing the risk from ionizing radiation it is necessary to know not only the absorbed dose but also the quality of the radiation; radiation quality is connected with the physical quantity linear energy transfer (LET). One of the methods of determination of LET is based on chemically etched track detectors. This contribution concerns with a spectrometer of LET based on the track detectors and discusses some results obtained at: ·high-energy radiation reference field created at the SPS accelerator at CERN; and ·onboard of International Space Station where track-etch based LET spectrometer has been exposed 273 days during 'Matrjoshka - R' experiment. Results obtained are compared with the results of studies at some lower-energy neutron sources; some conclusions on the registrability of neutrons and the ability of this spectrometer to determine dose equivalent in high-energy radiation fields are formulated

Differential Processing of Low and High LET Radiation Induced DNA Damage: Investigation of Switch from ATM to ATR Signaling

Science.gov (United States)

Saha, Janapriya; Wang, Minli; Hada, Megumi; Cucinotta, Francis A.

2011-01-01

The members of the phosphatidylinositol kinase-like kinase family of proteins namely ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are directly responsible for the maintenance of genomic integrity by mounting DDR through signaling and facilitating the recruitment of repair factors at the sites of DNA damage along with coordinating the deployment of cell cycle checkpoints to permit repair by phosphorylating Checkpoint kinase Chk1, Chk2 and p53. High LET radiation from GCR (Galactic Cosmic Rays) consisting mainly of protons and high energy and charged (HZE) particles from SPE (Solar Particle Event) pose a major health risk for astronauts on their space flight missions. The determination of these risks and the design of potential safeguards require sound knowledge of the biological consequences of lesion induction and the capability of the cells to counter them. We here strive to determine the coordination of ATM and ATR kinases at the break sites directly affecting checkpoint signaling and DNA repair and whether differential processing of breaks induced by low and high LET radiation leads to possible augmentation of swap of these damage sensors at the sites of DNA damage. Exposure of cells to IR triggers rapid autophosphorylation of serine-1981 that causes dimer dissociation and initiates monomer formation of ATM. ATM kinase activity depends on the disruption of the dimer, which allows access and phosphorylation of downstream ATM substrates like Chk2. Evidence suggests that ATM is activated by the alterations in higher-order chromatin structure although direct binding of ATM to DSB ends may be a crucial step in its activation. On the other hand, in case of ATR, RPA (replication protein A)-coated ssDNA (single-stranded DNA) generated as a result of stalled DNA replication or during processing of chromosomal lesions is crucial for the localization of ATR to sites of DNA damage in association with ATR-interacting protein (ATRIP). Although the

Mutational influences of low-dose and high let ionizing radiation in drosophila melanogaster

Science.gov (United States)

Lei, Huang; Fanjun, Kong; Sun, Yeqing

For cosmic environment consists of a varying kinds of radiation particles including high Z and energy ions which was charactered with low-dose and high RBE, it is important to determine the possible biofuctions of high LET radiation on human beings. To analyse the possible effectes of mutational influences of low-dose and high-LET ionizing radiation, wild fruit flies drosophila melanogaster were irradiated by 12C6+ ions in two LET levels (63.3 and 30 keV/µum) with different low doses from 2mGy to 2000mGy (2, 20, 200, 2000mGy) in HIRFL (Heavy ion radiation facility laboratory, lanzhou, China).In the same LET value group, the average polymorphic frequency was elevated along with adding doses of irradation, the frequency in 2000 mGy dose samples was significantly higher than other samples (p<0.01).These results suggest that genomic DNA sequence could be effected by low-dose and high-LET ionizing radiation, the irradiation dose is an important element in genomic mutation frequency origination.

mBAND analysis for high- and low-LET radiation-induced chromosome aberrations: A review

Energy Technology Data Exchange (ETDEWEB)

Hada, Megumi, E-mail: megumi.hada-1@nasa.gov [NASA Johnson Space Center, Houston, TX 77058 (United States); Universities Space Research Association, Houston, TX 77058 (United States); Wu Honglu; Cucinotta, Francis A. [NASA Johnson Space Center, Houston, TX 77058 (United States)

2011-06-03

During long-term space travel or cancer therapy, humans are exposed to high linear energy transfer (LET) energetic heavy ions. High-LET radiation is much more effective than low-LET radiation in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, and cytogenetic damage can be utilized as a biomarker for radiation insults. Epidemiological data, mainly from survivors of the atomic bomb detonations in Japan, have enabled risk estimation from low-LET radiation exposures. The identification of a cytogenetic signature that distinguishes high- from low-LET exposure remains a long-term goal in radiobiology. Recently developed fluorescence in situ hybridization (FISH)-painting methodologies have revealed unique endpoints related to radiation quality. Heavy-ions induce a high fraction of complex-type exchanges, and possibly unique chromosome rearrangements. This review will concentrate on recent data obtained with multicolor banding in situ hybridization (mBAND) methods in mammalian cells exposed to low- and high-LET radiations. Chromosome analysis with mBAND technique allows detection of both inter- and intrachromosomal exchanges, and also distribution of the breakpoints of aberrations.

Prophage λ induction by ionizing radiation of different LETs

International Nuclear Information System (INIS)

Bonev, M.N.; Kozubek, S.; Krasavin, E.A.; Amirtaev, K.G.

1988-01-01

The λ prophage induction caused by γ-irradiation and accelerated heavy ions with different LET was studied in variety Escherichia coli strains. The induction frequency on the dose I(D) shaped a curve with a maximum in the strains which possess recA + /lexA + genotype. The inductivity of these strains increases as well as LET and an alteration poor → rich media does it. Unlike I(D) for recA + /lexA + , the dependence I(D) for recA, lexA and recBC strains was a constant. 15 refs.; 6 figs.; 3 tabs

TH-CD-209-06: LET-Based Adjustment of IMPT Plans Using Prioritized Optimization

Energy Technology Data Exchange (ETDEWEB)

Unkelbach, J; Giantsoudi, D; Paganetti, H [Massachusetts General Hospital, Boston, MA (United States); Botas, P [Massachusetts General Hospital, Boston, MA (United States); Heidelberg University, Heidelberg, DE (Germany); Qin, N; Jia, X [The University of Texas Southwestern Medical Ctr, Dallas, TX (United States)

2016-06-15

Purpose: In-vitro experiments suggest an increase in proton relative biological effectiveness (RBE) towards the end of range. However, proton treatment planning and dose reporting for clinical outcome assessment has been based on physical dose and constant RBE. Therefore, treatment planning for intensity-modulated proton therapy (IMPT) is unlikely to transition radically to pure RBE-based planning. We suggest a hybrid approach where treatment plans are initially created based on physical dose constraints and prescriptions, and are subsequently altered to avoid high linear energy transfer (LET) in critical structures while limiting the degradation of the physical dose distribution. Methods: To allow fast optimization based on dose and LET we extended a GPU-based Monte-Carlo code towards providing dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dose objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of physical dose and LET (LETxD). To first approximation, LETxD represents a measure of the additional biological dose that is caused by high LET. Regarding optimization techniques, LETxD has the advantage of being a linear function of the pencil beam intensities. Results: The method is applicable to treatments where serial critical structures with maximum dose constraint are located in or near the target. We studied intra-cranial tumors (high-grade meningiomas, base-of-skull chordomas) where the target (CTV) overlaps with the brainstem and optic structures. Often, high LETxD in critical structures can be avoided while minimally compromising physical dose planning objectives. Conclusion: LET-based re-optimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose

Interactive extraction of neural structures with user-guided morphological diffusion

KAUST Repository

Yong Wan,; Otsuna, H.; Chi-Bin Chien,; Hansen, C.

2012-01-01

Extracting neural structures with their fine details from confocal volumes is essential to quantitative analysis in neurobiology research. Despite the abundance of various segmentation methods and tools, for complex neural structures, both manual and semi-automatic methods are ine ective either in full 3D or when user interactions are restricted to 2D slices. Novel interaction techniques and fast algorithms are demanded by neurobiologists to interactively and intuitively extract neural structures from confocal data. In this paper, we present such an algorithm-technique combination, which lets users interactively select desired structures from visualization results instead of 2D slices. By integrating the segmentation functions with a confocal visualization tool neurobiologists can easily extract complex neural structures within their typical visualization workflow.

Interactive extraction of neural structures with user-guided morphological diffusion

KAUST Repository

Yong Wan,

2012-10-01

Extracting neural structures with their fine details from confocal volumes is essential to quantitative analysis in neurobiology research. Despite the abundance of various segmentation methods and tools, for complex neural structures, both manual and semi-automatic methods are ine ective either in full 3D or when user interactions are restricted to 2D slices. Novel interaction techniques and fast algorithms are demanded by neurobiologists to interactively and intuitively extract neural structures from confocal data. In this paper, we present such an algorithm-technique combination, which lets users interactively select desired structures from visualization results instead of 2D slices. By integrating the segmentation functions with a confocal visualization tool neurobiologists can easily extract complex neural structures within their typical visualization workflow.

Additional user needs

International Nuclear Information System (INIS)

Rorschach, H.E.; Hayter, J.B.

1986-01-01

This paper summarizes the conclusions of a discussion group on users' needs held at the Workshop on an Advanced Steady-State Neutron Facility. The discussion was devoted to reactor characteristics, special facilities and siting considerations suggested by user needs. (orig.)

The Othering in Kazuo Ishiguro’s Never Let Me Go

Directory of Open Access Journals (Sweden)

Matava Vichiensing

2017-08-01

Full Text Available In this article, I will investigate the concept of ‘othering’ originally as part of a post-colonial theory. This concept is interested in many academic areas, including a literary study. In Kazuo Ishiguro’s novel Never Let Me Go is about human clones raised for organs. The clones are excluded and discriminated to be ‘the other’ from the normal people. The manifestations of othering in Never Let Me Go can be presented in the forms of linguistic features, indoctrination, objectification, and assimilation. Although the othering phenomenon can be found in the reality, it can be appeared in literary texts as well. The findings show that the study of Kazuo Ishiguro’s Never Let Me Go helps us to understand and aware of how the negative consequences of the othering process affect undesirable treatments in the society as a whole.

let-7 Modulates Chromatin Configuration and Target Gene Repression through Regulation of the ARID3B Complex

Directory of Open Access Journals (Sweden)

Tsai-Tsen Liao

2016-01-01

Full Text Available Let-7 is crucial for both stem cell differentiation and tumor suppression. Here, we demonstrate a chromatin-dependent mechanism of let-7 in regulating target gene expression in cancer cells. Let-7 directly represses the expression of AT-rich interacting domain 3B (ARID3B, ARID3A, and importin-9. In the absence of let-7, importin-9 facilitates the nuclear import of ARID3A, which then forms a complex with ARID3B. The nuclear ARID3B complex recruits histone demethylase 4C to reduce histone 3 lysine 9 trimethylation and promotes the transcription of stemness factors. Functionally, expression of ARID3B is critical for the tumor initiation in let-7-depleted cancer cells. An inverse association between let-7 and ARID3A/ARID3B and prognostic significance is demonstrated in head and neck cancer patients. These results highlight a chromatin-dependent mechanism where let-7 regulates cancer stemness through ARID3B.

Cytotoxic and mutagenic effects of high let charged particles on human skin fibroblasts

International Nuclear Information System (INIS)

Tsuboi, Koji.; Park, M.S.; Chen, D.J.; Yang, T.C.

1992-01-01

Cytotoxic and mutagenic effects of high LET charged particles were quantitatively measured using primary cultures of human skin fibroblasts. The span of LETs selected were from 25 keV/μm(330 MeV/u) to 920 keV/μm (600 MeV/u). Mutations were scored at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus using 6-thioguanine (6-TG) for selection. Exposure to these high LET charged particles resulted in exponential survival curves whereas mutant induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/μm. The inactivation cross-section (σ i ) and the action cross-section for mutant induction (σ m ) ranged from 2.2 to 92.0 μm 2 and 0.09 to 5.56 x 10 -3 μm 2 respectively, the maximum values were obtained by 56 Fe with an LET of 200 keV/μm. The mutagenicity (σ m /σ i ) ranged from 2.05 to 7.99 x 10 -5 with the maximum value at 150 keV/μm. Furthermore, the results of multiplex polymerase chain reaction (PCR) of some of the mutants induced by charged particles indicate that higher LET beams are more likely to cause larger deletions in the hprt locus. (author)

Let7a involves in neural stem cell differentiation relating with TLX level.

Science.gov (United States)

Song, Juhyun; Cho, Kyoung Joo; Oh, Yumi; Lee, Jong Eun

2015-07-10

Neural stem cells (NSCs) have the potential for differentiation into neurons known as a groundbreaking therapeutic solution for central nervous system (CNS) diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have focused on the study on microRNA's role in CNS. Some micro RNAs have been reported significant functions in NSC self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a) has known as the regulator of diverse cellular mechanisms including cell differentiation and proliferation. In present study, we investigated whether Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. We performed the following experiments: western blot analysis, TaqMan assay, RT-PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed that let7a play important roles in controlling NSC fate determination. Thus, manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency of NSC's neuronal differentiation for CNS disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The dependence of r.b.e. and o.e.r. of somatic aberration induction in tradescantia occidentalis on L.E.T. and event size spectra

International Nuclear Information System (INIS)

Dennis, J.A.

1979-01-01

The two target theory postulated by Neary and a two hit theory, identical in most respects to the dual radiation action theory of Kellerer and Rossi, have been formulated so that they may be used to express the limiting relative biological effectiveness and oxygen enhancement ratio in terms of the physical parmeters L.E.T. and event size. Both theories are comparatively successful in predicting the experimental induction of somatic aberrations in the staminal hair cells of Tradescantia occidentalis by monoenergetic neutron radiation. The two hit theory is marginally better, particularly when the possible effects of short tracks are considered and for small site diameters. In contrast the prediction of the oxygen enhancement ratio is better when large site diameters are considered. This may indicate that if oxygen is produced in the tracks of high L.E.T. particles it is less effective when produced in short tracks than when produced in long tracks. (Auth.)

High energy ion irradiation effects on polymer materials. LET dependence of G value of scission of polymethylmethacrylate (PMMA)

Energy Technology Data Exchange (ETDEWEB)

Kudoh, H; Sasuga, T; Seguchi, T [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

1997-03-01

Linear energy transfer (LET) dependence on the probability of main chain scission of polymethylmethacrylate (PMMA) was investigated. The probability was obtained from decreases in molecular weight measured by the gel permeation chromatography (GPC), and LET was evaluated by TRIM code. The scission probability as a function of LET was almost constant in the low LET, and decreased in the high LET ion irradiation. The mechanism was interpreted from the model of spur-overlapping along an ion`s path. (author)

Let-7b-mediated suppression of basigin expression and metastasis in mouse melanoma cells

International Nuclear Information System (INIS)

Fu, Tzu-Yen; Chang, Chia-Che; Lin, Chun-Ting; Lai, Cong-Hao; Peng, Shao-Yu; Ko, Yi-Ju; Tang, Pin-Chi

2011-01-01

Basigin (Bsg), also called extracellular matrix metalloproteinase inducer (EMMPRIN), is highly expressed on the surface of tumor cells and stimulates adjacent fibroblasts or tumor cells to produce matrix metalloproteinases (mmps). It has been shown that Bsg plays an important role in growth, development, cell differentiation, and tumor progression. MicroRNAs (miRNAs) are a class of short endogenous non-protein coding RNAs of 20-25 nucleotides (nt) that function as post-transcriptional regulators of gene expression by base-pairing to their target mRNAs and thereby mediate cleavage of target mRNAs or translational repression. In this study, let-7b, one of the let-7 family members, was investigated for its effect on the growth and invasiveness of the mouse melanoma cell line B16-F10. We have shown that let-7b can suppress the expression of Bsg in B16-F10 cells and also provided evidence that this suppression could result in the indirect suppression of mmp-9. The ability of B16-F10 cells transfected with let-7b to invade or migrate was significantly reduced. In addition, let-7b transfected B16-F10 cells displayed an inhibition of both cellular proliferation and colony formation. Furthermore, it was shown that the overexpression of let-7b in B16-F10 cells could reduce lung metastasis. Taken together, the present study identifies let-7b as a tumor suppressor that represses cancer cell proliferation and migration as well as tumor metastasis in mouse melanoma cells.

Let-7b-mediated suppression of basigin expression and metastasis in mouse melanoma cells

Energy Technology Data Exchange (ETDEWEB)

Fu, Tzu-Yen [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Chang, Chia-Che [Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, 91 Hsueh Shih Road, Taichung 40402, Taiwan (China); Lin, Chun-Ting [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Lai, Cong-Hao [Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Department of Life Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Peng, Shao-Yu; Ko, Yi-Ju [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Tang, Pin-Chi, E-mail: pctang@dragon.nchu.edu.tw [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China)

2011-02-15

Basigin (Bsg), also called extracellular matrix metalloproteinase inducer (EMMPRIN), is highly expressed on the surface of tumor cells and stimulates adjacent fibroblasts or tumor cells to produce matrix metalloproteinases (mmps). It has been shown that Bsg plays an important role in growth, development, cell differentiation, and tumor progression. MicroRNAs (miRNAs) are a class of short endogenous non-protein coding RNAs of 20-25 nucleotides (nt) that function as post-transcriptional regulators of gene expression by base-pairing to their target mRNAs and thereby mediate cleavage of target mRNAs or translational repression. In this study, let-7b, one of the let-7 family members, was investigated for its effect on the growth and invasiveness of the mouse melanoma cell line B16-F10. We have shown that let-7b can suppress the expression of Bsg in B16-F10 cells and also provided evidence that this suppression could result in the indirect suppression of mmp-9. The ability of B16-F10 cells transfected with let-7b to invade or migrate was significantly reduced. In addition, let-7b transfected B16-F10 cells displayed an inhibition of both cellular proliferation and colony formation. Furthermore, it was shown that the overexpression of let-7b in B16-F10 cells could reduce lung metastasis. Taken together, the present study identifies let-7b as a tumor suppressor that represses cancer cell proliferation and migration as well as tumor metastasis in mouse melanoma cells.

Harderian Gland Tumorigenesis: Low-Dose and LET Response

Energy Technology Data Exchange (ETDEWEB)

Chang, Polly Y. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cucinotta, Francis A. [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Bjornstad, Kathleen A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Bakke, James [SRI International, Menlo Park, CA (United States). Biosciences Div.; Rosen, Chris J. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Du, Nicholas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Fairchild, David G. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cacao, Eliedonna [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Blakely, Eleanor A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

2016-04-19

Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ~70 keV/μm) and 1,000 MeV/u titanium (LET ~100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

Combined chemo/radiotherapy of cancer: present state and prospects for use with high-LET radiotherapy

International Nuclear Information System (INIS)

Phillips, T.L.

1979-01-01

Cytotoxic chemotherapy added to low-LET radiotherapy has improved survival and in some cases local control. In some instances the combination has yielded increased normal tissue damage. Similar results can be expected, as confirmed by intestinal crypt cell experiments, with high-LET. Less interaction than with low-LET appears to occur with agents blocking sublethal damage repair or causing synchronization. (author)

Let´s go to the cinema! A movie recommender system for ephemeral groups of users

Directory of Open Access Journals (Sweden)

Guillermo Fernández

2015-08-01

Full Text Available Going to the cinema or watching television are social activities that generally take place in groups. In these cases, a recommender system for ephemeral groups of users is more suitable than (well-studied recommender systems for individuals. In this paper we present a recommendation system for groups of users that go to the cinema. The system uses the Slope One algorithm for computing individual predictions and the Multiplicative Utilitarian Strategy as a model to make a recommendation to an entire group. We show how we solved all practical aspects of the system; including its architecture and a mobile application for the service, the lack of user data (ramp-up and cold-start problems, the scaling fit of the group model strategy, and other improvements in order to reduce the response time. Finally, we validate the performance of the system with a set of experiments with 57 ephemeral groups.

Characterization and expression patterns of let-7 microRNA in the silkworm (Bombyx mori

Directory of Open Access Journals (Sweden)

Hong Kaili

2007-07-01

Full Text Available Abstract Background lin-4 and let-7, the two founding members of heterochronic microRNA genes, are firstly confirmed in Caenorhabditis elegans to control the proper timing of developmental programs in a heterochronic pathway. let-7 has been thought to trigger the onset of adulthood across animal phyla. Ecdysone and Broad-Complex are required for the temporal expression of let-7 in Drosophila melanogaster. For a better understanding of the conservation and functions of let-7, we seek to explore how it is expressed in the silkworm (Bombyx mori. Results One member of let-7 family has been identified in silkworm computationally and experimentally. All known members of this family share the same nucleotides at ten positions within the mature sequences. Sequence logo and phylogenetic tree show that they are not only conserved but diversify to some extent among some species. The bmo-let-7 was very lowly expressed in ova harvested from newborn unmated female adult and in individuals from the first molt to the early third instar, highly expressed after the third molt, and the most abundant expression was observed after mounting, particularly after pupation. The expression levels were higher at the end of each instar and at the beginning of each molt than at other periods, coinciding with the pulse of ecdysone and BR-C as a whole. Using cultured ovary cell line, BmN-SWU1, we examined the effect of altered ecdysone levels on bmo-let-7 expression. The expression was also detected in various tissues of day 3 of the fifth instar and of from day 7 of the fifth to pupa, suggesting a wide distributing pattern with various signal intensities. Conclusion bmo-let-7 is stage- and tissue-specifically expressed in the silkworm. Although no signals were detected during embryonic development and first larval instar stages, the expression of bmo-let-7 was observed from the first molt, suggesting that it might also function at early larval stage of the silkworm. The

Characterization and expression patterns of let-7 microRNA in the silkworm (Bombyx mori).

Science.gov (United States)

Liu, Shiping; Xia, Qingyou; Zhao, Ping; Cheng, Tingcai; Hong, Kaili; Xiang, Zhonghuai

2007-07-25

lin-4 and let-7, the two founding members of heterochronic microRNA genes, are firstly confirmed in Caenorhabditis elegans to control the proper timing of developmental programs in a heterochronic pathway. let-7 has been thought to trigger the onset of adulthood across animal phyla. Ecdysone and Broad-Complex are required for the temporal expression of let-7 in Drosophila melanogaster. For a better understanding of the conservation and functions of let-7, we seek to explore how it is expressed in the silkworm (Bombyx mori). One member of let-7 family has been identified in silkworm computationally and experimentally. All known members of this family share the same nucleotides at ten positions within the mature sequences. Sequence logo and phylogenetic tree show that they are not only conserved but diversify to some extent among some species. The bmo-let-7 was very lowly expressed in ova harvested from newborn unmated female adult and in individuals from the first molt to the early third instar, highly expressed after the third molt, and the most abundant expression was observed after mounting, particularly after pupation. The expression levels were higher at the end of each instar and at the beginning of each molt than at other periods, coinciding with the pulse of ecdysone and BR-C as a whole. Using cultured ovary cell line, BmN-SWU1, we examined the effect of altered ecdysone levels on bmo-let-7 expression. The expression was also detected in various tissues of day 3 of the fifth instar and of from day 7 of the fifth to pupa, suggesting a wide distributing pattern with various signal intensities. bmo-let-7 is stage- and tissue-specifically expressed in the silkworm. Although no signals were detected during embryonic development and first larval instar stages, the expression of bmo-let-7 was observed from the first molt, suggesting that it might also function at early larval stage of the silkworm. The detailed expression profiles in the whole life cycle and

Mutagenic effect of radiations of various LET on Salmonella cells

International Nuclear Information System (INIS)

Kozubek, S.; Krasavin, E.A.; Amirtaev, K.G.; Tokarova, B.; Basha, S.G.

1989-01-01

Regularities of mutagenic effect of heavy charged particles of helium, deuterium ions and protons on various strains of Salmonella typhimurium were studied. Linear dose dependences of mutation frequency in the range of low doses were revealed. A conclusion was made that mutation process at low dose irradiation is determined in various teststrains of Salmonella typhimurium by certain premutation injuries. Quite a different picture is observed in mutation process in case of high dose irradiation where effect of inducible SOS-repair is distinctly manifested. Not only spectra of primary DNA injuries but probability of their fixation into mutation can change with the increase of LET. If fixation probability doesn't change with LET increase for replicative mutagenesis which make basis contribution to linear component of dose dependence of mutation frequency the probability of fixation is increased for reparative mutagenesis. It accounts for increase of values of relative genetic efficiency with LET increase. 7 refs.; 6 figs.; 1 tab

Mechanism and significance of let-7 in diagnosis and treatment of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

HUO Tingting

2017-07-01

Full Text Available Abstract:MicroRNA (miRNA play important roles in post-transcriptional gene regulation. In recent years, miRNA has become a hot topic in the research on the development and progression of tumors, and gene targeting therapy for malignant tumors has achieved preliminary progress. As one of the first discovered miRNA, let-7 can regulate the cell cycle and angiogenesis and is involved in the proliferation, differentiation, and apoptosis of various tumor cells. Most members of the let-7 family can act as tumor suppressor gene and have low expression in various tumor tissues and high expression in the serum of patients with malignant tumors. Let-7 is closely associated with the invasion and drug resistance of hepatocellular carcinoma (HCC. The studies above show that let-7 might become a new marker for the early diagnosis of HCC and provide new targets for the treatment of HCC.

Owning, letting and demanding second homes in Denmark

DEFF Research Database (Denmark)

Bloze, Gintautas; Skak, Morten

with administrative register data and presents estimations of the probability of owning a second home, the decision to let the second home and the number of let weeks per year. Also income elasticities for primary and second housing demand are estimated. We find a conventional monotonic increase in demand...... elasticities for primary housing demand for non-owners of second homes; however, owners of second homes have the highest income elasticity in the middle income group.......An increasing number of households consume housing beyond the primary home as owners of a second home. Economic studies of non-speculative demand for second homeownership are still scarce, and the present empirical study fills this gap to some extent. It is based on Danish survey data combined...

Numerical Representations and User Behaviour in Social Networking Sites

DEFF Research Database (Denmark)

Sjöklint, Mimmi; Constantiou, Ioanna; Trier, Matthias

2013-01-01

The new technological enhancements and the accessibility to varieties of online applications, enable users to collect personal data and perform self-evaluation through test, comparison and experimentation. The sparked interest in numbers and numbers as self-representative visualisations is promin......The new technological enhancements and the accessibility to varieties of online applications, enable users to collect personal data and perform self-evaluation through test, comparison and experimentation. The sparked interest in numbers and numbers as self-representative visualisations...... theoretical pillars: self-determination theory, heuristic decision making and behavioural economics. A discussion departs from these convictions to investigate user reactions and behaviour when faced with numerical representations in the SNS....

Suppression of MicroRNA let-7a Expression by Agmatine Regulates Neural Stem Cell Differentiation.

Science.gov (United States)

Song, Juhyun; Oh, Yumi; Kim, Jong Youl; Cho, Kyoung Joo; Lee, Jong Eun

2016-11-01

Neural stem cells (NSCs) effectively reverse some severe central nervous system (CNS) disorders, due to their ability to differentiate into neurons. Agmatine, a biogenic amine, has cellular protective effects and contributes to cellular proliferation and differentiation in the CNS. Recent studies have elucidated the function of microRNA let-7a (let-7a) as a regulator of cell differentiation with roles in regulating genes associated with CNS neurogenesis. This study aimed to investigate whether agmatine modulates the expression of crucial regulators of NSC differentiation including DCX, TLX, c-Myc, and ERK by controlling let-7a expression. Our data suggest that high levels of let-7a promoted the expression of TLX and c-Myc, as well as repressed DCX and ERK expression. In addition, agmatine attenuated expression of TLX and increased expression of ERK by negatively regulating let-7a. Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders.

Generating Code with Polymorphic let: A Ballad of Value Restriction, Copying and Sharing

Directory of Open Access Journals (Sweden)

Oleg Kiselyov

2017-02-01

Full Text Available Getting polymorphism and effects such as mutation to live together in the same language is a tale worth telling, under the recurring refrain of copying vs. sharing. We add new stanzas to the tale, about the ordeal to generate code with polymorphism and effects, and be sure it type-checks. Generating well-typed-by-construction polymorphic let-expressions is impossible in the Hindley-Milner type system: even the author believed that. The polymorphic-let generator turns out to exist. We present its derivation and the application for the lightweight implementation of quotation via a novel and unexpectedly simple source-to-source transformation to code-generating combinators. However, generating let-expressions with polymorphic functions demands more than even the relaxed value restriction can deliver. We need a new deal for let-polymorphism in ML. We conjecture the weaker restriction and implement it in a practically-useful code-generation library. Its formal justification is formulated as the research program.

Let-7i-Induced Atg4B Suppression Is Essential for Autophagy of Placental Trophoblast in Preeclampsia.

Science.gov (United States)

Xu, Yinyan; Huang, Xinyan; Xie, Juan; Chen, Yanni; Fu, Jing; Wang, Li

2017-09-01

Autophagy, identified as type II programmed cell death, has already been known to be involved in the pathophysiology of preeclampsia (PE), which is a gestational disease with high morbidity. The present study aims to investigate the functional role of let-7i, a miRNA, in trophoblastic autophagy. Placental tissue used in this study was collected from patients with severe preeclampsia (SPE) or normal pregnant women. A decreased level of let-7i was found in placenta of SPE. In addition, autophagic vacuoles were observed in SPE and the expression of microtubule associated protein 1 light chain 3 (LC3) II/I was elevated. In vitro, let-7i mimics suppressed the autophagic activities in human HTR-8/SVneo trophoblast cell line (HTR-8) and human placental choriocarcinoma cell line JEG-3, whereas let-7i inhibitor enhanced the activities. As a potential target of let-7i, autophagy-related 4B cysteine peptidase (Atg4B) had an increased expression level in SPE. As expected, the increased expression of Atg4B was negatively regulated by let-7i using dual luciferase reporter assay. Furthermore, these trophoblast-like cells transfected with the let-7i mimic or inhibitors resulted in a significant change of Atg4B in both mRNA and protein level. More importantly, Atg4B overexpression could partly reverse let-7i mimic-reduced LC3II/I levels; whereas Atg4B silencing partly attenuated let-7i inhibitor-induced the level of LC3II/I expression. Taken together, these findings suggest that let-7i is able to regulate autophagic activity via regulating Atg4B expression, which might contribute to the pathogenesis of PE. J. Cell. Physiol. 232: 2581-2589, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

High LET Radiation Amplifies Centrosome Overduplication Through a Pathway of γ-Tubulin Monoubiquitination

Energy Technology Data Exchange (ETDEWEB)

Shimada, Mikio [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto (Japan); Hirayama, Ryoichi [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Komatsu, Kenshi, E-mail: komatsu@house.rbc.kyoto-u.ac.jp [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto (Japan)

2013-06-01

Purpose: Radiation induces centrosome overduplication, leading to mitotic catastrophe and tumorigenesis. Because mitotic catastrophe is one of the major tumor cell killing factors in high linear energy transfer (LET) radiation therapy and long-term survivors from such treatment have a potential risk of secondary tumors, we investigated LET dependence of radiation-induced centrosome overduplication and the underlying mechanism. Methods and Materials: Carbon and iron ion beams (13-200 keV/μm) and γ-rays (0.5 keV/μm) were used as radiation sources. To count centrosomes after IR exposure, human U2OS and mouse NIH3T3 cells were immunostained with antibodies of γ-tubulin and centrin 2. Similarly, Nbs1-, Brca1-, Ku70-, and DNA-PKcs-deficient mouse cells and their counterpart wild-type cells were used for measurement of centrosome overduplication. Results: The number of excess centrosome-containing cells at interphase and the resulting multipolar spindle at mitosis were amplified with increased LET, reaching a maximum level of 100 keV/μm, followed by sharp decrease in frequency. Interestingly, Ku70 and DNA-PKcs deficiencies marginally affected the induction of centrosome overduplication, whereas the cell killings were significantly enhanced. This was in contrast to observation that high LET radiation significantly enhanced frequencies of centrosome overduplication in Nbs1- and Brca1-deficient cells. Because NBS1/BRCA1 is implicated in monoubiquitination of γ-tubulin, we subsequently tested whether it is affected by high LET radiation. As a result, monoubiquitination of γ-tubulin was abolished in 48 to 72 hours after exposure to high LET radiation, although γ-ray exposure slightly decreased it 48 hours postirradiation and was restored to a normal level at 72 hours. Conclusions: High LET radiation significantly reduces NBS1/BRCA1-mediated monoubiquitination of γ-tubulin and amplifies centrosome overduplication with a peak at 100 keV/μm. In contrast, Ku70 and DNA

Effects of let-7b and TLX on the proliferation and differentiation of retinal progenitor cells in vitro.

Science.gov (United States)

Ni, Ni; Zhang, Dandan; Xie, Qing; Chen, Junzhao; Wang, Zi; Deng, Yuan; Wen, Xuyang; Zhu, Mengyu; Ji, Jing; Fan, Xianqun; Luo, Min; Gu, Ping

2014-10-20

MicroRNAs manifest significant functions in brain neural stem cell (NSC) self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. Let-7b is expressed in the mammalian brain and regulates NSC proliferation and differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal. Whether let-7b and TLX act as important regulators in retinal progenitor cell (RPC) proliferation and differentiation remains unknown. Here, our data show that let-7b and TLX play important roles in controlling RPC fate determination in vitro. Let-7b suppresses TLX expression to negatively regulate RPC proliferation and accelerate the neuronal and glial differentiation of RPCs. The overexpression of let-7b downregulates TLX levels in RPCs, leading to reduced RPC proliferation and increased neuronal and glial differentiation, whereas antisense knockdown of let-7b produces robust TLX expression,enhanced RPC proliferation and decreased differentiation. Moreover, the inhibition of endogenous TLX by small interfering RNA suppresses RPC proliferation and promotes RPC differentiation. Furthermore, overexpression of TLX rescues let-7b-induced proliferation deficiency and weakens the RPC differentiation enhancement caused by let-7b alone. These results suggest that let-7b, by forming a negative feedback loop with TLX, provides a novel model to regulate the proliferation and differentiation of retinal progenitors in vitro.

Review of relative biological effectiveness dependence on linear energy transfer for low-LET radiations

International Nuclear Information System (INIS)

Hunter, Nezahat; Muirhead, Colin R

2009-01-01

Information on Japanese A-bomb survivors exposed to gamma radiation has been used to estimate cancer risks for the whole range of photon (x-rays) and electron energies which are commonly encountered by radiation workers in the work place or by patients and workers in diagnostic radiology. However, there is some uncertainty regarding the radiation effectiveness of various low-linear energy transfer (low-LET) radiations (x-rays, gamma radiation and electrons). In this paper we review information on the effectiveness of low-LET radiations on the basis of epidemiological and in vitro radiobiological studies. Data from various experimental studies for chromosome aberrations and cell transformation in human lymphocytes and from epidemiological studies of the Japanese A-bomb survivors, patients medically exposed to radiation for diagnostic and therapeutic procedures, and occupational exposures of nuclear workers are considered. On the basis of in vitro cellular radiobiology, there is considerable evidence that the relative biological effectiveness (RBE) of high-energy low-LET radiation (gamma radiation, electrons) is less than that of low-energy low-LET radiation (x-rays, betas). This is a factor of about 3 to 4 for 29 kVp x-rays (e.g. as in diagnostic radiation exposures of the female breast) and for tritium beta-rays (encountered in parts of the nuclear industry) relative to Co-60 gamma radiation and 2-5 MeV gamma-rays (as received by the Japanese A-bomb survivors). In epidemiological studies, although for thyroid and breast cancer there appears to be a small tendency for the excess relative risks to decrease as the radiation energy increases for low-LET radiations, it is not statistically feasible to draw any conclusion regarding an underlying dependence of cancer risk on LET for the nominally low-LET radiations. (review)

Waste treatability guidance program. User`s guide. Revision 0

Energy Technology Data Exchange (ETDEWEB)

Toth, C.

1995-12-21

DOE sites across the country generate and manage radioactive, hazardous, mixed, and sanitary wastes. It is necessary for each site to find the technologies and associated capacities required to manage its waste. One role of DOE HQ Office of Environmental Restoration and Waste Management is to facilitate the integration of the site- specific plans into coherent national plans. DOE has developed a standard methodology for defining and categorizing waste streams into treatability groups based on characteristic parameters that influence waste management technology needs. This Waste Treatability Guidance Program automates the Guidance Document for the categorization of waste information into treatability groups; this application provides a consistent implementation of the methodology across the National TRU Program. This User`s Guide provides instructions on how to use the program, including installations instructions and program operation. This document satisfies the requirements of the Software Quality Assurance Plan.

High LET radiation enhances apoptosis in mutated p53 cancer cells through Caspase-9 activation

International Nuclear Information System (INIS)

Yamakawa, Nobuhiro; Takahashi, Akihisa; Mori, Eiichiro; Imai, Yuichiro; Ohnishi, Ken; Kirita, Tadaaki; Ohnishi, Takeo; Furusawa, Yoshiya

2008-01-01

Although mutations in the p53 gene can lead to resistance to radiotherapy, chemotherapy and thermotherapy, high linear energy transfer (LET) radiation induces apoptosis regardless of p53 gene status in cancer cells. The aim of this study was to clarify the mechanisms involved in high LET radiation-induced apoptosis. Human gingival cancer cells (Ca9-22 cells) containing a mutated p53 (mp53) gene were irradiated with X-rays, C-ion (13-100 KeV/μm), or Fe-ion beams (200 KeV/μm). Cellular sensitivities were determined using colony forming assays. Apoptosis was detected and quantified with Hoechst 33342 staining. The activity of Caspase-3 was analyzed with Western blotting and flow cytometry. Cells irradiated with high LET radiation showed a high sensitivity with a high frequency of apoptosis induction. The relative biological effectiveness (RBE) values for the surviving fraction and apoptosis induction increased in a LET-dependent manner. Both RBE curves reached a peak at 100 KeV/μm, and then decreased at values over 100 KeV/μm. When cells were irradiated with high LET radiation, Caspase-3 was cleaved and activated, leading to poly (ADP-ribose) polymerase (PARP) cleavage. In addition, Caspase-9 inhibitor suppressed Caspase-3 activation and apoptosis induction resulting from high LET radiation to a greater extent than Caspase-8 inhibitor. These results suggest that high LET radiation enhances apoptosis by activation of Caspase-3 through Caspase-9, even in the presence of mp53. (author)

SCP Tools user's guide: A knowledge base toolbox for documenting relationships among high-level issues and site studies planned for characterization of a repository site

International Nuclear Information System (INIS)

Korns, D.E.; Troy, K.S.

1988-03-01

This document describes a personal computer knowledge base system that ranges from issue identification to performance allocation of mined geologic disposal system site characteristics. With SCP Tools, a user can describe a system configuration, identify information needs and parameters and allocate performance of selected system characteristics. SCP Tools allows the user to define information needs for resolution of an issue; parameters required for an information need; measures of performance for parameters, and then link supporting parameters to performance parameters and performance parameters to performance measures. All this is done with computer tools that create non-redundant facts stored in a knowledge base. Unlike most information systems, the SCP Tools remember which facts were already collected, thus allowing greater flexibility and speed in appending facts and reducing the amount of hard disk storage

LET spectrum measurements in Cr-39 PNTD with AFM

Energy Technology Data Exchange (ETDEWEB)

Johnson, Carl Edward [Los Alamos National Laboratory; De Witt, Joel M [OSU, PHYSICS; Benton, Eric R [OSU, PHYSICS; Yasuda, Nakahiro [NIRS, HIMAC; Benton, Eugene V [UNIV OF SAN FRANCISCO

2010-01-01

Energetic protons, neutrons, and heavy ions undergoing collisions with target nuclei of varying Z can produce residual heavy recoil fragments via intra-nuclear cascade/evaporation reactions. The particles produced in these non-elastic collisions generally have such extremely short range ({approx}< 10 {mu}m) that they cannot be directly observed by conventional detection methods including CR-39 plastic nuclear track detector (PNTD) that has been chemically etched for analysis by standard visible light microscopy. However, high-LET recoil fragments having range on the order of several cell diameters can be produced in tissue during radiotherapy using proton and carbon beams. We have developed a method to analyze short-range, high-LET tracks in CR-39 plastic nuclear track detector (PNTD) using short duration chemical etching ({approx}< 1 {mu}m) followed by automated atomic force microscope (AFM) scanning. The post-scan data processing used in this work was based on semi-automated matrix analysis opposed to traditional grey-scale image analysis. This method takes advantage of the 3-D data obtained via AFM to achieve robust discrimination of nuclear tracks from other features. Through automation of AFM scanning, sufficient AFM scan frames were obtained to attain an LET spectrum spanning the LET range from 200-1500 keV/{mu}m. In addition to our experiments, simulations were carried out with the Monte Carlo transport code, FLUKA. To demonstrate this method, CR-39 PNTD was exposed to the proton therapy beam at Loma Linda University Medical Center (LLUMC) at 60 and 230 MeV. Additionally, detectors were exposed to I GeV protons at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL). For these exposures CR-39 PNTD, Al and Cu target foils were used between detector layers.

LET spectrum measurements in Cr-39 PNTD with AFM

International Nuclear Information System (INIS)

Johnson, Carl Edward; DeWitt, Joel M.; Benton, Eric R.; Yasuda, Nakahiro; Benton, Eugene V.

2010-01-01

Energetic protons, neutrons, and heavy ions undergoing collisions with target nuclei of varying Z can produce residual heavy recoil fragments via intra-nuclear cascade/evaporation reactions. The particles produced in these non-elastic collisions generally have such extremely short range (∼< 10 μm) that they cannot be directly observed by conventional detection methods including CR-39 plastic nuclear track detector (PNTD) that has been chemically etched for analysis by standard visible light microscopy. However, high-LET recoil fragments having range on the order of several cell diameters can be produced in tissue during radiotherapy using proton and carbon beams. We have developed a method to analyze short-range, high-LET tracks in CR-39 plastic nuclear track detector (PNTD) using short duration chemical etching (∼< 1 μm) followed by automated atomic force microscope (AFM) scanning. The post-scan data processing used in this work was based on semi-automated matrix analysis opposed to traditional grey-scale image analysis. This method takes advantage of the 3-D data obtained via AFM to achieve robust discrimination of nuclear tracks from other features. Through automation of AFM scanning, sufficient AFM scan frames were obtained to attain an LET spectrum spanning the LET range from 200-1500 keV/μm. In addition to our experiments, simulations were carried out with the Monte Carlo transport code, FLUKA. To demonstrate this method, CR-39 PNTD was exposed to the proton therapy beam at Loma Linda University Medical Center (LLUMC) at 60 and 230 MeV. Additionally, detectors were exposed to I GeV protons at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL). For these exposures CR-39 PNTD, Al and Cu target foils were used between detector layers.

Implementing Recommendations From Web Accessibility Guidelines: A Comparative Study of Nondisabled Users and Users With Visual Impairments.

Science.gov (United States)

Schmutz, Sven; Sonderegger, Andreas; Sauer, Juergen

2017-09-01

The present study examined whether implementing recommendations of Web accessibility guidelines would have different effects on nondisabled users than on users with visual impairments. The predominant approach for making Web sites accessible for users with disabilities is to apply accessibility guidelines. However, it has been hardly examined whether this approach has side effects for nondisabled users. A comparison of the effects on both user groups would contribute to a better understanding of possible advantages and drawbacks of applying accessibility guidelines. Participants from two matched samples, comprising 55 participants with visual impairments and 55 without impairments, took part in a synchronous remote testing of a Web site. Each participant was randomly assigned to one of three Web sites, which differed in the level of accessibility (very low, low, and high) according to recommendations of the well-established Web Content Accessibility Guidelines 2.0 (WCAG 2.0). Performance (i.e., task completion rate and task completion time) and a range of subjective variables (i.e., perceived usability, positive affect, negative affect, perceived aesthetics, perceived workload, and user experience) were measured. Higher conformance to Web accessibility guidelines resulted in increased performance and more positive user ratings (e.g., perceived usability or aesthetics) for both user groups. There was no interaction between user group and accessibility level. Higher conformance to WCAG 2.0 may result in benefits for nondisabled users and users with visual impairments alike. Practitioners may use the present findings as a basis for deciding on whether and how to implement accessibility best.

WE-H-BRA-05: Investigation of LET Spectral Dependence of the Biological Effects of Therapeutic Protons

Energy Technology Data Exchange (ETDEWEB)

Guan, F; Bronk, L; Kerr, M; Wang, X; Li, Y; Peeler, C; Sahoo, N; Patel, D; Mirkovic, D; Titt, U; Grosshans, D; Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: To investigate the dependence of biologic effect (BE) of therapeutic protons on LET spectra by comparing BEs with equal dose-averaged LET (LETd) derived from different LET spectra using high-throughput in vitro clonogenic survival assays. Methods: We used Geant4 to design the relevant experimental setups and perform the dose, LETd, and LET spectra calculations for spot-scanning protons. The clonogenic assay was performed using the H460 lung cancer cell line cultured in 96-well plates. In the first experimental setup (S1), cells were irradiated using 127.4 MeV protons with a 93.22 mm Lucite buildup resulting in a LETd value of 3.4 keV/µm in the cell layer. In the second experimental setup (S2), cells were irradiated by a combination of 127.4 MeV and 136.4 MeV protons with a 96.61 mm Lucite buildup. The LETd values in the cell layer were 11.4 keV/µm and 1.5 keV/µm respectively, but an average LETd of 3.4 keV/µm was obtained by adjusting the relative fluence of each beam. Ten discrete dose levels with 0.5 Gy increments were delivered. Results: In the two setups, the energies or LET spectra were different but resulted in identical LETd values. We quantified the dose contributions from high-LET (≥10 keV/µm, threshold determined by previous experiments) events in the LET spectra separately for these two setups as 3.2% and 10.5%. The biologic effects at each identical dose level yielded statistically significant different survival curves (extra sum-of-squares F-test, P<0.0001). The second setup with a higher contribution from high-LET events exhibited the higher biologic effect with a dose enhancement factor of 1.17±0.03 at 0.10 surviving fraction. Conclusion: The dose-averaged LET may not be an accurate indicator of the biological effects of protons. Detailed LET spectra may need to be considered explicitly to accurately quantify the biologic effects of protons. Funding Support: U19 CA021239-35, R21 CA187484-01 and MDACC-IRG.

Let the Right One In : Motion picture (2008)

OpenAIRE

Buhagiar, Celaine; Lauri Lucente, Gloria

2009-01-01

Twilight: A teenage girl risks everything when she falls in love with a vampire. Let the Right One In: Oskar, an overlooked and bullied boy, finds love and revenge through Eli, a beautiful but peculiar girl.

Cosmic ray LET spectra and doses on board Cosmos-2044 biosatellite

International Nuclear Information System (INIS)

Dudkin, V.E.; Kovalev, E.E.; Potapov, Yu.V.

1992-01-01

Results of the experiments on board Cosmos-2044 (Biosatellite 9) are presented. Various nuclear track detectors (NTD) (dielectric, AgCl-based, nuclear emulsions) were used to obtain the LET spectra inside and outside the satellite. The spectra from the different NTDs have proved to be in general agreement. The results of LET spectra calculations using two different models are also presented. The resultant LET distributions are used to calculate the absorbed and equivalent doses and the orbit-averaged quality factors (QF) of the cosmic rays (CR). Absorbed dose rates inside (∼ 20 g cm -2 shielding) and outside (1 g cm -2 ) the spacecraft, omitting electrons, were found to be 4.8 and 8.6 mrad d -1 , respectively, while the corresponding equivalent doses were 8.8 and 19.7 mrem d -1 . The effects of the flight parameters on the total fluence of, and on the dose from, the CR particles are analyzed. Integral dose distributions of the detected particles are also determined. The LET values which separate absorbed and equivalent doses into 50% intervals are estimated. The CR-39 dielectric NTD is shown to detect 20-30% of the absorbed dose and 60-70% of the equivalent dose in the Cosmos-2044 orbit. The influence of solar activity phase on the magnitude of the CR flux is discussed. (author)

Let Me Relax: Toward Automated Sedentary State Recognition and Ubiquitous Mental Wellness Solutions

Directory of Open Access Journals (Sweden)

Vijay Rajanna

2018-12-01

Full Text Available Advances in ubiquitous computing technology improve workplace productivity, reduce physical exertion, but ultimately result in a sedentary work style. Sedentary behavior is associated with an increased risk of stress, obesity, and other health complications. Let Me Relax is a fully automated sedentary-state recognition framework using a smartwatch and smartphone, which encourages mental wellness through interventions in the form of simple relaxation techniques. The system was evaluated through a comparative user study of 22 participants split into a test and a control group. An analysis of NASA Task Load Index pre- and post- study survey revealed that test subjects who followed relaxation methods, showed a trend of both increased activity as well as reduced mental stress. Reduced mental stress was found even in those test subjects that had increased inactivity. These results suggest that repeated interventions, driven by an intelligent activity recognition system, is an effective strategy for promoting healthy habits, which reduce stress, anxiety, and other health risks associated with sedentary workplaces.

Bevatron/Bevalac user's handbook: biology and medicine. Revision

International Nuclear Information System (INIS)

1985-04-01

The Bevalac Biomedical Facility develops a source of near-relativistic heavy ions for applications to radiation biology, radiation therapy and diagnostic radiology. Pulsed beams of high LET heavy ions with variable pulse width, frequency, intensity and energy are produced and delivered to the Biomedical Facility by the Bevatron/Bevalac accelerator complex. Dosimetry equipment under computer control provides accurate determinations of absorbed doses in all regions of the Bragg curve. Depth-dose modifying devices and precise specimen positioning equipment are available. Animal housing and tissue culture facilities are convenient to the experimenter. This handbook is designed to provide the user with the relevant information for planning, proposing and executing an experiment

Dosimetry and microdosimetry using LET spectrometer based on the track-etch detector: radiotherapy Bremsstrahlung beam, onboard aircraft radiation field

International Nuclear Information System (INIS)

Jadrnickova, I.; Spurny, F.

2006-01-01

The spectrometer of linear energy transfer (Let) based on the chemically etched poly-allyl-diglycol-carbonate (P.A.D.C.) track-etch detector was developed several years ago in our institute. This Let spectrometer enables determining Let of particles approximately from 10 to 700 keV/μm. From the Let spectra, dose characteristics can be calculated. The contribution presents the Let spectra and other dosimetric characteristics obtained onboard a commercial aircraft during more than 6 months long exposure and in the 18 MV radiotherapy Bremsstrahlung beam. (authors)

High-LET particle dosimetry in the ASTP-Biostack III: Zea mays experiment

International Nuclear Information System (INIS)

Peterson, D.D.; Benton, E.V.; Tran, M.; Yang, T.; Freeling, M.; Craise, L.; Tobias, C.A.

1977-01-01

High-LET particle hits in embryos of Zea mays (corn) seeds, flown as part of the ASTP-Biostack III, were determined via plastic nuclear track detectors. Based on etched particle-tracks measurements, 41 embryos were hit in seed layer 1 which contained 80 seeds, and 49 hits occurred in layer 2 which contained 79 seeds. The mean LET value and range of atomic numbers of recorded hits is, respectively, 210 +- 57 keV/μm and 9 approximately less than Z approximately less than 26. Detailed analysis of one particular seed showing marked growth anomalies revealed two hits in the central region of the embryo. These two hits had LET values in the region of 100 to 150 keV/μm, and Z less than approximately 20. (author)

Chemical protection from high LET radiation

International Nuclear Information System (INIS)

Ando, Koichi; Koike, Sachiko; Matsushita, Satoru; Kanai, Tatsuaki; Ohara, Hiroshi

1992-01-01

Radioprotection by WR151327 from high LET fast neutrons was investigated and compared with that from low LET radiation. Radiation damage in bone marrow, intestine, skin and leg length were all protected by a pretreatment with 400 mg/kg WR151327. Most prominent protection was observed for bone marrow, which gave a Dose Modifying Factor (DMF) of 2.2 against γ rays. Identical protection was observed between early and late radiation damage. WR151327 protected fast neutrons less efficiently than γ rays; 40% for bone marrow and 80% for skin leg. Pathological findings indicated that hyperplastic change in both dermis and epidermis associated with late skin shrinkage. Laser doppler flow-metry showed a good relationship between reduction of blood flow and late skin shrinkage. Irradiation of skin by heavy particle Carbon-12 indicated that skin shrinkage was modified by unirradiated surrounding normal tissues, which proposed a significant role of 'Volume Effect' in radiation damage. Tumor tissues were less protected by WR151327 than normal tissues. Dependence of radioprotection by WR151327 on tissue oxygen concentration is a probable reason to explain the difference between normal and tumor tissues. (author)

Let-7a is a direct EWS-FLI-1 target implicated in Ewing's sarcoma development.

Directory of Open Access Journals (Sweden)

Claudio De Vito

Full Text Available Ewing's sarcoma family tumors (ESFT are the second most common bone malignancy in children and young adults, characterized by unique chromosomal translocations that in 85% of cases lead to expression of the EWS-FLI-1 fusion protein. EWS-FLI-1 functions as an aberrant transcription factor that can both induce and suppress members of its target gene repertoire. We have recently demonstrated that EWS-FLI-1 can alter microRNA (miRNA expression and that miRNA145 is a direct EWS-FLI-1 target whose suppression is implicated in ESFT development. Here, we use miRNA arrays to compare the global miRNA expression profile of human mesenchymal stem cells (MSC and ESFT cell lines, and show that ESFT display a distinct miRNA signature that includes induction of the oncogenic miRNA 17-92 cluster and repression of the tumor suppressor let-7 family. We demonstrate that direct repression of let-7a by EWS-FLI-1 participates in the tumorigenic potential of ESFT cells in vivo. The mechanism whereby let-7a expression regulates ESFT growth is shown to be mediated by its target gene HMGA2, as let-7a overexpression and HMGA2 repression both block ESFT cell tumorigenicity. Consistent with these observations, systemic delivery of synthetic let-7a into ESFT-bearing mice restored its expression in tumor cells, decreased HMGA2 expression levels and resulted in ESFT growth inhibition in vivo. Our observations provide evidence that deregulation of let-7a target gene expression participates in ESFT development and identify let-7a as promising new therapeutic target for one of the most aggressive pediatric malignancies.

Mouse fecal microbiome after exposure to high LET radiation

Data.gov (United States)

National Aeronautics and Space Administration — Space travel is associated with continuous low-dose-rate exposure to high Linear Energy Transfer (LET) radiation. Pathophysiological manifestations after low-dose...

Oxygen as a product of water radiolysis in high-LET tracks. II. Radiobiological implications

International Nuclear Information System (INIS)

Baverstock, K.F.; Burns, W.G.

1981-01-01

Consideration is given to the possibility that molecular oxygen generated in the tracks of energetic heavy ions is responsible for the reduction in oxygen enhancement ratio (OER) with increasing linear energy transfer (LET) observed for the loss of reproductive capacity caused by radiation in many cellular organisms. Yields of oxygen relationship of OER to LET for two organisms, Chlamydomonas reinhardii and Shigella flexneri, using a simple diffusion kinetic model for radiobiological action which takes account of the diffusion of oxygen after its formation. The results of these calculations show that the model accounts well for the shape of the OER vs. LET relationship

Analysis of mutagenic effects induced by carbon beams at different LET in a red yeast strain

International Nuclear Information System (INIS)

Sun Haining; Wang Jufang; Ma Shuang; Lu Dong; Wu Xin; Li Wenjian

2011-01-01

To evaluate inactive and mutagenic effects of carbon beam at different LET, the inactivation cross section and mutation cross section induced by carbon beams of different LET values were investigated in a red yeast strain Rhodotorula glutinis AY 91015. It was found that the maximum inactivation cross section of 4.37μm 2 , which was very close to the average nucleus cross section, was at LET of 120.0 keV/μm. The maximum mutation cross section was at LET of 96.0 keV/μm. Meanwhile, the highest mutagenicity of carbon ion was found around 58.2 keV/μm. It implied that the most efficient LET to induce mutation in survival yeasts was 58.2 keV/μm, which corresponded to energy of 35 MeV/u carbon beam. The most effective carbon beam to induce inactivation and mutation located at different energy region. (authors)

LET’s start new a LETS: Learning from a case-study investigation in Brno, Czech Republic

Directory of Open Access Journals (Sweden)

Lukáš Kala

2013-12-01

Full Text Available This paper brings information about the operation of RozLEŤSe, a LETS (Local Exchange Trading System network, based inBrno. LETS are parallel sustainable monetary systems, in which local community networks attempt to extricate themselves from the international economy by using their own currency. LETS is supposed to promote sustainable development by localising economic development. Although, there used to be several LETS group in the Czech Republic, all of them vanished during the first few years of the new millennium.  RozLEŤSe was built from the remains of former LETS groups. Hence, the aim of this study is to determine possible threats to the future existence of the group and evaluate its current operations. This research is a sociological case study investigation examining the socio-demographic characteristics, motivations and organisational functioning of the group. We point out some serious threats to the group (lack of supply, growth in negative credit, decrease in trust and offer possible solutions. 

Exploring the Relationship Between Online Social Network Site Usage and the Impact on Quality of Life for Older and Younger Users: An Interaction Analysis.

Science.gov (United States)

Quinn, Darren; Chen, Liming; Mulvenna, Maurice D; Bond, Raymond

2016-09-29

Analyzing content generated by users of social network sites has been shown to be beneficial across a number of disciplines. Such analysis has revealed the precise behavior of users that details their distinct patterns of engagement. An issue is evident whereby without direct engagement with end users, the reasoning for anomalies can only be the subject of conjecture. Furthermore, the impact of engaging in social network sites on quality of life is an area which has received little attention. Of particular interest is the impact of online social networking on older users, which is a demographic that is specifically vulnerable to social isolation. A review of the literature reveals a lack of knowledge concerning the impact of these technologies on such users and even less is known regarding how this impact varies across different demographics. The objective of our study was to analyze user interactions and to survey the attitudes of social network users directly, capturing data in four key areas: (1) functional usage, (2) behavioral patterns, (3) technology, and (4) quality of life. An online survey was constructed, comprising 32 questions. Each question directly related to a research question. Respondents were recruited through a variety of methods including email campaigns, Facebook advertisements, and promotion from related organizations. In total, data was collected from 919 users containing 446 younger and 473 older users. In comparison to younger users, a greater proportion of older users (289/473, 61.1% older vs 218/446, 48.9% younger) (PFacebook had either a positive or huge impact on their quality of life. Furthermore, a greater percentage of older users strongly agreed that Facebook strengthened their relationship with other people (64/473, 13.5% older vs 40/446, 9.0%younger) (P=.02). In comparison to younger users, a greater proportion of older users had more positive emotions-classified as slightly better or very good-during their engagement with

Depth-Dose and LET Distributions of Antiproton Beams in Various Target Materials

DEFF Research Database (Denmark)

Herrmann, Rochus; Olsen, Sune; Petersen, Jørgen B.B.

the annihilation process. Materials We have investigated the impact of substituting the target material on  the depth-dose distribution of pristine and  spread out antiproton beams using the FLUKA Monte Carlo transport program. Classical ICRP targets are compared to water phantoms. In addition, track average...... unrestricted LET is calculated for all configurations. Finally, we investigate which concentrations of gadolinium and boron are needed in a water target in order to observe a significant change in the antiproton depth-dose distribution.  Results Results indicate, that there is no significant change...... in the depth-dose distribution and average LET when substituting the materials. Adding boron and gadolinium up to concentrations of 1 per 1000 atoms to a water phantom, did not change the depth-dose profile nor the average LET. Conclusions  According to our FLUKA calculations, antiproton neutron capture...

Experiences with on-site power sources at KCB

Energy Technology Data Exchange (ETDEWEB)

Heijnen, B. M.A. [Borssele Nuclear Power Station, N.V. P.Z.E.M., Postbus 48, 4330 AA Middleburg (Netherlands)

1986-02-15

The design of the nuclear power station is of the late sixties. The experiences with the on-site power sources, signal processing and some of the resulting modifications of the design of the power plant are mentioned. In order to let the design satisfy as much as possible present ideas about safety, it was decided to realize a total new and Independent decay heat removal System. With this system a second independent on-site power System is at disposal in case of accident situations. (author)

Internal high linear energy transfer (LET) targeted radiotherapy for cancer

International Nuclear Information System (INIS)

Allen, Barry J

2006-01-01

High linear energy transfer (LET) radiation for internal targeted therapy has been a long time coming on to the medical therapy scene. While fundamental principles were established many decades ago, the clinical implementation has been slow. Localized neutron capture therapy, and more recently systemic targeted alpha therapy, are at the clinical trial stage. What are the attributes of these therapies that have led a band of scientists and clinicians to dedicate so much of their careers? High LET means high energy density, causing double strand breaks in DNA, and short-range radiation, sparing adjacent normal tissues. This targeted approach complements conventional radiotherapy and chemotherapy. Such therapies fail on several fronts. Foremost is the complete lack of progress for the control of primary GBM, the holy grail for cancer therapies. Next is the inability to regress metastatic cancer on a systemic basis. This has been the task of chemotherapy, but palliation is the major application. Finally, there is the inability to inhibit the development of lethal metastatic cancer after successful treatment of the primary cancer. This review charts, from an Australian perspective, the developing role of local and systemic high LET, internal radiation therapy. (review)

Expression of hsa Let-7a MicroRNA of Macrophages Infected by Leishmania Major

Directory of Open Access Journals (Sweden)

Nooshin Hashemi

2016-10-01

Full Text Available Leishmaniasis is a vector-born disease caused by species of the genus Leishmania and is transmitted from host to host through the bite of an infected sandfly. MicroRNAs (miRNAs are non-coding small RNAs with 22-nucleotide length. They are involved in some biological and cellular processes. We aimed to evaluate the expression of let-7a in human macrophages miRNA when are infected by Leishmania major. We also evaluated the impact of Leishmania major infection on the expression of let-7a at two different times, 24 and 48 hours, after infection. Blood samples were collected from ten healthy volunteers with no history of leishmaniasis. Development of macrophages from peripheral monocytes and infection with stationary phase of Leishmania major promastigotes were done through serial cultures under 5% CO2 environment and 37C. To measure the expression levels of let-7a real-time PCR was performed with specific related primers using the SYBR® Green master mix Kit™. The real-time PCR showed let-7a was expressed in cells infected with parasites after 24 and 48h post-infection. Comparison of let-7a miRNA expression after 24 and 48 h revealed that let-7a miRNAs were down-regulated at 48 h post-infection more than 24h after infection. The results of this study suggest that according to the main function of miRNA in repression of mRNA translation it could be possible to manipulate host cells in order to alter miRNA levels and regulate macrophage functions after establishment of intracellular parasites such as Leishmania.

Microglial-derived miRNA let-7 and HMGB1 contribute to ethanol-induced neurotoxicity via TLR7.

Science.gov (United States)

Coleman, Leon G; Zou, Jian; Crews, Fulton T

2017-01-25

Toll-like receptor (TLR) signaling is emerging as an important component of neurodegeneration. TLR7 senses viral RNA and certain endogenous miRNAs to initiate innate immune responses leading to neurodegeneration. Alcoholism is associated with hippocampal degeneration, with preclinical studies linking ethanol-induced neurodegeneration with central innate immune induction and TLR activation. The endogenous miRNA let-7b binds TLR7 to cause neurodegeneration. TLR7 and other immune markers were assessed in postmortem human hippocampal tissue that was obtained from the New South Wales Tissue Bank. Rat hippocampal-entorhinal cortex (HEC) slice culture was used to assess specific effects of ethanol on TLR7, let-7b, and microvesicles. We report here that hippocampal tissue from postmortem human alcoholic brains shows increased expression of TLR7 and increased microglial activation. Using HEC slice culture, we found that ethanol induces TLR7 and let-7b expression. Ethanol caused TLR7-associated neuroimmune gene induction and initiated the release let-7b in microvesicles (MVs), enhancing TLR7-mediated neurotoxicity. Further, ethanol increased let-7b binding to the danger signaling molecule high mobility group box-1 (HMGB1) in MVs, while reducing let-7 binding to classical chaperone protein argonaute (Ago2). Flow cytometric analysis of MVs from HEC media and analysis of MVs from brain cell culture lines found that microglia were the primary source of let-7b and HMGB1-containing MVs. Our results identify that ethanol induces neuroimmune pathology involving the release of let-7b/HMGB1 complexes in microglia-derived microvesicles. This contributes to hippocampal neurodegeneration and may play a role in the pathology of alcoholism.

An End User Development Approach for Mobile Web Augmentation

Directory of Open Access Journals (Sweden)

Gabriela Bosetti

2017-01-01

Full Text Available The trend towards mobile devices usage has made it possible for the Web to be conceived not only as an information space but also as a ubiquitous platform where users perform all kinds of tasks. In some cases, users access the Web with native mobile applications developed for well-known sites, such as, LinkedIn, Facebook, and Twitter. These native applications might offer further (e.g., location-based functionalities to their users in comparison with their corresponding Web sites because they were developed with mobile features in mind. However, many Web applications have no native counterpart and users access them using a mobile Web browser. Although the access to context information is not a complex issue nowadays, not all Web applications adapt themselves according to it or diversely improve the user experience by listening to a wide range of sensors. At some point, users might want to add mobile features to these Web sites, even if those features were not originally supported. In this paper, we present a novel approach to allow end users to augment their preferred Web sites with mobile features. We support our claims by presenting a framework for mobile Web augmentation, an authoring tool, and an evaluation with 21 end users.

Let-7i attenuates human brain microvascular endothelial cell damage in oxygen glucose deprivation model by decreasing toll-like receptor 4 expression.

Science.gov (United States)

Xiang, Wei; Tian, Canhui; Peng, Shunli; Zhou, Liang; Pan, Suyue; Deng, Zhen

2017-11-04

The let-7 family of microRNAs (miRNAs) plays an important role on endothelial cell function. However, there have been few studies on their role under ischemic conditions. In this study, we demonstrate that let-7i, belonging to the let-7 family, rescues human brain microvascular endothelial cells (HBMECs) in an oxygen-glucose deprivation (OGD) model. Our data show that the expression of let-7 family miRNAs was downregulated after OGD. Overexpression of let-7i significantly alleviated cell death and improved survival of OGD-treated HBMECs. Let-7i also protected permeability in an in vitro blood brain barrier (BBB) model. Further, let-7i downregulated the expression of toll-like receptor 4 (TLR4), an inflammation trigger. Moreover, overexpression of let-7i decreased matrix metallopeptidase 9 (MMP9) and inducible nitric oxide synthase (iNOS) expression under OGD. Upon silencing TLR4 expression in HBMECs, the anti-inflammatory effect of let-7i was abolished. Our research suggests that let-7i promotes OGD-induced inflammation via downregulating TLR4 expression. Copyright © 2017 Elsevier Inc. All rights reserved.

Ionization chambers for LET determination

DEFF Research Database (Denmark)

Kaiser, Franz-Joachim; Bassler, Niels; Tölli, Heikki

2010-01-01

resolution and high sensitivity are necessary. For exact dosimetry which is done using ionization chambers (ICs), the recombination taking place in the IC has to be known. Up to now, recombination is corrected phenomenologically and more practical approaches are currently used. Nevertheless, Jaff´e's theory...... of columnar recombination was designed to model the detector efficiency of an ionization chamber. Here, we have shown that despite the approximations and simplification made, the theory is correct for the LETs typically found in clinical radiotherapy employing particles from protons to carbon ions...

Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc

Energy Technology Data Exchange (ETDEWEB)

Liu, Yongchao; Yin, Bingde; Zhang, Changcun; Zhou, Libin [Department of Urology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080 (China); Fan, Jie, E-mail: jief67@sina.com [Department of Urology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080 (China)

2012-01-06

Highlights: Black-Right-Pointing-Pointer This study is the first to test the let-7a/c-myc loop in renal cell carcinoma cell lines. Black-Right-Pointing-Pointer Let-7a down-regulated c-myc in three renal cell carcinoma cell lines. Black-Right-Pointing-Pointer c-myc target genes were down-regulated because of the let-7a-mediated down-regulation of c-myc. Black-Right-Pointing-Pointer The let-7a/c-myc loop has a significant function in renal cell carcinoma cell lines. -- Abstract: Widespread functions of the c-myc pathway play a crucial role in renal cell carcinoma (RCC) carcinogenesis. Thus, we evaluated the connection between proto-oncogenic c-myc and anti-neoplastic hsa-let-7a (let-7a) in RCC cell lines. The levels of c-myc and let-7a in 3 RCC cell lines (769P, Caki-1 and 786O) were measured after transfecting the cells with let-7a mimics or a negative control. The change in c-myc protein level was confirmed by Western blot. The anti-neoplastic function of let-7a was evaluated using cell counting kit-8 (CCK-8) for proliferation analysis and cell flow cytometry for cell cycle analysis. The changes of downstream targets of c-myc were measured using reverse transcription quantitative real-time PCR (qRT-PCR). Our results suggest for the first time that let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and the miR17-92 cluster, which is accompanied by proliferation inhibition and cell cycle arrest.

A method for radiobiological investigations in radiation fields with different LET and high dose rates

International Nuclear Information System (INIS)

Grundler, W.

1976-01-01

For investigations: 1. Performed in the field of radiobiology with different LET-radiation and a relatively high background dose rate of one component (e.g. investigations with fast and intermediate reactor neutrons) 2. Concerning radiation risk studies within a wide range 3. Of irradiations, covering a long time period (up to 100 days) a test system is necessary which on the one hand makes it possible to analyze the influence of different LET radiation and secondly shows a relative radiation resistant behaviour and allows a simple cell cycle regulation. A survey is given upon the installed device of a simple cell observation method, the biological test system used and the analysis of effects caused by dose, repair and LET. It is possible to analyze the behaviour of the nonsurvival cells and to demonstrate different reactions of the test parameters to the radiation of different LET. (author)

Effects of estrogen and gender on cataractogenesis induced by high-LET radiation

International Nuclear Information System (INIS)

Henderson, M.A.; Rusek, A.; Valluri, S.; Garrett, J.; Lopez, J.; Caperell-Grant, A.; Mendonca, M.; Bigsby, R.; Dynlacht, J.

2010-01-01

Planning for long-duration manned lunar and interplanetary missions requires an understanding of radiation-induced cataractogenesis. Previously, it was demonstrated that low-linear energy transfer (LET) irradiation with 10 Gy of 60 Co γ rays resulted in an increased incidence of cataracts in male rats compared to female rats. This gender difference was not due to differences in estrogen, since male rats treated with the major secreted estrogen 17-β-estradiol (E2) showed an identical increase compared to untreated males. We now compare the incidence and rate of progression of cataracts induced by high-LET radiation in male and female Sprague-Dawley rats. Rats received a single dose of 1 Gy of 600 MeV 56 Fe ions. Lens opacification was measured at 2-4 week intervals with a slit lamp. The incidence and rate of progression of radiation-induced cataracts was significantly increased in the animals in which estrogen was available from endogenous or exogenous sources. Male rats with E2 capsules implanted had significantly higher rates of progression compared to male rats with empty capsules implanted (P = 0.025) but not compared to the intact female rats. These results contrast with data obtained after low-LET irradiation and suggest the possibility that the different types of damage caused by high- and low-LET radiation may be influenced differentially by steroid sex hormones.

LET effect on irradiation of hydroxyphthal imide in alcohol solutions

International Nuclear Information System (INIS)

Nakagawa, S.; Murakami, T.

2005-01-01

Hydroxyphthalimide(C 6 H 4 (CO) 2 -NOH) was irradiated with C ion (290MeV/u) in isopropyl alcohol, methanol, ethanol, and acetonitrile. LET was 13.2 and 26.5 keV/m. Dose was 5 and 10 kGy. A little amount of phthalimide was produced. The G value of the production of phthalimide by ion irradiation was less than that by -irradiation except for in methanol. In methanol solution, the production rate of phthalimide increased with increasing the value of LET. The amount of the substitution for C 6 H 4 (CO) 2 -NOD in methanol-d decreased by ion irradiation. These results suggest that the reaction mechanism in ion irradiation is different from -irradiation. (author)

The induction of somatic mutations by high-LET radiations using the drosophila assay system

International Nuclear Information System (INIS)

Yoshikawa, Isao; Takatsuji, Toshihiro

2004-01-01

Two types of somatic mutation in Drosophila melanogaster were examined to evaluate the relative biological effectiveness (RBE) of 252 Cf neutrons and heavy ions (carbon ions and neon ions) accelerated with a synchrotron for inducing mutations as a function of linear energy transfer (LET). One is the loss of heterozygosity for wing-hair mutations and the other the reversion of the mutant white-ivory. The measurements were made using a combined mutation assay system; so that induced mutant wing-hair clones as well as revertant eye-color clones could be detected simultaneously in the same fly. Larvae were irradiated at the age of 3 days post-oviposition. The efficiency of 252 Cf neutrons for inducing wing-hair mosaic spots is very high, RBE=8.5, but that for eye-color mosaic spot is almost equal (RBE=1.2) to that of 137 Cs γ-rays. RBE-LET relationships were obtained for the induction of wing-hair and eye-color mosaic spots. The RBE of carbon and neon ions for producing wing-hair mosaic spots increased with increasing LET values. The RBE for the induction of eye-color mutants did not change with LET. These relationships suggest that more complex types of DNA damage such as non-rejoinable strand breaks or clustered double strand breaks that increase with LET may be responsible for inducing the wing-hair mutation, while simpler forms of molecular damage may induce reversion in the white-ivory allele. (author)

Tips for Older Dietary Supplement Users

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... Information for Consumers Tips for Older Dietary Supplement Users Share Tweet Linkedin Pin it More sharing options ... site are provided as a service to our users and do not represent FDA endorsement of these ...

A composite microdose Adaptive Response (AR) and Bystander Effect (BE) model-application to low LET and high LET AR and BE data.

Science.gov (United States)

Leonard, Bobby E

2008-08-01

It has been suggested that Adaptive Response (AR) may reduce risk of adverse health effects due to ionizing radiation. But very low dose Bystander Effects (BE) may impose dominant deleterious human risks. These conflicting behaviors have stimulated controversy regarding the Linear No-Threshold human risk model. A dose and dose rate-dependent microdose model, to examine AR behavior, was developed in prior work. In the prior work a number of in vitro and in vivo dose response data were examined with the model. Recent new data show AR behavior with some evidence of very low dose BE. The purpose of this work is to supplement the microdose model to encompass the Brenner and colleagues BaD (Bystander and Direct Damage) model and apply this composite model to obtain new knowledge regarding AR and BE and illustrate the use of the model to plan radio-biology experiments. The biophysical composite AR and BE Microdose Model quantifies the accumulation of hits (Poisson distributed, microdose specific energy depositions) to cell nucleus volumes. This new composite AR and BE model provides predictions of dose response at very low dose BE levels, higher dose AR levels and even higher dose Direct (linear-quadratic) Damage radiation levels. We find good fits of the model to both BE data from the Columbia University microbeam facility and combined AR and BE data for low Linear Energy Transfer (LET) and high LET data. A Bystander Factor of about 27,000 and an AR protection factor of 0.61 are obtained for the low LET in vivo mouse spleen exposures. A Bystander Factor of 317 and an AR protection factor of 0.53 are obtained for high LET radon alpha particles in human lymphocytes. In both cases the AR is activated at most by one or two radiation induced charged particle traversals through the cell nucleus. The results of the model analysis is consistent with a premise that both Bystander damage and Adaptive Response radioprotection can occur in the same cell type, derived from the same

Satellite communication from user to user

Science.gov (United States)

Gern, Manfred

Satellite communication systems which allow a multitude of user-to-user, point-to-point, and multipoint connections, are presented. The bit rates are 64 kbit/sec and multiples, up to 1.92 Mbit/sec. If required, the ground-stations are installed at the customer's site or at suitable locations in order to serve several customers. However, technical requirements for station location have also to be fulfulled, in order to avoid interference with terrestrial radio services. The increasing number of participants to Satellite Multi Service and INTELSAT Business Services imposes the solution of the problem of communication using cheap techniques. The changes of the German Federal Post Office also permit the economic use of satellite radio techniques for short distances.

Influence of chemical inhibitors on cell recovery after exposure to different LET radiation

Energy Technology Data Exchange (ETDEWEB)

Evstratova, Ekaterina S.; Petin, Vladislav G. [Medical Radiological Research Center, Obninsk (Russian Federation); Kim, Jin Kyu; KIm, Jin Hong [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

2016-12-15

Chemical radiosensitizers are often used to increase cell radiosensitivity. It is known that the ability of chemical drugs to increase cell radiosensitivity is related with inhibition of cell recovery from damage induced by ionizing radiation. However, there are little comparative investigations of cell sensitivity modification after exposure to radiation with high linear energy transfer (LET). Therefore, we studied the anticancer drugs cisplatin and endoxan and their impact on the ability of yeast cells to recover after cell exposure to radiations with different LET. The ability of cell recovery from radiation damage was less effective after exposure to high-LET radiation, when cells were irradiated without drug, with the increase in cisplatin concentration resulting in the disappearance of this difference. The increase of cisplatin concentration results in progressive increase in the fraction of irreversible damage independently of radiation quality.

Influence of chemical inhibitors on cell recovery after exposure to different LET radiation

International Nuclear Information System (INIS)

Evstratova, Ekaterina S.; Petin, Vladislav G.; Kim, Jin Kyu; KIm, Jin Hong

2016-01-01

Chemical radiosensitizers are often used to increase cell radiosensitivity. It is known that the ability of chemical drugs to increase cell radiosensitivity is related with inhibition of cell recovery from damage induced by ionizing radiation. However, there are little comparative investigations of cell sensitivity modification after exposure to radiation with high linear energy transfer (LET). Therefore, we studied the anticancer drugs cisplatin and endoxan and their impact on the ability of yeast cells to recover after cell exposure to radiations with different LET. The ability of cell recovery from radiation damage was less effective after exposure to high-LET radiation, when cells were irradiated without drug, with the increase in cisplatin concentration resulting in the disappearance of this difference. The increase of cisplatin concentration results in progressive increase in the fraction of irreversible damage independently of radiation quality.

Intracellular trafficking of LET-756, a fibroblast growth factor of C. elegans, is controlled by a balance of export and nuclear signals

International Nuclear Information System (INIS)

Popovici, Cornel; Fallet, Mathieu; Marguet, Didier; Birnbaum, Daniel; Roubin, Regine

2006-01-01

The superfamily of fibroblast growth factors (FGF), which counts 22 members in humans, exerts many functions during animal development and adult life. LET-756 is one of the two FGFs of the nematode C. elegans. Re-introduction of LET-756 in a null mutant strain restores viability, allowing the study of structural requirements for LET-756 trafficking and function. LET-756 protein has several regions and motifs, including a non-classical internal motif required for secretion. We show here that a main difference in the wild-type LET-756 molecule and a truncated molecule that mimics a partial loss-of-function mutant lies on subnuclear expression. Using Cos-1 cells and rescue activity we show that: (i) nuclear localization is due to various redundant NLS, one of them acting as a nucleolar localization signal; (ii) nuclear LET-756 is addressed to the speckles by a stretch of glutamine residues; (iii) nuclear LET-756 is trafficking between speckles and nucleoli; (iv) in the nucleolus, LET-756 is associated with proteins of the rRNA splicing compartment; (v) changing LET-756 secretion signal prevents its nuclear localization. We propose that LET-756 exerts its functions through a balance between secreted and nuclear forms due to two opposite addressing signals (i) synergy of several NLS and (ii) attenuated secretion signal

IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla

Science.gov (United States)

Ma, Shu; Liu, Genxia; Jin, Lin; Pang, Xiyao; Wang, Yanqiu; Wang, Zilu; Yu, Yan; Yu, Jinhua

2016-01-01

Insulin-like growth factor-1 (IGF-1) and its receptor IGF-1R play a paramount role in tooth/bone formation while hsa-let-7c actively participates in the osteogenic differentiation of mesenchymal stem cells. However, the interaction between IGF-1/IGF-1R and hsa-let-7c on the committed differentiation of stem cells from apical papilla (SCAPs) remains unclear. In this study, human SCAPs were isolated and treated with IGF-1 and hsa-let-7c over/low-expression viruses. The odonto/osteogenic differentiation of these stem cells and the involvement of mitogen-activated protein kinase (MAPK) pathway were subsequently investigated. Alizarin red staining showed that hsa-let-7c low-expression can significantly promote the mineralization of IGF-1 treated SCAPs, while hsa-let-7c over-expression can decrease the calcium deposition of IGF-1 treated SCAPs. Western blot assay and real-time reverse transcription polymerase chain reaction further demonstrated that the expression of odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, COL-I/COL-I, DSPP/DSP, and DMP-1/DMP-1) in IGF-1 treated SCAPs were significantly upregulated in Let-7c-low group. On the contrary, hsa-let-7c over-expression could downregulate the expression of these odonto/osteogenic markers. Moreover, western blot assay showed that the JNK and p38 MAPK signaling pathways were activated in Let-7c-low SCAPs but inhibited in Let-7c-over SCAPs. Together, the IGF-1/IGF-1R/hsa-let-7c axis can control the odonto/osteogenic differentiation of IGF-1-treated SCAPs via the regulation of JNK and p38 MAPK signaling pathways. PMID:27833148

Protective Effects of Let-7b on the Expression of Occludin by Targeting P38 MAPK in Preventing Intestinal Barrier Dysfunction

Directory of Open Access Journals (Sweden)

Zhihua Liu

2018-01-01

Full Text Available Background/Aims: Let-7b was dramatically reduced after a dicer knockout of mice with intestinal barrier function injuries. This paper aims to investigate the molecular mechanism of let-7b by targeting p38 MAPK in preventing intestinal barrier dysfunction. Methods: A total of 186 patients were enrolled, with 93 in the control group and 93 in the PRO group. Only 158 patients completed the entire study, whereas the others either did not meet the inclusion criteria or refused to participate. To further verify the role of let-7b, intestinal epithelial conditional knockout (IKO mice of mmu-let-7b model were established. Serum let-7b, zonulin, IL-6, and TNF-α concentrations were measured by ELISA or quantitative RT-PCR. Permeability assay was done by ussing chamber. The apoptotic cells were identified using an In Situ Cell Death Detection Kit. Protein was detected by western blot. Results: Probiotics can lower infection-related complications, as well as increase the serum and tissue let-7b levels. P38 MAPK was identified as the target of let-7b, as verified by NCM460 cells. P38 MAPK expression was increased, whereas tight-junction (TJ proteins were significantly decreased in let-7b IKO mice (both P<0.05. Negative regulation of p38 MAPK molecular signaling pathways was involved in the protective effects of let-7b on intestinal barrier function. Conclusion: Let-7b was identified as a novel diagnosis biomarker or a potential treatment target for preventing intestinal barrier dysfunction.

Protective Effects of Let-7b on the Expression of Occludin by Targeting P38 MAPK in Preventing Intestinal Barrier Dysfunction.

Science.gov (United States)

Liu, Zhihua; Tian, Yinghai; Jiang, Yanqiong; Chen, Shihua; Liu, Ting; Moyer, Mary Pat; Qin, Huanlong; Zhou, Xinke

2018-01-01

Let-7b was dramatically reduced after a dicer knockout of mice with intestinal barrier function injuries. This paper aims to investigate the molecular mechanism of let-7b by targeting p38 MAPK in preventing intestinal barrier dysfunction. A total of 186 patients were enrolled, with 93 in the control group and 93 in the PRO group. Only 158 patients completed the entire study, whereas the others either did not meet the inclusion criteria or refused to participate. To further verify the role of let-7b, intestinal epithelial conditional knockout (IKO) mice of mmu-let-7b model were established. Serum let-7b, zonulin, IL-6, and TNF-α concentrations were measured by ELISA or quantitative RT-PCR. Permeability assay was done by ussing chamber. The apoptotic cells were identified using an In Situ Cell Death Detection Kit. Protein was detected by western blot. Probiotics can lower infection-related complications, as well as increase the serum and tissue let-7b levels. P38 MAPK was identified as the target of let-7b, as verified by NCM460 cells. P38 MAPK expression was increased, whereas tight-junction (TJ) proteins were significantly decreased in let-7b IKO mice (both P<0.05). Negative regulation of p38 MAPK molecular signaling pathways was involved in the protective effects of let-7b on intestinal barrier function. Let-7b was identified as a novel diagnosis biomarker or a potential treatment target for preventing intestinal barrier dysfunction. © 2018 The Author(s). Published by S. Karger AG, Basel.

Inactive and mutagenic effects induced by carbon beams of different LET values in a red yeast strain

International Nuclear Information System (INIS)

Wang Jufang; Lu Dong; Wu Xin; Sun Haining; Ma Shuang; Li Renmin; Li Wenjian

2010-01-01

To evaluate biological action of microorganism exposed to charged particles during the long distance space exploration, induction of inactivation and mutation in a red yeast strain Rhodotorula glutinis AY 91015 by carbon beams of different LET values (14.9-120.0 keV μm -1 ) was investigated. It was found that survival curves were exponential, and mutation curves were linear for all LET values. The dependence of inactivation cross section on LET approached saturation near 120.0 keV μm -1 . The mutation cross section saturated when LET was higher than 58.2 keV μm -1 . Meanwhile, the highest RBE i for inactivation located at 120.0 keV μm -1 and the highest RBE m for mutation was at 58.2 keV μm -1 . The experiments imply that the most efficient mutagenic part of the depth dose profile of carbon ion is at the plateau region with intermediate LET value in which energy deposited is high enough to induce mutagenic lesions but too low to induce over kill effect in the yeast cells.

Inactive and mutagenic effects induced by carbon beams of different LET values in a red yeast strain

Science.gov (United States)

Wang, Jufang; Lu, Dong; Wu, Xin; Sun, Haining; Ma, Shuang; Li, Renmin; Li, Wenjian

2010-09-01

To evaluate biological action of microorganism exposed to charged particles during the long distance space exploration, induction of inactivation and mutation in a red yeast strain Rhodotorula glutinis AY 91015 by carbon beams of different LET values (14.9-120.0 keV μm -1) was investigated. It was found that survival curves were exponential, and mutation curves were linear for all LET values. The dependence of inactivation cross section on LET approached saturation near 120.0 keV μm -1. The mutation cross section saturated when LET was higher than 58.2 keV μm -1. Meanwhile, the highest RBE i for inactivation located at 120.0 keV μm -1 and the highest RBE m for mutation was at 58.2 keV μm -1. The experiments imply that the most efficient mutagenic part of the depth dose profile of carbon ion is at the plateau region with intermediate LET value in which energy deposited is high enough to induce mutagenic lesions but too low to induce over kill effect in the yeast cells.

MicroRNA let-7d regulates the TLX/microRNA-9 cascade to control neural cell fate and neurogenesis.

Science.gov (United States)

Zhao, Chunnian; Sun, GuoQiang; Ye, Peng; Li, Shengxiu; Shi, Yanhong

2013-01-01

MicroRNAs have important functions in the nervous system through post-transcriptional regulation of neurogenesis genes. Here we show that microRNA let-7d, which has been implicated in cocaine addiction and other neurological disorders, targets the neural stem cell regulator TLX. Overexpression of let-7d in vivo reduced neural stem cell proliferation and promoted premature neuronal differentiation and migration, a phenotype similar to those induced by TLX knockdown or overexpression of its negatively-regulated target, microRNA-9. We found a let-7d binding sequence in the tlx 3' UTR and demonstrated that let-7d reduced TLX expression levels in neural stem cells, which in turn, up-regulated miR-9 expression. Moreover, co-expression of let-7d and TLX lacking its 3' UTR in vivo restored neural stem cell proliferation and reversed the premature neuronal differentiation and migration. Therefore, manipulating let-7d and its downstream targets could be a novel strategy to unravel neurogenic signaling pathways and identify potential interventions for relevant neurological disorders.

Linear energy transfer (LET) effects in the radiation-induced inactivation of papain

International Nuclear Information System (INIS)

Bisby, R.H.; Cundall, R.B.; Sims, H.E.; Burns, W.G.

1977-01-01

The inactivation of dilute aqueous solutions of papain by radiations of varying linear energy transfer has been studied in N 2 , N 2 0 and O 2 -saturated solutions. The results obtained with low LET radiation are very similar to those previously reported by Lin et al (Radiation Res.;62:438(1975)). The additional data obtained at higher LET, when radical product yields are reduced and the yield of hydrogen peroxide is increased, show that the hydrogen atom is more important in the inactivation of papain than previously considered. (author)

SiteGuide: An example-based approach to web site development assistance

NARCIS (Netherlands)

Hollink, V.; de Boer, V.; van Someren, M.; Filipe, J.; Cordeiro, J.

2009-01-01

We present ‘SiteGuide’, a tool that helps web designers to decide which information will be included in a new web site and how the information will be organized. SiteGuide takes as input URLs of web sites from the same domain as the site the user wants to create. It automatically searches the pages

Testing the Effectiveness of Interactive Multimedia for Library-User Education

Science.gov (United States)

Markey, Karen; Armstrong, Annie; De Groote, Sandy; Fosmire, Michael; Fuderer, Laura; Garrett, Kelly; Georgas, Helen; Sharp, Linda; Smith, Cheri; Spaly, Michael; Warner, Joni E.

2005-01-01

A test of the effectiveness of interactive multimedia Web sites demonstrates that library users' topic knowledge was significantly greater after visiting the sites than before. Library users want more such sites about library services, their majors, and campus life generally. Librarians describe the roles they want to play on multimedia production…

CD95 is part of a let-7/p53/miR-34 regulatory network.

Directory of Open Access Journals (Sweden)

Annika Hau

Full Text Available The death receptor CD95 (APO-1/Fas mediates apoptosis induction upon ligation by its cognate ligand CD95L. Two types of CD95 signaling pathways have been identified, which are characterized by the absence (Type I or presence (Type II of mitochondrial involvement. Micro(miRNAs are small noncoding RNAs that negatively regulate gene expression. They are important regulators of differentiation processes and are found frequently deregulated in many human cancers. We recently showed that Type I cells express less of the differentiation marker miRNA let-7 and, hence, likely represent more advanced tumor cells than the let-7 high expressing Type II cells. We have now identified miR-34a as a selective marker for cells that are sensitive to CD95-mediated apoptosis. Both CD95 and miR-34a are p53 target genes, and consequently, both the sensitivity of cancer cells to CD95-mediated apoptosis and the ability to respond to p53 mediated DNA genotoxic stress are linked. Interestingly, while miR-34a was found to positively correlate with the ability of cells to respond to genotoxic stress, let-7 was negatively correlated. The expression level of CD95 inversely correlated with the expression of let-7 suggesting regulation of let-7 expression by CD95. To test a link between p53 and miR-34a, we altered the expression of CD95. This affected the ability of cells to activate p53 and to regulate miR-34a. Our data point to a novel regulatory network comprising p53, CD95, let-7, and miR-34a that affects cancer cell survival, differentiation, and sensitivity to apoptotic signals. The possible relevance of this regulatory network for cancer stem cells is discussed.

Safety for Users

CERN Multimedia

HR Department

2008-01-01

CERN welcomes more than 8000 Users every year. The PH Department as host to these scientific associates requires the highest safety standards. The PH Safety Office has published a Safety Flyer for Users. Important safety topics and procedures are presented. Although the Flyer is intended primarily to provide safety information for Users, the PH Safety Office invites all those on the CERN sites to keep a copy of the flyer as it gives guidance in matters of safety and explains what to do in the event of an emergency. Link: http://ph-dep.web.cern.ch/ph-dep/Safety/SafetyOffice.html PH-Safety Office PH Department

Safety for Users

CERN Multimedia

HR Department

2008-01-01

CERN welcomes more than 8000 Users every year. The PH Department as host to these scientific associates requires the highest safety standards. The PH Safety Office has published a safety flyer for Users. Important safety topics and procedures are presented. Although the flyer is intended primarily to provide safety information for Users, the PH Safety Office invites all those on the CERN sites to keep a copy of the flyer as it gives guidance in matters of safety and explains what to do in the event of an emergency. The flyer is available at: http://ph-dep.web.cern.ch/ph-dep/Safety/SafetyOffice.html PH-Safety Office PH Department

MicroRNA-let-7a regulates cell autophagy by targeting Rictor in gastric cancer cell lines MGC-803 and SGC-7901.

Science.gov (United States)

Fan, Hao; Jiang, Mingkun; Li, Bowen; He, Yu; Huang, Chi; Luo, Dakui; Xu, Hao; Yang, Li; Zhou, Jundong

2018-03-01

miR-let-7a is the most widely studied miRNA, whose functions have been well-established by scientists in both carcinogenesis and progression of human cancer, including gastric cancer (GC). However, to date there is a lack of information concerning the relationship between miR-let-7a and cellular autophagy. Using western blotting and immunofluorescence, we determined that upregulation of miR-let-7a led to increased cellular autophagic level, whereas miR-let-7a suppression decreased autophagy activity in GC cells. To further elucidate the mechanisms underlying this, we screened potential targets of miR-let-7a using bioinformatics analyses, validated by a series of assays. Our results indicated that Rptor independent companion of mTOR complex 2 (Rictor) was a direct target of miR-let-7a. In addition, rescue experiments in vitro showed that miR-let-7a promoted cellular autophagic level by inhibiting Rictor expression in GC cells. Furthermore, as an upstream executor of Akt-mTOR signaling pathway, we found that Rictor elaborated its effect on autophagy by phosphorylating Akt and mTOR, and this regulatory process could also be mediated by miR-let-7a. Taken together, our results present a novel role for miR-let-7a in GC which modulates autophagy by targeting Rictor, following the regulation of Akt-mTOR signal pathway.

Influence of high- and low-LET radiation on the cardiac differentiation of mouse embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Helm, Alexander

2013-07-19

The in utero exposure to ionising radiation poses a risk for the radiosensitive developing embryo. Effects of low-LET radiation on different developmental stages of the embryo are relatively well known due to experimental studies and epidemiological data. Data for effects on the very early stage of the embryonic development, particularly the effects of high-LET radiation instead are rather limited. However, unanticipated exposures of the early embryo to ionising radiation may occur through diagnostic or therapeutic applications or through radiation accidents. Additionally, protons and carbon ions are increasingly used in radiotherapy. Thus, a risk estimation of high-LET exposure especially to the early embryo is of a certain importance. To address this topic, pluripotent mouse embryonic stem cells resembling the blastocyst stage were irradiated with high-LET carbon ions or low-LET X-rays and subsequently differentiated to mimic the early embryonic development. The occurrence of spontaneously contracting cardiomyocytes was used as a marker to asses the radiation effects on the differentiation. Among others, cell inactivation, cell death and gene expression were analysed. A delay in the cardiac differentiation after radiation exposure was found. The results point to radiation-induced cell killing as the main effector of the developmental delay. Carbon ions were found to be more effective than X-rays.

Light-effect transistor (LET) with multiple independent gating controls for optical logic gates and optical amplification

Science.gov (United States)

Marmon, Jason; Rai, Satish; Wang, Kai; Zhou, Weilie; Zhang, Yong

The pathway for CMOS technology beyond the 5-nm technology node remains unclear for both physical and technological reasons. A new transistor paradigm is required. A LET (Marmon et. al., Front. Phys. 2016, 4, No. 8) offers electronic-optical hybridization at the component level, and is capable of continuing Moore's law to the quantum scale. A LET overcomes a FET's fabrication complexity, e.g., physical gate and doping, by employing optical gating and photoconductivity, while multiple independent, optical gates readily realize unique functionalities. We report LET device characteristics and novel digital and analog applications, such as optical logic gates and optical amplification. Prototype CdSe-nanowire-based LETs, incorporating an M-S-M structure, show output and transfer characteristics resembling advanced FETs, e.g., on/off ratios up to 106 with a source-drain voltage of 1.43V, gate-power of 260nW, and a subthreshold swing of 0.3nW/decade (excluding losses). A LET has potential for high-switching (THz) speeds and extremely low-switching energies (aJ) in the ballistic transport region. Our work offers new electronic-optical integration strategies for high speed and low energy computing approaches, which could potentially be extended to other materials and devices.

SYRMEP Tomo Project: a graphical user interface for customizing CT reconstruction workflows.

Science.gov (United States)

Brun, Francesco; Massimi, Lorenzo; Fratini, Michela; Dreossi, Diego; Billé, Fulvio; Accardo, Agostino; Pugliese, Roberto; Cedola, Alessia

2017-01-01

When considering the acquisition of experimental synchrotron radiation (SR) X-ray CT data, the reconstruction workflow cannot be limited to the essential computational steps of flat fielding and filtered back projection (FBP). More refined image processing is often required, usually to compensate artifacts and enhance the quality of the reconstructed images. In principle, it would be desirable to optimize the reconstruction workflow at the facility during the experiment (beamtime). However, several practical factors affect the image reconstruction part of the experiment and users are likely to conclude the beamtime with sub-optimal reconstructed images. Through an example of application, this article presents SYRMEP Tomo Project (STP), an open-source software tool conceived to let users design custom CT reconstruction workflows. STP has been designed for post-beamtime (off-line use) and for a new reconstruction of past archived data at user's home institution where simple computing resources are available. Releases of the software can be downloaded at the Elettra Scientific Computing group GitHub repository https://github.com/ElettraSciComp/STP-Gui.

Decreased expression of microRNA let-7i and its association with chemotherapeutic response in human gastric cancer

Directory of Open Access Journals (Sweden)

Liu Kun

2012-10-01

Full Text Available Abstract Background MicroRNA let-7i has been proven to be down-regulated in many human malignancies and correlated with tumor progression and anticancer drug resistance. Our study aims to characterize the contribution of miRNA let-7i to the initiation and malignant progression of locally advanced gastric cancer (LAGC, and evaluate its possible value in neoadjuvant chemotherapeutic efficacy prediction. Methods Eighty-six previously untreated LAGC patients who underwent preoperative chemotherapy and radical resection were included in our study. Let-7i expression was examined for pairs of cancer tissues and corresponding normal adjacent tissues (NATs, using quantitative RT-PCR. The relationship of let-7i level to clinicopathological characteristics, pathologic tumor regression grades after chemotherapy, and overall survival (OS was also investigated. Results Let-7i was significantly down-regulated in most tumor tissues (78/86: 91% compared with paired NATs (P P =0.024 independently of other clinicopathological factors, including tumor node metastasis (TNM stage (HR = 3.226, P = 0.013, depth of infiltration (HR = 4.167, P P = 0.037. Conclusions These findings indicate that let-7i may be a good candidate for use a therapeutic target and a potential tissue marker for the prediction of chemotherapeutic sensitivity and prognosis in LAGC patients.

Protein-directed modulation of high-LET hyperthermic radiosensitization

International Nuclear Information System (INIS)

Chang, P.Y.

1991-01-01

A pair of Chinese Hamster Ovary cell lines, the wild-type CHO-SC1, and its temperature-sensitive mutant (CHO-tsH1) was used to examine the importance of protein synthesis in the development of thermotolerance. The classical biphasic thermotolerant survival response to hyperthermia was observed in the SC1 cells after continuous heating at 41.5C to 42.5C, while tsH1 showed no thermotolerance. In separate experiments, each cell line was triggered and challenged at 45C. The heat doses were separated with graded incubaton periods at 35C or 40C for thermotolerance development. SC1 cells expressed thermoresistance, with the synthesis of heat shock proteins, under both incubation conditions. tsH1 cells expressed thermotolerance similar to that seen in the SC1 cells when incubated at 35C, but the survival response with the non-permissive 40C incubation was much reduced in the absence of protein synthesis. The combined effects of heavy-ion radiation and hyperthermia were examined using the same cell system. A mild heat dose of 41.5C was used in conjunction with Neon particle radiation of various high LET values. The cell killing effects were highly dependent on the sequence of application of heat and Neon radiation. Heat applied immediately after Neon irradiation was more cytotoxic to SC1 cells than when heat was applied prior to the irradiation. The ability of cells to synthesize new proteins plays a key role in this sequence-dependent thermal radiosensitization. In the absence of protein synthesis in the tsH1 cells, the high-LET thermal enhancement for cell-killing was unchanged regardless of the sequence. In the presence of protein synthetic activity in the SC1 cells, the thermal enhancement of radiation-induced cell killing was LET-dependent

Operation of a hemispherical detector for LET measurements

International Nuclear Information System (INIS)

Schell, M.C.; DeLuca, P.M. Jr.; Pearson, D.W.

1982-01-01

A hemispherical ΔE/E detector has been constructed and tested for the measurement of linear-energy-transfer distributions of charged particles induced by fast neutrons. The initial performance test results and LET distributions from 14.8-MeV monoenergetic neutron irradiation in free space of carbon, lead, and Al50-plastic are presented

LET dependence of the production of oxidative DNA damage in mammalian cells

International Nuclear Information System (INIS)

Ito, Atsushi; Furuichi, Wataru; Inoguchi, Hiroki; Hirayama, Ryoichi; Murayama, Chieko; Furusawa, Yoshiya

2006-01-01

Production of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in human leukemia HL-60 cells was examined upon irradiation with carbon, neon silicon ions. Cell suspension with the concentration of 1 x 10 7 /ml was irradiated tinder air-saturated condition. After irradiation cells were subjected to the DNA extraction using isopropanol, separation of DNA strands by heat treatment, digestion into nucleosides with nuclease P1 and alkaline phosphatase. A single peak of 8-OHdG on a chromatogram was observed using newly installed ECD detector (Coulochem III; ESA, Inc. U.S.A.). Reproducibility was also greatly improved with this detector. 8-OHdG yield was decreased with increasing linear energy transfer (LET) for carbon and silicon beam. These results are in good accordance with those of dG solution which was previously reported by us. Ion species dependence in 8-OHdG yield was not so apparent through the comparison of carbon and neon beam with an LET of 80 keV/μm and neon and silicon beam with an LET of 150 keV/μm. (author)

Comparison Analysis among Large Amount of SNS Sites

Science.gov (United States)

Toriumi, Fujio; Yamamoto, Hitoshi; Suwa, Hirohiko; Okada, Isamu; Izumi, Kiyoshi; Hashimoto, Yasuhiro

In recent years, application of Social Networking Services (SNS) and Blogs are growing as new communication tools on the Internet. Several large-scale SNS sites are prospering; meanwhile, many sites with relatively small scale are offering services. Such small-scale SNSs realize small-group isolated type of communication while neither mixi nor MySpace can do that. However, the studies on SNS are almost about particular large-scale SNSs and cannot analyze whether their results apply for general features or for special characteristics on the SNSs. From the point of view of comparison analysis on SNS, comparison with just several types of those cannot reach a statistically significant level. We analyze many SNS sites with the aim of classifying them by using some approaches. Our paper classifies 50,000 sites for small-scale SNSs and gives their features from the points of network structure, patterns of communication, and growth rate of SNS. The result of analysis for network structure shows that many SNS sites have small-world attribute with short path lengths and high coefficients of their cluster. Distribution of degrees of the SNS sites is close to power law. This result indicates the small-scale SNS sites raise the percentage of users with many friends than mixi. According to the analysis of their coefficients of assortativity, those SNS sites have negative values of assortativity, and that means users with high degree tend to connect users with small degree. Next, we analyze the patterns of user communication. A friend network of SNS is explicit while users' communication behaviors are defined as an implicit network. What kind of relationships do these networks have? To address this question, we obtain some characteristics of users' communication structure and activation patterns of users on the SNS sites. By using new indexes, friend aggregation rate and friend coverage rate, we show that SNS sites with high value of friend coverage rate activate diary postings

Inactive and mutagenic effects induced by carbon beams of different LET values in a red yeast strain

Energy Technology Data Exchange (ETDEWEB)

Wang Jufang, E-mail: jufangwang@impcas.ac.c [Institute of Modern Physics, Chinese Academy of Sciences, Nanchang Road No. 509, Lanzhou 730000 (China); Lu Dong; Wu Xin; Sun Haining; Ma Shuang; Li Renmin; Li Wenjian [Institute of Modern Physics, Chinese Academy of Sciences, Nanchang Road No. 509, Lanzhou 730000 (China)

2010-09-15

To evaluate biological action of microorganism exposed to charged particles during the long distance space exploration, induction of inactivation and mutation in a red yeast strain Rhodotorula glutinis AY 91015 by carbon beams of different LET values (14.9-120.0 keV {mu}m{sup -1}) was investigated. It was found that survival curves were exponential, and mutation curves were linear for all LET values. The dependence of inactivation cross section on LET approached saturation near 120.0 keV {mu}m{sup -1}. The mutation cross section saturated when LET was higher than 58.2 keV {mu}m{sup -1}. Meanwhile, the highest RBE{sub i} for inactivation located at 120.0 keV {mu}m{sup -1} and the highest RBE{sub m} for mutation was at 58.2 keV {mu}m{sup -1}. The experiments imply that the most efficient mutagenic part of the depth dose profile of carbon ion is at the plateau region with intermediate LET value in which energy deposited is high enough to induce mutagenic lesions but too low to induce over kill effect in the yeast cells.

PRIVACY CONCERNS IN FACEBOOK SITE

OpenAIRE

Vandana Singh

2014-01-01

Today social networking sites play an important role and inexpensive way to maintain existing relationships and present oneself. However, the increasing use of online sites give rise to privacy concerns and risks. All Internet sites are also under attack from phishers, fraudsters, and spammers. They aim to steal user information and expose users to unwanted spam. They have so many resources at their disposal.This paper studies the awareness of college students regarding the privacy in Faceboo...

A preliminary study on action mechanisms of surviving expression in cell apoptosis induced by high-LET radiation

International Nuclear Information System (INIS)

Jin Xiaodong; Li Qiang; Gong Li; Wu Qingfeng; Li Ping; Dai Zhongying; Liu Xinguo; Tao Jiajun

2010-01-01

It has been proven that over-expression of surviving in cancerous cell lines is related to the radioresistance of cells to high-LET radiation in previous work. In this study, action mechanisms of surviving gene in apoptosis induced by high-LET radiation were investigated. We found that inhibiting surviving by siRNA had no notable influence on Bcl-2 and Bax expressions induced by carbon ions. Surviving depressed cell apoptosis through the inhibition of the activities of caspase-3 and -9 possibly in cell apoptosis induced by high-LET radiation. (authors)

Designing a responsive web site

OpenAIRE

Fejzić , Diana

2016-01-01

Due to the increasing prevalence of smartphones and tablet computers design became a crucial part of web design. For a user, responsive web design enables the best user experience, regardless of whether a user is visiting the site via a mobile phone, a tablet or a computer. This thesis covers the process of planning, designing and responsive web site development, for a fictitious company named “Creative Design d.o.o.”, with the help of web technologies. In the initial part of the thesis, w...

Building the Realtime User Experience

CERN Document Server

Roden, Ted

2010-01-01

The Web is increasingly happening in realtime. With websites such as Facebook and Twitter leading the way, users are coming to expect that all sites should serve content as it occurs -- on smartphones as well as computers. This book shows you how to build realtime user experiences by adding chat, streaming content, and including more features on your site one piece at a time, without making big changes to the existing infrastructure. You'll also learn how to serve realtime content beyond the browser. Throughout the book are many practical JavaScript and Python examples that you can use on yo

Production of perhydroxy radical (HO2) and oxygen in the radiolysis of aqueous solution and the LET effects

International Nuclear Information System (INIS)

Imamura, Masashi

1987-01-01

This article aims to review the results concerning the production of perhydroxy radical (HO 2 ) and oxygen from irradiated aqueous solutions and the LET effects on these products, beginning with a brief introduction to the elementary primary processes in radiolysis of aqueous solution. Oxygen, if produced in the radiolysis of aqueous solution, may be considered responsible for the decreased oxygen enhancement ratio (OER) in biological systems exposed to high LET radiation. A Harwell's group has determined oxygen generated from aqueous ferrous solutions irradiated with heavy ions and concluded that the oxygen is a precursor of perhydroxy radicals. The LET-dependent yields for perhydroxy radical have been determined by LaVerne and Schuler; the analysis of their results sheds light into the reactions taking place in high-LET track cores. In conjunction with these results, the possible contributions to the LET effects are pointed out and discussed of the energetic secondary electrons ejected from the track core by knock-on collision with heavy ions and of the variation in the track core size with energy of the heavy particles. (author)

LET dependency of heavy-ion induced apoptosis in V79 cells

International Nuclear Information System (INIS)

Aoki, Mizuho; Furusawa, Yoshiya; Yamada, Takeshi

2000-01-01

We investigated the relationship between the LET values and cell death, defined as either apoptosis or loss of reproductive integrity (reproductive death), using Chinese hamster V79 cells. The cells were irradiated with X-rays or carbon-ion beams from the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences (NIRS). Apoptosis was defined based on the morphological change upon treating of cells with caffeine. The apoptotic index, the ratio of apoptotic cells to the total, after exposure to 2 Gy of X-rays was 0.043. Upon irradiation with carbon-ion beams, the index was gradually increased with increasing LET values, reaching a maximum of 0.076 at 110 keV/μm, and then decreased to 0.054 at 237 keV/μm. An analogous pattern of the LET dependence was observed between reproductive death and apoptotic death. The cell-survival values obtained after 2 Gy exposure (SF 2 ) were 0.64, 0.13, and 0.24, respectively. A similar trend was found for the RBE values calculated from the initial slope for both apoptosis and reproductive death. These results strongly suggest that the target for both types of cell death is the same. (author)

Calculated LET spectrum from antiproton beams stopping in water

CERN Document Server

Bassler, Niels

2009-01-01

Antiprotons have been proposed as a potential modality for radiotherapy because the annihilation at the end of range leads to roughly a doubling of physical dose in the Bragg peak region. So far it has been anticipated that the radiobiology of antiproton beams is similar to that of protons in the entry region of the beam, but very different in the annihilation region, due to the expected high-LET components resulting from the annihilation. On closer inspection we find that calculations of dose averaged LET in the entry region may suggest that the RBE of antiprotons in the plateau region could significantly differ from unity, which seems to warrant closer inspection of the radiobiology in this region. Materials and Methods. Monte Carlo simulations using FLUKA were performed for calculating the entire particle spectrum of a beam of 126 MeV antiprotons hitting a water phantom. Results and Discussion. In the plateau region of the simulated antiproton beam we observe a dose-averaged unrestrict...

Web site lets solar scientists inform and inspire students

Science.gov (United States)

Hauck, Karin

2012-07-01

Where on the Web can a middle school girl ask a female solar scientist about solar storms, the course and behavior of charged solar particles, and the origin of the Sun's dynamo—and also find out what the scientist was like as a child, whether the scientist has tattoos or enjoys snowboarding, what she likes and dislikes about her career, and how she balances her energy for work and family life? These kinds of exchanges happen at Solar Week (http://www.solarweek.org; see Figure 1). Established in 2000, Solar Week is an online resource for middle and lower high school students about the science of the Sun, sponsored by the Center for Science Education at the Space Sciences Laboratory (CSE@SSL) at the University of California, Berkeley (UC Berkeley). The Web site's goals are to educate students about the Sun and solar physics and to encourage future careers in science—especially for girls. One way is by giving solar scientists the chance to be relatable role models, to answer students' questions, and to share their experiences in an online forum.

miRNA let-7b modulates macrophage polarization and enhances tumor-associated macrophages to promote angiogenesis and mobility in prostate cancer.

Science.gov (United States)

Wang, Zhigang; Xu, Lu; Hu, Yinying; Huang, Yanqin; Zhang, Yujuan; Zheng, Xiufen; Wang, Shanshan; Wang, Yifan; Yu, Yanrong; Zhang, Meng; Yuan, Keng; Min, Weiping

2016-05-09

Macrophage polarization is a highly plastic physiological process that responds to a variety of environmental factors by changing macrophage phenotype and function. Tumor-associated macrophages (TAMs) are generally recognized as promoting tumor progression. As universal regulators, microRNAs (miRNAs) are functionally involved in numerous critical cellular processes including macrophage polarization. Let-7b, a miRNA, has differential expression patterns in inflamed tissues compared with healthy controls. However, whether and how miRNA let-7b regulates macrophage phenotype and function is unclear. In this report, we find that up-regulation of let-7b is characteristic of prostatic TAMs, and down-regulation of let-7b in TAMs leads to changes in expression profiles of inflammatory cytokines, such as IL-12, IL-23, IL-10 and TNF-α. As a result, TAMs treated with let-7b inhibitors reduce angiogenesis and prostate carcinoma (PCa) cell mobility. Let-7b may play a vital role in regulating macrophage polarization, thus modulating the prognosis of prostate cancer.

Social and parasocial relationships on social network sites and their differential relationships with users' psychological well-being.

Science.gov (United States)

Baek, Young Min; Bae, Young; Jang, Hyunmi

2013-07-01

With the advent of social network sites (SNSs), people can efficiently maintain preexisting social relationships and make online friendships without offline encounters. While such technological features of SNSs hold a variety of potential for individual and collective benefits, some scholars warn that use of SNSs might lead to socially negative consequences, such as social isolation, erosion of social cohesion, or SNS addiction. This study distinguishes types of SNS relationships, and investigates their relationships with social isolation, interpersonal trust, and SNS addiction. We classify SNS relationships into two types: (a) social relationships based on reciprocity between a user and his/her friends, and (b) parasocial relationships in which an ordinary user is aware of activities of a celebrity (e.g., famous actors, athletes, and others) but not vice versa. Based on achievements in studies of media effect and social psychology, we constructed a set of hypotheses, and tested them using a subsample of SNS users drawn from representative survey data in South Korea. We found that dependency on parasocial relationships is positively related with loneliness but negatively correlated with interpersonal distrust, while dependency on social relationship is negatively correlated with loneliness but positively related with trust. However, more dependency on both social and parasocial relationships are positively related with SNS addiction. Implications based on findings are also discussed.

Overexpression of let-7a increases neurotoxicity in a PC12 cell model of Alzheimer's disease via regulating autophagy.

Science.gov (United States)

Gu, Huizi; Li, Lan; Cui, Chen; Zhao, Zihui; Song, Guijun

2017-10-01

Increased deposition of β-amyloid (Aβ) protein is one of the typical characteristics of Alzheimer's disease (AD). Recent evidence has demonstrated that the microRNA let-7 family, which is highly expressed in the central nervous system, participates in the regulation of pathologic processes of AD. In the present study, the effect of let-7a overexpression on Aβ1-40-induced neurotoxicity was evaluated in PC12 and SK-N-SH cells. The results indicated that overexpression of let-7a enhanced the neurotoxicity induced by Aβ1-40 in PC12 and SK-N-SH cells. In addition, the apoptosis induced by Aβ1-40 in PC12 and SK-N-SH cells was increased by let-7a overexpression. Furthermore, Aβ1-40 treatment increased the protein levels of microtubule-associated protein 1A/1B-light chain 3 (LC3) and beclin-1 and increased the LC3 II/I ratio. The mRNA expression levels of beclin-1, autophagy protein 5 (Atg-5) and Atg-7 were also increased by Aβ1-40 treatment in PC12 cells. Let-7a overexpression further upregulated the above autophagy-related markers. Furthermore, the protein level of p62 was increased by Aβ1-40 treatment, and this was further enhanced by let-7a overexpression. Finally, the present results demonstrated that the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was involved in the autophagy regulation by let-7a. In conclusion, the present study demonstrates that the neurotoxicity induced by Aβ1-40 is augmented by let-7a overexpression via regulation of autophagy, and the PI3K/Akt/mTOR signaling pathway also serves a function in this process.

User and virtual organisation support in EGEE

CERN Document Server

Donno, Flavia

2006-01-01

User and virtual organisation support in EGEE Providing adequate user support in a grid environment is a very challenging task due to the distributed nature of the grid. The variety of users and the variety of Virtual Organizations (VO) with a wide range of applications in use add further to the challenge. The people asking for support are of various kinds. They can be generic grid beginners, users belonging to a given Virtual Organization and dealing with a specific set of applications, site administrators operating grid services and local computing infrastructures, grid monitoring operators who check the status of the grid and need to contact the specific site to report problems; to this list can be added network specialists and others. Wherever a user is located and whatever the problem experienced is, a user expects from a support infrastructure a given set of services. A non-exhaustive list is the following: a) a single access point for support; b) a portal with a well structured sources of information a...

Combinatorial DNA Damage Pairing Model Based on X-Ray-Induced Foci Predicts the Dose and LET Dependence of Cell Death in Human Breast Cells

Energy Technology Data Exchange (ETDEWEB)

Vadhavkar, Nikhil [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Pham, Christopher [University of Texas, Houston, TX (United States). MD Anderson Cancer Center; Georgescu, Walter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Deschamps, Thomas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Heuskin, Anne-Catherine [Univ. of Namur (Belgium). Namur Research inst. for Life Sciences (NARILIS), Research Center for the Physics of Matter and Radiation (PMR); Tang, Jonathan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Costes, Sylvain V. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

2014-09-01

In contrast to the classic view of static DNA double-strand breaks (DSBs) being repaired at the site of damage, we hypothesize that DSBs move and merge with each other over large distances (m). As X-ray dose increases, the probability of having DSB clusters increases as does the probability of misrepair and cell death. Experimental work characterizing the X-ray dose dependence of radiation-induced foci (RIF) in nonmalignant human mammary epithelial cells (MCF10A) is used here to validate a DSB clustering model. We then use the principles of the local effect model (LEM) to predict the yield of DSBs at the submicron level. Two mechanisms for DSB clustering, namely random coalescence of DSBs versus active movement of DSBs into repair domains are compared and tested. Simulations that best predicted both RIF dose dependence and cell survival after X-ray irradiation favored the repair domain hypothesis, suggesting the nucleus is divided into an array of regularly spaced repair domains of ~;;1.55 m sides. Applying the same approach to high-linear energy transfer (LET) ion tracks, we are able to predict experimental RIF/m along tracks with an overall relative error of 12percent, for LET ranging between 30 350 keV/m and for three different ions. Finally, cell death was predicted by assuming an exponential dependence on the total number of DSBs and of all possible combinations of paired DSBs within each simulated RIF. Relative biological effectiveness (RBE) predictions for cell survival of MCF10A exposed to high-LET showed an LET dependence that matches previous experimental results for similar cell types. Overall, this work suggests that microdosimetric properties of ion tracks at the submicron level are sufficient to explain both RIF data and survival curves for any LET, similarly to the LEM assumption. Conversely, high-LET death mechanism does not have to infer linear-quadratic dose formalism as done in the LEM. In addition, the size of repair domains derived in our model

Sci-Sat AM: Radiation Dosimetry and Practical Therapy Solutions - 10: Towards LET detection: A study on the effects of scintillator doping

Energy Technology Data Exchange (ETDEWEB)

Nusrat, Humza; Pang, Geordi; Ahmad, Syed; Keller, Brian; Sarfehnia, Arman [Ryerson University, Sunnybrook Health Sciences Centre (Canada)

2016-08-15

Purpose: In radiotherapy, the amount of radiation delivered is determined by optimizing the amount of absorbed dose to the tumor. Dose does not always correlate well with the actual biological effects of radiation. This work seeks to validate the LET-dependence of doped plastic scintillators for use in a radiation beam quality (LET) detector. Methods: The LET spectrum ([Φ]) can be resolved knowing the measured signals of uniquely LET-dependent detectors, [S], and the response of each LET-dependent detector to specific LETs ([R]), through the relation [Φ]=[S][R]{sup −1}. Plastic scintillator response is intrinsically LET dependent and can be varied via doping. Initial prototype consists of plastic scintillator and glass taper coupled to an optical fiber; components are housed in black acrylic, reducing effect of ambient light. In order to determine [R], the light response matrix, GEANT4.10.1 Monte Carlo (MC) was used. To validate MC, measurements were done using high energy electrons (9,12,15MeV) and orthovoltage x-rays (100,250kV); scintillator signal was normalized to dose measured simultaneously. Results: Stopping power was varied by changing particle type/energy; measurements indicated that as stopping power increased from 1.9 to 6.6MeV/cm, detector response increased by 263% (+/−29.2%) for 5%Pb-doped scintillator (155% in MC); 52% (+/−7.8%) increase observed when undoped scintillator was used (49% in MC). 5%Pb-doped discrepancy (100kV x-rays) is being investigated. Conclusions: This work validates that doping effects LET/energy response of scintillators; an effect that can be utilized for construction of an LET detector.

Production and excision of thymine damage in the DNA of mammalian cells exposed to high-LET radiations

International Nuclear Information System (INIS)

Mattern, M.R.; Welch, G.P.

1979-01-01

HeLa S3 and Chinese hamster ovary cells were irradiated with high doses of carbon ions having linear energy transfers (LETs) of 170 and 780 keV/μm. The DNA was analyzed for 5,6-dihydroxydihydrothymine (t'-type) radiation products both before and after postirradiation incubation at 37 0 C. In HeLa cells, 2.1 x 10 -5 ring-damaged thymines were produced per kilorad per 10 6 daltons after irradiation with high-LET carbon ions - approximately one-fifth the efficiency of t' formation in HeLa cells exposed to low-LET x rays. t' products were also formed less efficiently in Chinese hamster ovary cells exposed to carbon ions than in those exposed to x rays. In both cell lines, up to 80% of the t' formed initially was excised selectively from the DNA during 60 min of postirradiation incubation at 37 0 C. Product excision was accompanied by small amounts of DNA degradation (less than 1%). Radiation with LET of 170 keV/μm - nearly the most effective LET for cell killing and the generation of unrejoined DNA strand breaks - produced ring-damaged thymines that were removed selectively from the DNA. This result is consistent with the conclusion that t'-type products do not contribute substantially to lethality after high-LET irradiation, although the alternative possibilities remain that t' is not excised as efficiently after biological doses, or that a particular subclass of t' or defective postexcision events contribute to cell killing

Operational experience with CMS Tier-2 sites

International Nuclear Information System (INIS)

Gonzalez Caballero, I

2010-01-01

In the CMS computing model, more than one third of the computing resources are located at Tier-2 sites, which are distributed across the countries in the collaboration. These sites are the primary platform for user analyses; they host datasets that are created at Tier-1 sites, and users from all CMS institutes submit analysis jobs that run on those data through grid interfaces. They are also the primary resource for the production of large simulation samples for general use in the experiment. As a result, Tier-2 sites have an interesting mix of organized experiment-controlled activities and chaotic user-controlled activities. CMS currently operates about 40 Tier-2 sites in 22 countries, making the sites a far-flung computational and social network. We describe our operational experience with the sites, touching on our achievements, the lessons learned, and the challenges for the future.

User-generated content on Facebook: Implications from the perspective of two organisations

OpenAIRE

Kurian, Jayan

2016-01-01

The purpose of this study is to examine the implications (user benefits and costs) of user-generated content posted by users on Facebook from an organisational perspective. Though motivations to use social networking sites are widely researched and published, studies on implications eventuating from different types of content posted by users on social networking sites is sparse. Hence, this study addresses the gap in literature by an interpretive analysis of user-generated content posted by u...

SimLabel: a graphical user interface to simulate continuous wave EPR spectra from site-directed spin labeling experiments.

Science.gov (United States)

Etienne, E; Le Breton, N; Martinho, M; Mileo, E; Belle, V

2017-08-01

Site-directed spin labeling (SDSL) combined with continuous wave electron paramagnetic resonance (cw EPR) spectroscopy is a powerful technique to reveal, at the residue level, structural transitions in proteins. SDSL-EPR is based on the selective grafting of a paramagnetic label on the protein under study, followed by cw EPR analysis. To extract valuable quantitative information from SDSL-EPR spectra and thus give reliable interpretation on biological system dynamics, numerical simulations of the spectra are required. Such spectral simulations can be carried out by coding in MATLAB using functions from the EasySpin toolbox. For non-expert users of MATLAB, this could be a complex task or even impede the use of such simulation tool. We developed a graphical user interface called SimLabel dedicated to run cw EPR spectra simulations particularly coming from SDSL-EPR experiments. Simlabel provides an intuitive way to visualize, simulate, and fit such cw EPR spectra. An example of SDSL-EPR spectra simulation concerning the study of an intrinsically disordered region undergoing a local induced folding is described and discussed. We believe that this new tool will help the users to rapidly obtain reliable simulated spectra and hence facilitate the interpretation of their results. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Predicting User Views in Online News

DEFF Research Database (Denmark)

Hardt, Daniel; Rambow, Owen

2017-01-01

We analyze user viewing behavior on anonline news site. We collect data from64,000 news articles, and use text featuresto predict frequency of user views.We compare predictiveness of the headlineand “teaser” (viewed before clicking) andthe body (viewed after clicking). Both arepredictive of click...

Comparing Facebook Users and Facebook Non-Users: Relationship between Personality Traits and Mental Health Variables ? An Exploratory Study

OpenAIRE

Brailovskaia, Julia; Margraf, J?rgen

2016-01-01

Over one billion people use Facebook as a platform for social interaction and self-presentation making it one of the most popular online sites. The aim of the present study was to investigate differences in various personality traits and mental health variables between Facebook users and people who do not use this platform. The data of 945 participants (790 Facebook users, 155 Facebook non-users) were collected. Results indicate that Facebook users score significantly higher on narcissism, se...

Development of a site analysis tool for distributed wind projects

Energy Technology Data Exchange (ETDEWEB)

Shaw, Shawn [The Cadmus Group, Inc., Waltham MA (United States)

2012-02-28

The Cadmus Group, Inc., in collaboration with the National Renewable Energy Laboratory (NREL) and Encraft, was awarded a grant from the Department of Energy (DOE) to develop a site analysis tool for distributed wind technologies. As the principal investigator for this project, Mr. Shawn Shaw was responsible for overall project management, direction, and technical approach. The product resulting from this project is the Distributed Wind Site Analysis Tool (DSAT), a software tool for analyzing proposed sites for distributed wind technology (DWT) systems. This user-friendly tool supports the long-term growth and stability of the DWT market by providing reliable, realistic estimates of site and system energy output and feasibility. DSAT-which is accessible online and requires no purchase or download of software-is available in two account types; Standard: This free account allows the user to analyze a limited number of sites and to produce a system performance report for each; and Professional: For a small annual fee users can analyze an unlimited number of sites, produce system performance reports, and generate other customizable reports containing key information such as visual influence and wind resources. The tool’s interactive maps allow users to create site models that incorporate the obstructions and terrain types present. Users can generate site reports immediately after entering the requisite site information. Ideally, this tool also educates users regarding good site selection and effective evaluation practices.

Photon-Fluence-Weighted let for Radiation Fields Subjected to Epidemiological Studies.

Science.gov (United States)

Sasaki, Michiya

2017-08-01

In order to estimate the uncertainty of the radiation risk associated with the photon energy in epidemiological studies, photon-fluence-weighted LET values were quantified for photon radiation fields with the target organs and irradiation conditions taken into consideration. The photon fluences giving a unit absorbed dose to the target organ were estimated by using photon energy spectra together with the dose conversion coefficients given in ICRP Publication 116 for the target organs of the colon, bone marrow, stomach, lung, skin and breast with three irradiation geometries. As a result, it was demonstrated that the weighted LET values did not show a clear difference among the photon radiation fields subjected to epidemiological studies, regardless of the target organ and the irradiation geometry.

Epidemics of HIV, HCV and syphilis infection among synthetic drugs only users, heroin-only users and poly-drug users in Southwest China.

Science.gov (United States)

Su, Shu; Mao, Limin; Zhao, Jinxian; Chen, Liang; Jing, Jun; Cheng, Feng; Zhang, Lei

2018-04-26

The number of poly-drug users who mix use heroin and synthetic drugs (SD) is increasing worldwide. The objective of this study is to measure the risk factors for being infected with hepatitis C (HCV), human immunodeficiency virus (HIV) and syphilis among SD-only users, heroin-only users and poly-drug users. A cross-sectional study was conducted in 2015 from a national HIV surveillance site in Southwest China, 447 poly-drug, 526 SD-only and 318 heroin-only users were recruited. Poly-drug users have higher drug-use frequency, higher rates of drug-sharing and unsafe sexual acts than other users (p users experienced sexual arousal due to drug effects, which is higher than the rate among other drug users. Poly-drug users had the highest prevalence of HIV (10.5%) and syphilis (3.6%), but heroin-only users had the highest prevalence of HCV (66.0%) (all p users, having sex following drug consumption and using drugs ≥1/day were the major risk factors for both HIV (Adjusted odds ratio (AOR) = 2.4, 95% CI [1.8-3.4]; 2.3, [1.6-3.1]) and syphilis infection (AOR = 4.1, [2.1-6.9]; 3.9, [1.8-5.4]). Elevated risk of both HIV and syphilis infection have been established among poly-drug users.

Hanford Environmental Information System (HEIS). Volume 1, User`s guide

Energy Technology Data Exchange (ETDEWEB)

1994-01-14

The Hanford Environmental Information System (HEIS) is a consolidated set of automated resources that effectively manage the data gathered during environmental monitoring and restoration of the Hanford Site. HEIS includes an integrated database that provides consistent and current data to all users and promotes sharing of data by the entire user community. HEIS is an information system with an inclusive database. Although the database is the nucleus of the system, HEIS also provides user access software: query-by-form data entry, extraction, and browsing facilities; menu-driven reporting facilities; an ad hoc query facility; and a geographic information system (GIS). These features, with the exception of the GIS, are described in this manual set. Because HEIS contains data from the entire Hanford Site, many varieties of data are included and have.been divided into subject areas. Related subject areas comprise several volumes of the manual set. The manual set includes a data dictionary that lists all of the fields in the HEIS database, with their definitions and a cross reference of their locations in the database; definitions of data qualifiers for analytical results; and a mapping between the HEIS software functions and the keyboard keys for each of the supported terminals or terminal emulators.

Catalytic site identification—a web server to identify catalytic site structural matches throughout PDB

Science.gov (United States)

Kirshner, Daniel A.; Nilmeier, Jerome P.; Lightstone, Felice C.

2013-01-01

The catalytic site identification web server provides the innovative capability to find structural matches to a user-specified catalytic site among all Protein Data Bank proteins rapidly (in less than a minute). The server also can examine a user-specified protein structure or model to identify structural matches to a library of catalytic sites. Finally, the server provides a database of pre-calculated matches between all Protein Data Bank proteins and the library of catalytic sites. The database has been used to derive a set of hypothesized novel enzymatic function annotations. In all cases, matches and putative binding sites (protein structure and surfaces) can be visualized interactively online. The website can be accessed at http://catsid.llnl.gov. PMID:23680785

"Let the Circle be Unbroken" helps African-Americans prevent teen pregnancy.

Science.gov (United States)

Okwumabua, T M; Okwumabua, J O; Elliott, V

1998-01-01

Strategies must be developed to address the high rate of adolescent pregnancy among Blacks in the US and the adverse consequences of premature parenting. A number of programs and strategies have been developed and are being implemented in various sites across the US. The "Let the Circle Be Unbroken: Rites of Passage" program is an effort to incorporate an Afrocentric conceptual model into a prevention program. It involves adapting socialization processes often observed in African cultures, which openly acknowledge the need to formally help adolescents during their transition from childhood to adulthood. That socialization process tends to be a cultural experience which requires that ideology, education, training, and culture be taught before an activity or celebration marking the successful transition from one stage of development to another. The "Rites of Passage" approach follows these basic premises to teach adolescents the knowledge and skills needed to become responsible community members and spiritually mature adults. It is specifically designed to help young people build self-esteem; enhance self-image; develop leadership skills, cultural awareness, and appreciation; and make healthy, productive, and self-affirming life choices.

Track structure analysis illustrating the prominent role of low-energy electrons in radiobiological effects of low-LET radiations

International Nuclear Information System (INIS)

Nikjoo, H.; Goodhead, D.T.

1991-01-01

Monte Carlo track structure methods have been used to illustrate the importance of low-energy electrons produced by low-LET radiations. It is shown that these low-energy secondary electrons contribute substantially to the dose in all low-LET irradiations and are particularly efficient at producing highly localized clusters of atomic damage which may be responsible for a major part of the biological effectiveness of low-LET radiations. The data generated by Monte Carlo track structure techniques and by earlier semi-analytical methods based on the LET concept have been compared in terms of cumulative and differential fractions of total dose absorbed as a function of electron energy. The data show that low-energy secondary electrons account for up to nearly 50% of the total dose imparted to a medium when irradiated with electrons or photons. (author)

Supporting Regional Aged Care Nursing Staff to Manage Residents' Behavioural and Psychological Symptoms of Dementia, in Real Time, Using the Nurses' Behavioural Assistant (NBA): A Pilot Site 'End-User Attitudes' Trial.

Science.gov (United States)

Klein, Britt; Clinnick, Lisa; Chesler, Jessica; Stranieri, Andrew; Bignold, Adam; Dazeley, Richard; McLaren, Suzanne; Lauder, Sue; Balasubramanian, Venki

2018-01-01

This regional pilot site 'end-user attitudes' study explored nurses' experiences and impressions of using the Nurses' Behavioural Assistant (NBA) (a knowledge-based, interactive ehealth system) to assist them to better respond to behavioural and psychological symptoms of dementia (BPSD) and will be reported here. Focus groups were conducted, followed by a four-week pilot site 'end-user attitudes' trial of the NBA at a regional aged care residential facility (ACRF). Brief interviews were conducted with consenting nursing staff. Focus group feedback (N = 10) required only minor cosmetic changes to the NBA prototype. Post pilot site end-user interview data (N = 10) indicated that the regional ACRF nurses were positive and enthusiastic about the NBA, however several issues were also identified. Overall the results supported the utility of the NBA to promote a person centred care approach to managing BPSD. Slight modifications may be required to maximise its uptake across all ACRF nursing staff.

Let your communication skills equal your clinical skills.

Science.gov (United States)

Demarais, Ann; Baum, Neil

2012-01-01

Relating effectively with patients is among the most valued skills of clinical care. Honing your communication skills is an art that every physician needs to learn and understand. In this era of increased volume of patients there is a tendency to lose sight of the importance of having good communication skills. This article will review 11 suggestions for letting your communication skills equal your clinical skills.

Let’s Stop HIV Together: Jamar Rogers

Centers for Disease Control (CDC) Podcasts

2012-07-16

In this podcast, singer Jamar Rogers shares his personal story in the Let's Stop HIV Together Campaign.  Created: 7/16/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 7/16/2012.

The survival effects of V79 cells irradiated with carbon ions in different let

International Nuclear Information System (INIS)

Wang Jufang; Zhou Guangming; He Jing; Li Wenjian; Li Qiang; Dang Bingrong; Li Xinglin; Weng Xiaoqiong; Xie Hongmei; Wei Zengquan; Gao Qingxiang

2001-01-01

The survival of cultured Chinese V79 hamster cells irradiated with carbon ions with different LETs were investigated. Irradiation was performed at the heavy Ion Research Facility in Lanzhou (HIRFL). Results were compared with those obtained from the experiments with γ rats and could be concluded as follows: The survival curves for carbon ions showed as straight lines and were fitted to the one-target one-hit model, but for γ rays the curves with shoulders were fitted to the multi-target one-hit model. As the LETs were 125, 200 and 700 keV/μm for carbon ions, the inactivation cross section 35, 12 and 8 μm 2 , respectively, which suggested that under the experimental conditions, the lower the LET of carbon ions, the more seriously the irradiation killed cells. In the case of 125 keV/μm, the RBEs of carbon ions at the 0.1 and 0.37 survival levels were 1.47 and 2.19 respectively

Marketing E-Commerce by Social media using Product Recommendations and user Embedding

Science.gov (United States)

Ramalingam, V. V.; Pandian, A.; Masilamani, Kirthiga

2018-04-01

MarketingE-CommercebySodal media is the best way to improve marketing and business widely.The major issues faced with E-commerce and Social media interfacing is cold- start cross-site problem. The cold-start problem occurs at a situation when user is not having the history of purchase records.For the user who does not have a history of purchase records, we have introduced a method of finding the users’ interested product without knowing any of the demographic information of the user. The product is recommended on basesof visits i.e., the item which is most likely to be visited by the users occur in the hit list. This product is rated at the top position for the users to purchase. The e-commerce with social media sites uses the strategy of user embedding and product recommendations. The product recommendations are achieved by incorporating LatentDirichlet Allocation(LDA), Re Ranking and Collaborative Filtering algorithms. The proposed framework can enhance the recommendation system by embedding products and users. This shows the potential of solving cold-start cross-site problem across the e-commerce and social media sites and enhances the marketing strategy.

Water radiolysis in extreme conditions of temperature and LET. Scavenging of HO. by Br- ions

International Nuclear Information System (INIS)

Saffre, Dimitri

2011-01-01

The purpose of this thesis is to contribute to the understanding of the oxidation mechanism of Br - in which the HO . radical is involved. The HO . radiolytic yield is strongly connected with the oxidation yield of Br - , and therefore we have studied the influence of different physical and chemical parameters on this global yield: temperature, LET, dose rate, pH, saturation gas. The solutions have been irradiated with 4 types of ionizing rays: X-rays (from 13 to 18 keV), electrons (from 7 to 10 MeV), C 6+ -ions beam of 975 MeV and He 2+ -ions beam of 70 MeV. The development of an optical autoclave with solution flow, compatible with high LET ionizing rays has allowed us conduct the first experiments at constant high LET and high temperature. This cell has turned out to be compatible with the picosecond pump-probe experiments performed with the ELYSE accelerator. The HO . scavenging yield has been, therefore, estimated at both high LET and high temperature. A better understanding of the Br - oxidation mechanism has been achieved, in acid medium, in particular, by comparing the kinetics results with Monte Carlo Simulations for time scales inferior to the microsecond and with Chemsimul for the stable products (Br 2 .- and Br 3 - formations). (author) [fr

Social network sites: Indispensable or optional social tools?

DEFF Research Database (Denmark)

Shklovski, Irina

2012-01-01

Much research has enumerated potential benefits of online social network sites. Given the pervasiveness of these sites and the numbers of people that use them daily, both re-search and media tend to make the assumption that social network sites have become indispensible to their users. Based...... on the analysis of qualitative data from users of social network sites in Russia and Kazakhstan, this paper consid-ers under what conditions social network sites can become indispensable to their users and when these technologies remain on the periphery of life despite fulfilling useful func-tions. For some...... respondents, these sites had become indis-pensable tools as they were integrated into everyday rou-tines of communicating with emotionally important and proximal contacts and were often used for coordination of offline activities. For others social network sites remained spaces where they occasionally visited...

LET-99 functions in the astral furrowing pathway, where it is required for myosin enrichment in the contractile ring.

Science.gov (United States)

Price, Kari L; Rose, Lesilee S

2017-09-01

The anaphase spindle determines the position of the cytokinesis furrow, such that the contractile ring assembles in an equatorial zone between the two spindle poles. Contractile ring formation is mediated by RhoA activation at the equator by the centralspindlin complex and midzone microtubules. Astral microtubules also inhibit RhoA accumulation at the poles. In the Caenorhabditis elegans one-cell embryo, the astral microtubule-dependent pathway requires anillin, NOP-1, and LET-99. LET-99 is well characterized for generating the asymmetric cortical localization of the Gα-dependent force-generating complex that positions the spindle during asymmetric division. However, whether the role of LET-99 in cytokinesis is specific to asymmetric division and whether it acts through Gα to promote furrowing are unclear. Here we show that LET-99 contributes to furrowing in both asymmetrically and symmetrically dividing cells, independent of its function in spindle positioning and Gα regulation. LET-99 acts in a pathway parallel to anillin and is required for myosin enrichment into the contractile ring. These and other results suggest a positive feedback model in which LET-99 localizes to the presumptive cleavage furrow in response to the spindle and myosin. Once positioned there, LET-99 enhances myosin accumulation to promote furrowing in both symmetrically and asymmetrically dividing cells. © 2017 Price and Rose. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Let-7 microRNAs are developmentally regulated in circulating human erythroid cells

Directory of Open Access Journals (Sweden)

Reed Christopher

2009-11-01

Full Text Available Abstract Background MicroRNAs are ~22nt-long small non-coding RNAs that negatively regulate protein expression through mRNA degradation or translational repression in eukaryotic cells. Based upon their importance in regulating development and terminal differentiation in model systems, erythrocyte microRNA profiles were examined at birth and in adults to determine if changes in their abundance coincide with the developmental phenomenon of hemoglobin switching. Methods Expression profiling of microRNA was performed using total RNA from four adult peripheral blood samples compared to four cord blood samples after depletion of plasma, platelets, and nucleated cells. Labeled RNAs were hybridized to custom spotted arrays containing 474 human microRNA species (miRBase release 9.1. Total RNA from Epstein-Barr virus (EBV-transformed lymphoblastoid cell lines provided a hybridization reference for all samples to generate microRNA abundance profile for each sample. Results Among 206 detected miRNAs, 79% of the microRNAs were present at equivalent levels in both cord and adult cells. By comparison, 37 microRNAs were up-regulated and 4 microRNAs were down-regulated in adult erythroid cells (fold change > 2; p let-7 miRNA family consistently demonstrated increased abundance in the adult samples by array-based analyses that were confirmed by quantitative PCR (4.5 to 18.4 fold increases in 6 of 8 let-7 miRNA. Profiling studies of messenger RNA (mRNA in these cells additionally demonstrated down-regulation of ten let-7 target genes in the adult cells. Conclusion These data suggest that a consistent pattern of up-regulation among let-7 miRNA in circulating erythroid cells occurs in association with hemoglobin switching during the fetal-to-adult developmental transition in humans.

Applications of high-throughput clonogenic survival assays in high-LET particle microbeams

Directory of Open Access Journals (Sweden)

Antonios eGeorgantzoglou

2016-01-01

Full Text Available Charged particle therapy is increasingly becoming a valuable tool in cancer treatment, mainly due to the favorable interaction of particle radiation with matter. Its application is still limited due, in part, to lack of data regarding the radiosensitivity of certain cell lines to this radiation type, especially to high-LET particles. From the earliest days of radiation biology, the clonogenic survival assay has been used to provide radiation response data. This method produces reliable data but it is not optimized for high-throughput microbeam studies with high-LET radiation where high levels of cell killing lead to a very low probability of maintaining cells’ clonogenic potential. A new method, therefore, is proposed in this paper, which could potentially allow these experiments to be conducted in a high-throughput fashion. Cells are seeded in special polypropylene dishes and bright-field illumination provides cell visualization. Digital images are obtained and cell detection is applied based on corner detection, generating individual cell targets as x-y points. These points in the dish are then irradiated individually by a micron field size high-LET microbeam. Post-irradiation, time-lapse imaging follows cells’ response. All irradiated cells are tracked by linking trajectories in all time-frames, based on finding their nearest position. Cell divisions are detected based on cell appearance and individual cell temporary corner density. The number of divisions anticipated is low due to the high probability of cell killing from high-LET irradiation. Survival curves are produced based on cell’s capacity to divide at least 4-5 times. The process is repeated for a range of doses of radiation. Validation shows the efficiency of the proposed cell detection and tracking method in finding cell divisions.

Applications of High-Throughput Clonogenic Survival Assays in High-LET Particle Microbeams.

Science.gov (United States)

Georgantzoglou, Antonios; Merchant, Michael J; Jeynes, Jonathan C G; Mayhead, Natalie; Punia, Natasha; Butler, Rachel E; Jena, Rajesh

2015-01-01

Charged particle therapy is increasingly becoming a valuable tool in cancer treatment, mainly due to the favorable interaction of particle radiation with matter. Its application is still limited due, in part, to lack of data regarding the radiosensitivity of certain cell lines to this radiation type, especially to high-linear energy transfer (LET) particles. From the earliest days of radiation biology, the clonogenic survival assay has been used to provide radiation response data. This method produces reliable data but it is not optimized for high-throughput microbeam studies with high-LET radiation where high levels of cell killing lead to a very low probability of maintaining cells' clonogenic potential. A new method, therefore, is proposed in this paper, which could potentially allow these experiments to be conducted in a high-throughput fashion. Cells are seeded in special polypropylene dishes and bright-field illumination provides cell visualization. Digital images are obtained and cell detection is applied based on corner detection, generating individual cell targets as x-y points. These points in the dish are then irradiated individually by a micron field size high-LET microbeam. Post-irradiation, time-lapse imaging follows cells' response. All irradiated cells are tracked by linking trajectories in all time-frames, based on finding their nearest position. Cell divisions are detected based on cell appearance and individual cell temporary corner density. The number of divisions anticipated is low due to the high probability of cell killing from high-LET irradiation. Survival curves are produced based on cell's capacity to divide at least four to five times. The process is repeated for a range of doses of radiation. Validation shows the efficiency of the proposed cell detection and tracking method in finding cell divisions.

Low LET protons focused to submicrometer shows enhanced radiobiological effectiveness

Science.gov (United States)

Schmid, T. E.; Greubel, C.; Hable, V.; Zlobinskaya, O.; Michalski, D.; Girst, S.; Siebenwirth, C.; Schmid, E.; Molls, M.; Multhoff, G.; Dollinger, G.

2012-10-01

This study shows that enhanced radiobiological effectiveness (RBE) values can be generated focusing low linear energy transfer (LET) radiation and thus changing the microdose distribution. 20 MeV protons (LET = 2.65 keV µm-1) are focused to submicrometer diameter at the ion microprobe superconducting nanoprobe for applied nuclear (Kern) physics experiments of the Munich tandem accelerator. The RBE values, as determined by measuring micronuclei (RBEMN = 1.48 ± 0.07) and dicentrics (RBED = 1.92 ± 0.15), in human-hamster hybrid (AL) cells are significantly higher when 117 protons were focused to a submicrometer irradiation field within a 5.4 × 5.4 µm2 matrix compared to quasi homogeneous in a 1 × 1 µm2 matrix applied protons (RBEMN = 1.28 ± 0.07; RBED = 1.41 ± 0.14) at the same average dose of 1.7 Gy. The RBE values are normalized to standard 70 kV (dicentrics) or 200 kV (micronuclei) x-ray irradiation. The 117 protons applied per point deposit the same amount of energy like a 12C ion with 55 MeV total energy (4.48 MeV u-1). The enhancements are about half of that obtained for 12C ions (RBEMN = 2.20 ± 0.06 and RBED = 3.21 ± 0.10) and they are attributed to intertrack interactions of the induced damages. The measured RBE values show differences from predictions of the local effect model (LEM III) that is used to calculate RBE values for irradiation plans to treat tumors with high LET particles.

The drinking habits of users of an alcohol screening web site in Slovenia

Directory of Open Access Journals (Sweden)

Marko Kolšek

2011-09-01

Full Text Available Background: Heavy drinking is responsible for major health and social problems. Slovenia has few epidemiological studies about drinking, none of them have used the AUDIT questionnaire. Pilot studies have indicated that a Webbased screening is likely to be acceptable to young heavy drinkers. Methods: Cross sectional study. Visitors of a free website, older then 10 years, were offered screening with the Alcohol Use Disorder Identification Test (AUDIT. Their demographic data and information about their drinking habits were collected. All users who completed the questionnaire received a specially prepared feed-back message with an evaluation of their drinking. Data from the database for the first four months were collected for analysis on February 1, 2009. Results: In four months 3329 users filled in the questionnaire, 69.2 % completed it and 1790 participans completed it for themselves. Their mean age was 28.9 years, 62.7 % were between 19 and 34 years. 41 % were single, 49.4 % had finnished the secondary school. 0.1 % of men did not drink alcohol at all, 57.7 % drank hazardous or harmful amounts of alcohol. 50.6 % of women did not have risky drinking habits. Mean baseline AUDIT scores were 8.8 ± 1.3, 9.79 ± 2.1 for men and 7.68 ± 4.7 for women. Conclusions: The alcohol screening website was widely used, especially by young people. The percentage of hazardous male drinkers accessing the site was high. The website seems to be an accessible and useful tool for young people and it could contribute to health promotion and constitute an easier alternative to screening for hazardous and harmful drinking.

Algorithmic and user study of an autocompletion algorithm on a large medical vocabulary.

Science.gov (United States)

Sevenster, Merlijn; van Ommering, Rob; Qian, Yuechen

2012-02-01

Autocompletion supports human-computer interaction in software applications that let users enter textual data. We will be inspired by the use case in which medical professionals enter ontology concepts, catering the ongoing demand for structured and standardized data in medicine. Goal is to give an algorithmic analysis of one particular autocompletion algorithm, called multi-prefix matching algorithm, which suggests terms whose words' prefixes contain all words in the string typed by the user, e.g., in this sense, opt ner me matches optic nerve meningioma. Second we aim to investigate how well it supports users entering concepts from a large and comprehensive medical vocabulary (snomed ct). We give a concise description of the multi-prefix algorithm, and sketch how it can be optimized to meet required response time. Performance will be compared to a baseline algorithm, which gives suggestions that extend the string typed by the user to the right, e.g. optic nerve m gives optic nerve meningioma, but opt ner me does not. We conduct a user experiment in which 12 participants are invited to complete 40 snomed ct terms with the baseline algorithm and another set of 40 snomed ct terms with the multi-prefix algorithm. Our results show that users need significantly fewer keystrokes when supported by the multi-prefix algorithm than when supported by the baseline algorithm. The proposed algorithm is a competitive candidate for searching and retrieving terms from a large medical ontology. Copyright © 2011 Elsevier Inc. All rights reserved.

A critique of Katz's 'High LET constraint on low LET survival'

International Nuclear Information System (INIS)

Burch, P.R.J.; Chesters, M.S.

1979-01-01

Katz's interpretation of the connexion between RBE and LET is contrasted with a version published previously by Burch. The implications of Katz's model for dose-response relations apply only at ultra-high absorbed doses in Burch's model. In the latter, the shoulder on type-C survival curves for mammalian cells is explained in terms of Haynes' repair model. Under certain conditions the repair model becomes mathematically equivalent to the α-β model; under some other conditions it becomes equivalent to the 'two-component' model. The formulation of a new repair hypothesis, based on the idea of an inducible repair mechanism, is also set out. It is argued that Katz's supralinearity index' is appropriate to the induction of (rare) mutations but inappropriate to cell survival, for which an alternative index is proposed. Certain plausible hypotheses of radiobiological action conflict with Katz's 'logical constraint' which, it is contended, is neither logical nor valid. In conclusion, although experimental findings for some radiobiological systems conform to Katz's 'constraint', the frequently observed violations should not necessarily be regarded as artefacts. (author)

The role of long noncoding RNA-LET in cell proliferation and invasion of nasopharyngeal carcinoma and its mechanism

Directory of Open Access Journals (Sweden)

Chen L

2017-05-01

Full Text Available Lei Chen,1,* Lingling Sun,1,* Lei Dong,2 Peng Cui,3 Ziwei Xia,4 Chao Li,1 Yu Zhu5 1Department of Otolaryngology, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Pediatrics, Division of Hematology/Oncology, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA, USA; 3Department of Multidisciplinary Consultation Center of TCM and Western Medicine, The Affiliated Qingdao Hiser Hospital of Qingdao University, Qingdao, 4Department of Clinical Medicine, The Second Clinical Medical School of Tianjin Medical University, 5Department of Clinical Laboratory, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: LncRNA-LET, a recently identified long noncoding RNA, has been shown to act as a tumor suppressor; however, its biological function and mechanism have not been fully investigated. Our research found that there was less expression of LET in nasopharyngeal carcinoma (NPC tissues than normal tissues and that LET might inhibit proliferation, adhesion and invasion of NPC in vitro by enhancing its expression. By contrast, decreased LET expression could promote the proliferation, adhesion and invasion of NPC. In addition, the expression profiles of related genes and MAPK/ERK pathway were also regulated effectively via overexpression or silencing of LET. This result provides comprehensive evidence of LET’s antitumor effect on NPC in vitro, which might provide a new approach for clinical treatment. Keywords: LncRNA-LET, proliferation, invasion, nasopharyngeal carcinoma, MAPK/ERK pathway

CXCR4/Let-7a Axis Regulates Metastasis and Chemoresistance of Pancreatic Cancer Cells Through Targeting HMGA2

Directory of Open Access Journals (Sweden)

Guangfa Xiao

2017-09-01

Full Text Available Background/Aims: Pancreatic cancer cells (PCC is one of the most risky cancers and gemcitabine (GEM is the standard first-line drug for treating PCC. The PCC will develop drug resistance to GEM after a period of treatment. However, the detailed molecular mechanism of pathogenesis and drug resistance remains unresolved. Methods: we employed qRT-PCR and western blot to examine the expression level of CXCR4, let-7a and HMGA2. In addition, we used MTT assay to detect cell proliferation and transwell assay to measure migration and invasiveness. The expression level of epithelial marker E-cadherin and mesenthymal marker N-cadherin was detected by western blot. The apoptosis was determined using annexin V-FITC/PI apoptosis detection kit by flow cytometry. Results: we first proved that CXCR4 negatively regulated let-7a in PCC. Next, let-7a was confirmed to play crucial role in tumorigenesis, metastasis and drug resistance of pancreatic cancer cells Bxpc-3 and Panc-1 in vitro and in vivo. Finally, we identified HMGA2 as important downsteam target of let-7a in PCC and overexpression of HMGA2 restores cell proliferation, metastasis and chemosensitivity of GEM inhibited by let-7a. Conlusion: Taken together, we show an important signaling pathway involved in pathogenesis and drug resistance of PCC, thereby providing deeper insight into molecular mechanism by which CXCR4/let-7a regulates tumorigenesis and drug resistance of PCC. These findings will help us develop new strategies for diagnosis and treatment of PCC.

Depression of p53-independent Akt survival signals in human oral cancer cells bearing mutated p53 gene after exposure to high-LET radiation

Energy Technology Data Exchange (ETDEWEB)

Nakagawa, Yosuke [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Takahashi, Akihisa [Advanced Scientific Research Leader Development Unit, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Kajihara, Atsuhisa; Yamakawa, Nobuhiro; Imai, Yuichiro [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ota, Ichiro; Okamoto, Noritomo [Department of Otorhinolaryngology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Mori, Eiichiro [Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Noda, Taichi [Department of Dermatology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Furusawa, Yoshiya [Heavy-ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Kirita, Tadaaki [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ohnishi, Takeo, E-mail: tohnishi@naramed-u.ac.jp [Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan)

2012-07-13

Highlights: Black-Right-Pointing-Pointer High-LET radiation induces efficiently apoptosis regardless of p53 gene status. Black-Right-Pointing-Pointer We examined whether high-LET radiation depresses the Akt-survival signals. Black-Right-Pointing-Pointer High-LET radiation depresses of survival signals even in the mp53 cancer cells. Black-Right-Pointing-Pointer High-LET radiation activates Caspase-9 through depression of survival signals. Black-Right-Pointing-Pointer High-LET radiation suppresses cell growth through depression of survival signals. -- Abstract: Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6 h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G{sub 2}/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp

Finding Influential Users in Social Media Using Association Rule Learning

Directory of Open Access Journals (Sweden)

Fredrik Erlandsson

2016-04-01

Full Text Available Influential users play an important role in online social networks since users tend to have an impact on one other. Therefore, the proposed work analyzes users and their behavior in order to identify influential users and predict user participation. Normally, the success of a social media site is dependent on the activity level of the participating users. For both online social networking sites and individual users, it is of interest to find out if a topic will be interesting or not. In this article, we propose association learning to detect relationships between users. In order to verify the findings, several experiments were executed based on social network analysis, in which the most influential users identified from association rule learning were compared to the results from Degree Centrality and Page Rank Centrality. The results clearly indicate that it is possible to identify the most influential users using association rule learning. In addition, the results also indicate a lower execution time compared to state-of-the-art methods.

Environmentally-acceptable fossil energy site evaluation and selection: methodology and user's guide. Volume 1

Energy Technology Data Exchange (ETDEWEB)

Northrop, G.M.

1980-02-01

This report is designed to facilitate assessments of environmental and socioeconomic impacts of fossil energy conversion facilities which might be implemented at potential sites. The discussion of methodology and the User's Guide contained herein are presented in a format that assumes the reader is not an energy technologist. Indeed, this methodology is meant for application by almost anyone with an interest in a potential fossil energy development - planners, citizen groups, government officials, and members of industry. It may also be of instructional value. The methodology is called: Site Evaluation for Energy Conversion Systems (SELECS) and is organized in three levels of increasing sophistication. Only the least complicated version - the Level 1 SELECS - is presented in this document. As stated above, it has been expressly designed to enable just about anyone to participate in evaluating the potential impacts of a proposed energy conversion facility. To accomplish this objective, the Level 1 calculations have been restricted to ones which can be performed by hand in about one working day. Data collection and report preparation may bring the total effort required for a first or one-time application to two to three weeks. If repeated applications are made in the same general region, the assembling of data for a different site or energy conversion technology will probably take much less time.

Evaluering af ordning med psykologbehandling af personer med let til moderat depression

DEFF Research Database (Denmark)

Fjeldsted, Rita; Christensen, Kaj Sparle

Herværende rapport evaluerer den pr. 1.4.2008 indførte ordning med mulighed for henvisning til psykologbehandling med 60 % tilskud for patienter med let til moderat depression. Evalueringen har betjent sig af flere gensidigt supplerende metoder: spørgeskemaundersøgelser overfor patienter, psykolo......Herværende rapport evaluerer den pr. 1.4.2008 indførte ordning med mulighed for henvisning til psykologbehandling med 60 % tilskud for patienter med let til moderat depression. Evalueringen har betjent sig af flere gensidigt supplerende metoder: spørgeskemaundersøgelser overfor patienter...... tidligere evaluering af forsøgsordning af psykologbehandling af depression i perioden 2005-06. 18.419 personer i alderen 18-37 år blev henvist til psykolog i den undersøgte ordning i perioden 1.2.2009 – 31.1.2010, svarende til en henvisningshyppighed på 1,6 % af baggrundsbefolkningen i samme aldersgruppe....... Ordningen giver mulighed for én rehenvisning, og 9 % blev rehenvist i perioden. Spørgeskemaresultater viser, at kun 33 % af de henviste falder ind under henvisningskriteriet ” let til moderat depression” på tidspunktet for opstart af psykologbehandling, 39 % har ingen tegn på depression, og 28 % har svær...

Criminal Sanction for Users of Pornographic Content on Internet Sites: A Pornographic Law Perspecive

Directory of Open Access Journals (Sweden)

Ferry Irawan Febriansyah

2018-05-01

Full Text Available Inside the internet, information becomes something very important and really life. Mobility is so fast and can be downloaded, produced, and then uploaded again. The internet network is one of the most popular information sources today. Many internet users access pornographic websites because these pornographic websites supported by the development of rapid internet. The purpose of this study is to review Pornographic Law related to cyberporn.  This criminal act is called Cyberporn. Given the enormous impact that is caused by the act of pornography, especially on the internet site, the government legalized the bill against pornography into pornography law with clear criminal provisions. This research method using normative law research method, with a normative juridical approach related to pornography. In relation to this type of research is a normative legal research, then the source of legal material used is the legislation. In accordance with this type of research, the analysis used is a normative juridical analysis that relies on the ability of legal argumentation, legal interpretation, and legal reasoning related to criminal provisions in pornography law. From the results of research have found that criminal provisions in the law number 44 of 2008 on pornography is quite clear that everyone who access on porn sites on the internet threatened with criminal sanctions. Juridically, criminal provisions in pornography law provide legal certainty is quite clear.

[Analysis of Therapeutic Regularities and Characteristics of Blood-letting Therapy for Acne Patients Based on Data Mining].

Science.gov (United States)

Du, Yu-zhu; Jia, Chun-sheng; Wang, Jian-ling; Shi, Jing; Zhang, Xiao-xu; Liu, Xin; Gang, Wei-juan

2015-06-01

To analyze the therapeutic regularities and characteristics of blood-letting therapy for acne in the past clinical practice by using data mining. Original papers about acne treated by pricking blood therapy were searched and screened from common databases as Chinese National Knowledge Infrastructure Database (CNKI), WanFang Data, SinoMed, Ovid, ScienceDirect, Socolar, SciFinder, Foreign Medical Journal Full-Text Service (FMJS) and PubMed using keywords of acne+bleeding therapy, acne+blood-letting, acne+ pricking blood, followed by establishing a data plateform to conduct a data mining using Online Analytical Processing (OLAP). A total of 230 original journal articles about acne treated by pricking blood therapy were collected. The included acne cases with wind-heat pattern were predoment, being 56 in frequency-times and acounting for 24. 78 %. In the treatment of acne, the therapeutic tool, three-edged needle was often used, being 168 in frequency and acounting for 71.79%. The frequently employed acupoints were those of the Governor Vessel and Bladder Meridian, such as Dazhui (GV 14) and back-shu points. When auricular points used for blood-letting, Erjian (EX-HN 6) and the Vena of the auricular back were most frequently selected. In addition to blood-letting, other therapies such as Chinese herbal medicines, filiform needles, and otopoint-pellet pressure were also used in combination, being 166 in items and constituting 72. 17%. Generally, blood-letting treatment was conducted once every three days (twice a week) or once every two days (three times a week) for about 20 sessions for each acne patient. Blood-letting therapy is effective in the treatment of acne. But if used in combination with other therapies, the therapeutic effect would be better.

Earthdata Search: How Usability Drives Innovation To Enable A Broad User Base

Science.gov (United States)

Reese, M.; Siarto, J.; Lynnes, C.; Shum, D.

2017-12-01

Earthdata Search (https://search.earthdata.nasa.gov) is a modern web application allowing users to search, discover, visualize, refine, and access NASA Earth Observation data using a wide array of service offerings. Its goal is to ease the technical burden on data users by providing a high-quality application that makes it simple to interact with NASA Earth observation data, freeing them to spend more effort on innovative endeavors. This talk would detail how we put end users first in our design and development process, focusing on usability and letting usability needs drive requirements for the underlying technology. Just a few examples of how this plays out practically, Earthdata Search teams with a lightning fast metadata repository, allowing it to be an extremely responsive UI that updates as the user changes criteria not only at the dataset level, but also at the file level. This results in a better exploration experience as the time penalty is greatly reduced. Also, since Earthdata Search uses metadata from over 35,000 datasets that are managed by different data providers, metadata standards, quality and consistency will vary. We found that this was negatively impacting users' search and exploration experience. We have resolved this problem with the introduction of "humanizers", which is a community-driven process to both "smooth out" metadata values and provide non-jargonistic representations of some content within the Earthdata Search UI. This is helpful for both the experience data scientist and our users that are brand new to the discipline.

Eesti ja Soome kooliõpilased toovad lavale muusikali "Let Mamma Mia in!"

Index Scriptorium Estoniae

2006-01-01

21. okt. Kaja keskuses etendavad Tallinna 32. keskkooli ja Meri-Porin Lukio õpilased muusikali "Let Mamma Mia in". Muusikal koosneb muusikalihittidest, mille on looks kokku kirjutanud Sven Kivisildnik

Gas priority users consultation : government response

International Nuclear Information System (INIS)

2007-01-01

This consultation document presents the results of an updated analysis of gas priority users comments on the UK government's proposals for updating the current priority lists, amending the eligibility criteria for priority user status, and simplifying the administration of the scheme. The extension of Category C priority users to include sites where interruption of gas supplies would lead to damage exceeding fifty million pounds to a plant at another site is discussed. It is acknowledged that there is a preference for a reduction of gas demand as opposed to a cessation in the case of an emergency gas supply deficit and details are given of a Task Group set up to examine options for reducing demand rather than cessation for large industrial gas users. The role of the Network Emergency Co-ordinator, support for a more flexible approach, pre-agreed rota interruption, a long-duration emergency, demand reduction, and the establishment of a Government/Industry Gas/Electricity Task Group are discussed, and the raising of the load shedding threshold of 25,000 therms/yr is considered

SU-F-T-239: Evaluation of Plastic Scintillator Light Output for Various Lead Doping Concentrations: Towards LET Detection

International Nuclear Information System (INIS)

Nusrat, H; Pang, G; Sarfehnia, A

2016-01-01

Purpose: This work seeks to develop a beam quality meter using multiple differently doped plastic scintillators that are thus intrinsically beam-quality dependent. Plastic scintillators spontaneously emit visible light upon irradiation; the amount of light produced is dependent on stopping power (closely related to LET) according to Birks’ law. Doping plastic scintillators can be used to tune their sensitivity to specific LET ranges. Methods: GEANT4.10.1 Monte Carlo (MC) was used to evaluate the response of various scintillator dopant combinations. MC radiation transport and scintillator light response were validated against previously published literature. Current work involves evaluating detector response experimentally; to that end, a detector prototype with interchangeable scintillator housing was constructed. Measurement set-up guides light emitted by the scintillator to a photomultiplier tube via a glass taper junction coupled to an optical fiber. The resulting signal is measured by an electrometer, and normalized to dose readout from a diode. Measurements have been done using clinical electron and orthovoltage beams. MC response (simulated scintillator light normalized to dose scored inside the scintillating volume) was evaluated for four different LET radiations for an undoped and 1%Pb doped scintillator (σ=0.85%). Simulated incident electrons included: 0.05, 0.1, 0.2, 6, 12, and 18 MeV; these energies correspond to a range of stopping power (related to LET) values ranging from 1.824 to 11.09 MeVcm"2g"−"1 (SCOL from NIST-ESTAR). Results: Initial MC results show a distinct divergence in scintillator response as LET increases. The response for undoped plastic scintillator indicated a 35.0% increase in signal when going from 18 MeV (low LET) to 0.05 MeV (high LET) while 1%-Pb doped scintillator indicated a 100.9% increase. Conclusion: After validating MC against measurement, simulations will be used to test various concentrations (2%, 4%, 6%) of different

SU-F-T-239: Evaluation of Plastic Scintillator Light Output for Various Lead Doping Concentrations: Towards LET Detection

Energy Technology Data Exchange (ETDEWEB)

Nusrat, H [Ryerson University, Toronto, ON (Canada); Pang, G; Sarfehnia, A [Sunnybrook Health Sciences Centre, Toronto, ON (Canada)

2016-06-15

Purpose: This work seeks to develop a beam quality meter using multiple differently doped plastic scintillators that are thus intrinsically beam-quality dependent. Plastic scintillators spontaneously emit visible light upon irradiation; the amount of light produced is dependent on stopping power (closely related to LET) according to Birks’ law. Doping plastic scintillators can be used to tune their sensitivity to specific LET ranges. Methods: GEANT4.10.1 Monte Carlo (MC) was used to evaluate the response of various scintillator dopant combinations. MC radiation transport and scintillator light response were validated against previously published literature. Current work involves evaluating detector response experimentally; to that end, a detector prototype with interchangeable scintillator housing was constructed. Measurement set-up guides light emitted by the scintillator to a photomultiplier tube via a glass taper junction coupled to an optical fiber. The resulting signal is measured by an electrometer, and normalized to dose readout from a diode. Measurements have been done using clinical electron and orthovoltage beams. MC response (simulated scintillator light normalized to dose scored inside the scintillating volume) was evaluated for four different LET radiations for an undoped and 1%Pb doped scintillator (σ=0.85%). Simulated incident electrons included: 0.05, 0.1, 0.2, 6, 12, and 18 MeV; these energies correspond to a range of stopping power (related to LET) values ranging from 1.824 to 11.09 MeVcm{sup 2}g{sup −1} (SCOL from NIST-ESTAR). Results: Initial MC results show a distinct divergence in scintillator response as LET increases. The response for undoped plastic scintillator indicated a 35.0% increase in signal when going from 18 MeV (low LET) to 0.05 MeV (high LET) while 1%-Pb doped scintillator indicated a 100.9% increase. Conclusion: After validating MC against measurement, simulations will be used to test various concentrations (2%, 4%, 6%) of

Telephony user survey

CERN Multimedia

IT Department

2016-01-01

Let us know your needs to better plan the transition to a new CERN telephony system.   CERN is planning to upgrade its telephony network and replace the system with a new and modern VoIP infrastructure. We strive to make this transition as beneficial and smooth as possible for you. Please let us know more about your current working environment, expectations and suggestions by responding to this survey: https://cern.ch/tel-survey. The more answers we get, the better the new system will serve everyone in the future. The survey will take you about five minutes to complete; we are counting on your feedback!

The induction of somatic mutations by high-LET radiation observed using the Drosophila assay system

International Nuclear Information System (INIS)

Yoshikawa, Isao; Takatsuji, Toshihiro; Nagano, Masaaki; Hoshi, Masaharu; Takada, Jun; Endo, Satoru

1999-01-01

To evaluate the mutagenic potential of high-LET radiation, an analysis was made on the production of somatic mutations by 252 Cf fission neutron s and heavy particle ions accelerated by a synchrotron. A Drosophila strain that allows simultaneous detection of two types of mutations in an identical fly was constructed. One was a wing-hair mutation and the other was an eye-color mosaic spot mutation. Measurements were made using a combined assay system of both mutation assays. Larvae were exposed to radiation at the age of post-ovipositional day-3. The efficiency of 252 Cf neutrons for inducing wing-hair mosaic spots was very high, the relative biological effectiveness (RBE) = 8.5, but the efficiency for eye-color mosaic spot was nearly equal (RBE = 1.2) to that of 137 Cs γ-rays. The RBE of carbon ions for inducing wing-hair mosaic spots increased as an increase in LET values. The RBE for the induction of eye-color mutants did not change with LET. These relationships suggest that more complex types of DNA damages such as non-rejoinable strand break or clustered double strand break, which increase with LET may be responsible for the induction of wing-hair mutation, while simpler forms of molecular damage may induce a reversion in the white-ivory allele. (M.N.)

Low LET protons focused to submicrometer shows enhanced radiobiological effectiveness

International Nuclear Information System (INIS)

Schmid, T E; Zlobinskaya, O; Michalski, D; Molls, M; Multhoff, G; Greubel, C; Hable, V; Girst, S; Siebenwirth, C; Dollinger, G; Schmid, E

2012-01-01

This study shows that enhanced radiobiological effectiveness (RBE) values can be generated focusing low linear energy transfer (LET) radiation and thus changing the microdose distribution. 20 MeV protons (LET = 2.65 keV µm −1 ) are focused to submicrometer diameter at the ion microprobe superconducting nanoprobe for applied nuclear (Kern) physics experiments of the Munich tandem accelerator. The RBE values, as determined by measuring micronuclei (RBE MN = 1.48 ± 0.07) and dicentrics (RBE D = 1.92 ± 0.15), in human–hamster hybrid (A L ) cells are significantly higher when 117 protons were focused to a submicrometer irradiation field within a 5.4 × 5.4 µm 2 matrix compared to quasi homogeneous in a 1 × 1 µm 2 matrix applied protons (RBE MN = 1.28 ± 0.07; RBE D = 1.41 ± 0.14) at the same average dose of 1.7 Gy. The RBE values are normalized to standard 70 kV (dicentrics) or 200 kV (micronuclei) x-ray irradiation. The 117 protons applied per point deposit the same amount of energy like a 12 C ion with 55 MeV total energy (4.48 MeV u −1 ). The enhancements are about half of that obtained for 12 C ions (RBE MN = 2.20 ± 0.06 and RBE D = 3.21 ± 0.10) and they are attributed to intertrack interactions of the induced damages. The measured RBE values show differences from predictions of the local effect model (LEM III) that is used to calculate RBE values for irradiation plans to treat tumors with high LET particles. (paper)

PhosphoSiteAnalyzer

DEFF Research Database (Denmark)

Bennetzen, Martin V; Cox, Jürgen; Mann, Matthias

2012-01-01

an algorithm to retrieve kinase predictions from the public NetworKIN webpage in a semiautomated way and applies hereafter advanced statistics to facilitate a user-tailored in-depth analysis of the phosphoproteomic data sets. The interface of the software provides a high degree of analytical flexibility......Phosphoproteomic experiments are routinely conducted in laboratories worldwide, and because of the fast development of mass spectrometric techniques and efficient phosphopeptide enrichment methods, researchers frequently end up having lists with tens of thousands of phosphorylation sites...... and is designed to be intuitive for most users. PhosphoSiteAnalyzer is a freeware program available at http://phosphosite.sourceforge.net ....

Evaluation of normal tissue responses to high-LET radiations

International Nuclear Information System (INIS)

Halnan, K.E.

1979-01-01

Clinical results presented have been analysed to evaluate normal tissue responses to high-LET radiations. Damage to brain, spinal cord, gut, skin, connective tissue and bone has occurred. A high RBE is probable for brain and possible for spinal cord and gut but other reasons for damage are also discussed. A net gain seems likely. Random controlled trials are advocated. (author)

Let-7b is involved in the inflammation and immune responses associated with Helicobacter pylori infection by targeting Toll-like receptor 4.

Directory of Open Access Journals (Sweden)

Gui-gen Teng

Full Text Available OBJECTIVES: Toll-like receptors (TLRs are important initiators in native immune responses to microbial infections. TLR4 is up-regulated in response to H.pylori infection in gastric epithelial cells. However, the regulatory mechanisms for the expression of TLR4 in H.pylori infection have not been clearly defined. The aims of this study are to present the evidence that microRNA let-7b directly regulates TLR4 expression in human gastric epithelial cells, and subsequently influences the activation of NF-κB and the expression of the downstream genes in H.pylori infection. METHODS: The expression of let-7b was determined in gastric mucosa specimens and in two gastric epithelial cell lines using quantitative RT-PCR. The expression of TLR4 was determined by immunohistochemistry staining and RT-PCR. The potential target of let-7b was identified by luciferase reporter assay and Western blot. Let-7b mimics and inhibitors were used to examine the effects of let-7b on NF-κB activity. The expression of the downstream genes of NF-κB was also determined in cells infected with H.pylori 26695. RESULTS: Let-7b was significantly decreased in gastric mucosa specimens and in gastric epithelial cell lines (AGS, GES-1 infected with H.pylori 26695 (cagA+. Let-7b was complementary to the 3'-UTR of TLR4 mRNA and regulated TLR4 expression via post-transcriptional suppression in gastric epithelium. Infection of H.pylori induced the expression of TLR4 and activated NF-κB in AGS and GES-1 cells. Overexpression of let-7b by mimics downregulated TLR4, and subsequently attenuated NF-κB, MyD88, NF-κB1/p50, RelA/p65. The expression of IL-8, COX-2 and CyclinD1 was inhibited in H.pylori infected cells with let-7b overexpression. Both TAK-242 (TLR4 inhibitor and SN50 (NF-κB inhibitor significantly inhibited the H.pylori induced downregulation of let-7b. CONCLUSIONS: Let-7b targets at TLR4 mRNA, and regulates the activation of NF-κB and the expression of the downstream genes

The EGEE user support infrastructure

CERN Document Server

Antoni, T; Mills, A

2007-01-01

User support in a grid environment is a challenging task due to the distributed nature of the grid. The variety of users and VOs adds further to the challenge. One can find support requests by grid beginners, users with specific applications, site administrators, or grid monitoring operators. With the GGUS infrastructure, EGEE provides a portal where users can find support in their daily use of the grid. The current use of the system has shown that the goal has been achieved with success. The grid user support model in EGEE can be captioned ‘regional support with central coordination’. Users can submit a support request to the central GGUS service, or to their Regional Operations' Centre (ROC) or to their Virtual Organisation helpdesks. Within GGUS there are appropriate support groups for all support requests. The ROCs and VOs and the other project wide groups such as middleware groups (JRA), network groups (NA), service groups (SA) and other grid infrastructures (OSG, NorduGrid, etc.) are connected via a...

The EGEE user support infrastructure

CERN Document Server

Antoni, Torsten

2008-01-01

Grid user support is a challenging task due to the distributed nature of the Grid. The variety of users and Virtual Organisations adds further to the challenge. Support requests come from Grid beginners, from users with specific applications, from site administrators, or from Grid monitoring operators. With the GGUS infrastructure, EGEE provides a portal where users can find support in their daily use of the Grid. The current use of the system shows that the goal has been achieved with success. The Grid user support model in EGEE can be captioned "regional support with central coordination". This model is realised through a support process which is clearly defined and involves all the parties that are needed to run a project-wide support service. This process is sustained by a help desk system which consists of a central platform integrated with several satellite systems belonging to the Regional Operations Centres (ROCs) and the Virtual Organisations (VOs). The central system (Global Grid User Support, GGUS)...

Do Smartphone Power Users Protect Mobile Privacy Better than Nonpower Users? Exploring Power Usage as a Factor in Mobile Privacy Protection and Disclosure.

Science.gov (United States)

Kang, Hyunjin; Shin, Wonsun

2016-03-01

This study examines how consumers' competence at using smartphone technology (i.e., power usage) affects their privacy protection behaviors. A survey conducted with smartphone users shows that power usage influences privacy protection behavior not only directly but also indirectly through privacy concerns and trust placed in mobile service providers. A follow-up experiment indicates that the effects of power usage on smartphone users' information management can be a function of content personalization. Users, high on power usage, are less likely to share personal information on personalized mobile sites, but they become more revealing when they interact with nonpersonalized mobile sites.

pix-1 controls early elongation in parallel with mel-11 and let-502 in Caenorhabditis elegans.

Science.gov (United States)

Martin, Emmanuel; Harel, Sharon; Nkengfac, Bernard; Hamiche, Karim; Neault, Mathieu; Jenna, Sarah

2014-01-01

Cell shape changes are crucial for metazoan development. During Caenorhabditis elegans embryogenesis, epidermal cell shape changes transform ovoid embryos into vermiform larvae. This process is divided into two phases: early and late elongation. Early elongation involves the contraction of filamentous actin bundles by phosphorylated non-muscle myosin in a subset of epidermal (hypodermal) cells. The genes controlling early elongation are associated with two parallel pathways. The first one involves the rho-1/RHOA-specific effector let-502/Rho-kinase and mel-11/myosin phosphatase regulatory subunit. The second pathway involves the CDC42/RAC-specific effector pak-1. Late elongation is driven by mechanotransduction in ventral and dorsal hypodermal cells in response to body-wall muscle contractions, and involves the CDC42/RAC-specific Guanine-nucleotide Exchange Factor (GEF) pix-1, the GTPase ced-10/RAC and pak-1. In this study, pix-1 is shown to control early elongation in parallel with let-502/mel-11, as previously shown for pak-1. We show that pix-1, pak-1 and let-502 control the rate of elongation, and the antero-posterior morphology of the embryos. In particular, pix-1 and pak-1 are shown to control head, but not tail width, while let-502 controls both head and tail width. This suggests that let-502 function is required throughout the antero-posterior axis of the embryo during early elongation, while pix-1/pak-1 function may be mostly required in the anterior part of the embryo. Supporting this hypothesis we show that low pix-1 expression level in the dorsal-posterior hypodermal cells is required to ensure high elongation rate during early elongation.

An Equilibrium Model of User Generated Content

OpenAIRE

Dae-Yong Ahn; Jason A. Duan; Carl F. Mela

2011-01-01

This paper considers the joint creation and consumption of content on user generated content platforms (e.g., reviews or articles, chat, videos, etc.). On these platforms, users' utilities depend upon the participation of others; hence, users' expectations regarding the participation of others on the site becomes germane to their own involvement levels. Yet these beliefs are often assumed to be fixed. Accordingly, we develop a dynamic rational expectations equilibrium model of joint consumpti...

User's guide to the 'DISPOSALS' model

International Nuclear Information System (INIS)

Groom, M.S.; James, A.R.; Laundy, R.S.

1984-03-01

This report provides a User's Guide to the 'DISPOSALS' computer model and includes instructions on how to set up and run a specific problem together with details of the scope, theoretical basis, data requirements and capabilities of the model. The function of the 'DISPOSALS' model is to make assignments of nuclear waste material in an optimum manner to a number of disposal sites each subject to a number of constraints such as limits on the volume and activity. The user is able to vary the number of disposal sites, the range and limits of the constraints to be applied to each disposal site and the objective function for optimisation. The model is based on the Linear Programming technique and uses CAP Scientific's LAMPS and MAGIC packages. Currently the model has been implemented on CAP Scientific's VAX 11/750 minicomputer. (author)

Relation between track structure and LET effect on free radical formation for ion beam-irradiated alanine dosimeter

International Nuclear Information System (INIS)

Krushev, V.V.; Koizumi, Hitoshi; Ichikawa, Tsuneki; Yoshida, Hiroshi; Shibata, Hiromi; Tagawa, Seiichi; Yoshida, Yoichi

1994-01-01

The yield and local concentration of free radicals generated from alanine (α-aminopropionic acid) by irradiation with 3 MeV H + and He + ions were examined by means of electron spin resonance (ESR) and ESR power saturation methods at room temperature. The G-value of the radical formation showed a marked dependence on linear energy transfer (LET) of the ions. The G-value for the H + ion (average LET: 28 eV/nm) was almost the same as that for γ-irradiation and it was smaller by a factor of 1/4.7 for the He + ion (average LET: 225eV/nm). Combining the local concentration of the free radicals along the ion tracks with the G-values and the reported ion range, the radius of a track filled with free radicals was estimated to be 4 ∼ 5 nm by assuming a simple rod-shaped track with a constant radius and homogeneous distribution of the free radicals in it. The track radius scarcely depends on the LET within the range examined. The radiation energy deposited in the core region of the ion track was concluded to spread over the rod to generate free radicals. (author)

爸爸妈妈，请您放手%Mom and Dad,Please Let Go

Institute of Scientific and Technical Information of China (English)

谢青

2014-01-01

In daily life,most of the children lack of self-care ability,which is part of the reason is that parents,parents might as well let go,let the child practice and experience.%在日常生活中大部分幼儿都缺乏自理能力，其中，有部分原因在于家长，家长不妨放手，让孩子自己去动手、自己去体会。

Induction of λ prophage in lysogenic E.Coli exposed to ionizing radiation of different let

International Nuclear Information System (INIS)

Bonev, M.; Kozubek, S.; Krasavin, E.A.; Cherevatenko, A.P.

1988-01-01

Induction of λ prophage in lysogenic E. coli cells exposed to ionizing radiation of different LET was studied as a function of dose I(D). Activities of pleiotropic RecA protein were shown to contribute to the shape of the I(D) curve. The experimental data were fitted by the function I(D)=αD(1-exp(-D 0 -1 xD))exp(-βD). Inducibility α increased with increasing LET which was related to the increased incidence of DNA lesions being a SOS - system call

OASIS User Manual

CERN Document Server

Bojtar, L

2009-01-01

The OASIS system has been operational for years now. After a long development the project has reached a state where the number of features it provides exceeds largely what most of its users knows about. The author felt it was time to write a user manual explaining all the functionality of the viewer application. This document is a user manual, concentrating on the functionality of the viewer from the user’s point of view. There are already documents available on the project’s web site about the technical aspects at http://project-oasis.web.cern.ch/project-oasis/presentations.htm . There was an attempt to produce a tutorial on the viewer, but it didn’t get much further than the table of contents, that however is well thought. The structure of this user manual follows the same principle, the basic and most often used features are grouped together. Advanced or less often used features are described in a separate chapter. There is a second organizational principle, features belong to different levels: chann...

Implementing a user-driven online quality improvement toolkit for cancer care.

Science.gov (United States)

Luck, Jeff; York, Laura S; Bowman, Candice; Gale, Randall C; Smith, Nina; Asch, Steven M

2015-05-01

Peer-to-peer collaboration within integrated health systems requires a mechanism for sharing quality improvement lessons. The Veterans Health Administration (VA) developed online compendia of tools linked to specific cancer quality indicators. We evaluated awareness and use of the toolkits, variation across facilities, impact of social marketing, and factors influencing toolkit use. A diffusion of innovations conceptual framework guided the collection of user activity data from the Toolkit Series SharePoint site and an online survey of potential Lung Cancer Care Toolkit users. The VA Toolkit Series site had 5,088 unique visitors in its first 22 months; 5% of users accounted for 40% of page views. Social marketing communications were correlated with site usage. Of survey respondents (n = 355), 54% had visited the site, of whom 24% downloaded at least one tool. Respondents' awareness of the lung cancer quality performance of their facility, and facility participation in quality improvement collaboratives, were positively associated with Toolkit Series site use. Facility-level lung cancer tool implementation varied widely across tool types. The VA Toolkit Series achieved widespread use and a high degree of user engagement, although use varied widely across facilities. The most active users were aware of and active in cancer care quality improvement. Toolkit use seemed to be reinforced by other quality improvement activities. A combination of user-driven tool creation and centralized toolkit development seemed to be effective for leveraging health information technology to spread disease-specific quality improvement tools within an integrated health care system. Copyright © 2015 by American Society of Clinical Oncology.

Brain Gym: Let the User Beware

Science.gov (United States)

Kroeze, Kevin; Hyatt, Keith; Lambert, Chuck

2015-01-01

As part of the No Child Left behind Act of 2001 and the Individuals with Disabilities Education Improvement Act of 2004, schools are called upon to provide students with academic instruction using scientific, research-based methods whenever possible. One of these supposed research-based methods is a program by the name of Brain Gym®. Brain Gym® is…

CMS Dashboard Task Monitoring: A user-centric monitoring view

International Nuclear Information System (INIS)

Karavakis, Edward; Khan, Akram; Andreeva, Julia; Maier, Gerhild; Gaidioz, Benjamin

2010-01-01

We are now in a phase change of the CMS experiment where people are turning more intensely to physics analysis and away from construction. This brings a lot of challenging issues with respect to monitoring of the user analysis. The physicists must be able to monitor the execution status, application and grid-level messages of their tasks that may run at any site within the CMS Virtual Organisation. The CMS Dashboard Task Monitoring project provides this information towards individual analysis users by collecting and exposing a user-centric set of information regarding submitted tasks including reason of failure, distribution by site and over time, consumed time and efficiency. The development was user-driven with physicists invited to test the prototype in order to assemble further requirements and identify weaknesses with the application.

The Role of Cultural and Identity Differences in Self-expression of Iranian Users of Social Networking Sites; A Case Study of Students of Tehran University, Amirkabir University, and Sharif University of Technology

OpenAIRE

H. Molaei; Z. Majdizadeh

2017-01-01

Social media with their features such as interactivity, participatory, and user-generated content have provided a great opportunity for self-expression of the users. However, cultural differences affect the extent and modality of users’ self-expression. This study aims to investigate the modality of self-expression of Iranian users of the social networking sites. In doing so, an online survey was conducted among the students of three Iran universities: University of Tehran, Amirkabir Universi...

Measurement and protection of the oxidative damage induced by high-LET carbon-ion irradiation in salmon sperm DNA solution

International Nuclear Information System (INIS)

Moritake, T.; Nose, T.; Tsuboi, K.; Anzai, K.; Ikota, N.; Ozawa, T.; Ando, K.

2003-01-01

The aims of this study are to quantify the yield of hydroxyl radicals (OH) , and to evaluate the oxidative damage on DNA after high-linear energy transfer (LET) carbon-ion beams and x-rays. For this purpose, the relationship between the radiolytic yield of OH in aqueous solution and 8-hydroxydeoxyguanosine (8-OHdG) level in DNA solution were assessed after radiation. In addition, the anti-oxidative effect of 3-methyl-1-phenyl-2-pyrazonline-5-one (edaravone) on DNA was evaluated. Culture medium containing 200 mM 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was irradiated with doses of 0 to 20 Gy with an LET of 20 to 90 keV/μm, and the yields of OH were measured using an electron spin resonance (ESR) spectrometer. Salmon sperm DNA solution at a concentration of 1.0 mg/ml was irradiated with 10 Gy of x-rays or 290 MeV/nucleon carbon-ion beams with an LET range of 20-80 keV/μm. 8-OHdG levels in the DNA solution were measured by HPLC with an electrochemical detector (ECD) after each irradiation. Edaravone was added to the DNA solution in final concentrations of 10 μM to 1 mM and 8-OHdG levels were measured by the same method after irradiation. The yield of OH by carbon-ion radiolysis increased in proportion to the absorbed dose over the range of 0 to 20 Gy, and the yield of OH decreased as LET increased logarithmically from 20 to 90 keV/μm. The level of 8-OHdG increased dose-dependently after x-ray irradiation, and it was significantly suppressed by edaravone. Furthermore, the yield of 8-OHdG and the protection efficiency by edaravone decreased as LET value increased. These unique findings provide further understanding of the indirect effect of high-LET radiation, and chemical protection of oxidative damage on DNA is important for clinical application of high-LET radiation

Measurement and protection of the oxidative damage induced by high-LET carbon-ion irradiation in salmon sperm DNA solution

Energy Technology Data Exchange (ETDEWEB)

Moritake, T; Nose, T [University of Tsukuba, (Japan); Tsuboi, K [Institute of Clinical Medical Center, (Japan); Anzai, K; Ikota, N [National Institute of Radiological Sciences, (Japan); Ozawa, T [Redox Regulation Research Group, (Japan); Ando, K [Research Center of Charged Particle Therapy, (Japan). National Institution

2003-07-01

The aims of this study are to quantify the yield of hydroxyl radicals (OH) , and to evaluate the oxidative damage on DNA after high-linear energy transfer (LET) carbon-ion beams and x-rays. For this purpose, the relationship between the radiolytic yield of OH in aqueous solution and 8-hydroxydeoxyguanosine (8-OHdG) level in DNA solution were assessed after radiation. In addition, the anti-oxidative effect of 3-methyl-1-phenyl-2-pyrazonline-5-one (edaravone) on DNA was evaluated. Culture medium containing 200 mM 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was irradiated with doses of 0 to 20 Gy with an LET of 20 to 90 keV/{mu}m, and the yields of OH were measured using an electron spin resonance (ESR) spectrometer. Salmon sperm DNA solution at a concentration of 1.0 mg/ml was irradiated with 10 Gy of x-rays or 290 MeV/nucleon carbon-ion beams with an LET range of 20-80 keV/{mu}m. 8-OHdG levels in the DNA solution were measured by HPLC with an electrochemical detector (ECD) after each irradiation. Edaravone was added to the DNA solution in final concentrations of 10 {mu}M to 1 mM and 8-OHdG levels were measured by the same method after irradiation. The yield of OH by carbon-ion radiolysis increased in proportion to the absorbed dose over the range of 0 to 20 Gy, and the yield of OH decreased as LET increased logarithmically from 20 to 90 keV/{mu}m. The level of 8-OHdG increased dose-dependently after x-ray irradiation, and it was significantly suppressed by edaravone. Furthermore, the yield of 8-OHdG and the protection efficiency by edaravone decreased as LET value increased. These unique findings provide further understanding of the indirect effect of high-LET radiation, and chemical protection of oxidative damage on DNA is important for clinical application of high-LET radiation.

Enabling Interoperable and Selective Data Sharing among Social Networking Sites

Science.gov (United States)

Shin, Dongwan; Lopes, Rodrigo

With the widespread use of social networking (SN) sites and even introduction of a social component in non-social oriented services, there is a growing concern over user privacy in general, how to handle and share user profiles across SN sites in particular. Although there have been several proprietary or open source-based approaches to unifying the creation of third party applications, the availability and retrieval of user profile information are still limited to the site where the third party application is run, mostly devoid of the support for data interoperability. In this paper we propose an approach to enabling interopearable and selective data sharing among SN sites. To support selective data sharing, we discuss an authenticated dictionary (ADT)-based credential which enables a user to share only a subset of her information certified by external SN sites with applications running on an SN site. For interoperable data sharing, we propose an extension to the OpenSocial API so that it can provide an open source-based framework for allowing the ADT-based credential to be used seamlessly among different SN sites.

Impact of Entertainment Motivational Drivers on User Acceptance of Online Social Network Banner Advertising: A Gratification Perspective

Directory of Open Access Journals (Sweden)

Mir Imran Anwar

2017-05-01

Full Text Available Social media has phenomenally changed the communication landscape. Particularly social network sites have received enormous popularity and user acceptance globally. The business model of many social network sites is based on advertising. The survival of these social network sites depends on the user acceptance of advertising appearing on these websites. Users usually accept the advertising which is consistent with their motivations for using social network sites. The current study examines the underlying dimensions of entertainment motivation for using social network sites and their impact on user acceptance of social network advertising. Analysis of data from 450 university students show entertainment motivation for using social network sites a multidimensional (SNSs construct consisting of enjoyment, social escapism, relaxation and pass time factors. Furthermore, the results exhibit that SNSs entertainment motivation partially impacts user acceptance of social network advertising.

Preliminary investigations of Monte Carlo Simulations of neutron energy and LET spectra for fast neutron therapy facilities

International Nuclear Information System (INIS)

Kroc, T.K.

2009-01-01

No fast neutron therapy facility has been built with optimized beam quality based on a thorough understanding of the neutron spectrum and its resulting biological effectiveness. A study has been initiated to provide the information necessary for such an optimization. Monte Carlo studies will be used to simulate neutron energy spectra and LET spectra. These studies will be bench-marked with data taken at existing fast neutron therapy facilities. Results will also be compared with radiobiological studies to further support beam quality ptimization. These simulations, anchored by this data, will then be used to determine what parameters might be optimized to take full advantage of the unique LET properties of fast neutron beams. This paper will present preliminary work in generating energy and LET spectra for the Fermilab fast neutron therapy facility.

Let's Play: Exploring Literacy Practices in an Emerging Videogame Paratext

Science.gov (United States)

Burwell, Catherine; Miller, Thomas

2016-01-01

This article explores the literacy practices associated with Let's Play videos (or LPs) on YouTube. A hybrid of digital gaming and video, LPs feature gameplay footage accompanied by simultaneous commentary recorded by the player. Players may set out to promote, review, critique or satirize a game. In recent years, LPs have become hugely popular…

Rehab-let: touchscreen tablet for self-training impaired dexterity post stroke: study protocol for a pilot randomized controlled trial.

Science.gov (United States)

Rand, Debbie; Zeilig, Gabi; Kizony, Rachel

2015-06-18

Impaired dexterity of the weaker upper extremity is common post stroke and it is recommended that these individuals practice many repetitions of movement to regain function. However, stroke rehabilitation methods do not achieve the required intensity to be effective. Touchscreen tablet technology may be used as a motivating tool for self-training impaired dexterity of the weaker upper extremity post stroke. Rehab-let is a self-training protocol utilizing game apps on a touchscreen for practicing movement of the weaker upper extremity. We will conduct a pilot randomized controlled trial to assess Rehab-let compared to traditional self-training to improve dexterity of the weaker hand, and to increase self-training time and satisfaction in individuals with subacute stroke. Forty individuals with stroke undergoing subacute rehabilitation will be randomly allocated to Rehab-let or a traditional self-training program using therapeutic aids such as balls, blocks and pegs. All participants will be requested to perform self-training for 60 minutes a day, 5 times a week for 4 weeks. Dexterity assessed by The Nine Hole Peg Test is the main outcome measure. Assessments will be administered pre and post the self-training intervention by assessors blind to the group allocation. The outcomes of this study will inform the design of a fully powered randomized controlled trial to evaluate the effectiveness of Rehab-let. If found to be effective, Rehab-let can be used during subacute rehabilitation to increase treatment intensity and improve dexterity. Potentially, Rehab-let can also be used after discharge and might be ideal for individuals with mild stroke who are often not referred to formal rehabilitation. Current Controlled Trials NCT02136433 registered on 17 September 2014.

Modeling the yield of double-strand breaks due to formation of multiply damaged sites in irradiated plasmid DNA

International Nuclear Information System (INIS)

Xapsos, M.A.; Pogozelski, W.K.

1996-01-01

Although double-strand breaks have long been recognized as an important type of DNa lesion, it is well established that this broad class of damage does not correlate well with indicators of the effectiveness of radiation as the cellular level. Assays of double-strand breaks do not distinguish the degree of complexity or clustering of singly damaged sites produced in a single energy deposition event, which is currently hypothesized to be key to understanding cellular end points. As a step toward this understanding, double-strand breaks that are formed proportionally to dose in plasmid DNA are analyzed from the mechanistic aspect to evaluate the yield that arises from multiply damaged sites as hypothesized by Ward (Prog. Nucleic Acid Res. Mol. Biol. 35, 95-125, 1988) and Goodhead (Int. J. Radiat. Biol. 65, 7-17, 1994) as opposed to the yield that arises form single hydroxyl radicals as hypothesized by Siddiqi and Bothe (Radiat. Res. 112, 449-463, 1987). For low-LET radiation such as γ rays, the importance of multiply damaged sites is shown to increase with the solution's hydroxyl radical scavenging capacity. For moderately high-LET radiation such as 100 keV/μm helium ions, a much different behavior is observed. In this case, a large fraction of double-strand breaks are formed as a result of multiply damaged sties over a broad range of scavenging conditions. Results also indicate that the RBE for common cellular end points correlates more closely with the RBE for common cellular end points correlates more closely with the RBE for multiply damaged sites than with the RBE for total double-strand breaks over a range of LET up to at least 100 keV/μm. 22 refs., 3 figs., 2 tabs

When Your Back Hurts: Don't Let Back Pain Knock You Flat

Science.gov (United States)

... Your Back Hurts Don’t Let Back Pain Knock You Flat En español Send us your comments ... Complementary Health Approaches Halt the Hurt! References The SPORT Value Compass: Do the Extra Costs of Undergoing ...

Microdosimetric spectra and parameters of low LET-radiations

International Nuclear Information System (INIS)

Booz, J.

1976-01-01

The experimental methods used for the evaluation of the flux averaged lineal energy y and the energy averaged lineal energy ysub(D) are briefly described. The composition of the y-distribution of low LET-radiations are discussed taking into consideration the energy of the electrons causing the event and the influence of their W-values. Some published values of ysub(F) and ysub(D) and their relation to the dimensions of the sensitive volume are analyzed. The wall effect is briefly discussed

Frontpage and Dreamweaver users must use encryption

CERN Multimedia

Web Services Team

2006-01-01

In order to ensure document confidentiality and protect users from the possible theft of their passwords, all web authoring actions will be required to use encryption as of 15 February 2006. Most Frontpage and Dreamweaver users will have to slightly change the way they connect to their web sites in order to enable encryption. Please note that only the initial connection to the web site from Frontpage or Dreamweaver is affected: there is no change in the use of these applications after the initial connection, and the web site itself is not affected. Further details, as well as instructions on how to enable encryption, are available at: http://cern.ch/web/docs/AuthDoc/SecureAuthoring. In case of problems, please contact the computer helpdesk or web.support@cern.ch. The Web Services Team

Conceptual Web Users' Actions Prediction for Ontology-Based Browsing Recommendations

Science.gov (United States)

Robal, Tarmo; Kalja, Ahto

The Internet consists of thousands of web sites with different kinds of structures. However, users are browsing the web according to their informational expectations towards the web site searched, having an implicit conceptual model of the domain in their minds. Nevertheless, people tend to repeat themselves and have partially shared conceptual views while surfing the web, finding some areas of web sites more interesting than others. Herein, we take advantage of the latter and provide a model and a study on predicting users' actions based on the web ontology concepts and their relations.

The GridSite Web/Grid security system

International Nuclear Information System (INIS)

McNab, Andrew; Li Yibiao

2010-01-01

We present an overview of the current status of the GridSite toolkit, describing the security model for interactive and programmatic uses introduced in the last year. We discuss our experiences of implementing these internal changes and how they and previous rounds of improvements have been prompted by requirements from users and wider security trends in Grids (such as CSRF). Finally, we explain how these have improved the user experience of GridSite-based websites, and wider implications for portals and similar web/grid sites.

Let the Data Speak for Themselves: Opportunities and Caveats

Directory of Open Access Journals (Sweden)

Koenraad Debackere

2016-03-01

Full Text Available “Let the data speak for themselves” highlights the tremendous opportunities for scientific inquiry that emerge from the digital and data science revolution. It is obvious that the sophistication of novel data and information science methods offers tremendous opportunities for theory testing, theory advancement, and theory development. In order to fully capture those opportunities, it is important to avoid the slippery slope of pure induction.

acn-1, a C. elegans homologue of ACE, genetically interacts with the let-7 microRNA and other heterochronic genes.

Science.gov (United States)

Metheetrairut, Chanatip; Ahuja, Yuri; Slack, Frank J

2017-10-02

The heterochronic pathway in C. elegans controls the relative timing of cell fate decisions during post-embryonic development. It includes a network of microRNAs (miRNAs), such as let-7, and protein-coding genes, such as the stemness factors, LIN-28 and LIN-41. Here we identified the acn-1 gene, a homologue of mammalian angiotensin-converting enzyme (ACE), as a new suppressor of the stem cell developmental defects of let-7 mutants. Since acn-1 null mutants die during early larval development, we used RNAi to characterize the role of acn-1 in C. elegans seam cell development, and determined its interaction with heterochronic factors, including let-7 and its downstream interactors - lin-41, hbl-1, and apl-1. We demonstrate that although RNAi knockdown of acn-1 is insufficient to cause heterochronic defects on its own, loss of acn-1 suppresses the retarded phenotypes of let-7 mutants and enhances the precocious phenotypes of hbl-1, though not lin-41, mutants. Conversely, the pattern of acn-1 expression, which oscillates during larval development, is disrupted by lin-41 mutants but not by hbl-1 mutants. Finally, we show that acn-1(RNAi) enhances the let-7-suppressing phenotypes caused by loss of apl-1, a homologue of the Alzheimer's disease-causing amyloid precursor protein (APP), while significantly disrupting the expression of apl-1 during the L4 larval stage. In conclusion, acn-1 interacts with heterochronic genes and appears to function downstream of let-7 and its target genes, including lin-41 and apl-1.

Trends and preferences of Internet participants: differences between SNS users and non-users

NARCIS (Netherlands)

Lorenzo-Romero, C.; Constantinides, Efthymios; Alarcón-del-Amo, M.

2011-01-01

The staggering growth of online social networking and the potential of Social Networking Sites as marketing channels has become an issue of attention and interest by commercial organizations. This explorative study provides the basis for understanding the nature and behaviour of users of these

Eesti talendid raadiokonkurssidel "New Talent" ja "Let the Peoples Sing" / Karin Kopra

Index Scriptorium Estoniae

Kopra, Karin

2005-01-01

Bratislavas toimunud noorte interpreetide võistlusest "New Talent", kus osales ka pianist Mihkel Poll ning rahvusvahelisest amatöörkooride konkursist "Let the Peoples Sing" Kölnis, kus osalesid Eesti Televisiooni tütarlastekoor ja Tallinna Muusikakeskkooli lastekoor

Enhancing User Customization through Novel Software Architecture for Utility Scale Solar Siting Software

Energy Technology Data Exchange (ETDEWEB)

Brant Peery; Sam Alessi; Randy Lee; Leng Vang; Scott Brown; David Solan; Dan Ames

2014-06-01

There is a need for a spatial decision support application that allows users to create customized metrics for comparing proposed locations of a new solar installation. This document discusses how PVMapper was designed to overcome the customization problem through the development of loosely coupled spatial and decision components in a JavaScript plugin architecture. This allows the user to easily add functionality and data to the system. The paper also explains how PVMapper provides the user with a dynamic and customizable decision tool that enables them to visually modify the formulas that are used in the decision algorithms that convert data to comparable metrics. The technologies that make up the presentation and calculation software stack are outlined. This document also explains the architecture that allows the tool to grow through custom plugins created by the software users. Some discussion is given on the difficulties encountered while designing the system.

Electronic Cigarette Marketing Online: a Multi-Site, Multi-Product Comparison.

Science.gov (United States)

Chu, Kar-Hai; Sidhu, Anupreet K; Valente, Thomas W

2015-01-01

Electronic cigarette awareness and use has been increasing rapidly. E-cigarette brands have utilized social networking sites to promote their products, as the growth of the e-cigarette industry has paralleled that of Web 2.0. These online platforms are cost-effective and have unique technological features and user demographics that can be attractive for selective marketing. The popularity of multiple sites also poses a risk of exposure to social networks where e-cigarette brands might not have a presence. To examine the marketing strategies of leading e-cigarette brands on multiple social networking sites, and to identify how affordances of the digital media are used to their advantage. Secondary analyses include determining if any brands are benefitting from site demographics, and exploring cross-site diffusion of marketing content through multi-site users. We collected data from two e-cigarette brands from four social networking sites over approximately 2.5 years. Content analysis is used to search for themes, population targeting, marketing strategies, and cross-site spread of messages. Twitter appeared to be the most frequently used social networking site for interacting directly with product users. Facebook supported informational broadcasts, such as announcements regarding political legislation. E-cigarette brands also differed in their approaches to their users, from informal conversations to direct product marketing. E-cigarette makers use different strategies to market their product and engage their users. There was no evidence of direct targeting of vulnerable populations, but the affordances of the different sites are exploited to best broadcast context-specific messages. We developed a viable method to study cross-site diffusion, although additional refinement is needed to account for how different types of digital media are used.

Mono-uridylation of pre-microRNA as a key step in the biogenesis of group II let-7 microRNAs.

Science.gov (United States)

Heo, Inha; Ha, Minju; Lim, Jaechul; Yoon, Mi-Jeong; Park, Jong-Eun; Kwon, S Chul; Chang, Hyeshik; Kim, V Narry

2012-10-26

RNase III Drosha initiates microRNA (miRNA) maturation by cleaving a primary miRNA transcript and releasing a pre-miRNA with a 2 nt 3' overhang. Dicer recognizes the 2 nt 3' overhang structure to selectively process pre-miRNAs. Here, we find that, unlike prototypic pre-miRNAs (group I), group II pre-miRNAs acquire a shorter (1 nt) 3' overhang from Drosha processing and therefore require a 3'-end mono-uridylation for Dicer processing. The majority of let-7 and miR-105 belong to group II. We identify TUT7/ZCCHC6, TUT4/ZCCHC11, and TUT2/PAPD4/GLD2 as the terminal uridylyl transferases responsible for pre-miRNA mono-uridylation. The TUTs act specifically on dsRNAs with a 1 nt 3' overhang, thereby creating a 2 nt 3' overhang. Depletion of TUTs reduces let-7 levels and disrupts let-7 function. Although the let-7 suppressor, Lin28, induces inhibitory oligo-uridylation in embryonic stem cells, mono-uridylation occurs in somatic cells lacking Lin28 to promote let-7 biogenesis. Our study reveals functional duality of uridylation and introduces TUT7/4/2 as components of the miRNA biogenesis pathway. Copyright © 2012 Elsevier Inc. All rights reserved.

Learning Hierarchical User Interest Models from Web Pages

Institute of Scientific and Technical Information of China (English)

无

2006-01-01

We propose an algorithm for learning hierarchical user interest models according to the Web pages users have browsed. In this algorithm, the interests of a user are represented into a tree which is called a user interest tree, the content and the structure of which can change simultaneously to adapt to the changes in a user's interests. This expression represents a user's specific and general interests as a continuum. In some sense, specific interests correspond to short-term interests, while general interests correspond to long-term interests. So this representation more really reflects the users' interests. The algorithm can automatically model a user's multiple interest domains, dynamically generate the interest models and prune a user interest tree when the number of the nodes in it exceeds given value. Finally, we show the experiment results in a Chinese Web Site.

FLI-1 Flightless-1 and LET-60 Ras control germ line morphogenesis in C. elegans

Directory of Open Access Journals (Sweden)

Dentler William L

2008-05-01

Full Text Available Abstract Background In the C. elegans germ line, syncytial germ line nuclei are arranged at the cortex of the germ line as they exit mitosis and enter meiosis, forming a nucleus-free core of germ line cytoplasm called the rachis. Molecular mechanisms of rachis formation and germ line organization are not well understood. Results Mutations in the fli-1 gene disrupt rachis organization without affecting meiotic differentiation, a phenotype in C. elegans referred to here as the germ line morphogenesis (Glm phenotype. In fli-1 mutants, chains of meiotic germ nuclei spanned the rachis and were partially enveloped by invaginations of germ line plasma membrane, similar to nuclei at the cortex. Extensions of the somatic sheath cells that surround the germ line protruded deep inside the rachis and were associated with displaced nuclei in fli-1 mutants. fli-1 encodes a molecule with leucine-rich repeats and gelsolin repeats similar to Drosophila flightless 1 and human Fliih, which have been shown to act as cytoplasmic actin regulators as well as nuclear transcriptional regulators. Mutations in let-60 Ras, previously implicated in germ line development, were found to cause the Glm phenotype. Constitutively-active LET-60 partially rescued the fli-1 Glm phenotype, suggesting that LET-60 Ras and FLI-1 might act together to control germ line morphogenesis. Conclusion FLI-1 controls germ line morphogenesis and rachis organization, a process about which little is known at the molecular level. The LET-60 Ras GTPase might act with FLI-1 to control germ line morphogenesis.

Polarisation analysis on the LET time-of-flight spectrometer

Science.gov (United States)

Nilsen, G. J.; Košata, J.; Devonport, M.; Galsworthy, P.; Bewley, R. I.; Voneshen, D. J.; Dalgliesh, R.; Stewart, J. R.

2017-06-01

We present a design for implementing uniaxial polarisation analysis on the LET cold neutron time-of-flight spectrometer, installed on the second target station at ISIS. The polarised neutron beam is to be produced by a transmission-based supermirror polariser with the polarising mirrors arranged in a “double-V” formation. This will be followed by a Mezei-type precession coil spin flipper, selected for its small spatial requirements, as well as a permanent magnet guide field to transport the beam polarisation to the sample position. The sample area will contain a set of holding field coils, whose purpose is to produce a highly homogenous magnetic field for the wide-angle 3He analyser cell. To facilitate fast cell changes and reduce the risk of cell failure, we intend to separate the cell and cryostat from the vacuum of the sample tank by installing both in a vessel at atmospheric pressure. When the instrument upgrade is complete, the performance of LET is expected to be commensurate with existing and planned polarised cold neutron spectrometers at other sources. Finally, we discuss the implications of performing uniaxial polarisation analysis only, and identify quasi-elastic neutron scattering (QENS) on ionic conducting materials as an interesting area to apply the technique.

Who are your users?

DEFF Research Database (Denmark)

Nielsen, Lene; Salminen, joni; Jung, Soon-Gyo

2017-01-01

One of the reasons for using personas is to align user understandings across project teams and sites. As part of a larger persona study, at Al Jazeera English (AJE), we conducted 16 qualitative interviews with media producers, the end users of persona descriptions. We asked the participants about...... their understanding of a typical AJE media consumer, and the variety of answers shows that the understandings are not aligned and are built on a mix of own experiences, own self, assumptions, and data given by the company. The answers are sometimes aligned with the data-driven personas and sometimes not. The end...

Improving ATLAS grid site reliability with functional tests using HammerCloud

Science.gov (United States)

Elmsheuser, Johannes; Legger, Federica; Medrano Llamas, Ramon; Sciacca, Gianfranco; van der Ster, Dan

2012-12-01

With the exponential growth of LHC (Large Hadron Collider) data in 2011, and more coming in 2012, distributed computing has become the established way to analyse collider data. The ATLAS grid infrastructure includes almost 100 sites worldwide, ranging from large national computing centers to smaller university clusters. These facilities are used for data reconstruction and simulation, which are centrally managed by the ATLAS production system, and for distributed user analysis. To ensure the smooth operation of such a complex system, regular tests of all sites are necessary to validate the site capability of successfully executing user and production jobs. We report on the development, optimization and results of an automated functional testing suite using the HammerCloud framework. Functional tests are short lightweight applications covering typical user analysis and production schemes, which are periodically submitted to all ATLAS grid sites. Results from those tests are collected and used to evaluate site performances. Sites that fail or are unable to run the tests are automatically excluded from the PanDA brokerage system, therefore avoiding user or production jobs to be sent to problematic sites.

Acrolein decreases endothelial cell migration and insulin sensitivity through induction of let-7a.

Science.gov (United States)

O'Toole, Timothy E; Abplanalp, Wesley; Li, Xiaohong; Cooper, Nigel; Conklin, Daniel J; Haberzettl, Petra; Bhatnagar, Aruni

2014-08-01

Acrolein is a major reactive component of vehicle exhaust, and cigarette and wood smoke. It is also present in several food substances and is generated endogenously during inflammation and lipid peroxidation. Although previous studies have shown that dietary or inhalation exposure to acrolein results in endothelial activation, platelet activation, and accelerated atherogenesis, the basis for these effects is unknown. Moreover, the effects of acrolein on microRNA (miRNA) have not been studied. Using AGILENT miRNA microarray high-throughput technology, we found that treatment of cultured human umbilical vein endothelial cells with acrolein led to a significant (>1.5-fold) upregulation of 12, and downregulation of 15, miRNAs. Among the miRNAs upregulated were members of the let-7 family and this upregulation was associated with decreased expression of their protein targets, β3 integrin, Cdc34, and K-Ras. Exposure to acrolein attenuated β3 integrin-dependent migration and reduced Akt phosphorylation in response to insulin. These effects of acrolein on endothelial cell migration and insulin signaling were reversed by expression of a let-7a inhibitor. Also, inhalation exposure of mice to acrolein (1 ppm x 6 h/day x 4 days) upregulated let-7a and led to a decrease in insulin-stimulated Akt phosphorylation in the aorta. These results suggest that acrolein exposure has broad effects on endothelial miRNA repertoire and that attenuation of endothelial cell migration and insulin signaling by acrolein is mediated in part by the upregulation of let-7a. This mechanism may be a significant feature of vascular injury caused by inflammation, oxidized lipids, and exposure to environmental pollutants. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Revised user's guide to the 'DISPOSALS' model

International Nuclear Information System (INIS)

Laundy, R.S.; James, A.R.; Groom, M.S.; LeJeune, S.R.

1985-04-01

This report provides a User's Guide to the 'DISPOSALS' computer model and includes instructions on how to set up and run a specific problem together with details of the scope, theoretical basis, data requirements and capabilities of the model. The function of the 'DISPOSALS' model is to make assignments of nuclear waste material in an optimum manner to a number of disposal sites each subject to a number of constraints such as limits on the volume and activity. The user is able to vary the number of disposal sites, the range and limits of the constraints to be applied to each disposal site and the objective function for optimisation. The model is based on the Linear Programming technique and uses CAP Scientific's LAMPS and MAGIC packages. Currently the model has been implemented on CAP Scientific's VAX 11/750 minicomputer. (author)

Potential influence of Web 2.0 usage and security practices of online users on information management

Directory of Open Access Journals (Sweden)

R.J. Rudman

2009-02-01

Full Text Available The proliferation of Web 2.0 applications was the impetus for this survey-based research into practices that online users currently employ when using Web 2.0 sites. As part of the study, the popularity of Web 2.0 technologies and sites among online users at a university was investigated to determine the extent of the potential threat to corporate security, arising from Web 2.0 use and access. The results of this study indicate that the use of Web 2.0 sites is very popular among students, as a proxy for the potential future business users, and that users are not necessarily aware of the risks associated with these sites. The respondents indicated that they regularly visit Web 2.0 sites, and that they post personal information on these sites. This is of concern in protecting arguably the most valuable asset of a business.

Factors for Successful Use of Social Networking Sites in Higher Education

Directory of Open Access Journals (Sweden)

L Schlenkrich

2012-09-01

Full Text Available Social networking sites are extremely popular online destinations that offer users easy ways to build and maintain relationships with each other, and to disseminate information in an activity referred to as social networking. Students, lecturers, teachers, parents and businesses, in increasing numbers, use tools available on social networking sites to communicate with each other in a fast and cost-effective manner. The use of social networking sites to support educational initiatives has received much attention. However, the full potential of social network sites has yet to be achieved as users continue to strive for optimal ways of using these sites, as well as battle to overcome the negative characteristics (for example, privacy, security, governance, user behaviour, information quality of these sites. This paper proposes factors for successful use of social networking sites in higher educational institutions. These success factors need to be adopted by users in order to develop the positive aspects of social networking, while at the same time mitigating the negative characteristics. An initial set of factors for successful use of social networking sites, as well as measures to test successful use of social networking sites were derived from the literature. These factors were tested by means of an online survey of students at a university, the results of which informed the final factors for successful use of social networking sites. The factors enable users to overcome the negative characteristics associated with social networking sites. If used successfully, social networking sites can offer lecturers and students a useful tool with which to develop their relationship and contribute to their learning experience.

P.R. and advertising campaign 'Let us stop smoking together'

International Nuclear Information System (INIS)

Kacena, Michal

1999-01-01

CEZ is the main supplier of electricity in the Czech republic. (72% of production from coal, 22% of people agree to continue; 25% of production from nuclear, 55% of people agree to continue, but, it is much more politically sensitive). In 1998 a huge six-year ecological programme ended. The CEZ Communication targets are: to point the succesful finishing of the ecological program and its good results, to iprove the company image, to change the public opinion on pollution issues. Communication problems are: how to make the technical topic interesting and understandable to the general public, and how to avoid a criticism and contra-productivity of the advertising? The solution proposed are: to give the information a social 'added value'- our power plants are going to stop smoking. We know it is not easy, so that we want to motivate and help you - try it yourself together with us. 'Let us stop smoking together!'; to combine the advertising and P.R. activities. Now CEZ can continue with the communication about its activities and plans on the new level. The inspiration for the communication about nuclear power plants: 'NPPs do not smoke at a. Let us think about it together!'

User Centric Policy Management

Science.gov (United States)

Cheek, Gorrell P.

2013-01-01

Internet use, in general, and online social networking sites, in particular, are experiencing tremendous growth with hundreds of millions of active users. As a result, there is a tremendous amount of privacy information and content online. Protecting this information is a challenge. Access control policy composition is complex, laborious and…

Measurements of LET Spectra of the JINR Phasotron Radiotherapy Proton Beam

Czech Academy of Sciences Publication Activity Database

Kubančák, Ján; Molokanov, A. G.

2013-01-01

Roč. 2013, č. 6 (2013), s. 90-92 ISSN 1562-6016 R&D Projects: GA MŠk LA08002 Institutional support: RVO:61389005 Keywords : LET spectra * proton beam Subject RIV: BO - Biophysics Impact factor: 0.102, year: 2013 http:// vant .kipt.kharkov.ua/ARTICLE/ VANT _2013_6/article_2013_6_90.pdf

Space Communications Artificial Intelligence for Link Evaluation Terminal (SCAILET)

Science.gov (United States)

Shahidi, Anoosh

1991-01-01

A software application to assis end-users of the Link Evaluation Terminal (LET) for satellite communication is being developed. This software application incorporates artificial intelligence (AI) techniques and will be deployed as an interface to LET. The high burst rate (HBR) LET provides 30 GHz transmitting/20 GHz receiving, 220/110 Mbps capability for wideband communications technology experiments with the Advanced Communications Technology Satellite (ACTS). The HBR LET and ACTS are being developed at the NASA Lewis Research Center. The HBR LET can monitor and evaluate the integrity of the HBR communications uplink and downlink to the ACTS satellite. The uplink HBR transmission is performed by bursting the bit-pattern as a modulated signal to the satellite. By comparing the transmitted bit pattern with the received bit pattern, HBR LET can determine the bit error rate BER) under various atmospheric conditions. An algorithm for power augmentation is applied to enhance the system's BER performance at reduced signal strength caused by adverse conditions. Programming scripts, defined by the design engineer, set up the HBR LET terminal by programming subsystem devices through IEEE488 interfaces. However, the scripts are difficult to use, require a steep learning curve, are cryptic, and are hard to maintain. The combination of the learning curve and the complexities involved with editing the script files may discourage end-users from utilizing the full capabilities of the HBR LET system. An intelligent assistant component of SCAILET that addresses critical end-user needs in the programming of the HBR LET system as anticipated by its developers is described. A close look is taken at the various steps involved in writing ECM software for a C&P, computer and at how the intelligent assistant improves the HBR LET system and enhances the end-user's ability to perform the experiments.

Drupal 7 Multilingual Sites

CERN Document Server

Pol, Kristen

2012-01-01

A practical book with plenty of screenshots to guide you through the many features of multilingual Drupal. A demo ecommerce site is provided if you want to practice on a sample site, although you can apply the techniques learnt in the book directly to your site too. Any Drupal users who know the basics of building a Drupal site and are familiar with the Drupal UI, will benefit from this book. No previous knowledge of localization or internationalization is required.

Recommending access control decisions to social media users

OpenAIRE

Misra, Gaurav; Such, Jose M.

2017-01-01

Social media has become an integral part of the Internet and has revolutionized interpersonal communication. The lines of separation between content creators and content consumers have blurred as normal users have platforms such as social media sites, blogs and microblogs at their disposal on which they can create and consume content as well as have the opportunity to interact with other users. This change has also led to several well documented privacy problems for the users. The privacy pro...

Savannah River Site computing architecture

Energy Technology Data Exchange (ETDEWEB)

1991-03-29

A computing architecture is a framework for making decisions about the implementation of computer technology and the supporting infrastructure. Because of the size, diversity, and amount of resources dedicated to computing at the Savannah River Site (SRS), there must be an overall strategic plan that can be followed by the thousands of site personnel who make decisions daily that directly affect the SRS computing environment and impact the site`s production and business systems. This plan must address the following requirements: There must be SRS-wide standards for procurement or development of computing systems (hardware and software). The site computing organizations must develop systems that end users find easy to use. Systems must be put in place to support the primary function of site information workers. The developers of computer systems must be given tools that automate and speed up the development of information systems and applications based on computer technology. This document describes a proposal for a site-wide computing architecture that addresses the above requirements. In summary, this architecture is standards-based data-driven, and workstation-oriented with larger systems being utilized for the delivery of needed information to users in a client-server relationship.

Differential profiles of crack users in respondent-driven and institutional samples: a three-site comparison

OpenAIRE

Oteo Pérez, A.; Benschop, A.; Korf, D.J.

2012-01-01

Background/Aim: Respondent-driven sampling (RDS) is increasingly applied in social epidemiological surveys among ‘hidden populations’ of hard drug users. The objective of the present study was to assess whether the profile of frequent crack users recruited through RDS differed from those surveyed in two random institutional samples, i.e. low-threshold opiate substitution treatment (ST) and user rooms (URs). Methods: A total of 1,039 crack users (mean age 45.1 8 9.1 years; 81.5% males; 49.5% n...

Siting uncertainties and challenges in Appalachia

International Nuclear Information System (INIS)

Vincenti, J.R.

1992-01-01

The purpose of this paper is to discuss the uncertainties and challenges facing users of radioactive isotopes and the generators of low-level radioactive waste (LLRW) in the United States. This paper focuses specially on those user/generators in Delaware, Maryland, Pennsylvania, and West Virginia, which make up the Appalachian States Compact. These uncertainties are based on legal and political actions that have thwarted siting and licensing of LLRW throughout the United States. The challenges facing users of radioactive isotopes are numerous. They stem from the need to reduce or minimize waste volume and to treat or eliminate the generation of waste, especially mixed waste. The basic problem, after the attention to waste management, is that some users are still left with a waste that must be disposed of in a regional or national site for long-term storage and monitoring. This problem will not go away

A new polymorphism biomarker rs629367 associated with increased risk and poor survival of gastric cancer in chinese by up-regulated miRNA-let-7a expression.

Directory of Open Access Journals (Sweden)

Qian Xu

Full Text Available BACKGROUND: Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP associated with the risk and prognosis of gastric cancer (GC as predicting biomarkers, and furthermore, its possible mechanisms. METHODS: A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588 in 107 GC patients, 107 atrophic gastritis (AG, and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls using Sequenom MassARRAY platform and sequencing. RESULTS: We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004. We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043. Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (P<0.001. CONCLUSIONS: pri-let-7a-2 rs629367 CC genotype could increase the risks of gastric cancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer.

Hanford Environmental Information System (HEIS) user's manual

International Nuclear Information System (INIS)

1991-10-01

The Hanford Environmental Information System (HEIS) is a consolidated set of automated resources that effectively manage the data gathered during environmental monitoring and restoration of the Hanford Site. The HEIS includes an integrated database that provides consistent and current data to all users and promotes sharing of data by the entire user community. Data stored in the HEIS are collected under several regulatory programs. Currently these include the Comprehensive Environmental Response, Compensation and Liability Act of 1980 (CERCLA); the Resource Conservation and Recovery Act of 1976 (RCRA); and the Ground-Water Environmental Surveillance Project, managed by the Pacific Northwest Laboratory. The HEIS is an information system with an inclusive database. The manual, the HEIS User's Manual, describes the facilities available to the scientist, engineer, or manager who uses the system for environmental monitoring, assessment, and restoration planning; and to the regulator who is responsible for reviewing Hanford Site operations against regulatory requirements and guidelines

Usability Testing in a Library Web Site Redesign Project.

Science.gov (United States)

McMullen, Susan

2001-01-01

Discusses the need for an intuitive library information gateway to meet users' information needs and describes the process involved in redesigning a library Web site based on experiences at Roger Williams University. Explains usability testing methods that were used to discover how users were interacting with the Web site interface. (Author/LRW)

A New Polymorphism Biomarker rs629367 Associated with Increased Risk and Poor Survival of Gastric Cancer in Chinese by Up-Regulated miRNA-let-7a Expression

Science.gov (United States)

Xu, Qian; Dong, Qiguan; He, Caiyun; Liu, Wenjing; Sun, Liping; Liu, Jingwei; Xing, Chengzhong; Li, Xiaohang; Wang, Bengang; Yuan, Yuan

2014-01-01

Background Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP) associated with the risk and prognosis of gastric cancer (GC) as predicting biomarkers, and furthermore, its possible mechanisms. Methods A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588) in 107 GC patients, 107 atrophic gastritis (AG), and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls) using Sequenom MassARRAY platform and sequencing. Results We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004). We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043). Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (Pcancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer. PMID:24760009

Radiosensitization by inhibiting survivin in human hepatoma HepG2 cells to high-LET radiation

International Nuclear Information System (INIS)

Jin Xiaodong; Li Qiang; Wu Qingfeng; Li Ping; Gong Li; Hao Jifang; Dai Zhongying; Matsumoto, Yoshitaka; Furusawa, Yoshiya

2011-01-01

In this study, whether survivin plays a direct role in mediating high-linear energy transfer (LET) radiation resistance in human hepatoma cells was investigated. Small interfering RNA (siRNA) targeting survivin mRNA was designed and transfected into human hepatoma HepG2 cells. Real-time polymerase chain reaction (PCR) and western blotting analyses revealed that survivin expression in HepG2 cells decreased at both transcriptional and post-transcriptional levels after treatment with survivin-specific siRNA. Caspase-3 activity was determined with a microplate reader assay as well. Following exposure to high-LET carbon ions, a reduced clonogenic survival effect, increased apoptotic rates and caspase-3 activity were observed in the cells treated with the siRNA compared to those untreated with the siRNA. The cells with transfection of the survivin-specific siRNA also increased the level of G 2 /M arrest. These results suggest that survivin definitely plays a role in mediating the resistance of HepG2 cells to high-LET radiation and depressing survivin expression might be useful to improve the therapeutic efficacy of heavy ions for radioresistant solid tumors. (author)

Universal Access in Heritage Sites: A Case Study on Historic Sites in Jaipur, India.

Science.gov (United States)

Vardia, Shweta; Khare, Rachna; Khare, Ajay

2016-01-01

A nation is recognized by a range of its significant historical, cultural and natural properties. These properties are generally preserved and maintained either by national administration or by private owners and charitable trusts due to higher value of their cultural inheritance and termed globally as heritage or historic sites. Heritage sites are a significant asset, a unique and irreplaceable resource which reflects a rich and diverse expression of past societies and forms an integral part of local, regional and national cultural identity. Today, heritage sites also play an important role in communication and knowledge exchange. Thus the rapidly increasing heritage tourism industry faces several challenges too. One of the challenges is that there is a segment of society who is not yet able to equally enjoy the visit to historic structures/sites and attractions, facilities and services. This paper aims to study the experience and develop understanding regarding the heritage structures/sites approached and interacted by diverse users. This study is an outcome of a hands on workshop conducted with diverse users at various historic sites in the city of Jaipur viz. at The City Palace Complex, Jaipur, Jaigarh Fort and the Haveli at Kanota near to Jaipur India.

Users education in the virtual public library. Resources and procedures in the Spanish public libraries

Directory of Open Access Journals (Sweden)

Francisco Javier García Gómez

2004-01-01

Full Text Available Some Spanish public libraries have sites Web in a new digital work environment. These libraries are already delivered some services in their virtual branches. We are interesting to analyze user education in their sites Web. We are reviewed and tested some digital resources and services for user education in public libraries at World Wide Web. Level developing obtained in this library work is shown in conclusions. Likewise, we contributed some references about public library web sites design focused in user education and library instruction

Synchronizing Education to Adolescent Biology: "Let Teens Sleep, Start School Later"

Science.gov (United States)

Kelley, Paul; Lockley, Steven W.; Foster, Russell G.; Kelley, Jonathan

2015-01-01

Arne Duncan, US Secretary of State for Education, tweeted in 2013: "let teens sleep, start school later". This paper examines early starts and their negative consequences in the light of key research in the last 30 years in sleep medicine and circadian neuroscience. An overview of the circadian timing system in adolescence leading to…

Tri-P-LETS: Changing the Face of High School Computer Science

Science.gov (United States)

Sherrell, Linda; Malasri, Kriangsiri; Mills, David; Thomas, Allen; Greer, James

2012-01-01

From 2004-2007, the University of Memphis carried out the NSF-funded Tri-P-LETS (Three P Learning Environment for Teachers and Students) project to improve local high-school computer science curricula. The project reached a total of 58 classrooms in eleven high schools emphasizing problem solving skills, programming concepts as opposed to syntax,…

Let's Burn Them All: A Librarian's View

Science.gov (United States)

Werner, Roye

2014-01-01

In this rejoinder to "Let's Burn Them All," a librarian supports the author's case for eliminating textbooks in the teaching of management and organizational behavior. A move away from textbooks would free libraries from worrying about whether and to what extent to provide expensive textbook access to students, a long-standing…

Light-effect transistor (LET with multiple independent gating controls for optical logic gates and optical amplification

Directory of Open Access Journals (Sweden)

Jason eMarmon

2016-03-01

Full Text Available Modern electronics are developing electronic-optical integrated circuits, while their electronic backbone, e.g. field-effect transistors (FETs, remains the same. However, further FET down scaling is facing physical and technical challenges. A light-effect transistor (LET offers electronic-optical hybridization at the component level, which can continue Moore’s law to quantum region without requiring a FET’s fabrication complexity, e.g. physical gate and doping, by employing optical gating and photoconductivity. Multiple independent gates are therefore readily realized to achieve unique functionalities without increasing chip space. Here we report LET device characteristics and novel digital and analog applications, such as optical logic gates and optical amplification. Prototype CdSe-nanowire-based LETs show output and transfer characteristics resembling advanced FETs, e.g. on/off ratios up to ~1.0x106 with a source-drain voltage of ~1.43 V, gate-power of ~260 nW, and subthreshold swing of ~0.3 nW/decade (excluding losses. Our work offers new electronic-optical integration strategies and electronic and optical computing approaches.

Comparison of CREME (cosmic-ray effects on microelectronics) model LET (linear energy transfer) spaceflight dosimetry data

Energy Technology Data Exchange (ETDEWEB)

Letaw, J.R.; Adams, J.H.

1986-07-15

The galactic cosmic radiation (GCR) component of space radiation is the dominant cause of single-event phenomena in microelectronic circuits when Earth's magnetic shielding is low. Spaceflights outside the magnetosphere and in high inclination orbits are examples of such circumstances. In high-inclination orbits, low-energy (high LET) particles are transmitted through the field only at extreme latitudes, but can dominate the orbit-averaged dose. GCR is an important part of the radiation dose to astronauts under the same conditions. As a test of the CREME environmental model and particle transport codes used to estimate single event upsets, we have compiled existing measurements of HZE doses were compiled where GCR is expected to be important: Apollo 16 and 17, Skylab, Apollo Soyuz Test Project, and Kosmos 782. The LET spectra, due to direct ionization from GCR, for each of these missions has been estimated. The resulting comparisons with data validate the CREME model predictions of high-LET galactic cosmic-ray fluxes to within a factor of two. Some systematic differences between the model and data are identified.

Personhood: Fukuyama’s Caveats and Ishiguro’s Never Let Me Go

Directory of Open Access Journals (Sweden)

Kristine Brown

2015-07-01

Full Text Available Together, fiction and rhetoric not only illustrate grim possibilities, but also the processes and rationale by which they occur. Kazuo Ishiguro’s dystopian novel Never Let Me Go (2005 documents the lives of cloned children in twentieth century England whose sole purpose is to provide organs to keep their human predecessors alive. While the children mature to become donors or caregivers to peers undergoing donation, nothing exempts them from death following repeated organ harvesting. However unnerving, the novel tells of potential realities associated with genetic engineering, a trend bioconservative political scientist Francis Fukuyama addresses in his work Our Post Human Future. This article endeavors to present Never Let Me Go as a fictional, yet appropriate supplement to Fukuyama’s writing, incorporating new historicism and accentuating Fukuyama’s points of caution in Ishiguro’s novel. Through dissecting and discerning the complementary relationship of the two works, readers may garner enriched perspectives in debates on cloning and other forms of bioengineering.   Keywords: genetic engineering; cloning; eugenics; ethics; dystopia; speculation

Liquid ionization chambers for LET determination

DEFF Research Database (Denmark)

Kaiser, Franz-Joachim; Bassler, Niels; Tölli, Heikki

Liquid ionization chambers [1] (LICs) have have been used in the last decades as background dosemeters. Since a few years LICs are also commercially available for dosimetry and are used for measurements of dose distributions where a high spatial distribution is necessary. Also in the last decades...... a differential equation applying several simplifications and approximations leading to discrepancies between theory and experiments [3]. The theory predicts the collection efficiency as a function of the electrical field and was applied for both air filled ionization chambers and liquid filled ionization...... chambers. For liquids the LET can be roughly deduced from the collection efficiency dependency on the electrical field inside a liquid ionization chambers [4] using an extrapolation method. We solved the fundamental differential equation again presented by Jaffe numerically, but now taking into account...

Exploring users motivation in innovation communities

OpenAIRE

Ståhlbröst, Anna; Bergvall-Kåreborn, Birgitta

2011-01-01

A rapid growth of technologies supporting user interaction on the Internet, such as social networking sites and other virtual communities, can be seen today. These virtual communities have been shown to be of great value to companies that want to involve users in their innovation processes. However, in order to guide organisations on how to utilise their innovation intermediary communities, more knowledge is needed regarding who they are and their motivational drivers for participating in a c...

The Role of Cultural and Identity Differences in Self-expression of Iranian Users of Social Networking Sites; A Case Study of Students of Tehran University, Amirkabir University, and Sharif University of Technology

Directory of Open Access Journals (Sweden)

H. Molaei

2017-12-01

Full Text Available Social media with their features such as interactivity, participatory, and user-generated content have provided a great opportunity for self-expression of the users. However, cultural differences affect the extent and modality of users’ self-expression. This study aims to investigate the modality of self-expression of Iranian users of the social networking sites. In doing so, an online survey was conducted among the students of three Iran universities: University of Tehran, Amirkabir University of Technology, and Sharif University of Technology. A total of 371 students participated in the study. Having conducted quantitative analysis, the study results showed that women and ethnic minorities are more inclined to support their cultural differences compared to men and ethnic majority group. Supporting cultural differences was observed more among Shia religious majority group. Religious minorities expressed less tendency to create content in social networking sites and as a result support their religious identity.

Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM.

Directory of Open Access Journals (Sweden)

Dejuan Kong

Full Text Available The emergence of castrate-resistant prostate cancer (CRPC contributes to the high mortality of patients diagnosed with prostate cancer (PCa, which in part could be attributed to the existence and the emergence of cancer stem cells (CSCs. Recent studies have shown that deregulated expression of microRNAs (miRNAs contributes to the initiation and progression of PCa. Among several known miRNAs, let-7 family appears to play a key role in the recurrence and progression of PCa by regulating CSCs; however, the mechanism by which let-7 family contributes to PCa aggressiveness is unclear. Enhancer of Zeste homolog 2 (EZH2, a putative target of let-7 family, was demonstrated to control stem cell function. In this study, we found loss of let-7 family with corresponding over-expression of EZH2 in human PCa tissue specimens, especially in higher Gleason grade tumors. Overexpression of let-7 by transfection of let-7 precursors decreased EZH2 expression and repressed clonogenic ability and sphere-forming capacity of PCa cells, which was consistent with inhibition of EZH2 3'UTR luciferase activity. We also found that the treatment of PCa cells with BR-DIM (formulated DIM: 3,3'-diindolylmethane by Bio Response, Boulder, CO, abbreviated as BR-DIM up-regulated let-7 and down-regulated EZH2 expression, consistent with inhibition of self-renewal and clonogenic capacity. Moreover, BR-DIM intervention in our on-going phase II clinical trial in patients prior to radical prostatectomy showed upregulation of let-7 consistent with down-regulation of EZH2 expression in PCa tissue specimens after BR-DIM intervention. These results suggest that the loss of let-7 mediated increased expression of EZH2 contributes to PCa aggressiveness, which could be attenuated by BR-DIM treatment, and thus BR-DIM is likely to have clinical impact.

Industrial gamma radiography on a building site with a portable device. Recommendations to operators - gammagraphy sheet ED 4243; Recommendations to intervening companies (subcontractors) -gammagraphy sheet ED 4244; Recommendations to user companies - gammagraphy sheet ED 4245

International Nuclear Information System (INIS)

Vaisseau, Bernard; Bourdon, Patrick; Laurent, Pierre; Servent, Jean-Pierre; Biau, Alain

2006-12-01

Based on best practices, three sheets indicate sets of recommendations regarding the use of an industrial gamma radiography portable device on a building site either by operators, intervening companies (or subcontractors), or user companies. As far as operators are concerned, recommendations concern preparation and transport, arrival on the building site, examination performance, end of examination, occurrence of an incident other than radiological, and occurrence of a radiological incident. As far as subcontractors are concerned, recommendations concern the actors of the intervening company, the permanent storage site of portable devices, the film development laboratory, portable devices and their accessories, other equipment used for examination, vehicles, operators, intervention preparation, the return on experience, and the immediate processing of anomalies. As far as user companies are concerned, recommendations concern actors of the user company, the definition of the operation, the previous inspection of premises and the definition of a prevention plan, the storage of equipment containing depleted uranium, loading and unloading operations, the coordination of exposure doses, the immediate processing of anomalies, and the return on experience. Moreover, the three sheets indicate the associated legal texts

A direct comparison of the biological effects of protons and α-particles having the same LET

International Nuclear Information System (INIS)

Mill, A.J.; Hall, S.C.; Allen, L.A.; Goodhead, D.T.

1991-01-01

The authors suggest that the findings of Belli et al. (1989) are not universal. A higher effectiveness for protons compared with α-particles appears to be either small or absent in the systems reported in this paper (C 3 H 10T1/2 mouse cells and HeLa human cells). However, the possible existence of such an effect places cons-traints on understanding of the mechanisms of radiation action. On a practical level these small differences in effectiveness are not significant for radiological protection issues and LET remains a suitable parameter for the determination of the risk from high-LET radiations. (UK)

DEPENDENCE ON SOCIAL NETWORKING SITES IN ADOLESCENTS

OpenAIRE

Ranjith; Santosh; Amita Rao; Ramgopal; Ashvij

2016-01-01

BACKGROUND Social Networking Sites (SNSs) are “web-based services” that allow individuals to: (1) Construct a public or semi-public profile within a bounded system, (2) Articulate a list of other users with whom they share a connection, and (3) View and traverse their list of connections and those made by others within the system.” Social networking sites like Facebook, WhatsApp, Snapchat, Twitter, etc. are virtual communities where users can create individual public profiles,...

Dosimetry and LET spectrometry in C 290 MeV/n and Ne 400 MeV/n HIMAC ion beam by different TLD's, TED based LET spectrometers, and Si energy-deposition spectrometer

International Nuclear Information System (INIS)

Spurny, F.; Brabcova, K.; Jadrnickova, I.; Uchihori, Y.; Kitamura, H.; Yasuda, N.; Molokanov, A. G.

2009-01-01

The sets of track etched detectors based (TED) spectrometer's of the linear energy transfer (LET) have been, together with two types of thermoluminescent detectors (TLD)and MDU- Liulin energy deposition spectrometer exposed in the C 290 MeV/n and Ne 400 MeV/n ion beams at the HlMAC installation at NIRS, Chiba, Japan. The experiment has been performed in the frame of NPI project 20P241 agreed by HlMAC P AC at the beginning of 2008 year. Up to now, moxstle only results obtained in C-ion beam have been treated and analyzed. Sets of TED spectrometer's and TLD detectors have been exposed in 19 depths in the C-ion beam with expected LET values of primary particles from 13 keV/μm in water, through the Bragg peak area up to two depth behind the Bragg peak. The contribution of fragments to total number of events, and to the energy absorbed in Si has been determined, when possible separately for different fragments. In all cases also total contribution of fragments (and other secondary particles) to the total number of energy deposition events and to the absorbed dose has been estimated. LET and energy deposition spectra obtained will be compared together , a good agreement of data has bee stated. Some of results have been also compared with those obtained by calculation by means of PHITS code. (authors)

Users Manual for the FEHMN application

International Nuclear Information System (INIS)

Zyvoloski, G.A.; Robinson, B.A.; Dash, Z.V.; Trease, L.L.

1996-01-01

The user's manual documents the use of the Yucca Mountain Site Characterization Projects Finite element heat and mass transfer code (FEHMN) application. The manual covers: Program considerations, data files, input data, output, system interface, and examples

THE LET ME LEARN PROFESSIONAL LEARNING PROCESS FOR TEACHER TRANSFORMATION

OpenAIRE

Calleja, Colin

2013-01-01

This research set out to explore how a group of nine educators from a Catholic Church school in Malta, who have attended the Let Me Learn professional Learning process (LMLpLp), experienced personal and professional transformation. This study investigates those factors influencing participants in their transformative learning journey. It also explores the dynamics of transformative learning and whether individual transformation affects the school’s transformative learning experience. More spe...

Savannah River Site computing architecture

Energy Technology Data Exchange (ETDEWEB)

1991-03-29

A computing architecture is a framework for making decisions about the implementation of computer technology and the supporting infrastructure. Because of the size, diversity, and amount of resources dedicated to computing at the Savannah River Site (SRS), there must be an overall strategic plan that can be followed by the thousands of site personnel who make decisions daily that directly affect the SRS computing environment and impact the site's production and business systems. This plan must address the following requirements: There must be SRS-wide standards for procurement or development of computing systems (hardware and software). The site computing organizations must develop systems that end users find easy to use. Systems must be put in place to support the primary function of site information workers. The developers of computer systems must be given tools that automate and speed up the development of information systems and applications based on computer technology. This document describes a proposal for a site-wide computing architecture that addresses the above requirements. In summary, this architecture is standards-based data-driven, and workstation-oriented with larger systems being utilized for the delivery of needed information to users in a client-server relationship.

Proposal for a Similar Question Search System on a Q&A Site

Directory of Open Access Journals (Sweden)

Katsutoshi Kanamori

2014-06-01

Full Text Available There is a service to help Internet users obtain answers to specific questions when they visit a Q&A site. A Q&A site is very useful for the Internet user, but posted questions are often not answered immediately. This delay in answering occurs because in most cases another site user is answering the question manually. In this study, we propose a system that can present a question that is similar to a question posted by a user. An advantage of this system is that a user can refer to an answer to a similar question. This research measures the similarity of a candidate question based on word and dependency parsing. In an experiment, we examined the effectiveness of the proposed system for questions actually posted on the Q&A site. The result indicates that the system can show the questioner the answer to a similar question. However, the system still has a number of aspects that should be improved.

What value do users derive from social networking applications?

OpenAIRE

Neale, Larry; Russell-Bennett, Rebekah

2009-01-01

Why do users of social networking sites recommend some applications to their friends while rejecting others? What value do they obtain from applications? This exploratory study investigates the value users derive from ‘cool’ Facebook applications, and explores the features that either encourage or discourage users to recommend applications to their friends. Our qualitative data reveal consumers derive a combination of functional value along with either social or emotional value from the app...

Differential effects of p53 on bystander phenotypes induced by gamma ray and high LET heavy ion radiation

Science.gov (United States)

He, Mingyuan; Dong, Chen; Konishi, Teruaki; Tu, Wenzhi; Liu, Weili; Shiomi, Naoko; Kobayashi, Alisa; Uchihori, Yukio; Furusawa, Yoshiya; Hei, Tom K.; Dang, Bingrong; Shao, Chunlin

2014-04-01

High LET particle irradiation has several potential advantages over γ-rays such as p53-independent response. The purpose of this work is to disclose the effect of p53 on the bystander effect induced by different LET irradiations and underlying mechanism. Lymphocyte cells of TK6 (wild type p53) and HMy2.CIR (mutated p53) were exposed to either low or high LET irradiation, then their mitochondrial dysfunction and ROS generation were detected. The micronuclei (MN) induction in HL-7702 hepatocytes co-cultured with irradiated lymphocytes was also measured. It was found that the mitochondrial dysfunction, p66Shc activation, and intracellular ROS were enhanced in TK6 but not in HMy2.CIR cells after γ-ray irradiation, but all of them were increased in both cell lines after carbon and iron irradiation. Consistently, the bystander effect of MN formation in HL-7702 cells was only triggered by γ-irradiated TK6 cells but not by γ-irradiated HMy2.CIR cells. But this bystander effect was induced by both lymphocyte cell lines after heavy ion irradiation. PFT-μ, an inhibitor of p53, only partly inhibited ROS generation and bystander effect induced by 30 keV/μm carbon-irradiated TK6 cells but failed to suppress the bystander effect induced by the TK6 cells irradiated with either 70 keV/μm carbon or 180 keV/μm iron. The mitochondrial inhibitors of rotenone and oligomycin eliminated heavy ion induced ROS generation in TK6 and HMy2.CIR cells and hence diminished the bystander effect on HL-7702 cells. These results clearly demonstrate that the bystander effect is p53-dependent for low LET irradiation, but it is p53-independent for high LET irradiation which may be because of p53-independent ROS generation due to mitochondrial dysfunction.

miR-Let7A Controls the Cell Death and Tight Junction Density of Brain Endothelial Cells under High Glucose Condition.

Science.gov (United States)

Song, Juhyun; Yoon, So Ra; Kim, Oh Yoen

2017-01-01

Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor- α ), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases.

Detection of micro RNA hsa-let-7e in peripheral blood mononuclear cells infected with dengue virus serotype-2: preliminary study

Science.gov (United States)

Masyeni, S.; Hadi, U.; Kuntaman; Yohan, B.; Margyaningsih, N. I.; Sasmono, R. T.

2018-03-01

Pathogenesis of dengue infection is still obscure. Recently, the role of microRNA has been associated with the cytokine storm which leads to plasma leakage in endothelial cells. The objective of our study was to determine whether particular microRNA is overexpressed in PBMCs infected with DENV and to assess its correlation to the expression of suppressor of cytokine signaling 3 (SOCS3) proteins to increase the production of pro-inflammatory cytokines. We report the result of a preliminary study on the expression of microRNA hsa-let-7e. The peripheral blood mononuclear cells (PBMCs) from the healthy volunteer were infected with the clinical isolate of DENV-2. RNA was extracted with miRCURYLNATMExiqon. Quantitative Real-Time PCR was used to measure the relative expression of hsa-let-7e micro RNA and the mRNA of SOCS3 proteins. MicroRNA hsa-let-7e expression was increased in PBMCs upon DENV-2 infection. The relative expression of hsa-let-7e is detected at 1.46 folds relative to uninfected PBMCs in 4 hours post-infection and decreased in 19 hours post infection. In contrast, the expression of mRNA of SOCS3 was inversely expressed with hsa-let-7 expression. MicroRNA was overexpressed in PBMCs upon infection with DENV-2. This microRNA may bind the SOCS3 and contribute to the pathogenesis of dengue infection.

Exploration of 'over kill effect' of high-LET Ar- and Fe-ions by evaluating the fraction of non-hit cell and interphase death

International Nuclear Information System (INIS)

Mehnati, P.; Sasaki, Hiroshi; Morimoto, Shigeko; Yatagai, Fumio; Hanaoka, Fumio; Furusawa, Yoshiya; Kanai, Tatsuaki; Kobayashi, Yasuhiko; Wada, Seiichi

2005-01-01

The reason why relative biological effectiveness (RBE) for cell killing fell to less than unity (1.0) with very high-linear energy transfer (LET) heavy-ions ( 40 Ar: 1,640 keV/μm; 56 Fe: 780, 1,200, 2,000 keV/μm) was explored by evaluating the fraction of non-hit cell (time-lapse observation) and cells undergoing interphase death (calculation based on our previous data). Chinese hamster ovary (CHO) cells were exposed to 4 Gy (30% survival dose) of Ar (1,640 keV/μm) or Fe-ions (2,000 keV/μm). About 20% of all cells were judged to be non-hit, and about 10% cells survived radiation damage. About 70% cells died after dividing at least once (reproductive death) or without dividing (interphase death). RBE for reproductive (RBE[R]) and interphase (RBE[I]) death showed a similar LET dependence with maximum around 200 keV/μm. In this LET region, at 30% survival level, about 10% non-survivors underwent interphase death. The corresponding value for very high-LET Fe-ions (2,000 keV/μm) was not particularly high (-15%), whereas that for X-rays was less than 3%. However, reproductive death (67%) predominated over interphase death (33%) even in regard to rather severely damaged cells (1% survival level) after exposure to Fe-ions (2,000 keV/μm). These indicate that interphase death is a type of cell death characteristic for the cells exposed to high-LET radiation and is not caused by 'cellular over kill effect'. Both NHF37 (non-hit fraction at 37% survival) and inactivation cross-section for reproductive death (σ[R]) began to increase when LET exceeded 100 keV/μm. The exclusion of non-hit fraction in the calculation of surviving fraction partially prevented the fall of RBE[R] when LET exceeded 200 keV/μm. On the other hand, the mean number of lethal damage per unit dose (NLD/Gy) showed the same LET-dependent pattern as RBE[R]. These suggest that the increase in non-hit fraction and σ[R] with an increasing LET is caused by enhanced clustering of ionization and DNA damage

Neutron dose equivalent next to the target shield of a neutron therapy facility using an LET counter

International Nuclear Information System (INIS)

Stinchcomb, T.G.; Kuchnir, F.T.

1981-01-01

The use of a spherical tissue-equivalent proportional counter for measurements of the lineal energy (y) and derivations of the linear energy transfer (LET) for fast neutrons has the advantage of giving distributions of dose and dose equivalent as functions of either LET or y. A measurement next to the target shielding of the neutron therapy facility at the University of Chicago Hospitals and Clinics (UCHC) is described, and the data processing is outlined. The distributions are presented and compared to those from measurements in the neutron beam. The average quality factors are presented

Comparing Facebook Users and Facebook Non-Users: Relationship between Personality Traits and Mental Health Variables - An Exploratory Study.

Science.gov (United States)

Brailovskaia, Julia; Margraf, Jürgen

2016-01-01

Over one billion people use Facebook as a platform for social interaction and self-presentation making it one of the most popular online sites. The aim of the present study was to investigate differences in various personality traits and mental health variables between Facebook users and people who do not use this platform. The data of 945 participants (790 Facebook users, 155 Facebook non-users) were collected. Results indicate that Facebook users score significantly higher on narcissism, self-esteem and extraversion than Facebook non-users. Furthermore, they have significantly higher values of social support, life satisfaction and subjective happiness. Facebook non-users have (marginally) significantly higher values of depression symptoms than Facebook users. In both groups, extraversion, self-esteem, happiness, life satisfaction, resilience and social support, on the one hand, and depression, anxiety and stress symptoms, on the other hand, are negatively correlated. Neuroticism is positively associated with depression, anxiety and stress symptoms. However, significant differences exist between Facebook users and Facebook non-users regarding some associations of personality traits and mental health variables. Compared to Facebook non-users, the present results indicate that Facebook users have higher values of certain personality traits and positive variables protecting mental health. These findings are of particular interest considering the high importance of social online-platforms in the daily life of many people.

Comparing Facebook Users and Facebook Non-Users: Relationship between Personality Traits and Mental Health Variables - An Exploratory Study.

Directory of Open Access Journals (Sweden)

Julia Brailovskaia

Full Text Available Over one billion people use Facebook as a platform for social interaction and self-presentation making it one of the most popular online sites. The aim of the present study was to investigate differences in various personality traits and mental health variables between Facebook users and people who do not use this platform. The data of 945 participants (790 Facebook users, 155 Facebook non-users were collected. Results indicate that Facebook users score significantly higher on narcissism, self-esteem and extraversion than Facebook non-users. Furthermore, they have significantly higher values of social support, life satisfaction and subjective happiness. Facebook non-users have (marginally significantly higher values of depression symptoms than Facebook users. In both groups, extraversion, self-esteem, happiness, life satisfaction, resilience and social support, on the one hand, and depression, anxiety and stress symptoms, on the other hand, are negatively correlated. Neuroticism is positively associated with depression, anxiety and stress symptoms. However, significant differences exist between Facebook users and Facebook non-users regarding some associations of personality traits and mental health variables. Compared to Facebook non-users, the present results indicate that Facebook users have higher values of certain personality traits and positive variables protecting mental health. These findings are of particular interest considering the high importance of social online-platforms in the daily life of many people.

Reading level of privacy policies on Internet health Web sites.

Science.gov (United States)

Graber, Mark A; D'Alessandro, Donna M; Johnson-West, Jill

2002-07-01

Most individuals would like to maintain the privacy of their medical information on the World Wide Web (WWW). In response, commercial interests and other sites post privacy policies that are designed to inform users of how their information will be used. However, it is not known if these statements are comprehensible to most WWW users. The purpose of this study was to determine the reading level of privacy statements on Internet health Web sites and to determine whether these statements can inform users of their rights. This was a descriptive study. Eighty Internet health sites were examined and the readability of their privacy policies was determined. The selected sample included the top 25 Internet health sites as well as other sites that a user might encounter while researching a common problem such as high blood pressure. Sixty percent of the sites were commercial (.com), 17.5% were organizations (.org), 8.8% were from the United Kingdom (.uk), 3.8% were United States governmental (.gov), and 2.5% were educational (.edu). The readability level of the privacy policies was calculated using the Flesch, the Fry, and the SMOG readability levels. Of the 80 Internet health Web sites studied, 30% (including 23% of the commercial Web sites) had no privacy policy posted. The average readability level of the remaining sites required 2 years of college level education to comprehend, and no Web site had a privacy policy that was comprehensible by most English-speaking individuals in the United States. The privacy policies of health Web sites are not easily understood by most individuals in the United States and do not serve to inform users of their rights. Possible remedies include rewriting policies to make them comprehensible and protecting online health information by using legal statutes or standardized insignias indicating compliance with a set of privacy standards (eg, "Health on the Net" [HON] http://www.hon.ch).

User's Manual for the New England Water-Use Data System (NEWUDS)

Science.gov (United States)

Horn, Marilee A.

2003-01-01

Water is used in a variety of ways that need to be understood for effective management of water resources. Water-use activities need to be categorized and included in a database management system to understand current water uses and to provide information to water-resource management policy decisionmakers. The New England Water-Use Data System (NEWUDS) is a complex database developed to store water-use information that allows water to be tracked from a point of water-use activity (called a 'Site'), such as withdrawal from a resource (reservoir or aquifer), to a second Site, such as distribution to a user (business or irrigator). NEWUDS conceptual model consists of 10 core entities: system, owner, address, location, site, data source, resource, conveyance, transaction/rate, and alias, with tables available to store user-defined details. Three components--site (with both a From Site and a To Site), a conveyance that connects them, and a transaction/rate associated with the movement of water over a specific time interval form the core of the basic NEWUDS network model. The most important step in correctly translating real-world water-use activities into a storable format in NEWUDS depends on choosing the appropriate sites and linking them correctly in a network to model the flow of water from the initial From Site to the final To Site. Ten water-use networks representing real-world activities are described--three withdrawal networks, three return networks, two user networks, two complex community-system networks. Ten case studies of water use, one for each network, also are included in this manual to illustrate how to compile, store, and retrieve the appropriate data. The sequence of data entry into tables is critical because there are many foreign keys. The recommended core entity sequence is (1) system, (2) owner, (3) address, (4) location, (5) site, (6) data source, (7) resource, (8) conveyance, (9) transaction, and (10) rate; with (11) alias and (12) user

The conceptualization and empirical validation of website user satisfaction

NARCIS (Netherlands)

Moenaert, R.K.; Muylle, S.; Despontin, M.

2004-01-01

This article addresses the concern for effective web site design by means of the conceptualization and empirical validation of a web site user satisfaction construct. Based on IS success theory, hypermedia design theory, a qualitative exploratory pilot study, and a quantitative online critical

Molecular nature of mutations induced by high-LET irradiation with argon and carbon ions in Arabidopsis thaliana

International Nuclear Information System (INIS)

Hirano, Tomonari; Kazama, Yusuke; Ohbu, Sumie; Shirakawa, Yuki; Liu Yang; Kambara, Tadashi; Fukunishi, Nobuhisa; Abe, Tomoko

2012-01-01

Linear energy transfer (LET) is an important parameter to be considered in heavy-ion mutagenesis. However, in plants, no quantitative data are available on the molecular nature of the mutations induced with high-LET radiation above 101–124 keV μm −1 . In this study, we irradiated dry seeds of Arabidopsis thaliana with Ar and C ions with an LET of 290 keV μm −1 . We analyzed the DNA alterations caused by the higher-LET radiation. Mutants were identified from the M 2 pools. In total, 14 and 13 mutated genes, including bin2, egy1, gl1, gl2, hy1, hy3–5, ttg1, and var2, were identified in the plants derived from Ar- and C-ions irradiation, respectively. In the mutants from both irradiations, deletion was the most frequent type of mutation; 13 of the 14 mutated genes from the Ar ion-irradiated plants and 11 of the 13 mutated genes from the C ion-irradiated plants harbored deletions. Analysis of junction regions generated by the 2 types of irradiation suggested that alternative non-homologous end-joining was the predominant pathway of repair of break points. Among the deletions, the proportion of large deletions (>100 bp) was about 54% for Ar-ion irradiation and about 64% for C-ion irradiation. Both current results and previously reported data revealed that the proportions of the large deletions induced by 290-keV μm −1 radiations were higher than those of the large deletions induced by lower-LET radiations (6% for 22.5–30.0 keV μm −1 and 27% for 101–124 keV μm −1 ). Therefore, the 290 keV μm −1 heavy-ion beams can effectively induce large deletions and will prove useful as novel mutagens for plant breeding and analysis of gene functions, particularly tandemly arrayed genes.

Molecular nature of mutations induced by high-LET irradiation with argon and carbon ions in Arabidopsis thaliana

Energy Technology Data Exchange (ETDEWEB)

Hirano, Tomonari; Kazama, Yusuke [Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Innovation Center, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Ohbu, Sumie; Shirakawa, Yuki; Liu Yang; Kambara, Tadashi; Fukunishi, Nobuhisa [Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Abe, Tomoko, E-mail: tomoabe@riken.jp [Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Innovation Center, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

2012-07-01

Linear energy transfer (LET) is an important parameter to be considered in heavy-ion mutagenesis. However, in plants, no quantitative data are available on the molecular nature of the mutations induced with high-LET radiation above 101-124 keV {mu}m{sup -1}. In this study, we irradiated dry seeds of Arabidopsis thaliana with Ar and C ions with an LET of 290 keV {mu}m{sup -1}. We analyzed the DNA alterations caused by the higher-LET radiation. Mutants were identified from the M{sub 2} pools. In total, 14 and 13 mutated genes, including bin2, egy1, gl1, gl2, hy1, hy3-5, ttg1, and var2, were identified in the plants derived from Ar- and C-ions irradiation, respectively. In the mutants from both irradiations, deletion was the most frequent type of mutation; 13 of the 14 mutated genes from the Ar ion-irradiated plants and 11 of the 13 mutated genes from the C ion-irradiated plants harbored deletions. Analysis of junction regions generated by the 2 types of irradiation suggested that alternative non-homologous end-joining was the predominant pathway of repair of break points. Among the deletions, the proportion of large deletions (>100 bp) was about 54% for Ar-ion irradiation and about 64% for C-ion irradiation. Both current results and previously reported data revealed that the proportions of the large deletions induced by 290-keV {mu}m{sup -1} radiations were higher than those of the large deletions induced by lower-LET radiations (6% for 22.5-30.0 keV {mu}m{sup -1} and 27% for 101-124 keV {mu}m{sup -1}). Therefore, the 290 keV {mu}m{sup -1} heavy-ion beams can effectively induce large deletions and will prove useful as novel mutagens for plant breeding and analysis of gene functions, particularly tandemly arrayed genes.

Let-7 microRNA and HMGA2 levels of expression are not inversely linked in adipocytic tumors: analysis of 56 lipomas and liposarcomas with molecular cytogenetic data.

Science.gov (United States)

Bianchini, Laurence; Saâda, Esma; Gjernes, Elisabet; Marty, Marion; Haudebourg, Juliette; Birtwisle-Peyrottes, Isabelle; Keslair, Frédérique; Chignon-Sicard, Bérangère; Chamorey, Emmanuel; Pedeutour, Florence

2011-06-01

The aim of our study was first to assess the role of HMGA2 expression in the pathogenesis of adipocytic tumors (AT) and, second, to seek a potential correlation between overexpression of HMGA2 and let-7 expression inhibition by analyzing a series of 56 benign and malignant AT with molecular cytogenetic data. We measured the levels of expression of HMGA2 mRNA and of eight members of the let-7 microRNA family using quantitative RT-PCR and expression of HMGA2 protein using immunohistochemistry. HMGA2 was highly overexpressed in 100% of well-differentiated/dedifferentiated liposarcomas (WDLPS/DDLPS), all with HMGA2 amplification, and 100% of lipomas with HMGA2 rearrangement. Overexpression of HMGA2 mRNA was detected in 76% of lipomas without HMGA2 rearrangement. HMGA2 protein expression was detected in 100% of lipomas with HMGA2 rearrangement and 48% of lipomas without HMGA2 rearrangement. We detected decreased expression levels of some let-7 members in a significant proportion of AT. Notably, let-7b and let-7g were inhibited in 61% of WDLPS/DDLPS. In lipomas, each type of let-7 was inhibited in approximately one-third of the cases. Although overexpression of both HMGA2 mRNA and protein in a majority of ordinary lipomas without HMGA2 structural rearrangement may have suggested a potential role for let-7 microRNAs, we did not observe a significant link with let-7 inhibition in such cases. Our results indicate that inhibition of let-7 microRNA expression may participate in the deregulation of HMGA2 in AT but that this inhibition is neither a prominent stimulator for HMGA2 overexpression nor a surrogate to genomic HMGA2 rearrangements. Copyright © 2011 Wiley-Liss, Inc.

Beyond Information Architecture: A Systems Integration Approach to Web-site Design

Directory of Open Access Journals (Sweden)

Krisellen Maloney

2017-09-01

Full Text Available Users' needs and expectations regarding access to information have fundamentally changed, creating a disconnect between how users expect to use a library Web site and how the site was designed. At the same time, library technical infrastructures include legacy systems that were not designedf or the Web environment. The authors propose a framework that combines elements of information architecture with approaches to incremental system design and implementation. The framework allows for the development of a Web site that is responsive to changing user needs, while recognizing the need for libraries to adopt a cost-effective approach to implementation and maintenance.

Disposal Site Information Management System

International Nuclear Information System (INIS)

Larson, R.A.; Jouse, C.A.; Esparza, V.

1986-01-01

An information management system for low-level waste shipped for disposal has been developed for the Nuclear Regulatory Commission (NRC). The Disposal Site Information Management System (DSIMS) was developed to provide a user friendly computerized system, accessible through NRC on a nationwide network, for persons needing information to facilitate management decisions. This system has been developed on NOMAD VP/CSS, and the data obtained from the operators of commercial disposal sites are transferred to DSIMS semiannually. Capabilities are provided in DSIMS to allow the user to select and sort data for use in analysis and reporting low-level waste. The system also provides means for describing sources and quantities of low-level waste exceeding the limits of NRC 10 CFR Part 61 Class C. Information contained in DSIMS is intended to aid in future waste projections and economic analysis for new disposal sites

The gga-let-7 family post-transcriptionally regulates TGFBR1 and LIN28B during the differentiation process in early chick development.

Science.gov (United States)

Lee, Sang In; Jeon, Mi-Hyang; Kim, Jeom Sun; Jeon, Ik-Soo; Byun, Sung June

2015-12-01

Early chick embryogenesis is governed by a complex mechanism involving transcriptional and post-transcriptional regulation, although how post-transcriptional processes influence the balance between pluripotency and differentiation during early chick development have not been previously investigated. Here, we characterized the microRNA (miRNA) signature associated with differentiation in the chick embryo, and found that as expression of the gga-let-7 family increases through early development, expression of their direct targets, TGFBR1 and LIN28B, decreases; indeed, gga-let-7a-5p and gga-let-7b miRNAs directly bind to TGFBR1 and LIN28B transcripts. Our data further indicate that TGFBR1 and LIN28B maintain pluripotency by regulating POUV, NANOG, and CRIPTO. Therefore, gga-let-7 miRNAs act as post-transcriptional regulators of differentiation in blastodermal cells by repressing the expression of the TGFBR1 and LIN28B, which intrinsically controls blastodermal cell differentiation in early chick development. © 2015 Wiley Periodicals, Inc.

Towards Achieving the Full Clinical Potential of Proton Therapy by Inclusion of LET and RBE Models

Energy Technology Data Exchange (ETDEWEB)

Jones, Bleddyn [Gray Laboratory, CRUK/MRC Oxford Oncology Institute, The University of Oxford, ORCRB-Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

2015-03-17

Despite increasing use of proton therapy (PBT), several systematic literature reviews show limited gains in clinical outcomes, with publications mostly devoted to recent technical developments. The lack of randomised control studies has also hampered progress in the acceptance of PBT by many oncologists and policy makers. There remain two important uncertainties associated with PBT, namely: (1) accuracy and reproducibility of Bragg peak position (BPP); and (2) imprecise knowledge of the relative biological effect (RBE) for different tissues and tumours, and at different doses. Incorrect BPP will change dose, linear energy transfer (LET) and RBE, with risks of reduced tumour control and enhanced toxicity. These interrelationships are discussed qualitatively with respect to the ICRU target volume definitions. The internationally accepted proton RBE of 1.1 was based on assays and dose ranges unlikely to reveal the complete range of RBE in the human body. RBE values are not known for human (or animal) brain, spine, kidney, liver, intestine, etc. A simple efficiency model for estimating proton RBE values is described, based on data of Belli et al. and other authors, which allows linear increases in α and β with LET, with a gradient estimated using a saturation model from the low LET α and β radiosensitivity parameter input values, and decreasing RBE with increasing dose. To improve outcomes, 3-D dose-LET-RBE and bio-effectiveness maps are required. Validation experiments are indicated in relevant tissues. Randomised clinical studies that test the invariant 1.1 RBE allocation against higher values in late reacting tissues, and lower tumour RBE values in the case of radiosensitive tumours, are also indicated.

Towards Achieving the Full Clinical Potential of Proton Therapy by Inclusion of LET and RBE Models

International Nuclear Information System (INIS)

Jones, Bleddyn

2015-01-01

Despite increasing use of proton therapy (PBT), several systematic literature reviews show limited gains in clinical outcomes, with publications mostly devoted to recent technical developments. The lack of randomised control studies has also hampered progress in the acceptance of PBT by many oncologists and policy makers. There remain two important uncertainties associated with PBT, namely: (1) accuracy and reproducibility of Bragg peak position (BPP); and (2) imprecise knowledge of the relative biological effect (RBE) for different tissues and tumours, and at different doses. Incorrect BPP will change dose, linear energy transfer (LET) and RBE, with risks of reduced tumour control and enhanced toxicity. These interrelationships are discussed qualitatively with respect to the ICRU target volume definitions. The internationally accepted proton RBE of 1.1 was based on assays and dose ranges unlikely to reveal the complete range of RBE in the human body. RBE values are not known for human (or animal) brain, spine, kidney, liver, intestine, etc. A simple efficiency model for estimating proton RBE values is described, based on data of Belli et al. and other authors, which allows linear increases in α and β with LET, with a gradient estimated using a saturation model from the low LET α and β radiosensitivity parameter input values, and decreasing RBE with increasing dose. To improve outcomes, 3-D dose-LET-RBE and bio-effectiveness maps are required. Validation experiments are indicated in relevant tissues. Randomised clinical studies that test the invariant 1.1 RBE allocation against higher values in late reacting tissues, and lower tumour RBE values in the case of radiosensitive tumours, are also indicated

Space Communication Artificial Intelligence for Link Evaluation Terminal (SCAILET)

Science.gov (United States)

Shahidi, Anoosh K.; Schlegelmilch, Richard F.; Petrik, Edward J.; Walters, Jerry L.

1992-01-01

A software application to assist end-users of the high burst rate (HBR) link evaluation terminal (LET) for satellite communications is being developed. The HBR LET system developed at NASA Lewis Research Center is an element of the Advanced Communications Technology Satellite (ACTS) Project. The HBR LET is divided into seven major subsystems, each with its own expert. Programming scripts, test procedures defined by design engineers, set up the HBR LET system. These programming scripts are cryptic, hard to maintain and require a steep learning curve. These scripts were developed by the system engineers who will not be available for the end-users of the system. To increase end-user productivity a friendly interface needs to be added to the system. One possible solution is to provide the user with adequate documentation to perform the needed tasks. With the complexity of this system the vast amount of documentation needed would be overwhelming and the information would be hard to retrieve. With limited resources, maintenance is another reason for not using this form of documentation. An advanced form of interaction is being explored using current computer techniques. This application, which incorporates a combination of multimedia and artificial intelligence (AI) techniques to provided end-users with an intelligent interface to the HBR LET system, is comprised of an intelligent assistant, intelligent tutoring, and hypermedia documentation. The intelligent assistant and tutoring systems address the critical programming needs of the end-user.

'The Gentle Art of Letting the Other Fellow Have Your Own Way ...

African Journals Online (AJOL)

'The Gentle Art of Letting the Other Fellow Have Your Own Way': Viewpoints on a Media Narrative used to Promote the Proposed N2 Toll Road. ... We highlight the importance of developing 'media literacy' – reading skills which enable the critical deconstruction of media texts. We explore, more specifically, the public ...

The downregulation of microRNA let-7a contributes to the excessive expression of type I collagen in systemic and localized scleroderma.

Science.gov (United States)

Makino, Katsunari; Jinnin, Masatoshi; Hirano, Ayaka; Yamane, Keitaro; Eto, Mitsuhiko; Kusano, Takamitsu; Honda, Noritoshi; Kajihara, Ikko; Makino, Takamitsu; Sakai, Keisuke; Masuguchi, Shinichi; Fukushima, Satoshi; Ihn, Hironobu

2013-04-15

Systemic and localized scleroderma (SSc and LSc) is characterized by excessive deposition of collagen and tissue fibrosis in the skin. Although they have fundamental common characteristics including autoimmunity, little is known about the exact mechanism that mediates the excessive collagen expression in these disorders. In the current study, we tried to evaluate the possibility that microRNAs (miRNAs) play some roles in the pathogenesis of fibrosis seen in these diseases. miRNA expression patterns were evaluated by miRNA array analysis, real-time PCR, and in situ hybridization. The function of miRNAs in dermal fibroblasts was assessed using miRNA inhibitors, precursors, or protectors. In the mouse model of bleomycin-induced dermal sclerosis, the overexpression of miRNAs was performed by i.p. miRNA injection. We demonstrated let-7a expression was downregulated in SSc and LSc skin both in vivo and in vitro, compared with normal or keloid skin. The inhibition or overexpression of let-7a in human or mouse skin fibroblasts affected the protein expression of type I collagen or luciferase activity of collagen 3'-untranslated region. Also, we found let-7a was detectable and quantitative in the serum and investigated serum let-7a levels in patients with SSc or LSc. let-7a concentration was significantly decreased in these patients, especially in LSc patients. Moreover, we revealed that the intermittent overexpression of let-7a in the skin by i.p. miRNA injection improved the skin fibrosis induced by bleomycin in mice. Investigation of more detailed mechanisms of miRNA-mediated regulation of collagen expression may lead to new therapeutic approaches against SSc and LSc.

Micro-RNAs Let7e and 126 in Plasma as Markers of Metabolic Dysfunction in 10 to 12 Years Old Children.

Directory of Open Access Journals (Sweden)

Bernardo J Krause

Full Text Available Growing evidence shows that metabolic syndrome (MetS is already starting in childhood however there is no consensus regarding how to diagnose this condition in pediatric population. Studies in adults show that altered levels of specific micro-RNAs are related with components of the MetS.We determined the plasma levels of four MetS-associated micro-RNAs (miR-126, miR-132, mir-145 and Let-7e in 10 to 12 years old children with or without MetS traits.Pediatric subjects were selected from a cohort of 3325 school-age children, and clustered by the absence (control, n = 30, or the presence of 1 (n = 50, 2 (n = 41 or 3 (n = 35 MetS traits according to Cook´s criteria. Micro-RNAs were isolated from plasma, and levels of miR-126, miR-132, miR-145 and Let-7e were determined by Taqman qPCR.Regression analysis of the different MetS traits regarding the different miRNAs analyzed showed that Let-7e presented a negative association with HDL-C levels, but a positive correlation with the number of MetS traits. Levels of miR-126 presented a positive correlation with waist circumference, waist to hip ratio, BMI, and plasma triglycerides and VLDL-C. Levels of miR-132 showed a positive correlation with waist to hip ratio. Plasma levels of Let-7e were increased (~3.4 fold in subjects with 3 MetS traits, and showed significant AUC (0.681; 95%CI = [0.58, 0.78]; p < 0.001 in the ROC analysis which were improved when miR-126 was included in the analysis (AUC 0.729; p < 0.001. In silico analysis of the interaction of proteins derived from mRNAs targeted by Let7 and miR-126 showed an important effect of both Let-7e and miR-126 regulating the insulin signaling pathway.These results suggest that changes in the plasma levels of Let-7e and miR-126 could represent early markers of metabolic dysfunction in children with MetS traits.

Smashing UX design foundations for designing online user experiences

CERN Document Server

Allen, Jesmond

2012-01-01

The ultimate guide to UX from the world's most popular resource for web designers and developers Smashing Magazine is the world's most popular resource for web designers and developers and with this book, the authors provide the pinnacle resource to becoming savvy with User Experience Design (UX). The authors first provide an overview of UX and chart its rise to becoming a valuable and necessary practice for narrowing the gap between Web sites, applications, and users in order to make a user's experience a happy, easy, and successful one.Examines the essential aspects of User Experience Design

Influence of LET on repair of DNA damages in Deinococcus radiodurans

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, Y; Tanaka, A; Kikuchi, M; Shimizu, T; Watanabe, H [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment; Cao, J P; Taucher-Scholz, G

1997-03-01

Inactivation caused by heavy ions was studied in dry cells of radioresistant bacterium Deinococcus radiodurans. All survival curves were characterized by a large shoulder of the curves. No final slopes of the exponential part of survival curves for heavy ion irradiation were steeper than that for 2.0 MeV electron irradiation. The plots of RBE versus LET showed no obvious peaks, suggesting that this bacterium can repair not only DNA double strand breaks (DSBs) but also clustered damage in DNA which may be induced by heavy ions. The genomic DNA of D. radiodurans was cleaved into large fragments with restriction enzyme Not I after post-irradiation incubation and the fragments were separated using pulsed-field gel electrophoresis (PFGE). DSBs induction and rejoining process were analyzed by detection of the reappearance of ladder pattern of DNA fragments. The required repair time after heavy ions irradiation was longer than the repair time for electrons at the same dose of irradiation, however, the rate of repair enzyme induction was almost similar to each other between electrons and heavy ions, suggesting that the same repair system is likely to be used after both low and high LET irradiations. (author)

Let's say goodbye : The moralising practices of gap year organisations in the Netherlands

NARCIS (Netherlands)

Hermann, I. (Inge)

2013-01-01

http://cts.som.surrey.ac.uk/publication/lets-say-goodbye-the-moralising-practices-of-gap-year-organisations-in-the-netherlands/wppa_open/   Responding to the growing appeal of the gap year amongst young people, the higher education sector, governmental institutions and, perhaps foremost, the

Managing Dynamic User Communities in a Grid of Autonomous Resources

CERN Document Server

Alfieri, R; Gianoli, A; Spataro, F; Ciaschini, Vincenzo; dell'Agnello, L; Bonnassieux, F; Broadfoot, P; Lowe, G; Cornwall, L; Jensen, J; Kelsey, D; Frohner, A; Groep, DL; Som de Cerff, W; Steenbakkers, M; Venekamp, G; Kouril, D; McNab, A; Mulmo, O; Silander, M; Hahkala, J; Lhorentey, K

2003-01-01

One of the fundamental concepts in Grid computing is the creation of Virtual Organizations (VO's): a set of resource consumers and providers that join forces to solve a common problem. Typical examples of Virtual Organizations include collaborations formed around the Large Hadron Collider (LHC) experiments. To date, Grid computing has been applied on a relatively small scale, linking dozens of users to a dozen resources, and management of these VO's was a largely manual operation. With the advance of large collaboration, linking more than 10000 users with a 1000 sites in 150 counties, a comprehensive, automated management system is required. It should be simple enough not to deter users, while at the same time ensuring local site autonomy. The VO Management Service (VOMS), developed by the EU DataGrid and DataTAG projects[1, 2], is a secured system for managing authorization for users and resources in virtual organizations. It extends the existing Grid Security Infrastructure[3] architecture with embedded VO ...

The Role of miRNA in Papillary Thyroid Cancer in the Context of miRNA Let-7 Family

Directory of Open Access Journals (Sweden)

Ewelina Perdas

2016-06-01

Full Text Available Papillary thyroid carcinoma (PTC is the most common endocrine malignancy. RET/PTC rearrangement is the most common genetic modification identified in this category of cancer, increasing proliferation and dedifferentiation by the activation of the RET/PTC-RAS-BRAF-MAPK-ERK signaling pathway. Recently, let-7 miRNA was found to reduce RAS levels, acting as a tumor suppressor gene. Circulating miRNA profiles of the let-7 family may be used as novel noninvasive diagnostic, prognostic, treatment and surveillance markers for PTC.

Understanding and Targeting Indonesian Young Adult Internet Users

Directory of Open Access Journals (Sweden)

Andreas Chang

2010-11-01

Full Text Available As the number of global internet users increases, companies’ online advertisement expenditure also grows rapidly. Companies face challenges in targeting the right customers. Understanding which websites are often visited by target users and what they do on the internet will help companies direct their online advertisement to the right target. Using questionnaires, this study examines which sites are most often visited by Indonesian young adult internet users and what they do on the internet. It aims to understand the patterns of behavior of these users. The findings of this study provide some understanding to the marketers. Of consequence, such understanding would help them to select where and what to do with their advertisements when they are targeting the young adult internet users in Indonesia. 

Comparing Facebook Users and Facebook Non-Users: Relationship between Personality Traits and Mental Health Variables – An Exploratory Study

Science.gov (United States)

2016-01-01

Over one billion people use Facebook as a platform for social interaction and self-presentation making it one of the most popular online sites. The aim of the present study was to investigate differences in various personality traits and mental health variables between Facebook users and people who do not use this platform. The data of 945 participants (790 Facebook users, 155 Facebook non-users) were collected. Results indicate that Facebook users score significantly higher on narcissism, self-esteem and extraversion than Facebook non-users. Furthermore, they have significantly higher values of social support, life satisfaction and subjective happiness. Facebook non-users have (marginally) significantly higher values of depression symptoms than Facebook users. In both groups, extraversion, self-esteem, happiness, life satisfaction, resilience and social support, on the one hand, and depression, anxiety and stress symptoms, on the other hand, are negatively correlated. Neuroticism is positively associated with depression, anxiety and stress symptoms. However, significant differences exist between Facebook users and Facebook non-users regarding some associations of personality traits and mental health variables. Compared to Facebook non-users, the present results indicate that Facebook users have higher values of certain personality traits and positive variables protecting mental health. These findings are of particular interest considering the high importance of social online-platforms in the daily life of many people. PMID:27907020

Ombud's corner: About letting go…

CERN Multimedia

Sudeshna Datta-Cockerill

2015-01-01

New year, old problems? The best way to start 2015 is by not carrying over any frustration from 2014. Instead, let it go and move forward.   As I blew out the candle to celebrate my first anniversary of my position as the CERN Ombud, I found myself reflecting back over the past year, wondering what I could share with you, and the following recurring situation came to mind… Often, people come to the Ombud’s office either because they feel mistreated or because they consider themselves to be facing an unfair situation. When this happens, we work through the problems together and identify different options by which to tackle the situation.  Sometimes they ask to be coached through the way in which to go back and deal with the issues themselves; at other times they prefer to address the issue with the other person, in the presence of the Ombud, and request mediation. In both cases, the objective is the same: to ensure that both points of view are understood...

LncRNA-LET inhibits cell viability, migration and EMT while induces apoptosis by up-regulation of TIMP2 in human granulosa-like tumor cell line KGN.

Science.gov (United States)

Han, Qingfang; Zhang, Wenke; Meng, Jinlai; Ma, Li; Li, Aihua

2018-04-01

Polycystic ovary syndrome (PCOS) is a common endocrine disease characterized by hyperandrogenism, irregular menses, and polycystic ovaries. Several long non-coding RNAs (lncRNAs) are aberrantly expressed in PCOS patients; however, little is known about the effects of the lncRNA-low expression in tumor (lncRNA-LET) on PCOS. We aimed to explore the effects of lncRNA-LET on human granulosa-like tumor cell line, KGN. Expression of lncRNA-LET in normal IOSE80 cells and granulosa cells was determined by qRT-PCR. KGN cell viability, apoptosis and migration were measured by trypan blue exclusion method, flow cytometry assay and wound healing assay, respectively. TGF-β1 was used to induce epithelial-mesenchymal transition (EMT) process. LncRNA-LET expression and mRNA expressions of TIMP2 and EMT-related proteins were measured by qRT-PCR. Western blot analysis was used to measure the protein expression of apoptosis-related proteins, EMT-related proteins, TIMP2, and the proteins in the Wnt/β-catenin and Notch signaling pathways. lncRNA-LET was down-regulated in KGN cells, and its overexpression inhibited cell viability and migration, and promoted apoptosis in KGN cells. Overexpression of lncRNA-LET increased the expression of E-cadherin and decreased the expressions of N-cadherin and vimentin in KGN cells. These effects of lncRNA-LET on KGN cells were reversed by TIMP2 suppression. Overexpression of TIMP2 inhibited cell viability, migration and EMT process, and increased apoptosis by activating the Wnt/β-catenin and Notch pathways. Overexpression of lncRNA-LET inhibits cell viability, migration and EMT process, and increases apoptosis in KGN cells by up-regulating the expression of TIMP2 and activating the Wnt/β-catenin and notch signaling pathways. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The Effects of Profile Pictures and Friends' Comments on Social Network Site Users' Body Image and Adherence to the Norm.

Science.gov (United States)

Flynn, Mark A

2016-04-01

This study sought to explore the effects of exposure to Facebook body ideal profile pictures and norm conforming comments on users' body image. In addition, the social identity and self-categorization theoretical frameworks were used to explore users' endorsement of a body ideal norm. A mock Facebook page was used to conduct a pretest posttest 2 × 2 between-group web-based experiment that featured body ideal profile pictures (body ideal vs. no body) and body ideal comments (conforming vs. nonconforming). Five hundred and one participants completed the experiment and passed all manipulation checks. Participants viewed pictures and comments on the status page and were able to leave their own comment before exiting. Results demonstrated no significant main effects. However, predispositional body satisfaction significantly moderated the relationship between body ideal pictures and body satisfaction. Most comments supported the body ideal norm. However, in support of self-categorization theory, participants exposed to nonconforming comments made nonconforming comments themselves significantly more than those exposed to conforming comments. The findings demonstrated the importance of continued body image research in social network sites, as well as the potential for self-categorization theory to guide such research.

LET and dose rate effect on radiation-induced copolymerization of maleimide with styrene in 2-propanol solution

Energy Technology Data Exchange (ETDEWEB)

Nakagawa, Seiko, E-mail: Nakagawa.Seiko@iri-tokyo.jp [Tokyo Metropolitan Industrial Technology Research Institute, 2-4-10 Aoumi, Koto-ku, Tokyo 135-0064 (Japan); Taguchi, Mitsumasa; Kimura, Atsushi [Environmental Radiation Processing Group, Environment and Industrial Materials Research Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan)

2011-11-15

N{sub 2}-saturated 2-propanol solutions containing styrene and maleimide were irradiated by electron, proton, He and C-ion beams. The styrene-maleimide copolymer was produced by radical polymerization induced during irradiation. The effects of the radical distribution, which depends on the LET or dose rate, on the molecular weight and the polymer yield were discussed. - Highlights: > Maleimide with styrene in N{sub 2}-saturated 2-propanol was irradiated by electron and heavy ions. > LET and dose rate effects of radical polymerization induced by irradiation were studied. > Results have shown the relation between radical distribution and efficiency of polymerization.

Fast neutrons: Inexpensive and reliable tool to investigate high-LET particle radiobiology

International Nuclear Information System (INIS)

Gueulette, J.; Slabbert, J.P.; Bischoff, P.; Denis, J.M.; Wambersie, A.; Jones, D.

2010-01-01

Radiation therapy with carbon ions as well as missions into outer space have boosted the interest for high-LET particle radiobiology. Optimization of treatments in accordance with technical developments, as well as the radioprotection of cosmonauts during long missions require that research in these domains continue. Therefore suitable radiation fields are needed. Fast neutrons and carbon ions exhibit comparable LET values and similar radiobiological properties. Consequently, the findings obtained with each radiation quality could be shared to benefit knowledge in all concerned domains. The p(66+Be) neutron therapy facilities of iThemba LABS (South Africa) and the p(65)+Be neutron facility of Louvain-la-Neuve (Belgium) are in constant use to do radiobiological research for clinical applications with fast neutrons. These beams - which comply with all physical and technical requirements for clinical applications - are now fully reliable, easy to use and frequently accessible for radiobiological investigations. These facilities thus provide unique opportunities to undertake radiobiological experimentation, especially for investigations that require long irradiation times and/or fractionated treatments.

Dashboard applications to monitor experiment activities at sites

Energy Technology Data Exchange (ETDEWEB)

Andreeva, Julia; Gaidioz, Benjamin; Grigoras, Costin; Kokoszkiewicz, Lukasz; Lanciotti, Elisa; Rocha, Ricardo; Saiz, Pablo; Santinelli, Roberto; Sidorova, Irina; Sciaba, Andrea [CERN, European Organization for Nuclear Research (Switzerland); Belforte, Stefano [INFN Trieste (Italy); Boehm, Max [EDS, an HP Company, Plano, TX (United States); Casajus, Adrian [Universitat de Barcelona (Spain); Flix, Josep [PIC, Port d' Informacio CientIfica, Bellaterra (Spain); Tsaregorodtsev, Andrei, E-mail: Elisa.Lanciotti@cern.c, E-mail: Pablo.Saiz@cern.c [CPPM Marseille (France)

2010-04-01

In the framework of a distributed computing environment, such as WLCG, monitoring has a key role in order to keep under control activities going on in sites located in different countries and involving people based in many different sites. To be able to cope with such a large scale heterogeneous infrastructure, it is necessary to have monitoring tools providing a complete and reliable view of the overall performance of the sites. Moreover, the structure of a monitoring system critically depends on the object to monitor and on the users it is addressed to. In this article we will describe two different monitoring systems both aimed to monitor activities and services provided in the WLCG framework, but designed in order to meet the requirements of different users: Site Status Board has an overall view of the services available in all the sites supporting an experiment, whereas Siteview provides a complete view of all the activities going on at a site, for all the experiments supported by the site.

Dashboard applications to monitor experiment activities at sites

International Nuclear Information System (INIS)

Andreeva, Julia; Gaidioz, Benjamin; Grigoras, Costin; Kokoszkiewicz, Lukasz; Lanciotti, Elisa; Rocha, Ricardo; Saiz, Pablo; Santinelli, Roberto; Sidorova, Irina; Sciaba, Andrea; Belforte, Stefano; Boehm, Max; Casajus, Adrian; Flix, Josep; Tsaregorodtsev, Andrei

2010-01-01

In the framework of a distributed computing environment, such as WLCG, monitoring has a key role in order to keep under control activities going on in sites located in different countries and involving people based in many different sites. To be able to cope with such a large scale heterogeneous infrastructure, it is necessary to have monitoring tools providing a complete and reliable view of the overall performance of the sites. Moreover, the structure of a monitoring system critically depends on the object to monitor and on the users it is addressed to. In this article we will describe two different monitoring systems both aimed to monitor activities and services provided in the WLCG framework, but designed in order to meet the requirements of different users: Site Status Board has an overall view of the services available in all the sites supporting an experiment, whereas Siteview provides a complete view of all the activities going on at a site, for all the experiments supported by the site.

Site report for the office information management conference

Energy Technology Data Exchange (ETDEWEB)

Thompson, G.P.

1989-12-31

The charter of the End User Services Section is to plan and support office information systems for Savannah River Site organizations and be the first point of contact for users of Information Resource Management Department computer services. This includes personal workstation procurement, electronic mail, computer aided design, operations analysis, and access to information systems both on and off site. The mission also includes the training and support of personnel in the effective use of the new and existing systems.

Site report for the office information management conference

Energy Technology Data Exchange (ETDEWEB)

Thompson, G.P.

1989-01-01

The charter of the End User Services Section is to plan and support office information systems for Savannah River Site organizations and be the first point of contact for users of Information Resource Management Department computer services. This includes personal workstation procurement, electronic mail, computer aided design, operations analysis, and access to information systems both on and off site. The mission also includes the training and support of personnel in the effective use of the new and existing systems.

On the use of distributions of stopping pions as an indicator of the spatial distribution of the high-LET dose in negative pion radiotherapy

International Nuclear Information System (INIS)

Brenner, D.J.

1991-01-01

A semi-empirical across the treatment volume of a therapeutic negative pion beam. Such beams deliver dose partially at high LET (through alphas and heavier particles produced both directly in pion stars and via intermediate star-produced neutrons), and partially at low LET (through scattering of pions, electrons and muons, as well as protons produced directly from pion stars and via intermediate neutrons). The problem is how to understand the spatial distribution of the high-LET dose, which is responsible for the potentially improved biological response in the treatment volume

Reduction in OER with LET: evidence supporting the ''oxygen-in-the-track'' hypothesis

International Nuclear Information System (INIS)

Bryant, P.E.

1976-01-01

To account for the reduction in OER with increasing LET which is observed for a wide variety of cell systems. Neary (1965) invoked the hypothesis that molecular oxygen is generated within the particle tracks of the more densely ionizing radiations. With the proviso that the product generated may be a species other than oxygen, but with similar sensitizing properties, produced by different qualities of radiation in two different organisms: the alga Chlamydomonas reinhardii and the bacterium Shigella flexneri were calculated. These effective concentrations should be the same for any given quality if the formation of the product is a function only of physico-chemical events occurring within the tracks of particles, and is independent of the biological material in which energy deposition is taking place. A prerequisite for the calculation of effective amounts of oxygen in tracks of ionizing particles is a knowledge of how radiosentivity varies with oxygen concentration at low LET

User experience with HydroHelp programs

Energy Technology Data Exchange (ETDEWEB)

Verner, J.S. [Brookfield Power, Gatineau, PQ (Canada)

2009-07-01

Advances in the field of geographical information systems (GIS) have simplified the process of finding suitable sites for new hydroelectric projects. However, estimating the construction cost remains a challenge. The HydroHelp program is a cost evaluation program developed specifically to determine if a project will be economically feasible. The program is made up of 4 programs, depending on the type of turbine suitable for the site. Once a turbine selection is made, users can choose the program according to Kaplan, Impulse or Francis turbines. Users must rely on GIS, since the program requires a thorough understanding of the site geology and topography. Knowledge of hydroelectric plants is also necessary in order to obtain a credible construction cost. This paper demonstrated the capacity and flexibility of the software along with its different functions and available options. A detailed cost breakdown can be obtained along with an energy estimate and project specifications. In addition, the software can be used to optimize the project through different options by changing the facility's layout in terms of the type of dam, spillway, conduit length and diameter, turbine type and flood level. 17 figs.

Evolution of user analysis on the grid in ATLAS

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00218990; The ATLAS collaboration; Dewhurst, Alastair

2017-01-01

More than one thousand physicists analyse data collected by the ATLAS experiment at the Large Hadron Collider (LHC) at CERN through 150 computing facilities around the world. Efficient distributed analysis requires optimal resource usage and the interplay of several factors: robust grid and software infrastructures, and system capability to adapt to different workloads. The continuous automatic validation of grid sites and the user support provided by a dedicated team of expert shifters have been proven to provide a solid distributed analysis system for ATLAS users. Typical user workflows on the grid, and their associated metrics, are discussed. Measurements of user job performance and typical requirements are also shown.

Primary processes in radiation chemistry. LET (Linear Energy Transfer) effect in water radiolysis

International Nuclear Information System (INIS)

Trupin-Wasselin, V.

2000-01-01

The effect of ionizing radiations on aqueous solutions leads to water ionization and then to the formation of radical species and molecular products (e - aq , H . , OH . , H 2 O 2 , H 2 ). It has been shown that the stopping power, characterized by the LET value (Linear Energy Transfer) becomes different when the nature of the ionizing radiations is different. Few data are nowadays available for high LET radiations such as protons and high energy heavy ions. These particles have been used to better understand the primary processes in radiation chemistry. The yield of a chemical dosimeter (the Fricke dosimeter) and those of the hydrogen peroxide have been determined for different LET. The effect of the dose rate on the Fricke dosimeter yield and on the H 2 O 2 yield has been studied too. When the dose rate increases, an increase of the molecular products yield is observed. At very high dose rate, this yield decreases on account of the attack of the molecular products by radicals. The H 2 O 2 yield in alkaline medium decreases when the pH reaches 12. This decrease can be explained by a slowing down of the H 2 O 2 formation velocity in alkaline medium. Superoxide radical has also been studied in this work. A new detection method: the time-resolved chemiluminescence has been perfected for this radical. This technique is more sensitive than the absorption spectroscopy. Experiments with heavy ions have allowed to determine the O 2 .- yield directly in the irradiation cell. The experimental results have been compared with those obtained with a Monte Carlo simulation code. (O.M.)

Sub-LET Threshold SEE Cross Section Dependency with Ion Energy

CERN Document Server

Garcia Alia, Ruben; Brandenburg, Sytze; Brugger, Markus; Daly, Eamonn; Ferlet-Cavrois, Veronique; Gaillard, Remi; Hoeffgen, Stefan; Menicucci, Alessandra; Metzger, Stefan; Zadeh, Ali; Muschitiello, Michele; Noordeh, Emil; Santin, Giovanni; CERN. Geneva. ATS Department

2015-01-01

This study focuses on the ion species and energy dependence of the heavy ion SEE cross section in the sub-let threshold region through a set of experimental data. In addition, a Monte Carlo based model is introduced and applied, showing a good agreement with the data in the several hundred MeV/n range while evidencing large discrepancies with the measurements in the 10-30 MeV/n interval, notably for the NE ion. Such discrepancies are carefully analysed and discussed.

Forget about the future - let's get on with the past!

DEFF Research Database (Denmark)

McQuaid, Sara Dybris

'Forget about the Future - Let's get on with the Past! Trails of truth recovery and provisional justice in Northern Ireland' Abstract: In Northern Ireland an agreed and comprehensive framework for ‘dealing with the past’ has yet to be worked out. In this policy vacuum a bricolage of different met...... demonstrate how initiatives conceived to serve a particular function can often transmute to serve other or additional functions with severe consequences for both the peace process and future policies for the past....

Let-7b regulates the expression of the growth hormone receptor gene in deletion-type dwarf chickens.

Science.gov (United States)

Lin, Shumao; Li, Hongmei; Mu, Heping; Luo, Wen; Li, Ying; Jia, Xinzheng; Wang, Sibing; Jia, Xiaolu; Nie, Qinghua; Li, Yugu; Zhang, Xiquan

2012-07-10

A deletion mutation in the growth hormone receptor (GHR) gene results in the inhibition of skeletal muscle growth and fat deposition in dwarf chickens. We used microarray techniques to determine microRNA (miRNA) and mRNA expression profiles of GHR in the skeletal muscles of 14-day-old embryos as well as 7-week-old deletion-type dwarf and normal-type chickens. Our aim was to elucidate the miRNA regulation of GHR expression with respect to growth inhibition and fat deposition. At the same developmental stages, different expression profiles in skeletal muscles of dwarf and normal chickens occurred for four miRNAs (miR-1623, miR-181b, let-7b, and miR-128). At different developmental stages, there was a significant difference in the expression profiles of a greater number of miRNAs. Eleven miRNAs were up-regulated and 18 down-regulated in the 7-week-old dwarf chickens when compared with profiles in 14-day-old embryos. In 7-week-old normal chickens, seven miRNAs were up-regulated and nine down-regulated compared with those in 14-day-old embryos. In skeletal muscles, 22 genes were up-regulated and 33 down-regulated in 14-day-old embryos compared with 7-week-old dwarf chickens. Sixty-five mRNAs were up-regulated and 108 down-regulated in 14-day-old embryos as compared with 7-week-old normal chickens. Thirty-four differentially expressed miRNAs were grouped into 18 categories based on overlapping seed and target sequences. Only let-7b was found to be complementary to its target in the 3' untranslated region of GHR, and was able to inhibit its expression. Kyoto Encyclopedia of Genes and Genomes pathway analysis and quantitative polymerase chain reactions indicated there were three main signaling pathways regulating skeletal muscle growth and fat deposition of chickens. These were influenced by let-7b-regulated GHR. Suppression of the cytokine signaling 3 (SOCS3) gene was found to be involved in the signaling pathway of adipocytokines. There is a critical miRNA, let-7b

SiteFind: A software tool for introducing a restriction site as a marker for successful site-directed mutagenesis

Directory of Open Access Journals (Sweden)

Evans Paul M

2005-12-01

Full Text Available Abstract Background Site-directed mutagenesis is a widely-used technique for introducing mutations into a particular DNA sequence, often with the goal of creating a point mutation in the corresponding amino acid sequence but otherwise leaving the overall sequence undisturbed. However, this method provides no means for verifying its success other than sequencing the putative mutant construct: This can quickly become an expensive method for screening for successful mutations. An alternative to sequencing is to simultaneously introduce a restriction site near the point mutation in manner such that the restriction site has no effect on the translated amino acid sequence. Thus, the novel restriction site can be used as a marker for successful mutation which can be quickly and easily assessed. However, finding a restriction site that does not disturb the corresponding amino acid sequence is a time-consuming task even for experienced researchers. A fast and easy to use computer program is needed for this task. Results We wrote a computer program, called SiteFind, to help us design a restriction site within the mutation primers without changing the peptide sequence. Because of the redundancy of genetic code, a given peptide can be encoded by many different DNA sequences. Since the list of possible restriction sites for a given DNA sequence is not always obvious, SiteFind automates this task. The number of possible sequences a computer program must search through increases exponentially as the sequence length increases. SiteFind uses a novel "moving window" algorithm to reduce the number of possible sequences to be searched to a manageable level. The user enters a nucleotide sequence, specifies what amino acid residues should be changed in the mutation, and SiteFind generates a list of possible restriction sites and what nucleotides must be changed to introduce that site. As a demonstration of its use, we successfully generated a single point mutation

Reversal of diuretic-associated impaired glucose tolerance and new-onset diabetes: results of the STAR-LET study.

Science.gov (United States)

Bakris, George; Molitch, Mark; Zhou, Qian; Sarafidis, Pantelis; Champion, Annette; Bacher, Peter; Sowers, James R

2008-01-01

Reversal of new-onset diabetes secondary to thiazide diuretic use remains questionable. STAR-LET was a 6-month extension of the Study of Trandolapril/Verapamil SR and Insulin Resistance (STAR), which assessed the effects of a fixed-dose renin-angiotensin system inhibitor (RASI)/hydrochlorothiazide (HCTZ) combination on changes in 2-hour oral glucose tolerance test (OGTT) results. STAR-LET explored whether the glycemic impact of HCTZ could be reversed by conversion to a RASI/verapamil combination. The primary outcome was change in 2-hour OGTT results. Fifty-one percent of the STAR patients were enrolled in STAR-LET. The 2-hour OGTT value (mmol/L) was unchanged from STAR baseline in the RASI/verapamil group (7.7+/-2.4 vs 8.1+/-3.3; P=.18) and improved in those who were switched from RASI/HCTZ to RASI/verapamil (8.5+/-3.0 vs 7.2+/-2.3; P<.001). This exploratory study suggests that the impairment in glycemic control seen with use of a thiazide diuretic combined with a RASI can be reversed by switching to a regimen that does not include a diuretic.

User driven innovation in mobile technologies?

DEFF Research Database (Denmark)

Larsen, Casper Schultz; Koch, Christian

2007-01-01

by systems already in function. Stories of prior business successes can be an important tool to ensure further innovative investments since lack of enterprise strategies is often an obstacle for innovation, especially user driven. Both small and large software houses develops dedicated software for coupling...... technology systems relying on the concept of affordance. This paper examines how innovation processes mediate between user orientations and technology offers. There is a great potential for mobile handheld ICT-systems to support numerous work processes in the AEC-industry and this can be substantiated...... site practises, and headquarters - inspired by specific user needs for optimizing work processes. The most important mechanisms evoked for creating the mediating found in the paper are ‘hybrids’ where professionals from AEC establishes a software house, developing ICT-products for specific on...

MicroRNA let-7 modulates the immune response to Mycobacterium tuberculosis infection via control of A20, an inhibitor of the NF-κB pathway.

Science.gov (United States)

Kumar, Manish; Sahu, Sanjaya Kumar; Kumar, Ranjeet; Subuddhi, Arijita; Maji, Ranjan Kumar; Jana, Kuladip; Gupta, Pushpa; Raffetseder, Johanna; Lerm, Maria; Ghosh, Zhumur; van Loo, Geert; Beyaert, Rudi; Gupta, Umesh D; Kundu, Manikuntala; Basu, Joyoti

2015-03-11

The outcome of the interaction between Mycobacterium tuberculosis (Mtb) and a macrophage depends on the interplay between host defense and bacterial immune subversion mechanisms. MicroRNAs critically regulate several host defense mechanisms, but their role in the Mtb-macrophage interplay remains unclear. MicroRNA profiling of Mtb-infected macrophages revealed the downregulation of miR-let-7f in a manner dependent on the Mtb secreted effector ESAT-6. We establish that let-7f targets A20, a feedback inhibitor of the NF-κB pathway. Expression of let-7f decreases and A20 increases with progression of Mtb infection in mice. Mtb survival is attenuated in A20-deficient macrophages, and the production of TNF, IL-1β, and nitrite, which are mediators of immunity to Mtb, is correspondingly increased. Further, let-7f overexpression diminishes Mtb survival and augments the production of cytokines including TNF and IL-1β. These results uncover a role for let-7f and its target A20 in regulating immune responses to Mtb and controlling bacterial burden. Copyright © 2015 Elsevier Inc. All rights reserved.

Improving ATLAS grid site reliability with functional tests using HammerCloud

CERN Document Server

Legger, F; The ATLAS collaboration

2012-01-01

With the exponential growth of LHC (Large Hadron Collider) data in 2011, and more coming in 2012, distributed computing has become the established way to analyse collider data. The ATLAS grid infrastructure includes almost 100 sites worldwide, ranging from large national computing centers to smaller university clusters. These facilities are used for data reconstruction and simulation, which are centrally managed by the ATLAS production system, and for distributed user analysis. To ensure the smooth operation of such a complex system, regular tests of all sites are necessary to validate the site capability of successfully executing user and production jobs. We report on the development, optimization and results of an automated functional testing suite using the HammerCloud framework. Functional tests are short light-weight applications covering typical user analysis and production schemes, which are periodically submitted to all ATLAS grid sites. Results from those tests are collected and used to evaluate site...

Let's Refuse to Be What We Are (Supposed to Be)! / Airi Triisberg

Index Scriptorium Estoniae

Triisberg, Airi, 1982-

2010-01-01

Rahvusvaheline kaasaegse kunsti näitus "Räägime rahvuslusest! Ideoloogia ja identiteedi vahel" ("Let's Talk About Nationalism! Between Ideology and Identity") Kumu Kunstimuuseumis 5.02.-25.04.2010. Kuraator Rael Artel. Katarina Zdjelari (Rotterdam), Tanja Muravskaja (Eesti), Jens Haaningu (Kopenhaagen), Artur Żmijewski (Varssavi), Joanna Rajkowska (Varssavi) ja John Phillip Mäkineni (Helsingi) töödest näitusel

Differential profiles of crack users in respondent-driven and institutional samples: a three-site comparison

NARCIS (Netherlands)

Oteo Pérez, A.; Benschop, A.; Korf, D.J.

2012-01-01

Background/Aim: Respondent-driven sampling (RDS) is increasingly applied in social epidemiological surveys among ‘hidden populations’ of hard drug users. The objective of the present study was to assess whether the profile of frequent crack users recruited through RDS differed from those surveyed in

Don't Let Asthma Define You: Sylvia Granados-Maready Uses Her Competitive Edge Against Condition

Science.gov (United States)

... Define You Sylvia Granados-Maready uses her competitive edge against condition Photo: Kevin Gbolie When Sylvia Granados- ... she said. “If you’ve got that competitive edge, accept it but know your limits.” She let ...

How 'Social' are Social News Sites? Exploring the Motivations for Using Reddit.com

DEFF Research Database (Denmark)

Bogers, Toine; Nordenhoff Wernersen, Rasmus

2014-01-01

present a tiered framework of motivational factors for participating on social news sites, based on a comprehensive literature review, drawn from fields like social media research, sociology, (social) psychology, and behavioral economics. We then validate this framework through a survey deployed on Reddit...... surprisingly, the social aspect of social news sites is not a motivating factor for the majority of Reddit users. Influencing the placement and reception of news stories in their niche communities of interest is what draws people to sites such as Reddit.......Social news sites allow their users to submit and vote on online news stories, thereby bypassing the authority and power of traditional newspaper editors. In this paper we explore what motivates users of social news sites, such as Reddit, to participate in this collaborative editorial process. We...

Medium-sized Universities Connect to Their Libraries: Links on University Home Pages and User Group Pages

Directory of Open Access Journals (Sweden)

Pamela Harpel-Burk

2006-03-01

Full Text Available From major tasks—such as recruitment of new students and staff—to the more mundane but equally important tasks—such as providing directions to campus—college and university Web sites perform a wide range of tasks for a varied assortment of users. Overlapping functions and user needs meld to create the need for a Web site with three major functions: promotion and marketing, access to online services, and providing a means of communication between individuals and groups. In turn, college and university Web sites that provide links to their library home page can be valuable assets for recruitment, public relations, and for helping users locate online services.

Relational Leading – Appreciating Letting Go, and Not Knowing Where You Are Going

DEFF Research Database (Denmark)

Larsen, Mette Vinther

2016-01-01

In this article we meet Steven,the manager of a Danish regional regional medical supply organization. With him, we explore how – even for leaders – it can feel liberating to let go of existing knowledge and understanding and embark on a journey with others with the certainty that no one knows where...

Users' abilities to review website pages

NARCIS (Netherlands)

Elling, Sanne; Lentz, Leo; de Jong, Menno D.T.

2012-01-01

Web sites increasingly encourage users to provide comments on the quality of the content by clicking on a feedback button and filling out a feedback form. Little is known about users’ abilities to provide such feedback. To guide the development of evaluation tools, this study examines to what extent

Geospatial Optimization of Siting Large-Scale Solar Projects

Energy Technology Data Exchange (ETDEWEB)

Macknick, Jordan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Quinby, Ted [National Renewable Energy Lab. (NREL), Golden, CO (United States); Caulfield, Emmet [Stanford Univ., CA (United States); Gerritsen, Margot [Stanford Univ., CA (United States); Diffendorfer, Jay [U.S. Geological Survey, Boulder, CO (United States); Haines, Seth [U.S. Geological Survey, Boulder, CO (United States)

2014-03-01

Recent policy and economic conditions have encouraged a renewed interest in developing large-scale solar projects in the U.S. Southwest. However, siting large-scale solar projects is complex. In addition to the quality of the solar resource, solar developers must take into consideration many environmental, social, and economic factors when evaluating a potential site. This report describes a proof-of-concept, Web-based Geographical Information Systems (GIS) tool that evaluates multiple user-defined criteria in an optimization algorithm to inform discussions and decisions regarding the locations of utility-scale solar projects. Existing siting recommendations for large-scale solar projects from governmental and non-governmental organizations are not consistent with each other, are often not transparent in methods, and do not take into consideration the differing priorities of stakeholders. The siting assistance GIS tool we have developed improves upon the existing siting guidelines by being user-driven, transparent, interactive, capable of incorporating multiple criteria, and flexible. This work provides the foundation for a dynamic siting assistance tool that can greatly facilitate siting decisions among multiple stakeholders.

Privacy in social networking sites

OpenAIRE

Λεονάρδος, Γεώργιος; Leonardos, Giorgos

2016-01-01

The purpose of this study is to explore the aspects of privacy over the use of social networks web sites. More specific, we will show the types of social networks, their privacy mechanisms that are different in each social network site, their privacy options that are offered to users. We will report some serious privacy violations incidents of the most popular social networks sites such as Facebook, Twitter, LinkedIn. Also, we will report some important surveys about social networks and pr...

Conceptualizing of Social Networking Sites

OpenAIRE

J. S. Sodhi; Shilpi Sharma

2012-01-01

People often move to their friends, families and colleagues when they feel urge and having doubts or queries to solve. Participation in social networking site has dramatically increased in recent years. Many social networking sites boost with million of members using their network on regular basis to communicate, share , create and collaborate with others. In this paper we explore the phenomenon of using social networking site to trace a link of the search from the community of users for bett...

User Interface Technology to Reduce Mental Transformations for Tangible Remote Dismantling Simulator

Energy Technology Data Exchange (ETDEWEB)

Hyun, Dongjun; Kim, Ikjune; Lee, Jonghwan; Kim, Geun-Ho; Jeong, Kwan-Seong; Choi, Byung-Seon; Moon, Jeikwon; Choi, Jong-Won [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-10-15

High-level radiation of the major components restricts access by human workers, and makes an accident or outage during the dismantling process more difficult to deal with. Since unexpected situations causes waste of budget and an aggravation of safety, the preliminary verification of the dismantling processes and equipment by the tangible remote dismantling simulator is very important. The design optimization of the dismantling processes and equipment is one of the most important objectives of the tangible remote dismantling simulator, as well. This paper proposes a user interface technology to reduce mental transformations for the tangible remote dismantling simulator. At the dismantling process simulation using the tangible remote dismantling simulator, the most difficult work is the remote operation handling the high degrees-of-freedom (DOF) manipulator due to complex mental transformations. The proposed user interface technology reduces mental transformations with constraints using the point projection and direction projection. The test result of the cutting process over the closure head of the RPV demonstrates that the proposed mental transformation reduction technology is operated successfully in the tangible remote dismantling simulator, and lets the operator be easy to control the high DOF manipulator even in the most difficult operation by reducing DOFs to be controlled manually.

User Interface Technology to Reduce Mental Transformations for Tangible Remote Dismantling Simulator

International Nuclear Information System (INIS)

Hyun, Dongjun; Kim, Ikjune; Lee, Jonghwan; Kim, Geun-Ho; Jeong, Kwan-Seong; Choi, Byung-Seon; Moon, Jeikwon; Choi, Jong-Won

2015-01-01

High-level radiation of the major components restricts access by human workers, and makes an accident or outage during the dismantling process more difficult to deal with. Since unexpected situations causes waste of budget and an aggravation of safety, the preliminary verification of the dismantling processes and equipment by the tangible remote dismantling simulator is very important. The design optimization of the dismantling processes and equipment is one of the most important objectives of the tangible remote dismantling simulator, as well. This paper proposes a user interface technology to reduce mental transformations for the tangible remote dismantling simulator. At the dismantling process simulation using the tangible remote dismantling simulator, the most difficult work is the remote operation handling the high degrees-of-freedom (DOF) manipulator due to complex mental transformations. The proposed user interface technology reduces mental transformations with constraints using the point projection and direction projection. The test result of the cutting process over the closure head of the RPV demonstrates that the proposed mental transformation reduction technology is operated successfully in the tangible remote dismantling simulator, and lets the operator be easy to control the high DOF manipulator even in the most difficult operation by reducing DOFs to be controlled manually

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

Energy Technology Data Exchange (ETDEWEB)

Giantsoudi, Drosoula; Sethi, Roshan V. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (United States); Eaton, Bree R. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Ebb, David H. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Caruso, Paul A.; Rapalino, Otto [Department of Radiology (O.R.) at the Massachusetts General Hospital, Boston, Massachusetts (United States); Chen, Yen-Lin E.; Adams, Judith A.; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M., E-mail: smacdonald@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2016-05-01

Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

International Nuclear Information System (INIS)

Giantsoudi, Drosoula; Sethi, Roshan V.; Yeap, Beow Y.; Eaton, Bree R.; Ebb, David H.; Caruso, Paul A.; Rapalino, Otto; Chen, Yen-Lin E.; Adams, Judith A.; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald; MacDonald, Shannon M.

2016-01-01

Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury.

Science.gov (United States)

Giantsoudi, Drosoula; Sethi, Roshan V; Yeap, Beow Y; Eaton, Bree R; Ebb, David H; Caruso, Paul A; Rapalino, Otto; Chen, Yen-Lin E; Adams, Judith A; Yock, Torunn I; Tarbell, Nancy J; Paganetti, Harald; MacDonald, Shannon M

2016-05-01

Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET. Published by Elsevier Inc.

A framework for unsupervised spam detection in social networking sites

NARCIS (Netherlands)

Bosma, M.; Meij, E.; Weerkamp, W.

2012-01-01

Social networking sites offer users the option to submit user spam reports for a given message, indicating this message is inappropriate. In this paper we present a framework that uses these user spam reports for spam detection. The framework is based on the HITS web link analysis framework and is

Differentially expressed plasma microRNAs and the potential regulatory function of Let-7b in chronic thromboembolic pulmonary hypertension.

Directory of Open Access Journals (Sweden)

Lijuan Guo

Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a progressive disease characterized by misguided thrombolysis and remodeling of pulmonary arteries. MicroRNAs are small non-coding RNAs involved in multiple cell processes and functions. During CTEPH, circulating microRNA profile endued with characteristics of diseased cells could be identified as a biomarker, and might help in recognition of pathogenesis. Thus, in this study, we compared the differentially expressed microRNAs in plasma of CTEPH patients and healthy controls and investigated their potential functions. Microarray was used to identify microRNA expression profile and qRT-PCR for validation. The targets of differentially expressed microRNAs were identified in silico, and the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes pathway database were used for functional investigation of target gene profile. Targets of let-7b were validated by fluorescence reporter assay. Protein expression of target genes was determined by ELISA or western blotting. Cell migration was evaluated by wound healing assay. The results showed that 1 thirty five microRNAs were differentially expressed in CTEPH patients, among which, a signature of 17 microRNAs, which was shown to be related to the disease pathogenesis by in silico analysis, gave diagnostic efficacy of both sensitivity and specificity >0.9. 2 Let-7b, one of the down-regulated anti-oncogenic microRNAs in the signature, was validated to decrease to about 0.25 fold in CTEPH patients. 3 ET-1 and TGFBR1 were direct targets of let-7b. Altering let-7b level influenced ET-1 and TGFBR1 expression in pulmonary arterial endothelial cells (PAECs as well as the migration of PAECs and pulmonary arterial smooth muscle cells (PASMCs. These results suggested that CTEPH patients had aberrant microRNA signature which might provide some clue for pathogenesis study and biomarker screening. Reduced let-7b might be involved in the pathogenesis of

Differentially Expressed Plasma MicroRNAs and the Potential Regulatory Function of Let-7b in Chronic Thromboembolic Pulmonary Hypertension

Science.gov (United States)

Guo, Lijuan; Yang, Yuanhua; Liu, Jie; Wang, Lei; Li, Jifeng; Wang, Ying; Liu, Yan; Gu, Song; Gan, Huili; Cai, Jun; Yuan, Jason X.-J.; Wang, Jun; Wang, Chen

2014-01-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease characterized by misguided thrombolysis and remodeling of pulmonary arteries. MicroRNAs are small non-coding RNAs involved in multiple cell processes and functions. During CTEPH, circulating microRNA profile endued with characteristics of diseased cells could be identified as a biomarker, and might help in recognition of pathogenesis. Thus, in this study, we compared the differentially expressed microRNAs in plasma of CTEPH patients and healthy controls and investigated their potential functions. Microarray was used to identify microRNA expression profile and qRT-PCR for validation. The targets of differentially expressed microRNAs were identified in silico, and the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes pathway database were used for functional investigation of target gene profile. Targets of let-7b were validated by fluorescence reporter assay. Protein expression of target genes was determined by ELISA or western blotting. Cell migration was evaluated by wound healing assay. The results showed that 1) thirty five microRNAs were differentially expressed in CTEPH patients, among which, a signature of 17 microRNAs, which was shown to be related to the disease pathogenesis by in silico analysis, gave diagnostic efficacy of both sensitivity and specificity >0.9. 2) Let-7b, one of the down-regulated anti-oncogenic microRNAs in the signature, was validated to decrease to about 0.25 fold in CTEPH patients. 3) ET-1 and TGFBR1 were direct targets of let-7b. Altering let-7b level influenced ET-1 and TGFBR1 expression in pulmonary arterial endothelial cells (PAECs) as well as the migration of PAECs and pulmonary arterial smooth muscle cells (PASMCs). These results suggested that CTEPH patients had aberrant microRNA signature which might provide some clue for pathogenesis study and biomarker screening. Reduced let-7b might be involved in the pathogenesis of CTEPH by

Simulations of chopper jitter at the LET neutron spectrometer at the ISIS TS2

DEFF Research Database (Denmark)

Klenø, Kaspar Hewitt; Lefmann, Kim; Willendrup, Peter Kjær

2014-01-01

The effect of uncertainty in chopper phasing (jitter) has been investigated for the high-resolution time-of-flight spectrometer LET at the ISIS second target station. The investigation is carried out using virtual experiments, with the neutron simulation package McStas, where the chopper jitter i...

Learning, Leading and Letting go of Control

DEFF Research Database (Denmark)

Jensen, Annie Aarup; Kjær-Rasmussen, Lone Krogh; Iversen, Ann-Merete

Learning, leading and letting go of control – Learner Led Approaches in Education Annie Aarup Jensen, Lone Krogh Kjær-Rasmussen, Ann-Merete Iversen and Anni Stavnskær Pedersen Abstract The aim of the paper is to introduce a new term in teaching in Higher Education: Learner Led Approaches...... in Education: LED. The sources of inspiration are many as are the experiences we draw from. Problem-based project work (PBL) being one, various classical teacher centered methods, and last but not least a variety of methods aiming towards developing creativity, innovational skills and entrepreneurship. LED...... is inspired by collaboration between professors from Aalborg University, Cornwall College and University College of Northern Denmark. Moravec (2008) claims that educational systems still operate in 1.0 or perhaps 2.0 mode while the surrounding cultures and societies operate in 3.0 mode. The amount...