Math Academy: Let's Go to the Mall! Explorations in Combinatorics. Book 5: Supplemental Math Materials for Grades 3-8

ERIC Educational Resources Information Center

Rimbey, Kimberly

2008-01-01

Created by teachers for teachers, the Math Academy tools and activities included in this booklet were designed to create hands-on activities and a fun learning environment for the teaching of mathematics to the students. This booklet contains the "Math Academy--Let's Go to the Mall! Explorations in Combinatorics," which teachers can use to enhance…

Analysis Tools (AT)

Treesearch

Larry J. Gangi

2006-01-01

The FIREMON Analysis Tools program is designed to let the user perform grouped or ungrouped summary calculations of single measurement plot data, or statistical comparisons of grouped or ungrouped plot data taken at different sampling periods. The program allows the user to create reports and graphs, save and print them, or cut and paste them into a word processor....

Developing Formal Object-oriented Requirements Specifications: A Model, Tool and Technique.

ERIC Educational Resources Information Center

Jackson, Robert B.; And Others

1995-01-01

Presents a formal object-oriented specification model (OSS) for computer software system development that is supported by a tool that automatically generates a prototype from an object-oriented analysis model (OSA) instance, lets the user examine the prototype, and permits the user to refine the OSA model instance to generate a requirements…

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

DTIC Science & Technology

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

A Compositional Relevance Model for Adaptive Information Retrieval

NASA Technical Reports Server (NTRS)

Mathe, Nathalie; Chen, James; Lu, Henry, Jr. (Technical Monitor)

1994-01-01

There is a growing need for rapid and effective access to information in large electronic documentation systems. Access can be facilitated if information relevant in the current problem solving context can be automatically supplied to the user. This includes information relevant to particular user profiles, tasks being performed, and problems being solved. However most of this knowledge on contextual relevance is not found within the contents of documents, and current hypermedia tools do not provide any easy mechanism to let users add this knowledge to their documents. We propose a compositional relevance network to automatically acquire the context in which previous information was found relevant. The model records information on the relevance of references based on user feedback for specific queries and contexts. It also generalizes such information to derive relevant references for similar queries and contexts. This model lets users filter information by context of relevance, build personalized views of documents over time, and share their views with other users. It also applies to any type of multimedia information. Compared to other approaches, it is less costly and doesn't require any a priori statistical computation, nor an extended training period. It is currently being implemented into the Computer Integrated Documentation system which enables integration of various technical documents in a hypertext framework.

Software Architecture for a Virtual Environment for Nano Scale Assembly (VENSA).

PubMed

Lee, Yong-Gu; Lyons, Kevin W; Feng, Shaw C

2004-01-01

A Virtual Environment (VE) uses multiple computer-generated media to let a user experience situations that are temporally and spatially prohibiting. The information flow between the user and the VE is bidirectional and the user can influence the environment. The software development of a VE requires orchestrating multiple peripherals and computers in a synchronized way in real time. Although a multitude of useful software components for VEs exists, many of these are packaged within a complex framework and can not be used separately. In this paper, an architecture is presented which is designed to let multiple frameworks work together while being shielded from the application program. This architecture, which is called the Virtual Environment for Nano Scale Assembly (VENSA), has been constructed for interfacing with an optical tweezers instrument for nanotechnology development. However, this approach can be generalized for most virtual environments. Through the use of VENSA, the programmer can rely on existing solutions and concentrate more on the application software design.

Software Architecture for a Virtual Environment for Nano Scale Assembly (VENSA)

PubMed Central

Lee, Yong-Gu; Lyons, Kevin W.; Feng, Shaw C.

2004-01-01

A Virtual Environment (VE) uses multiple computer-generated media to let a user experience situations that are temporally and spatially prohibiting. The information flow between the user and the VE is bidirectional and the user can influence the environment. The software development of a VE requires orchestrating multiple peripherals and computers in a synchronized way in real time. Although a multitude of useful software components for VEs exists, many of these are packaged within a complex framework and can not be used separately. In this paper, an architecture is presented which is designed to let multiple frameworks work together while being shielded from the application program. This architecture, which is called the Virtual Environment for Nano Scale Assembly (VENSA), has been constructed for interfacing with an optical tweezers instrument for nanotechnology development. However, this approach can be generalized for most virtual environments. Through the use of VENSA, the programmer can rely on existing solutions and concentrate more on the application software design. PMID:27366610

Single event upset suspectibility testing of the Xilinx Virtex II FPGA

NASA Technical Reports Server (NTRS)

Carmichael, C.; Swift, C.; Yui, G.

2002-01-01

Heavy ion testing of the Xilinx Virtex II was conducted on the configuration, block RAM and user flip flop cells to determine their static single-event upset susceptibility using LETs of 1.2 to 60 MeVcm^2/mg. A software program specifically designed to count errors in the FPGA was used to reveal L1/e, values (the LET at which the cross section is l/e times the saturation cross-section) and single-event functional-interrupt failures.

User-Centered Indexing for Adaptive Information Access

NASA Technical Reports Server (NTRS)

Chen, James R.; Mathe, Nathalie

1996-01-01

We are focusing on information access tasks characterized by large volume of hypermedia connected technical documents, a need for rapid and effective access to familiar information, and long-term interaction with evolving information. The problem for technical users is to build and maintain a personalized task-oriented model of the information to quickly access relevant information. We propose a solution which provides user-centered adaptive information retrieval and navigation. This solution supports users in customizing information access over time. It is complementary to information discovery methods which provide access to new information, since it lets users customize future access to previously found information. It relies on a technique, called Adaptive Relevance Network, which creates and maintains a complex indexing structure to represent personal user's information access maps organized by concepts. This technique is integrated within the Adaptive HyperMan system, which helps NASA Space Shuttle flight controllers organize and access large amount of information. It allows users to select and mark any part of a document as interesting, and to index that part with user-defined concepts. Users can then do subsequent retrieval of marked portions of documents. This functionality allows users to define and access personal collections of information, which are dynamically computed. The system also supports collaborative review by letting users share group access maps. The adaptive relevance network provides long-term adaptation based both on usage and on explicit user input. The indexing structure is dynamic and evolves over time. Leading and generalization support flexible retrieval of information under similar concepts. The network is geared towards more recent information access, and automatically manages its size in order to maintain rapid access when scaling up to large hypermedia space. We present results of simulated learning experiments.

New SECAA/ NSSDC Capabilities for Accessing ITM Data

NASA Astrophysics Data System (ADS)

Bilitza, D.; Papitashvili, N.; McGuire, R.

NASA's National Space Science Data Center (NSSDC) archives a large volume of data and models that are of relevance to the International Living with a Star (ILWS) project. Working with NSSDC its sister organization the Sun Earth Connection Active Archive (SECAA) has developed a number of data access and browse tools to facilitate user access to this important data source. For the most widely used empirical models (IRI, IGRF, MSIS/CIRA, AE/AP-8) Java-based web interfaces let users compute, list, plot, and download model parameters. We will report about recent enhancements and extensions of these data and model services in the area of ionospheric-thermospheric-mesospheric (ITM) physics. The ATMOWeb system (http://nssdc.gsfc.nasa.gov/atmoweb/) includes data from many of the ITM satellite missions of the sixties, seventies, and eighties (BE-B, DME-A, Alouette 2, AE-B, OGO-6, ISIS-1, ISIS-2, AEROS-A, AE-C, AE-D, AE-E, DE-2, and Hinotori). New capabilities of the ATMOWeb system include in addition to time series plots and data retrievals, ATMOWeb now lets user generate scatter plots and linear regression fits for any pair of parameters. Optional upper and lower boundaries let users filter out specific segments of the data and/or certain ranges of orbit parameters (altitude, longitude, local time, etc.). Data from TIMED is being added to the CDAWeb system, including new web service capabilities, to be available jointly with the broad scope of space physics data already served by CDAWeb. We will also present the newest version of the NSSDC/SECAA models web pages. The layout and sequence of these entry pages to the models catalog, archive, and web interfaces was greatly simplified and broad up-to-date.

Self-enforcing Private Inference Control

NASA Astrophysics Data System (ADS)

Yang, Yanjiang; Li, Yingjiu; Weng, Jian; Zhou, Jianying; Bao, Feng

Private inference control enables simultaneous enforcement of inference control and protection of users' query privacy. Private inference control is a useful tool for database applications, especially when users are increasingly concerned about individual privacy nowadays. However, protection of query privacy on top of inference control is a double-edged sword: without letting the database server know the content of user queries, users can easily launch DoS attacks. To assuage DoS attacks in private inference control, we propose the concept of self-enforcing private inference control, whose intuition is to force users to only make inference-free queries by enforcing inference control themselves; otherwise, penalty will inflict upon the violating users.

Professional Writing in the English Classroom: Let's Get Real--Using Usability to Connect Writers, Readers, and Texts

ERIC Educational Resources Information Center

Bush, Jonathan, Ed.; Zuidema, Leah, Ed.

2012-01-01

In professional writing, usability testing investigates how well users can find, understand, and use a document (Lannon). Usability testing involves gathering feedback from users, analyzing how successfully they used the document, and drawing on the test results to change or refine the design. From the authors' experiences as writers and teachers,…

SCAILET: An intelligent assistant for satellite ground terminal operations

NASA Technical Reports Server (NTRS)

Shahidi, A. K.; Crapo, J. A.; Schlegelmilch, R. F.; Reinhart, R. C.; Petrik, E. J.; Walters, J. L.; Jones, R. E.

1993-01-01

NASA Lewis Research Center has applied artificial intelligence to an advanced ground terminal. This software application is being deployed as an experimenter interface to the link evaluation terminal (LET) and was named Space Communication Artificial Intelligence for the Link Evaluation Terminal (SCAILET). The high-burst-rate (HBR) LET provides 30-GHz-transmitting and 20-GHz-receiving, 220-Mbps capability for wide band communications technology experiments with the Advanced Communication Technology Satellite (ACTS). The HBR-LET terminal consists of seven major subsystems. A minicomputer controls and monitors these subsystems through an IEEE-488 or RS-232 protocol interface. Programming scripts (test procedures defined by design engineers) configure the HBR-LET and permit data acquisition. However, the scripts are difficult to use, require a steep learning curve, are cryptic, and are hard to maintain. This discourages experimenters from utilizing the full capabilities of the HBR-LET system. An intelligent assistant module was developed as part of the SCAILET software. The intelligent assistant addresses critical experimenter needs by solving and resolving problems that are encountered during the configuring of the HBR-LET system. The intelligent assistant is a graphical user interface with an expert system running in the background. In order to further assist and familiarize an experimenter, an on-line hypertext documentation module was developed and included in the SCAILET software.

Geodetic Strain Analysis Tool

NASA Technical Reports Server (NTRS)

Kedar, Sharon; Baxter, Sean C.; Parker, Jay W.; Webb, Frank H.; Owen, Susan E.; Sibthorpe, Anthony J.; Dong, Danan

2011-01-01

A geodetic software analysis tool enables the user to analyze 2D crustal strain from geodetic ground motion, and create models of crustal deformation using a graphical interface. Users can use any geodetic measurements of ground motion and derive the 2D crustal strain interactively. This software also provides a forward-modeling tool that calculates a geodetic velocity and strain field for a given fault model, and lets the user compare the modeled strain field with the strain field obtained from the user s data. Users may change parameters on-the-fly and obtain a real-time recalculation of the resulting strain field. Four data products are computed: maximum shear, dilatation, shear angle, and principal components. The current view and data dependencies are processed first. The remaining data products and views are then computed in a round-robin fashion to anticipate view changes. When an analysis or display parameter is changed, the affected data products and views are invalidated and progressively re-displayed as available. This software is designed to facilitate the derivation of the strain fields from the GPS and strain meter data that sample it to facilitate the understanding of the strengths and weaknesses of the strain field derivation from continuous GPS (CGPS) and other geodetic data from a variety of tectonic settings, to converge on the "best practices" strain derivation strategy for the Solid Earth Science ESDR System (SESES) project given the CGPS station distribution in the western U.S., and to provide SESES users with a scientific and educational tool to explore the strain field on their own with user-defined parameters.

Charliecloud

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

Priedhorsky, Reid; Randles, Tim

Charliecloud is a set of scripts to let users run a virtual cluster of virtual machines (VMs) on a desktop or supercomputer. Key functions include: 1. Creating (typically by installing an operating system from vendor media) and updating VM images; 2. Running a single VM; 3. Running multiple VMs in a virtual cluster. The virtual machines can talk to one another over the network and (in some cases) the outside world. This is accomplished by calling external programs such as QEMU and the Virtual Distributed Ethernet (VDE) suite. The goal is to let users have a virtual cluster containing nodesmore » where they have privileged access, while isolating that privilege within the virtual cluster so it cannot affect the physical compute resources. Host configuration enforces security; this is not included in Charliecloud, though security guidelines are included in its documentation and Charliecloud is designed to facilitate such configuration. Charliecloud manages passing information from host computers into and out of the virtual machines, such as parameters of the virtual cluster, input data specified by the user, output data from virtual compute jobs, VM console display, and network connections (e.g., SSH or X11). Parameters for the virtual cluster (number of VMs, RAM and disk per VM, etc.) are specified by the user or gathered from the environment (e.g., SLURM environment variables). Example job scripts are included. These include computation examples (such as a "hello world" MPI job) as well as performance tests. They also include a security test script to verify that the virtual cluster is appropriately sandboxed. Tests include: 1. Pinging hosts inside and outside the virtual cluster to explore connectivity; 2. Port scans (again inside and outside) to see what services are available; 3. Sniffing tests to see what traffic is visible to running VMs; 4. IP address spoofing to test network functionality in this case; 5. File access tests to make sure host access permissions are enforced. This test script is not a comprehensive scanner and does not test for specific vulnerabilities. Importantly, no information about physical hosts or network topology is included in this script (or any of Charliecloud); while part of a sensible test, such information is specified by the user when the test is run. That is, one cannot learn anything about the LANL network or computing infrastructure by examining Charliecloud code.« less

Breast cancer stem-like cells are sensitized to tamoxifen induction of self-renewal inhibition with enforced Let-7c dependent on Wnt blocking

PubMed Central

Meng, Jinying; Wang, Jichang; Tang, Shou-Ching; Qin, Sida; Du, Ning; Li, Gang

2018-01-01

Let-7 microRNAs have been reported to have tumor suppressive functions; however, the effect of Let-7 when used in combination with chemotherapies is uncertain, but may have potential for use in clinical practice. In this study, we used RT-qPCR, western blot analysis, cell proliferation assay, flow cytometry analysis, immunohistochemistry (IHC) staining, luciferase assays, cell sorting analysis and xenografted tumor model to explore the role of Let-7 in the chemotherapy sensitivity of breast cancer stem cells. The findings of the current study indicated that Let-7 enhances the effects of endocrine therapy potentially by regulating the self-renewal of cancer stem cells. Let-7c increased the anticancer functions of tamoxifen and reduced the ratio of cancer stem-like cells (CSCs), sensitizing cells to therapy-induced repression in an estrogen receptor (ER)-dependent manner. Notably, Let-7 decreased the tumor formation ability of estrogen-treated breast CSCs in vivo and suppressed Wnt signaling, which further consolidated the previously hypothesis that Let-7 decreases the self-renewal ability, contributing to reduced tumor formation ability of stem cells. The suppressive effects exerted by Let-7 on stem-like cells involved Let-7c/ER/Wnt signaling, and the functions of Let-7c exerted with tamoxifen were dependent on ER. Taken together, the findings identified a biochemical and functional link between Let-7 and endocrine therapy in breast CSCs, which may facilitate clinical treatment in the future using delivery of suppressive Let-7. PMID:29336465

Adaptive User Profiles in Pervasive Advertising Environments

NASA Astrophysics Data System (ADS)

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.

Bistable switch in let-7 miRNA biogenesis pathway involving Lin28.

PubMed

Shi, Fei; Yu, Wenbao; Wang, Xia

2014-10-21

miRNAs are small noncoding RNAs capable of regulating gene expression at the post-transcriptional level. A growing body of evidence demonstrated that let-7 family of miRNAs, as one of the highly conserved miRNAs, plays an important role in cell differentiation and development, as well as tumor suppressor function depending on their levels of expression. To explore the physiological significance of let-7 in regulating cell fate decisions, we present a coarse grained model of let-7 biogenesis network, in which let-7 and its regulator Lin28 inhibit mutually. The dynamics of this minimal network architecture indicates that, as the concentration of Lin28 increases, the system undergoes a transition from monostability to a bistability and then to a one-way switch with increasing strength of positive feedback of let-7, while in the absence of Lin28 inhibition, the system loses bistability. Moreover, the ratio of degradation rates of let-7 and Lin28 is critical for the switching sensitivity and resistance to stimulus fluctuations. These findings may highlight why let-7 is required for normal gene expression in the context of embryonic development and oncogenesis, which will facilitate the development of approaches to exploit this regulatory pathway by manipulating Lin28/let-7 axis for novel treatments of human diseases.

Genome contact map explorer: a platform for the comparison, interactive visualization and analysis of genome contact maps

PubMed Central

Kumar, Rajendra; Sobhy, Haitham

2017-01-01

Abstract Hi-C experiments generate data in form of large genome contact maps (Hi-C maps). These show that chromosomes are arranged in a hierarchy of three-dimensional compartments. But to understand how these compartments form and by how much they affect genetic processes such as gene regulation, biologists and bioinformaticians need efficient tools to visualize and analyze Hi-C data. However, this is technically challenging because these maps are big. In this paper, we remedied this problem, partly by implementing an efficient file format and developed the genome contact map explorer platform. Apart from tools to process Hi-C data, such as normalization methods and a programmable interface, we made a graphical interface that let users browse, scroll and zoom Hi-C maps to visually search for patterns in the Hi-C data. In the software, it is also possible to browse several maps simultaneously and plot related genomic data. The software is openly accessible to the scientific community. PMID:28973466

Role-Based And Adaptive User Interface Designs In A Teledermatology Consult System: A Way To Secure And A Way To Enhance

PubMed Central

Lin, Yi-Jung; Speedie, Stuart

2003-01-01

User interface design is one of the most important parts of developing applications. Nowadays, a quality user interface must not only accommodate interaction between machines and users, but also needs to recognize the differences and provide functionalities for users from role-to-role or even individual-to-individual. With the web-based application of our Teledermatology consult system, the development environment provides us highly useful opportunities to create dynamic user interfaces, which lets us to gain greater access control and has the potential to increase efficiency of the system. We will describe the two models of user interfaces in our system: Role-based and Adaptive. PMID:14728419

Designing an operator interface? Consider user`s `psychology`

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

Toffer, D.E.

The modern operator interface is a channel of communication between operators and the plant that, ideally, provides them with information necessary to keep the plant running at maximum efficiency. Advances in automation technology have increased information flow from the field to the screen. New and improved Supervisory Control and Data Acquisition (SCADA) packages provide designers with powerful and open design considerations. All too often, however, systems go to the field designed for the software rather than the operator. Plant operators` jobs have changed fundamentally, from controlling their plants from out in the field to doing so from within control rooms.more » Control room-based operation does not denote idleness. Trained operators should be engaged in examination of plant status and cognitive evaluation of plant efficiencies. Designers who are extremely computer literate, often do not consider demographics of field operators. Many field operators have little knowledge of modern computer systems. As a result, they do not take full advantage of the interface`s capabilities. Designers often fail to understand the true nature of how operators run their plants. To aid field operators, designers must provide familiar controls and intuitive choices. To achieve success in interface design, it is necessary to understand the ways in which humans think conceptually, and to understand how they process this information physically. The physical and the conceptual are closely related when working with any type of interface. Designers should ask themselves: {open_quotes}What type of information is useful to the field operator?{close_quotes} Let`s explore an integration model that contains the following key elements: (1) Easily navigated menus; (2) Reduced chances for misunderstanding; (3) Accurate representations of the plant or operation; (4) Consistent and predictable operation; (5) A pleasant and engaging interface that conforms to the operator`s expectations. 4 figs.« less

EarthCube Data Discovery Hub: Enhancing, Curating and Finding Data across Multiple Geoscience Data Sources.

NASA Astrophysics Data System (ADS)

Zaslavsky, I.; Valentine, D.; Richard, S. M.; Gupta, A.; Meier, O.; Peucker-Ehrenbrink, B.; Hudman, G.; Stocks, K. I.; Hsu, L.; Whitenack, T.; Grethe, J. S.; Ozyurt, I. B.

2017-12-01

EarthCube Data Discovery Hub (DDH) is an EarthCube Building Block project using technologies developed in CINERGI (Community Inventory of EarthCube Resources for Geoscience Interoperability) to enable geoscience users to explore a growing portfolio of EarthCube-created and other geoscience-related resources. Over 1 million metadata records are available for discovery through the project portal (cinergi.sdsc.edu). These records are retrieved from data facilities, including federal, state and academic sources, or contributed by geoscientists through workshops, surveys, or other channels. CINERGI metadata augmentation pipeline components 1) provide semantic enhancement based on a large ontology of geoscience terms, using text analytics to generate keywords with references to ontology classes, 2) add spatial extents based on place names found in the metadata record, and 3) add organization identifiers to the metadata. The records are indexed and can be searched via a web portal and standard search APIs. The added metadata content improves discoverability and interoperability of the registered resources. Specifically, the addition of ontology-anchored keywords enables faceted browsing and lets users navigate to datasets related by variables measured, equipment used, science domain, processes described, geospatial features studied, and other dataset characteristics that are generated by the pipeline. DDH also lets data curators access and edit the automatically generated metadata records using the CINERGI metadata editor, accept or reject the enhanced metadata content, and consider it in updating their metadata descriptions. We consider several complex data discovery workflows, in environmental seismology (quantifying sediment and water fluxes using seismic data), marine biology (determining available temperature, location, weather and bleaching characteristics of coral reefs related to measurements in a given coral reef survey), and river geochemistry (discovering observations relevant to geochemical measurements outside the tidal zone, given specific discharge conditions).

An Organizational Effectiveness Officer Tackles a Management Job: A follow-Up OE Case Study

DTIC Science & Technology

1981-06-01

time, the COPPER "users manual " had not been updated to reflect the current methods and procedures of the PPSD. RAJ Johnson felt that documentation of...Users’ Manual , now known as PPSD Users’ Manual , to document every action and show document ilow with a flow chart. Also prior to implementing the change...comments is a document to work from. I’ll use it from my level, but let’s push it down in the organizacion ." When interviewed in December, RAJ Johnson was

The NeMO Explorer Web Site: Interactive Exploration of a Recent Submarine Eruption and Hydrothermal Vents, Axial Volcano, Juan de Fuca Ridge

NASA Astrophysics Data System (ADS)

Weiland, C.; Chadwick, W. W.; Embley, R. W.

2001-12-01

To help visualize the submarine volcanic landscape at NOAA's New Millennium Observatory (NeMO), we have created the NeMO Explorer web site: http://www.pmel.noaa.gov/vents/nemo/explorer.html. This web site takes visitors a mile down beneath the ocean surface to explore Axial Seamount, an active submarine volcano 300 miles off the Oregon coast. We use virtual reality to put visitors in a photorealistic 3-D model of the seafloor that lets them view hydrothermal vents and fresh lava flows as if they were really on the seafloor. At each of six virtual sites there is an animated tour and a 360o panorama in which users can view the volcanic landscape and see biological communities within a spatially accurate context. From the six sites there are hyperlinks to 50 video clips taken by a remotely operated vehicle. Each virtual site concentrates on a different topic, including the dynamics of the 1998 eruption at Axial volcano (Rumbleometer), high-temperature hydrothermal vents (CASM and ASHES), diffuse hydrothermal venting (Marker33), subsurface microbial blooms (The Pit), and the boundary between old and new lavas (Castle vent). In addition to exploring the region geographically, visitors can also explore the web site via geological concepts. The concepts gallery lets you quickly find information about mid-ocean ridges, hydrothermal vents, vent fauna, lava morphology, and more. Of particular interest is an animation of the January 1998 eruption, which shows the rapid inflation (by over 3 m) and draining of the sheet flow. For more info see Fox et al., Nature, v.412, p.727, 2001. This project was funded by NOAA's High Performance Computing and Communication (HPCC) and Vents Programs. Our goal is to present a representative portion of the vast collection of NOAA's multimedia imagery to the public in a way that is easy to use and understand. These data are particularly challenging to present because of their high data rates and low contextual information. The 3-D models create effective context and new video technology allows us to present good quality video at lower data rates. Related curriculum materials for middle- and high-school students are also available from the NeMO web site at http://www.pmel.noaa.gov/vents/nemo/education.html. >http://www.pmel.noaa.gov/vents/nemo/explorer.html

Multiverse data-flow control.

PubMed

Schindler, Benjamin; Waser, Jürgen; Ribičić, Hrvoje; Fuchs, Raphael; Peikert, Ronald

2013-06-01

In this paper, we present a data-flow system which supports comparative analysis of time-dependent data and interactive simulation steering. The system creates data on-the-fly to allow for the exploration of different parameters and the investigation of multiple scenarios. Existing data-flow architectures provide no generic approach to handle modules that perform complex temporal processing such as particle tracing or statistical analysis over time. Moreover, there is no solution to create and manage module data, which is associated with alternative scenarios. Our solution is based on generic data-flow algorithms to automate this process, enabling elaborate data-flow procedures, such as simulation, temporal integration or data aggregation over many time steps in many worlds. To hide the complexity from the user, we extend the World Lines interaction techniques to control the novel data-flow architecture. The concept of multiple, special-purpose cursors is introduced to let users intuitively navigate through time and alternative scenarios. Users specify only what they want to see, the decision which data are required is handled automatically. The concepts are explained by taking the example of the simulation and analysis of material transport in levee-breach scenarios. To strengthen the general applicability, we demonstrate the investigation of vortices in an offline-simulated dam-break data set.

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

NASA Astrophysics Data System (ADS)

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.

The value of metaphorical reasoning in bioethics: An empirical-ethical study.

PubMed

Olsman, Erik; Veneberg, Bert; van Alfen, Claudia; Touwen, Dorothea

2017-01-01

Metaphors are often used within the context of ethics and healthcare but have hardly been explored in relation to moral reasoning. To describe a central set of metaphors in one case and to explore their contribution to moral reasoning. Semi-structured interviews were conducted with 16 parents of a child suffering from the neurodegenerative disease CLN3. The interviews were recorded, transcribed, and metaphors were analyzed. The researchers wrote memos and discussed about their analyses until they reached consensus. Ethical considerations: Participants gave oral and written consent and their confidentiality and anonymity were respected. A central set of metaphors referred to the semantic field of the hands and arms and consisted of two central metaphors that existed in a dialectical relationship: grasping versus letting go. Participants used these metaphors to describe their child's experiences, who had to "let go" of abilities, while "clinging" to structures and the relationship with their parent(s). They also used it to describe their own experiences: participants tried to "grab" the good moments with their child and had to "let go" of their child when (s)he approached death. Participants, in addition, "held" onto caring for their child while being confronted with the necessity to "let go" of this care, leaving it to professional caregivers. The ethical analysis of the findings shows that thinking in terms of the dialectical relationship between "grasping" and "letting go" helps professional caregivers to critically think about images of good care for children with CLN3. It also helps them to bear witness to the vulnerable, dependent, and embodied nature of the moral self of children with CLN3 and their parents. Metaphorical reasoning may support the inclusion of marginalized perspectives in moral reasoning. Future studies should further explore the contribution of metaphorical reasoning to moral reasoning in other cases.

MAPPER: A personal computer map projection tool

NASA Technical Reports Server (NTRS)

Bailey, Steven A.

1993-01-01

MAPPER is a set of software tools designed to let users create and manipulate map projections on a personal computer (PC). The capability exists to generate five popular map projections. These include azimuthal, cylindrical, mercator, lambert, and sinusoidal projections. Data for projections are contained in five coordinate databases at various resolutions. MAPPER is managed by a system of pull-down windows. This interface allows the user to intuitively create, view and export maps to other platforms.

Edible Oil Barriers for Treatment of Perchlorate Contaminated Groundwater

DTIC Science & Technology

2006-02-16

perchlorate is relatively recent. Work performed in soil at Longhorn Army Ammunition Plant in Texas identified chicken manure, cow manure, and...Missile Plant , NC Pilot July-Aug. 2004 Recirculation of emulsion through source area Other DoD Facilities Confidential Site, MD Pilot Oct...G.M. Birk, 2004. A Dash of Oil and Let Marinate. Pollution Engineering, May 2004, pages 30-34. 6.3 End-User Issues Potential end users of the

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

NASA Astrophysics Data System (ADS)

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.

Letting Go and Letting the Angels Grow: Using Etienne Wenger's Community of Practice Theory to Facilitate Teacher Education

ERIC Educational Resources Information Center

Breen, Paul

2015-01-01

This paper describes a small-scale qualitative research study conducted within a community of English Language teachers, and explores how teacher development workshops can be used to foster or cultivate Communities of Practice. The study was situated in a Language Centre within the domain of UK Higher Education where there was an institutional…

Hsa-let-7c controls the committed differentiation of IGF-1-treated mesenchymal stem cells derived from dental pulps by targeting IGF-1R via the MAPK pathways.

PubMed

Liu, Gen-Xia; Ma, Shu; Li, Yao; Yu, Yan; Zhou, Yi-Xiang; Lu, Ya-Die; Jin, Lin; Wang, Zi-Lu; Yu, Jin-Hua

2018-04-13

The putative tumor suppressor microRNA let-7c is extensively associated with the biological properties of cancer cells. However, the potential involvement of let-7c in the differentiation of mesenchymal stem cells has not been fully explored. In this study, we investigated the influence of hsa-let-7c (let-7c) on the proliferation and differentiation of human dental pulp-derived mesenchymal stem cells (DPMSCs) treated with insulin-like growth factor 1 (IGF-1) via flow cytometry, CCK-8 assays, alizarin red staining, real-time RT-PCR, and western blotting. In general, the proliferative capabilities and cell viability of DPMSCs were not significantly affected by the overexpression or deletion of let-7c. However, overexpression of let-7c significantly inhibited the expression of IGF-1 receptor (IGF-1R) and downregulated the osteo/odontogenic differentiation of DPMSCs, as indicated by decreased levels of several osteo/odontogenic markers (osteocalcin, osterix, runt-related transcription factor 2, dentin sialophosphoprotein, dentin sialoprotein, alkaline phosphatase, type 1 collagen, and dentin matrix protein 1) in IGF-1-treated DPMSCs. Inversely, deletion of let-7c resulted in increased IGF-1R levels and enhanced osteo/odontogenic differentiation. Furthermore, the ERK, JNK, and P38 MAPK pathways were significantly inhibited following the overexpression of let-7c in DPMSCs. Deletion of let-7c promoted the activation of the JNK and P38 MAPK pathways. Our cumulative findings indicate that Let-7c can inhibit the osteo/odontogenic differentiation of IGF-1-treated DPMSCs by targeting IGF-1R via the JNK/P38 MAPK signaling pathways.

[Role of let-7 in maintaining characteristics of breast cancer stem cells].

PubMed

Sun, Xin; Fan, Chong; Hu, Li-juan; Du, Ning; Xu, Chong-wen; Ren, Hong

2012-08-01

To observe the expression of let-7 in breast cancer stem cells and explore the role of let-7 in maintaining the characteristics of breast cancer stem cells. We separated breast cancer stem cells (SP and NSP) from MCF-7 cell line using SP sorting, and observed the expression of let-7a/b/c on SP and NSP cells using quantitative real-time PCR and the expressions of Ras and ERK using Western blotting to study the mechanism by which let-7 maintains the characteristics of breast cancer stem cells. The SP cells accounted for 3.3% in MCF-7 cells, however, the rate dropped to 0.4% when verapamil was added into the process of seperation. The level of Let-7a/b/c in SP cells were lower than that in NSP cells, and among let-7 miRNAs, let-7b/c showed the most obvious difference. The expressions of t-Ras and t-ERK showed no difference between SP and NSP cells, nevertheless, the expressions of p-Ras, p-ERK were higher in SP cells than in NSP cells. SP sorting is an effective method to separate cancer stem cells. There do exist cancer stem cells in MCF-7 breast cancer cell line. Let-7 is down-regulated in SP cells, and the down-regulation makes let-7 lose the opportunity to restrain Ras mRNA, finally, p-Ras and p-ERK are activated. They play an important role in maintaining the characteristics of breast cancer stem cells.

Dive and Explore: An Interactive Web Visualization that Simulates Making an ROV Dive to an Active Submarine Volcano

NASA Astrophysics Data System (ADS)

Weiland, C.; Chadwick, W. W.

2004-12-01

Several years ago we created an exciting and engaging multimedia exhibit for the Hatfield Marine Science Center that lets visitors simulate making a dive to the seafloor with the remotely operated vehicle (ROV) named ROPOS. The exhibit immerses the user in an interactive experience that is naturally fun but also educational. The public display is located at the Hatfield Marine Science Visitor Center in Newport, Oregon. We are now completing a revision to the project that will make this engaging virtual exploration accessible to a much larger audience. With minor modifications we will be able to put the exhibit onto the world wide web so that any person with internet access can view and learn about exciting volcanic and hydrothermal activity at Axial Seamount on the Juan de Fuca Ridge. The modifications address some cosmetic and logistic ISSUES confronted in the museum environment, but will mainly involve compressing video clips so they can be delivered more efficiently over the internet. The web version, like the museum version, will allow users to choose from 1 of 3 different dives sites in the caldera of Axial Volcano. The dives are based on real seafloor settings at Axial seamount, an active submarine volcano on the Juan de Fuca Ridge (NE Pacific) that is also the location of a seafloor observatory called NeMO. Once a dive is chosen, then the user watches ROPOS being deployed and then arrives into a 3-D computer-generated seafloor environment that is based on the real world but is easier to visualize and navigate. Once on the bottom, the user is placed within a 360 degree panorama and can look in all directions by manipulating the computer mouse. By clicking on markers embedded in the scene, the user can then either move to other panorama locations via movies that travel through the 3-D virtual environment, or they can play video clips from actual ROPOS dives specifically related to that scene. Audio accompanying the video clips informs the user where they are going or what they are looking at. After the user is finished exploring the dive site they end the dive by leaving the bottom and watching the ROV being recovered onto the ship at the surface. Within the three simulated dives there are a total of 6 arrival and departure movies, 7 seafloor panoramas, 12 travel movies, and 23 ROPOS video clips. This virtual exploration is part of the NeMO web site and will be at this URL http://www.pmel.noaa.gov/vents/dive.html

Let Me Show You How It’s Done! Desktop Sharing for Distance Learning from the D. Samuel Gottesman Library

PubMed Central

Glassman, Nancy R.; Habousha, Racheline G.; Minuti, Aurelia; Schwartz, Rachel; Sorensen, Karen

2009-01-01

Due to the proliferation of electronic resources, fewer users visit the library. Traditional classroom instruction and in-person consultations are no longer sufficient in assisting library users. Librarians are constantly seeking new ways to interact with patrons and facilitate efficient use of electronic resources. This article describes the development, implementation, and evaluation of a project in which desktop-sharing software was used to reach out to users at remote locations. Various ways of using this tool are described, and challenges and implications for future expansion are discussed. PMID:20183031

EPA UNMIX 6.0 USER GUIDE

EPA Science Inventory

The underlying philosophy of Unmix is to let the data speak for itself. Unmix seeks to solve the general mixture problem where the data are assumed to be a linear combination of an unknown number of sources of unknown composition, which contribute an unknown amount to each sample...

EXOMARS IRAS (DOSE) radiation measurements.

NASA Astrophysics Data System (ADS)

Federico, C.; Di Lellis, A. M.; Fonte, S.; Pauselli, C.; Reitz, G.; Beaujean, R.

The characterization and the study of the radiations on their interaction with organic matter is of great interest in view of the human exploration on Mars. The Ionizing RAdiation Sensor (IRAS) selected in the frame of the ExoMars/Pasteur ESA mission is a lightweight particle spectrometer combining various techniques of radiation detection in space. It characterizes the first time the radiation environment on the Mars surface, and provide dose and dose equivalent rates as precursor information absolutely necessary to develop ways to mitigate the radiation risks for future human exploration on Mars. The Martian radiation levels are much higher than those found on Earth and they are relatively low for space. Measurements on the surface will show if they are similar or not to those seen in orbit (modified by the presence of ``albedo'' neutrons produced in the regolith and by the thin Martian atmosphere). IRAS consists of a telescope based on segmented silicon detectors of about 40\\userk\\milli\\metre\\user;k diameter and 300\\user;k\\micro\\metre\\user;k thickness, a segmented organic scintillator, and of a thermoluminescence dosimeter. The telescope will continuously monitor temporal variation of the particle count rate, the dose rate, particle and LET (Linear Energy Transfer) spectra. Tissue equivalent BC430 scintillator material will be used to measure the neutron dose. Neutrons are selected by a criteria requiring no signal in the anti-coincidence. Last, the passive thermoluminescence dosimeter, based on LiF:Mg detectors, regardless the on board operation timing, will measure the total dose accumulated during the exposure period and due to beta and gamma radiation, with a responsivity very close to that of a human tissue.

Multiple-Objective Stepwise Calibration Using Luca

USGS Publications Warehouse

Hay, Lauren E.; Umemoto, Makiko

2007-01-01

This report documents Luca (Let us calibrate), a multiple-objective, stepwise, automated procedure for hydrologic model calibration and the associated graphical user interface (GUI). Luca is a wizard-style user-friendly GUI that provides an easy systematic way of building and executing a calibration procedure. The calibration procedure uses the Shuffled Complex Evolution global search algorithm to calibrate any model compiled with the U.S. Geological Survey's Modular Modeling System. This process assures that intermediate and final states of the model are simulated consistently with measured values.

Development of a Web-Based Distributed Interactive Simulation (DIS) Environment Using JavaScript

DTIC Science & Technology

2014-09-01

scripting that let users change or interact with web content depending on user input, which is in contrast with server-side scripts such as PHP, Java and...transfer, DIS usually broadcasts or multicasts its PDUs based on UDP socket. 3. JavaScript JavaScript is the scripting language of the web, and all...IDE) for developing desktop, mobile and web applications with JAVA , C++, HTML5, JavaScript and more. b. Framework The DIS implementation of

The sweet-home project: audio technology in smart homes to improve well-being and reliance.

PubMed

Vacher, Michel; Istrate, Dan; Portet, François; Joubert, Thierry; Chevalier, Thierry; Smidtas, Serge; Meillon, Brigitte; Lecouteux, Benjamin; Sehili, Mohamed; Chahuara, Pedro; Méniard, Sylvain

2011-01-01

The Sweet-Home project aims at providing audio-based interaction technology that lets the user have full control over their home environment, at detecting distress situations and at easing the social inclusion of the elderly and frail population. This paper presents an overview of the project focusing on the multimodal sound corpus acquisition and labelling and on the investigated techniques for speech and sound recognition. The user study and the recognition performances show the interest of this audio technology.

Uniform Interfaces for Distributed Systems.

DTIC Science & Technology

1980-05-01

in data str ’.ctures on stable storage (such as disk). The Virtual Terminals associated with a particular user (i.e., rM display terminal) are all...vec MESSAGESIZE let error = nil [S ReceiveAny (msg) // The copy is made so that lower-level routines may // munge the message template without losing

Let's Not Forget: Learning Analytics Are about Learning

ERIC Educational Resources Information Center

Gaševic, Dragan; Dawson, Shane; Siemens, George

2015-01-01

The analysis of data collected from the interaction of users with educational and information technology has attracted much attention as a promising approach for advancing our understanding of the learning process. This promise motivated the emergence of the new research field, learning analytics, and its closely related discipline, educational…

Character Sets for PLATO/NovaNET: An Expository Catalog.

ERIC Educational Resources Information Center

Gilpin, John B.

The PLATO and NovaNET computer-based instructional systems use a fixed system character set ("normal font") and an author-definable character set ("alternate font"). The alternate font lets the author construct his own symbols and bitmapped pictures. This expository catalog allows users to determine quickly (1) whether there is…

The use, misuse and abuse of dabigatran.

PubMed

Attia, John R; Pearce, Robert

2013-04-15

The tale of dabigatran sounds some cautionary notes about proper critical appraisal of new randomised controlled trials,care in deciding on the generalisability of results, judicious screening of patients and lessons about the politics around increasingly lucrative drugs. The old lesson of caveat utilitor still holds: let the user beware!

Do "Digital Certificates" Hold the Key to Colleges' On-Line Activities?

ERIC Educational Resources Information Center

Olsen, Florence

1999-01-01

Examines the increasing use of "digital certificates" to validate computer user identity in various applications on college and university campuses, including letting students register for courses, monitoring access to Internet2, and monitoring access to databases and electronic journals. The methodology has been developed by the…

Exploring system interconnection architectures with VIPACES: from direct connections to NOCs

NASA Astrophysics Data System (ADS)

Sánchez-Peña, Armando; Carballo, Pedro P.; Núñez, Antonio

2007-05-01

This paper presents a simple environment for the verification of AMBA 3 AXI systems in Verification IP (VIP) production called VIPACES (Verification Interface Primitives for the development of AXI Compliant Elements and Systems). These primitives are presented as a not compiled library written in SystemC where interfaces are the core of the library. The definition of interfaces instead of generic modules let the user construct custom modules improving the resources spent during the verification phase as well as easily adapting his modules to the AMBA 3 AXI protocol. This topic is the main discussion in the VIPACES library. The paper focuses on comparing and contrasting the main interconnection schemes for AMBA 3 AXI as modeled by VIPACES. For assessing these results we propose a validation scenario with a particular architecture belonging to the domain of MPEG4 video decoding, which is compound by an AXI bus connecting an IDCT and other processing resources.

Differential Processing of let-7a Precursors Influences RRM2 Expression and Chemosensitivity in Pancreatic Cancer: Role of LIN-28 and SET Oncoprotein

PubMed Central

Bhutia, Yangzom Doma; Hung, Sau Wai; Krentz, Madeline; Patel, Dimal; Lovin, Dylan; Manoharan, Radhika; Thomson, J. Michael; Govindarajan, Rajgopal

2013-01-01

Overexpression of ribonucleotide reductase subunit M2 (RRM2), involved in deoxyribonucleotide synthesis, drives the chemoresistance of pancreatic cancer to nucleoside analogs (e.g., gemcitabine). While silencing RRM2 by synthetic means has shown promise in reducing chemoresistance, targeting endogenous molecules, especially microRNAs (miRNAs), to advance chemotherapeutic outcomes has been poorly explored. Based on computational predictions, we hypothesized that the let-7 tumor suppressor miRNAs will inhibit RRM2-mediated gemcitabine chemoresistance in pancreatic cancer. Reduced expression of the majority of let-7 miRNAs with an inverse relationship to RRM2 expression was identified in innately gemcitabine-resistant pancreatic cancer cell lines. Direct binding of let-7 miRNAs to the 3′ UTR of RRM2 transcripts identified post-transcriptional regulation of RRM2 influencing gemcitabine chemosensitivity. Intriguingly, overexpression of human precursor-let-7 miRNAs led to differential RRM2 expression and chemosensitivity responses in a poorly differentiated pancreatic cancer cell line, MIA PaCa-2. Defective processing of let-7a precursors to mature forms, in part, explained the discrepancies observed with let-7a expressional outcomes. Consistently, the ratios of mature to precursor let-7a were progressively reduced in gemcitabine-sensitive L3.6pl and Capan-1 cell lines induced to acquire gemcitabine resistance. Besides known regulators of let-7 biogenesis (e.g., LIN-28), short hairpin RNA library screening identified several novel RNA binding proteins, including the SET oncoprotein, to differentially impact let-7 biogenesis and chemosensitivity in gemcitabine-sensitive versus -resistant pancreatic cancer cells. Further, LIN-28 and SET knockdown in the cells led to profound reductions in cellular proliferation and colony-formation capacities. Finally, defective processing of let-7a precursors with a positive correlation to RRM2 overexpression was identified in patient-derived pancreatic ductal adenocarcinoma (PDAC) tissues. These data demonstrate an intricate post-transcriptional regulation of RRM2 and chemosensitivity by let-7a and that the manipulation of regulatory proteins involved in let-7a transcription/processing may provide a mechanism for improving chemotherapeutic and/or tumor growth control responses in pancreatic cancer. PMID:23335963

Planetary Data Systems (PDS) Imaging Node Atlas II

NASA Technical Reports Server (NTRS)

Stanboli, Alice; McAuley, James M.

2013-01-01

The Planetary Image Atlas (PIA) is a Rich Internet Application (RIA) that serves planetary imaging data to the science community and the general public. PIA also utilizes the USGS Unified Planetary Coordinate system (UPC) and the on-Mars map server. The Atlas was designed to provide the ability to search and filter through greater than 8 million planetary image files. This software is a three-tier Web application that contains a search engine backend (MySQL, JAVA), Web service interface (SOAP) between server and client, and a GWT Google Maps API client front end. This application allows for the search, retrieval, and download of planetary images and associated meta-data from the following missions: 2001 Mars Odyssey, Cassini, Galileo, LCROSS, Lunar Reconnaissance Orbiter, Mars Exploration Rover, Mars Express, Magellan, Mars Global Surveyor, Mars Pathfinder, Mars Reconnaissance Orbiter, MESSENGER, Phoe nix, Viking Lander, Viking Orbiter, and Voyager. The Atlas utilizes the UPC to translate mission-specific coordinate systems into a unified coordinate system, allowing the end user to query across missions of similar targets. If desired, the end user can also use a mission-specific view of the Atlas. The mission-specific views rely on the same code base. This application is a major improvement over the initial version of the Planetary Image Atlas. It is a multi-mission search engine. This tool includes both basic and advanced search capabilities, providing a product search tool to interrogate the collection of planetary images. This tool lets the end user query information about each image, and ignores the data that the user has no interest in. Users can reduce the number of images to look at by defining an area of interest with latitude and longitude ranges.

Computer Architecture's Changing Role in Rebooting Computing

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

DeBenedictis, Erik P.

In this paper, Windows 95 started the Wintel era, in which Microsoft Windows running on Intel x86 microprocessors dominated the computer industry and changed the world. Retaining the x86 instruction set across many generations let users buy new and more capable microprocessors without having to buy software to work with new architectures.

So You Need Information About Mexican Americans? Let ERIC Help!

ERIC Educational Resources Information Center

Quezada, Manuela L., Comp.; Chabran, Richard, Comp.

The guide is intended to explain and demonstrate by example how to use the Educational Resources Information Center (ERIC) system, especially to find information pertaining to Mexican Americans. An overview of ERIC and ERIC/CRESS (ERIC Clearinghouse on Rural Education and Small Schools) is given, noting definitions, potential users, types of…

NERISK: AN EXPERT SYSTEM TO ENHANCE THE INTEGRATION OF PESTICIDES WITH ARTHROPOD BIOLOGICAL CONTROL

EPA Science Inventory

An expert system termed NERISK was developed to evaluate the effects of pesticides on arthropod predators and parasitoids in a variety of agroecosystems. ased on a shell system (RECOG) with minor coding modifications, the system was designed to let even a novice user access the v...

Computer Architecture's Changing Role in Rebooting Computing

DOE PAGES

DeBenedictis, Erik P.

2017-04-26

In this paper, Windows 95 started the Wintel era, in which Microsoft Windows running on Intel x86 microprocessors dominated the computer industry and changed the world. Retaining the x86 instruction set across many generations let users buy new and more capable microprocessors without having to buy software to work with new architectures.

VoIP to the Rescue

ERIC Educational Resources Information Center

Milner, Jacob

2005-01-01

Voice over Internet Protocol (VoIP) is everywhere. The technology lets users make and receive phone calls over the Internet, transporting voice traffic alongside data traffic such as instant messages (IMs) and e-mail. While the number of consumer customers using VoIP increases every week, the technology is finding its way into K-12 education as…

Let ABE Do It. Basic Education in the Workplace.

ERIC Educational Resources Information Center

Mark, Jorie Lester, Ed.

This publication highlights business, industry, union, and Job Training Partnership Act (JTPA)-supported efforts to provide public and private employees, as well as some prospective employees, with the basic literacy skills they need to perform in the workplace. Basic or remedial education users listed in this directory include 198 companies or…

A Network of Chromatin Factors Is Regulating the Transition to Postembryonic Development in Caenorhabditis elegans

PubMed Central

Erdelyi, Peter; Wang, Xing; Suleski, Marina; Wicky, Chantal

2016-01-01

Mi2 proteins are evolutionarily conserved, ATP-dependent chromatin remodelers of the CHD family that play key roles in stem cell differentiation and reprogramming. In Caenorhabditis elegans, the let-418 gene encodes one of the two Mi2 homologs, which is part of at least two chromatin complexes, namely the Nucleosome Remodeling and histone Deacetylase (NuRD) complex and the MEC complex, and functions in larval development, vulval morphogenesis, lifespan regulation, and cell fate determination. To explore the mechanisms involved in the action of LET-418/Mi2, we performed a genome-wide RNA interference (RNAi) screen for suppressors of early larval arrest associated with let-418 mutations. We identified 29 suppressor genes, of which 24 encode chromatin regulators, mostly orthologs of proteins present in transcriptional activator complexes. The remaining five genes vary broadly in their predicted functions. All suppressor genes could suppress multiple aspects of the let-418 phenotype, including developmental arrest and ectopic expression of germline genes in the soma. Analysis of available transcriptomic data and quantitative PCR revealed that LET-418 and the suppressors of early larval arrest are regulating common target genes. These suppressors might represent direct competitors of LET-418 complexes for chromatin regulation of crucial genes involved in the transition to postembryonic development. PMID:28007841

A Network of Chromatin Factors Is Regulating the Transition to Postembryonic Development in Caenorhabditis elegans.

PubMed

Erdelyi, Peter; Wang, Xing; Suleski, Marina; Wicky, Chantal

2017-02-09

Mi2 proteins are evolutionarily conserved, ATP-dependent chromatin remodelers of the CHD family that play key roles in stem cell differentiation and reprogramming. In Caenorhabditis elegans , the let-418 gene encodes one of the two Mi2 homologs, which is part of at least two chromatin complexes, namely the Nucleosome Remodeling and histone Deacetylase (NuRD) complex and the MEC complex, and functions in larval development, vulval morphogenesis, lifespan regulation, and cell fate determination. To explore the mechanisms involved in the action of LET-418/Mi2, we performed a genome-wide RNA interference (RNAi) screen for suppressors of early larval arrest associated with let-418 mutations. We identified 29 suppressor genes, of which 24 encode chromatin regulators, mostly orthologs of proteins present in transcriptional activator complexes. The remaining five genes vary broadly in their predicted functions. All suppressor genes could suppress multiple aspects of the let-418 phenotype, including developmental arrest and ectopic expression of germline genes in the soma. Analysis of available transcriptomic data and quantitative PCR revealed that LET-418 and the suppressors of early larval arrest are regulating common target genes. These suppressors might represent direct competitors of LET-418 complexes for chromatin regulation of crucial genes involved in the transition to postembryonic development. Copyright © 2017 Erdelyi et al.

Molecular characterisation of murine acute myeloid leukaemia induced by 56Fe ion and 137Cs gamma ray irradiation.

PubMed

Steffen, Leta S; Bacher, Jeffery W; Peng, Yuanlin; Le, Phuong N; Ding, Liang-Hao; Genik, Paula C; Ray, F Andrew; Bedford, Joel S; Fallgren, Christina M; Bailey, Susan M; Ullrich, Robert L; Weil, Michael M; Story, Michael D

2013-01-01

Exposure to sparsely ionising gamma- or X-ray irradiation is known to increase the risk of leukaemia in humans. However, heavy ion radiotherapy and extended space exploration will expose humans to densely ionising high linear energy transfer (LET) radiation for which there is currently no understanding of leukaemia risk. Murine models have implicated chromosomal deletion that includes the hematopoietic transcription factor gene, PU.1 (Sfpi1), and point mutation of the second PU.1 allele as the primary cause of low-LET radiation-induced murine acute myeloid leukaemia (rAML). Using array comparative genomic hybridisation, fluorescence in situ hybridisation and high resolution melt analysis, we have confirmed that biallelic PU.1 mutations are common in low-LET rAML, occurring in 88% of samples. Biallelic PU.1 mutations were also detected in the majority of high-LET rAML samples. Microsatellite instability was identified in 42% of all rAML samples, and 89% of samples carried increased microsatellite mutant frequencies at the single-cell level, indicative of ongoing instability. Instability was also observed cytogenetically as a 2-fold increase in chromatid-type aberrations. These data highlight the similarities in molecular characteristics of high-LET and low-LET rAML and confirm the presence of ongoing chromosomal and microsatellite instability in murine rAML.

Let the Dogs Out: Using Bobble Head Toys to Explore Force and Motion.

ERIC Educational Resources Information Center

Foster, Andrea S.

2003-01-01

Introduces an activity in which students learn principles of force and motion, systems, and simple machines by exploring the best position of the dogs on the dashboard. Includes a sample lesson plan written in the five instructional models: (1) engagement; (2) exploration; (3) explanation; (4) elaboration; and (5) evaluation. (KHR)

Random Testing and Model Checking: Building a Common Framework for Nondeterministic Exploration

NASA Technical Reports Server (NTRS)

Groce, Alex; Joshi, Rajeev

2008-01-01

Two popular forms of dynamic analysis, random testing and explicit-state software model checking, are perhaps best viewed as search strategies for exploring the state spaces introduced by nondeterminism in program inputs. We present an approach that enables this nondeterminism to be expressed in the SPIN model checker's PROMELA language, and then lets users generate either model checkers or random testers from a single harness for a tested C program. Our approach makes it easy to compare model checking and random testing for models with precisely the same input ranges and probabilities and allows us to mix random testing with model checking's exhaustive exploration of non-determinism. The PROMELA language, as intended in its design, serves as a convenient notation for expressing nondeterminism and mixing random choices with nondeterministic choices. We present and discuss a comparison of random testing and model checking. The results derive from using our framework to test a C program with an effectively infinite state space, a module in JPL's next Mars rover mission. More generally, we show how the ability of the SPIN model checker to call C code can be used to extend SPIN's features, and hope to inspire others to use the same methods to implement dynamic analyses that can make use of efficient state storage, matching, and backtracking.

The Sweet-Home project: audio processing and decision making in smart home to improve well-being and reliance.

PubMed

Vacher, Michel; Chahuara, Pedro; Lecouteux, Benjamin; Istrate, Dan; Portet, Francois; Joubert, Thierry; Sehili, Mohamed; Meillon, Brigitte; Bonnefond, Nicolas; Fabre, Sébastien; Roux, Camille; Caffiau, Sybille

2013-01-01

The Sweet-Home project aims at providing audio-based interaction technology that lets the user have full control over their home environment, at detecting distress situations and at easing the social inclusion of the elderly and frail population. This paper presents an overview of the project focusing on the implemented techniques for speech and sound recognition as context-aware decision making with uncertainty. A user experiment in a smart home demonstrates the interest of this audio-based technology.

Using the TSAR Electromagnetic modeling system

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

Pennock, S.T.; Laguna, G.W.

1993-09-01

A new user, upon receipt of the TSAR EM modeling system, may be overwhelmed by the number of software packages to learn and the number of manuals associated with those packages. This is a document to describe the creation of a simple TSAR model, beginning with an MGED solid and continuing the process through final results from TSAR. It is not intended to be a complete description of all the parts of the TSAR package. Rather, it is intended simply to touch on all the steps in the modeling process and to take a new user through the system frommore » start to finish. There are six basic parts to the TSAR package. The first, MGED, is part of the BRL-CAD package and is used to create a solid model. The second part, ANASTASIA, is the program used to sample the solid model and create a finite -- difference mesh. The third program, IMAGE, lets the user view the mesh itself and verify its accuracy. If everything about the mesh is correct, the process continues to the fourth step, SETUP-TSAR, which creates the parameter files for compiling TSAR and the input file for running a particular simulation. The fifth step is actually running TSAR, the field modeling program. Finally, the output from TSAR is placed into SIG, B2RAS or another program for post-processing and plotting. Each of these steps will be described below. The best way to learn to use the TSAR software is to actually create and run a simple test problem. As an example of how to use the TSAR package, let`s create a sphere with a rectangular internal cavity, with conical and cylindrical penetrations connecting the outside to the inside, and find the electric field inside the cavity when the object is exposed to a Gaussian plane wave. We will begin with the solid modeling software, MGED, a part of the BRL-CAD modeling release.« less

Down-regulation of let-7 microRNA increased K-ras expression in lung damage induced by radon.

PubMed

Chen, Zhihai; Wang, Dapeng; Gu, Chao; Liu, Xing; Pei, Weiwei; Li, Jianxiang; Cao, Yi; Jiao, Yang; Tong, Jian; Nie, Jihua

2015-09-01

Radon has long been recognized as a human carcinogen leading to lung cancer, but the underlying mechanisms remain obscure. Recent studies have shown that the let-7 microRNA and K-ras play an important role in the development of various cancers. However, the exact role between let-7 and K-ras in radon induced lung damage has not been explored so far. In the present study, wistar rats and human bronchial epithelial (HBE) cells were long-term exposed to radon, and then alterations in histological pathology of rat lung tissue, ROS, antioxidant enzymes activities and clonogenic formation in HBE cells, as well as changes in let-7 and K-ras expression were determined to observe the adverse effects induced by radon. The results showed that long-term exposure to radon produced severe lung damage in rats, significantly increased ROS production and clonogenic formation ratios and decreased SOD activities in HBE cells. In addition, an obvious down-regulation of let-7 and up-regulation of K-ras were also revealed both in mRNA and in protein level in lung tissue of rats and HBE cells exposed to radon. Furthermore, a significant down-regulation of K-ras was then confirmed in both let-7b-3p and let-7a-2-3p transfected HBE cells. Taken together, the present results propose an involvement of let-7 microRNA and K-ras in radon induced lung damage both in vivo and in vitro, which may thus be of potential value in early diagnosis and therapy of radon-induced lung tumorgenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

Qanimarisaj Qano'jib'alil--Engrandezcamos Nuestro Pensamiento (Let's Broaden Our Thinking). [CD-ROM].

ERIC Educational Resources Information Center

Academy for Educational Development, Washington, DC.

This CD-ROM is part of an interactive and dynamic multimedia package of information and games for learning K'iche' and Ixil. The CD-ROMs help bilingual pre-service teachers improve their reading, writing, and listening comprehension skills in their own Mayan language. After a musical and colorful introduction, users may choose introductions to…

Let's Talk about Digital Learners in the Digital Era

ERIC Educational Resources Information Center

Gallardo-Echenique, Eliana Esther; Marqués-Molías, Luis; Bullen, Mark; Strijbos, Jan-Willem

2015-01-01

This paper reports on a literature review of the concept of "Digital Natives" and related terms. More specifically, it reports on the idea of a homogeneous generation of prolific and skilled users of digital technology born between 1980 and 1994. In all, 127 articles published between 1991 and 2014 were reviewed. On the basis of the…

Stay connected | National Oceanic and Atmospheric Administration

Science.gov Websites

areas and people. Please note: Some links below will lead to non-governmental websites visit the site disclaimer to see how these links are handled. Facebook icon. Facebook Facebook lets users follow people and ;a visual discovery tool that you can use to find ideas for all your projects and interests."

Faculty/Student Surveys Using Open Source Software

ERIC Educational Resources Information Center

Kaceli, Sali

2004-01-01

This session will highlight an easy survey package which lets non-technical users create surveys, administer surveys, gather results, and view statistics. This is an open source application all managed online via a web browser. By using phpESP, the faculty is given the freedom of creating various surveys at their convenience and link them to their…

Books, Books, Books--Let Us Read: A Library Serving Sheltered and Incarcerated Youth.

ERIC Educational Resources Information Center

Carlson, Pam

1994-01-01

Describes the growth and development of a library program serving a shelter for abused and neglected children and youth and a juvenile detention center in Orange County (California). Program funding, materials preferred by teen users, library management, special events, and problems are discussed. Teen patrons and their use of the services are…

Brain Gym: Let the User Beware

ERIC Educational Resources Information Center

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…

The IRI/LDEO Climate Data Library: Helping People use Climate Data

NASA Astrophysics Data System (ADS)

Blumenthal, M. B.; Grover-Kopec, E.; Bell, M.; del Corral, J.

2005-12-01

The IRI Climate Data Library (http://iridl.ldeo.columbia.edu/) is a library of datasets. By library we mean a collection of things, collected from both near and far, designed to make them more accessible for the library's users. Our datasets come from many different sources, many different "data cultures", many different formats. By dataset we mean a collection of data organized as multidimensional dependent variables, independent variables, and sub-datasets, along with the metadata (particularly use-metadata) that makes it possible to interpret the data in a meaningful manner. Ingrid, which provides the infrastructure for the Data Library, is an environment that lets one work with datasets: read, write, request, serve, view, select, calculate, transform, ... . It hides an extraordinary amount of technical detail from the user, letting the user think in terms of manipulations to datasets rather that manipulations of files of numbers. Among other things, this hidden technical detail could be accessing data on servers in other places, doing only the small needed portion of an enormous calculation, or translating to and from a variety of formats and between "data cultures". These operations are presented as a collection of virtual directories and documents on a web server, so that an ordinary web client can instantiate a calculation simply by requesting the resulting document or image. Building on this infrastructure, we (and others) have created collections of dynamically-updated images to faciliate monitoring aspects of the climate system, as well as linking these images to the underlying data. We have also created specialized interfaces to address the particular needs of user groups that IRI needs to support.

Dynamic User Interfaces for Service Oriented Architectures in Healthcare.

PubMed

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.

Semantics by analogy for illustrative volume visualization☆

PubMed Central

Gerl, Moritz; Rautek, Peter; Isenberg, Tobias; Gröller, Eduard

2012-01-01

We present an interactive graphical approach for the explicit specification of semantics for volume visualization. This explicit and graphical specification of semantics for volumetric features allows us to visually assign meaning to both input and output parameters of the visualization mapping. This is in contrast to the implicit way of specifying semantics using transfer functions. In particular, we demonstrate how to realize a dynamic specification of semantics which allows to flexibly explore a wide range of mappings. Our approach is based on three concepts. First, we use semantic shader augmentation to automatically add rule-based rendering functionality to static visualization mappings in a shader program, while preserving the visual abstraction that the initial shader encodes. With this technique we extend recent developments that define a mapping between data attributes and visual attributes with rules, which are evaluated using fuzzy logic. Second, we let users define the semantics by analogy through brushing on renderings of the data attributes of interest. Third, the rules are specified graphically in an interface that provides visual clues for potential modifications. Together, the presented methods offer a high degree of freedom in the specification and exploration of rule-based mappings and avoid the limitations of a linguistic rule formulation. PMID:23576827

LncRNA-LET inhibits cell viability, migration and EMT while induces apoptosis by up-regulation of TIMP2 in human granulosa-like tumor cell line KGN.

PubMed

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.

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

NASA Technical Reports Server (NTRS)

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.

New Tools for Sea Ice Data Analysis and Visualization: NSIDC's Arctic Sea Ice News and Analysis

NASA Astrophysics Data System (ADS)

Vizcarra, N.; Stroeve, J.; Beam, K.; Beitler, J.; Brandt, M.; Kovarik, J.; Savoie, M. H.; Skaug, M.; Stafford, T.

2017-12-01

Arctic sea ice has long been recognized as a sensitive climate indicator and has undergone a dramatic decline over the past thirty years. Antarctic sea ice continues to be an intriguing and active field of research. The National Snow and Ice Data Center's Arctic Sea Ice News & Analysis (ASINA) offers researchers and the public a transparent view of sea ice data and analysis. We have released a new set of tools for sea ice analysis and visualization. In addition to Charctic, our interactive sea ice extent graph, the new Sea Ice Data and Analysis Tools page provides access to Arctic and Antarctic sea ice data organized in seven different data workbooks, updated daily or monthly. An interactive tool lets scientists, or the public, quickly compare changes in ice extent and location. Another tool allows users to map trends, anomalies, and means for user-defined time periods. Animations of September Arctic and Antarctic monthly average sea ice extent and concentration may also be accessed from this page. Our tools help the NSIDC scientists monitor and understand sea ice conditions in near real time. They also allow the public to easily interact with and explore sea ice data. Technical innovations in our data center helped NSIDC quickly build these tools and more easily maintain them. The tools were made publicly accessible to meet the desire from the public and members of the media to access the numbers and calculations that power our visualizations and analysis. This poster explores these tools and how other researchers, the media, and the general public are using them.

Let It Roll

ERIC Educational Resources Information Center

Trundle, Kathy Cabe; Smith, Mandy McCormick

2011-01-01

Some of children's earliest explorations focus on movement of their own bodies. Quickly, children learn to further explore movement by using objects like a ball or car. They recognize that a ball moves differently than a pushed block. As they grow, children enjoy their experiences with motion and movement, including making objects move, changing…

Dexter: Data Extractor for scanned graphs

NASA Astrophysics Data System (ADS)

Demleitner, Markus

2011-12-01

The NASA Astrophysics Data System (ADS) now holds 1.3 million scanned pages, containing numerous plots and figures for which the original data sets are lost or inaccessible. The availability of scans of the figures can significantly ease the regeneration of the data sets. For this purpose, the ADS has developed Dexter, a Java applet that supports the user in this process. Dexter's basic functionality is to let the user manually digitize a plot by marking points and defining the coordinate transformation from the logical to the physical coordinate system. Advanced features include automatic identification of axes, tracing lines and finding points matching a template.

Enhancements to the SHARP Build System and NEK5000 Coupling

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

McCaskey, Alex; Bennett, Andrew R.; Billings, Jay Jay

The SHARP project for the Department of Energy's Nuclear Energy Advanced Modeling and Simulation (NEAMS) program provides a multiphysics framework for coupled simulations of advanced nuclear reactor designs. It provides an overall coupling environment that utilizes custom interfaces to couple existing physics codes through a common spatial decomposition and unique solution transfer component. As of this writing, SHARP couples neutronics, thermal hydraulics, and structural mechanics using PROTEUS, Nek5000, and Diablo respectively. This report details two primary SHARP improvements regarding the Nek5000 and Diablo individual physics codes: (1) an improved Nek5000 coupling interface that lets SHARP achieve a vast increase inmore » overall solution accuracy by manipulating the structure of the internal Nek5000 spatial mesh, and (2) the capability to seamlessly couple structural mechanics calculations into the framework through improvements to the SHARP build system. The Nek5000 coupling interface now uses a barycentric Lagrange interpolation method that takes the vertex-based power and density computed from the PROTEUS neutronics solver and maps it to the user-specified, general-order Nek5000 spectral element mesh. Before this work, SHARP handled this vertex-based solution transfer in an averaging-based manner. SHARP users can now achieve higher levels of accuracy by specifying any arbitrary Nek5000 spectral mesh order. This improvement takes the average percentage error between the PROTEUS power solution and the Nek5000 interpolated result down drastically from over 23 % to just above 2 %, and maintains the correct power profile. We have integrated Diablo into the SHARP build system to facilitate the future coupling of structural mechanics calculations into SHARP. Previously, simulations involving Diablo were done in an iterative manner, requiring a large amount manual work, and left only as a task for advanced users. This report will detail a new Diablo build system that was implemented using GNU Autotools, mirroring much of the current SHARP build system, and easing the use of structural mechanics calculations for end-users of the SHARP multiphysics framework. It lets users easily build and use Diablo as a stand-alone simulation, as well as fully couple with the other SHARP physics modules. The top-level SHARP build system was modified to allow Diablo to hook in directly. New dependency handlers were implemented to let SHARP users easily build the framework with these new simulation capabilities. The remainder of this report will describe this work in full, with a detailed discussion of the overall design philosophy of SHARP, the new solution interpolation method introduced, and the Diablo integration work. We will conclude with a discussion of possible future SHARP improvements that will serve to increase solution accuracy and framework capability.« less

Let's Explore Aviation

ERIC Educational Resources Information Center

Arvin, Jean

1977-01-01

Presents an intermediate level social studies unit dealing with air education, social aspects of aviation, and the importance of aviation to industry and transportation. Includes objectives, twelve activities, and evaluative procedures. (SL)

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

PubMed

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 cultured cell line of silkworm showed a clear association with ecdysone pulse and a variety of biological processes.

ADS's Dexter Data Extraction Applet

NASA Astrophysics Data System (ADS)

Demleitner, M.; Accomazzi, A.; Eichhorn, G.; Grant, C. S.; Kurtz, M. J.; Murray, S. S.

The NASA Astrophysics Data System (ADS) now holds 1.3 million scanned pages, containing numerous plots and figures for which the original data sets are lost or inaccessible. The availability of scans of the figures can significantly ease the regeneration of the data sets. For this purpose, the ADS has developed Dexter, a Java applet that supports the user in this process. Dexter's basic functionality is to let the user manually digitize a plot by marking points and defining the coordinate transformation from the logical to the physical coordinate system. Advanced features include automatic identification of axes, tracing lines and finding points matching a template. This contribution both describes the operation of Dexter from a user's point of view and discusses some of the architectural issues we faced during implementation.

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

Quam, W.; Del Duca, T.; Plake, W.

This paper describes a pocket-calculator-sized, neutron-sensitive, REM-responding personnel dosimeter that uses three tissue-equivalent cylindrical proportional counters as neutron-sensitive detectors. These are conventionally called Linear Energy Transfer (LET) counters. Miniaturized hybrid circuits are used for the linear pulse handling electronics, followed by a 256-channel ADC. A CMOS microprocessor is used to calculate REM exposure from the basic rads-tissue data supplied by the LET counters and also to provide timing and display functions. The instrument is used to continuously accumulate time in hours since reset, total counts accumulated, rads-tissue, and REM. The user can display any one of these items or amore » channel number (an aid in calibration) at any time. Such data are provided with a precision of +- 3% for a total exposure of 1 mREM over eight hours.« less

FIIDOS--A Computer Code for the Computation of Fallout Inhalation and Ingestion Dose to Organs Computer User’s Guide (Revision 4)

DTIC Science & Technology

2007-05-01

35 5 Actinide product radionuclides... actinides , and fission products in fallout. Doses from low-linear energy transfer (LET) radiation (beta particles and gamma rays) are reported separately...assumptions about the critical parameters used in calculating internal doses – resuspension factor, breathing rate, fractionation, and scenario elements – to

75 FR 76506 - Self-Regulatory Organizations; The Depository Trust Company; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

... let the user know to use pledge code 01 instead. Effective December 2, 2010, DTC will extend the end... one code. The extended period for pledge affords greater flexibility in determining and securing... the respective rights of DTC or persons using the service. At any time within 60 days of the filing of...

Do-It-Yourself Learning Games: Software That Lets You Pick the Questions--and Answers.

ERIC Educational Resources Information Center

Hively, Wells

1984-01-01

Reviews user-adaptable learning games that can be customized for any subject, including Tic Tac Show and the Game Show from Computer Advanced Ideas, which are question-answer learning programs based on game shows, and Master Match from Computer Advanced Ideas and Square Pairs from Scholastic Inc., which are based on the card game Concentration.…

"Let's Talk about Sex": Pilot Study of an Interactive CD-ROM to Prevent HIV/STIS in Female Adolescents

ERIC Educational Resources Information Center

Ito, Kristin E.; Kalyanaraman, Sri; Ford, Carol A.; Brown, Jane D.; Miller, William C.

2008-01-01

The purpose of this study was to develop and pilot-test an interactive CD-ROM aimed at the prevention of sexually transmitted infections (STIs) in female adolescents. The CD-ROM includes prevention information, models skills for negotiating abstinence and consistent condom use, teaches media literacy, and allows the user to choose a culturally…

Letting Students Use Web 2.0 Tools to Hook One Another on Reading

ERIC Educational Resources Information Center

Ercegovac, Zorana

2012-01-01

In the rapidly changing globalized world, school librarians cannot prepare today's students for every possible outcome, but they can give them the skills that will make them adaptable in 21st-century learning and work settings. The mission for school library programs is to ensure that students are effective users of ideas and information by being…

Integrated Information Support System (IISS). Volume 8. User Interface Subsystem. Part 20. Report Writer Development Specification.

DTIC Science & Technology

1985-11-01

13I OR (STARTUPV SILECT I CREATE FORN P1 Prompt At Let, *TaI: Item TAUK At 2 8 1 31:: 5 I CREATE PORN P2 . . . eeeeeee ooe. .... eeee... Child IICount I ----------------- 4 +---------------- I Last I- Box I I Child I Size +---------------- ----------------- i Module i-bIBox I I Margins

MYPLAN - A Mobile Phone Application for Supporting People at Risk of Suicide.

PubMed

Skovgaard Larsen, Jette L; Frandsen, Hanne; Erlangsen, Annette

2016-05-01

Safety plans have been suggested as an intervention for people at risk of suicide. Given the impulsive character of suicidal ideation, a safety plan in the format of a mobile phone application is likely to be more available and useful than traditional paper versions. The study describes MYPLAN, a mobile phone application designed to support people at risk of suicide by letting them create a safety plan. MYPLAN was developed in collaboration with clinical psychiatric staff at Danish suicide preventive clinics. The mobile application lets the user create an individualized safety plan by filling in templates with strategies, actions, and direct links to contact persons. MYPLAN was developed in 2013 and is freely available in Denmark and Norway. It is designed for iPhone and android platforms. As of December 2015, the application has been downloaded almost 8,000 times. Users at risk of suicide as well as clinical staff have provided positive feedback on the mobile application. Support via mobile phone applications might be particularly useful for younger age groups at risk of suicide as well as in areas or countries where support options are lacking. Yet, it is important to examine the effectiveness of this type of intervention.

Coalescent: an open-source and scalable framework for exact calculations in coalescent theory

PubMed Central

2012-01-01

Background Currently, there is no open-source, cross-platform and scalable framework for coalescent analysis in population genetics. There is no scalable GUI based user application either. Such a framework and application would not only drive the creation of more complex and realistic models but also make them truly accessible. Results As a first attempt, we built a framework and user application for the domain of exact calculations in coalescent analysis. The framework provides an API with the concepts of model, data, statistic, phylogeny, gene tree and recursion. Infinite-alleles and infinite-sites models are considered. It defines pluggable computations such as counting and listing all the ancestral configurations and genealogies and computing the exact probability of data. It can visualize a gene tree, trace and visualize the internals of the recursion algorithm for further improvement and attach dynamically a number of output processors. The user application defines jobs in a plug-in like manner so that they can be activated, deactivated, installed or uninstalled on demand. Multiple jobs can be run and their inputs edited. Job inputs are persisted across restarts and running jobs can be cancelled where applicable. Conclusions Coalescent theory plays an increasingly important role in analysing molecular population genetic data. Models involved are mathematically difficult and computationally challenging. An open-source, scalable framework that lets users immediately take advantage of the progress made by others will enable exploration of yet more difficult and realistic models. As models become more complex and mathematically less tractable, the need for an integrated computational approach is obvious. Object oriented designs, though has upfront costs, are practical now and can provide such an integrated approach. PMID:23033878

Making large amounts of meteorological plots easily accessible to users

NASA Astrophysics Data System (ADS)

Lamy-Thepaut, Sylvie; Siemen, Stephan; Sahin, Cihan; Raoult, Baudouin

2015-04-01

The European Centre for Medium-Range Weather Forecasts (ECMWF) is an international organisation providing its member organisations with forecasts in the medium time range of 3 to 15 days, and some longer-range forecasts for up to a year ahead, with varying degrees of detail. As part of its mission, ECMWF generates an increasing number of forecast data products for its users. To support the work of forecasters and researchers and to let them make best use of ECMWF forecasts, the Centre also provides tools and interfaces to visualise their products. This allows users to make use of and explore forecasts without having to transfer large amounts of raw data. This is especially true for products based on ECMWF's 50 member ensemble forecast, where some specific processing and visualisation are applied to extract information. Every day, thousands of raw data are being pushed to the ECMWF's interactive web charts application called ecCharts, and thousands of products are processed and pushed to ECMWF's institutional web site ecCharts provides a highly interactive application to display and manipulate recent numerical forecasts to forecasters in national weather services and ECMWF's commercial customers. With ecCharts forecasters are able to explore ECMWF's medium-range forecasts in far greater detail than has previously been possible on the web, and this as soon as the forecast becomes available. All ecCharts's products are also available through a machine-to-machine web map service based on the OGC Web Map Service (WMS) standard. ECMWF institutional web site provides access to a large number of graphical products. It was entirely redesigned last year. It now shares the same infrastructure as ECMWF's ecCharts, and can benefit of some ecCharts functionalities, for example the dashboard. The dashboard initially developed for ecCharts allows users to organise their own collection of products depending on their work flow, and is being further developed. In its first implementation, It presents the user's products in a single interface with fast access to the original product, and possibilities of synchronous animations between them. But its functionalities are being extended to give users the freedom to collect not only ecCharts's 2D maps and graphs, but also other ECMWF Web products such as monthly and seasonal products, scores, and observation monitoring. The dashboard will play a key role to help the user to interpret the large amount of information that ECMWF is providing. This talk will present examples of how the new user interface can organise complex meteorological maps and graphs and show the new possibilities users have gained by using the web as a medium.

Creating an Immersive Mars Experience Using Unity3D

NASA Technical Reports Server (NTRS)

Miles, Sarah

2011-01-01

Between the two Mars Exploration Rovers, Spirit and Opportunity, NASA has collected over 280,000 images while studying the Martian surface. This number will continue to grow, with Opportunity continuing to send images and with another rover, Curiosity, launching soon. Using data collected by and for these Mars rovers, I am contributing to the creation of virtual experiences that will expose the general public to Mars. These experiences not only work to increase public knowledge, but they attempt to do so in an engaging manner more conducive to knowledge retention by letting others view Mars through the rovers' eyes. My contributions include supporting image viewing (for example, allowing users to click on panoramic images of the Martian surface to access closer range photos) as well as enabling tagging of points of interest. By creating a more interactive way of viewing the information we have about Mars, we are not just educating the public about a neighboring planet. We are showing the importance of doing such research.

OpenSim: open-source software to create and analyze dynamic simulations of movement.

PubMed

Delp, Scott L; Anderson, Frank C; Arnold, Allison S; Loan, Peter; Habib, Ayman; John, Chand T; Guendelman, Eran; Thelen, Darryl G

2007-11-01

Dynamic simulations of movement allow one to study neuromuscular coordination, analyze athletic performance, and estimate internal loading of the musculoskeletal system. Simulations can also be used to identify the sources of pathological movement and establish a scientific basis for treatment planning. We have developed a freely available, open-source software system (OpenSim) that lets users develop models of musculoskeletal structures and create dynamic simulations of a wide variety of movements. We are using this system to simulate the dynamics of individuals with pathological gait and to explore the biomechanical effects of treatments. OpenSim provides a platform on which the biomechanics community can build a library of simulations that can be exchanged, tested, analyzed, and improved through a multi-institutional collaboration. Developing software that enables a concerted effort from many investigators poses technical and sociological challenges. Meeting those challenges will accelerate the discovery of principles that govern movement control and improve treatments for individuals with movement pathologies.

Advanced communications technology satellite high burst rate link evaluation terminal power control and rain fade software test plan, version 1.0

NASA Technical Reports Server (NTRS)

Reinhart, Richard C.

1993-01-01

The Power Control and Rain Fade Software was developed at the NASA Lewis Research Center to support the Advanced Communications Technology Satellite High Burst Rate Link Evaluation Terminal (ACTS HBR-LET). The HBR-LET is an experimenters terminal to communicate with the ACTS for various experiments by government, university, and industry agencies. The Power Control and Rain Fade Software is one segment of the Control and Performance Monitor (C&PM) Software system of the HBR-LET. The Power Control and Rain Fade Software automatically controls the LET uplink power to compensate for signal fades. Besides power augmentation, the C&PM Software system is also responsible for instrument control during HBR-LET experiments, control of the Intermediate Frequency Switch Matrix on board the ACTS to yield a desired path through the spacecraft payload, and data display. The Power Control and Rain Fade Software User's Guide, Version 1.0 outlines the commands and procedures to install and operate the Power Control and Rain Fade Software. The Power Control and Rain Fade Software Maintenance Manual, Version 1.0 is a programmer's guide to the Power Control and Rain Fade Software. This manual details the current implementation of the software from a technical perspective. Included is an overview of the Power Control and Rain Fade Software, computer algorithms, format representations, and computer hardware configuration. The Power Control and Rain Fade Test Plan provides a step-by-step procedure to verify the operation of the software using a predetermined signal fade event. The Test Plan also provides a means to demonstrate the capability of the software.

The DEDUCE Guided Query Tool: Providing Simplified Access to Clinical Data for Research and Quality Improvement

PubMed Central

Horvath, Monica M.; Winfield, Stephanie; Evans, Steve; Slopek, Steve; Shang, Howard; Ferranti, Jeffrey

2011-01-01

In many healthcare organizations, comparative effectiveness research and quality improvement (QI) investigations are hampered by a lack of access to data created as a byproduct of patient care. Data collection often hinges upon either manual chart review or ad hoc requests to technical experts who support legacy clinical systems. In order to facilitate this needed capacity for data exploration at our institution (Duke University Health System), we have designed and deployed a robust Web application for cohort identification and data extraction—the Duke Enterprise Data Unified Content Explorer (DEDUCE). DEDUCE is envisioned as a simple, web-based environment that allows investigators access to administrative, financial, and clinical information generated during patient care. By using business intelligence tools to create a view into Duke Medicine's enterprise data warehouse, DEDUCE provides a guided query functionality using a wizard-like interface that lets users filter through millions of clinical records, explore aggregate reports, and, export extracts. Researchers and QI specialists can obtain detailed patient- and observation-level extracts without needing to understand structured query language or the underlying database model. Developers designing such tools must devote sufficient training and develop application safeguards to ensure that patient-centered clinical researchers understand when observation-level extracts should be used. This may mitigate the risk of data being misunderstood and consequently used in an improper fashion. PMID:21130181

The DEDUCE Guided Query tool: providing simplified access to clinical data for research and quality improvement.

PubMed

Horvath, Monica M; Winfield, Stephanie; Evans, Steve; Slopek, Steve; Shang, Howard; Ferranti, Jeffrey

2011-04-01

In many healthcare organizations, comparative effectiveness research and quality improvement (QI) investigations are hampered by a lack of access to data created as a byproduct of patient care. Data collection often hinges upon either manual chart review or ad hoc requests to technical experts who support legacy clinical systems. In order to facilitate this needed capacity for data exploration at our institution (Duke University Health System), we have designed and deployed a robust Web application for cohort identification and data extraction--the Duke Enterprise Data Unified Content Explorer (DEDUCE). DEDUCE is envisioned as a simple, web-based environment that allows investigators access to administrative, financial, and clinical information generated during patient care. By using business intelligence tools to create a view into Duke Medicine's enterprise data warehouse, DEDUCE provides a Guided Query functionality using a wizard-like interface that lets users filter through millions of clinical records, explore aggregate reports, and, export extracts. Researchers and QI specialists can obtain detailed patient- and observation-level extracts without needing to understand structured query language or the underlying database model. Developers designing such tools must devote sufficient training and develop application safeguards to ensure that patient-centered clinical researchers understand when observation-level extracts should be used. This may mitigate the risk of data being misunderstood and consequently used in an improper fashion. Copyright © 2010 Elsevier Inc. All rights reserved.

Spatial Coverage Planning for Exploration Robots

NASA Technical Reports Server (NTRS)

Gaines, Daniel; Estlin, Tara; Chouinard, Caroline

2007-01-01

A report discusses an algorithm for an onboard planning and execution technology to support the exploration and characterization of geological features by autonomous rovers. A rover that is capable of deciding which observations are more important relieves the engineering team from much of the burden of attempting to make accurate predictions of what the available rover resources will be in the future. Instead, the science and engineering teams can uplink a set of observation requests that may potentially oversubscribe resources and let the rover use observation priorities and its current assessment of available resources to make decisions about which observations to perform and when to perform them. The algorithm gives the rover the ability to model spatial coverage quality based on data from different scientific instruments, to assess the impact of terrain on coverage quality, to incorporate user-defined priorities among subregions of the terrain to be covered, and to update coverage quality rankings of observations when terrain knowledge changes. When the rover is exploring large geographical features such as craters, channels, or boundaries between two different regions, an important factor in assessing the quality of a mission plan is how the set of chosen observations spatially cover the area of interest. The algorithm allows the rover to evaluate which observation to perform and to what extent the candidate observation will increase the spatial coverage of the plan.

Speleothems and Sand Castles

ERIC Educational Resources Information Center

Hance, Trevor; Befus, Kevin

2015-01-01

The idea of building sand castles evokes images of lazy summer days at the beach, listening to waves crash, enjoying salty breezes, and just unplugging for a while to let our inner child explore the wonderful natural toys beneath our feet. The idea of exploring caves might evoke feelings and images of claustrophobia or pioneers and Native…

Let the Right One In: Ethnic Boundaries in a Colombian Immigrant Youth Program

ERIC Educational Resources Information Center

Pineda, Claudia G.

2017-01-01

Although research on minority youth has established the value of coethnic spaces for safe ethnic identity exploration, research has seldom examined how youth in these spaces draw ethnic boundaries or offered appropriate frameworks addressing boundary-setting. This study uses Berry's acculturation framework to explore ethnic boundary-setting within…

Overexpression of Lin28 inhibits the proliferation, migration and cell cycle progression and induces apoptosis of BGC-823 gastric cancer cells.

PubMed

Song, Hu; Xu, Wei; Song, Jun; Liang, Yong; Fu, Wei; Zhu, Xiao-Cheng; Li, Chao; Peng, Jun-Sheng; Zheng, Jun-Nian

2015-02-01

Lin28 plays important roles in the development, maintenance of pluripotency and progression of various types of cancers. Lin28 represses the biogenesis of let-7 microRNAs and is implicated in both development and tumorigenesis. Oncogenic regulation of let-7 microRNAs has been demonstrated in several human malignancies, yet their correlation with Lin28 has not yet been studied in gastric cancer. Therefore, in the present study, we explored the possible mechanisms involved in the effects by Lin28 on the proliferation, migration, cell cycle arrest and apoptosis in gastric cancer cells via alteration of let-7 miRNA. The expression levels of Lin28 and let-7 were detected by real-time PCR in gastric cancer cell lines in vitro. Lin28 was overexpressed in the BGC-823 cells via lentiviral transfection, and let-7 expression was assessed. Cell proliferation and migration capabilities were investigated by MTT and Transwell assays, while cell cycle distribution and the apoptosis rate were detected using flow cytometry. The expression of Lin28 was moderately expressed in the GES cells while underexpressed in the BGC-823, SGC-7901 and HGC-27 cells. Let-7a miRNA was highly expressed in the GES, BGC-823, SGC-7901 and HGC-27 cells. Overexpression of Lin28 was inversely correlated with the downregulated expression of let-7a, and markedly suppressed the proliferation, migration, cell cycle progression and induced apoptosis in the BGC-823 cells. These findings demonstrated that overexpression of Lin28 can suppress the biological behavior of gastric cancer in vitro, and let-7 miRNA may play an important role in the process. We suggest that Lin28 may be a candidate predictor or an anticancer therapeutic target for gastric cancer patients.

Evolution of the Deep-space Galactic Cosmic Ray Lineal Energy Transfer Spectrum through Tissue Equivalent Plastic

NASA Astrophysics Data System (ADS)

Case, A. W.; Kasper, J. C.; Spence, H. E.; Golightly, M. J.; Schwadron, N. A.; Mazur, J. E.; Blake, J. B.; Looper, M. D.; Townsend, L.; Zeitlin, C. J.

2011-12-01

The Cosmic Ray Telescope for the Effects of Radiation is an energetic particle telescope that resides on the Lunar Reconnaissance Orbiter spacecraft, currently in a 50 km circular lunar polar orbit. The telescope consists of 6 silicon semi-conductor detectors placed in pairs that surround two pieces of Tissue Equivalent Plastic (TEP), which serve to absorb energy from particles as they transit through the instrument. Particles with energies greater than 12 MeV/nucleon can penetrate the outermost shield and be measured by the instrument. The primary measurement made by the instrument is of the Linear Energy Transfer (LET) of energetic particles as they transit through the telescope. CRaTER measures the LET spectrum with unprecedented energy resolution and has done so during a period of historically low solar activity that led to record high intensities of Galactic Cosmic Rays (GCR). These LET spectra are used to study changes in the properties of the incoming particles, and to make detailed measurements of the radiation doses human explorers will experience in deep space on missions to the moon, to asteroids, or to Mars. We present LET spectra accumulated during 2009 and 2010. We show how the LET spectrum evolves through the instrument as the GCR interact with the TEP. Due to the importance of these measurements for human effects, our extensive absolute calibration procedures are presented. Of particular note is a significant reduction in the flux of particles with LET greater than 10 keV/um for detectors that lie deeper within the telescope stack, due to the attenuation of high LET particles within the TEP. By measuring this attenuation we can estimate the depth in human tissue where the highest LET particles that are most likely to cause genetic damage pose the greatest threat to humans in space.

Single event upset susceptibility testing of the Xilinx Virtex II FPGA

NASA Technical Reports Server (NTRS)

Yui, C.; Swift, G.; Carmichael, C.

2002-01-01

Heavy ion testing of the Xilinx Virtex IZ was conducted on the configuration, block RAM and user flip flop cells to determine their single event upset susceptibility using LETs of 1.2 to 60 MeVcm^2/mg. A software program specifically designed to count errors in the FPGA is used to reveal L1/e values and single-event-functional interrupt failures.

Best kept secrets ... Source Data Systems, Inc. (SDS).

PubMed

Andrew, W F

1991-03-01

The SDS/MEDNET system is a cost-effective option for small- to medium-size hospitals (up to 400 beds). The parameter-driven system lets users control operations with only occasional SDS assistance. A full application set, available for modular selection to reduce upfront costs while facilitating steady growth and protecting client investment, is adaptable to multi-facility environments. The industry-standard, Intel-based multi-user processors, network communications and protocols assure high efficiency, low-cost solutions independent of any one hardware vendor. Sustained growth in both client base and product offerings point to a high level of responsiveness and healthcare industry commitment. Corporate emphasis on user involvement and open systems integration assures clients of leading-edge capabilities. SDS/MEDNET will be a strong contender in selected marketing environments.

Understanding User Preferences and Awareness: Privacy Mechanisms in Location-Based Services

NASA Astrophysics Data System (ADS)

Burghardt, Thorben; Buchmann, Erik; Müller, Jens; Böhm, Klemens

Location based services (LBS) let people retrieve and share information related to their current position. Examples are Google Latitude or Panoramio. Since LBS share user-related content, location information etc., they put user privacy at risk. Literature has proposed various privacy mechanisms for LBS. However, it is unclear which mechanisms humans really find useful, and how they make use of them. We present a user study that addresses these issues. To obtain realistic results, we have implemented a geotagging application on the web and on GPS cellphones, and our study participants use this application in their daily lives. We test five privacy mechanisms that differ in the awareness, mental effort and degree of informedness required from the users. Among other findings, we have observed that in situations where a single simple mechanism does not meet all privacy needs, people want to use simple and sophisticated mechanisms in combination. Further, individuals are concerned about the privacy of others, even when they do not value privacy for themselves.

The Landsat Image Mosaic of Antarctica

NASA Astrophysics Data System (ADS)

Bindschadler, R.; Vornberger, P.; Fleming, A.; Fox, A.; Morin, P.

2008-12-01

The first-ever true-color, high-resolution digital mosaic of Antarctica has been produced from nearly 1100 Landsat-7 ETM+ images collected between 1999 and 2003. The Landsat Image Mosaic of Antarctica (LIMA) project was an early benchmark data set of the International Polar Year and represents a close and successful collaboration between NASA, USGS, the British Antarctic Survey and the National Science Foundation. The mosaic was successfully merged with lower resolution MODIS data south of Landsat coverage to produce a complete true-color data set of the entire continent. LIMA is being used as a platform for a variety of education and outreach activities. Central to this effort is the NASA website 'Faces of Antarctica' that offers the web visitor the opportunity to explore the data set and to learn how these data are used to support scientific research. Content is delivered through a set of mysteries designed to pique the user's interest and to motivate them to delve deeper into the website where there are various videos and scientific articles for downloading. Detailed lesson plans written by teachers are provided for classroom use and Java applets let the user track the motion of ice in sequential Landsat images. Web links take the user to other sites where they can roam over the imagery using standard pan and zoom functions, or search for any named feature in the Antarctic Geographic Names data base that returns to the user a centered true-color view of any named feature. LIMA also has appeared is a host of external presentations from museum exhibits, to postcards and large posters. It has attracted various value-added providers that increase LIMA's accessibility by allowing users to specify subsets of the very large data set for individual downloads. The ultimate goal of LIMA in the public and educational sector is to enable everyone to become more familiar with Antarctica.

Validating the usability of an interactive Earth Observation based web service for landslide investigation

NASA Astrophysics Data System (ADS)

Albrecht, Florian; Weinke, Elisabeth; Eisank, Clemens; Vecchiotti, Filippo; Hölbling, Daniel; Friedl, Barbara; Kociu, Arben

2017-04-01

Regional authorities and infrastructure maintainers in almost all mountainous regions of the Earth need detailed and up-to-date landslide inventories for hazard and risk management. Landslide inventories usually are compiled through ground surveys and manual image interpretation following landslide triggering events. We developed a web service that uses Earth Observation (EO) data to support the mapping and monitoring tasks for improving the collection of landslide information. The planned validation of the EO-based web service does not only cover the analysis of the achievable landslide information quality but also the usability and user friendliness of the user interface. The underlying validation criteria are based on the user requirements and the defined tasks and aims in the work description of the FFG project Land@Slide (EO-based landslide mapping: from methodological developments to automated web-based information delivery). The service will be validated in collaboration with stakeholders, decision makers and experts. Users are requested to test the web service functionality and give feedback with a web-based questionnaire by following the subsequently described workflow. The users will operate the web-service via the responsive user interface and can extract landslide information from EO data. They compare it to reference data for quality assessment, for monitoring changes and for assessing landslide-affected infrastructure. An overview page lets the user explore a list of example projects with resulting landslide maps and mapping workflow descriptions. The example projects include mapped landslides in several test areas in Austria and Northern Italy. Landslides were extracted from high resolution (HR) and very high resolution (VHR) satellite imagery, such as Landsat, Sentinel-2, SPOT-5, WorldView-2/3 or Pléiades. The user can create his/her own project by selecting available satellite imagery or by uploading new data. Subsequently, a new landslide extraction workflow can be initiated through the functionality that the web service provides: (1) a segmentation of the image into spectrally homogeneous objects, (2) a classification of the objects into landslide and non-landslide areas and (3) an editing tool for the manual refinement of extracted landslide boundaries. In addition, the user interface of the web service provides tools that enable the user (4) to perform a monitoring that identifies changes between landslide maps of different points in time, (5) to perform a validation of the landslide maps by comparing them to reference data, and (6) to perform an assessment of affected infrastructure by comparing the landslide maps to respective infrastructure data. After exploring the web service functionality, the users are asked to fill in the online validation protocol in form of a questionnaire in order to provide their feedback. Concerning usability, we evaluate how intuitive the web service functionality can be operated, how well the integrated help information guides the users, and what kind of background information, e.g. remote sensing concepts and theory, is necessary for a practitioner to fully exploit the value of EO data. The feedback will be used for improving the user interface and for the implementation of additional functionality.

Integrating natural language processing and web GIS for interactive knowledge domain visualization

NASA Astrophysics Data System (ADS)

Du, Fangming

Recent years have seen a powerful shift towards data-rich environments throughout society. This has extended to a change in how the artifacts and products of scientific knowledge production can be analyzed and understood. Bottom-up approaches are on the rise that combine access to huge amounts of academic publications with advanced computer graphics and data processing tools, including natural language processing. Knowledge domain visualization is one of those multi-technology approaches, with its aim of turning domain-specific human knowledge into highly visual representations in order to better understand the structure and evolution of domain knowledge. For example, network visualizations built from co-author relations contained in academic publications can provide insight on how scholars collaborate with each other in one or multiple domains, and visualizations built from the text content of articles can help us understand the topical structure of knowledge domains. These knowledge domain visualizations need to support interactive viewing and exploration by users. Such spatialization efforts are increasingly looking to geography and GIS as a source of metaphors and practical technology solutions, even when non-georeferenced information is managed, analyzed, and visualized. When it comes to deploying spatialized representations online, web mapping and web GIS can provide practical technology solutions for interactive viewing of knowledge domain visualizations, from panning and zooming to the overlay of additional information. This thesis presents a novel combination of advanced natural language processing - in the form of topic modeling - with dimensionality reduction through self-organizing maps and the deployment of web mapping/GIS technology towards intuitive, GIS-like, exploration of a knowledge domain visualization. A complete workflow is proposed and implemented that processes any corpus of input text documents into a map form and leverages a web application framework to let users explore knowledge domain maps interactively. This workflow is implemented and demonstrated for a data set of more than 66,000 conference abstracts.

Long-term Autophagy and Nrf2 Signaling in the Hippocampi of Developing Mice after Carbon Ion Exposure

NASA Astrophysics Data System (ADS)

Ye, Fei; Zhao, Ting; Liu, Xiongxiong; Jin, Xiaodong; Liu, Xinguo; Wang, Tieshan; Li, Qiang

2015-12-01

To explore charged particle radiation-induced long-term hippocampus damage, we investigated the expression of autophagy and antioxidant Nrf2 signaling-related proteins in the mouse hippocampus after carbon ion radiation. Heads of immature female Balb/c mice were irradiated with carbon ions of different LETs at various doses. Behavioral tests were performed on the mice after maturation. Acute and chronic expression of LC3-II, p62/SQSTM1, nuclear Nrf2, activated caspase-3 and the Bax/Bcl-2 ratio were measured in the hippocampi. Secondary X-ray insult was adopted to amplify potential damages. Long-term behavioral changes were observed in high-LET carbon ion-irradiated mice. There were no differences in the rates of LC3-II induction and p62/SQSTM1 degradation compared to the control group regardless of whether the mice received the secondary X-ray insult. A high nuclear Nrf2 content and low apoptosis level in hippocampal cells subjected to secondary X-rays were observed for the mice exposed to relatively low-LET carbon ions. Therefore, carbon ion exposure in the immature mouse led to an LET-dependent behavioral change after maturation. Although autophagy was intact, the persistently high nuclear Nrf2 content in the hippocampus might account for the unchanged behavioral pattern in mice exposed to the relatively low-LET carbon ions and the subsequent increased radioresistance of the hippocampus.

A new programming metaphor for image processing procedures

NASA Technical Reports Server (NTRS)

Smirnov, O. M.; Piskunov, N. E.

1992-01-01

Most image processing systems, besides an Application Program Interface (API) which lets users write their own image processing programs, also feature a higher level of programmability. Traditionally, this is a command or macro language, which can be used to build large procedures (scripts) out of simple programs or commands. This approach, a legacy of the teletypewriter has serious drawbacks. A command language is clumsy when (and if! it attempts to utilize the capabilities of a multitasking or multiprocessor environment, it is but adequate for real-time data acquisition and processing, it has a fairly steep learning curve, and the user interface is very inefficient,. especially when compared to a graphical user interface (GUI) that systems running under Xll or Windows should otherwise be able to provide. ll these difficulties stem from one basic problem: a command language is not a natural metaphor for an image processing procedure. A more natural metaphor - an image processing factory is described in detail. A factory is a set of programs (applications) that execute separate operations on images, connected by pipes that carry data (images and parameters) between them. The programs function concurrently, processing images as they arrive along pipes, and querying the user for whatever other input they need. From the user's point of view, programming (constructing) factories is a lot like playing with LEGO blocks - much more intuitive than writing scripts. Focus is on some of the difficulties of implementing factory support, most notably the design of an appropriate API. It also shows that factories retain all the functionality of a command language (including loops and conditional branches), while suffering from none of the drawbacks outlined above. Other benefits of factory programming include self-tuning factories and the process of encapsulation, which lets a factory take the shape of a standard application both from the system and the user's point of view, and thus be used as a component of other factories. A bare-bones prototype of factory programming was implemented under the PcIPS image processing system, and a complete version (on a multitasking platform) is under development.

Draft Specification of the Common APSE (Ada Programming Support Environments) Interface Set (CAIS). Version 1.1.

DTIC Science & Technology

1983-09-30

Ideally, all APSE tools DD, vLAm 147 COTON or I NOv 66is oSwLEtEaUCASII SN )02 IF St. 06,SECURITY CLASSIFICATION Of THIS 1PAG9 (ft;..Data X-014 I.N...has finished all the modifications/entries that are desired, the user presses a special key (function key or enter key) which causes the modified

Extending Cross-Generational Knowledge Flow Research in Edge Organizations

DTIC Science & Technology

2008-06-01

letting Protégé generate the basic user interface, and then gradually write widgets and plug-ins to customize its look-and- feel and behavior . 4 3.0...2007a) focused on cross-generational knowledge flows in edge organizations. We found that cross- generational biases affect tacit knowledge transfer...the software engineering field, many matured methodologies already exist, such as Rational Unified Process (Hunt, 2003) or Extreme Programming (Beck

Don't Let Micropayments Penalize You--Experience from the City University of Hong Kong

ERIC Educational Resources Information Center

Ching, Steve H.; Tai, Alice; Pong, Joanna; Cheng, Michael

2009-01-01

Self-service is the trend of today's libraries. The Run Run Shaw Library at the City University of Hong Kong therefore is transforming itself in the same direction and offers to its users what it calls the Easy-service. However, the need to handle cash-based micropayments at the service counter is a stumbling block. There is an urgent need for the…

Activity Monitors Help Users Get Optimum Sun Exposure

NASA Technical Reports Server (NTRS)

2015-01-01

Goddard scientist Shahid Aslam was investigating alternative methods for measuring extreme ultraviolet radiation on the Solar Dynamics Observatory when he hit upon semiconductors that measured wavelengths pertinent to human health. As a result, he and a partner established College Park, Maryland-based Sensor Sensor LLC and developed UVA+B SunFriend, a wrist monitor that lets people know when they've received their optimal amounts of sunlight for the day.

AIDE - Advanced Intrusion Detection Environment

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

Smith, Cathy L.

2013-04-28

Would you like to know when someone has dropped an undesirable executable binary on our system? What about something less malicious such as a software installation by a user? What about the user who decides to install a newer version of mod_perl or PHP on your web server without letting you know beforehand? Or even something as simple as when an undocumented config file change is made by another member of the admin group? Do you even want to know about all the changes that happen on a daily basis on your server? The purpose of an intrusion detection systemmore » (IDS) is to detect unauthorized, possibly malicious activity. The purpose of a host-based IDS, or file integrity checker, is check for unauthorized changes to key system files, binaries, libraries, and directories on the system. AIDE is an Open Source file and directory integrity checker. AIDE will let you know when a file or directory has been added, deleted, modified. It is included with the Red Hat Enterprise 6. It is available for other Linux distros. This is a case study describing the process of configuring AIDE on an out of the box RHEL6 installation. Its goal is to illustrate the thinking and the process by which a useful AIDE configuration is built.« less

[Research of λ-cyhalothrin affect synaptic development in hippocampus by interfering with estrogen action].

PubMed

Zhang, Long; Wang, Qunan; Xia, Xin; Li, Nian; Yang, Chengwei

2015-08-01

To explore the effects of λ-cyhalothrin on hippocampus by interfering with estrogen. The healthy female ICR mice of postnatal 28 days were random divided into 12 groups, 4 of those were sham-operation include control, λ-cyhalothrin (LCT, 3.0 µg/g), Letrozole (Let, 1.0 µg/g), and LCT (3.0 µg/g)+Let (1.0 µg/g); and the last 8 were ovariectomized include OVX, Estradiol (E2, 10.0 µg/g), LCT, Let, E2+LCT, E2+Let, LCT+Let, E2+LCT+Let. 10 mice in every group received drugs by intraperitoneal injection for 2 days. Then half of every group initiate the ethological test (open field test and Morris water maze) 24 h later. The last half animals were sacrificed to made frozen section for immunofluorescent assay of postsynaptic density protein 95 (PSD95). In ethological test, campared with Sham, OVX can lengthen incubation period in the first grid and to get on the platform (P < 0.05); campared with OVX, OVX+E2 can increase the total numbers of through grid and shorten the incubation period to get on the platform (P < 0.05); campared with OVX+E2, OVX+E2+LCT can reduce the number of grid and standing, lengthen incubation period to the platform (P < 0.05); campared with Sham, Sham+LCT can lengthen incubation period to the platform of Sham mice (P < 0.05), but campared with OVX, OVX+LCT can shoten incubation period in the first grid and to get on the platform in OVX mice (P < 0.05); campared with Sham+Let, Sham+LCT+Let can lengthen incubation period in the first grid, reduce the the number of grid and standing (P < 0.05). In the Immunohistochemical fluorescence experiment we find that, campared with Sham, OVX can reduce the expression of PSD95 in CA1,CA3 and DG (P < 0.05); however campared with OVX, E2 or LCT can both inhibit the effect of OVX (P < 0.05); campared with Sham, Sham+LCT can reduce the expression of PSD95, the same result when OVX+E2+LCT campared with OVX+E2 (P < 0.05); campared with OVX+E2+Let, OVX+E2+LCT+Let can reduce the expression of PSD95 in CA3 (P < 0.05); campared with OVX+Let, OVX+LCT+Let can increase the expression of PSD95 in DG (P < 0.05). When few estrogen exist in the body, LCT can show estrogen-like action to promote hippocampal synaptic development; but when circulating estrogen exist, LCT can inhibit synaptic development by interfering estrogen.

Communicating Knowing through Communities of Practice: Exploring Internal Communicative Processes and Differences among CoPs

ERIC Educational Resources Information Center

Iverson, Joel O.; McPhee, Robert D.

2008-01-01

Knowing is an enacted, communicated process that is difficult to observe, let alone manage, in organizations. Communities of practice (CoPs) offer a productive solution for improving knowledge and knowledge management, but the communicative processes that enact CoPs have not been explored, leaving CoPs as an organizational black box. This research…

Reversal of diuretic-associated impaired glucose tolerance and new-onset diabetes: results of the STAR-LET study.

PubMed

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.

Let's get real about virtual: online health is here to stay.

PubMed

Prainsack, Barbara

2013-08-01

A lot has been written about the opportunities of the Internet for medicine, and lately, also for disease research specifically. Although it remains to be seen how significant and sustainable a change this will result in, some recent developments are highly relevant for the area of genetic research. User-friendly, low-threshold web-based tools do not only provide information to patients and other users, but they also supply user-generated data that can be utilized by both medical practice and medical research. Many of these developments have been below the radar of mainstream academic research so far. Issues related to data quality and standardization, as well as data protection and privacy, still need to be addressed. Dismissing these platforms as fads of a tiny privileged minority risks missing the opportunity to have our say in these debates.

Inhibition of neurotensin receptor 1 induces intrinsic apoptosis via let-7a-3p/Bcl-w axis in glioblastoma.

PubMed

Dong, Zhen; Lei, Qian; Yang, Rui; Zhu, Shunqin; Ke, Xiao-Xue; Yang, Liqun; Cui, Hongjuan; Yi, Liang

2017-06-06

Backgroud:Glioblastoma is a kind of highly malignant and aggressive tumours in the central nervous system. Previously, we found that neurotensin (NTS) and its high-affinity receptor 1 (NTSR1) had essential roles in cell proliferation and invasiveness of glioblastoma. Unexpectedly, cell death also appeared by inhibition of NTSR1 except for cell cycle arrest. However, the mechanisms were remained to be further explored. Cells treated with SR48692, a selective antagonist of NTSR1, or NTSR1 shRNA were stained with Annexin V-FITC/PI and the apoptosis was assessed by flow cytometry. Cytochrome c release was detected by using immunofluorescence. Mitochondrial membrane potential (MMP, ΔΨm) loss was stained by JC-1 and detected by immunofluorescence or flow cytometry. Apoptosis antibody array and microRNA microarray were performed to seek the potential regulators of NTSR1 inhibition-induced apoptosis. Interaction between let-7a-3p and Bcl-w 3'UTR was evaluated by using luciferase assay. SR48692 induced massive apoptosis, which was related to mitochondrial cytochrome c release and MMP loss. Knockdown of NTSR1 induced slight apoptosis and significant MMP loss. In addition, NTSR1 inhibition sensitised glioblastoma cells to actinomycin D or doxorubicin-induced apoptosis. Consistently, NTSR1 inhibition-induced mitochondrial apoptosis was accompanied by downregulation of Bcl-w and Bcl-2. Restoration of Bcl-w partly rescued NTSR1 deficiency-induced apoptosis. In addition, NTSR1 deficiency promoted higher let-7a-3p expression and inhibition let-7a-3p partly rescued NTSR1 inhibition-induced apoptosis. In addition, let-7a-3p inhibition promoted 3'UTR activities of Bcl-w and the expression of c-Myc and LIN28, which were the upstream of let-7a-3p, decreased after NTSR1 inhibition. NTSR1 had an important role in protecting glioblastoma from intrinsic apoptosis via c-Myc/LIN28/let-7a-3p/Bcl-w axis.

Building a COTS archive for satellite data

NASA Technical Reports Server (NTRS)

Singer, Ken; Terril, Dave; Kelly, Jack; Nichols, Cathy

1994-01-01

The goal of the NOAA/NESDIS Active Archive was to provide a method of access to an online archive of satellite data. The archive had to manage and store the data, let users interrogate the archive, and allow users to retrieve data from the archive. Practical issues of the system design such as implementation time, cost and operational support were examined in addition to the technical issues. There was a fixed window of opportunity to create an operational system, along with budget and staffing constraints. Therefore, the technical solution had to be designed and implemented subject to constraint imposed by the practical issues. The NOAA/NESDIS Active Archive came online in July of 1994, meeting all of its original objectives.

Hormonal regulation of Drosophila microRNA let-7 and miR-125 that target innate immunity.

PubMed

Garbuzov, Alina; Tatar, Marc

2010-01-01

The steroid 20-hydroxy-ecdysone (20-HE) and the sesquiterpenoid Juvenile Hormone (JH) coordinate insect life stage transitions. 20-HE exerts these effects by the sequential induction of response genes. In the nematode Caenorhabditis elegans hormones also play a role in such transitions, but notably, microRNA such as let-7 and lin-4 have likewise been found to help order developmental steps. Little is known about the corresponding function of homologous microRNA in Drosophila melanogaster, and the way microRNA might be regulated by 20-HE in the fly is ambiguous. Here we used Drosophila S2 cells to analyze the effects of 20-HE on D. melanogaster microRNA let-7 and miR-125, the homolog of lin-4. The induction by 20-HE of let-7 and miR-125 in S2 cells is inhibited by RNAi knockdown of the ecdysone receptor and, as previously shown, by knockdown of its cofactor broad-complex C. To help resolve the currently ambiguous role of 20-HE in the control of microRNA, we show that nanomolar concentrations of 20-HE primes cells to subsequently express microRNA when exposed to micromolar levels of 20-HE. We then explore the role microRNA plays in the established relationship between 20-HE and the induction of innate immunity. We show that the 3'UTR of the antimicrobial peptide diptericin has a let-7 binding site and that let-7 represses translation from this site. We conclude that 20-HE facilitates the initial expression of innate immunity while it simultaneously induces negative regulation via microRNA control of antimicrobial peptide translation.

Geschlechtertausch II.

ERIC Educational Resources Information Center

Holschuh, Albrecht

1993-01-01

Describes how mental experiments can be used to turn expository writing into games and even self-exploration in an advanced language course. Through a class project on sex change, for example, learners acquire more knowledge about themselves as well as heightened language skills. (LET)

Growth and Your 1- to 2-Year-Old

MedlinePlus

... doctor. Encourage activity and exploration by providing a safe environment that lets your child be active every day. ... the area of language. Continue to provide a safe and healthy environment to support your child's growth and development. Talk ...

Military Application of Networking by Touch in Collaborative Planning and Tactical Environments

DTIC Science & Technology

2007-09-01

the network. For example, processing, or understanding, four plus pages per second, let alone 1500 pages, far surpasses a normal user’s ability to...discovering rapid, evolutionary approaches for filtering four to 1500 pages per second into knowledgeable forms relevant to the user. Unless we...weapons at the ready when the TL receives a slight vibration in the upper right quadrant of a vest he is wearing. The familiar tactile sensation

Self-Aware Computing

DTIC Science & Technology

2009-06-01

to floating point , to multi-level logic. 2 Overview Self-aware computation can be distinguished from existing computational models which are...systems have advanced to the point that the time is ripe to realize such a system. To illustrate, let us examine each of the key aspects of self...servers for each service, there are no single points of failure in the system. If an OS or user core has a failure, one of several introspection cores

Handheld Computing

DTIC Science & Technology

2005-06-01

company has devel- oped an exciting prototype technology: … that lets users of PDAs and similar mobile devices put data into their handheld systems...for a class of small, easily carried electronic devices used to store and retrieve infor- mation” [2], were at one time viewed as lit- tle more than...some of the many ways that PDA technology is currently being used within the DoD: • The Pocket-Sized Forward Entry Device (PFED) is a ruggedized PDA

Facility Composer Design Wizards: A Method for Extensible Codified Design Logic Based on Explicit Facility Criteria

DTIC Science & Technology

2004-11-01

institutionalized approaches to solving problems, company/client specific mission priorities (for example, State Department vs . Army Reserve and... independent variables that let the user leave a particular step before fin- ishing all the items, and to return at a later time without any data loss. One...Sales, Main Exchange, Miscellane- ous Shops, Post Office, Restaurant , and Theater.) Authorized customers served 04 Other criteria pro- vided by the

Long-term Autophagy and Nrf2 Signaling in the Hippocampi of Developing Mice after Carbon Ion Exposure

PubMed Central

Ye, Fei; Zhao, Ting; Liu, Xiongxiong; Jin, Xiaodong; Liu, Xinguo; Wang, Tieshan; Li, Qiang

2015-01-01

To explore charged particle radiation-induced long-term hippocampus damage, we investigated the expression of autophagy and antioxidant Nrf2 signaling-related proteins in the mouse hippocampus after carbon ion radiation. Heads of immature female Balb/c mice were irradiated with carbon ions of different LETs at various doses. Behavioral tests were performed on the mice after maturation. Acute and chronic expression of LC3-II, p62/SQSTM1, nuclear Nrf2, activated caspase-3 and the Bax/Bcl-2 ratio were measured in the hippocampi. Secondary X-ray insult was adopted to amplify potential damages. Long-term behavioral changes were observed in high-LET carbon ion-irradiated mice. There were no differences in the rates of LC3-II induction and p62/SQSTM1 degradation compared to the control group regardless of whether the mice received the secondary X-ray insult. A high nuclear Nrf2 content and low apoptosis level in hippocampal cells subjected to secondary X-rays were observed for the mice exposed to relatively low-LET carbon ions. Therefore, carbon ion exposure in the immature mouse led to an LET-dependent behavioral change after maturation. Although autophagy was intact, the persistently high nuclear Nrf2 content in the hippocampus might account for the unchanged behavioral pattern in mice exposed to the relatively low-LET carbon ions and the subsequent increased radioresistance of the hippocampus. PMID:26689155

Triggers and monitoring in intelligent personal health record.

PubMed

Luo, Gang

2012-10-01

Although Web-based personal health records (PHRs) have been widely deployed, the existing ones have limited intelligence. Previously, we introduced expert system technology and Web search technology into the PHR domain and proposed the concept of an intelligent PHR (iPHR). iPHR provides personalized healthcare information to facilitate users' daily activities of living. The current iPHR is passive and follows the pull model of information distribution. This paper introduces triggers and monitoring into iPHR to make iPHR become active. Our idea is to let medical professionals pre-compile triggers and store them in iPHR's knowledge base. Each trigger corresponds to an abnormal event that may have potential medical impact. iPHR keeps collecting, processing, and analyzing the user's medical data from various sources such as wearable sensors. Whenever an abnormal event is detected from the user's medical data, the corresponding trigger fires and the related personalized healthcare information is pushed to the user using natural language generation technology, expert system technology, and Web search technology.

Let's Tweet in Chinese! Exploring How Learners of Chinese as a Foreign Language Self-Direct Their Use of Microblogging to Learn Chinese

ERIC Educational Resources Information Center

Hsiao, Ya Ping; Broeder, Peter

2014-01-01

Twitter is becoming increasingly popular as a medium for language learning. This study explores self-directed learning via social interactions that use Twitter as an interactive learning environment. The participants in this study were thirty university students of Chinese as a foreign language at levels 1 and 2 of the "Hanyu Shuiping…

Body Temperature Regulation in Hot Environments.

PubMed

Nilsson, Jan-Åke; Molokwu, Mary Ngozi; Olsson, Ola

2016-01-01

Organisms in hot environments will not be able to passively dissipate metabolically generated heat. Instead, they have to revert to evaporative cooling, a process that is energetically expensive and promotes excessive water loss. To alleviate these costs, birds in captivity let their body temperature increase, thereby entering a state of hyperthermia. Here we explore the use of hyperthermia in wild birds captured during the hot and dry season in central Nigeria. We found pronounced hyperthermia in several species with the highest body temperatures close to predicted lethal levels. Furthermore, birds let their body temperature increase in direct relation to ambient temperatures, increasing body temperature by 0.22°C for each degree of increased ambient temperature. Thus to offset the costs of thermoregulation in ambient temperatures above the upper critical temperature, birds are willing to let their body temperatures increase by up to 5°C above normal temperatures. This flexibility in body temperature may be an important mechanism for birds to adjust to predicted increasing ambient temperatures in the future.

Body Temperature Regulation in Hot Environments

PubMed Central

Nilsson, Jan-Åke; Molokwu, Mary Ngozi; Olsson, Ola

2016-01-01

Organisms in hot environments will not be able to passively dissipate metabolically generated heat. Instead, they have to revert to evaporative cooling, a process that is energetically expensive and promotes excessive water loss. To alleviate these costs, birds in captivity let their body temperature increase, thereby entering a state of hyperthermia. Here we explore the use of hyperthermia in wild birds captured during the hot and dry season in central Nigeria. We found pronounced hyperthermia in several species with the highest body temperatures close to predicted lethal levels. Furthermore, birds let their body temperature increase in direct relation to ambient temperatures, increasing body temperature by 0.22°C for each degree of increased ambient temperature. Thus to offset the costs of thermoregulation in ambient temperatures above the upper critical temperature, birds are willing to let their body temperatures increase by up to 5°C above normal temperatures. This flexibility in body temperature may be an important mechanism for birds to adjust to predicted increasing ambient temperatures in the future. PMID:27548758

Let's Be Blunt: Consumption Methods Matter Among Black Marijuana Smokers.

PubMed

Montgomery, LaTrice; Bagot, Kara

2016-05-01

Despite the high prevalence of blunt (i.e., hollowed-out cigars that are filled with marijuana) use among Black marijuana smokers, few studies have examined if and how blunt users differ from traditional joint users. The current study compared the prevalence and patterns of use for those who smoked blunts in the past month (i.e., blunt users) with those who used marijuana through other methods (i.e., other marijuana users). The sample included 935 Black past-month marijuana smokers participating in the 2013 National Survey on Drug Use and Health. Among past-month marijuana smokers, 73.2% were blunt users and 26.8% were other marijuana users. Overall, blunt users initiated marijuana use at an earlier age (15.9 vs. 17.3 years, p < .01) and reported more days of marijuana use in the past month (16 vs. 8 days, p < .01) than did other marijuana users. There were also differences by gender. Among females, blunt users reported a higher odds of past-year marijuana abuse or dependence (23.8%) than other marijuana users (11.2%) (adjusted odds ratio = 1.23, 95% CI [1.12, 3.17], p < .01). However, blunt-using males reported similar odds of past-year marijuana abuse or dependence (approximately 25%) as other marijuana-using males. These findings highlight the need for targeted interventions for blunt users as a subgroup of marijuana users, especially among Black females, who may be at increased risk for developing a marijuana use disorder as a result of blunt smoking.

Declining Black Employment.

ERIC Educational Resources Information Center

Vedder, Richard; Gallaway, Lowell

1993-01-01

Explores income inequality during declining African-American employment, examines current welfare systems, and suggests ways to improve the economic disadvantages of minority groups. Letting markets work can improve the economic status of African Americans. The present dual African-American economy, a market economy and an entitlement economy, is…

Large Scale Data Analytics of User Behavior for Improving Content Delivery

DTIC Science & Technology

2014-12-01

video streaming, web browsing To Achan and Amma iv Abstract The Internet is fast becoming the de facto content delivery network of the world...operators everywhere and they seek to de - sign and manage their networks better to improve content delivery and provide better quality of experience...Anjali, Kriti and Ruta have been great company and have let me partake in their delicious homecooked food more times than I can remember. My friends

Visual task performance using a monocular see-through head-mounted display (HMD) while walking.

PubMed

Mustonen, Terhi; Berg, Mikko; Kaistinen, Jyrki; Kawai, Takashi; Häkkinen, Jukka

2013-12-01

A monocular see-through head-mounted display (HMD) allows the user to view displayed information while simultaneously interacting with the surrounding environment. This configuration lets people use HMDs while they are moving, such as while walking. However, sharing attention between the display and environment can compromise a person's performance in any ongoing task, and controlling one's gait may add further challenges. In this study, the authors investigated how the requirements of HMD-administered visual tasks altered users' performance while they were walking. Twenty-four university students completed 3 cognitive tasks (high- and low-working memory load, visual vigilance) on an HMD while seated and while simultaneously performing a paced walking task in a controlled environment. The results show that paced walking worsened performance (d', reaction time) in all HMD-administered tasks, but visual vigilance deteriorated more than memory performance. The HMD-administered tasks also worsened walking performance (speed, path overruns) in a manner that varied according to the overall demands of the task. These results suggest that people's ability to process information displayed on an HMD may worsen while they are in motion. Furthermore, the use of an HMD can critically alter a person's natural performance, such as their ability to guide and control their gait. In particular, visual tasks that involve constant monitoring of the HMD should be avoided. These findings highlight the need for careful consideration of the type and difficulty of information that can be presented through HMDs while still letting the user achieve an acceptable overall level of performance in various contexts of use. PsycINFO Database Record (c) 2013 APA, all rights reserved.

"Let's Throw That Big Stick in the River": An Exploration of Gender in the Construction of Shared Narratives around Outdoor Spaces

ERIC Educational Resources Information Center

Waller, Tim

2010-01-01

This paper will explore the role of gender in the construction of shared narratives around outdoor spaces. The paper draws on findings from a long-term project investigating young children's learning and the outdoor curriculum. The project is ongoing and involves children aged 3- to 4-years in a nursery school in England. The children are given…

NASA Software Lets You Explore Mars, the Asteroid Vesta and the Moon

NASA Image and Video Library

2016-10-06

NASA wants you to use your web browser to explore Mars, the Moon and the asteroid Vesta! The three portals are some of NASA's planetary mapping and modeling web portals. It makes it easy for mission planners, scientists, students and the public to visualize details on the surface of Mars, the Moon and Vesta, as seen with a variety of instruments aboard a number of spacecraft.

"Let Me Show You a Trick!": A Toddler's Use of Humor to Explore, Interpret, and Negotiate Her Familial Environment during a Day in the Life

ERIC Educational Resources Information Center

Cameron, E. Leslie; Kennedy, Katherine M.; Cameron, Catherine Ann

2008-01-01

Children employ different types of humor as they explore, interpret, and negotiate their environments. Whereas an appreciation of verbal incongruity has been a hallmark of older preschooler humor (e.g., McGhee, 1989), more recently, other violations of expectations and clowning also have been identified as ubiquitous during the first two years of…

High Resolution, High Frame Rate Video Technology

NASA Technical Reports Server (NTRS)

1990-01-01

Papers and working group summaries presented at the High Resolution, High Frame Rate Video (HHV) Workshop are compiled. HHV system is intended for future use on the Space Shuttle and Space Station Freedom. The Workshop was held for the dual purpose of: (1) allowing potential scientific users to assess the utility of the proposed system for monitoring microgravity science experiments; and (2) letting technical experts from industry recommend improvements to the proposed near-term HHV system. The following topics are covered: (1) State of the art in the video system performance; (2) Development plan for the HHV system; (3) Advanced technology for image gathering, coding, and processing; (4) Data compression applied to HHV; (5) Data transmission networks; and (6) Results of the users' requirements survey conducted by NASA.

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

PubMed

Nowak, Markus; Castellini, Claudio

2016-01-01

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.

Online Education: Let's Start the Conversation

ERIC Educational Resources Information Center

Dixon, Robert J.

2017-01-01

National shortages of school psychologists have started conversations about training, the number of training programs needed, and how to initiate new programs. This article discusses the difficulties associated with traditional training programs for school psychologists and proposes exploring online education and virtual school psychology service…

Nematology—Status and Prospects: Let's Take Off Our Blinders and Broaden Our Horizons

PubMed Central

Van Gundy, Seymour D.

1980-01-01

Some aspects of current fundamental nematological research and teaching in agriculture, soil zoology, biology and medicine, and parasitology are explored as they relate to the Society of Nematologists and the science of nematology in its broadest sense. PMID:19300689

Let's Start the Music.

ERIC Educational Resources Information Center

Ivankovic, Patricia; Gilpatrick, Ingrid

1994-01-01

A preschool/kindergarten program that serves 18 students with deafness/hearing impairments and 11 hearing children uses music activities to develop speech, audition, language, and movement and to further explore current classroom themes. A deaf teacher models body movements, signs, rhythm, and facial expressions while a hearing teacher models…

Social Media: Challenges and Concerns for Families.

PubMed

O'Keeffe, Gwenn Schurgin

2016-10-01

This article explores the impact of social media on child development and family health. Why do we allow our children to use social media sites before their privacy policies allow? Why do we let them lie about their ages to use these sites? What is it about technology that lets us bend these rules in a way we would never do in the unplugged world? Gaining insight into the answers to these questions and what is positive and negative about social media and the digital world allows us to talk to families about this world, allay their concerns, and keep children of all age safe when using social media. Copyright © 2016 Elsevier Inc. All rights reserved.

Full Dome Development for Interactive Immersive Training Capabilities

DTIC Science & Technology

2015-04-03

called the the vDome Player. This application serves as a familiar user interface for direct media playback. Modeled after the widely used VLC ...charrette challenge to task. Below are my notes on where everyone is in planning thei r f inal proj ects . Please let me know (comments or emai l...space with a lot of sound and feeling. What is challenging ? The challenge is how to get depth of field in the dome. Trying to gently allure people into

State-of-the-Art in Improved Parts Programming for Numerically Controlled Machines

DTIC Science & Technology

1976-10-01

than expected let sizes for IIC. Cincinnati lilbcron, Inc., has built a $1.25 million Computer Ilumerical Control ( CNC ) 1,4nufacturing Center to "rw’ t...point-to- point user. Lathe and other turning operations are essentially two-axis opera- tions, and there has been some dissatisfaction over APT’s...a.particular machi-ne (50)." "Software is the key to CNC , the costs of which are easily overlooked. The cost of software development is growing in relation to

Trust-based Anonymous Communication: Adversary Models and Routing Algorithms

DTIC Science & Technology

2011-10-01

pages 169–187. Springer-Verlag, LNCS 3621, August 2005. [6] D . Chaum . Untraceable electronic mail, return addresses, and digital pseudonyms...Communications of the ACM, 4(2), 1981. [7] D . Chaum . The dining cryptographers problem: Unconditional sender and recipient untraceability. Journal of...U ∪R∪ D , where U is a set of users1, R is a set of onion routers, and D is a set of destinations. 2. Let E ⊆ ( V 2 ) be the set of network links

Analysis of Defects in Trouser Manufacturing: Development of a Knowledge-Based Framework. Volume 1. Final Technical Report

DTIC Science & Technology

1992-02-28

the primary goal of instituting remedial measures. Many apparel plants, as they function today in the United States, do not maintain an accu- rate...type of usage is the primary functional mode for FDAS. Alternatively, the user could suggest a defect to FDAS and let it find out if the defect is...Endeavor The primary objective of the research effort is to develop a knowledge-based system to an- alyze the causes of defects in apparel

Consumer Financial Protection Bureau

MedlinePlus

... Resources for Libraries Resources for Tax Preparers Your Money, Your Goals Order free brochures Explore financial well-being survey results See ... Blog Sixty-one organizations join the 2018 Your Money, Your Goals cohort NOV 13, 2017 ... Blog Has having more access to free credit scores made a difference? Let us know! ...

Multigraph: Interactive Data Graphs on the Web

NASA Astrophysics Data System (ADS)

Phillips, M. B.

2010-12-01

Many aspects of geophysical science involve time dependent data that is often presented in the form of a graph. Considering that the web has become a primary means of communication, there are surprisingly few good tools and techniques available for presenting time-series data on the web. The most common solution is to use a desktop tool such as Excel or Matlab to create a graph which is saved as an image and then included in a web page like any other image. This technique is straightforward, but it limits the user to one particular view of the data, and disconnects the graph from the data in a way that makes updating a graph with new data an often cumbersome manual process. This situation is somewhat analogous to the state of mapping before the advent of GIS. Maps existed only in printed form, and creating a map was a laborious process. In the last several years, however, the world of mapping has experienced a revolution in the form of web-based and other interactive computer technologies, so that it is now commonplace for anyone to easily browse through gigabytes of geographic data. Multigraph seeks to bring a similar ease of access to time series data. Multigraph is a program for displaying interactive time-series data graphs in web pages that includes a simple way of configuring the appearance of the graph and the data to be included. It allows multiple data sources to be combined into a single graph, and allows the user to explore the data interactively. Multigraph lets users explore and visualize "data space" in the same way that interactive mapping applications such as Google Maps facilitate exploring and visualizing geography. Viewing a Multigraph graph is extremely simple and intuitive, and requires no instructions. Creating a new graph for inclusion in a web page involves writing a simple XML configuration file and requires no programming. Multigraph can read data in a variety of formats, and can display data from a web service, allowing users to "surf" through large data sets, downloading only those the parts of the data that are needed for display. Multigraph is currently in use on several web sites including the US Drought Portal (www.drought.gov), the NOAA Climate Services Portal (www.climate.gov), the Climate Reference Network (www.ncdc.noaa.gov/crn), NCDC's State of the Climate Report (www.ncdc.noaa.gov/sotc), and the US Forest Service's Forest Change Assessment Viewer (ews.forestthreats.org/NPDE/NPDE.html). More information about Multigraph is available from the web site www.multigraph.org. Interactive Graph of Global Temperature Anomalies from ClimateWatch Magazine (http://www.climatewatch.noaa.gov/2009/articles/climate-change-global-temperature)

Superoxide Dismutase Protects Osteoprogenitors from Irradiation with Low-LET but Not High-LET Species

NASA Technical Reports Server (NTRS)

Schreurs, A.-S.; Tran, L.; Alwood, J. S.; Tahimic, C. G.; Globus, R. K.

2016-01-01

Ionizing radiation-induced bone loss appears to be a two-stage process: first an early increase in pro-resorption cytokines and increased bone resorption by osteoclasts, followed by a decrease in bone formation by osteoblasts. This results in a net loss of mass in mineralized bone tissue. The molecular mechanisms underlying the imbalance in bone remodeling caused by exposure to radiation are not fully understood. We hypothesized that the radiation-induced rise in reactive oxygen species (ROS) damages osteoblast progenitors, leading to a decrease in number and activity of differentiated progeny. We have shown that a diet high in antioxidant capacity prevents radiation-induced bone loss in adult mice (Schreurs et al. 2016) by reducing the early increase in pro-resotption cytokines. Here, we investigated the damaging effects of radiation exposure on cells in the osteoblast lineage, testing if addition of the exogenous antioxidant enzyme, superoxide dismutase (SOD) can mitigate radiation damage. Osteoprogenitors were grown in vitro from the marrow of 16wk old, male C57Bl/6 mice. Cells were irradiated 3 days after plating (day 0) with either gamma (Cs-137, 0.1-5Gy) or iron (Fe-56, 600 MeV/n, 0.5-2Gy), and then grown until day 10. SOD or vehicle was added 2 hours before irradiation (SOD at 200U/ml), twice a day and up to day 5, for a total of 2 days treatment. Cell behavior was assessed by: (a) colony number (counted on day 7), (b) DNA content (surrogate for cell number) to assess cell growth (percent change between day 3 and day 10) and (c) alkaline phosphatase activity (osteoblast differentiation marker). Results show that SOD protected cells from the adverse effects of low-LET ionizing radiation, but not high-LET radiation. These novel results provide an interesting platform to explore further diverse effects and damages caused by low-LET and high-LET, pointing toward different mechanisms and possible intervention strategies for radiation-induced bone loss.

“Thanks for Letting Us All Share Your Mammogram Experience Virtually”: Developing a Web-Based Hub for Breast Cancer Screening

PubMed Central

2017-01-01

Background The decision around whether to attend breast cancer screening can often involve making sense of confusing and contradictory information on its risks and benefits. The Word of Mouth Mammogram e-Network (WoMMeN) project was established to create a Web-based resource to support decision making regarding breast cancer screening. This paper presents data from our user-centered approach in engaging stakeholders (both health professionals and service users) in the design of this Web-based resource. Our novel approach involved creating a user design group within Facebook to allow them access to ongoing discussion between researchers, radiographers, and existing and potential service users. Objective This study had two objectives. The first was to examine the utility of an online user design group for generating insight for the creation of Web-based health resources. We sought to explore the advantages and limitations of this approach. The second objective was to analyze what women want from a Web-based resource for breast cancer screening. Methods We recruited a user design group on Facebook and conducted a survey within the group, asking questions about design considerations for a Web-based breast cancer screening hub. Although the membership of the Facebook group varied over time, there were 71 members in the Facebook group at the end point of analysis. We next conducted a framework analysis on 70 threads from Facebook and a thematic analysis on the 23 survey responses. We focused additionally on how the themes were discussed by the different stakeholders within the context of the design group. Results Two major themes were found across both the Facebook discussion and the survey data: (1) the power of information and (2) the hub as a place for communication and support. Information was considered as empowering but also recognized as threatening. Communication and the sharing of experiences were deemed important, but there was also recognition of potential miscommunication within online discussion. Health professionals and service users expressed the same broad concerns, but there were subtle differences in their opinions. Importantly, the themes were triangulated between the Facebook discussions and the survey data, supporting the validity of an online user design group. Conclusions Online user design groups afford a useful method for understanding stakeholder needs. In contrast to focus groups, they afford access to users from diverse geographical locations and traverse time constraints, allowing more follow-ups to responses. The use of Facebook provides a familiar and naturalistic setting for discussion. Although we acknowledge the limitations in the sample, this approach has allowed us to understand the views of stakeholders in the user-centered design of the WoMMeN hub for breast cancer screening. PMID:29079555

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

PubMed

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.

A dual-input nonlinear system analysis of autonomic modulation of heart rate

NASA Technical Reports Server (NTRS)

Chon, K. H.; Mullen, T. J.; Cohen, R. J.

1996-01-01

Linear analyses of fluctuations in heart rate and other hemodynamic variables have been used to elucidate cardiovascular regulatory mechanisms. The role of nonlinear contributions to fluctuations in hemodynamic variables has not been fully explored. This paper presents a nonlinear system analysis of the effect of fluctuations in instantaneous lung volume (ILV) and arterial blood pressure (ABP) on heart rate (HR) fluctuations. To successfully employ a nonlinear analysis based on the Laguerre expansion technique (LET), we introduce an efficient procedure for broadening the spectral content of the ILV and ABP inputs to the model by adding white noise. Results from computer simulations demonstrate the effectiveness of broadening the spectral band of input signals to obtain consistent and stable kernel estimates with the use of the LET. Without broadening the band of the ILV and ABP inputs, the LET did not provide stable kernel estimates. Moreover, we extend the LET to the case of multiple inputs in order to accommodate the analysis of the combined effect of ILV and ABP effect on heart rate. Analyzes of data based on the second-order Volterra-Wiener model reveal an important contribution of the second-order kernels to the description of the effect of lung volume and arterial blood pressure on heart rate. Furthermore, physiological effects of the autonomic blocking agents propranolol and atropine on changes in the first- and second-order kernels are also discussed.

Suddenly Sexy: Creative Nonfiction Rear-ends Composition.

ERIC Educational Resources Information Center

Bishop, Wendy

2003-01-01

Suggests that there is a real chance right now for letting the possibilities of creative nonfiction infuse, improve, and invigorate the teaching of composition. Concludes that when allowed to explore literary nonfiction, writing students will develop a substantial set of strengths from which to undertake other disciplinary writing challenges as…

Flexible Processing and the Design of Grammar

ERIC Educational Resources Information Center

Sag, Ivan A.; Wasow, Thomas

2015-01-01

We explore the consequences of letting the incremental and integrative nature of language processing inform the design of competence grammar. What emerges is a view of grammar as a system of local monotonic constraints that provide a direct characterization of the signs (the form-meaning correspondences) of a given language. This…

The Freakonomics of Tenure

ERIC Educational Resources Information Center

Chronicle of Higher Education, 2007

2007-01-01

The ever-simmering question of whether the tenure system should be reformed lit up the blogosphere, ignited by an online essay from the (tenured) professor Steven D. Levitt, co-author of the publishing phenomenon "Freakonomics: A Rogue Economist Explores the Hidden Side of Everything" and the popular blog Freakonomics. When Levitt posted "Let's…

Let's Talk... Analytics

ERIC Educational Resources Information Center

Oblinger, Diana G.

2012-01-01

Talk about analytics seems to be everywhere. Everyone is talking about analytics. Yet even with all the talk, many in higher education have questions about--and objections to--using analytics in colleges and universities. In this article, the author explores the use of analytics in, and all around, higher education. (Contains 1 note.)

"Let's Not Leave This Problem": Exploring Inclusive Education in Rural South Africa

ERIC Educational Resources Information Center

Mitchell, Claudia; De Lange, Naydene; Thuy, Nguyen-Thi Xuan

2008-01-01

Inclusive education represents a new agenda for educational reform that spans a wide range of socio-political, cultural, ethical, personal and interpersonal dimensions. Working towards educational inclusion demands commitments, responsibilities and initiatives on the part of all parties to take into consideration the meanings and purpose of…

Personalizing the Food Pyramid. Teaching Techniques.

ERIC Educational Resources Information Center

Allen, Donna

1996-01-01

Presents a strategy for health and home economics teachers to use in evaluating secondary students' eating and nutritional patterns. Students keep two-day food journals then complete a colorful personal food pyramid with the results. This creates a personal pyramid of food choices that lets students explore their eating habits. (SM)

Evidence-Based Management Education

ERIC Educational Resources Information Center

Burke-Smalley, Lisa A.

2014-01-01

In this rejoinder to "Let's Burn Them All: Reflections on the Learning-Inhibitory Nature of Introduction to Management and Introduction to Organizational Behavior Textbooks," by Robert A. Snyder (see EJ1039748), Lisa Burke-Smalley touches upon a number of Snyder's claims and explores questions sparked by his essay. She argues…

Let's Have Fun! Teaching Social Skills through Stories, Telecommunications, and Activities

ERIC Educational Resources Information Center

Zhang, Kaili Chen

2011-01-01

This article concerns social skills interventions for children with emotional/behavioral disorders. Drawing on the author's teaching experience and the findings of research on social skills training in schools, and exploring effective ways to facilitate children's social skill development, the paper describes how social skills interventions can be…

Sexualisation's Four Faces: Sexualisation and Gender Stereotyping in the "Bailey Review"

ERIC Educational Resources Information Center

Barker, Meg; Duschinsky, Robbie

2012-01-01

This paper explores the considerations of sexualisation and gender stereotyping in the recent UK government report "Letting Children be Children". This report, the "Bailey Review", claimed to represent the views of parents. However, closer reading reveals that, while the parents who were consulted were concerned about both the…

Concept of adaptability in space modules.

PubMed

Cooper, M

1990-10-01

The space program is aiming towards the permanent use of space; to build and establish an orbital space station, a Moon base and depart to Mars and beyond. We must look after the total independency from the Earth's natural resources and work in the design of a modular space base in which each module is capable of duplicating one natural process, and that all these modules in combination take us to conceive a space base capable of sustaining life. Every area of human knowledge must be involved. This modular concept will let us see other space goals as extensions of the primary project. The basic technology has to be defined, then relatively minor adjustments will let us reach new objectives such as a first approach for a lunar base and for a Mars manned mission. This concept aims towards an open technology in which standards and recommendations will be created to assemble huge space bases and spaceships from specific modules that perform certain functions, that in combination will let us reach the status of permanent use and exploration of space.

"Visual Learning Is the Best Learning--It Lets You Be Creative while Learning": Exploring Ways to Begin Guided Writing in Second Language Learning through the Use of Comics

ERIC Educational Resources Information Center

Rossetto, Marietta; Chiera-Macchia, Antonella

2011-01-01

This study investigated the use of comics (Cary, 2004) in a guided writing experience in secondary school Italian language learning. The main focus of the peer group interaction task included the exploration of visual sequencing and visual integration (Bailey, O'Grady-Jones, & McGown, 1995) using image and text to create a comic strip narrative in…

User involvement in the implementation of clinical guidelines for common mental health disorders: a review and compilation of strategies and resources.

PubMed

Moreno, Eliana M; Moriana, Juan Antonio

2016-08-09

There is now broad consensus regarding the importance of involving users in the process of implementing guidelines. Few studies, however, have addressed this issue, let alone the implementation of guidelines for common mental health disorders. The aim of this study is to compile and describe implementation strategies and resources related to common clinical mental health disorders targeted at service users. The literature was reviewed and resources for the implementation of clinical guidelines were compiled using the PRISMA model. A mixed qualitative and quantitative analysis was performed based on a series of categories developed ad hoc. A total of 263 items were included in the preliminary analysis and 64 implementation resources aimed at users were analysed in depth. A wide variety of types, sources and formats were identified, including guides (40%), websites (29%), videos and leaflets, as well as instruments for the implementation of strategies regarding information and education (64%), self-care, or users' assessment of service quality. The results reveal the need to establish clear criteria for assessing the quality of implementation materials in general and standardising systems to classify user-targeted strategies. The compilation and description of key elements of strategies and resources for users can be of interest in designing materials and specific actions for this target audience, as well as improving the implementation of clinical guidelines.

Interactive design optimization of magnetorheological-brake actuators using the Taguchi method

NASA Astrophysics Data System (ADS)

Erol, Ozan; Gurocak, Hakan

2011-10-01

This research explored an optimization method that would automate the process of designing a magnetorheological (MR)-brake but still keep the designer in the loop. MR-brakes apply resistive torque by increasing the viscosity of an MR fluid inside the brake. This electronically controllable brake can provide a very large torque-to-volume ratio, which is very desirable for an actuator. However, the design process is quite complex and time consuming due to many parameters. In this paper, we adapted the popular Taguchi method, widely used in manufacturing, to the problem of designing a complex MR-brake. Unlike other existing methods, this approach can automatically identify the dominant parameters of the design, which reduces the search space and the time it takes to find the best possible design. While automating the search for a solution, it also lets the designer see the dominant parameters and make choices to investigate only their interactions with the design output. The new method was applied for re-designing MR-brakes. It reduced the design time from a week or two down to a few minutes. Also, usability experiments indicated significantly better brake designs by novice users.

Setting Priorities in Behavioral Interventions: An Application to Reducing Phishing Risk.

PubMed

Canfield, Casey Inez; Fischhoff, Baruch

2018-04-01

Phishing risk is a growing area of concern for corporations, governments, and individuals. Given the evidence that users vary widely in their vulnerability to phishing attacks, we demonstrate an approach for assessing the benefits and costs of interventions that target the most vulnerable users. Our approach uses Monte Carlo simulation to (1) identify which users were most vulnerable, in signal detection theory terms; (2) assess the proportion of system-level risk attributable to the most vulnerable users; (3) estimate the monetary benefit and cost of behavioral interventions targeting different vulnerability levels; and (4) evaluate the sensitivity of these results to whether the attacks involve random or spear phishing. Using parameter estimates from previous research, we find that the most vulnerable users were less cautious and less able to distinguish between phishing and legitimate emails (positive response bias and low sensitivity, in signal detection theory terms). They also accounted for a large share of phishing risk for both random and spear phishing attacks. Under these conditions, our analysis estimates much greater net benefit for behavioral interventions that target these vulnerable users. Within the range of the model's assumptions, there was generally net benefit even for the least vulnerable users. However, the differences in the return on investment for interventions with users with different degrees of vulnerability indicate the importance of measuring that performance, and letting it guide interventions. This study suggests that interventions to reduce response bias, rather than to increase sensitivity, have greater net benefit. © 2017 Society for Risk Analysis.

Teaching Arturo Ui: Triumph of Whose Will?

ERIC Educational Resources Information Center

Rhiel, Mary

1993-01-01

Describes a unit on teaching Brecht in an introductory literature course, and suggests that students are better able to read and discuss Brecht's Hitler play if they first view and discuss Leni Riefenstahl's film Triumph of the Will. Guidelines are provided on how best to present and explore the two works with students. (LET)

"Leave Me Alone--Simply Let Me Teach": An Exploration of Teacher Professionalism in Kyrgyzstan

ERIC Educational Resources Information Center

Teleshaliyev, Nurbek

2013-01-01

This article examines how, in the context of the increasing deprofessionalization of the teaching professional both nationally and internationally, teachers have attempted to reshape the notion of "professionalism" in a post-Soviet Kyrgyzstan, where teachers function within a top-down, bureaucratic education system. The article employs…

Let's Talk about Solutions!

ERIC Educational Resources Information Center

Finlay, Grace

2011-01-01

This article explores the effectiveness of using Solution Focused Brief Therapy (SFBT) in an adult learning environment. Within this discourse, special attention is given to show how SFBT can be used effectively to support the increasing number of adults who find themselves out of work who are now returning to education. Key ideas within SFBT will…

"Let's Change Already": Community Activism and Pro-Social Play in Egypt

ERIC Educational Resources Information Center

Gerber, Hannah R.; Gaitan, Luis

2017-01-01

This article explores the design processes in creating a pro-social mobile game, "Litter Leader." Following the Egyptian Revolution, "Litter Leader," a game designed for Android devices, was created to foster community change among Egyptian youth. By tracing the meaning-making that occurred with 20 Egyptian youth who playtested…

Let's Talk Math: Encouraging Children To Explore Ideas.

ERIC Educational Resources Information Center

Lilburn, Pat; Rawson, Pam

This book presents mathematics activities to help children talk and write mathematically. Children are encouraged to talk about and share their ideas, to use everyday language to describe mathematical situations, and to restate problems in their own words. There are two sections in this book. Part 1 discusses the following issues and implications…

Pushing the Red Wheelbarrow: From Age Five to Sixty-Five.

ERIC Educational Resources Information Center

Garrison, Peggy

1998-01-01

Aims for students to explore spontaneous ways of finding material for their poems by suppressing control over their subject matter and letting their unconscious minds do the work. Uses a poem of William Carlos Williams, "Red Wheelbarrow," both with K-2 students and adults in a poetry workshop. Illustrates class procedures and activities…

Let's Lunch and Learn: Professional Knowledge Sharing in Teachers' Lounges and Other Congregational Spaces

ERIC Educational Resources Information Center

Mawhinney, Lynnette

2010-01-01

Teachers' lounges are often thought as places that breed negativity. This two-year ethnography conducted in the United States explored teachers' interactions within teachers' lounges and congregational spaces. This article discusses that an important occurrence in these spaces, professional knowledge sharing, took place instead of perpetual…

Let's Go Toy Shopping! Exploring Early Anticipatory Socialization for Careers and Gender Expectations

ERIC Educational Resources Information Center

Jones-Bodie, Ashley

2016-01-01

Courses: Gender Communication, Communication and Careers, Organizational Communication. Objectives: At the end of the activity, students will be able: to identify and analyze the socialization of gender expectations, to recognize and describe how early this type of socialization can occur, to critique the early socialization of gendered career…

"Let's Talk about the Books": The Complexity of Book Discussions in a Multilingual Preschool Classroom

ERIC Educational Resources Information Center

Fassler, Rebekah

2014-01-01

This sociolinguistic study explores complexities of supporting preschool emergent bilinguals' communicative competence in multilingual classrooms. These complexities were highlighted in the author's qualitative research of a three-month school-home literacy project in one Head Start classroom. This article investigates what supported the…

Let's Dance the "Robot Hokey-Pokey!": Children's Programming Approaches and Achievement throughout Early Cognitive Development

ERIC Educational Resources Information Center

Flannery, Louise P.; Bers, Marina Umaschi

2013-01-01

Young learners today generate, express, and interact with sophisticated ideas using a range of digital tools to explore interactive stories, animations, computer games, and robotics. In recent years, new developmentally appropriate robotics kits have been entering early childhood classrooms. This paper presents a retrospective analysis of one…

Let's Get Charged Up

ERIC Educational Resources Information Center

Duran, Emilio; Worch, Eric; Boros, Amy; Keeley, Page

2017-01-01

One of the most powerful strategies to support next generation science instruction is the use of instructional models. The Biological Sciences Curriculum Study 5E (Engage, Explore, Explain, Elaborate, and Evaluate) instructional model is arguably the most widely used version of a learning cycle in today's classrooms. The use of the 5Es as an…

Exploring the Solar System? Let the Math Teachers Help!

ERIC Educational Resources Information Center

Charles, Karen; Canales, J. D.; Smith, Angela; Zimmerman, Natalie

2012-01-01

Scale measurement and ratio and proportion are topics that fall clearly in the middle-grades mathematics curriculum in Texas. So does the solar system. In their experience, the authors have found that students have trouble manipulating, much less comprehending, very large numbers and very small numbers. These concepts can be brought into students'…

Hold on Tight or Let Go: Exploring the Parental Role in First-Year Students' College Adjustment

ERIC Educational Resources Information Center

Sax, Linda J.; Weintraub, Dayna S.

2016-01-01

Using a sample of 995 students living in residential housing at a selective, public research university, this study examined the relationship between student-parent interactions and adjustment to college and investigated differences between student-mother interactions and student-father interactions. Results indicate that students are generally…

"Let Your Data Tell a Story:" Climate Change Experts and Students Navigating Disciplinary Argumentation in the Classroom

ERIC Educational Resources Information Center

Walsh, Elizabeth Mary; McGowan, Veronica Cassone

2017-01-01

Science education trends promote student engagement in authentic knowledge in practice to tackle personally consequential problems. This study explored how partnering scientists and students on a social media platform supported students' development of disciplinary practice knowledge through practice-based learning with experts during two pilot…

Let's Not Forget the "Career" in College and Career Ready

ERIC Educational Resources Information Center

Gillis, Victoria R.; Jones-Moore, Lisa; Haynes, Chris J.; Van Wig, Ann

2016-01-01

The recent focus on preparing K-12 students to be college and career ready has increased the attention to college-level literacies but has almost ignored career and technical courses as part of the landscape of adolescent literacy. This article explores literacies embedded in career and technical education courses, provides examples from…

Let's Get Messy!: Exploring Sensory and Art Activities with Infants and Toddlers

ERIC Educational Resources Information Center

Schwarz, Trudi; Luckenbill, Julia

2012-01-01

Infant/toddler teachers take a child-centered, emergent approach, meaning that they observe the children at play, ask themselves what they are interested in learning, and design developmentally appropriate curricula to meet and extend those interests. This curriculum development technique leads to "possibilities for the child to develop deeper…

Open the Door, Let's Explore More! Field Trips of Discovery for Young Children.

ERIC Educational Resources Information Center

Redleaf, Rhoda

Designed as a resource for teachers and parents, this guide contains activities to help children in primary grades learn from walks and field trips. Chapter 1, "Experience and Learning," discusses general information about how young children learn and the contribution of field trips to children's perception, language, memory, and logical…

"Letting Go": An Auto-Ethnography of Higher Degree Supervision in Music

ERIC Educational Resources Information Center

Harrison, Scott D.

2012-01-01

This paper examines my role as supervisor of research higher degree music students. Within this dyad, the pedagogical design has centred on conventional delivery, conceptualized in terms of the time-honoured top-down, supervisor-candidate interaction rather than exploration of a co-mentoring collaboration. Many doctoral candidates in music…

Let's Turn Things on Their Head--Teaching Counterintuitive Science

ERIC Educational Resources Information Center

Kumar, David

2017-01-01

Teaching science through counterintuitive events is an effective way of engaging students in exploring science; such events motivate and involve students in solving problems with a high degree of creativity and critical thinking. This can push students into a seeking explanation mode, setting the stage for discovery. In this article, the author…

MakeHERspaces: STEM, Girls, and the Maker Movement. CRB Short Subjects. S­-14-­022

ERIC Educational Resources Information Center

Martin, Pamela

2014-01-01

Few innovations have galvanized libraries, schools, and museums like the maker movement. "Makerspaces" are community centers that combine manufacturing equipment with education in a way that lets people collaborate, explore and innovate. In makerspaces, people apply scientific and engineering principles in a hands-on environment to…

AN ANALYSIS OF SUMMER YOUTH DEMONSTRATION PROGRAMS, 1966.

ERIC Educational Resources Information Center

NELLUM, ALBERT L.; AND OTHERS

SUMMER YOUTH EMPLOYMENT PROGRAMS ARE DESIGNED TO (1) OFFER YOUTH WHOLESOME, INCOME-PRODUCING ACTIVITY WHILE THEY ARE OUT OF SCHOOL, (2) GIVE THEM THE OPPORTUNITY TO BECOME ACQUAINTED WITH JOBS AND WORK, (3) LET THEM EXPLORE VOCATIONAL POSSIBILITIES, AND (4) TEACH THEM SOMETHING OF THE EXPECTATIONS AND REQUIREMENTS OF EMPLOYERS, AS WELL AS THEIR…

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

McCaskey, Alexander J.

Hybrid programming models for beyond-CMOS technologies will prove critical for integrating new computing technologies alongside our existing infrastructure. Unfortunately the software infrastructure required to enable this is lacking or not available. XACC is a programming framework for extreme-scale, post-exascale accelerator architectures that integrates alongside existing conventional applications. It is a pluggable framework for programming languages developed for next-gen computing hardware architectures like quantum and neuromorphic computing. It lets computational scientists efficiently off-load classically intractable work to attached accelerators through user-friendly Kernel definitions. XACC makes post-exascale hybrid programming approachable for domain computational scientists.

A Secure Mobile-Based Authentication System for e-Banking

NASA Astrophysics Data System (ADS)

Rifà-Pous, Helena

Financial information is extremely sensitive. Hence, electronic banking must provide a robust system to authenticate its customers and let them access their data remotely. On the other hand, such system must be usable, affordable, and portable. We propose a challenge-response based one-time password (OTP) scheme that uses symmetric cryptography in combination with a hardware security module. The proposed protocol safeguards passwords from keyloggers and phishing attacks. Besides, this solution provides convenient mobility for users who want to bank online anytime and anywhere, not just from their own trusted computers.

Genomic DNA Copy-Number Alterations of the let-7 Family in Human Cancers

PubMed Central

Greshock, Joel; Shen, Liang; Yang, Xiaojun; Shao, Zhongjun; Liang, Shun; Tanyi, Janos L.; Sood, Anil K.; Zhang, Lin

2012-01-01

In human cancer, expression of the let-7 family is significantly reduced, and this is associated with shorter survival times in patients. However, the mechanisms leading to let-7 downregulation in cancer are still largely unclear. Since an alteration in copy-number is one of the causes of gene deregulation in cancer, we examined copy number alterations of the let-7 family in 2,969 cancer specimens from a high-resolution SNP array dataset. We found that there was a reduction in the copy number of let-7 genes in a cancer-type specific manner. Importantly, focal deletion of four let-7 family members was found in three cancer types: medulloblastoma (let-7a-2 and let-7e), breast cancer (let-7a-2), and ovarian cancer (let-7a-3/let-7b). For example, the genomic locus harboring let-7a-3/let-7b was deleted in 44% of the specimens from ovarian cancer patients. We also found a positive correlation between the copy number of let-7b and mature let-7b expression in ovarian cancer. Finally, we showed that restoration of let-7b expression dramatically reduced ovarian tumor growth in vitro and in vivo. Our results indicate that copy number deletion is an important mechanism leading to the downregulation of expression of specific let-7 family members in medulloblastoma, breast, and ovarian cancers. Restoration of let-7 expression in tumor cells could provide a novel therapeutic strategy for the treatment of cancer. PMID:22970210

Potential health effects of space radiation

NASA Technical Reports Server (NTRS)

Yang, Chui-Hsu; Craise, Laurie M.

1993-01-01

Crewmembers on missions to the Moon or Mars will be exposed to radiation belts, galactic cosmic rays, and possibly solar particle events. The potential health hazards due to these space radiations must be considered carefully to ensure the success of space exploration. Because there is no human radioepidemiological data for acute and late effects of high-LET (Linear-Energy-Transfer) radiation, the biological risks of energetic charged particles have to be estimated from experimental results on animals and cultured cells. Experimental data obtained to date indicate that charged particle radiation can be much more effective than photons in causing chromosome aberrations, cell killing, mutation, and tumor induction. The relative biological effectiveness (RBE) varies with biological endpoints and depends on the LET of heavy ions. Most lesions induced by low-LET radiation can be repaired in mammalian cells. Energetic heavy ions, however, can produce large complex DNA damages, which may lead to large deletions and are irreparable. For high-LET radiation, therefore, there are less or no dose rate effects. Physical shielding may not be effective in minimizing the biological effects on energetic heavy ions, since fragments of the primary particles can be effective in causing biological effects. At present the uncertainty of biological effects of heavy particles is still very large. With further understanding of the biological effects of space radiation, the career doses can be kept at acceptable levels so that the space radiation environment need not be a barrier to the exploitation of the promise of space.

Poster — Thur Eve — 45: Comparison of different Monte Carlo methods of scoring linear energy transfer in modulated proton therapy beams

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

Granville, DA; Sawakuchi, GO

2014-08-15

In this work, we demonstrate inconsistencies in commonly used Monte Carlo methods of scoring linear energy transfer (LET) in proton therapy beams. In particle therapy beams, the LET is an important parameter because the relative biological effectiveness (RBE) depends on it. LET is often determined using Monte Carlo techniques. We used a realistic Monte Carlo model of a proton therapy nozzle to score proton LET in spread-out Bragg peak (SOBP) depth-dose distributions. We used three different scoring and calculation techniques to determine average LET at varying depths within a 140 MeV beam with a 4 cm SOBP and a 250more » MeV beam with a 10 cm SOBP. These techniques included fluence-weighted (Φ-LET) and dose-weighted average (D-LET) LET calculations from: 1) scored energy spectra converted to LET spectra through a lookup table, 2) directly scored LET spectra and 3) accumulated LET scored ‘on-the-fly’ during simulations. All protons (primary and secondary) were included in the scoring. Φ-LET was found to be less sensitive to changes in scoring technique than D-LET. In addition, the spectral scoring methods were sensitive to low-energy (high-LET) cutoff values in the averaging. Using cutoff parameters chosen carefully for consistency between techniques, we found variations in Φ-LET values of up to 1.6% and variations in D-LET values of up to 11.2% for the same irradiation conditions, depending on the method used to score LET. Variations were largest near the end of the SOBP, where the LET and energy spectra are broader.« less

Sketching Uncertainty into Simulations.

PubMed

Ribicic, H; Waser, J; Gurbat, R; Sadransky, B; Groller, M E

2012-12-01

In a variety of application areas, the use of simulation steering in decision making is limited at best. Research focusing on this problem suggests that most user interfaces are too complex for the end user. Our goal is to let users create and investigate multiple, alternative scenarios without the need for special simulation expertise. To simplify the specification of parameters, we move from a traditional manipulation of numbers to a sketch-based input approach. Users steer both numeric parameters and parameters with a spatial correspondence by sketching a change onto the rendering. Special visualizations provide immediate visual feedback on how the sketches are transformed into boundary conditions of the simulation models. Since uncertainty with respect to many intertwined parameters plays an important role in planning, we also allow the user to intuitively setup complete value ranges, which are then automatically transformed into ensemble simulations. The interface and the underlying system were developed in collaboration with experts in the field of flood management. The real-world data they have provided has allowed us to construct scenarios used to evaluate the system. These were presented to a variety of flood response personnel, and their feedback is discussed in detail in the paper. The interface was found to be intuitive and relevant, although a certain amount of training might be necessary.

Choosing blindly but wisely: differentially private solicitation of DNA datasets for disease marker discovery.

PubMed

Zhao, Yongan; Wang, Xiaofeng; Jiang, Xiaoqian; Ohno-Machado, Lucila; Tang, Haixu

2015-01-01

To propose a new approach to privacy preserving data selection, which helps the data users access human genomic datasets efficiently without undermining patients' privacy. Our idea is to let each data owner publish a set of differentially-private pilot data, on which a data user can test-run arbitrary association-test algorithms, including those not known to the data owner a priori. We developed a suite of new techniques, including a pilot-data generation approach that leverages the linkage disequilibrium in the human genome to preserve both the utility of the data and the privacy of the patients, and a utility evaluation method that helps the user assess the value of the real data from its pilot version with high confidence. We evaluated our approach on real human genomic data using four popular association tests. Our study shows that the proposed approach can help data users make the right choices in most cases. Even though the pilot data cannot be directly used for scientific discovery, it provides a useful indication of which datasets are more likely to be useful to data users, who can therefore approach the appropriate data owners to gain access to the data. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association.

Using the TSAR electromagnetic modeling system

NASA Astrophysics Data System (ADS)

Pennock, S. T.; Laguna, G. W.

1993-09-01

A new user, upon receipt of the TSAR EM modeling system, may be overwhelmed by the number of software packages to learn and the number of manuals associated with those packages. This is a document to describe the creation of a simple TSAR model, beginning with an MGED solid and continuing the process through final results from TSAR. It is not intended to be a complete description of all the parts of the TSAR package. Rather, it is intended simply to touch on all the steps in the modeling process and to take a new user through the system from start to finish. There are six basic parts to the TSAR package. The first, MGED, is part of the BRL-CAD package and is used to create a solid model. The second part, ANASTASIA, is the program used to sample the solid model and create a finite-difference mesh. The third program, IMAGE, lets the user view the mesh itself and verify its accuracy. If everything about the mesh is correct, the process continues to the fourth step, SETUP-TSAR, which creates the parameter files for compiling TSAR and the input file for running a particular simulation. The fifth step is actually running TSAR, the field modeling program. Finally, the output from TSAR is placed into SIG, B2RAS or another program for post-processing and plotting. Each of these steps will be described below. The best way to learn to use the TSAR software is to actually create and run a simple test problem. As an example of how to use the TSAR package, let's create a sphere with a rectangular internal cavity, with conical and cylindrical penetrations connecting the outside to the inside, and find the electric field inside the cavity when the object is exposed to a Gaussian plane wave. We will begin with the solid modeling software, MGED, a part of the BRL-CAD modeling release.

Stepwise assembly of multiple Lin28 proteins on the terminal loop of let-7 miRNA precursors

PubMed Central

Desjardins, Alexandre; Bouvette, Jonathan; Legault, Pascale

2014-01-01

Lin28 inhibits the biogenesis of let-7 miRNAs through direct interactions with let-7 precursors. Previous studies have described seemingly inconsistent Lin28 binding sites on pre-let-7 RNAs. Here, we reconcile these data by examining the binding mechanism of Lin28 to the terminal loop of pre-let-7g (TL-let-7g) using biochemical and biophysical methods. First, we investigate Lin28 binding to TL-let-7g variants and short RNA fragments and identify three independent binding sites for Lin28 on TL-let-7g. We then determine that Lin28 assembles in a stepwise manner on TL-let-7g to form a stable 1:3 complex. We show that the cold-shock domain (CSD) of Lin28 is responsible for remodelling the terminal loop of TL-let-7g, whereas the NCp7-like domain facilitates the initial binding of Lin28 to TL-let-7g. This stable binding of multiple Lin28 molecules to the terminal loop of pre-let-7g extends to other precursors of the let-7 family, but not to other pre-miRNAs tested. We propose a model for stepwise assembly of the 1:1, 1:2 and 1:3 pre-let-7g/Lin28 complexes. Stepwise multimerization of Lin28 on pre-let-7 is required for maximum inhibition of Dicer cleavage for a least one member of the let-7 family and may be important for orchestrating the activity of the several factors that regulate let-7 biogenesis. PMID:24452802

Modeling Goal-Directed User Exploration in Human-Computer Interaction

DTIC Science & Technology

2011-02-01

scent, other factors including the layout position and grouping of options in the user-interface also affect user exploration and the likelihood of...grouping of options in the user-interface also affect user exploration and the likelihood of success. This dissertation contributes a new model of goal...better inform UI design. 1.1 RESEARCH GAPS IN MODELING In addition to infoscent, the layout of the UI also affects the choices made during

[Problem Solving Activities.

ERIC Educational Resources Information Center

Wisconsin Univ. - Stout, Menomonie. Center for Vocational, Technical and Adult Education.

The teacher directed problem solving activities package contains 17 units: Future Community Design, Let's Build an Elevator, Let's Construct a Catapult, Let's Design a Recreational Game, Let's Make a Hand Fishing Reel, Let's Make a Wall Hanging, Let's Make a Yo-Yo, Marooned in the Past, Metrication, Mousetrap Vehicles, The Multi System…

"Thanks for Letting Us All Share Your Mammogram Experience Virtually": Developing a Web-Based Hub for Breast Cancer Screening.

PubMed

Galpin, Adam; Meredith, Joanne; Ure, Cathy; Robinson, Leslie

2017-10-27

The decision around whether to attend breast cancer screening can often involve making sense of confusing and contradictory information on its risks and benefits. The Word of Mouth Mammogram e-Network (WoMMeN) project was established to create a Web-based resource to support decision making regarding breast cancer screening. This paper presents data from our user-centered approach in engaging stakeholders (both health professionals and service users) in the design of this Web-based resource. Our novel approach involved creating a user design group within Facebook to allow them access to ongoing discussion between researchers, radiographers, and existing and potential service users. This study had two objectives. The first was to examine the utility of an online user design group for generating insight for the creation of Web-based health resources. We sought to explore the advantages and limitations of this approach. The second objective was to analyze what women want from a Web-based resource for breast cancer screening. We recruited a user design group on Facebook and conducted a survey within the group, asking questions about design considerations for a Web-based breast cancer screening hub. Although the membership of the Facebook group varied over time, there were 71 members in the Facebook group at the end point of analysis. We next conducted a framework analysis on 70 threads from Facebook and a thematic analysis on the 23 survey responses. We focused additionally on how the themes were discussed by the different stakeholders within the context of the design group. Two major themes were found across both the Facebook discussion and the survey data: (1) the power of information and (2) the hub as a place for communication and support. Information was considered as empowering but also recognized as threatening. Communication and the sharing of experiences were deemed important, but there was also recognition of potential miscommunication within online discussion. Health professionals and service users expressed the same broad concerns, but there were subtle differences in their opinions. Importantly, the themes were triangulated between the Facebook discussions and the survey data, supporting the validity of an online user design group. Online user design groups afford a useful method for understanding stakeholder needs. In contrast to focus groups, they afford access to users from diverse geographical locations and traverse time constraints, allowing more follow-ups to responses. The use of Facebook provides a familiar and naturalistic setting for discussion. Although we acknowledge the limitations in the sample, this approach has allowed us to understand the views of stakeholders in the user-centered design of the WoMMeN hub for breast cancer screening. ©Adam Galpin, Joanne Meredith, Cathy Ure, Leslie Robinson. Originally published in JMIR Cancer (http://cancer.jmir.org), 27.10.2017.

Scenario driven data modelling: a method for integrating diverse sources of data and data streams

PubMed Central

2011-01-01

Background Biology is rapidly becoming a data intensive, data-driven science. It is essential that data is represented and connected in ways that best represent its full conceptual content and allows both automated integration and data driven decision-making. Recent advancements in distributed multi-relational directed graphs, implemented in the form of the Semantic Web make it possible to deal with complicated heterogeneous data in new and interesting ways. Results This paper presents a new approach, scenario driven data modelling (SDDM), that integrates multi-relational directed graphs with data streams. SDDM can be applied to virtually any data integration challenge with widely divergent types of data and data streams. In this work, we explored integrating genetics data with reports from traditional media. SDDM was applied to the New Delhi metallo-beta-lactamase gene (NDM-1), an emerging global health threat. The SDDM process constructed a scenario, created a RDF multi-relational directed graph that linked diverse types of data to the Semantic Web, implemented RDF conversion tools (RDFizers) to bring content into the Sematic Web, identified data streams and analytical routines to analyse those streams, and identified user requirements and graph traversals to meet end-user requirements. Conclusions We provided an example where SDDM was applied to a complex data integration challenge. The process created a model of the emerging NDM-1 health threat, identified and filled gaps in that model, and constructed reliable software that monitored data streams based on the scenario derived multi-relational directed graph. The SDDM process significantly reduced the software requirements phase by letting the scenario and resulting multi-relational directed graph define what is possible and then set the scope of the user requirements. Approaches like SDDM will be critical to the future of data intensive, data-driven science because they automate the process of converting massive data streams into usable knowledge. PMID:22165854

An analytical dose-averaged LET calculation algorithm considering the off-axis LET enhancement by secondary protons for spot-scanning proton therapy.

PubMed

Hirayama, Shusuke; Matsuura, Taeko; Ueda, Hideaki; Fujii, Yusuke; Fujii, Takaaki; Takao, Seishin; Miyamoto, Naoki; Shimizu, Shinichi; Fujimoto, Rintaro; Umegaki, Kikuo; Shirato, Hiroki

2018-05-22

To evaluate the biological effects of proton beams as part of daily clinical routine, fast and accurate calculation of dose-averaged linear energy transfer (LET d ) is required. In this study, we have developed the analytical LET d calculation method based on the pencil-beam algorithm (PBA) considering the off-axis enhancement by secondary protons. This algorithm (PBA-dLET) was then validated using Monte Carlo simulation (MCS) results. In PBA-dLET, LET values were assigned separately for each individual dose kernel based on the PBA. For the dose kernel, we employed a triple Gaussian model which consists of the primary component (protons that undergo the multiple Coulomb scattering) and the halo component (protons that undergo inelastic, nonelastic and elastic nuclear reaction); the primary and halo components were represented by a single Gaussian and the sum of two Gaussian distributions, respectively. Although the previous analytical approaches assumed a constant LET d value for the lateral distribution of a pencil beam, the actual LET d increases away from the beam axis, because there are more scattered and therefore lower energy protons with higher stopping powers. To reflect this LET d behavior, we have assumed that the LETs of primary and halo components can take different values (LET p and LET halo ), which vary only along the depth direction. The values of dual-LET kernels were determined such that the PBA-dLET reproduced the MCS-generated LET d distribution in both small and large fields. These values were generated at intervals of 1 mm in depth for 96 energies from 70.2 to 220 MeV and collected in the look-up table. Finally, we compared the LET d distributions and mean LET d (LET d,mean ) values of targets and organs at risk between PBA-dLET and MCS. Both homogeneous phantom and patient geometries (prostate, liver, and lung cases) were used to validate the present method. In the homogeneous phantom, the LET d profiles obtained by the dual-LET kernels agree well with the MCS results except for the low-dose region in the lateral penumbra, where the actual dose was below 10% of the maximum dose. In the patient geometry, the LET d profiles calculated with the developed method reproduces MCS with the similar accuracy as in the homogeneous phantom. The maximum differences in LET d,mean for each structure between the PBA-dLET and the MCS were 0.06 keV/μm in homogeneous phantoms and 0.08 keV/μm in patient geometries under all tested conditions, respectively. We confirmed that the dual-LET-kernel model well reproduced the MCS, not only in the homogeneous phantom but also in complex patient geometries. The accuracy of the LET d was largely improved from the single-LET-kernel model, especially at the lateral penumbra. The model is expected to be useful, especially for proper recognition of the risk of side effects when the target is next to critical organs. © 2018 American Association of Physicists in Medicine.

Questionnaire Design in Broad-Based Evaluation Studies: Letting Someone Else Collect Comparison Group Data.

ERIC Educational Resources Information Center

Clark, Sheldon B.; Boser, Judith A.

A context in which existing items may provide a convenient source of questions for questionnaires was explored through a case study making use of existing comparison groups. Two programs at Oak Ridge Associated Universities (ORAU), the Science and Engineering Research Semester (SERS) and the Laboratory Graduate Research Participation (Lab Grad)…

Let Me Blow Your Mind: Hip Hop Feminist Futures in Theory and Praxis

ERIC Educational Resources Information Center

Lindsey, Treva B.

2015-01-01

This essay brings together key theoretical interventions in hip-hop feminism to explore the continued, but undervalued, significance of hip-hop feminism in urban education. More specifically, the essay challenges narrow conceptualizations of the "hip hop subject" as Black and male by using hip-hop feminist theory to incorporate the lived…

Open the Door Let's Explore: Neighborhood Field Trips for Young Children.

ERIC Educational Resources Information Center

Redleaf, Rhoda

Designed as a resource for teachers and parents, this guide contains activities to help children from 2 to 8 years old learn from neighborhood walks and field trips. Information is presented on: field trips as an approach to learning, learning processes of children, and techniques to make trips meaningful. Teaching material for each trip includes…

Access and Inclusion for Children with Autistic Spectrum Disorders: "Let Me In."

ERIC Educational Resources Information Center

Hesmondhalgh, Matthew; Breakey, Christine

Based on pioneering work at a school in Sheffield, England, this book explores the universal issues of access and inclusion in employment and education for children and young people with Autism Spectrum Disorders (ASD). It describes the challenges educators faced in establishing and running an integrated resource room for children with ASD within…

A Summer Camp Experience of Primary Student: Let's Learn Astronomy, Explore the Space Summer Camp

ERIC Educational Resources Information Center

Aktamis, Hilal; Acar, Esin; Unal Coban, Gul

2015-01-01

It is important to structure children's knowledge and arouse their interest in subjects like astronomy and space. Although we now talk of travelling to the moon, space tourism etc., knowledge about astronomy and space is limited and perceptions of these subjects do not reflect scientific reality. Primary level students often have misconceptions…

77 FR 63413 - Early Scoping Notification for the Alternatives Analysis of the Federal Way Transit Extension...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-16

... costs, and other factors that the public and agencies believe should be considered in analyzing the....'' The alternatives analysis lets an agency evaluate the costs, benefits, and impacts of a range of... scoping notice to advise other agencies and the public that they intend to explore potential alternatives...

Let's Take a Trip: Exploring the Effect of Listening Styles

ERIC Educational Resources Information Center

Dailey, Stephanie L.

2014-01-01

Listening is a core component of developing effective communication skills. Thus, a common objective of many basic communication courses is to help students become better listeners (Johnson & Long, 2007). Often, the teacher's goal is to show students that there are different listening styles or preferences and that people decode messages…

"Just Let Us Teach!": Living Literacy Policy in and around Maplewood Elementary School

ERIC Educational Resources Information Center

Morton-Rose, Cindy Anne

2013-01-01

Through a sociocultural lens this study explored how four teachers, a reading teacher, and their principal lived literacy policy in practice in and around Maplewood Elementary School. This work grew out of three questions: (a) How do six policy stakeholders at one elementary school--four teachers, one administrator, and one reading teacher-make…

Learn about Earth Science: Weather. [CD-ROM].

ERIC Educational Resources Information Center

2000

This CD-ROM, designed for students in grades K-2, explores the world of weather. Students investigate weather to learn about climate and the seasons, how animals adapt to weather changes, how clouds tell us about conditions, and how weather plays a part in our everyday lives. The weather calendar lets students record and write about conditions…

The Development and Publication of Elementary Mathematics Textbooks: Let the Buyer Beware!

ERIC Educational Resources Information Center

Reys, Barbara J.; Reys, Robert E.

2006-01-01

Mathematics textbooks are critical tools for student learning in American classrooms. Teachers use them daily to plan and deliver lessons, and students use them in class to explore and learn mathematics. Given textbooks' potential to support student learning, it is important to understand how they are developed. While pressure is growing on…

How Do Your Climates Show? Let Us Count Some Ways. Research Report No. 8.

ERIC Educational Resources Information Center

Schneider, Benjamin

Some "hidden" consequences of an organization's goals, practices, and procedures on the climates created for employees were reviewed, beginning with an exploration of some potential impacts of a lack of fit between goals and means to obtain goals on climate and eventual employee behavior, referring particularly to differences between product- and…

LETs and NETs: Exploring How Teachers from Diverse Cultural Backgrounds Impact Student Motivation and Preferences

ERIC Educational Resources Information Center

Wong, Ruth

2014-01-01

This paper, an exploratory case study, examines how students' preferences and motivation to learn English are influenced by their perceptions of teaching practices--both of native English teachers and local English teachers. To better understand the context of this research question, this study adopts a method of triangulation in collecting data:…

"Let Them See a Different Path": Social Attitudes towards Sport, Education and Development in Samoa

ERIC Educational Resources Information Center

Kwauk, Christina Ting

2016-01-01

Drawing on ethnographic data collected over 12 months of field research, this paper contributes to the growing body of literature on sport for development (SFD) by giving voice to alternative constructions of the educative potential of SFD. It does this by exploring the social attitudes of youth, educators, community leaders and government…

Let's Add R.I.C.E. (Relevant, Intercultural, Childhood Experiences) to Our Curriculum Menu!

ERIC Educational Resources Information Center

Willmott, Kathleen E.; Lee-Harris, Stephanie

In the United States and other countries experiencing large influxes of immigrants, how to acknowledge and address the increased diversity has been a challenge for early childhood education. This article explores the use of children's literature in this process, and includes a brief description and evaluation of five culturally diverse children's…

Let's Bring Back the Magic of Song for Teaching Reading

ERIC Educational Resources Information Center

Iwasaki, Becky; Rasinski, Timothy; Yildirim, Kasim; Zimmerman, Belinda S.

2013-01-01

Based on a first grade teacher's search for approaches to promote successful reading acquisition in her first grade classroom, the authors present a curricular engagement in which the teacher explored using music, specifically singing songs, as a fun and motivating way to accelerate reading progress. The premise is that singing (while at the…

"Let His Voice Be Heard": A Community's Response to Inclusion of an Indigenous Counter-Narrative in the District Curriculum

ERIC Educational Resources Information Center

McCarthy, Glenda; Stanton, Christine Rogers

2017-01-01

Curricular counter-narratives can affirm the experiences of marginalized youth, but, given their complexity and unfamiliarity, they can also generate discord between community members. This case study analyzes documents, observations, and interviews to explore ways an Indigenous counter-narrative can create space for multicultural education within…

The Challenge of Creating a More Diverse Economics: Lessons from the UCR Minority Pipeline Project

ERIC Educational Resources Information Center

Dymski, Gary A.

2017-01-01

This paper reflects on the experience of the 1999-2002 minority pipeline program (MPP) at the University of California, Riverside. With support from the American Economic Association, the MPP identified students of color interested in economics, let them explore economic issues affecting minority communities, and encouraged them to consider…

Let's Think Creatively: Designing a High School Lesson on Metaphorical Creativity for English L2 Learners

ERIC Educational Resources Information Center

Wang, Hung-chun

2018-01-01

This article reports on a practitioner research study exploring how creative thinking activities can be designed and integrated into high school English classes. It delineates the process of developing a metaphorical creativity workshop for year 11 students in Taiwan and demonstrates the students' workshop experiences and learning outcomes.…

Lessons in "Letting Go": Exploring Constraints on the Culturally Relevant Teaching of Mathematics in Bermuda

ERIC Educational Resources Information Center

Matthews, Lou Edward

2008-01-01

Culturally relevant pedagogy has been highly regarded in its ability to impact the mathematics education outcomes of Black children as it is framed from the "wisdom-of-practice" of exemplary teachers, and recasts teaching as an intellectual, cultural, political, and social endeavor. This study illuminates the challenges in drawing…

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

PubMed

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.

Let-7 miRNA Precursors Co-express with LIN28B in Cervical Cells.

PubMed

Zamora-Contreras, Aida Margarita; Alvarez-Salas, Luis Marat

2018-01-01

The let-7 microRNAs (miRNAs) are frequently dysregulated in carcinogenic processes, including cervical cancer. LIN28 proteins regulate let-7 biogenesis by binding to conserved sequences within the pre-miRNA structure. Nevertheless, recent research has shown that some let-7 miRNAs may escape LIN28 regulation. Correlate pre-let-7 miRNAs and LIN28B levels in cervical cell lines with different malignancy and HPV content. Pre-let-7 levels were determined by RTqPCR. LIN28B and other let-7 targets were analyzed by immunoblot. In silico tools were used to correlate let-7 and LIN28B expression and to analyze prelet- 7 sequences and structures. Lin28B protein was detected in all tested cell lines although it was more expressed in tumor cell lines. High levels of pre-let-7c/f-1 and pre-miR-98 were present in almost all cell lines regardless malignancy and LIN28B expression. Pre-let-7g/i were mainly expressed in tumor cell lines, pre-let-7e and pre-let-7-a3 were absent in all cell lines and pre-let-7a-2 showed indistinct expression. LIN28B showed positive correlation with pre-let-7i/g/f-1 and pre-miR-98 in tumor cell lines, suggesting escape from regulation. Sequence alignment and analysis of pre-let-7 miRNAs showed distinctive structural features within the preE region that may influence the ideal pre-let-7 structuring for LIN28B interaction. Short preE-stems were present in pre-let-7 that may escape LIN28B regulation, but long preEstems were mostly associated with high-level pre-let-7 miRNAs. The observed differences of pre-let-7 levels in cervical cell lines may be the result of alternative preE structuring affecting interaction with LIN28B thus resulting in differential let-7 regulation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

let-7 Contributes to Diabetic Retinopathy but Represses Pathological Ocular Angiogenesis

PubMed Central

Zhou, Qinbo; Frost, Robert J. A.; Anderson, Chastain; Zhao, Fangkun; Ma, Jing; Yu, Bo

2017-01-01

ABSTRACT The in vivo function of microRNAs (miRs) in diabetic retinopathy (DR) and age-related macular degeneration (AMD) remains unclear. We report here that let-7 family members are expressed in retinal and choroidal endothelial cells (ECs). In ECs, overexpression of let-7 by adenovirus represses EC proliferation, migration, and networking in vitro, whereas inhibition of the let-7 family with a locked nucleic acid (LNA)–anti-miR has the opposite effect. Mechanistically, silencing of the let-7 target HMGA2 gene mimics the phenotype of let-7 overexpression in ECs. let-7 transgenic (let-7-Tg) mice show features of nonproliferative DR, including tortuous retinal vessels and defective pericyte coverage. However, these mice develop significantly less choroidal neovascularization (CNV) compared to wild-type controls after laser injury. Consistently, silencing of let-7 in the eye increased laser-induced CNV in wild-type mice. Together, our data establish a causative role of let-7 in nonproliferative diabetic retinopathy and a repressive function of let-7 in pathological angiogenesis, suggesting distinct implications of let-7 in the pathogenesis of DR and AMD. PMID:28584193

An anti-let-7 sponge decoys and decays endogenous let-7 functions

PubMed Central

Yang, Xiangling; Rutnam, Zina Jeyapalan; Jiao, Chunwei; Wei, Duo; Xie, Yizhen; Du, Jun; Zhong, Ling; Yang, Burton B.

2012-01-01

The let-7 family contains 12 members, which share identical seed regions, suggesting that they may target the same mRNAs. It is essential to develop a means that can regulate the functions of all members. Using a DNA synthesis technique, we have generated an anti-let-7 sponge aiming to modulate the function of all members. We found that products of the anti-let-7 construct could bind and inactivate all members of the let-7 family, producing decoy and decay effects. To test the role of the anti-let-7 sponge, we stably expressed the anti-let-7 construct in two types of cells, the breast carcinoma cells MT-1 and the oldest and most commonly used human cervical cancer cell line, HeLa cells. We found that expression of anti-let-7 increased cell survival, invasion and adhesion, which corroborate with known functions of let-7 family members. We further identified a novel target site across all species of the let-7 family in hyaluronan synthase 2 (HAS2). HAS2 overexpression produced similar effects as the anti-let-7 sponge. Silencing HAS2 expression by siRNAs produced opposite effects to anti-let-7 on cell survival and invasion. The ability of anti-let-7 to regulate multiple members of the let-7 family allows us to observe their multiple functions using a single reagent. This approach can be applied to other family members with conserved sequences. PMID:22871741

Ethics of Engagement: User-Centered Design and Rhetorical Methodology.

ERIC Educational Resources Information Center

Salvo, Michael J.

2001-01-01

Explores the shift from observation of users to participation with users, describing and investigating three examples of user-centered design practice in order to consider the new ethical demands being made of technical communicators. Explores Pelle Ehn's participatory design method, Roger Whitehouse's design of tactile signage for blind users,…

Let's Orbit Mars: A Proposal to Explore Mars Now

NASA Technical Reports Server (NTRS)

Landis, Geoffrey A.

2004-01-01

Mars is an exciting target for the human exploration; the next destination toward the ultimate human colonization of the solar system. But the price of proposed missions to Mars is a daunting barrier. Expensive missions make it a slow and difficult process to achieve the political consensus to make a commitment to exploration. In today's deficit-conscious era (and what era is not?), it is as difficult-- perhaps impossible-- task to justify to a skeptical and cost-conscious public the need to invest in exploration. It seems far too easy to postpone exploration into a future that never seems to arrive. It would be terrific to explore Mars in small steps, where each step makes progress toward human exploration and settlement, and each step also is not only exciting to the public, but also justifiable on its own scientific merits.

Analysis of the track- and dose-averaged LET and LET spectra in proton therapy using the GEANT4 Monte Carlo code

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

Guan, Fada; Peeler, Christopher; Taleei, Reza

Purpose: The motivation of this study was to find and eliminate the cause of errors in dose-averaged linear energy transfer (LET) calculations from therapeutic protons in small targets, such as biological cell layers, calculated using the GEANT 4 Monte Carlo code. Furthermore, the purpose was also to provide a recommendation to select an appropriate LET quantity from GEANT 4 simulations to correlate with biological effectiveness of therapeutic protons. Methods: The authors developed a particle tracking step based strategy to calculate the average LET quantities (track-averaged LET, LET{sub t} and dose-averaged LET, LET{sub d}) using GEANT 4 for different tracking stepmore » size limits. A step size limit refers to the maximally allowable tracking step length. The authors investigated how the tracking step size limit influenced the calculated LET{sub t} and LET{sub d} of protons with six different step limits ranging from 1 to 500 μm in a water phantom irradiated by a 79.7-MeV clinical proton beam. In addition, the authors analyzed the detailed stochastic energy deposition information including fluence spectra and dose spectra of the energy-deposition-per-step of protons. As a reference, the authors also calculated the averaged LET and analyzed the LET spectra combining the Monte Carlo method and the deterministic method. Relative biological effectiveness (RBE) calculations were performed to illustrate the impact of different LET calculation methods on the RBE-weighted dose. Results: Simulation results showed that the step limit effect was small for LET{sub t} but significant for LET{sub d}. This resulted from differences in the energy-deposition-per-step between the fluence spectra and dose spectra at different depths in the phantom. Using the Monte Carlo particle tracking method in GEANT 4 can result in incorrect LET{sub d} calculation results in the dose plateau region for small step limits. The erroneous LET{sub d} results can be attributed to the algorithm to determine fluctuations in energy deposition along the tracking step in GEANT 4. The incorrect LET{sub d} values lead to substantial differences in the calculated RBE. Conclusions: When the GEANT 4 particle tracking method is used to calculate the average LET values within targets with a small step limit, such as smaller than 500 μm, the authors recommend the use of LET{sub t} in the dose plateau region and LET{sub d} around the Bragg peak. For a large step limit, i.e., 500 μm, LET{sub d} is recommended along the whole Bragg curve. The transition point depends on beam parameters and can be found by determining the location where the gradient of the ratio of LET{sub d} and LET{sub t} becomes positive.« less

The ideal self at play: the appeal of video games that let you be all you can be.

PubMed

Przybylski, Andrew K; Weinstein, Netta; Murayama, Kou; Lynch, Martin F; Ryan, Richard M

2012-01-01

Video games constitute a popular form of entertainment that allows millions of people to adopt virtual identities. In our research, we explored the idea that the appeal of games is due in part to their ability to provide players with novel experiences that let them "try on" ideal aspects of their selves that might not find expression in everyday life. We found that video games were most intrinsically motivating and had the greatest influence on emotions when players' experiences of themselves during play were congruent with players' conceptions of their ideal selves. Additionally, we found that high levels of immersion in gaming environments, as well as large discrepancies between players' actual-self and ideal-self characteristics, magnified the link between intrinsic motivation and the experience of ideal-self characteristics during play.

Guided exploration in virtual environments

NASA Astrophysics Data System (ADS)

Beckhaus, Steffi; Eckel, Gerhard; Strothotte, Thomas

2001-06-01

We describe an application supporting alternating interaction and animation for the purpose of exploration in a surround- screen projection-based virtual reality system. The exploration of an environment is a highly interactive and dynamic process in which the presentation of objects of interest can give the user guidance while exploring the scene. Previous systems for automatic presentation of models or scenes need either cinematographic rules, direct human interaction, framesets or precalculation (e.g. precalculation of paths to a predefined goal). We report on the development of a system that can deal with rapidly changing user interest in objects of a scene or model as well as with dynamic models and changes of the camera position introduced interactively by the user. It is implemented as a potential-field based camera data generating system. In this paper we describe the implementation of our approach in a virtual art museum on the CyberStage, our surround-screen projection-based stereoscopic display. The paradigm of guided exploration is introduced describing the freedom of the user to explore the museum autonomously. At the same time, if requested by the user, guided exploration provides just-in-time navigational support. The user controls this support by specifying the current field of interest in high-level search criteria. We also present an informal user study evaluating this approach.

Multiple Functions of Let-23, a Caenorhabditis Elegans Receptor Tyrosine Kinase Gene Required for Vulval Induction

PubMed Central

Aroian, R. V.; Sternberg, P. W.

1991-01-01

The let-23 gene, which encodes a putative tyrosine kinase of the epidermal growth factor (EGF) receptor subfamily, has multiple functions during Caenorhabditis elegans development. We show that let-23 function is required for vulval precursor cells (VPCs) to respond to the signal that induces vulval differentiation: a complete loss of let-23 function results in no induction. However, some let-23 mutations that genetically reduce but do not eliminate let-23 function result in VPCs apparently hypersensitive to inductive signal: as many as five of six VPCs can adopt vulval fates, in contrast to the three that normally do. These results suggest that the let-23 receptor tyrosine kinase controls two opposing pathways, one that stimulates vulval differentiation and another that negatively regulates vulval differentiation. Furthermore, analysis of 16 new let-23 mutations indicates that the let-23 kinase functions in at least five tissues. Since various let-23 mutant phenotypes can be obtained independently, the let-23 gene is likely to have tissue-specific functions. PMID:2071015

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

PubMed Central

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

MicroRNA let-7c Inhibits Cell Proliferation and Induces Cell Cycle Arrest by Targeting CDC25A in Human Hepatocellular Carcinoma

PubMed Central

Zhu, Xiuming; Wu, Lingjiao; Yao, Jian; Jiang, Han; Wang, Qiangfeng; Yang, Zhijian; Wu, Fusheng

2015-01-01

Down-regulation of the microRNA let-7c plays an important role in the pathogenesis of human hepatocellular carcinoma (HCC). The aim of the present study was to determine whether the cell cycle regulator CDC25A is involved in the antitumor effect of let-7c in HCC. The expression levels of let-7c in HCC cell lines were examined by quantitative real-time PCR, and a let-7c agomir was transfected into HCC cells to overexpress let-7c. The effects of let-7c on HCC proliferation, apoptosis and cell cycle were analyzed. The in vivo tumor-inhibitory efficacy of let-7c was evaluated in a xenograft mouse model of HCC. Luciferase reporter assays and western blotting were conducted to identify the targets of let-7c and to determine the effects of let-7c on CDC25A, CyclinD1, CDK6, pRb and E2F2 expression. The results showed that the expression levels of let-7c were significantly decreased in HCC cell lines. Overexpression of let-7c repressed cell growth, induced cell apoptosis, led to G1 cell cycle arrest in vitro, and suppressed tumor growth in a HepG2 xenograft model in vivo. The luciferase reporter assay showed that CDC25A was a direct target of let-7c, and that let-7c inhibited the expression of CDC25A protein by directly targeting its 3ʹ UTR. Restoration of CDC25A induced a let-7c-mediated G1-to-S phase transition. Western blot analysis demonstrated that overexpression of let-7c decreased CyclinD1, CDK6, pRb and E2F2 protein levels. In conclusion, this study indicates that let-7c suppresses HCC progression, possibly by directly targeting the cell cycle regulator CDC25A and indirectly affecting its downstream target molecules. Let-7c may therefore be an effective therapeutic target for HCC. PMID:25909324

Human interface to large multimedia databases

NASA Astrophysics Data System (ADS)

Davis, Ben; Marks, Linn; Collins, Dave; Mack, Robert; Malkin, Peter; Nguyen, Tam

1994-04-01

The emergence of high-speed networking for multimedia will have the effect of turning the computer screen into a window on a very large information space. As this information space increases in size and complexity, providing users with easy and intuitive means of accessing information will become increasingly important. Providing access to large amounts of text has been the focus of work for hundreds of years and has resulted in the evolution of a set of standards, from the Dewey Decimal System for libraries to the recently proposed ANSI standards for representing information on-line: KIF, Knowledge Interchange Format, and CG's, Conceptual Graphs. Certain problems remain unsolved by these efforts, though: how to let users know the contents of the information space, so that they know whether or not they want to search it in the first place, how to facilitate browsing, and, more specifically, how to facilitate visual browsing. These issues are particularly important for users in educational contexts and have been the focus of much of our recent work. In this paper we discuss some of the solutions we have prototypes: specifically, visual means, visual browsers, and visual definitional sequences.

Multidisciplinary Aerospace Systems Optimization: Computational AeroSciences (CAS) Project

NASA Technical Reports Server (NTRS)

Kodiyalam, S.; Sobieski, Jaroslaw S. (Technical Monitor)

2001-01-01

The report describes a method for performing optimization of a system whose analysis is so expensive that it is impractical to let the optimization code invoke it directly because excessive computational cost and elapsed time might result. In such situation it is imperative to have user control the number of times the analysis is invoked. The reported method achieves that by two techniques in the Design of Experiment category: a uniform dispersal of the trial design points over a n-dimensional hypersphere and a response surface fitting, and the technique of krigging. Analyses of all the trial designs whose number may be set by the user are performed before activation of the optimization code and the results are stored as a data base. That code is then executed and referred to the above data base. Two applications, one of the airborne laser system, and one of an aircraft optimization illustrate the method application.

Reengineering a database for clinical trials management: lessons for system architects.

PubMed

Brandt, C A; Nadkarni, P; Marenco, L; Karras, B T; Lu, C; Schacter, L; Fisk, J M; Miller, P L

2000-10-01

This paper describes the process of enhancing Trial/DB, a database system for clinical studies management. The system's enhancements have been driven by the need to maximize the effectiveness of developer personnel in supporting numerous and diverse users, of study designers in setting up new studies, and of administrators in managing ongoing studies. Trial/DB was originally designed to work over a local area network within a single institution, and basic architectural changes were necessary to make it work over the Internet efficiently as well as securely. Further, as its use spread to diverse communities of users, changes were made to let the processes of study design and project management adapt to the working styles of the principal investigators and administrators for each study. The lessons learned in the process should prove instructive for system architects as well as managers of electronic patient record systems.

NASA Electronic Parts and Packaging Field Programmable Gate Array Single Event Effects Test Guideline Update

NASA Technical Reports Server (NTRS)

Berg, Melanie D.; LaBel, Kenneth A.

2018-01-01

The following are updated or new subjects added to the FPGA SEE Test Guidelines manual: academic versus mission specific device evaluation, single event latch-up (SEL) test and analysis, SEE response visibility enhancement during radiation testing, mitigation evaluation (embedded and user-implemented), unreliable design and its affects to SEE Data, testing flushable architectures versus non-flushable architectures, intellectual property core (IP Core) test and evaluation (addresses embedded and user-inserted), heavy-ion energy and linear energy transfer (LET) selection, proton versus heavy-ion testing, fault injection, mean fluence to failure analysis, and mission specific system-level single event upset (SEU) response prediction. Most sections within the guidelines manual provide information regarding best practices for test structure and test system development. The scope of this manual addresses academic versus mission specific device evaluation and visibility enhancement in IP Core testing.

NASA Electronic Parts and Packaging (NEPP) Field Programmable Gate Array (FPGA) Single Event Effects (SEE) Test Guideline Update

NASA Technical Reports Server (NTRS)

Berg, Melanie D.; LaBel, Kenneth A.

2018-01-01

The following are updated or new subjects added to the FPGA SEE Test Guidelines manual: academic versus mission specific device evaluation, single event latch-up (SEL) test and analysis, SEE response visibility enhancement during radiation testing, mitigation evaluation (embedded and user-implemented), unreliable design and its affects to SEE Data, testing flushable architectures versus non-flushable architectures, intellectual property core (IP Core) test and evaluation (addresses embedded and user-inserted), heavy-ion energy and linear energy transfer (LET) selection, proton versus heavy-ion testing, fault injection, mean fluence to failure analysis, and mission specific system-level single event upset (SEU) response prediction. Most sections within the guidelines manual provide information regarding best practices for test structure and test system development. The scope of this manual addresses academic versus mission specific device evaluation and visibility enhancement in IP Core testing.

SIRTF Tools for DIRT

NASA Astrophysics Data System (ADS)

Pound, M. W.; Wolfire, M. G.; Amarnath, N. S.

2003-12-01

The Dust InfraRed ToolBox (DIRT - a part of the Web Infrared ToolShed, or WITS, located at http://dustem.astro.umd.edu) is a Java applet for modeling astrophysical processes in circumstellar shells around young and evolved stars. DIRT has been used by the astrophysics community for about 5 years. Users can automatically and efficiently search grids of pre-calculated models to fit their data. A large set of physical parameters and dust types are included in the model database, which contains over 500,000 models. We are adding new functionality to DIRT to support new missions like SIRTF and SOFIA. A new Instrument module allows for plotting of the model points convolved with the spatial and spectral responses of the selected instrument. This lets users better fit data from specific instruments. Currently, we have implemented modules for the Infrared Array Camera (IRAC) and Multiband Imaging Photometer (MIPS) on SIRTF.

Full Scale Software Support on Mobile Lightweight Devices by Utilization of All Types of Wireless Technologies

NASA Astrophysics Data System (ADS)

Krejcar, Ondrej

New kind of mobile lightweight devices can run full scale applications with same comfort as on desktop devices only with several limitations. One of them is insufficient transfer speed on wireless connectivity. Main area of interest is in a model of a radio-frequency based system enhancement for locating and tracking users of a mobile information system. The experimental framework prototype uses a wireless network infrastructure to let a mobile lightweight device determine its indoor or outdoor position. User location is used for data prebuffering and pushing information from server to user’s PDA. All server data is saved as artifacts along with its position information in building or larger area environment. The accessing of prebuffered data on mobile lightweight device can highly improve response time needed to view large multimedia data. This fact can help with design of new full scale applications for mobile lightweight devices.

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

Fox, Kevin

The software provides a simple web api to allow users to request a time window where a file will not be removed from cache. HPSS provides the concept of a "purge lock". When a purge lock is set on a file, the file will not be removed from disk, entering tape only state. A lot of network file protocols assume a file is on disk so it is good to purge lock a file before transferring using one of those protocols. HPSS's purge lock system is very coarse grained though. A file is either purge locked or not. Nothing enforcesmore » quotas, timely unlocking of purge locks, or managing the races inherent with multiple users wanting to lock/unlock the same file. The Purge Lock Server lets you, through a simple REST API, specify a list of files to purge lock and an expire time, and the system will ensure things happen properly.« less

What Google Maps can do for biomedical data dissemination: examples and a design study.

PubMed

Jianu, Radu; Laidlaw, David H

2013-05-04

Biologists often need to assess whether unfamiliar datasets warrant the time investment required for more detailed exploration. Basing such assessments on brief descriptions provided by data publishers is unwieldy for large datasets that contain insights dependent on specific scientific questions. Alternatively, using complex software systems for a preliminary analysis may be deemed as too time consuming in itself, especially for unfamiliar data types and formats. This may lead to wasted analysis time and discarding of potentially useful data. We present an exploration of design opportunities that the Google Maps interface offers to biomedical data visualization. In particular, we focus on synergies between visualization techniques and Google Maps that facilitate the development of biological visualizations which have both low-overhead and sufficient expressivity to support the exploration of data at multiple scales. The methods we explore rely on displaying pre-rendered visualizations of biological data in browsers, with sparse yet powerful interactions, by using the Google Maps API. We structure our discussion around five visualizations: a gene co-regulation visualization, a heatmap viewer, a genome browser, a protein interaction network, and a planar visualization of white matter in the brain. Feedback from collaborative work with domain experts suggests that our Google Maps visualizations offer multiple, scale-dependent perspectives and can be particularly helpful for unfamiliar datasets due to their accessibility. We also find that users, particularly those less experienced with computer use, are attracted by the familiarity of the Google Maps API. Our five implementations introduce design elements that can benefit visualization developers. We describe a low-overhead approach that lets biologists access readily analyzed views of unfamiliar scientific datasets. We rely on pre-computed visualizations prepared by data experts, accompanied by sparse and intuitive interactions, and distributed via the familiar Google Maps framework. Our contributions are an evaluation demonstrating the validity and opportunities of this approach, a set of design guidelines benefiting those wanting to create such visualizations, and five concrete example visualizations.

What google maps can do for biomedical data dissemination: examples and a design study

PubMed Central

2013-01-01

Background Biologists often need to assess whether unfamiliar datasets warrant the time investment required for more detailed exploration. Basing such assessments on brief descriptions provided by data publishers is unwieldy for large datasets that contain insights dependent on specific scientific questions. Alternatively, using complex software systems for a preliminary analysis may be deemed as too time consuming in itself, especially for unfamiliar data types and formats. This may lead to wasted analysis time and discarding of potentially useful data. Results We present an exploration of design opportunities that the Google Maps interface offers to biomedical data visualization. In particular, we focus on synergies between visualization techniques and Google Maps that facilitate the development of biological visualizations which have both low-overhead and sufficient expressivity to support the exploration of data at multiple scales. The methods we explore rely on displaying pre-rendered visualizations of biological data in browsers, with sparse yet powerful interactions, by using the Google Maps API. We structure our discussion around five visualizations: a gene co-regulation visualization, a heatmap viewer, a genome browser, a protein interaction network, and a planar visualization of white matter in the brain. Feedback from collaborative work with domain experts suggests that our Google Maps visualizations offer multiple, scale-dependent perspectives and can be particularly helpful for unfamiliar datasets due to their accessibility. We also find that users, particularly those less experienced with computer use, are attracted by the familiarity of the Google Maps API. Our five implementations introduce design elements that can benefit visualization developers. Conclusions We describe a low-overhead approach that lets biologists access readily analyzed views of unfamiliar scientific datasets. We rely on pre-computed visualizations prepared by data experts, accompanied by sparse and intuitive interactions, and distributed via the familiar Google Maps framework. Our contributions are an evaluation demonstrating the validity and opportunities of this approach, a set of design guidelines benefiting those wanting to create such visualizations, and five concrete example visualizations. PMID:23642009

“It is not the fading candle that one expects”: general practitioners’ perspectives on life-preserving versus “letting go” decision-making in end-of-life home care

PubMed Central

Renterghem, Veerle Van; Pype, Peter; Aelbrecht, Karolien; Derese, Anselme; Deveugele, Myriam

2015-01-01

Background Many general practitioners (GPs) are willing to provide end-of-life (EoL) home care for their patients. International research on GPs’ approach to care in patients’ final weeks of life showed a combination of palliative measures with life-preserving actions. Aim To explore the GP’s perspective on life-preserving versus “letting go” decision-making in EoL home care. Design Qualitative analysis of semi-structured interviews with 52 Belgian GPs involved in EoL home care. Results Nearly all GPs adopted a palliative approach and an accepting attitude towards death. The erratic course of terminal illness can challenge this approach. Disruptive medical events threaten the prospect of a peaceful end-phase and death at home and force the GP either to maintain the patient’s (quality of) life for the time being or to recognize the event as a step to life closure and “letting the patient go”. Making the “right” decision was very difficult. Influencing factors included: the nature and time of the crisis, a patient’s clinical condition at the event itself, a GP’s level of determination in deciding and negotiating “letting go” and the patient’s/family’s wishes and preparedness regarding this death. Hospitalization was often a way out. Conclusions GPs regard alternation between palliation and life-preservation as part of palliative care. They feel uncertain about their mandate in deciding and negotiating the final step to life closure. A shortage of knowledge of (acute) palliative medicine as one cause of difficulties in letting-go decisions may be underestimated. Sharing all these professional responsibilities with the specialist palliative home care teams would lighten a GP’s burden considerably.Key PointsA late transition from a life-preserving mindset to one of “letting go” has been reported as a reason why physicians resort to life-preserving actions in an end-of-life (EoL) context. We investigated GPs’ perspectives on this matter.Not all GPs involved in EoL home care adopt a “letting go” mindset. For those who do, this mindset is challenged by the erratic course of terminal illness.GPs prioritize the quality of the remaining life and the serenity of the dying process, which is threatened by disruptive medical events.Making the “right” decision is difficult. GPs feel uncertain about their own role and responsibility in deciding and negotiating the final step to life closure. PMID:26654583

"It is not the fading candle that one expects": general practitioners' perspectives on life-preserving versus "letting go" decision-making in end-of-life home care.

PubMed

Sercu, Maria; Renterghem, Veerle Van; Pype, Peter; Aelbrecht, Karolien; Derese, Anselme; Deveugele, Myriam

2015-01-01

Many general practitioners (GPs) are willing to provide end-of-life (EoL) home care for their patients. International research on GPs' approach to care in patients' final weeks of life showed a combination of palliative measures with life-preserving actions. To explore the GP's perspective on life-preserving versus "letting go" decision-making in EoL home care. Qualitative analysis of semi-structured interviews with 52 Belgian GPs involved in EoL home care. Nearly all GPs adopted a palliative approach and an accepting attitude towards death. The erratic course of terminal illness can challenge this approach. Disruptive medical events threaten the prospect of a peaceful end-phase and death at home and force the GP either to maintain the patient's (quality of) life for the time being or to recognize the event as a step to life closure and "letting the patient go". Making the "right" decision was very difficult. Influencing factors included: the nature and time of the crisis, a patient's clinical condition at the event itself, a GP's level of determination in deciding and negotiating "letting go" and the patient's/family's wishes and preparedness regarding this death. Hospitalization was often a way out. GPs regard alternation between palliation and life-preservation as part of palliative care. They feel uncertain about their mandate in deciding and negotiating the final step to life closure. A shortage of knowledge of (acute) palliative medicine as one cause of difficulties in letting-go decisions may be underestimated. Sharing all these professional responsibilities with the specialist palliative home care teams would lighten a GP's burden considerably. Key Points A late transition from a life-preserving mindset to one of "letting go" has been reported as a reason why physicians resort to life-preserving actions in an end-of-life (EoL) context. We investigated GPs' perspectives on this matter. Not all GPs involved in EoL home care adopt a "letting go" mindset. For those who do, this mindset is challenged by the erratic course of terminal illness. GPs prioritize the quality of the remaining life and the serenity of the dying process, which is threatened by disruptive medical events. Making the "right" decision is difficult. GPs feel uncertain about their own role and responsibility in deciding and negotiating the final step to life closure.

Let's Go Exploring. Nutrition Comes Alive. Level 1. Nutrition Educator's Guide and Work Sheets, Letters to Parents, Recipes. Revised Edition.

ERIC Educational Resources Information Center

Farrell, Tracy J.

This guide provides a nutrition education program for elementary school students that spans kindergarten through Grade 3 as well as providing activities for specific levels. Nutrition education objectives are stated for each grade level: (1) kindergarten--students will become familiar with and motivated to eat a variety of foods; (2) grade…

Let's Talk about Sex, Maybe: Interviewers, Respondents, and Sexual Behavior Reporting in Rural South Africa

ERIC Educational Resources Information Center

Houle, Brian; Angotti, Nicole; Clark, Samuel J.; Williams, Jill; Gómez-Olivé, F. Xavier; Menken, Jane; Kabudula, Chodziwadziwa; Klipstein-Grobusch, Kerstin; Tollman, Stephen M.

2016-01-01

Researchers are often skeptical of sexual behavior surveys: Respondents may lie or forget details of their intimate lives, and interviewers may exercise authority in how they capture responses. We use data from a 2010-2011 cross-sectional sexual behavior survey in rural South Africa to explore who says what to whom about their sexual lives.…

Let's Go to Market! Field Trips to Discover Economics and Cultures

ERIC Educational Resources Information Center

Gomez, Diana

2010-01-01

In this article, the author describes how her first grade class embarked on a journey of learning through a unit of study about local food markets. The study was a rich exploration of the cultural diversity of the city of Philadelphia, Pennsylvania, as well as an introduction to basic concepts about economics. Through their trips to a farm and…

Alien Contact: Proof Positive or a Case of Let's Play Pretend?

ERIC Educational Resources Information Center

DiSpezio, Michael A.

2011-01-01

Explore claims of extraterrestrial life and our efforts to communicate with inhabitants of worlds outside our solar system. Even though there's no "proof positive" for extraterrestrial life-forms of any flavor, we've set the stage for applying a battery of critical-thinking skills to the valid analysis of scientific data. (Contains 3 figures and 5…

Let's Play: The Use of Improv Games in Change Management Training: A Case Study

ERIC Educational Resources Information Center

Rajeev, Priya Nair; Kalpathi, Subramanian

2016-01-01

This paper is based on the concept of Improv games as a promising mechanism and design principle for enhancing an organization's capacity for learning and adaptability. The study explores how Improv games can be used to create a mindset conducive to change, facilitate ideation and guide discussions on bringing about systemic change. In the case…

"Let's Talk Autism"--A School-Based Project for Students to Explore and Share Their Experiences of Being Autistic

ERIC Educational Resources Information Center

Stevenson, Kathryn; Cornell, Katie; Hinchcliffe, Vivian

2016-01-01

Understanding what autism means on a personal level can be an important process for young people on the autistic spectrum, and being able to reflect on this and discuss with autistic peers can be particularly helpful. However, opportunities may be restricted by reluctance to talk about diagnosis and because of difficulties in communication…

"Let's See if It Won't Go Away by Itself." LGBT Microaggressions among Teachers in South Africa

ERIC Educational Resources Information Center

Francis, Dennis A.; Reygan, Finn

2016-01-01

We explored types and qualities of microaggressions or subtle forms of discrimination towards lesbian, gay, bisexual and transgender (LGBT) people among teachers in South Africa. For data collection, we used in-depth interviews. Twenty-five Life Orientation teachers, nine men and 16 women, from both rural and urban schools throughout the Free…

Exploring of New Models of Research Pedagogy: Time to Let Go of Master-Apprentice Style Supervision?

ERIC Educational Resources Information Center

Harrison, Scott; Grant, Catherine

2015-01-01

While the time-honoured one-to-one supervisory model of higher research degree training has its advantages, recent research suggests that the model also has significant drawbacks, including its hierarchical nature. Nevertheless, this pedagogical model remains the default for higher research pedagogy. Using the discipline of music as a case study,…

"What Do You Think?" Let Me Tell You: Discourse about Texts and the Literature Classroom

ERIC Educational Resources Information Center

Mason, Jessica; Giovanelli, Marcello

2017-01-01

This article examines the practice of studying texts in secondary school English lessons as a particular type of reading experience. Through a critical stylistic analysis of a popular edition of John Steinbeck's "Of Mice and Men", the article explores how reading the text is framed by educational editions, and how this might present the…

Jung and Mr. Punch as mythologems.

PubMed

Mathers, Dale

2018-06-01

This paper explores how we can make our own mythological version of 'Jung' say whatever we want. Excessive veneration gets in the way of his theories being allowed to stand on their own. Understanding 'Jung' as a mythologem provides a way out of this intoxication with identification by letting us recollect and re-connect to the Collective Unconscious. © 2018, The Society of Analytical Psychology.

Let's Get Physical: K-12 Students Using Wearable Devices to Obtain and Learn about Data from Physical Activities

ERIC Educational Resources Information Center

Lee, Victor R.; Drake, Joel; Williamson, Kylie

2015-01-01

Accessibility to wearable technology has exploded in the last decade. As such, this technology has potential to be used in classrooms in uniquely interactive and personally meaningful ways. Seeing this as a possible future for schools, we have been exploring approaches for designing activities to incorporate wearable physical activity data…

Experience and meaning of user involvement: some explorations from a community mental health project.

PubMed

Truman, Carole; Raine, Pamela

2002-05-01

With an increased interest in and policy commitment to involving service users in the planning and delivery of health service provision, there is a clear need to explore both the rhetoric and realities of what user involvement entails. In the present paper, by drawing upon an evaluation of a community-based exercise facility for people with mental health problems, the authors explore ways in which the reality of user involvement is subject to a range of configurations within health services. The paper describes a piece of qualitative research that was undertaken within a participatory framework to explore the nature of user involvement within the facility. The data have been analysed using a grounded theory approach to provide insights into: the organisational context in which user involvement takes place; factors which encourage meaningful participation on the part of service users; perceived barriers to user involvement; and issues of sustainability and continuity. This research approach has enabled the authors to explore the views and experiences of users, service providers and referral agencies in relation to the nature and potential for user involvement. The findings illustrate ways in which user involvement may take place under both flexible and formal arrangements across a variety of activities. The present paper provides an account of some of the meanings and experiences of what 'successful' user participation may involve and the conditions which underpin 'success'. The authors conclude that successful and meaningful user involvement should enable and support users to recognise their existing skills, and to develop new ones, at a pace that suits their particular circumstances and personal resources. This process may require adaptation not only by organisations, but also by service providers and non-involved users.

The Design and Development of BMI Calc Android Application

NASA Astrophysics Data System (ADS)

Mohd Ali, Iliana; Samsudin, Nooraida

2016-11-01

Body mass index is a familiar term for those who are weight conscious. It is the term that let user know about the overall body composition in terms of fat.The available body mass index calculators whether online or on Play Store do not provide Malaysian meal suggestions. Hence, this paper proposes an application for body mass index calculator together with Malaysian meal suggestion. The objectives of the study are to design and develop BMI Calc android application for the purpose of calculating body mass index while embedding meal suggestion module. The design and methodology involve in the process are also presented.

Mixed-Initiative Tutorial System to Aid Users of the On-Line System (NLS)

DTIC Science & Technology

1974-11-30

PIE 3A1 RHUBARB 3A2 BLUEBERRY 3B STRAWBERRY SHORTCAKE 3C ICE CREAM 3C1 PEPPERMINT ^C2 MAPLENUT 3C3 CHOCOLATE EDIT C: Done OK: ; Please tear the...QUESTIONS? THE RENUMBERED FILE Now let me show you what happens when I try to delete the statement containing " BLUEBERRY " which used to follow the...containing " BLUEBERRY " which was formerly 3A2 was ’promoted’ to become statement 3A1. So to delete the statement containing " BLUEBERRY " we would have to

3Dmol.js: molecular visualization with WebGL.

PubMed

Rego, Nicholas; Koes, David

2015-04-15

3Dmol.js is a modern, object-oriented JavaScript library that uses the latest web technologies to provide interactive, hardware-accelerated three-dimensional representations of molecular data without the need to install browser plugins or Java. 3Dmol.js provides a full featured API for developers as well as a straightforward declarative interface that lets users easily share and embed molecular data in websites. 3Dmol.js is distributed under the permissive BSD open source license. Source code and documentation can be found at http://3Dmol.csb.pitt.edu dkoes@pitt.edu. © The Author 2014. Published by Oxford University Press.

Users Get Routed: Traffic Correlation on Tor by Realistic Adversaries

DTIC Science & Technology

2013-11-01

the number of TorPS samples, and let D (x) be the absolute difference between the empirical CDF and the true CDF at x. The Dvoretzky– Kiefer–Wolfowitz...0.05 0.06 0.07 Fraction of streams 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Cu m ul at iv e pr ob ab ili ty typical bittorrent irc worst best ( d ...Adversaries) IRC (2 Adversaries) IRC (3 Adversaries) Typical (1 Adversary) Typical (2 Adversaries) Typical (3 Adversaries) ( d ) Varying time to first

Program Operating Procedures for the Integrated Command ASW Prediction System (ICAPS). Volume 1, Revision A.

DTIC Science & Technology

1981-06-01

RETIIN. •4 C H’T SE’LE(T Till’E S()NAR S TO EI Sonai r’ types are specified INCI.’I)EI) IN TIllI. RAN( G ’ individually. Prompt repeats PR I(’ICTION...complete revision, Revision A. Symbols are not used in this revision to identify changes with respect to the pre- vious issue, due to the exten- g siveness...maintenance such as source editing, compiling, and debugging. In addition, it provides the user with a simple and uniform interface for transfcrrin g files of

A truly international lunar base as the next logical step for human spaceflight

NASA Astrophysics Data System (ADS)

Bonneville, R.

2018-06-01

A human mission to Mars has been highlighted as the long term goal for space exploration, with intermediate stages such as missions to the Moon and/or to asteroids, but a human mission to Mars will not be feasible before several decades. For the time being the major ambitious accomplishment in the field of human spaceflight is the International Space Station but a human spaceflight programme which would be restricted to Low Earth orbit (LEO) has indeed little interest. Thus the next step in the field of human exploration should be the definition of a new exploration programme beyond LEO, built within a long term perspective. We must acknowledge that science is not the main driver of human space exploration and that the main success of the ISS is to have allowed its partners to work together. The main goal of a new human exploration programme will be to promote international cooperation between the major space-faring countries. The only sensible and feasible objective of a near/mid-term human spaceflight programme should be the edification of a lunar base, under the condition that this base is built as a truly international venture. The ISS in the 1990s had illustrated a calmed relation between the USA, together with Europe, Canada and Japan, and Russia; a lunar base would be the symbol of a similar calmed relation between the same partners and China, and possibly others such as India. For the benefit of all humankind this extra continent, the Moon, should be used only for peaceful purposes like Antarctica today, and should not become the theatre or the stake of conflicts. Such a programme is technically feasible and financially affordable in a rather short term. So let us go to the Moon, but let us get there together.

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

PubMed Central

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

2010-01-01

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. PMID:20133835

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

PubMed

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.

Functional Genomic Analysis of the let-7 Regulatory Network in Caenorhabditis elegans

PubMed Central

Zisoulis, Dimitrios G.; Lovci, Michael T.; Melnik-Martinez, Katya V.; Yeo, Gene W.; Pasquinelli, Amy E.

2013-01-01

The let-7 microRNA (miRNA) regulates cellular differentiation across many animal species. Loss of let-7 activity causes abnormal development in Caenorhabditis elegans and unchecked cellular proliferation in human cells, which contributes to tumorigenesis. These defects are due to improper expression of protein-coding genes normally under let-7 regulation. While some direct targets of let-7 have been identified, the genome-wide effect of let-7 insufficiency in a developing animal has not been fully investigated. Here we report the results of molecular and genetic assays aimed at determining the global network of genes regulated by let-7 in C. elegans. By screening for mis-regulated genes that also contribute to let-7 mutant phenotypes, we derived a list of physiologically relevant potential targets of let-7 regulation. Twenty new suppressors of the rupturing vulva or extra seam cell division phenotypes characteristic of let-7 mutants emerged. Three of these genes, opt-2, prmt-1, and T27D12.1, were found to associate with Argonaute in a let-7–dependent manner and are likely novel direct targets of this miRNA. Overall, a complex network of genes with various activities is subject to let-7 regulation to coordinate developmental timing across tissues during worm development. PMID:23516374

Loss of MYC and E-box3 binding contributes to defective MYC-mediated transcriptional suppression of human MC-let-7a-1~let-7d in glioblastoma

PubMed Central

Wang, Zifeng; Lin, Sheng; Zhang, Ji; Xu, Zhenhua; Xiang, Yu; Yao, Hong; Ge, Lei; Xie, Dan; Kung, Hsiang-fu; Lu, Gang; Poon, Wai Sang; Liu, Quentin; Lin, Marie Chia-mi

2016-01-01

Previously, we reported that MYC oncoprotein down-regulates the transcription of human MC-let-7a-1~let-7d microRNA cluster in hepatocarcinoma (HCC). Surprisingly, in silico analysis indicated that let-7 miRNA expression levels are not reduced in glioblastoma (GBM). Here we investigated the molecular basis of this differential expression. Using human GBM U87 and U251 cells, we first demonstrated that forced over-expression of MYC indeed could not down-regulate the expression of human MC-let-7a-1~let-7d microRNA cluster in GBM. Furthermore, analysis of MC-let-7a-1~let-7d promoter in GBM indicated that MYC failed to inhibit the promoter activity. Pearson's correlation and Linear Regression analysis using the expression data from GSE55092 (HCC) and GSE4290 (GBM) demonstrated a converse relationship of MC-let-7a-1~let-7d and MYC only in HCC but not in GBM. To understand the underlying mechanisms, we examined whether MYC could bind to the non-canonical E-box 3 located in the promoter of MC-let-7a-1~let-7d. Results from both chromatin immune-precipitation (ChIP) and super-shift assays clearly demonstrated the loss of MYC and E-box 3 binding in GBM, suggesting for the first time that a defective MYC and E-box3 binding in GBM is responsible for the differential MYC mediated transcriptional inhibition of MC-let-7a-1~let-7d and potentially other tumor suppressors. MYC and let-7 are key oncoprotein and tumor suppressor, respectively. Understanding the molecular mechanisms of their regulations will provide new insight and have important implications in the therapeutics of GBM as well as other cancers. PMID:27409345

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

PubMed

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.

Linear energy transfer incorporated intensity modulated proton therapy optimization

NASA Astrophysics Data System (ADS)

Cao, Wenhua; Khabazian, Azin; Yepes, Pablo P.; Lim, Gino; Poenisch, Falk; Grosshans, David R.; Mohan, Radhe

2018-01-01

The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton therapy (IMPT) plans. Because increased LET correlates with increased biological effectiveness of protons, high LETs in target volumes and low LETs in critical structures and normal tissues are preferred in an IMPT plan. However, if not explicitly incorporated into the optimization criteria, different IMPT plans may yield similar physical dose distributions but greatly different LET, specifically dose-averaged LET, distributions. Conventionally, the IMPT optimization criteria (or cost function) only includes dose-based objectives in which the relative biological effectiveness (RBE) is assumed to have a constant value of 1.1. In this study, we added LET-based objectives for maximizing LET in target volumes and minimizing LET in critical structures and normal tissues. Due to the fractional programming nature of the resulting model, we used a variable reformulation approach so that the optimization process is computationally equivalent to conventional IMPT optimization. In this study, five brain tumor patients who had been treated with proton therapy at our institution were selected. Two plans were created for each patient based on the proposed LET-incorporated optimization (LETOpt) and the conventional dose-based optimization (DoseOpt). The optimized plans were compared in terms of both dose (assuming a constant RBE of 1.1 as adopted in clinical practice) and LET. Both optimization approaches were able to generate comparable dose distributions. The LET-incorporated optimization achieved not only pronounced reduction of LET values in critical organs, such as brainstem and optic chiasm, but also increased LET in target volumes, compared to the conventional dose-based optimization. However, on occasion, there was a need to tradeoff the acceptability of dose and LET distributions. Our conclusion is that the inclusion of LET-dependent criteria in the IMPT optimization could lead to similar dose distributions as the conventional optimization but superior LET distributions in target volumes and normal tissues. This may have substantial advantages in improving tumor control and reducing normal tissue toxicities.

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

PubMed

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.

Library Users' Service Desires: A LibQUAL+ Study

ERIC Educational Resources Information Center

Thompson, Bruce; Kyrillidou, Martha; Cook, Colleen

2008-01-01

The present study was conducted to explore library users' desired service quality levels on the twenty-two core LibQUAL+ items. Specifically, we explored similarities and differences in users' desired library service quality levels across user groups (i.e., undergraduate students, graduate students, and faculty), across geographic locations (i.e.,…

Luminal esophageal temperature monitoring with a deflectable esophageal temperature probe and intracardiac echocardiography may reduce esophageal injury during atrial fibrillation ablation procedures: results of a pilot study.

PubMed

Leite, Luiz R; Santos, Simone N; Maia, Henrique; Henz, Benhur D; Giuseppin, Fábio; Oliverira, Anderson; Zanatta, André R; Peres, Ayrton K; Novakoski, Clarissa; Barreto, Jose R; Vassalo, Fabrício; d'Avila, Andre; Singh, Sheldon M

2011-04-01

Luminal esophageal temperature (LET) monitoring is one strategy to minimize esophageal injury during atrial fibrillation ablation procedures. However, esophageal ulceration and fistulas have been reported despite adequate LET monitoring. The objective of this study was to assess a novel approach to LET monitoring with a deflectable LET probe on the rate of esophageal injury in patients undergoing atrial fibrillation ablation. Forty-five consecutive patients undergoing an atrial fibrillation ablation procedure followed by esophageal endoscopy were included in this prospective observational pilot study. LET monitoring was performed with a 7F deflectable ablation catheter that was positioned as close as possible to the site of left atrial ablation using the deflectable component of the catheter guided by visualization of its position on intracardiac echocardiography. Ablation in the posterior left atrial was limited to 25 W and terminated when the LET increased 2°C from baseline. Endoscopy was performed 1 to 2 days after the procedure. All patients had at least 1 LET elevation >2°C necessitating cessation of ablation. Deflection of the LET probe was needed to accurately measure LET in 5% of patients when ablating near the left pulmonary veins, whereas deflection of the LET probe was necessary in 88% of patients when ablating near the right pulmonary veins. The average maximum increase in LET was 2.5±1.5°C. No patients had esophageal thermal injury on follow-up endoscopy. A strategy of optimal LET probe placement using a deflectable LET probe and intracardiac echocardiography guidance, combined with cessation of radiofrequency ablation with a 2°C rise in LET, may reduce esophageal thermal injury during left atrial ablation procedures.

TU-EF-304-09: Quantifying the Biological Effects of Therapeutic Protons by LET Spectrum Analysis

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

Guan, F; Bronk, L; Kerr, M

2015-06-15

Purpose: To correlate in vitro cell kill with linear energy transfer (LET) spectra using Monte Carlo simulations and knowledge obtained from previous high-throughput in vitro proton relative biological effectiveness (RBE) measurements. Methods: The Monte Carlo simulation toolkit Geant4 was used to design the experimental setups and perform the dose, dose-averaged LET, and LET spectra calculations. The clonogenic assay was performed using the H460 lung cancer cell line in standard 6-well plates. Using two different experimental setups, the same dose and dose-averaged LET (12.6 keV/µm) was delivered to the cell layer; however, each respective energy or LET spectrum was different. Wemore » quantified the dose contributions from high-LET (≥10 keV/µm, threshold determined by previous RBE measurements) events in the LET spectra separately for these two setups as 39% and 53%. 8 dose levels with 1 Gy increments were delivered. The photon reference irradiation was performed using 6 MV x-rays from a LINAC. Results: The survival curves showed that both proton irradiations demonstrated an increased RBE compared to the reference photon irradiation. Within the proton-irradiated cells, the setup with 53% dose contribution from high-LET events exhibited the higher biological effectiveness. Conclusion: The experimental results indicate that the dose-averaged LET may not be an appropriate indicator to quantify the biological effects of protons when the LET spectrum is broad enough to contain both low- and high-LET events. Incorporating the LET spectrum distribution into robust intensity-modulated proton therapy optimization planning may provide more accurate biological dose distribution than using the dose-averaged LET. NIH Program Project Grant 2U19CA021239-35.« less

Dose- and LET-painting with particle therapy.

PubMed

Bassler, Niels; Jäkel, Oliver; Søndergaard, Christian Skou; Petersen, Jørgen B

2010-10-01

Tumour hypoxia is one of the limiting factors in obtaining tumour control in radiotherapy. The high-LET region of a beam of heavy charged particles such as carbon ions is located in the distal part of the Bragg peak. A modulated or spread out Bragg peak (SOBP) is a weighted function of several Bragg peaks at various energies, which however results in a dilution of the dose-average LET in the target volume. Here, we investigate the possibility to redistribute the LET by dedicated treatment plan optimisation, in order to maximise LET in the target volume. This may be a strategy to potentially overcome hypoxia along with dose escalation or dose painting. The high-LET region can be shaped in very different ways, while maintaining the distribution of the absorbed dose or biological effective dose. Treatment plans involving only carbon ion beams, show very different LET distributions depending on how the fields are arranged. Alternatively, a LET boost can be applied in multi-modal treatment planning, such as combining carbon ions with protons and/or photons. For such mixed radiation modalities, significant "LET boosts" can be achieved at nearly arbitrary positions within the target volume. Following the general understanding of the relationship between hypoxia, LET and the oxygen enhancement ratio (OER), we conclude, that an additional therapeutic advantage can be achieved by confining the high-LET part of the radiation in hypoxic compartments of the tumour, and applying low-LET radiation to the normoxic tissue. We also anticipate that additional advantages may be achieved by deliberate sparing of normal tissue from high LET regions. Consequently, treatment planning based on simultaneous dose and LET optimisation has a potential to achieve higher tumour control and/or reduced normal tissue control probability (NTCP).

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

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

Tian, Yuan; Hao, Shaobo; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052

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 brainmore » 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.« less

Beta Androstenediol Mitigates the Damage of 1 GeV/n Fe Ion Particle Radiation to the Hematopoietic System

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

Loria R.; Guida P.; Loria, R.

2010-09-07

Space exploration is associated with exposure to 1-3 Gy solar particle radiation and galactic cosmic radiation that could increase cancer rates. Effective nontoxic countermeasures to high linear energy transfer (LET) radiation exposure are highly desirable but currently not available. The aim was to determine whether a single subcutaneous injection of androstenediol ({Delta}(5) androsten-3{beta}, 17{beta}-diol [AED]) could mitigate and restore the mouse hematopoetic system from the radiation-mediated injury of 3 Gy whole-body high LET (56)Fe(26+) exposure. The findings show that postradiation AED treatment has an overall positive and significant beneficial effect to restore the levels of hematopoeitic elements (p < 0.001).more » Androstenediol treatment significantly increased monocyte levels at days 4, 7, and 14 and, similarly, increased red blood cell, hemoglobin, and platelet counts. Flow cytometry analysis 14 days after radiation and AED treatment demonstrated an increase (p < 0.05) in bone marrow cells counts. Ex vivo osteoclastogenesis studies show that AED treatment is necessary and advantageous for the development and restoration of osteoclastogenesis after radiation exposure. These findings clearly show that androstenediol functions as a countermeasure to remedy hematopoeitic injury mediated by high LET iron ion radiation. Presently, no other agent has been shown to have such properties.« less

Protective Effects of Let-7a and Let-7b on Oxidized Low-Density Lipoprotein Induced Endothelial Cell Injuries

PubMed Central

Bao, Mei-hua; Zhang, Yi-wen; Lou, Xiao-ya; Cheng, Yu; Zhou, Hong-hao

2014-01-01

Lectin-like low-density lipoprotein receptor 1 (LOX-1) is a receptor for oxidized low density lipoprotein (oxLDL) in endothelial cells. The activation of LOX-1 by oxLDL stimulates the apoptosis and dysfunction of endothelial cells, and contributes to atherogenesis. However, the regulatory factors for LOX-1 are still unclear. MicroRNAs are small, endogenous, non-coding RNAs that regulate gene expressions at a post-transcriptional level. The let-7 family is the second microRNA been discovered, which plays important roles in cardiovascular diseases. Let-7a and let-7b were predicted to target LOX-1 3′-UTR and be highly expressed in endothelial cells. The present study demonstrated that LOX-1 was a target of let-7a and let-7b. They inhibited the expression of LOX-1 by targeting the positions of 310-316 in LOX-1 3′-UTR. Over-expression of let-7a and let-7b inhibited the oxLDL-induced endothelial cell apoptosis, NO deficiency, ROS over-production, LOX-1 upregulation and endothelial nitric oxide synthase (eNOS) downregulation. Moreover, we found that oxLDL treatment induced p38MAPK phosphorylation, NF-κB nuclear translocation, IκB degradation and PKB dephosphorylation. Let-7a or let-7b over-expression attenuated these alterations significantly. The present study may provide a new insight into the protective properties of let-7a and let-7b in preventing the endothelial dysfunction associated with cardiovascular disease, such as atherosclerosis. PMID:25247304

HybridPLAY: A New Technology to Foster Outdoors Physical Activity, Verbal Communication and Teamwork.

PubMed

Díaz, Diego José; Boj, Clara; Portalés, Cristina

2016-04-23

This paper presents HybridPLAY, a novel technology composed of a sensor and mobile-based video games that transforms urban playgrounds into game scenarios. With this technology we aim to stimulate physical activity and playful learning by creating an entertaining environment in which users can actively participate and collaborate. HybridPLAY is different from other existing technologies that enhance playgrounds, as it is not integrated in them but can be attached to the different elements of the playgrounds, making its use more ubiquitous (i.e., not restricted to the playgrounds). HybridPLAY was born in 2007 as an artistic concept, and evolved after different phases of research and testing by almost 2000 users around the world (in workshops, artistic events, conferences, etc.). Here, we present the temporal evolution of HybridPLAY with the different versions of the sensors and the video games, and a detailed technical description of the sensors and the way interactions are produced. We also present the outcomes after the evaluation by users at different events and workshops. We believe that HybridPLAY has great potential to contribute to increased physical activity in kids, and also to improve the learning process and monitoring at school centres by letting users create the content of the apps, leading to new narratives and fostering creativity.

HybridPLAY: A New Technology to Foster Outdoors Physical Activity, Verbal Communication and Teamwork

PubMed Central

Díaz, Diego José; Boj, Clara; Portalés, Cristina

2016-01-01

This paper presents HybridPLAY, a novel technology composed of a sensor and mobile-based video games that transforms urban playgrounds into game scenarios. With this technology we aim to stimulate physical activity and playful learning by creating an entertaining environment in which users can actively participate and collaborate. HybridPLAY is different from other existing technologies that enhance playgrounds, as it is not integrated in them but can be attached to the different elements of the playgrounds, making its use more ubiquitous (i.e., not restricted to the playgrounds). HybridPLAY was born in 2007 as an artistic concept, and evolved after different phases of research and testing by almost 2000 users around the world (in workshops, artistic events, conferences, etc.). Here, we present the temporal evolution of HybridPLAY with the different versions of the sensors and the video games, and a detailed technical description of the sensors and the way interactions are produced. We also present the outcomes after the evaluation by users at different events and workshops. We believe that HybridPLAY has great potential to contribute to increased physical activity in kids, and also to improve the learning process and monitoring at school centres by letting users create the content of the apps, leading to new narratives and fostering creativity. PMID:27120601

Twitter and the health reforms in the English National Health Service.

PubMed

King, Dominic; Ramirez-Cano, Daniel; Greaves, Felix; Vlaev, Ivo; Beales, Steve; Darzi, Ara

2013-05-01

Social media (for example Facebook and YouTube) uses online and mobile technologies to allow individuals to participate in, comment on and create user-generated content. Twitter is a widely used social media platform that lets users post short publicly available text-based messages called tweets that other users can respond to. Alongside traditional media outlets, Twitter has been a focus for discussions about the controversial and radical reforms to the National Health Service (NHS) in England that were recently passed into law by the current coalition Government. Looking at over 120,000 tweets made about the health reforms, we have investigated whether any insights can be obtained about the role of Twitter in informing, debating and influencing opinion in a specific area of health policy. In particular we have looked at how the sentiment of tweets changed with the passage of the Health and Social Care Bill through Parliament, and how this compared to conventional opinion polls taken over the same time period. We examine which users appeared to have the most influence in the 'Twittersphere' and suggest how a widely used metric of academic impact - the H-index - could be applied to measure context-dependent influence on Twitter. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A parallel coordinates style interface for exploratory volume visualization.

PubMed

Tory, Melanie; Potts, Simeon; Möller, Torsten

2005-01-01

We present a user interface, based on parallel coordinates, that facilitates exploration of volume data. By explicitly representing the visualization parameter space, the interface provides an overview of rendering options and enables users to easily explore different parameters. Rendered images are stored in an integrated history bar that facilitates backtracking to previous visualization options. Initial usability testing showed clear agreement between users and experts of various backgrounds (usability, graphic design, volume visualization, and medical physics) that the proposed user interface is a valuable data exploration tool.

Intersubject synchronization of cortical activity during natural vision.

PubMed

Hasson, Uri; Nir, Yuval; Levy, Ifat; Fuhrmann, Galit; Malach, Rafael

2004-03-12

To what extent do all brains work alike during natural conditions? We explored this question by letting five subjects freely view half an hour of a popular movie while undergoing functional brain imaging. Applying an unbiased analysis in which spatiotemporal activity patterns in one brain were used to "model" activity in another brain, we found a striking level of voxel-by-voxel synchronization between individuals, not only in primary and secondary visual and auditory areas but also in association cortices. The results reveal a surprising tendency of individual brains to "tick collectively" during natural vision. The intersubject synchronization consisted of a widespread cortical activation pattern correlated with emotionally arousing scenes and regionally selective components. The characteristics of these activations were revealed with the use of an open-ended "reverse-correlation" approach, which inverts the conventional analysis by letting the brain signals themselves "pick up" the optimal stimuli for each specialized cortical area.

Ribosomal protein RPS-14 modulates let-7 microRNA function in Caenorhabditis elegans

PubMed Central

Chan, Shih-Peng; Slack, Frank J.

2009-01-01

The let-7 microRNA (miRNA) regulates developmental timing at the larval-to-adult transition in Caenorhabditis elegans. Dysregulation of let-7 results in irregular hypodermal and vulval development. Disrupted let-7 function is also a feature of human lung cancer. However, little is known about the mechanism and co-factors of let-7. Here we demonstrate that ribosomal protein RPS-14 is able to modulate let-7 function in C. elegans. The RPS-14 protein co-immunoprecipitated with the nematode Argonaute homolog, ALG-1. Reduction of rps-14 gene expression by RNAi suppressed the aberrant vulva and hypodermis development phenotypes of let-7(n2853) mutant animals and the mis-regulation of a reporter bearing the lin-41 3′UTR, a well established let-7 target. Our results indicate an interactive relationship between let-7 miRNA function and ribosomal protein RPS-14 in regulation of terminal differentiation that may help in understanding the mechanism of translational control by miRNAs. PMID:19627982

"Man You've Been a Naughty Boy, You Let Your Face Grow Long": On the Celebration of Negative Affect in Adolescence

ERIC Educational Resources Information Center

Cooper, Paul; Kakos, Michalis

2013-01-01

In this paper the authors explore the phenomena of positive attitudes towards negative affect among young adolescent as reflected in the appearance and behaviours of "radical peer crowds", such as Punks, Goths and Emos. The authors consider the significance of this in relation to the history of melancholy and theories of identity…

"Let's Do Some Jumping Together": Intergenerational Participation in the Use of Remote Technology to Co-Construct Social Relations over Distance

ERIC Educational Resources Information Center

Kelly, Clare

2015-01-01

This article discusses a small-scale study that explores how members of one family based in Australia and the United Kingdom use remote technology to develop and maintain family relationships across generations and distance. Of particular interest was the manner in which Skype computer software was mediated to develop intersubjectivity between a…

Planet App: Kids' Book Apps Are Everywhere. But Are They Any Good?

ERIC Educational Resources Information Center

Bird, Elizabeth

2011-01-01

A proper picture book app lets a parent and child read, listen to, or explore a book in a fun and interactive manner. Typical options offered in these apps include turning off the sound (so that a parent or child can read on their own), changing from one language to another, and small interactive features, such as making the characters move. To…

Let's SQUiNK about It! A Metacognitive Approach to Exploring Text in a Second Grade Classroom

ERIC Educational Resources Information Center

Capraro, Karen

2011-01-01

In this article the author describes SQUiNK, a useful tool in interacting with text for all children and at varying levels and abilities. Initially the author sought to address the needs of readers with strong skills by more fully engaging them with expository text. But through the introduction to a strategy for addressing the needs of "all"…

Letting Schools off the Hook? Exploring the Role of Australian Secondary Schools in the COAG Year 12 Attainment Agenda

ERIC Educational Resources Information Center

Keating, Jack; Savage, Glenn C.; Polesel, John

2013-01-01

In 2009, the Council of Australian Governments (COAG) set a target to lift Australia's Year 12 or equivalent attainment rate from 83.5 to 90% by 2015. In the context of global financial uncertainty, the target was rationalised as a means for boosting national productivity and developing human capital to help Australia compete in the global…

What Can the Self-Conscious Emotion of Guilt Tell Us about Primary School Teachers' Moral Purpose and the Relationships They Have with Their Pupils?

ERIC Educational Resources Information Center

Farouk, Shaalan

2012-01-01

Based on interviews and adopting and phenomenological approach this article explores primary school teachers' experiences of guilt. Teachers described feeling guilty when they held themselves responsible for having let down or upset their pupils and on occasion their colleagues. Some teachers also recalled experiencing guilt when some of their…

"Let It Go": Exploring the Image of the Child as a Producer, Consumer, and Inventor

ERIC Educational Resources Information Center

Rowsell, Jennifer; Harwood, Debra

2015-01-01

iPads are increasingly being put in the hands of children in schools and educational contexts, yet there continues to be larger questions about how they fit into the fabric of daily classroom life and what new stories will emerge (de Certeau, 1984, 1984/2000). In this article, we feature vignettes of data from a 2-year government-funded research…

"Let's Talk about Race": Exploring Racial Stereotypes Using Popular Culture in Social Studies Classrooms

ERIC Educational Resources Information Center

Childs, David Jason

2014-01-01

Imagery and sounds from television, film, music, the Internet, and other media bombard American youth; dictating to them how they should act, think, or what they should believe. They often do not realize that they find much of their identity and belief systems in messages put forth to them by popular culture (Du Gay 1997; Hall 1997). Young people…

The Scholarship of Teaching and Learning--Done by Sociologists: Let's Make that the Sociology of Higher Education

ERIC Educational Resources Information Center

Hanson, Chad

2005-01-01

In May of 2000, the American Sociological Association hosted a Scholarship of Teaching and Learning conference at James Madison University. The goal was to create a forum where faculty from across the country could reflect on the role of sociology in the burgeoning new scholarship of teaching and learning. In this article, the author explores the…

Judgement on "hit or non-hit" of CHO cells exposed to accelerated heavy-ions (Fe- or Ar-ions) using division delay and CR-39 plastics as an indicator.

PubMed

Mehnati, P; Yatagai, F; Tsuzuki, T; Hanaoka, F; Sasaki, H

2001-03-01

The cell killing effect of ionizing radiation depends on the degree of linear energy transfer (LET). The relative biological effectiveness (RBE) reaches a maximum at LET of around 100-200 keV/micron and decreases at higher levels. The ion clusters produced by high-LET radiation are not uniformly distributed. The incidence of non-hit cell events is higher in high LET irradiation than in the cases of low-LET irradiation. This fact could explain the decrease in the cell killing effect at higher levels of LET irradiation. Since the cell killing effect may be related to the nuclear traversal of heavy-ions, it is necessary to establish methods to distinguish the hit cells from the non-hit cells, especially in case with high LET irradiation. Using time-lapse photography, we first examined the hit events by observing the division delay in the cells caused by high-LET irradiation. In addition, we explored the use of CR-39 plastics to detect the exact position of heavy-ion traversal on the surface of a flask where cells were growing. When Chinese hamster ovary (CHO-K1) cells were exposed to 4 Gy of accelerated Fe-ions (2000 keV/micron) or Ar (1640 keV/micron)-ions, the surviving fraction decreased to about 30% in both cases of irradiation. Eighty percent of the irradiated cells, suffered a division delay in contrast to the remaining 20% of the cells which showed a normal division time (12-13 hrs). The later 20% of the cells is considered to be a population of cells which were not actually traversed by heavy-ions. The difference between the higher values of the surviving fraction (approximately 30%) and the non-hit cell population (20%) indicates that some hit cells can grow even after being hit by heavy-ions. The fraction of recovered cells determined by the time-lapse photography method was 10%, and this value closely correlated with the difference between the surviving fraction and the non-hit cells. We used the Poisson distribution of the hit-events by heavy-ions among the cell population in order to calculate the fraction of cells receiving at least a single-hit in the cell nucleus (130 micron 2 in average size). From this calculation we determined that 80% of the cells had a single hit to their nuclei by a heavy-ion which induced such early cellular responses as division delay. Our finding in the experiments using CR-39 plastics as a detector for hit-sites further supported the idea that the hit lethality of a cell is related to heavy-ion traversal through its nucleus. This study indicates the possible usefulness of both the division delay and CR-39 plastic methods for evaluating the biological effects of heavy-ions, especially when these two methods are combined.

Downregulation of long non-coding RNA LET predicts poor prognosis and increases Notch signaling in non-small cell lung cancer

PubMed Central

Li, Shengwen; Zhao, Hui; Li, Jianqiang; Zhang, Aizheng; Wang, Haibin

2018-01-01

Long non-coding RNAs (lncRNAs) have been found to be dysregulated in a variety of tumors. The lncRNA-Low Expression in Tumor (LET) is a recently identified lncRNA, but its expression pattern and biological significance in human non-small cell lung cancer (NSCLC) are still largely unknown. In this study, we found that lncRNA-LET was significantly downregulated in human NSCLC lung tissues and cell lines. Decreased lncRNA-LET expression was strongly associated with advanced tumor stages and poorer overall survival of NSCLC patients. Functionally, overexpression of lncRNA-LET in NSCLC H292 cells significantly suppressed cell proliferation, migration and invasion, and promoted cell cycle arrest and apoptosis, while knockdown of lncRNA-LET in NSCLC H1975 cells showed an opposite effect, pointing to a tumor-suppressive role for lncRNA-LET in NSCLC. Mechanistically, we demonstrated that lncRNA-LET overexpression significantly reduced the expression of Notch1 intracellular Domain (NICD1) in H292 cells while knockdown of lncRNA-LET increased NICD1 expression in H1975 cells. Similarly, NSCLC lung tissues with high levels of lncRNA-LET had lower NICD1 expression. Thus, our results provide a strong rationale for lncRNA-LET to be used as a prognostic indicator and a potent therapeutic target for NSCLC patients, and highlight a novel lncRNA-LET/Notch axis in regulating NSCLC cell fate and tumor progression. PMID:29416684

MicroRNA Let-7b inhibits keratinocyte migration in cutaneous wound healing by targeting IGF2BP2.

PubMed

Wu, Yan; Zhong, Julia Li; Hou, Ning; Sun, Yaolan; Ma, Benting; Nisar, Muhammad Farrukh; Teng, Yan; Tan, Zhaoli; Chen, Keping; Wang, Youliang; Yang, Xiao

2017-02-01

Wound healing is a complex process which involves proliferation and migration of keratinocyte for closure of epidermal injuries. A member of microRNA family, let-7b, has been expressed in mammalian skin, but its exact role in keratinocyte migration is still not in knowledge. Here, we showed that let-7b regulates keratinocyte migration by targeting the insulin-like growth factor IGF2BP2. Overexpression of let-7b led to reduced HaCaT cell migration, while knockdown of let-7b resulted in enhanced migration. Furthermore, let-7b was decreased during wound healing in wild-type mice, which led us to construct the transgenic mice with overexpression of let-7b in skin. The re-epithelialization of epidermis of let-7b transgenic mice was reduced during wound healing. Using bioinformatics prediction software and a reporter gene assay, we found that IGF2BP2 was a target of let-7b, which contributes to keratinocyte migration. Introduction of an expression vector of IGF2BP2 also rescued let-7b-induced migration deficiency, which confirms that IGF2BP2 is an important target for let-7b regulation. Our findings suggest that let-7b significantly delayed the re-epithelialization possibly due to reduction of keratinocyte migration and restraints IGF2BP2 during skin wound healing. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ajax Architecture Implementation Techniques

NASA Astrophysics Data System (ADS)

Hussaini, Syed Asadullah; Tabassum, S. Nasira; Baig, Tabassum, M. Khader

2012-03-01

Today's rich Web applications use a mix of Java Script and asynchronous communication with the application server. This mechanism is also known as Ajax: Asynchronous JavaScript and XML. The intent of Ajax is to exchange small pieces of data between the browser and the application server, and in doing so, use partial page refresh instead of reloading the entire Web page. AJAX (Asynchronous JavaScript and XML) is a powerful Web development model for browser-based Web applications. Technologies that form the AJAX model, such as XML, JavaScript, HTTP, and XHTML, are individually widely used and well known. However, AJAX combines these technologies to let Web pages retrieve small amounts of data from the server without having to reload the entire page. This capability makes Web pages more interactive and lets them behave like local applications. Web 2.0 enabled by the Ajax architecture has given rise to a new level of user interactivity through web browsers. Many new and extremely popular Web applications have been introduced such as Google Maps, Google Docs, Flickr, and so on. Ajax Toolkits such as Dojo allow web developers to build Web 2.0 applications quickly and with little effort.

Quantitation of Radiation Induced Deletion and Recombination Events Associated with Repeated DNA Sequences

NASA Technical Reports Server (NTRS)

Sinden, Richard R.

1999-01-01

Manned exploration of space exposes the explorers to a complex and novel radiation environment. The galactic cosmic ray and trapped belt radiation (predominantly proton) components of this environment are relatively constant, and the variations with the solar cycle are well understood and predictable. The level of radiation encountered in low earth orbits is determined by several factors, including altitude, inclination of orbit with respect to the equator, and spacecraft shielding. At higher altitudes, and on a Mars mission, the level of radiation exposure will increase significantly. A significant fraction of the dose may be delivered by solar particle events which vary dramatically in dose rate and incident particle spectrum. High-LET radiation is of particular concern. High-LET radiation, a component of galactic cosmic rays (GCR), is comprised of a variety of charged particles of various energies (10 MeV/n to 10 GeV/n), including about 87% photons, 12% helium ions, and heavy ions (including iron). These high energy particles can cause significant damage to target cells. The different particle types and energies result in different patterns of energy deposition at the molecular and cellular level in a primary target cell. They can also cause significant damage to other, nearby cells as a result of secondary particles. Protons, for instance produce secondaries that include photons, neutrons, pions, heavy particles, as well as gamma rays. Heavy ions deposit energy in a "track" in which the magnitude of the damage varies as the particle loses energy. Heavy ions produce secondary delta rays, or electrons. The distribution of damage through tissue is described by a Bragg curve which will be characteristic for different energies. Needless to say there are differences in the RBE of protons and a particles. High-LET heavy ions are particularly damaging to cells as they do continual damage throughout their track. Differences in these energy deposition patterns can significantly influence the nature of DNA damage and the ability of cellular systems to repair such damage. It has been suspected that these differences also affect the spatial distribution of damage within the DNA of the interphase cell nucleus and produce corresponding differences in endpoints related to health effects. The interaction of a single high-LET particle with chromatin has been suggested to cause multiple double strand breaks within a relatively short distance. In part this is due to the organization of DNA into chromatin fibers in which distant regions of the DNA helix can be physically juxtaposed by the various levels of coiling of the DNA. This prediction was confirmed by the detection of the generation of double strand DNA fragments of 100-2000 bp following exposure to high-LET ions (including iron).

The let-7 microRNA interfaces extensively with the translation machinery to regulate cell differentiation

PubMed Central

Ding, Xavier C.; Slack, Frank J.; Großhans, Helge

2010-01-01

MicroRNAs (miRNAs) are noncoding RNAs that regulate numerous target genes through a posttranscriptional mechanism and thus control major developmental pathways. The phylogenetically conserved let-7 miRNA regulates cell proliferation and differentiation, thus functioning as a key regulator of developmental timing in C. elegans and a tumor suppressor gene in humans. Using a reverse genetic screen, we have identified genetic interaction partners of C. elegans let-7, including known and novel potential target genes. Initial identification of several translation initiation factors as suppressors of a let-7 mutation led us to systematically examine genetic interaction between let-7 and the translational machinery, which we found to be widespread. In the presence of wild-type let-7, depletion of the translation initiation factor eIF3 resulted in precocious cell differentiation, suggesting that developmental timing is translationally regulated, possibly by let-7. As overexpression of eIF3 in humans promotes translation of mRNAs that are also targets of let-7-mediated repression, we suggest that eIF3 may directly or indirectly oppose let-7 activity. This might provide an explanation for the opposite functions of let-7 and eIF3 in regulating tumorigenesis. PMID:18818519

Monte Carlo simulations of a low energy proton beamline for radiobiological experiments.

PubMed

Dahle, Tordis J; Rykkelid, Anne Marit; Stokkevåg, Camilla H; Mairani, Andrea; Görgen, Andreas; Edin, Nina J; Rørvik, Eivind; Fjæra, Lars Fredrik; Malinen, Eirik; Ytre-Hauge, Kristian S

2017-06-01

In order to determine the relative biological effectiveness (RBE) of protons with high accuracy, radiobiological experiments with detailed knowledge of the linear energy transfer (LET) are needed. Cell survival data from high LET protons are sparse and experiments with low energy protons to achieve high LET values are therefore required. The aim of this study was to quantify LET distributions from a low energy proton beam by using Monte Carlo (MC) simulations, and to further compare to a proton beam representing a typical minimum energy available at clinical facilities. A Markus ionization chamber and Gafchromic films were employed in dose measurements in the proton beam at Oslo Cyclotron Laboratory. Dose profiles were also calculated using the FLUKA MC code, with the MC beam parameters optimized based on comparisons with the measurements. LET spectra and dose-averaged LET (LET d ) were then estimated in FLUKA, and compared with LET calculated from an 80 MeV proton beam. The initial proton energy was determined to be 15.5 MeV, with a Gaussian energy distribution of 0.2% full width at half maximum (FWHM) and a Gaussian lateral spread of 2 mm FWHM. The LET d increased with depth, from approximately 5 keV/μm in the entrance to approximately 40 keV/μm in the distal dose fall-off. The LET d values were considerably higher and the LET spectra were much narrower than the corresponding spectra from the 80 MeV beam. MC simulations accurately modeled the dose distribution from the proton beam and could be used to estimate the LET at any position in the setup. The setup can be used to study the RBE for protons at high LET d , which is not achievable in clinical proton therapy facilities.

Proposed linear energy transfer areal detector for protons using radiochromic film.

PubMed

Mayer, Rulon; Lin, Liyong; Fager, Marcus; Douglas, Dan; McDonough, James; Carabe, Alejandro

2015-04-01

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured at a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%-10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%-15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.

MiRNA Analysis by Quantitative PCR in Preterm Human Breast Milk Reveals Daily Fluctuations of hsa-miR-16-5p.

PubMed

Floris, Ilaria; Billard, Hélène; Boquien, Clair-Yves; Joram-Gauvard, Evelyne; Simon, Laure; Legrand, Arnaud; Boscher, Cécile; Rozé, Jean-Christophe; Bolaños-Jiménez, Francisco; Kaeffer, Bertrand

2015-01-01

Human breast milk is an extremely dynamic fluid containing many biologically-active components which change throughout the feeding period and throughout the day. We designed a miRNA assay on minimized amounts of raw milk obtained from mothers of preterm infants. We investigated changes in miRNA expression within month 2 of lactation and then over the course of 24 hours. Analyses were performed on pooled breast milk, made by combining samples collected at different clock times from the same mother donor, along with time series collected over 24 hours from four unsynchronized mothers. Whole milk, lipids or skim milk fractions were processed and analyzed by qPCR. We measured hsa-miR-16-5p, hsa-miR-21-5p, hsa-miR-146-5p, and hsa-let-7a, d and g (all -5p). Stability of miRNA endogenous controls was evaluated using RefFinder, a web tool integrating geNorm, Normfinder, BestKeeper and the comparative ΔΔCt method. MiR-21 and miR-16 were stably expressed in whole milk collected within month 2 of lactation from four mothers. Analysis of lipids and skim milk revealed that miR-146b and let-7d were better references in both fractions. Time series (5H-23H) allowed the identification of a set of three endogenous reference genes (hsa-let-7d, hsa-let-7g and miR-146b) to normalize raw quantification cycle (Cq) data. We identified a daily oscillation of miR-16-5p. Our assay allows exploring miRNA levels of breast milk from mother with preterm baby collected in time series over 48-72 hours.

TH-CD-201-03: A Real-Time Method to Simultaneously Measure Linear Energy Transfer and Dose for Proton Therapy Using Organic Scintillators

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

Alsanea, F; Therriault-Proulx, F; Sawakuchi, G

Purpose: The light generated in organic scintillators depends on both the radiation dose and the linear energy transfer (LET). The LET dependence leads to an under-response of the detector in the Bragg peak of proton beams. This phenomenon, called ionization quenching, must be corrected to obtain accurate dose measurements of proton beams. This work exploits the ionization quenching phenomenon to provide a method of measuring LET and auto correcting quenching. Methods: We exposed simultaneously four different organic scintillators (BCF-12, PMMA, PVT, and LSD; 1mm in diameter) and a plane parallel ionization chamber in passively scattered proton beams to doses betweenmore » 32 and 43 cGy and fluence averaged LET values from 0.47 to 1.26 keV/µm. The LET values for each irradiation condition were determined using a validated Monte Carlo model of the beam line. We determined the quenching parameter in the Birk’s equation for scintillation in BCF-12 for dose measurements. One set of irradiation conditions was used to correlate the scintillation response ratio to the LET values and plot a scintillation response ratio versus LET calibration curve. Irradiation conditions independent from the calibration ones were used to validate this method. Comparisons to the expected values were made on both the basis of dose and LET. Results: Among all the scintillators investigated, the ratio of PMMA to BCF-12 provided the best correlation to LET values and was used as the LET calibration curve. The expected LET values in the validation set were within 2%±6%, which resulted in dose accuracy of 1.5%±5.8% for the range of LET values investigated in this work. Conclusion: We have demonstrated the feasibility of using the ratio between the light output of two organic scintillators to simultaneously measure LET and dose of therapeutic proton beams. Further studies are needed to verify the response in higher LET values.« less

The RBE-LET relationship for rodent intestinal crypt cell survival, testes weight loss, and multicellular spheroid cell survival after heavy-ion irradiation

NASA Technical Reports Server (NTRS)

Rodriguez, A.; Alpen, E. L.; Powers-Risius, P.

1992-01-01

This report presents data for survival of mouse intestinal crypt cells, mouse testes weight loss as an indicator of survival of spermatogonial stem cells, and survival of rat 9L spheroid cells after irradiation in the plateau region of unmodified particle beams ranging in mass from 4He to 139La. The LET values range from 1.6 to 953 keV/microns. These studies examine the RBE-LET relationship for two normal tissues and for an in vitro tissue model, multicellular spheroids. When the RBE values are plotted as a function of LET, the resulting curve is characterized by a region in which RBE increases with LET, a peak RBE at an LET value of 100 keV/microns, and a region of decreasing RBE at LETs greater than 100 keV/microns. Inactivation cross sections (sigma) for these three biological systems have been calculated from the exponential terminal slope of the dose-response relationship for each ion. For this determination the dose is expressed as particle fluence and the parameter sigma indicates effect per particle. A plot of sigma versus LET shows that the curve for testes weight loss is shifted to the left, indicating greater radiosensitivity at lower LETs than for crypt cell and spheroid cell survival. The curves for cross section versus LET for all three model systems show similar characteristics with a relatively linear portion below 100 keV/microns and a region of lessened slope in the LET range above 100 keV/microns for testes and spheroids. The data indicate that the effectiveness per particle increases as a function of LET and, to a limited extent, Z, at LET values greater than 100 keV/microns. Previously published results for spread Bragg peaks are also summarized, and they suggest that RBE is dependent on both the LET and the Z of the particle.

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

PubMed

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.

Cocaine Modulates the Expression of Opioid Receptors and miR-let-7d in Zebrafish Embryos

PubMed Central

López-Bellido, Roger; Barreto-Valer, Katherine; Sánchez-Simón, Fátima Macho; Rodríguez, Raquel E.

2012-01-01

Prenatal exposure to cocaine, in mammals, has been shown to interfere with the expression of opioid receptors, which can have repercussions in its activity. Likewise, microRNAs, such as let-7, have been shown to regulate the expression of opioid receptors and hence their functions in mammals and in vitro experiments. In light of this, using the zebrafish embryos as a model our aim here was to evaluate the actions of cocaine in the expression of opioid receptors and let-7d miRNA during embryogenesis. In order to determine the effects produced by cocaine on the opioid receptors (zfmor, zfdor1 and zfdor2) and let-7d miRNA (dre-let-7d) and its precursors (dre-let-7d-1 and dre-let-7d-2), embryos were exposed to 1.5 µM cocaine hydrochloride (HCl). Our results revealed that cocaine upregulated dre-let-7d and its precursors, and also increased the expression of zfmor, zfdor1 and zfdor2 during early developmental stages and decreased them in late embryonic stages. The changes observed in the expression of opioid receptors might occur through dre-let-7d, since DNA sequences and the morpholinos of opioid receptors microinjections altered the expression of dre-let-7d and its precursors. Likewise, opioid receptors and dre-let-7d showed similar distributions in the central nervous system (CNS) and at the periphery, pointing to a possible interrelationship between them. In conclusion, the silencing and overexpression of opioid receptors altered the expression of dre-let-7d, which points to the notion that cocaine via dre-let-7 can modulate the expression of opioid receptors. Our study provides new insights into the actions of cocaine during zebrafish embryogenesis, indicating a role of miRNAs, let-7d, in development and its relationship with gene expression of opioid receptors, related to pain and addiction process. PMID:23226419

Evolution of Fish Let-7 MicroRNAs and Their Expression Correlated to Growth Development in Blunt Snout Bream

PubMed Central

Zhao, Bo-Wen; Zhou, Lai-Fang; Liu, Yu-Long; Wan, Shi-Ming; Gao, Ze-Xia

2017-01-01

The lethal-7 (let-7) miRNA, known as one of the first founding miRNAs, is present in multiple copies in a genome and has diverse functions in animals. In this study, comparative genomic analysis of let-7 miRNAs members in fish species indicated that let-7 miRNA is a sequence conserved family in fish, while different species have the variable gene copy numbers. Among the ten members including let-7a/b/c/d/e/f/g/h/i/j, the let-7a precursor sequence was more similar to ancestral sequences, whereas other let-7 miRNA members were separate from the late differentiation of let-7a. The mostly predicted target genes of let-7 miRNAs are involved in biological process, especially developmental process and growth through Gene Ontology (GO) enrichment analysis. In order to identify the possible different functions of these ten miRNAs in fish growth development, their expression levels were quantified in adult males and females of Megalobrama amblycephala, as well as in 3-, 6-, and 12-months-old individuals with relatively slow- and fast-growth rates. These ten miRNAs had similar tissue expression patterns between males and females, with higher expression levels in the brain and pituitary than that in other tissues (p < 0.05). Among these miRNAs, the relative expression level of let-7a was the highest among almost all the tested tissues, followed by let-7b, let-7d and let-7c/e/f/g/h/i/j. As to the groups with different growth rates, the expression levels of let-7 miRNAs in pituitary and brain from the slow-growth group were always significantly higher than that in the fast-growth group (p < 0.05). These results suggest that let-7 miRNA members could play an important role in the regulation of growth development in M. amblycephala through negatively regulating expression of their target genes. PMID:28300776

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

PubMed Central

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

Two small ncRNAs jointly govern virulence and transmission in Legionella pneumophila

PubMed Central

Sahr, Tobias; Brüggemann, Holger; Jules, Matthieu; Lomma, Mariella; Albert-Weissenberger, Christiane; Cazalet, Christel; Buchrieser, Carmen

2009-01-01

Summary To transit from intra- to extracellular environments, L. pneumophila differentiates from a replicative/non-virulent to a transmissive/virulent form using the two-component system LetA/LetS and the global repressor protein CsrA. While investigating how both regulators act coordinately we characterized two ncRNAs, RsmY and RsmZ that link the LetA/LetS and CsrA regulatory networks. We demonstrate that LetA directly regulates their expression and show that RsmY and RsmZ are functional in E. coli and are able to bind CsrA in vitro. Single mutants have no (ΔrsmY) or a little (ΔrsmZ) impact on virulence, but the ΔrsmYZ strain shows a drastic defect in intracellular growth in Acanthamoeba castellanii and THP-1 monocyte-derived macrophages. Analysis of the transcriptional programs of the ΔletA, ΔletS and ΔrsmYZ strains revealed that the switch to the transmissive phase is partially blocked. One major difference between the ΔletA, ΔletS and ΔrsmYZ strains was that the latter synthesizes flagella. Taken together, LetA activates transcription of RsmY and RsmZ, which sequester CsrA and abolish its post-transcriptional repressive activity. However, the RsmYZ-CsrA pathway appears not to be the main or only regulatory circuit governing flagella synthesis. We suggest that rather RpoS and LetA, by influencing LetE and probably cyclic-di-GMP levels, regulate motility in L. pneumophila. PMID:19400772

Aromatase inhibitor regulates let-7 expression and let-7f induced cell migration in endometrial cells from women with endometriosis

PubMed Central

Cho, SiHyun; Mutlu, Levent; Zhou, Yuping; Taylor, Hugh S.

2018-01-01

Objectives To evaluate associations between aromatase inhibitor (AI) treatment and let-7 family microRNA expression in endometriosis. Design In vitro study using Ishikawa cells and human endometrial stromal cells (HESC) obtained from patients with endometriosis Setting University research center. Patients Women undergoing laparoscopic surgery for endometriosis Interventions HESCs and Ishikawa cells treated with various letrozol concentrations and transfected with a mimic of let-7 subtypes of interest Main Outcome Measures microRNAs let7a-f and aromatase expression were evaluated. Migration potential after transfection with a let-7f mimic were analyzed. Results After letrozole treatment for 48 hours, all let-7 subtypes showed a trend toward increased expression in a dose dependent manner in Ishikawa cells, and significant differences were found in let-7b and let-7f between controls and the 20 μmol/L treated groups. Further, let-7f showed significant differences between control and 1.0 μmol/L treatment group, a typical therapeutic level, in HESCs. Transfection of a let-7f mimic decreased aromatase expression in both Ishikawa cells and HESC, and led to a significant decrease in number of migrating cells in both cell types. Conclusions AI treatment significantly increased expression of let-7f in Ishikawa cells and HESCs from patient with endometriosis; increased lef-7f expression effectively reduced the migration of endometrial cells. Modulation of miRNAs involved in the pathogenesis of endometriosis may have therapeutic potential for endometriosis. PMID:27320036

let-7d-3p is associated with apoptosis and response to neoadjuvant chemotherapy in ovarian cancer.

PubMed

García-Vázquez, Raúl; Gallardo Rincón, Dolores; Ruiz-García, Erika; Meneses García, Abelardo; Hernández De La Cruz, Olga N; Astudillo-De La Vega, Horacio; Isla-Ortiz, David; Marchat, Laurence A; Salinas-Vera, Yarely M; Carlos-Reyes, Ángeles; López-González, Sullivan; Ramos-Payan, Rosalio; López-Camarillo, César

2018-06-01

Altered expression of microRNAs contributes to the heterogeneous biological behavior of human malignancies and it may correlate with the clinical pathological features of patients. The let-7 microRNA family is frequently downregulated in human cancers and its aberrant expression may be a useful marker for prediction of the clinical response to therapy in patients. In the present study, we analyzed the expression of three members of the let-7 family (let-7a-3p, let-7d-3p and let-7f), which remains largely uncharacterized in ovarian cancer tissues. We also investigated the function of let-7d-3p in the apoptosis and sensitization to chemotherapy in ovarian cancer cells. Our data from stem-loop quantitative RT-PCR showed that expression of let-7a-3p and let-7d-3p, but not let-7f, was significantly (P<0.04) upregulated in ovarian tumors relative to that noted in normal ovarian tissues. Markedly, an increased expression of let‑7d-3p (also known as let-7d-3*) was associated with positive response to carboplatin/paclitaxel treatment in ovarian cancer patients. To investigate the biological relevance of let‑7d-3p, we knocked down its expression in SKOV-3 ovarian cancer cell line using antagomiRs. Loss of function analysis showed that inhibition of let-7d-3p significantly (P<0.05) impaired cell proliferation and activated apoptosis. In contrast, scratch/wound healing and Transwell chamber assays showed that migration and invasion abilities were not affected in the let-7d-3p-deficient SKOV-3 cancer cells. Notably, Annexin V assays showed a significant (P<0.05) increase in cell death of cancer cells treated with the let-7d-3p inhibitor plus carboplatin indicating a synergistic effect of the drug with antagomiR therapy. Gene ontology classification of predicted targets of let-7d-3p identified a number of genes involved in cellular pathways associated with therapy resistance such as ABC transporters, HIF-1, RAS and ErbB signaling. In summary, our findings showed that inhibition of let-7d-3 activates apoptosis and that its upregulation is associated with a positive response of ovarian cancer patients to carboplatin/paclitaxel chemotherapy.

Impact of Spatial Scales on the Intercomparison of Climate Scenarios

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

Luo, Wei; Steptoe, Michael; Chang, Zheng

2017-01-01

Scenario analysis has been widely applied in climate science to understand the impact of climate change on the future human environment, but intercomparison and similarity analysis of different climate scenarios based on multiple simulation runs remain challenging. Although spatial heterogeneity plays a key role in modeling climate and human systems, little research has been performed to understand the impact of spatial variations and scales on similarity analysis of climate scenarios. To address this issue, the authors developed a geovisual analytics framework that lets users perform similarity analysis of climate scenarios from the Global Change Assessment Model (GCAM) using a hierarchicalmore » clustering approach.« less

Proposed linear energy transfer areal detector for protons using radiochromic film

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

Mayer, Rulon; Lin, Liyong; Fager, Marcus

2015-04-15

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured atmore » a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%–10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%–15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.« less

Interaction Junk: User Interaction-Based Evaluation of Visual Analytic Systems

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

Endert, Alexander; North, Chris

2012-10-14

With the growing need for visualization to aid users in understanding large, complex datasets, the ability for users to interact and explore these datasets is critical. As visual analytic systems have advanced to leverage powerful computational models and data analytics capabilities, the modes by which users engage and interact with the information are limited. Often, users are taxed with directly manipulating parameters of these models through traditional GUIs (e.g., using sliders to directly manipulate the value of a parameter). However, the purpose of user interaction in visual analytic systems is to enable visual data exploration – where users can focusmore » on their task, as opposed to the tool or system. As a result, users can engage freely in data exploration and decision-making, for the purpose of gaining insight. In this position paper, we discuss how evaluating visual analytic systems can be approached through user interaction analysis, where the goal is to minimize the cognitive translation between the visual metaphor and the mode of interaction (i.e., reducing the “Interactionjunk”). We motivate this concept through a discussion of traditional GUIs used in visual analytics for direct manipulation of model parameters, and the importance of designing interactions the support visual data exploration.« less

Readiness for School Involves an Array of Skills: Let's Not Forget Fine Motor Development. NCRECE In Focus. Volume 1, Issue 5

ERIC Educational Resources Information Center

Goffin, Stacie G.

2010-01-01

Interest in children's success as readers has existed for a long time. With growing attention to our nation's global competitiveness, school success with math and science is joining reading as important topic areas for children's early learning. As a result, new research is exploring predictors of school success with math and science as well as…

Multi-Metric Sustainability Analysis

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

Cowlin, Shannon; Heimiller, Donna; Macknick, Jordan

2014-12-01

A readily accessible framework that allows for evaluating impacts and comparing tradeoffs among factors in energy policy, expansion planning, and investment decision making is lacking. Recognizing this, the Joint Institute for Strategic Energy Analysis (JISEA) funded an exploration of multi-metric sustainability analysis (MMSA) to provide energy decision makers with a means to make more comprehensive comparisons of energy technologies. The resulting MMSA tool lets decision makers simultaneously compare technologies and potential deployment locations.

MiR-let-7a inhibits cell proliferation, migration, and invasion by down-regulating PKM2 in cervical cancer

PubMed Central

Guo, Man; Zhao, Xinying; Yuan, Xiaolei; Jiang, Jing; Li, Peiling

2017-01-01

In recent decades, miRNA has been reported as a crucial modulator in some biology progressions. This work aims to assess the expression and role of miR-let-7a and pyruvate kinase muscle isozyme M2 (PKM2) in CC tissues and cell lines. Here, we identified that miR-let-7a expression was decreased in CC tissues, and SiHa and HeLa cells (all P < 0.001), however, PKM2 expression was increased in these samples. Statistically, miR-let-7a was inversely associated with PKM2 mRNA or protein (p = 0.013, p = 0.015, respectively). In-vitro assays revealed that ectopic miR-let-7a expression repressed SiHa and HeLa cell proliferation, migration and invasion, and enhanced SiHa and HeLa cell apoptosis. Furthermore, luciferase reporter assays revealed the 3′-UTR of PKM2 was identified a target of miR-let-7a, by which miR-let-7a affected the expression of PKM2 in SiHa and HeLa cells. Besides, PKM2 plasmids partially abrogated the inhibitory effects of miR-let-7a, while si-PKM2 enhanced the inhibitory effects of miR-let-7a. In vivo, miR-let-7a mimics indeed repressed tumor growth in mice xenograft model. In conclusion, our results demonstrated that miR-let-7a inhibits cell proliferation, migration and invasion by down-regulation of PKM2 in cervical cancer. miR-let-7a/PKM2 pathway may be a useful therapeutic target for CC patients. PMID:28415668

RACK-1 regulates let-7 microRNA expression and terminal cell differentiation in Caenorhabditis elegans

PubMed Central

Chu, Yu-De; Wang, Wei-Chieh; Chen, Shi-An A; Hsu, Yen-Ting; Yeh, Meng-Wei; Slack, Frank J; Chan, Shih-Peng

2014-01-01

The let-7 microRNA (miRNA) regulates cell cycle exit and terminal differentiation in the C. elegans heterochronic gene pathway. Low expression of let-7 results in retarded vulva and hypodermal cell development in C. elegans and has been associated with several human cancers. Previously, the versatile scaffold protein receptor for activated C kinase 1 (RACK1) was proposed to facilitate recruitment of the miRNA-induced silencing complex (miRISC) to the polysome and to be required for miRNA function in C. elegans and humans. Here, we show that depletion of C. elegans RACK-1 by RNAi increases let-7 miRNA levels and suppresses the retarded terminal differentiation of lateral hypodermal seam cells in mutants carrying the hypomorphic let-7(n2853) allele or lacking the let-7 family miRNA genes mir-48 and mir-241. Depletion of RACK-1 also increases the levels of precursor let-7 miRNA. When Dicer is knocked down and pre-miRNA processing is inhibited, depletion of RACK-1 still leads to increased levels of pre-let-7, suggesting that RACK-1 affects a biogenesis mechanism upstream of Dicer. No changes in the activity of the let-7 promoter or the levels of primary let-7 miRNA are associated with depletion of RACK-1, suggesting that RACK-1 affects let-7 miRNA biogenesis at the post-transcriptional level. Interestingly, rack-1 knockdown also increases the levels of a few other precursor miRNAs. Our results reveal that RACK-1 controls the biogenesis of a subset of miRNAs, including let-7, and in this way plays a role in the heterochronic gene pathway during C. elegans development. PMID:24776851

Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training

NASA Astrophysics Data System (ADS)

Raber, Jacob; Weber, Sydney J.; Kronenberg, Amy; Turker, Mitchell S.

2016-06-01

The space radiation environment includes energetic charged particles that may impact behavioral and cognitive performance. The relationship between the dose and the ionization density of the various types of charged particles (expressed as linear energy transfer or LET), and cognitive performance is complex. In our earlier work, whole body exposure to 28Si ions (263 MeV/n, LET = 78keV / μ m ; 1.6 Gy) affected contextual fear memory in C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation but this was not the case following exposure to 48Ti ions (1 GeV/n, LET = 107keV / μ m ; 0.2 or 0.4 Gy). As an increased understanding of the impact of charged particle exposures is critical for assessment of risk to the CNS of astronauts during and following missions, in this study we used 40Ca ion beams (942 MeV/n, LET = 90keV / μm) to determine the behavioral and cognitive effects for the LET region between that of Si ions and Ti ions. 40Ca ion exposure reduced baseline activity in a novel environment in a dose-dependent manner, which suggests reduced motivation to explore and/or a diminished level of curiosity in a novel environment. In addition, exposure to 40Ca ions had sex-dependent effects on response to shock. 40Ca ion irradiation reduced the response to shock in female, but not male, mice. In contrast, 40Ca ion irradiation did not affect fear learning, memory, or extinction of fear memory for either gender at the doses employed in this study. Thus 40Ca ion irradiation affected behavioral, but not cognitive, performance. The effects of 40Ca ion irradiation on behavioral performance are relevant, as a combination of novelty and aversive environmental stimuli is pertinent to conditions experienced by astronauts during and following space missions.

Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training.

PubMed

Raber, Jacob; Weber, Sydney J; Kronenberg, Amy; Turker, Mitchell S

2016-06-01

The space radiation environment includes energetic charged particles that may impact behavioral and cognitive performance. The relationship between the dose and the ionization density of the various types of charged particles (expressed as linear energy transfer or LET), and cognitive performance is complex. In our earlier work, whole body exposure to (28)Si ions (263 MeV/n, LET=78keV/μm; 1.6 Gy) affected contextual fear memory in C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation but this was not the case following exposure to (48)Ti ions (1 GeV/n, LET=107keV/μm; 0.2 or 0.4 Gy). As an increased understanding of the impact of charged particle exposures is critical for assessment of risk to the CNS of astronauts during and following missions, in this study we used (40)Ca ion beams (942 MeV/n, LET=90keV/μm) to determine the behavioral and cognitive effects for the LET region between that of Si ions and Ti ions. (40)Ca ion exposure reduced baseline activity in a novel environment in a dose-dependent manner, which suggests reduced motivation to explore and/or a diminished level of curiosity in a novel environment. In addition, exposure to (40)Ca ions had sex-dependent effects on response to shock. (40)Ca ion irradiation reduced the response to shock in female, but not male, mice. In contrast, (40)Ca ion irradiation did not affect fear learning, memory, or extinction of fear memory for either gender at the doses employed in this study. Thus (40)Ca ion irradiation affected behavioral, but not cognitive, performance. The effects of (40)Ca ion irradiation on behavioral performance are relevant, as a combination of novelty and aversive environmental stimuli is pertinent to conditions experienced by astronauts during and following space missions. Copyright © 2016 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

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

PubMed Central

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

Optimal solutions for complex design problems: Using isoperformance software for human factors trade offs

NASA Technical Reports Server (NTRS)

Kennedy, Robert S.; Jones, Marshall B.; Baltzley, Dennis R.

1988-01-01

A major application of isoperformance is as a trade-off methodology of the three major drivers of system design; equipment, training variables, and user characteristics. The flexibility of isoperformance allows each of these three components to be nearly any rational variation. For example, aptitude may be military Armed Forces Qualification Testing (AFQT) categories, cutoff scores within a selection procedure, or simply dichotomizing high and low scorers (pass/fail). Equipment may be new versus old, 'smart' versus dumb, high versus low resolution, etc. Training may be short versus long or varieties of media types (lecture versus CAI/CBI versus self-paced workbooks). In its final computerized form isoperformance lets the user set an operational level of performance (e.g., a jet pilot in a simulated emergency must take prescribed corrective action and clear the plane in several seconds, pilot astronauts will check out all shuttle flight systems within 30 minutes, or Mission Specialists must handle sucdessfully a required number of job elements). At this point the computer program guides the user through any requested trade-offs of the three components while maintaining the specified operational level of performance through isoperformance curves. A demonstration of the computer program is currently available.

Low LET proton microbeam to understand high-LET RBE by shaping spatial dose distribution

NASA Astrophysics Data System (ADS)

Greubel, Christoph; Ilicic, Katarina; Rösch, Thomas; Reindl, Judith; Siebenwirth, Christian; Moser, Marcus; Girst, Stefanie; Walsh, Dietrich W. M.; Schmid, Thomas E.; Dollinger, Günther

2017-08-01

High LET radiation, like heavy ions, are known to have a higher biological effectiveness (RBE) compared to low LET radiation, like X- or γ -rays. Theories and models attribute these higher effectiveness mostly to their extremely inhomogeneous dose deposition, which is concentrated in only a few micron sized spots. At the ion microprobe SNAKE, low LET 20 MeV protons (LET in water of 2.6 keV/μm) can be applied to cells either randomly distributed or focused to submicron spots, approximating heavy ion dose deposition. Thus, the transition between low and high LET energy deposition is experimentally accessible and the effect of different spatial dose distributions can be analysed. Here, we report on the technical setup to cultivate and irradiate 104 cells with submicron spots of low LET protons to measure cell survival in unstained cells. In addition we have taken special care to characterise the beam spot of the 20 MeV proton microbeam with fluorescent nuclear track detectors.

Collaboration using open standards and open source software (examples of DIAS/CEOS Water Portal)

NASA Astrophysics Data System (ADS)

Miura, S.; Sekioka, S.; Kuroiwa, K.; Kudo, Y.

2015-12-01

The DIAS/CEOS Water Portal is a part of the DIAS (Data Integration and Analysis System, http://www.editoria.u-tokyo.ac.jp/projects/dias/?locale=en_US) systems for data distribution for users including, but not limited to, scientists, decision makers and officers like river administrators. One of the functions of this portal is to enable one-stop search and access variable water related data archived multiple data centers located all over the world. This portal itself does not store data. Instead, according to requests made by users on the web page, it retrieves data from distributed data centers on-the-fly and lets them download and see rendered images/plots. Our system mainly relies on the open source software GI-cat (http://essi-lab.eu/do/view/GIcat) and open standards such as OGC-CSW, Opensearch and OPeNDAP protocol to enable the above functions. Details on how it works will be introduced during the presentation. Although some data centers have unique meta data format and/or data search protocols, our portal's brokering function enables users to search across various data centers at one time. And this portal is also connected to other data brokering systems, including GEOSS DAB (Discovery and Access Broker). As a result, users can search over thousands of datasets, millions of files at one time. Users can access the DIAS/CEOS Water Portal system at http://waterportal.ceos.org/.

Effects of long non-coding RNA HOST2 on cell migration and invasion by regulating MicroRNA let-7b in breast cancer.

PubMed

Lu, Peng-Wei; Li, Lin; Wang, Fang; Gu, Yuan-Ting

2018-06-01

The study intends to investigate the effects of long non-coding RNA HOST2 (lncRNA HOST2) on cell migration and invasion by regulating microRNA let-7b (let-7b) in breast cancer. Breast cancer and adjacent normal tissues were collected from 98 patients with breast cancer. Breast cancer MCF-7 cells were divided into the blank, negative control (NC), pcDNA3-Mock, siHOST2, let-7b inhibitor, pcDNA3-HOST2, let-7b mimic, pcDNA3-HOST2 + let-7b mimic, and siHOST2 + let-7b inhibitor groups. RT-qPCR was used to detect the mRNA expressions of HOST2, let-7b, and c-Myc. Western blotting was conducted to measure the c-Myc expression. Scratch test and Transwell assay were applied to detect the cell motility, migration, and invasion. Xenograft tumor in nude mice was performed to evaluate the effect of different transfection on the tumor growth. Compared with adjacent normal tissues, HOST2 expression was higher but let-7b expression lower in breast cancer tissues. HOST2 expression in breast cancer cells was remarkably increased compared with that in the normal breast epithelial MCF-10A cells. In MCF-7 cells, in comparison with the blank and NC groups, expressions of HOST2 and c-Myc were reduced, but let-7b expression was remarkably elevated in the siHOST2 and let-7b mimic groups; the let-7b inhibitor group exhibited higher expressions of HOST2 and c-Myc but lower let-7b expression. Overexpression of HOST2 could promote cell motility, migration and invasion, thus enhancing the growth of breast cancer tumor. By inhibiting HOST2, opposite trends were found. LncRNA HOST2 promotes cell migration and invasion by inhibiting let-7b in breast cancer patients. © 2017 Wiley Periodicals, Inc.

Using Generalized Annotated Programs to Solve Social Network Diffusion Optimization Problems

DTIC Science & Technology

2013-01-01

as follows: —Let kall be the k value for the SNDOP-ALL query and for each SNDOP query i, let ki be the k for that query. For each query i, set ki... kall − 1. —Number each element of vi ∈ V such that gI(vi) and V C(vi) are true. For the ith SNDOP query, let vi be the corresponding element of V —Let...vertices of S. PROOF. We set up |V | SNDOP-queries as follows: —Let kall be the k value for the SNDOP-ALL query and and for each SNDOP-query i, let ki be

The Design and Implementation of a Parallel Persistent Object System

DTIC Science & Technology

1992-02-01

Semantica JilP L Add descriptor (FP.L) to active pool JMPF r L If Frames, FP+r.O-0 Add descriptor (FP,L) to active pool Else Add descriptor (FP, IP+l...Syntax Semantica STARTO rl r2 Let FP’ = Frames[FP+rl] Let IP’ - Frames[FP+r2] Add (FP.IP+I) to active pool Add (FP I, P’ ) to active pool STARTI rl r2 r3...deadlock. 119 Syntaz Semantica ALLOCFRANE ri rj Let CallerFP - Frames [FP+ri] Let ResultIP - Frames [FP+ri+1] Let SignalIP = Frames [FP+ri+2] Let ResSlot

Epstein-Barr Virus EBNA1 Protein Regulates Viral Latency through Effects on let-7 MicroRNA and Dicer

PubMed Central

Mansouri, Sheila; Pan, Qun; Blencowe, Benjamin J.; Claycomb, Julie M.

2014-01-01

ABSTRACT The EBNA1 protein of Epstein-Barr virus (EBV) plays multiple roles in EBV latent infection, including altering cellular pathways relevant for cancer. Here we used microRNA (miRNA) cloning coupled with high-throughput sequencing to identify the effects of EBNA1 on cellular miRNAs in two nasopharyngeal carcinoma cell lines. EBNA1 affected a small percentage of cellular miRNAs in both cell lines, in particular, upregulating multiple let-7 family miRNAs, including let-7a. The effects of EBNA1 on let-7a were verified by demonstrating that EBNA1 silencing in multiple EBV-positive carcinomas downregulated let-7a. Accordingly, the let-7a target, Dicer, was found to be partially downregulated by EBNA1 expression (at the mRNA and protein levels) and upregulated by EBNA1 silencing in EBV-positive cells. Reporter assays based on the Dicer 3′ untranslated region with and without let-7a target sites indicated that the effects of EBNA1 on Dicer were mediated by let-7a. EBNA1 was also found to induce the expression of let-7a primary RNAs in a manner dependent on the EBNA1 transcriptional activation region, suggesting that EBNA1 induces let-7a by transactivating the expression of its primary transcripts. Consistent with previous reports that Dicer promotes EBV reactivation, we found that a let-7a mimic inhibited EBV reactivation to the lytic cycle, while a let-7 sponge increased reactivation. The results provide a mechanism by which EBNA1 could promote EBV latency by inducing let-7 miRNAs. IMPORTANCE The EBNA1 protein of Epstein-Barr virus (EBV) contributes in multiple ways to the latent mode of EBV infection that leads to lifelong infection. In this study, we identify a mechanism by which EBNA1 helps to maintain EBV infection in a latent state. This involves induction of a family of microRNAs (let-7 miRNAs) that in turn decreases the level of the cellular protein Dicer. We demonstrate that let-7 miRNAs inhibit the reactivation of latent EBV, providing an explanation for our previous observation that EBNA1 promotes latency. In addition, since decreased levels of Dicer have been associated with metastatic potential, EBNA1 may increase metastases by downregulating Dicer. PMID:25031339

A Grammar-based Approach for Modeling User Interactions and Generating Suggestions During the Data Exploration Process.

PubMed

Dabek, Filip; Caban, Jesus J

2017-01-01

Despite the recent popularity of visual analytics focusing on big data, little is known about how to support users that use visualization techniques to explore multi-dimensional datasets and accomplish specific tasks. Our lack of models that can assist end-users during the data exploration process has made it challenging to learn from the user's interactive and analytical process. The ability to model how a user interacts with a specific visualization technique and what difficulties they face are paramount in supporting individuals with discovering new patterns within their complex datasets. This paper introduces the notion of visualization systems understanding and modeling user interactions with the intent of guiding a user through a task thereby enhancing visual data exploration. The challenges faced and the necessary future steps to take are discussed; and to provide a working example, a grammar-based model is presented that can learn from user interactions, determine the common patterns among a number of subjects using a K-Reversible algorithm, build a set of rules, and apply those rules in the form of suggestions to new users with the goal of guiding them along their visual analytic process. A formal evaluation study with 300 subjects was performed showing that our grammar-based model is effective at capturing the interactive process followed by users and that further research in this area has the potential to positively impact how users interact with a visualization system.

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

PubMed Central

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

2014-01-01

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. PMID:25327364

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

PubMed

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.

GrouseFlocks: steerable exploration of graph hierarchy space.

PubMed

Archambault, Daniel; Munzner, Tamara; Auber, David

2008-01-01

Several previous systems allow users to interactively explore a large input graph through cuts of a superimposed hierarchy. This hierarchy is often created using clustering algorithms or topological features present in the graph. However, many graphs have domain-specific attributes associated with the nodes and edges, which could be used to create many possible hierarchies providing unique views of the input graph. GrouseFlocks is a system for the exploration of this graph hierarchy space. By allowing users to see several different possible hierarchies on the same graph, the system helps users investigate graph hierarchy space instead of a single fixed hierarchy. GrouseFlocks provides a simple set of operations so that users can create and modify their graph hierarchies based on selections. These selections can be made manually or based on patterns in the attribute data provided with the graph. It provides feedback to the user within seconds, allowing interactive exploration of this space.

Three visualization approaches for communicating and exploring PIT tag data

USGS Publications Warehouse

Letcher, Benjamin; Walker, Jeffrey D.; O'Donnell, Matthew; Whiteley, Andrew R.; Nislow, Keith; Coombs, Jason

2018-01-01

As the number, size and complexity of ecological datasets has increased, narrative and interactive raw data visualizations have emerged as important tools for exploring and understanding these large datasets. As a demonstration, we developed three visualizations to communicate and explore passive integrated transponder tag data from two long-term field studies. We created three independent visualizations for the same dataset, allowing separate entry points for users with different goals and experience levels. The first visualization uses a narrative approach to introduce users to the study. The second visualization provides interactive cross-filters that allow users to explore multi-variate relationships in the dataset. The last visualization allows users to visualize the movement histories of individual fish within the stream network. This suite of visualization tools allows a progressive discovery of more detailed information and should make the data accessible to users with a wide variety of backgrounds and interests.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-21

... the Nation's museum, library, and information services. The policy research, analysis, and data..., 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...

Beta Androstenediol Mitigates the Damage of 1 GeV/n Fe Ion Particle Radiation to the Hematopoietic System

PubMed Central

Beckman, Mathew; Contaifer, Daniel; Tamariz, Francisco; Gibb, David; Thompson, Laura; Guida, Peter

2011-01-01

Abstract Space exploration is associated with exposure to 1–3 Gy solar particle radiation and galactic cosmic radiation that could increase cancer rates. Effective nontoxic countermeasures to high linear energy transfer (LET) radiation exposure are highly desirable but currently not available. The aim was to determine whether a single subcutaneous injection of androstenediol (Δ5 androsten-3β, 17β-diol [AED]) could mitigate and restore the mouse hematopoetic system from the radiation-mediated injury of 3 Gy whole-body high LET 56Fe26+ exposure. The findings show that postradiation AED treatment has an overall positive and significant beneficial effect to restore the levels of hematopoeitic elements (p<0.001). Androstenediol treatment significantly increased monocyte levels at days 4, 7, and 14 and, similarly, increased red blood cell, hemoglobin, and platelet counts. Flow cytometry analysis 14 days after radiation and AED treatment demonstrated an increase (p<0.05) in bone marrow cells counts. Ex vivo osteoclastogenesis studies show that AED treatment is necessary and advantageous for the development and restoration of osteoclastogenesis after radiation exposure. These findings clearly show that androstenediol functions as a countermeasure to remedy hematopoeitic injury mediated by high LET iron ion radiation. Presently, no other agent has been shown to have such properties. PMID:21790310

Web 2.0, Library 2.0, and Librarian 2.0:Preparing for the 2.0 World

NASA Astrophysics Data System (ADS)

Abram, S.

2007-10-01

There is a global conversation going on right now about the next generation of the web. It's happening under the name of Web 2.0. It's the McLuhanesque hot web where true human interaction takes precedence over merely `cool' information delivery and e-mail. It's about putting information into the real context of our users' lives, research, work and play. Concurrently, a group of information professionals are having a conversation about the vision for what Library 2.0 will look like in this Web 2.0 ecosystem. Some are even going so far as to talk about Web 3.0! Web 2.0 is coming fast and it's BIG! What are the skills and competencies that Librarian 2.0 will need? Come and hear an overview of Web 2.0 and a draft vision for Library 2.0 and an opinion about what adaptations we'll need to make to thrive in this future scenario. Let's talk about the Librarian 2.0 in our users' future!

Normal families and value distribution in connection with composite functions

NASA Astrophysics Data System (ADS)

Clifford, E. F.

2005-12-01

We prove a value distribution result which has several interesting corollaries. Let , let and let f be a transcendental entire function with order less than 1/2. Then for every nonconstant entire function g, we have that (f[circle, open]g)(k)-[alpha] has infinitely many zeros. This result also holds when k=1, for every transcendental entire function g. We also prove the following result for normal families. Let , let f be a transcendental entire function with [rho](f)<1/k, and let a0,...,ak-1,a be analytic functions in a domain [Omega]. Then the family of analytic functions g such that in [Omega], is a normal family.

Flexible processing and the design of grammar.

PubMed

Sag, Ivan A; Wasow, Thomas

2015-02-01

We explore the consequences of letting the incremental and integrative nature of language processing inform the design of competence grammar. What emerges is a view of grammar as a system of local monotonic constraints that provide a direct characterization of the signs (the form-meaning correspondences) of a given language. This "sign-based" conception of grammar has provided precise solutions to the key problems long thought to motivate movement-based analyses, has supported three decades of computational research developing large-scale grammar implementations, and is now beginning to play a role in computational psycholinguistics research that explores the use of underspecification in the incremental computation of partial meanings.

NASA Lunar and Planetary Mapping and Modeling

NASA Astrophysics Data System (ADS)

Day, B. H.; Law, E.

2016-12-01

NASA's Lunar and Planetary Mapping and Modeling Portals provide web-based suites of interactive visualization and analysis tools to enable mission planners, planetary scientists, students, and the general public to access mapped lunar data products from past and current missions for the Moon, Mars, and Vesta. New portals for additional planetary bodies are being planned. This presentation will recap significant enhancements to these toolsets during the past year and look forward to the results of the exciting work currently being undertaken. Additional data products and tools continue to be added to the Lunar Mapping and Modeling Portal (LMMP). These include both generalized products as well as polar data products specifically targeting potential sites for the Resource Prospector mission. Current development work on LMMP also includes facilitating mission planning and data management for lunar CubeSat missions, and working with the NASA Astromaterials Acquisition and Curation Office's Lunar Apollo Sample database in order to help better visualize the geographic contexts from which samples were retrieved. A new user interface provides, among other improvements, significantly enhanced 3D visualizations and navigation. Mars Trek, the project's Mars portal, has now been assigned by NASA's Planetary Science Division to support site selection and analysis for the Mars 2020 Rover mission as well as for the Mars Human Landing Exploration Zone Sites. This effort is concentrating on enhancing Mars Trek with data products and analysis tools specifically requested by the proposing teams for the various sites. Also being given very high priority by NASA Headquarters is Mars Trek's use as a means to directly involve the public in these upcoming missions, letting them explore the areas the agency is focusing upon, understand what makes these sites so fascinating, follow the selection process, and get caught up in the excitement of exploring Mars. The portals also serve as outstanding resources for education and outreach. As such, they have been designated by NASA's Science Mission Directorate as key supporting infrastructure for the new education programs selected through the division's recent CAN.

Identifying the values and preferences of prosthetic users: a case study series using the repertory grid technique.

PubMed

Schaffalitzky, Elisabeth; NiMhurchadha, Sinead; Gallagher, Pamela; Hofkamp, Susan; MacLachlan, Malcolm; Wegener, Stephen T

2009-06-01

The matching of prosthetic devices to the needs of the individual is a challenge for providers and patients. The aims of this study are to explore the values and preferences that prosthetic users have of their prosthetic devices; to investigate users' perceptions of alternative prosthetic options and to demonstrate a novel method for exploring the values and preferences of prosthetic users. This study describes four case studies of upper limb and lower limb high tech and conventional prosthetic users. Participants were interviewed using the repertory grid technique (RGT), a qualitative technique to explore individual values and preferences regarding specific choices and events. The participants generated distinctive patterns of personal constructs and ratings regarding prosthetic use and different prosthetic options available. The RGT produced a unique profile of preferences regarding prosthetic technologies for each participant. User choice is an important factor when matching prosthetic technology to the user. The consumer's values regarding different prosthetic options are likely to be a critical factor in prosthetic acceptance and ultimate quality of life. The RGT offers a structured method of exploring these attitudes and values without imposing researcher or practitioner bias and identifies personalized dimensions for providers and users to evaluate the individuals' preferences in prosthetic technology.

Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells

PubMed Central

Wells, Alexandria C; Daniels, Keith A; Angelou, Constance C; Fagerberg, Eric; Burnside, Amy S; Markstein, Michele; Alfandari, Dominique; Welsh, Raymond M; Pobezinskaya, Elena L; Pobezinsky, Leonid A

2017-01-01

The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naive phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor-mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc and Eomesodermin. Ultimately, we have identified a novel let-7-mediated mechanism, which acts as a molecular brake controlling the magnitude of CD8 T cell responses. DOI: http://dx.doi.org/10.7554/eLife.26398.001 PMID:28737488

CellShape: A user-friendly image analysis tool for quantitative visualization of bacterial cell factories inside.

PubMed

Goñi-Moreno, Ángel; Kim, Juhyun; de Lorenzo, Víctor

2017-02-01

Visualization of the intracellular constituents of individual bacteria while performing as live biocatalysts is in principle doable through more or less sophisticated fluorescence microscopy. Unfortunately, rigorous quantitation of the wealth of data embodied in the resulting images requires bioinformatic tools that are not widely extended within the community-let alone that they are often subject to licensing that impedes software reuse. In this context we have developed CellShape, a user-friendly platform for image analysis with subpixel precision and double-threshold segmentation system for quantification of fluorescent signals stemming from single-cells. CellShape is entirely coded in Python, a free, open-source programming language with widespread community support. For a developer, CellShape enhances extensibility (ease of software improvements) by acting as an interface to access and use existing Python modules; for an end-user, CellShape presents standalone executable files ready to open without installation. We have adopted this platform to analyse with an unprecedented detail the tridimensional distribution of the constituents of the gene expression flow (DNA, RNA polymerase, mRNA and ribosomal proteins) in individual cells of the industrial platform strain Pseudomonas putida KT2440. While the CellShape first release version (v0.8) is readily operational, users and/or developers are enabled to expand the platform further. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

76 FR 71080 - Notice of Proposed Information Collection Requests: Let's Move Museums, Let's Move Gardens

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-16

..., library, and information services. The policy research, analysis, and data collection is used to: Identify... Requests: Let's Move Museums, Let's Move Gardens AGENCY: Institute of Museum and Library Services, National.... SUMMARY: The Institute of Museum and Library Services (IMLS), as part of its continuing effort to reduce...

Hormonal activation of let-7-C microRNAs via EcR is required for adult Drosophila melanogaster morphology and function

PubMed Central

Chawla, Geetanjali; Sokol, Nicholas S.

2012-01-01

Steroid hormones and their nuclear receptors drive developmental transitions in diverse organisms, including mammals. In this study, we show that the Drosophila steroid hormone 20-hydroxyecdysone (20E) and its nuclear receptor directly activate transcription of the evolutionarily conserved let-7-complex (let-7-C) locus, which encodes the co-transcribed microRNAs miR-100, let-7 and miR-125. These small RNAs post-transcriptionally regulate the expression of target genes, and are required for the remodeling of the Drosophila neuromusculature during the larval-to-adult transition. Deletion of three 20E responsive elements located in the let-7-C locus results in reduced levels of let-7-C microRNAs, leading to neuromuscular and behavioral defects in adults. Given the evolutionary conservation of let-7-C microRNA sequences and temporal expression profiles, these findings indicate that steroid hormone-coupled control of let-7-C microRNAs is part of an ancestral pathway controlling the transition from larval-to-reproductive animal forms. PMID:22510985

Let-7 Sensitizes KRAS Mutant Tumor Cells to Chemotherapy

PubMed Central

Dai, Xin; Jiang, Ying; Tan, Chalet

2015-01-01

KRAS is the most commonly mutated oncogene in human cancers and is associated with poor prognosis and drug resistance. Let-7 is a family of tumor suppressor microRNAs that are frequently suppressed in solid tumors, where KRAS mutations are highly prevalent. In this study, we investigated the potential use of let-7 as a chemosensitizer. We found that let-7b repletion selectively sensitized KRAS mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine. Transfection of let-7b mimic downregulated the expression of mutant but not wild-type KRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished MEK/ERK and PI3K/AKT signaling concurrently, triggered the onset of apoptosis, and reverted the epithelial-mesenchymal transition in KRAS mutant tumor cells. In addition, let-7b repletion downregulated the expression of β-tubulin III and ribonucleotide reductase subunit M2, two proteins known to mediate tumor resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new class of chemosensitizer for the treatment of KRAS mutant tumors. PMID:25946136

Hsa-Let-7g miRNA Targets Caspase-3 and Inhibits the Apoptosis Induced by ox-LDL in Endothelial Cells

PubMed Central

Zhang, Yefei; Chen, Naiyun; Zhang, Jihao; Tong, Yaling

2013-01-01

It has been well confirmed ox-LDL plays key roles in the development of atherosclerosis via binding to LOX-1 and inducing apoptosis in vascular endothelial cells. Recent studies have shown ox-LDL can suppress microRNA has-let-7g, which in turn inhibits the ox-LDL induced apoptosis. However, details need to be uncovered. To determine the anti-atherosclerosis effect of microRNA has-let-7g, and to evaluate the possibility of CASP3 as an anti-atherosclerotic drug target by has-let-7g, the present study determined the role of hsa-let-7g miRNA in ox-LDL induced apoptosis in the vascular endothelial cells. We found that miRNA has-let-7g was suppressed during the ox-LDL-induced apoptosis in EAhy926 endothelial cells. In addition, overexpression of has-let-7g negatively regulated apoptosis in the endothelial cells by targeting caspase-3 expression. Therefore, miRNA let-7g may play important role in endothelial apoptosis and atherosclerosis. PMID:24252910

Let7a involves in neural stem cell differentiation relating with TLX level

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

Song, Juhyun; Cho, Kyoung Joo; Oh, Yumi

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 ofmore » 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.« less

The 14-3-3 Protein PAR-5 Regulates the Asymmetric localization of the LET-99 Spindle Positioning Protein

PubMed Central

Rose, Lesilee S.

2016-01-01

PAR proteins play important roles in establishing cytoplasmic polarity as well as regulating spindle positioning during asymmetric division. However, the molecular mechanisms by which the PAR proteins generate asymmetry in different cell types are still being elucidated. Previous studies in C. elegans revealed that PAR-3 and PAR-1 regulate the asymmetric localization of LET-99, which in turn controls spindle positioning by affecting the distribution of the conserved force generating complex. In wild-type embryos, LET-99 is localized in a lateral cortical band pattern, via inhibition at the anterior by PAR-3 and at the posterior by PAR-1. In this report, we show that the 14-3-3 protein PAR-5 is also required for cortical LET-99 asymmetry. PAR-5 associated with LET-99 in pull-down assays, and two PAR-5 binding sites were identified in LET-99 using the yeast two-hybrid assay. Mutation of these sites abolished binding in yeast and altered LET-99 localization in vivo: LET-99 was present at the highest levels at the posterior pole of the embryo instead of a band in par-5 embryos. Together the results indicate that PAR-5 acts in a mechanism with PAR-1 to regulate LET-99 cortical localization. PMID:26921457

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

PubMed

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.

Analytical calculation of proton linear energy transfer in voxelized geometries including secondary protons

NASA Astrophysics Data System (ADS)

Sanchez-Parcerisa, D.; Cortés-Giraldo, M. A.; Dolney, D.; Kondrla, M.; Fager, M.; Carabe, A.

2016-02-01

In order to integrate radiobiological modelling with clinical treatment planning for proton radiotherapy, we extended our in-house treatment planning system FoCa with a 3D analytical algorithm to calculate linear energy transfer (LET) in voxelized patient geometries. Both active scanning and passive scattering delivery modalities are supported. The analytical calculation is much faster than the Monte-Carlo (MC) method and it can be implemented in the inverse treatment planning optimization suite, allowing us to create LET-based objectives in inverse planning. The LET was calculated by combining a 1D analytical approach including a novel correction for secondary protons with pencil-beam type LET-kernels. Then, these LET kernels were inserted into the proton-convolution-superposition algorithm in FoCa. The analytical LET distributions were benchmarked against MC simulations carried out in Geant4. A cohort of simple phantom and patient plans representing a wide variety of sites (prostate, lung, brain, head and neck) was selected. The calculation algorithm was able to reproduce the MC LET to within 6% (1 standard deviation) for low-LET areas (under 1.7 keV μm-1) and within 22% for the high-LET areas above that threshold. The dose and LET distributions can be further extended, using radiobiological models, to include radiobiological effectiveness (RBE) calculations in the treatment planning system. This implementation also allows for radiobiological optimization of treatments by including RBE-weighted dose constraints in the inverse treatment planning process.

Analytical calculation of proton linear energy transfer in voxelized geometries including secondary protons.

PubMed

Sanchez-Parcerisa, D; Cortés-Giraldo, M A; Dolney, D; Kondrla, M; Fager, M; Carabe, A

2016-02-21

In order to integrate radiobiological modelling with clinical treatment planning for proton radiotherapy, we extended our in-house treatment planning system FoCa with a 3D analytical algorithm to calculate linear energy transfer (LET) in voxelized patient geometries. Both active scanning and passive scattering delivery modalities are supported. The analytical calculation is much faster than the Monte-Carlo (MC) method and it can be implemented in the inverse treatment planning optimization suite, allowing us to create LET-based objectives in inverse planning. The LET was calculated by combining a 1D analytical approach including a novel correction for secondary protons with pencil-beam type LET-kernels. Then, these LET kernels were inserted into the proton-convolution-superposition algorithm in FoCa. The analytical LET distributions were benchmarked against MC simulations carried out in Geant4. A cohort of simple phantom and patient plans representing a wide variety of sites (prostate, lung, brain, head and neck) was selected. The calculation algorithm was able to reproduce the MC LET to within 6% (1 standard deviation) for low-LET areas (under 1.7 keV μm(-1)) and within 22% for the high-LET areas above that threshold. The dose and LET distributions can be further extended, using radiobiological models, to include radiobiological effectiveness (RBE) calculations in the treatment planning system. This implementation also allows for radiobiological optimization of treatments by including RBE-weighted dose constraints in the inverse treatment planning process.

Taking Charge and Letting Go: Exploring the Ways a Transition to Adulthood Project for Teenagers with Duchenne Muscular Dystrophy Has Supported Parents to Prepare for the Future

ERIC Educational Resources Information Center

Hoskin, Janet

2017-01-01

The new Special Educational Needs and Disability legislation in the Children and Families Act 2014 intends to raise the aspirations of young people with special educational needs and their families, and improve their life outcomes. But what do raised aspirations and better outcomes look like for young people who have a life-limiting impairment?…

The oncogenic triangle of HMGA2, LIN28B and IGF2BP1 antagonizes tumor-suppressive actions of the let-7 family.

PubMed

Busch, Bianca; Bley, Nadine; Müller, Simon; Glaß, Markus; Misiak, Danny; Lederer, Marcell; Vetter, Martina; Strauß, Hans-Georg; Thomssen, Christoph; Hüttelmaier, Stefan

2016-05-05

The tumor-suppressive let-7 microRNA family targets various oncogene-encoding mRNAs. We identify the let-7 targets HMGA2, LIN28B and IGF2BP1 to form a let-7 antagonizing self-promoting oncogenic triangle. Surprisingly, 3'-end processing of IGF2BP1 mRNAs is unaltered in aggressive cancers and tumor-derived cells although IGF2BP1 synthesis was proposed to escape let-7 attack by APA-dependent (alternative polyadenylation) 3' UTR shortening. However, the expression of the triangle factors is inversely correlated with let-7 levels and promoted by LIN28B impairing let-7 biogenesis. Moreover, IGF2BP1 enhances the expression of all triangle factors by recruiting the respective mRNAs in mRNPs lacking AGO proteins and let-7 miRNAs. This indicates that the downregulation of let-7, largely facilitated by LIN28B upregulation, and the protection of let-7 target mRNAs by IGF2BP1-directed shielding in mRNPs synergize in enhancing the expression of triangle factors. The oncogenic potential of this triangle was confirmed in ovarian cancer (OC)-derived ES-2 cells transduced with let-7 targeting decoys. In these, the depletion of HMGA2 only diminishes tumor cell growth under permissive conditions. The depletion of LIN28B and more prominently IGF2BP1 severely impairs tumor cell viability, self-renewal and 2D as well as 3D migration. In conclusion, this suggests the targeting of the HMGA2-LIN28B-IGF2BP1 triangle as a promising strategy in cancer treatment. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

The oncogenic triangle of HMGA2, LIN28B and IGF2BP1 antagonizes tumor-suppressive actions of the let-7 family

PubMed Central

Busch, Bianca; Bley, Nadine; Müller, Simon; Glaß, Markus; Misiak, Danny; Lederer, Marcell; Vetter, Martina; Strauß, Hans-Georg; Thomssen, Christoph; Hüttelmaier, Stefan

2016-01-01

The tumor-suppressive let-7 microRNA family targets various oncogene-encoding mRNAs. We identify the let-7 targets HMGA2, LIN28B and IGF2BP1 to form a let-7 antagonizing self-promoting oncogenic triangle. Surprisingly, 3′-end processing of IGF2BP1 mRNAs is unaltered in aggressive cancers and tumor-derived cells although IGF2BP1 synthesis was proposed to escape let-7 attack by APA-dependent (alternative polyadenylation) 3′ UTR shortening. However, the expression of the triangle factors is inversely correlated with let-7 levels and promoted by LIN28B impairing let-7 biogenesis. Moreover, IGF2BP1 enhances the expression of all triangle factors by recruiting the respective mRNAs in mRNPs lacking AGO proteins and let-7 miRNAs. This indicates that the downregulation of let-7, largely facilitated by LIN28B upregulation, and the protection of let-7 target mRNAs by IGF2BP1-directed shielding in mRNPs synergize in enhancing the expression of triangle factors. The oncogenic potential of this triangle was confirmed in ovarian cancer (OC)-derived ES-2 cells transduced with let-7 targeting decoys. In these, the depletion of HMGA2 only diminishes tumor cell growth under permissive conditions. The depletion of LIN28B and more prominently IGF2BP1 severely impairs tumor cell viability, self-renewal and 2D as well as 3D migration. In conclusion, this suggests the targeting of the HMGA2-LIN28B-IGF2BP1 triangle as a promising strategy in cancer treatment. PMID:26917013

A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic Phenotypes of Polycystic Ovary Syndrome in Female Mice1

PubMed Central

Kauffman, Alexander S.; Thackray, Varykina G.; Ryan, Genevieve E.; Tolson, Kristen P.; Glidewell-Kenney, Christine A.; Semaan, Sheila J.; Poling, Matthew C.; Iwata, Nahoko; Breen, Kellie M.; Duleba, Antoni J.; Stener-Victorin, Elisabet; Shimasaki, Shunichi; Webster, Nicholas J.; Mellon, Pamela L.

2015-01-01

Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent in other models. Given the advantages of using genetic and transgenic mouse models, we investigated whether LET produces a similar PCOS phenotype in mice. Pubertal female C57BL/6N mice were treated for 5 wk with LET, which resulted in increased serum testosterone and normal diestrus levels of estradiol, similar to the hyperandrogenemia and follicular phase estrogen levels of PCOS women. As in PCOS, ovaries from LET mice were larger, polycystic, and lacked corpora lutea versus controls. Most LET females were acyclic, and all were infertile. LET females displayed elevated serum LH levels and higher Lhb mRNA in the pituitary. In contrast, serum FSH and Fshb were significantly reduced in LET females, demonstrating differential effects on gonadotropins, as in PCOS. Within the ovary, LET females had higher Cyp17, Cyp19, and Fsh receptor mRNA expression. In the hypothalamus, LET females had higher kisspeptin receptor mRNA expression but lower progesterone receptor mRNA levels. LET females also gained more weight than controls, had increased abdominal adiposity and adipocyte size, elevated adipose inflammatory mRNA levels, and impaired glucose tolerance, mirroring the metabolic phenotype in PCOS women. This is the first report of a LET paradigm in mice that recapitulates both reproductive and metabolic PCOS phenotypes and will be useful to genetically probe the PCOS condition. PMID:26203175

Utility of esophageal temperature monitoring during pulmonary vein isolation for atrial fibrillation using duty-cycled phased radiofrequency ablation.

PubMed

Deneke, Thomas; Bünz, Kathrin; Bastian, Annely; Päsler, Marcus; Anders, Helge; Lehmann, Rainer; Meuser, Wolfgang; de Groot, Joris R; Horlitz, Marc; Haberkorn, Ron; Mügge, Andreas; Shin, Dong-In

2011-03-01

A novel ablation system has been introduced for rapid treatment of atrial fibrillation (AF). This system delivers duty-cycled phased radiofrequency (RF) energy via an over-the-wire catheter (PVAC® , Medtronic) to achieve pulmonary vein (PV) isolation. Lower power and depth control suggests that collateral damage might be minimized. However, no studies have investigated the potential for thermal effect and damage to the esophagus. Ninety consecutive patients undergoing PV-isolation were evaluated. Group A (48 patients) had continuous luminal esophageal temperature (LET) monitoring using a temperature probe with 3 metal electrodes located in the vicinity of the targeted PV ostia. Ablation ceased when LET exceeded 40 °C. Only patients with LET ≥ 39 °C underwent endoscopic evaluation to assess esophageal damage. Group B (42 patients) excluded LET monitoring but all patients underwent endoscopy. In Group A, 27 (56%) patients showed LET ≥ 39 °C (mean LET 40.5 °C). Endoscopy revealed esophageal alterations in 5 (8%) (3 erythema and 2 intramural bleeding). One hundred eighty-nine out of 190 (99.5%) targeted PVs were successfully isolated, with 1 PV unsuccessful due to high LET. In Group B all 165 targeted PVs (100%) were successfully isolated. Endoscopy in Group 2 revealed no esophageal alterations. Using a duty-cycled, phased RF ablation system is safe and effective to isolate PVs. No Eso alteration was documented after ablation when LET was not monitored. This suggests that the LET probe may contribute to the thermal effect. Whether the documented increments in LET are due to direct tissue heating or possible interaction between the LET probe requires further investigation. © 2010 Wiley Periodicals, Inc.

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

PubMed Central

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

Leukaemia mortality and low-dose ionising radiation in the WISMUT uranium miner cohort (1946-2013).

PubMed

Kreuzer, Michaela; Sobotzki, Christina; Fenske, Nora; Marsh, James W; Schnelzer, Maria

2017-03-01

To examine the risk of death from leukaemia in relation to occupational chronic low-level external and internal radiation exposure in a cohort of 58 972 former German uranium miners with mortality follow-up from 1946 to 2013. The red bone marrow (RBM) dose from low-linear energy transfer (LET) (mainly external γ-radiation) and high-LET (mainly radon gas) radiation was estimated based on a job-exposure matrix and biokinetic/dosimetric models. Linear excess relative risks (ERR) and 95% CIs were estimated via Poisson regression for chronic lymphatic leukaemia (CLL) and non-CLL. The mean cumulative low-LET and high-LET RBM doses among the 86% radiation-exposed workers were 48 and 9 mGy, respectively. There was a positive non-significant dose-response for mortality from non-CLL (n=120) in relation to low-LET (ERR/Gy=2.18; 95% CI -0.41 to 6.37) and high-LET radiation (ERR/Gy=16.65; 95% -1.13 to 46.75). A statistically significant excess was found for the subgroup chronic myeloid leukaemia (n=31) in relation to low-LET radiation (ERR/Gy=7.20; 95% CI 0.48 to 24.54) and the subgroup myeloid leukaemia (n=99) (ERR/Gy=26.02; 95% CI 2.55 to 68.99) for high-LET radiation. The ERR/Gy tended to be about five to ten times higher for high-LET versus low-LET radiation; however, the CIs largely overlapped. Results indicate no association of death from CLL (n=70) with either type of radiation. Our findings indicate an increased risk of death for specific subtypes from non-CLL in relation to chronic low-LET and high-LET radiation, but no such relation for CLL. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Let-7b Inhibits Human Cancer Phenotype by Targeting Cytochrome P450 Epoxygenase 2J2

PubMed Central

Yang, Shenglan; Gong, Wei; Wang, Yan; Cianflone, Katherine; Tang, Jiarong; Wang, Dao Wen

2012-01-01

Background MicroRNAs (miRNAs) are small, noncoding RNA molecules of 20 to 22 nucleotides that regulate gene expression by binding to their 3′ untranslated region (3′UTR). Increasing data implicate altered miRNA participation in the progress of cancer. We previously reported that CYP2J2 epoxygenase promotes human cancer phenotypes. But whether and how CYP2J2 is regulated by miRNA is not understood. Methods and Results Using bioinformatics analysis, we found potential target sites for miRNA let-7b in 3′UTR of human CYP2J2. Luciferase and western blot assays revealed that CYP2J2 was regulated by let-7b. In addition, let-7b decreased the enzymatic activity of endogenous CYP2J2. Furthermore, let-7b may diminish cell proliferation and promote cell apoptosis of tumor cells via posttranscriptional repression of CYP2J2. Tumor xenografts were induced in nude mice by subcutaneous injection of MDA-MB-435 cells. The let-7b expression vector, pSilencer-let-7b, was injected through tail vein every 3 weeks. Let-7b significantly inhibited the tumor phenotype by targeting CYP2J2. Moreover, quantitative real-time polymerase chain reaction and western blotting were used to determine the expression levels of let-7b and CYP2J2 protein from 18 matched lung squamous cell cancer and adjacent normal lung tissues; the expression level of CYP2J2 was inversely proportional to that of let-7b. Conclusions Our results demonstrated that the decreased expression of let-7b could lead to the high expression of CYP2J2 protein in cancerous tissues. These findings suggest that miRNA let-7b reduces CYP2J2 expression, which may contribute to inhibiting tumor phenotypes. PMID:22761738

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

PubMed Central

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

MicroRNA Let-7f Inhibits Tumor Invasion and Metastasis by Targeting MYH9 in Human Gastric Cancer

PubMed Central

Miao, Yu; Gu, Yong; Guo, Changcun; Xue, Zengfu; Dou, Weijia; Hu, Fengrong; Wu, Kaichun; Nie, Yongzhan; Fan, Daiming

2011-01-01

Background MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. A previous report has shown that let-7 family members can act as tumor suppressors in many cancers. Through miRNA array, we found that let-7f was downregulated in the highly metastatic potential gastric cancer cell lines GC9811-P and SGC7901-M, when compared with their parental cell lines, GC9811 and SGC7901-NM; however, the mechanism was not clear. In this study, we investigate whether let-7f acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers. Methodology/Principal Real-time PCR showed decreased levels of let-7f expression in metastatic gastric cancer tissues and cell lines that are potentially highly metastatic. Cell invasion and migration were significantly impaired in GC9811-P and SGC7901-M cell lines after transfection with let-7f-mimics. Nude mice with xenograft models of gastric cancer confirmed that let-7f could inhibit gastric cancer metastasis in vivo after transfection by the lentivirus pGCsil-GFP- let-7f. Luciferase reporter assays demonstrated that let-7f directly binds to the 3′UTR of MYH9, which codes for myosin IIA, and real-time PCR and Western blotting further indicated that let-7f downregulated the expression of myosin IIA at the mRNA and protein levels. Conclusions/Significance Our study demonstrated that overexpression of let-7f in gastric cancer could inhibit invasion and migration of gastric cancer cells through directly targeting the tumor metastasis-associated gene MYH9. These data suggest that let-7f may be a novel therapeutic candidate for gastric cancer, given its ability to reduce cell invasion and metastasis. PMID:21533124

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

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

Nakagawa, Yosuke; Takahashi, Akihisa; Kajihara, Atsuhisa

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 suggestedmore » 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 mp53 bearing cancer cells.« less

SU-D-304-06: Measurement of LET in Patient-Specific Proton Therapy Treatment Fields Using Optically Stimulated Luminescence Detectors

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

Granville, DA; Sahoo, N; Sawakuchi, GO

Purpose: To investigate the use of optically stimulated luminescence (OSL) detectors (OSLDs) for measurements of dose-averaged linear energy transfer (LET) in patient-specific proton therapy treatment fields. Methods: We used Al{sub 2}O{sub 3}:C OSLDs made from the same material as commercially available nanoDot OSLDs from Landauer, Inc. We calibrated two parameters of the OSL signal as functions of LET in therapeutic proton beams: the ratio of the ultraviolet and blue emission intensities (UV/blue ratio) and the OSL curve shape. These calibration curves were created by irradiating OSLDs in passively scattered beams of known LET (0.96 to 3.91 keV/µm). The LET valuesmore » were determined using a validated Monte Carlo model of the beamline. We then irradiated new OSLDs with the prescription dose (16 to 74 cGy absorbed dose to water) at the center of the spread-out Bragg peak (SOBP) of four patient-specific treatment fields. From readouts of these OSLDs, we determined both the UV/blue ratio and OSL curve shape parameters. Combining these parameters with the calibration curves, we were able to measure LET using the OSLDs. The measurements were compared to the theoretical LET values obtained from Monte Carlo simulations of the patient-specific treatments fields. Results: Using the UV/blue ratio parameter, we were able to measure LET within 3.8%, 6.2%, 5.6% and 8.6% of the Monte Carlo value for each of the patient fields. Similarly, using the OSL curve shape parameter, LET measurements agreed within 0.5%, 11.0%, 2.5% and 7.6% for each of the four fields. Conclusion: We have demonstrated a method to verify LET in patient-specific proton therapy treatment fields using OSLDs. The possibility of enhancing biological effectiveness of proton therapy treatment plans by including LET in the optimization has been previously shown. The LET verification method we have demonstrated will be useful in the quality assurance of such LET optimized treatment plans. DA Granville received financial support from the Natural Sciences and Engineering Research Council of Canada.« less

Exploration of Web Users' Search Interests through Automatic Subject Categorization of Query Terms.

ERIC Educational Resources Information Center

Pu, Hsiao-tieh; Yang, Chyan; Chuang, Shui-Lung

2001-01-01

Proposes a mechanism that carefully integrates human and machine efforts to explore Web users' search interests. The approach consists of a four-step process: extraction of core terms; construction of subject taxonomy; automatic subject categorization of query terms; and observation of users' search interests. Research findings are proved valuable…

"Pretty Rad": Explorations in User Satisfaction with a Discovery Layer at Ryerson University

ERIC Educational Resources Information Center

Lundrigan, Courtney; Manuel, Kevin; Yan, May

2015-01-01

Web-scale discovery systems are becoming prevalent in research libraries. Although a number of studies have explored various impacts of discovery systems, few studies exist on user satisfaction. The investigators of this study evaluated user satisfaction with the discovery service Summon at Ryerson University, using online questionnaires and…

Seed: a user-friendly tool for exploring and visualizing microbial community data.

PubMed

Beck, Daniel; Dennis, Christopher; Foster, James A

2015-02-15

In this article we present Simple Exploration of Ecological Data (Seed), a data exploration tool for microbial communities. Seed is written in R using the Shiny library. This provides access to powerful R-based functions and libraries through a simple user interface. Seed allows users to explore ecological datasets using principal coordinate analyses, scatter plots, bar plots, hierarchal clustering and heatmaps. Seed is open source and available at https://github.com/danlbek/Seed. danlbek@gmail.com Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

Continuum-wise expansiveness for generic diffeomorphisms

NASA Astrophysics Data System (ADS)

Lee, Manseob

2018-06-01

Let M be a closed smooth manifold and let be a diffeomorphism. C 1-generically, a continuum-wise expansive satisfies Axiom A without cycles. Let and let . There are a C 1 neighborhood of and a residual set such that for any , g is not continuum-wise expansive, where is the set of all robustly transitive diffeomorphisms on

Letting go of the present: mind-wandering is associated with reduced delay discounting.

PubMed

Smallwood, Jonathan; Ruby, Florence J M; Singer, Tania

2013-03-01

The capacity to self-generate mental content that is unrelated to the current environment is a fundamental characteristic of the mind, and the current experiment explored how this experience is related to the decisions that people make in daily life. We examined how task-unrelated thought (TUT) varies with the length of time participants are willing to wait for an economic reward, as measured using an inter-temporal discounting task. When participants performed a task requiring minimal attention, the greater the amount of time spent engaged in TUT the longer the individual was prepared to wait for an economic reward. These data indicate that self-generated thought engages processes associated with the successful management of long-term goals. Although immersion in the here and now is undeniably advantageous, under appropriate conditions the capacity to let go of the present and consider more pertinent personal goals may have its own rewards. Copyright © 2012 Elsevier Inc. All rights reserved.

A new perspective of carcinogenesis from protracted high-let radiation arises from the two-stage clonal expansion model

NASA Astrophysics Data System (ADS)

Curtis, S. B.; Luebeck, E. G.; Hazelton, W. D.; Moolgavkar, S. H.

When applied to the Colorado Plateau miner population, the two-stage clonal expansion (TSCE) model of radiation carcinogenesis predicts that radiation-induced promotion dominates radiation-induced initiation. Thus, according to the model, at least for alpha-particle radiation from inhaled radon daughters, lung cancer induction over long periods of protracted irradiation appears to be dominated by radiation-induced modification of the proliferation kinetics of already-initiated cells rather than by direct radiation-induced initiation (i.e., mutation) of normal cells. We explore the possible consequences of this result for radiation exposures to space travelers on long missions. Still unknown is the LET dependence of this effect. Speculations of the cause of this phenomenon include the suggestion that modification of cell kinetics is caused by a "bystander" effect, i.e., the traversal of normal cells by alpha particles, followed by the signaling of these cells to nearby initiated cells which then modify their proliferation kinetics.

PlantTribes: a gene and gene family resource for comparative genomics in plants

PubMed Central

Wall, P. Kerr; Leebens-Mack, Jim; Müller, Kai F.; Field, Dawn; Altman, Naomi S.; dePamphilis, Claude W.

2008-01-01

The PlantTribes database (http://fgp.huck.psu.edu/tribe.html) is a plant gene family database based on the inferred proteomes of five sequenced plant species: Arabidopsis thaliana, Carica papaya, Medicago truncatula, Oryza sativa and Populus trichocarpa. We used the graph-based clustering algorithm MCL [Van Dongen (Technical Report INS-R0010 2000) and Enright et al. (Nucleic Acids Res. 2002; 30: 1575–1584)] to classify all of these species’ protein-coding genes into putative gene families, called tribes, using three clustering stringencies (low, medium and high). For all tribes, we have generated protein and DNA alignments and maximum-likelihood phylogenetic trees. A parallel database of microarray experimental results is linked to the genes, which lets researchers identify groups of related genes and their expression patterns. Unified nomenclatures were developed, and tribes can be related to traditional gene families and conserved domain identifiers. SuperTribes, constructed through a second iteration of MCL clustering, connect distant, but potentially related gene clusters. The global classification of nearly 200 000 plant proteins was used as a scaffold for sorting ∼4 million additional cDNA sequences from over 200 plant species. All data and analyses are accessible through a flexible interface allowing users to explore the classification, to place query sequences within the classification, and to download results for further study. PMID:18073194

LocusExplorer: a user-friendly tool for integrated visualization of human genetic association data and biological annotations.

PubMed

Dadaev, Tokhir; Leongamornlert, Daniel A; Saunders, Edward J; Eeles, Rosalind; Kote-Jarai, Zsofia

2016-03-15

: In this article, we present LocusExplorer, a data visualization and exploration tool for genetic association data. LocusExplorer is written in R using the Shiny library, providing access to powerful R-based functions through a simple user interface. LocusExplorer allows users to simultaneously display genetic, statistical and biological data for humans in a single image and allows dynamic zooming and customization of the plot features. Publication quality plots may then be produced in a variety of file formats. LocusExplorer is open source and runs through R and a web browser. It is available at www.oncogenetics.icr.ac.uk/LocusExplorer/ or can be installed locally and the source code accessed from https://github.com/oncogenetics/LocusExplorer tokhir.dadaev@icr.ac.uk. © The Author 2015. Published by Oxford University Press.

Inhibition of Let-7 microRNA attenuates myocardial remodeling and improves cardiac function postinfarction in mice

PubMed Central

Tolonen, Anna-Maria; Magga, Johanna; Szabó, Zoltán; Viitala, Pirkko; Gao, Erhe; Moilanen, Anne-Mari; Ohukainen, Pauli; Vainio, Laura; Koch, Walter J; Kerkelä, Risto; Ruskoaho, Heikki; Serpi, Raisa

2014-01-01

The members of lethal-7 (Let-7) microRNA (miRNA) family are involved in regulation of cell differentiation and reprogramming of somatic cells into induced pluripotent stem cells. However, their function in the heart is not known. In this study, we examined the effect of inhibiting the function of Let-7c miRNA on the progression of postinfarction left ventricular (LV) remodeling in mice. Myocardial infarction was induced with permanent ligation of left anterior descending coronary artery with a 4-week follow-up period. Let-7c miRNA was inhibited with a specific antagomir administered intravenously. The inhibition of Let-7c miRNA downregulated the levels of mature Let-7c miRNA and its other closely related members of Let-7 family in the heart and resulted in increased expression of pluripotency-associated genes Oct4 and Sox2 in cardiac fibroblasts in vitro and in adult mouse heart in vivo. Importantly, Let-7c inhibitor prevented the deterioration of cardiac function postinfarction, as demonstrated by preserved LV ejection fraction and elevated cardiac output. Improvement in cardiac function by Let-7c inhibitor postinfarction was associated with decreased apoptosis, reduced fibrosis, and reduction in the number of discoidin domain receptor 2–positive fibroblasts, while the number of c-kit+ cardiac stem cells and Ki-67+ proliferating cells remained unaltered. In conclusion, inhibition of Let-7 miRNA may be beneficial for the prevention of postinfarction LV remodeling and progression of heart failure. PMID:25505600

Radiobiological description of the LET dependence of the cell survival of oxic and anoxic cells irradiated by carbon ions.

PubMed

Antonovic, L; Brahme, A; Furusawa, Y; Toma-Dasu, I

2013-01-01

Light-ion radiation therapy against hypoxic tumors is highly curative due to reduced dependence on the presence of oxygen in the tumor at elevated linear energy transfer (LET) towards the Bragg peak. Clinical ion beams using spread-out Bragg peak (SOBP) are characterized by a wide spectrum of LET values. Accurate treatment optimization requires a method that can account for influence of the variation in response for a broad range of tumor hypoxia, absorbed doses and LETs. This paper presents a parameterization of the Repairable Conditionally-Repairable (RCR) cell survival model that can describe the survival of oxic and hypoxic cells over a wide range of LET values, and investigates the relationship between hypoxic radiation resistance and LET. The biological response model was tested by fitting cell survival data under oxic and anoxic conditions for V79 cells irradiated with LETs within the range of 30-500 keV/µm. The model provides good agreement with experimental cell survival data for the range of LET investigated, confirming the robustness of the parameterization method. This new version of the RCR model is suitable for describing the biological response of mixed populations of oxic and hypoxic cells and at the same time taking into account the distribution of doses and LETs in the incident beam and its variation with depth in tissue. The model offers a versatile tool for the selection of LET and dose required in the optimization of the therapeutic effect, without severely affecting normal tissue in realistic tumors presenting highly heterogeneous oxic and hypoxic regions.

Identification of the long non‑coding RNA LET as a novel tumor suppressor in gastric cancer.

PubMed

Tian, Jingjing; Hu, Xibao; Gao, Wei; Zhang, Jie; Chen, Ming; Zhang, Xinrong; Ma, Junhong; Yuan, Hongxia

2017-04-01

Long non-coding RNAs (lncRNAs) have emerged recently as important factors in regulating fundamental biological processes. Alterations in the expression and function of lncRNAs have been observed to promote tumor formation, progression and metastasis. Although downregulation of the expression levels of LET lncRNA in several tumors has been reported, its role in gastric cancer remains unknown. The aim of the present study was to investigate the expression and function of LET in gastric cancer development. The expression levels of LET in 37 pairs of gastric cancer and adjacent non‑tumor tissues were detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). In addition, LET expression in gastric cancer cell lines was analyzed by RT‑qPCR assay analysis. Furthermore, the impact of LET on cell proliferation, migration and apoptosis were detected using the cell counting kit‑8, wound scratch and ELISA assays, respectively. The results demonstrated that the expression level of LET was downregulated in gastric cancer tissues and cell lines (SGC‑7901 and MGC‑803) compared with normal tissues and a normal human gastric epithelial cell line (GES‑1). Restoration of LET expression using a synthesized recombinant overexpression vector transfected into SGC‑7901 and MGC‑803 cells, significantly inhibited cell proliferation and migration, and promoted cell apoptosis in vitro. The present study is the first to demonstrate that LET may function as a tumor suppressor in gastric cancer. The results indicate that LET may be a promising biomarker and/or a therapeutic target for gastric cancer.

Repair of DNA double-strand breaks and cell killing by charged particles

NASA Astrophysics Data System (ADS)

Eguchi-Kasai, K.; Murakami, M.; Itsukaichi, H.; Fukutsu, K.; Yatagai, F.; Kanai, T.; Ohara, H.; Sato, K.

It has been suggested that it is not simple double-strand breaks (dsb) but the non-reparable breaks which correlate well with the high biological effectiveness of high LET radiations for cell killing. We have compared the effects of charged particles on cell death in 3 pairs of cell lines which are normal or defective in the repair of DNA dsbs. For the cell lines SL3-147, M10, and SX10 which are deficient in DNA dsb repair, RBE values were close to unity for cell killing induced by charged particles with linear energy transfer (LET) up to 200 keV/mum and were even smaller than unity for the LET region greater than 300 keV/mum. The inactivation cross section (ICS) increased with LET for all 3 pairs. The ICS of dsb repair deficient mutants was always larger than that of their parents for all the LET ranges, but with increasing LET the difference in ICS between the mutant and its parent became smaller. Since a small difference in ICS remained at LET of about 300 keV/mum, dsb repair may still take place at this high LET, even if its role is apparently small. These results suggest that the DNA repair system does not play a major role in protection against the attack of high LET radiations and that a main cause of cell death is non-reparable dsb which are produced at a higher yield compared with low LET radiations. No correlation was observed between DNA content or nuclear area and ICS.

The 14-3-3 protein PAR-5 regulates the asymmetric localization of the LET-99 spindle positioning protein.

PubMed

Wu, Jui-Ching; Espiritu, Eugenel B; Rose, Lesilee S

2016-04-15

PAR proteins play important roles in establishing cytoplasmic polarity as well as regulating spindle positioning during asymmetric division. However, the molecular mechanisms by which the PAR proteins generate asymmetry in different cell types are still being elucidated. Previous studies in Caenorhabditis elegans revealed that PAR-3 and PAR-1 regulate the asymmetric localization of LET-99, which in turn controls spindle positioning by affecting the distribution of the conserved force generating complex. In wild-type embryos, LET-99 is localized in a lateral cortical band pattern, via inhibition at the anterior by PAR-3 and at the posterior by PAR-1. In this report, we show that the 14-3-3 protein PAR-5 is also required for cortical LET-99 asymmetry. PAR-5 associated with LET-99 in pull-down assays, and two PAR-5 binding sites were identified in LET-99 using the yeast two-hybrid assay. Mutation of these sites abolished binding in yeast and altered LET-99 localization in vivo: LET-99 was present at the highest levels at the posterior pole of the embryo instead of a band in par-5 embryos. Together the results indicate that PAR-5 acts in a mechanism with PAR-1 to regulate LET-99 cortical localization. Copyright © 2016 Elsevier Inc. All rights reserved.

Lin28B promotes Müller glial cell de-differentiation and proliferation in the regenerative rat retinas

PubMed Central

Tao, Zui; Zhao, Chen; Jian, Qian; Gillies, Mark; Xu, Haiwei; Yin, Zheng Qin

2016-01-01

Retinal regeneration and repair are severely impeded in higher mammalian animals. Although Müller cells can be activated and show some characteristics of progenitor cells when injured or under pathological conditions, they quickly form gliosis scars. Unfortunately, the basic mechanisms that impede retinal regeneration remain unknown. We studied retinas from Royal College of Surgeon (RCS) rats and found that let-7 family molecules, let-7e and let-7i, were significantly overexpressed in Müller cells of degenerative retinas. It demonstrated that down-regulation of the RNA binding protein Lin28B was one of the key factors leading to the overexpression of let-7e and let-7i. Lin28B ectopic expression in the Müller cells suppressed overexpression of let-7e and let-7i, stimulated and mobilized Müller glia de-differentiation, proliferation, promoted neuronal commitment, and inhibited glial fate acquisition of de-differentiated Müller cells. ERG recordings revealed that the amplitudes of a-wave and b-wave were improved significantly after Lin28B was delivered into the subretinal space of RCS rats. In summary, down-regulation of Lin28B as well as up-regulation of let-7e and let-7i may be the main factors that impede Müller cell de-differentiation and proliferation in the retina of RCS rats. PMID:27384999

Monte Carlo simulation of chemistry following radiolysis with TOPAS-nBio

NASA Astrophysics Data System (ADS)

Ramos-Méndez, J.; Perl, J.; Schuemann, J.; McNamara, A.; Paganetti, H.; Faddegon, B.

2018-05-01

Simulation of water radiolysis and the subsequent chemistry provides important information on the effect of ionizing radiation on biological material. The Geant4 Monte Carlo toolkit has added chemical processes via the Geant4-DNA project. The TOPAS tool simplifies the modeling of complex radiotherapy applications with Geant4 without requiring advanced computational skills, extending the pool of users. Thus, a new extension to TOPAS, TOPAS-nBio, is under development to facilitate the configuration of track-structure simulations as well as water radiolysis simulations with Geant4-DNA for radiobiological studies. In this work, radiolysis simulations were implemented in TOPAS-nBio. Users may now easily add chemical species and their reactions, and set parameters including branching ratios, dissociation schemes, diffusion coefficients, and reaction rates. In addition, parameters for the chemical stage were re-evaluated and updated from those used by default in Geant4-DNA to improve the accuracy of chemical yields. Simulation results of time-dependent and LET-dependent primary yields Gx (chemical species per 100 eV deposited) produced at neutral pH and 25 °C by short track-segments of charged particles were compared to published measurements. The LET range was 0.05–230 keV µm‑1. The calculated Gx values for electrons satisfied the material balance equation within 0.3%, similar for protons albeit with long calculation time. A smaller geometry was used to speed up proton and alpha simulations, with an acceptable difference in the balance equation of 1.3%. Available experimental data of time-dependent G-values for agreed with simulated results within 7%  ±  8% over the entire time range; for over the full time range within 3%  ±  4% for H2O2 from 49%  ±  7% at earliest stages and 3%  ±  12% at saturation. For the LET-dependent Gx, the mean ratios to the experimental data were 1.11  ±  0.98, 1.21  ±  1.11, 1.05  ±  0.52, 1.23  ±  0.59 and 1.49  ±  0.63 (1 standard deviation) for , , H2, H2O2 and , respectively. In conclusion, radiolysis and subsequent chemistry with Geant4-DNA has been successfully incorporated in TOPAS-nBio. Results are in reasonable agreement with published measured and simulated data.

The Lin28/let-7 axis regulates glucose metabolism

PubMed Central

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

Radiation-induced phenomena in ethylene-co-tetrafluoroethylene polymer. Temperature and LET effects

NASA Astrophysics Data System (ADS)

Oshima, Akihiro; Washio, Masakazu

2003-08-01

Irradiation temperature and linear energy transfer (LET) dependency on radiation-induced reactions of ethylene-co-tetrafluoroethylene polymer (ETFE) were investigated precisely by using low and high LET beams, and in a wide range of irradiation temperatures from 77 to 573 K including its melting temperature, respectively. At various temperatures irradiation by low LET beam such as γ-rays or electron beams, significant changes were observed in the photo-absorption spectra in the wavelength region between 200 and 500 nm. The general tendency is that the absorption band shifts to longer wavelengths with higher irradiation temperatures. The enhancement of the photo-absorption at 200-500 nm is due to the formation of conjugated double bonds in ETFE by irradiation. By high LET beam irradiation at room temperature such as ion beams, the photo-absorption spectra was different from those of low LET beams, i.e. the new absorption bands around 250-450 nm was appeared. It could be suggested that the high LET beams induced the production of intermediate species in a localized area such as track structure. As a result, reaction kinetics are different from low LET beams.

FunRich proteomics software analysis, let the fun begin!

PubMed

Benito-Martin, Alberto; Peinado, Héctor

2015-08-01

Protein MS analysis is the preferred method for unbiased protein identification. It is normally applied to a large number of both small-scale and high-throughput studies. However, user-friendly computational tools for protein analysis are still needed. In this issue, Mathivanan and colleagues (Proteomics 2015, 15, 2597-2601) report the development of FunRich software, an open-access software that facilitates the analysis of proteomics data, providing tools for functional enrichment and interaction network analysis of genes and proteins. FunRich is a reinterpretation of proteomic software, a standalone tool combining ease of use with customizable databases, free access, and graphical representations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Science-based stockpile stewardship at LANSCE

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

Browne, J.

1995-10-01

Let me tell you a little about the Los Alamos Neutron Science Center (LANSCE) and how some of the examples you heard about from Sig Hecker and John Immele fit together in this view of a different world in the future where defense, basic and industrial research overlap. I am going to talk about science-based stockpile stewardship at LANSCE; the accelerator production of tritium (APT), which I think has a real bearing on the neutron road map; the world-class neutron science user facility, for which I will provide some examples so you can see the connection with defense science; andmore » lastly, testing concepts for a high-power spallation neutron target and waste transmutation.« less

Using Technology To Improve Remote User Support: A Report from the "In Your Face" Working Committee.

ERIC Educational Resources Information Center

Schlabach, Marty; Callais, Donna; Davis, Phil; Kehoe, Bill; Trelease, Ben

In July 1996, the Library Director of Cornell University's Mann Library formed a working committee to explore the technology solutions to providing a library presence with remote users. The committee began its explorations by brainstorming possible services that would utilize technology to bring the library closer to the remote user. After…

An Indoor Location-Based Control System Using Bluetooth Beacons for IoT Systems.

PubMed

Huh, Jun-Ho; Seo, Kyungryong

2017-12-19

The indoor location-based control system estimates the indoor position of a user to provide the service he/she requires. The major elements involved in the system are the localization server, service-provision client, user application positioning technology. The localization server controls access of terminal devices (e.g., Smart Phones and other wireless devices) to determine their locations within a specified space first and then the service-provision client initiates required services such as indoor navigation and monitoring/surveillance. The user application provides necessary data to let the server to localize the devices or allow the user to receive various services from the client. The major technological elements involved in this system are indoor space partition method, Bluetooth 4.0, RSSI (Received Signal Strength Indication) and trilateration. The system also employs the BLE communication technology when determining the position of the user in an indoor space. The position information obtained is then used to control a specific device(s). These technologies are fundamental in achieving a "Smart Living". An indoor location-based control system that provides services by estimating user's indoor locations has been implemented in this study (First scenario). The algorithm introduced in this study (Second scenario) is effective in extracting valid samples from the RSSI dataset but has it has some drawbacks as well. Although we used a range-average algorithm that measures the shortest distance, there are some limitations because the measurement results depend on the sample size and the sample efficiency depends on sampling speeds and environmental changes. However, the Bluetooth system can be implemented at a relatively low cost so that once the problem of precision is solved, it can be applied to various fields.

TOOLKIT, Version 2. 0

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

Schroeder, E.; Bagot, B.; McNeill, R.L.

1990-05-09

The purpose of this User's Guide is to show by example many of the features of Toolkit II. Some examples will be copies of screens as they appear while running the Toolkit. Other examples will show what the user should enter in various situations; in these instances, what the computer asserts will be in boldface and what the user responds will be in regular type. The User's Guide is divided into four sections. The first section, FOCUS Databases'', will give a broad overview of the Focus administrative databases that are available on the VAX; easy-to-use reports are available for mostmore » of them in the Toolkit. The second section, Getting Started'', will cover the steps necessary to log onto the Computer Center VAX cluster and how to start Focus and the Toolkit. The third section, Using the Toolkit'', will discuss some of the features in the Toolkit -- the available reports and how to access them, as well as some utilities. The fourth section, Helpful Hints'', will cover some useful facts about the VAX and Focus as well as some of the more common problems that can occur. The Toolkit is not set in concrete but is continually being revised and improved. If you have any opinions as to changes that you would like to see made to the Toolkit or new features that you would like included, please let us know. Since we do try to respond to the needs of the user and make periodic improvement to the Toolkit, this User's Guide may not correspond exactly to what is available in the computer. In general, changes are made to provide new options or features; rarely is an existing feature deleted.« less

AIRSAR Web-Based Data Processing

NASA Technical Reports Server (NTRS)

Chu, Anhua; Van Zyl, Jakob; Kim, Yunjin; Hensley, Scott; Lou, Yunling; Madsen, Soren; Chapman, Bruce; Imel, David; Durden, Stephen; Tung, Wayne

2007-01-01

The AIRSAR automated, Web-based data processing and distribution system is an integrated, end-to-end synthetic aperture radar (SAR) processing system. Designed to function under limited resources and rigorous demands, AIRSAR eliminates operational errors and provides for paperless archiving. Also, it provides a yearly tune-up of the processor on flight missions, as well as quality assurance with new radar modes and anomalous data compensation. The software fully integrates a Web-based SAR data-user request subsystem, a data processing system to automatically generate co-registered multi-frequency images from both polarimetric and interferometric data collection modes in 80/40/20 MHz bandwidth, an automated verification quality assurance subsystem, and an automatic data distribution system for use in the remote-sensor community. Features include Survey Automation Processing in which the software can automatically generate a quick-look image from an entire 90-GB SAR raw data 32-MB/s tape overnight without operator intervention. Also, the software allows product ordering and distribution via a Web-based user request system. To make AIRSAR more user friendly, it has been designed to let users search by entering the desired mission flight line (Missions Searching), or to search for any mission flight line by entering the desired latitude and longitude (Map Searching). For precision image automation processing, the software generates the products according to each data processing request stored in the database via a Queue management system. Users are able to have automatic generation of coregistered multi-frequency images as the software generates polarimetric and/or interferometric SAR data processing in ground and/or slant projection according to user processing requests for one of the 12 radar modes.

Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

PubMed Central

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

Role of genetic background in induced instability

NASA Technical Reports Server (NTRS)

Kadhim, Munira A.; Nelson, G. A. (Principal Investigator)

2003-01-01

Genomic instability is effectively induced by ionizing radiation. Recently, evidence has accumulated supporting a relationship between genetic background and the radiation-induced genomic instability phenotype. This is possibly due to alterations in proteins responsible for maintenance of genomic integrity or altered oxidative metabolism. Studies in human cell lines, human primary cells, and mouse models have been performed predominantly using high linear energy transfer (LET) radiation, or high doses of low LET radiation. The interplay between genetics, radiation response, and genomic instability has not been fully determined at low doses of low LET radiation. However, recent studies using low doses of low LET radiation suggest that the relationship between genetic background and radiation-induced genomic instability may be more complicated than these same relationships at high LET or high doses of low LET radiation. The complexity of this relationship at low doses of low LET radiation suggests that more of the population may be at risk than previously recognized and may have implications for radiation risk assessment.

Affective loop experiences: designing for interactional embodiment.

PubMed

Höök, Kristina

2009-12-12

Involving our corporeal bodies in interaction can create strong affective experiences. Systems that both can be influenced by and influence users corporeally exhibit a use quality we name an affective loop experience. In an affective loop experience, (i) emotions are seen as processes, constructed in the interaction, starting from everyday bodily, cognitive or social experiences; (ii) the system responds in ways that pull the user into the interaction, touching upon end users' physical experiences; and (iii) throughout the interaction the user is an active, meaning-making individual choosing how to express themselves-the interpretation responsibility does not lie with the system. We have built several systems that attempt to create affective loop experiences with more or less successful results. For example, eMoto lets users send text messages between mobile phones, but in addition to text, the messages also have colourful and animated shapes in the background chosen through emotion-gestures with a sensor-enabled stylus pen. Affective Diary is a digital diary with which users can scribble their notes, but it also allows for bodily memorabilia to be recorded from body sensors mapping to users' movement and arousal and placed along a timeline. Users can see patterns in their bodily reactions and relate them to various events going on in their lives. The experiences of building and deploying these systems gave us insights into design requirements for addressing affective loop experiences, such as how to design for turn-taking between user and system, how to create for 'open' surfaces in the design that can carry users' own meaning-making processes, how to combine modalities to create for a 'unity' of expression, and the importance of mirroring user experience in familiar ways that touch upon their everyday social and corporeal experiences. But a more important lesson gained from deploying the systems is how emotion processes are co-constructed and experienced inseparable from all other aspects of everyday life. Emotion processes are part of our social ways of being in the world; they dye our dreams, hopes and bodily experiences of the world. If we aim to design for affective interaction experiences, we need to place them into this larger picture.

Affective loop experiences: designing for interactional embodiment

PubMed Central

Höök, Kristina

2009-01-01

Involving our corporeal bodies in interaction can create strong affective experiences. Systems that both can be influenced by and influence users corporeally exhibit a use quality we name an affective loop experience. In an affective loop experience, (i) emotions are seen as processes, constructed in the interaction, starting from everyday bodily, cognitive or social experiences; (ii) the system responds in ways that pull the user into the interaction, touching upon end users' physical experiences; and (iii) throughout the interaction the user is an active, meaning-making individual choosing how to express themselves—the interpretation responsibility does not lie with the system. We have built several systems that attempt to create affective loop experiences with more or less successful results. For example, eMoto lets users send text messages between mobile phones, but in addition to text, the messages also have colourful and animated shapes in the background chosen through emotion-gestures with a sensor-enabled stylus pen. Affective Diary is a digital diary with which users can scribble their notes, but it also allows for bodily memorabilia to be recorded from body sensors mapping to users' movement and arousal and placed along a timeline. Users can see patterns in their bodily reactions and relate them to various events going on in their lives. The experiences of building and deploying these systems gave us insights into design requirements for addressing affective loop experiences, such as how to design for turn-taking between user and system, how to create for ‘open’ surfaces in the design that can carry users' own meaning-making processes, how to combine modalities to create for a ‘unity’ of expression, and the importance of mirroring user experience in familiar ways that touch upon their everyday social and corporeal experiences. But a more important lesson gained from deploying the systems is how emotion processes are co-constructed and experienced inseparable from all other aspects of everyday life. Emotion processes are part of our social ways of being in the world; they dye our dreams, hopes and bodily experiences of the world. If we aim to design for affective interaction experiences, we need to place them into this larger picture. PMID:19884153

Charge, energy and LET spectra of high LET primary and secondary particles in CR-39 plastic nuclear track detectors of the P0006 experiment

NASA Technical Reports Server (NTRS)

Csige, I.; Frigo, L. A.; Benton, E. V.; Oda, K.

1995-01-01

We have measured the charge, energy and linear energy transfer (LET) spectra of about 800 high LET (LET(sub infinity) H2O greater than 50 keV/micron) particles in CR-39 plastic nuclear track detectors in the P0006 experiment of LDEF. Primary particles with residual range at the reference surface greater than about 2 microns and secondary particles produced in the detector material with total range greater than about 4 microns were measured. We have used a multi-etch technique and an internal calibration to identify and measure the energy of the particles at the reference surface. The LET spectrum was obtained from the charge and energy distribution of the particles.

Science Engagement Through Hands-On Activities that Promote Scientific Thinking and Generate Excitement and Awareness of NASA Assets, Missions, and Science

NASA Technical Reports Server (NTRS)

Graff, P. V.; Foxworth, S.; Miller, R.; Runco, S.; Luckey, M. K.; Maudlin, E.

2018-01-01

The public with hands-on activities that infuse content related to NASA assets, missions, and science and reflect authentic scientific practices promotes understanding and generates excitement about NASA science, research, and exploration. These types of activities expose our next generation of explorers to science they may be inspired to pursue as a future STEM career and expose people of all ages to unique, exciting, and authentic aspects of NASA exploration. The activities discussed here (Blue Marble Matches, Lunar Geologist Practice, Let's Discover New Frontiers, Target Asteroid, and Meteorite Bingo) have been developed by Astromaterials Research and Exploration Science (ARES) Science Engagement Specialists in conjunction with ARES Scientists at the NASA Johnson Space Center. Activities are designed to be usable across a variety of educational environments (formal and informal) and reflect authentic scientific content and practices.

Renewable Energy Data Explorer User Guide

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

Cox, Sarah L; Grue, Nicholas W; Tran, July

This publication provides a user guide for the Renewable Energy Data Explorer and technical potential tool within the Explorer. The Renewable Energy Data Explorer is a dynamic, web-based geospatial analysis tool that facilitates renewable energy decision-making, investment, and deployment. It brings together renewable energy resource data and other modeled or measured geographic information system (GIS) layers, including land use, weather, environmental, population density, administrative, and grid data.

Learning Partners: Escribamos! Leamos! Juguemos a las Ciencias! Juguemos a las Matematicas! (Learning Partners: Let's Write! Let's Read! Let's Play Mathematics! Let's Play Science!)

ERIC Educational Resources Information Center

Office of Educational Research and Improvement (ED), Washington, DC.

This Spanish-language document consists of four single-sheet sets of guidelines developed by the Family Involvement Partnership for Learning to assist parents in facilitating their children's elementary school success. The front part of the sheets describes general ways parents can support their children, including modeling writing, reading aloud,…

WE-D-17A-06: Optically Stimulated Luminescence Detectors as ‘LET-Meters’ in Proton Beams

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

Granville, D; Sahoo, N; Sawakuchi, GO

Purpose: To demonstrate and evaluate the potential of optically stimulated luminescence (OSL) detectors (OSLDs) for measurements of linear energy transfer (LET) in therapeutic proton beams. Methods: Batches of Al2O2:C OSLDs were irradiated with an absorbed dose of 0.2 Gy in un-modulated proton beams of varying LET (0.67 keV/μm to 2.58 keV/μm). The OSLDs were read using continuous wave (CW-OSL) and pulsed (P-OSL) stimulation modes. We parameterized and calibrated three characteristics of the OSL signals as functions of LET: CW-OSL curve shape, P-OSL curve shape and the ratio of the two OSL emission band intensities (ultraviolet/blue ratio). Calibration curves were createdmore » for each of these characteristics to describe their behaviors as functions of LET. The true LET values were determined using a validated Monte Carlo model of the proton therapy nozzle used to irradiate the OSLDs. We then irradiated batches of OSLDs with an absorbed dose of 0.2 Gy at various depths in two modulated proton beams (140 MeV, 4 cm wide spread-out Bragg peak (SOBP) and 250 MeV, 10 cm wide SOBP). The LET values were calculated using the OSL response and the calibration curves. Finally, measured LET values were compared to the true values determined using Monte Carlo simulations. Results: The CW-OSL curve shape, P-OSL curve shape and the ultraviolet/blue-ratio provided proton LET estimates within 12.4%, 5.7% and 30.9% of the true values, respectively. Conclusion: We have demonstrated that LET can be measured within 5.7% using Al2O3:C OSLDs in the therapeutic proton beams used in this investigation. From a single OSLD readout, it is possible to measure both the absorbed dose and LET. This has potential future applications in proton therapy quality assurance, particularly for treatment plans based on optimization of LET distributions. This research was partially supported by the Natural Sciences and Engineering Research Council of Canada.« less

Let’s Explore Health Services Delivery with Rams or A Vision for an Air Force Medical Home Concept of Operations

DTIC Science & Technology

2013-07-01

operational medical technicians, occupational health nurses, and physician assistants ) to effectively and efficiently provide occupational and operational...team and a provider/medical assistant triad. 8 A provider assigned to a squadron medical element only contributes 0.5 FTEs. 21 Distribution A...up appointments although medical assistants often perform that function during the post-visit. The front desk staff also makes confirmation calls to

The Legionella pneumophila global regulatory protein LetA affects DotA and Mip.

PubMed

Shi, Chunwei; Forsbach-Birk, Vera; Marre, Reinhard; McNealy, Tamara L

2006-02-01

Several genes have been identified in Legionella pneumophila which are necessary for its virulence properties. These genes include the dot/icm type IV secretion system (T4SS), mip and letA. Genes of the dot/icm system, in particular dotA, have been found to be essential for intracellular growth. The macrophage infectivity protein (Mip) is also necessary for full virulence of the bacteria. Although these genes are well characterized, the regulation of such virulence factors is not. The LetA transcriptional activator interacts with the global regulator CsrA in controlling the switch from the replicative, non-infectious to the transmissive, highly infectious form of L. pneumophila. Regulation by LetA of the dot/icm genes has also been previously postulated. Here we show that the letA mutation exerts effects not only on DotA but on a substrate of the secretion system, RalF as well. LetA was found to be necessary for full transcriptional expression of the dotA and ralF genes. Although at the transcriptional level dotA was reduced, this did not result in a decrease of DotA protein in whole cell lysates. The letA mutation, however, does result in decreased amounts of the DotA protein found in the membrane and increased amounts in the culture supernatant. Additionally, the letA mutation dramatically decreased the secretion of Mip. This work demonstrates the participation of the global regulatory protein LetA in the regulation of an essential part of the dot/icm T4SS. Also shown is the presence of secreted Mip and a decrease in this secretion in the letA(-) strain. Exactly how LetA is regulating these virulence factors remains to be elucidated but it obviously occurs at both transcriptional and post-transcriptional levels.

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

PubMed

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.

Participatory Exploration: The Role of the User Contribution System

NASA Technical Reports Server (NTRS)

Skytland, Nicholas G.

2009-01-01

This viewgraph presentation explores how NASA can apply the global shift in demographics, the popularity of collaborative technology and the desire for participation to the future of space exploration. Included in this is a review of the evolution of work, the engagement gap, user contribution systems and a case study concerning the "digital astronaut".

Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission

PubMed Central

McMillan, Dayton D.; Maeda, Junko; Bell, Justin J.; Genet, Matthew D.; Phoonswadi, Garrett; Mann, Kelly A.; Kraft, Susan L.; Kitamura, Hisashi; Fujimori, Akira; Yoshii, Yukie; Furukawa, Takako; Fujibayashi, Yasuhisa; Kato, Takamitsu A.

2015-01-01

Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a 64Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of 64Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from 64Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair–deficient xrs5 cells were exposed to 64Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D10 values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that 64Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from 64Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after 64Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that 64Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of 64Cu-ATSM as a cancer treatment modality for hypoxic tumors. PMID:26251463

Impact of Treatment Subsidies and Cash Payouts on Treatment Choices at the End of Life.

PubMed

Finkelstein, Eric; Malhotra, Chetna; Chay, Junxing; Ozdemir, Semra; Chopra, Akhil; Kanesvaran, Ravindran

To examine the extent to which financial assistance, in the form of subsidies for life-extending treatments (LETs) or cash payouts, distorts the demand for end-of-life treatments. A discrete choice experiment was administered to 290 patients with cancer in Singapore to elicit preferences for LETs and only palliative care (PC). Responses were fitted to a latent class conditional logistic regression model. We also quantified patients' willingness to pay to avoid and willingness to accept a less effective LET or PC-only. We then simulated the effects of various LET subsidy and cash payout policies on treatment choices. We identified three classes of patients according to their preferences. The first class (26.1% of the sample) had a strong preference for PC and were willing to give up life expectancy gains and even pay for receiving only PC. The second class (29.8% of the sample) had a strong preference for LETs and preferred to extend life regardless of cost or quality of life. The final class (44.1% of the sample) preferred LETs to PC, but actively traded off costs and length and quality of life when making end-of-life treatment choices. Policy simulations showed that LET subsidies increase demand for LETs at the expense of demand for PC, but an equivalent cash payout was not shown to distort demand. Patients with cancer have heterogeneous end-of-life preferences. LET subsidies and cash payouts have differing effects on the use of LETs. Policymakers should be mindful of these differences when designing health care financing schemes for patients with life-limiting illnesses. Copyright © 2016. Published by Elsevier Inc.

MiRNA Analysis by Quantitative PCR in Preterm Human Breast Milk Reveals Daily Fluctuations of hsa-miR-16-5p

PubMed Central

Floris, Ilaria; Billard, Hélène; Boquien, Clair-Yves; Joram-Gauvard, Evelyne; Simon, Laure; Legrand, Arnaud; Boscher, Cécile; Rozé, Jean-Christophe; Bolaños-Jiménez, Francisco; Kaeffer, Bertrand

2015-01-01

Background and Aims Human breast milk is an extremely dynamic fluid containing many biologically-active components which change throughout the feeding period and throughout the day. We designed a miRNA assay on minimized amounts of raw milk obtained from mothers of preterm infants. We investigated changes in miRNA expression within month 2 of lactation and then over the course of 24 hours. Materials and Methods Analyses were performed on pooled breast milk, made by combining samples collected at different clock times from the same mother donor, along with time series collected over 24 hours from four unsynchronized mothers. Whole milk, lipids or skim milk fractions were processed and analyzed by qPCR. We measured hsa-miR-16-5p, hsa-miR-21-5p, hsa-miR-146-5p, and hsa-let-7a, d and g (all -5p). Stability of miRNA endogenous controls was evaluated using RefFinder, a web tool integrating geNorm, Normfinder, BestKeeper and the comparative ΔΔCt method. Results MiR-21 and miR-16 were stably expressed in whole milk collected within month 2 of lactation from four mothers. Analysis of lipids and skim milk revealed that miR-146b and let-7d were better references in both fractions. Time series (5H-23H) allowed the identification of a set of three endogenous reference genes (hsa-let-7d, hsa-let-7g and miR-146b) to normalize raw quantification cycle (Cq) data. We identified a daily oscillation of miR-16-5p. Perspectives Our assay allows exploring miRNA levels of breast milk from mother with preterm baby collected in time series over 48–72 hours. PMID:26474056

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

PubMed

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.

An Arduino Investigation of Simple Harmonic Motion

NASA Astrophysics Data System (ADS)

Galeriu, Calin; Edwards, Scott; Esper, Geoffrey

2014-03-01

We cannot hope for a new generation of scientists and engineers if we don't let our young students take ownership of their scientific and engineering explorations, if we don't let them enjoy the hands-on cycle of design and production, and if we don't let them implant their creativity into a technologically friendly environment. With this educational philosophy in mind, Massimo Banzi and his team have developed and popularized the open source Arduino microcontroller board. The Arduino board has helped countless people in their science, electronics, robotics, or engineering projects, allowing them to build things that we have not even dreamed of. Physics instructors have also realized the advantages of using Arduino boards for lab experiments. The schools are saving money because the homemade experimental equipment is much cheaper than the commercial alternatives. The students are thankful for an educational experience that is more interesting, more loaded with STEM content, and more fun. As further proof of this new trend in physics education, Vernier5 is now documenting the use of their probes with Arduino boards. This is why we have developed an Arduino-based physics investigation of the simple harmonic motion (SHM) of a mass on a spring. The experimental data are collected with the help of an ultrasonic distance sensor and an Arduino Uno board. The data are then graphed and analyzed using Origin 9. This rich cross-curricular STEM activity integrates electronics, computer programming, physics, and mathematics in a way that is both experimentally exciting and intellectually rewarding.

Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs

PubMed Central

Frost, Robert J. A.; Olson, Eric N.

2011-01-01

Diabetes mellitus is the most common metabolic disorder worldwide and a major risk factor for cardiovascular disease. MicroRNAs are negative regulators of gene expression that have been implicated in many biological processes, including metabolism. Here we show that the Let-7 family of microRNAs regulates glucose metabolism in multiple organs. Global and pancreas-specific overexpression of Let-7 in mice resulted in impaired glucose tolerance and reduced glucose-induced pancreatic insulin secretion. Mice overexpressing Let-7 also had decreased fat mass and body weight, as well as reduced body size. Global knockdown of the Let-7 family with an antimiR was sufficient to prevent and treat impaired glucose tolerance in mice with diet-induced obesity, at least in part by improving insulin sensitivity in liver and muscle. AntimiR treatment of mice on a high-fat diet also resulted in increased lean and muscle mass, but not increased fat mass, and prevented ectopic fat deposition in the liver. These findings demonstrate that Let-7 regulates multiple aspects of glucose metabolism and suggest antimiR-induced Let-7 knockdown as a potential treatment for type 2 diabetes mellitus. Furthermore, our Cre-inducible Let-7-transgenic mice provide a unique model for studying tissue-specific aspects of body growth and type 2 diabetes. PMID:22160727

Down-regulated let-7b-5p represses glycolysis metabolism by targeting AURKB in asthenozoospermia.

PubMed

Zhou, Ran; Zhang, Yan; Du, Guizhen; Han, Li; Zheng, Sinian; Liang, Jian; Huang, Xiaomin; Qin, Yufeng; Wu, Wei; Chen, Minjian; Wu, Di; Song, Ling; Fu, Guangbo; Lv, Shuyan; Xia, Yankai; Lu, Chuncheng; Wang, Xinru

2018-07-15

Glycolysis, through anaerobic respiration, can supply energy for human sperm motility. MicroRNAs (miRNAs) could participate in the glycolytic pathway through regulating target genes. To investigate the potential role of glycolysis-related miRNAs in asthenozoospermia, TaqMan Low Density Array (TLDA) was used to screen potentially functional miRNAs, and seven glycolysis-related miRNAs were isolated to be related to asthenozoospermia. After qRT-PCR validation, only one seminal plasma miRNA, let-7b-5p, was found significantly decreased in severe asthenozoospermia cases compared with healthy controls. To further understand whether let-7b-5p is involved in asthenozoospermia by regulating the glycolytic pathway, we carried out gain-and-loss function study of let-7b-5p in GC-2 cells and detected the glycolytic activities. Our results showed that knocking down let-7b-5p could inhibit glycolytic activities. Besides, we also found overexpressed Aurkb (a target gene of let-7b-5p) could recapitulate the effects of knocking down let-7b-5p. Our findings indicated that low expression of let-7b-5p could repress glycolysis in asthenozoospermia by targeting AURKB. Copyright © 2018 Elsevier B.V. All rights reserved.

Virtual Character Animation Based on Affordable Motion Capture and Reconfigurable Tangible Interfaces.

PubMed

Lamberti, Fabrizio; Paravati, Gianluca; Gatteschi, Valentina; Cannavo, Alberto; Montuschi, Paolo

2018-05-01

Software for computer animation is generally characterized by a steep learning curve, due to the entanglement of both sophisticated techniques and interaction methods required to control 3D geometries. This paper proposes a tool designed to support computer animation production processes by leveraging the affordances offered by articulated tangible user interfaces and motion capture retargeting solutions. To this aim, orientations of an instrumented prop are recorded together with animator's motion in the 3D space and used to quickly pose characters in the virtual environment. High-level functionalities of the animation software are made accessible via a speech interface, thus letting the user control the animation pipeline via voice commands while focusing on his or her hands and body motion. The proposed solution exploits both off-the-shelf hardware components (like the Lego Mindstorms EV3 bricks and the Microsoft Kinect, used for building the tangible device and tracking animator's skeleton) and free open-source software (like the Blender animation tool), thus representing an interesting solution also for beginners approaching the world of digital animation for the first time. Experimental results in different usage scenarios show the benefits offered by the designed interaction strategy with respect to a mouse & keyboard-based interface both for expert and non-expert users.

Snapchat elicits more jealousy than Facebook: a comparison of Snapchat and Facebook use.

PubMed

Utz, Sonja; Muscanell, Nicole; Khalid, Cameran

2015-03-01

Recent news in the media has suggested that younger people are using popular social media such as Facebook less and are quickly adopting newer media, such as the self-destructing app Snapchat. Snapchat is unique in that it erases messages several seconds after they have been sent, affording its users a higher level of privacy. Yet, little research exists on Snapchat use in general, let alone its broader psychological implications. This article offers a preliminary comparison of Snapchat and Facebook use and psychological effects on romantic jealousy. General motives for using Snapchat and Facebook are examined, as well as the nature of the content that Snapchat users most frequently share. Further, because of the differences in privacy and persistence of information, potential psychological effects in the domain of romantic jealousy are also examined, which has been widely studied on Facebook in the last few years. Findings show that the main difference in motives were that Snapchat was used more for flirting and finding new love interests, whereas Facebook was still the main social networking site used for keeping in touch with friends. Further, when presenting users with a series of potentially jealousy provoking scenarios, Snapchat elicited higher levels of jealousy than did Facebook. These findings are explained based on an affordance approach.

A Review: Some biological effects of high LET radiations

NASA Technical Reports Server (NTRS)

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.

DNA Repair Domain Modeling Can Predict Cell Death and Mutation Frequency for Wide Range Spectrum of Radiation

NASA Technical Reports Server (NTRS)

Viger, Louise; Ponomarev, Artem L.; Plante, Ianik; Evain, Trevor; Penninckx, Sebastien; Blattnig, Steve R.; Costes, Sylvain V.

2017-01-01

Exploration missions to Mars and other destinations raise many questions about the health of astronauts. The continuous exposure of astronauts to galactic cosmic rays is one of the main concerns for long-term missions. Cosmic ionizing radiations are composed of different ions of various charges and energies notably, highly charged energy (HZE) particles. The HZE particles have been shown to be more carcinogenic than low-LET radiation, suggesting the severity of chromosomal aberrations induced by HZE particles is one possible explanation. However, most mathematical models predicting cell death and mutation frequency are based on directly fitting various HZE dose response and are in essence empirical approaches. In this work, we assume a simple biological mechanism to model DNA repair and use it to simultaneously explain the low- and high-LET response using the exact same fitting parameters. Our work shows that the geometrical position of DNA repair along tracks of heavy ions are sufficient to explain why high-LET particles can induce more death and mutations. Our model is based on assuming DNA double strand breaks (DSBs) are repaired within repair domain, and that any DSBs located within the same repair domain cluster into one repair unit, facilitating chromosomal rearrangements and increasing the probability of cell death. We introduced this model in 2014 using simplified microdosimetry profiles to predict cell death. In this work, we collaborated with NASA Johnson Space Center to generate more accurate microdosimetry profiles derived by Monte Carlo techniques, taking into account track structure of HZE particles and simulating DSBs in realistic cell geometry. We simulated 224 data points (D, A, Z, E) with the BDSTRACKS model, leading to a large coverage of LET from 10 to 2,400 keV/µm. This model was used to generate theoretical RBE for various particles and energies for both cell death and mutation frequencies. The RBE LET dependence is in agreement with experimental data known in human and murine cells. It suggests that cell shape and its orientation with respect to the HZE particle beam can modify the biological response to radiation. Such discovery will be tested experimentally and, if proven accurate, will be another strong supporting evidence for DNA repair domains and their critical role in interpreting cosmic radiation sensitivity.

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

PubMed Central

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. PMID:23435502

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

PubMed

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.

Defining Transcriptional Regulatory Mechanisms for Primary let-7 miRNAs

PubMed Central

Gaeta, Xavier; Le, Luat; Lin, Ying; Xie, Yuan; Lowry, William E.

2017-01-01

The let-7 family of miRNAs have been shown to control developmental timing in organisms from C. elegans to humans; their function in several essential cell processes throughout development is also well conserved. Numerous studies have defined several steps of post-transcriptional regulation of let-7 production; from pri-miRNA through pre-miRNA, to the mature miRNA that targets endogenous mRNAs for degradation or translational inhibition. Less-well defined are modes of transcriptional regulation of the pri-miRNAs for let-7. let-7 pri-miRNAs are expressed in polycistronic fashion, in long transcripts newly annotated based on chromatin-associated RNA-sequencing. Upon differentiation, we found that some let-7 pri-miRNAs are regulated at the transcriptional level, while others appear to be constitutively transcribed. Using the Epigenetic Roadmap database, we further annotated regulatory elements of each polycistron identified putative promoters and enhancers. Probing these regulatory elements for transcription factor binding sites identified factors that regulate transcription of let-7 in both promoter and enhancer regions, and identified novel regulatory mechanisms for this important class of miRNAs. PMID:28052101

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

PubMed

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.

Expression of microRNA let-7a positively correlates with hepatitis B virus replication in hepatocellular carcinoma tissues

PubMed Central

Chen, Jian; Liu, Jie; Luo, Zhongguang; Jiang, Weiru; Huang, Jianping; Qiu, Zhibing; Yue, Wenjie; Wu, Lijun

2017-01-01

Let-7a miRNA is downregulated in various cancers. However, in hepatocellular carcinoma (HCC) patients infected with hepatitis B virus (HBV), the relationship between let-7a and HBV replication has not been fully elucidated. Liver specimens were collected from 23 HCC patients with chronically active HBV. The serum levels of the HBV antigens hepatitis B surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg), and the HBV antibodies, anti-HBs, anti-HBe and anti-hepatitis B core antigen (anti-HBc) were measured using the microparticle enzyme immunoassay. Let-7a levels and HBV DNA copy numbers were measured by quantitative real-time PCR (qRT-PCR) and analyzed statistically. A let-7a specific antisense oligonucleotide was introduced to the HBV-producing cell line HepG2.2.15 and a change in HBV DNA copy numbers was assessed by qRT-PCR. HCC patients with highly active HBV replication (>106 DNA copies/mL) showed higher levels of serum HBsAg and anti-HBc than patients with less active HBV replication (<103 DNA copies/mL). The level of let-7a was lower in malignant tissues than in adjacent normal tissues. However, patients with highly active HBV replication demonstrated a significantly higher level of let-7a in hepatocarcinoma tissue than patients with less active HBV replication (P < 0.05). A higher level of let-7a was observed in the HBV-producing cell line HepG2.2.15 than in HepG2 cells (P < 0.05), and let-7a down-regulation by antisense oligonucleotides led to a reduction in HBV DNA copy numbers (P < 0.05), indicating a correlation between the let-7a level and HBV replication. Down-regulation of let-7a reduces HBV replication and could prevent the development of HCC, suggesting it could be an effective therapeutic treatment for HBV infection. Impact statement Although interferon and nucleic acid analogues effectively suppress HBV replication in HBV patients, there is no treatment which eradicates the virus. Moreover, the therapeutic effect can be reduced by virus mutations or drug resistance. Let-7a is a miRNA initially found in the nematode as a master regulator of developmental processes, but also exists in humans. It has been reported that the transcription of let-7a was much lower in HCC than in normal liver tissues and specific miRNA could directly promote virus replication. Therefore we hypothesized that transcription of let-7a promotes HBV replication, which might compromise the therapeutic effects of antivirus treatments. In our present study, we demonstrated a correlation between let-7a transcription and HBV replication in surgical specimens obtained from patients with HCC, as well as in HCC cell lines. Our finding might be the base for a new approach to improve HBV infection treatments in the future. PMID:28440732

Exploring the Integration of Technology into Jewish Education: Multi-User Virtual Environments and Supplementary School Settings

ERIC Educational Resources Information Center

Sohn, Johannah Eve

2014-01-01

This descriptive case study explores the implementation of a multi-user virtual environment (MUVE) in a Jewish supplemental school setting. The research was conducted to present the recollections and reflections of three constituent populations of a new technology exploring constructivist education in the context of supplemental and online…

Visual Information for the Desktop, version 1.0

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

2006-03-29

VZIN integrates visual analytics capabilities into popular desktop tools to aid a user in searching and understanding an information space. VZIN allows users to Drag-Drop-Visualize-Explore-Organize information within tools such as Microsoft Office, Windows Explorer, Excel, and Outlook. VZIN is tailorable to specific client or industry requirements. VZIN follows the desktop metaphors so that advanced analytical capabilities are available with minimal user training.

JHelioviewer: Open-Source Software for Discovery and Image Access in the Petabyte Age (Invited)

NASA Astrophysics Data System (ADS)

Mueller, D.; Dimitoglou, G.; Langenberg, M.; Pagel, S.; Dau, A.; Nuhn, M.; Garcia Ortiz, J. P.; Dietert, H.; Schmidt, L.; Hughitt, V. K.; Ireland, J.; Fleck, B.

2010-12-01

The unprecedented torrent of data returned by the Solar Dynamics Observatory is both a blessing and a barrier: a blessing for making available data with significantly higher spatial and temporal resolution, but a barrier for scientists to access, browse and analyze them. With such staggering data volume, the data is bound to be accessible only from a few repositories and users will have to deal with data sets effectively immobile and practically difficult to download. From a scientist's perspective this poses three challenges: accessing, browsing and finding interesting data while avoiding the proverbial search for a needle in a haystack. To address these challenges, we have developed JHelioviewer, an open-source visualization software that lets users browse large data volumes both as still images and movies. We did so by deploying an efficient image encoding, storage, and dissemination solution using the JPEG 2000 standard. This solution enables users to access remote images at different resolution levels as a single data stream. Users can view, manipulate, pan, zoom, and overlay JPEG 2000 compressed data quickly, without severe network bandwidth penalties. Besides viewing data, the browser provides third-party metadata and event catalog integration to quickly locate data of interest, as well as an interface to the Virtual Solar Observatory to download science-quality data. As part of the Helioviewer Project, JHelioviewer offers intuitive ways to browse large amounts of heterogeneous data remotely and provides an extensible and customizable open-source platform for the scientific community.

Causation mechanisms in car-to-vulnerable road user crashes: implications for active safety systems.

PubMed

Habibovic, Azra; Davidsson, Johan

2012-11-01

Vulnerable road users (VRUs), such as pedestrians and bicyclists, are often involved in crashes with passenger cars. One way to prevent these crashes is to deploy active safety systems that support the car drivers and/or VRUs. However, to develop such systems, a thorough understanding of crash causation mechanisms is required. The aim of this study is to identify crash causation mechanisms from the perspective of the VRUs, and to explore the implications of these mechanisms for the development of active safety systems. Data originate from the European project SafetyNet, where 995 crashes were in-depth investigated using the SafetyNet Accident Causation System (SNACS). To limit the scope, this study analyzed only intersection crashes involving VRUs. A total of 56 VRU crashes were aggregated. Results suggest that, while 30% of the VRUs did not see the conflict car due to visual obstructions in the traffic environment, 70% of the VRUs saw the car before the collision, but still misunderstood the traffic situation and/or made an inadequate plan of action. An important implication that follows from this is that, while detection of cars is clearly an issue that needs to be addressed, it is even more important to help the VRUs to correctly understand traffic situation (e.g., does the driver intend to slow down, and if s/he does, is it to let the VRU cross or for some other reason?). The former issue suggests a role for various cooperative active safety systems, as the obstacles are generally impenetrable with regular sensors. The latter issue is less straightforward. While various systems can be proposed, such as providing gap size estimation and reducing the car speed variability, the functional merits of each such a system need to be further investigated. Copyright © 2012 Elsevier Ltd. All rights reserved.

Interactive Modelling of Salinity Intrusion in the Rhine-Meuse Delta

NASA Astrophysics Data System (ADS)

Baart, F.; Kranenburg, W.; Luijendijk, A.

2015-12-01

In many delta's of the world salinity intrusion imposes limits to fresh water availability. With increasing population and industry, the need for fresh water increases. But also salinity intrusion is expected to increase due to changes in river discharge, sea level and storm characteristics. In the Rhine-Meuse delta salt intrusion is impacted by human activities as well, like deepening of waterways and opening of delta-branches closed earlier. All these developments call for increasing the understanding of the system, but also for means for policy makers, coastal planners and engineers to assess effects of changes and to explore and design measures. In our presentation we present the developments in interactive modelling of salinity intrusion in the Rhine-Meuse delta. In traditional process-based numerical modelling, impacts are investigated by researchers and engineers by following the steps of pre-defining scenario's, running the model and post-processing the results. Interactive modelling lets users adjust simulations while running. Users can for instance change river discharges or bed levels, and can add measures like changes to geometry. The model will take the adjustments into account immediately, and will directly compute the effect. In this way, a tool becomes available with which coastal planners, policy makers and engineers together can develop and evaluate ideas and designs by interacting with the numerical model. When developing interactive numerical engines, one of the challenges is to optimize the exchange of variables as e.g. salt concentration. In our case we exchange variables on a 3D grid every time step. For this, the numerical model adheres to the Basic Model Interface (http://csdms.colorado.edu/wiki), which allows external control and the exchange of variables through pointers while the model is running. In our presentation we further explain our method and show examples of interactive design of salinity intrusion measures in the Rhine-Meuse delta.

Dexmedetomidine Protects PC12 Cells from Lidocaine-Induced Cytotoxicity Through Downregulation of COL3A1 Mediated by miR-let-7b.

PubMed

Wang, Qiong; She, Yingjun; Bi, Xiaobao; Zhao, Baisong; Ruan, Xiangcai; Tan, Yonghong

2017-07-01

Safety concerns of some local anesthetics, such as lidocaine, have been raised in recent years due to potential neurological impairment. Dexmedetomidine may protect humans from neurotoxicity, and miR-let-7b is activated by nerve injury; however, the roles of miR-let-7b and its target gene in lidocaine-induced cytotoxicity are not well known. Through bioinformatics and a luciferase reporter assay, COL3A1 was suggested as a direct target gene of miR-let-7b. Here, we confirmed by measuring mRNA and protein levels that miR-let-7b was downregulated and COL3A1 was upregulated in lidocaine-treated cells, an observation that was reversed by dexmedetomidine. Similar to miR-let-7b mimics or knockdown of COL3A1, dexmedetomidine treatment reduced the expression of COL3A1, suppressed cell apoptosis and cell migration/invasion ability, and induced cell cycle progression and cell proliferation in PC12 cells, effects that were reversed by the miR-let-7b inhibitor. Meanwhile, proteins involved in cell apoptosis, such as Bcl2 and caspase 3, were impacted as well. Taken together, dexmedetomidine may protect PC12 cells from lidocaine-induced cytotoxicity through miR-let-7b and COL3A1, while also increasing Bcl2 and inhibiting caspase 3. Therefore, miR-let-7b and COL3A1 might play critical roles in neuronal injury, and they are potential therapeutic targets.

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

Nusrat, Humza; Pang, Geordi; Ahmad, Syed

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. Initialmore » 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.« less

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

PubMed

Vral, A; Thierens, H; Baeyens, A; De Ridder, L

2002-04-01

To determine by means of the G2 assay the number of chromatid breaks induced by low-LET gamma-rays and high-LET neutrons, and to compare the kinetics of chromatid break rejoining for radiations of different quality. The G2 assay was performed on blood samples of four healthy donors who were irradiated with low-LET gamma-rays and high-LET neutrons. In a first set of experiments a dose-response curve for the formation of chromatid breaks was carried out for gamma-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 were investigated after a dose of 0.5 Gy using post-irradiation times ranging between 0.5 and 3.5 h. For the highest dose of 0.5 Gy, the number of isochromatid breaks was also scored. No significant differences in the number of chromatid breaks were observed between low-LET gamma-rays and high-LET neutrons for the four donors at any of the doses given. The dose-response curves for the formation of chromatid breaks are linear for both radiation qualities and RBEs = 1 were obtained. Scoring of isochromatid breaks at the highest dose of 0.5 Gy revealed that high-LET neutrons were, however, more effective at inducing isochromatid breaks (RBE = 6.2). The rejoining experiments further showed that the kinetics of disappearance of chromatid breaks following irradiation with low-LET gamma-rays or high-LET neutrons were not significantly different. Half-times of 0.92 h for gamma-rays and 0.84 h for neutrons were obtained. Applying the G2 assay, the results demonstrate that at low doses of irradiation, the induction as well as the disappearance of chromatid breaks is independent of the LET of the radiation qualities used (0.24 keV x microm(-1) 60Co gamma-rays and 20 keV x microm(-1) fast neutrons). As these radiation qualities produce the same initial number of double-strand breaks, the results support the signal model that proposes that chromatid breaks are the result of an exchange process which is triggered by a single double-strand break.

[Beyond suffering, schizophrenic improvisation and therapeutic challenges].

PubMed

Bizot, Tatiana

2016-01-01

Led jointly by an actress and an occupational therapist, an 'improvisation' activity has been set up within the Sainte-Anne University Hospital SHU Sector 14 for hospitalised patients, on medical prescription. This containing environment provides psychological support and encourages patients with schizophrenia to explore their creativity and to 'let go' so as to discover new physical possibilities. The group thereby becomes a support for the relationship and the development of verbal and non-verbal communication. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Selections from JEN-MIN JIH-PAO, Peiping, on Geology, Exploration, Weather Forecasting, and Cartography.

DTIC Science & Technology

1961-03-06

and area of cultivation land. Otherwise, we cannot keep an accurate account of land and Water, and in the straight - line planning there will be...of production. If we let the masses possess a production direction map and the straight - line planning method, and at the same time formulate them...supplies needed, we not only can use these as the basis for straight - line planning, but we also can list the results attained by straight - line planning

Therapeutic Inhibitors of LIN28/let-7 Pathway in Ovarian Cancer

DTIC Science & Technology

2015-09-01

of-function cell lines to complement our already generated shRNA lines, we are developing handson experience with CrispR /Cas9 technology to...generate stable cell lines where our genes of interest will be inactivated. The advantage of the CrispR /Cas9 method is that stable lines can be...ovarian cancer cell lines using two distinct RNAi methods, shRNA and siRNA. We plan to explore the feasibility of using the CrispR /Cas9 system to

Cognitive Support for Transportation Planners: A Collaborative Course of Action Exploration Tool

DTIC Science & Technology

2011-06-01

smaller problem . We chose to work with MIDAS , for the pragmatic reason that MIDAS developers were at Raytheon BBN Technologies, and were accessible to...overall framework we built up to let the planner interact with MIDAS . In [Scott, 2009b], the problem under discussion is the design of a “Joint...previously been used for and what we now want to use it for - we are using MIDAS for a set of problems for which it has not previously been used. It

Virtual Space Exploration: Let's Use Web-Based Computer Game Technology to Boost IYA 2009 Public Interest

NASA Astrophysics Data System (ADS)

Hussey, K.; Doronila, P.; Kulikov, A.; Lane, K.; Upchurch, P.; Howard, J.; Harvey, S.; Woodmansee, L.

2008-09-01

With the recent releases of both Google's "Sky" and Microsoft's "WorldWide Telescope" and the large and increasing popularity of video games, the time is now for using these tools, and those crafted at NASA's Jet Propulsion Laboratory, to engage the public in astronomy like never before. This presentation will use "Cassini at Saturn Interactive Explorer " (CASSIE) to demonstrate the power of web-based video-game engine technology in providing the public a "first-person" look at space exploration. The concept of virtual space exploration is to allow the public to "see" objects in space as if they were either riding aboard or "flying" next to an ESA/NASA spacecraft. Using this technology, people are able to immediately "look" in any direction from their virtual location in space and "zoom-in" at will. Users can position themselves near Saturn's moons and observe the Cassini Spacecraft's "encounters" as they happened. Whenever real data for their "view" exists it is incorporated into the scene. Where data is missing, a high-fidelity simulation of the view is generated to fill in the scene. The observer can also change the time of observation into the past or future. Our approach is to utilize and extend the Unity 3d game development tool, currently in use by the computer gaming industry, along with JPL mission specific telemetry and instrument data to build our virtual explorer. The potential of the application of game technology for the development of educational curricula and public engagement are huge. We believe this technology can revolutionize the way the general public and the planetary science community views ESA/NASA missions and provides an educational context that is attractive to the younger generation. This technology is currently under development and application at JPL to assist our missions in viewing their data, communicating with the public and visualizing future mission plans. Real-time demonstrations of CASSIE and other applications in development will be shown. Astronomy is one of the oldest basic sciences. We should use one of today's newest communications technologies available to engage the public. We should embrace the use of web-based gaming technology to prepare the world for the International Year of Astronomy 2009.

Radiosensitivity and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study

PubMed Central

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

2014-01-01

Cancer treatment with high LET heavy ion beam, especially, carbon ion beam (12C), is becoming very popular over conventional radiotherapy like low LET gamma or X-ray. Combination of Poly(ADP-ribose) polymerase (PARP) inhibitor with xenotoxic drugs or conventional radiation (gamma or X-ray) is the newer approach for cancer therapy. The aim of our study was to compare the radiosensitivity and induction of apoptosis by high LET 12C and low LET gamma radiation in HeLa and PARP-1 knocked down cells. We did comet assay to detect DNA breaks, clonogenic survival assay, and cell cycle analysis to measure recovery after DNA damage. We measured apoptotic parameters like nuclear fragmentation and caspase-3 activation. DNA damage, cell killing, and induction of apoptosis were significantly higher for 12C than gamma radiation in HeLa. Cell killing and apoptosis were further elevated upon knocking down of PARP-1. Both 12C and gamma induced G2/M arrest although the 12C had greater effect. Unlike the gamma, 12C irradiation affects DNA replication as detected by S-phase delay in cell cycle analysis. So, we conclude that high LET 12C has greater potential over low LET gamma radiation in killing cells and radiosensitization upon PARP-1 inhibition was several folds greater for 12C than gamma. PMID:25018892

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

PubMed Central

Price, Kari L.; Rose, Lesilee S.

2017-01-01

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. PMID:28701343

WE-FG-202-09: Voxel-Level Analysis of Adverse Treatment Response in Pediatric Patients Treated for Ependymoma with Passive Scattering Proton Therapy

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

Peeler, C; The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX; Mirkovic, D

2016-06-15

Purpose: We identified patients treated for ependymoma with passive scattering proton therapy who subsequently developed treatment-related imaging changes on MRI. We sought to determine if there is any spatial correlation between imaged response, dose, and LET. Methods: A group of 14 patients treated for ependymoma were identified as having post-treatment MR imaging changes observable as T2-FLAIR hyperintensity with or without enhancement on T1 post-contrast sequences. MR images were registered with treatment planning CT images and regions of treatment-related change contoured by a practicing radiation oncologist. The contoured regions were identified as response with voxels represented as 1 while voxels withinmore » the brain outside of the response region were represented as 0. An in-house Monte Carlo system was used to recalculate treatment plans to obtain dose and LET information. Voxels were binned according to LET values in 0.3 keV µm{sup −1} bins. Dose and corresponding response value (0 or 1) for each voxel for a given LET bin were then plotted and fit with the Lyman-Kutcher-Burman dose response model to determine TD{sub 50} and m parameters for each LET value. Response parameters from all patients were then collated, and linear fits of the data were performed. Results: The response parameters TD50 and m both show trends with LET. Outliers were observed due to low numbers of response voxels in some cases. TD{sub 50} values decreased with LET while m increased with LET. The former result would indicate that for higher LET values, the dose is more effective, which is consistent with relative biological effectiveness (RBE) models for proton therapy. Conclusion: A novel method of voxel-level analysis of image biomarker-based adverse patient treatment response in proton therapy according to dose and LET has been presented. Fitted TD{sub 50} values show a decreasing trend with LET supporting the typical models of proton RBE. Funding provided by NIH Program Project Grant 2U19CA021239-35.« less

A phenomenological biological dose model for proton therapy based on linear energy transfer spectra.

PubMed

Rørvik, Eivind; Thörnqvist, Sara; Stokkevåg, Camilla H; Dahle, Tordis J; Fjaera, Lars Fredrik; Ytre-Hauge, Kristian S

2017-06-01

The relative biological effectiveness (RBE) of protons varies with the radiation quality, quantified by the linear energy transfer (LET). Most phenomenological models employ a linear dependency of the dose-averaged LET (LET d ) to calculate the biological dose. However, several experiments have indicated a possible non-linear trend. Our aim was to investigate if biological dose models including non-linear LET dependencies should be considered, by introducing a LET spectrum based dose model. The RBE-LET relationship was investigated by fitting of polynomials from 1st to 5th degree to a database of 85 data points from aerobic in vitro experiments. We included both unweighted and weighted regression, the latter taking into account experimental uncertainties. Statistical testing was performed to decide whether higher degree polynomials provided better fits to the data as compared to lower degrees. The newly developed models were compared to three published LET d based models for a simulated spread out Bragg peak (SOBP) scenario. The statistical analysis of the weighted regression analysis favored a non-linear RBE-LET relationship, with the quartic polynomial found to best represent the experimental data (P = 0.010). The results of the unweighted regression analysis were on the borderline of statistical significance for non-linear functions (P = 0.053), and with the current database a linear dependency could not be rejected. For the SOBP scenario, the weighted non-linear model estimated a similar mean RBE value (1.14) compared to the three established models (1.13-1.17). The unweighted model calculated a considerably higher RBE value (1.22). The analysis indicated that non-linear models could give a better representation of the RBE-LET relationship. However, this is not decisive, as inclusion of the experimental uncertainties in the regression analysis had a significant impact on the determination and ranking of the models. As differences between the models were observed for the SOBP scenario, both non-linear LET spectrum- and linear LET d based models should be further evaluated in clinically realistic scenarios. © 2017 American Association of Physicists in Medicine.

Using Case Studies to Teach Interdisciplinary Water Resource Sustainability

NASA Astrophysics Data System (ADS)

Orr, C. H.; Tillotson, K.

2012-12-01

Teaching about water resources and often emphasizes the biophysical sciences to understand highly complex hydrologic, ecologic and engineering systems, yet most impediments to improving management emerge from social processes. Challenges to more sustainable management often result from trade-offs among stakeholders (e.g., ecosystem services, energy, municipal use, and agriculture) and occur while allocating resources to competing goals of economic development, social equity, and efficient governance. Competing interests operating across multiple scales can increase tensions and prevent collaborative resolution of resource management problems. Here we discuss using specific, place-based cases to teach the interdisciplinary context of water management. Using a case approach allows instructors to first explore the geologic and hydrologic setting of a specific problem to let students understand where water comes from, then how it is used by people and ecosystems, and finally what conflicts arise from mismatches between water quality, quantity, timing, human demand, and ecosystem needs. The case approach helps students focus on specific problem to understand how the landscape influences water availability, without needing to first learn everything about the relevant fields. We look at geology, hydrology and climate in specific watersheds before addressing the human and ecosystem aspects of the broader, integrated system. This gives students the context to understand what limits water availability and how a water budget constrains possible solutions to sustainability problems. It also mimics the approach we have taken in research addressing these problems. In an example case the Spokane Coeur D'Alene basin, spanning the border between SE Washington and NW Idaho, includes a sole source aquifer system with high exchange between surface water and a highly conductive aquifer. The Spokane River does not meet water quality standards and is likely to face climate driven shifts in precipitation which will alter both water availability and dilution capacity. Possible stakeholders include not only municipal, agricultural and industrial water users but also several levels of regulatory governance as the watershed crosses state lines and includes tribal lands. While the water system is bound by the limits of stratigraphy and hydrology, there are feedbacks to the physical system revealed feedbacks to the physical system resulting from decisions, preferences, and beliefs of the stakeholders. The complexity of these feedbacks are most easily explored through discussion of the specific case, which can then be generalized. The course design encourages participation and let students discuss, argue, and think critically about real problems they can identify with and that interest them. Walking through the cases shows students how complicated environmental problem-solving can be in a way that they internalize and how these ideas are then transferable to other situations.

Biomedical effects of protons with different levels of LET

NASA Astrophysics Data System (ADS)

Bulinina, Taisia; Vorozhtsova, Svetlana; Abrosimova, Alla; Ivanov, Alexander; Molokanov, Alexander

Protons compose 80% of space radiation, thus, if the average energy of protons is 45 MeV, then there is a proton range much differing on the LET level available. In this regard, the study of protons radiobiological effects with different levels of LET is relevant. On the basis of the JINR Phasotron we designed the special device allowing to irradiate experimental animals - mice at the various regions of proton beam differing more than 3 times on the level of LET. The experiments were carried out on outbred CD-1 females mice and C57Bl6 males. Animals were irradiated at two points of the depth dose distribution - at the entrance of the proton beam and at the modified Bragg peak, extended with a ridge filter. Total irradiation of mice was conducted by a proton beam with energy of 171 MeV at doses of 1.0, 2.5 and 5.0 Gy at the JINR Phasotron beam, is used for the treatment of patients. LET of 171 MeV protons was 0.49 keV/mkm, the dose rate was 0.37 Gy/min. Range of energy at the modified Bragg peak is 0-30 MeV. Dose rate was 0.8 Gy/min. Average value of LET at the modified Bragg peak was 1.6 keV/mkm. In the modified Bragg peak the contribution to the absorbed dose of protons with low-LET radiation was about 67%, with LET 25-50 keV/mkm was 23% and with high -LET (50-100 keV/mkm) was 10%. For comparison irradiation of 60Co γ-rays was conducted on the device for remote radiation therapy Rokus-M MTC JINR in the same doses. The average dose of (60) Co gammaγ-rays with LET of 0.3 keV/mkm was 1 Gy/min. The experiments showed that after 24 hours of both proton irradiation with a high level of LET, and with 171 MeV proton beam in the object, a clear dose-dependent loss of bone marrow hematopoiesis is observed, the depth of destruction after irradiation by protons with a high level of increased from 1.14 to 1.36 with increasing doses of irradiation from 1.0 to 5.0 Gy. Restoration of bone marrow cellularity by the 8th day after exposure also was reduced in mice irradiated by protons with a high level of LET. After irradiation at a dose of 5.0 Gy with a high level of LET we noted deeper defeat of the cytogenetic apparatus of bone marrow cells and slow elimination of chromosomal aberrations in comparison with protons at the entrance of the object and gammaγ-rays (60) Co. The distinction in the defeat and the restoration of the number of white blood cells in the peripheral blood, thymus and spleen had a more complicated character. The obtained results showed that the striking effects of protons with a high level of LET radiation are significantly higher in comparison with other groups: mice irradiated by protons with LET 0.49 keV/mkm and gammaγ-rays (60) Co with LET 0.3 keV/mkm.

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.

PubMed

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.

SU-E-T-354: Peak Temperature Ratio of TLD Glow Curves to Investigate the Spatial Dependence of LET in a Clinical Proton Beam

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

Reft, C; Pankuch, M; Ramirez, H

Purpose: Use the ratio of the two high temperature peaks (HTR) in TLD 700 glow curves to investigate spatial dependence of the linear energy transfer (LET) in proton beams. Studies show that the relative biological effectiveness (RBE) depends upon the physical dose as well as its spatial distribution. Although proton therapy uses a spatially invariant RBE of 1.1, studies suggest that the RBE increases in the distal edge of a spread out Bragg peak (SOBP) due to the increased LET. Methods: Glow curve studies in TLD 700 show that the 280 C temperature peak is more sensitive to LET radiationmore » than the 210 C temperature peak. Therefore, the areas under the individual temperature peaks for TLDs irradiated in a proton beam normalized to the peak ratio for 6 MV photons are used to determine the HTR to obtain information on its LET. TLD 700 chips with dimensions 0.31×0.31×0.038 cc are irradiated with 90 MeV protons at varying depths in a specially designed blue wax phantom to investigate LET spatial dependence. Results: Five TLDs were placed at five different depths of the percent depth dose curve (PDD) of range 16.2 cm: center of the SOPB and approximately at the 99% distal edge, 90%, 75% and 25% of the PDD, respectively. HTR was 1.3 at the center of the SOBP and varied from 2.2 to 3.9 which can be related to an LET variation from 0.5 to 18 KeV/μ via calibration with radiation beams of varying LET. Conclusion: HTR data show a spatially invariant LET slightly greater than the 6 MV radiations in the SOBP, but a rapidly increasing LET at the end of the proton range. These results indicate a spatial variation in RBE with potential treatment consequences when selecting treatment margins to minimize the uncertainties in proton RBE.« less

Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission.

PubMed

McMillan, Dayton D; Maeda, Junko; Bell, Justin J; Genet, Matthew D; Phoonswadi, Garrett; Mann, Kelly A; Kraft, Susan L; Kitamura, Hisashi; Fujimori, Akira; Yoshii, Yukie; Furukawa, Takako; Fujibayashi, Yasuhisa; Kato, Takamitsu A

2015-09-01

Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a (64)Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of (64)Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from (64)Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair-deficient xrs5 cells were exposed to (64)Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D(10) values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that (64)Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from (64)Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after (64)Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that (64)Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of (64)Cu-ATSM as a cancer treatment modality for hypoxic tumors. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

A model for the relative biological effectiveness of protons: the tissue specific parameter α/β of photons is a predictor for the sensitivity to LET changes.

PubMed

Wedenberg, Minna; Lind, Bengt K; Hårdemark, Björn

2013-04-01

The biological effects of particles are often expressed in relation to that of photons through the concept of relative biological effectiveness, RBE. In proton radiotherapy, a constant RBE of 1.1 is usually assumed. However, there is experimental evidence that RBE depends on various factors. The aim of this study is to develop a model to predict the RBE based on linear energy transfer (LET), dose, and the tissue specific parameter α/β of the linear-quadratic model for the reference radiation. Moreover, the model should capture the basic features of the RBE using a minimum of assumptions, each supported by experimental data. The α and β parameters for protons were studied with respect to their dependence on LET. An RBE model was proposed where the dependence of LET is affected by the (α/β)phot ratio of photons. Published cell survival data with a range of well-defined LETs and cell types were selected for model evaluation rendering a total of 10 cell lines and 24 RBE values. A statistically significant relation was found between α for protons and LET. Moreover, the strength of that relation varied significantly with (α/β)phot. In contrast, no significant relation between β and LET was found. On the whole, the resulting RBE model provided a significantly improved fit (p-value < 0.01) to the experimental data compared to the standard constant RBE. By accounting for the α/β ratio of photons, clearer trends between RBE and LET of protons were found, and our results suggest that late responding tissues are more sensitive to LET changes than early responding tissues and most tumors. An advantage with the proposed RBE model in optimization and evaluation of treatment plans is that it only requires dose, LET, and (α/β)phot as input parameters. Hence, no proton specific biological parameters are needed.

FLOWS WITH CROSS SECTIONS

PubMed Central

Verjovsky, Alberto

1970-01-01

Let M be a compact connected C∞-manifold, of dimension n, without boundary. Let ft: M → M be a Cr-flow with cross section. Let Dr(M) be the topological group of diffeomorphisms of M with Cr-topology (1 ≤ r ≤ ∞) and let Dor(M) be its connected component of the identity. Let [unk](M) be the group of I-cobordism classes in Dr(M) generated by orientation-preserving diffeomorphisms. For fεDr(M) denote by [f] its I-cobordism class. Theorem 1 deals with the dependence of M(f) on [f]. Theorem 2: S6 × S1 has at least 28 distinct differentiable structures. Let xoεS1 and let [unk]r be the set of Cr-flows (r ≥ 1) in M × S1 with cross section M × {xo} and inducing in it the identity. Theorem 3: Intuitively to a loop in Dor based at the identity there corresponds a flow in [unk]r, and to homotopic loops correspond isotopic flows. COROLLARY. complete analysis of [unk]r/ [unk] for dim M = 2. Theorems 4 and 5 refer to Anosov flows for dim M > 3. PMID:16591849

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

PubMed

Hada, Megumi; Wu, Honglu; Cucinotta, Francis A

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. 2011 Elsevier B.V. All rights reserved.

Displacement Damage Induced Catastrophic Second Breakdown in Silicon Carbide Schottky Power Diodes

NASA Technical Reports Server (NTRS)

Scheick, Leif; Selva, Luis; Selva, Luis

2004-01-01

A novel catastrophic breakdown mode in reversed biased Silicon carbide diodes has been seen for low LET particles. These particles are too low in LET to induce SEB, however SEB was seen from particles of higher LET. The low LET mechanism correlates with second breakdown in diodes due to increase leakage and assisted charge injection from incident particles. Percolation theory was used to predict some basic responses of the devices, but the inherent reliability issue with silicon carbide have proven challenging.

Let Our Powers Combine! Harnessing NASA's Earth Observatory Natural Event Tracker (EONET) in Worldview

NASA Technical Reports Server (NTRS)

Wong, Min Minnie; Ward, Kevin; Boller, Ryan; Gunnoe, Taylor; Baynes, Kathleen; King, Benjamin

2016-01-01

Constellations of NASA Earth Observing System (EOS) satellites orbit the earth to collect images and data about the planet in near real-time. Within hours of satellite overpass, you can discover where the latest wildfires, severe storms, volcanic eruptions, and dust and haze events are occurring using NASA's Worldview web application. By harnessing a repository of curated natural event metadata from NASA Earth Observatory's Natural Event Tracker (EONET), Worldview has moved natural event discovery to the forefront and allows users to select events-of-interest from a curated list, zooms to the area, and adds the most relevant imagery layers for that type of natural event. This poster will highlight NASA Worldviews new natural event feed functionality.

i3Drive, a 3D interactive driving simulator.

PubMed

Ambroz, Miha; Prebil, Ivan

2010-01-01

i3Drive, a wheeled-vehicle simulator, can accurately simulate vehicles of various configurations with up to eight wheels in real time on a desktop PC. It presents the vehicle dynamics as an interactive animation in a virtual 3D environment. The application is fully GUI-controlled, giving users an easy overview of the simulation parameters and letting them adjust those parameters interactively. It models all relevant vehicle systems, including the mechanical models of the suspension, power train, and braking and steering systems. The simulation results generally correspond well with actual measurements, making the system useful for studying vehicle performance in various driving scenarios. i3Drive is thus a worthy complement to other, more complex tools for vehicle-dynamics simulation and analysis.

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

Giantsoudi, D; Adams, J; MacDonald, S

Purpose: In proton radiation therapy of posterior fossa tumors, to spare other sensitive structures, the preferred beam geometry results in placing the treatment field distal edge within or just beyond the brainstem, including in at least partially in the treatment volume. Concerns for brainstem toxicity are increased and a controversy exists as to weather the beam’s distal edge should be placed within the brainstem or beyond it, to avoid elevated linear energy transfer (LET) and relative biological effectiveness (RBE) within the brainstem. The dosimetric efficacy of these techniques was examined, accounting for LET- and dose-dependent variable RBE distributions. Methods: Threemore » treatment planning techniques were applied in six ependymoma cases: (a) three-field dose-sparing, with beams’ distal edge within the brainstem; (b) three-field LET-sparing, using same beam directions as (a) but extended field ranges beyond the brainstem; (c) two-posterior-oblique LET-sparing, with extended ranges as (b). Monte Carlo calculated dose, LET and RBE-weighted dose distributions were compared. Results: Lower LET values in the brainstem were accompanied by higher median dose: 53.7 Gy[RBE] and 54.3 Gy[RBE] for techniques (b) and (c) versus 52.1 Gy[RBE] for (a). Accounting for variable RBE, a 15% increase of the brainstem volume receiving at least 60 Gy[RBE] was observed for technique (c) versus (a). Maximum variable-RBE-weighted brainstem dose was comparable for all techniques. Conclusion: Extending the treatment beam range beyond the brainstem, significantly increased its volume receiving high dose radiation, even when accounting for the decreased LET values. The dosimetric benefits of techniques limiting the brainstem dose may outweigh the impact of LET reduction achieved through this technique, especially since clinical consequences of increased LET at the end of range have not been proven yet.« less

Let Us Use LET: A Quality Improvement Initiative.

PubMed

Sherman, Joshua M; Sheppard, Patrick; Hoppa, Eric; Krief, William; Avarello, Jahn

2016-07-01

Well-managed pain is associated with faster recovery, fewer complications, and decreased use of resources. In children, pain relief is also associated with higher patient and parent satisfaction. Studies have shown that there are deficiencies in pediatric pain management. LET gel (lidocaine 4%, epinephrine 0.1%, and tetracaine 0.5%) is a topical anesthetic that is routinely used before laceration repair. The aim of this study was to determine if educational initiatives as part of a quality improvement initiative lead to increased rates of early topical anesthetic usage in a large urban pediatric emergency department. The initiative consisted of an educational session and a triage booth poster. We then reviewed the charts of patients with facial and scalp lacerations for the month before the initiative, the month after the initiative, and 1 year after the initiative. We assessed if LET gel usage and time to administration improved and were sustainable. We reviewed 138 charts. Before the initiative, only 57.4% received LET gel before facial laceration repair with a mean time to application of 58.3 minutes. One month after the initiative, there was an increase in LET gel application by 20.1% with a reduction in time to application by 35.9 minutes (P < 0.05). In addition, these improvements were significantly sustainable. One year after the interventions, 82.4% received LET before facial laceration repair, and the time to LET application was 27.8 minutes. Simple educational initiatives can improve the use of topical anesthetics. By using educational tools as part of a quality improvement initiative, we were able to significantly improve the rates of LET gel application for facial lacerations in children and decrease the time to administration.

Let-7a modulates particulate matter (≤ 2.5 μm)-induced oxidative stress and injury in human airway epithelial cells by targeting arginase 2.

PubMed

Song, Lei; Li, Dan; Gu, Yue; Li, Xiaoping; Peng, Liping

2016-10-01

Epidemiological studies show that particulate matter (PM) with an aerodynamic diameter ≤ 2.5 μm (PM2.5) is associated with cardiorespiratory diseases via the induction of excessive oxidative stress. However, the precise mechanism underlying PM2.5-mediated oxidative stress injury has not been fully elucidated. Accumulating evidence has indicated the microRNA let-7 family might play a role in PM-mediated pathological processes. In this study, we investigated the role of let-7a in oxidative stress and cell injury in human bronchial epithelial BEAS2B (B2B) cells after PM2.5 exposure. The let-7a level was the most significantly decreased in B2B cells after PM2.5 exposure. The overexpression of let-7a suppressed intracellular reactive oxygen species levels and the percentage of apoptotic cells after PM2.5 exposure, while the let-7a level decreased arginase 2 (ARG2) mRNA and protein levels in B2B cells by directly targeting the ARG2 3'-untranslated region. ARG2 expression was upregulated in B2B cells during PM2.5 treatment, and ARG2 knockdown could remarkably reduce oxidative stress and cellular injury. Moreover, its restoration could abrogate the protective effects of let-7a against PM2.5-induced injury. In conclusion, let-7a decreases and ARG2 increases resulting from PM2.5 exposure may exacerbate oxidative stress, cell injury and apoptosis of B2B cells. The let-7a/ARG2 axis is a likely therapeutic target for PM2.5-induced airway epithelial injury. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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

PubMed Central

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

2016-01-01

Purpose 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. Materials and Methods 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. Results 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. Conclusion Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders. PMID:27593875

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

PubMed

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.

Installation of the National Transport Code Collaboration Data Server at the ITPA International Multi-tokamak Confinement Profile Database

NASA Astrophysics Data System (ADS)

Roach, Colin; Carlsson, Johan; Cary, John R.; Alexander, David A.

2002-11-01

The National Transport Code Collaboration (NTCC) has developed an array of software, including a data client/server. The data server, which is written in C++, serves local data (in the ITER Profile Database format) as well as remote data (by accessing one or several MDS+ servers). The client, a web-invocable Java applet, provides a uniform, intuitive, user-friendly, graphical interface to the data server. The uniformity of the interface relieves the user from the trouble of mastering the differences between different data formats and lets him/her focus on the essentials: plotting and viewing the data. The user runs the client by visiting a web page using any Java capable Web browser. The client is automatically downloaded and run by the browser. A reference to the data server is then retrieved via the standard Web protocol (HTTP). The communication between the client and the server is then handled by the mature, industry-standard CORBA middleware. CORBA has bindings for all common languages and many high-quality implementations are available (both Open Source and commercial). The NTCC data server has been installed at the ITPA International Multi-tokamak Confinement Profile Database, which is hosted by the UKAEA at Culham Science Centre. The installation of the data server is protected by an Internet firewall. To make it accessible to clients outside the firewall some modifications of the server were required. The working version of the ITPA confinement profile database is not open to the public. Authentification of legitimate users is done utilizing built-in Java security features to demand a password to download the client. We present an overview of the NTCC data client/server and some details of how the CORBA firewall-traversal issues were resolved and how the user authentification is implemented.

JHelioviewer: Open-Source Software for Discovery and Image Access in the Petabyte Age

NASA Astrophysics Data System (ADS)

Mueller, D.; Dimitoglou, G.; Garcia Ortiz, J.; Langenberg, M.; Nuhn, M.; Dau, A.; Pagel, S.; Schmidt, L.; Hughitt, V. K.; Ireland, J.; Fleck, B.

2011-12-01

The unprecedented torrent of data returned by the Solar Dynamics Observatory is both a blessing and a barrier: a blessing for making available data with significantly higher spatial and temporal resolution, but a barrier for scientists to access, browse and analyze them. With such staggering data volume, the data is accessible only from a few repositories and users have to deal with data sets effectively immobile and practically difficult to download. From a scientist's perspective this poses three challenges: accessing, browsing and finding interesting data while avoiding the proverbial search for a needle in a haystack. To address these challenges, we have developed JHelioviewer, an open-source visualization software that lets users browse large data volumes both as still images and movies. We did so by deploying an efficient image encoding, storage, and dissemination solution using the JPEG 2000 standard. This solution enables users to access remote images at different resolution levels as a single data stream. Users can view, manipulate, pan, zoom, and overlay JPEG 2000 compressed data quickly, without severe network bandwidth penalties. Besides viewing data, the browser provides third-party metadata and event catalog integration to quickly locate data of interest, as well as an interface to the Virtual Solar Observatory to download science-quality data. As part of the ESA/NASA Helioviewer Project, JHelioviewer offers intuitive ways to browse large amounts of heterogeneous data remotely and provides an extensible and customizable open-source platform for the scientific community. In addition, the easy-to-use graphical user interface enables the general public and educators to access, enjoy and reuse data from space missions without barriers.

An Indoor Location-Based Control System Using Bluetooth Beacons for IoT Systems

PubMed Central

Huh, Jun-Ho; Seo, Kyungryong

2017-01-01

The indoor location-based control system estimates the indoor position of a user to provide the service he/she requires. The major elements involved in the system are the localization server, service-provision client, user application positioning technology. The localization server controls access of terminal devices (e.g., Smart Phones and other wireless devices) to determine their locations within a specified space first and then the service-provision client initiates required services such as indoor navigation and monitoring/surveillance. The user application provides necessary data to let the server to localize the devices or allow the user to receive various services from the client. The major technological elements involved in this system are indoor space partition method, Bluetooth 4.0, RSSI (Received Signal Strength Indication) and trilateration. The system also employs the BLE communication technology when determining the position of the user in an indoor space. The position information obtained is then used to control a specific device(s). These technologies are fundamental in achieving a “Smart Living”. An indoor location-based control system that provides services by estimating user’s indoor locations has been implemented in this study (First scenario). The algorithm introduced in this study (Second scenario) is effective in extracting valid samples from the RSSI dataset but has it has some drawbacks as well. Although we used a range-average algorithm that measures the shortest distance, there are some limitations because the measurement results depend on the sample size and the sample efficiency depends on sampling speeds and environmental changes. However, the Bluetooth system can be implemented at a relatively low cost so that once the problem of precision is solved, it can be applied to various fields. PMID:29257044

Let-7b inhibits cancer-promoting effects of breast cancer-associated fibroblasts through IL-8 repression

PubMed Central

Al-Harbi, Bothina; Hendrayani, Siti-Fauziah; Silva, Gabriela; Aboussekhra, Abdelilah

2018-01-01

Cancer-associated fibroblasts (CAFs) are major players in the development and spread of breast carcinomas through non-cell-autonomous signaling. These paracrine effects are under the control of several genes and microRNAs. We present here clear evidence that let-7b, a tumor suppressor microRNA, plays key roles in the persistent activation of breast stromal fibroblasts and their functional interplay with cancer cells. We have first shown that let-7b is down-regulated in CAFs as compared to their corresponding normal adjacent fibroblasts, and transient specific let-7b inhibition permanently activated breast fibroblasts through induction of the IL-6-related positive feedback loop. More importantly, let-7b-deficient cells promoted the epithelial-to-mesenchymal transition process in breast cancer cells in an IL-8-dependent manner, and also enhanced orthotopic tumor growth in vivo. On the other hand, overexpression of let-7b by mimic permanently suppressed breast myofibroblasts through blocking the positive feedback loop, which inhibited their paracrine pro-carcinogenic effects. Furthermore, we have shown that let-7b negatively controls IL-8, which showed higher expression in the majority of CAF cells as compared to their adjacent normal counterparts, indicating that IL-8 plays a major role in the carcinoma/stroma cross-talk. These findings support targeting active stromal fibroblasts through restoration of let-7b/IL-8 expression as a therapeutic option for breast carcinomas. PMID:29707149

Antiandrogen Treatment Ameliorates Reproductive and Metabolic Phenotypes in the Letrozole-Induced Mouse Model of PCOS.

PubMed

Ryan, Genevieve E; Malik, Shaddy; Mellon, Pamela L

2018-04-01

Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by hyperandrogenism, anovulation, and polycystic ovaries. Although its etiology is unknown, excess androgens are thought to be a critical factor driving the pathology of PCOS. We previously demonstrated that continuous exposure to the aromatase inhibitor letrozole (LET) in mice produces many hallmarks of PCOS, including elevated testosterone (T) and luteinizing hormone, anovulation, and obesity. In the current study, we sought to determine whether androgen receptor (AR) actions are responsible for any of the phenotypes observed in LET mice. C57BL/6 female mice were subcutaneously implanted with LET or placebo control and subsequently treated with the nonsteroidal AR antagonist flutamide or vehicle control. Flutamide treatment in LET females reversed elevated T levels and restored ovarian expression of Cyp17a1 (critical for androgen synthesis) to normal levels. Pituitary expression of Lhb was decreased in LET females that received flutamide treatment, with no changes in expression of Fshb or Gnrhr. Flutamide treatment also restored estrous cycling and reduced the number of ovarian cyst-like follicles in LET females. Furthermore, body weight and adipocyte size were decreased in flutamide-treated LET females. Altogether, our findings provide strong evidence that AR signaling is responsible for many key reproductive and metabolic PCOS phenotypes and further establish the LET mouse model as an important tool for the study of androgen excess.

Exploration of ethical debates through Desai's The Inheritance of Loss, Ishiguro's Never Let Me Go and Smith's On Beauty.

PubMed

Misra, Jahnavi

2014-09-01

This essay examines debates over alternative ethical formulations that break from the Kantian model through contemporary fiction--Kiran Desai's The Inheritance of Loss (2006), Kazuo Ishiguro's Never Let Me Go (2005) and Zadie Smith's On Beauty (2005). The essay returns to the theory, the ethics of care, put forward by Carol Gilligan in In a Different Voice (1982), which has regained significance in the context of questions surrounding care in contemporary ethical thinking. While the three novels are concerned with ideas of care, beauty, justice and the tyranny of the mainstream, this essay examines particular themes in particular texts which suggest that ideas with otherwise subversive potential--like care or beauty or justice--lose their radicalism when they are incorporated within the impersonal, masculinist mainstream. Carol Gilligan's feminine ethics of care, with its respect for the particular, is not only still important as the stimulus to thinking about alternatives to overarching ethical discourses, but it could also re-confer these concepts of care, beauty and justice their revolutionary potential.

Nurse faculty experiences in problem-based learning: an interpretive phenomenologic analysis.

PubMed

Paige, Jane B; Smith, Regina O

2013-01-01

This study explored the nurse faculty experience of participating in a problem-based learning (PBL) faculty development program. Utilizing PBL as a pedagogical method requires a paradigm shift in the way faculty think about teaching, learning, and the teacher-student relationship. An interpretive phenomenological analysis approach was used to explore the faculty experience in a PBL development program. Four themes emerged: change in perception of the teacher-student relationship, struggle in letting go, uncertainty, and valuing PBL as a developmental process. Epistemic doubt happens when action and intent toward the PBL teaching perspective do not match underlying beliefs. Findings from this study call for ongoing administrative support for education on PBL while faculty take time to uncover hidden epistemological beliefs.

Goddard In The Galaxy [Music Video

NASA Image and Video Library

2014-07-14

This video highlights the many ways NASA Goddard Space Flight Center explores the universe. So crank up your speakers and let the music be your guide. "My Songs Know What You Did In The Dark (Light Em Up)" Performed by Fall Out Boy Courtesy of Island Def Jam Music Group under license from Universal Music Enterprises Download the video here: svs.gsfc.nasa.gov/goto?11378 NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

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

Krause, Josua; Dasgupta, Aritra; Fekete, Jean-Daniel

Dealing with the curse of dimensionality is a key challenge in high-dimensional data visualization. We present SeekAView to address three main gaps in the existing research literature. First, automated methods like dimensionality reduction or clustering suffer from a lack of transparency in letting analysts interact with their outputs in real-time to suit their exploration strategies. The results often suffer from a lack of interpretability, especially for domain experts not trained in statistics and machine learning. Second, exploratory visualization techniques like scatter plots or parallel coordinates suffer from a lack of visual scalability: it is difficult to present a coherent overviewmore » of interesting combinations of dimensions. Third, the existing techniques do not provide a flexible workflow that allows for multiple perspectives into the analysis process by automatically detecting and suggesting potentially interesting subspaces. In SeekAView we address these issues using suggestion based visual exploration of interesting patterns for building and refining multidimensional subspaces. Compared to the state-of-the-art in subspace search and visualization methods, we achieve higher transparency in showing not only the results of the algorithms, but also interesting dimensions calibrated against different metrics. We integrate a visually scalable design space with an iterative workflow guiding the analysts by choosing the starting points and letting them slice and dice through the data to find interesting subspaces and detect correlations, clusters, and outliers. We present two usage scenarios for demonstrating how SeekAView can be applied in real-world data analysis scenarios.« less

VISTILES: Coordinating and Combining Co-located Mobile Devices for Visual Data Exploration.

PubMed

Langner, Ricardo; Horak, Tom; Dachselt, Raimund

2017-08-29

We present VISTILES, a conceptual framework that uses a set of mobile devices to distribute and coordinate visualization views for the exploration of multivariate data. In contrast to desktop-based interfaces for information visualization, mobile devices offer the potential to provide a dynamic and user-defined interface supporting co-located collaborative data exploration with different individual workflows. As part of our framework, we contribute concepts that enable users to interact with coordinated & multiple views (CMV) that are distributed across several mobile devices. The major components of the framework are: (i) dynamic and flexible layouts for CMV focusing on the distribution of views and (ii) an interaction concept for smart adaptations and combinations of visualizations utilizing explicit side-by-side arrangements of devices. As a result, users can benefit from the possibility to combine devices and organize them in meaningful spatial layouts. Furthermore, we present a web-based prototype implementation as a specific instance of our concepts. This implementation provides a practical application case enabling users to explore a multivariate data collection. We also illustrate the design process including feedback from a preliminary user study, which informed the design of both the concepts and the final prototype.

Diversity in fathers' food parenting practices: A qualitative exploration within a heterogeneous sample.

PubMed

Khandpur, Neha; Charles, Jo; Blaine, Rachel E; Blake, Christine; Davison, Kirsten

2016-06-01

Food parenting practices (FPPs) are important in shaping children's dietary behaviors. However, existing FPP knowledge is largely based on research with mothers. This study (1) identified fathers' FPPs; (2) described differences in FPP use by fathers' education and residential status. Semi-structured interviews were conducted with 40 fathers (39 ± 9.1 years; 37.5% non-residential; 40% ≥college education). Interviews were audio-recorded and transcribed. NVivo 10 was used for theme detection, categorization and classification using inductive and deductive approaches. FPPs were identified and their relative distribution was examined across education and residential status. Twenty FPPs were identified - 13 responsive practices and 7 unresponsive practices. Having food rules was the most common responsive FPP (81.5%), followed by feeding on schedule (60%) and making healthy food accessible (60%). Common unresponsive FPPs were letting child dictate preferences (70%), incentivizing food consumption (60%) and pressuring the child to eat (35%). Compared to fathers with a college education, more fathers without a college education reported letting child dictate preferences (92% vs. 37%), educating their children about food (37% vs 12%), fewer reported feeding on schedule (50% vs. 75%), modeling healthy practices (29% vs. 50%), and using distraction to feed (4% vs. 37%). Compared to residential fathers, more non-residential fathers monitored (60% vs. 40%) or encouraged (60% vs. 36%) child food intake and let child dictate preferences (87% vs. 60%). Fathers used an extensive variety of FPPs, similar to those identified in mothers. Further study on the influence of fathers' education and residential status on FPP use is warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of the Functional microRNA Expression in Immune Cell Subsets of Neonates and Adults

PubMed Central

Yu, Hong-Ren; Hsu, Te-Yao; Huang, Hsin-Chun; Kuo, Ho-Chang; Li, Sung-Chou; Yang, Kuender D.; Hsieh, Kai-Sheng

2016-01-01

Diversity of biological molecules in newborn and adult immune cells contributes to differences in cell function and atopic properties. Micro RNAs (miRNAs) are reported to involve in the regulation of immune system. Therefore, determining the miRNA expression profile of leukocyte subpopulations is important for understanding immune system regulation. In order to explore the unique miRNA profiling that contribute to altered immune in neonates, we comprehensively analyzed the functional miRNA signatures of eight leukocyte subsets (polymorphonuclear cells, monocytes, CD4+ T cells, CD8+ T cells, natural killer cells, B cells, plasmacytoid dendritic cells, and myeloid dendritic cells) from both neonatal and adult umbilical cord and peripheral blood samples, respectively. We observed distinct miRNA profiles between adult and neonatal blood leukocyte subsets, including unique miRNA signatures for each cell lineage. Leukocyte miRNA signatures were altered after stimulation. Adult peripheral leukocytes had higher let-7b-5p expression levels compared to neonatal cord leukocytes across multiple subsets, irrespective of stimulation. Transfecting neonatal monocytes with a let-7b-5p mimic resulted in a reduction of LPS-induced interleukin (IL)-6 and TNF-α production, while transfection of a let-7b-5p inhibitor into adult monocytes enhanced IL-6 and TNF-α production. With this functional approach, we provide intact differential miRNA expression profiling of specific immune cell subsets between neonates and adults. These studies serve as a basis to further understand the altered immune response observed in neonates and advance the development of therapeutic strategies. PMID:28066425

Circulating microRNAs in follicular fluid, powerful tools to explore in vitro fertilization process.

PubMed

Scalici, E; Traver, S; Mullet, T; Molinari, N; Ferrières, A; Brunet, C; Belloc, S; Hamamah, S

2016-04-22

Circulating or "extracellular" microRNAs (miRNAs) detected in biological fluids, could be used as potential diagnostic and prognostic biomarkers of several disease, such as cancer, gynecological and pregnancy disorders. However, their contributions in female infertility and in vitro fertilization (IVF) remain unknown. This study investigated the expression profiles of five circulating miRNAs (let-7b, miR-29a, miR-30a, miR-140 and miR-320a) in human follicular fluid from 91 women with normal ovarian reserve and 30 with polycystic ovary syndrome (PCOS) and their ability to predict IVF outcomes. The combination of FF miR-30a, miR-140 and let-7b expression levels discriminated between PCOS and normal ovarian reserve with a specificity of 83.8% and a sensitivity of 70% (area under the ROC curve, AUC = 0.83 [0.73-0.92]; p < 0.0001). FF samples related to low number of mature oocytes (≤2) contained significant less miR-320a levels than those related to a number of mature oocytes >2 (p = 0.04). Moreover, FF let-7b predicted the development of expanded blastocysts with 70% sensitivity and 64.3% specificity (AUC = 0.67 [0.54-0.79]; p = 0.02) and FF miR-29a potential to predict clinical pregnancy outcome reached 0.68 [0.55-0.79] with a sensitivity of 83.3% and a specificity of 53.5% (p = 0.01). Therefore, these miRNAs could provide new helpful biomarkers to facilitate personalized medical care during IVF.

Let him not be alone: perspectives of older British South Asian minority ethnic patients on dying in acute hospitals.

PubMed

Venkatasalu, Munikumar Ramasamy

2017-09-02

To investigate older British South Asians' views on dying at acute hospitals. Older people, including those from ethnic minorities prefer 'home as a haven' for their last days of life; however, they are more likely to die in hospital. Constructive grounded theory was used as a methodological approach that informed data collection to data analysis. Open meetings with 11 local South Asian community organisations enabled the researchers to recruit a total of 55 older South Asians in this study. Data were collected using gender-based focus groups (n=5) and in-depth, semi-structured interviews (n=29). Transcripts were analysed using Nvivo 9. Three key themes were identified: 'mistrust', 'let him not be alone' and 'family as a protective shield'. The theme 'mistrust' is explored through examination of beliefs, attitudes and expectations about 'hospital' as a place in the care of the dying. The theme of 'let him not be alone' draws the family's preferences and concerns in relation to leaving their older dying relative alone in the hospital. The final theme of 'family as a protective shield' describes the element of family care as a protective shield for their older one to have peaceful end-of-life care moments in the hospital. Allowing older relatives to die in hospital seems to evoke feelings of missed filial responsibilities and guilt among family carers among older ethnic minorities. The presence of cultural paranoia and mistrust often led minorities to experience sub-standard end-of-life care in acute hospitals.

Diversity in fathers’ food parenting practices: A qualitative exploration within a heterogeneous sample

PubMed Central

Khandpur, Neha; Charles, Jo; Blaine, Rachel E.; Blake, Christine; Davison, Kirsten

2017-01-01

Background Food parenting practices (FPPs) are important in shaping children’s dietary behaviors. However, existing FPP knowledge is largely based on research with mothers. Purpose This study (1) identified fathers’ FPPs; (2) described differences in FPP use by fathers’ education and residential status. Methods Semi-structured interviews were conducted with 40 fathers (39 ± 9.1 years; 37.5% non-residential; 40% ≥college education). Interviews were audio-recorded and transcribed. NVivo 10 was used for theme detection, categorization and classification using inductive and deductive approaches. FPPs were identified and their relative distribution was examined across education and residential status. Results Twenty FPPs were identified - 13 responsive practices and 7 unresponsive practices. Having food rules was the most common responsive FPP (81.5%), followed by feeding on schedule (60%) and making healthy food accessible (60%). Common unresponsive FPPs were letting child dictate preferences (70%), incentivizing food consumption (60%) and pressuring the child to eat (35%). Compared to fathers with a college education, more fathers without a college education reported letting child dictate preferences (92% vs. 37%), educating their children about food (37% vs 12%), fewer reported feeding on schedule (50% vs. 75%), modeling healthy practices (29% vs. 50%), and using distraction to feed (4% vs. 37%). Compared to residential fathers, more non-residential fathers monitored (60% vs. 40%) or encouraged (60% vs. 36%) child food intake and let child dictate preferences (87% vs. 60%). Conclusions Fathers used an extensive variety of FPPs, similar to those identified in mothers. Further study on the influence of fathers’ education and residential status on FPP use is warranted. PMID:26930383

MTVis: tree exploration using a multitouch interface

NASA Astrophysics Data System (ADS)

Andrews, David; Teoh, Soon Tee

2010-01-01

We present MTVis, a multi-touch interactive tree visualization system. The multi-touch interface display hardware is built using the LED-LP technology, and the tree layout is based on RINGS, but enhanced with multitouch interactions. We describe the features of the system, and how the multi-touch interface enhances the user's experience in exploring the tree data structure. In particular, the multi-touch interface allows the user to simultaneously control two child nodes of the root, and rotate them so that some nodes are magnified, while preserving the layout of the tree. We also describe the other meaninful touch screen gestures the users can use to intuitively explore the tree.

CET exSim: mineral exploration experience via simulation

NASA Astrophysics Data System (ADS)

Wong, Jason C.; Holden, Eun-Jung; Kovesi, Peter; McCuaig, T. Campbell; Hronsky, Jon

2013-08-01

Undercover mineral exploration is a challenging task as it requires understanding of subsurface geology by relying heavily on remotely sensed (i.e. geophysical) data. Cost-effective exploration is essential in order to increase the chance of success using finite budgets. This requires effective decision-making in both the process of selecting the optimum data collection methods and in the process of achieving accuracy during subsequent interpretation. Traditionally, developing the skills, behaviour and practices of exploration decision-making requires many years of experience through working on exploration projects under various geological settings, commodities and levels of available resources. This implies long periods of sub-optimal exploration decision-making, before the necessary experience has been successfully obtained. To address this critical industry issue, our ongoing research focuses on the development of the unique and novel e-learning environment, exSim, which simulates exploration scenarios where users can test their strategies and learn the consequences of their choices. This simulator provides an engaging platform for self-learning and experimentation in exploration decision strategies, providing a means to build experience more effectively. The exSim environment also provides a unique platform on which numerous scenarios and situations (e.g. deposit styles) can be simulated, potentially allowing the user to become virtually familiarised with a broader scope of exploration practices. Harnessing the power of computer simulation, visualisation and an intuitive graphical user interface, the simulator provides a way to assess the user's exploration decisions and subsequent interpretations. In this paper, we present the prototype functionalities in exSim including: simulation of geophysical surveys, follow-up drill testing and interpretation assistive tools.

High-LET radiation-induced aberrations in prematurely condensed G2 chromosomes of human fibroblasts

NASA Technical Reports Server (NTRS)

Kawata, T.; Gotoh, E.; Durante, M.; Wu, H.; George, K.; Furusawa, Y.; Cucinotta, F. A.; Dicello, J. F. (Principal Investigator)

2000-01-01

PURPOSE: To determine the number of initial chromatid breaks induced by low- or high-LET irradiations, and to compare the kinetics of chromatid break rejoining for radiations of different quality. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290MeV/u), silicon (490MeV/u) and iron (200 and 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Chromatid breaks and exchanges in G2 cells were scored. PCC were collected after several post-irradiation incubation times, ranging from 5 to 600 min. RESULTS: The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components representing a rapid and a slow time constant. Chromatid breaks decreased rapidly during the first 10min after exposure, then continued to decrease at a slower rate. The rejoining kinetics were similar for exposure to each type of radiation. Chromatid exchanges were also formed quickly. Compared to low-LET radiation, isochromatid breaks were produced more frequently and the proportion of unrejoined breaks was higher for high-LET radiation. CONCLUSIONS: Compared with gamma-rays, isochromatid breaks were observed more frequently in high-LET irradiated samples, suggesting that an increase in isochromatid breaks is a signature of high-LET radiation exposure.

LETS: Lunar Environments Test System

NASA Technical Reports Server (NTRS)

Vaughn, Jason A.; Schneider, Todd; Craven, Paul; Norwood, Joey

2008-01-01

The Environmental Effects Branch (EM50) at the Marshall Space Flight Center has developed a unique capability within the agency, namely the Lunar Environment Test System (LETS). LETS is a cryo-pumped vacuum chamber facility capable of high vacuum (10-7 Torr). LETS is a cylindrical chamber, 30 in. (0.8 m) diameter by 48 in. (1.2 m) long thermally controlled vacuum system. The chamber is equipped with a full array of radiation sources including vacuum ultraviolet, electron, and proton radiation. The unique feature of LETS is that it contains a large lunar simulant bed (18 in. x 40 in. x 6 in.) holding 75 kg of JSC-1a simulant while operating at a vacuum of 10-7 Torr. This facility allows three applications: 1) to study the charging, levitation and migration of dust particles, 2) to simulate the radiation environment on the lunar surface, and 3) to electrically charge the lunar simulant enhancing the attraction and adhesion of dust particles to test articles more closely simulating the lunar surface dust environment. LETS has numerous diagnostic instruments including TREK electrostatic probes, residual gas analyzer (RGA), temperature controlled quartz crystal microbalance (TQCM), and particle imaging velocimeter (PIV). Finally, LETS uses continuous Labview data acquisition for computer monitoring and system control.

Effects of target fragmentation on evaluation of LET spectra from space radiations: implications for space radiation protection studies

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Wilson, J. W.; Shinn, J. L.; Badavi, F. F.; Badhwar, G. D.

1996-01-01

We present calculations of linear energy transfer (LET) spectra in low earth orbit from galactic cosmic rays and trapped protons using the HZETRN/BRYNTRN computer code. The emphasis of our calculations is on the analysis of the effects of secondary nuclei produced through target fragmentation in the spacecraft shield or detectors. Recent improvements in the HZETRN/BRYNTRN radiation transport computer code are described. Calculations show that at large values of LET (> 100 keV/micrometer) the LET spectra seen in free space and low earth orbit (LEO) are dominated by target fragments and not the primary nuclei. Although the evaluation of microdosimetric spectra is not considered here, calculations of LET spectra support that the large lineal energy (y) events are dominated by the target fragments. Finally, we discuss the situation for interplanetary exposures to galactic cosmic rays and show that current radiation transport codes predict that in the region of high LET values the LET spectra at significant shield depths (> 10 g/cm2 of Al) is greatly modified by target fragments. These results suggest that studies of track structure and biological response of space radiation should place emphasis on short tracks of medium charge fragments produced in the human body by high energy protons and neutrons.

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

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

Guan, F; Bronk, L; Kerr, M

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/µmmore » 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.« less

Finding and Exploring Health Information with a Slider-Based User Interface.

PubMed

Pang, Patrick Cheong-Iao; Verspoor, Karin; Pearce, Jon; Chang, Shanton

2016-01-01

Despite the fact that search engines are the primary channel to access online health information, there are better ways to find and explore health information on the web. Search engines are prone to problems when they are used to find health information. For instance, users have difficulties in expressing health scenarios with appropriate search keywords, search results are not optimised for medical queries, and the search process does not account for users' literacy levels and reading preferences. In this paper, we describe our approach to addressing these problems by introducing a novel design using a slider-based user interface for discovering health information without the need for precise search keywords. The user evaluation suggests that the interface is easy to use and able to assist users in the process of discovering new information. This study demonstrates the potential value of adopting slider controls in the user interface of health websites for navigation and information discovery.

Understanding the online health information user profiles in Korea: from a psychological perspective.

PubMed

Shin, Sung Hee; Yun, Eun Kyoung

2011-06-01

This study was conducted to explore the profiles of online health information users in terms of certain psychological characteristics and to suggest guidelines for the provision of better user-oriented health information service. The cross-sectional study design was used with convenient sampling by Web-based questionnaire survey in Korea. To analyze health information user profiles on the Internet, a two-step cluster analysis was conducted. The results reveal that online health information users can be classified into four groups according to their level of subjective knowledge and health concern. The findings also suggest that four clusters that exhibit distinct profile patterns exist. The findings of this study would be useful for health portal developers who would like to understand users' characteristics and behaviors and to provide more user-oriented service in a satisfactory manner. It is suggested that to develop a full understanding of users' behaviors regarding Internet health information service, further research would be needed to explore users' various needs, their preferences, and relevant factors among users across a variety of health problem-addressing Web sites at different professional levels.

Monte Carlo simulation of chemistry following radiolysis with TOPAS-nBio.

PubMed

Ramos-Méndez, J; Perl, J; Schuemann, J; McNamara, A; Paganetti, H; Faddegon, B

2018-05-17

Simulation of water radiolysis and the subsequent chemistry provides important information on the effect of ionizing radiation on biological material. The Geant4 Monte Carlo toolkit has added chemical processes via the Geant4-DNA project. The TOPAS tool simplifies the modeling of complex radiotherapy applications with Geant4 without requiring advanced computational skills, extending the pool of users. Thus, a new extension to TOPAS, TOPAS-nBio, is under development to facilitate the configuration of track-structure simulations as well as water radiolysis simulations with Geant4-DNA for radiobiological studies. In this work, radiolysis simulations were implemented in TOPAS-nBio. Users may now easily add chemical species and their reactions, and set parameters including branching ratios, dissociation schemes, diffusion coefficients, and reaction rates. In addition, parameters for the chemical stage were re-evaluated and updated from those used by default in Geant4-DNA to improve the accuracy of chemical yields. Simulation results of time-dependent and LET-dependent primary yields G x (chemical species per 100 eV deposited) produced at neutral pH and 25 °C by short track-segments of charged particles were compared to published measurements. The LET range was 0.05-230 keV µm -1 . The calculated G x values for electrons satisfied the material balance equation within 0.3%, similar for protons albeit with long calculation time. A smaller geometry was used to speed up proton and alpha simulations, with an acceptable difference in the balance equation of 1.3%. Available experimental data of time-dependent G-values for [Formula: see text] agreed with simulated results within 7%  ±  8% over the entire time range; for [Formula: see text] over the full time range within 3%  ±  4%; for H 2 O 2 from 49%  ±  7% at earliest stages and 3%  ±  12% at saturation. For the LET-dependent G x , the mean ratios to the experimental data were 1.11  ±  0.98, 1.21  ±  1.11, 1.05  ±  0.52, 1.23  ±  0.59 and 1.49  ±  0.63 (1 standard deviation) for [Formula: see text], [Formula: see text], H 2 , H 2 O 2 and [Formula: see text], respectively. In conclusion, radiolysis and subsequent chemistry with Geant4-DNA has been successfully incorporated in TOPAS-nBio. Results are in reasonable agreement with published measured and simulated data.

An AGEF-1/Arf GTPase/AP-1 Ensemble Antagonizes LET-23 EGFR Basolateral Localization and Signaling during C. elegans Vulva Induction

PubMed Central

Skorobogata, Olga; Escobar-Restrepo, Juan M.; Rocheleau, Christian E.

2014-01-01

LET-23 Epidermal Growth Factor Receptor (EGFR) signaling specifies the vulval cell fates during C. elegans larval development. LET-23 EGFR localization on the basolateral membrane of the vulval precursor cells (VPCs) is required to engage the LIN-3 EGF-like inductive signal. The LIN-2 Cask/LIN-7 Veli/LIN-10 Mint (LIN-2/7/10) complex binds LET-23 EGFR, is required for its basolateral membrane localization, and therefore, vulva induction. Besides the LIN-2/7/10 complex, the trafficking pathways that regulate LET-23 EGFR localization have not been defined. Here we identify vh4, a hypomorphic allele of agef-1, as a strong suppressor of the lin-2 mutant Vulvaless (Vul) phenotype. AGEF-1 is homologous to the mammalian BIG1 and BIG2 Arf GTPase guanine nucleotide exchange factors (GEFs), which regulate secretory traffic between the Trans-Golgi network, endosomes and the plasma membrane via activation of Arf GTPases and recruitment of the AP-1 clathrin adaptor complex. Consistent with a role in trafficking we show that AGEF-1 is required for protein secretion and that AGEF-1 and the AP-1 complex regulate endosome size in coelomocytes. The AP-1 complex has previously been implicated in negative regulation of LET-23 EGFR, however the mechanism was not known. Our genetic data indicate that AGEF-1 is a strong negative regulator of LET-23 EGFR signaling that functions in the VPCs at the level of the receptor. In line with AGEF-1 being an Arf GEF, we identify the ARF-1.2 and ARF-3 GTPases as also negatively regulating signaling. We find that the agef-1(vh4) mutation results in increased LET-23 EGFR on the basolateral membrane in both wild-type and lin-2 mutant animals. Furthermore, unc-101(RNAi), a component of the AP-1 complex, increased LET-23 EGFR on the basolateral membrane in lin-2 and agef-1(vh4); lin-2 mutant animals. Thus, an AGEF-1/Arf GTPase/AP-1 ensemble functions opposite the LIN-2/7/10 complex to antagonize LET-23 EGFR basolateral membrane localization and signaling. PMID:25329472

Germline Genetic Variants Disturbing the Let-7/LIN28 Double-Negative Feedback Loop Alter Breast Cancer Susceptibility

PubMed Central

Fan, Lei; Li, Ji-Yu; Yang, Chen; Huang, A-Ji; Shao, Zhi-Ming

2011-01-01

Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP) located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7–induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn down-regulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300) demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR) of 1.25 (P = 0.0091), which was successfully replicated in a second independent study (n = 1,156) with community-based controls. The combined P-value of the two studies was 8.0×10−5. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk. PMID:21912531

Targeted expression of suicide gene by tissue-specific promoter and microRNA regulation for cancer gene therapy.

PubMed

Danda, Ravikanth; Krishnan, Gopinath; Ganapathy, Kalaivani; Krishnan, Uma Maheswari; Vikas, Khetan; Elchuri, Sailaja; Chatterjee, Nivedita; Krishnakumar, Subramanian

2013-01-01

In order to realise the full potential of cancer suicide gene therapy that allows the precise expression of suicide gene in cancer cells, we used a tissue specific Epithelial cell adhesion molecule (EpCAM) promoter (EGP-2) that directs transgene Herpes simplex virus-thymidine kinase (HSV-TK) expression preferentially in EpCAM over expressing cancer cells. EpCAM levels are considerably higher in retinoblastoma (RB), a childhood eye cancer with limited expression in normal cells. Use of miRNA regulation, adjacent to the use of the tissue-specific promoter, would provide the second layer of control to the transgene expression only in the tumor cells while sparing the normal cells. To test this hypothesis we cloned let-7b miRNA targets in the 3'UTR region of HSV-TK suicide gene driven by EpCAM promoter because let-7 family miRNAs, including let-7b, were found to be down regulated in the RB tumors and cell lines. We used EpCAM over expressing and let-7 down regulated RB cell lines Y79, WERI-Rb1 (EpCAM (+ve)/let-7b(down-regulated)), EpCAM down regulated, let-7 over expressing normal retinal Müller glial cell line MIO-M1(EpCAM (-ve)/let-7b(up-regulated)), and EpCAM up regulated, let-7b up-regulated normal thyroid cell line N-Thy-Ori-3.1(EpCAM (+ve)/let-7b(up-regulated)) in the study. The cell proliferation was measured by MTT assay, apoptosis was measured by probing cleaved Caspase3, EpCAM and TK expression were quantified by Western blot. Our results showed that the EGP2-promoter HSV-TK (EGP2-TK) construct with 2 or 4 copies of let-7b miRNA targets expressed TK gene only in Y79, WERI-Rb-1, while the TK gene did not express in MIO-M1. In summary, we have developed a tissue-specific, miRNA-regulated dual control vector, which selectively expresses the suicide gene in EpCAM over expressing cells.

Proteomics and Pathway Analysis Identifies JNK Signaling as Critical for High Linear Energy Transfer Radiation-induced Apoptosis in Non-small Lung Cancer Cells*S⃞

PubMed Central

Ståhl, Sara; Fung, Eva; Adams, Christopher; Lengqvist, Johan; Mörk, Birgitta; Stenerlöw, Bo; Lewensohn, Rolf; Lehtiö, Janne; Zubarev, Roman; Viktorsson, Kristina

2009-01-01

During the past decade, we have witnessed an explosive increase in generation of large proteomics data sets, not least in cancer research. There is a growing need to extract and correctly interpret information from such data sets to generate biologically relevant hypotheses. A pathway search engine (PSE) has recently been developed as a novel tool intended to meet these requirements. Ionizing radiation (IR) is an anticancer treatment modality that triggers multiple signal transduction networks. In this work, we show that high linear energy transfer (LET) IR induces apoptosis in a non-small cell lung cancer cell line, U-1810, whereas low LET IR does not. PSE was applied to study changes in pathway status between high and low LET IR to find pathway candidates of importance for high LET-induced apoptosis. Such pathways are potential clinical targets, and they were further validated in vitro. We used an unsupervised shotgun proteomics approach where high resolution mass spectrometry coupled to nanoflow liquid chromatography determined the identity and relative abundance of expressed proteins. Based on the proteomics data, PSE suggested the JNK pathway (p = 6·10−6) as a key event in response to high LET IR. In addition, the Fas pathway was found to be activated (p = 3·10−5) and the p38 pathway was found to be deactivated (p = 0.001) compared with untreated cells. Antibody-based analyses confirmed that high LET IR caused an increase in phosphorylation of JNK. Moreover pharmacological inhibition of JNK blocked high LET-induced apoptotic signaling. In contrast, neither an activation of p38 nor a role for p38 in high LET IR-induced apoptotic signaling was found. We conclude that, in contrast to conventional low LET IR, high LET IR can trigger activation of the JNK pathway, which in turn is critical for induction of apoptosis in these cells. Thus PSE predictions were largely confirmed, and PSE was proven to be a useful hypothesis-generating tool. PMID:19168796

Proteomics and pathway analysis identifies JNK signaling as critical for high linear energy transfer radiation-induced apoptosis in non-small lung cancer cells.

PubMed

Ståhl, Sara; Fung, Eva; Adams, Christopher; Lengqvist, Johan; Mörk, Birgitta; Stenerlöw, Bo; Lewensohn, Rolf; Lehtiö, Janne; Zubarev, Roman; Viktorsson, Kristina

2009-05-01

During the past decade, we have witnessed an explosive increase in generation of large proteomics data sets, not least in cancer research. There is a growing need to extract and correctly interpret information from such data sets to generate biologically relevant hypotheses. A pathway search engine (PSE) has recently been developed as a novel tool intended to meet these requirements. Ionizing radiation (IR) is an anticancer treatment modality that triggers multiple signal transduction networks. In this work, we show that high linear energy transfer (LET) IR induces apoptosis in a non-small cell lung cancer cell line, U-1810, whereas low LET IR does not. PSE was applied to study changes in pathway status between high and low LET IR to find pathway candidates of importance for high LET-induced apoptosis. Such pathways are potential clinical targets, and they were further validated in vitro. We used an unsupervised shotgun proteomics approach where high resolution mass spectrometry coupled to nanoflow liquid chromatography determined the identity and relative abundance of expressed proteins. Based on the proteomics data, PSE suggested the JNK pathway (p = 6.10(-6)) as a key event in response to high LET IR. In addition, the Fas pathway was found to be activated (p = 3.10(-5)) and the p38 pathway was found to be deactivated (p = 0.001) compared with untreated cells. Antibody-based analyses confirmed that high LET IR caused an increase in phosphorylation of JNK. Moreover pharmacological inhibition of JNK blocked high LET-induced apoptotic signaling. In contrast, neither an activation of p38 nor a role for p38 in high LET IR-induced apoptotic signaling was found. We conclude that, in contrast to conventional low LET IR, high LET IR can trigger activation of the JNK pathway, which in turn is critical for induction of apoptosis in these cells. Thus PSE predictions were largely confirmed, and PSE was proven to be a useful hypothesis-generating tool.

An AGEF-1/Arf GTPase/AP-1 ensemble antagonizes LET-23 EGFR basolateral localization and signaling during C. elegans vulva induction.

PubMed

Skorobogata, Olga; Escobar-Restrepo, Juan M; Rocheleau, Christian E

2014-10-01

LET-23 Epidermal Growth Factor Receptor (EGFR) signaling specifies the vulval cell fates during C. elegans larval development. LET-23 EGFR localization on the basolateral membrane of the vulval precursor cells (VPCs) is required to engage the LIN-3 EGF-like inductive signal. The LIN-2 Cask/LIN-7 Veli/LIN-10 Mint (LIN-2/7/10) complex binds LET-23 EGFR, is required for its basolateral membrane localization, and therefore, vulva induction. Besides the LIN-2/7/10 complex, the trafficking pathways that regulate LET-23 EGFR localization have not been defined. Here we identify vh4, a hypomorphic allele of agef-1, as a strong suppressor of the lin-2 mutant Vulvaless (Vul) phenotype. AGEF-1 is homologous to the mammalian BIG1 and BIG2 Arf GTPase guanine nucleotide exchange factors (GEFs), which regulate secretory traffic between the Trans-Golgi network, endosomes and the plasma membrane via activation of Arf GTPases and recruitment of the AP-1 clathrin adaptor complex. Consistent with a role in trafficking we show that AGEF-1 is required for protein secretion and that AGEF-1 and the AP-1 complex regulate endosome size in coelomocytes. The AP-1 complex has previously been implicated in negative regulation of LET-23 EGFR, however the mechanism was not known. Our genetic data indicate that AGEF-1 is a strong negative regulator of LET-23 EGFR signaling that functions in the VPCs at the level of the receptor. In line with AGEF-1 being an Arf GEF, we identify the ARF-1.2 and ARF-3 GTPases as also negatively regulating signaling. We find that the agef-1(vh4) mutation results in increased LET-23 EGFR on the basolateral membrane in both wild-type and lin-2 mutant animals. Furthermore, unc-101(RNAi), a component of the AP-1 complex, increased LET-23 EGFR on the basolateral membrane in lin-2 and agef-1(vh4); lin-2 mutant animals. Thus, an AGEF-1/Arf GTPase/AP-1 ensemble functions opposite the LIN-2/7/10 complex to antagonize LET-23 EGFR basolateral membrane localization and signaling.

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

Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Botas, Pablo; Faculty of Physics, Ruprecht-Karls-Universität Heidelberg, Heidelberg

Purpose: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. Methods and Materials: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide 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 dosemore » objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET. Results: The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives. Conclusion: LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.« less

Formation of Clustered DNA Damage after High-LET Irradiation: A Review

NASA Technical Reports Server (NTRS)

Hada, Megumi; Georgakilas, Alexandros G.

2008-01-01

Radiation can cause as well as cure cancer. The risk of developing radiation-induced cancer has traditionally been estimated from cancer incidence among survivors of the atomic bombs in Hiroshima and Nagasaki. These data provide the best estimate of human cancer risk over the dose range for low linear energy transfer (LET) radiations, such as X- or gamma-rays. The situation of estimating the real biological effects becomes even more difficult in the case of high LET particles encountered in space or as the result of domestic exposure to particles from radon gas emitters or other radioactive emitters like uranium-238. Complex DNA damage, i.e., the signature of high-LET radiations comprises by closely spaced DNA lesions forming a cluster of DNA damage. The two basic groups of complex DNA damage are double strand breaks (DSBs) and non-DSB oxidative clustered DNA lesions (OCDL). Theoretical analysis and experimental evidence suggest there is increased complexity and severity of complex DNA damage with increasing LET (linear energy transfer) and a high mutagenic or carcinogenic potential. Data available on the formation of clustered DNA damage (DSBs and OCDL) by high-LET radiations are often controversial suggesting a variable response to dose and type of radiation. The chemical nature and cellular repair mechanisms of complex DNA damage have been much less characterized than those of isolated DNA lesions like an oxidized base or a single strand break especially in the case of high-LET radiation. This review will focus on the induction of clustered DNA damage by high-LET radiations presenting the earlier and recent relative data.