Active learning of introductory optics: real-time physics labs, interactive lecture demonstrations and magic

NASA Astrophysics Data System (ADS)

Sokoloff, David R.

2005-10-01

Widespread physics education research has shown that most introductory physics students have difficulty learning essential optics concepts - even in the best of traditional courses, and that well-designed active learning approaches can remedy this problem. This mini-workshop and the associated poster session will provide direct experience with methods for promoting students' active involvement in the learning process in lecture and laboratory. Participants will have hands-on experience with activities from RealTime Physics labs and Interactive Lecture Demonstrations - a learning strategy for large (and small) lectures, including specially designed Optics Magic Tricks. The poster will provide more details on these highly effective curricula.

Understanding Task-in-Process through the Lens of Laughter: Activity Designs, Instructional Materials, Learner Orientations, and Interpersonal Relationships

ERIC Educational Resources Information Center

Hasegawa, Atsushi

2018-01-01

Using the framework of conversation analysis, this study investigated the interactional workings of laughter in task-based interactions. The analysis was drawn from 160 cases of pair work interactions, collected in 2nd-semester Japanese-as-a-foreign-language classrooms. The pair work activities examined in this study are mostly grammar-focused,…

Computer-aided drug design for AMP-activated protein kinase activators.

PubMed

Wang, Zhanli; Huo, Jianxin; Sun, Lidan; Wang, Yongfu; Jin, Hongwei; Yu, Hui; Zhang, Liangren; Zhou, Lishe

2011-09-01

AMP-activated protein kinase (AMPK) is an important therapeutic target for the potential treatment of metabolic disorders, cardiovascular disease and cancer. Recently, various classes of compounds that activate AMPK by direct or indirect interactions have been reported. The importance of computer-aided drug design approaches in the search for potent activators of AMPK is now established, including structure-based design, ligand-based design, fragment-based design, as well as structural analysis. This review article highlights the computer-aided drug design approaches utilized to discover of activators targeting AMPK. The principles, advantages or limitation of the different methods are also being discussed together with examples of applications taken from the literatures.

Confronting Analytical Dilemmas for Understanding Complex Human Interactions in Design-Based Research from a Cultural-Historical Activity Theory (CHAT) Framework

ERIC Educational Resources Information Center

Yamagata-Lynch, Lisa C.

2007-01-01

Understanding human activity in real-world situations often involves complicated data collection, analysis, and presentation methods. This article discusses how Cultural-Historical Activity Theory (CHAT) can inform design-based research practices that focus on understanding activity in real-world situations. I provide a sample data set with…

Students' experiences with interactivity and learning in a high school physics multimedia distance learning course

NASA Astrophysics Data System (ADS)

Villarreal-Stewart, Irene

The purpose guiding this research has been to learn about and describe the phenomena of interactivity from the learners' perspectives and to learn which of the interactivity affordances and practices were actually used by students and why in the process of learning physics using an interactive multimedia distance learning course system. The bigger purpose behind learning about and describing interactivity has been to gain knowledge and perspective for its instructional design to benefit the learner, the school as curriculum implementer, and instructional media designers to create better products. Qualitative methodology in the interpretivist tradition was used, that is, in-depth interviews and on-site observations, to gain understanding of interactivity from the learners' perspective and to gain understanding of the student learning context impacting and shaping the students' interactivity experiences. NVivo was used to sort, organize and index data. All data were read on three levels: literally, interpretively, and reflexively; and were read comparatively to other perspectives to get descriptions and interpretations that were holistic to the implementation and had potential insight to improve practice for instructional designers, teachers, administrators, specifically to improve the learning experience for students. Site-Specific Findings: Students watched videos, resisted using phone and e-mail, and worked math problems to demonstrate learning, which resulted in very little interactivity, virtually no dialogue about physics, no physical activity, one-way communication, multifaceted dissatisfaction, student need for teacher involvement in the learning enterprise, student appreciation for interactivity, and expressed desire for a real, live teacher. I also found that some students did experience the system as interactive, did experience learner control and self-directed learning, and despite dissatisfaction, liked and appreciated the course. Wider Applications: Interactivity, a design element, requires scaffolding and nurturing in implementation. The variable and changing context of implementation suggests the requirement for its consideration in design work. The study suggests that during implementation the integrity of design as a whole and flexibility within the design are important continuing considerations. Recommendations. (1) implementation supervision by the school district, (2) use of a language and activity-based theory of learning and teaching and (3) dialogic inquiry (Wells, 1999) to continue learning about interactivity.

Structure-Based Design of Novel HIV-1 Protease Inhibitors to Combat Drug Resistance

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

Ghosh,A.; Sridhar, P.; Leshchenko, S.

2006-01-01

Structure-based design and synthesis of novel HIV protease inhibitors are described. The inhibitors are designed specifically to interact with the backbone of HIV protease active site to combat drug resistance. Inhibitor 3 has exhibited exceedingly potent enzyme inhibitory and antiviral potency. Furthermore, this inhibitor maintains impressive potency against a wide spectrum of HIV including a variety of multi-PI-resistant clinical strains. The inhibitors incorporated a stereochemically defined 5-hexahydrocyclopenta[b]furanyl urethane as the P2-ligand into the (R)-(hydroxyethylamino)sulfonamide isostere. Optically active (3aS,5R,6aR)-5-hydroxy-hexahydrocyclopenta[b]furan was prepared by an enzymatic asymmetrization of meso-diacetate with acetyl cholinesterase, radical cyclization, and Lewis acid-catalyzed anomeric reduction as the key steps.more » A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease (1.35 Angstroms resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone. This design strategy may lead to novel inhibitors that can combat drug resistance.« less

Degrees of connectivity: Systems model for upstream risk assessment and mitigation.

PubMed

Gambatese, John; AlOmari, Kasim

2016-08-01

There is growing recognition that in order to further improve safety performance, attention needs to be given beyond the immediate working conditions and worker actions. A systems approach to construction safety enables considering: multiple project elements simultaneously; connections between different elements; and all system elements affected by safety risk. This paper describes recent and current research to conceptualize a typical building project in terms of connections between workers, activities, and design elements, and to verify and analyze impacts of the design and worker interactions on worker safety. Prior research provides the basis for a network tying the design elements, construction activities, and work crews on a typical building project together along with the extent of interaction between each of the system elements in terms of safety. In conjunction with this systems approach, the researchers propose a concept for viewing and managing construction safety through four different types of connections, or "degrees of connectivity," between the different workers, activities, and design elements in the system. The degrees of connectivity are defined as: interacting with the design element during its construction (DoC #1); interacting with the design element in its final form to attach another component to it (DoC #2) or by working in the vicinity of it (DoC #3); and indirectly interacting with the design element through another worker (DoC #4). To support and verify the presence of the concept in practice, the researchers conducted a survey of construction personnel. The survey results confirm that the four different degrees of connectivity are present and felt during construction operations, and indicate that attention should be given to all design elements, activities, and workers to which a worker is "connected". According to the survey respondents, DoC's #1 and #2 are recognized as the most widely present on construction sites. Eighty percent of the respondents believe that the design element has a moderate or greater impact on worker safety while it is being constructed. These initial research steps provide the starting point for continuing study that aims to develop and demonstrate the degrees of connectivity concept linking workers and design elements, with the goal of understanding how to design a project and work operations in order to improve safety during construction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Math Puzzlers: 25 Reproducible Puzzles, Games, and Activities that Boost the Math Skills and Up the Fun! Grades 2-5.

ERIC Educational Resources Information Center

Kimble-Ellis, Sonya

Puzzles, games, and activities provide perfect opportunities for students to work in groups, interact, communicate with each other, and discuss strategies. The activities, games, and puzzles contained in this book are designed to help students learn mathematics in a fun yet challenging way. The activities are designed to encourage students to…

Developing Interactive E-Learning Activities

ERIC Educational Resources Information Center

Watkins, Ryan

2005-01-01

Although e-learning can offer interactive and engaging learning experiences, the creative ideas that are necessary to create such environments are not always easy to come up with when designing, developing, or teaching e-learning courses. E-learning activities use online technologies such as chat rooms, discussion boards, or email to facilitate…

Interactive Simulations as Implicit Support for Guided-Inquiry

ERIC Educational Resources Information Center

Moore, Emily B.; Herzog, Timothy A.; Perkins, Katherine K.

2013-01-01

We present the results of a study designed to provide insight into interactive simulation use during guided-inquiry activities in chemistry classes. The PhET Interactive Simulations project at the University of Colorado develops interactive simulations that utilize implicit--rather than explicit--scaffolding to support student learning through…

Design of HIV-1 Protease Inhibitors with Amino-bis-tetrahydrofuran Derivatives as P2-Ligands to Enhance Backbone-Binding Interactions. Synthesis, Biological Evaluation, and Protein-Ligand X-ray Studies

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

Ghosh, Arun K.; Martyr, Cuthbert D.; Osswald, Heather L.

Structure-based design, synthesis, and biological evaluation of a series of very potent HIV-1 protease inhibitors are described. In an effort to improve backbone ligand–binding site interactions, we have incorporated basic-amines at the C4 position of the bis-tetrahydrofuran (bis-THF) ring. We speculated that these substituents would make hydrogen bonding interactions in the flap region of HIV-1 protease. Synthesis of these inhibitors was performed diastereoselectively. A number of inhibitors displayed very potent enzyme inhibitory and antiviral activity. Inhibitors 25f, 25i, and 25j were evaluated against a number of highly-PI-resistant HIV-1 strains, and they exhibited improved antiviral activity over darunavir. Two high resolutionmore » X-ray structures of 25f- and 25g-bound HIV-1 protease revealed unique hydrogen bonding interactions with the backbone carbonyl group of Gly48 as well as with the backbone NH of Gly48 in the flap region of the enzyme active site. These ligand–binding site interactions are possibly responsible for their potent activity.« less

Computer-Aided Drug Design Methods.

PubMed

Yu, Wenbo; MacKerell, Alexander D

2017-01-01

Computational approaches are useful tools to interpret and guide experiments to expedite the antibiotic drug design process. Structure-based drug design (SBDD) and ligand-based drug design (LBDD) are the two general types of computer-aided drug design (CADD) approaches in existence. SBDD methods analyze macromolecular target 3-dimensional structural information, typically of proteins or RNA, to identify key sites and interactions that are important for their respective biological functions. Such information can then be utilized to design antibiotic drugs that can compete with essential interactions involving the target and thus interrupt the biological pathways essential for survival of the microorganism(s). LBDD methods focus on known antibiotic ligands for a target to establish a relationship between their physiochemical properties and antibiotic activities, referred to as a structure-activity relationship (SAR), information that can be used for optimization of known drugs or guide the design of new drugs with improved activity. In this chapter, standard CADD protocols for both SBDD and LBDD will be presented with a special focus on methodologies and targets routinely studied in our laboratory for antibiotic drug discoveries.

Interactive Multimedia in University Teaching and Learning: Some Pointers to Help Promote Discussion of Design Criteria.

ERIC Educational Resources Information Center

Trevitt, Chris

This paper addresses criteria in the design and development of computer-based courseware. The term "interactive multimedia" describes both the technology and the demands placed on the user. It implies that the user becomes actively engaged with the subject, thereby improving the likelihood that net learning takes place. However, nothing…

An Examination of Instructional Interactions between Volunteer-Tutors and Students Who Show Differential Gains in Reading Comprehension

ERIC Educational Resources Information Center

Newcomer, Laurie J.

2010-01-01

It is essential to provide high quality interventions designed to improve struggling readers' reading comprehension while making use of limited resources. This study explored, through an holistic, multiple-case study design, volunteer-student interactions and activities in an after school reading program utilizing minimally-trained volunteers. The…

Interactive Print: The Design of Cognitive Tasks in Blended Augmented Reality and Print Documents

ERIC Educational Resources Information Center

Nadolny, Larysa

2017-01-01

The combination of print materials and augmented reality in education is increasingly accessible due to advances in mobile technologies. Using familiar paper-based activities overlaid with digital items, also known as interactive print, educators can create a custom learning experience for students. There is very little guidance on the design of…

Analysis of Peer Interaction in Learning Activities with Personal Handhelds and Shared Displays

ERIC Educational Resources Information Center

Liu, Chen-Chung; Chung, Chen-Wei; Chen, Nian-Shing; Liu, Baw-Jhiune

2009-01-01

Collaborative learning is extensively applied in classroom activities, but the screens on handheld devices are designed for individual-user mobile applications and may constrain interaction among group learners. The small screen size may lead to fragmented and tete-a-tete communication patterns and frequently obstruct the externalization of the…

Social Interaction and the Formation of Entrepreneurial Characteristics: A Case Study in Authentic Enterprise Activity

ERIC Educational Resources Information Center

Yu, Christina W. M.; Man, Thomas W. Y.

2009-01-01

Purpose: This paper is an empirical study which aims to investigate the development of social interaction and their impacts on developing learners' entrepreneurial characteristics throughout their participation in an authentic enterprise activity. Design/methodology/approach: The sample of this study was drawn from the participants of an…

The physical environment, activity and interaction in residential care facilities for older people: a comparative case study.

PubMed

Nordin, Susanna; McKee, Kevin; Wallinder, Maria; von Koch, Lena; Wijk, Helle; Elf, Marie

2017-12-01

The physical environment is of particular importance for supporting activities and interactions among older people living in residential care facilities (RCFs) who spend most of their time inside the facility. More knowledge is needed regarding the complex relationships between older people and environmental aspects in long-term care. The present study aimed to explore how the physical environment influences resident activities and interactions at two RCFs by using a mixed-method approach. Environmental assessments were conducted via the Swedish version of the Sheffield Care Environment Assessment Matrix (S-SCEAM), and resident activities, interactions and locations were assessed through an adapted version of the Dementia Care Mapping (DCM). The Observed Emotion Rating Scale (OERS) was used to assess residents' affective states. Field notes and walk-along interviews were also used. Findings indicate that the design of the physical environment influenced the residents' activities and interactions. Private apartments and dining areas showed high environmental quality at both RCFs, whereas the overall layout had lower quality. Safety was highly supported. Despite high environmental quality in general, several factors restricted resident activities. To optimise care for older people, the design process must clearly focus on accessible environments that provide options for residents to use the facility independently. © 2016 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.

Rational Design of Orthogonal Multipolar Interactions with Fluorine in Protein–Ligand Complexes

DOE PAGES

Pollock, Jonathan; Borkin, Dmitry; Lund, George; ...

2015-08-19

Multipolar interactions involving fluorine and the protein backbone have been frequently observed in protein–ligand complexes. Such fluorine–backbone interactions may substantially contribute to the high affinity of small molecule inhibitors. Here we found that introduction of trifluoromethyl groups into two different sites in the thienopyrimidine class of menin–MLL inhibitors considerably improved their inhibitory activity. In both cases, trifluoromethyl groups are engaged in short interactions with the backbone of menin. In order to understand the effect of fluorine, we synthesized a series of analogues by systematically changing the number of fluorine atoms, and we determined high-resolution crystal structures of the complexes withmore » menin. Here, we found that introduction of fluorine at favorable geometry for interactions with backbone carbonyls may improve the activity of menin–MLL inhibitors as much as 5- to 10-fold. In order to facilitate the design of multipolar fluorine–backbone interactions in protein–ligand complexes, we developed a computational algorithm named FMAP, which calculates fluorophilic sites in proximity to the protein backbone. We demonstrated that FMAP could be used to rationalize improvement in the activity of known protein inhibitors upon introduction of fluorine. Furthermore, FMAP may also represent a valuable tool for designing new fluorine substitutions and support ligand optimization in drug discovery projects. Analysis of the menin–MLL inhibitor complexes revealed that the backbone in secondary structures is particularly accessible to the interactions with fluorine. Lastly, considering that secondary structure elements are frequently exposed at protein interfaces, we postulate that multipolar fluorine–backbone interactions may represent a particularly attractive approach to improve inhibitors of protein–protein interactions.« less

Interactions of a designed peptide with lipopolysaccharide: Bound conformation and anti-endotoxic activity

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

Bhunia, Anirban; Chua, Geok Lin; Domadia, Prerna N.

Designed peptides that would selectively interact with lipopolysaccharide (LPS) or endotoxin and fold into specific conformations could serve as important scaffolds toward the development of antisepsis compounds. Here, we describe solution structure of a designed amphipathic peptide, H{sub 2}N-YVKLWRMIKFIR-CONH{sub 2} (YW12D) in complex with endotoxin as determined by transferred nuclear Overhauser effect spectroscopy. The conformation of the isolated peptide is highly flexible, but undergoes a dramatic structural stabilization in the presence of LPS. Structure calculations reveal that the peptide presents two amphipathic surfaces in its bound state to LPS whereby each surface is characterized by two positive charges and amore » number of aromatic and/or aliphatic residues. ITC data suggests that peptide interacts with two molecules of lipid A. In activity assays, YW12D exhibits neutralization of LPS toxicity with very little hemolysis of red blood cells. Structural and functional properties of YW12D would be applicable in designing low molecular weight non-toxic antisepsis molecules.« less

Designing EvoRoom: An Immersive Simulation Environment for Collective Inquiry in Secondary Science

NASA Astrophysics Data System (ADS)

Lui, Michelle Mei Yee

This dissertation investigates the design of complex inquiry for co-located students to work as a knowledge community within a mixed-reality learning environment. It presents the design of an immersive simulation called EvoRoom and corresponding collective inquiry activities that allow students to explore concepts around topics of evolution and biodiversity in a Grade 11 Biology course. EvoRoom is a room-sized simulation of a rainforest, modeled after Borneo in Southeast Asia, where several projected displays are stitched together to form a large, animated simulation on each opposing wall of the room. This serves to create an immersive environment in which students work collaboratively as individuals, in small groups and a collective community to investigate science topics using the simulations as an evidentiary base. Researchers and a secondary science teacher co-designed a multi-week curriculum that prepared students with preliminary ideas and expertise, then provided them with guided activities within EvoRoom, supported by tablet-based software as well as larger visualizations of their collective progress. Designs encompassed the broader curriculum, as well as all EvoRoom materials (e.g., projected displays, student tablet interfaces, collective visualizations) and activity sequences. This thesis describes a series of three designs that were developed and enacted iteratively over two and a half years, presenting key features that enhanced students' experiences within the immersive environment, their interactions with peers, and their inquiry outcomes. Primary research questions are concerned with the nature of effective design for such activities and environments, and the kinds of interactions that are seen at the individual, collaborative and whole-class levels. The findings fall under one of three themes: 1) the physicality of the room, 2) the pedagogical script for student observation and reflection and collaboration, and 3) ways of including collective visualizations in the activity. Discrete findings demonstrate how the above variables, through their design as inquiry components (i.e., activity, room, scripts and scaffolds on devices, collective visualizations), can mediate the students' interactions with one another, with their teacher, and impact the outcomes of their inquiry. A set of design recommendations is drawn from the results of this research to guide future design or research efforts.

Using Activity Theory to Understand Learning Design Requirements of Patient Self-Management Environments

ERIC Educational Resources Information Center

Schaffer, Scott P.; Reyes, Lisette; Kim, Hannah; Collins, Bart

2010-01-01

Learning designs aimed at supporting transformational change could significantly benefit from the adoption of socio-historical and socio-cultural analysis approaches. Such systemic perspectives are gaining more importance in education as they facilitate understanding of complex interactions between learning environments and human activity. The…

Factors Influencing Teachers' Engagement in Informal Learning Activities

ERIC Educational Resources Information Center

Lohman, Margaret C.

2006-01-01

Purpose: The purpose of this study is to examine factors influencing the engagement of public school teachers in informal learning activities. Design/methodology/approach: This study used a survey research design. Findings: Analysis of the data found that teachers rely to a greater degree on interactive than on independent informal learning…

Activation loop targeting strategy for design of receptor-interacting protein kinase 2 (RIPK2) inhibitors.

PubMed

Suebsuwong, Chalada; Pinkas, Daniel M; Ray, Soumya S; Bufton, Joshua C; Dai, Bing; Bullock, Alex N; Degterev, Alexei; Cuny, Gregory D

2018-02-15

Development of selective kinase inhibitors remains a challenge due to considerable amino acid sequence similarity among family members particularly in the ATP binding site. Targeting the activation loop might offer improved inhibitor selectivity since this region of kinases is less conserved. However, the strategy presents difficulties due to activation loop flexibility. Herein, we report the design of receptor-interacting protein kinase 2 (RIPK2) inhibitors based on pan-kinase inhibitor regorafenib that aim to engage basic activation loop residues Lys169 or Arg171. We report development of CSR35 that displayed >10-fold selective inhibition of RIPK2 versus VEGFR2, the target of regorafenib. A co-crystal structure of CSR35 with RIPK2 revealed a resolved activation loop with an ionic interaction between the carboxylic acid installed in the inhibitor and the side-chain of Lys169. Our data provides principle feasibility of developing activation loop targeting type II inhibitors as a complementary strategy for achieving improved selectivity. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Towards a capabilities database to inform inclusive design: experimental investigation of effective survey-based predictors of human-product interaction.

PubMed

Tenneti, Raji; Johnson, Daniel; Goldenberg, Liz; Parker, Richard A; Huppert, Felicia A

2012-07-01

A key issue in the field of inclusive design is the ability to provide designers with an understanding of people's range of capabilities. Since it is not feasible to assess product interactions with a large sample, this paper assesses a range of proxy measures of design-relevant capabilities. It describes a study that was conducted to identify which measures provide the best prediction of people's abilities to use a range of products. A detailed investigation with 100 respondents aged 50-80 years was undertaken to examine how they manage typical household products. Predictor variables included self-report and performance measures across a variety of capabilities (vision, hearing, dexterity and cognitive function), component activities used in product interactions (e.g. using a remote control, touch screen) and psychological characteristics (e.g. self-efficacy, confidence with using electronic devices). Results showed, as expected, a higher prevalence of visual, hearing, dexterity, cognitive and product interaction difficulties in the 65-80 age group. Regression analyses showed that, in addition to age, performance measures of vision (acuity, contrast sensitivity) and hearing (hearing threshold) and self-report and performance measures of component activities are strong predictors of successful product interactions. These findings will guide the choice of measures to be used in a subsequent national survey of design-relevant capabilities, which will lead to the creation of a capability database. This will be converted into a tool for designers to understand the implications of their design decisions, so that they can design products in a more inclusive way. Copyright © 2011 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Design, Development, Testing, and Evaluation: Human Factors Engineering

NASA Technical Reports Server (NTRS)

Adelstein, Bernard; Hobbs, Alan; OHara, John; Null, Cynthia

2006-01-01

While human-system interaction occurs in all phases of system development and operation, this chapter on Human Factors in the DDT&E for Reliable Spacecraft Systems is restricted to the elements that involve "direct contact" with spacecraft systems. Such interactions will encompass all phases of human activity during the design, fabrication, testing, operation, and maintenance phases of the spacecraft lifespan. This section will therefore consider practices that would accommodate and promote effective, safe, reliable, and robust human interaction with spacecraft systems. By restricting this chapter to what the team terms "direct contact" with the spacecraft, "remote" factors not directly involved in the development and operation of the vehicle, such as management and organizational issues, have been purposely excluded. However, the design of vehicle elements that enable and promote ground control activities such as monitoring, feedback, correction and reversal (override) of on-board human and automation process are considered as per NPR8705.2A, Section 3.3.

Requirements for psychological models to support design: Towards ecological task analysis

NASA Technical Reports Server (NTRS)

Kirlik, Alex

1991-01-01

Cognitive engineering is largely concerned with creating environmental designs to support skillful and effective human activity. A set of necessary conditions are proposed for psychological models capable of supporting this enterprise. An analysis of the psychological nature of the design product is used to identify a set of constraints that models must meet if they can usefully guide design. It is concluded that cognitive engineering requires models with resources for describing the integrated human-environment system, and that these models must be capable of describing the activities underlying fluent and effective interaction. These features are required in order to be able to predict the cognitive activity that will be required given various design concepts, and to design systems that promote the acquisition of fluent, skilled behavior. These necessary conditions suggest that an ecological approach can provide valuable resources for psychological modeling to support design. Relying heavily on concepts from Brunswik's and Gibson's ecological theories, ecological task analysis is proposed as a framework in which to predict the types of cognitive activity required to achieve productive behavior, and to suggest how interfaces can be manipulated to alleviate certain types of cognitive demands. The framework is described in terms, and illustrated with an example from the previous research on modeling skilled human-environment interaction.

Methods to enable the design of bioactive small molecules targeting RNA

PubMed Central

Disney, Matthew D.; Yildirim, Ilyas; Childs-Disney, Jessica L.

2014-01-01

RNA is an immensely important target for small molecule therapeutics or chemical probes of function. However, methods that identify, annotate, and optimize RNA-small molecule interactions that could enable the design of compounds that modulate RNA function are in their infancies. This review describes recent approaches that have been developed to understand and optimize RNA motif-small molecule interactions, including Structure-Activity Relationships Through Sequencing (StARTS), quantitative structure-activity relationships (QSAR), chemical similarity searching, structure-based design and docking, and molecular dynamics (MD) simulations. Case studies described include the design of small molecules targeting RNA expansions, the bacterial A-site, viral RNAs, and telomerase RNA. These approaches can be combined to afford a synergistic method to exploit the myriad of RNA targets in the transcriptome. PMID:24357181

Methods to enable the design of bioactive small molecules targeting RNA.

PubMed

Disney, Matthew D; Yildirim, Ilyas; Childs-Disney, Jessica L

2014-02-21

RNA is an immensely important target for small molecule therapeutics or chemical probes of function. However, methods that identify, annotate, and optimize RNA-small molecule interactions that could enable the design of compounds that modulate RNA function are in their infancies. This review describes recent approaches that have been developed to understand and optimize RNA motif-small molecule interactions, including structure-activity relationships through sequencing (StARTS), quantitative structure-activity relationships (QSAR), chemical similarity searching, structure-based design and docking, and molecular dynamics (MD) simulations. Case studies described include the design of small molecules targeting RNA expansions, the bacterial A-site, viral RNAs, and telomerase RNA. These approaches can be combined to afford a synergistic method to exploit the myriad of RNA targets in the transcriptome.

Designing and Evaluating Tutoring Feedback Strategies for Digital Learning Environments on the Basis of the Interactive Tutoring Feedback Model

ERIC Educational Resources Information Center

Narciss, Susanne

2013-01-01

This paper describes the interactive tutoring feedback model (ITF-model; Narciss, 2006; 2008), and how it can be applied to the design and evaluation of feedback strategies for digital learning environments. The ITF-model conceptualizes formative tutoring feedback as a multidimensional instructional activity that aims at contributing to the…

Using Tablet Computers in Preschool: How Does the Design of Applications Influence Participation, Interaction and Dialogues?

ERIC Educational Resources Information Center

Palmér, Hanna

2015-01-01

The results in this article explore whether and how the design of applications used on tablet computers influences the interaction and dialogues that occur between children and pedagogues, the participation of children in the activities and the mathematics that can be learned. While mathematics offered a lens to explore the use of tablet devices,…

Considering the Activity in Interactivity: A Multimodal Perspective

ERIC Educational Resources Information Center

Schwartz, Ruth N.

2010-01-01

What factors contribute to effective multimedia learning? Increasingly, interactivity is considered a critical component that can foster learning in multimedia environments, including simulations and games. Although a number of recent studies investigate interactivity as a factor in the effective design of multimedia instruction, most examine only…

Monitoring Student Interaction during Collaborative Learning: Design and Evaluation of a Training Program for Pre-Service Teachers

ERIC Educational Resources Information Center

Kaendler, Celia; Wiedmann, Michael; Leuders, Timo; Rummel, Nikol; Spada, Hans

2016-01-01

The monitoring by teachers of collaborative, cognitive, and meta-cognitive student activities in collaborative learning is crucial for fostering beneficial student interaction. In a quasi-experimental study, we trained pre-service teachers (N = 74) to notice behavioral indicators for these three dimensions of student activities. Video clips of…

The Science of Chocolate: Interactive Activities on Phase Transitions, Emulsification, and Nucleation

ERIC Educational Resources Information Center

Rowat, Amy C.; Hollar, Kathryn A.; Stone, Howard A.; Rosenberg, Daniel

2011-01-01

Nearly everyone loves chocolate, which makes this an excellent topic for communicating scientific concepts to the general public and to students in the classroom. Here we present the outline and activities for an interactive presentation on the science of chocolate for nonspecialists and their children ages 6 and up. We design the presentation…

Designing an Interactive Activity to Integrate Animal Physiology in the Context of Different Disciplines

ERIC Educational Resources Information Center

Escribano, Begona M.; Aguera, Estrella I.; Tovar, Pura

2011-01-01

In this article, the authors propose an activity which revolves around three elements (interactivity, team learning, and peer-to-peer instruction) and consists of the drafting of a "newspaper." The different characteristics of each of its sections permits the approach to the teaching/learning process, in the context of physiological…

Effects of checklist interface on non-verbal crew communications

NASA Technical Reports Server (NTRS)

Segal, Leon D.

1994-01-01

The investigation looked at the effects of the spatial layout and functionality of cockpit displays and controls on crew communication. Specifically, the study focused on the intra-cockpit crew interaction, and subsequent task performance, of airline pilots flying different configurations of a new electronic checklist, designed and tested in a high-fidelity simulator at NASA Ames Research Center. The first part of this proposal establishes the theoretical background for the assumptions underlying the research, suggesting that in the context of the interaction between a multi-operator crew and a machine, the design and configuration of the interface will affect interactions between individual operators and the machine, and subsequently, the interaction between operators. In view of the latest trends in cockpit interface design and flight-deck technology, in particular, the centralization of displays and controls, the introduction identifies certain problems associated with these modern designs and suggests specific design issues to which the expected results could be applied. A detailed research program and methodology is outlined and the results are described and discussed. Overall, differences in cockpit design were shown to impact the activity within the cockpit, including interactions between pilots and aircraft and the cooperative interactions between pilots.

Dimensions of Human-Work Domain Interaction: A Preliminary Analysis for the Design of a Corporate Digital Library.

ERIC Educational Resources Information Center

Xie, Hong

2003-01-01

Applies the cognitive system engineering approach to investigate human-work interaction at a corporate setting. Reports preliminary analysis of data collected from diary analysis and interview of 20 subjects. Results identify three dimensions for each of four interactive activities involved in human-work interaction and their relationships.…

A Model for Enhancing Social Communication and Interaction in Everyday Activities for Primary School Children with ASD

ERIC Educational Resources Information Center

Peters, Brenda

2016-01-01

Children with a diagnosis of Autism Spectrum Disorder may find the social aspects of learning particularly challenging because of the traits of diffculty with social communication and interaction. This paper evaluates the impact of an interactive model designed to support social communication and interaction for twelve students with ASD, who…

Teaching Ethics for Design for Sustainable Behaviour: A Pilot Study

ERIC Educational Resources Information Center

Lilley, Debra; Lofthouse, Vicky

2010-01-01

Design for sustainable behaviour is an emerging activity under the banner of sustainable design which aims to reduce the environmental and social impacts of products by moderating users' interaction with them. The intended outcome of design for sustainable behaviour is to reduce negative environmental and societal impacts. However, designers'…

Communication and cooperation in networked environments: an experimental analysis.

PubMed

Galimberti, C; Ignazi, S; Vercesi, P; Riva, G

2001-02-01

Interpersonal communication and cooperation do not happen exclusively face to face. In work contexts, as in private life, there are more and more situations of mediated communication and cooperation in which new online tools are used. However, understanding how to use the Internet to support collaborative interaction presents a substantial challenge for the designers and users of this emerging technology. First, collaborative Internet environments are designed to serve a purpose, so must be designed with intended users' tasks and goals explicitly considered. Second, in cooperative activities the key content of communication is the interpretation of the situations in which actors are involved. So, the most effective way of clarifying the meaning of messages is to connect them to a shared context of meaning. However, this is more difficult in the Internet than in other computer-based activities. This paper tries to understand the characteristics of cooperative activities in networked environments--shared 3D virtual worlds--through two different studies. The first used the analysis of conversations to explore the characteristics of the interaction during the cooperative task; the second analyzed whether and how the level of immersion in the networked environments influenced the performance and the interactional process. The results are analyzed to identify the psychosocial roots used to support cooperation in a digital interactive communication.

Impact of technology-infused interactive learning environments on college professors' instructional decisions and practices

NASA Astrophysics Data System (ADS)

Kuda Malwathumullage, Chamathca Priyanwada

Recent advancements in instructional technology and interactive learning space designs have transformed how undergraduate classrooms are envisioned and conducted today. Large number of research studies have documented the impact of instructional technology and interactive learning spaces on elevated student learning gains, positive attitudes, and increased student engagement in undergraduate classrooms across nation. These research findings combined with the movement towards student-centered instructional strategies have motivated college professors to explore the unfamiliar territories of instructional technology and interactive learning spaces. Only a limited number of research studies that explored college professors' perspective on instructional technology and interactive learning space use in undergraduate classrooms exist in the education research literature. Since college professors are an essential factor in undergraduate students' academic success, investigating how college professors perceive and utilize instructional technology and interactive learning environments can provide insights into designing effective professional development programs for college professors across undergraduate institutions. Therefore, the purpose of this study was to investigate college professors' pedagogical reasoning behind incorporating different types of instructional technologies and teaching strategies to foster student learning in technology-infused interactive learning environments. Furthermore, this study explored the extent to which college professors' instructional decisions and practices are affected by teaching in an interactive learning space along with their overall perception of instructional technology and interactive learning spaces. Four college professors from a large public Midwestern university who taught undergraduate science courses in a classroom based on the 'SCALE-UP model' participated in this study. Major data sources included classroom observations, interviews and questionnaires. An enumerative approach and the constant comparative method were utilized to analyze the data. According to the results obtained, all the participating college professors of this study employed a variety of instructional technologies and learning space features to actively engage their students in classroom activities. Participants were largely influenced by the instructional technology and the learning space features at lesson planning and execution stages whereas this influence was less notable at the student assessment stage. Overall, college professors perceive technology-infused interactive learning environments to be advantageous in terms of enabling flexibility and creativity along with easy facilitation of classroom activities. However, they felt challenged when designing effective classroom activities and preferred continuous professional development support. Overall, college professors' pedagogical decision making process, their perceived benefits and challenges seemed to be interrelated and centered on the learners and the learning process. Primary implication of this study is to implement effective professional development programs for college professors which enable them to familiarize themselves with student-centered pedagogy and effective classroom activity design along with the novel trends in learning space design and instructional technologies. Furthermore, higher education institutions need to devise incentives and recognition measures to appreciate college professors' contributions to advance scholarship of teaching and learning.

Optimal active vibration absorber: Design and experimental results

NASA Technical Reports Server (NTRS)

Lee-Glauser, Gina; Juang, Jer-Nan; Sulla, Jeffrey L.

1992-01-01

An optimal active vibration absorber can provide guaranteed closed-loop stability and control for large flexible space structures with collocated sensors/actuators. The active vibration absorber is a second-order dynamic system which is designed to suppress any unwanted structural vibration. This can be designed with minimum knowledge of the controlled system. Two methods for optimizing the active vibration absorber parameters are illustrated: minimum resonant amplitude and frequency matched active controllers. The Controls-Structures Interaction Phase-1 Evolutionary Model at NASA LaRC is used to demonstrate the effectiveness of the active vibration absorber for vibration suppression. Performance is compared numerically and experimentally using acceleration feedback.

Feel the Fear: Learning Graphic Design in Affective Places and Online Spaces

ERIC Educational Resources Information Center

Nottingham, Anitra

2017-01-01

This article explores the idea of pedagogic affect in both onsite and online graphic design learning spaces, and speculates on the role that this affect plays in the formation of the design student. I argue that embodied design knowledge is built by interactions with design professionals, activities that mimic the daily work of designers, and…

Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

PubMed

Giraldo, N A; Amariles, P; Monsalve, M; Faus, M J

Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV ® ) was developed. A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Ligand-regulated peptides: a general approach for modulating protein-peptide interactions with small molecules.

PubMed

Binkowski, Brock F; Miller, Russell A; Belshaw, Peter J

2005-07-01

We engineered a novel ligand-regulated peptide (LiRP) system where the binding activity of intracellular peptides is controlled by a cell-permeable small molecule. In the absence of ligand, peptides expressed as fusions in an FKBP-peptide-FRB-GST LiRP scaffold protein are free to interact with target proteins. In the presence of the ligand rapamycin, or the nonimmunosuppressive rapamycin derivative AP23102, the scaffold protein undergoes a conformational change that prevents the interaction of the peptide with the target protein. The modular design of the scaffold enables the creation of LiRPs through rational design or selection from combinatorial peptide libraries. Using these methods, we identified LiRPs that interact with three independent targets: retinoblastoma protein, c-Src, and the AMP-activated protein kinase. The LiRP system should provide a general method to temporally and spatially regulate protein function in cells and organisms.

Graphing Calculators, the CBL2[TM] and TI-Interactive[TM] in High School Science.

ERIC Educational Resources Information Center

Molnar, Bill

This collection of activities is designed to show how TI-Interactive[TM] and Calculator-based Laboratories (CBL) can be used to explore topics in high school science. The activities address such topics as specific heat, Boyle's Law, Newton's Law of Cooling, and Antarctic Ozone Levels. Teaching notes and calculator instructions are included as are…

Use of a PhET Interactive Simulation in General Chemistry Laboratory: Models of the Hydrogen Atom

ERIC Educational Resources Information Center

Clark, Ted M.; Chamberlain, Julia M.

2014-01-01

An activity supporting the PhET interactive simulation, Models of the Hydrogen Atom, has been designed and used in the laboratory portion of a general chemistry course. This article describes the framework used to successfully accomplish implementation on a large scale. The activity guides students through a comparison and analysis of the six…

Insight into the C-F bond mechanism of molecular analogs for antibacterial drug design.

PubMed

Liu, Junna; Lv, Biyu; Liu, Huaqing; Li, Xin; Yin, Weiping

2018-06-01

The activities of biological molecules usually rely on both of intra-molecular and intermolecular interactions between their function groups. These interactions include interonic attraction theory, Van der Waal's forces and the function of geometry on the individual molecules, whether they are naturally or synthetic. The purpose of this study was to evaluate the antibacterial activity of C-F bond compound using combination of experiments verification and theoretical calculation. We target on the insect natural products from the maggots of Chrysomyis megacephala Fabricius. Based on density functional theory(DFT) and B3LYP method, a theoretical study of the C-F bond on fluoride was designed to explore compounds 2 and 4 antibacterial structure-activity relationship. With the progress in DFT, first-principle calculation based on DFT has gradually become a routine method for drug design, quantum chemistry and other science fields.

Tangible User Interfaces and Contrasting Cases as a Preparation for Future Learning

NASA Astrophysics Data System (ADS)

Schneider, Bertrand; Blikstein, Paulo

2018-04-01

In this paper, we describe an experiment that compared the use of a Tangible User Interface (physical objects augmented with digital information) and a set of Contrasting Cases as a preparation for future learning. We carried out an experiment (N = 40) with a 2 × 2 design: the first factor compared traditional instruction ("Tell & Practice") with a constructivist activity designed using the Preparation for Future Learning framework (PFL). The second factor contrasted state-of-the-art PFL learning activity (i.e., students studying Contrasting Cases) with an interactive tabletop featuring digitally enhanced manipulatives. In agreement with prior work, we found that dyads of students who followed the PFL activity achieved significantly higher learning gains compared to their peers who followed a traditional "Tell & Practice" instruction (large effect size). A similar effect was found in favor of the interactive tabletop compared to the Contrasting Cases (small-to-moderate effect size). We discuss implications for designing socio-constructivist activities using new computer interfaces.

Building inhabitant feedback: Creating a reflective practice for environmental design using activity theory

NASA Astrophysics Data System (ADS)

Cunningham, Dara Suzanne

The way buildings are designed now, there is little feedback from use involved in the design process. Attempts to correct this problem have been made in the form of Post Occupancy Evaluations (POEs) for 50-years but have largely failed. POEs are the accepted method for environmental designers to collect feedback about buildings in use. They are infrequently conducted, after the building is built, in a one-time only evaluation, and not funded as part of the build process. Other products receive feedback about the design in use from online critiques. Online critiques could provide a platform for feedback from actors engaged with buildings in use for environmental designers to utilize in developing reflective design rationale to avoid adverse consequences in future designs or correct consequences in past and current designs. Since buildings constitute such a large part of the human environment, it's important to research the effects of buildings on their inhabitants. In order for environmental designers to act on feedback from situated use, designers need to have access to that feedback and all actors interacting with the building design need to have an easy, inexpensive, and accessible method to submit feedback. These needs can be addressed by utilizing modern networked and mobile computing to collect and access building feedback. The analysis presented in this dissertation is informed by a thorough evaluation of the theory of reflective practice, activity theory, environmental design, and cognitive science research. From this analysis, I developed the following contributions. First, I expanded Schon's reflective practice by combining his theory with a modified version of activity theory, using activity theory to enrich reflective practice and create Reflective Activity Systems Theory (RAST), which provides a new framework to develop design rationale based on feedback from use and a focus on the activity. Second, I suggest the design of an activity information system, Socio-Technical Environments for Evolutionary Design (STEED), which provides an interactive platform for actor and artifact feedback from the use situation. Third, I discuss implications for practice by discussing how the feedback from actors and artifacts in situated use can be used to create reflective design rationale.

Mission-based Scenario Research: Experimental Design And Analysis

DTIC Science & Technology

2012-01-01

neurotechnologies called Brain-Computer Interaction Technologies. 15. SUBJECT TERMS neuroimaging, EEG, task loading, neurotechnologies , ground... neurotechnologies called Brain-Computer Interaction Technologies. INTRODUCTION Imagine a system that can identify operator fatigue during a long-term...BCIT), a class of neurotechnologies , that aim to improve task performance by incorporating measures of brain activity to optimize the interactions

Development and Evaluation of an Interactive Electronic Laboratory Manual for Cooperative Learning of Medical Histology

ERIC Educational Resources Information Center

Khalil, Mohammed K.; Kirkley, Debbie L.; Kibble, Jonathan D.

2013-01-01

This article describes the development of an interactive computer-based laboratory manual, created to facilitate the teaching and learning of medical histology. The overarching goal of developing the manual is to facilitate self-directed group interactivities that actively engage students during laboratory sessions. The design of the manual…

Effects of Interactive Chat versus Independent Writing on L2 Learning

ERIC Educational Resources Information Center

Tare, Medha; Golonka, Ewa M.; Vatz, Karen; Bonilla, Carrie L.; Crooks, Carolyn; Strong, Rachel

2014-01-01

This study examines the importance of interaction for second language (L2) acquisition by analyzing outcomes from two types of out-of-class activities. The study compared: (a) interactive homework, completed via text chat, and (b) individual homework, completed via independent writing. In a between-subjects design, participants in two…

A Multi-Perspective Investigation into Learners' Interaction in Asynchronous Computer-Mediated Communication (CMC)

ERIC Educational Resources Information Center

Çardak, Çigdem Suzan

2016-01-01

This article focusses on graduate level students' interactions during asynchronous CMC activities of an online course about the teaching profession in Turkey. The instructor of the course designed and facilitated a semester-long asynchronous CMC on forum discussions, and investigated the interaction of learners in multiple perspectives: learners'…

Future Technology Workshop: A Collaborative Method for the Design of New Learning Technologies and Activities

ERIC Educational Resources Information Center

Vavoula, Giasemi N.; Sharples, Mike

2007-01-01

We describe the future technology workshop (FTW), a method whereby people with everyday knowledge or experience in a specific area of technology use (such as using digital cameras) envision and design the interactions between current and future technology and activity. Through a series of structured workshop sessions, participants collaborate to…

Different designs of kinase-phosphatase interactions and phosphatase sequestration shapes the robustness and signal flow in the MAPK cascade

PubMed Central

2012-01-01

Background The three layer mitogen activated protein kinase (MAPK) signaling cascade exhibits different designs of interactions between its kinases and phosphatases. While the sequential interactions between the three kinases of the cascade are tightly preserved, the phosphatases of the cascade, such as MKP3 and PP2A, exhibit relatively diverse interactions with their substrate kinases. Additionally, the kinases of the MAPK cascade can also sequester their phosphatases. Thus, each topologically distinct interaction design of kinases and phosphatases could exhibit unique signal processing characteristics, and the presence of phosphatase sequestration may lead to further fine tuning of the propagated signal. Results We have built four architecturally distinct types of models of the MAPK cascade, each model with identical kinase-kinase interactions but unique kinases-phosphatases interactions. Our simulations unravelled that MAPK cascade’s robustness to external perturbations is a function of nature of interaction between its kinases and phosphatases. The cascade’s output robustness was enhanced when phosphatases were sequestrated by their target kinases. We uncovered a novel implicit/hidden negative feedback loop from the phosphatase MKP3 to its upstream kinase Raf-1, in a cascade resembling the B cell MAPK cascade. Notably, strength of the feedback loop was reciprocal to the strength of phosphatases’ sequestration and stronger sequestration abolished the feedback loop completely. An experimental method to verify the presence of the feedback loop is also proposed. We further showed, when the models were activated by transient signal, memory (total time taken by the cascade output to reach its unstimulated level after removal of signal) of a cascade was determined by the specific designs of interaction among its kinases and phosphatases. Conclusions Differences in interaction designs among the kinases and phosphatases can differentially shape the robustness and signal response behaviour of the MAPK cascade and phosphatase sequestration dramatically enhances the robustness to perturbations in each of the cascade. An implicit negative feedback loop was uncovered from our analysis and we found that strength of the negative feedback loop is reciprocally related to the strength of phosphatase sequestration. Duration of output phosphorylation in response to a transient signal was also found to be determined by the individual cascade’s kinase-phosphatase interaction design. PMID:22748295

Design of copper DNA intercalators with leishmanicidal activity.

PubMed

Navarro, Maribel; Cisneros-Fajardo, Efrén José; Sierralta, Aníbal; Fernández-Mestre, Mercedes; Silva, Pedro; Arrieche, Dwight; Marchán, Edgar

2003-04-01

The complexes [Cu(dppz)(NO(3))]NO(3) (1), [Cu(dppz)(2)(NO(3))]NO(3) (2), [Cu(dpq)(NO(3))]NO(3) (3), and [Cu(dpq)(2)(NO(3))]NO(3) (4) were synthesized and characterized by elemental analysis, FAB-mass spectrometry, EPR, UV, and IR spectroscopies, and molar conductivity. DNA interaction studies showed that intercalation is an important way of interacting with DNA for these complexes. The biological activity of these copper complexes was evaluated on Leishmania braziliensis promastigotes, and the results showed leishmanicidal activity. Preliminary ultrastructural studies with the most active complex (2) at 1 h revealed parasite swelling and binucleated cells. This finding suggests that the leishmanicidal activity of the copper complexes could be associated with their interaction with the parasitic DNA.

Spatio-temporal imaging of EGF-induced activation of protein kinase A by FRET in living cells

NASA Astrophysics Data System (ADS)

Wang, Jin Jun; Chen, Xiao-Chuan; Xing, Da

2004-07-01

Intracellular molecular interaction is important for the study of cell physiology, yet current relevant methods require fixation or microinjection and lack temporal or spatial resolution. We introduced a new method -- fluorescence resonance energy transfer (FRET) to detect molecular interaction in living cells. On the basis of FRET principle, A-kinase activity reporter (AKAR) protein was designed to consist of the fusions of cyan fluorescent protein (CFP), a phosphoamino acid binding domain, a consensus substrate for protein kinase-A (PKA), and yellow fluorescent protein (YFP). In this study, the designed pAKAR plasmid was used to transfect a human lung cancer cell line (ASTC-a-1). When the AKAR-transfected cells were treated by forskolin (Fsk), we were able to observe the efficient transfer of energy from excited CFP to YFP within the AKAR molecule by fluorescence microcopy, whereas no FRET was detected in the transfected cells without the treatment of Fsk. When the cells were treated by Epidermal growth factor (EGF), the change of FRET was observed at different subcellular locations, reflecting PKA activation inside the cells upon EGF stimulation. The successful design of a fluorescence reporter of PKA activation and its application demonstrated the superiority of this technology in the research of intracellular protein-protein interaction.

Establishment of a Digital Knowledge Conversion Architecture Design Learning with High User Acceptance

ERIC Educational Resources Information Center

Wu, Yun-Wu; Weng, Apollo; Weng, Kuo-Hua

2017-01-01

The purpose of this study is to design a knowledge conversion and management digital learning system for architecture design learning, helping students to share, extract, use and create their design knowledge through web-based interactive activities based on socialization, internalization, combination and externalization process in addition to…

Posting behaviour patterns in an online smoking cessation social network: implications for intervention design and development.

PubMed

Healey, Benjamin; Hoek, Janet; Edwards, Richard

2014-01-01

Online Cessation Support Networks (OCSNs) are associated with increased quit success rates, but few studies have examined their use over time. We identified usage patterns in New Zealand's largest OCSN over two years and explored implications for OCSN intervention design and evaluation. We analysed metadata relating to 133,096 OCSN interactions during 2011 and 2012. Metrics covered aggregate network activity, user posting activity and longevity, and between-user commenting. Binary logistic regression models were estimated to investigate the feasibility of predicting low user engagement using early interaction data. Repeating periodic peaks and troughs in aggregate activity related not only to seasonality (e.g., New Year), but also to day of the week. Out of 2,062 unique users, 69 Highly Engaged Users (180+ interactions each) contributed 69% of all OCSN interactions in 2012 compared to 1.3% contributed by 864 Minimally Engaged Users (< = 2 items each). The proportion of Highly Engaged Users increased with network growth between 2011 and 2012 (with marginal significance), but the proportion of Minimally Engaged Users did not decline substantively. First week interaction data enabled identification of Minimally Engaged Users with high specificity and sensitivity (AUROC= 0.94). Results suggest future research should develop and test interventions that promote activity, and hence cessation support, amongst specific user groups or at key time points. For example, early usage information could help identify Minimally Engaged Users for tests of targeted messaging designed to improve their integration into, or re-engagement with, the OCSN. Furthermore, although we observed strong growth over time on varied metrics including posts and comments, this change did not coincide with large gains in first-time user persistence. Researchers assessing intervention effects should therefore examine multiple measures when evaluating changes in network dynamics over time.

Highly Potent HIV-1 Protease Inhibitors with Novel Tricyclic P2-ligands: Design, Synthesis, and Protein-ligand X-Ray Studies

PubMed Central

Ghosh, Arun K.; Parham, Garth L.; Martyr, Cuthbert D.; Nyalapatla, Prasanth R.; Osswald, Heather L.; Agniswamy, Johnson; Wang, Yuan-Fang; Amano, Masayuki; Weber, Irene T.; Mitsuya, Hiroaki

2013-01-01

The design, synthesis, and biological evaluation of a series of HIV-1 protease inhibitors incorporating stereochemically defined fused tricyclic P2-ligands are described. Various substituent effects were investigated in order to maximize the ligand-binding site interactions in the protease active site. Inhibitors 16a and 16f showed excellent enzyme inhibitory and antiviral activity while incorporation of sulfone functionality resulted in a decrease in potency. Both inhibitors 16a and 16f have maintained activity against a panel of multidrug resistant HIV-1 variants. A high-resolution X-ray crystal structure of 16a-bound HIV-1 protease revealed important molecular insights into the ligand-binding site interactions which may account for the inhibitor’s potent antiviral activity and excellent resistance profiles. PMID:23947685

Toward a Psychological Science of Advanced Technology Design for Older Adults

PubMed Central

Fisk, Arthur D.

2010-01-01

Objectives. Technology represents advances in knowledge that change the way humans perform tasks. Ideally, technology will make the task easier, more efficient, safer, or perhaps more pleasurable. Unfortunately, new technologies can sometimes make a task more difficult, slower, dangerous, or perhaps more frustrating. Older adults interact with a variety of technologies in the course of their daily activities and thus products should be designed to be used by people of varying ages. Methods. In this article, we provide an overview of what psychology has to offer to the design of technology—from understanding what people need, to identifying their preferences for design characteristics, and to defining their capabilities and limitations that will influence technology interactions. Results. We identify how research in the field of psychology and aging has advanced understanding of technology interactions and how research on technology interactions can inform theories of aging. Discussion. Design for aging involves understanding the unique capabilities and limitations of older adults; identifying their needs, preferences, and desires for technology in their lives; and involving them in the design process. PMID:20833690

[Design of new anti-tumor agents interrupting deregulated signaling pathways induced by tyrosine kinase proteins. Inhibition of protein-protein interaction involving Grb2].

PubMed

Vidal, Michel; Liu, Wang Qing; Gril, Brunile; Assayag, Franck; Poupon, Marie-France; Garbay, Christiane

2004-01-01

Cellular signaling pathways induced by growth-factor receptors are frequently deregulated in cancer. Anti-tumor agents that inhibit their enzymatic tyrosine kinase activity have been designed and are now used in human chemotherapy. We propose here an alternative way to interrupt over-expressed signaling by inhibiting protein-protein interactions that involve either the over-expressed proteins or proteins located downstream. The adaptor protein Grb2 over-expressed in connection with HER2/ErbB2/neu in Ras signaling pathway was chosen as a target. Peptides with very high affinity for Grb2 were rationally designed from structural data. Their capacity to interrupt the signaling pathway, their anti-proliferative activity as well as their potential anti-tumor properties are described.

Collaborative Research Methodology for Investigating Teaching and Learning: The Use of Interactive Whiteboard Technology

ERIC Educational Resources Information Center

Armstrong, Victoria; Barnes, Sally; Sutherland, Rosamund; Curran, Sarah; Mills, Simon; Thompson, Ian

2005-01-01

This paper discusses the results of a research project which aimed to capture, analyse and communicate the complex interactions between students, teachers and technology that occur in the classroom. Teachers and researchers used an innovative research design developed through the InterActive Education Project (Sutherland et al., 2003). Video case…

Interactive simulations as teaching tools for engineering mechanics courses

NASA Astrophysics Data System (ADS)

Carbonell, Victoria; Romero, Carlos; Martínez, Elvira; Flórez, Mercedes

2013-07-01

This study aimed to gauge the effect of interactive simulations in class as an active teaching strategy for a mechanics course. Engineering analysis and design often use the properties of planar sections in calculations. In the stress analysis of a beam under bending and torsional loads, cross-sectional properties are used to determine stress and displacement distributions in the beam cross section. The centroid, moments and products of inertia of an area made up of several common shapes (rectangles usually) may thus be obtained by adding the moments of inertia of the component areas (U-shape, L-shape, C-shape, etc). This procedure is used to calculate the second moments of structural shapes in engineering practice because the determination of their moments of inertia is necessary for the design of structural components. This paper presents examples of interactive simulations developed for teaching the ‘Mechanics and mechanisms’ course at the Universidad Politecnica de Madrid, Spain. The simulations focus on fundamental topics such as centroids, the properties of the moment of inertia, second moments of inertia with respect to two axes, principal moments of inertia and Mohr's Circle for plane stress, and were composed using Geogebra software. These learning tools feature animations, graphics and interactivity and were designed to encourage student participation and engagement in active learning activities, to effectively explain and illustrate course topics, and to build student problem-solving skills.

Does the Room Matter? Active Learning in Traditional and Enhanced Lecture Spaces

ERIC Educational Resources Information Center

Stoltzfus, Jon R.; Libarkin, Julie

2016-01-01

SCALE-UP-type classrooms, originating with the Student-Centered Active Learning Environment with Upside-down Pedagogies project, are designed to facilitate active learning by maximizing opportunities for interactions between students and embedding technology in the classroom. Positive impacts when active learning replaces lecture are well…

Tool-Mediated Authentic Learning in an Educational Technology Course: A Designed-Based Innovation

ERIC Educational Resources Information Center

Amory, Alan

2014-01-01

This design-based research project is concerned with the design, development and deployment of interactive technological learning environments to support contemporary education. The use of technologies in education often replicates instructivist positions and practices. However, the use of Cultural Historical Activity Theory (C), authentic…

Designing Asynchronous Communication Tools for Optimization of Patient-Clinician Coordination

PubMed Central

Eschler, Jordan; Liu, Leslie S.; Vizer, Lisa M.; McClure, Jennifer B.; Lozano, Paula; Pratt, Wanda; Ralston, James D.

2015-01-01

Asynchronous communication outside the clinical setting has both enriched and complicated patient-clinician interactions. Many patients can now interact with a patient portal 24 hours a day, asking questions of their clinicians via secure message, checking lab results, ordering medication refills, or making appointments. However, the mode of communication (asynchronous) and the nature of the interaction (lacking tone or body language) strip valuable information from each side of patient-clinician asynchronous communication. Using interviews with 34 individuals who actively manage a chronic illness of their own, or for a child or partner, we elicited narratives about patients’ experiences and expectations for using asynchronous communication to address medical issues with their clinicians. Based on these perspectives, we present opportunities for designing asynchronous communication tools to better facilitate understanding of and coordination around care activities between patients and clinicians. PMID:26958188

Land & Water Interactions in the Great Lakes. Earth Systems - Education Activities for Great Lakes Schools (ES-EAGLS).

ERIC Educational Resources Information Center

Sheaffer, Amy L., Ed.

This activity book is part of a series designed to take a concept or idea from the existing school curriculum and develop it in the context of the Great Lakes using teaching approaches and materials appropriate for students in middle and high school. The subject of this book is land and water interactions. Students examine how the Great Lakes were…

Show Yourself, Asparaginase: An Enzymatic Reaction Explained through a Hands-On Interactive Activity

PubMed Central

2017-01-01

Determining the catalytic activity of an enzyme can be the perfect method for its identification, for example during purification procedures or for isolation purposes. Herein, we used a pharmaceutically relevant protein to bring the concept of enzymatic activity to the classroom. We designed a hands-on interactive activity in which a medically relevant enzyme, asparaginase, was distinguished from a nonenzymatic protein based on its specific enzymatic activity. The experiment was carried out in the classroom, designed to impact different educational levels from elementary to high school. Our main purposes were to promote the emerging field of protein-based drugs as a source of scientific careers in bionanotechnology and to show the students an image of a “scientist” as that of a common and educated person working in an exciting profession. In addition of being inexpensive, this activity proved to be adaptable for various educational levels and can be easily implemented in different scenarios, for example, scientific fairs, some schools, and so forth. PMID:29599566

Biological Activity Predictions and Hydrogen Bonding Analysis in Quinolines

NASA Astrophysics Data System (ADS)

Gupta, Palvi; Kamni

The paper has been designed to make a comprehensive review of a particular series of organic molecular assembly in the form of compendium. An overview of general description of fifteen quinoline derivatives has been given. The biological activity spectra of quinoline derivatives have been correlated on structure activity relationships base which provides the different Pa (possibility of activity) and Pi (possibility of inactivity) values. Expositions of the role of intermolecular interactions in the identified derivatives have been discussed with the standard distance and angle cut-off criteria criteria as proposed by Desiraju and Steiner (1999) in an International monogram on crystallography. Distance-angle scatter plots for intermolecular interactions are presented for a better understanding of the packing interactions which exist in quinoline derivatives.

Agent Technologies Designed to Facilitate Interactive Knowledge Construction

ERIC Educational Resources Information Center

Graesser, Arthur C.; Jeon, Moongee; Dufty, David

2008-01-01

During the last decade, interdisciplinary researchers have developed technologies with animated pedagogical agents that interact with the student in language and other communication channels (such as facial expressions and gestures). These pedagogical agents model good learning strategies and coach the students in actively constructing knowledge…

Conflict Management in Collaborative Engineering Design: Basic Research in Fundamental Theory, Modeling Framework, and Computer Support for Collaborative Engineering Activities

DTIC Science & Technology

2002-01-01

behaviors are influenced by social interactions, and to how modern IT sys- tems should be designed to support these group technical activities. The...engineering disciplines to behavior, decision, psychology, organization, and the social sciences. “Conflict manage- ment activity in collaborative...Researchers instead began to search for an entirely new paradigm, starting from a theory in social science, to construct a conceptual framework to describe

Catalysis by a de novo zinc-mediated protein interface: implications for natural enzyme evolution and rational enzyme engineering.

PubMed

Der, Bryan S; Edwards, David R; Kuhlman, Brian

2012-05-08

Here we show that a recent computationally designed zinc-mediated protein interface is serendipitously capable of catalyzing carboxyester and phosphoester hydrolysis. Although the original motivation was to design a de novo zinc-mediated protein-protein interaction (called MID1-zinc), we observed in the homodimer crystal structure a small cleft and open zinc coordination site. We investigated if the cleft and zinc site at the designed interface were sufficient for formation of a primitive active site that can perform hydrolysis. MID1-zinc hydrolyzes 4-nitrophenyl acetate with a rate acceleration of 10(5) and a k(cat)/K(M) of 630 M(-1) s(-1) and 4-nitrophenyl phosphate with a rate acceleration of 10(4) and a k(cat)/K(M) of 14 M(-1) s(-1). These rate accelerations by an unoptimized active site highlight the catalytic power of zinc and suggest that the clefts formed by protein-protein interactions are well-suited for creating enzyme active sites. This discovery has implications for protein evolution and engineering: from an evolutionary perspective, three-coordinated zinc at a homodimer interface cleft represents a simple evolutionary path to nascent enzymatic activity; from a protein engineering perspective, future efforts in de novo design of enzyme active sites may benefit from exploring clefts at protein interfaces for active site placement.

The impact of computer display height and desk design on muscle activity during information technology work by young adults.

PubMed

Straker, L; Pollock, C; Burgess-Limerick, R; Skoss, R; Coleman, J

2008-08-01

Computer display height and desk design are believed to be important workstation features and are included in international standards and guidelines. However, the evidence base for these guidelines is lacking a comparison of neck/shoulder muscle activity during computer and paper tasks and whether forearm support can be provided by desk design. This study measured the spinal and upper limb muscle activity in 36 young adults whilst they worked in different computer display, book and desk conditions. Display height affected spinal muscle activity with paper tasks resulting in greater mean spinal and upper limb muscle activity. A curved desk resulted in increased proximal muscle activity. There was no substantial interaction between display and desk.

Reconfigurable engineered motile semiconductor microparticles.

PubMed

Ohiri, Ugonna; Shields, C Wyatt; Han, Koohee; Tyler, Talmage; Velev, Orlin D; Jokerst, Nan

2018-05-03

Locally energized particles form the basis for emerging classes of active matter. The design of active particles has led to their controlled locomotion and assembly. The next generation of particles should demonstrate robust control over their active assembly, disassembly, and reconfiguration. Here we introduce a class of semiconductor microparticles that can be comprehensively designed (in size, shape, electric polarizability, and patterned coatings) using standard microfabrication tools. These custom silicon particles draw energy from external electric fields to actively propel, while interacting hydrodynamically, and sequentially assemble and disassemble on demand. We show that a number of electrokinetic effects, such as dielectrophoresis, induced charge electrophoresis, and diode propulsion, can selectively power the microparticle motions and interactions. The ability to achieve on-demand locomotion, tractable fluid flows, synchronized motility, and reversible assembly using engineered silicon microparticles may enable advanced applications that include remotely powered microsensors, artificial muscles, reconfigurable neural networks and computational systems.

Traditional Culture into Interactive Arts: The Cases of Lion Dance in Temple Lecture

NASA Astrophysics Data System (ADS)

Lee, Wen-Hui; Chen, Chih-Tung; He, Ming-Yu; Hsu, Tao-I.

The lion dance in Chinese culture is one of profound arts. This work aims to bridge traditional culture and modern multimedia technology and application of network cameras for the interactive tool to design a set of activities to promote the lion as the main body. There consists of the imaging systems and interactive multimedia applications.

Designing for the Next Web.

ERIC Educational Resources Information Center

Bremser, Wayne

1998-01-01

Discusses how to choose from the available interactive graphic-design possibilities for the World Wide Web. Compatibility and appropriateness are discussed; and DHTML (Dynamic Hypertext Markup Language), Java, CSS (Cascading Style Sheets), plug-ins, ActiveX, and Push and channel technologies are described. (LRW)

Pathomimetic cancer avatars for live-cell imaging of protease activity

PubMed Central

Ji, Kyungmin; Heyza, Joshua; Cavallo-Medved, Dora; Sloane, Bonnie F.

2016-01-01

Proteases are essential for normal physiology as well as multiple diseases, e.g., playing a causative role in cancer progression, including in tumor angiogenesis, invasion, and metastasis. Identification of dynamic alterations in protease activity may allow us to detect early stage cancers and to assess the efficacy of anti-cancer therapies. Despite the clinical importance of proteases in cancer progression, their functional roles individually and within the context of complex protease networks have not yet been well defined. These gaps in our understanding might be addressed with: 1) accurate and sensitive tools and methods to directly identify changes in protease activities in live cells, and 2) pathomimetic avatars for cancer that recapitulate in vitro the tumor in the context of its cellular and non-cellular microenvironment. Such avatars should be designed to facilitate mechanistic studies that can be translated to animal models and ultimately the clinic. Here, we will describe basic principles and recent applications of live-cell imaging for identification of active proteases. The avatars optimized by our laboratory are three-dimensional (3D) human breast cancer models in a matrix of reconstituted basement membrane (rBM). They are designated mammary architecture and microenvironment engineering (MAME) models as they have been designed to mimic the structural and functional interactions among cell types in the normal and cancerous human breast. We have demonstrated the usefulness of these pathomimetic avatars for following dynamic and temporal changes in cell:cell interactions and quantifying changes in protease activity associated with these interactions in real-time (4D). We also briefly describe adaptation of the avatars to custom-designed and fabricated tissue architecture and microenvironment engineering (TAME) chambers that enhance our ability to analyze concomitant changes in the malignant phenotype and the associated tumor microenvironment. PMID:26375517

Pathomimetic cancer avatars for live-cell imaging of protease activity.

PubMed

Ji, Kyungmin; Heyza, Joshua; Cavallo-Medved, Dora; Sloane, Bonnie F

2016-03-01

Proteases are essential for normal physiology as well as multiple diseases, e.g., playing a causative role in cancer progression, including in tumor angiogenesis, invasion, and metastasis. Identification of dynamic alterations in protease activity may allow us to detect early stage cancers and to assess the efficacy of anti-cancer therapies. Despite the clinical importance of proteases in cancer progression, their functional roles individually and within the context of complex protease networks have not yet been well defined. These gaps in our understanding might be addressed with: 1) accurate and sensitive tools and methods to directly identify changes in protease activities in live cells, and 2) pathomimetic avatars for cancer that recapitulate in vitro the tumor in the context of its cellular and non-cellular microenvironment. Such avatars should be designed to facilitate mechanistic studies that can be translated to animal models and ultimately the clinic. Here, we will describe basic principles and recent applications of live-cell imaging for identification of active proteases. The avatars optimized by our laboratory are three-dimensional (3D) human breast cancer models in a matrix of reconstituted basement membrane (rBM). They are designated mammary architecture and microenvironment engineering (MAME) models as they have been designed to mimic the structural and functional interactions among cell types in the normal and cancerous human breast. We have demonstrated the usefulness of these pathomimetic avatars for following dynamic and temporal changes in cell:cell interactions and quantifying changes in protease activity associated with these interactions in real-time (4D). We also briefly describe adaptation of the avatars to custom-designed and fabricated tissue architecture and microenvironment engineering (TAME) chambers that enhance our ability to analyze concomitant changes in the malignant phenotype and the associated tumor microenvironment. Copyright © 2015. Published by Elsevier B.V.

Double-edged swords as cancer therapeutics: novel, orally active, small molecules simultaneously inhibit p53-MDM2 interaction and the NF-κB pathway.

PubMed

Zhuang, Chunlin; Miao, Zhenyuan; Wu, Yuelin; Guo, Zizhao; Li, Jin; Yao, Jianzhong; Xing, Chengguo; Sheng, Chunquan; Zhang, Wannian

2014-02-13

Simultaneous inactivation of p53 and hyperactivation of nuclear factor-κB (NF-κB) is a common occurrence in human cancer. Currently, antitumor agents are being designed to selectively activate p53 or inhibit NF-κB. However, there is no concerted effort yet to deliberately design inhibitors that can simultaneously do both. This paper provided a proof-of-concept study that p53-MDM2 interaction and NF-κB pathway can be simultaneously targeted by a small-molecule inhibitor. A series of pyrrolo[3,4-c]pyrazole derivatives were rationally designed and synthesized as the first-in-class inhibitors of p53-MDM2 interaction and NF-κB pathway. Most of the compounds were identified to possess nanomolar p53-MDM2 inhibitory activity. Compounds 5q and 5s suppressed NF-κB activation through inhibition of IκBα phosphorylation and elevation of the cytoplasmic levels of p65 and phosphorylated IKKα/β. Biochemical assay for the kinases also supported the fact that pyrrolo[3,4-c]pyrazole compounds directly targeted the NF-κB pathway. In addition, four compounds (5j, 5q, 5s, and 5u) effectively inhibited tumor growth in the A549 xenograft model. Further pharmacokinetic study revealed that compound 5q exhibited excellent oral bioavailability (72.9%).

Is Free Recall Active: The Testing Effect through the ICAP Lens

ERIC Educational Resources Information Center

Bruchok, Christiana; Mar, Christopher; Craig, Scotty D.

2017-01-01

Amidst evidence in favor of "active learning," online instruction widely implements passive design and tests learners' retrieval performance as opposed to learners' understanding. Literature reporting the testing effect promotes recall as a learning tool. The Interactive>Constructive>Active>Passive taxonomy would place quizzing…

Object Oriented Modeling and Design

NASA Technical Reports Server (NTRS)

Shaykhian, Gholam Ali

2007-01-01

The Object Oriented Modeling and Design seminar is intended for software professionals and students, it covers the concepts and a language-independent graphical notation that can be used to analyze problem requirements, and design a solution to the problem. The seminar discusses the three kinds of object-oriented models class, state, and interaction. The class model represents the static structure of a system, the state model describes the aspects of a system that change over time as well as control behavior and the interaction model describes how objects collaborate to achieve overall results. Existing knowledge of object oriented programming may benefit the learning of modeling and good design. Specific expectations are: Create a class model, Read, recognize, and describe a class model, Describe association and link, Show abstract classes used with multiple inheritance, Explain metadata, reification and constraints, Group classes into a package, Read, recognize, and describe a state model, Explain states and transitions, Read, recognize, and describe interaction model, Explain Use cases and use case relationships, Show concurrency in activity diagram, Object interactions in sequence diagram.

SIG -- The Role of Human-Computer Interaction in Next-Generation Control Rooms

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

Ronald L. Boring; Jacques Hugo; Christian Richard

2005-04-01

The purpose of this CHI Special Interest Group (SIG) is to facilitate the convergence between human-computer interaction (HCI) and control room design. HCI researchers and practitioners actively need to infuse state-of-the-art interface technology into control rooms to meet usability, safety, and regulatory requirements. This SIG outlines potential HCI contributions to instrumentation and control (I&C) and automation in control rooms as well as to general control room design.

Hot particles attract in a cold bath

NASA Astrophysics Data System (ADS)

Tanaka, Hidenori; Lee, Alpha A.; Brenner, Michael P.

2017-04-01

Controlling interactions out of thermodynamic equilibrium is crucial for designing addressable and functional self-organizing structures. These active interactions also underpin collective behavior in biological systems. Here we study a general setting of active particles in a bath of passive particles and demonstrate a mechanism for long-range attraction between active particles. The mechanism operates when the translational persistence length of the active particle motion is smaller than the particle diameter. In this limit, the system reduces to particles of higher diffusivity ("hot" particles) in a bath of particles with lower diffusivity ("cold" particles). This attractive interaction arises as a hot particle pushes cold particles away to create a large hole around itself, and the holes interact via a depletion-like attraction. Strikingly, the interaction range is more than an order of magnitude larger than the particle radius, well beyond the range of the conventional depletion force. Although the mechanism occurs outside the parameter regime of typical biological swimmers, the mechanism could be realized in the laboratory.

Effects of a videotape feedback package on the peer interactions of children with serious behavioral and emotional challenges.

PubMed Central

Kern-Dunlap, L; Dunlap, G; Clarke, S; Childs, K E; White, R L; Stewart, M P

1992-01-01

Peer interactions are among the greatest challenges experienced by children who have severe emotional and behavioral problems. This study evaluated an intervention package designed to increase the ratio of these children's desirable to undesirable interactions. The package included three principal components: (a) observation of videotapes following regularly scheduled peer activity sessions; (b) self-evaluation of the children's peer interactions observed on the videotapes; and (c) delayed feedback and reinforcement for desirable peer interactions. Five students from two elementary schools participated. Multiple baseline designs and one reversal were used to evaluate the effects of the intervention package. The results showed that the intervention produced lower levels of undesirable peer interactions and higher ratios of desirable to undesirable interactions for all participants. The results are discussed in regard to their conceptual and applied implications and in terms of specific directions for future research. PMID:1634428

Randomized trial of a question prompt list to increase patient active participation during interactions with black patients and their oncologists.

PubMed

Eggly, Susan; Hamel, Lauren M; Foster, Tanina S; Albrecht, Terrance L; Chapman, Robert; Harper, Felicity W K; Thompson, Hayley; Griggs, Jennifer J; Gonzalez, Richard; Berry-Bobovski, Lisa; Tkatch, Rifky; Simon, Michael; Shields, Anthony; Gadgeel, Shirish; Loutfi, Randa; Ali, Haythem; Wollner, Ira; Penner, Louis A

2017-05-01

Communication during racially-discordant interactions is often of poor quality and may contribute to racial treatment disparities. We evaluated an intervention designed to increase patient active participation and other communication-related outcomes during interactions between Black patients and non-Black oncologists. Participants were 18 non-Black medical oncologists and 114 Black patients at two cancer hospitals in Detroit, Michigan, USA. Before a clinic visit to discuss treatment, patients were randomly assigned to usual care or to one of two question prompt list (QPL) formats: booklet (QPL-Only), or booklet and communication coach (QPL-plus-Coach). Patient-oncologist interactions were video recorded. Patients reported perceptions of the intervention, oncologist communication, role in treatment decisions, and trust in the oncologist. Observers assessed interaction length, patient active participation, and oncologist communication. The intervention was viewed positively and did not increase interaction length. The QPL-only format increased patient active participation; the QPL-plus-Coach format decreased patient perceptions of oncologist communication. No other significant effects were found. This QPL booklet is acceptable and increases patient active participation in racially-discordant oncology interactions. Future research should investigate whether adding physician-focused interventions might improve other outcomes. This QPL booklet is acceptable and can improve patient active participation in racially-discordant oncology interactions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Integrating Computer Architectures into the Design of High-Performance Controllers

NASA Technical Reports Server (NTRS)

Jacklin, Stephen A.; Leyland, Jane A.; Warmbrodt, William

1986-01-01

Modern control systems must typically perform real-time identification and control, as well as coordinate a host of other activities related to user interaction, on-line graphics, and file management. This paper discusses five global design considerations that are useful to integrate array processor, multimicroprocessor, and host computer system architecture into versatile, high-speed controllers. Such controllers are capable of very high control throughput, and can maintain constant interaction with the non-real-time or user environment. As an application example, the architecture of a high-speed, closed-loop controller used to actively control helicopter vibration will be briefly discussed. Although this system has been designed for use as the controller for real-time rotorcraft dynamics and control studies in a wind-tunnel environment, the control architecture can generally be applied to a wide range of automatic control applications.

Harnessing the web information ecosystem with wiki-based visualization dashboards.

PubMed

McKeon, Matt

2009-01-01

We describe the design and deployment of Dashiki, a public website where users may collaboratively build visualization dashboards through a combination of a wiki-like syntax and interactive editors. Our goals are to extend existing research on social data analysis into presentation and organization of data from multiple sources, explore new metaphors for these activities, and participate more fully in the web!s information ecology by providing tighter integration with real-time data. To support these goals, our design includes novel and low-barrier mechanisms for editing and layout of dashboard pages and visualizations, connection to data sources, and coordinating interaction between visualizations. In addition to describing these technologies, we provide a preliminary report on the public launch of a prototype based on this design, including a description of the activities of our users derived from observation and interviews.

Aligning Game Activity with Educational Goals: Following a Constrained Design Approach to Instructional Computer Games

ERIC Educational Resources Information Center

Shelton, Brett E.; Scoresby, Jon

2011-01-01

We discuss the design, creation and implementation of an instructional game for use in a high school poetry class following a commitment to an educational game design principle of "alignment". We studied groups of instructional designers and an interactive fiction computer game they built. The game was implemented in a 9th grade English classroom…

Energy Based Topology Optimization of Morphing Wings a Multidisciplinary Global/Local Design Approach

DTIC Science & Technology

2006-12-01

subsystem that drives the active materials to achieve the desired shape changes. As opposed to fixed wing structures in which the aerodynamic and...structures and aerodynamics occur in conjunction with the active material and electronic subsystem interactions that involve transfer of energy from a source...which the aerodynamic and structure integration for the entire wing is the most important interaction mechanism, in the case of a morphing wing

Influence of active site location on catalytic activity in de novo-designed zinc metalloenzymes.

PubMed

Zastrow, Melissa L; Pecoraro, Vincent L

2013-04-17

While metalloprotein design has now yielded a number of successful metal-bound and even catalytically active constructs, the question of where to put a metal site along a linear, repetitive sequence has not been thoroughly addressed. Often several possibilities in a given sequence may exist that would appear equivalent but may in fact differ for metal affinity, substrate access, or protein dynamics. We present a systematic variation of active site location for a hydrolytically active ZnHis3O site contained within a de novo-designed three-stranded coiled coil. We find that the maximal rate, substrate access, and metal-binding affinity are dependent on the selected position, while catalytic efficiency for p-nitrophenyl acetate hydrolysis can be retained regardless of the location of the active site. This achievement demonstrates how efficient, tailor-made enzymes which control rate, pKa, substrate and solvent access (and selectivity), and metal-binding affinity may be realized. These findings may be applied to the more advanced de novo design of constructs containing secondary interactions, such as hydrogen-bonding channels. We are now confident that changes to location for accommodating such channels can be achieved without location-dependent loss of catalytic efficiency. These findings bring us closer to our ultimate goal of incorporating the secondary interactions we believe will be necessary in order to improve both active site properties and the catalytic efficiency to be competitive with the native enzyme, carbonic anhydrase.

An Active Learning Activity to Reinforce the Design Components of the Corticosteroids

PubMed Central

Mandela, Prashant

2018-01-01

Despite the popularity of active learning applications over the past few decades, few activities have been reported for the field of medicinal chemistry. The purpose of this study is to report a new active learning activity, describe participant contributions, and examine participant performance on the assessment questions mapped to the objective covered by the activity. In this particular activity, students are asked to design two novel corticosteroids as a group (6–8 students per group) based on the design characteristics of marketed corticosteroids covered in lecture coupled with their pharmaceutics knowledge from the previous semester and then defend their design to the class through an interactive presentation model. Although class performance on the objective mapped to this material on the assessment did not reach statistical significance, use of this activity has allowed fruitful discussion of misunderstood concepts and facilitated multiple changes to the lecture presentation. As pharmacy schools continue to emphasize alternative learning pedagogies, publication of previously implemented activities demonstrating their use will help others apply similar methodologies. PMID:29401733

An Active Learning Activity to Reinforce the Design Components of the Corticosteroids.

PubMed

Slauson, Stephen R; Mandela, Prashant

2018-02-05

Despite the popularity of active learning applications over the past few decades, few activities have been reported for the field of medicinal chemistry. The purpose of this study is to report a new active learning activity, describe participant contributions, and examine participant performance on the assessment questions mapped to the objective covered by the activity. In this particular activity, students are asked to design two novel corticosteroids as a group (6-8 students per group) based on the design characteristics of marketed corticosteroids covered in lecture coupled with their pharmaceutics knowledge from the previous semester and then defend their design to the class through an interactive presentation model. Although class performance on the objective mapped to this material on the assessment did not reach statistical significance, use of this activity has allowed fruitful discussion of misunderstood concepts and facilitated multiple changes to the lecture presentation. As pharmacy schools continue to emphasize alternative learning pedagogies, publication of previously implemented activities demonstrating their use will help others apply similar methodologies.

Participatory design of healthcare technology with children.

PubMed

Sims, Tara

2018-02-12

Purpose There are many frameworks and methods for involving children in design research. Human-Computer Interaction provides rich methods for involving children when designing technologies. The paper aims to discuss these issues. Design/methodology/approach This paper examines various approaches to involving children in design, considering whether users view children as study objects or active participants. Findings The BRIDGE method is a sociocultural approach to product design that views children as active participants, enabling them to contribute to the design process as competent and resourceful partners. An example is provided, in which BRIDGE was successfully applied to developing upper limb prostheses with children. Originality/value Approaching design in this way can provide children with opportunities to develop social, academic and design skills and to develop autonomy.

When a robot is social: spatial arrangements and multimodal semiotic engagement in the practice of social robotics.

PubMed

Alac, Morana; Movellan, Javier; Tanaka, Fumihide

2011-12-01

Social roboticists design their robots to function as social agents in interaction with humans and other robots. Although we do not deny that the robot's design features are crucial for attaining this aim, we point to the relevance of spatial organization and coordination between the robot and the humans who interact with it. We recover these interactions through an observational study of a social robotics laboratory and examine them by applying a multimodal interactional analysis to two moments of robotics practice. We describe the vital role of roboticists and of the group of preverbal infants, who are involved in a robot's design activity, and we argue that the robot's social character is intrinsically related to the subtleties of human interactional moves in laboratories of social robotics. This human involvement in the robot's social agency is not simply controlled by individual will. Instead, the human-machine couplings are demanded by the situational dynamics in which the robot is lodged.

Simulating Social Networks of Online Communities: Simulation as a Method for Sociability Design

NASA Astrophysics Data System (ADS)

Ang, Chee Siang; Zaphiris, Panayiotis

We propose the use of social simulations to study and support the design of online communities. In this paper, we developed an Agent-Based Model (ABM) to simulate and study the formation of social networks in a Massively Multiplayer Online Role Playing Game (MMORPG) guild community. We first analyzed the activities and the social network (who-interacts-with-whom) of an existing guild community to identify its interaction patterns and characteristics. Then, based on the empirical results, we derived and formalized the interaction rules, which were implemented in our simulation. Using the simulation, we reproduced the observed social network of the guild community as a means of validation. The simulation was then used to examine how various parameters of the community (e.g. the level of activity, the number of neighbors of each agent, etc) could potentially influence the characteristic of the social networks.

Learning Microbiology through Cooperation: Designing Cooperative Learning Activities That Promote Interdependence, Interaction, and Accountability.

ERIC Educational Resources Information Center

Trempy, Janine E.; Skinner, Monica M.; Siebold, William A.

2002-01-01

Describes the course "The World According to Microbes" which puts science, mathematics, engineering, and technology majors into teams of students charged with problem solving activities that are microbial in origin. Describes the development of learning activities that utilize key components of cooperative learning including positive…

Carrageenan activates monocytes via type-specific binding with interleukin-8: an implication for design of immuno-active biomaterials.

PubMed

Chan, Weng-I; Zhang, Guangpan; Li, Xin; Leung, Chung-Hang; Ma, Dik-Lung; Dong, Lei; Wang, Chunming

2017-02-28

Polymers that can activate the immune system may become useful biomaterials tools, given that the mechanisms underlying their actions are well understood. Herein, we report a novel type of interaction between polymers and immune cells - in studying the influence of the three major types of carrageenan (CGN) polysaccharides on monocyte behaviour in vitro, we found only the λ-type induced monocyte adhesion and this action requires the presence of an adequate amount of serum. Further analyses indicated λ-CGN bound interleukin-8 (IL-8) in the serum and activated the cultured monocytes through an IL-8-dependent pathway. This is the first demonstration that a polymer, with a renowned immunostimulatory effect, activates the immune system via binding and harnessing the function of a specific cytokine in the microenvironment. This is a new mechanism underlying polymer-immunity interactions that may shed light on future design and application of biomaterials tools targeting the immune system for a wide variety of therapeutic applications.

Fragment-based discovery of novel pentacyclic triterpenoid derivatives as cholesteryl ester transfer protein inhibitors.

PubMed

Chang, Yongzhi; Zhou, Shuxi; Li, Enqin; Zhao, Wenfeng; Ji, Yanpeng; Wen, Xiaoan; Sun, Hongbin; Yuan, Haoliang

2017-01-27

Cholesteryl Ester Transfer Protein (CETP) is an important therapeutic target for the treatment of atherosclerotic cardiovascular disease. Our molecular modeling study revealed that pentacyclic triterpenoid compounds could mimic the protein-ligand interactions of the endogenous ligand cholesteryl ester (CE) by occupying its binding site. Alignment of the docking conformations of oleanolic acid (OA), ursolic acid (UA) and the crystal conformations of known CETP inhibitor Torcetrapib in the active site proposed the applicability of fragment-based drug design (FBDD) approaches in this study. Accordingly, a series of pentacyclic triterpenoid derivatives have been designed and synthesized as novel CETP inhibitors. The most potent compound 12e (IC 50 :0.28 μM) validated our strategy for molecular design. Molecular dynamics simulations illustrated that the more stable hydrogen bond interaction of the UA derivative 12e with Ser191 and stronger hydrophobic interactions with Val198, Phe463 than those of OA derivative 12b mainly led to their significantly different CETP inhibitory activity. These novel potent CETP inhibitors based on ursane-type scaffold should deserve further investigation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Gene–Physical Activity Interactions: Overview of Human Studies

PubMed Central

Rankinen, Tuomo; Bouchard, Claude

2009-01-01

Physical activity level is an important component of the total daily energy expenditure and as such contributes to body weight regulation. A body of data indicates that the level of physical activity plays a role in the risk of excessive weight gain, in weight loss programs, and particularly in the prevention of weight regain. Most studies dealing with potential gene–physical activity interaction effects use an exercise and fitness or performance paradigm as opposed to an obesity-driven model. From these studies, it is clear that there are considerable individual differences in the response to an exercise regimen and that there is a substantial familial aggregation component to the observed heterogeneity. Few studies have focused on the role of specific genes in accounting for the highly prevalent gene–exercise interaction effects. Results for specific genes have been inconsistent with few exceptions. Progress is likely to come when studies will be designed to truly address gene–exercise or physical activity interaction issues and with sample sizes that will provide adequate statistical power. PMID:19037212

Distributed Emotions in the Design of Learning Technologies

ERIC Educational Resources Information Center

Kim, Beaumie; Kim, Mi Song

2010-01-01

Learning is a social activity, which requires interactions with the environment, tools, people, and also ourselves (e.g., our previous experiences). Each interaction provides different meanings to learners, and the associated emotion affects their learning and performance. With the premise that emotion and cognition are distributed, the authors…

The Early Childhood Interactive Technology Literacy Curriculum Project: A Final Report.

ERIC Educational Resources Information Center

Hutinger, Patricia; Robinsosn, Linda; Schneider, Carol; Johanson, Joyce

This final report describes the activities and outcomes of the Interactive Technology Literacy Curriculum (ITLC) project. This federally funded 5-year model demonstration project was designed to advance the availability, quality, use and effectiveness of computer technology in addressing the acquisition of emergent literacy among young children…

Brave New (Interactive) Worlds: A Review of the Design Affordances and Constraints of Two 3D Virtual Worlds as Interactive Learning Environments

ERIC Educational Resources Information Center

Dickey, Michele D.

2005-01-01

Three-dimensional virtual worlds are an emerging medium currently being used in both traditional classrooms and for distance education. Three-dimensional (3D) virtual worlds are a combination of desk-top interactive Virtual Reality within a chat environment. This analysis provides an overview of Active Worlds Educational Universe and Adobe…

DHM simulation in virtual environments: a case-study on control room design.

PubMed

Zamberlan, M; Santos, V; Streit, P; Oliveira, J; Cury, R; Negri, T; Pastura, F; Guimarães, C; Cid, G

2012-01-01

This paper will present the workflow developed for the application of serious games in the design of complex cooperative work settings. The project was based on ergonomic studies and development of a control room among participative design process. Our main concerns were the 3D human virtual representation acquired from 3D scanning, human interaction, workspace layout and equipment designed considering ergonomics standards. Using Unity3D platform to design the virtual environment, the virtual human model can be controlled by users on dynamic scenario in order to evaluate the new work settings and simulate work activities. The results obtained showed that this virtual technology can drastically change the design process by improving the level of interaction between final users and, managers and human factors team.

Disruption of relative reward value by reversible disconnection of orbitofrontal and rhinal cortex using DREADDs in rhesus monkeys

PubMed Central

Eldridge, Mark A G; Lerchner, Walter; Saunders, Richard C; Kaneko, Hiroyuki; Krausz, Kristopher W; Gonzalez, Frank J; Ji, Bin; Higuchi, Makoto; Minamimoto, Takafumi; Richmond, Barry J

2015-01-01

To study how the interaction between orbitofrontal (OFC) and rhinal (Rh) cortices influences the judgment of reward size, we reversibly disconnected these regions using the hM4Di-DREADD (Designer Receptor Exclusively Activated by Designer Drug). Repeated inactivation reduced sensitivity to differences in reward size in two monkeys. Results suggest that retrieval of relative stimulus values from memory appears to depend on interaction between Rh and OFC. PMID:26656645

Designing algorithm visualization on mobile platform: The proposed guidelines

NASA Astrophysics Data System (ADS)

Supli, A. A.; Shiratuddin, N.

2017-09-01

This paper entails an ongoing study about the design guidelines of algorithm visualization (AV) on mobile platform, helping students learning data structures and algorithm (DSA) subject effectively. Our previous review indicated that design guidelines of AV on mobile platform are still few. Mostly, previous guidelines of AV are developed for AV on desktop and website platform. In fact, mobile learning has been proved to enhance engagement in learning circumstances, and thus effect student's performance. In addition, the researchers highly recommend including UI design and Interactivity in designing effective AV system. However, the discussions of these two aspects in previous AV design guidelines are not comprehensive. The UI design in this paper describes the arrangement of AV features in mobile environment, whereas interactivity is about the active learning strategy features based on learning experiences (how to engage learners). Thus, this study main objective is to propose design guidelines of AV on mobile platform (AVOMP) that entails comprehensively UI design and interactivity aspects. These guidelines are developed through content analysis and comparative analysis from various related studies. These guidelines are useful for AV designers to help them constructing AVOMP for various topics on DSA.

A comparative study of patients' activities and interactions in a stroke unit before and after reconstruction-The significance of the built environment.

PubMed

Anåker, Anna; von Koch, Lena; Sjöstrand, Christina; Bernhardt, Julie; Elf, Marie

2017-01-01

Early mobilization and rehabilitation, multidisciplinary stroke expertise and comprehensive therapies are fundamental in a stroke unit. To achieve effective and safe stroke care, the physical environment in modern stroke units should facilitate the delivery of evidence-based care. Therefore, the purpose of this study was to explore patients' activities and interactions in a stroke unit before the reconstruction of the physical environment, while in a temporary location and after reconstruction. This case study examined a stroke unit as an integrated whole. The data were collected using a behavioral mapping technique at three different time points: in the original unit, in the temporary unit and in the new unit. A total of 59 patients were included. The analysis included field notes from observations of the physical environment and examples from planning and design documents. The findings indicated that in the new unit, the patients spent more time in their rooms, were less active, and had fewer interactions with staff and family than the patients in the original unit. The reconstruction involved a change from a primarily multi-bed room design to single-room accommodations. In the new unit, the patients' lounge was located in a far corner of the unit with a smaller entrance than the patients' lounge in the old unit, which was located at the end of a corridor with a noticeable entrance. Changes in the design of the stroke unit may have influenced the patients' activities and interactions. This study raises the question of how the physical environment should be designed in the future to facilitate the delivery of health care and improve outcomes for stroke patients. This research is based on a case study, and although the results should be interpreted with caution, we strongly recommend that environmental considerations be included in future stroke guidelines.

High tech cognitive and acoustic enrichment for captive elephants.

PubMed

French, Fiona; Mancini, Clara; Sharp, Helen

2018-04-15

This paper investigates the potential for using technology to support the development of sensory and cognitive enrichment activities for captive elephants. It explores the usefulness of applying conceptual frameworks from interaction design and game design to the problem of developing species-specific smart toys that promote natural behaviours and provide stimulation. We adopted a Research through Design approach, and describe how scientific inquiry supported our design process, while the creation of artefacts guided our investigations into possible future solutions. Our fieldwork resulted in the development of an interactive prototype of an acoustic toy that elephants are able to control using interface elements constructed from a range of natural materials. Copyright © 2017 Elsevier B.V. All rights reserved.

"It's all about incentive": Social technology as a potential facilitator for self-determined physical activity participation for young people with physical disabilities.

PubMed

Knibbe, Tara Joy; McPherson, Amy C; Gladstone, Brenda; Biddiss, Elaine

2017-09-29

To investigate the perceived role of social technologies in promoting physical activity participation for young people with physical disabilities and to identify design considerations that should be addressed when creating social technologies to promote physical activity. Interactive design workshops for young people with physical disabilities aged 12-18 (n = 8) were held. Data were analyzed using interpretive thematic analysis. Young people perceived significant benefit for social technologies to promote physical activity as they have the potential to overcome many barriers to physical activity participation. Design features recommended by the participants included (1) options for diverse interests and preferences, (2) provision of informational support, (3) support through equitable technology design, (4) incentive through competition and play, and (5) opportunities to develop community. Social technology has potential to provide tailored, equitable opportunities for social engagement and physical activity participation for young people with physical disabilities through needs- and preference-specific design.

Exploratory qualitative case study of lab-type activity interactions in an online graduate geoscience course

NASA Astrophysics Data System (ADS)

Ciavarella, Veronica C.

This exploratory qualitative case study investigated the use of lab-type activities in an online graduate geoscience course. Constructivism is the theoretical framework used to explain how learning happens in lab-type activity, and provided the goals to which successful learning in lab-type activity is compared. This study focused on the learner-instructor, learner-learner, and perceptions of the learner-content interactions that occurred related to lab-type activities in an online graduate geoscience course to determine: if the instructor appeared as a facilitator of the learning process in the interactions over the activities; if students engaged in discussion and reflection about the activities; if students perceived the activities as meaningful and authentic; and if students perceived using higher order thinking and prior knowledge while interacting with the content. Ten graduate students from three offerings of the course participated in this study, as well as the instructor and designer of the course content and lab-type activities. Data were collected through interviews, and observation and analysis of the lab-type activities, instructor feedback to students in their graded activities, and discussion that occurred between the instructor and students and among students about the lab-type activities in discussion forums. The nature of the instructor's interactions in discussion forums, in feedback to students on graded activities, and reported by students' in interviews supported that, in the learner-instructor interactions, the instructor of this course was a facilitator who guided and scaffolded the students towards successfully completing the activities. Students engaged in discussion and reflected on the activities, but most learner-learner interactions in discussion forums about the lab-type activities appeared to occur for the purpose of comparison of results, support, and empathy. Students' success at higher order thinking type questions in lab-type activities and their perceptions reported in interviews of using higher order thinking in their interactions with the lab-type activities supported that the learner-content interactions involved higher order thinking. Students also reported finding the activities realistic, meaningful and authentic, and this increased their interest with the activities, and the activities aided their understanding of the content.

Design, Implementation and Evaluation of Innovative Science Teaching Strategies for Non-Formal Learning in a Natural History Museum

ERIC Educational Resources Information Center

Çil, Emine; Maccario, Nihal; Yanmaz, Durmus

2016-01-01

Background: Museums are useful educational resources in science teaching. Teaching strategies which promote hands-on activities, student-centred learning, and rich social interaction must be designed and implemented throughout the museum visit for effective science learning. Purpose: This study aimed to design and implement innovative teaching…

Molecular design of new aggrecanases-2 inhibitors.

PubMed

Shan, Zhi Jie; Zhai, Hong Lin; Huang, Xiao Yan; Li, Li Na; Zhang, Xiao Yun

2013-10-01

Aggrecanases-2 is a very important potential drug target for the treatment of osteoarthritis. In this study, a series of known aggrecanases-2 inhibitors was analyzed by the technologies of three-dimensional quantitative structure-activity relationships (3D-QSAR) and molecular docking. Two 3D-QSAR models, which based on comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods, were established. Molecular docking was employed to explore the details of the interaction between inhibitors and aggrecanases-2 protein. According to the analyses for these models, several new potential inhibitors with higher activity predicted were designed, and were supported by the simulation of molecular docking. This work propose the fast and effective approach to design and prediction for new potential inhibitors, and the study of the interaction mechanism provide a better understanding for the inhibitors binding into the target protein, which will be useful for the structure-based drug design and modifications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Design, Synthesis, Biological Evaluation, and X-ray Studies of HIV-1 Protease Inhibitors with Modified P2′ Ligands of Darunavir

PubMed Central

Fyvie, W. Sean; Brindisi, Margherita; Steffey, Melinda; Agniswamy, Johnson; Wang, Yuan-Fang; Aoki, Manabu; Amano, Masayuki; Weber, Irene T.; Mitsuya, Hiroaki

2018-01-01

The structure-based design, synthesis, and biological evaluation of a series of nonpeptidic HIV-1 protease inhibitors with rationally designed P2′ ligands are described. The inhibitors are designed to enhance backbone binding interactions, particularly at the S2′ subsite. Synthesis of inhibitors was carried out efficiently. The stereochemistry of alcohol functionalities of the P2′ ligands was set by asymmetric reduction of the corresponding ketone using (R,R)- or (S,S)-Noyori catalysts. A number of inhibitors displayed very potent enzyme inhibitory and antiviral activity. Inhibitors 3g and 3h showed enzyme Ki values of 27.9 and 49.7 pM and antiviral activity of 6.2 and 3.9 nM, respectively. These inhibitors also remained quite potent against darunavir-resistant HIV-1 variants. An X-ray structure of inhibitor 3g in complex with HIV-1 protease revealed key interactions in the S2′ subsite. PMID:29110408

Closing the door on pharma? A national survey of family medicine residencies regarding industry interactions.

PubMed

Fugh-Berman, Adriane; Brown, Steven R; Trippett, Rachel; Bell, Alicia M; Clark, Paige; Fleg, Anthony; Siwek, Jay

2011-05-01

To assess the extent and type of interactions U.S. family medicine residencies permit industry to have with medical students and residents. In 2008, the authors e-mailed a four-question survey to residency directors or coordinators at all 460 accredited U.S. family medicine residencies concerning the types of industry support and interaction permitted. The authors conducted quantitative and qualitative analyses of survey responses and written comments. Residencies that did not permit any industry food, gifts, samples, or support of residency activities were designated "pharma-free." The survey response rate was 62.2% (286/460). Among responding family medicine residencies, 52.1% refused drug samples, 48.6% disallowed industry gifts or food, 68.5% forbade industry-sponsored residency activities, and 44.1% denied industry access to students and residents at the family medicine center. Seventy-five residencies (26.2%) were designated as "pharma-free." Medical-school-based and medical-school-administered residencies were no more likely than community-based residencies to be pharma-free. Among the 211 programs that permitted interaction, 68.7% allowed gifts or food, 61.1% accepted drug samples, 71.1% allowed industry representatives access to trainees in the family medicine center, and 37.9% allowed industry-sponsored residency activities. Respondents commented on challenges inherent to limiting industry interactions. Many programs noted recent changes in plans or practices. Most family medicine residencies limit industry interaction with trainees. Because industry interactions can have adverse effects on rational prescribing, residency programs should assess the benefits and harms of these relationships. Copyright © by the Association of American medical Colleges.

Novel Television-Based Cognitive Training Improves Working Memory and Executive Function

PubMed Central

Shatil, Evelyn; Mikulecká, Jaroslava; Bellotti, Francesco; Bureš, Vladimír

2014-01-01

The main study objective was to investigate the effect of interactive television-based cognitive training on cognitive performance of 119 healthy older adults, aged 60–87 years. Participants were randomly allocated to a cognitive training group or to an active control group in a single-blind controlled two-group design. Before and after training interactive television cognitive performance was assessed on well validated tests of fluid, higher-order ability, and system usability was evaluated. The participants in the cognitive training group completed a television-based cognitive training programme, while the participants in the active control group completed a TV-based programme of personally benefiting activities. Significant improvements were observed in well validated working memory and executive function tasks in the cognitive training but not in the control group. None of the groups showed statistically significant improvement in life satisfaction score. Participants' reports of “adequate” to “high” system usability testify to the successful development and implementation of the interactive television-based system and compliant cognitive training contents. The study demonstrates that cognitive training delivered by means of an interactive television system can generate genuine cognitive benefits in users and these are measurable using well-validated cognitive tests. Thus, older adults who cannot use or afford a computer can easily use digital interactive television to benefit from advanced software applications designed to train cognition. PMID:24992187

Computational approaches for drug discovery.

PubMed

Hung, Che-Lun; Chen, Chi-Chun

2014-09-01

Cellular proteins are the mediators of multiple organism functions being involved in physiological mechanisms and disease. By discovering lead compounds that affect the function of target proteins, the target diseases or physiological mechanisms can be modulated. Based on knowledge of the ligand-receptor interaction, the chemical structures of leads can be modified to improve efficacy, selectivity and reduce side effects. One rational drug design technology, which enables drug discovery based on knowledge of target structures, functional properties and mechanisms, is computer-aided drug design (CADD). The application of CADD can be cost-effective using experiments to compare predicted and actual drug activity, the results from which can used iteratively to improve compound properties. The two major CADD-based approaches are structure-based drug design, where protein structures are required, and ligand-based drug design, where ligand and ligand activities can be used to design compounds interacting with the protein structure. Approaches in structure-based drug design include docking, de novo design, fragment-based drug discovery and structure-based pharmacophore modeling. Approaches in ligand-based drug design include quantitative structure-affinity relationship and pharmacophore modeling based on ligand properties. Based on whether the structure of the receptor and its interaction with the ligand are known, different design strategies can be seed. After lead compounds are generated, the rule of five can be used to assess whether these have drug-like properties. Several quality validation methods, such as cost function analysis, Fisher's cross-validation analysis and goodness of hit test, can be used to estimate the metrics of different drug design strategies. To further improve CADD performance, multi-computers and graphics processing units may be applied to reduce costs. © 2014 Wiley Periodicals, Inc.

Nano-assembly of Surfactants with Interfacial Drug-Interactive Motifs as Tailor-Designed Drug Carriers

PubMed Central

Gao, Xiang; Huang, Yixian; Makhov, Alexander M.; Epperly, Michael; Lu, Jianqin; Grab, Sheila; Zhang, Peijun; Rohan, Lisa; Xie, Xiang-qun (Sean); Wipf, Peter; Greenberger, Joel; Li, Song

2012-01-01

PEGylated lipopeptide surfactants carrying drug-interactive motifs specific for a peptide-nitroxide antioxidant, JP4-039, were designed and constructed to facilitate the solubilization of this drug candidate as micelles and emulsion nanoparticles. A simple screening process based on the ability that prevents the formation of crystals of JP4-039 in aqueous solution was used to identify agents that have potential drug-interactive activities. Several protected lysine derivatives possessing this activity were identified, of which α-Fmoc-ε-tBoc lysine is the most potent, followed by α-Cbz- and α-iso-butyloxycarbonyl-ε-tBoc-lysine. Using polymer-supported liquid-phase synthesis approach, a series of synthetic lipopeptide surfactants with PEG head group, varied numbers and geometries of α-Fmoc or α-Cbz-lysyl groups located at interfacial region as the drug-interactive domains, and oleoyl chains as the hydrophobic tails were synthesized. All α-Fmoc-lysyl-containing lipopeptide surfactants were able to solubilize JP4-039 as micelles, with enhanced solubilizing activity for surfactants with increased numbers of α-Fmoc groups. The PEGylated lipopeptide surfactants with α-Fmoc-lysyl groups alone tend to form filamentous or worm-like micelles. The presence of JP4-039 transformed α-Fmoc-containing filamentous micelles into dots and bar-like mixed micelles with substantially reduced sizes. Fluorescence quenching and NMR studies revealed that the drug and surfactant molecules were in a close proximity in the complex. JP4-039-loaded emulsion carrying α-Cbz-containing surfactants demonstrated enhanced stability over drug loaded emulsion without lipopeptide surfactants. JP4-039-emulsion showed significant mitigation effect on mice exposed to a lethal dose of radiation. PEGylated lipopeptides with an interfacially located drug-interactive domain are therefore tailor-designed formulation materials potentially useful for drug development. PMID:23244299

Interactive video dance games for healthy older adults.

PubMed

Studenski, S; Perera, S; Hile, E; Keller, V; Spadola-Bogard, J; Garcia, J

2010-12-01

Physical activity promotes health in older adults but participation rates are low. Interactive video dance games can increase activity in young persons but have not been designed for use with older adults. The purpose of this research was to evaluate healthy older adults' interest and participation in a dance game adapted for an older user. Healthy older adults were recruited from 3 senior living settings and offered three months of training and supervision using a video dance game designed for older people. Before and after the program, data was collected on vital signs, physical function and self reported quality of life. Feedback was obtained during and after training. Of 36 persons who entered (mean age 80.1 + 5.4 years, 83 % female), 25 completed the study. Completers were healthier than noncompleters. Completers showed gains in narrow walk time, self-reported balance confidence and mental health. While there were no serious adverse events, 4 of 11 noncompleters withdrew due to musculoskeletal complaints. Adapted Interactive video dance is feasible for some healthy older adults and may help achieve physical activity goals.

High-speed, automatic controller design considerations for integrating array processor, multi-microprocessor, and host computer system architectures

NASA Technical Reports Server (NTRS)

Jacklin, S. A.; Leyland, J. A.; Warmbrodt, W.

1985-01-01

Modern control systems must typically perform real-time identification and control, as well as coordinate a host of other activities related to user interaction, online graphics, and file management. This paper discusses five global design considerations which are useful to integrate array processor, multimicroprocessor, and host computer system architectures into versatile, high-speed controllers. Such controllers are capable of very high control throughput, and can maintain constant interaction with the nonreal-time or user environment. As an application example, the architecture of a high-speed, closed-loop controller used to actively control helicopter vibration is briefly discussed. Although this system has been designed for use as the controller for real-time rotorcraft dynamics and control studies in a wind tunnel environment, the controller architecture can generally be applied to a wide range of automatic control applications.

Posting Behaviour Patterns in an Online Smoking Cessation Social Network: Implications for Intervention Design and Development

PubMed Central

Healey, Benjamin; Hoek, Janet; Edwards, Richard

2014-01-01

Objectives Online Cessation Support Networks (OCSNs) are associated with increased quit success rates, but few studies have examined their use over time. We identified usage patterns in New Zealand's largest OCSN over two years and explored implications for OCSN intervention design and evaluation. Methods We analysed metadata relating to 133,096 OCSN interactions during 2011 and 2012. Metrics covered aggregate network activity, user posting activity and longevity, and between-user commenting. Binary logistic regression models were estimated to investigate the feasibility of predicting low user engagement using early interaction data. Results Repeating periodic peaks and troughs in aggregate activity related not only to seasonality (e.g., New Year), but also to day of the week. Out of 2,062 unique users, 69 Highly Engaged Users (180+ interactions each) contributed 69% of all OCSN interactions in 2012 compared to 1.3% contributed by 864 Minimally Engaged Users (< = 2 items each). The proportion of Highly Engaged Users increased with network growth between 2011 and 2012 (with marginal significance), but the proportion of Minimally Engaged Users did not decline substantively. First week interaction data enabled identification of Minimally Engaged Users with high specificity and sensitivity (AUROC  = 0.94). Implications Results suggest future research should develop and test interventions that promote activity, and hence cessation support, amongst specific user groups or at key time points. For example, early usage information could help identify Minimally Engaged Users for tests of targeted messaging designed to improve their integration into, or re-engagement with, the OCSN. Furthermore, although we observed strong growth over time on varied metrics including posts and comments, this change did not coincide with large gains in first-time user persistence. Researchers assessing intervention effects should therefore examine multiple measures when evaluating changes in network dynamics over time. PMID:25192174

The NASA controls-structures interaction technology program

NASA Technical Reports Server (NTRS)

Newsom, Jerry R.; Layman, W. E.; Waites, H. B.; Hayduk, R. J.

1990-01-01

The interaction between a flexible spacecraft structure and its control system is commonly referred to as controls-structures interaction (CSI). The CSI technology program is developing the capability and confidence to integrate the structure and control system, so as to avoid interactions that cause problems and to exploit interactions to increase spacecraft capability. A NASA program has been initiated to advance CSI technology to a point where it can be used in spacecraft design for future missions. The CSI technology program is a multicenter program utilizing the resources of the NASA Langley Research Center (LaRC), the NASA Marshall Space Flight Center (MSFC), and the NASA Jet Propulsion Laboratory (JPL). The purpose is to describe the current activities, results to date, and future activities of the NASA CSI technology program.

An Observational Assessment of Physical Activity Levels and Social Behaviour during Elementary School Recess

ERIC Educational Resources Information Center

Roberts, Simon J.; Fairclough, Stuart J.; Ridgers, Nicola D.; Porteous, Conor

2013-01-01

Objective: The purpose of the present study was to assess children's physical activity, social play behaviour, activity type and social interactions during elementary school recess using a pre-validated systematic observation system. Design: Cross-sectional. Setting: Two elementary schools located in Merseyside, England. Method: Fifty-six…

Behavioral science and the study of gene-nutrition and gene-physical activity interactions in obesity research.

PubMed

Faith, Myles S

2008-12-01

This report summarizes emerging opportunities for behavioral science to help advance the field of gene-environment and gene-behavior interactions, based on presentations at The National Cancer Institute (NCI) Workshop, "Gene-Nutrition and Gene-Physical Activity Interactions in the Etiology of Obesity." Three opportunities are highlighted: (i) designing potent behavioral "challenges" in experiments, (ii) determining viable behavioral phenotypes for genetics studies, and (iii) identifying specific measures of the environment or environmental exposures. Additional points are underscored, including the need to incorporate novel findings from neuroimaging studies regarding motivation and drive for eating and physical activity. Advances in behavioral science theory and methods can play an important role in advancing understanding of gene-brain-behavior relationships in obesity onset.

Discovery of HDAC Inhibitors That Lack an Active Site Zn(2+)-Binding Functional Group.

PubMed

Vickers, Chris J; Olsen, Christian A; Leman, Luke J; Ghadiri, M Reza

2012-06-14

Natural and synthetic histone deacetylase (HDAC) inhibitors generally derive their strong binding affinity and high potency from a key functional group that binds to the Zn(2+) ion within the enzyme active site. However, this feature is also thought to carry the potential liability of undesirable off-target interactions with other metalloenzymes. As a step toward mitigating this issue, here, we describe the design, synthesis, and structure-activity characterizations of cyclic α3β-tetrapeptide HDAC inhibitors that lack the presumed indispensable Zn(2+)-binding group. The lead compounds (e.g., 15 and 26) display good potency against class 1 HDACs and are active in tissue culture against various human cancer cell lines. Importantly, enzymological analysis of 26 indicates that the cyclic α3β-tetrapeptide is a fast-on/off competitive inhibitor of HDACs 1-3 with K i values of 49, 33, and 37 nM, respectively. Our proof of principle study supports the idea that novel classes of HDAC inhibitors, which interact at the active-site opening, but not with the active site Zn(2+), can have potential in drug design.

Design, implementation and evaluation of innovative science teaching strategies for non-formal learning in a natural history museum

NASA Astrophysics Data System (ADS)

Çil, Emine; Maccario, Nihal; Yanmaz, Durmuş

2016-09-01

Background: Museums are useful educational resources in science teaching. Teaching strategies which promote hands-on activities, student-centred learning, and rich social interaction must be designed and implemented throughout the museum visit for effective science learning.

Design and experimental validation of a flutter suppression controller for the active flexible wing

NASA Technical Reports Server (NTRS)

Waszak, Martin R.; Srinathkumar, S.

1992-01-01

The synthesis and experimental validation of an active flutter suppression controller for the Active Flexible Wing wind tunnel model is presented. The design is accomplished with traditional root locus and Nyquist methods using interactive computer graphics tools and extensive simulation based analysis. The design approach uses a fundamental understanding of the flutter mechanism to formulate a simple controller structure to meet stringent design specifications. Experimentally, the flutter suppression controller succeeded in simultaneous suppression of two flutter modes, significantly increasing the flutter dynamic pressure despite modeling errors in predicted flutter dynamic pressure and flutter frequency. The flutter suppression controller was also successfully operated in combination with another controller to perform flutter suppression during rapid rolling maneuvers.

JPL control/structure interaction test bed real-time control computer architecture

NASA Technical Reports Server (NTRS)

Briggs, Hugh C.

1989-01-01

The Control/Structure Interaction Program is a technology development program for spacecraft that exhibit interactions between the control system and structural dynamics. The program objectives include development and verification of new design concepts - such as active structure - and new tools - such as combined structure and control optimization algorithm - and their verification in ground and possibly flight test. A focus mission spacecraft was designed based upon a space interferometer and is the basis for design of the ground test article. The ground test bed objectives include verification of the spacecraft design concepts, the active structure elements and certain design tools such as the new combined structures and controls optimization tool. In anticipation of CSI technology flight experiments, the test bed control electronics must emulate the computation capacity and control architectures of space qualifiable systems as well as the command and control networks that will be used to connect investigators with the flight experiment hardware. The Test Bed facility electronics were functionally partitioned into three units: a laboratory data acquisition system for structural parameter identification and performance verification; an experiment supervisory computer to oversee the experiment, monitor the environmental parameters and perform data logging; and a multilevel real-time control computing system. The design of the Test Bed electronics is presented along with hardware and software component descriptions. The system should break new ground in experimental control electronics and is of interest to anyone working in the verification of control concepts for large structures.

NASA/DOD Control/Structures Interaction Technology, 1986

NASA Technical Reports Server (NTRS)

Wright, Robert L. (Compiler)

1986-01-01

Control/structures interactions, deployment dynamics and system performance of large flexible spacecraft are discussed. Spacecraft active controls, deployable truss structures, deployable antennas, solar power systems for space stations, pointing control systems for space station gimballed payloads, computer-aided design for large space structures, and passive damping for flexible structures are among the topics covered.

Graphical Interaction Analysis Impact on Groups Collaborating through Blogs

ERIC Educational Resources Information Center

Fessakis, Georgios; Dimitracopoulou, Angelique; Palaiodimos, Aggelos

2013-01-01

This paper presents empirical research results regarding the impact of Interaction Analysis (IA) graphs on groups of students collaborating through online blogging according to a "learning by design" scenario. The IA graphs used are of two categories; the first category summarizes quantitatively the activity of the users for each blog,…

Using Interactive "Shiny" Applications to Facilitate Research-Informed Learning and Teaching

ERIC Educational Resources Information Center

Fawcett, Lee

2018-01-01

In this article we discuss our attempt to incorporate research-informed learning and teaching activities into a final year undergraduate Statistics course. We make use of the Shiny web-based application framework for R to develop "Shiny apps" designed to help facilitate student interaction with methods from recently published papers in…

Snapshots of Interactive Multimedia at Work Across the Curriculum in Deaf Education: Implications for Public Address Training

ERIC Educational Resources Information Center

Parton, Becky Sue

2006-01-01

A review of the literature yields many intriguing applications of interactive multimedia technology that can be seen through a series of "snapshots" describing current projects and initiatives for deaf education. The five main categories chosen to represent these activities are: instructional design, communication bridges, skill development…

An Interactive Robotic Fish Exhibit for Designed Settings in Informal Science Learning

ERIC Educational Resources Information Center

Phamduy, Paul; Leou, Mary; Milne, Catherine; Porfiri, Maurizio

2017-01-01

Informal science learning aims to improve public understanding of STEM. Free-choice learners can be engaged in a wide range of experiences, ranging from watching entertaining educational videos to actively participating in hands-on projects. Efforts in informal science learning are often gauged by their ability to elicit interaction, to foster…

Interaction Support for Information Finding and Comparative Analysis in Online Video

ERIC Educational Resources Information Center

Xia, Jinyue

2017-01-01

Current online video interaction is typically designed with a focus on straightforward distribution and passive consumption of individual videos. This "click play, sit back and watch" context is typical of videos for entertainment. However, there are many task scenarios that require active engagement and analysis of video content as a…

Play Time/Social Time: Organizing Your Classroom To Build Interaction Skills.

ERIC Educational Resources Information Center

Odom, Samuel L.; McConnell, Scott R.; Ostrosky, Michaelene; Peterson, Carla; Skellenger, Annette; Spicuzza, Richard; Chandler, Lynette K.; McEvoy, Mary A.

This curriculum guide provides classroom organizational guidelines, activities, and lesson plans to promote social interaction and the development of social competence in preschool children with disabilities or at risk for developmental problems or delays. The program is designed to include peers who are either developing normally or have higher…

State College Scavenger: Evaluating the Perspectives of Mobile Computing Interactions within Community Spaces

ERIC Educational Resources Information Center

Hoffman, Blaine

2013-01-01

This work focuses on the impact of mobile computing on individuals' perspectives of places within their community. A technological intervention is designed and deployed to augment the user experience of visiting different locations around town, physically exploring them while also interacting with an online tool. The tool-supported activity serves…

The Reading Disc: Learning to Read Using Interactive CD.

ERIC Educational Resources Information Center

Shaw, Simon

1991-01-01

Describes the development of an interactive compact disc on CD-ROM XA that was designed to help adults learn to read. The application of technology to learning is discussed, differences in learner control in computer-based systems are considered, virtual writing is described, and assessment activities available on the disc are explained. (five…

Design and Structure-Guided Development of Novel Inhibitors of the Xeroderma Pigmentosum Group A (XPA) Protein-DNA Interaction.

PubMed

Gavande, Navnath S; VanderVere-Carozza, Pamela; Mishra, Akaash K; Vernon, Tyler L; Pawelczak, Katherine S; Turchi, John J

2017-10-12

XPA is a unique and essential protein required for the nucleotide excision DNA repair pathway and represents a therapeutic target in oncology. Herein, we are the first to develop novel inhibitors of the XPA-DNA interaction through structure-guided drug design efforts. Ester derivatives of the compounds 1 (X80), 22, and 24 displayed excellent inhibitory activity (IC 50 of 0.82 ± 0.18 μM and 1.3 ± 0.22 μM, respectively) but poor solubility. We have synthesized novel amide derivatives that retain potency and have much improved solubility. Furthermore, compound 1 analogs exhibited good specificity for XPA over RPA (replication protein A), another DNA-binding protein that participates in the nucleotide excision repair (NER) pathway. Importantly, there were no significant interactions observed by the X80 class of compounds directly with DNA. Molecular docking studies revealed a mechanistic model for the interaction, and these studies could serve as the basis for continued analysis of structure-activity relationships and drug development efforts of this novel target.

Efficient and Effective Change Principles in Active Videogames

PubMed Central

Fenner, Ashley A.; Howie, Erin K.; Feltz, Deborah L.; Gray, Cindy M.; Lu, Amy Shirong; Mueller, Florian “Floyd”; Simons, Monique; Barnett, Lisa M.

2015-01-01

Abstract Active videogames have the potential to enhance population levels of physical activity but have not been successful in achieving this aim to date. This article considers a range of principles that may be important to the design of effective and efficient active videogames from diverse discipline areas, including behavioral sciences (health behavior change, motor learning, and serious games), business production (marketing and sales), and technology engineering and design (human–computer interaction/ergonomics and flow). Both direct and indirect pathways to impact on population levels of habitual physical activity are proposed, along with the concept of a game use lifecycle. Examples of current active and sedentary electronic games are used to understand how such principles may be applied. Furthermore, limitations of the current usage of theoretical principles are discussed. A suggested list of principles for best practice in active videogame design is proposed along with suggested research ideas to inform practice to enhance physical activity. PMID:26181680

Efficient and Effective Change Principles in Active Videogames.

PubMed

Straker, Leon M; Fenner, Ashley A; Howie, Erin K; Feltz, Deborah L; Gray, Cindy M; Lu, Amy Shirong; Mueller, Florian Floyd; Simons, Monique; Barnett, Lisa M

2015-02-01

Active videogames have the potential to enhance population levels of physical activity but have not been successful in achieving this aim to date. This article considers a range of principles that may be important to the design of effective and efficient active videogames from diverse discipline areas, including behavioral sciences (health behavior change, motor learning, and serious games), business production (marketing and sales), and technology engineering and design (human-computer interaction/ergonomics and flow). Both direct and indirect pathways to impact on population levels of habitual physical activity are proposed, along with the concept of a game use lifecycle. Examples of current active and sedentary electronic games are used to understand how such principles may be applied. Furthermore, limitations of the current usage of theoretical principles are discussed. A suggested list of principles for best practice in active videogame design is proposed along with suggested research ideas to inform practice to enhance physical activity.

Cyberpsychology: a human-interaction perspective based on cognitive modeling.

PubMed

Emond, Bruno; West, Robert L

2003-10-01

This paper argues for the relevance of cognitive modeling and cognitive architectures to cyberpsychology. From a human-computer interaction point of view, cognitive modeling can have benefits both for theory and model building, and for the design and evaluation of sociotechnical systems usability. Cognitive modeling research applied to human-computer interaction has two complimentary objectives: (1) to develop theories and computational models of human interactive behavior with information and collaborative technologies, and (2) to use the computational models as building blocks for the design, implementation, and evaluation of interactive technologies. From the perspective of building theories and models, cognitive modeling offers the possibility to anchor cyberpsychology theories and models into cognitive architectures. From the perspective of the design and evaluation of socio-technical systems, cognitive models can provide the basis for simulated users, which can play an important role in usability testing. As an example of application of cognitive modeling to technology design, the paper presents a simulation of interactive behavior with five different adaptive menu algorithms: random, fixed, stacked, frequency based, and activation based. Results of the simulation indicate that fixed menu positions seem to offer the best support for classification like tasks such as filing e-mails. This research is part of the Human-Computer Interaction, and the Broadband Visual Communication research programs at the National Research Council of Canada, in collaboration with the Carleton Cognitive Modeling Lab at Carleton University.

Evaluation for the design of experience in virtual environments: modeling breakdown of interaction and illusion.

PubMed

Marsh, T; Wright, P; Smith, S

2001-04-01

New and emerging media technologies have the potential to induce a variety of experiences in users. In this paper, it is argued that the inducement of experience presupposes that users are absorbed in the illusion created by these media. Looking to another successful visual medium, film, this paper borrows from the techniques used in "shaping experience" to hold spectators' attention in the illusion of film, and identifies what breaks the illusion/experience for spectators. This paper focuses on one medium, virtual reality (VR), and advocates a transparent or "invisible style" of interaction. We argue that transparency keeps users in the "flow" of their activities and consequently enhances experience in users. Breakdown in activities breaks the experience and subsequently provides opportunities to identify and analyze potential causes of usability problems. Adopting activity theory, we devise a model of interaction with VR--through consciousness and activity--and introduce the concept of breakdown in illusion. From this, a model of effective interaction with VR is devised and the occurrence of breakdown in interaction and illusion is identified along a continuum of engagement. Evaluation guidelines for the design of experience are proposed and applied to usability problems detected in an empirical study of a head-mounted display (HMD) VR system. This study shows that the guidelines are effective in the evaluation of VR. Finally, we look at the potential experiences that may be induced in users and propose a way to evaluate user experience in virtual environments (VEs) and other new and emerging media.

Co-creating value through demand and supply integration in senior industry-observations on 33 senior enterprises in Taiwan.

PubMed

Yang, Ya-Ting; Iqbal, Usman; Chen, Ya-Mei; Su, Shyi; Chang, Yao-Mao; Handa, Yujiro; Lin, Neng-Pai; Hsu, Yi-Hsin Elsa

2016-09-01

With global population aging, great business opportunities are driven by the various needs that the elderly face in everyday living. Internet development makes information spread faster, also allows elderly and their caregivers to more easily access information and actively participate in value co-creation in the services. This study aims to investigate the designs of value co-creation by the supply and demand sides of the senior industry. This study investigated senior industry in Taiwan and analyzed bussiness models of 33 selected successful senior enterprises in 2013. We adopted series field observation, reviews of documentations, analysis of meeting records and in-depth interviews with 65 CEOs and managers. Thirty-three quality enterprises in senior industry. Sixty-five CEOs and managers in 33 senior enterprises. None. Value co-creation design, value co-creating process. We constructed a conceptual model that comprehensively describes essential aspects of value co-creation and categorized the value co-creation designs into four types applying for different business models: (i) interaction in experience spaces co-creation design, (ii) on-site interacting co-creation design, (iii) social networking platform co-creation design and (iv) empowering customers co-creation design. Through value co-creation platform design, the senior enterprises have converted the originally passive roles of the elderly and caregivers into active participants in the value co-creation process. The new paradigm of value co-creation designs not only promote innovative development during the interactive process, lead enterprises reveal and meet customers' needs but also increase markets and profits. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Engineering antimicrobial peptides with improved antimicrobial and hemolytic activities.

PubMed

Zhao, Jun; Zhao, Chao; Liang, Guizhao; Zhang, Mingzhen; Zheng, Jie

2013-12-23

The rapid rise of antibiotic resistance in pathogens becomes a serious and growing threat to medicine and public health. Naturally occurring antimicrobial peptides (AMPs) are an important line of defense in the immune system against invading bacteria and microbial infection. In this work, we present a combined computational and experimental study of the biological activity and membrane interaction of the computationally designed Bac2A-based peptide library. We used the MARTINI coarse-grained molecular dynamics with adaptive biasing force method and the umbrella sampling technique to investigate the translocation of a total of 91 peptides with different amino acid substitutions through a mixed anionic POPE/POPG (3:1) bilayer and a neutral POPC bilayer, which mimic the bacterial inner membrane and the human red blood cell (hRBC) membrane, respectively. Potential of mean force (PMF, free energy profile) was obtained to measure the free energy barrier required to transfer the peptides from the bulk water phase to the water-membrane interface and to the bilayer interior. Different PMF profiles can indeed identify different membrane insertion scenarios by mapping out peptide-lipid energy landscapes, which are correlated with antimicrobial activity and hemolytic activity. Computationally designed peptides were further tested experimentally for their antimicrobial and hemolytic activities using bacteria growth inhibition assay and hemolysis assay. Comparison of PMF data with cell assay results reveals a good correlation of the peptides between predictive transmembrane activity and antimicrobial/hemolytic activity. Moreover, the most active mutants with the balanced substitutions of positively charged Arg and hydrophobic Trp residues at specific positions were discovered to achieve the improved antimicrobial activity while minimizing red blood cell lysis. Such substitutions provide more effective and cooperative interactions to distinguish the peptide interaction with different lipid bilayers. This work provides a useful computational tool to better understand the mechanism and energetics of membrane insertion of AMPs and to rationally design more effective AMPs.

Affective Education Handbook for Vocational Education.

ERIC Educational Resources Information Center

Odum, Nancy L.; And Others

Designed to introduce the vocational teacher to activities through which peer interaction promotes the understanding of self and others in a working environment, this handbook provides activities that focus on attitudes, interests, and values development. The first topic, work habits, deals with absenteeism, coffee break abuse, communication…

Structural Insights into the Role of the Cyclic Backbone in a Squash Trypsin Inhibitor*

PubMed Central

Daly, Norelle L.; Thorstholm, Louise; Greenwood, Kathryn P.; King, Gordon J.; Rosengren, K. Johan; Heras, Begoña; Martin, Jennifer L.; Craik, David J.

2013-01-01

MCoTI-II is a head-to-tail cyclic peptide with potent trypsin inhibitory activity and, on the basis of its exceptional proteolytic stability, is a valuable template for the design of novel drug leads. Insights into inhibitor dynamics and interactions with biological targets are critical for drug design studies, particularly for protease targets. Here, we show that the cyclization and active site loops of MCoTI-II are flexible in solution, but when bound to trypsin, the active site loop converges to a single well defined conformation. This finding of reduced flexibility on binding is in contrast to a recent study on the homologous peptide MCoTI-I, which suggested that regions of the peptide are more flexible upon binding to trypsin. We provide a possible explanation for this discrepancy based on degradation of the complex over time. Our study also unexpectedly shows that the cyclization loop, not present in acyclic homologues, facilitates potent trypsin inhibitory activity by engaging in direct binding interactions with trypsin. PMID:24169696

Designing a highly active soluble PQQ-glucose dehydrogenase for efficient glucose biosensors and biofuel cells

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

Durand, Fabien; Stines-Chaumeil, Claire; Flexer, Victoria

2010-11-26

Research highlights: {yields} A new mutant of PQQ-GDH designed for glucose biosensors application. {yields} First mutant of PQQ-GDH with higher activity for D-glucose than the Wild type. {yields} Position N428 is a key point to increase the enzyme activity. {yields} Molecular modeling shows that the N428 C mutant displays a better interaction for PQQ than the WT. -- Abstract: We report for the first time a soluble PQQ-glucose dehydrogenase that is twice more active than the wild type for glucose oxidation and was obtained by combining site directed mutagenesis, modelling and steady-state kinetics. The observed enhancement is attributed to amore » better interaction between the cofactor and the enzyme leading to a better electron transfer. Electrochemical experiments also demonstrate the superiority of the new mutant for glucose oxidation and make it a promising enzyme for the development of high-performance glucose biosensors and biofuel cells.« less

Assessing Empathy and Self-Efficacy Levels of Pharmacy Students in an Elective Diabetes Management Course

PubMed Central

Stahnke, Amanda M.; Behnen, Erin M.

2015-01-01

Objective. To assess the impact of a 6-week patient/provider interaction simulation on empathy and self-efficacy levels of diabetes management skills in third-year pharmacy students. Design. Pharmacy students enrolled in a diabetes elective course were paired to act as a patient with diabetes or as a provider assisting in the management of that patient during a 6-week simulation activity. After 3 weeks, students switched roles. The simulation was designed with activities to build empathy. Assessment. The Jefferson Scale of Empathy (JSE) and a self-efficacy survey were administered to assess change in empathy and confidence levels from baseline to the end of the activity. Completion of the activity resulted in significant improvement in total JSE scores. Additionally, significant improvements in overall self-efficacy scores regarding diabetes management were noted. Conclusion. The 6-week patient/provider interaction simulation improved empathy and self-efficacy levels in third-year pharmacy students. PMID:25995517

Control/structure interaction design methodology

NASA Technical Reports Server (NTRS)

Briggs, Hugh C.; Layman, William E.

1989-01-01

The Control Structure Interaction Program is a technology development program for spacecraft that exhibit interactions between the control system and structural dynamics. The program objectives include development and verification of new design concepts (such as active structure) and new tools (such as a combined structure and control optimization algorithm) and their verification in ground and possibly flight test. The new CSI design methodology is centered around interdisciplinary engineers using new tools that closely integrate structures and controls. Verification is an important CSI theme and analysts will be closely integrated to the CSI Test Bed laboratory. Components, concepts, tools and algorithms will be developed and tested in the lab and in future Shuttle-based flight experiments. The design methodology is summarized in block diagrams depicting the evolution of a spacecraft design and descriptions of analytical capabilities used in the process. The multiyear JPL CSI implementation plan is described along with the essentials of several new tools. A distributed network of computation servers and workstations was designed that will provide a state-of-the-art development base for the CSI technologies.

Comparison of designed and randomly generated catalysts for simple chemical reactions.

PubMed

Kipnis, Yakov; Baker, David

2012-09-01

There has been recent success in designing enzymes for simple chemical reactions using a two-step protocol. In the first step, a geometric matching algorithm is used to identify naturally occurring protein scaffolds at which predefined idealized active sites can be realized. In the second step, the residues surrounding the transition state model are optimized to increase transition state binding affinity and to bolster the primary catalytic side chains. To improve the design methodology, we investigated how the set of solutions identified by the design calculations relate to the overall set of solutions for two different chemical reactions. Using a TIM barrel scaffold in which catalytically active Kemp eliminase and retroaldolase designs were obtained previously, we carried out activity screens of random libraries made to be compositionally similar to active designs. A small number of active catalysts were found in screens of 10³ variants for each of the two reactions, which differ from the computational designs in that they reuse charged residues already present in the native scaffold. The results suggest that computational design considerably increases the frequency of catalyst generation for active sites involving newly introduced catalytic residues, highlighting the importance of interaction cooperativity in enzyme active sites. Copyright © 2012 The Protein Society.

Interaction between Calpain 5, Peroxisome proliferator-activated receptor-gamma and Peroxisome proliferator-activated receptor-delta genes: a polygenic approach to obesity

PubMed Central

Sáez, María E; Grilo, Antonio; Morón, Francisco J; Manzano, Luis; Martínez-Larrad, María T; González-Pérez, Antonio; Serrano-Hernando, Javier; Ruiz, Agustín; Ramírez-Lorca, Reposo; Serrano-Ríos, Manuel

2008-01-01

Context Obesity is a multifactorial disorder, that is, a disease determined by the combined effect of genes and environment. In this context, polygenic approaches are needed. Objective To investigate the possibility of the existence of a crosstalk between the CALPAIN 10 homologue CALPAIN 5 and nuclear receptors of the peroxisome proliferator-activated receptors family. Design Cross-sectional, genetic association study and gene-gene interaction analysis. Subjects The study sample comprise 1953 individuals, 725 obese (defined as body mass index ≥ 30) and 1228 non obese subjects. Results In the monogenic analysis, only the peroxisome proliferator-activated receptor delta (PPARD) gene was associated with obesity (OR = 1.43 [1.04–1.97], p = 0.027). In addition, we have found a significant interaction between CAPN5 and PPARD genes (p = 0.038) that reduces the risk for obesity in a 55%. Conclusion Our results suggest that CAPN5 and PPARD gene products may also interact in vivo. PMID:18657264

The Effects of Structured Physical Activity Program on Social Interaction and Communication for Children with Autism.

PubMed

Zhao, Mengxian; Chen, Shihui

2018-01-01

The purpose of this study was to investigate the effects of structured physical activity program on social interaction and communication of children with autism spectrum disorder (ASD). Fifty children with ASD from a special school were randomly divided into experimental and control groups. 25 children with ASD were placed in the experimental group, and the other 25 children as the control group participated in regular physical activity. A total of forty-one participants completed the study. A 12-week structured physical activity program was implemented with a total of 24 exercise sessions targeting social interaction and communication of children with ASD, and a quasi-experimental design was used for this study. Data were collected using quantitative and qualitative instruments. SSIS and ABLLS-R results showed that an overall improvement in social skills and social interaction for the experimental group across interim and posttests, F = 8.425, p = 0.001 ( p < 0.005), and significant improvements appeared in communication, cooperation, social interaction, and self-control subdomains ( p < 0.005). Conversely, no statistically significant differences were found in the control group ( p > 0.005). The study concluded that the special structured physical activity program positively influenced social interaction and communication skills of children with ASD, especially in social skills, communication, prompt response, and frequency of expression.

Temporal Interactions between Cortical Rhythms

PubMed Central

Roopun, Anita K.; Kramer, Mark A.; Carracedo, Lucy M.; Kaiser, Marcus; Davies, Ceri H.; Traub, Roger D.; Kopell, Nancy J.; Whittington, Miles A.

2008-01-01

Multiple local neuronal circuits support different, discrete frequencies of network rhythm in neocortex. Relationships between different frequencies correspond to mechanisms designed to minimise interference, couple activity via stable phase interactions, and control the amplitude of one frequency relative to the phase of another. These mechanisms are proposed to form a framework for spectral information processing. Individual local circuits can also transform their frequency through changes in intrinsic neuronal properties and interactions with other oscillating microcircuits. Here we discuss a frequency transformation in which activity in two co-active local circuits may combine sequentially to generate a third frequency whose period is the concatenation sum of the original two. With such an interaction, the intrinsic periodicity in each component local circuit is preserved – alternate, single periods of each original rhythm form one period of a new frequency – suggesting a robust mechanism for combining information processed on multiple concurrent spatiotemporal scales. PMID:19225587

Visual design for the user interface, Part 1: Design fundamentals.

PubMed

Lynch, P J

1994-01-01

Digital audiovisual media and computer-based documents will be the dominant forms of professional communication in both clinical medicine and the biomedical sciences. The design of highly interactive multimedia systems will shortly become a major activity for biocommunications professionals. The problems of human-computer interface design are intimately linked with graphic design for multimedia presentations and on-line document systems. This article outlines the history of graphic interface design and the theories that have influenced the development of today's major graphic user interfaces.

Local signaling from a retinal prosthetic in a rodent retinitis pigmentosa model in vivo

NASA Astrophysics Data System (ADS)

Fransen, James W.; Pangeni, Gobinda; Pardue, Machelle T.; McCall, Maureen A.

2014-08-01

Objective. In clinical trials, retinitis pigmentosa patients implanted with a retinal prosthetic device show enhanced spatial vision, including the ability to read large text and navigate. New prosthetics aim to increase spatial resolution by decreasing pixel/electrode size and limiting current spread. To examine spatial resolution of a new prosthetic design, we characterized and compared two photovoltaic array (PVA) designs and their interaction with the retina after subretinal implantation in transgenic S334ter line 3 rats (Tg S334ter-3). Approach. PVAs were implanted subretinally at two stages of degeneration and assessed in vivo using extracellular recordings in the superior colliculus (SC). Several aspects of this interaction were evaluated by varying duration, irradiance and position of a near infrared laser focused on the PVA. These characteristics included: activation threshold, response linearity, SC signal topography and spatial localization. The major design difference between the two PVA designs is the inclusion of local current returns in the newer design. Main results. When tested in vivo, PVA-evoked response thresholds were independent of pixel/electrode size, but differ between the new and old PVA designs. Response thresholds were independent of implantation age and duration (⩽7.5 months). For both prosthesis designs, threshold intensities were within established safety limits. PVA-evoked responses require inner retina synaptic transmission and do not directly activate retinal ganglion cells. The new PVA design evokes local retinal activation, which is not found with the older PVA design that lacks local current returns. Significance. Our study provides in vivo evidence that prosthetics make functional contacts with the inner nuclear layer at several stages of degeneration. The new PVA design enhances local activation within the retina and SC. Together these results predict that the new design can potentially harness the inherent processing within the retina and is likely to produce higher spatial resolution in patients.

Increased Diels-Alderase activity through backbone remodeling guided by Foldit players.

PubMed

Eiben, Christopher B; Siegel, Justin B; Bale, Jacob B; Cooper, Seth; Khatib, Firas; Shen, Betty W; Players, Foldit; Stoddard, Barry L; Popovic, Zoran; Baker, David

2012-01-22

Computational enzyme design holds promise for the production of renewable fuels, drugs and chemicals. De novo enzyme design has generated catalysts for several reactions, but with lower catalytic efficiencies than naturally occurring enzymes. Here we report the use of game-driven crowdsourcing to enhance the activity of a computationally designed enzyme through the functional remodeling of its structure. Players of the online game Foldit were challenged to remodel the backbone of a computationally designed bimolecular Diels-Alderase to enable additional interactions with substrates. Several iterations of design and characterization generated a 24-residue helix-turn-helix motif, including a 13-residue insertion, that increased enzyme activity >18-fold. X-ray crystallography showed that the large insertion adopts a helix-turn-helix structure positioned as in the Foldit model. These results demonstrate that human creativity can extend beyond the macroscopic challenges encountered in everyday life to molecular-scale design problems.

National meeting to review IPAD status and goals. [Integrated Programs for Aerospace-vehicle Design

NASA Technical Reports Server (NTRS)

Fulton, R. E.

1980-01-01

A joint NASA/industry project called Integrated Programs for Aerospace-vehicle Design (IPAD) is described, which has the goal of raising aerospace-industry productivity through the application of computers to integrate company-wide management of engineering data. Basically a general-purpose interactive computing system developed to support engineering design processes, the IPAD design is composed of three major software components: the executive, data management, and geometry and graphics software. Results of IPAD activities include a comprehensive description of a future representative aerospace vehicle design process and its interface to manufacturing, and requirements and preliminary design of a future IPAD software system to integrate engineering activities of an aerospace company having several products under simultaneous development.

Social interaction recruits mentalizing and reward systems in middle childhood.

PubMed

Alkire, Diana; Levitas, Daniel; Warnell, Katherine Rice; Redcay, Elizabeth

2018-06-08

Social cognition develops in the context of reciprocal social interaction. However, most neuroimaging studies of mentalizing have used noninteractive tasks that may fail to capture important aspects of real-world mentalizing. In adults, social-interactive context modulates activity in regions linked to social cognition and reward, but few interactive studies have been done with children. The current fMRI study examines children aged 8-12 using a novel paradigm in which children believed they were interacting online with a peer. We compared mental and non-mental state reasoning about a live partner (Peer) versus a story character (Character), testing the effects of mentalizing and social interaction in a 2 × 2 design. Mental versus Non-Mental reasoning engaged regions identified in prior mentalizing studies, including the temporoparietal junction, superior temporal sulcus, and dorsomedial prefrontal cortex. Moreover, peer interaction, even in conditions without explicit mentalizing demands, activated many of the same mentalizing regions. Peer interaction also activated areas outside the traditional mentalizing network, including the reward system. Our results demonstrate that social interaction engages multiple neural systems during middle childhood and contribute further evidence that social-interactive paradigms are needed to fully capture how the brain supports social processing in the real world. © 2018 Wiley Periodicals, Inc.

More Discussion Activities To Develop Skills in Intercultural Communication for Japanese University Students in EFL.

ERIC Educational Resources Information Center

Kresovich, Brant M.

1989-01-01

Ten speaking and listening activities designed to improve the intercultural communication skills of intermediate and advanced learners of English are presented. The activities are based on seven goals of cultural instruction: (1) sense of culturally controlled behavior; (2) interaction of language and social variables such as gender, age, and…

4 out of 5 Students Surveyed Would Recommend this Activity (Comparing Chewing Gum Flavor Durations)

ERIC Educational Resources Information Center

Richardson, Mary; Rogness, Neal; Gajewski, Byron

2005-01-01

This paper describes an interactive activity developed for illustrating hypothesis tests on the mean for paired or matched samples. The activity is extended to illustrate assessing normality, the Wilcoxon signed rank test, Kaplan-Meier survival functions, two-way analysis of variance, and the randomized block design. (Contains 6 tables and 13…

Multidisciplinary Wildlife Teaching Activities.

ERIC Educational Resources Information Center

Hernbrode, William R., Ed.

This guide provides information and activities descriptions designed to allow the teacher to use wildlife concepts in the teaching of various subjects. The author suggests that wildlife and animals are tremendous motivators for children and hold their attention. In the process, concepts of wildlife interaction with man and the environment are…

Electromechanical modelling and design for phase control of locked modes in the DIII-D tokamak

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

Olofsson, K. E. J.; Choi, W.; Humphreys, D. A.

A basic nonlinear electromechanical model is developed for the interaction between a pre-existing near-saturated tearing-mode, a conducting wall, active coils internal to the wall, and active coils external to the wall. The tearing-mode is represented by a perturbed helical surface current and its island has a small but finite moment of inertia. The model is shown to have several properties that are qualitatively consistent with the experimental observations of mode-wall and mode-coil interactions. The main purpose of the model is to guide the design of a phase control system for locked modes (LMs) in tokamaks. Such a phase controller maymore » become an important component in integrated disruption avoidance systems. A realistic feedback controller for the LM phase is designed and tested for the electromechanical model. The results indicate that a simple fixed-gain controller can perform phase control of LMs with a range of sizes, and at arbitrary misalignment relative to a realistically dimensioned background error field. Finally, the basic model is expected to be a useful minimal dynamical system representation also for other aspects of mode-wall-coil interactions.« less

Electromechanical modelling and design for phase control of locked modes in the DIII-D tokamak

DOE PAGES

Olofsson, K. E. J.; Choi, W.; Humphreys, D. A.; ...

2016-02-05

A basic nonlinear electromechanical model is developed for the interaction between a pre-existing near-saturated tearing-mode, a conducting wall, active coils internal to the wall, and active coils external to the wall. The tearing-mode is represented by a perturbed helical surface current and its island has a small but finite moment of inertia. The model is shown to have several properties that are qualitatively consistent with the experimental observations of mode-wall and mode-coil interactions. The main purpose of the model is to guide the design of a phase control system for locked modes (LMs) in tokamaks. Such a phase controller maymore » become an important component in integrated disruption avoidance systems. A realistic feedback controller for the LM phase is designed and tested for the electromechanical model. The results indicate that a simple fixed-gain controller can perform phase control of LMs with a range of sizes, and at arbitrary misalignment relative to a realistically dimensioned background error field. Finally, the basic model is expected to be a useful minimal dynamical system representation also for other aspects of mode-wall-coil interactions.« less

Further evaluation of a functional analysis of moderate-to-vigorous physical activity in young children.

PubMed

Larson, Tracy A; Normand, Matthew P; Morley, Allison J; Miller, Bryon G

2014-01-01

Inadequate physical activity increases the risks related to several health problems in children; however, increasing physical activity mitigates these risks. In this study, we examined the relations between moderate-to-vigorous physical activity (MVPA) and several environmental conditions (attention, interactive play, alone, escape) with 4 preschool children. We compared the experimental conditions to a control condition and a naturalistic baseline according to a combined multielement and reversal design. Results indicated that all participants were most active in the interactive play condition and that the percentage of MVPA varied across experimental and control conditions. In addition, the frequency and duration of bouts of MVPA were greatest in the interactive play condition. The current study presents a methodology for the identification of environmental contingencies that support increased levels of MVPA in young children, and it holds promise for improving our understanding of the variables related to physical activity. © Society for the Experimental Analysis of Behavior.

Designing Social Online Math Activities

ERIC Educational Resources Information Center

Gedeborg, Samuel

2016-01-01

One of the major benefits of the face-to-face teaching environment is that social interaction opportunities are a natural part of the course: Learners meet in the same room for the same allotted period of time each week. This social opportunity is not organic to online courses; therefore, to have this social interaction as a part of online classes…

Use of Swivel Desks and Aisle Space to Promote Interaction in Mid-Sized College Classrooms

ERIC Educational Resources Information Center

Henshaw, Robert G.; Edwards, Phillip M.; Bagley, Erika J.

2011-01-01

Traditional designs for most mid-sized college classrooms discourage 1) face-to-face interaction among students, 2) instructor movement in the classroom, and 3) efficient transitions between different kinds of learning activities. An experimental classroom piloted during Spring Semester 2011 at the University of North Carolina at Chapel Hill uses…

Synthesis of indole analogs as potent β-glucuronidase inhibitors.

PubMed

Baharudin, Mohd Syukri; Taha, Muhammad; Imran, Syahrul; Ismail, Nor Hadiani; Rahim, Fazal; Javid, Muhammad Tariq; Khan, Khalid Mohammed; Ali, Muhammad

2017-06-01

Natural products are the main source of motivation to design and synthesize new molecules for drug development. Designing new molecules against β-glucuronidase inhibitory is utmost essential. In this study indole analogs (1-35) were synthesized, characterized using various spectroscopic techniques including 1 H NMR and EI-MS and evaluated for their β-glucuronidase inhibitory activity. Most compounds were identified as potent inhibitors for the enzyme with IC 50 values ranging between 0.50 and 53.40μM, with reference to standard d-saccharic acid 1,4-lactone (IC 50 =48.4±1.25μM). Structure-activity relationship had been also established. The results obtained from docking studies for the most active compound 10 showed that hydrogen bond donor features as well as hydrogen bonding with (Oε1) of nucleophilic residue Glu540 is believed to be the most importance interaction in the inhibition activity. It was also observed that hydroxyl at fourth position of benzylidene ring acts as a hydrogen bond donor and interacts with hydroxyl (OH) on the side chain of catalysis residue Tyr508. The enzyme-ligand complexed were being stabilized through electrostatic π-anion interaction with acid-base catalyst Glu451 (3.96Å) and thus preventing Glu451 from functioning as proton donor residue. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterizing the Hot Spots Involved in RON-MSPβ Complex Formation Using In Silico Alanine Scanning Mutagenesis and Molecular Dynamics Simulation

PubMed Central

Zarei, Omid; Hamzeh-Mivehroud, Maryam; Benvenuti, Silvia; Ustun-Alkan, Fulya; Dastmalchi, Siavoush

2017-01-01

Purpose: Implication of protein-protein interactions (PPIs) in development of many diseases such as cancer makes them attractive for therapeutic intervention and rational drug design. RON (Recepteur d’Origine Nantais) tyrosine kinase receptor has gained considerable attention as promising target in cancer therapy. The activation of RON via its ligand, macrophage stimulation protein (MSP) is the most common mechanism of activation for this receptor. The aim of the current study was to perform in silico alanine scanning mutagenesis and to calculate binding energy for prediction of hot spots in protein-protein interface between RON and MSPβ chain (MSPβ). Methods: In this work the residues at the interface of RON-MSPβ complex were mutated to alanine and then molecular dynamics simulation was used to calculate binding free energy. Results: The results revealed that Gln193, Arg220, Glu287, Pro288, Glu289, and His424 residues from RON and Arg521, His528, Ser565, Glu658, and Arg683 from MSPβ may play important roles in protein-protein interaction between RON and MSP. Conclusion: Identification of these RON hot spots is important in designing anti-RON drugs when the aim is to disrupt RON-MSP interaction. In the same way, the acquired information regarding the critical amino acids of MSPβ can be used in the process of rational drug design for developing MSP antagonizing agents, the development of novel MSP mimicking peptides where inhibition of RON activation is required, and the design of experimental site directed mutagenesis studies. PMID:28507948

Flutter suppression for the Active Flexible Wing - Control system design and experimental validation

NASA Technical Reports Server (NTRS)

Waszak, M. R.; Srinathkumar, S.

1992-01-01

The synthesis and experimental validation of a control law for an active flutter suppression system for the Active Flexible Wing wind-tunnel model is presented. The design was accomplished with traditional root locus and Nyquist methods using interactive computer graphics tools and with extensive use of simulation-based analysis. The design approach relied on a fundamental understanding of the flutter mechanism to formulate understanding of the flutter mechanism to formulate a simple control law structure. Experimentally, the flutter suppression controller succeeded in simultaneous suppression of two flutter modes, significantly increasing the flutter dynamic pressure despite errors in the design model. The flutter suppression controller was also successfully operated in combination with a rolling maneuver controller to perform flutter suppression during rapid rolling maneuvers.

An active visual search interface for Medline.

PubMed

Xuan, Weijian; Dai, Manhong; Mirel, Barbara; Wilson, Justin; Athey, Brian; Watson, Stanley J; Meng, Fan

2007-01-01

Searching the Medline database is almost a daily necessity for many biomedical researchers. However, available Medline search solutions are mainly designed for the quick retrieval of a small set of most relevant documents. Because of this search model, they are not suitable for the large-scale exploration of literature and the underlying biomedical conceptual relationships, which are common tasks in the age of high throughput experimental data analysis and cross-discipline research. We try to develop a new Medline exploration approach by incorporating interactive visualization together with powerful grouping, summary, sorting and active external content retrieval functions. Our solution, PubViz, is based on the FLEX platform designed for interactive web applications and its prototype is publicly available at: http://brainarray.mbni.med.umich.edu/Brainarray/DataMining/PubViz.

Older Adults Co-Creating Meaningful Individualized Social Activities Online for Healthy Ageing.

PubMed

Blusi, Madeleine; Nilsson, Ingeborg; Lindgren, Helena

2018-01-01

Social isolation and loneliness among older people is a growing problem with negative effects on physical and mental health. In co-creation with older adults individualized social activities were designed where older adults through computer mediated communication were able to participate in social activities without leaving their homes. Four types of activities were designed; outdoor activity, music event, visiting a friend and leisure activity. A participatory action research design was applied, where end users together with scientists from two research fields developed, tested and evaluated online participation in the activities. Usability and safety of the systems were major concerns among older adults. The evaluation pointed out that level of simplicity, usability and audio-video quality determined the level of satisfaction with the human interaction during the activity, thereby affecting the meaningfulness of the activity. The research presented in this paper constitutes the first step in a long-term research process aiming at developing a digital coaching system that gives older adults personalized support for increasing participation in meaningful social activities.

A network dedicated to sciences dissemination : Scité

NASA Astrophysics Data System (ADS)

Botman, M.; Scité Network

2005-11-01

The activities of the network Scité are destined for the schools and the general public and include laboratories visits, training periods, seminars, conferences, adult courses specially designed for teachers, etc. Since 2002, collaborations between universities and enterprises are enhanced and developed to bring to light the variety of jobs linked to science and the multi-disciplinary process leading to industrial application of scientific findings. Activities will include, enterprises visits preparation of CD and video support presenting "passionate" jobs, and the set up of interactive workshops for students. Systematic relations and interactions with scientific as well as global media are established and formalised. Activities enhancing such interactions include the development of media-universities interface assuring the quality and the adequacy of scientific information transfer and vulgarisation. Based on the wide expertise accumulated through recent projects, Scité Network develop innovative activities involving a wide range of actors: universities, enterprises, media, schools, general public.

Unique battery with an active membrane separator having uniform physico-chemically functionalized ion channels and a method making the same

DOEpatents

Gerald, II, Rex E.; Ruscic, Katarina J [Chicago, IL; Sears, Devin N [Spruce Grove, CA; Smith, Luis J [Natick, MA; Klingler, Robert J [Glenview, IL; Rathke, Jerome W [Homer Glen, IL

2012-02-21

The invention relates to a unique battery having an active, porous membrane and method of making the same. More specifically the invention relates to a sealed battery system having a porous, metal oxide membrane with uniform, physicochemically functionalized ion channels capable of adjustable ionic interaction. The physicochemically-active porous membrane purports dual functions: an electronic insulator (separator) and a unidirectional ion-transporter (electrolyte). The electrochemical cell membrane is activated for the transport of ions by contiguous ion coordination sites on the interior two-dimensional surfaces of the trans-membrane unidirectional pores. The membrane material is designed to have physicochemical interaction with ions. Control of the extent of the interactions between the ions and the interior pore walls of the membrane and other materials, chemicals, or structures contained within the pores provides adjustability of the ionic conductivity of the membrane.

Camp Invention Fosters Creativity.

ERIC Educational Resources Information Center

Landona, Nancy

2001-01-01

This article describes Camp Invention, a summer one-week day camp program for students in grades 2-6 that is designed to develop creativity in gifted students. The curriculum of the camp features hands-on, interactive activities in science, history, math, and the arts. Examples of activities undertaken in 2001 are provided. (Contains one…

Integrating Science, Mathematics, and Sociology in an Inquiry-Based Study of Changing Population Density.

ERIC Educational Resources Information Center

Schlenker, Richard M.; Schlenker, Karl R.

2000-01-01

Presents a five-activity sequence designed to help students understand the effects of population doubling. Activities consider the effects of population doubling on human interactions, drinking water supplies, and food supply. Students also develop graphs of data and write research papers. (WRM)

OpenSim-Supported Virtual Learning Environment: Transformative Content Representation, Facilitation, and Learning Activities

ERIC Educational Resources Information Center

Kim, Heesung; Ke, Fengfeng

2016-01-01

The pedagogical and design considerations for the use of a virtual reality (VR) learning environment are important for prospective and current teachers. However, empirical research investigating how preservice teachers interact with transformative content representation, facilitation, and learning activities in a VR educational simulation is still…

Optimization of an interactive distributive computer network

NASA Technical Reports Server (NTRS)

Frederick, V.

1985-01-01

The activities under a cooperative agreement for the development of a computer network are briefly summarized. Research activities covered are: computer operating systems optimization and integration; software development and implementation of the IRIS (Infrared Imaging of Shuttle) Experiment; and software design, development, and implementation of the APS (Aerosol Particle System) Experiment.

Making Diversity Awareness Part of Your Teaching.

ERIC Educational Resources Information Center

Kirk, Rea; Nkemnji, John; Gudgeon, Katherine; Hardy, Sarah; Hooker, Gina; Lowry, Mark; Roberts, Brionne

This paper presents a series of interactive activities designed to help educators make diversity awareness part of their teaching. The activities are: "Best Friends," which helps people recognize the role race plays in their perceptions of people and in their values; "Conclusion Jumping," which helps people identify common stereotypes and raise…

A Framework for the Instructional Design of Multi-Structured Educational Applications.

ERIC Educational Resources Information Center

Buendia, F.; Diaz, P.; Benlloch, J. V.

An instructional application consists of a set of resources and activities that implement interacting, interrelated and structured experiences oriented towards achieving specific educational objectives. Computer-based instructional applications have to be looked at as any other development activity following a well defined process. With this…

Detection of Protein Interactions in T3S Systems Using Yeast Two-Hybrid Analysis.

PubMed

Nilles, Matthew L

2017-01-01

Two-hybrid systems, sometimes termed interaction traps, are genetic systems designed to find and analyze interactions between proteins. The most common systems are yeast based (commonly Saccharomyces cerevisae) and rely on the functional reconstitution of the GAL4 transcriptional activator. Reporter genes, such as the lacZ gene of Escherichia coli (encodes β-galactosidase), are placed under GAL4-dependent transcriptional control to provide quick and reliable detection of protein interactions. In this method the use of a yeast-based two-hybrid system is described to study protein interactions between components of type III secretion systems.

A Perspective on Computational Human Performance Models as Design Tools

NASA Technical Reports Server (NTRS)

Jones, Patricia M.

2010-01-01

The design of interactive systems, including levels of automation, displays, and controls, is usually based on design guidelines and iterative empirical prototyping. A complementary approach is to use computational human performance models to evaluate designs. An integrated strategy of model-based and empirical test and evaluation activities is particularly attractive as a methodology for verification and validation of human-rated systems for commercial space. This talk will review several computational human performance modeling approaches and their applicability to design of display and control requirements.

Population Growth. Understanding Global Change: Earth Science and Human Impacts. Global Change Instruction Program.

ERIC Educational Resources Information Center

Jacobsen, Judith E.

The Global Change Instruction Program was designed by college professors to fill a need for interdisciplinary materials on the emerging science of global change. This instructional module concentrates on interactions between population growth and human activities that produce global change. The materials are designed for undergraduate students…

The Participatory Design of a (Today and) Future Digital Entomology Lab

ERIC Educational Resources Information Center

Hai-Jew, Shalin

2011-01-01

This article showcases a virtual interactive participatory design activity for building a digital entomology lab. Conceptualized as a virtual complement to a general entomology course at Kansas State University, the lab would allow learners to explore morphological aspects of insects--their various forms and functions--in order to understand…

An Attempt To Design Synchronous Collaborative Learning Environments for Peer Dyads on the World Wide Web.

ERIC Educational Resources Information Center

Lee, Fong-Lok; Liang, Steven; Chan, Tak-Wai

1999-01-01

Describes the design, implementation, and preliminary evaluation of three synchronous distributed learning prototype systems: Co-Working System, Working Along System, and Hybrid System. Each supports a particular style of interaction, referred to a socio-activity learning model, between members of student dyads (pairs). All systems were…

From Tacit Sensorimotor Coupling to Articulated Mathematical Reasoning in an Embodied Design for Proportional Reasoning

ERIC Educational Resources Information Center

Abrahamson, Dor; Gutierrez, Jose F.; Lee, Rosa G.; Reinholz, Daniel; Trninic, Dragan

2011-01-01

Mathematics education designers and researchers are beginning to appreciate the pedagogical potential of embodied interaction (EI) instructional activities, yet little theory is available to understand its historical roots, sociocognitive mechanisms, and implementation practice. We draw on empirical data (n = 22) from a Grades 4-6 EI…

Mind the Gap: Task Design and Technology in Novice Language Teachers' Practice

ERIC Educational Resources Information Center

Smits, Tom F. H.; Oberhofer, Margret; Colpaert, Jozef

2016-01-01

This paper focuses on the possibilities/challenges for English as a Foreign Language (EFL) teachers designing tasks grounded in Task-Based Language Teaching (TBLT) and taking advantage of the affordances of technology--Interactive WhiteBoards (IWBs). Teachers have been shown to confuse tasks with exercises or activities. The interactive…

Mapping lexical-semantic networks and determining hemispheric language dominance: Do task design, sex, age, and language performance make a difference?

PubMed

Chang, Yu-Hsuan A; Javadi, Sogol S; Bahrami, Naeim; Uttarwar, Vedang S; Reyes, Anny; McDonald, Carrie R

2018-04-01

Blocked and event-related fMRI designs are both commonly used to localize language networks and determine hemispheric dominance in research and clinical settings. We compared activation profiles on a semantic monitoring task using one of the two designs in a total of 43 healthy individual to determine whether task design or subject-specific factors (i.e., age, sex, or language performance) influence activation patterns. We found high concordance between the two designs within core language regions, including the inferior frontal, posterior temporal, and basal temporal region. However, differences emerged within inferior parietal cortex. Subject-specific factors did not influence activation patterns, nor did they interact with task design. These results suggest that despite high concordance within perisylvian regions that are robust to subject-specific factors, methodological differences between blocked and event-related designs may contribute to parietal activations. These findings provide important information for researchers incorporating fMRI results into meta-analytic studies, as well as for clinicians using fMRI to guide pre-surgical planning. Copyright © 2018 Elsevier Inc. All rights reserved.

Human-computer interaction in distributed supervisory control tasks

NASA Technical Reports Server (NTRS)

Mitchell, Christine M.

1989-01-01

An overview of activities concerned with the development and applications of the Operator Function Model (OFM) is presented. The OFM is a mathematical tool to represent operator interaction with predominantly automated space ground control systems. The design and assessment of an intelligent operator aid (OFMspert and Ally) is particularly discussed. The application of OFM to represent the task knowledge in the design of intelligent tutoring systems, designated OFMTutor and ITSSO (Intelligent Tutoring System for Satellite Operators), is also described. Viewgraphs from symposia presentations are compiled along with papers addressing the intent inferencing capabilities of OFMspert, the OFMTutor system, and an overview of intelligent tutoring systems and the implications for complex dynamic systems.

Design and Mechanism of Tetrahydrothiophene-based GABA Aminotransferase Inactivators

PubMed Central

Le, Hoang V.; Hawker, Dustin D.; Wu, Rui; Doud, Emma; Widom, Julia; Sanishvili, Ruslan; Liu, Dali; Kelleher, Neil L.; Silverman, Richard B.

2015-01-01

Low levels of γ-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the blood-brain barrier and inhibit the activity of γ-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally-restricted, tetrahydrothiophene-based GABA analogs with a properly-positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. One compound in the series is eight times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bond interactions with Arg-192, a π-π interaction with Phe-189, and a weak nonbonded S···O=C interaction with Glu-270, thereby inactivating the enzyme. PMID:25781189

Pharmacokinetic and Pharmacodynamic Drug Interaction Study of Piragliatin, a Glucokinase Activator, and Glyburide, a Sulfonylurea, in Type 2 Diabetic Patients.

PubMed

Zhai, S; Georgy, A; Liang, Z; Zhi, J

2016-11-01

A glucokinase activator and a sulfonylurea might be coprescribed to synergize treatment success for type 2 diabetes (T2D). This clinical pharmacology study was designed to investigate the potential glucose-lowering effect or pharmacodynamic (PD), pharmacokinetic (PK), and safety/tolerability interactions between piragliatin and glyburide in T2D patients already taking glyburide but not adequately controlled. This was an open-label, multiple-dose, 3-period, single-sequence crossover design: on days -1, 6, and 12, PD and PK samples were drawn with glyburide alone (period 0), piragliatin + glyburide (period 1), and piragliatin alone (period 2) treatments. The glucose-lowering effect, including fasting plasma glucose (FPG), of piragliatin was more pronounced when it was administered concomitantly with glyburide as compared to piragliatin or glyburide administered alone. However, this enhancement cannot be explained by a potential PK interaction between piragliatin and glyburide. Other than hypoglycemia, there were no clinically relevant safety findings. Thus, the enhanced PD effect warrants further investigation to define the optimal dose combination between glucokinase activators and sulfonylureas with regard to efficacy, safety, and tolerability. © 2016, The American College of Clinical Pharmacology.

Design and Mechanism of Tetrahydrothiophene-Based γ-Aminobutyric Acid Aminotransferase Inactivators

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

Le, Hoang V.; Hawker, Dustin D.; Wu, Rui

Low levels of gamma-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinsons disease, Alzheimers disease, Huntingtons disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the bloodbrain barrier and inhibit the activity of gamma-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally restricted tetrahydrothiophene-based GABA analogues with a properly positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. Onemore » compound in the series is 8 times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bonding interactions with Arg-192, a pi-pi interaction with Phe-189, and a weak nonbonded (SO)-O-...=C interaction with Glu-270, thereby inactivating the enzyme.« less

Design and mechanism of tetrahydrothiophene-based γ-aminobutyric acid aminotransferase inactivators.

PubMed

Le, Hoang V; Hawker, Dustin D; Wu, Rui; Doud, Emma; Widom, Julia; Sanishvili, Ruslan; Liu, Dali; Kelleher, Neil L; Silverman, Richard B

2015-04-08

Low levels of γ-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinson's disease, Alzheimer's disease, Huntington's disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the blood-brain barrier and inhibit the activity of γ-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally restricted tetrahydrothiophene-based GABA analogues with a properly positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. One compound in the series is 8 times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bonding interactions with Arg-192, a π-π interaction with Phe-189, and a weak nonbonded S···O═C interaction with Glu-270, thereby inactivating the enzyme.

The Particular Aspects of Science Museum Exhibits That Encourage Students' Engagement

NASA Astrophysics Data System (ADS)

Shaby, Neta; Assaraf, Orit Ben-Zvi; Tal, Tali

2017-06-01

This research explores learning in science museums through the most common activity in a science museum—interaction with exhibits. The goal of this study was to characterize the learning behaviors exhibited by students as they engage with interactive exhibits in order to draw insight regarding the design of the exhibits. In order to do so, we used a qualitative method of observation as well as the Visitor Engagement Framework (VEF) model, a visitor-based framework for assessing visitors' learning experiences with exhibits in a science center setting. The combined method produced a framework of nine learning behaviors exhibited during the visitors' interaction with the exhibits, grouped into three categories that reflect increasing levels of engagement and depth of the learning experience. Our research participants consisted of a total 1800 students aged 10-12 (4th, 5th, and 6th graders) who came to the museum with their class for a day visit. We observed nine exhibits, each visited by 200 students. Our observations revealed several design elements that contribute to engagement with exhibits in science museums. For example, exhibits that have familiar activation encourage visitors' interaction, exhibits that facilitate social interaction are more likely to increase engagement, and the highest levels of engagement can be found in exhibits that support large groups.

Blogging in a biostatistics and research design graduate dental course: for learning or interaction?

PubMed

El Tantawi, Maha M A

2010-04-01

The use of the Internet in health professions education has markedly increased in recent years. There is a need to understand the methods used by students to benefit from Internet-based teaching methods, especially those initially designed to promote social interaction such as blogs. This study describes how students used a blog in a biostatistics and research design graduate dental course. The aims of the blog were to offer exercises to train students for the exam and to enhance interaction among students and between students and instructor. Some features of the blog were modified to suit the course. Posts and comments were counted and classified by type, and their time statistics were analyzed. Students filled out a questionnaire to indicate whether and how exactly they used the blog or reasons for not using it. The relation between final exam scores and different methods of using the blog was assessed. Most of the posts were by the instructor offering exercises and model answers, whereas most of the comments were by students answering the exercises. Students were significantly more satisfied with blog uses related to interaction than with uses related to exercises (9.15+/-1.19, 8.73+/-1.34, P=0.001). The most frequently cited reason for not using the blog was lack of time. The most frequently reported method of using the blog was reading exercises and answers without actively contributing to the blog. Methods of using the blog significantly associated with higher scores in the final exam were actively contributing to the blog by posts or comments and interacting with colleagues. The main advantage of using the blog was promoting interaction between students and instructor, which is essential for the success of online learning in particular and adult learning in general.

Multivalent small molecule pan-RAS inhibitors

PubMed Central

Welsch, Matthew E.; Kaplan, Anna; Chambers, Jennifer M.; Stokes, Michael E.; Bos, Pieter H.; Zask, Arie; Zhang, Yan; Sanchez-Martin, Marta; Badgley, Michael A.; Huang, Christine S.; Tran, Timothy H.; Akkiraju, Hemanth; Brown, Lewis M.; Nandakumar, Renu; Cremers, Serge; Yang, Wan S.; Tong, Liang; Olive, Kenneth P.; Ferrando, Adolfo; Stockwell, Brent R.

2017-01-01

SUMMARY Design of small molecules that disrupt protein-protein interactions, including the interaction of RAS proteins and their effectors, have potential use as chemical probes and therapeutic agents. We describe here the synthesis and testing of potential small molecule pan-RAS ligands, which were designed to interact with adjacent sites on the surface of oncogenic KRAS. One compound, termed 3144, was found to bind to RAS proteins using microscale thermophoresis, nuclear magnetic resonance spectroscopy and isothermal titration calorimetry, and to exhibit lethality in cells partially dependent on expression of RAS proteins. This compound was metabolically stable in liver microsomes and displayed anti-tumor activity in xenograft mouse cancer models. These findings suggest that pan-RAS inhibition may be an effective therapeutic strategy for some cancers, and that structure-based design of small molecules targeting multiple adjacent sites to create multivalent inhibitors may be effective for some proteins. PMID:28235199

Active vibration control activities at the LaRC - Present and future

NASA Technical Reports Server (NTRS)

Newsom, J. R.

1990-01-01

The NASA Controls-Structures-Interaction (CSI) program is presented with a description of the ground testing element objectives and approach. The goal of the CSI program is to develop and validate the technology required to design, verify and operate space systems in which the structure and the controls interact beneficially to meet the needs of future NASA missions. The operational Mini-Mast ground testbed and some sample active vibration control experimental results are discussed along with a description of the CSI Evolutionary Model testbed presently under development. Initial results indicate that embedded sensors and actuators are effective in controlling a large truss/reflector structure.

How Do Small Things Make a Big Difference? Activities to Teach about Human-Microbe Interactions

ERIC Educational Resources Information Center

Jasti, Chandana; Hug, Barbara; Waters, Jillian L.; Whitaker, Rachel J.

2014-01-01

Recent scientific studies are providing increasing evidence for how microbes living in and on us are essential to our good health. However, many students still think of microbes only as germs that harm us. The classroom activities presented here are designed to shift student thinking on this topic. In these guided inquiry activities, students…

Sunlight, Skyscrapers, and Soda Pop: The Wherever-You-Look Science Book.

ERIC Educational Resources Information Center

Bennett, Andrea T.; Kessler, James H.

This book contains a series of hands-on science activities for young children. The activities are designed to be done by children with an adult partner. An interactive learning feature is also included. Through these activities, children can discover that science is all around them and that science helps to explain why things happen the way they…

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…

Communal space design as student interaction in polnep campus

NASA Astrophysics Data System (ADS)

Hasriyanti, N.; Zulestari, A.; Judhi, J.; Ikayanti, P.

2018-03-01

Communal space is a means to do for social interaction, from private to the public. The purpose of this study was conducted to explore the phenomenon of communal space setting of Pontianak State Polytechnic students from 8 departments of study both indoor and outdoor spaces. The research method used is a rationalistic study. The planned activities to be undertaken include the determination of communal places (indoor and outdoor), sample determination, data collection with surveys and interviews, presenting data and analysis and drawing conclusions as a basis for designing communal space for Polnep students. The research were analyzed of building and space character, analysis of space organization and circulation, space requirement analysis, material and color analysis, site analysis, and analysis of inner space elements and outer space elements. From the results of this study, it can be concluded that Polnep campus environment requires the addition of public space for students in conducting formal activities outside lectures. Some activity which to do some student such as activity to waiting lecturer, do some coursework, discussion, relaxation, extracurricular activities, and other informal activities still require adequate space infrastructure and are equipped with street furnitures such as garden lights, benches, outer space markers and shade vegetation.

New insights into the interaction between pyrrolyl diketoacids and HIV-1 integrase active site and comparison with RNase H.

PubMed

Corona, Angela; di Leva, Francesco Saverio; Rigogliuso, Giuseppe; Pescatori, Luca; Madia, Valentina Noemi; Subra, Frederic; Delelis, Olivier; Esposito, Francesca; Cadeddu, Marta; Costi, Roberta; Cosconati, Sandro; Novellino, Ettore; di Santo, Roberto; Tramontano, Enzo

2016-10-01

HIV-1 integrase (IN) inhibitors are one of the most recent innovations in the treatment of HIV infection. The selection of drug resistance viral strains is however a still open issue requiring constant efforts to identify new anti-HIV-1 drugs. Pyrrolyl diketo acid (DKA) derivatives inhibit HIV-1 replication by interacting with the Mg 2+ cofactors within the HIV-1 IN active site or within the HIV-1 reverse-transcriptase associated ribonuclease H (RNase H) active site. While the interaction mode of pyrrolyl DKAs with the RNase H active site has been recently reported and substantiated by mutagenesis experiments, their interaction within the IN active site still lacks a detailed understanding. In this study, we investigated the binding mode of four pyrrolyl DKAs to the HIV-1 IN active site by molecular modeling coupled with site-directed mutagenesis studies showing that the DKA pyrrolyl scaffold primarily interacts with the IN amino residues P145, Q146 and Q148. Importantly, the tested DKAs demonstrated good effectiveness against HIV-1 Raltegravir resistant Y143A and N155H INs, thus showing an interaction pattern with relevant differences if compared with the first generation IN inhibitors. These data provide precious insights for the design of new HIV inhibitors active on clinically selected Raltegravir resistant variants. Furthermore, this study provides new structural information to modulate IN and RNase H inhibitory activities for development of dual-acting anti-HIV agents. Copyright © 2016 Elsevier B.V. All rights reserved.

A design for living technology: experiments with the mind time machine.

PubMed

Ikegami, Takashi

2013-01-01

Living technology aims to help people expand their experiences in everyday life. The environment offers people ways to interact with it, which we call affordances. Living technology is a design for new affordances. When we experience something new, we remember it by the way we perceive and interact with it. Recent studies in neuroscience have led to the idea of a default mode network, which is a baseline activity of a brain system. The autonomy of artificial life must be understood as a sort of default mode that self-organizes its baseline activity, preparing for its external inputs and its interaction with humans. I thus propose a method for creating a suitable default mode as a design principle for living technology. I built a machine called the mind time machine (MTM), which runs continuously for 10 h per day and receives visual data from its environment using 15 video cameras. The MTM receives and edits the video inputs while it self-organizes the momentary now. Its base program is a neural network that includes chaotic dynamics inside the system and a meta-network that consists of video feedback systems. Using this system as the hardware and a default mode network as a conceptual framework, I describe the system's autonomous behavior. Using the MTM as a testing ground, I propose a design principle for living technology.

Virology Interest Group | Center for Cancer Research

Cancer.gov

The Virology Interest Group comprises researchers at NIH and in the local area who are interested in virology. The group organizes activities designed to promote interactions and exchange of information.

Participatory Design With Seniors: Design of Future Services and Iterative Refinements of Interactive eHealth Services for Old Citizens

PubMed Central

2013-01-01

Background There is an increasing social isolation among the elderly today. This will be an even larger issue in the future with growing numbers of elderly and less resources, for example, in terms of economy and staff. Loneliness and social isolation can, however, be addressed in several ways using different interactive eHealth services. Objective This case study investigated novel eHealth services for the elderly, and their usage of a social interactive device designed especially for them. Methods In this work, we used an innovative mobile communication device connected to the television (TV), which worked as a remotely controlled large interactive screen. The device was tested by 8 volunteers who visited a senior center. They were between 65 and 80 years of age and lived in their own homes. Throughout the 1.5 year-long project, 7 design workshops were held with the seniors and the staff at the center. During these workshops, demands and preferences regarding existing and new services were gathered. At the end of the project the participants’ experience of the device and of the services was elaborated in 3 workshops to get ideas for improved or new meaningful services. During the data analyses and development process, what seniors thought would be useful in relation to what was feasible was prioritized by the development company. Results Regarding daily usage, the seniors reported that they mainly used the service for receiving information from the senior center and for communication with other participants in the group or with younger relatives. They also read information about events at the senior center and they liked to perform a weekly sent out workout exercise. Further, they played games such as Memory and Sudoku using the device. The service development focused on three categories of services: cognitive activities, social activities, and physical activities. A cognitive activity service that would be meaningful to develop was a game for practicing working memory. In the social activities category, the seniors wanted different quizzes and multi-player games. For physical activities, the seniors desired more workout exercises and suggestions for guided walking routes. A new category, “information and news”, was suggested since they lacked services like senior-customized global and local news. Conclusions This study showed the importance of input from a group of seniors when designing new services for elderly citizens. Besides input to interactive eHealth service development for seniors, this study showed the importance of a social context around such work. The seniors were very engaged throughout the project and workshops were frequently visited and the seniors became friends. The high amount of input from the seniors could be explained in terms of social inclusion; they belonged to a group and each member was considered important for the work. The friendly workshop atmosphere facilitated new ideas and redesign of the services. PMID:25075235

Participatory Design With Seniors: Design of Future Services and Iterative Refinements of Interactive eHealth Services for Old Citizens.

PubMed

Scandurra, Isabella; Sjölinder, Marie

2013-01-01

There is an increasing social isolation among the elderly today. This will be an even larger issue in the future with growing numbers of elderly and less resources, for example, in terms of economy and staff. Loneliness and social isolation can, however, be addressed in several ways using different interactive eHealth services. This case study investigated novel eHealth services for the elderly, and their usage of a social interactive device designed especially for them. In this work, we used an innovative mobile communication device connected to the television (TV), which worked as a remotely controlled large interactive screen. The device was tested by 8 volunteers who visited a senior center. They were between 65 and 80 years of age and lived in their own homes. Throughout the 1.5 year-long project, 7 design workshops were held with the seniors and the staff at the center. During these workshops, demands and preferences regarding existing and new services were gathered. At the end of the project the participants' experience of the device and of the services was elaborated in 3 workshops to get ideas for improved or new meaningful services. During the data analyses and development process, what seniors thought would be useful in relation to what was feasible was prioritized by the development company. Regarding daily usage, the seniors reported that they mainly used the service for receiving information from the senior center and for communication with other participants in the group or with younger relatives. They also read information about events at the senior center and they liked to perform a weekly sent out workout exercise. Further, they played games such as Memory and Sudoku using the device. The service development focused on three categories of services: cognitive activities, social activities, and physical activities. A cognitive activity service that would be meaningful to develop was a game for practicing working memory. In the social activities category, the seniors wanted different quizzes and multi-player games. For physical activities, the seniors desired more workout exercises and suggestions for guided walking routes. A new category, "information and news", was suggested since they lacked services like senior-customized global and local news. This study showed the importance of input from a group of seniors when designing new services for elderly citizens. Besides input to interactive eHealth service development for seniors, this study showed the importance of a social context around such work. The seniors were very engaged throughout the project and workshops were frequently visited and the seniors became friends. The high amount of input from the seniors could be explained in terms of social inclusion; they belonged to a group and each member was considered important for the work. The friendly workshop atmosphere facilitated new ideas and redesign of the services.

Student participation and interactivity using asynchronous computer-mediated communication for resolution of an undergraduate capstone management case study.

PubMed

Miller, Paulette J

2012-01-01

Online discussion activities are designed for computer-mediated learning activities in face-to-face, hybrid, and totally online courses. The use of asynchronous computer-mediated communication (A-CMC) coupled with authentic workplace case studies provides students in the protected learning environment with opportunities to practice workplace decision making and communication. In this study, communication behaviors of transmitter and receiver were analyzed to determine participation and interactivity in communication among small-group participants in a health information management capstone management course.

De novo design, synthesis, and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.

PubMed

Potin, Dominique; Launay, Michele; Nicolai, Eric; Fabreguette, Maud; Malabre, Patrice; Caussade, François; Besse, Dominique; Skala, Stacey; Stetsko, Dawn K; Todderud, Gordon; Beno, Brett R; Cheney, Daniel L; Chang, Chiehying J; Sheriff, Steven; Hollenbaugh, Diane L; Barrish, Joel C; Iwanowicz, Edwin J; Suchard, Suzanne J; Dhar, T G Murali

2005-02-15

LFA-1 (leukocyte function-associated antigen-1), is a member of the beta(2)-integrin family and is expressed on all leukocytes. The LFA-1/ICAM interaction promotes tight adhesion between activated leukocytes and the endothelium, as well as between T cells and antigen-presenting cells. Evidence from both animal models and clinical trials provides support for LFA-1 as a target in several different inflammatory diseases. This paper describes the de novo design, synthesis and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.

Status of integrated multidisciplinary rotorcraft optimization research at the Langley Research Center

NASA Technical Reports Server (NTRS)

Mantay, Wayne R.; Adelman, Howard M.

1990-01-01

This paper describes a joint NASA/Army research activity at the Langley Research Center to develop optimization procedures aimed at improving the rotor blade design process by integrating appropriate disciplines and accounting for important interactions among the disciplines. The activity is being guided by a Steering Committee made up of key NASA and Army researchers and managers. The paper describes the optimization formulation in terms of the objective function, design variables, and constraints. The analysis aspects are discussed, and the interdisciplinary interactions are defined in terms of the information that must be transferred among disciplinary analyses as well as the trade-offs between disciplines in determining the details of the design. At this writing, some significant progress has been made. Results given in the paper represent accomplishments in rotor aerodynamic performance optimization for minimum horsepower, rotor dynamic optimization for vibration reduction, approximate analysis of frequencies and mode shapes, rotor structural optimization for minimum weight, and integrated aerodynamic load/dynamics optimization for minimum vibration and weight.

Molecular response of Escherichia coli adhering onto nanoscale topography

NASA Astrophysics Data System (ADS)

Rizzello, Loris; Galeone, Antonio; Vecchio, Giuseppe; Brunetti, Virgilio; Sabella, Stefania; Pompa, Pier Paolo

2012-10-01

Bacterial adhesion onto abiotic surfaces is an important issue in biology and medicine since understanding the bases of such interaction represents a crucial aspect in the design of safe implant devices with intrinsic antibacterial characteristics. In this framework, we investigated the effects of nanostructured metal substrates on Escherichia coli adhesion and adaptation in order to understand the bio-molecular dynamics ruling the interactions at the interface. In particular, we show how highly controlled nanostructured gold substrates impact the bacterial behavior in terms of morphological changes and lead to modifications in the expression profile of several genes, which are crucially involved in the stress response and fimbrial synthesis. These results mainly demonstrate that E. coli cells are able to sense even slight changes in surface nanotopography and to actively respond by activating stress-related pathways. At the same time, our findings highlight the possibility of designing nanoengineered substrates able to trigger specific bio-molecular effects, thus opening the perspective of smartly tuning bacterial behavior by biomaterial design.

The Effects of Structured Physical Activity Program on Social Interaction and Communication for Children with Autism

PubMed Central

Zhao, Mengxian

2018-01-01

The purpose of this study was to investigate the effects of structured physical activity program on social interaction and communication of children with autism spectrum disorder (ASD). Fifty children with ASD from a special school were randomly divided into experimental and control groups. 25 children with ASD were placed in the experimental group, and the other 25 children as the control group participated in regular physical activity. A total of forty-one participants completed the study. A 12-week structured physical activity program was implemented with a total of 24 exercise sessions targeting social interaction and communication of children with ASD, and a quasi-experimental design was used for this study. Data were collected using quantitative and qualitative instruments. SSIS and ABLLS-R results showed that an overall improvement in social skills and social interaction for the experimental group across interim and posttests, F = 8.425, p = 0.001 (p < 0.005), and significant improvements appeared in communication, cooperation, social interaction, and self-control subdomains (p < 0.005). Conversely, no statistically significant differences were found in the control group (p > 0.005). The study concluded that the special structured physical activity program positively influenced social interaction and communication skills of children with ASD, especially in social skills, communication, prompt response, and frequency of expression. PMID:29568743

PARO robot affects diverse interaction modalities in group sensory therapy for older adults with dementia.

PubMed

Šabanović, Selma; Bennett, Casey C; Chang, Wan-Ling; Huber, Lesa

2013-06-01

We evaluated the seal-like robot PARO in the context of multi-sensory behavioral therapy in a local nursing home. Participants were 10 elderly nursing home residents with varying levels of dementia. We report three principle findings from our observations of interactions between the residents, PARO, and a therapist during seven weekly therapy sessions. Firstly, we show PARO provides indirect benefits for users by increasing their activity in particular modalities of social interaction, including visual, verbal, and physical interaction, which vary between primary and non-primary interactors. Secondly, PARO's positive effects on older adults' activity levels show steady growth over the duration of our study, suggesting they are not due to short-term "novelty effects." Finally, we show a variety of ways in which individual participants interacted with PARO and relate this to the "interpretive flexibility" of its design.

An Analysis of a Comprehensive Evaluation Model for Guided Group Interaction Techniques with Juvenile Delinquents. Final Report.

ERIC Educational Resources Information Center

Silverman, Mitchell

Reported are the first phase activities of a longitudinal project designed to evaluate the effectiveness of Guided Group Interaction (GGI) technique as a meaningful approach in the field of corrections. The main findings relate to the establishment of reliability for the main components of the Revised Behavior Scores System developed to assess the…

Training Teaching Staff to Facilitate Spontaneous Communication in Children with Autism: Adult Interactive Style Intervention (AISI)

ERIC Educational Resources Information Center

Kossyvaki, Lila; Jones, Glenys; Guldberg, Karen

2016-01-01

Previous research has demonstrated that the way adults interact with children with autism can have a great impact on their spontaneous communication. However, to date, few studies have focused on modifying adults' behaviour and even fewer have been conducted in school settings which actively involve teaching staff in designing the intervention.…

A Comparison Study of Augmented Reality versus Interactive Simulation Technology to Support Student Learning of a Socio-Scientific Issue

ERIC Educational Resources Information Center

Chang, Hsin-Yi; Hsu, Ying-Shao; Wu, Hsin-Kai

2016-01-01

We investigated the impact of an augmented reality (AR) versus interactive simulation (IS) activity incorporated in a computer learning environment to facilitate students' learning of a socio-scientific issue (SSI) on nuclear power plants and radiation pollution. We employed a quasi-experimental research design. Two classes (a total of 45…

"Mao Might Cheat": The Interactional Construction of the Imaginary Situation in a Fifth Dimension After-School Setting

ERIC Educational Resources Information Center

Poole, Deborah

2011-01-01

This article explores Vygtosky's (1978) notion of the imaginary situation through analysis of interaction and activity in a Fifth Dimension after-school setting, one of a network of programs designed with an aim to realize developmental concepts proposed by Vygotsky and others in the cultural-historical tradition (see, e.g., Cole & the…

The Use of Flexible, Interactive, Situation-Focused Software for the E-Learning of Mathematics.

ERIC Educational Resources Information Center

Farnsworth, Ralph Edward

This paper discusses the classroom, home, and distance use of new, flexible, interactive, application-oriented software known as Active Learning Suite. The actual use of the software, not just a controlled experiment, is reported on. Designed for the e-learning of university mathematics, the program was developed by a joint U.S.-Russia team and…

The solvent at antigen-binding site regulated C3d-CR2 interactions through the C-terminal tail of C3d at different ion strengths: insights from molecular dynamics simulation.

PubMed

Zhang, Yan; Guo, Jingjing; Li, Lanlan; Liu, Xuewei; Yao, Xiaojun; Liu, Huanxiang

2016-10-01

The interactions of complement receptor 2 (CR2) and the degradation fragment C3d of complement component C3 play important links between the innate and adaptive immune systems. Due to the importance of C3d-CR2 interaction in the design of vaccines and inhibitors, a number of studies have been performed to investigate C3d-CR2 interaction. Many studies have indicated C3d-CR2 interactions are ionic strength-dependent. To investigate the molecular mechanism of C3d-CR2 interaction and the origin of effects of ionic strength, molecular dynamics simulations for C3d-CR2 complex together with the energetic and structural analysis were performed. Our results revealed the increased interactions between charged protein and ions weaken C3d-CR2 association, as ionic strengths increase. Moreover, ion strengths have similar effects on antigen-binding site and CR2 binding site. Meanwhile, Ala17 and Gln20 will transform between the activated and non-activated states mediated by His133 and Glu135 at different ion strengths. Our results reveal the origins of the effects of ionic strengths on C3d-CR2 interactions are due to the changes of water, ion occupancies and distributions. This study uncovers the origin of the effect of ionic strength on C3d-CR2 interaction and deepens the understanding of the molecular mechanism of their interaction, which is valuable for the design of vaccines and small molecule inhibitors. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification of New Potential Scientific and Technology Areas for DoD Application. Summary of Activities

DTIC Science & Technology

1986-07-31

designer will be able to more rapid- ly assemble a total software package from perfected modules that can be easily de - bugged or replaced with more...antinuclear interactions e. gravitational effects of antimatter 2. possible machine parameters and lattice design 3. electron and stochastic cooling needs 4...implementation, reliability requirements; development of design environments and of experimental methodology; technology transfer methods from

Design of Novel Chemotherapeutic Agents Targeting Checkpoint Kinase 1 Using 3D-QSAR Modeling and Molecular Docking Methods.

PubMed

Balupuri, Anand; Balasubramanian, Pavithra K; Cho, Seung J

2016-01-01

Checkpoint kinase 1 (Chk1) has emerged as a potential therapeutic target for design and development of novel anticancer drugs. Herein, we have performed three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking analyses on a series of diazacarbazoles to design potent Chk1 inhibitors. 3D-QSAR models were developed using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Docking studies were performed using AutoDock. The best CoMFA and CoMSIA models exhibited cross-validated correlation coefficient (q2) values of 0.631 and 0.585, and non-cross-validated correlation coefficient (r2) values of 0.933 and 0.900, respectively. CoMFA and CoMSIA models showed reasonable external predictabilities (r2 pred) of 0.672 and 0.513, respectively. A satisfactory performance in the various internal and external validation techniques indicated the reliability and robustness of the best model. Docking studies were performed to explore the binding mode of inhibitors inside the active site of Chk1. Molecular docking revealed that hydrogen bond interactions with Lys38, Glu85 and Cys87 are essential for Chk1 inhibitory activity. The binding interaction patterns observed during docking studies were complementary to 3D-QSAR results. Information obtained from the contour map analysis was utilized to design novel potent Chk1 inhibitors. Their activities and binding affinities were predicted using the derived model and docking studies. Designed inhibitors were proposed as potential candidates for experimental synthesis.

Query2Question: Translating Visualization Interaction into Natural Language.

PubMed

Nafari, Maryam; Weaver, Chris

2015-06-01

Richly interactive visualization tools are increasingly popular for data exploration and analysis in a wide variety of domains. Existing systems and techniques for recording provenance of interaction focus either on comprehensive automated recording of low-level interaction events or on idiosyncratic manual transcription of high-level analysis activities. In this paper, we present the architecture and translation design of a query-to-question (Q2Q) system that automatically records user interactions and presents them semantically using natural language (written English). Q2Q takes advantage of domain knowledge and uses natural language generation (NLG) techniques to translate and transcribe a progression of interactive visualization states into a visual log of styled text that complements and effectively extends the functionality of visualization tools. We present Q2Q as a means to support a cross-examination process in which questions rather than interactions are the focus of analytic reasoning and action. We describe the architecture and implementation of the Q2Q system, discuss key design factors and variations that effect question generation, and present several visualizations that incorporate Q2Q for analysis in a variety of knowledge domains.

Molecular docking, 3D-QSAR and structural optimization on imidazo-pyridine derivatives dually targeting AT1 and PPARγ

PubMed Central

Zhang, Jun; Hao, Qing-Qing; Liu, Xin; Jing, Zhi; Jia, Wen-Qing; Wang, Shu-Qing; Xu, Wei-Ren; Cheng, Xian-Chao; Wang, Run-Ling

2017-01-01

Telmisartan, a bifunctional agent of blood pressure lowering and glycemia reduction, was previously reported to antagonize angiotensin II type 1 (AT1) receptor and partially activate peroxisome proliferator-activated receptor γ (PPARγ) simultaneously. Through the modification to telmisartan, researchers designed and obtained imidazo-\\pyridine derivatives with the IC50s of 0.49∼94.1 nM against AT1 and EC50s of 20∼3640 nM towards PPARγ partial activation. For minutely inquiring the interaction modes with the relevant receptor and analyzing the structure-activity relationships, molecular docking and 3D-QSAR (Quantitative structure-activity relationships) analysis of these imidazo-\\pyridines on dual targets were conducted in this work. Docking approaches of these derivatives with both receptors provided explicit interaction behaviors and excellent matching degree with the binding pockets. The best CoMFA (Comparative Molecular Field Analysis) models exhibited predictive results of q2=0.553, r2=0.954, SEE=0.127, r2pred=0.779 for AT1 and q2=0.503, r2=1.00, SEE=0.019, r2pred=0.604 for PPARγ, respectively. The contour maps from the optimal model showed detailed information of structural features (steric and electrostatic fields) towards the biological activity. Combining the bioisosterism with the valuable information from above studies, we designed six molecules with better predicted activities towards AT1 and PPARγ partial activation. Overall, these results could be useful for designing potential dual AT1 antagonists and partial PPARγ agonists. PMID:28445965

Molecular docking, 3D-QSAR and structural optimization on imidazo-pyridine derivatives dually targeting AT1 and PPARg.

PubMed

Zhang, Jun; Hao, Qing-Qing; Liu, Xin; Jing, Zhi; Jia, Wen-Qing; Wang, Shu-Qing; Xu, Wei-Ren; Cheng, Xian-Chao; Wang, Run-Ling

2017-04-11

Telmisartan, a bifunctional agent of blood pressure lowering and glycemia reduction, was previously reported to antagonize angiotensin II type 1 (AT1) receptor and partially activate peroxisome proliferator-activated receptor γ (PPARγ) simultaneously. Through the modification to telmisartan, researchers designed and obtained imidazo-\\pyridine derivatives with the IC50s of 0.49~94.1 nM against AT1 and EC50s of 20~3640 nM towards PPARγ partial activation. For minutely inquiring the interaction modes with the relevant receptor and analyzing the structure-activity relationships, molecular docking and 3D-QSAR (Quantitative structure-activity relationships) analysis of these imidazo-\\pyridines on dual targets were conducted in this work. Docking approaches of these derivatives with both receptors provided explicit interaction behaviors and excellent matching degree with the binding pockets. The best CoMFA (Comparative Molecular Field Analysis) models exhibited predictive results of q2=0.553, r2=0.954, SEE=0.127, r2pred=0.779 for AT1 and q2=0.503, r2=1.00, SEE=0.019, r2pred=0.604 for PPARγ, respectively. The contour maps from the optimal model showed detailed information of structural features (steric and electrostatic fields) towards the biological activity. Combining the bioisosterism with the valuable information from above studies, we designed six molecules with better predicted activities towards AT1 and PPARγ partial activation. Overall, these results could be useful for designing potential dual AT1 antagonists and partial PPARγ agonists.

Steering the conversation: A linguistic exploration of natural language interactions with a digital assistant during simulated driving.

PubMed

Large, David R; Clark, Leigh; Quandt, Annie; Burnett, Gary; Skrypchuk, Lee

2017-09-01

Given the proliferation of 'intelligent' and 'socially-aware' digital assistants embodying everyday mobile technology - and the undeniable logic that utilising voice-activated controls and interfaces in cars reduces the visual and manual distraction of interacting with in-vehicle devices - it appears inevitable that next generation vehicles will be embodied by digital assistants and utilise spoken language as a method of interaction. From a design perspective, defining the language and interaction style that a digital driving assistant should adopt is contingent on the role that they play within the social fabric and context in which they are situated. We therefore conducted a qualitative, Wizard-of-Oz study to explore how drivers might interact linguistically with a natural language digital driving assistant. Twenty-five participants drove for 10 min in a medium-fidelity driving simulator while interacting with a state-of-the-art, high-functioning, conversational digital driving assistant. All exchanges were transcribed and analysed using recognised linguistic techniques, such as discourse and conversation analysis, normally reserved for interpersonal investigation. Language usage patterns demonstrate that interactions with the digital assistant were fundamentally social in nature, with participants affording the assistant equal social status and high-level cognitive processing capability. For example, participants were polite, actively controlled turn-taking during the conversation, and used back-channelling, fillers and hesitation, as they might in human communication. Furthermore, participants expected the digital assistant to understand and process complex requests mitigated with hedging words and expressions, and peppered with vague language and deictic references requiring shared contextual information and mutual understanding. Findings are presented in six themes which emerged during the analysis - formulating responses; turn-taking; back-channelling, fillers and hesitation; vague language; mitigating requests and politeness and praise. The results can be used to inform the design of future in-vehicle natural language systems, in particular to help manage the tension between designing for an engaging dialogue (important for technology acceptance) and designing for an effective dialogue (important to minimise distraction in a driving context). Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of a skin for intuitive interaction with an assistive robot.

PubMed

Markham, Heather C; Brewer, Bambi R

2009-01-01

Assistive robots for persons with physical limitations need to interact with humans in a manner that is safe to the user and the environment. Early work in this field centered on task specific robots. Recent work has focused on the use of the MANUS ARM and the development of different interfaces. The most intuitive interaction with an object is through touch. By creating a skin for the robot arm which will directly control its movement compliance, we have developed a novel and intuitive method of interaction. This paper describes the development of a skin which acts as a switch. When activated through touch, the skin will put the arm into compliant mode allowing it to be moved to the desired location safely, and when released will put the robot into non-compliant mode thereby keeping it in place. We investigated four conductive materials and four insulators, selecting the best combination based on our design goals of the need for a continuous activation surface, the least amount of force required for skin activation, and the most consistent voltage change between the conductive surfaces measured during activation.

Continued Development of the Rapid Cycle Amine (RCA) System for Advanced Extravehicular Activity Systems

NASA Technical Reports Server (NTRS)

Papale, William; Chullen, Cinda; Campbell, Colin; Conger, Bruce; McMillin, Summer; Jeng, Frank

2014-01-01

Development activities related to the Rapid Cycle Amine (RCA) Carbon Dioxide (CO2) and Humidity control system have progressed to the point of integrating the RCA into an advanced Primary Life Support System (PLSS 2.0) to evaluate the interaction of the RCA among other PLSS components in a ground test environment. The RCA 2.0 assembly (integrated into PLSS 2.0) consists of a valve assembly with commercial actuator motor, a sorbent canister, and a field-programmable gate array (FPGA)-based process node controller. Continued design and development activities for RCA 3.0 have been aimed at optimizing the canister size and incorporating greater fidelity in the valve actuator motor and valve position feedback design. Further, the RCA process node controller is envisioned to incorporate a higher degree of functionality to support a distributed PLSS control architecture. This paper will describe the progression of technology readiness levels of RCA 1.0, 2.0 and 3.0 along with a review of the design and manufacturing successes and challenges for 2.0 and 3.0 units. The anticipated interfaces and interactions with the PLSS 2.0/2.5/3.0 assemblies will also be discussed.

Teaching the Absorption of Light Colours Using an Artificial Rainbow

ERIC Educational Resources Information Center

Yurumezoglu, Kemal; Isik, Hakan; Arikan, Gizem; Kabay, Gozde

2015-01-01

This paper presents an experimental activity based on the absorption of light colours by pigments. The activity is constructed using a stepwise design and offers an opportunity for students and teachers to compare and generalize the interactions between light and pigment colours. The light colours composing an artificial rainbow produced in the…

Collaborative Production of Learning Objects on French Literary Works Using the LOC Software

ERIC Educational Resources Information Center

Penman, Christine

2015-01-01

This case study situates the collaborative design of learning objects (interactive online learning material) using the LOC (Learning Object Creator) software in the context of language activities external to the core learning activities of language students at a UK university. It describes the creative and pedagogical processes leading to the…

Analyzing the Learning Process of an Online Role-Playing Discussion Activity

ERIC Educational Resources Information Center

Hou, Huei-Tse

2012-01-01

Instructional activities based on online discussion strategies have gained prevalence in recent years. Within this context, a crucial research topic is to design innovative and appropriate online discussion strategies that assist learners in attaining a deeper level of interaction and higher cognitive skills. By analyzing the process of online…

LSQuiz: A Collaborative Classroom Response System to Support Active Learning through Ubiquitous Computing

ERIC Educational Resources Information Center

Caceffo, Ricardo; Azevedo, Rodolfo

2014-01-01

The constructivist theory indicates that knowledge is not something finished and complete. However, the individuals must construct it through the interaction with the physical and social environment. The Active Learning is a methodology designed to support the constructivism through the involvement of students in their learning process, allowing…

Young Children's Engagement and Learning Opportunities in a Cooking Activity with Parents and Older Siblings

ERIC Educational Resources Information Center

Finn, Lauren; Vandermaas-Peeler, Maureen

2013-01-01

Parents teach their children through informal social interactions in a process known as guided participation (Rogoff, 1990). Although most research focuses on parent-child dyads, young children also learn from older siblings and parents through shared participation in daily activities. Utilizing a structured observational design, the authors…

Agriculture Education SimFarm(TM). Technology Learning Activity. Teacher Edition.

ERIC Educational Resources Information Center

Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

This Technology Learning Activity (TLA) for agriculture education in grades 6-10 is designed to help students learn the basic terminology of a farm system while they experience the responsibility of keeping a profitable farm in operation through use of the interactive SimFarm software. Introductory materials provide an overview of technology…

The Global Product: Internationalization of the Auto Industry.

ERIC Educational Resources Information Center

Stanford Univ., CA. Stanford Program on International and Cross Cultural Education.

This secondary level unit, designed for use in a social studies or introductory economics course, has students participate in decision-making activities about global auto production. Although Japan-United States interaction is emphasized, the concepts, terms and activities employed in the unit apply to other countries as well. The unit includes 11…

Flap effectiveness appraisal for winged re-entry vehicles

NASA Astrophysics Data System (ADS)

de Rosa, Donato; Pezzella, Giuseppe; Donelli, Raffaele S.; Viviani, Antonio

2016-05-01

The interactions between shock waves and boundary layer are commonplace in hypersonic aerodynamics. They represent a very challenging design issue for hypersonic vehicle. A typical example of shock wave boundary layer interaction is the flowfield past aerodynamic surfaces during control. As a consequence, such flow interaction phenomena influence both vehicle aerodynamics and aerothermodynamics. In this framework, the present research effort describes the numerical activity performed to simulate the flowfield past a deflected flap in hypersonic flowfield conditions for a winged re-entry vehicle.

Good, Better, Best: Using Universal Design and Digital Technology to Develop Great Products

ERIC Educational Resources Information Center

Tauke, Beth; Story, Mary Follette; Ostroff, Elaine

2004-01-01

Industrial design and technology are lab-based disciplines with highly visual products, hands-on activities, and frequent interactions between faculty and students. As a result, the ways that online resources are used in these courses tend to be different from other subject areas with more lecture-oriented modes of learning. This article addresses…

Working Collectively to Design Online Teacher Education Curriculum: How Do Teacher Educators Manage to Do It?

ERIC Educational Resources Information Center

Milewski, Amanda; Gürsel, Umut; Herbst, Patricio

2017-01-01

This paper is part of a three-year inquiry that supports and investigates the work of groups of mathematics teacher educators using technological tools to design and implement multimedia practice-based teacher education curriculum materials. This paper describes the kinds of activities, interactions, and tools used by mathematics teacher educators…

Towards a Pedagogical Model for Science Education: Bridging Educational Contexts through a Blended Learning Approach

ERIC Educational Resources Information Center

Bidarra, José; Rusman, Ellen

2017-01-01

This paper proposes a design framework to support science education through blended learning, based on a participatory and interactive approach supported by ICT-based tools, called "Science Learning Activities Model" (SLAM). The development of this design framework started as a response to complex changes in society and education (e.g.…

Designing Experiments on Thermal Interactions by Secondary-School Students in a Simulated Laboratory Environment

ERIC Educational Resources Information Center

Lefkos, Ioannis; Psillos, Dimitris; Hatzikraniotis, Euripides

2011-01-01

Background and purpose: The aim of this study was to explore the effect of investigative activities with manipulations in a virtual laboratory on students' ability to design experiments. Sample: Fourteen students in a lower secondary school in Greece attended a teaching sequence on thermal phenomena based on the use of information and…

OOMMPPAA: A Tool To Aid Directed Synthesis by the Combined Analysis of Activity and Structural Data

PubMed Central

2014-01-01

There is an ever increasing resource in terms of both structural information and activity data for many protein targets. In this paper we describe OOMMPPAA, a novel computational tool designed to inform compound design by combining such data. OOMMPPAA uses 3D matched molecular pairs to generate 3D ligand conformations. It then identifies pharmacophoric transformations between pairs of compounds and associates them with their relevant activity changes. OOMMPPAA presents this data in an interactive application providing the user with a visual summary of important interaction regions in the context of the binding site. We present validation of the tool using openly available data for CDK2 and a GlaxoSmithKline data set for a SAM-dependent methyl-transferase. We demonstrate OOMMPPAA’s application in optimizing both potency and cell permeability and use OOMMPPAA to highlight nuanced and cross-series SAR. OOMMPPAA is freely available to download at http://oommppaa.sgc.ox.ac.uk/OOMMPPAA/. PMID:25244105

Robot-assisted therapy for improving social interactions and activity participation among institutionalized older adults: a pilot study.

PubMed

Sung, Huei-Chuan; Chang, Shu-Min; Chin, Mau-Yu; Lee, Wen-Li

2015-03-01

Animal-assisted therapy is gaining popularity as part of therapeutic activities for older adults in many long-term care facilities. However, concerns about dog bites, allergic responses to pets, disease, and insufficient available resources to care for a real pet have led to many residential care facilities to ban this therapy. There are situations where a substitute artificial companion, such as robotic pet, may serve as a better alternative. This pilot study used a one-group pre- and posttest design to evaluate the effect of a robot-assisted therapy for older adults. Sixteen eligible participants participated in the study and received a group robot-assisted therapy using a seal-like robot pet for 30 minutes twice a week for 4 weeks. All participants received assessments of their communication and interaction skills using the Assessment of Communication and Interaction Skills (ACIS-C) and activity participation using the Activity Participation Scale at baseline and at week 4. A total of 12 participants completed the study. Wilcoxon signed rank test showed that participants' communication and interaction skills (z = -2.94, P = 0.003) and activity participation (z = -2.66, P = 0.008) were significantly improved after receiving 4-week robot-assisted therapy. By interacting with a robot pet, such as Paro, the communication, interaction skills, and activity participation of the older adults can be improved. The robot-assisted therapy can be provided as a routine activity program and has the potential to improve social health of older adults in residential care facilities. Copyright © 2014 Wiley Publishing Asia Pty Ltd.

Experimental design affects social behavior outcomes in adult zebrafish developmentally exposed to lead.

PubMed

Weber, Daniel N; Ghorai, Jugal K

2013-09-01

Lead (Pb(2+)) affects neuronal and endocrine systems that influence social interactions. By providing potential hiding locations, spatial heterogeneity may affect Pb(2+)-induced behavioral outcomes. Therefore, a test chamber was designed into which a refuge could be inserted. The refuge allowed test subjects to escape from the mirror image that stimulated agonistic interactions. Behaviors with a mirror were compared with baseline activity patterns without a mirror. Adult (12-month old) male and female zebrafish, exposed to Pb(2+) (0-10 μM) as embryos (2-24 hours post fertilization), were tested individually for 5 min in each chamber design within 2 h of feeding. Behaviors were evaluated for % time in mirror zone, distance traveled (=activity level), and attacks on the mirror image. When there was no refuge, significant concentration-dependent increases occurred in male % time in mirror zone, activity level, and number of attacks. Increases in these variables were less pronounced in females. When there was a refuge, there were significant differences for males only in activity level and attacks at the higher developmental exposure concentrations; % time in mirror zone followed a similar pattern and level as without refuge. Females displayed Pb(2+)-induced behavioral changes only for attacks on mirror. Since the presence of refuges that is, environmental enrichment, reduced Pb(2+)-induced agonistic behavior in both sexes, experimental spatial design can be considered an important factor when interpreting behavioral outcomes.

Human interaction as environmental enrichment for pair-housed wolves and wolf-dog crosses.

PubMed

Mehrkam, Lindsay R; Verdi, Nicolle T; Wynne, Clive D L

2014-01-01

Private nonhuman animal sanctuaries are often financially limited in their ability to implement traditional environmental enrichment strategies. One possible solution may be to provide socialized animals with human interaction sessions. However, the merit of human interaction as enrichment has received little empirical attention to date. The present study aimed to evaluate whether human interaction could be enriching for socialized, pair-housed wolves and wolf-dog crosses at a private sanctuary. Observations of each subject were conducted in a reversal design to measure species-typical affiliation, activity levels, and aberrant behaviors when caretakers were both present and absent. The results demonstrate significantly higher levels of conspecific-directed affiliation and activity levels and reduced aberrant behavior when human interaction was available. Social play also increased when caregivers were present, supporting the hypothesis that play among conspecifics may be maintained by positive changes in an animal's environment. The potential for human interaction to be established as a scientifically validated, cost-effective enrichment strategy is supported by these findings.

NASA/USRA advanced design program activity, 1991-1992

NASA Astrophysics Data System (ADS)

Dorrity, J. Lewis; Patel, Suneer

The School of Textile and Fiber Engineering continued to pursue design projects with the Mechanical Engineering School giving the students an outstanding opportunity to interact with students from another discipline. Four problems were defined which had aspects which would be reasonably assigned to an interdisciplinary team. The design problems are described. The projects included lunar preform manufacturing, dust control for Enabler, an industrial sewing machine variable speed controllor, Enabler operation station, and design for producing fiberglass fabric in a lunar environment.

NASA/USRA advanced design program activity, 1991-1992

NASA Technical Reports Server (NTRS)

Dorrity, J. Lewis; Patel, Suneer

1992-01-01

The School of Textile and Fiber Engineering continued to pursue design projects with the Mechanical Engineering School giving the students an outstanding opportunity to interact with students from another discipline. Four problems were defined which had aspects which would be reasonably assigned to an interdisciplinary team. The design problems are described. The projects included lunar preform manufacturing, dust control for Enabler, an industrial sewing machine variable speed controllor, Enabler operation station, and design for producing fiberglass fabric in a lunar environment.

Mechanical design of DNA nanostructures

NASA Astrophysics Data System (ADS)

Castro, Carlos E.; Su, Hai-Jun; Marras, Alexander E.; Zhou, Lifeng; Johnson, Joshua

2015-03-01

Structural DNA nanotechnology is a rapidly emerging field that has demonstrated great potential for applications such as single molecule sensing, drug delivery, and templating molecular components. As the applications of DNA nanotechnology expand, a consideration of their mechanical behavior is becoming essential to understand how these structures will respond to physical interactions. This review considers three major avenues of recent progress in this area: (1) measuring and designing mechanical properties of DNA nanostructures, (2) designing complex nanostructures based on imposed mechanical stresses, and (3) designing and controlling structurally dynamic nanostructures. This work has laid the foundation for mechanically active nanomachines that can generate, transmit, and respond to physical cues in molecular systems.Structural DNA nanotechnology is a rapidly emerging field that has demonstrated great potential for applications such as single molecule sensing, drug delivery, and templating molecular components. As the applications of DNA nanotechnology expand, a consideration of their mechanical behavior is becoming essential to understand how these structures will respond to physical interactions. This review considers three major avenues of recent progress in this area: (1) measuring and designing mechanical properties of DNA nanostructures, (2) designing complex nanostructures based on imposed mechanical stresses, and (3) designing and controlling structurally dynamic nanostructures. This work has laid the foundation for mechanically active nanomachines that can generate, transmit, and respond to physical cues in molecular systems. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07153k

Anion-π interactions in active centers of superoxide dismutases.

PubMed

Ribić, Vesna R; Stojanović, Srđan Đ; Zlatović, Mario V

2018-01-01

We investigated 1060 possible anion-π interactions in a data set of 41 superoxide dismutase active centers. Our observations indicate that majority of the aromatic residues are capable to form anion-π interactions, mainly by long-range contacts, and that there is preference of Trp over other aromatic residues in these interactions. Furthermore, 68% of total predicted interactions in the dataset are multiple anion-π interactions. Anion-π interactions are distance and orientation dependent. We analyzed the energy contribution resulting from anion-π interactions using ab initio calculations. The results showed that, while most of their interaction energies lay in the range from -0 to -4kcalmol -1 , those energies can be up to -9kcalmol -1 and about 34% of interactions were found to be repulsive. Majority of the suggested anion-π interacting residues in ternary complexes are metal-assisted. Stabilization centers for these proteins showed that all the six residues found in predicted anion-π interactions are important in locating one or more of such centers. The anion-π interacting residues in these proteins were found to be highly conserved. We hope that these studies might contribute useful information regarding structural stability and its interaction in future designs of novel metalloproteins. Copyright © 2017 Elsevier B.V. All rights reserved.

A comparative study of occupancy and patient care quality in four different types of intensive care units in a children's hospital.

PubMed

Smith, Thomas J

2012-01-01

This paper reports a comparative study of occupancy and patient care quality in four types of intensive care units in a children's hospital,: an Infant Care Center (ICC), a Medical/Surgical (Med/Surg) unit, a Neonatal Intensive Care Unit (NICU), and a Pediatric Intensive Care Unit (PICU), each featuring a mix of multi-bed and private room (PR) patient care environments. The project is prompted by interest by the project sponsor in a pre-occupancy analysis, before the units are upgraded to exclusive PR designs. Methods comprised, for each unit: (1) observations of ergonomic design features; (2) task activity analyses of job performance of selected staff; and (3) use of a survey to collect perceptions by unit nursing and house staff (HS) of indicators of occupancy and patient care quality. (1) the five most common task activities are interaction with patients, charting, and interaction with equipment, co-workers and family members; (2) job satisfaction, patient care, work environment, job, patient care team interaction, and general occupancy quality rankings by ICC and/or NICU respondents are significantly higher than those by other staff respondents; and (3) ergonomic design shortcomings noted are excess noise, problems with equipment, and work environment, job-related health, and patient care quality issues.

DHM and serious games: a case-study oil and gas laboratories.

PubMed

Santos, V; Zamberlan, M; Streit, P; Oliveira, J; Guimarães, C; Pastura, F; Cid, G

2012-01-01

The aim in this paper is to present a research on the application of serious games for the design of laboratories in the oil and gas industries. The focus is in human virtual representation acquired from 3D scanning, human interaction, workspace layout and equipment designed considering ergonomics standards. The laboratory studies were simulated in Unity3D platform, which allows the users to control the DHM1 on the dynamic virtual scenario, in order to simulate work activities. This methodology can change the design process by improving the level of interaction between final users, managers and human factor teams. That helps to better visualize future work settings and improve the level of participation between all stakeholders.

A Novel Terpenoid from Elephantopus Scaber – Antibacterial Activity on Staphylococcus Aureus: A Substantiate Computational Approach

PubMed Central

Daisy, P.; Mathew, Salu; Suveena, S.; Rayan, Nirmala A.

2008-01-01

Staphylococcus aureus has gained much attention in the last decade as it is a major cause of the Urinary Tract Infection in Diabetic patients. The Extended Spectrum β-Lactamases (ESβL) producers are highly resistant to several conventional antibiotics. This limits the therapeutic options.Hence efforts are now taken to screen few medicinal plants, which are both economic and less toxic. Among the several plants screened, we have chosen the acetone extract of Elephantopus scaber from which we purified a new terpenoid for our study. Its structure was generated using CHEMSKETCH software and the activity prediction was done using PASS PREDICTION software. We have confirmed the mechanism of anti-bacterial effect of terpenoid using Computer – Aided Drug Design (CADD) with computational methods to simulate drug – receptor interactions. The Protein-Ligand interaction plays a significant role in the structural based drug designing. In this present study we have taken the Autolysin, the bacteriolytic enzyme, that digest the cell wall peptidoglycon. The autolysin and terpenoid were docked using HEX docking software and the docking score with minimum energy value of -209.54 was calculated. It infers that the terpenoid can inhibit the activity of autolysin by forming a strong atomic interaction with the active site residues. Hence the terpenoid can act as a drug for bacterial infections. Further investigations can be carried out to predict the activity of terpeniod on other targets. PMID:23675090

Development of Support Service for Prevention and Recovery from Dementia and Science of Lethe

NASA Astrophysics Data System (ADS)

Otake, Mihoko

Purpose of this study is to explore service design method through the development of support service for prevention and recovery from dementia towards science of lethe. We designed and implemented conversation support service via coimagination method based on multiscale service design method, both were proposed by the author. Multiscale service model consists of tool, event, human, network, style and rule. Service elements at different scales are developed according to the model. Interactive conversation supported by coimagination method activates cognitive functions so as to prevent progress of dementia. This paper proposes theoretical bases for science of lethe. Firstly, relationship among coimagination method and three cognitive functions including division of attention, planning, episodic memory which decline at mild cognitive imparement. Secondly, thought state transition model during conversation which describes cognitive enhancement via interactive communication. Thirdly, Set Theoretical Measure of Interaction is proposed for evaluating effectiveness of conversation to cognitive enhancement. Simulation result suggests that the ideas which cannot be explored by each speaker are explored during interactive conversation. Finally, coimagination method compared with reminiscence therapy and its possibility for collaboration is discussed.

Hepatitis C Virus NS3/4A Protease Inhibitors Incorporating Flexible P2 Quinoxalines Target Drug Resistant Viral Variants.

PubMed

Matthew, Ashley N; Zephyr, Jacqueto; Hill, Caitlin J; Jahangir, Muhammad; Newton, Alicia; Petropoulos, Christos J; Huang, Wei; Kurt-Yilmaz, Nese; Schiffer, Celia A; Ali, Akbar

2017-07-13

A substrate envelope-guided design strategy is reported for improving the resistance profile of HCV NS3/4A protease inhibitors. Analogues of 5172-mcP1P3 were designed by incorporating diverse quinoxalines at the P2 position that predominantly interact with the invariant catalytic triad of the protease. Exploration of structure-activity relationships showed that inhibitors with small hydrophobic substituents at the 3-position of P2 quinoxaline maintain better potency against drug resistant variants, likely due to reduced interactions with residues in the S2 subsite. In contrast, inhibitors with larger groups at this position were highly susceptible to mutations at Arg155, Ala156, and Asp168. Excitingly, several inhibitors exhibited exceptional potency profiles with EC 50 values ≤5 nM against major drug resistant HCV variants. These findings support that inhibitors designed to interact with evolutionarily constrained regions of the protease, while avoiding interactions with residues not essential for substrate recognition, are less likely to be susceptible to drug resistance.

The solar activity measurements experiments (SAMEX) for improved scientific understanding of solar activity

NASA Technical Reports Server (NTRS)

1989-01-01

The Solar Activity Measurements Experiments (SAMEX) mission is described. It is designed to provide a look at the interactions of magnetic fields and plasmas that create flares and other explosive events on the sun in an effort to understand solar activity and the nature of the solar magnetic field. The need for this mission, the instruments to be used, and the expected benefits of SAMEX are discussed.

In silico development of new acetylcholinesterase inhibitors.

PubMed

Pascoini, A L; Federico, L B; Arêas, A L F; Verde, B A; Freitas, P G; Camps, I

2018-04-19

In this work, we made use of fragment-based drug design (FBDD) and de novo design to obtain more powerful acetylcholinesterase (AChE) inhibitors. AChE is associated with Alzheimer's disease (AD). It was found that the cholinergic pathways in the cerebral cortex are compromised in AD and the accompanying cholinergic deficiency contributes to the cognitive deterioration of AD patients. In the FBDD approach, fragments are docked into the active site of the protein. As fragments are molecular groups with a low number of atoms, it is possible to study their interaction with localized amino acids. Once the interactions are measured, the fragments are organized by affinity and then linked together to form new molecules with a high degree of interaction with the active site. In the other approach, we used the de novo design technique starting from reference drugs used in the AD treatment. These drugs were broken into fragments (seeds). In the growing strategy, fragments were added to each seed, growing new molecules. In the linking strategy, two or more separated seeds were linked with different fragments. Both strategies combined produced a library of more than 2 million compounds. This library was filtered using absorption, distribution, metabolism, and excretion properties. The resulting library with around six thousand compounds was filtered again. In this case, structures with Tanimoto coefficients >.85 were discarded. The final library with 1500 compounds was submitted to docking studies. As a result, 10 compounds with better interaction energy than the reference drugs were obtained.

An Analysis of the Impact of Student-Scientist Interaction in a Technology Design Activity, Using the Expectancy-Value Model of Achievement Related Choice

ERIC Educational Resources Information Center

Masson, Anne-Lotte; Klop, Tanja; Osseweijer, Patricia

2016-01-01

Many education initiatives in science and technology education aim to create enthusiasm among young people to pursue a career in Science, Technology, Engineering, and Mathematics (STEM). Research suggests that personal interaction between secondary school students and scientists could be a success factor, but there is a need for more in-depth…

Designing for sustained adoption: A model of developing educational innovations for successful propagation

NASA Astrophysics Data System (ADS)

Khatri, Raina; Henderson, Charles; Cole, Renée; Froyd, Jeffrey E.; Friedrichsen, Debra; Stanford, Courtney

2016-06-01

[This paper is part of the Focused Collection on Preparing and Supporting University Physics Educators.] The physics education research community has produced a wealth of knowledge about effective teaching and learning of college level physics. Based on this knowledge, many research-proven instructional strategies and teaching materials have been developed and are currently available to instructors. Unfortunately, these intensive research and development activities have failed to influence the teaching practices of many physics instructors. This paper describes interim results of a larger study to develop a model of designing materials for successful propagation. The larger study includes three phases, the first two of which are reported here. The goal of the first phase was to characterize typical propagation practices of education developers, using data from a survey of 1284 National Science Foundation (NSF) principal investigators and focus group data from eight disciplinary groups of NSF program directors. The goal of the second phase was to develop an understanding of successful practice by studying three instructional strategies that have been well propagated. The result of the first two phases is a tentative model of designing for successful propagation, which will be further validated in the third phase through purposeful sampling of additional well-propagated instructional strategies along with typical education development projects. We found that interaction with potential adopters was one of the key missing ingredients in typical education development activities. Education developers often develop a polished product before getting feedback, rely on mass-market communication channels for dissemination, and do not plan for supporting adopters during implementation. The tentative model resulting from this study identifies three key propagation activities: interactive development, interactive dissemination, and support of adopters. Interactive development uses significant feedback from potential adopters to develop a strong product suitable for use in many settings. Interactive dissemination uses personal interactions to reach and motivate potential users. Support of adopters is missing from typical propagation practice and is important to reduce the burden of implementation and increases the likelihood of successful adoption.

78 FR 37803 - Agency Information Collection Activities; Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

... identify substances that have the potential to interact with the estrogen, androgen, or thyroid hormone... or thyroid hormone systems may proceed to Tier 2, which is designed to identify any adverse endocrine...

Neglected Children: Suggestions for Early Childhood Educators.

ERIC Educational Resources Information Center

Peterson, Karen L.; Roscoe, Bruce

1983-01-01

Discusses enhancing the development and improving the quality of life of neglected children through acquiring a special understanding and style of interacting with them and by using activities designed specifically to meet their developmental needs. (RH)

Design of Intelligent Robot as A Tool for Teaching Media Based on Computer Interactive Learning and Computer Assisted Learning to Improve the Skill of University Student

NASA Astrophysics Data System (ADS)

Zuhrie, M. S.; Basuki, I.; Asto B, I. G. P.; Anifah, L.

2018-01-01

The focus of the research is the teaching module which incorporates manufacturing, planning mechanical designing, controlling system through microprocessor technology and maneuverability of the robot. Computer interactive and computer-assisted learning is strategies that emphasize the use of computers and learning aids (computer assisted learning) in teaching and learning activity. This research applied the 4-D model research and development. The model is suggested by Thiagarajan, et.al (1974). 4-D Model consists of four stages: Define Stage, Design Stage, Develop Stage, and Disseminate Stage. This research was conducted by applying the research design development with an objective to produce a tool of learning in the form of intelligent robot modules and kit based on Computer Interactive Learning and Computer Assisted Learning. From the data of the Indonesia Robot Contest during the period of 2009-2015, it can be seen that the modules that have been developed confirm the fourth stage of the research methods of development; disseminate method. The modules which have been developed for students guide students to produce Intelligent Robot Tool for Teaching Based on Computer Interactive Learning and Computer Assisted Learning. Results of students’ responses also showed a positive feedback to relate to the module of robotics and computer-based interactive learning.

Robots As Intentional Agents: Using Neuroscientific Methods to Make Robots Appear More Social

PubMed Central

Wiese, Eva; Metta, Giorgio; Wykowska, Agnieszka

2017-01-01

Robots are increasingly envisaged as our future cohabitants. However, while considerable progress has been made in recent years in terms of their technological realization, the ability of robots to interact with humans in an intuitive and social way is still quite limited. An important challenge for social robotics is to determine how to design robots that can perceive the user’s needs, feelings, and intentions, and adapt to users over a broad range of cognitive abilities. It is conceivable that if robots were able to adequately demonstrate these skills, humans would eventually accept them as social companions. We argue that the best way to achieve this is using a systematic experimental approach based on behavioral and physiological neuroscience methods such as motion/eye-tracking, electroencephalography, or functional near-infrared spectroscopy embedded in interactive human–robot paradigms. This approach requires understanding how humans interact with each other, how they perform tasks together and how they develop feelings of social connection over time, and using these insights to formulate design principles that make social robots attuned to the workings of the human brain. In this review, we put forward the argument that the likelihood of artificial agents being perceived as social companions can be increased by designing them in a way that they are perceived as intentional agents that activate areas in the human brain involved in social-cognitive processing. We first review literature related to social-cognitive processes and mechanisms involved in human–human interactions, and highlight the importance of perceiving others as intentional agents to activate these social brain areas. We then discuss how attribution of intentionality can positively affect human–robot interaction by (a) fostering feelings of social connection, empathy and prosociality, and by (b) enhancing performance on joint human–robot tasks. Lastly, we describe circumstances under which attribution of intentionality to robot agents might be disadvantageous, and discuss challenges associated with designing social robots that are inspired by neuroscientific principles. PMID:29046651

Robots As Intentional Agents: Using Neuroscientific Methods to Make Robots Appear More Social.

PubMed

Wiese, Eva; Metta, Giorgio; Wykowska, Agnieszka

2017-01-01

Robots are increasingly envisaged as our future cohabitants. However, while considerable progress has been made in recent years in terms of their technological realization, the ability of robots to interact with humans in an intuitive and social way is still quite limited. An important challenge for social robotics is to determine how to design robots that can perceive the user's needs, feelings, and intentions, and adapt to users over a broad range of cognitive abilities. It is conceivable that if robots were able to adequately demonstrate these skills, humans would eventually accept them as social companions. We argue that the best way to achieve this is using a systematic experimental approach based on behavioral and physiological neuroscience methods such as motion/eye-tracking, electroencephalography, or functional near-infrared spectroscopy embedded in interactive human-robot paradigms. This approach requires understanding how humans interact with each other, how they perform tasks together and how they develop feelings of social connection over time, and using these insights to formulate design principles that make social robots attuned to the workings of the human brain. In this review, we put forward the argument that the likelihood of artificial agents being perceived as social companions can be increased by designing them in a way that they are perceived as intentional agents that activate areas in the human brain involved in social-cognitive processing. We first review literature related to social-cognitive processes and mechanisms involved in human-human interactions, and highlight the importance of perceiving others as intentional agents to activate these social brain areas. We then discuss how attribution of intentionality can positively affect human-robot interaction by (a) fostering feelings of social connection, empathy and prosociality, and by (b) enhancing performance on joint human-robot tasks. Lastly, we describe circumstances under which attribution of intentionality to robot agents might be disadvantageous, and discuss challenges associated with designing social robots that are inspired by neuroscientific principles.

Design for interaction between humans and intelligent systems during real-time fault management

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Schreckenghost, Debra L.; Thronesbery, Carroll G.

1992-01-01

Initial results are reported to provide guidance and assistance for designers of intelligent systems and their human interfaces. The objective is to achieve more effective human-computer interaction (HCI) for real time fault management support systems. Studies of the development of intelligent fault management systems within NASA have resulted in a new perspective of the user. If the user is viewed as one of the subsystems in a heterogeneous, distributed system, system design becomes the design of a flexible architecture for accomplishing system tasks with both human and computer agents. HCI requirements and design should be distinguished from user interface (displays and controls) requirements and design. Effective HCI design for multi-agent systems requires explicit identification of activities and information that support coordination and communication between agents. The effects are characterized of HCI design on overall system design and approaches are identified to addressing HCI requirements in system design. The results include definition of (1) guidance based on information level requirements analysis of HCI, (2) high level requirements for a design methodology that integrates the HCI perspective into system design, and (3) requirements for embedding HCI design tools into intelligent system development environments.

Active printed materials for complex self-evolving deformations.

PubMed

Raviv, Dan; Zhao, Wei; McKnelly, Carrie; Papadopoulou, Athina; Kadambi, Achuta; Shi, Boxin; Hirsch, Shai; Dikovsky, Daniel; Zyracki, Michael; Olguin, Carlos; Raskar, Ramesh; Tibbits, Skylar

2014-12-18

We propose a new design of complex self-evolving structures that vary over time due to environmental interaction. In conventional 3D printing systems, materials are meant to be stable rather than active and fabricated models are designed and printed as static objects. Here, we introduce a novel approach for simulating and fabricating self-evolving structures that transform into a predetermined shape, changing property and function after fabrication. The new locally coordinated bending primitives combine into a single system, allowing for a global deformation which can stretch, fold and bend given environmental stimulus.

Active Printed Materials for Complex Self-Evolving Deformations

PubMed Central

Raviv, Dan; Zhao, Wei; McKnelly, Carrie; Papadopoulou, Athina; Kadambi, Achuta; Shi, Boxin; Hirsch, Shai; Dikovsky, Daniel; Zyracki, Michael; Olguin, Carlos; Raskar, Ramesh; Tibbits, Skylar

2014-01-01

We propose a new design of complex self-evolving structures that vary over time due to environmental interaction. In conventional 3D printing systems, materials are meant to be stable rather than active and fabricated models are designed and printed as static objects. Here, we introduce a novel approach for simulating and fabricating self-evolving structures that transform into a predetermined shape, changing property and function after fabrication. The new locally coordinated bending primitives combine into a single system, allowing for a global deformation which can stretch, fold and bend given environmental stimulus. PMID:25522053

Reducing the distance: providing challenging and engaging online postgraduate education in pain management.

PubMed

Devonshire, Elizabeth; Henderson, Sarah E

2012-05-01

1. Health professionals need access to flexible, high-quality, advanced education in pain management. 2. There are multiple pedagogical distances to be negotiated in the delivery of effective postgraduate education. 3. A critical consideration in the design and delivery of effective online learning for postgraduate education in pain management is how to: actively engage students in the learning process; and encourage students to become lifelong learners. 4. Conceptual frameworks for encouraging student interaction online provide a useful tool in the design of postgraduate online learning activities.

Cycling the hot CNO: a teaching methodology

NASA Astrophysics Data System (ADS)

Frost-Schenk, J. W.; Diget, C. Aa; Bentley, M. A.; Tuff, A.

2018-03-01

An interactive activity to teach the hot Carbon, Nitrogen and Oxygen (HCNO) cycle is proposed. Justification for why the HCNO cycle is important is included via an example of x-ray bursts. The activity allows teaching and demonstration of half-life, nuclear isotopes, nuclear reactions, protons and α-particles, and catalytic processes. Whilst the process example is specific to astrophysics it may be used to teach more broadly about catalytic processes. This practical is designed for use with 10-20 participants, with the intention that the exercise will convey nuclear physics principles in a fun and interactive manner.

Discovery of novel high potent and cellular active ADC type PTP1B inhibitors with selectivity over TC-PTP via modification interacting with C site.

PubMed

Du, Yongli; Zhang, Yanhui; Ling, Hao; Li, Qunyi; Shen, Jingkang

2018-01-20

PTP1B serving as a key negative regulator of insulin signaling is a novel target for type 2 diabetes and obesity. Modification at ring B of N-{4-[(3-Phenyl-ureido)-methyl]-phenyl}-methane-sulfonamide template to interact with residues Arg47 and Lys41 in the C site of PTP1B by molecular docking aided design resulted in the discovery of a series of novel high potent and selective inhibitors of PTP1B. The structure activity relationship interacting with the C site of PTP1B was well illustrated. Compounds 8 and 18 were shown to be the high potent and most promising PTP1B inhibitors with cellular activity and great selectivity over the highly homologous TCPTP and other PTPs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Alterations of social interaction through genetic and environmental manipulation of the 22q11.2 gene Sept5 in the mouse brain.

PubMed

Harper, Kathryn M; Hiramoto, Takeshi; Tanigaki, Kenji; Kang, Gina; Suzuki, Go; Trimble, William; Hiroi, Noboru

2012-08-01

Social behavior dysfunction is a symptomatic element of schizophrenia and autism spectrum disorder (ASD). Although altered activities in numerous brain regions are associated with defective social cognition and perception, the causative relationship between these altered activities and social cognition and perception-and their genetic underpinnings-are not known in humans. To address these issues, we took advantage of the link between hemizygous deletion of human chromosome 22q11.2 and high rates of social behavior dysfunction, schizophrenia and ASD. We genetically manipulated Sept5, a 22q11.2 gene, and evaluated its role in social interaction in mice. Sept5 deficiency, against a high degree of homogeneity in a congenic genetic background, selectively impaired active affiliative social interaction in mice. Conversely, virally guided overexpression of Sept5 in the hippocampus or, to a lesser extent, the amygdala elevated levels of active affiliative social interaction in C57BL/6J mice. Congenic knockout mice and mice overexpressing Sept5 in the hippocampus or amygdala were indistinguishable from control mice in novelty and olfactory responses, anxiety or motor activity. Moreover, post-weaning individual housing, an environmental condition designed to reduce stress in male mice, selectively raised levels of Sept5 protein in the amygdala and increased active affiliative social interaction in C57BL/6J mice. These findings identify this 22q11.2 gene in the hippocampus and amygdala as a determinant of social interaction and suggest that defective social interaction seen in 22q11.2-associated schizophrenia and ASD can be genetically and environmentally modified by altering this 22q11.2 gene.

The mysterious atmosphere of the Earth. ATLAS: Instruction guide with activities

NASA Technical Reports Server (NTRS)

1993-01-01

This teacher's guide presents lesson plans addressing various aspects of atmospheric physics and chemistry; the interactions between land, air, and sea; air pollution; and the mechanisms of climate change. The science concepts in this guide have been designed to complement the middle school curriculum. However, many activities can be used with younger or older students.

Employment Skills for the 21st Century: Applied Activities To Develop a Competitive American Workforce. Teacher Edition.

ERIC Educational Resources Information Center

Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

This publication is a collection of 201 activities designed to give students practice in developing and applying in meaningful real-life settings both basic academic skills in reading, writing, and computation, and the more advanced higher-order skills of problem solving, critical thinking, group interaction, and oral communication. These…

An Action Research Study on the Effect of Interactive Technology and Active Learning on Student Performance

ERIC Educational Resources Information Center

Bear, Teresa J.

2013-01-01

This quantitative action science research study utilized a causal-comparative experimental research design in order to determine if the use of student response systems (clickers), as an active learning strategy in a community college course, improved student performance in the course. Students in the experimental group (n = 26) used clickers to…

Designing and Applying Web Assisted Activities to Be Used in Flipped Classroom Model

ERIC Educational Resources Information Center

Çetinkaya, Murat

2017-01-01

The purpose of this study is to develop personalized web assisted activities for the flipped classroom model applied in the "Human and Environment Interactions" unit of science lesson and to research its effect on students' achievement. The study was conducted with the 74 participation of 7th grade science lesson students within a period…

When the display matters: A multifaceted perspective on 3D geovisualizations

NASA Astrophysics Data System (ADS)

Juřík, Vojtěch; Herman, Lukáš; Šašinka, Čeněk; Stachoň, Zdeněk; Chmelík, Jiří

2017-04-01

This study explores the influence of stereoscopic (real) 3D and monoscopic (pseudo) 3D visualization on the human ability to reckon altitude information in noninteractive and interactive 3D geovisualizations. A two phased experiment was carried out to compare the performance of two groups of participants, one of them using the real 3D and the other one pseudo 3D visualization of geographical data. A homogeneous group of 61 psychology students, inexperienced in processing of geographical data, were tested with respect to their efficiency at identifying altitudes of the displayed landscape. The first phase of the experiment was designed as non-interactive, where static 3D visual displayswere presented; the second phase was designed as interactive and the participants were allowed to explore the scene by adjusting the position of the virtual camera. The investigated variables included accuracy at altitude identification, time demands and the amount of the participant's motor activity performed during interaction with geovisualization. The interface was created using a Motion Capture system, Wii Remote Controller, widescreen projection and the passive Dolby 3D technology (for real 3D vision). The real 3D visual display was shown to significantly increase the accuracy of the landscape altitude identification in non-interactive tasks. As expected, in the interactive phase there were differences in accuracy flattened out between groups due to the possibility of interaction, with no other statistically significant differences in completion times or motor activity. The increased number of omitted objects in real 3D condition was further subjected to an exploratory analysis.

The central role of wood biology in understanding the durability of wood-coating interactions

Treesearch

Alex C. Wiedenhoeft

2007-01-01

To design effectively for durability, one must actively and honestly assess the material properties and limitations of each of the components in the design system; wood or wood composite, and the coating. Inasmuch as wood coatings are manufactured to specified tolerances from known materials, we have control of that component of the system. Compared to manmade...

Posture, Musculoskeletal Activities, and Possible Musculoskeletal Discomfort among Children Using Laptops or Tablet Computers for Educational Purposes: A Literature Review

ERIC Educational Resources Information Center

Binboga, Elif; Korhan, Orhan

2014-01-01

Educational ergonomics focuses on the interaction between educational performance and educational design. By improving the design or pointing out the possible problems, educational ergonomics can be utilized to have positive impacts on the student performance and thus on education process. Laptops and tablet computers are becoming widely used by…

Kinematic design to improve ergonomics in human machine interaction.

PubMed

Schiele, André; van der Helm, Frans C T

2006-12-01

This paper introduces a novel kinematic design paradigm for ergonomic human machine interaction. Goals for optimal design are formulated generically and applied to the mechanical design of an upper-arm exoskeleton. A nine degree-of-freedom (DOF) model of the human arm kinematics is presented and used to develop, test, and optimize the kinematic structure of an human arm interfacing exoskeleton. The resulting device can interact with an unprecedented portion of the natural limb workspace, including motions in the shoulder-girdle, shoulder, elbow, and the wrist. The exoskeleton does not require alignment to the human joint axes, yet is able to actuate each DOF of our redundant limb unambiguously and without reaching into singularities. The device is comfortable to wear and does not create residual forces if misalignments exist. Implemented in a rehabilitation robot, the design features of the exoskeleton could enable longer lasting training sessions, training of fully natural tasks such as activities of daily living and shorter dress-on and dress-off times. Results from inter-subject experiments with a prototype are presented, that verify usability over the entire workspace of the human arm, including shoulder and shoulder girdle.

Sorption of water alkalinity and hardness from high-strength wastewater on bifunctional activated carbon: process optimization, kinetics and equilibrium studies.

PubMed

Amosa, Mutiu K

2016-08-01

Sorption optimization and mechanism of hardness and alkalinity on bifunctional empty fruit bunch-based powdered activation carbon (PAC) were studied. The PAC possessed both high surface area and ion-exchange properties, and it was utilized in the treatment of biotreated palm oil mill effluent. Batch adsorption experiments designed with Design Expert(®) were conducted in correlating the singular and interactive effects of the three adsorption parameters: PAC dosage, agitation speed and contact time. The sorption trends of the two contaminants were sequentially assessed through a full factorial design with three factor interaction models and a central composite design with polynomial models of quadratic order. Analysis of variance revealed the significant factors on each design response with very high R(2) values indicating good agreement between model and experimental values. The optimum operating conditions of the two contaminants differed due to their different regions of operating interests, thus necessitating the utility of desirability factor to get consolidated optimum operation conditions. The equilibrium data for alkalinity and hardness sorption were better represented by the Langmuir isotherm, while the pseudo-second-order kinetic model described the adsorption rates and behavior better. It was concluded that chemisorption contributed majorly to the adsorption process.

Lesson Plan Prototype for International Space Station's Interactive Video Education Events

NASA Technical Reports Server (NTRS)

Zigon, Thomas

1999-01-01

The outreach and education components of the International Space Station Program are creating a number of materials, programs, and activities that educate and inform various groups as to the implementation and purposes of the International Space Station. One of the strategies for disseminating this information to K-12 students involves an electronic class room using state of the art video conferencing technology. K-12 classrooms are able to visit the JSC, via an electronic field trip. Students interact with outreach personnel as they are taken on a tour of ISS mockups. Currently these events can be generally characterized as: Being limited to a one shot events, providing only one opportunity for students to view the ISS mockups; Using a "one to many" mode of communications; Using a transmissive, lecture based method of presenting information; Having student interactions limited to Q&A during the live event; Making limited use of media; and Lacking any formal, performance based, demonstration of learning on the part of students. My project involved developing interactive lessons for K-12 students (specifically 7th grade) that will reflect a 2nd generation design for electronic field trips. The goal of this design will be to create electronic field trips that will: Conform to national education standards; More fully utilize existing information resources; Integrate media into field trip presentations; Make support media accessible to both presenters and students; Challenge students to actively participate in field trip related activities; and Provide students with opportunities to demonstrate learning

A Development of Game-Based Learning Environment to Activate Interaction among Learners

NASA Astrophysics Data System (ADS)

Takaoka, Ryo; Shimokawa, Masayuki; Okamoto, Toshio

Many studies and systems that incorporate elements such as “pleasure” and “fun” in the game to improve a learner's motivation have been developed in the field of learning environments. However, few are the studies of situations where many learners gather at a single computer and participate in a game-based learning environment (GBLE), and where the GBLE designs the learning process by controlling the interactions between learners such as competition, collaboration, and learning by teaching. Therefore, the purpose of this study is to propose a framework of educational control that induces and activates interaction between learners intentionally to create a learning opportunity that is based on the knowledge understanding model of each learner. In this paper, we explain the design philosophy and the framework of our GBLE called “Who becomes the king in the country of mathematics?” from a game viewpoint and describe the method of learning support control in the learning environment. In addition, we report the results of the learning experiment with our GBLE, which we carried out in a junior high school, and include some comments by a principal and a teacher. From the results of the experiment and some comments, we noticed that a game may play a significant role in weakening the learning relationship among students and creating new relationships in the world of the game. Furthermore, we discovered that learning support control of the GBLE has led to activation of the interaction between learners to some extent.

Interactive computer-assisted instruction in acid-base physiology for mobile computer platforms.

PubMed

Longmuir, Kenneth J

2014-03-01

In this project, the traditional lecture hall presentation of acid-base physiology in the first-year medical school curriculum was replaced by interactive, computer-assisted instruction designed primarily for the iPad and other mobile computer platforms. Three learning modules were developed, each with ∼20 screens of information, on the subjects of the CO2-bicarbonate buffer system, other body buffer systems, and acid-base disorders. Five clinical case modules were also developed. For the learning modules, the interactive, active learning activities were primarily step-by-step learner control of explanations of complex physiological concepts, usually presented graphically. For the clinical cases, the active learning activities were primarily question-and-answer exercises that related clinical findings to the relevant basic science concepts. The student response was remarkably positive, with the interactive, active learning aspect of the instruction cited as the most important feature. Also, students cited the self-paced instruction, extensive use of interactive graphics, and side-by-side presentation of text and graphics as positive features. Most students reported that it took less time to study the subject matter with this online instruction compared with subject matter presented in the lecture hall. However, the approach to learning was highly examination driven, with most students delaying the study of the subject matter until a few days before the scheduled examination. Wider implementation of active learning computer-assisted instruction will require that instructors present subject matter interactively, that students fully embrace the responsibilities of independent learning, and that institutional administrations measure instructional effort by criteria other than scheduled hours of instruction.

DREADD in parvalbumin interneurons of the dentate gyrus modulates anxiety, social interaction and memory extinction.

PubMed

Zou, D; Chen, L; Deng, D; Jiang, D; Dong, F; McSweeney, C; Zhou, Y; Liu, L; Chen, G; Wu, Y; Mao, Y

2016-01-01

Parvalbumin (PV)-positive interneurons in the hippocampus play a critical role in animal memory, such as spatial working memory. However, how PV-positive interneurons in the subregions of the hippocampus affect animal behaviors remains poorly defined. Here, we achieved specific and reversible activation of PV-positive interneurons using designer receptors exclusively activated by designer drugs (DREADD) technology. Inducible DREADD expression was demonstrated in vitro in cultured neurons, in which co-transfection of the hM3D-Gq-mCherry vector with a Cre plasmid resulted in a cellular response to hM3Dq ligand clozapine-N-oxide (CNO) stimulation. In addition, the dentate gyrus (DG) of PV-Cre mice received bilateral injection of control lentivirus or lentivirus expressing double floxed hM3D-Gq-mCherry. Selective activation of PV-positive interneurons in the DG did not affect locomotor activity or depression-related behavior in mice. Interestingly, stimulation of PV-positive interneurons induced an anxiolytic effect. Activation of PVpositive interneurons appears to impair social interaction to novelty, but has no effect on social motivation. However, this defect is likely due to the anxiolytic effect as the exploratory behavior of mice expressing hM3DGq is significantly increased. Mice expressing hM3D-Gq did not affect novel object recognition. Activation of PV-positive interneurons in the DG maintains intact cued and contextual fear memory but facilitates fear extinction. Collectively, our results demonstrated that proper control of PV interneurons activity in the DG is critical for regulation of the anxiety, social interaction and fear extinction. These results improve our fundamental understanding of the physiological role of PV-positive interneurons in the hippocampus.

Probing the interactions between ionic liquids and water: experimental and quantum chemical approach.

PubMed

Khan, Imran; Kurnia, Kiki A; Mutelet, Fabrice; Pinho, Simão P; Coutinho, João A P

2014-02-20

For an adequate choice or design of ionic liquids, the knowledge of their interaction with other solutes and solvents is an essential feature for predicting the reactivity and selectivity of systems involving these compounds. In this work, the activity coefficient of water in several imidazolium-based ionic liquids with the common cation 1-butyl-3-methylimidazolium was measured at 298.2 K. To contribute to a deeper insight into the interaction between ionic liquids and water, COSMO-RS was used to predict the activity coefficient of water in the studied ionic liquids along with the excess enthalpies. The results showed good agreement between experimental and predicted activity coefficient of water in ionic liquids and that the interaction of water and ionic liquids was strongly influenced by the hydrogen bonding of the anion with water. Accordingly, the intensity of interaction of the anions with water can be ranked as the following: [CF3SO3](-) < [SCN](-) < [TFA](-) < Br(-) < [TOS](-) < Cl(-) < [CH3SO3](-) [DMP](-) < [Ac](-). In addition, fluorination and aromatization of anions are shown to reduce their interaction with water. The effect of temperature on the activity coefficient of water at infinite dilution was measured by inverse gas chromatography and predicted by COSMO-RS. Further analysis based on COSMO-RS provided information on the nature of hydrogen bonding between water and anion as well as the possibility of anion-water complex formation.

Simultaneous anionic and cationic redox

NASA Astrophysics Data System (ADS)

Jung, Sung-Kyun; Kang, Kisuk

2017-12-01

It is challenging to unlock anionic redox activity, accompanied by full utilization of available cationic redox process, to boost capacity of battery cathodes. Now, material design by tuning the metal-oxygen interaction is shown to be a promising solution.

Life in Tropical Rain Forests.

ERIC Educational Resources Information Center

NatureScope, 1989

1989-01-01

Discusses the diversity of rain forest life, the adaptations of rain forest plants and animals, and ways these organisms interact. Includes activities on canopy critters with a copyable sheet, rain forest revue, design a plant, and jungle sleuths. (RT)

Structural determinants for the inhibitory ligands of orotidine-5′-monophosphate decarboxylase

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

Meza-Avina, Maria Elena; Wei, Lianhu; Liu, Yan

2010-06-14

In recent years, orotidine-5{prime}-monophosphate decarboxylase (ODCase) has gained renewed attention as a drug target. As a part of continuing efforts to design novel inhibitors of ODCase, we undertook a comprehensive study of potent, structurally diverse ligands of ODCase and analyzed their structural interactions in the active site of ODCase. These ligands comprise of pyrazole or pyrimidine nucleotides including the mononucleotide derivatives of pyrazofurin, barbiturate ribonucleoside, and 5-cyanouridine, as well as, in a computational approach, 1,4-dihydropyridine-based non-nucleoside inhibitors such as nifedipine and nimodipine. All these ligands bind in the active site of ODCase exhibiting distinct interactions paving the way to designmore » novel inhibitors against this interesting enzyme. We propose an empirical model for the ligand structure for rational modifications in new drug design and potentially new lead structures.« less

Human Engineering Operations and Habitability Assessment: A Process for Advanced Life Support Ground Facility Testbeds

NASA Technical Reports Server (NTRS)

Connolly, Janis H.; Arch, M.; Elfezouaty, Eileen Schultz; Novak, Jennifer Blume; Bond, Robert L. (Technical Monitor)

1999-01-01

Design and Human Engineering (HE) processes strive to ensure that the human-machine interface is designed for optimal performance throughout the system life cycle. Each component can be tested and assessed independently to assure optimal performance, but it is not until full integration that the system and the inherent interactions between the system components can be assessed as a whole. HE processes (which are defining/app lying requirements for human interaction with missions/systems) are included in space flight activities, but also need to be included in ground activities and specifically, ground facility testbeds such as Bio-Plex. A unique aspect of the Bio-Plex Facility is the integral issue of Habitability which includes qualities of the environment that allow humans to work and live. HE is a process by which Habitability and system performance can be assessed.

The examination of headache activity using time-series research designs.

PubMed

Houle, Timothy T; Remble, Thomas A; Houle, Thomas A

2005-05-01

The majority of research conducted on headache has utilized cross-sectional designs which preclude the examination of dynamic factors and principally rely on group-level effects. The present article describes the application of an individual-oriented process model using time-series analytical techniques. The blending of a time-series approach with an interactive process model allows consideration of the relationships of intra-individual dynamic processes, while not precluding the researcher to examine inter-individual differences. The authors explore the nature of time-series data and present two necessary assumptions underlying the time-series approach. The concept of shock and its contribution to headache activity is also presented. The time-series approach is not without its problems and two such problems are specifically reported: autocorrelation and the distribution of daily observations. The article concludes with the presentation of several analytical techniques suited to examine the time-series interactive process model.

Launch Vehicle Design Process Description and Training Formulation

NASA Technical Reports Server (NTRS)

Atherton, James; Morris, Charles; Settle, Gray; Teal, Marion; Schuerer, Paul; Blair, James; Ryan, Robert; Schutzenhofer, Luke

1999-01-01

A primary NASA priority is to reduce the cost and improve the effectiveness of launching payloads into space. As a consequence, significant improvements are being sought in the effectiveness, cost, and schedule of the launch vehicle design process. In order to provide a basis for understanding and improving the current design process, a model has been developed for this complex, interactive process, as reported in the references. This model requires further expansion in some specific design functions. Also, a training course for less-experienced engineers is needed to provide understanding of the process, to provide guidance for its effective implementation, and to provide a basis for major improvements in launch vehicle design process technology. The objective of this activity is to expand the description of the design process to include all pertinent design functions, and to develop a detailed outline of a training course on the design process for launch vehicles for use in educating engineers whose experience with the process has been minimal. Building on a previously-developed partial design process description, parallel sections have been written for the Avionics Design Function, the Materials Design Function, and the Manufacturing Design Function. Upon inclusion of these results, the total process description will be released as a NASA TP. The design function sections herein include descriptions of the design function responsibilities, interfaces, interactive processes, decisions (gates), and tasks. Associated figures include design function planes, gates, and tasks, along with other pertinent graphics. Also included is an expanded discussion of how the design process is divided, or compartmentalized, into manageable parts to achieve efficient and effective design. A detailed outline for an intensive two-day course on the launch vehicle design process has been developed herein, and is available for further expansion. The course is in an interactive lecture/workshop format to engage the participants in active learning. The course addresses the breadth and depth of the process, requirements, phases, participants, multidisciplinary aspects, tasks, critical elements,as well as providing guidance from previous lessons learned. The participants are led to develop their own understanding of the current process and how it can be improved. Included are course objectives and a session-by-session outline of course content. Also included is an initial identification of visual aid requirements.

The Effect of Light-Intensity Cycling on Mood and Working Memory in Response to a Randomized, Placebo-Controlled Design.

PubMed

Lindheimer, Jacob B; OʼConnor, Patrick J; McCully, Kevin K; Dishman, Rod K

Prior attempts to measure psychological responses to exercise are potentially limited by a failure to account for participants' expectations, the absence of a valid exercise placebo, and demand characteristics. The purpose of this study was to explore the main and interactive effects of a manipulation designed to increase expectations about the psychological benefits of an acute bout of active, light-intensity (treatment), and passive (placebo) cycling on mood and cognition. Demand characteristics were attenuated during recruitment, informed consent, and interactions with test administrators by communicating to participants that the study purpose was to assess the effects of active and passive cycling on respiration, heart rate, and muscle activation. A repeated-measures, randomized, placebo-controlled design (n = 60) was used with cycling (active, passive) and information (informed, not informed) as between-subjects factors. State anxiety, feelings of energy, and working memory (percent accuracy and reaction time for correct responses) were measured at baseline (time 1), immediately after cycling (time 2) and 20 minutes after cycling (time 3). Most participants did not guess the purpose of the study (~92%) or expect a reduction in state anxiety (85%) or an increase in energy (80%) or cognitive performance (~93%). Mood and cognitive performance were not improved by active or passive cycling (all p values ≥ .12). The methods used here to disguise the experimental hypotheses provide a potential framework for reducing demand characteristics and placebo responses in future investigations of psychological responses to exercise.

Dual-tail approach to discovery of novel carbonic anhydrase IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site.

PubMed

Hou, Zhuang; Lin, Bin; Bao, Yu; Yan, Hai-Ning; Zhang, Miao; Chang, Xiao-Wei; Zhang, Xin-Xin; Wang, Zi-Jie; Wei, Gao-Fei; Cheng, Mao-Sheng; Liu, Yang; Guo, Chun

2017-05-26

Dual-tail approach was employed to design novel Carbonic Anhydrase (CA) IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site, which also contains a zinc ion as part of the catalytic center. The classic sulfanilamide moiety was used as the zinc binding group. An amino glucosamine fragment was chosen as the hydrophilic part and a cinnamamide fragment as the hydrophobic part in order to draw favorable interactions with the corresponding halves of the active site. In comparison with sulfanilamide which is largely devoid of the hydrophilic and hydrophobic interactions with the two halves of the active site, the compounds so designed and synthesized in this study showed 1000-fold improvement in binding affinity. Most of the compounds inhibited the CA effectively with IC 50 values in the range of 7-152 nM. Compound 14e (IC 50 : 7 nM) was more effective than the reference drug acetazolamide (IC 50 : 30 nM). The results proved that the dual-tail approach to simultaneously matching the hydrophobic and hydrophilic halves of the active site by linking hydrophobic and hydrophilic fragments was useful for designing novel CA inhibitors. The effectiveness of those compounds was elucidated by both the experimental data and molecular docking simulations. This work laid a solid foundation for further development of novel CA IX inhibitors for cancer treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Impact of Backbone Tether Length and Structure on the Electrochemical Performance of Viologen Redox Active Polymers

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

Burgess, Mark; Chénard, Etienne; Hernández-Burgos, Kenneth

The design of chemically stable and electrochemically reversible redox active polymers (RAPs) is of great interest for energy storage technologies. Particularly, RAPs are new players for flow batteries relying on a size-exclusion based mechanism of electrolyte separation, but few studies have provided detailed molecular understanding of redox polymers in solution. Here, we use a systematic molecular design approach to investigate the impact of linker and redox-pendant electronic interactions on the performance of viologen RAPs. We used scanning electrochemical microscopy, cyclic voltammetry, bulk electrolysis, temperature-dependent absorbance, and spectroelectrochemistry to study the redox properties, charge transfer kinetics, and self-exchange of electrons throughmore » redox active dimers and their equivalent polymers. Stark contrast was observed between the electrochemical properties of viologen dimers and their corresponding polymers. Electron self-exchange kinetics in redox active dimers that only differ by their tether length and rigidity influences their charge transfer properties. Predictions from the Marcus Hush theory were consistent with observations in redox active dimers, but they failed to fully capture the behavior of macromolecular systems. For example, polymer bound viologen pendants, if too close in proximity, do not retain chemical reversibility. In contrast to polymer films, small modifications to the backbone structure decisively impact the bulk electrolysis of polymer solutions. This first comprehensive study highlights the careful balance between electronic interactions and backbone rigidity required to design RAPs with superior electrochemical performance.« less

In-situ implant containing PCL-curcumin nanoparticles developed using design of experiments.

PubMed

Kasinathan, Narayanan; Amirthalingam, Muthukumar; Reddy, Neetinkumar D; Jagani, Hitesh V; Volety, Subrahmanyam M; Rao, Josyula Venkata

2016-01-01

Polymeric delivery system is useful in reducing pharmacokinetic limitations viz., poor absorption and rapid elimination associated with clinical use of curcumin. Design of experiment is a precise and cost effective tool useful in analyzing the effect of independent variables and their interaction on the product attributes. To evaluate the effect of process variables involved in preparation of curcumin-loaded polycaprolactone (PCL) nanoparticles (CPN). In the present experiment, CPNs were prepared by emulsification solvent evaporation technique. The effect of independent variables on the dependent variable was analyzed using design of experiments. Anticancer activity of CPN was studied using Ehrlich ascites carcinoma (EAC) model. In-situ implant was developed using PLGA as polymer. The effect of independent variables was studied in two stages. First, the effect of drug-polymer ratio, homogenization speed and surfactant concentration on size was studied using factorial design. The interaction of homogenization speed with homogenization time on mean particle size of CPN was then evaluated using central composite design. In the second stage, the effect of these variables (under the conditions optimized for producing particles <500 nm) on percentage drug encapsulation was evaluated using factorial design. CPN prepared under optimized conditions were able to control the development of EAC in Swiss albino mice and enhanced their survival time. PLGA based in-situ implant containing CPN prepared under optimized conditions showed sustained drug release. This implant could be further evaluated for pharmacological activities.

Designing "Interaction": How Do Interaction Design Students Address Interaction?

ERIC Educational Resources Information Center

Karlgren, Klas; Ramberg, Robert; Artman, Henrik

2016-01-01

Interaction design is usually described as being concerned with interactions with and through artifacts but independent of a specific implementation. Design work has been characterized as a conversation between the designer and the situation and this conversation poses a particular challenge for interaction design as interactions can be elusive…

The interaction between design and occupier behaviour in the safety of new homes.

PubMed

McDermott, Hilary; Haslam, Roger; Gibb, Alistair

2007-03-01

The design of new homes includes many safety features intended to protect occupiers from injury or ill health within the home, however the effectiveness of these primary intervention measures is likely to be affected by user behaviour. This study examined the interaction between user activity and dwelling design and how this might affect health and safety. It aimed to identify how people use features within new homes and how this may limit the protection afforded by building design, codes and regulations. Forty, home-based, semi-structured, in-depth interviews and home inspections were conducted with individuals recently inhabiting a new home. A range of behaviours were reported in relation to building features including fire doors, pipes and cables, and loft access, which may lead to increased risk of injury or ill-health. For example, occupiers described interfering with the self-closing mechanisms on fire doors and drilling into walls without considering the location of services. They also reported knowingly engaging in unsafe behaviour when accessing the loft, increasing their risk of falls. The accounts suggest that designers and builders need to give greater consideration to how occupier behaviour interacts with building features so that improvements in both design and occupier education can lead to improved health and safety.

Department of Defense High Performance Computing Modernization Program. 2007 Annual Report

DTIC Science & Technology

2008-03-01

Directorate, Kirtland AFB, NM Applications of Time-Accurate CFD in Order to Account for Blade -Row Interactions and Distortion Transfer in the Design of...Patterson AFB, OH Direct Numerical Simulations of Active Control for Low- Pressure Turbine Blades Herman Fasel, University of Arizona, Tucson, AZ (Air Force...interactions with the rotor wake . These HI-ARMS computations compare favorably with available wind tunnel test measurements of surface and flowfield

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

Trahan, Alexis Chanel

The objectives of this presentation are to introduce the basic physics of neutron production, interactions and detection; identify the processes that generate neutrons; explain the most common neutron mechanism, spontaneous and induced fission and (a,n) reactions; describe the properties of neutron from different sources; recognize advantages of neutron measurements techniques; recognize common neutrons interactions; explain neutron cross section measurements; describe the fundamental of 3He detector function and designs; and differentiate between passive and active assay techniques.

Interactive Peer Coaching/Mentoring Project for Preparing Teachers of Students with Severe Behavioral Disorders Final Report. Volume 1: Project Narrative and Briefing Papers [and] Volume 2: Appendices.

ERIC Educational Resources Information Center

North Dakota Center for Persons with Disabilities, Minot.

This final report discusses the activities and outcomes of the Interactive Peer Coaching/Mentoring (IPCM) Project, a program designed to prepare teachers of students with severe behavioral disorders (SED) residing in a rural, remote area in North Dakota. The IPCM project was conducted from July 1997 through July 2000 and developed an…

Project PEGS! Practices in Effective Guidance Strategies: Interactive CD-ROM Series for Educators To Practice Positive Behavior Management Skills, October 1, 1999-December 30, 2002. Final Performance Report.

ERIC Educational Resources Information Center

Quirk, Constance A.

This final report describes the activities and outcomes of a federally funded project designed to produce and field-test two computer-based interactive CD-ROMs: "PEGS! for Preschool" and "PEGS! for Secondary School". These programs, in a game format, provide beginning general and special educators with independent practice in…

Interactive Genetic Algorithm - An Adaptive and Interactive Decision Support Framework for Design of Optimal Groundwater Monitoring Plans

NASA Astrophysics Data System (ADS)

Babbar-Sebens, M.; Minsker, B. S.

2006-12-01

In the water resources management field, decision making encompasses many kinds of engineering, social, and economic constraints and objectives. Representing all of these problem dependant criteria through models (analytical or numerical) and various formulations (e.g., objectives, constraints, etc.) within an optimization- simulation system can be a very non-trivial issue. Most models and formulations utilized for discerning desirable traits in a solution can only approximate the decision maker's (DM) true preference criteria, and they often fail to consider important qualitative and incomputable phenomena related to the management problem. In our research, we have proposed novel decision support frameworks that allow DMs to actively participate in the optimization process. The DMs explicitly indicate their true preferences based on their subjective criteria and the results of various simulation models and formulations. The feedback from the DMs is then used to guide the search process towards solutions that are "all-rounders" from the perspective of the DM. The two main research questions explored in this work are: a) Does interaction between the optimization algorithm and a DM assist the system in searching for groundwater monitoring designs that are robust from the DM's perspective?, and b) How can an interactive search process be made more effective when human factors, such as human fatigue and cognitive learning processes, affect the performance of the algorithm? The application of these frameworks on a real-world groundwater long-term monitoring (LTM) case study in Michigan highlighted the following salient advantages: a) in contrast to the non-interactive optimization methodology, the proposed interactive frameworks were able to identify low cost monitoring designs whose interpolation maps respected the expected spatial distribution of the contaminants, b) for many same-cost designs, the interactive methodologies were able to propose multiple alternatives that met the DM's preference criteria, therefore allowing the expert to select among several strong candidate designs depending on her/his LTM budget, c) two of the methodologies - Case-Based Micro Interactive Genetic Algorithm (CBMIGA) and Interactive Genetic Algorithm with Mixed Initiative Interaction (IGAMII) - were also able to assist in controlling human fatigue and adapt to the DM's learning process.

Mapping Protein–Protein Interactions of the Resistance-Related Bacterial Zeta Toxin–Epsilon Antitoxin Complex (ε2ζ2) with High Affinity Peptide Ligands Using Fluorescence Polarization

PubMed Central

Fernández-Bachiller, María Isabel; Brzozowska, Iwona; Odolczyk, Norbert; Zielenkiewicz, Urszula; Zielenkiewicz, Piotr; Rademann, Jörg

2016-01-01

Toxin–antitoxin systems constitute a native survival strategy of pathogenic bacteria and thus are potential targets of antibiotic drugs. Here, we target the Zeta–Epsilon toxin–antitoxin system, which is responsible for the stable maintenance of certain multiresistance plasmids in Gram-positive bacteria. Peptide ligands were designed on the basis of the ε2ζ2 complex. Three α helices of Zeta forming the protein–protein interaction (PPI) site were selected and peptides were designed conserving the residues interacting with Epsilon antitoxin while substituting residues binding intramolecularly to other parts of Zeta. Designed peptides were synthesized with an N-terminal fluoresceinyl-carboxy-residue for binding assays and provided active ligands, which were used to define the hot spots of the ε2ζ2 complex. Further shortening and modification of the binding peptides provided ligands with affinities <100 nM, allowing us to determine the most relevant PPIs and implement a robust competition binding assay. PMID:27438853

Mapping Protein-Protein Interactions of the Resistance-Related Bacterial Zeta Toxin-Epsilon Antitoxin Complex (ε₂ζ₂) with High Affinity Peptide Ligands Using Fluorescence Polarization.

PubMed

Fernández-Bachiller, María Isabel; Brzozowska, Iwona; Odolczyk, Norbert; Zielenkiewicz, Urszula; Zielenkiewicz, Piotr; Rademann, Jörg

2016-07-16

Toxin-antitoxin systems constitute a native survival strategy of pathogenic bacteria and thus are potential targets of antibiotic drugs. Here, we target the Zeta-Epsilon toxin-antitoxin system, which is responsible for the stable maintenance of certain multiresistance plasmids in Gram-positive bacteria. Peptide ligands were designed on the basis of the ε₂ζ₂ complex. Three α helices of Zeta forming the protein-protein interaction (PPI) site were selected and peptides were designed conserving the residues interacting with Epsilon antitoxin while substituting residues binding intramolecularly to other parts of Zeta. Designed peptides were synthesized with an N-terminal fluoresceinyl-carboxy-residue for binding assays and provided active ligands, which were used to define the hot spots of the ε₂ζ₂ complex. Further shortening and modification of the binding peptides provided ligands with affinities <100 nM, allowing us to determine the most relevant PPIs and implement a robust competition binding assay.

Automated analysis of short responses in an interactive synthetic tutoring system for introductory physics

NASA Astrophysics Data System (ADS)

Nakamura, Christopher M.; Murphy, Sytil K.; Christel, Michael G.; Stevens, Scott M.; Zollman, Dean A.

2016-06-01

Computer-automated assessment of students' text responses to short-answer questions represents an important enabling technology for online learning environments. We have investigated the use of machine learning to train computer models capable of automatically classifying short-answer responses and assessed the results. Our investigations are part of a project to develop and test an interactive learning environment designed to help students learn introductory physics concepts. The system is designed around an interactive video tutoring interface. We have analyzed 9 with about 150 responses or less. We observe for 4 of the 9 automated assessment with interrater agreement of 70% or better with the human rater. This level of agreement may represent a baseline for practical utility in instruction and indicates that the method warrants further investigation for use in this type of application. Our results also suggest strategies that may be useful for writing activities and questions that are more appropriate for automated assessment. These strategies include building activities that have relatively few conceptually distinct ways of perceiving the physical behavior of relatively few physical objects. Further success in this direction may allow us to promote interactivity and better provide feedback in online learning systems. These capabilities could enable our system to function more like a real tutor.

Using a dual safeguard web-based interactive teaching approach in an introductory physics class

NASA Astrophysics Data System (ADS)

Li, Lie-Ming; Li, Bin; Luo, Ying

2015-06-01

We modified the Just-in-Time Teaching approach and developed a dual safeguard web-based interactive (DGWI) teaching system for an introductory physics course. The system consists of four instructional components that improve student learning by including warm-up assignments and online homework. Student and instructor activities involve activities both in the classroom and on a designated web site. An experimental study with control groups evaluated the effectiveness of the DGWI teaching method. The results indicate that the DGWI method is an effective way to improve students' understanding of physics concepts, develop students' problem-solving abilities through instructor-student interactions, and identify students' misconceptions through a safeguard framework based on questions that satisfy teaching requirements and cover all of the course material. The empirical study and a follow-up survey found that the DGWI method increased student-teacher interaction and improved student learning outcomes.

Immobilized Cytochrome P450 2C9 (CYP2C9): Applications for Metabolite Generation, Monitoring Protein-Protein Interactions, and Improving In-vivo Predictions Using Enhanced In-vitro Models

NASA Astrophysics Data System (ADS)

Wollenberg, Lance A.

Cytochrome P450 (P450) enzymes are a family of oxoferroreductase enzymes containing a heme moiety and are well known to be involved in the metabolism of a wide variety of endogenous and xenobiotic materials. It is estimated that roughly 75% of all pharmaceutical compounds are metabolized by these enzymes. Traditional reconstituted in-vitro incubation studies using recombinant P450 enzymes are often used to predict in-vivo kinetic parameters of a drug early in development. However, in many cases, these reconstituted incubations are prone to aggregation which has been shown to affect the catalytic activity of an enzyme. Moreover, the presence of other isoforms of P450 enzymes present in a metabolic incubation, as is the case with microsomal systems, may affect the catalytic activity of an enzyme through isoform-specific protein-protein interactions. Both of these effects may result in inaccurate prediction of in-vivo drug metabolism using in-vitro experiments. Here we described the development of immobilized P450 constructs designed to elucidate the effects of aggregation and protein-protein interactions between P450 isoforms on catalytic activities. The long term objective of this project is to develop a system to control the oligomeric state of Cytochrome P450 enzymes to accurately elucidate discrepancies between in vitro reconstituted systems and actual in vivo drug metabolism for the precise prediction of metabolic activity. This approach will serve as a system to better draw correlations between in-vivo and in-vitro drug metabolism data. The central hypothesis is that Cytochrome P450 enzymes catalytic activity can be altered by protein-protein interactions occurring between Cytochrome P450 enzymes involved in drug metabolism, and is dependent on varying states of protein aggregation. This dissertation explains the details of the construction and characterization of a nanostructure device designed to control the state of aggregation of a P450 enzyme. Moreover, applications of immobilized P450 enzyme constructs will also be used for monitoring protein-protein interaction and metabolite production with the use of immobilized-P450 bioreactor constructs. This work provides insight into the effect on catalytic activity caused by both P450 aggregation as well as isoform-specific protein-protein interactions and provides insight in the production of biosynthetically produced drug metabolites

Specificity and mechanism of action of alpha-helical membrane-active peptides interacting with model and biological membranes by single-molecule force spectroscopy.

PubMed

Sun, Shiyu; Zhao, Guangxu; Huang, Yibing; Cai, Mingjun; Shan, Yuping; Wang, Hongda; Chen, Yuxin

2016-07-01

In this study, to systematically investigate the targeting specificity of membrane-active peptides on different types of cell membranes, we evaluated the effects of peptides on different large unilamellar vesicles mimicking prokaryotic, normal eukaryotic, and cancer cell membranes by single-molecule force spectroscopy and spectrum technology. We revealed that cationic membrane-active peptides can exclusively target negatively charged prokaryotic and cancer cell model membranes rather than normal eukaryotic cell model membranes. Using Acholeplasma laidlawii, 3T3-L1, and HeLa cells to represent prokaryotic cells, normal eukaryotic cells, and cancer cells in atomic force microscopy experiments, respectively, we further studied that the single-molecule targeting interaction between peptides and biological membranes. Antimicrobial and anticancer activities of peptides exhibited strong correlations with the interaction probability determined by single-molecule force spectroscopy, which illustrates strong correlations of peptide biological activities and peptide hydrophobicity and charge. Peptide specificity significantly depends on the lipid compositions of different cell membranes, which validates the de novo design of peptide therapeutics against bacteria and cancers.

Participatory interaction design in user requirements specification in healthcare.

PubMed

Martikainen, Susanna; Ikävalko, Pauliina; Korpela, Mikko

2010-01-01

Healthcare information systems are accused of poor usability even in the popular media in Finland. Doctors especially have been very critical and actively expressed their opinions in public. User involvement and user-centered design methods are seen as the key solution to usability problems. In this paper we describe a research case where participatory methods were experimented within healthcare information systems development in medicinal care in a hospital. The study was part of a larger research project on Activity-driven Information Systems Development in healthcare. The study started by finding out about and modeling the present state of medicinal care in the hospital. After that it was important to define and model the goal state. The goal state, facilitated by the would-be software package, was modeled with the help of user interface drawings as one way of prototyping. Traditional usability methods were extended during the study. According to the health professionals' feedback, the use of participatory and user-centered interaction design methods, particularly user interface drawings enabled them to describe their requirements and create common understanding with the system developers.

How do users design? The case of sugar cane harvester machines.

PubMed

Narimoto, Lidiane Regina; Camarotto, João Alberto

2017-01-01

Design in use and inventiveness are key concepts in ergonomics. It is well-known that users design but is not explored in the literature how they manage to do that. This paper aims to contribute to the discussion of how users actually design, by showing a research conducted in sugar cane harvesting in Brazil and in Australia. Through the methodology of the Ergonomic Work Analysis (EWA), the design modifications made by the harvesting teams were identified as well as their elaboration process. Three categories of modifications in machines' design were identified: structural, functional and operational and they were more numerous in Brazilian situations. It is proposed that two theories underlying the theme are intertwined: the instrument-mediated activity approach and the design as bricolage. It is argued that users design through the articulation of: a) the operators' activity, b) the mechanical technicians' inventory to practice bricolage as a way of designing and c) the work organisation and the existence of social spaces of interaction between these two subjects.

Molecular dynamics, flexible docking, virtual screening, ADMET predictions, and molecular interaction field studies to design novel potential MAO-B inhibitors.

PubMed

Braun, Glaucia H; Jorge, Daniel M M; Ramos, Henrique P; Alves, Raquel M; da Silva, Vinicius B; Giuliatti, Silvana; Sampaio, Suley Vilela; Taft, Carlton A; Silva, Carlos H T P

2008-02-01

Monoamine oxidase is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known targets for antidepressant, Parkinson's disease, and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened the way for the molecular modeling studies. In this work we have used molecular modeling, density functional theory with correlation, virtual screening, flexible docking, molecular dynamics, ADMET predictions, and molecular interaction field studies in order to design new molecules with potential higher selectivity and enzymatic inhibitory activity over MAO-B.

From Paper to PDA: Design and Evaluation of a Clinical Ward Instruction on a Mobile Device

NASA Astrophysics Data System (ADS)

Kanstrup, Anne Marie; Stage, Jan

Mobile devices with small screens and minimal facilities for interaction are increasingly being used in complex human activities for accessing and processing information, while the user is moving. This paper presents a case study of the design and evaluation of a mobile system, which involved transformation of complex text and tables to digital format on a PDA. The application domain was an emergency medical ward, and the user group was junior registrars. We designed a PDA-based system for accessing information, focusing on the ward instruction, implemented a prototype and evaluated it for usability and utility. The evaluation results indicate significant problems in the interaction with the system as well as the extent to which the system is useful for junior registrars in their daily work.

Turning K-12 Science Education Inside Out, Knocking Down Walls and Empowering the Disenchanted.

NASA Astrophysics Data System (ADS)

Lin, A. Y. M.

2016-12-01

For a 'user' there are several genres of citizen science activities one can enlist themselves in, from microtasked analytics to data collection. Often times design conversation for these efforts are focused around the goal of collecting high quality data for an urgent scientific question. However, there is much to be discussed around the opportunity to expand upon the interaction experience of the 'user'. This is particularly relevant in the integration of citizen science in the classroom. Here we explore the role of citizen science in formal K-12 science education through the lens of "Project Based Learning", examining design challenges in classroom adoption (including standards alignment) as well as interaction design focused around long term user/student motivation and engagement in the science exploration.

Overview of computational control research at UT Austin

NASA Technical Reports Server (NTRS)

Bong, Wie

1989-01-01

An overview of current research activities at UT Austin is presented to discuss certain technical issues in the following areas: (1) Computer-Aided Nonlinear Control Design: In this project, the describing function method is employed for the nonlinear control analysis and design of a flexible spacecraft equipped with pulse modulated reaction jets. INCA program has been enhanced to allow the numerical calculation of describing functions as well as the nonlinear limit cycle analysis capability in the frequency domain; (2) Robust Linear Quadratic Gaussian (LQG) Compensator Synthesis: Robust control design techniques and software tools are developed for flexible space structures with parameter uncertainty. In particular, an interactive, robust multivariable control design capability is being developed for INCA program; and (3) LQR-Based Autonomous Control System for the Space Station: In this project, real time implementation of LQR-based autonomous control system is investigated for the space station with time-varying inertias and with significant multibody dynamic interactions.

Behavior sensitivities for control augmented structures

NASA Technical Reports Server (NTRS)

Manning, R. A.; Lust, R. V.; Schmit, L. A.

1987-01-01

During the past few years it has been recognized that combining passive structural design methods with active control techniques offers the prospect of being able to find substantially improved designs. These developments have stimulated interest in augmenting structural synthesis by adding active control system design variables to those usually considered in structural optimization. An essential step in extending the approximation concepts approach to control augmented structural synthesis is the development of a behavior sensitivity analysis capability for determining rates of change of dynamic response quantities with respect to changes in structural and control system design variables. Behavior sensitivity information is also useful for man-machine interactive design as well as in the context of system identification studies. Behavior sensitivity formulations for both steady state and transient response are presented and the quality of the resulting derivative information is evaluated.

Using Research-Based Interactive Video Vignettes to Enhance Out-of-Class Learning in Introductory Physics

NASA Astrophysics Data System (ADS)

Laws, Priscilla W.; Willis, Maxine C.; Jackson, David P.; Koenig, Kathleen; Teese, Robert

2015-02-01

Ever since the first generalized computer-assisted instruction system (PLATO1) was introduced over 50 years ago, educators have been adding computer-based materials to their classes. Today many textbooks have complete online versions that include video lectures and other supplements. In the past 25 years the web has fueled an explosion of online homework and course management systems, both as blended learning and online courses. Meanwhile, introductory physics instructors have been implementing new approaches to teaching based on the outcomes of Physics Education Research (PER). A common theme of PER-based instruction has been the use of active-learning strategies designed to help students overcome alternative conceptions that they often bring to the study of physics.2 Unfortunately, while classrooms have become more active, online learning typically relies on passive lecture videos or Kahn-style3 tablet drawings. To bring active learning online, the LivePhoto Physics Group has been developing Interactive Video Vignettes (IVVs) that add interactivity and PER-based elements to short presentations. These vignettes incorporate web-based video activities that contain interactive elements and typically require students to make predictions and analyze real-world phenomena.

Fatty Acid-binding Proteins Interact with Comparative Gene Identification-58 Linking Lipolysis with Lipid Ligand Shuttling*

PubMed Central

Hofer, Peter; Boeszoermenyi, Andras; Jaeger, Doris; Feiler, Ursula; Arthanari, Haribabu; Mayer, Nicole; Zehender, Fabian; Rechberger, Gerald; Oberer, Monika; Zimmermann, Robert; Lass, Achim; Haemmerle, Guenter; Breinbauer, Rolf; Zechner, Rudolf; Preiss-Landl, Karina

2015-01-01

The coordinated breakdown of intracellular triglyceride (TG) stores requires the exquisitely regulated interaction of lipolytic enzymes with regulatory, accessory, and scaffolding proteins. Together they form a dynamic multiprotein network designated as the “lipolysome.” Adipose triglyceride lipase (Atgl) catalyzes the initiating step of TG hydrolysis and requires comparative gene identification-58 (Cgi-58) as a potent activator of enzyme activity. Here, we identify adipocyte-type fatty acid-binding protein (A-Fabp) and other members of the fatty acid-binding protein (Fabp) family as interaction partners of Cgi-58. Co-immunoprecipitation, microscale thermophoresis, and solid phase assays proved direct protein/protein interaction between A-Fabp and Cgi-58. Using nuclear magnetic resonance titration experiments and site-directed mutagenesis, we located a potential contact region on A-Fabp. In functional terms, A-Fabp stimulates Atgl-catalyzed TG hydrolysis in a Cgi-58-dependent manner. Additionally, transcriptional transactivation assays with a luciferase reporter system revealed that Fabps enhance the ability of Atgl/Cgi-58-mediated lipolysis to induce the activity of peroxisome proliferator-activated receptors. Our studies identify Fabps as crucial structural and functional components of the lipolysome. PMID:25953897

Task Analytic Models to Guide Analysis and Design: Use of the Operator Function Model to Represent Pilot-Autoflight System Mode Problems

NASA Technical Reports Server (NTRS)

Degani, Asaf; Mitchell, Christine M.; Chappell, Alan R.; Shafto, Mike (Technical Monitor)

1995-01-01

Task-analytic models structure essential information about operator interaction with complex systems, in this case pilot interaction with the autoflight system. Such models serve two purposes: (1) they allow researchers and practitioners to understand pilots' actions; and (2) they provide a compact, computational representation needed to design 'intelligent' aids, e.g., displays, assistants, and training systems. This paper demonstrates the use of the operator function model to trace the process of mode engagements while a pilot is controlling an aircraft via the, autoflight system. The operator function model is a normative and nondeterministic model of how a well-trained, well-motivated operator manages multiple concurrent activities for effective real-time control. For each function, the model links the pilot's actions with the required information. Using the operator function model, this paper describes several mode engagement scenarios. These scenarios were observed and documented during a field study that focused on mode engagements and mode transitions during normal line operations. Data including time, ATC clearances, altitude, system states, and active modes and sub-modes, engagement of modes, were recorded during sixty-six flights. Using these data, seven prototypical mode engagement scenarios were extracted. One scenario details the decision of the crew to disengage a fully automatic mode in favor of a semi-automatic mode, and the consequences of this action. Another describes a mode error involving updating aircraft speed following the engagement of a speed submode. Other scenarios detail mode confusion at various phases of the flight. This analysis uses the operator function model to identify three aspects of mode engagement: (1) the progress of pilot-aircraft-autoflight system interaction; (2) control/display information required to perform mode management activities; and (3) the potential cause(s) of mode confusion. The goal of this paper is twofold: (1) to demonstrate the use of the operator functio model methodology to describe pilot-system interaction while engaging modes And monitoring the system, and (2) to initiate a discussion of how task-analytic models might inform design processes. While the operator function model is only one type of task-analytic representation, the hypothesis of this paper is that some type of task analytic structure is a prerequisite for the design of effective human-automation interaction.

Study and selection of in vivo protein interactions by coupling bimolecular fluorescence complementation and flow cytometry.

PubMed

Morell, Montse; Espargaro, Alba; Aviles, Francesc Xavier; Ventura, Salvador

2008-01-01

We present a high-throughput approach to study weak protein-protein interactions by coupling bimolecular fluorescent complementation (BiFC) to flow cytometry (FC). In BiFC, the interaction partners (bait and prey) are fused to two rationally designed fragments of a fluorescent protein, which recovers its function upon the binding of the interacting proteins. For weak protein-protein interactions, the detected fluorescence is proportional to the interaction strength, thereby allowing in vivo discrimination between closely related binders with different affinity for the bait protein. FC provides a method for high-speed multiparametric data acquisition and analysis; the assay is simple, thousands of cells can be analyzed in seconds and, if required, selected using fluorescence-activated cell sorting (FACS). The combination of both methods (BiFC-FC) provides a technically straightforward, fast and highly sensitive method to validate weak protein interactions and to screen and identify optimal ligands in biologically synthesized libraries. Once plasmids encoding the protein fusions have been obtained, the evaluation of a specific interaction, the generation of a library and selection of active partners using BiFC-FC can be accomplished in 5 weeks.

Educational interactive multimedia software: The impact of interactivity on learning

NASA Astrophysics Data System (ADS)

Reamon, Derek Trent

This dissertation discusses the design, development, deployment and testing of two versions of educational interactive multimedia software. Both versions of the software are focused on teaching mechanical engineering undergraduates about the fundamentals of direct-current (DC) motor physics and selection. The two versions of Motor Workshop software cover the same basic materials on motors, but differ in the level of interactivity between the students and the software. Here, the level of interactivity refers to the particular role of the computer in the interaction between the user and the software. In one version, the students navigate through information that is organized by topic, reading text, and viewing embedded video clips; this is referred to as "low-level interactivity" software because the computer simply presents the content. In the other version, the students are given a task to accomplish---they must design a small motor-driven 'virtual' vehicle that competes against computer-generated opponents. The interaction is guided by the software which offers advice from 'experts' and provides contextual information; we refer to this as "high-level interactivity" software because the computer is actively participating in the interaction. The software was used in two sets of experiments, where students using the low-level interactivity software served as the 'control group,' and students using the highly interactive software were the 'treatment group.' Data, including pre- and post-performance tests, questionnaire responses, learning style characterizations, activity tracking logs and videotapes were collected for analysis. Statistical and observational research methods were applied to the various data to test the hypothesis that the level of interactivity effects the learning situation, with higher levels of interactivity being more effective for learning. The results show that both the low-level and high-level interactive versions of the software were effective in promoting learning about the subject of motors. The focus of learning varied between users of the two versions, however. The low-level version was more effective for teaching concepts and terminology, while the high-level version seemed to be more effective for teaching engineering applications.

eLearning and eMaking: 3D Printing Blurring the Digital and the Physical

ERIC Educational Resources Information Center

Loy, Jennifer

2014-01-01

This article considers the potential of 3D printing as an eLearning tool for design education and the role of eMaking in bringing together the virtual and the physical in the design studio. eLearning has matured from the basics of lecture capture into sophisticated, interactive learning activities for students. At the same time, laptops and…

Increasing Active Learning and End-Client Interaction in the Systems Analysis and Design and Capstone Courses

ERIC Educational Resources Information Center

Reinicke, Bryan A.; Janicki, Thomas N.

2010-01-01

Systems analysis and design (SAD) is one of the core courses offered in most IS programs, yet this class can be challenging for students and instructors alike. The concepts can be abstract, and getting students to appreciate their importance can be difficult. This paper discusses the implementation of a two semester sequence in which the students…

Pedagogical-Research Designs to Capture the Symbiotic Nature of Professional Knowledge and Learning about e-Learning in Initial Teacher Education in the UK

ERIC Educational Resources Information Center

Turvey, Keith

2010-01-01

This paper argues that if new communications technologies and online spaces are to yield "new relationship[s] with learners" then research that is tuned to recognize, capture and explain the pedagogical processes at the center of such interactions is vital. This has implications for the design of pedagogical activities within Initial…

Assessing Online Learning Objects: Student Evaluation of a Guide on the Side Interactive Learning Tutorial Designed by SRJC Libraries

ERIC Educational Resources Information Center

Virtue, Alicia; Dean, Ellen; Matheson, Molly

2014-01-01

More and more of today's scholars conduct their research in a digital realm rather than using a print collection. The University of Arizona Libraries Guide on the Side tutorial software offers an opportunity to apply the principles of active learning with real world research scenarios. This paper reports on the design and introduction of…

A Within-subjects Experimental Protocol to Assess the Effects of Social Input on Infant EEG.

PubMed

St John, Ashley M; Kao, Katie; Chita-Tegmark, Meia; Liederman, Jacqueline; Grieve, Philip G; Tarullo, Amanda R

2017-05-03

Despite the importance of social interactions for infant brain development, little research has assessed functional neural activation while infants socially interact. Electroencephalography (EEG) power is an advantageous technique to assess infant functional neural activation. However, many studies record infant EEG only during one baseline condition. This protocol describes a paradigm that is designed to comprehensively assess infant EEG activity in both social and nonsocial contexts as well as tease apart how different types of social inputs differentially relate to infant EEG. The within-subjects paradigm includes four controlled conditions. In the nonsocial condition, infants view objects on computer screens. The joint attention condition involves an experimenter directing the infant's attention to pictures. The joint attention condition includes three types of social input: language, face-to-face interaction, and the presence of joint attention. Differences in infant EEG between the nonsocial and joint attention conditions could be due to any of these three types of input. Therefore, two additional conditions (one with language input while the experimenter is hidden behind a screen and one with face-to-face interaction) were included to assess the driving contextual factors in patterns of infant neural activation. Representative results demonstrate that infant EEG power varied by condition, both overall and differentially by brain region, supporting the functional nature of infant EEG power. This technique is advantageous in that it includes conditions that are clearly social or nonsocial and allows for examination of how specific types of social input relate to EEG power. This paradigm can be used to assess how individual differences in age, affect, socioeconomic status, and parent-infant interaction quality relate to the development of the social brain. Based on the demonstrated functional nature of infant EEG power, future studies should consider the role of EEG recording context and design conditions that are clearly social or nonsocial.

Design Issues Related to the Evaluation of Learner--Computer Interaction in a Web-Based Environment: Activities v. Tasks

ERIC Educational Resources Information Center

Hemard, Dominique

2006-01-01

If web-based technology is increasingly becoming the central plank of contemporary teaching and learning processes, there is still too little evidence to suggest that it is delivering purposeful learning activities beyond its widely perceived potential as a learning resource providing content and learning objects. This is due in part to the…

The Cooperative Extension System's Use of USDA's Online Food and Physical Activity Tracker-Supertracker

ERIC Educational Resources Information Center

Hongu, Nobuko; Martinez, Cathy L.; Billias, Natalia N.; Wyatt, Melissa A.; Turner, Rachel J.; Manore, Melinda M.

2014-01-01

Nutrition professionals within the Cooperative Extension system use the USDA's interactive online tool SuperTracker, which is designed to help individuals track diet and physical activity (PA) to apply healthy eating patterns and improve PA. An investigation of all 50 states' Extension websites and interviews of Extension educators…

Boundary Interaction: Towards Developing a Mobile Technology-Enabled Science Curriculum to Integrate Learning in the Informal Spaces

ERIC Educational Resources Information Center

Sun, Daner; Looi, Chee-Kit

2018-01-01

This paper explores the crossover between formal learning and learning in informal spaces supported by mobile technology, and proposes design principles for educators to carry out a science curriculum, namely Boundary Activity-based Science Curriculum (BAbSC). The conceptualization of the boundary object, and the principles of boundary activity as…

Learning Processes and Learning Outcomes

DTIC Science & Technology

1992-06-01

establish and maintain activation levels) may process information faster because the relevant traces in long - term memory are already activated...drill and practice, and discovery. Finally, implications for the design of computerized instructional environments are indicated. 14. SUBJECT TERMS lI...outcome. This impact may be direct, or may interact with characteristics of the learner to effect learning outcome. INITIAL STATES Conative and cognitive

"Finger Kits:" An Interactive Demonstration of Biomaterials and Engineering for Elementary School Students

ERIC Educational Resources Information Center

Canavan, Heather E.; Stanton, Michael; Lopez, Kaori; Grubin, Catherine; Graham, Daniel J.

2008-01-01

This article describes a hands-on activity and demonstration developed at the University of Washington and further reined at the University of New Mexico. In this activity, the authors present a real-world problem to the student: Someone has an injured finger joint, and the students in the class need to design an implant to replace it. After…

Active vibration control techniques for flexible space structures

NASA Technical Reports Server (NTRS)

Parlos, Alexander G.; Jayasuriya, Suhada

1990-01-01

Two proposed control system design techniques for active vibration control in flexible space structures are detailed. Control issues relevant only to flexible-body dynamics are addressed, whereas no attempt was made to integrate the flexible and rigid-body spacecraft dynamics. Both of the proposed approaches revealed encouraging results; however, further investigation of the interaction of the flexible and rigid-body dynamics is warranted.

Molecular Dynamic Simulation Insights into the Normal State and Restoration of p53 Function

PubMed Central

Fu, Ting; Min, Hanyi; Xu, Yong; Chen, Jianzhong; Li, Guohui

2012-01-01

As a tumor suppressor protein, p53 plays a crucial role in the cell cycle and in cancer prevention. Almost 50 percent of all human malignant tumors are closely related to a deletion or mutation in p53. The activity of p53 is inhibited by over-active celluar antagonists, especially by the over-expression of the negative regulators MDM2 and MDMX. Protein-protein interactions, or post-translational modifications of the C-terminal negative regulatory domain of p53, also regulate its tumor suppressor activity. Restoration of p53 function through peptide and small molecular inhibitors has become a promising strategy for novel anti-cancer drug design and development. Molecular dynamics simulations have been extensively applied to investigate the conformation changes of p53 induced by protein-protein interactions and protein-ligand interactions, including peptide and small molecular inhibitors. This review focuses on the latest MD simulation research, to provide an overview of the current understanding of interactions between p53 and its partners at an atomic level. PMID:22949826

Discovery of novel inhibitors disrupting HIF-1α/von Hippel–Lindau interaction through shape-based screening and cascade docking

PubMed Central

Xue, Xin; Zhao, Ning-Yi; Yu, Hai-Tao; Sun, Yuan; Kang, Chen; Huang, Qiong-Bin; Sun, Hao-Peng

2016-01-01

Major research efforts have been devoted to the discovery and development of new chemical entities that could inhibit the protein–protein interaction between HIF-1α and the von Hippel–Lindau protein (pVHL), which serves as the substrate recognition subunit of an E3 ligase and is regarded as a crucial drug target in cancer, chronic anemia, and ischemia. Currently there is only one class of compounds available to interdict the HIF-1α/pVHL interaction, urging the need to discover chemical inhibitors with more diversified structures. We report here a strategy combining shape-based virtual screening and cascade docking to identify new chemical scaffolds for the designing of novel inhibitors. Based on this strategy, nine active hits have been identified and the most active hit, 9 (ZINC13466751), showed comparable activity to pVHL with an IC50 of 2.0 ± 0.14 µM, showing the great potential of utilizing these compounds for further optimization and serving as drug candidates for the inhibition of HIF-1α/von Hippel–Lindau interaction. PMID:27994971

Peroxidase-Mimicking Nanozyme with Enhanced Activity and High Stability Based on Metal-Support Interactions.

PubMed

Li, Zhihao; Yang, Xiangdong; Yang, Yanbing; Tan, Yaning; He, Yue; Liu, Meng; Liu, Xinwen; Yuan, Quan

2018-01-09

Peroxidase-mimicking nanozymes offer unique advantages in terms of high stability and low cost over natural peroxidase for applications in bioanalysis, biomedicine, and the treatment of pollution. However, the design of high-efficiency peroxidase-mimicking nanozymes remains a great challenge. In this study, we adopted a structural-design approach through hybridization of cube-CeO 2 and Pt nanoparticles to create a new peroxidase-mimicking nanozyme with high efficiency and excellent stability. Relative to pure cube-CeO 2 and Pt nanoparticles, the as-hybridized Pt/cube-CeO 2 nanocomposites display much improved activities because of the strong metal-support interaction. Meanwhile, the nanocomposites also maintain high catalytic activity after long-term storage and multiple recycling. Based on their excellent properties, Pt/cube-CeO 2 nanocomposites were used to construct high-performance colorimetric biosensors for the sensitive detection of metabolites, including H 2 O 2 and glucose. Our findings highlight opportunities for the development of high-efficiency peroxidase-mimicking nanozymes with potential applications such as diagnostics, biomedicine, and the treatment of pollution. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

3D-quantitative structure-activity relationship study for the design of novel enterovirus A71 3C protease inhibitors.

PubMed

Nie, Quandeng; Xu, Xiaoyi; Zhang, Qi; Ma, Yuying; Yin, Zheng; Shang, Luqing

2018-06-07

A three-dimensional quantitative structure-activity relationships model of enterovirus A71 3C protease inhibitors was constructed in this study. The protein-ligand interaction fingerprint was analyzed to generate a pharmacophore model. A predictive and reliable three-dimensional quantitative structure-activity relationships model was built based on the Flexible Alignment of AutoGPA. Moreover, three novel compounds (I-III) were designed and evaluated for their biochemical activity against 3C protease and anti-enterovirus A71 activity in vitro. III exhibited excellent inhibitory activity (IC 50 =0.031 ± 0.005 μM, EC 50 =0.036 ± 0.007 μM). Thus, this study provides a useful quantitative structure-activity relationships model to develop potent inhibitors for enterovirus A71 3C protease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The molecular mechanism for interaction of ceruloplasmin and myeloperoxidase

NASA Astrophysics Data System (ADS)

Bakhautdin, Bakytzhan; Bakhautdin, Esen Göksöy

2016-04-01

Ceruloplasmin (Cp) is a copper-containing ferroxidase with potent antioxidant activity. Cp is expressed by hepatocytes and activated macrophages and has been known as physiologic inhibitor of myeloperoxidase (MPO). Enzymatic activity of MPO produces anti-microbial agents and strong prooxidants such as hypochlorous acid and has a potential to damage host tissue at the sites of inflammation and infection. Thus Cp-MPO interaction and inhibition of MPO has previously been suggested as an important control mechanism of excessive MPO activity. Our aim in this study was to identify minimal Cp domain or peptide that interacts with MPO. We first confirmed Cp-MPO interaction by ELISA and surface plasmon resonance (SPR). SPR analysis of the interaction yielded 30 nM affinity between Cp and MPO. We then designed and synthesized 87 overlapping peptides spanning the entire amino acid sequence of Cp. Each of the peptides was tested whether it binds to MPO by direct binding ELISA. Two of the 87 peptides, P18 and P76 strongly interacted with MPO. Amino acid sequence analysis of identified peptides revealed high sequence and structural homology between them. Further structural analysis of Cp's crystal structure by PyMOL software unfolded that both peptides represent surface-exposed sites of Cp and face nearly the same direction. To confirm our finding we raised anti-P18 antisera in rabbit and demonstrated that this antisera disrupts Cp-MPO binding and rescues MPO activity. Collectively, our results confirm Cp-MPO interaction and identify two nearly identical sites on Cp that specifically bind MPO. We propose that inhibition of MPO by Cp requires two nearly identical sites on Cp to bind homodimeric MPO simultaneously and at an angle of at least 120 degrees, which, in turn, exerts tension on MPO and results in conformational change.

InterACTIVE Interpreted Interviews (I3): A multi-lingual, mobile method to examine the neighbourhood environment with older adults.

PubMed

Tong, Catherine; Sims-Gould, Joanie; McKay, Heather

2016-11-01

The global population is aging and older adults overwhelmingly wish to age in place. A positive neighbourhood context is crucial for the wellbeing of older adults. The ability to age in place is predicated on mobility; mobility is the capacity to move oneself around the home and community using a variety of modes. Segments of the population have been entirely overlooked within the mobility and built environment literature; we know surprisingly little about foreign-born older adults (FBOAs). We sought to understand the impact of the neighbourhood environment on the mobility and physical activity of FBOAs. To do so we endeavoured to develop an interview tool that would allow us to interact with the environment alongside, or through the eyes of, our participants. This article outlines lessons learned following design and implementation of an interview approach that we conducted with FBOAs -- "InterACTIVE Interpreted Interviews (I 3 )". We used the interACTIVE interview approach in a large mixed-method study on FBOA mobility in Vancouver, Canada. All aspects of the study were offered in Hindi, Punjabi, Cantonese, Mandarin and English, with the aid of professional interpreters. Twenty FBOAs completed in-depth qualitative interviews. Of these, thirteen completed the mobile, interACTIVE interview. The interACTIVE interview consisted of a neighbourhood walk, guided by the participant. Our approach integrated elements of participant observation, researcher participation, and unstructured interviewing to enrich discussions with participants. The interACTIVE approach deepened our understanding of neighbourhood context and allowed researchers and participants to overcome issues inherent in language interpretation. We were able to overcome concerns of privacy, safety and comfort to successfully implement this observational tool and recommend it as an attractive, alternative approach for those conducting studies with FBOAs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification and Characterization of ART-27, a Novel Coactivator for the Androgen Receptor N Terminus

PubMed Central

Markus, Steven M.; Taneja, Samir S.; Logan, Susan K.; Li, Wenhui; Ha, Susan; Hittelman, Adam B.; Rogatsky, Inez; Garabedian, Michael J.

2002-01-01

The androgen receptor (AR) is a ligand-regulated transcription factor that stimulates cell growth and differentiation in androgen-responsive tissues. The AR N terminus contains two activation functions (AF-1a and AF-1b) that are necessary for maximal transcriptional enhancement by the receptor; however, the mechanisms and components regulating AR transcriptional activation are not fully understood. We sought to identify novel factors that interact with the AR N terminus from an androgen-stimulated human prostate cancer cell library using a yeast two-hybrid approach designed to identify proteins that interact with transcriptional activation domains. A 157-amino acid protein termed ART-27 was cloned and shown to interact predominantly with the AR153–336, containing AF-1a and a part of AF-1b, localize to the nucleus and increase the transcriptional activity of AR when overexpressed in cultured mammalian cells. ART-27 also enhanced the transcriptional activation by AR153–336 fused to the LexA DNA-binding domain but not other AR N-terminal subdomains, suggesting that ART-27 exerts its effect via an interaction with a defined region of the AR N terminus. ART-27 interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent manner. Interestingly, velocity gradient sedimentation of HeLa nuclear extracts suggests that native ART-27 is part of a multiprotein complex. ART-27 is expressed in a variety of human tissues, including sites of androgen action such as prostate and skeletal muscle, and is conserved throughout evolution. Thus, ART-27 is a novel cofactor that interacts with the AR N terminus and plays a role in facilitating receptor-induced transcriptional activation. PMID:11854421

Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus.

PubMed

Markus, Steven M; Taneja, Samir S; Logan, Susan K; Li, Wenhui; Ha, Susan; Hittelman, Adam B; Rogatsky, Inez; Garabedian, Michael J

2002-02-01

The androgen receptor (AR) is a ligand-regulated transcription factor that stimulates cell growth and differentiation in androgen-responsive tissues. The AR N terminus contains two activation functions (AF-1a and AF-1b) that are necessary for maximal transcriptional enhancement by the receptor; however, the mechanisms and components regulating AR transcriptional activation are not fully understood. We sought to identify novel factors that interact with the AR N terminus from an androgen-stimulated human prostate cancer cell library using a yeast two-hybrid approach designed to identify proteins that interact with transcriptional activation domains. A 157-amino acid protein termed ART-27 was cloned and shown to interact predominantly with the AR(153-336), containing AF-1a and a part of AF-1b, localize to the nucleus and increase the transcriptional activity of AR when overexpressed in cultured mammalian cells. ART-27 also enhanced the transcriptional activation by AR(153-336) fused to the LexA DNA-binding domain but not other AR N-terminal subdomains, suggesting that ART-27 exerts its effect via an interaction with a defined region of the AR N terminus. ART-27 interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent manner. Interestingly, velocity gradient sedimentation of HeLa nuclear extracts suggests that native ART-27 is part of a multiprotein complex. ART-27 is expressed in a variety of human tissues, including sites of androgen action such as prostate and skeletal muscle, and is conserved throughout evolution. Thus, ART-27 is a novel cofactor that interacts with the AR N terminus and plays a role in facilitating receptor-induced transcriptional activation.

Research on Building Education & Workforce Capacity in Systems Engineering

DTIC Science & Technology

2011-02-07

manufacturing or design sites where students could observe engineering processes related to their projects Mentors with the highest level of student ... engagement interacted with students in every single activity area and with frequency, while others provided only intermittent correspondence. Note

Footwear Physics.

ERIC Educational Resources Information Center

Blaser, Mark; Larsen, Jamie

1996-01-01

Presents five interactive, computer-based activities that mimic scientific tests used by sport researchers to help companies design high-performance athletic shoes, including impact tests, flexion tests, friction tests, video analysis, and computer modeling. Provides a platform for teachers to build connections between chemistry (polymer science),…

Motivating Students in Credit-Based Information Literacy Courses: Theories and Practice.

ERIC Educational Resources Information Center

Jacobson, Trudi E.; Xu, Lijuan

2002-01-01

Discusses methods for enhancing student motivation, particularly in information literacy courses in higher education. Topics include Keller's ARCS (Attention, Relevance, Confidence, Satisfaction). motivation model; course design; teaching behaviors; teacher enthusiasm; clarity in presenting materials; interaction; active engagement; cooperative…

Microwave remote sensing: Active and passive. Volume 1 - Microwave remote sensing fundamentals and radiometry

NASA Technical Reports Server (NTRS)

Ulaby, F. T.; Moore, R. K.; Fung, A. K.

1981-01-01

The three components of microwave remote sensing (sensor-scene interaction, sensor design, and measurement techniques), and the applications to geoscience are examined. The history of active and passive microwave sensing is reviewed, along with fundamental principles of electromagnetic wave propagation, antennas, and microwave interaction with atmospheric constituents. Radiometric concepts are reviewed, particularly for measurement problems for atmospheric and terrestrial sources of natural radiation. Particular attention is given to the emission by atmospheric gases, clouds, and rain as described by the radiative transfer function. Finally, the operation and performance characteristics of radiometer receivers are discussed, particularly for measurement precision, calibration techniques, and imaging considerations.

Improving parent-child interactions for families of children with developmental disabilities.

PubMed

Harrold, M; Lutzker, J R; Campbell, R V; Touchette, P E

1992-06-01

Child Management Training (CMT) involves compliance training with a focus on consistent use of antecedents and consequences. Planned Activities Training (PAT) focuses on teaching parents to plan for and engage in activities with their children. A multiple probe design counterbalancing PAT and CMT showed that PAT and CMT were about equally effective in improving mother-child interactions in four families with children with developmental disabilities. Responses to a social validation questionnaire indicated that parents were satisfied with the services received, and that PAT was the slightly preferred treatment. Prior research demonstrated that PAT enhanced the results of CMT. The practical advantages of PAT over CMT are discussed.

Small Molecule Docking from Theoretical Structural Models

NASA Astrophysics Data System (ADS)

Novoa, Eva Maria; de Pouplana, Lluis Ribas; Orozco, Modesto

Structural approaches to rational drug design rely on the basic assumption that pharmacological activity requires, as necessary but not sufficient condition, the binding of a drug to one or several cellular targets, proteins in most cases. The traditional paradigm assumes that drugs that interact only with a single cellular target are specific and accordingly have little secondary effects, while promiscuous molecules are more likely to generate undesirable side effects. However, current examples indicate that often efficient drugs are able to interact with several biological targets [1] and in fact some dirty drugs, such as chlorpromazine, dextromethorphan, and ibogaine exhibit desired pharmacological properties [2]. These considerations highlight the tremendous difficulty of designing small molecules that both have satisfactory ADME properties and the ability of interacting with a limited set of target proteins with a high affinity, avoiding at the same time undesirable interactions with other proteins. In this complex and challenging scenario, computer simulations emerge as the basic tool to guide medicinal chemists during the drug discovery process.

The interaction of high voltage systems with the environments of the Moon and Mars

NASA Technical Reports Server (NTRS)

Hillard, G. Barry; Kolecki, Joseph C.

1993-01-01

High voltage systems designed for use on the lunar and Martian surfaces or in orbit will interact with environmental components such as electrically charged dust, low pressure atmospheres, ionospheric plasmas and neutrals, and chemically reactive species. As the Space Exploration Initiative (SEI) advances from the realm of feasibility study to that of conceptual design, guidelines will be required to ensure that these effects are properly accounted for. A first step in providing such guidelines is the prioritization of interactions for each of the space or surface environments that will be encountered. For those issues that are identified as high priority, the state of environmental knowledge, emphasizing essential data, must be determined. This report describes possible means of obtaining such information, including ground tests, modeling and analysis, and flight experiments. The development of computational tools which will enable engineers to simulate and thereby quantify the interactions will be especially considered. Our analysis is drawn from various study and workshop activities undertaken within the last two years.

Pharmaceutical cocrystals, salts and multicomponent systems; intermolecular interactions and property based design.

PubMed

Berry, David J; Steed, Jonathan W

2017-08-01

As small molecule drugs become harder to develop and less cost effective for patient use, efficient strategies for their property improvement become increasingly important to global health initiatives. Improvements in the physical properties of Active Pharmaceutical Ingredients (APIs), without changes in the covalent chemistry, have long been possible through the application of binary component solids. This was first achieved through the use of pharmaceutical salts, within the last 10-15years with cocrystals and more recently coamorphous systems have also been consciously applied to this problem. In order to rationally discover the best multicomponent phase for drug development, intermolecular interactions need to be considered at all stages of the process. This review highlights the current thinking in this area and the state of the art in: pharmaceutical multicomponent phase design, the intermolecular interactions in these phases, the implications of these interactions on the material properties and the pharmacokinetics in a patient. Copyright © 2017 Elsevier B.V. All rights reserved.

Living Liquid: Design and Evaluation of an Exploratory Visualization Tool for Museum Visitors.

PubMed

Ma, J; Liao, I; Ma, Kwan-Liu; Frazier, J

2012-12-01

Interactive visualizations can allow science museum visitors to explore new worlds by seeing and interacting with scientific data. However, designing interactive visualizations for informal learning environments, such as museums, presents several challenges. First, visualizations must engage visitors on a personal level. Second, visitors often lack the background to interpret visualizations of scientific data. Third, visitors have very limited time at individual exhibits in museums. This paper examines these design considerations through the iterative development and evaluation of an interactive exhibit as a visualization tool that gives museumgoers access to scientific data generated and used by researchers. The exhibit prototype, Living Liquid, encourages visitors to ask and answer their own questions while exploring the time-varying global distribution of simulated marine microbes using a touchscreen interface. Iterative development proceeded through three rounds of formative evaluations using think-aloud protocols and interviews, each round informing a key visualization design decision: (1) what to visualize to initiate inquiry, (2) how to link data at the microscopic scale to global patterns, and (3) how to include additional data that allows visitors to pursue their own questions. Data from visitor evaluations suggests that, when designing visualizations for public audiences, one should (1) avoid distracting visitors from data that they should explore, (2) incorporate background information into the visualization, (3) favor understandability over scientific accuracy, and (4) layer data accessibility to structure inquiry. Lessons learned from this case study add to our growing understanding of how to use visualizations to actively engage learners with scientific data.

Interactive E-learning module in pharmacology: a pilot project at a rural medical college in India.

PubMed

Gaikwad, Nitin; Tankhiwale, Suresh

2014-01-01

Many medical educators are experimenting with innovative ways of E-learning. E-learning provides opportunities to students for self-directed learning in addition to other advantages. In this study, we designed and evaluated an interactive E-learning module in pharmacology for effectiveness, acceptability and feasibility, with the aim of promoting active learning in this fact-filled subject. A quasi-experimental single-group pre-test/post-test study was conducted with fourth-semester students of the second professionals course (II MBBS), selected using non-probability convenience sampling method. An E-learning module in endocrine pharmacology was designed to comprise three units of interactive PowerPoint presentations. The pre-validated presentations were uploaded on the website according to a predefined schedule and the 42 registered students were encouraged to self-learning using these interactive presentations. Cognitive gain was assessed using an online pre- and post-test for each unit. Students' perceptions were recorded using an online feedback questionnaire on a 5-point Likert scale. Finally, focused group discussion was conducted to further explore students' views on E-learning activity. Significant attrition was observed during the E-learning activity. Of the 42 registered students, only 16 students completed the entire E-learning module. The summed average score of all three units (entire module) was increased significantly from 38.42 % (summed average pre-test score: 11.56/30 ± 2.90) to 66.46 % (summed average post-test score: 19.94/30 ± 6.13). The class-average normalized gain for the entire module was 0.4542 (45.42). The students accepted this E-learning activity well as they perceived it to be innovative, convenient, flexible and useful. The average rating was between 4 (agree) and 5 (strongly agree). The interactive E-learning module in pharmacology was moderately effective and well perceived by the students. The simple, cost-effective and readily available Microsoft PowerPoint tool appealed to medical educators to use this kind of simple E-learning technology blended with traditional teaching to encourage active learning among students especially in a rural setup is attractive.

Prediction of Binding Energy of Keap1 Interaction Motifs in the Nrf2 Antioxidant Pathway and Design of Potential High-Affinity Peptides.

PubMed

Karttunen, Mikko; Choy, Wing-Yiu; Cino, Elio A

2018-06-07

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor and principal regulator of the antioxidant pathway. The Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) binds to motifs in the N-terminal region of Nrf2, promoting its degradation. There is interest in developing ligands that can compete with Nrf2 for binding to Kelch, thereby activating its transcriptional activities and increasing antioxidant levels. Using experimental Δ G bind values of Kelch-binding motifs determined previously, a revised hydrophobicity-based model was developed for estimating Δ G bind from amino acid sequence and applied to rank potential uncharacterized Kelch-binding motifs identified from interaction databases and BLAST searches. Model predictions and molecular dynamics (MD) simulations suggested that full-length MAD2A binds Kelch more favorably than a high-affinity 20-mer Nrf2 E78P peptide, but that the motif in isolation is not a particularly strong binder. Endeavoring to develop shorter peptides for activating Nrf2, new designs were created based on the E78P peptide, some of which showed considerable propensity to form binding-competent structures in MD, and were predicted to interact with Kelch more favorably than the E78P peptide. The peptides could be promising new ligands for enhancing the oxidative stress response.

Rationale and design of active play @ home: a parent-led physical activity program for children with and without disability

PubMed Central

2014-01-01

Background Compared to other children, those with disability have additional challenges to being physically active. Prader-Willi Syndrome is a genetic form of childhood obesity that is characterized by hypotonia, growth hormone deficiency, behavioral, and cognitive disability. In children, the low prevalence of this syndrome (1 in 10,000 to 15,000 live births) makes group-based physical activity interventions difficult. In contrast, the home environment presents a natural venue to establish a physical activity routine for this population. This manuscript describes the design of a parent-led physical activity intervention incorporating playground and interactive console-based games to increase physical activity participation in youth with and without Prader-Willi Syndrome. Methods/Design The study participants will be 115 youth ages 8-15 y (45 with the syndrome and 70 without the syndrome but categorized as obese). The study will use a parallel design with the control group receiving the intervention after serving as control. Participants will be expected to complete a physical activity curriculum 4 days a week for 6 months including playground games 2 days a week and interactive console games 2 days a week. Parents will be trained at baseline and then provided with a curriculum and equipment to guide their implementation of the program. Tips related to scheduling and coping with barriers to daily program implementation will be provided. Throughout, parents will be contacted by phone once a week (weeks 1-4) and then every other week to receive support in between visits. Measurements of children and parents will be obtained at baseline, 12 weeks, and at the end (week 24) of the intervention. Children main outcomes include physical activity (accelerometry), body composition (dual x-ray absorptiometry), motor proficiency (Bruininks-Oseretsky Test of Motor Proficiency), quality of life and physical activity self-efficacy (questionnaires). Intervention compliance will be monitored using mail-in daily self-report checklists. Discussion This parent-guided physical activity intervention aims to increase physical activity by using a curriculum that builds physical activity related self-confidence through the development and/or enhancement of motor skill competency. Ultimately, helping children develop these skills as well as joy in being physically active will translate into sustained behavior change. Trial registration Current Controlled Trial: NCT02058342 PMID:24529259

Adaptive software architecture based on confident HCI for the deployment of sensitive services in Smart Homes.

PubMed

Vega-Barbas, Mario; Pau, Iván; Martín-Ruiz, María Luisa; Seoane, Fernando

2015-03-25

Smart spaces foster the development of natural and appropriate forms of human-computer interaction by taking advantage of home customization. The interaction potential of the Smart Home, which is a special type of smart space, is of particular interest in fields in which the acceptance of new technologies is limited and restrictive. The integration of smart home design patterns with sensitive solutions can increase user acceptance. In this paper, we present the main challenges that have been identified in the literature for the successful deployment of sensitive services (e.g., telemedicine and assistive services) in smart spaces and a software architecture that models the functionalities of a Smart Home platform that are required to maintain and support such sensitive services. This architecture emphasizes user interaction as a key concept to facilitate the acceptance of sensitive services by end-users and utilizes activity theory to support its innovative design. The application of activity theory to the architecture eases the handling of novel concepts, such as understanding of the system by patients at home or the affordability of assistive services. Finally, we provide a proof-of-concept implementation of the architecture and compare the results with other architectures from the literature.

Design, Synthesis and Evaluation of 2,5-Diketopiperazines as Inhibitors of the MDM2-p53 Interaction.

PubMed

Pettersson, Mariell; Quant, Maria; Min, Jaeki; Iconaru, Luigi; Kriwacki, Richard W; Waddell, M Brett; Guy, R Kiplin; Luthman, Kristina; Grøtli, Morten

2015-01-01

The transcription factor p53 is the main tumour suppressor in cells and many cancer types have p53 mutations resulting in a loss of its function. In tumours that retain wild-type p53 function, p53 activity is down-regulated by MDM2 (human murine double minute 2) via a direct protein-protein interaction. We have designed and synthesised two series of 2,5-diketopiperazines as inhibitors of the MDM2-p53 interaction. The first set was designed to directly mimic the α-helical region of the p53 peptide, containing key residues in the i, i+4 and i+7 positions of a natural α-helix. Conformational analysis indicated that 1,3,6-trisubstituted 2,5-diketopiperazines were able to place substituents in the same spatial orientation as an α-helix template. The key step of the synthesis involved the cyclisation of substituted dipeptides. The other set of tetrasubstituted 2,5-diketopiperazines were designed based on structure-based docking studies and the Ugi multicomponent reaction was used for the synthesis. This latter set comprised the most potent inhibitors which displayed micromolar IC50-values in a biochemical fluorescence polarisation assay.

Design, Synthesis and Evaluation of 2,5-Diketopiperazines as Inhibitors of the MDM2-p53 Interaction

PubMed Central

Pettersson, Mariell; Quant, Maria; Min, Jaeki; Iconaru, Luigi; Kriwacki, Richard W.; Waddell, M. Brett; Guy, R. Kiplin; Luthman, Kristina; Grøtli, Morten

2015-01-01

The transcription factor p53 is the main tumour suppressor in cells and many cancer types have p53 mutations resulting in a loss of its function. In tumours that retain wild-type p53 function, p53 activity is down-regulated by MDM2 (human murine double minute 2) via a direct protein—protein interaction. We have designed and synthesised two series of 2,5-diketopiperazines as inhibitors of the MDM2-p53 interaction. The first set was designed to directly mimic the α-helical region of the p53 peptide, containing key residues in the i, i+4 and i+7 positions of a natural α-helix. Conformational analysis indicated that 1,3,6-trisubstituted 2,5-diketopiperazines were able to place substituents in the same spatial orientation as an α-helix template. The key step of the synthesis involved the cyclisation of substituted dipeptides. The other set of tetrasubstituted 2,5-diketopiperazines were designed based on structure-based docking studies and the Ugi multicomponent reaction was used for the synthesis. This latter set comprised the most potent inhibitors which displayed micromolar IC50-values in a biochemical fluorescence polarisation assay. PMID:26427060

De Novo Enzyme Design Using Rosetta3

PubMed Central

Richter, Florian; Leaver-Fay, Andrew; Khare, Sagar D.; Bjelic, Sinisa; Baker, David

2011-01-01

The Rosetta de novo enzyme design protocol has been used to design enzyme catalysts for a variety of chemical reactions, and in principle can be applied to any arbitrary chemical reaction of interest, The process has four stages: 1) choice of a catalytic mechanism and corresponding minimal model active site, 2) identification of sites in a set of scaffold proteins where this minimal active site can be realized, 3) optimization of the identities of the surrounding residues for stabilizing interactions with the transition state and primary catalytic residues, and 4) evaluation and ranking the resulting designed sequences. Stages two through four of this process can be carried out with the Rosetta package, while stage one needs to be done externally. Here, we demonstrate how to carry out the Rosetta enzyme design protocol from start to end in detail using for illustration the triosephosphate isomerase reaction. PMID:21603656

The building blocks of a 'Liveable Neighbourhood': Identifying the key performance indicators for walking of an operational planning policy in Perth, Western Australia.

PubMed

Hooper, Paula; Knuiman, Matthew; Foster, Sarah; Giles-Corti, Billie

2015-11-01

Planning policy makers are requesting clearer guidance on the key design features required to build neighbourhoods that promote active living. Using a backwards stepwise elimination procedure (logistic regression with generalised estimating equations adjusting for demographic characteristics, self-selection factors, stage of construction and scale of development) this study identified specific design features (n=16) from an operational planning policy ("Liveable Neighbourhoods") that showed the strongest associations with walking behaviours (measured using the Neighbourhood Physical Activity Questionnaire). The interacting effects of design features on walking behaviours were also investigated. The urban design features identified were grouped into the "building blocks of a Liveable Neighbourhood", reflecting the scale, importance and sequencing of the design and implementation phases required to create walkable, pedestrian friendly developments. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Parametric Geometry Computational Fluid Dynamics (CFD) Study Utilizing Design of Experiments (DOE)

NASA Technical Reports Server (NTRS)

Rhew, Ray D.; Parker, Peter A.

2007-01-01

Design of Experiments (DOE) was applied to the LAS geometric parameter study to efficiently identify and rank primary contributors to integrated drag over the vehicles ascent trajectory in an order of magnitude fewer CFD configurations thereby reducing computational resources and solution time. SME s were able to gain a better understanding on the underlying flowphysics of different geometric parameter configurations through the identification of interaction effects. An interaction effect, which describes how the effect of one factor changes with respect to the levels of other factors, is often the key to product optimization. A DOE approach emphasizes a sequential approach to learning through successive experimentation to continuously build on previous knowledge. These studies represent a starting point for expanded experimental activities that will eventually cover the entire design space of the vehicle and flight trajectory.

CHILDSPLA: a collaboration between children and researchers to design and animate health states.

PubMed

Abrines Jaume, N; Abbiss, M; Wray, J; Ashworth, J; Brown, K L; Cairns, J

2015-11-01

The children's health state preferences learnt from animation (CHILDSPLA) project developed an interactive application presented on a touch screen device using an animated character to collect information from children about their health. The underlying hypothesis was that health information could be directly collected from children as young as 4 years old by the use of animated characters. This paper describes in detail how children were involved in the development of the application, and recounts both the challenges and benefits of that process. A child psychologist and an animation filmmaker worked closely with children to design a character and to animate it to represent different health states. Children were recruited from a local primary school (n = 38) and a paediatric specialist hospital (n = 36). Diverse interactive activities were organized to help children give feedback and guide the design process. The activities for each session were adjusted to the children's needs, based on the experience of previous sessions. The character and the animations were modified according to the feedback provided by the children. Developing the CHILDSPLA app in collaboration with children was a worthwhile and enriching experience, despite the required iteration and extension of the design process, as it enabled us to adjust the tool to the children's needs. © 2015 John Wiley & Sons Ltd.

Creating a Model of Acceptance: Preservice Teachers Interact with Non-English-Speaking Latino Parents Using Culturally Relevant Mathematics and Science Activities at Family Learning Events

ERIC Educational Resources Information Center

Ramirez, Olga; McCollough, Cherie A.; Diaz, Zulmaris

2016-01-01

The following describes a culturally relevant mathematics and science content program implemented by preservice teachers (PSTs) at Family Math/Science Learning Events (FM/SLEs) conducted through two different university programs in south Texas. These experiences are required course activities designed to inform PSTs of the importance of…

The Determinants of Staff and Resident Activity in Residential Services for People with Severe Intellectual Disability: Moving beyond Size, Building Design, Location and Number of Staff.

ERIC Educational Resources Information Center

Felce, David

1998-01-01

Draws together the results of seven studies that investigated factors influencing the effects of service quality in community-based residential services for people with severe mental retardation. Results found that quality of staff and resident activity is dependent on an interaction between the structure, orientation, and procedures followed…

Synthetic Molecular Evolution of Membrane-Active Peptides

NASA Astrophysics Data System (ADS)

Wimley, William

The physical chemistry of membrane partitioning largely determines the function of membrane active peptides. Membrane-active peptides have potential utility in many areas, including in the cellular delivery of polar compounds, cancer therapy, biosensor design, and in antibacterial, antiviral and antifungal therapies. Yet, despite decades of research on thousands of known examples, useful sequence-structure-function relationships are essentially unknown. Because peptide-membrane interactions within the highly fluid bilayer are dynamic and heterogeneous, accounts of mechanism are necessarily vague and descriptive, and have little predictive power. This creates a significant roadblock to advances in the field. We are bypassing that roadblock with synthetic molecular evolution: iterative peptide library design and orthogonal high-throughput screening. We start with template sequences that have at least some useful activity, and create small, focused libraries using structural and biophysical principles to design the sequence space around the template. Orthogonal high-throughput screening is used to identify gain-of-function peptides by simultaneously selecting for several different properties (e.g. solubility, activity and toxicity). Multiple generations of iterative library design and screening have enabled the identification of membrane-active sequences with heretofore unknown properties, including clinically relevant, broad-spectrum activity against drug-resistant bacteria and enveloped viruses as well as pH-triggered macromolecular poration.

Creative Arts.

ERIC Educational Resources Information Center

Castellano, Richard J.; Fleming, Mary Ann

Educational goals and objectives, student activities, and visual aids are included in this guide to a three-dimensional design unit that combines creative art and industrial arts skills. Course goals include challenging students' creative skills, encouraging student interaction and successful group work, and providing an atmosphere of fun and…

Spatial interpretation of NASA's Marshall Space Flight Center Payload Operations Control Center using virtual reality technology

NASA Technical Reports Server (NTRS)

Lindsey, Patricia F.

1993-01-01

In its search for higher level computer interfaces and more realistic electronic simulations for measurement and spatial analysis in human factors design, NASA at MSFC is evaluating the functionality of virtual reality (VR) technology. Virtual reality simulation generates a three dimensional environment in which the participant appears to be enveloped. It is a type of interactive simulation in which humans are not only involved, but included. Virtual reality technology is still in the experimental phase, but it appears to be the next logical step after computer aided three-dimensional animation in transferring the viewer from a passive to an active role in experiencing and evaluating an environment. There is great potential for using this new technology when designing environments for more successful interaction, both with the environment and with another participant in a remote location. At the University of North Carolina, a VR simulation of a the planned Sitterson Hall, revealed a flaw in the building's design that had not been observed during examination of the more traditional building plan simulation methods on paper and on computer aided design (CAD) work station. The virtual environment enables multiple participants in remote locations to come together and interact with one another and with the environment. Each participant is capable of seeing herself and the other participants and of interacting with them within the simulated environment.

Screening of benzamidine-based thrombin inhibitors via a linear interaction energy in continuum electrostatics model

NASA Astrophysics Data System (ADS)

Nicolotti, Orazio; Giangreco, Ilenia; Miscioscia, Teresa Fabiola; Convertino, Marino; Leonetti, Francesco; Pisani, Leonardo; Carotti, Angelo

2010-02-01

A series of 27 benzamidine inhibitors covering a wide range of biological activity and chemical diversity was analysed to derive a Linear Interaction Energy in Continuum Electrostatics (LIECE) model for analysing the thrombin inhibitory activity. The main interactions occurring at the thrombin binding site and the preferred binding conformations of inhibitors were explicitly biased by including into the LIECE model 10 compounds extracted from X-ray solved thrombin-inhibitor complexes available from the Protein Data Bank (PDB). Supported by a robust statistics ( r 2 = 0.698; q 2 = 0.662), the LIECE model was successful in predicting the inhibitory activity for about 76% of compounds ( r ext 2 ≥ 0.600) from a larger external test set encompassing 88 known thrombin inhibitors and, more importantly, in retrieving, at high sensitivity and with better performance than docking and shape-based methods, active compounds from a thrombin combinatorial library of 10240 mimetic chemical products. The herein proposed LIECE model has the potential for successfully driving the design of novel thrombin inhibitors with benzamidine and/or benzamidine-like chemical structure.

The neural basis of deception in strategic interactions

PubMed Central

Volz, Kirsten G.; Vogeley, Kai; Tittgemeyer, Marc; von Cramon, D. Yves; Sutter, Matthias

2015-01-01

Communication based on informational asymmetries abounds in politics, business, and almost any other form of social interaction. Informational asymmetries may create incentives for the better-informed party to exploit her advantage by misrepresenting information. Using a game-theoretic setting, we investigate the neural basis of deception in human interaction. Unlike in most previous fMRI research on deception, the participants decide themselves whether to lie or not. We find activation within the right temporo-parietal junction (rTPJ), the dorsal anterior cingulate cortex (ACC), the (pre)cuneus (CUN), and the anterior frontal gyrus (aFG) when contrasting lying with truth telling. Notably, our design also allows for an investigation of the neural foundations of sophisticated deception through telling the truth—when the sender does not expect the receiver to believe her (true) message. Sophisticated deception triggers activation within the same network as plain lies, i.e., we find activity within the rTPJ, the CUN, and aFG. We take this result to show that brain activation can reveal the sender's veridical intention to deceive others, irrespective of whether in fact the sender utters the factual truth or not. PMID:25729358

The neural basis of deception in strategic interactions.

PubMed

Volz, Kirsten G; Vogeley, Kai; Tittgemeyer, Marc; von Cramon, D Yves; Sutter, Matthias

2015-01-01

Communication based on informational asymmetries abounds in politics, business, and almost any other form of social interaction. Informational asymmetries may create incentives for the better-informed party to exploit her advantage by misrepresenting information. Using a game-theoretic setting, we investigate the neural basis of deception in human interaction. Unlike in most previous fMRI research on deception, the participants decide themselves whether to lie or not. We find activation within the right temporo-parietal junction (rTPJ), the dorsal anterior cingulate cortex (ACC), the (pre)cuneus (CUN), and the anterior frontal gyrus (aFG) when contrasting lying with truth telling. Notably, our design also allows for an investigation of the neural foundations of sophisticated deception through telling the truth-when the sender does not expect the receiver to believe her (true) message. Sophisticated deception triggers activation within the same network as plain lies, i.e., we find activity within the rTPJ, the CUN, and aFG. We take this result to show that brain activation can reveal the sender's veridical intention to deceive others, irrespective of whether in fact the sender utters the factual truth or not.

Modelling Ecological Cognitive Rehabilitation Therapies for Building Virtual Environments in Brain Injury.

PubMed

Martínez-Moreno, J M; Sánchez-González, P; Luna, M; Roig, T; Tormos, J M; Gómez, E J

2016-01-01

Brain Injury (BI) has become one of the most common causes of neurological disability in developed countries. Cognitive disorders result in a loss of independence and patients' quality of life. Cognitive rehabilitation aims to promote patients' skills to achieve their highest degree of personal autonomy. New technologies such as virtual reality or interactive video allow developing rehabilitation therapies based on reproducible Activities of Daily Living (ADLs), increasing the ecological validity of the therapy. However, the lack of frameworks to formalize and represent the definition of this kind of therapies can be a barrier for widespread use of interactive virtual environments in clinical routine. To provide neuropsychologists with a methodology and an instrument to design and evaluate cognitive rehabilitation therapeutic interventions strategies based on ADLs performed in interactive virtual environments. The proposed methodology is used to model therapeutic interventions during virtual ADLs considering cognitive deficit, expected abnormal interactions and therapeutic hypotheses. It allows identifying abnormal behavioural patterns and designing interventions strategies in order to achieve errorless-based rehabilitation. An ADL case study ('buying bread') is defined according to the guidelines established by the ADL intervention model. This case study is developed, as a proof of principle, using interactive video technology and is used to assess the feasibility of the proposed methodology in the definition of therapeutic intervention procedures. The proposed methodology provides neuropsychologists with an instrument to design and evaluate ADL-based therapeutic intervention strategies, attending to solve actual limitation of virtual scenarios, to be use for ecological rehabilitation of cognitive deficit in daily clinical practice. The developed case study proves the potential of the methodology to design therapeutic interventions strategies; however our current work is devoted to designing more experiments in order to present more evidence about its values.

Template-based de novo design for type II kinase inhibitors and its extented application to acetylcholinesterase inhibitors.

PubMed

Su, Bo-Han; Huang, Yi-Syuan; Chang, Chia-Yun; Tu, Yi-Shu; Tseng, Yufeng J

2013-10-31

There is a compelling need to discover type II inhibitors targeting the unique DFG-out inactive kinase conformation since they are likely to possess greater potency and selectivity relative to traditional type I inhibitors. Using a known inhibitor, such as a currently available and approved drug or inhibitor, as a template to design new drugs via computational de novo design is helpful when working with known ligand-receptor interactions. This study proposes a new template-based de novo design protocol to discover new inhibitors that preserve and also optimize the binding interactions of the type II kinase template. First, sorafenib (Nexavar) and nilotinib (Tasigna), two type II inhibitors with different ligand-receptor interactions, were selected as the template compounds. The five-step protocol can reassemble each drug from a large fragment library. Our procedure demonstrates that the selected template compounds can be successfully reassembled while the key ligand-receptor interactions are preserved. Furthermore, to demonstrate that the algorithm is able to construct more potent compounds, we considered kinase inhibitors and other protein dataset, acetylcholinesterase (AChE) inhibitors. The de novo optimization was initiated using a template compound possessing a less than optimal activity from a series of aminoisoquinoline and TAK-285 inhibiting type II kinases, and E2020 derivatives inhibiting AChE respectively. Three compounds with greater potency than the template compound were discovered that were also included in the original congeneric series. This template-based lead optimization protocol with the fragment library can help to design compounds with preferred binding interactions of known inhibitors automatically and further optimize the compounds in the binding pockets.

Small Stories for Learning: A Sociocultural Analysis of Children's Participation in Informal Science Education

NASA Astrophysics Data System (ADS)

Desjardins, Elia Nelson

2011-12-01

This dissertation examines the ways children use language to construct scientific knowledge in designed informal learning environments such as museums, aquariums, and zoos, with particular attention to autobiographical storytelling. This study takes as its foundation cultural-historical activity theory, defining learning as increased participation in meaningful, knowledge-based activity. It aims to improve experience design in informal learning environments by facilitating and building upon language interactions that are already in use by learners in these contexts. Fieldwork consists of audio recordings of individual children aged 4--12 as they explored a museum of science and technology with their families. Recordings were transcribed and coded according to the activity (task) and context (artifact/exhibit) in which the child was participating during each sequence of utterances. Additional evidence is provided by supplemental interviews with museum educators. Analysis suggests that short autobiographical stories can provide opportunities for learners to access metacognitive knowledge, for educators to assess learners' prior experience and knowledge, and for designers to engage affective pathways in order to increase participation that is both active and contemplative. Design implications are discussed and a design proposal for a distributed informal learning environment is presented.

Structural Analysis of Charge Discrimination in the Binding of Inhibitors to Human Carbonic Anhydrases I and II

PubMed Central

Srivastava, D. K.; Jude, Kevin M.; Banerjee, Abir L.; Haldar, Manas; Manokaran, Sumathra; Kooren, Joel; Mallik, Sanku; Christianson, David W.

2008-01-01

Despite the similarity in the active site pockets of carbonic anhydrase (CA) isozymes I and II, the binding affinities of benzenesulfonamide inhibitors are invariably higher with CA II as compared to CA I. To explore the structural basis of this molecular recognition phenomenon, we have designed and synthesized simple benzenesulfonamide inhibitors substituted at the para position with positively-charged, negatively-charged, and neutral functional groups, and we have determined the affinities and X-ray crystal structures of their enzyme complexes. The para-substituents are designed to bind in the midsection of the 15 Å deep active site cleft, where interactions with enzyme residues and solvent molecules are possible. We find that a para-substituted positively-charged amino group is more poorly tolerated in the active site of CA I compared with CA II. In contrast, a para-substituted negatively-charged carboxylate substituent is tolerated equally well in the active sites of both CA isozymes. Notably, enzyme-inhibitor affinity increases upon neutralization of inhibitor charged groups by amidation or esterification. These results inform the design of short molecular linkers connecting the benzenesulfonamide group and a para-substituted tail group in “two-prong” CA inhibitors: an optimal linker segment will be electronically neutral, yet capable of engaging in at least some hydrogen bond interactions with protein residues and/or solvent. Microcalorimetric data reveal that inhibitor binding to CA I is enthalpically less favorable and entropically more favorable than inhibitor binding to CA II. This contrasting behavior may arise in part from differences in active site desolvation and the conformational entropy of inhibitor binding to each isozyme active site. PMID:17407288

Improving science and mathematics education with computational modelling in interactive engagement environments

NASA Astrophysics Data System (ADS)

Neves, Rui Gomes; Teodoro, Vítor Duarte

2012-09-01

A teaching approach aiming at an epistemologically balanced integration of computational modelling in science and mathematics education is presented. The approach is based on interactive engagement learning activities built around computational modelling experiments that span the range of different kinds of modelling from explorative to expressive modelling. The activities are designed to make a progressive introduction to scientific computation without requiring prior development of a working knowledge of programming, generate and foster the resolution of cognitive conflicts in the understanding of scientific and mathematical concepts and promote performative competency in the manipulation of different and complementary representations of mathematical models. The activities are supported by interactive PDF documents which explain the fundamental concepts, methods and reasoning processes using text, images and embedded movies, and include free space for multimedia enriched student modelling reports and teacher feedback. To illustrate, an example from physics implemented in the Modellus environment and tested in undergraduate university general physics and biophysics courses is discussed.

The Eugenides Foundation Interactive Exhibition of Science and Technology

NASA Astrophysics Data System (ADS)

Kontogiannis, Ioannis

2010-01-01

The Interactive Exhibition of Science and Technology is installed in an area of 1200 m2 at the Eugenides Foundation. 65 interactive exhibits, designed by the "Cites des Science et de l' Industrie" are organised in themes, stimulate the visitors' mind and provoke scientific thinking. Parallel activities take place inside the exhibition, such as live science demonstrations, performed by young scientists. Extra material such as news bulletins (short news, science comics and portraits), educational paths and treasure-hunting based games, all available online as well, are prepared on a monthly basis and provided along with the visit to the exhibition. Through these exhibits and activities, scientific facts are made simple and easy to comprehend using modern presentation tools. We present details on how this exhibition acts complementary to the science education provided by schools, making it a highly sophisticated educational tool.

A systematic quantitative approach to rational drug design and discovery of novel human carbonic anhydrase IX inhibitors.

PubMed

Sethi, Kalyan K; Verma, Saurabh M

2014-08-01

Drug design involves the design of small molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed for a series of carbonic anhydrase IX inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques with the help of SYBYL 7.1 software. The large set of 36 different aromatic/heterocyclic sulfamates carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, such as hCA IX, was chosen for this study. The conventional ligand-based 3D-QSAR studies were performed based on the low energy conformations employing database alignment rule. The ligand-based model gave q(2) values 0.802 and 0.829 and r(2) values 1.000 and 0.994 for CoMFA and CoMSIA, respectively, and the predictive ability of the model was validated. The predicted r(2) values are 0.999 and 0.502 for CoMFA and CoMSIA, respectively. SEA (steric, electrostatic, hydrogen bond acceptor) of CoMSIA has the significant contribution for the model development. The docking of inhibitors into hCA IX active site using Glide XP (Schrödinger) software revealed the vital interactions and binding conformation of the inhibitors. The CoMFA and CoMSIA field contour maps are well in agreement with the structural characteristics of the binding pocket of hCA IX active site, which suggests that the information rendered by 3D-QSAR models and the docking interactions can provide guidelines for the development of improved hCA IX inhibitors as leads for various types of metastatic cancers including those of cervical, renal, breast and head and neck origin.

Disruption of the Interaction of the Androgen Receptor with Chromatin: A Novel Therapeutic Approach in Prostate Cancer

DTIC Science & Technology

2016-10-01

DISTRIBUTION STATEMENT: Approved for Public Release; Distribution Unlimited The views, opinions and/or findings contained in this report are those of...interface between AR -FOXA1 plays important roles in AR responsiveness and activity. We have designed, synthesized, and tested a panel of peptides...peptidomimetics to disrupt the interaction between AR and FOXA1. The effects of these candidate compounds have been tested in multiple assays and various

Soundscapes/Artabilitation - Evolution of a Hybrid Human Performance Concept, Method & Apparatus Where Digital Interactive Media, The Arts, & Entertainment are Combined

NASA Astrophysics Data System (ADS)

Brooks, A. L.

'SoundScapes' is a body of empirical research that for almost two decades has focused upon investigating noninvasive gesture control of multi-sensory stimuli and potential uses in therapy and the arts. In this context noninvasive gesture refers to motion in invisible activity zones of a system input device utilizing technology outside of human vision. Especially targeted are disabled people of all ages, and special focus has been on the profoundly impaired who especially have limited opportunities for creative self-articulation and playful interaction. The concept has been explored in various situations including: - live stage performances; interactive room installations for museums, workshops, and festivals; and in health-care sessions at hospitals, institutes and special schools. Multifaceted aspects continuously cross-inform in a systemic manner, and each situation where the motion-sensitive environment is applied is considered as a hybrid system. Whilst simplistic in concept, i.e. learning by playful and creative doings, inherent are complexities of optimizing the interactive system to user-experience and evaluation of same. This chapter presents the system in context to its conceived-for-target community; it also presents the parallel practice-led investigations in performance art. Reciprocal design and reflective cross-analysis of the activities has resulted such that performance informs design and strategies of intervention and evaluation with impaired users, and vice versa.

Heterocyclic HIV-protease inhibitors.

PubMed

Calugi, C; Guarna, A; Trabocchi, A

2013-01-01

In the panorama of HIV protease inhibitors (HIV PIs), many efforts have been devoted to the development of new compounds with reduced peptidic nature in order to improve pharmacokinetics and pharmacodynamics features. The introduction of cyclic scaffolds in the design of new chemical entities reduces flexibility and affords more rigid inhibitors. Specifically, common dipeptide isosteres are replaced by a central cyclic scaffold designed to address the key interactions with catalytic aspartic acids and residues belonging to the flap region of the active site. The current interest in cyclic chemotypes addressing key interactions of HIV protease is motivated by the different nature of interactions formed with the enzyme, although maintaining key structural resemblance to a peptide substrate, hopefully giving rise to novel HIV-1 PIs displaying an improved profile towards multidrug resistant strains. This approach has been demonstrated for Tipranavir, which is a potent FDA approved HIV-1 PI representing the most famous example of heterocyclic aspartic protease inhibitors.

Architecting Learning Continuities for Families Across Informal Science Experiences

NASA Astrophysics Data System (ADS)

Perin, Suzanne Marie

By first recognizing the valuable social and scientific practices taking place within families as they learn science together across multiple, everyday settings, this dissertation addresses questions of how to design and scaffold activities that build and expand on those practices to foster a deep understanding of science, and how the aesthetic experience of learning science builds connections across educational settings. Families were invited to visit a natural history museum, an aquarium, and a place or activity of the family's choice that they associated with science learning. Some families were asked to use a set of activities during their study visits based on the practices of science (National Research Council, 2012), which were delivered via smartphone app or on paper cards. I use design-based research, video data analysis and interaction analysis to examine how families build connections between informal science learning settings. Chapter 2 outlines the research-based design process of creating activities for families that fostered connections across multiple learning settings, regardless of the topical content of those settings. Implications of this study point to means for linking everyday family social practices such as questioning, observing, and disagreeing to the practices of science through activities that are not site-specific. The next paper delves into aesthetic experience of science learning, and I use video interaction analysis and linguistic analysis to show how notions of beauty and pleasure (and their opposites) are perfused throughout learning activity. Designing for aesthetic experience overtly -- building on the sensations of enjoyment and pleasure in the learning experience -- can motivate those who might feel alienated by the common conception of science as merely a dispassionate assembly of facts, discrete procedures or inaccessible theory. The third paper, a case study of a family who learns about salmon in each of the sites they visit, highlights the contributions of multiple sites of learning in an ecological view of learning. Finally, the dissertations' conclusion highlights the broad implications for conceiving of the many varied learning settings in a community as an educational infrastructure, and reflections on using aesthetic experience for broadening participation the sciences through the design of informal environments.

Understanding safety-critical interactions with a home medical device through Distributed Cognition.

PubMed

Rajkomar, Atish; Mayer, Astrid; Blandford, Ann

2015-08-01

As healthcare shifts from the hospital to the home, it is becoming increasingly important to understand how patients interact with home medical devices, to inform the safe and patient-friendly design of these devices. Distributed Cognition (DCog) has been a useful theoretical framework for understanding situated interactions in the healthcare domain. However, it has not previously been applied to study interactions with home medical devices. In this study, DCog was applied to understand renal patients' interactions with Home Hemodialysis Technology (HHT), as an example of a home medical device. Data was gathered through ethnographic observations and interviews with 19 renal patients and interviews with seven professionals. Data was analyzed through the principles summarized in the Distributed Cognition for Teamwork methodology. In this paper we focus on the analysis of system activities, information flows, social structures, physical layouts, and artefacts. By explicitly considering different ways in which cognitive processes are distributed, the DCog approach helped to understand patients' interaction strategies, and pointed to design opportunities that could improve patients' experiences of using HHT. The findings highlight the need to design HHT taking into consideration likely scenarios of use in the home and of the broader home context. A setting such as home hemodialysis has the characteristics of a complex and safety-critical socio-technical system, and a DCog approach effectively helps to understand how safety is achieved or compromised in such a system. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Methods for the In Vitro Characterization of Nanomedicines—Biological Component Interaction

PubMed Central

Fornaguera, Cristina; Solans, Conxita

2017-01-01

The design of colloidal nanosystems intended for biomedical applications, specifically in the field of personalized medicine, has increased notably in the last years. Consequently, a variety of characterization techniques devoted to studying nanomedicine interactions with proteins and cells have been developed, since a deep characterization of nanosystems is required before starting preclinical and clinical studies. In this context, this review aims to summarize the main techniques used to assess the interaction of nanomedicines with biological systems, highlighting their advantages and disadvantages. Testing designed nanomaterials with these techniques is required in order to have more information about their behavior on a physiological environment. Moreover, techniques used to study the interaction of nanomedicines with proteins, such as albumin and fibrinogen, are summarized. These interactions are not desired, since they usually are the first signal to the body for the activation of the immune system, which leads to the clearance of the exogenous components. On the other hand, techniques for studying the cell toxicity of nanosystems are also summarized, since this information is required before starting preclinical steps. The translation of knowledge from novel designed nanosystems at a research laboratory scale to real human therapies is usually a limiting or even a final point due to the lack of systematic studies regarding these two aspects: nanoparticle interaction with biological components and nanoparticle cytotoxicity. In conclusion, this review will be a useful support for those scientists aiming to develop nanosystems for nanomedicine purposes. PMID:28134833

Protein design to understand peptide ligand recognition by tetratricopeptide repeat proteins.

PubMed

Cortajarena, Aitziber L; Kajander, Tommi; Pan, Weilan; Cocco, Melanie J; Regan, Lynne

2004-04-01

Protein design aims to understand the fundamentals of protein structure by creating novel proteins with pre-specified folds. An equally important goal is to understand protein function by creating novel proteins with pre-specified activities. Here we describe the design and characterization of a tetratricopeptide (TPR) protein, which binds to the C-terminal peptide of the eukaryotic chaperone Hsp90. The design emphasizes the importance of both direct, short-range protein-peptide interactions and of long-range electrostatic optimization. We demonstrate that the designed protein binds specifically to the desired peptide and discriminates between it and the similar C-terminal peptide of Hsp70.

The Interactive Planetarium: Student-led Investigations of Naked-Eye Astronomy and Planetary Motion

NASA Astrophysics Data System (ADS)

Rice, Emily L.; McCrady, N.

2007-12-01

We have developed a set of interactive, learner-centered planetarium lab activities for the introductory astronomy course for non-majors at UCLA. A planetarium is ideal for the visualization of the celestial sphere as a 2D projection in 3D space and for the direct spatial simulation of geometric relationships. These concepts are fundamental to content areas frequently covered in introductory courses but are notoriously difficult for non-specialists. Opportunities for engaging students in actively learning content and process skills are limited in the traditional "sky show” approach typically employed in a planetarium setting. The novel aspect of our activities is that they actively engage students in learning: students make predictions, design observational tests, and direct the motion of the planetarium sky in order to evaluate their hypotheses. We have also developed complementary, kinesthetic lab activities that take place outside the planetarium with overlapping content and process goals. Several hundred schools, colleges, and universities across the country have immediate access to a planetarium as a classroom, and our method represents a novel way to use the planetarium as interactive lab equipment in college-level introductory astronomy courses.

Activity loss by H46A mutation in Mycobacterium tuberculosis isocitrate lyase is due to decrease in structural plasticity and collective motions of the active site.

PubMed

Shukla, Rohit; Shukla, Harish; Tripathi, Timir

2018-01-01

Mycobacterium tuberculosis isocitrate lyase (MtbICL) is a crucial enzyme of the glyoxylate cycle and is a validated anti-tuberculosis drug target. Structurally distant, non-active site mutation (H46A) in MtbICL has been found to cause loss of enzyme activity. The aim of the present work was to explore the structural alterations induced by H46A mutation that caused the loss of enzyme activity. The structural and dynamic consequences of H46A mutation were studied using multiple computational methods such as docking, molecular dynamics simulation and residue interaction network analysis (RIN). Principal component analysis and cross correlation analysis revealed the difference in conformational flexibility and collective modes of motions between the wild-type and mutant enzyme, particularly in the active site region. RIN analysis revealed that the active site geometry was disturbed in the mutant enzyme. Thus, the dynamic perturbation of the active site led to enzyme transition from its active form to inactive form upon mutation. The computational analyses elucidated the mutant-specific conformational alterations, differential dominant motions, and anomalous residue level interactions that contributed to the abrogated function of mutant MtbICL. An understanding of interactions of mutant enzymes may help in modifying the existing drugs and designing improved drugs for successful control of tuberculosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Resveratrol serves as a protein-substrate interaction stabilizer in human SIRT1 activation

NASA Astrophysics Data System (ADS)

Hou, Xuben; Rooklin, David; Fang, Hao; Zhang, Yingkai

2016-11-01

Resveratrol is a natural compound found in red wine that has been suggested to exert its potential health benefit through the activation of SIRT1, a crucial member of the mammalian NAD+-dependent deacetylases. SIRT1 has emerged as an attractive therapeutic target for many aging related diseases, however, how its activity can only be activated toward some specific substrates by resveratrol has been poorly understood. Herein, by employing extensive molecular dynamics simulations as well as fragment-centric topographical mapping of binding interfaces, we have clarified current controversies in the literature and elucidated that resveratrol plays an important activation role by stabilizing SIRT1/peptide interactions in a substrate-specific manner. This new mechanism highlights the importance of the N-terminal domain in substrate recognition, explains the activity restoration role of resveratrol toward some “loose-binding” substrates of SIRT1, and has significant implications for the rational design of new substrate-specific SIRT1 modulators.

Resveratrol serves as a protein-substrate interaction stabilizer in human SIRT1 activation.

PubMed

Hou, Xuben; Rooklin, David; Fang, Hao; Zhang, Yingkai

2016-11-30

Resveratrol is a natural compound found in red wine that has been suggested to exert its potential health benefit through the activation of SIRT1, a crucial member of the mammalian NAD + -dependent deacetylases. SIRT1 has emerged as an attractive therapeutic target for many aging related diseases, however, how its activity can only be activated toward some specific substrates by resveratrol has been poorly understood. Herein, by employing extensive molecular dynamics simulations as well as fragment-centric topographical mapping of binding interfaces, we have clarified current controversies in the literature and elucidated that resveratrol plays an important activation role by stabilizing SIRT1/peptide interactions in a substrate-specific manner. This new mechanism highlights the importance of the N-terminal domain in substrate recognition, explains the activity restoration role of resveratrol toward some "loose-binding" substrates of SIRT1, and has significant implications for the rational design of new substrate-specific SIRT1 modulators.

Quantitative insights for the design of substrate-based SIRT1 inhibitors.

PubMed

Kokkonen, Piia; Mellini, Paolo; Nyrhilä, Olli; Rahnasto-Rilla, Minna; Suuronen, Tiina; Kiviranta, Päivi; Huhtiniemi, Tero; Poso, Antti; Jarho, Elina; Lahtela-Kakkonen, Maija

2014-08-01

Sirtuin 1 (SIRT1) is the most studied human sirtuin and it catalyzes the deacetylation reaction of acetylated lysine residues of its target proteins, for example histones. It is a promising drug target in the treatment of age-related diseases, such as neurodegenerative diseases and cancer. In this study, a series of known substrate-based sirtuin inhibitors was analyzed with comparative molecular field analysis (CoMFA), which is a three-dimensional quantitative structure-activity relationships (3D-QSAR) technique. The CoMFA model was validated both internally and externally, producing the statistical values concordance correlation coefficient (CCC) of 0.88, the mean value r(2)m of 0.66 and Q(2)F3 of 0.89. Based on the CoMFA interaction contours, 13 new potential inhibitors with high predicted activity were designed, and the activities were verified by in vitro measurements. This work proposes an effective approach for the design and activity prediction of new potential substrate-based SIRT1 inhibitors. Copyright © 2014 Elsevier B.V. All rights reserved.

Ubiquitous learning model using interactive internet messenger group (IIMG) to improve engagement and behavior for smart campus

NASA Astrophysics Data System (ADS)

Umam, K.; Mardi, S. N. S.; Hariadi, M.

2017-01-01

The recent popularity of internet messenger based smartphone technologies has motivated some university lecturers to use them for educational activities. These technologies have enormous potential to enhance the teaching and ubiquitous learning experience for smart campus development. However, the design ubiquitous learning model using interactive internet messenger group (IIMG) and empirical evidence that would favor a broad application of mobile and ubiquitous learning in smart campus settings to improve engagement and behavior is still limited. In addition, the expectation that mobile learning could improve engagement and behavior on smart campus cannot be confirmed because the majority of the reviewed studies followed instructions paradigms. This article aims to present ubiquitous learning model design and showing learners’ experiences in improved engagement and behavior using IIMG for learner-learner and learner-lecturer interactions. The method applied in this paper includes design process and quantitative analysis techniques, with the purpose of identifying scenarios of ubiquitous learning and realize the impressions of learners and lecturers about engagement and behavior aspect, and its contribution to learning.

Use of an Adverse Outcome Pathway for Hepatic Steatosis to Build Chemical Groups

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework systematically documents the mechanisms underlying effects of chemicals starting with the initial interaction of chemicals with the biological system, i.e. the molecular initiating event (MIE). Chemical activity in assays designed to mo...

NUTRIENT AVAILABILITY ALTERS BELOWGROUND RESPIRATION OF OZONE-EXPOSED PONDEROSE PINE

EPA Science Inventory

Exposure to ozone (0-3) and changes in soil fertility influence both the metabolism of plant roots and their interaction with rhizosphere organisms. Because one indication of altered root metabolism is a change in belowground respiratory activity, we used specially designed measu...

School Maker Faires

ERIC Educational Resources Information Center

Harlow, Danielle; Hansen, Alexandria

2018-01-01

The Maker Movement (Dougherty 2012) highlights innovation and creativity through "activities focused on designing, building, modifying, and/or repurposing material objects, for playful or useful ends, oriented toward making a 'product' of some sort that can be used, interacted with, or demonstrated" (Martin 2015, p. 31). When engaged in…

Interaction of vitamin E and exercise training on oxidative stress and antioxidant enzyme activities in rat skeletal muscles.

PubMed

Chang, Chen-Kang; Huang, Hui-Yu; Tseng, Hung-Fu; Hsuuw, Yan-Der; Tso, Tim K

2007-01-01

It has been shown that free radicals are increased during intensive exercise. We hypothesized that vitamin E (vit E) deficiency, which will increase oxidative stress, would augment the training-induced adaptation of antioxidant enzymes. This study investigated the interaction effect of vit E and exercise training on oxidative stress markers and activities of antioxidant enzymes in red quadriceps and white gastrocnemius of rats in a 2x2 design. Thirty-two male rats were divided into trained vit E-adequate, trained vit E-deficient, untrained vit E-adequate, and untrained vit E-deficient groups. The two trained groups swam 6 h/day, 6 days/week for 8 weeks. The two vit E-deficient groups consumed vit E-free diet for 8 weeks. Vitamin E-training interaction effect was significant on thiobarbituric acid reactive substances (TBARSs), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in both muscles. The trained vit E-deficient group showed the highest TBARS and GPX activity and the lowest SOD activity in both muscles. A significant vit E effect on glutathione reductase and catalase was present in both muscles. Glutathione reductase and catalase activities were significantly lower in the two vit E-adequate groups combined than in the two vit E-deficient groups combined in both muscles. This study shows that vit E status and exercise training have interactive effect on oxidative stress and GPX and SOD activities in rat skeletal muscles. Vitamin E deprivation augmented the exercise-induced elevation in GPX activity while inhibiting exercise-induced SOD activity, possibly through elevated oxidative stress.

Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition.

PubMed

van der Meer, Dennis; Hartman, Catharina A; van Rooij, Daan; Franke, Barbara; Heslenfeld, Dirk J; Oosterlaan, Jaap; Faraone, Stephen V; Buitelaar, Jan K; Hoekstra, Pieter J

2017-03-01

Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that individuals carrying the ADHD risk alleles of the dopamine receptor D4 ( DRD4 ) and dopamine transporter ( DAT1 ) genes may be especially sensitive to their effects. Functional MRI data, information on prenatal adversities and genetic data were available for 239 adolescents and young adults participating in the multicentre ADHD cohort study NeuroIMAGE (average age 17.3 yr). We analyzed the effects of DRD4 and DAT1 , prenatal exposure to alcohol and smoking and their interactions on ADHD severity, response inhibition and neural activity. We found no significant gene × environment interaction effects. We did find that the DRD4 7-repeat allele was associated with less superior frontal and parietal brain activity and with greater activity in the frontal pole and occipital cortex. Prenatal exposure to smoking was also associated with lower superior frontal activity, but with greater activity in the parietal lobe. Further, those exposed to alcohol had more activity in the lateral orbitofrontal cortex, and the DAT1 risk variant was associated with lower cerebellar activity. Retrospective reports of maternal substance use and the cross-sectional study design restrict causal inference. While we found no evidence of gene × environment interactions, the risk factors under investigation influenced activity of brain regions associated with response inhibition, suggesting they may add to problems with inhibiting behaviour.

Neighborhood Design, Physical Activity, and Wellbeing: Applying the Walkability Model.

PubMed

Zuniga-Teran, Adriana A; Orr, Barron J; Gimblett, Randy H; Chalfoun, Nader V; Guertin, David P; Marsh, Stuart E

2017-01-13

Neighborhood design affects lifestyle physical activity, and ultimately human wellbeing. There are, however, a limited number of studies that examine neighborhood design types. In this research, we examine four types of neighborhood designs: traditional development, suburban development, enclosed community, and cluster housing development, and assess their level of walkability and their effects on physical activity and wellbeing. We examine significant associations through a questionnaire ( n = 486) distributed in Tucson, Arizona using the Walkability Model. Among the tested neighborhood design types, traditional development showed significant associations and the highest value for walkability, as well as for each of the two types of walking (recreation and transportation) representing physical activity. Suburban development showed significant associations and the highest mean values for mental health and wellbeing. Cluster housing showed significant associations and the highest mean value for social interactions with neighbors and for perceived safety from crime. Enclosed community did not obtain the highest means for any wellbeing benefit. The Walkability Model proved useful in identifying the walkability categories associated with physical activity and perceived crime. For example, the experience category was strongly and inversely associated with perceived crime. This study provides empirical evidence of the importance of including vegetation, particularly trees, throughout neighborhoods in order to increase physical activity and wellbeing. Likewise, the results suggest that regular maintenance is an important strategy to improve mental health and overall wellbeing in cities.

Neighborhood Design, Physical Activity, and Wellbeing: Applying the Walkability Model

PubMed Central

Zuniga-Teran, Adriana A.; Orr, Barron J.; Gimblett, Randy H.; Chalfoun, Nader V.; Guertin, David P.; Marsh, Stuart E.

2017-01-01

Neighborhood design affects lifestyle physical activity, and ultimately human wellbeing. There are, however, a limited number of studies that examine neighborhood design types. In this research, we examine four types of neighborhood designs: traditional development, suburban development, enclosed community, and cluster housing development, and assess their level of walkability and their effects on physical activity and wellbeing. We examine significant associations through a questionnaire (n = 486) distributed in Tucson, Arizona using the Walkability Model. Among the tested neighborhood design types, traditional development showed significant associations and the highest value for walkability, as well as for each of the two types of walking (recreation and transportation) representing physical activity. Suburban development showed significant associations and the highest mean values for mental health and wellbeing. Cluster housing showed significant associations and the highest mean value for social interactions with neighbors and for perceived safety from crime. Enclosed community did not obtain the highest means for any wellbeing benefit. The Walkability Model proved useful in identifying the walkability categories associated with physical activity and perceived crime. For example, the experience category was strongly and inversely associated with perceived crime. This study provides empirical evidence of the importance of including vegetation, particularly trees, throughout neighborhoods in order to increase physical activity and wellbeing. Likewise, the results suggest that regular maintenance is an important strategy to improve mental health and overall wellbeing in cities. PMID:28098785

Stable isotope-assisted NMR characterization of interaction between lipid A and sarcotoxin IA, a cecropin-type antibacterial peptide

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

Yagi-Utsumi, Maho; Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603; Yamaguchi, Yoshiki

Highlights: ► Recombinant sarcotoxin IA was successfully produced with {sup 13}C- and {sup 15}N-labeling. ► Sarcotoxin IA adopts an N-terminal α-helix upon binding to lipid A-embedding micelles. ► Two lysine residues are involved in lipid A-mediated antibacterial activities. -- Abstract: Sarcotoxin IA is a 39-residue cecropin-type peptide from Sarcophaga peregrina. This peptide exhibits antibacterial activity against Gram-negative bacteria through its interaction with lipid A, a core component of lipopolysaccharides. To acquire detailed structural information on this specific interaction, we performed NMR analysis using bacterially expressed sarcotoxin IA analogs with {sup 13}C- and {sup 15}N-labeling along with lipid A-embedding micelles composedmore » of dodecylphosphocholine. By inspecting the stable isotope-assisted NMR data, we revealed that the N-terminal segment (Leu3–Arg18) of sarcotoxin IA formed an amphiphilic α-helix upon its interaction with the aqueous micelles. Furthermore, chemical shift perturbation data indicated that the amino acid residues displayed on this α-helix were involved in the specific interaction with lipid A. On the basis of these data, we successfully identified Lys4 and Lys5 as key residues in the interaction with lipid A and the consequent antibacterial activity. Therefore, these results provide unique information for designing chemotherapeutics based on antibacterial peptide structures.« less

The application of quantum mechanics in structure-based drug design.

PubMed

Mucs, Daniel; Bryce, Richard A

2013-03-01

Computational chemistry has become an established and valuable component in structure-based drug design. However the chemical complexity of many ligands and active sites challenges the accuracy of the empirical potentials commonly used to describe these systems. Consequently, there is a growing interest in utilizing electronic structure methods for addressing problems in protein-ligand recognition. In this review, the authors discuss recent progress in the development and application of quantum chemical approaches to modeling protein-ligand interactions. The authors specifically consider the development of quantum mechanics (QM) approaches for studying large molecular systems pertinent to biology, focusing on protein-ligand docking, protein-ligand binding affinities and ligand strain on binding. Although computation of binding energies remains a challenging and evolving area, current QM methods can underpin improved docking approaches and offer detailed insights into ligand strain and into the nature and relative strengths of complex active site interactions. The authors envisage that QM will become an increasingly routine and valued tool of the computational medicinal chemist.

The effects of Andrographis paniculata (Burm.f.) Nees extract and diterpenoids on the CYP450 isoforms' activities, a review of possible herb-drug interaction risks.

PubMed

Tan, Mei Lan; Lim, Lin Ee

2015-01-01

Andrographis paniculata (Burm.f.) Nees is a popular medicinal plant and its components are used in various traditional product preparations. However, its herb-drug interactions risks remain unclear. This review specifically discusses the various published studies carried out to evaluate the effects of Andrographis paniculata (Burm.f.) Nees plant extracts and diterpenoids on the CYP450 metabolic enzyme and if the plant components pose a possible herb-drug interaction risk. Unfortunately, the current data are insufficient to indicate if the extracts or diterpenoids can be labeled as in vitro CYP1A2, CYP2C9 or CYP3A4 inhibitors. A complete CYP inhibition assay utilizing human liver microsomes and the derivation of relevant parameters to predict herb-drug interaction risks may be necessary for these isoforms. However, based on the current studies, none of the extracts and diterpenoids exhibited CYP450 induction activity in human hepatocytes or human-derived cell lines. It is crucial that a well-defined experimental design is needed to make a meaningful herb-drug interaction prediction.

Criteria for Public Open Space Enhancement to Achieve Social Interaction: a Review Paper

NASA Astrophysics Data System (ADS)

Salih, S. A.; Ismail, S.

2017-12-01

A This paper presents a various literatures, studies, transcripts and papers aiming to provide an overview of some theories and existing research on the significance of natural environments and green open spaces to achieve social interaction and outdoor recreation. The main objective of the paper is to identify the factors that affecting social interaction in green open spaces, through proving that an appropriate open spaces is important to enhance social interaction and community. This study employs (qualitative) summarizing content analysis method which mainly focused on collect and summarizing of documentation such as transcripts, articles, papers, and books from more than 25 source, regarding the importance of public open spaces for the community. The summarizing content analysis of this paper is the fundament for a qualitative oriented procedure of text interpretation used to analyse the information gathered. Results of this study confirms that sound social interaction need an appropriate physical space including criteria of: design, activities, access and linkage, administration and maintenance, place attachment and users’ characteristics, also previous studies in this area have a health perspective with measures of physical activity of open spaces in general.

Effects of interactive technology, teacher scaffolding and feedback on university students' conceptual development in motion and force concepts

NASA Astrophysics Data System (ADS)

Stecklein, Jason Jeffrey

The utilization of interactive technologies will affect learning in science classrooms of the future. And although these technologies have improved in form and function, their effective employment in university science classrooms has lagged behind the rapid development of new constructivist pedagogies and means of instruction. This dissertation examines the enlistment of instructional technologies, in particular tablet PCs and DyKnow Interactive Software, in a technologically enhanced, university-level, introductory physics course. Results of this qualitative case study of three university students indicate that (1) the use of interactive technology positively affects both student learning within force and motion and self-reported beliefs about physics, (2) ad hoc use of instructional technologies may not sufficient for effective learning in introductory physics, (3) student learners dictate the leveraging of technology in any classroom, and (4) that purposeful teacher structuring of classroom activities with technologies are essential for student construction of knowledge. This includes designing activities to elicit attention and make knowledge visible for low-level content, while augmenting student interactions and modelling procedural steps for higher-level content.

Delivering health information about self-medication to older adults: use of touchscreen-equipped notebook computers.

PubMed

Neafsey, P J; Strickler, Z; Shellman, J; Padula, A T

2001-11-01

Preventing Drug Interactions in Active Older Adults is an educational intervention to prevent prescription and over-the-counter (OTC) drug and alcohol interactions in active, community-living older adults. The objectives of the program are to increase older adults' knowledge of potential interactions of prescription medications with OTC drugs and alcohol and to increase their confidence (self-efficacy) about how to avoid such interactions. An interactive multimedia computer software program (Personal Education Program or PEP) was designed for the learning styles and psychomotor skills of older adults. Focus groups of older adults evaluated PEP components in a formative manner during development. The program content dealing with antacids, calcium supplements, and acid reducers was pilot tested with 60 older adults recruited from local senior centers. Participants used the PEP on notebook computers equipped with infrared-sensitive touchscreens. Users of PEP had greater knowledge and self-efficacy scores than controls. Participants indicated a high degree of satisfaction with the PEP and reported their intent to make specific changes in self-medication behaviors.

Automatic Scheduling and Planning (ASAP) in future ground control systems

NASA Technical Reports Server (NTRS)

Matlin, Sam

1988-01-01

This report describes two complementary approaches to the problem of space mission planning and scheduling. The first is an Expert System or Knowledge-Based System for automatically resolving most of the activity conflicts in a candidate plan. The second is an Interactive Graphics Decision Aid to assist the operator in manually resolving the residual conflicts which are beyond the scope of the Expert System. The two system designs are consistent with future ground control station activity requirements, support activity timing constraints, resource limits and activity priority guidelines.

Touch increases autonomic coupling between romantic partners

PubMed Central

Chatel-Goldman, Jonas; Congedo, Marco; Jutten, Christian; Schwartz, Jean-Luc

2014-01-01

Interpersonal touch is of paramount importance in human social bonding and close relationships, allowing a unique channel for affect communication. So far the effect of touch on human physiology has been studied at an individual level. The present study aims at extending the study of affective touch from isolated individuals to truly interacting dyads. We have designed an ecological paradigm where romantic partners interact only via touch and we manipulate their empathic states. Simultaneously, we collected their autonomic activity (skin conductance, pulse, respiration). Fourteen couples participated to the experiment. We found that interpersonal touch increased coupling of electrodermal activity between the interacting partners, regardless the intensity and valence of the emotion felt. In addition, physical touch induced strong and reliable changes in physiological states within individuals. These results support an instrumental role of interpersonal touch for affective support in close relationships. Furthermore, they suggest that touch alone allows the emergence of a somatovisceral resonance between interacting individuals, which in turn is likely to form the prerequisites for emotional contagion and empathy. PMID:24734009

An Elective Course in Aromatherapy Science

PubMed Central

Bystrek, Mary V.; Klein, JoAnn S.

2014-01-01

Objective. To evaluate the impact of an innovative team-taught elective course on second-year (P2) students’ knowledge and skills relating to the relationship between aromatherapy and pharmacy. Design. An Aromatherapy Science elective course was offered to P2 students in an accelerated doctor of pharmacy (PharmD) degree program and was designed to provide an elective course experience while focusing on active-learning skills such as group work, student-led presentations, and in-class activities. Lectures were designed to reinforce core curricular threads from the basic sciences within the pharmaceutical sciences department while highlighting key aromatherapy principles. Assessment. Course evaluations, grades, and student self-assessments were used to evaluate student fulfillment and knowledge gained. Students agreed this hands-on course integrated pharmaceutical science experiences, enriched their pharmacy education, and provided knowledge to enhance their confidence in describing essential oil uses, drug interactions, and key aromatherapy clinical implications. Conclusion. Students agreed this course prepared them to identify essential oil therapeutic uses and potential essential oil-drug interactions, and interpret literature. The introduction of aromatherapy principles to pharmacy students will prepare a new generation of healthcare professionals on the role of alternative medicines. PMID:24850941

Binding of [alpha, alpha]-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design

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

Ilies, Monica; Di Costanzo, Luigi; Dowling, Daniel P.

Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to form L-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase I, we now report the first study of the binding of {alpha},{alpha}-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase Imore » and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the L-stereoisomer; the additional {alpha}-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase.« less

Active Correction of Aperture Discontinuities-Optimized Stroke Minimization. I. A New Adaptive Interaction Matrix Algorithm

NASA Astrophysics Data System (ADS)

Mazoyer, J.; Pueyo, L.; N'Diaye, M.; Fogarty, K.; Zimmerman, N.; Leboulleux, L.; St. Laurent, K. E.; Soummer, R.; Shaklan, S.; Norman, C.

2018-01-01

Future searches for bio-markers on habitable exoplanets will rely on telescope instruments that achieve extremely high contrast at small planet-to-star angular separations. Coronagraphy is a promising starlight suppression technique, providing excellent contrast and throughput for off-axis sources on clear apertures. However, the complexity of space- and ground-based telescope apertures goes on increasing over time, owing to the combination of primary mirror segmentation, the secondary mirror, and its support structures. These discontinuities in the telescope aperture limit the coronagraph performance. In this paper, we present ACAD-OSM, a novel active method to correct for the diffractive effects of aperture discontinuities in the final image plane of a coronagraph. Active methods use one or several deformable mirrors that are controlled with an interaction matrix to correct for the aberrations in the pupil. However, they are often limited by the amount of aberrations introduced by aperture discontinuities. This algorithm relies on the recalibration of the interaction matrix during the correction process to overcome this limitation. We first describe the ACAD-OSM technique and compare it to the previous active methods for the correction of aperture discontinuities. We then show its performance in terms of contrast and off-axis throughput for static aperture discontinuities (segmentation, struts) and for some aberrations evolving over the life of the instrument (residual phase aberrations, artifacts in the aperture, misalignments in the coronagraph design). This technique can now obtain the Earth-like planet detection threshold of {10}10 contrast on any given aperture over at least a 10% spectral bandwidth, with several coronagraph designs.

Mesoscale Thermodynamic Analysis of Atomic-Scale Dislocation-Obstacle Interactions Simulated by Molecular Dynamics

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

Monet, Giath; Bacon, David J; Osetskiy, Yury N

2010-01-01

Given the time and length scales in molecular dynamics (MD) simulations of dislocation-defect interactions, quantitative MD results cannot be used directly in larger scale simulations or compared directly with experiment. A method to extract fundamental quantities from MD simulations is proposed here. The first quantity is a critical stress defined to characterise the obstacle resistance. This mesoscopic parameter, rather than the obstacle 'strength' designed for a point obstacle, is to be used for an obstacle of finite size. At finite temperature, our analyses of MD simulations allow the activation energy to be determined as a function of temperature. The resultsmore » confirm the proportionality between activation energy and temperature that is frequently observed by experiment. By coupling the data for the activation energy and the critical stress as functions of temperature, we show how the activation energy can be deduced at a given value of the critical stress.« less

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

Li, Yong; Choi, Mihwa; Cavey, Greg

The orphan nuclear receptor steroidogenic factor 1 (SF-1) regulates the differentiation and function of endocrine glands. Although SF-1 is constitutively active in cell-based assays, it is not known whether this transcriptional activity is modulated by ligands. Here, we describe the 1.5 {angstrom} crystal structure of the SF-1 ligand binding domain in complex with an LXXLL motif from a coregulator protein. The structure reveals the presence of a phospholipid ligand in a surprisingly large pocket ({approx}1600 {angstrom}{sup 3}), with the receptor adopting the canonical active conformation. The bound phospholipid is readily exchanged and modulates SF-1 interactions with coactivators. Mutations designed tomore » reduce the size of the SF-1 pocket or to disrupt hydrogen bonds with the phospholipid abolish SF-1/coactivator interactions and significantly reduce SF-1 transcriptional activity. These findings provide evidence that SF-1 is regulated by endogenous ligands and suggest an unexpected relationship between phospholipids and endocrine development and function.« less

Virtual screening of selective inhibitors of phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis

NASA Astrophysics Data System (ADS)

Podshivalov, D. D.; Timofeev, V. I.; Sidorov-Biryukov, D. D.; Kuranova, I. P.

2017-05-01

Bacterial phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis (PPAT Mt) is a convenient target protein for the directed search for selective inhibitors as potent antituberculosis drugs. Four compounds suitable for the detailed investigation of their interactions with PPAT Mt were found by virtual screening. The active-site region of the enzyme was chosen as the ligand-binding site. The positions of the ligands found by the docking were refined by molecular dynamics simulation. The nearest environment of the ligands, the positions of which in the active site of the enzyme were found in a computational experiment, was analyzed. The compounds under consideration were shown to directly interact with functionally important active-site amino-acid residues and block access of substrates to the active site. Therefore, these compounds can be used for the design of selective inhibitors of PPAT Mt as potent antituberculosis drugs.

Evaluating differences in the active-site electronics of supported Au nanoparticle catalysts using Hammett and DFT studies

NASA Astrophysics Data System (ADS)

Kumar, Gaurav; Tibbitts, Luke; Newell, Jaclyn; Panthi, Basu; Mukhopadhyay, Ahana; Rioux, Robert M.; Pursell, Christopher J.; Janik, Michael; Chandler, Bert D.

2018-03-01

Supported metal catalysts, which are composed of metal nanoparticles dispersed on metal oxides or other high-surface-area materials, are ubiquitous in industrially catalysed reactions. Identifying and characterizing the catalytic active sites on these materials still remains a substantial challenge, even though it is required to guide rational design of practical heterogeneous catalysts. Metal-support interactions have an enormous impact on the chemistry of the catalytic active site and can determine the optimum support for a reaction; however, few direct probes of these interactions are available. Here we show how benzyl alcohol oxidation Hammett studies can be used to characterize differences in the catalytic activity of Au nanoparticles hosted on various metal-oxide supports. We combine reactivity analysis with density functional theory calculations to demonstrate that the slope of experimental Hammett plots is affected by electron donation from the underlying oxide support to the Au particles.

Decentralized Control of Sound Radiation using a High-Authority/Low-Authority Control Strategy with Anisotropic Actuators

NASA Technical Reports Server (NTRS)

Schiller, Noah H.; Cabell, Randolph H.; Fuller, Chris R.

2008-01-01

This paper describes a combined control strategy designed to reduce sound radiation from stiffened aircraft-style panels. The control architecture uses robust active damping in addition to high-authority linear quadratic Gaussian (LQG) control. Active damping is achieved using direct velocity feedback with triangularly shaped anisotropic actuators and point velocity sensors. While active damping is simple and robust, stability is guaranteed at the expense of performance. Therefore the approach is often referred to as low-authority control. In contrast, LQG control strategies can achieve substantial reductions in sound radiation. Unfortunately, the unmodeled interaction between neighboring control units can destabilize decentralized control systems. Numerical simulations show that combining active damping and decentralized LQG control can be beneficial. In particular, augmenting the in-bandwidth damping supplements the performance of the LQG control strategy and reduces the destabilizing interaction between neighboring control units.

Regulation of PLCβ2 by the electrostatic and mechanical properties of lipid bilayers

PubMed Central

Arduin, Alessia; Gaffney, Piers R. J.; Ces, Oscar

2015-01-01

Phosphoinositide-specific phospholipase C (PLC) is an important family of enzymes constituting a junction between phosphoinositide lipid signaling and the trans-membrane signal transduction processes that are crucial to many living cells. However, the regulatory mechanism of PLC is not yet understood in detail. To address this issue, activity studies were carried out using lipid vesicles in a model system that was specifically designed to study protein-protein and lipid-protein interactions in concert. Evidence was found for a direct interaction between PLC and the GTPases that mediate phospholipase activation. Furthermore, for the first time, the relationships between PLC activity and substrate presentation in lipid vesicles of various sizes, as well as lipid composition and membrane mechanical properties, were analyzed. PLC activity was found to depend upon the electrostatic potential and the stored curvature elastic stress of the lipid membranes. PMID:26243281

Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side.

PubMed

Lin, Kuan-Hung; Ali, Akbar; Rusere, Linah; Soumana, Djade I; Kurt Yilmaz, Nese; Schiffer, Celia A

2017-05-15

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein with high affinity for DENV protease. In this study, we designed a series of cyclic peptides interacting with both sides of the active site as inhibitors of dengue virus protease. The design was based on two aprotinin loops and aimed to leverage both key specific interactions of substrate sequences and the entropic advantage driving aprotinin's high affinity. By optimizing the cyclization linker, length, and amino acid sequence, the tightest cyclic peptide achieved a K i value of 2.9 μM against DENV3 wild-type (WT) protease. These inhibitors provide proof of concept that both sides of DENV protease active site can be exploited to potentially achieve specificity and lower hydrophilicity in the design of inhibitors targeting DENV. IMPORTANCE Viruses of the flaviviral family, including DENV and Zika virus transmitted by Aedes aegypti , continue to be a threat to global health by causing major outbreaks in tropical and subtropical regions, with no available direct-acting antivirals for treatment. A better understanding of the molecular requirements for the design of potent and specific inhibitors against flaviviral proteins will contribute to the development of targeted therapies for infections by these viruses. The cyclic peptides reported here as DENV protease inhibitors provide novel scaffolds that enable exploiting the prime side of the protease active site, with the aim of achieving better specificity and lower hydrophilicity than those of current scaffolds in the design of antiflaviviral inhibitors. Copyright © 2017 American Society for Microbiology.

Molecular docking, molecular modeling, and molecular dynamics studies of azaisoflavone as dual COX-2 inhibitors and TP receptor antagonists.

PubMed

Hadianawala, Murtuza; Mahapatra, Amarjyoti Das; Yadav, Jitender K; Datta, Bhaskar

2018-02-26

Designed multi-target ligand (DML) is an emerging strategy for the development of new drugs and involves the engagement of multiple targets with the same moiety. In the context of NSAIDs it has been suggested that targeting the thromboxane prostanoid (TP) receptor along with cyclooxygenase-2 (COX-2) may help to overcome cardiovascular (CVS) complications associated with COXIBs. In the present work, azaisoflavones were studied for their COX-2 and TP receptor binding activities using structure based drug design (SBDD) techniques. Flavonoids were selected as a starting point based on their known COX-2 inhibitory and TP receptor antagonist activity. Iterative design and docking studies resulted in the evolution of a new class scaffold replacing the benzopyran-4-one ring of flavonoids with quinolin-4-one. The docking and binding parameters of these new compounds are found to be promising in comparison to those of selective COX-2 inhibitors, such as SC-558 and celecoxib. Owing to the lack of structural information, a model for the TP receptor was generated using a threading base alignment method with loop optimization performed using an ab initio method. The model generated was validated against known antagonists for TP receptor using docking/MMGBSA. Finally, the molecules that were designed for selective COX-2 inhibition were docked into the active site of the TP receptor. Iterative structural modifications and docking on these molecules generated a series which displays optimum docking scores and binding interaction for both targets. Molecular dynamics studies on a known TP receptor antagonist and a designed molecule show that both molecules remain in contact with protein throughout the simulation and interact in similar binding modes. Graphical abstract ᅟ.

Design Elements and Feasibility of an Organized Multiplayer Mobile Active Videogame for Primary School-Aged Children.

PubMed

McKenzie, Sophie; Bangay, Shaun; Barnett, Lisa M; Ridgers, Nicola D; Salmon, Jo

2014-12-01

This article describes the design, development, and implementation feasibility of a purpose-built mobile active videogame (M-AVG) named "Pirate Adventure," which was designed for primary school-aged children to engage in physical activity (PA) and fundamental movement skills (FMS), such as hopping, sidestepping, jumping, or running, in an afterschool setting. The design of "Pirate Adventure" was the result of a collaboration between games designers and health researchers. "Pirate Adventure" was designed and developed using Android(®) (Google, Mountain View, CA) phone sensors to respond to player actions within a playground environment. Using an interactive game framework, players solve clues and complete PA and FMS challenges via sensing the physical world through marked-out key game locations. Fourteen primary school-aged children participated in the feasibility evaluation, which took place in four afternoon sessions. The game was evaluated using Android phone telemetry data and a post-gameplay survey for children on their opinions and enjoyment of the game. The "Pirate Adventure" game design facilitated an enjoyable treasure hunt game (average of 11 minutes of activity per game) with narrative elements supporting children's engagement with movement activities. The majority of children (n=9/13) reported that they would like to play the game again. Combining real world and virtual world content through "Pirate Adventure" was moderately successful, with multiple gameplay sessions occurring. Further implementation feasibility testing, under more controlled conditions, needs to be conducted to assert the benefits of using a M-AVG for children's PA and FMS.

Urban Space Explorer: A Visual Analytics System for Urban Planning.

PubMed

Karduni, Alireza; Cho, Isaac; Wessel, Ginette; Ribarsky, William; Sauda, Eric; Dou, Wenwen

2017-01-01

Understanding people's behavior is fundamental to many planning professions (including transportation, community development, economic development, and urban design) that rely on data about frequently traveled routes, places, and social and cultural practices. Based on the results of a practitioner survey, the authors designed Urban Space Explorer, a visual analytics system that utilizes mobile social media to enable interactive exploration of public-space-related activity along spatial, temporal, and semantic dimensions.

Calorimetric studies of the interactions of metalloenzyme active site mimetics with zinc-binding inhibitors.

PubMed

Robinson, Sophia G; Burns, Philip T; Miceli, Amanda M; Grice, Kyle A; Karver, Caitlin E; Jin, Lihua

2016-07-19

The binding of drugs to metalloenzymes is an intricate process that involves several interactions, including binding of the drug to the enzyme active site metal, as well as multiple interactions between the drug and the enzyme residues. In order to determine the free energy contribution of Zn(2+) binding by known metalloenzyme inhibitors without the other interactions, valid active site zinc structural mimetics must be formed and binding studies need to be performed in biologically relevant conditions. The potential of each of five ligands to form a structural mimetic with Zn(2+) was investigated in buffer using Isothermal Titration Calorimetry (ITC). All five ligands formed strong 1 : 1 (ligand : Zn(2+)) binary complexes. The complexes were used in further ITC experiments to study their interaction with 8-hydroxyquinoline (8-HQ) and/or acetohydroxamic acid (AHA), two bidentate anionic zinc-chelating enzyme inhibitors. It was found that tetradentate ligands were not suitable for creating zinc structural mimetics for inhibitor binding in solution due to insufficient coordination sites remaining on Zn(2+). A stable binary complex, [Zn(BPA)](2+), which was formed by a tridentate ligand, bis(2-pyridylmethyl)amine (BPA), was found to bind one AHA in buffer or a methanol : buffer mixture (60 : 40 by volume) at pH 7.25 or one 8-HQ in the methanol : buffer mixture at pH 6.80, making it an effective structural mimetic for the active site of zinc metalloenzymes. These results are consistent with the observation that metalloenzyme active site zinc ions have three residues coordinated to them, leaving one or two sites open for inhibitors to bind. Our findings indicate that Zn(BPA)X2 can be used as an active site structural mimetic for zinc metalloenzymes for estimating the free energy contribution of zinc binding to the overall inhibitor active site interactions. Such use will help aid in the rational design of inhibitors to a variety of zinc metalloenzymes.

Arginine 26 and aspartic acid 69 of the regulatory subunit are key residues of subunits interaction of acetohydroxyacid synthase isozyme III from E. coli.

PubMed

Zhao, Yuefang; Wen, Xin; Niu, Congwei; Xi, Zhen

2012-11-05

Acetohydroxyacid synthase (AHAS), which catalyzes the first step in the biosynthesis of branched-chain amino acids, is composed of catalytic and regulatory subunits. The enzyme exhibits full activity only when the regulatory subunit (RSU) binds to the catalytic subunit (CSU). However, the crystal structure of the holoenzyme has not been reported yet, and the molecular interaction between the CSU and RSU is also unknown. Herein, we introduced a global-surface, site-directed labeling scanning method to determine the potential interaction region of the RSU. This approach relies on the insertion of a bulky fluorescent probe at the designated site on the surface of the RSU to cause a dramatic change in holoenzyme activity by perturbing subunit interaction. Then, the key amino acid residues in the potential interaction regions were identified by site-directed mutagenesis. Compared to the wild-type, the single-point mutants R26A and D69A showed 54 and 64 % activity, respectively, whereas the double mutant (R26A+D69A) gave 14 %, thus suggesting that residues Arg26 and Asp69 are the key residues of subunit interaction with cooperative action. Additionally, the results of GST pull-down assays and pH-dependence experiments suggested that polar interaction is the main force for subunits interaction. A plausible protein-protein interaction model of the holoenzyme of Escherichia coli AHAS III is proposed, based on the mutagenesis and protein docking studies. The protocol established here should be useful for the identification of the molecular interactions between proteins. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Active penetration of Trypanosoma cruzi into host cells: historical considerations and current concepts

PubMed Central

de Souza, Wanderley; de Carvalho, Tecia M. Ulisses

2013-01-01

In the present short review, we analyze past experiments that addressed the interactions of intracellular pathogenic protozoa (Trypanosoma cruzi, Toxoplasma gondii, and Plasmodium) with host cells and the initial use of the term active penetration to indicate that a protozoan “crossed the host cell membrane, penetrating into the cytoplasm.” However, the subsequent use of transmission electron microscopy showed that, for all of the protozoans and cell types examined, endocytosis, classically defined as involving the formation of a membrane-bound vacuole, took place during the interaction process. As a consequence, the recently penetrated parasites are always within a vacuole, designated the parasitophorous vacuole (PV). PMID:23355838

Bauhinia proteinase inhibitor-based synthetic fluorogenic substrates for enzymes isolated from insect midgut and caterpillar bristles.

PubMed

Andrade, Sonia A; Santomauro-Vaz, Eugênio M; Lopes, Adriana R; Chudzinski-Tavassi, Ana M; Juliano, Maria A; Terra, Walter R; Sampaio, Misako U; Sampaio, Claudio A M; Oliva, Maria Luiza V

2003-03-01

Bauhinia ungulata factor Xa inhibitor (BuXI) inactivates factor Xa and LOPAP, a prothrombin activator proteinase isolated from the venom of Lonomia obliqua caterpillar bristles. The reactive site of the enzyme-inhibitor interaction was explored to design specific substrates for both enzymes. Methionine is crucial for LOPAP and factor Xa substrate interaction, since the change of both Met residues in the substrates abolished the hydrolysis. Synthetic substrates containing the sequence around the reactive site of BbKI, a plasma kallikrein inhibitor, were shown to be specific for trypsin hydrolysis. Therefore, these substrates may be an alternative in studies aiming at a characterization of trypsin-like enzyme activities, especially non-mammalian enzymes.

Recent Developments in Smart Adaptive Structures for Solar Sailcraft

NASA Technical Reports Server (NTRS)

Whorton, M. S.; Kim, Y. K.; Oakley, J.; Adetona, O.; Keel, L. H.

2007-01-01

The "Smart Adaptive Structures for Solar Sailcraft" development activity at MSFC has investigated issues associated with understanding how to model and scale the subsystem and multi-body system dynamics of a gossamer solar sailcraft with the objective of designing sailcraft attitude control systems. This research and development activity addressed three key tasks that leveraged existing facilities and core competencies of MSFC to investigate dynamics and control issues of solar sails. Key aspects of this effort included modeling and testing of a 30 m deployable boom; modeling of the multi-body system dynamics of a gossamer sailcraft; investigation of control-structures interaction for gossamer sailcraft; and development and experimental demonstration of adaptive control technologies to mitigate control-structures interaction.

Orbital operations study. Appendix A: Interactivity analysis

NASA Technical Reports Server (NTRS)

1972-01-01

Supplemental analyses conducted to verify that safe, feasible, design concepts exist for accomplishing the attendant interface activities of the orbital operations mission are presented. The data are primarily concerned with functions and concepts common to more than one of the interfacing activities or elements. Specific consideration is given to state vector update, payload deployment, communications links, jet plume impingement, attached element operations, docking and structural interface assessment, and propellant transfer.

Design and Synthesis of Highly Potent HIV-1 Protease Inhibitors Containing Tricyclic Fused Ring Systems as Novel P2 Ligands: Structure-Activity Studies, Biological and X-ray Structural Analysis.

PubMed

Ghosh, Arun K; R Nyalapatla, Prasanth; Kovela, Satish; Rao, Kalapala Venkateswara; Brindisi, Margherita; Osswald, Heather L; Amano, Masayuki; Aoki, Manabu; Agniswamy, Johnson; Wang, Yuan-Fang; Weber, Irene T; Mitsuya, Hiroaki

2018-05-24

The design, synthesis, and biological evaluation of a new class of HIV-1 protease inhibitors containing stereochemically defined fused tricyclic polyethers as the P2 ligands and a variety of sulfonamide derivatives as the P2' ligands are described. A number of ring sizes and various substituent effects were investigated to enhance the ligand-backbone interactions in the protease active site. Inhibitors 5c and 5d containing this unprecedented fused 6-5-5 ring system as the P2 ligand, an aminobenzothiazole as the P2' ligand, and a difluorophenylmethyl as the P1 ligand exhibited exceptional enzyme inhibitory potency and maintained excellent antiviral activity against a panel of highly multidrug-resistant HIV-1 variants. The umbrella-like P2 ligand for these inhibitors has been synthesized efficiently in an optically active form using a Pauson-Khand cyclization reaction as the key step. The racemic alcohols were resolved efficiently using a lipase catalyzed enzymatic resolution. Two high resolution X-ray structures of inhibitor-bound HIV-1 protease revealed extensive interactions with the backbone atoms of HIV-1 protease and provided molecular insight into the binding properties of these new inhibitors.

Web-Based Intervention for Women With Type 1 Diabetes in Pregnancy and Early Motherhood: Critical Analysis of Adherence to Technological Elements and Study Design.

PubMed

Berg, Marie; Linden, Karolina; Adolfsson, Annsofie; Sparud Lundin, Carina; Ranerup, Agneta

2018-05-02

Numerous Web-based interventions have been implemented to promote health and health-related behaviors in persons with chronic conditions. Using randomized controlled trials to evaluate such interventions creates a range of challenges, which in turn can influence the study outcome. Applying a critical perspective when evaluating Web-based health interventions is important. The objective of this study was to critically analyze and discuss the challenges of conducting a Web-based health intervention as a randomized controlled trial. The MODIAB-Web study was critically examined using an exploratory case study methodology and the framework for analysis offered through the Persuasive Systems Design model. Focus was on technology, study design, and Web-based support usage, with special focus on the forum for peer support. Descriptive statistics and qualitative content analysis were used. The persuasive content and technological elements in the design of the randomized controlled trial included all four categories of the Persuasive Systems Design model, but not all design principles were implemented. The study duration was extended to a period of four and a half years. Of 81 active participants in the intervention group, a maximum of 36 women were simultaneously active. User adherence varied greatly with a median of 91 individual log-ins. The forum for peer support was used by 63 participants. Although only about one-third of the participants interacted in the forum, there was a fairly rich exchange of experiences and advice between them. Thus, adherence in terms of social interactions was negatively affected by limited active participation due to prolonged recruitment process and randomization effects. Lessons learned from this critical analysis are that technology and study design matter and might mutually influence each other. In Web-based interventions, the use of design theories enables utilization of the full potential of technology and promotes adherence. The randomization element in a randomized controlled trial design can become a barrier to achieving a critical mass of user interactions in Web-based interventions, especially when social support is included. For extended study periods, the technology used may need to be adapted in line with newly available technical options to avoid the risk of becoming outdated in the user realm, which in turn might jeopardize study validity in terms of randomized controlled trial designs. On the basis of lessons learned in this randomized controlled trial, we give recommendations to consider when designing and evaluating Web-based health interventions. ©Marie Berg, Karolina Linden, Annsofie Adolfsson, Carina Sparud Lundin, Agneta Ranerup. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 02.05.2018.

An active site–tail interaction in the structure of hexahistidine-tagged Thermoplasma acidophilum citrate synthase

PubMed Central

Murphy, Jesse R.; Donini, Stefano; Kappock, T. Joseph

2015-01-01

Citrate synthase (CS) plays a central metabolic role in aerobes and many other organisms. The CS reaction comprises two half-reactions: a Claisen aldol condensation of acetyl-CoA (AcCoA) and oxaloacetate (OAA) that forms citryl-CoA (CitCoA), and CitCoA hydrolysis. Protein conformational changes that ‘close’ the active site play an important role in the assembly of a catalytically competent condensation active site. CS from the thermoacidophile Thermoplasma acidophilum (TpCS) possesses an endogenous Trp fluorophore that can be used to monitor the condensation reaction. The 2.2 Å resolution crystal structure of TpCS fused to a C-terminal hexahistidine tag (TpCSH6) reported here is an ‘open’ structure that, when compared with several liganded TpCS structures, helps to define a complete path for active-site closure. One active site in each dimer binds a neighboring His tag, the first nonsubstrate ligand known to occupy both the AcCoA and OAA binding sites. Solution data collectively suggest that this fortuitous interaction is stabilized by the crystalline lattice. As a polar but almost neutral ligand, the active site–tail interaction provides a new starting point for the design of bisubstrate-analog inhibitors of CS. PMID:26457521

An active site-tail interaction in the structure of hexahistidine-tagged Thermoplasma acidophilum citrate synthase

DOE PAGES

Murphy, Jesse R.; Donini, Stefano; Kappock, T. Joseph

2015-10-01

Citrate synthase (CS) plays a central metabolic role in aerobes and many other organisms. The CS reaction comprises two half-reactions: a Claisen aldol condensation of acetyl-CoA (AcCoA) and oxaloacetate (OAA) that forms citryl-CoA (CitCoA), and CitCoA hydrolysis. Protein conformational changes that `close' the active site play an important role in the assembly of a catalytically competent condensation active site. CS from the thermoacidophile Thermoplasma acidophilum (TpCS) possesses an endogenous Trp fluorophore that can be used to monitor the condensation reaction. The 2.2 Å resolution crystal structure of TpCS fused to a C-terminal hexahistidine tag (TpCSH6) reported here is an `open'more » structure that, when compared with several liganded TpCS structures, helps to define a complete path for active-site closure. One active site in each dimer binds a neighboring His tag, the first nonsubstrate ligand known to occupy both the AcCoA and OAA binding sites. Solution data collectively suggest that this fortuitous interaction is stabilized by the crystalline lattice. In conclusion, as a polar but almost neutral ligand, the active site-tail interaction provides a new starting point for the design of bisubstrate-analog inhibitors of CS.« less

An active site-tail interaction in the structure of hexahistidine-tagged Thermoplasma acidophilum citrate synthase.

PubMed

Murphy, Jesse R; Donini, Stefano; Kappock, T Joseph

2015-10-01

Citrate synthase (CS) plays a central metabolic role in aerobes and many other organisms. The CS reaction comprises two half-reactions: a Claisen aldol condensation of acetyl-CoA (AcCoA) and oxaloacetate (OAA) that forms citryl-CoA (CitCoA), and CitCoA hydrolysis. Protein conformational changes that `close' the active site play an important role in the assembly of a catalytically competent condensation active site. CS from the thermoacidophile Thermoplasma acidophilum (TpCS) possesses an endogenous Trp fluorophore that can be used to monitor the condensation reaction. The 2.2 Å resolution crystal structure of TpCS fused to a C-terminal hexahistidine tag (TpCSH6) reported here is an `open' structure that, when compared with several liganded TpCS structures, helps to define a complete path for active-site closure. One active site in each dimer binds a neighboring His tag, the first nonsubstrate ligand known to occupy both the AcCoA and OAA binding sites. Solution data collectively suggest that this fortuitous interaction is stabilized by the crystalline lattice. As a polar but almost neutral ligand, the active site-tail interaction provides a new starting point for the design of bisubstrate-analog inhibitors of CS.

Inhibitors for the Vitamin D Receptor–Coregulator Interaction

PubMed Central

Teske, Kelly A.; Yu, Olivia; Arnold, Leggy A.

2016-01-01

The vitamin D receptor (VDR) belongs to the superfamily of nuclear receptors and is activated by the endogenous ligand 1,25-dihydroxyvitamin D3. The genomic effects mediated by VDR consist of the activation and repression of gene transcription, which includes the formation of multi-protein complexes with coregulator proteins. Coregulators bind many nuclear receptors and can be categorized according their role as coactivators (gene activation) or corepressors (gene repression). Herein, different approaches to develop compounds that modulate the interaction between VDR and coregulators are summarized. This include coregulator peptides that were identified by creating phage display libraries. Subsequent modification of these peptides including the introduction of a tether or non-hydrolysable bonds resulted in the first direct VDR–coregulator inhibitors. Later, small molecules that inhibit VDR–coregulator inhibitors were identified using rational drug design and high throughput screening. Early on, allosteric inhibition of VDR–coregulator interactions was achieved with VDR antagonists that change the conformation of VDR and modulate the interactions with coregulators. A detailed discussion of their dual agonist/antagonist effects is given as well as a summary of their biological effects in cell-based assays and in vivo studies. PMID:26827948

Importance of sequence specific hydrophobicity in synthetic protein transduction domain mimics.

PubMed

Sgolastra, Federica; Minter, Lisa M; Osborne, Barbara A; Tew, Gregory N

2014-03-10

A new series of synthetic protein transduction domain mimics (PTDMs) was designed to analyze the importance of guanidine and phenyl group segregation along the backbone on their membrane interaction and cellular internalization abilities. ROMP was utilized to synthesize three polymers: nonsegregated homopolymers, intermediately segregated gradient copolymers, and strongly segregated block copolymers. In order to understand the role of functional group segregation on activity, it was important to design monomers that enabled these three different polymer topologies, or constitutional macromolecular isomers, to be prepared with identical chemical compositions. The structure-activity relationships were evaluated by both a biophysical assay, using dye-loaded vesicles, and by in vitro cellular uptake studies of fluorescently labeled chains. The results showed that functional group segregation impacts activity. In general, the nonsegregated homopolymer was the most active in both assays but also showed larger, ill-defined aggregates compared to either the gradient or block copolymers. It was also the most cytotoxic of the three isomers. As a result, the gradient copolymer with intermediate segregation optimizes activity and solubility with low cytotoxicity. This study gives new design guidelines for the development of PTDMs.

Inhibition of neuraminidase by Ganoderma triterpenoids and implications for neuraminidase inhibitor design

PubMed Central

Zhu, Qinchang; Bang, Tran Hai; Ohnuki, Koichiro; Sawai, Takashi; Sawai, Ken; Shimizu, Kuniyoshi

2015-01-01

Neuraminidase (NA) inhibitors are the dominant antiviral drugs for treating influenza in the clinic. Increasing prevalence of drug resistance makes the discovery of new NA inhibitors a high priority. Thirty-one triterpenoids from the medicinal mushroom Ganoderma lingzhi were analyzed in an in vitro NA inhibition assay, leading to the discovery of ganoderic acid T-Q and TR as two inhibitors of H5N1 and H1N1 NAs. Structure-activity relationship studies revealed that the corresponding triterpenoid structure is a potential scaffold for the design of NA inhibitors. Using these triterpenoids as probes we found, through further in silico docking and interaction analysis, that interactions with the amino-acid residues Arg292 and/or Glu119 of NA are critical for the inhibition of H5N1 and H1N1. These findings should prove valuable for the design and development of NA inhibitors. PMID:26307417

Developing an e-pedagogy for interprofessional learning: Lecturers' thinking on curriculum design.

PubMed

Gordon, Frances; Booth, Karen; Bywater, Helen

2010-09-01

E-learning is seen as offering possible solutions to the barriers of large scale interprofessional education. This paper discusses a study that explored the underlying pedagogical thinking employed by lecturers when planning e-learning materials for interprofessional education. The themes uncovered in the data were: "reflective spaces for creativity"; "from logistics to learner autonomy"; "authentic"; "constructivist approaches"; "inter-active learning to promote collaboration" and "bringing the patient/service user into the classroom". Discussions about e-learning can focus on the technological aspects of design and delivery. However the findings of this study revealed that technology was not a consideration for the lecturers who saw e-learning as a vehicle to promote interactive learning. Their prime focus was revealed as the application of learning theory to the design of materials that would support students' acquisition of collaborative skills and the generation of new interprofessional knowledge.

Creep-Fatigue Interaction Testing

NASA Technical Reports Server (NTRS)

Halford, Gary R.

2001-01-01

Fatigue fives in metals are nominally time independent below 0.5 T(sub Melt). At higher temperatures, fatigue lives are altered due to time-dependent, thermally activated creep. Conversely, creep rates are altered by super. imposed fatigue loading. Creep and fatigue generally interact synergistically to reduce material lifetime. Their interaction, therefore, is of importance to structural durability of high-temperature structures such as nuclear reactors, reusable rocket engines, gas turbine engines, terrestrial steam turbines, pressure vessel and piping components, casting dies, molds for plastics, and pollution control devices. Safety and lifecycle costs force designers to quantify these interactions. Analytical and experimental approaches to creep-fatigue began in the era following World War II. In this article experimental and life prediction approaches are reviewed for assessing creep-fatigue interactions of metallic materials. Mechanistic models are also discussed briefly.

Methodical foundations of the preparation of highly valued personnel for high-rise construction

NASA Astrophysics Data System (ADS)

Belyaeva, Svetlana; Belyantseva, Oksana; Safonova, Nataliya; Vasilyeva, Olga

2018-03-01

When carrying out design and survey and construction and installation works for such an innovative type of activity as high-rise construction, the problem of personnel qualification becomes urgent. The article poses a research problem, identifies the main reasons for the need for training highly qualified specialists in construction, and suggests areas for improving training. The expediency of development of mentoring system was proved, the corresponding model of interaction between educational institutions and construction enterprises was offered, key interaction effects were evaluated.

Does zoning winter recreationists reduce recreation conflict?

Treesearch

Aubrey Miller; Jerry J. Vaske; John R. Squires; Lucretia E. Olson

2016-01-01

Parks and protected area managers use zoning to decrease interpersonal conflict between recreationists. Zoning, or segregation, of recreation - often by nonmotorized and motorized activity - is designed to limit physical interaction while providing recreation opportunities to both groups. This article investigated the effectiveness of zoning to reduce recreation...

Does zoning winter recreationists reduce recreation conflict?

Treesearch

Aubrey D. Miller; Jerry J. Vaske; John R. Squires; Lucretia E. Olson; Elizabeth K. Roberts

2017-01-01

Parks and protected area managers use zoning to decrease interpersonal conflict between recreationists. Zoning, or segregation, of recreation - often by nonmotorized and motorized activity - is designed to limit physical interaction while providing recreation opportunities to both groups. This article investigated the effectiveness of zoning to reduce recreation...

Simulations in a Science and Society Course.

ERIC Educational Resources Information Center

Maier, Mark H.; Venanzi, Thomas

1984-01-01

Provides a course outline which includes simulation exercises designed as in-class activities related to science and society interactions. Simulations focus on the IQ debate, sociobiology, nuclear weapons and nulcear strategy, nuclear power and radiation, computer explosion, and cosmology. Indicates that learning improves when students take active…

Flexible Classroom Furniture

ERIC Educational Resources Information Center

Kim Hassell,

2011-01-01

Classroom design for the 21st-century learning environment should accommodate a variety of learning skills and needs. The space should be large enough so it can be configured to accommodate a number of learning activities. This also includes furniture that provides flexibility and accommodates collaboration and interactive work among students and…

Designing Digital Environments for Art Education/Exploration.

ERIC Educational Resources Information Center

Milekic, Slavko

2000-01-01

Examines the role of digital technology in the context of art education and art exploration. Discusses the development of digital environments as the next step in the evolution of traditional computers, whose main characteristic is support for simultaneous multiple-user interactions and for social and collaborative activities. (LRW)

Improving Relationships: Serving up a Slice of "Enemy Pie"

ERIC Educational Resources Information Center

Hall, P. Cougar; McIntyre, Emily

2011-01-01

The "14 Characteristics of Effective Health Education Curricula" identified by the Centers for Disease Control and Prevention, Division of Adolescent and School Health promote teaching ideas designed to personalize information and engage students through activities which are both student centered and interactive. Effective health education efforts…

Lifestyle Improvement Program for Seniors.

ERIC Educational Resources Information Center

Barclay, Ralph

The Wayne State College Lifestyle Improvement Program for Seniors, based on the wellness concept, is designed to facilitate social interaction and health through physical activities. It is adaptable to a variety of individual needs and preferences, including exercises for cardiac rehabilitation patients. Any person over 50 can participate at no…

Designing an eMap to Teach Multimedia Applications Online

ERIC Educational Resources Information Center

Ruffini, Michael F.

2004-01-01

Teachers and students use multimedia software to create interactive presentations and content projects. Popular multimedia programs include: Microsoft's PowerPoint[R], Knowledge Adventure's HyperStudio[R], and Macromedia's Director MX 2004[R]. Creating multimedia projects engage students in active learning and thinking as they complete projects…

Aspirational Model Teaching Criteria for Psychology

ERIC Educational Resources Information Center

Richmond, Aaron S.; Boysen, Guy A.; Gurung, Regan A. R.; Tazeau, Yvette N.; Meyers, Steven A.; Sciutto, Mark J.

2014-01-01

In 2011, the Society for the Teaching of Psychology commissioned a presidential task force to document teaching criteria for model psychology teachers in undergraduate education. The resulting list of criteria reflects activities related to face-to-face course interaction and online teaching, training, and education; course design; implementation…

Teaching about Ethics and the Environment.

ERIC Educational Resources Information Center

Brevard County School Board, Cocoa, FL.

This unit consists of activities designed to develop value systems related to the interactions of humans and their environment. The overall objectives are to teach students to evaluate their actions within an environmental context, make rational decisions in resolving environmental problems, and function in a democratic society by reaching…

Exploring dynamic lighting, colour and form with smart textiles

NASA Astrophysics Data System (ADS)

Cabral, I.; Silva, C.; Worbin, L.; Souto, A. P.

2017-10-01

This paper addresses an ongoing research, aiming at the development of smart textiles that transform the incident light that passes through them - light transmittance - to design dynamic light without acting upon the light source. A colour and shape change prototype was developed with the objective of studying textile changes in time; to explore temperature as a dynamic variable through electrical activation of the smart materials and conductive threads integrated in the textile substrate; and to analyse the relation between textile chromic and morphologic behaviour in interaction with light. Based on the experiments conducted, results have highlighted some considerations of the dynamic parameters involved in the behaviour of thermo-responsive textiles and demonstrated design possibilities to create interactive lighting scenarios.

Robots to assist daily activities: views of older adults with Alzheimer's disease and their caregivers.

PubMed

Wang, Rosalie H; Sudhama, Aishwarya; Begum, Momotaz; Huq, Rajibul; Mihailidis, Alex

2017-01-01

Robots have the potential to both enable older adults with dementia to perform daily activities with greater independence, and provide support to caregivers. This study explored perspectives of older adults with Alzheimer's disease (AD) and their caregivers on robots that provide stepwise prompting to complete activities in the home. Ten dyads participated: Older adults with mild-to-moderate AD and difficulty completing activity steps, and their family caregivers. Older adults were prompted by a tele-operated robot to wash their hands in the bathroom and make a cup of tea in the kitchen. Caregivers observed interactions. Semi-structured interviews were conducted individually. Transcribed interviews were thematically analyzed. Three themes summarized responses to robot interactions: contemplating a future with assistive robots, considering opportunities with assistive robots, and reflecting on implications for social relationships. Older adults expressed opportunities for robots to help in daily activities, were open to the idea of robotic assistance, but did not want a robot. Caregivers identified numerous opportunities and were more open to robots. Several wanted a robot, if available. Positive consequences of robots in caregiving scenarios could include decreased frustration, stress, and relationship strain, and increased social interaction via the robot. A negative consequence could be decreased interaction with caregivers. Few studies have investigated in-depth perspectives of older adults with dementia and their caregivers following direct interaction with an assistive prompting robot. To fulfill the potential of robots, continued dialogue between users and developers, and consideration of robot design and caregiving relationship factors are necessary.

Effect of noncovalent interaction on the self-assembly of a designed peptide and its potential use as a carrier for controlled bFGF release

PubMed Central

Liu, Yanfei; Zhang, Ling; Wei, Wei

2017-01-01

Peptide self-assembly is one of the promising bottom-up approaches for creating synthetic supermolecular architectures. Noncovalent interactions such as hydrophobic packing, electrostatic interaction, and polypeptide chain entropy (ΔSC) are the most relevant factors that affect the folding and self-assembly of peptides and the stability of supermolecular structures. The GVGV tetrapeptide is an abundant repeat in elastin, an extracellular matrix protein. In this study, four GVGV-containing peptides were designed with the aim of understanding the effects of these weak interactions on peptide self-assembly. Transmission electron microscopy, circular dichroism spectroscopy, dynamic light scattering measurements, and rheometry assays were used to study the structural features of the peptides. Because self-assembling peptides with different amino acid sequences may significantly affect protein release, basic fibroblast growth factor (bFGF) was used as a model molecule and encapsulated within the P2 (RLDLGVGVRLDLGVGV) hydrogel to study the release kinetics. The results showed that the balance among hydrophobic effects, electrostatic interactions, and chain entropy determined the molecular state and self-assembly of the peptide. Moreover, encapsulation of bFGF within the P2 hydrogel allowed its sustained release without causing changes in the secondary structure. The release profiles could be tuned by adjusting the P2 hydrogel concentration. Cell Counting Kit-8 and Western blot assays demonstrated that the encapsulated and released bFGFs were biologically active and capable of promoting the proliferation of murine fibroblast NIH-3T3 cells, most likely due to the activation of downstream signaling pathways. PMID:28176898

Mixed Initiative Visual Analytics Using Task-Driven Recommendations

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

Cook, Kristin A.; Cramer, Nicholas O.; Israel, David

2015-12-07

Visual data analysis is composed of a collection of cognitive actions and tasks to decompose, internalize, and recombine data to produce knowledge and insight. Visual analytic tools provide interactive visual interfaces to data to support tasks involved in discovery and sensemaking, including forming hypotheses, asking questions, and evaluating and organizing evidence. Myriad analytic models can be incorporated into visual analytic systems, at the cost of increasing complexity in the analytic discourse between user and system. Techniques exist to increase the usability of interacting with such analytic models, such as inferring data models from user interactions to steer the underlying modelsmore » of the system via semantic interaction, shielding users from having to do so explicitly. Such approaches are often also referred to as mixed-initiative systems. Researchers studying the sensemaking process have called for development of tools that facilitate analytic sensemaking through a combination of human and automated activities. However, design guidelines do not exist for mixed-initiative visual analytic systems to support iterative sensemaking. In this paper, we present a candidate set of design guidelines and introduce the Active Data Environment (ADE) prototype, a spatial workspace supporting the analytic process via task recommendations invoked by inferences on user interactions within the workspace. ADE recommends data and relationships based on a task model, enabling users to co-reason with the system about their data in a single, spatial workspace. This paper provides an illustrative use case, a technical description of ADE, and a discussion of the strengths and limitations of the approach.« less

Interactive Environment Design in Smart City

NASA Astrophysics Data System (ADS)

Deng, DeXiang; Chen, LanSha; Zhou, Xi

2017-08-01

The interactive environment design of smart city is not just an interactive progress or interactive mode design, rather than generate an environment such as the “organic” life entity as human beings through interactive design, forming a smart environment with perception, memory, thinking, and reaction.

Simulation-Based Design for Wearable Robotic Systems: An Optimization Framework for Enhancing a Standing Long Jump.

PubMed

Ong, Carmichael F; Hicks, Jennifer L; Delp, Scott L

2016-05-01

Technologies that augment human performance are the focus of intensive research and development, driven by advances in wearable robotic systems. Success has been limited by the challenge of understanding human-robot interaction. To address this challenge, we developed an optimization framework to synthesize a realistic human standing long jump and used the framework to explore how simulated wearable robotic devices might enhance jump performance. A planar, five-segment, seven-degree-of-freedom model with physiological torque actuators, which have variable torque capacity depending on joint position and velocity, was used to represent human musculoskeletal dynamics. An active augmentation device was modeled as a torque actuator that could apply a single pulse of up to 100 Nm of extension torque. A passive design was modeled as rotational springs about each lower limb joint. Dynamic optimization searched for physiological and device actuation patterns to maximize jump distance. Optimization of the nominal case yielded a 2.27 m jump that captured salient kinematic and kinetic features of human jumps. When the active device was added to the ankle, knee, or hip, jump distance increased to between 2.49 and 2.52 m. Active augmentation of all three joints increased the jump distance to 3.10 m. The passive design increased jump distance to 3.32 m by adding torques of 135, 365, and 297 Nm to the ankle, knee, and hip, respectively. Dynamic optimization can be used to simulate a standing long jump and investigate human-robot interaction. Simulation can aid in the design of performance-enhancing technologies.

Discovery of small molecule inhibitors of the Wnt/β-catenin signaling pathway by targeting β-catenin/Tcf4 interactions.

PubMed

Yan, Maocai; Li, Guanqun; An, Jing

2017-06-01

The Wnt/β-catenin signaling pathway typically shows aberrant activation in various cancer cells, especially colorectal cancer cells. This signaling pathway regulates the expression of a variety of tumor-related proteins, including c-myc and cyclin D1, and plays essential roles in tumorigenesis and in the development of many cancers. Small molecules that block the interactions between β-catenin and Tcf4, a downstream stage of activation of the Wnt/β-catenin signaling pathway, could efficiently cut off this signal transduction and thereby act as a novel class of anticancer drugs. This paper reviews the currently reported inhibitors that target β-catenin/Tcf4 interactions, focusing on the discovery approaches taken in the design of these inhibitors and their bioactivities. A brief perspective is then shared on the future discovery and development of this class of inhibitors. Impact statement This mini-review summarized the current knowledge of inhibitors of interactions of beta-catenin/Tcf4 published to date according to their discovery approaches, and discussed their in vitro and in vivo activities, selectivities, and pharmacokinetic properties. Several reviews presently available now in this field describe modulators of the Wnt/beta-catenin pathway, but are generally focused on the bioactivities of these inhibitors. By contrast, this review focused on the drug discovery approaches taken in identifying these types of inhibitors and provided our perspective on further strategies for future drug discoveries. This review also integrated many recently published and important works on highly selective inhibitors as well as rational drug design. We believe that the findings and strategies summarized in this review have broad implications and will be of interest throughout the biochemical and pharmaceutical research community.

Designing of Protein Kinase C β-II Inhibitors against Diabetic complications: Structure Based Drug Design, Induced Fit docking and analysis of active site conformational changes

PubMed Central

Vijayakumar, Balakrishnan; Velmurugan, Devadasan

2012-01-01

Protein Kinase C β-II (PKC β-II) is an important enzyme in the development of diabetic complications like cardiomyopathy, retinopathy, neuropathy, nephropathy and angiopathy. PKC β-II is activated in vascular tissues during diabetic vascular abnormalities. Thus, PKC β-II is considered as a potent drug target and the crystal structure of the kinase domain of PKC β-II (PDB id: 2I0E) was used to design inhibitors using Structure-Based Drug Design (SBDD) approach. Sixty inhibitors structurally similar to Staurosporine were retrieved from PubChem Compound database and High Throughput Virtual screening (HTVs) was carried out with PKC β-II. Based on the HTVs results and the nature of active site residues of PKC β-II, Staurosporine inhibitors were designed using SBDD. Induced Fit Docking (IFD) studies were carried out between kinase domain of PKC β-II and the designed inhibitors. These IFD complexes showed favorable docking score, glide energy, glide emodel and hydrogen bond and hydrophobic interactions with the active site of PKC β-II. Binding free energy was calculated for IFD complexes using Prime MM-GBSA method. The conformational changes induced by the inhibitor at the active site of PKC β-II were observed for the back bone Cα atoms and side-chain chi angles. PASS prediction tool was used to analyze the biological activities for the designed inhibitors. The various physicochemical properties were calculated for the compounds. One of the designed inhibitors successively satisfied all the in silico parameters among the others and seems to be a potent inhibitor against PKC β-II. PMID:22829732

Evaluation of a multifunctional technology system in a memory care unit: Opportunities for innovation in dementia care.

PubMed

Lazar, Amanda; Demiris, George; Thompson, Hilaire J

2016-12-01

Stimulating recreational and leisure activities (RLAs) are essential to physical and mental well-being; however, people living in memory care units (MCUs) may lack access to them. Technology has the potential to facilitate and enrich activity engagement in this context. In this 6-month study, we evaluated a commercially available system designed to encourage the engagement of people with dementia in activities and social interactions, using a mixed-methods approach in a MCU. Quantitative measures included those to evaluate cognition, depression, quality of life, and resource utilization. We qualitatively evaluated the system using semi-structured interviews with family members and staff. Five residents with dementia, four family members, and seven staff were included in the 6-month study. Staff and family members reported benefits for residents such as enjoyment, interactions and connections with others, and mental stimulation. Findings also highlight challenges such as technical and ethical concerns. Factors that influence system use and integration are also discussed. It was feasible to introduce a system designed for recreation and engagement in a MCU, and staff, family members, and residents experienced benefits. However, barriers existed in the introduction and use of the system.

Excellence in Physics Education Award: SCALE-UP, Student Centered Active Learning Environment with Upside-down Pedagogies

NASA Astrophysics Data System (ADS)

Beichner, Robert

2016-03-01

The Student-Centered Active Learning Environment with Upside-down Pedagogies (SCALE-UP) Project combines curricula and a specially-designed instructional space to enhance learning. SCALE-UP students practice communication and teamwork skills while performing activities that enhance their conceptual understanding and problem solving skills. This can be done with small or large classes and has been implemented at more than 250 institutions. Educational research indicates that students should collaborate on interesting tasks and be deeply involved with the material they are studying. SCALE-UP classtime is spent primarily on ``tangibles'' and ``ponderables''--hands-on measurements/observations and interesting questions. There are also computer simulations (called ``visibles'') and hypothesis-driven labs. Students sit at tables designed to facilitate group interactions. Instructors circulate and engage in Socratic dialogues. The setting looks like a banquet hall, with lively interactions nearly all the time. Impressive learning gains have been measured at institutions across the US and internationally. This talk describes today's students, how lecturing got started, what happens in a SCALE-UP classroom, and how the approach has spread. The SCALE-UP project has greatly benefitted from numerous Grants made by NSF and FIPSE to NCSU and other institutions.

Inhibitors of Ras-SOS Interactions.

PubMed

Lu, Shaoyong; Jang, Hyunbum; Zhang, Jian; Nussinov, Ruth

2016-04-19

Activating Ras mutations are found in about 30 % of human cancers. Ras activation is regulated by guanine nucleotide exchange factors, such as the son of sevenless (SOS), which form protein-protein interactions (PPIs) with Ras and catalyze the exchange of GDP by GTP. This is the rate-limiting step in Ras activation. However, Ras surfaces lack any evident suitable pockets where a molecule might bind tightly, rendering Ras proteins still 'undruggable' for over 30 years. Among the alternative approaches is the design of inhibitors that target the Ras-SOS PPI interface, a strategy that is gaining increasing recognition for treating Ras mutant cancers. Herein we focus on data that has accumulated over the past few years pertaining to the design of small-molecule modulators or peptide mimetics aimed at the interface of the Ras-SOS PPI. We emphasize, however, that even if such Ras-SOS therapeutics are potent, drug resistance may emerge. To counteract this development, we propose "pathway drug cocktails", that is, drug combinations aimed at parallel (or compensatory) pathways. A repertoire of classified cancer, cell/tissue, and pathway/protein combinations would be beneficial toward this goal. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of a multifunctional technology system in a memory care unit: Opportunities for innovation in dementia care

PubMed Central

Lazar, Amanda; Demiris, George; Thompson, Hilaire J.

2016-01-01

Introduction Stimulating recreational and leisure activities (RLAs) are essential to physical and mental well-being; however, people living in memory care units (MCUs) may lack access to them. Technology has the potential to facilitate and enrich activity engagement in this context. Objectives In this 6-month study, we evaluated a commercially available system designed to encourage the engagement of people with dementia in activities and social interactions, using a mixed-methods approach in a MCU. Methods Quantitative measures included those to evaluate cognition, depression, quality of life, and resource utilization. We qualitatively evaluated the system using semi-structured interviews with family members and staff. Five residents with dementia, four family members, and seven staff were included in the 6-month study. Results Staff and family members reported benefits for residents such as enjoyment, interactions and connections with others, and mental stimulation. Findings also highlight challenges such as technical and ethical concerns. Factors that influence system use and integration are also discussed. Conclusion It was feasible to introduce a system designed for recreation and engagement in a MCU, and staff, family members, and residents experienced benefits. However, barriers existed in the introduction and use of the system. PMID:26819070

Using the VEPP website in a Master of Education in Earth Sciences course (Invited)

NASA Astrophysics Data System (ADS)

Richardson, E.

2010-12-01

Secondary science teachers are better able to transmit the excitement of the process of science when they have access to real-time or near-real-time datasets. Large digital databases are ubiquitous in many subfields of the geosciences; the experience of working with such data is valuable as an authentic teaching and learning tool. In Penn State’s Master of Education in Earth Sciences program, course activities are carefully designed keeping in mind the twin goals of the program: teachers will participate in the process of science by interacting with genuine scientific data, and teachers will observe the process of science by reading and discussing scientific papers. A second objective is for teachers to be able to repurpose any activities and datasets for their own classrooms. Therefore, course activities must use openly available data in a format requiring little or no pre-processing. Here I present an example of such an activity involving near-real-time data made available by the Volcano Exploration Project at Pu’u O’o (VEPP). It is designed as a problem set housed in a week-long lesson concerning volcanic eruptions. Students read a paper in which recent volcanic activity at Kilauea’s east flank is described based on observations from several instruments. They use the figures and data presented in the paper to predict hypothetical instrument responses to certain volcanic activities, and calculate the rate of magma movement based on measured seismicity. Next, students must interact with the web-based VALVE software package available at the VEPP website which allows them to visualize several kinds of geophysical data sources collected at Pu’u O’o. Their assignment is to discover and describe a recent deflation-inflation caldera event recorded simultaneously by seismometers, GPS stations, and tiltmeters. The course in which this problem set is given has been taught twice since this activity was designed: spring and summer semesters 2010. Students were able to interact effectively with the VEPP website as well as the VALVE3 software. They reported in an informal poll that their experience working with this data enabled them to convey to their own students the importance of making scientific observations with a variety of instruments that work in concert to monitor a system of interest.

A retrospective study on changes in residents' physical activities, social interactions, and neighborhood cohesion after moving to a walkable community.

PubMed

Zhu, Xuemei; Yu, Chia-Yuan; Lee, Chanam; Lu, Zhipeng; Mann, George

2014-12-01

This study is to examine changes in residents' physical activities, social interactions, and neighborhood cohesion after they moved to a walkable community in Austin, Texas. Retrospective surveys (N=449) were administered in 2013-2014 to collect pre- and post-move data about the outcome variables and relevant personal, social, and physical environmental factors. Walkability of each resident's pre-move community was measured using the Walk Score. T tests were used to examine the pre-post move differences in the outcomes in the whole sample and across sub-groups with different physical activity levels, neighborhood conditions, and neighborhood preferences before the move. After the move, total physical activity increased significantly in the whole sample and all sub-groups except those who were previously sufficiently active; lived in communities with high walkability, social interactions, or neighborhood cohesion; or had moderate preference for walkable neighborhoods. Walking in the community increased in the whole sample and all subgroups except those who were previously sufficiently active, moved from high-walkability communities, or had little to no preference for walkable neighborhoods. Social interactions and neighborhood cohesion increased significantly after the move in the whole sample and all sub-groups. This study explored potential health benefits of a walkable community in promoting physically and socially active lifestyles, especially for populations at higher risk of obesity. The initial result is promising, suggesting the need for more work to further examine the relationships between health and community design using pre-post assessments. Copyright © 2014 Elsevier Inc. All rights reserved.

Design of Omni Directional Remotely Operated Vehicle (ROV)

NASA Astrophysics Data System (ADS)

Rahimuddin; Hasan, Hasnawiya; Rivai, Haryanti A.; Iskandar, Yanu; Claudio, P.

2018-02-01

Nowadays, underwater activities are increased with the increase of oil resources finding. The gap between demand and supply of oil and gas cause engineers to find oil and gas resources in deep water. In other side, high risk of working in deep underwater environment can cause a dangerous situation for human. Therefore, many research activities are developing an underwater vehicle to replace the human’s work such as ROV or Remotely Operated Vehicles. The vehicle operated using tether to transport the signals and electric power from the surface vehicle. Arrangements of weight, buoyancy, and the propeller placements are significant aspect in designing the vehicle’s performance. This paper presents design concept of ROV for survey and observation the underwater objects with interaction vectored propellers used for vehicle’s motions.

Spectroelectrochemical insights into structural and redox properties of immobilized endonuclease III and its catalytically inactive mutant

NASA Astrophysics Data System (ADS)

Moe, Elin; Rollo, Filipe; Silveira, Célia M.; Sezer, Murat; Hildebrandt, Peter; Todorovic, Smilja

2018-01-01

Endonuclease III is a Fe-S containing bifunctional DNA glycosylase which is involved in the repair of oxidation damaged DNA. Here we employ surface enhanced IR spectroelectrochemistry and electrochemistry to study the enzyme from the highly radiation- and desiccation-resistant bacterium Deinococcus radiodurans (DrEndoIII2). The experiments are designed to shed more light onto specific parameters that are currently proposed to govern damage search and recognition by endonucleases III. We demonstrate that electrostatic interactions required for the redox activation of DrEndoIII2 may result in high electric fields that alter its structural and thermodynamic properties. Analysis of inactive DrEndoIII2 (K132A/D150A double mutant) interacting with undamaged DNA, and the active enzyme interacting with damaged DNA also indicate that the electron transfer is modulated by subtle differences in the protein-DNA complex.

Interaction among multiple microorganisms and effects of nitrogen and carbon supplementations on lignin degradation.

PubMed

Lv, Yuancai; Chen, Yuancai; Sun, Shiying; Hu, Yongyou

2014-03-01

The mutual interactions among the consortium constructed by four indigenous bacteria and five inter-kingdom fusants and the effects of nitrogen and carbon supplementations on lignin degradation and laccase activity were investigated. Analyzed by Plackett-Burman and central composite design, the microbial consortium were optimized, Bacillus sp. (B) and PE-9 and Pseudomonas putida (Pp) and PE-9 had significant interactions on lignin degradation based on a 5% level of significance. The nitrogen and carbon supplementations played an important role in lignin degradation and laccase production. The ultimate lignin degradation efficiency of 96.0% and laccase activity of 268U/L were obtained with 0.5g/L of ammonium chloride and 2g/L of sucrose. Results suggested that a stable and effective microbial consortium in alkalescent conditions was successfully achieved through the introduction of fusants, which was significant for its industrial application. Copyright © 2013 Elsevier Ltd. All rights reserved.

Spectroelectrochemical insights into structural and redox properties of immobilized endonuclease III and its catalytically inactive mutant.

PubMed

Moe, Elin; Rollo, Filipe; Silveira, Célia M; Sezer, Murat; Hildebrandt, Peter; Todorovic, Smilja

2018-01-05

Endonuclease III is a Fe-S containing bifunctional DNA glycosylase which is involved in the repair of oxidation damaged DNA. Here we employ surface enhanced IR spectroelectrochemistry and electrochemistry to study the enzyme from the highly radiation- and desiccation-resistant bacterium Deinococcus radiodurans (DrEndoIII 2 ). The experiments are designed to shed more light onto specific parameters that are currently proposed to govern damage search and recognition by endonucleases III. We demonstrate that electrostatic interactions required for the redox activation of DrEndoIII 2 may result in high electric fields that alter its structural and thermodynamic properties. Analysis of inactive DrEndoIII 2 (K132A/D150A double mutant) interacting with undamaged DNA, and the active enzyme interacting with damaged DNA also indicate that the electron transfer is modulated by subtle differences in the protein-DNA complex. Copyright © 2017 Elsevier B.V. All rights reserved.

Techniques for optimizing human-machine information transfer related to real-time interactive display systems

NASA Technical Reports Server (NTRS)

Granaas, Michael M.; Rhea, Donald C.

1989-01-01

In recent years the needs of ground-based researcher-analysts to access real-time engineering data in the form of processed information has expanded rapidly. Fortunately, the capacity to deliver that information has also expanded. The development of advanced display systems is essential to the success of a research test activity. Those developed at the National Aeronautics and Space Administration (NASA), Western Aeronautical Test Range (WATR), range from simple alphanumerics to interactive mapping and graphics. These unique display systems are designed not only to meet basic information display requirements of the user, but also to take advantage of techniques for optimizing information display. Future ground-based display systems will rely heavily not only on new technologies, but also on interaction with the human user and the associated productivity with that interaction. The psychological abilities and limitations of the user will become even more important in defining the difference between a usable and a useful display system. This paper reviews the requirements for development of real-time displays; the psychological aspects of design such as the layout, color selection, real-time response rate, and interactivity of displays; and an analysis of some existing WATR displays.

Ergonomics and sustainability in the design of everyday use products.

PubMed

Tosi, Francesca

2012-01-01

The relationship between Ergonomics and Design is a key element in the sustainability project, as well as in many other areas of experimental design. In the Design for Sustainability field, Ergonomics is a strategic factor for design culture innovation, providing designers with the necessary knowledge and skills regarding human characteristics and capabilities, as well as user needs and desires during use and interaction with products in work activities and everyday life. Ergonomics is also a strategic innovative factor in design development and manufacturing processes. In fact, ergonomics provides a methodological approach in user-product interaction evaluation processes through the use of participatory design and survey methods, user trials, direct observation, savings and resource conservation, etc.On the other hand, design offers solutions able to interpret user needs and expectations, at the same time suggesting new behaviors and lifestyles.In Design for Sustainability, the ergonomic and user-centered approach contributes greatly to lifestyles and innovative use of products--making it possible to understand and interpret real people needs and expectations in their everyday actions and behavior.New consumption patterns, new awareness of lifestyles, energy source consumption, purchasing methods and consumption style etc. can be supported by design innovation, responding to expressed and unexpressed user needs. With this in mind, the ergonomic approach represents the starting point for design choices and at the same time, a tool for assessing their appropriateness and effectiveness.

Tuning complement activation and pathway through controlled molecular architecture of dextran chains in nanoparticle corona.

PubMed

Coty, Jean-Baptiste; Eleamen Oliveira, Elquio; Vauthier, Christine

2017-11-05

The understanding of complement activation by nanomaterials is a key to a rational design of safe and efficient nanomedicines. This work proposed a systematic study investigating how molecular design of nanoparticle coronas made of dextran impacts on mechanisms that trigger complement activation. The nanoparticles used for this work consisted of dextran-coated poly(isobutylcyanoacrylate) (PIBCA) nanoparticles have already been thoroughly characterized. Their different capacity to trigger complement activation established on the cleavage of the protein C3 was also already described making these nanoparticles good models to investigate the relation between the molecular feature of their corona and the mechanism by which they triggered complement activation. Results of this new study show that complement activation pathways can be selected by distinct architectures formed by dextran chains composing the nanoparticle corona. Assumptions that explain the relation between complement activation mechanisms triggered by the nanoparticles and the nanoparticle corona molecular feature were proposed. These results are of interest to better understand how the design of dextran-coated nanomaterials will impact interactions with the complement system. It can open perspectives with regard to the selection of a preferential complement activation pathway or prevent the nanoparticles to activate the complement system, based on a rational choice of the corona configuration. Copyright © 2017 Elsevier B.V. All rights reserved.

Solvent-driven reductive activation of carbon dioxide by gold anions.

PubMed

Knurr, Benjamin J; Weber, J Mathias

2012-11-14

Catalytic activation and electrochemical reduction of CO(2) for the formation of chemically usable feedstock and fuel are central goals for establishing a carbon neutral fuel cycle. The role of solvent molecules in catalytic processes is little understood, although solvent-solute interactions can strongly influence activated intermediate species. We use vibrational spectroscopy of mass-selected Au(CO(2))(n)(-) cluster ions to probe the solvation of AuCO(2)(-) as a model for a reactive intermediate in the reductive activation of a CO(2) ligand by a single-atom catalyst. For the first few solvent molecules, solvation of the complex preferentially occurs at the CO(2) moiety, enhancing reductive activation through polarization of the excess charge onto the partially reduced ligand. At higher levels of solvation, direct interaction of additional solvent molecules with the Au atom diminishes reduction. The results show how the solvation environment can enhance or diminish the effects of a catalyst, offering design criteria for single-atom catalyst engineering.

Measurements of weak interactions between truncated substrates and a hammerhead ribozyme by competitive kinetic analyses: implications for the design of new and efficient ribozymes with high sequence specificity

PubMed Central

Kasai, Yasuhiro; Shizuku, Hideki; Takagi, Yasuomi; Warashina, Masaki; Taira, Kazunari

2002-01-01

Exploitation of ribozymes in a practical setting requires high catalytic activity and strong specificity. The hammerhead ribozyme R32 has considerable potential in this regard since it has very high catalytic activity. In this study, we have examined how R32 recognizes and cleaves a specific substrate, focusing on the mechanism behind the specificity. Comparing rates of cleavage of a substrate in a mixture that included the correct substrate and various substrates with point mutations, we found that R32 cleaved the correct substrate specifically and at a high rate. To clarify the source of this strong specificity, we quantified the weak interactions between R32 and various truncated substrates, using truncated substrates as competitive inhibitors since they were not readily cleaved during kinetic measurements of cleavage of the correct substrate, S11. We found that the strong specificity of the cleavage reaction was due to a closed form of R32 with a hairpin structure. The self-complementary structure within R32 enabled the ribozyme to discriminate between the correct substrate and a mismatched substrate. Since this hairpin motif did not increase the Km (it did not inhibit the binding interaction) or decrease the kcat (it did not decrease the cleavage rate), this kind of hairpin structure might be useful for the design of new ribozymes with strong specificity and high activity. PMID:12034825

Design of aromatic-containing cell-penetrating peptide mimics with structurally modified π electronics.

PubMed

deRonde, Brittany M; Birke, Alexander; Tew, Gregory N

2015-02-09

Cell-penetrating peptides (CPPs) and their synthetic mimics (CPPMs) represent a class of molecules that facilitate the intracellular delivery of various cargo. Previous studies indicated that the presence of aromatic functionalities improved CPPM activity. Given that aromatic functionalities play prominent roles in membrane biology and participate in various π interactions, we explored whether these interactions could be optimized for improved CPPM activity. CPPMs were synthesized by ring-opening metathesis polymerization by using monomers that contained aromatic rings substituted with electron-donating and electron-withdrawing groups and covered an electrostatic potential range from -29.69 to +15.57 kcal mol(-1) . These groups altered the quadrupole moments of the aromatic systems and were used to test if such structural modifications changed CPPM activity. CPPMs were added to dye-loaded vesicles and the release of carboxyfluorescein was monitored as a function of polymer concentration. Changes in the effective polymer concentration to release 50% of the dye (effective concentration, EC50 ) were monitored. Results from this assay showed that the strength of the electron-donating and electron-withdrawing groups incorporated in the CPPMs did not alter polymer EC50 values or activity. This suggests that other design parameters may have a stronger impact on CPPM activity. In addition, these results indicate that a wide range of aromatic groups can be incorporated without negatively impacting polymer activity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Balancing the stability and the catalytic specificities of OP hydrolases with enhanced V-agent activities.

PubMed

Reeves, T E; Wales, M E; Grimsley, J K; Li, P; Cerasoli, D M; Wild, J R

2008-06-01

Rational site-directed mutagenesis and biophysical analyses have been used to explore the thermodynamic stability and catalytic capabilities of organophosphorus hydrolase (OPH) and its genetically modified variants. There are clear trade-offs in the stability of modifications that enhance catalytic activities. For example, the H254R/H257L variant has higher turnover numbers for the chemical warfare agents VX (144 versus 14 s(-1) for the native enzyme (wild type) and VR (Russian VX, 465 versus 12 s(-1) for wild type). These increases are accompanied by a loss in stability in which the total Gibb's free energy for unfolding is 19.6 kcal/mol, which is 5.7 kcal/mol less than that of the wild-type enzyme. X-ray crystallographic studies support biophysical data that suggest amino acid residues near the active site contribute to the chemical and thermal stability through hydrophobic and cation-pi interactions. The cation-pi interactions appear to contribute an additional 7 kcal/mol to the overall global stability of the enzyme. Using rational design, it has been possible to make amino acid changes in this region that restored the stability, yet maintained effective V-agent activities, with turnover numbers of 68 and 36 s(-1) for VX and VR, respectively. This study describes the first rationally designed, stability/activity balance for an OPH enzyme with a legitimate V-agent activity, and its crystal structure.

Rehabilitating drug-induced long-QT promoters: In-silico design of hERG-neutral cisapride analogues with retained pharmacological activity

PubMed Central

2014-01-01

Background The human ether-a-go-go related gene 1 (hERG1), which codes for a potassium ion channel, is a key element in the cardiac delayed rectified potassium current, IKr, and plays an important role in the normal repolarization of the heart’s action potential. Many approved drugs have been withdrawn from the market due to their prolongation of the QT interval. Most of these drugs have high potencies for their principal targets and are often irreplaceable, thus “rehabilitation” studies for decreasing their high hERG1 blocking affinities, while keeping them active at the binding sites of their targets, have been proposed to enable these drugs to re-enter the market. Methods In this proof-of-principle study, we focus on cisapride, a gastroprokinetic agent withdrawn from the market due to its high hERG1 blocking affinity. Here we tested an a priori strategy to predict a compound’s cardiotoxicity using de novo drug design with molecular docking and Molecular Dynamics (MD) simulations to generate a strategy for the rehabilitation of cisapride. Results We focused on two key receptors, a target interaction with the (adenosine) receptor and an off-target interaction with hERG1 channels. An analysis of the fragment interactions of cisapride at human A2A adenosine receptors and hERG1 central cavities helped us to identify the key chemical groups responsible for the drug activity and hERG1 blockade. A set of cisapride derivatives with reduced cardiotoxicity was then proposed using an in-silico two-tier approach. This set was compared against a large dataset of commercially available cisapride analogs and derivatives. Conclusions An interaction decomposition of cisapride and cisapride derivatives allowed for the identification of key active scaffolds and functional groups that may be responsible for the unwanted blockade of hERG1. PMID:24606761

Rehabilitating drug-induced long-QT promoters: in-silico design of hERG-neutral cisapride analogues with retained pharmacological activity.

PubMed

Durdagi, Serdar; Randall, Trevor; Duff, Henry J; Chamberlin, Adam; Noskov, Sergei Y

2014-03-08

The human ether-a-go-go related gene 1 (hERG1), which codes for a potassium ion channel, is a key element in the cardiac delayed rectified potassium current, IKr, and plays an important role in the normal repolarization of the heart's action potential. Many approved drugs have been withdrawn from the market due to their prolongation of the QT interval. Most of these drugs have high potencies for their principal targets and are often irreplaceable, thus "rehabilitation" studies for decreasing their high hERG1 blocking affinities, while keeping them active at the binding sites of their targets, have been proposed to enable these drugs to re-enter the market. In this proof-of-principle study, we focus on cisapride, a gastroprokinetic agent withdrawn from the market due to its high hERG1 blocking affinity. Here we tested an a priori strategy to predict a compound's cardiotoxicity using de novo drug design with molecular docking and Molecular Dynamics (MD) simulations to generate a strategy for the rehabilitation of cisapride. We focused on two key receptors, a target interaction with the (adenosine) receptor and an off-target interaction with hERG1 channels. An analysis of the fragment interactions of cisapride at human A2A adenosine receptors and hERG1 central cavities helped us to identify the key chemical groups responsible for the drug activity and hERG1 blockade. A set of cisapride derivatives with reduced cardiotoxicity was then proposed using an in-silico two-tier approach. This set was compared against a large dataset of commercially available cisapride analogs and derivatives. An interaction decomposition of cisapride and cisapride derivatives allowed for the identification of key active scaffolds and functional groups that may be responsible for the unwanted blockade of hERG1.

Usability and Accessibility of eBay by Screen Reader

NASA Astrophysics Data System (ADS)

Buzzi, Maria Claudia; Buzzi, Marina; Leporini, Barbara; Akhter, Fahim

The evolution of Information and Communication Technology and the rapid growth of the Internet have fuelled a great diffusion of eCommerce websites. Usually these sites have complex layouts crowded with active elements, and thus are difficult to navigate via screen reader. Interactive environments should be properly designed and delivered to everyone, including the blind, who usually use screen readers to interact with their computers. In this paper we investigate the interaction of blind users with eBay, a popular eCommerce website, and discuss how using the W3C Accessible Rich Internet Applications (WAI-ARIA) suite could improve the user experience when navigating via screen reader.

Information for Successful Interaction with Autonomous Systems

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Johnson, Kathy A.

2003-01-01

Interaction in heterogeneous mission operations teams is not well matched to classical models of coordination with autonomous systems. We describe methods of loose coordination and information management in mission operations. We describe an information agent and information management tool suite for managing information from many sources, including autonomous agents. We present an integrated model of levels of complexity of agent and human behavior, which shows types of information processing and points of potential error in agent activities. We discuss the types of information needed for diagnosing problems and planning interactions with an autonomous system. We discuss types of coordination for which designs are needed for autonomous system functions.

Computer-aided rational design of novel EBF analogues with an aromatic ring.

PubMed

Wang, Shanshan; Sun, Yufeng; Du, Shaoqing; Qin, Yaoguo; Duan, Hongxia; Yang, Xinling

2016-06-01

Odorant binding proteins (OBPs) are important in insect olfactory recognition. These proteins bind specifically to insect semiochemicals and induce their seeking, mating, and alarm behaviors. Molecular docking and molecular dynamics simulations were performed to provide computational insight into the interaction mode between AgamOBP7 and novel (E)-β-farnesene (EBF) analogues with an aromatic ring. The ligand-binding cavity in OBP7 was found to be mostly hydrophobic due to the presence of several nonpolar residues. The interactions between the EBF analogues and the hydrophobic residues in the binding cavity increased in strength as the distance between them decreased. The EBF analogues with an N-methyl formamide or ester linkage had higher docking scores than those with an amide linkage. Moreover, delocalized π-π and electrostatic interactions were found to contribute significantly to the binding between the ligand benzene ring and nearby protein residues. To design new compounds with higher activity, four EBF analogues D1-D4 with a benzene ring were synthesized and evaluated based on their docking scores and binding affinities. D2, which had an N-methyl formamide group linkage, exhibited stronger binding than D1, which had an amide linkage. D4 exhibited particularly strong binding due to multiple hydrophobic interactions with the protein. This study provides crucial foundations for designing novel EBF analogues based on the OBP structure. Graphical abstract The design strategy of new EBF analogues based on the OBP7 structure.

Development of Interactive Learning Media on Kinetic Gas Theory at SMAN 2 Takalar

NASA Astrophysics Data System (ADS)

Yanti, M.; Ihsan, N.; Subaer

2017-02-01

Learning media is the one of the most factor in supporting successfully in the learning process. The purpose of this interactive media is preparing students to improve skills in laboratory practice without need for assistance and are not bound by time and place. The subject of this study was 30 students grade XI IPA SMAN 2 Takalar. This paper discuss about the development of learning media based in theory of gas kinetic. This media designed to assist students in learning independently. This media made using four software, they are Microsoft word, Snagit Editor, Macromedia Flash Player and Lectora. This media are interactive, dynamic and could support the users desires to learn and understand course of gas theory. The development produce followed the four D models. Consisted of definition phase, design phase, development phase and disseminate phase. The results showed 1) the media were valid and reliable, 2) learning tools as well as hardcopy and softcopy which links to website 3) activity learners above 80% and 4) according to the test results, the concept of comprehension of student was improved than before given interactive media.

Synthetic microbial ecology and the dynamic interplay between microbial genotypes.

PubMed

Dolinšek, Jan; Goldschmidt, Felix; Johnson, David R

2016-11-01

Assemblages of microbial genotypes growing together can display surprisingly complex and unexpected dynamics and result in community-level functions and behaviors that are not readily expected from analyzing each genotype in isolation. This complexity has, at least in part, inspired a discipline of synthetic microbial ecology. Synthetic microbial ecology focuses on designing, building and analyzing the dynamic behavior of ‘ecological circuits’ (i.e. a set of interacting microbial genotypes) and understanding how community-level properties emerge as a consequence of those interactions. In this review, we discuss typical objectives of synthetic microbial ecology and the main advantages and rationales of using synthetic microbial assemblages. We then summarize recent findings of current synthetic microbial ecology investigations. In particular, we focus on the causes and consequences of the interplay between different microbial genotypes and illustrate how simple interactions can create complex dynamics and promote unexpected community-level properties. We finally propose that distinguishing between active and passive interactions and accounting for the pervasiveness of competition can improve existing frameworks for designing and predicting the dynamics of microbial assemblages.

Structure-based design of competitive ligands to target Spon2 in gastric cancer: An integration of molecular modeling and in vitro assay.

PubMed

Xu, Zhenglei; Yu, Zhichao; Nai, Shumei; Shi, Ruiyue; Tang, Qinhong; Zhang, Haiyang; Ye, Lijuan; Wang, Lisheng; Hong, Yincai

2017-10-01

Spon2 is a proto-oncogene matrix protein that plays an essential role in the tumorigenesis and metastasis of gastric cancer. The protein has recently been found to function as a guanine nucleotide exchange factor through the activation of RhoGTPase. Here, computational modeling and bioinformatics analysis were employed to investigate the molecular mechanism and biological implication underlying Spon2 autoinhibition. It is revealed that the binding of PxxP motif to SH domain can stabilize the intramolecular interaction between the N-terminal helix and DH domain of Spon2, thus shifting the protein into an autoinhibitory state. Here, we proposed releasing Spon2 autoinhibition by targeting SH domain with competitive peptide ligands. To verify this notion, the PxxP sequence was adopted as the start to derive an array of efficient SH binders by using a structure-based rational design strategy, which were then substantiated with fluorescence spectroscopy analysis and guanine nucleotide exchange test. Consequently, the obtained peptide ligands were determined to have a moderate or high affinity for SH domain; they can also enhance Spon2 exchange activity by 1.2-6.1 folds, exhibiting a significant correlation with their SH-binding affinity (Pearson's coefficient=0.92). In addition, neutral substitution of conserved residues in a high-affinity peptide ligand can largely reduce its Spon2-activating potency, confirming that the designed peptide activates Spon2 by competitively disrupting SH-PxxP interaction. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs

NASA Astrophysics Data System (ADS)

Dror, Ron O.; Green, Hillary F.; Valant, Celine; Borhani, David W.; Valcourt, James R.; Pan, Albert C.; Arlow, Daniel H.; Canals, Meritxell; Lane, J. Robert; Rahmani, Raphaël; Baell, Jonathan B.; Sexton, Patrick M.; Christopoulos, Arthur; Shaw, David E.

2013-11-01

The design of G-protein-coupled receptor (GPCR) allosteric modulators, an active area of modern pharmaceutical research, has proved challenging because neither the binding modes nor the molecular mechanisms of such drugs are known. Here we determine binding sites, bound conformations and specific drug-receptor interactions for several allosteric modulators of the M2 muscarinic acetylcholine receptor (M2 receptor), a prototypical family A GPCR, using atomic-level simulations in which the modulators spontaneously associate with the receptor. Despite substantial structural diversity, all modulators form cation-π interactions with clusters of aromatic residues in the receptor extracellular vestibule, approximately 15Å from the classical, `orthosteric' ligand-binding site. We validate the observed modulator binding modes through radioligand binding experiments on receptor mutants designed, on the basis of our simulations, either to increase or to decrease modulator affinity. Simulations also revealed mechanisms that contribute to positive and negative allosteric modulation of classical ligand binding, including coupled conformational changes of the two binding sites and electrostatic interactions between ligands in these sites. These observations enabled the design of chemical modifications that substantially alter a modulator's allosteric effects. Our findings thus provide a structural basis for the rational design of allosteric modulators targeting muscarinic and possibly other GPCRs.

Using Technology Effectively to Teach about Fractions

ERIC Educational Resources Information Center

Hensberry, Karina K. R.; Moore, Emily B.; Perkins, Katherine

2015-01-01

In this article, the authors describe classroom use of technology that successfully engaged fourth grade students (typically aged 9-10) in the United States in learning about fractions. The activities involved the use of an interactive simulation designed to support student learning of fractions, and whole-class discussion where students were…

Engaging New Software.

ERIC Educational Resources Information Center

Allen, Denise

1994-01-01

Reviews three educational computer software products: (1) a compact disc-read only memory (CD-ROM) bundle of five mathematics programs from the Apple Education Series; (2) "Sammy's Science House," with science activities for preschool through second grade (Edmark); and (3) "The Cat Came Back," an interactive CD-ROM game designed to build language…

LMOOCs, Classifying Design: Survey Findings from LMOOC Providers

ERIC Educational Resources Information Center

Beirne, Elaine; Mhichíl, Mairéad Nic Giolla; Cleircín, Gearóid Ó

2017-01-01

Many of the major Massive Open Online Course (MOOC) platforms support learning approaches which can be roughly categorised as transmission-based and asynchronous (Morris & Lambe, 2014), with limited forms of interactive elements. Language learning is viewed within this study as an active process which includes knowledge, skills, and cultural…

Students' Ideas about Their Conceptualization: Their Elicitation through Instruction.

ERIC Educational Resources Information Center

Hennessey, M. Gertrude

Project META (Metacognitive Enhancing Teaching Activities) is a 3-year naturalistic case study designed to explicitly enhance the metacognitive capabilities of learners in order to illuminate the nature of metacognitive interactions among elementary students and to describe the impact this type of enhancement has on the formation of students'…

Increasing Fruit and Vegetable Consumption among Preschoolers: Evaluation of "Color Me Healthy"

ERIC Educational Resources Information Center

Witt, Kendra E.; Dunn, Carolyn

2012-01-01

Objective: Determine whether "Color Me Healthy" (CMH), an interactive nutrition and physical activity program for preschool children, increases fruit and vegetable consumption. Design: Intervention study. Data were collected at baseline, 1 week post-intervention, and 3 months post-intervention. Setting: Child care centers. Participants: Preschool…

Annelids. A Multimedia CD-ROM. [CD-ROM].

ERIC Educational Resources Information Center

2001

This CD-ROM is designed for classroom and individual use to teach and learn about annelids. Integrated animations, custom graphics, three-dimensional representations, photographs, and sound are featured for use in user-controlled activities. Interactive lessons are available to reinforce the subject material. Pre- and post-testing sections are…

Virtual Reality and Cyberspace: From Science Fiction to Science Fact.

ERIC Educational Resources Information Center

Stone, Robert J.

1991-01-01

Traces the history of virtual reality (VR), or cyberspace, and describes some of the research and development efforts currently being carried out in the United Kingdom, Europe, and the United States. Applications of VR in interactive computer-aided design (CAD), the military, leisure activities, spaceflight, teleconferencing, and medicine are…

Social Skills Training: A Three-Pronged Approach for Developmentally Disabled Adolescents and Young Adults.

ERIC Educational Resources Information Center

Coyne, Phyllis

The document is designed to provide practical information for teachers, parents, group home workers, work activity personnel, and others interested in developing social interaction skills and appropriate social behaviors in developmentally disabled adolescents and young adults. An introductory section discusses social problems of the…

Planning and Implementing the Daily Routine in Slovene Kindergartens and Reggio Emilia Concept

ERIC Educational Resources Information Center

Bercnik, Sanja; Devjak, Tatjana

2012-01-01

Authors in this paper present the design and implementation of daily routines in Slovenian kindergartens. Slovenian national document for preschool education, "Curriculum for Kindergartens" (1999), describes daily kindergarten activities (communication and interaction with and among children, use of compliment and reprehension, and rules…

UNITE 3D Rover Summer Workshop: An Overview and Assessment

ERIC Educational Resources Information Center

Hsiung, Steve C.; Deal, Walter F.; Tuluri, Francis

2017-01-01

UNITE is a program sponsored by the Army Educational Outreach Program (AEOP, 2015). The STEM Enrichment Activities of AEOP are designed to spark student interest in science, technology, engineering, and mathematics, especially among the underserved and those in earlier grades and educators by providing exciting, engaging, interactive, hands-on…