Transport properties in the atmosphere of Jupiter

NASA Technical Reports Server (NTRS)

Biolsi, L., Jr.

1979-01-01

Activities reported include: (1) testing of the computer program used to obtain transport properties for the Hulburt-Hirschfelder potential; (2) calculation of transport properties for the C2-C interaction; (3) preliminary calculations for the C2-C2 interaction; (4) calculation of transport properties for the C2H-He interaction; (5) consideration of the effect of inelastic collisions on the transport properties; and (6) the use of the Hulburt-Hirschfelder potential to model ion-atom interactions.

Metaphors for the Nature of Human-Computer Interaction in an Empowering Environment: Interaction Style Influences the Manner of Human Accomplishment.

ERIC Educational Resources Information Center

Weller, Herman G.; Hartson, H. Rex

1992-01-01

Describes human-computer interface needs for empowering environments in computer usage in which the machine handles the routine mechanics of problem solving while the user concentrates on its higher order meanings. A closed-loop model of interaction is described, interface as illusion is discussed, and metaphors for human-computer interaction are…

Host-pathogen interactions between the human innate immune system and Candida albicans—understanding and modeling defense and evasion strategies

PubMed Central

Dühring, Sybille; Germerodt, Sebastian; Skerka, Christine; Zipfel, Peter F.; Dandekar, Thomas; Schuster, Stefan

2015-01-01

The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given. PMID:26175718

Human-Computer Interaction and Information Management Research Needs

DTIC Science & Technology

2003-10-01

Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be...hand-held personal digital assistants, networked sensors and actuators, and low-power computers on satellites. 5 most complex tools that humans have...calculations using data on external media such as tapes evolved into our multi-functional 21st century systems. More ideas came as networks of computing

Is Human-Computer Interaction Social or Parasocial?

ERIC Educational Resources Information Center

Sundar, S. Shyam

Conducted in the attribution-research paradigm of social psychology, a study examined whether human-computer interaction is fundamentally social (as in human-human interaction) or parasocial (as in human-television interaction). All 30 subjects (drawn from an undergraduate class on communication) were exposed to an identical interaction with…

Monoamine receptor interaction profiles of 4-thio-substituted phenethylamines (2C-T drugs).

PubMed

Luethi, Dino; Trachsel, Daniel; Hoener, Marius C; Liechti, Matthias E

2018-05-15

4-Thio-substituted phenethylamines (2C-T drugs) are potent psychedelics with poorly defined pharmacological properties. Because of their psychedelic effects, 2C-T drugs are sometimes sold as new psychoactive substances (NPSs). The aim of the present study was to characterize the monoamine receptor and transporter interaction profiles of a series of 2C-T drugs. We determined the binding affinities of 2C-T drugs at monoamine receptors and transporters in human cells that were transfected with the respective receptors or transporters. We also investigated the functional activation of serotonergic 5-hydroxytryptamine 2A (5-HT 2A ) and 5-HT 2B receptors, activation of human trace amine-associated receptor 1 (TAAR 1 ), and inhibition of monoamine uptake transporters. 2C-T drugs had high affinity for 5-HT 2A and 5-HT 2C receptors (1-54 nM and 40-350 nM, respectively). With activation potencies of 1-53 nM and 44-370 nM, the drugs were potent 5-HT 2A receptor and 5-HT 2B receptor, respectively, partial agonists. An exception to this were the benzylthiophenethylamines, which did not potently activate the 5-HT 2B receptor (EC 50  > 3000 nM). Furthermore, the compounds bound to serotonergic 5-HT 1A and adrenergic receptors. The compounds had high affinity for the rat TAAR 1 (5-68 nM) and interacted with the mouse but not human TAAR 1 . The 2C-T drugs did not potently interact with monoamine transporters (K i  > 4000 nM). The receptor binding profile of 2C-T drugs predicts psychedelic effects that are mediated by potent 5-HT 2 receptor interactions. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.' Copyright © 2017 Elsevier Ltd. All rights reserved.

Design and verification of halogen-bonding system at the complex interface of human fertilization-related MUP PDZ5 domain with CAMK's C-terminal peptide.

PubMed

Wang, Juan; Guo, Yunjie; Zhang, Xue

2018-02-01

Calmodulin-dependent protein kinase (CAMK) is physiologically activated in fertilized human oocytes and is involved in the Ca 2+ response pathways that link the fertilization calmodulin signal to meiosis resumption and cortical granule exocytosis. The kinase has an unstructured C-terminal tail that can be recognized and bound by the PDZ5 domain of its cognate partner, the multi-PDZ domain protein (MUP). In the current study, we reported a rational biomolecular design of halogen-bonding system at the complex interface of CAMK's C-terminal peptide with MUP PDZ5 domain by using high-level computational approaches. Four organic halogens were employed as atom probes to explore the structural geometry and energetic property of designed halogen bonds in the PDZ5-peptide complex. It was found that the heavier halogen elements such as bromine Br and iodine I can confer stronger halogen bond but would cause bad atomic contacts and overlaps at the complex interface, while fluorine F cannot form effective halogen bond in the complex. In addition, the halogen substitution at different positions of peptide's aromatic ring would result in distinct effects on the halogen-bonding system. The computational findings were then verified by using fluorescence analysis; it is indicated that the halogen type and substitution position play critical role in the interaction strength of halogen bonds, and thus the PDZ5-peptide binding affinity can be improved considerably by optimizing their combination. Copyright © 2017 Elsevier Ltd. All rights reserved.

A male-specific QTL for social interaction behavior in mice mapped with automated pattern detection by a hidden Markov model incorporated into newly developed freeware.

PubMed

Arakawa, Toshiya; Tanave, Akira; Ikeuchi, Shiho; Takahashi, Aki; Kakihara, Satoshi; Kimura, Shingo; Sugimoto, Hiroki; Asada, Nobuhiko; Shiroishi, Toshihiko; Tomihara, Kazuya; Tsuchiya, Takashi; Koide, Tsuyoshi

2014-08-30

Owing to their complex nature, social interaction tests normally require the observation of video data by a human researcher, and thus are difficult to use in large-scale studies. We previously established a statistical method, a hidden Markov model (HMM), which enables the differentiation of two social states ("interaction" and "indifference"), and three social states ("sniffing", "following", and "indifference"), automatically in silico. Here, we developed freeware called DuoMouse for the rapid evaluation of social interaction behavior. This software incorporates five steps: (1) settings, (2) video recording, (3) tracking from the video data, (4) HMM analysis, and (5) visualization of the results. Using DuoMouse, we mapped a genetic locus related to social interaction. We previously reported that a consomic strain, B6-Chr6C(MSM), with its chromosome 6 substituted for one from MSM/Ms, showed more social interaction than C57BL/6 (B6). We made four subconsomic strains, C3, C5, C6, and C7, each of which has a shorter segment of chromosome 6 derived from B6-Chr6C, and conducted social interaction tests on these strains. DuoMouse indicated that C6, but not C3, C5, and C7, showed higher interaction, sniffing, and following than B6, specifically in males. The data obtained by human observation showed high concordance to those from DuoMouse. The results indicated that the MSM-derived chromosomal region present in C6-but not in C3, C5, and C7-associated with increased social behavior. This method to analyze social interaction will aid primary screening for difference in social behavior in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

Young Investigator Program (8.5): Preventing Complex Failures of Human Interactive Systems with Erroneous Behavior Generation and Robust Human Task Behavior Patterns

DTIC Science & Technology

2017-11-13

behavior . The International Journal of Human-Computer Studies , 108, 105-121. https://doi.org/10.1016/j.ijhcs.2017.06.006 A second journal article...documenting the erroneous behavior generation approach and the case study analyses is currently being written. Planned submission is Spring 2017. RPPR...Belvoir, 2010. [3] A task-based taxonomy of erroneous human behavior . International Journal of Human-Computer Studies , 108:105–121, 2017. [4] M. L

Issues in Interaction Language Specification and Representation.

DTIC Science & Technology

1983-11-01

of Dialogues for Human-Computer Interfaces," to be submitted for publication (1983). IHEINL75] Heindel, L. and J. Roberto . "LANG-PAK: An Interactive...22043 Bolling Air Force Base Washington, D.C. 20332 Dr. Paul E. Lehner PAR Technology Corp. AFHRL/LRS TDC P.O. Box 2005 Attn: Susan Ewing Reston, VA 22090

On the Rhetorical Contract in Human-Computer Interaction.

ERIC Educational Resources Information Center

Wenger, Michael J.

1991-01-01

An exploration of the rhetorical contract--i.e., the expectations for appropriate interaction--as it develops in human-computer interaction revealed that direct manipulation interfaces were more likely to establish social expectations. Study results suggest that the social nature of human-computer interactions can be examined with reference to the…

Development of an Anatomically Accurate Finite Element Human Ocular Globe Model for Blast-Related Fluid-Structure Interaction Studies

DTIC Science & Technology

2017-02-01

ARL-TR-7945 ● FEB 2017 US Army Research Laboratory Development of an Anatomically Accurate Finite Element Human Ocular Globe...ARL-TR-7945 ● FEB 2017 US Army Research Laboratory Development of an Anatomically Accurate Finite Element Human Ocular Globe Model... Finite Element Human Ocular Globe Model for Blast-Related Fluid-Structure Interaction Studies 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

Occupational stress in human computer interaction.

PubMed

Smith, M J; Conway, F T; Karsh, B T

1999-04-01

There have been a variety of research approaches that have examined the stress issues related to human computer interaction including laboratory studies, cross-sectional surveys, longitudinal case studies and intervention studies. A critical review of these studies indicates that there are important physiological, biochemical, somatic and psychological indicators of stress that are related to work activities where human computer interaction occurs. Many of the stressors of human computer interaction at work are similar to those stressors that have historically been observed in other automated jobs. These include high workload, high work pressure, diminished job control, inadequate employee training to use new technology, monotonous tasks, por supervisory relations, and fear for job security. New stressors have emerged that can be tied primarily to human computer interaction. These include technology breakdowns, technology slowdowns, and electronic performance monitoring. The effects of the stress of human computer interaction in the workplace are increased physiological arousal; somatic complaints, especially of the musculoskeletal system; mood disturbances, particularly anxiety, fear and anger; and diminished quality of working life, such as reduced job satisfaction. Interventions to reduce the stress of computer technology have included improved technology implementation approaches and increased employee participation in implementation. Recommendations for ways to reduce the stress of human computer interaction at work are presented. These include proper ergonomic conditions, increased organizational support, improved job content, proper workload to decrease work pressure, and enhanced opportunities for social support. A model approach to the design of human computer interaction at work that focuses on the system "balance" is proposed.

Experimental Tests of Normative Group Influence and Representation Effects in Computer-Mediated Communication: When Interacting Via Computers Differs from Interacting With Computers.

ERIC Educational Resources Information Center

Lee, Eun-Ju; Nass, Clifford

2002-01-01

Presents two experiments to address the questions of if and how normative social influence operates in anonymous computer-mediated communication and human-computer interaction. Finds that the perception of interaction partner (human vs. computer) moderated the group conformity effect such that the undergraduate student subjects expressed greater…

Human-computer interaction in multitask situations

NASA Technical Reports Server (NTRS)

Rouse, W. B.

1977-01-01

Human-computer interaction in multitask decisionmaking situations is considered, and it is proposed that humans and computers have overlapping responsibilities. Queueing theory is employed to model this dynamic approach to the allocation of responsibility between human and computer. Results of simulation experiments are used to illustrate the effects of several system variables including number of tasks, mean time between arrivals of action-evoking events, human-computer speed mismatch, probability of computer error, probability of human error, and the level of feedback between human and computer. Current experimental efforts are discussed and the practical issues involved in designing human-computer systems for multitask situations are considered.

Modeling Human-Computer Decision Making with Covariance Structure Analysis.

ERIC Educational Resources Information Center

Coovert, Michael D.; And Others

Arguing that sufficient theory exists about the interplay between human information processing, computer systems, and the demands of various tasks to construct useful theories of human-computer interaction, this study presents a structural model of human-computer interaction and reports the results of various statistical analyses of this model.…

Enhancing Learning through Human Computer Interaction

ERIC Educational Resources Information Center

McKay, Elspeth, Ed.

2007-01-01

Enhancing Learning Through Human Computer Interaction is an excellent reference source for human computer interaction (HCI) applications and designs. This "Premier Reference Source" provides a complete analysis of online business training programs and e-learning in the higher education sector. It describes a range of positive outcomes for linking…

A model based on spectrofluorimetry to study the interaction between glyphosate and serum albumin of Salminus brasiliensis

NASA Astrophysics Data System (ADS)

Escobar, Marta Araujo Cyrino; Cortez, Celia Martins; Silva, Dilson; Neto, Jayme da Cunha Bastos

2017-11-01

The aim of this work is to initiate an investigation on the albumin of Salminus brasiliensis (gold fish) as a biomarker of environmental actions of glyphosate. We started using a mathematical-computational model based on spectrofluorimetric measurements to study the interaction of glyphosate with gold fish albumin and human serum albumin. Salminus brasiliensis is a migratory freshwater fish species found in southern and central-western Brazil, mainly in the Prata river basin, where most of soybean plantations are set. Glyphosate is a very used herbicide in this type of crop. Differently from the organophosphorate methyl parathion, glyphosate does not form complex with HSA, and the quenching constants estimated for its binding with gold fish albumin at 20 °C and 25 °C is 1.3(± 0.3) × 104 / M e 2.5 (± 0.3) × 104 / M, respectively.

Can Robots and Humans Get Along?

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

Scholtz, Jean

2007-06-01

Now that robots have moved into the mainstream—as vacuum cleaners, lawn mowers, autonomous vehicles, tour guides, and even pets—it is important to consider how everyday people will interact with them. A robot is really just a computer, but many researchers are beginning to understand that human-robot interactions are much different than human-computer interactions. So while the metrics used to evaluate the human-computer interaction (usability of the software interface in terms of time, accuracy, and user satisfaction) may also be appropriate for human-robot interactions, we need to determine whether there are additional metrics that should be considered.

The Dimensionality and Correlates of Flow in Human-Computer Interactions.

ERIC Educational Resources Information Center

Webster, Jane; And Others

1993-01-01

Defines playfulness in human-computer interactions in terms of flow theory and explores the dimensionality of the flow concept. Two studies are reported that investigated the factor structure and correlates of flow in human-computer interactions: one examined MBA students using Lotus 1-2-3 spreadsheet software, and one examined employees using…

Towards Better Human Robot Interaction: Understand Human Computer Interaction in Social Gaming Using a Video-Enhanced Diary Method

NASA Astrophysics Data System (ADS)

See, Swee Lan; Tan, Mitchell; Looi, Qin En

This paper presents findings from a descriptive research on social gaming. A video-enhanced diary method was used to understand the user experience in social gaming. From this experiment, we found that natural human behavior and gamer’s decision making process can be elicited and speculated during human computer interaction. These are new information that we should consider as they can help us build better human computer interfaces and human robotic interfaces in future.

Natural Tasking of Robots Based on Human Interaction Cues

DTIC Science & Technology

2005-06-01

MIT. • Matthew Marjanovic , researcher, ITA Software. • Brian Scasselatti, Assistant Professor of Computer Science, Yale. • Matthew Williamson...2004. 25 [74] Charlie C. Kemp. Shoes as a platform for vision. 7th IEEE International Symposium on Wearable Computers, 2004. [75] Matthew Marjanovic ...meso: Simulated muscles for a humanoid robot. Presentation for Humanoid Robotics Group, MIT AI Lab, August 2001. [76] Matthew J. Marjanovic . Teaching

Troponin structure: its modulation by Ca(2+) and phosphorylation studied by molecular dynamics simulations.

PubMed

Zamora, Juan Eiros; Papadaki, Maria; Messer, Andrew E; Marston, Steven B; Gould, Ian R

2016-07-27

The only available crystal structure of the human cardiac troponin molecule (cTn) in the Ca(2+) activated state does not include crucial segments, including the N-terminus of the cTn inhibitory subunit (cTnI). We have applied all-atom molecular dynamics (MD) simulations to study the structure and dynamics of cTn, both in the unphosphorylated and bis-phosphorylated states at Ser23/Ser24 of cTnI. We performed multiple microsecond MD simulations of wild type (WT) cTn (6, 5 μs) and bisphosphorylated (SP23/SP24) cTn (9 μs) on a 419 amino acid cTn model containing human sequence cTnC (1-161), cTnI (1-171) and cTnT (212-298), including residues not present in the crystal structure. We have compared our results to previous computational studies, and proven that longer simulations and a water box of at least 25 Å are needed to sample the interesting conformational shifts both in the native and bis-phosphorylated states. As a consequence of the introduction into the model of the C-terminus of cTnT that was missing in previous studies, cTnC-cTnI interactions that are responsible for the cTn dynamics are altered. We have also shown that phosphorylation does not increase cTn fluctuations, and its effects on the protein-protein interaction profiles cannot be assessed in a significant way. Finally, we propose that phosphorylation could provoke a loss of Ca(2+) by stabilizing out-of-coordination distances of the cTnC's EF hand II residues, and in particular Ser 69.

Language evolution and human-computer interaction

NASA Technical Reports Server (NTRS)

Grudin, Jonathan; Norman, Donald A.

1991-01-01

Many of the issues that confront designers of interactive computer systems also appear in natural language evolution. Natural languages and human-computer interfaces share as their primary mission the support of extended 'dialogues' between responsive entities. Because in each case one participant is a human being, some of the pressures operating on natural languages, causing them to evolve in order to better support such dialogue, also operate on human-computer 'languages' or interfaces. This does not necessarily push interfaces in the direction of natural language - since one entity in this dialogue is not a human, this is not to be expected. Nonetheless, by discerning where the pressures that guide natural language evolution also appear in human-computer interaction, we can contribute to the design of computer systems and obtain a new perspective on natural languages.

Disease-modifying anti-Alzheimer's drugs: inhibitors of human cholinesterases interfering with β-amyloid aggregation.

PubMed

Brogi, Simone; Butini, Stefania; Maramai, Samuele; Colombo, Raffaella; Verga, Laura; Lanni, Cristina; De Lorenzi, Ersilia; Lamponi, Stefania; Andreassi, Marco; Bartolini, Manuela; Andrisano, Vincenza; Novellino, Ettore; Campiani, Giuseppe; Brindisi, Margherita; Gemma, Sandra

2014-07-01

We recently described multifunctional tools (2a-c) as potent inhibitors of human Cholinesterases (ChEs) also able to modulate events correlated with Aβ aggregation. We herein propose a thorough biological and computational analysis aiming at understanding their mechanism of action at the molecular level. We determined the inhibitory potency of 2a-c on Aβ1-42 self-aggregation, the interference of 2a with the toxic Aβ oligomeric species and with the postaggregation states by capillary electrophoresis analysis and transmission electron microscopy. The modulation of Aβ toxicity was assessed for 2a and 2b on human neuroblastoma cells. The key interactions of 2a with Aβ and with the Aβ-preformed fibrils were computationally analyzed. 2a-c toxicity profile was also assessed (human hepatocytes and mouse fibroblasts). Our prototypical pluripotent analogue 2a interferes with Aβ oligomerization process thus reducing Aβ oligomers-mediated toxicity in human neuroblastoma cells. 2a also disrupts preformed fibrils. Computational studies highlighted the bases governing the diversified activities of 2a. Converging analytical, biological, and in silico data explained the mechanism of action of 2a on Aβ1-42 oligomers formation and against Aβ-preformed fibrils. This evidence, combined with toxicity data, will orient the future design of safer analogues. © 2014 John Wiley & Sons Ltd.

The Study of Surface Computer Supported Cooperative Work and Its Design, Efficiency, and Challenges

ERIC Educational Resources Information Center

Hwang, Wu-Yuin; Su, Jia-Han

2012-01-01

In this study, a Surface Computer Supported Cooperative Work paradigm is proposed. Recently, multitouch technology has become widely available for human-computer interaction. We found it has great potential to facilitate more awareness of human-to-human interaction than personal computers (PCs) in colocated collaborative work. However, other…

Creative Multimodal Learning Environments and Blended Interaction for Problem-Based Activity in HCI Education

ERIC Educational Resources Information Center

Ioannou, Andri; Vasiliou, Christina; Zaphiris, Panayiotis; Arh, Tanja; Klobucar, Tomaž; Pipan, Matija

2015-01-01

This exploratory case study aims to examine how students benefit from a multimodal learning environment while they engage in collaborative problem-based activity in a Human Computer Interaction (HCI) university course. For 12 weeks, 30 students, in groups of 5-7 each, participated in weekly face-to-face meetings and online interactions.…

Computational identification of gene–social environment interaction at the human IL6 locus

PubMed Central

Cole, Steven W.; Arevalo, Jesusa M. G.; Takahashi, Rie; Sloan, Erica K.; Lutgendorf, Susan K.; Sood, Anil K.; Sheridan, John F.; Seeman, Teresa E.

2010-01-01

To identify genetic factors that interact with social environments to impact human health, we used a bioinformatic strategy that couples expression array–based detection of environmentally responsive transcription factors with in silico discovery of regulatory polymorphisms to predict genetic loci that modulate transcriptional responses to stressful environments. Tests of one predicted interaction locus in the human IL6 promoter (SNP rs1800795) verified that it modulates transcriptional response to β-adrenergic activation of the GATA1 transcription factor in vitro. In vivo validation studies confirmed links between adverse social conditions and increased transcription of GATA1 target genes in primary neural, immune, and cancer cells. Epidemiologic analyses verified the health significance of those molecular interactions by documenting increased 10-year mortality risk associated with late-life depressive symptoms that occurred solely for homozygous carriers of the GATA1-sensitive G allele of rs1800795. Gating of depression-related mortality risk by IL6 genotype pertained only to inflammation-related causes of death and was associated with increased chronic inflammation as indexed by plasma C-reactive protein. Computational modeling of molecular interactions, in vitro biochemical analyses, in vivo animal modeling, and human molecular epidemiologic analyses thus converge in identifying β-adrenergic activation of GATA1 as a molecular pathway by which social adversity can alter human health risk selectively depending on individual genetic status at the IL6 locus. PMID:20176930

Transportable Applications Environment (TAE) Tenth Users' Conference

NASA Technical Reports Server (NTRS)

Rouff, Chris (Editor); Harris, Elfrieda (Editor); Yeager, Arleen (Editor)

1993-01-01

Conference proceedings are represented in graphic visual-aid form. Presentation and panel discussion topics include user experiences with C++ and Ada; the design and interaction of the user interface; the history and goals of TAE; commercialization and testing of TAE Plus; Computer-Human Interaction Models (CHIMES); data driven objects; item-to-item connections and object dependencies; and integration with other software. There follows a list of conference attendees.

Intermolecular interactions between σ- and π-holes of bromopentafluorobenzene and pyridine: computational and experimental investigations.

PubMed

Yang, Fang-Ling; Yang, Xing; Wu, Rui-Zhi; Yan, Chao-Xian; Yang, Fan; Ye, Weichun; Zhang, Liang-Wei; Zhou, Pan-Pan

2018-04-25

The characters of σ- and π-holes of bromopentafluorobenzene (C6F5Br) enable it to interact with an electron-rich atom or group like pyridine which possesses an electron lone-pair N atom and a π ring. Theoretical studies of intermolecular interactions between C6F5Br and C5H5N have been carried out at the M06-2X/aug-cc-pVDZ level without and with the counterpoise method, together with single point calculations at M06-2X/TZVP, wB97-XD/aug-cc-pVDZ and CCSD(T)/aug-cc-pVDZ levels. The σ- and π-holes of C6F5Br exhibiting positive electrostatic potentials make these sites favorably interact with the N atom and the π ring of C5H5N with negative electrostatic potentials, leading to five different dimers connected by a σ-holen bond, a σ-holeπ bond or a π-holeπ bond. Their geometrical structures, characteristics, nature and spectroscopy behaviors were systematically investigated. EDA analyses reveal that the driving forces in these dimers are different. NCI, QTAIM and NBO analyses confirm the existence of intermolecular interactions formed via σ- and π-holes of C6F5Br and the N atom and the π ring of C5H5N. The experimental IR and Raman spectra gave us important information about the formation of molecular complexes between C6F5Br and C5H5N. We expect that the results could provide valuable insights into the investigation of intermolecular interactions involving σ- and π-holes.

Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin.

PubMed

Tromp, Angelino T; Van Gent, Michiel; Abrial, Pauline; Martin, Amandine; Jansen, Joris P; De Haas, Carla J C; Van Kessel, Kok P M; Bardoel, Bart W; Kruse, Elisabeth; Bourdonnay, Emilie; Boettcher, Michael; McManus, Michael T; Day, Christopher J; Jennings, Michael P; Lina, Gérard; Vandenesch, François; Van Strijp, Jos A G; Jan Lebbink, Robert; Haas, Pieter-Jan A; Henry, Thomas; Spaan, András N

2018-05-07

The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1 KI ) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1 KI mice. Compared to humans, murine hC5aR1 KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV. By performing a genome-wide CRISPR-Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1 KI mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL.

Delayed system response times affect immediate physiology and the dynamics of subsequent button press behavior.

PubMed

Kohrs, Christin; Hrabal, David; Angenstein, Nicole; Brechmann, André

2014-11-01

System response time research is an important issue in human-computer interactions. Experience with technical devices and general rules of human-human interactions determine the user's expectation, and any delay in system response time may lead to immediate physiological, emotional, and behavioral consequences. We investigated such effects on a trial-by-trial basis during a human-computer interaction by measuring changes in skin conductance (SC), heart rate (HR), and the dynamics of button press responses. We found an increase in SC and a deceleration of HR for all three delayed system response times (0.5, 1, 2 s). Moreover, the data on button press dynamics was highly informative since subjects repeated a button press with more force in response to delayed system response times. Furthermore, the button press dynamics could distinguish between correct and incorrect decisions and may thus even be used to infer the uncertainty of a user's decision. Copyright © 2014 Society for Psychophysiological Research.

Human-Computer Interaction and Sociological Insight: A Theoretical Examination and Experiment in Building Affinity in Small Groups

ERIC Educational Resources Information Center

Oren, Michael Anthony

2011-01-01

The juxtaposition of classic sociological theory and the, relatively, young discipline of human-computer interaction (HCI) serves as a powerful mechanism for both exploring the theoretical impacts of technology on human interactions as well as the application of technological systems to moderate interactions. It is the intent of this dissertation…

Elucidation of the Binding Mode of the Carboxyterminal Region of Peptide YY to the Human Y2 Receptor.

PubMed

Xu, Bo; Vasile, Silvana; Østergaard, Søren; Paulsson, Johan F; Pruner, Jasna; Åqvist, Johan; Wulff, Birgitte S; Gutiérrez-de-Terán, Hugo; Larhammar, Dan

2018-04-01

Understanding the agonist-receptor interactions in the neuropeptide Y (NPY)/peptide YY (PYY) signaling system is fundamental for the design of novel modulators of appetite regulation. We report here the results of a multidisciplinary approach to elucidate the binding mode of the native peptide agonist PYY to the human Y 2 receptor, based on computational modeling, peptide chemistry and in vitro pharmacological analyses. The preserved binding orientation proposed for full-length PYY and five analogs, truncated at the amino terminus, explains our pharmacological results where truncations of the N-terminal proline helix showed little effect on peptide affinity. This was followed by receptor mutagenesis to investigate the roles of several receptor positions suggested by the modeling. As a complement, PYY-(3-36) analogs were synthesized with modifications at different positions in the common PYY/NPY C-terminal fragment ( 32 TRQRY 36 -amide). The results were assessed and interpreted by molecular dynamics and Free Energy Perturbation (FEP) simulations of selected mutants, providing a detailed map of the interactions of the PYY/NPY C-terminal fragment with the transmembrane cavity of the Y 2 receptor. The amidated C-terminus would be stabilized by polar interactions with Gln288 6.55 and Tyr219 5.39 , while Gln130 3.32 contributes to interactions with Q 34 in the peptide and T 32 is close to the tip of TM7 in the receptor. This leaves the core, α -helix of the peptide exposed to make potential interactions with the extracellular loops. This model agrees with most experimental data available for the Y 2 system and can be used as a basis for optimization of Y 2 receptor agonists. Copyright © 2018 by The Author(s).

Computer Aided Conceptual Design of Submarines

DTIC Science & Technology

1984-06-01

Department 5f i ngi eering . May 19134 Certified by: Thesi Supervisor Accepted Y.’.I Cr’rman, (IeaV gineer ing Departmental Comimitte C - nuusý"(Xwa has...the equilibrium polygon. The Package interfaces with a pressure hull design module developed separately in an O.E. thesis by Marvin Meade. Interactive...computers or computer aided design systems. c- A𔃺ccession -or4 Thesis Supervisor: Dr. David V. Burke NI R~ Title: Professor of Ocean Engineering DTIC

Analysing the Effect of Mutation on Protein Function and Discovering Potential Inhibitors of CDK4: Molecular Modelling and Dynamics Studies

PubMed Central

N, Nagasundaram; Zhu, Hailong; Liu, Jiming; V, Karthick; C, George Priya Doss; Chakraborty, Chiranjib; Chen, Luonan

2015-01-01

The cyclin-dependent kinase 4 (CDK4)-cyclin D1 complex plays a crucial role in the transition from the G1 phase to S phase of the cell cycle. Among the CDKs, CDK4 is one of the genes most frequently affected by somatic genetic variations that are associated with various forms of cancer. Thus, because the abnormal function of the CDK4-cyclin D1 protein complex might play a vital role in causing cancer, CDK4 can be considered a genetically validated therapeutic target. In this study, we used a systematic, integrated computational approach to identify deleterious nsSNPs and predict their effects on protein-protein (CDK4-cyclin D1) and protein-ligand (CDK4-flavopiridol) interactions. This analysis resulted in the identification of possible inhibitors of mutant CDK4 proteins that bind the conformations induced by deleterious nsSNPs. Using computational prediction methods, we identified five nsSNPs as highly deleterious: R24C, Y180H, A205T, R210P, and R246C. From molecular docking and molecular dynamic studies, we observed that these deleterious nsSNPs affected CDK4-cyclin D1 and CDK4-flavopiridol interactions. Furthermore, in a virtual screening approach, the drug 5_7_DIHYDROXY_ 2_ (3_4_5_TRI HYDROXYPHENYL) _4H_CHROMEN_ 4_ONE displayed good binding affinity for proteins with the mutations R24C or R246C, the drug diosmin displayed good binding affinity for the protein with the mutation Y180H, and the drug rutin displayed good binding affinity for proteins with the mutations A205T and R210P. Overall, this computational investigation of the CDK4 gene highlights the link between genetic variation and biological phenomena in human cancer and aids in the discovery of molecularly targeted therapies for personalized treatment. PMID:26252490

Human-Computer Interaction and Virtual Environments

NASA Technical Reports Server (NTRS)

Noor, Ahmed K. (Compiler)

1995-01-01

The proceedings of the Workshop on Human-Computer Interaction and Virtual Environments are presented along with a list of attendees. The objectives of the workshop were to assess the state-of-technology and level of maturity of several areas in human-computer interaction and to provide guidelines for focused future research leading to effective use of these facilities in the design/fabrication and operation of future high-performance engineering systems.

Multimodal approaches for emotion recognition: a survey

NASA Astrophysics Data System (ADS)

Sebe, Nicu; Cohen, Ira; Gevers, Theo; Huang, Thomas S.

2004-12-01

Recent technological advances have enabled human users to interact with computers in ways previously unimaginable. Beyond the confines of the keyboard and mouse, new modalities for human-computer interaction such as voice, gesture, and force-feedback are emerging. Despite important advances, one necessary ingredient for natural interaction is still missing-emotions. Emotions play an important role in human-to-human communication and interaction, allowing people to express themselves beyond the verbal domain. The ability to understand human emotions is desirable for the computer in several applications. This paper explores new ways of human-computer interaction that enable the computer to be more aware of the user's emotional and attentional expressions. We present the basic research in the field and the recent advances into the emotion recognition from facial, voice, and physiological signals, where the different modalities are treated independently. We then describe the challenging problem of multimodal emotion recognition and we advocate the use of probabilistic graphical models when fusing the different modalities. We also discuss the difficult issues of obtaining reliable affective data, obtaining ground truth for emotion recognition, and the use of unlabeled data.

Multimodal approaches for emotion recognition: a survey

NASA Astrophysics Data System (ADS)

Sebe, Nicu; Cohen, Ira; Gevers, Theo; Huang, Thomas S.

2005-01-01

Recent technological advances have enabled human users to interact with computers in ways previously unimaginable. Beyond the confines of the keyboard and mouse, new modalities for human-computer interaction such as voice, gesture, and force-feedback are emerging. Despite important advances, one necessary ingredient for natural interaction is still missing-emotions. Emotions play an important role in human-to-human communication and interaction, allowing people to express themselves beyond the verbal domain. The ability to understand human emotions is desirable for the computer in several applications. This paper explores new ways of human-computer interaction that enable the computer to be more aware of the user's emotional and attentional expressions. We present the basic research in the field and the recent advances into the emotion recognition from facial, voice, and physiological signals, where the different modalities are treated independently. We then describe the challenging problem of multimodal emotion recognition and we advocate the use of probabilistic graphical models when fusing the different modalities. We also discuss the difficult issues of obtaining reliable affective data, obtaining ground truth for emotion recognition, and the use of unlabeled data.

Antagonist interaction with the human 5-HT7 receptor mediates the rapid and potent inhibition of non-G-protein-stimulated adenylate cyclase activity: a novel GPCR effect

PubMed Central

Klein, MT; Teitler, M

2011-01-01

BACKGROUND AND PURPOSE The human 5-hydroxytryptamine7 (h5-HT7) receptor is Gs-coupled and stimulates the production of the intracellular signalling molecule cAMP. Previously, we reported a novel property of the h5-HT7 receptor: pseudo-irreversible antagonists irreversibly inhibit forskolin-stimulated (non-receptor-mediated) cAMP production. Herein, we sought to determine if competitive antagonists also affect forskolin-stimulated activity and if this effect is common among other Gs-coupled receptors. EXPERIMENTAL APPROACH Recombinant cell lines expressing h5-HT7 receptors or other receptors of interest were briefly exposed to antagonists; cAMP production was then stimulated by forskolin and quantified by an immunocompetitive assay. KEY RESULTS In human embryonic kidney 293 cells stably expressing h5-HT7 receptors, all competitive antagonists inhibited nearly 100% of forskolin-stimulated cAMP production. This effect was insensitive to pertussis toxin, that is, not Gi/o-mediated. Potency to inhibit forskolin-stimulated activity strongly correlated with h5-HT7 binding affinity (r2= 0.91), indicating that the antagonists acted through h5-HT7 receptors to inhibit forskolin. Potency and maximal effects of clozapine, a prototypical competitive h5-HT7 antagonist, were unaffected by varying forskolin concentration. Antagonist interaction with h5-HT6, human β1, β2, and β3 adrenoceptors did not inhibit forskolin's activity. CONCLUSIONS AND IMPLICATIONS The inhibition of adenylate cyclase, as measured by forskolin's activity, is an underlying property of antagonist interaction with h5-HT7 receptors; however, this is not a common property of other Gs-coupled receptors. This phenomenon may be involved in the roles played by h5-HT7 receptors in human physiology. Development of h5-HT7 antagonists that do not elicit this effect would aid in the elucidation of its mechanisms and shed light on its possible physiological relevance. PMID:21198551

The BioC-BioGRID corpus: full text articles annotated for curation of protein–protein and genetic interactions

PubMed Central

Kim, Sun; Chatr-aryamontri, Andrew; Chang, Christie S.; Oughtred, Rose; Rust, Jennifer; Wilbur, W. John; Comeau, Donald C.; Dolinski, Kara; Tyers, Mike

2017-01-01

A great deal of information on the molecular genetics and biochemistry of model organisms has been reported in the scientific literature. However, this data is typically described in free text form and is not readily amenable to computational analyses. To this end, the BioGRID database systematically curates the biomedical literature for genetic and protein interaction data. This data is provided in a standardized computationally tractable format and includes structured annotation of experimental evidence. BioGRID curation necessarily involves substantial human effort by expert curators who must read each publication to extract the relevant information. Computational text-mining methods offer the potential to augment and accelerate manual curation. To facilitate the development of practical text-mining strategies, a new challenge was organized in BioCreative V for the BioC task, the collaborative Biocurator Assistant Task. This was a non-competitive, cooperative task in which the participants worked together to build BioC-compatible modules into an integrated pipeline to assist BioGRID curators. As an integral part of this task, a test collection of full text articles was developed that contained both biological entity annotations (gene/protein and organism/species) and molecular interaction annotations (protein–protein and genetic interactions (PPIs and GIs)). This collection, which we call the BioC-BioGRID corpus, was annotated by four BioGRID curators over three rounds of annotation and contains 120 full text articles curated in a dataset representing two major model organisms, namely budding yeast and human. The BioC-BioGRID corpus contains annotations for 6409 mentions of genes and their Entrez Gene IDs, 186 mentions of organism names and their NCBI Taxonomy IDs, 1867 mentions of PPIs and 701 annotations of PPI experimental evidence statements, 856 mentions of GIs and 399 annotations of GI evidence statements. The purpose, characteristics and possible future uses of the BioC-BioGRID corpus are detailed in this report. Database URL: http://bioc.sourceforge.net/BioC-BioGRID.html PMID:28077563

Triazolopyridinyl-acrylonitrile derivatives as antimicrotubule agents: Synthesis, in vitro and in silico characterization of antiproliferative activity, inhibition of tubulin polymerization and binding thermodynamics.

PubMed

Briguglio, Irene; Laurini, Erik; Pirisi, Maria Antonietta; Piras, Sandra; Corona, Paola; Fermeglia, Maurizio; Pricl, Sabrina; Carta, Antonio

2017-12-01

In this paper we report the synthesis, in vitro anticancer activity, and the experimental/computational characterization of mechanism of action of a new series of E isomers of triazolo[4,5-b/c]pyridin-acrylonitrile derivatives (6c-g, 7d-e, 8d-e, 9c-f, 10d-e, 11d-e). All new compounds are endowed with moderate to interesting antiproliferative activity against 9 different cancer cell lines derived from solid and hematological human tumors. Fluorescence-based assays prove that these molecules interfere with tubulin polymerization. Furthermore, isothermal titration calorimetry (ITC) provides full tubulin/compound binding thermodynamics, thereby ultimately qualifying and quantifying the interactions of these molecular series with the target protein. Lastly, the analysis based on the tight coupling of in vitro and in silico modeling of the interactions between tubulin and the title compounds allows to propose a molecular rationale for their biological activity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Human Factors Considerations in System Design

NASA Technical Reports Server (NTRS)

Mitchell, C. M. (Editor); Vanbalen, P. M. (Editor); Moe, K. L. (Editor)

1983-01-01

Human factors considerations in systems design was examined. Human factors in automated command and control, in the efficiency of the human computer interface and system effectiveness are outlined. The following topics are discussed: human factors aspects of control room design; design of interactive systems; human computer dialogue, interaction tasks and techniques; guidelines on ergonomic aspects of control rooms and highly automated environments; system engineering for control by humans; conceptual models of information processing; information display and interaction in real time environments.

Rapid Human-Computer Interactive Conceptual Design of Mobile and Manipulative Robot Systems

DTIC Science & Technology

2015-05-19

algorithm based on Age-Fitness Pareto Optimization (AFPO) ([9]) with an additional user prefer- ence objective and a neural network-based user model, we...greater than 40, which is about 5 times further than any robot traveled in our experiments. 6 3.3 Methods The algorithm uses a client -server computational...architecture. The client here is an interactive pro- gram which takes a pair of controllers as input, simulates4 two copies of the robot with

Accelerating epistasis analysis in human genetics with consumer graphics hardware.

PubMed

Sinnott-Armstrong, Nicholas A; Greene, Casey S; Cancare, Fabio; Moore, Jason H

2009-07-24

Human geneticists are now capable of measuring more than one million DNA sequence variations from across the human genome. The new challenge is to develop computationally feasible methods capable of analyzing these data for associations with common human disease, particularly in the context of epistasis. Epistasis describes the situation where multiple genes interact in a complex non-linear manner to determine an individual's disease risk and is thought to be ubiquitous for common diseases. Multifactor Dimensionality Reduction (MDR) is an algorithm capable of detecting epistasis. An exhaustive analysis with MDR is often computationally expensive, particularly for high order interactions. This challenge has previously been met with parallel computation and expensive hardware. The option we examine here exploits commodity hardware designed for computer graphics. In modern computers Graphics Processing Units (GPUs) have more memory bandwidth and computational capability than Central Processing Units (CPUs) and are well suited to this problem. Advances in the video game industry have led to an economy of scale creating a situation where these powerful components are readily available at very low cost. Here we implement and evaluate the performance of the MDR algorithm on GPUs. Of primary interest are the time required for an epistasis analysis and the price to performance ratio of available solutions. We found that using MDR on GPUs consistently increased performance per machine over both a feature rich Java software package and a C++ cluster implementation. The performance of a GPU workstation running a GPU implementation reduces computation time by a factor of 160 compared to an 8-core workstation running the Java implementation on CPUs. This GPU workstation performs similarly to 150 cores running an optimized C++ implementation on a Beowulf cluster. Furthermore this GPU system provides extremely cost effective performance while leaving the CPU available for other tasks. The GPU workstation containing three GPUs costs $2000 while obtaining similar performance on a Beowulf cluster requires 150 CPU cores which, including the added infrastructure and support cost of the cluster system, cost approximately $82,500. Graphics hardware based computing provides a cost effective means to perform genetic analysis of epistasis using MDR on large datasets without the infrastructure of a computing cluster.

Development of an E-Prime Based Computer Simulation of an Interactive Human Rights Violation Negotiation Script (Developpement d’un Programme de Simulation par Ordinateur Fonde sur le Logiciel E Prime pour la Negociation Interactive en cas de Violation des Droits de la Personne)

DTIC Science & Technology

2010-12-01

Base ( CFB ) Kingston. The computer simulation developed in this project is intended to be used for future research and as a possible training platform...DRDC Toronto No. CR 2010-055 Development of an E-Prime based computer simulation of an interactive Human Rights Violation negotiation script...Abstract This report describes the method of developing an E-Prime computer simulation of an interactive Human Rights Violation (HRV) negotiation. An

Construction of high-quality Caco-2 three-frame cDNA library and its application to yeast two-hybrid for the human astrovirus protein-protein interaction.

PubMed

Zhao, Wei; Li, Xin; Liu, Wen-Hui; Zhao, Jian; Jin, Yi-Ming; Sui, Ting-Ting

2014-09-01

Human epithelial colorectal adenocarcinoma (Caco-2) cells are widely used as an in vitro model of the human small intestinal mucosa. Caco-2 cells are host cells of the human astrovirus (HAstV) and other enteroviruses. High quality cDNA libraries are pertinent resources and critical tools for protein-protein interaction research, but are currently unavailable for Caco-2 cells. To construct a three-open reading frame, full length-expression cDNA library from the Caco-2 cell line for application to HAstV protein-protein interaction screening, total RNA was extracted from Caco-2 cells. The switching mechanism at the 5' end of the RNA transcript technique was used for cDNA synthesis. Double-stranded cDNA was digested by Sfi I and ligated to reconstruct a pGADT7-Sfi I three-frame vector. The ligation mixture was transformed into Escherichia coli HST08 premium electro cells by electroporation to construct the primary cDNA library. The library capacity was 1.0×10(6)clones. Gel electrophoresis results indicated that the fragments ranged from 0.5kb to 4.2kb. Randomly picked clones show that the recombination rate was 100%. The three-frame primary cDNA library plasmid mixture (5×10(5)cfu) was also transformed into E. coli HST08 premium electro cells, and all clones were harvested to amplify the cDNA library. To detect the sufficiency of the cDNA library, HAstV capsid protein as bait was screened and tested against the Caco-2 cDNA library by a yeast two-hybrid (Y2H) system. A total of 20 proteins were found to interact with the capsid protein. These results showed that a high-quality three-frame cDNA library from Caco-2 cells was successfully constructed. This library was efficient for the application to the Y2H system, and could be used for future research. Copyright © 2014 Elsevier B.V. All rights reserved.

Human-Computer Interaction: A Review of the Research on Its Affective and Social Aspects.

ERIC Educational Resources Information Center

Deaudelin, Colette; Dussault, Marc; Brodeur, Monique

2003-01-01

Discusses a review of 34 qualitative and non-qualitative studies related to affective and social aspects of student-computer interactions. Highlights include the nature of the human-computer interaction (HCI); the interface, comparing graphic and text types; and the relation between variables linked to HCI, mainly trust, locus of control,…

Assessing the attractive/repulsive force balance in axial cyclohexane C-Hax ···Yax contacts: A combined computational analysis in monosubstituted cyclohexanes.

PubMed

Silva Lopez, Carlos; Nieto Faza, Olalla; De Proft, Frank; Kolocouris, Antonios

2016-11-15

The interactions of axial substituents in monosubstituted cyclohexane rings are studied in this work using an array of different computational techniques. Additionally, the anomalous axial preference for some bulky substituents is related to stabilizing dispersion interactions. We find that the C-H ax ···Y ax contacts for various substituents with distances ranging from 2 to ∼5 Å may include attractive dispersion forces that can affect the conformational equilibrium; these forces co-exist with Pauli repulsive forces effected by Y ax group due to van der Waals sphere penetration. At distances between 2 and 3 Å stabilizing electron transfer interactions were calculated and the combination of natural bond orbital and QTAIM analysis showed that, in certain cases, Y ax  =  t Bu, C ax -O or C ax  = O or S ax  = O or C ax  = S this interaction can be characterized as an improper H-bond. DFT-D3 and non-covalent interactions calculations (NCIs) in cyclohexane derivatives with Y ax  = SiOR 3 including H Yax ···H cy surfaces at distances ranging between 4 and 6 Å suggest that dispersion has a clear effect on the experimentally observed stabilization of the axial conformer. NCIs computed from the reduced density gradient help to visually identify and analyze these interactions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Human-Robot Teams for Unknown and Uncertain Environments

NASA Technical Reports Server (NTRS)

Fong, Terry

2015-01-01

Man-robot interaction is the study of interactions between humans and robots. It is often referred as HRI by researchers. Human-robot interaction is a multidisciplinary field with contributions from human-computer interaction, artificial intelligence.

Agent Interaction with Human Systems in Complex Environments: Requirements for Automating the Function of CapCom in Apollo 17

NASA Technical Reports Server (NTRS)

Clancey, William J.

2003-01-01

A human-centered approach to computer systems design involves reframing analysis in terms of people interacting with each other, not only human-machine interaction. The primary concern is not how people can interact with computers, but how shall we design computers to help people work together? An analysis of astronaut interactions with CapCom on Earth during one traverse of Apollo 17 shows what kind of information was conveyed and what might be automated today. A variety of agent and robotic technologies are proposed that deal with recurrent problems in communication and coordination during the analyzed traverse.

Short-term and long-term plasticity interaction in human primary motor cortex.

PubMed

Iezzi, Ennio; Suppa, Antonio; Conte, Antonella; Li Voti, Pietro; Bologna, Matteo; Berardelli, Alfredo

2011-05-01

Repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) elicits changes in motor evoked potential (MEP) size thought to reflect short- and long-term forms of synaptic plasticity, resembling short-term potentiation (STP) and long-term potentiation/depression (LTP/LTD) observed in animal experiments. We designed this study in healthy humans to investigate whether STP as elicited by 5-Hz rTMS interferes with LTP/LTD-like plasticity induced by intermittent and continuous theta-burst stimulation (iTBS and cTBS). The effects induced by 5-Hz rTMS and iTBS/cTBS were indexed as changes in MEP size. We separately evaluated changes induced by 5-Hz rTMS, iTBS and cTBS applied alone and those induced by iTBS and cTBS delivered after priming 5-Hz rTMS. Interactions between 5-Hz rTMS and iTBS/cTBS were investigated under several experimental conditions by delivering 5-Hz rTMS at suprathreshold and subthreshold intensity, allowing 1 and 5 min intervals to elapse between 5-Hz rTMS and TBS, and delivering one and ten 5-Hz rTMS trains. We also investigated whether 5-Hz rTMS induces changes in intracortical excitability tested with paired-pulse transcranial magnetic stimulation. When given alone, 5-Hz rTMS induced short-lasting and iTBS/cTBS induced long-lasting changes in MEP amplitudes. When M1 was primed with 10 suprathreshold 5-Hz rTMS trains at 1 min before iTBS or cTBS, the iTBS/cTBS-induced after-effects disappeared. The 5-Hz rTMS left intracortical excitability unchanged. We suggest that STP elicited by suprathreshold 5-Hz rTMS abolishes iTBS/cTBS-induced LTP/LTD-like plasticity through non-homeostatic metaplasticity mechanisms. Our study provides new information on interactions between short-term and long-term rTMS-induced plasticity in human M1. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Electrostatic contributions drive the interaction between Staphylococcus aureus protein Efb-C and its complement target C3d.

PubMed

Haspel, Nurit; Ricklin, Daniel; Geisbrecht, Brian V; Kavraki, Lydia E; Lambris, John D

2008-11-01

The C3-inhibitory domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb-C) defines a novel three-helix bundle motif that regulates complement activation. Previous crystallographic studies of Efb-C bound to its cognate subdomain of human C3 (C3d) identified Arg-131 and Asn-138 of Efb-C as key residues for its activity. In order to characterize more completely the physical and chemical driving forces behind this important interaction, we employed in this study a combination of structural, biophysical, and computational methods to analyze the interaction of C3d with Efb-C and the single-point mutants R131A and N138A. Our results show that while these mutations do not drastically affect the structure of the Efb-C/C3d recognition complex, they have significant adverse effects on both the thermodynamic and kinetic profiles of the resulting complexes. We also characterized other key interactions along the Efb-C/C3d binding interface and found an intricate network of salt bridges and hydrogen bonds that anchor Efb-C to C3d, resulting in its potent complement inhibitory properties.

Neo-Symbiosis: The Next Stage in the Evolution of Human Information Interaction

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

Griffith, Douglas; Greitzer, Frank L.

We re-address the vision of human-computer symbiosis expressed by J. C. R. Licklider nearly a half-century ago, when he wrote: “The hope is that in not too many years, human brains and computing machines will be coupled together very tightly, and that the resulting partnership will think as no human brain has ever thought and process data in a way not approached by the information-handling machines we know today.” (Licklider, 1960). Unfortunately, little progress was made toward this vision over four decades following Licklider’s challenge, despite significant advancements in the fields of human factors and computer science. Licklider’s vision wasmore » largely forgotten. However, recent advances in information science and technology, psychology, and neuroscience have rekindled the potential of making the Licklider’s vision a reality. This paper provides a historical context for and updates the vision, and it argues that such a vision is needed as a unifying framework for advancing IS&T.« less

Rapid discovery of inhibitors of Toxoplasma gondii using hybrid structure-based computational approach

NASA Astrophysics Data System (ADS)

Kortagere, Sandhya; Mui, Ernest; McLeod, Rima; Welsh, William J.

2011-05-01

Toxoplasma (T.) gondii, the causative agent of toxoplasmosis, is a ubiquitous opportunistic pathogen that infects individuals worldwide, and is a leading cause of severe congenital neurologic and ocular disease in humans. No vaccine to protect humans is available, and hypersensitivity and toxicity limit the use of the few available medicines. Therefore, safer and more effective medicines to treat toxoplasmosis are urgently needed. Using the Hybrid Structure Based (HSB) method, we have previously identified small molecule inhibitors of P. falciparum that seem to target a novel protein-protein interaction between the Myosin tail interacting protein and myosin light chain. This pathway has been hypothesized to be involved in invasion of host erythrocytes by the parasite and is broadly conserved among the apicomplexans. Guided by similar computational drug design approaches, we investigated this series of small molecules as potential inhibitors of T. gondii. Compound C3-21, identified as the most active inhibitor in this series, exhibited an IC50 value 500 nM against T. gondii. Among the 16 structural analogs of C3-21 tested thus far, nine additional compounds were identified with IC50 values <10.0 μM. In vitro assays have revealed that C3-21 markedly limits intracellular growth of T. gondii tachyzoites, but has no effect on host cell human foreskin fibroblasts (HFF) at concentrations more than a log greater than the concentration that inhibits the parasites.

Automated Intelligent Agents: Are They Trusted Members of Military Teams?

DTIC Science & Technology

2008-12-01

computer -based team firefighting game (C3Fire). The order of presentation of the two trials (human – human vs. human – automation) was...agent. All teams played a computer -based team firefighting game (C3Fire). The order of presentation of the two trials (human – human vs. human...26 b. Participants’ Computer ..................27 C. VARIABLES .........................................27 1. Independent Variables

Implementations of the CC'01 Human-Computer Interaction Guidelines Using Bloom's Taxonomy

ERIC Educational Resources Information Center

Manaris, Bill; Wainer, Michael; Kirkpatrick, Arthur E.; Stalvey, RoxAnn H.; Shannon, Christine; Leventhal, Laura; Barnes, Julie; Wright, John; Schafer, J. Ben; Sanders, Dean

2007-01-01

In today's technology-laden society human-computer interaction (HCI) is an important knowledge area for computer scientists and software engineers. This paper surveys existing approaches to incorporate HCI into computer science (CS) and such related issues as the perceived gap between the interests of the HCI community and the needs of CS…

Computer Human Interaction for Image Information Systems.

ERIC Educational Resources Information Center

Beard, David Volk

1991-01-01

Presents an approach to developing viable image computer-human interactions (CHI) involving user metaphors for comprehending image data and methods for locating, accessing, and displaying computer images. A medical-image radiology workstation application is used as an example, and feedback and evaluation methods are discussed. (41 references) (LRW)

Synthesis, molecular structure, Hirshfeld surface, spectral investigations and molecular docking study of 3-(5-bromo-2-thienyl)-1-(4-fluorophenyl)-3-acetyl-2-pyrazoline (2) by DFT method

NASA Astrophysics Data System (ADS)

Sathish, M.; Meenakshi, G.; Xavier, S.; Sebastian, S.; Periandy, S.; Ahmad, NoorAisyah; Jamalis, Joazaizulfazli; Rosli, MohdMustaqim; Fun, Hoong-Kun

2018-07-01

The 3-(5-Bromo-2-thienyl)-1-(4-fluorophenyl)-3-acetyl-2-pyrazoline (2) (BTFA) was synthesized from condensation of thiophenechalcone (1) and hydrazine hydrate. The compound was characterized by FT-IR, 1H and 13C NMR. Crystal structure of this compound was determined using X-ray diffraction technique. The data of the geometry is compared with the optimized structure of the compound obtained using B3LYP functional with 6-311++G (d,p) basis set. The fundamental modes of vibrations are assigned using VEDA software with the PED assignments, and compared with data obtained from theoretical methods. The deviations are widely discussed and analyzed. The intermolecular interaction of the crystal structure was analyzed using Hirshfeld and fingerprint analysis. The chemical shift of the NMR for 13C and 1H are observed and computational data are computed using Gauge independent atomic orbital (GIAO) using B3LYP/6-311++G (d,p). The electronic and optical properties like absorption of wavelengths, excitation energy, dipole moment and frontier molecular orbital energies are computed with TD-SCF method using the above theoretical method. The antiviral nature of the molecule is also analyzed and the compound is docked in non-small cell lung cancer and human collapsin response mediator protein-1study exhibits its activity.

Prosodic alignment in human-computer interaction

NASA Astrophysics Data System (ADS)

Suzuki, N.; Katagiri, Y.

2007-06-01

Androids that replicate humans in form also need to replicate them in behaviour to achieve a high level of believability or lifelikeness. We explore the minimal social cues that can induce in people the human tendency for social acceptance, or ethopoeia, toward artifacts, including androids. It has been observed that people exhibit a strong tendency to adjust to each other, through a number of speech and language features in human-human conversational interactions, to obtain communication efficiency and emotional engagement. We investigate in this paper the phenomena related to prosodic alignment in human-computer interactions, with particular focus on human-computer alignment of speech characteristics. We found that people exhibit unidirectional and spontaneous short-term alignment of loudness and response latency in their speech in response to computer-generated speech. We believe this phenomenon of prosodic alignment provides one of the key components for building social acceptance of androids.

Prediction of virus-host protein-protein interactions mediated by short linear motifs.

PubMed

Becerra, Andrés; Bucheli, Victor A; Moreno, Pedro A

2017-03-09

Short linear motifs in host organisms proteins can be mimicked by viruses to create protein-protein interactions that disable or control metabolic pathways. Given that viral linear motif instances of host motif regular expressions can be found by chance, it is necessary to develop filtering methods of functional linear motifs. We conduct a systematic comparison of linear motifs filtering methods to develop a computational approach for predicting motif-mediated protein-protein interactions between human and the human immunodeficiency virus 1 (HIV-1). We implemented three filtering methods to obtain linear motif sets: 1) conserved in viral proteins (C), 2) located in disordered regions (D) and 3) rare or scarce in a set of randomized viral sequences (R). The sets C,D,R are united and intersected. The resulting sets are compared by the number of protein-protein interactions correctly inferred with them - with experimental validation. The comparison is done with HIV-1 sequences and interactions from the National Institute of Allergy and Infectious Diseases (NIAID). The number of correctly inferred interactions allows to rank the interactions by the sets used to deduce them: D∪R and C. The ordering of the sets is descending on the probability of capturing functional interactions. With respect to HIV-1, the sets C∪R, D∪R, C∪D∪R infer all known interactions between HIV1 and human proteins mediated by linear motifs. We found that the majority of conserved linear motifs in the virus are located in disordered regions. We have developed a method for predicting protein-protein interactions mediated by linear motifs between HIV-1 and human proteins. The method only use protein sequences as inputs. We can extend the software developed to any other eukaryotic virus and host in order to find and rank candidate interactions. In future works we will use it to explore possible viral attack mechanisms based on linear motif mimicry.

Conceptualizing, Designing, and Investigating Locative Media Use in Urban Space

NASA Astrophysics Data System (ADS)

Diamantaki, Katerina; Rizopoulos, Charalampos; Charitos, Dimitris; Kaimakamis, Nikos

This chapter investigates the social implications of locative media (LM) use and attempts to outline a theoretical framework that may support the design and implementation of location-based applications. Furthermore, it stresses the significance of physical space and location awareness as important factors that influence both human-computer interaction and computer-mediated communication. The chapter documents part of the theoretical aspect of the research undertaken as part of LOcation-based Communication Urban NETwork (LOCUNET), a project that aims to investigate the way users interact with one another (human-computer-human interaction aspect) and with the location-based system itself (human-computer interaction aspect). A number of relevant theoretical approaches are discussed in an attempt to provide a holistic theoretical background for LM use. Additionally, the actual implementation of the LOCUNET system is described and some of the findings are discussed.

The Study on Human-Computer Interaction Design Based on the Users’ Subconscious Behavior

NASA Astrophysics Data System (ADS)

Li, Lingyuan

2017-09-01

Human-computer interaction is human-centered. An excellent interaction design should focus on the study of user experience, which greatly comes from the consistence between design and human behavioral habit. However, users’ behavioral habits often result from subconsciousness. Therefore, it is smart to utilize users’ subconscious behavior to achieve design's intention and maximize the value of products’ functions, which gradually becomes a new trend in this field.

Embodied cognition for autonomous interactive robots.

PubMed

Hoffman, Guy

2012-10-01

In the past, notions of embodiment have been applied to robotics mainly in the realm of very simple robots, and supporting low-level mechanisms such as dynamics and navigation. In contrast, most human-like, interactive, and socially adept robotic systems turn away from embodiment and use amodal, symbolic, and modular approaches to cognition and interaction. At the same time, recent research in Embodied Cognition (EC) is spanning an increasing number of complex cognitive processes, including language, nonverbal communication, learning, and social behavior. This article suggests adopting a modern EC approach for autonomous robots interacting with humans. In particular, we present three core principles from EC that may be applicable to such robots: (a) modal perceptual representation, (b) action/perception and action/cognition integration, and (c) a simulation-based model of top-down perceptual biasing. We describe a computational framework based on these principles, and its implementation on two physical robots. This could provide a new paradigm for embodied human-robot interaction based on recent psychological and neurological findings. Copyright © 2012 Cognitive Science Society, Inc.

A rapid method for selecting suitable animal species for studying pathogen interactions with plasma protein ligands in vivo.

PubMed

Naudin, Clément; Schumski, Ariane; Salo-Ahen, Outi M H; Herwald, Heiko; Smeds, Emanuel

2017-05-01

Species tropism constitutes a serious problem for developing relevant animal models of infection. Human pathogens can express virulence factors that show specific selectivity to human proteins, while their affinity for orthologs from other species can vary significantly. Suitable animal species must be used to analyse whether virulence factors are potential targets for drug development. We developed an assay that rapidly predicts applicable animal species for studying virulence factors binding plasma proteins. We used two well-characterized Staphylococcus aureus proteins, SSL7 and Efb, to develop an ELISA-based inhibition assay using plasma from different animal species. The interaction between SSL7 and human C5 and the binding of Efb to human fibrinogen and human C3 was studied. Affinity experiments and Western blot analyses were used to validate the assay. Human, monkey and cat plasma interfered with binding of SSL7 to human C5. Binding of Efb to human fibrinogen was blocked in human, monkey, gerbil and pig plasma, while human, monkey, gerbil, rabbit, cat and guinea pig plasma inhibited the binding of Efb to human C3. These results emphasize the importance of choosing correct animal models, and thus, our approach is a rapid and cost-effective method that can be used to prevent unnecessary animal experiments. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

The Promise of Interactive Video: An Affective Search.

ERIC Educational Resources Information Center

Hon, David

1983-01-01

Argues that factors that create a feeling of interactivity in the human situation--response time, spontaneity, lack of distractors--should be included as prime elements in the design of human/machine systems, e.g., computer assisted instruction and interactive video. A computer/videodisc learning system for cardio-pulmonary resuscitation and its…

The Human-Computer Interaction of Cross-Cultural Gaming Strategy

ERIC Educational Resources Information Center

Chakraborty, Joyram; Norcio, Anthony F.; Van Der Veer, Jacob J.; Andre, Charles F.; Miller, Zachary; Regelsberger, Alexander

2015-01-01

This article explores the cultural dimensions of the human-computer interaction that underlies gaming strategies. The article is a desktop study of existing literature and is organized into five sections. The first examines the cultural aspects of knowledge processing. The social constructs technology interaction is discussed. Following this, the…

Evaluation of an eye-pointer interaction device for human-computer interaction.

PubMed

Cáceres, Enrique; Carrasco, Miguel; Ríos, Sebastián

2018-03-01

Advances in eye-tracking technology have led to better human-computer interaction, and involve controlling a computer without any kind of physical contact. This research describes the transformation of a commercial eye-tracker for use as an alternative peripheral device in human-computer interactions, implementing a pointer that only needs the eye movements of a user facing a computer screen, thus replacing the need to control the software by hand movements. The experiment was performed with 30 test individuals who used the prototype with a set of educational videogames. The results show that, although most of the test subjects would prefer a mouse to control the pointer, the prototype tested has an empirical precision similar to that of the mouse, either when trying to control its movements or when attempting to click on a point of the screen.

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.

Visualization and Interaction in Research, Teaching, and Scientific Communication

NASA Astrophysics Data System (ADS)

Ammon, C. J.

2017-12-01

Modern computing provides many tools for exploring observations, numerical calculations, and theoretical relationships. The number of options is, in fact, almost overwhelming. But the choices provide those with modest programming skills opportunities to create unique views of scientific information and to develop deeper insights into their data, their computations, and the underlying theoretical data-model relationships. I present simple examples of using animation and human-computer interaction to explore scientific data and scientific-analysis approaches. I illustrate how valuable a little programming ability can free scientists from the constraints of existing tools and can facilitate the development of deeper appreciation data and models. I present examples from a suite of programming languages ranging from C to JavaScript including the Wolfram Language. JavaScript is valuable for sharing tools and insight (hopefully) with others because it is integrated into one of the most powerful communication tools in human history, the web browser. Although too much of that power is often spent on distracting advertisements, the underlying computation and graphics engines are efficient, flexible, and almost universally available in desktop and mobile computing platforms. Many are working to fulfill the browser's potential to become the most effective tool for interactive study. Open-source frameworks for visualizing everything from algorithms to data are available, but advance rapidly. One strategy for dealing with swiftly changing tools is to adopt common, open data formats that are easily adapted (often by framework or tool developers). I illustrate the use of animation and interaction in research and teaching with examples from earthquake seismology.

The role of voice input for human-machine communication.

PubMed Central

Cohen, P R; Oviatt, S L

1995-01-01

Optimism is growing that the near future will witness rapid growth in human-computer interaction using voice. System prototypes have recently been built that demonstrate speaker-independent real-time speech recognition, and understanding of naturally spoken utterances with vocabularies of 1000 to 2000 words, and larger. Already, computer manufacturers are building speech recognition subsystems into their new product lines. However, before this technology can be broadly useful, a substantial knowledge base is needed about human spoken language and performance during computer-based spoken interaction. This paper reviews application areas in which spoken interaction can play a significant role, assesses potential benefits of spoken interaction with machines, and compares voice with other modalities of human-computer interaction. It also discusses information that will be needed to build a firm empirical foundation for the design of future spoken and multimodal interfaces. Finally, it argues for a more systematic and scientific approach to investigating spoken input and performance with future language technology. PMID:7479803

Plateaus, Dips, and Leaps: Where to Look for Inventions and Discoveries during Skilled Performance

ERIC Educational Resources Information Center

Gray, Wayne D.; Lindstedt, John K.

2017-01-01

The framework of "plateaus, dips, and leaps" shines light on periods when individuals may be inventing new methods of skilled performance. We begin with a review of the role "performance plateaus" have played in (a) experimental psychology, (b) human-computer interaction, and (c) cognitive science. We then reanalyze two classic…

Design Science in Human-Computer Interaction: A Model and Three Examples

ERIC Educational Resources Information Center

Prestopnik, Nathan R.

2013-01-01

Humanity has entered an era where computing technology is virtually ubiquitous. From websites and mobile devices to computers embedded in appliances on our kitchen counters and automobiles parked in our driveways, information and communication technologies (ICTs) and IT artifacts are fundamentally changing the ways we interact with our world.…

Evaluation of a computerized aid for creating human behavioral representations of human-computer interaction.

PubMed

Williams, Kent E; Voigt, Jeffrey R

2004-01-01

The research reported herein presents the results of an empirical evaluation that focused on the accuracy and reliability of cognitive models created using a computerized tool: the cognitive analysis tool for human-computer interaction (CAT-HCI). A sample of participants, expert in interacting with a newly developed tactical display for the U.S. Army's Bradley Fighting Vehicle, individually modeled their knowledge of 4 specific tasks employing the CAT-HCI tool. Measures of the accuracy and consistency of task models created by these task domain experts using the tool were compared with task models created by a double expert. The findings indicated a high degree of consistency and accuracy between the different "single experts" in the task domain in terms of the resultant models generated using the tool. Actual or potential applications of this research include assessing human-computer interaction complexity, determining the productivity of human-computer interfaces, and analyzing an interface design to determine whether methods can be automated.

One pair of hands is not like another: caudate BOLD response in dogs depends on signal source and canine temperament

PubMed Central

Cook, Peter F.; Spivak, Mark

2014-01-01

Having previously used functional MRI to map the response to a reward signal in the ventral caudate in awake unrestrained dogs, here we examined the importance of signal source to canine caudate activation. Hand signals representing either incipient reward or no reward were presented by a familiar human (each dog’s respective handler), an unfamiliar human, and via illustrated images of hands on a computer screen to 13 dogs undergoing voluntary fMRI. All dogs had received extensive training with the reward and no-reward signals from their handlers and with the computer images and had minimal exposure to the signals from strangers. All dogs showed differentially higher BOLD response in the ventral caudate to the reward versus no reward signals, and there was a robust effect at the group level. Further, differential response to the signal source had a highly significant interaction with a dog’s general aggressivity as measured by the C-BARQ canine personality assessment. Dogs with greater aggressivity showed a higher differential response to the reward signal versus no-reward signal presented by the unfamiliar human and computer, while dogs with lower aggressivity showed a higher differential response to the reward signal versus no-reward signal from their handler. This suggests that specific facets of canine temperament bear more strongly on the perceived reward value of relevant communication signals than does reinforcement history, as each of the dogs were reinforced similarly for each signal, regardless of the source (familiar human, unfamiliar human, or computer). A group-level psychophysiological interaction (PPI) connectivity analysis showed increased functional coupling between the caudate and a region of cortex associated with visual discrimination and learning on reward versus no-reward trials. Our findings emphasize the sensitivity of the domestic dog to human social interaction, and may have other implications and applications pertinent to the training and assessment of working and pet dogs. PMID:25289182

Monoamine transporter and receptor interaction profiles in vitro predict reported human doses of novel psychoactive stimulants and psychedelics.

PubMed

Luethi, Dino; Liechti, Matthias E

2018-05-29

Pharmacological profiles of new psychoactive substances (NPSs) can be established rapidly in vitro and provide information on potential psychoactive effects in humans. The present study investigated whether specific in vitro monoamine transporter and receptor interactions can predict effective psychoactive doses in humans. We correlated previously assessed in vitro data of stimulants and psychedelics with human doses that are reported on the Internet and in books. For stimulants, dopamine and norepinephrine transporter inhibition potency was positively correlated with human doses, whereas serotonin transporter inhibition potency was inversely correlated with human doses. Serotonin 5-hydroxytryptamine-2A (5-HT2A) and 5-HT2C receptor affinity was significantly correlated with psychedelic doses, but 5-HT1A receptor affinity and 5-HT2A and 5-HT2B receptor activation potency were not. The rapid assessment of in vitro pharmacological profiles of NPSs can help to predict psychoactive doses and effects in humans and facilitate the appropriate scheduling of NPSs.

Conformational analysis of some 4‧-substituted 2-(phenylselanyl)- 2-(methoxy)- acetophenones

NASA Astrophysics Data System (ADS)

Traesel, Henrique J.; Olivato, Paulo R.; Valença, J.; Rodrigues, Daniel N. S.; Zukerman-Schpector, Julio; Colle, Maurizio Dal

2018-04-01

A conformational study of some 4‧-substituited 2-(phenylselanyl)-2-(methoxy)-acetophenones (OMe 1, H 2, and Cl 3) was performed using IR carbonyl stretching band analysis supported by NBO and PCM calculations at the B3LYP/6-31 + G (d,p) level for 1-3 and using X-ray diffraction for 1 and 2. The computational results indicated the existence of three stable conformers for the series (c2, c3, and c1 in order of decreasing stability), whose relative abundance changes with solvent permittivity. The experimental trend observed for the components of the triplet carbonyl band in all solvents matches well with computational results and thus allows for their assignment to distinct conformers. The relative population of the c1 conformer increases in more polar solvents, becoming the most stable conformer in the highest permittivity solvent, acetonitrile, as indicated by IR spectra and PCM calculations. These findings are related to the quasi parallel geometry assumed by the Cδ+ = Oδ- and Cδ+-Oδ- dipoles, which favour stronger solvation. NBO analysis shows that the sum of the energies (ΣE) of the relevant orbital interactions stabilizes the c3 conformer of 1-3 slightly, likely due to the minor contribution of the LPO5→σ*C3sbnd Se10 interaction. However, only the c1 conformer is significantly destabilized by the Oδ-(1)CO … Oδ-(5)OMe short contact electrostatic repulsion, which is also responsible for its highest νCO frequency. In addition, the LPO5→ σ*C2sbnd C3 orbital interaction accounts for the lowest νCO frequency of c3 conformer. X-ray single crystal analysis of compounds 1 and 2 indicates that in the solid state they assume the least stable c1 conformation found in the gas phase. Molecules of these compounds are stabilized in the crystal through a series of Csbnd H⋯O and Csbnd H … π intermolecular interactions.

SDI Software Technology Program Plan Version 1.5

DTIC Science & Technology

1987-06-01

computer generation of auditory communication of meaningful speech. Most speech synthesizers are based on mathematical models of the human vocal tract, but...oral/ auditory and multimodal communications. Although such state-of-the-art interaction technology has not fully matured, user experience has...superior I pattern matching capabilities and the subliminal intuitive deduction capability. The error performance of humans can be helped by careful

Assess program: Interactive data management systems for airborne research

NASA Technical Reports Server (NTRS)

Munoz, R. M.; Reller, J. O., Jr.

1974-01-01

Two data systems were developed for use in airborne research. Both have distributed intelligence and are programmed for interactive support among computers and with human operators. The C-141 system (ADAMS) performs flight planning and telescope control functions in addition to its primary role of data acquisition; the CV-990 system (ADDAS) performs data management functions in support of many research experiments operating concurrently. Each system is arranged for maximum reliability in the first priority function, precision data acquisition.

Sorting Nexin 1 Loss Results in D5 Dopamine Receptor Dysfunction in Human Renal Proximal Tubule Cells and Hypertension in Mice*

PubMed Central

Villar, Van Anthony M.; Jones, John Edward; Armando, Ines; Asico, Laureano D.; Escano, Crisanto S.; Lee, Hewang; Wang, Xiaoyan; Yang, Yu; Pascua-Crusan, Annabelle M.; Palmes-Saloma, Cynthia P.; Felder, Robin A.; Jose, Pedro A.

2013-01-01

The peripheral dopaminergic system plays a crucial role in blood pressure regulation through its actions on renal hemodynamics and epithelial ion transport. The dopamine D5 receptor (D5R) interacts with sorting nexin 1 (SNX1), a protein involved in receptor retrieval from the trans-Golgi network. In this report, we elucidated the spatial, temporal, and functional significance of this interaction in human renal proximal tubule cells and HEK293 cells stably expressing human D5R and in mice. Silencing of SNX1 expression via RNAi resulted in the failure of D5R to internalize and bind GTP, blunting of the agonist-induced increase in cAMP production and decrease in sodium transport, and up-regulation of angiotensin II receptor expression, of which expression was previously shown to be negatively regulated by D5R. Moreover, siRNA-mediated depletion of renal SNX1 in C57BL/6J and BALB/cJ mice resulted in increased blood pressure and blunted natriuretic response to agonist in salt-loaded BALB/cJ mice. These data demonstrate a crucial role for SNX1 in D5R trafficking and that SNX1 depletion results in D5R dysfunction and thus may represent a novel mechanism for the pathogenesis of essential hypertension. PMID:23152498

Pedagogical Agents as Learning Companions: The Impact of Agent Emotion and Gender

ERIC Educational Resources Information Center

Kim, Yanghee; Baylor, A. L.; Shen, E.

2007-01-01

The potential of emotional interaction between human and computer has recently interested researchers in human-computer interaction. The instructional impact of this interaction in learning environments has not been established, however. This study examined the impact of emotion and gender of a pedagogical agent as a learning companion (PAL) on…

PAH Interactions with Soil and Effects on Bioaccessibility and Bioavailability to Humans

DTIC Science & Technology

2017-02-01

FINAL REPORT PAH Interactions with Soil and Effects on Bioaccessibility and Bioavailability to Humans SERDP Project ER-1743 FEBRUARY...COVERED (From - To) 2010-2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W912HQ-10-C-0010 PAH Interactions with Soil and Effects on Bioaccessibility...assessments and remedial decisions to focus research where it can be most effective ; Task 2) Develop an understanding of the mechanisms by which PAHs

Functionalized Fullerene Targeting Human Voltage-Gated Sodium Channel, hNav1.7.

PubMed

Hilder, Tamsyn A; Robinson, Anna; Chung, Shin-Ho

2017-08-16

Mutations of hNa v 1.7 that cause its activities to be enhanced contribute to severe neuropathic pain. Only a small number of hNa v 1.7 specific inhibitors have been identified, most of which interact with the voltage-sensing domain of the voltage-activated sodium ion channel. In our previous computational study, we demonstrated that a [Lys 6 ]-C 84 fullerene binds tightly (affinity of 46 nM) to Na v Ab, the voltage-gated sodium channel from the bacterium Arcobacter butzleri. Here, we extend this work and, using molecular dynamics simulations, demonstrate that the same [Lys 6 ]-C 84 fullerene binds strongly (2.7 nM) to the pore of a modeled human sodium ion channel hNa v 1.7. In contrast, the fullerene binds only weakly to a mutated model of hNa v 1.7 (I1399D) (14.5 mM) and a model of the skeletal muscle hNa v 1.4 (3.7 mM). Comparison of one representative sequence from each of the nine human sodium channel isoforms shows that only hNa v 1.7 possesses residues that are critical for binding the fullerene derivative and blocking the channel pore.

Online mentalising investigated with functional MRI.

PubMed

Kircher, Tilo; Blümel, Isabelle; Marjoram, Dominic; Lataster, Tineke; Krabbendam, Lydia; Weber, Jochen; van Os, Jim; Krach, Sören

2009-05-01

For successful interpersonal communication, inferring intentions, goals or desires of others is highly advantageous. Increasingly, humans also interact with computers or robots. In this study, we sought to determine to what degree an interactive task, which involves receiving feedback from social partners that can be used to infer intent, engaged the medial prefrontal cortex, a region previously associated with Theory of Mind processes among others. Participants were scanned using fMRI as they played an adapted version of the Prisoner's Dilemma Game with alleged human and computer partners who were outside the scanner. The medial frontal cortex was activated when both human and computer partner were played, while the direct contrast revealed significantly stronger signal change during the human-human interaction. The results suggest a link between activity in the medial prefrontal cortex and the partner played in a mentalising task. This signal change was also present for to the computers partner. Implying agency or a will to non-human actors might be an innate human resource that could lead to an evolutionary advantage.

Defining protein electrostatic recognition processes

NASA Astrophysics Data System (ADS)

Getzoff, Elizabeth D.; Roberts, Victoria A.

The objective is to elucidate the nature of electrostatic forces controlling protein recognition processes by using a tightly coupled computational and interactive computer graphics approach. The TURNIP program was developed to determine the most favorable precollision orientations for two molecules by systematic search of all orientations and evaluation of the resulting electrostatic interactions. TURNIP was applied to the transient interaction between two electron transfer metalloproteins, plastocyanin and cytochrome c. The results suggest that the productive electron-transfer complex involves interaction of the positive region of cytochrome c with the negative patch of plastocyanin, consistent with experimental data. Application of TURNIP to the formation of the stable complex between the HyHEL-5 antibody and its protein antigen lysozyme showed that long-distance electrostatic forces guide lysozyme toward the HyHEL-5 binding site, but do not fine tune its orientation. Determination of docked antigen/antibody complexes requires including steric as well as electrostatic interactions, as was done for the U10 mutant of the anti-phosphorylcholine antibody S107. The graphics program Flex, a convenient desktop workstation program for visualizing molecular dynamics and normal mode motions, was enhanced. Flex now has a user interface and was rewritten to use standard graphics libraries, so as to run on most desktop workstations.

C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro.

PubMed

Grebinyk, A; Prylutska, S; Grynyuk, I; Kolp, B; Hurmach, V; Sliva, T; Amirkhanov, V; Trush, V; Matyshevska, O; Slobodyanik, M; Prylutskyy, Yu; Frohme, M; Ritter, U

2018-03-09

New representative of carbacylamidophosphates - diphenyl-N-(trichloroacetyl)-amidophosphate (HL), which contains two phenoxy substituents near the phosphoryl group, was synthesized, identified by elemental analysis and IR and NMR spectroscopy, and tested as a cytotoxic agent itself and in combination with C 60 fullerene.According to molecular simulation results, C 60 fullerene and HL could interact with DNA and form a rigid complex stabilized by stacking interactions of HL phenyl groups with C 60 fullerene and DNA G nucleotide, as well as by interactions of HL CCl 3 group by ion-π bonds with C 60 molecule and by electrostatic bonds with DNA G nucleotide.With the use of MTT test, the cytotoxic activity of HL against human leukemic CCRF-CM cells with IC 50 value detected at 10 μM concentration at 72 h of cells treatment was shown. Under combined action of 16 μM C 60 fullerene and HL, the value of IC 50 was detected at lower 5 μM HL concentration and at earlier 48 h period of incubation, besides the cytotoxic effect of HL was observed at a low 2.5 μM concentration at which HL by itself had no influence on cell viability. Binding of C 60 fullerene and HL with minor DNA groove with formation of a stable complex is assumed to be one of the possible reasons of their synergistic inhibition of CCRF-CЕM cells proliferation.Application of C 60 fullerene in combination with 2.5 μM HL was shown to have no harmful effect on structural stability of blood erythrocytes membrane. Thus, combined action of C 60 fullerene and HL in a low concentration potentiated HL cytotoxic effect against human leukemic cells and was not followed by hemolytic effect.

C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro

NASA Astrophysics Data System (ADS)

Grebinyk, A.; Prylutska, S.; Grynyuk, I.; Kolp, B.; Hurmach, V.; Sliva, T.; Amirkhanov, V.; Trush, V.; Matyshevska, O.; Slobodyanik, M.; Prylutskyy, Yu.; Frohme, M.; Ritter, U.

2018-03-01

New representative of carbacylamidophosphates - diphenyl-N-(trichloroacetyl)-amidophosphate (HL), which contains two phenoxy substituents near the phosphoryl group, was synthesized, identified by elemental analysis and IR and NMR spectroscopy, and tested as a cytotoxic agent itself and in combination with C60 fullerene. According to molecular simulation results, C60 fullerene and HL could interact with DNA and form a rigid complex stabilized by stacking interactions of HL phenyl groups with C60 fullerene and DNA G nucleotide, as well as by interactions of HL CCl3 group by ion-π bonds with C60 molecule and by electrostatic bonds with DNA G nucleotide. With the use of MTT test, the cytotoxic activity of HL against human leukemic CCRF-CM cells with IC50 value detected at 10 μM concentration at 72 h of cells treatment was shown. Under combined action of 16 μM C60 fullerene and HL, the value of IC50 was detected at lower 5 μM HL concentration and at earlier 48 h period of incubation, besides the cytotoxic effect of HL was observed at a low 2.5 μM concentration at which HL by itself had no influence on cell viability. Binding of C60 fullerene and HL with minor DNA groove with formation of a stable complex is assumed to be one of the possible reasons of their synergistic inhibition of CCRF-CEM cells proliferation. Application of C60 fullerene in combination with 2.5 μM HL was shown to have no harmful effect on structural stability of blood erythrocytes membrane. Thus, combined action of C60 fullerene and HL in a low concentration potentiated HL cytotoxic effect against human leukemic cells and was not followed by hemolytic effect.

On the interactions of nitriles and fluoro-substituted pyridines with silicon tetrafluoride: Computations and thin film IR spectroscopy

NASA Astrophysics Data System (ADS)

Hora, Nicholas J.; Wahl, Benjamin M.; Soares, Camilla; Lara, Skylee A.; Lanska, John R.; Phillips, James A.

2018-04-01

The nature of the interactions between silicon tetrafluoride and series of nitrogen bases, including nitriles (RCN, with R > CH3), pyridine, and various fluoro-substituted pyridines, has been investigated via quantum-chemical computations, low-temperature IR spectroscopy, and bulk reactivity experiments. Using (primarily) M06 with the 6-311+G(2df,2pd) basis set, we obtained equilibrium structures, binding energies, harmonic frequencies, and N-Si potentials in the gas-phase and in bulk dielectric media for an extensive series of 1:1 molecular complexes, including: C6H5CH2CN-SiF4, CH3CH2CN-SiF4, (CH3)3CCN-SiF4, C5H5N-SiF4, 4-FC5H4N-SiF4, 3,5-C5F2H3N-SiF4, 2,6-C5F2H3N-SiF4 and 3,4,5-C5F3H2N-SiF4. In addition, for the analogous 2:1 complexes of pyridine and 3,5-difluororpyridine, we obtained equilibrium structures, binding energies, and harmonic frequencies. The N-Si distances in the 1:1 nitrile complexes are fairly long, ranging from 2.84 Å to 2.88 Å, and the binding energies range from 4.0 to 4.2 kcal/mol (16.7-17.6 kJ/mol). Also, computations predict extremely anharmonic N-Si potentials, for which the inner portions of the curve are preferentially stabilized in dielectric media, which predict an enhancement of these interactions in condensed-phases. However, we see no evidence of bulk reactivity between C6H5CH2CN, CH3CH2CN, or (CH3)3CCN and SiF4, nor any significant interaction between (CH3)3CCN and SiF4 in low temperature IR spectra of solid, (CH3)3CCN/SiF4 thin films. Conversely, the interactions in four of the five 1:1, pyridine-SiF4 complexes are generally stronger; binding energies range from 5.7 to 9.6 kcal/mol (23.8-40.2 kJ/mol), and correspondingly the N-Si distances are relatively short (2.12-2.25 Å). The exception is 2,6-C5F2H3N-SiF4, for which the binding energy is only 3.6 kcal/mol (15.1 kJ/mol), and the N-Si distance is quite long (3.12 Å). In addition, both pyridine and 3,5-difluororpyridine were found to form stable reaction products with SiF4; but no analogous product was obtained with 2,6-difluororpyridine and SiF4, nor was any significant interaction indicated in low-temperature IR spectra of 2,6-difluororpyridine/SiF4 films. By contrast, low temperature spectra of pyridine/SiF4 and 3,5-difluororpyridine/SiF4 thin films are consistent with the presence of a distinct 2:1 reaction product. Moreover, the observed frequencies agree reasonably well with those predicted for the cis, octahedral coordination isomers of the 2:1 molecular complexes, in which the N-Si bonds are compressed slightly relative to those in the predicted gas-phase structures.

Computer modeling and simulation of human movement. Applications in sport and rehabilitation.

PubMed

Neptune, R R

2000-05-01

Computer modeling and simulation of human movement plays an increasingly important role in sport and rehabilitation, with applications ranging from sport equipment design to understanding pathologic gait. The complex dynamic interactions within the musculoskeletal and neuromuscular systems make analyzing human movement with existing experimental techniques difficult but computer modeling and simulation allows for the identification of these complex interactions and causal relationships between input and output variables. This article provides an overview of computer modeling and simulation and presents an example application in the field of rehabilitation.

The Human-Computer Interface and Information Literacy: Some Basics and Beyond.

ERIC Educational Resources Information Center

Church, Gary M.

1999-01-01

Discusses human/computer interaction research, human/computer interface, and their relationships to information literacy. Highlights include communication models; cognitive perspectives; task analysis; theory of action; problem solving; instructional design considerations; and a suggestion that human/information interface may be a more appropriate…

Enhancing Human-Computer Interaction Design Education: Teaching Affordance Design for Emerging Mobile Devices

ERIC Educational Resources Information Center

Faiola, Anthony; Matei, Sorin Adam

2010-01-01

The evolution of human-computer interaction design (HCID) over the last 20 years suggests that there is a growing need for educational scholars to consider new and more applicable theoretical models of interactive product design. The authors suggest that such paradigms would call for an approach that would equip HCID students with a better…

Integrating HCI into IDT: Charting the Human Computer Interaction Competencies Necessary for Instructional Media Production Coursework

ERIC Educational Resources Information Center

Brown, Abbie; Sugar, William

2004-01-01

A report on the efforts made to describe the range of human-computer interaction skills necessary to complete a program of study in Instructional Design Technology. Educators responsible for instructional media production courses have not yet articulated which among the wide range of possible interactions students must master for instructional…

Simulating Humans as Integral Parts of Spacecraft Missions

NASA Technical Reports Server (NTRS)

Bruins, Anthony C.; Rice, Robert; Nguyen, Lac; Nguyen, Heidi; Saito, Tim; Russell, Elaine

2006-01-01

The Collaborative-Virtual Environment Simulation Tool (C-VEST) software was developed for use in a NASA project entitled "3-D Interactive Digital Virtual Human." The project is oriented toward the use of a comprehensive suite of advanced software tools in computational simulations for the purposes of human-centered design of spacecraft missions and of the spacecraft, space suits, and other equipment to be used on the missions. The C-VEST software affords an unprecedented suite of capabilities for three-dimensional virtual-environment simulations with plug-in interfaces for physiological data, haptic interfaces, plug-and-play software, realtime control, and/or playback control. Mathematical models of the mechanics of the human body and of the aforementioned equipment are implemented in software and integrated to simulate forces exerted on and by astronauts as they work. The computational results can then support the iterative processes of design, building, and testing in applied systems engineering and integration. The results of the simulations provide guidance for devising measures to counteract effects of microgravity on the human body and for the rapid development of virtual (that is, simulated) prototypes of advanced space suits, cockpits, and robots to enhance the productivity, comfort, and safety of astronauts. The unique ability to implement human-in-the-loop immersion also makes the C-VEST software potentially valuable for use in commercial and academic settings beyond the original space-mission setting.

Bio-Physicochemical Interactions of Engineered Nanomaterials in In Vitro Cell Culture Model

DTIC Science & Technology

2012-08-14

viz. human hepatocarcinoma cell line (Hep G2), human adinocarcinoma cell line (A549), human embryonic kidney cell line (HEK 293), human neuroblastoma...Glutamine, 1% Na-Pyruvate and 10 ml/L antibiotic solution at 37oC under a humidified atmosphere of 5% CO2/95% air.  Human hepatocarcinoma cell line

Toward Multimodal Human-Robot Interaction to Enhance Active Participation of Users in Gait Rehabilitation.

PubMed

Gui, Kai; Liu, Honghai; Zhang, Dingguo

2017-11-01

Robotic exoskeletons for physical rehabilitation have been utilized for retraining patients suffering from paraplegia and enhancing motor recovery in recent years. However, users are not voluntarily involved in most systems. This paper aims to develop a locomotion trainer with multiple gait patterns, which can be controlled by the active motion intention of users. A multimodal human-robot interaction (HRI) system is established to enhance subject's active participation during gait rehabilitation, which includes cognitive HRI (cHRI) and physical HRI (pHRI). The cHRI adopts brain-computer interface based on steady-state visual evoked potential. The pHRI is realized via admittance control based on electromyography. A central pattern generator is utilized to produce rhythmic and continuous lower joint trajectories, and its state variables are regulated by cHRI and pHRI. A custom-made leg exoskeleton prototype with the proposed multimodal HRI is tested on healthy subjects and stroke patients. The results show that voluntary and active participation can be effectively involved to achieve various assistive gait patterns.

Why we interact: on the functional role of the striatum in the subjective experience of social interaction.

PubMed

Pfeiffer, Ulrich J; Schilbach, Leonhard; Timmermans, Bert; Kuzmanovic, Bojana; Georgescu, Alexandra L; Bente, Gary; Vogeley, Kai

2014-11-01

There is ample evidence that human primates strive for social contact and experience interactions with conspecifics as intrinsically rewarding. Focusing on gaze behavior as a crucial means of human interaction, this study employed a unique combination of neuroimaging, eye-tracking, and computer-animated virtual agents to assess the neural mechanisms underlying this component of behavior. In the interaction task, participants believed that during each interaction the agent's gaze behavior could either be controlled by another participant or by a computer program. Their task was to indicate whether they experienced a given interaction as an interaction with another human participant or the computer program based on the agent's reaction. Unbeknownst to them, the agent was always controlled by a computer to enable a systematic manipulation of gaze reactions by varying the degree to which the agent engaged in joint attention. This allowed creating a tool to distinguish neural activity underlying the subjective experience of being engaged in social and non-social interaction. In contrast to previous research, this allows measuring neural activity while participants experience active engagement in real-time social interactions. Results demonstrate that gaze-based interactions with a perceived human partner are associated with activity in the ventral striatum, a core component of reward-related neurocircuitry. In contrast, interactions with a computer-driven agent activate attention networks. Comparisons of neural activity during interaction with behaviorally naïve and explicitly cooperative partners demonstrate different temporal dynamics of the reward system and indicate that the mere experience of engagement in social interaction is sufficient to recruit this system. Copyright © 2014 Elsevier Inc. All rights reserved.

To bend or not to bend: experimental and computational studies of structural preference in Ln(Tp(iPr)2)2 (Ln = Sm, Tm).

PubMed

Momin, Aurélien; Carter, Lee; Yang, Yi; McDonald, Robert; Essafi Labouille, Stéphanie; Nief, François; Del Rosal, Iker; Sella, Andrea; Maron, Laurent; Takats, Josef

2014-11-17

The synthesis and characterization of Ln(Tp(iPr2))2 (Ln = Sm, 3Sm; Tm, 3Tm) are reported. While the simple (1)H NMR spectra of the compounds indicate a symmetrical solution structure, with equivalent pyrazolyl groups, the solid-state structure revealed an unexpected, "bent sandwich-like" geometry. By contrast, the structure of the less sterically congested Tm(Tp(Me2,4Et))2 (4) adopts the expected symmetrical structure with a linear B-Tm-B arrangement. Computational studies to investigate the origin of the unexpected bent structure of the former compounds indicate that steric repulsion between the isopropyl groups forces the Tp ligands apart and permits the development of unusual interligand C-H···N hydrogen-bonding interactions that help stabilize the structure. These results find support in the similar geometry of the Tm(III) analogue [Tm(Tp(iPr2))2]I, 3Tm(+), and confirm that the low symmetry is not the result of a metal-ligand interaction. The relevance of these results to the general question of the coordination geometry of MX2 and M(C5R5)2 (M = heavy alkaline earth and Ln(II), X = halide, and C5R5 = bulky persubstituted cyclopentadienyl) complexes and the importance of secondary H-bonding and nonbonding interactions on the structure are highlighted.

31 CFR 132.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... transaction provider, or any interactive computer service or telecommunications service); and (5) Does not include— (i) Any activity governed by the securities laws (as that term is defined in section 3(a)(47) of the Securities Exchange Act of 1934 (15 U.S.C. 78c(a)(47)) for the purchase or sale of securities (as...

12 CFR 233.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... transaction provider, or any interactive computer service or telecommunications service); and (5) Does not include— (i) Any activity governed by the securities laws (as that term is defined in section 3(a)(47) of the Securities Exchange Act of 1934 (15 U.S.C. 78c(a)(47)) for the purchase or sale of securities (as...

12 CFR 233.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... transaction provider, or any interactive computer service or telecommunications service); and (5) Does not include— (i) Any activity governed by the securities laws (as that term is defined in section 3(a)(47) of the Securities Exchange Act of 1934 (15 U.S.C. 78c(a)(47)) for the purchase or sale of securities (as...

31 CFR 132.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... transaction provider, or any interactive computer service or telecommunications service); and (5) Does not include— (i) Any activity governed by the securities laws (as that term is defined in section 3(a)(47) of the Securities Exchange Act of 1934 (15 U.S.C. 78c(a)(47)) for the purchase or sale of securities (as...

12 CFR 233.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... transaction provider, or any interactive computer service or telecommunications service); and (5) Does not include— (i) Any activity governed by the securities laws (as that term is defined in section 3(a)(47) of the Securities Exchange Act of 1934 (15 U.S.C. 78c(a)(47)) for the purchase or sale of securities (as...

12 CFR 233.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... transaction provider, or any interactive computer service or telecommunications service); and (5) Does not include— (i) Any activity governed by the securities laws (as that term is defined in section 3(a)(47) of the Securities Exchange Act of 1934 (15 U.S.C. 78c(a)(47)) for the purchase or sale of securities (as...

The Effectiveness of Gaze-Contingent Control in Computer Games.

PubMed

Orlov, Paul A; Apraksin, Nikolay

2015-01-01

Eye-tracking technology and gaze-contingent control in human-computer interaction have become an objective reality. This article reports on a series of eye-tracking experiments, in which we concentrated on one aspect of gaze-contingent interaction: Its effectiveness compared with mouse-based control in a computer strategy game. We propose a measure for evaluating the effectiveness of interaction based on "the time of recognition" the game unit. In this article, we use this measure to compare gaze- and mouse-contingent systems, and we present the analysis of the differences as a function of the number of game units. Our results indicate that performance of gaze-contingent interaction is typically higher than mouse manipulation in a visual searching task. When tested on 60 subjects, the results showed that the effectiveness of gaze-contingent systems over 1.5 times higher. In addition, we obtained that eye behavior stays quite stabile with or without mouse interaction. © The Author(s) 2015.

Catalytic Upgrading of Biomass-Derived Compounds via C-C Coupling Reactions. Computational and Experimental Studies of Acetaldehyde and Furan Reactions in HZSM-5

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

Liu, Cong; Evans, Tabitha J.; Cheng, Lei

2015-10-02

These catalytic C–C coupling and deoxygenation reactions are essential for upgrading of biomass-derived oxygenates to fuel-range hydrocarbons. Detailed understanding of mechanistic and energetic aspects of these reactions is crucial to enabling and improving the catalytic upgrading of small oxygenates to useful chemicals and fuels. Using periodic density functional theory (DFT) calculations, we have investigated the reactions of furan and acetaldehyde in an HZSM-5 zeolite catalyst, a representative system associated with the catalytic upgrading of pyrolysis vapors. Comprehensive energy profiles were computed for self-reactions (i.e., acetaldehyde coupling and furan coupling) and cross-reactions (i.e., acetaldehyde + furan) of this representative mixture. Majormore » products proposed from the computations are further confirmed using temperature controlled mass spectra measurements. Moreover, the computational results show that furan interacts with acetaldehyde in HZSM-5 via an alkylation mechanism, which is more favorable than the self-reactions, indicating that mixing furans with aldehydes could be a promising approach to maximize effective C–C coupling and dehydration while reducing the catalyst deactivation (e.g., coke formation) from aldehyde condensation.« less

An evaluative model of system performance in manned teleoperational systems

NASA Technical Reports Server (NTRS)

Haines, Richard F.

1989-01-01

Manned teleoperational systems are used in aerospace operations in which humans must interact with machines remotely. Manual guidance of remotely piloted vehicles, controling a wind tunnel, carrying out a scientific procedure remotely are examples of teleoperations. A four input parameter throughput (Tp) model is presented which can be used to evaluate complex, manned, teleoperations-based systems and make critical comparisons among candidate control systems. The first two parameters of this model deal with nominal (A) and off-nominal (B) predicted events while the last two focus on measured events of two types, human performance (C) and system performance (D). Digital simulations showed that the expression A(1-B)/C+D) produced the greatest homogeneity of variance and distribution symmetry. Results from a recently completed manned life science telescience experiment will be used to further validate the model. Complex, interacting teleoperational systems may be systematically evaluated using this expression much like a computer benchmark is used.

Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs).

PubMed

Rickli, Anna; Luethi, Dino; Reinisch, Julian; Buchy, Danièle; Hoener, Marius C; Liechti, Matthias E

2015-12-01

N-2-methoxybenzyl-phenethylamines (NBOMe drugs) are newly used psychoactive substances with poorly defined pharmacological properties. The aim of the present study was to characterize the receptor binding profiles of a series of NBOMe drugs compared with their 2,5-dimethoxy-phenethylamine analogs (2C drugs) and lysergic acid diethylamide (LSD) in vitro. We investigated the binding affinities of 2C drugs (2C-B, 2C-C, 2C-D, 2C-E, 2C-H, 2C-I, 2C-N, 2C-P, 2C-T-2, 2C-T-4, 2C-T-7, and mescaline), their NBOMe analogs, and LSD at monoamine receptors and determined functional 5-hydroxytryptamine-2A (5-HT2A) and 5-HT2B receptor activation. Binding at and the inhibition of monoamine uptake transporters were also determined. Human cells that were transfected with the respective human receptors or transporters were used (with the exception of trace amine-associated receptor-1 [TAAR1], in which rat/mouse receptors were used). All of the compounds potently interacted with serotonergic 5-HT2A, 5-HT2B, 5-HT2C receptors and rat TAAR1 (most Ki and EC50: <1 μM). The N-2-methoxybenzyl substitution of 2C drugs increased the binding affinity at serotonergic 5-HT2A, 5-HT2C, adrenergic α1, dopaminergic D1-3, and histaminergic H1 receptors and monoamine transporters but reduced binding to 5-HT1A receptors and TAAR1. As a result, NBOMe drugs were very potent 5-HT2A receptor agonists (EC50: 0.04-0.5 μM) with high 5-HT2A/5-HT1A selectivity and affinity for adrenergic α1 receptors (Ki: 0.3-0.9 μM) and TAAR1 (Ki: 0.06-2.2 μM), similar to LSD, but not dopaminergic D1-3 receptors (most Ki:>1 μM), unlike LSD. The binding profile of NBOMe drugs predicts strong hallucinogenic effects, similar to LSD, but possibly more stimulant properties because of α1 receptor interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Proteome of the Isolated Chlamydia trachomatis Containing Vacuole Reveals a Complex Trafficking Platform Enriched for Retromer Components

PubMed Central

Fischer, Martina; Jehmlich, Nico; Rose, Laura; Koch, Sophia; Laue, Michael; Renard, Bernhard Y.; Schmidt, Frank; Heuer, Dagmar

2015-01-01

Chlamydia trachomatis is an important human pathogen that replicates inside the infected host cell in a unique vacuole, the inclusion. The formation of this intracellular bacterial niche is essential for productive Chlamydia infections. Despite its importance for Chlamydia biology, a holistic view on the protein composition of the inclusion, including its membrane, is currently missing. Here we describe the host cell-derived proteome of isolated C. trachomatis inclusions by quantitative proteomics. Computational analysis indicated that the inclusion is a complex intracellular trafficking platform that interacts with host cells’ antero- and retrograde trafficking pathways. Furthermore, the inclusion is highly enriched for sorting nexins of the SNX-BAR retromer, a complex essential for retrograde trafficking. Functional studies showed that in particular, SNX5 controls the C. trachomatis infection and that retrograde trafficking is essential for infectious progeny formation. In summary, these findings suggest that C. trachomatis hijacks retrograde pathways for effective infection. PMID:26042774

Toward Usable Interactive Analytics: Coupling Cognition and Computation

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

Endert, Alexander; North, Chris; Chang, Remco

Interactive analytics provide users a myriad of computational means to aid in extracting meaningful information from large and complex datasets. Much prior work focuses either on advancing the capabilities of machine-centric approaches by the data mining and machine learning communities, or human-driven methods by the visualization and CHI communities. However, these methods do not yet support a true human-machine symbiotic relationship where users and machines work together collaboratively and adapt to each other to advance an interactive analytic process. In this paper we discuss some of the inherent issues, outlining what we believe are the steps toward usable interactive analyticsmore » that will ultimately increase the effectiveness for both humans and computers to produce insights.« less

Insights into the mechanism of C5aR inhibition by PMX53 via implicit solvent molecular dynamics simulations and docking

PubMed Central

2014-01-01

Background The complement protein C5a acts by primarily binding and activating the G-protein coupled C5a receptor C5aR (CD88), and is implicated in many inflammatory diseases. The cyclic hexapeptide PMX53 (sequence Ace-Phe-[Orn-Pro-dCha-Trp-Arg]) is a full C5aR antagonist of nanomolar potency, and is widely used to study C5aR function in disease. Results We construct for the first time molecular models for the C5aR:PMX53 complex without the a priori use of experimental constraints, via a computational framework of molecular dynamics (MD) simulations, docking, conformational clustering and free energy filtering. The models agree with experimental data, and are used to propose important intermolecular interactions contributing to binding, and to develop a hypothesis for the mechanism of PMX53 antagonism. Conclusion This work forms the basis for the design of improved C5aR antagonists, as well as for atomic-detail mechanistic studies of complement activation and function. Our computational framework can be widely used to develop GPCR-ligand structural models in membrane environments, peptidomimetics and other chemical compounds with potential clinical use. PMID:25170421

Parkinson Patients' Initial Trust in Avatars: Theory and Evidence.

PubMed

Javor, Andrija; Ransmayr, Gerhard; Struhal, Walter; Riedl, René

2016-01-01

Parkinson's disease (PD) is a neurodegenerative disease that affects the motor system and cognitive and behavioral functions. Due to these impairments, PD patients also have problems in using the computer. However, using computers and the Internet could help these patients to overcome social isolation and enhance information search. Specifically, avatars (defined as virtual representations of humans) are increasingly used in online environments to enhance human-computer interaction by simulating face-to-face interaction. Our laboratory experiment investigated how PD patients behave in a trust game played with human and avatar counterparts, and we compared this behavior to the behavior of age, income, education and gender matched healthy controls. The results of our study show that PD patients trust avatar faces significantly more than human faces. Moreover, there was no significant difference between initial trust of PD patients and healthy controls in avatar faces, while PD patients trusted human faces significantly less than healthy controls. Our data suggests that PD patients' interaction with avatars may constitute an effective way of communication in situations in which trust is required (e.g., a physician recommends intake of medication). We discuss the implications of these results for several areas of human-computer interaction and neurological research.

Parkinson Patients’ Initial Trust in Avatars: Theory and Evidence

PubMed Central

Javor, Andrija; Ransmayr, Gerhard; Struhal, Walter; Riedl, René

2016-01-01

Parkinson’s disease (PD) is a neurodegenerative disease that affects the motor system and cognitive and behavioral functions. Due to these impairments, PD patients also have problems in using the computer. However, using computers and the Internet could help these patients to overcome social isolation and enhance information search. Specifically, avatars (defined as virtual representations of humans) are increasingly used in online environments to enhance human-computer interaction by simulating face-to-face interaction. Our laboratory experiment investigated how PD patients behave in a trust game played with human and avatar counterparts, and we compared this behavior to the behavior of age, income, education and gender matched healthy controls. The results of our study show that PD patients trust avatar faces significantly more than human faces. Moreover, there was no significant difference between initial trust of PD patients and healthy controls in avatar faces, while PD patients trusted human faces significantly less than healthy controls. Our data suggests that PD patients’ interaction with avatars may constitute an effective way of communication in situations in which trust is required (e.g., a physician recommends intake of medication). We discuss the implications of these results for several areas of human-computer interaction and neurological research. PMID:27820864

pulver: an R package for parallel ultra-rapid p-value computation for linear regression interaction terms.

PubMed

Molnos, Sophie; Baumbach, Clemens; Wahl, Simone; Müller-Nurasyid, Martina; Strauch, Konstantin; Wang-Sattler, Rui; Waldenberger, Melanie; Meitinger, Thomas; Adamski, Jerzy; Kastenmüller, Gabi; Suhre, Karsten; Peters, Annette; Grallert, Harald; Theis, Fabian J; Gieger, Christian

2017-09-29

Genome-wide association studies allow us to understand the genetics of complex diseases. Human metabolism provides information about the disease-causing mechanisms, so it is usual to investigate the associations between genetic variants and metabolite levels. However, only considering genetic variants and their effects on one trait ignores the possible interplay between different "omics" layers. Existing tools only consider single-nucleotide polymorphism (SNP)-SNP interactions, and no practical tool is available for large-scale investigations of the interactions between pairs of arbitrary quantitative variables. We developed an R package called pulver to compute p-values for the interaction term in a very large number of linear regression models. Comparisons based on simulated data showed that pulver is much faster than the existing tools. This is achieved by using the correlation coefficient to test the null-hypothesis, which avoids the costly computation of inversions. Additional tricks are a rearrangement of the order, when iterating through the different "omics" layers, and implementing this algorithm in the fast programming language C++. Furthermore, we applied our algorithm to data from the German KORA study to investigate a real-world problem involving the interplay among DNA methylation, genetic variants, and metabolite levels. The pulver package is a convenient and rapid tool for screening huge numbers of linear regression models for significant interaction terms in arbitrary pairs of quantitative variables. pulver is written in R and C++, and can be downloaded freely from CRAN at https://cran.r-project.org/web/packages/pulver/ .

Human-Computer Interaction in Smart Environments

PubMed Central

Paravati, Gianluca; Gatteschi, Valentina

2015-01-01

Here, we provide an overview of the content of the Special Issue on “Human-computer interaction in smart environments”. The aim of this Special Issue is to highlight technologies and solutions encompassing the use of mass-market sensors in current and emerging applications for interacting with Smart Environments. Selected papers address this topic by analyzing different interaction modalities, including hand/body gestures, face recognition, gaze/eye tracking, biosignal analysis, speech and activity recognition, and related issues.

Real-time non-invasive eyetracking and gaze-point determination for human-computer interaction and biomedicine

NASA Technical Reports Server (NTRS)

Talukder, Ashit; Morookian, John-Michael; Monacos, S.; Lam, R.; Lebaw, C.; Bond, A.

2004-01-01

Eyetracking is one of the latest technologies that has shown potential in several areas including human-computer interaction for people with and without disabilities, and for noninvasive monitoring, detection, and even diagnosis of physiological and neurological problems in individuals.

Identification of drug interactions in hospitals--computerized screening vs. bedside recording.

PubMed

Blix, H S; Viktil, K K; Moger, T A; Reikvam, A

2008-04-01

Managing drug interactions in hospitalized patients is important and challenging. The objective of the study was to compare two methods for identification of drug interactions (DDIs)--computerized screening and prospective bedside recording--with regard to capability of identifying DDIs. Patient characteristics were recorded for patients admitted to five hospitals. By bedside evaluation drug-related problems, including DDIs, were prospectively recorded by pharmacists and discussed in multidisciplinary teams. A computer screening programme was used to identify DDIs retrospectively--dividing DDIs into four classes: A, avoid; B, avoid/take precautions; C, take precautions; D, no action needed. Among 827 patients, computer screening identified DDIs in 544 patients (66%); 351 had DDIs introduced in hospital. The 1513 computer-identified DDIs had the following distribution: type A 78; type B 915; type C 38; type D 482. By bedside evaluation, 99 DDIs were identified in 73 patients (9%). The proportions of computer recorded DDIs which were also identified at the bedside were: 5%, 8%, 8%, 2% DDIs of types A, B, C and D respectively. In 10 patients, DDIs not registered by computer screening were identified by bedside evaluation. The drugs most frequently involved in DDIs, identified by computerized screening were acetylsalicylic acid, warfarin, furosemide and digitoxin compared with warfarin, simvastatin, theophylline and carbamazepine, by bedside evaluation. Despite an active prospective bedside search for DDIs, this approach identified less than one in 10 of the DDIs recorded by computer screening, including those regarded as hazardous. However, computer screening overestimates considerably when the objective is to identify clinically relevant DDIs.

The experience of agency in human-computer interactions: a review

PubMed Central

Limerick, Hannah; Coyle, David; Moore, James W.

2014-01-01

The sense of agency is the experience of controlling both one’s body and the external environment. Although the sense of agency has been studied extensively, there is a paucity of studies in applied “real-life” situations. One applied domain that seems highly relevant is human-computer-interaction (HCI), as an increasing number of our everyday agentive interactions involve technology. Indeed, HCI has long recognized the feeling of control as a key factor in how people experience interactions with technology. The aim of this review is to summarize and examine the possible links between sense of agency and understanding control in HCI. We explore the overlap between HCI and sense of agency for computer input modalities and system feedback, computer assistance, and joint actions between humans and computers. An overarching consideration is how agency research can inform HCI and vice versa. Finally, we discuss the potential ethical implications of personal responsibility in an ever-increasing society of technology users and intelligent machine interfaces. PMID:25191256

Cognitive control over learning: Creating, clustering and generalizing task-set structure

PubMed Central

Collins, Anne G.E.; Frank, Michael J.

2013-01-01

Executive functions and learning share common neural substrates essential for their expression, notably in prefrontal cortex and basal ganglia. Understanding how they interact requires studying how cognitive control facilitates learning, but also how learning provides the (potentially hidden) structure, such as abstract rules or task-sets, needed for cognitive control. We investigate this question from three complementary angles. First, we develop a new computational “C-TS” (context-task-set) model inspired by non-parametric Bayesian methods, specifying how the learner might infer hidden structure and decide whether to re-use that structure in new situations, or to create new structure. Second, we develop a neurobiologically explicit model to assess potential mechanisms of such interactive structured learning in multiple circuits linking frontal cortex and basal ganglia. We systematically explore the link betweens these levels of modeling across multiple task demands. We find that the network provides an approximate implementation of high level C-TS computations, where manipulations of specific neural mechanisms are well captured by variations in distinct C-TS parameters. Third, this synergism across models yields strong predictions about the nature of human optimal and suboptimal choices and response times during learning. In particular, the models suggest that participants spontaneously build task-set structure into a learning problem when not cued to do so, which predicts positive and negative transfer in subsequent generalization tests. We provide evidence for these predictions in two experiments and show that the C-TS model provides a good quantitative fit to human sequences of choices in this task. These findings implicate a strong tendency to interactively engage cognitive control and learning, resulting in structured abstract representations that afford generalization opportunities, and thus potentially long-term rather than short-term optimality. PMID:23356780

Category 3: Sound Generation by Interacting With a Gust

NASA Technical Reports Server (NTRS)

Envia, Edmane

2004-01-01

Solve the time-dependent inviscid flow equations for this geometry subject to the specified inflow/outflow mean conditions and the fluctuating inflow velocity distortion. (1) Compute the unsteady solution until periodicity in pressure is achieved by showing that at least two successive periods are identical. Periodicity must be achieved on both the airfoil surface and the inflow/outflow boundaries. (2) Once periodicity is achieved, compute the pressure frequency spectra on the reference airfoil on both the upper and lower surfaces at x=(-0.25c,0.00, +0.25c), on the inflow boundary at (x,y)={1.5c,-0.3c), (-1.5c,0.0),(-1.5c,0.3c)} and on the outflow boundary at (x,y)= {(1.5c,-0.3c),(1.5c,0.0), (1.5c,0.3c)}. Express the spectral results in dB using the standard definition 20 log(P(sub(r.m.s)/P(sub ref), where p(sub ref) == 20 microPa. (3) Extract the harmonic pressure distributions on the inflow and outflow boundaries (i.e., on x= -/+ 1.5c lines) at the fundamental frequency omega and apply a Fourier transform in y direction to identify the spatial (i.e., mode order) structure of the pressure perturbations. Express the result in dB for each mode order. Repeat the process for the frequencies 2omega and 3omega.

Cognitive Architectures and Human-Computer Interaction. Introduction to Special Issue.

ERIC Educational Resources Information Center

Gray, Wayne D.; Young, Richard M.; Kirschenbaum, Susan S.

1997-01-01

In this introduction to a special issue on cognitive architectures and human-computer interaction (HCI), editors and contributors provide a brief overview of cognitive architectures. The following four architectures represented by articles in this issue are: Soar; LICAI (linked model of comprehension-based action planning and instruction taking);…

Factors Influencing Adoption of Ubiquitous Internet amongst Students

ERIC Educational Resources Information Center

Juned, Mohammad; Adil, Mohd

2015-01-01

Weiser's (1991) conceptualisation of a world wherein human's interaction with computer technology would no longer be limited to conventional input and output devices, has now been translated into a reality with human's constant interaction with multiple interconnected computers and sensors embedded in rooms, furniture, clothes, tools, and other…

Comparison of the protein-coding gene content of Chlamydia trachomatis and Protochlamydia amoebophila using a Raspberry Pi computer.

PubMed

Robson, James F; Barker, Daniel

2015-10-13

To demonstrate the bioinformatics capabilities of a low-cost computer, the Raspberry Pi, we present a comparison of the protein-coding gene content of two species in phylum Chlamydiae: Chlamydia trachomatis, a common sexually transmitted infection of humans, and Candidatus Protochlamydia amoebophila, a recently discovered amoebal endosymbiont. Identifying species-specific proteins and differences in protein families could provide insights into the unique phenotypes of the two species. Using a Raspberry Pi computer, sequence similarity-based protein families were predicted across the two species, C. trachomatis and P. amoebophila, and their members counted. Examples include nine multi-protein families unique to C. trachomatis, 132 multi-protein families unique to P. amoebophila and one family with multiple copies in both. Most families unique to C. trachomatis were polymorphic outer-membrane proteins. Additionally, multiple protein families lacking functional annotation were found. Predicted functional interactions suggest one of these families is involved with the exodeoxyribonuclease V complex. The Raspberry Pi computer is adequate for a comparative genomics project of this scope. The protein families unique to P. amoebophila may provide a basis for investigating the host-endosymbiont interaction. However, additional species should be included; and further laboratory research is required to identify the functions of unknown or putative proteins. Multiple outer membrane proteins were found in C. trachomatis, suggesting importance for host evasion. The tyrosine transport protein family is shared between both species, with four proteins in C. trachomatis and two in P. amoebophila. Shared protein families could provide a starting point for discovery of wide-spectrum drugs against Chlamydiae.

Computational studies of H5N1 hemagglutinin binding with SA-{alpha}-2, 3-Gal and SA-{alpha}-2, 6-Gal

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

Li Minyong; Wang Binghe

2006-09-01

For influenza H5N1 hemagglutinin, a switch from SA-{alpha}-2, 3-Gal to SA-{alpha}-2, 6-Gal receptor specificity is a critical step leading to the conversion from avian-to-human to human-to-human infection. Therefore, the understanding of the binding modes of SA-{alpha}-2, 3-Gal and SA-{alpha}-2, 6-Gal to H5N1 hemagglutinin will be very important for the examination of possible mutations needed for going from an avian to a human flu virus. Based on the available H5N1 hemagglutinin crystal structure, the binding profiles between H5N1 hemagglutinin and two saccharide ligands, SA-{alpha}-2, 3-Gal and SA-{alpha}-2, 6-Gal, were investigated by ab initio quantum mechanics, molecular docking, molecular mechanics, and molecularmore » dynamics simulations. It was found that SA-{alpha}-2, 3-Gal has strong multiple hydrophobic and hydrogen bond interactions in its trans conformation with H5N1 hemagglutinin, whereas the SA-{alpha}-2, 6-Gal only shows weak interactions in a different conformation (cis type)« less

Action and language integration: from humans to cognitive robots.

PubMed

Borghi, Anna M; Cangelosi, Angelo

2014-07-01

The topic is characterized by a highly interdisciplinary approach to the issue of action and language integration. Such an approach, combining computational models and cognitive robotics experiments with neuroscience, psychology, philosophy, and linguistic approaches, can be a powerful means that can help researchers disentangle ambiguous issues, provide better and clearer definitions, and formulate clearer predictions on the links between action and language. In the introduction we briefly describe the papers and discuss the challenges they pose to future research. We identify four important phenomena the papers address and discuss in light of empirical and computational evidence: (a) the role played not only by sensorimotor and emotional information but also of natural language in conceptual representation; (b) the contextual dependency and high flexibility of the interaction between action, concepts, and language; (c) the involvement of the mirror neuron system in action and language processing; (d) the way in which the integration between action and language can be addressed by developmental robotics and Human-Robot Interaction. Copyright © 2014 Cognitive Science Society, Inc.

Using Interactive Computer to Communicate Scientific Information.

ERIC Educational Resources Information Center

Selnow, Gary W.

1988-01-01

Asks whether the computer is another channel of communication, if its interactive qualities make it an information source, or if it is an undefined hybrid. Concludes that computers are neither the medium nor the source but will in the future provide the possibility of a sophisticated interaction between human intelligence and artificial…

Categorisation of visualisation methods to support the design of Human-Computer Interaction Systems.

PubMed

Li, Katie; Tiwari, Ashutosh; Alcock, Jeffrey; Bermell-Garcia, Pablo

2016-07-01

During the design of Human-Computer Interaction (HCI) systems, the creation of visual artefacts forms an important part of design. On one hand producing a visual artefact has a number of advantages: it helps designers to externalise their thought and acts as a common language between different stakeholders. On the other hand, if an inappropriate visualisation method is employed it could hinder the design process. To support the design of HCI systems, this paper reviews the categorisation of visualisation methods used in HCI. A keyword search is conducted to identify a) current HCI design methods, b) approaches of selecting these methods. The resulting design methods are filtered to create a list of just visualisation methods. These are then categorised using the approaches identified in (b). As a result 23 HCI visualisation methods are identified and categorised in 5 selection approaches (The Recipient, Primary Purpose, Visual Archetype, Interaction Type, and The Design Process). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A hybrid parallel architecture for electrostatic interactions in the simulation of dissipative particle dynamics

NASA Astrophysics Data System (ADS)

Yang, Sheng-Chun; Lu, Zhong-Yuan; Qian, Hu-Jun; Wang, Yong-Lei; Han, Jie-Ping

2017-11-01

In this work, we upgraded the electrostatic interaction method of CU-ENUF (Yang, et al., 2016) which first applied CUNFFT (nonequispaced Fourier transforms based on CUDA) to the reciprocal-space electrostatic computation and made the computation of electrostatic interaction done thoroughly in GPU. The upgraded edition of CU-ENUF runs concurrently in a hybrid parallel way that enables the computation parallelizing on multiple computer nodes firstly, then further on the installed GPU in each computer. By this parallel strategy, the size of simulation system will be never restricted to the throughput of a single CPU or GPU. The most critical technical problem is how to parallelize a CUNFFT in the parallel strategy, which is conquered effectively by deep-seated research of basic principles and some algorithm skills. Furthermore, the upgraded method is capable of computing electrostatic interactions for both the atomistic molecular dynamics (MD) and the dissipative particle dynamics (DPD). Finally, the benchmarks conducted for validation and performance indicate that the upgraded method is able to not only present a good precision when setting suitable parameters, but also give an efficient way to compute electrostatic interactions for huge simulation systems. Program Files doi:http://dx.doi.org/10.17632/zncf24fhpv.1 Licensing provisions: GNU General Public License 3 (GPL) Programming language: C, C++, and CUDA C Supplementary material: The program is designed for effective electrostatic interactions of large-scale simulation systems, which runs on particular computers equipped with NVIDIA GPUs. It has been tested on (a) single computer node with Intel(R) Core(TM) i7-3770@ 3.40 GHz (CPU) and GTX 980 Ti (GPU), and (b) MPI parallel computer nodes with the same configurations. Nature of problem: For molecular dynamics simulation, the electrostatic interaction is the most time-consuming computation because of its long-range feature and slow convergence in simulation space, which approximately take up most of the total simulation time. Although the parallel method CU-ENUF (Yang et al., 2016) based on GPU has achieved a qualitative leap compared with previous methods in electrostatic interactions computation, the computation capability is limited to the throughput capacity of a single GPU for super-scale simulation system. Therefore, we should look for an effective method to handle the calculation of electrostatic interactions efficiently for a simulation system with super-scale size. Solution method: We constructed a hybrid parallel architecture, in which CPU and GPU are combined to accelerate the electrostatic computation effectively. Firstly, the simulation system is divided into many subtasks via domain-decomposition method. Then MPI (Message Passing Interface) is used to implement the CPU-parallel computation with each computer node corresponding to a particular subtask, and furthermore each subtask in one computer node will be executed in GPU in parallel efficiently. In this hybrid parallel method, the most critical technical problem is how to parallelize a CUNFFT (nonequispaced fast Fourier transform based on CUDA) in the parallel strategy, which is conquered effectively by deep-seated research of basic principles and some algorithm skills. Restrictions: The HP-ENUF is mainly oriented to super-scale system simulations, in which the performance superiority is shown adequately. However, for a small simulation system containing less than 106 particles, the mode of multiple computer nodes has no apparent efficiency advantage or even lower efficiency due to the serious network delay among computer nodes, than the mode of single computer node. References: (1) S.-C. Yang, H.-J. Qian, Z.-Y. Lu, Appl. Comput. Harmon. Anal. 2016, http://dx.doi.org/10.1016/j.acha.2016.04.009. (2) S.-C. Yang, Y.-L. Wang, G.-S. Jiao, H.-J. Qian, Z.-Y. Lu, J. Comput. Chem. 37 (2016) 378. (3) S.-C. Yang, Y.-L. Zhu, H.-J. Qian, Z.-Y. Lu, Appl. Chem. Res. Chin. Univ., 2017, http://dx.doi.org/10.1007/s40242-016-6354-5. (4) Y.-L. Zhu, H. Liu, Z.-W. Li, H.-J. Qian, G. Milano, Z.-Y. Lu, J. Comput. Chem. 34 (2013) 2197.

Structure and Bonding in CE5- (E=Al-Tl) Clusters: Planar Tetracoordinate Carbon versus Pentacoordinate Carbon.

PubMed

Ravell, Estefanía; Jalife, Said; Barroso, Jorge; Orozco-Ic, Mesías; Hernández-Juárez, Gerardo; Ortiz-Chi, Filiberto; Pan, Sudip; Cabellos, José Luis; Merino, Gabriel

2018-03-24

The structure, bonding, and stability of clusters with the empirical formula CE 5 - (E=Al-Tl) have been analyzed by means of high-level computations. The results indicate that, whereas aluminum and gallium clusters have C 2v structures with a planar tetracoordinate carbon (ptC), their heavier homologues prefer three-dimensional C 4v forms with a pentacoordinate carbon center over the ptC one. The reason for such a preference is a delicate balance between the interaction energy of the fifth E atom with CE 4 and the distortion energy. Moreover, bonding analysis shows that the ptC systems can be better described as CE 4 - , with 17-valence electrons interacting with E. The ptC core in these systems exhibits double aromatic (both σ and π) behavior, but the σ contribution is dominating. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities.

PubMed

Doehmer, Johannes; Weiss, Gabriele; McGregor, Gerard P; Appel, Kurt

2011-02-01

The effect of a standardised dry extract from Silybum marianum (HEPAR-PASC®) on the enzyme kinetics of cytochrome-P450 isoenzymes (CYP) was investigated with primary human hepatocytes and human liver microsomes in order to assess the potential for drug-drug interactions. A cytotoxic effect on hepatocytes was observed at concentrations at and above 50 μg/ml. The EC(50) value was calculated to be 72.0 μg/ml. Therefore, the chosen test concentrations for CYP induction on human hepatocytes were 50, 10, and 1.5 μg/ml, which allowed for interpretation of the clinical significance of the data with a range of 50-1-fold c(max) at maximal recommended doses. No induction was observed at the lowest concentration of 1.5 μg/ml, which is close to c(max). The extract did not induce CYP 3A4 at any of the tested concentrations. A low or marginal induction of 1A2, 2B6, and 2E1 at the maximum concentration of 50 μg/ml was observed. CYP inhibition on human microsomes was tested at concentrations of 150, 15, and 1.5 μg/ml. No or minor CYP inhibition was observed for all CYPs tested at the lowest concentration of 1.5 μg/ml, i.e. CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. At concentrations of 15 and 150 μg/ml the extract significantly inhibited CYP 2B6, 2C8, 2C9, 2C19, 2E1, and 3A4. In these cases, K(i) values were determined. All K(i) values exceeded c(max) by at least a factor of 10-fold. According to FDA regulations 1>c(max)/K(i)>0.1 indicates, that drug-drug interactions are possible for CYPs 2C8, and 2C9, but not likely, and are remote for CYPs 2C19, 2D6, and 3A4. Copyright © 2010 Elsevier Ltd. All rights reserved.

Controlled English for Effective Communication during Coalition Operations

DTIC Science & Technology

2013-06-01

Linguistic variations and cultural differences often create unexpected challenges for effective communication and thus for Command and Control (C2...CE), and CE-based tools to improve cross- linguistic /cross-cultural communication. We will discuss various types of linguistic variations and cultural...human-computer interaction, reasoning, and explanation CE and CE-based tools can play an important role in facilitating cross- linguistic and cross

Questioning Mechanisms During Tutoring, Conversation, and Human-Computer Interaction

DTIC Science & Technology

1993-06-01

of Psychology Los Angesles, CA 90024 Pittsburgh, PA 15213 Dr. Eduardo Cascallar Dr. Ruth Chabay Dr. Paul G. Chapin Educational Testing Service CDEC...Sharon Deny Educational Testing Service Applied Science Associates Florida State University Mail Stop 22-T P.O. Box 1072 Dept. of Psychology ...Department of Psychology , Department of Mathematical Sciences, and the Institute for Intelligent Systems Mailing address: Arthur C. Graesser Department.of

ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5.

PubMed

Hsu, H; Solovyev, I; Colombero, A; Elliott, R; Kelley, M; Boyle, W J

1997-05-23

Members of tumor necrosis factor receptor (TNFR) family signal largely through interactions with death domain proteins and TRAF proteins. Here we report the identification of a novel TNFR family member ATAR. Human and mouse ATAR contain 283 and 276 amino acids, respectively, making them the shortest known members of the TNFR superfamily. The receptor is expressed mainly in spleen, thymus, bone marrow, lung, and small intestine. The intracellular domains of human and mouse ATAR share only 25% identity, yet both interact with TRAF5 and TRAF2. This TRAF interaction domain resides at the C-terminal 20 amino acids. Like most other TRAF-interacting receptors, overexpression of ATAR activates the transcription factor NF-kappaB. Co-expression of ATAR with TRAF5, but not TRAF2, results in synergistic activation of NF-kappaB, suggesting potentially different roles for TRAF2 and TRAF5 in post-receptor signaling.

Direct and indirect reputation formation in nonhuman great apes (Pan paniscus, Pan troglodytes, Gorilla gorilla, Pongo pygmaeus) and human children (Homo sapiens).

PubMed

Herrmann, Esther; Keupp, Stefanie; Hare, Brian; Vaish, Amrisha; Tomasello, Michael

2013-02-01

Humans make decisions about when and with whom to cooperate based on their reputations. People either learn about others by direct interaction or by observing third-party interactions or gossip. An important question is whether other animal species, especially our closest living relatives, the nonhuman great apes, also form reputations of others. In Study 1, chimpanzees, bonobos, orangutans, and 2.5-year-old human children experienced a nice experimenter who tried to give food/toys to the subject and a mean experimenter who interrupted the food/toy giving. In studies 2 and 3, nonhuman great apes and human children could only passively observe a similar interaction, in which a nice experimenter and a mean experimenter interacted with a third party. Orangutans and 2.5-year-old human children preferred to approach the nice experimenter rather than the mean one after having directly experienced their respective behaviors. Orangutans, chimpanzees, and 2.5-year-old human children also took into account experimenter actions toward third parties in forming reputations. These studies show that the human ability to form direct and indirect reputation judgment is already present in young children and shared with at least some of the other great apes. PsycINFO Database Record (c) 2013 APA, all rights reserved

Touchless interaction with software in interventional radiology and surgery: a systematic literature review.

PubMed

Mewes, André; Hensen, Bennet; Wacker, Frank; Hansen, Christian

2017-02-01

In this article, we systematically examine the current state of research of systems that focus on touchless human-computer interaction in operating rooms and interventional radiology suites. We further discuss the drawbacks of current solutions and underline promising technologies for future development. A systematic literature search of scientific papers that deal with touchless control of medical software in the immediate environment of the operation room and interventional radiology suite was performed. This includes methods for touchless gesture interaction, voice control and eye tracking. Fifty-five research papers were identified and analyzed in detail including 33 journal publications. Most of the identified literature (62 %) deals with the control of medical image viewers. The others present interaction techniques for laparoscopic assistance (13 %), telerobotic assistance and operating room control (9 % each) as well as for robotic operating room assistance and intraoperative registration (3.5 % each). Only 8 systems (14.5 %) were tested in a real clinical environment, and 7 (12.7 %) were not evaluated at all. In the last 10 years, many advancements have led to robust touchless interaction approaches. However, only a few have been systematically evaluated in real operating room settings. Further research is required to cope with current limitations of touchless software interfaces in clinical environments. The main challenges for future research are the improvement and evaluation of usability and intuitiveness of touchless human-computer interaction and the full integration into productive systems as well as the reduction of necessary interaction steps and further development of hands-free interaction.

The human factors of workstation telepresence

NASA Technical Reports Server (NTRS)

Smith, Thomas J.; Smith, Karl U.

1990-01-01

The term workstation telepresence has been introduced to describe human-telerobot compliance, which enables the human operator to effectively project his/her body image and behavioral skills to control of the telerobot itself. Major human-factors considerations for establishing high fidelity workstation telepresence during human-telerobot operation are discussed. Telerobot workstation telepresence is defined by the proficiency and skill with which the operator is able to control sensory feedback from direct interaction with the workstation itself, and from workstation-mediated interaction with the telerobot. Numerous conditions influencing such control have been identified. This raises the question as to what specific factors most critically influence the realization of high fidelity workstation telepresence. The thesis advanced here is that perturbations in sensory feedback represent a major source of variability in human performance during interactive telerobot operation. Perturbed sensory feedback research over the past three decades has established that spatial transformations or temporal delays in sensory feedback engender substantial decrements in interactive task performance, which training does not completely overcome. A recently developed social cybernetic model of human-computer interaction can be used to guide this approach, based on computer-mediated tracking and control of sensory feedback. How the social cybernetic model can be employed for evaluating the various modes, patterns, and integrations of interpersonal, team, and human-computer interactions which play a central role is workstation telepresence are discussed.

Choice of Human-Computer Interaction Mode in Stroke Rehabilitation.

PubMed

Mousavi Hondori, Hossein; Khademi, Maryam; Dodakian, Lucy; McKenzie, Alison; Lopes, Cristina V; Cramer, Steven C

2016-03-01

Advances in technology are providing new forms of human-computer interaction. The current study examined one form of human-computer interaction, augmented reality (AR), whereby subjects train in the real-world workspace with virtual objects projected by the computer. Motor performances were compared with those obtained while subjects used a traditional human-computer interaction, that is, a personal computer (PC) with a mouse. Patients used goal-directed arm movements to play AR and PC versions of the Fruit Ninja video game. The 2 versions required the same arm movements to control the game but had different cognitive demands. With AR, the game was projected onto the desktop, where subjects viewed the game plus their arm movements simultaneously, in the same visual coordinate space. In the PC version, subjects used the same arm movements but viewed the game by looking up at a computer monitor. Among 18 patients with chronic hemiparesis after stroke, the AR game was associated with 21% higher game scores (P = .0001), 19% faster reaching times (P = .0001), and 15% less movement variability (P = .0068), as compared to the PC game. Correlations between game score and arm motor status were stronger with the AR version. Motor performances during the AR game were superior to those during the PC game. This result is due in part to the greater cognitive demands imposed by the PC game, a feature problematic for some patients but clinically useful for others. Mode of human-computer interface influences rehabilitation therapy demands and can be individualized for patients. © The Author(s) 2015.

Human-computer interface

DOEpatents

Anderson, Thomas G.

2004-12-21

The present invention provides a method of human-computer interfacing. Force feedback allows intuitive navigation and control near a boundary between regions in a computer-represented space. For example, the method allows a user to interact with a virtual craft, then push through the windshield of the craft to interact with the virtual world surrounding the craft. As another example, the method allows a user to feel transitions between different control domains of a computer representation of a space. The method can provide for force feedback that increases as a user's locus of interaction moves near a boundary, then perceptibly changes (e.g., abruptly drops or changes direction) when the boundary is traversed.

The Design and Implementation of a Graphical VHDL (VHSIC Hardware Description Language) User Interface

DTIC Science & Technology

1988-12-01

VHSIC Program Office appropriately summarized the motivation behind VHDL as follows: Computer -aided engineering is a nightmare of incompatible formats and... Computer Science Branch. Interactive VHDL Workstation: Program Status Review Report, 8 October 1987. Air Force Contract F33615-85-C-1862. Information Systems...Typical Program Structure .................................. 14 3 Figure 4. GVUI Top-Level SADT Diagram ............................... .24 Figure 5

Principles for Integrating Mars Analog Science, Operations, and Technology Research

NASA Technical Reports Server (NTRS)

Clancey, William J.

2003-01-01

During the Apollo program, the scientific community and NASA used terrestrial analog sites for understanding planetary features and for training astronauts to be scientists. Human factors studies (Harrison, Clearwater, & McKay 1991; Stuster 1996) have focused on the effects of isolation in extreme environments. More recently, with the advent of wireless computing, we have prototyped advanced EVA technologies for navigation, scheduling, and science data logging (Clancey 2002b; Clancey et al., in press). Combining these interests in a single expedition enables tremendous synergy and authenticity, as pioneered by Pascal Lee's Haughton-Mars Project (Lee 2001; Clancey 2000a) and the Mars Society s research stations on a crater rim on Devon Island in the High Canadian Arctic (Clancey 2000b; 2001b) and the Morrison Formation of southeast Utah (Clancey 2002a). Based on this experience, the following principles are proposed for conducting an integrated science, operations, and technology research program at analog sites: 1) Authentic work; 2) PI-based projects; 3) Unencumbered baseline studies; 4) Closed simulations; and 5) Observation and documentation. Following these principles, we have been integrating field science, operations research, and technology development at analog sites on Devon Island and in Utah over the past five years. Analytic methods include work practice simulation (Clancey 2002c; Sierhuis et a]., 2000a;b), by which the interaction of human behavior, facilities, geography, tools, and procedures are formalized in computer models. These models are then converted into the runtime EVA system we call mobile agents (Clancey 2002b; Clancey et al., in press). Furthermore, we have found that the Apollo Lunar Surface Journal (Jones, 1999) provides a vast repository or understanding astronaut and CapCom interactions, serving as a baseline for Mars operations and quickly highlighting opportunities for computer automation (Clancey, in press).

Human agency beliefs influence behaviour during virtual social interactions.

PubMed

Caruana, Nathan; Spirou, Dean; Brock, Jon

2017-01-01

In recent years, with the emergence of relatively inexpensive and accessible virtual reality technologies, it is now possible to deliver compelling and realistic simulations of human-to-human interaction. Neuroimaging studies have shown that, when participants believe they are interacting via a virtual interface with another human agent, they show different patterns of brain activity compared to when they know that their virtual partner is computer-controlled. The suggestion is that users adopt an "intentional stance" by attributing mental states to their virtual partner. However, it remains unclear how beliefs in the agency of a virtual partner influence participants' behaviour and subjective experience of the interaction. We investigated this issue in the context of a cooperative "joint attention" game in which participants interacted via an eye tracker with a virtual onscreen partner, directing each other's eye gaze to different screen locations. Half of the participants were correctly informed that their partner was controlled by a computer algorithm ("Computer" condition). The other half were misled into believing that the virtual character was controlled by a second participant in another room ("Human" condition). Those in the "Human" condition were slower to make eye contact with their partner and more likely to try and guide their partner before they had established mutual eye contact than participants in the "Computer" condition. They also responded more rapidly when their partner was guiding them, although the same effect was also found for a control condition in which they responded to an arrow cue. Results confirm the influence of human agency beliefs on behaviour in this virtual social interaction context. They further suggest that researchers and developers attempting to simulate social interactions should consider the impact of agency beliefs on user experience in other social contexts, and their effect on the achievement of the application's goals.

Use of parallel computing for analyzing big data in EEG studies of ambiguous perception

NASA Astrophysics Data System (ADS)

Maksimenko, Vladimir A.; Grubov, Vadim V.; Kirsanov, Daniil V.

2018-02-01

Problem of interaction between human and machine systems through the neuro-interfaces (or brain-computer interfaces) is an urgent task which requires analysis of large amount of neurophysiological EEG data. In present paper we consider the methods of parallel computing as one of the most powerful tools for processing experimental data in real-time with respect to multichannel structure of EEG. In this context we demonstrate the application of parallel computing for the estimation of the spectral properties of multichannel EEG signals, associated with the visual perception. Using CUDA C library we run wavelet-based algorithm on GPUs and show possibility for detection of specific patterns in multichannel set of EEG data in real-time.

Harnessing the Power of Interactivity for Instruction.

ERIC Educational Resources Information Center

Borsook, Terry K.

Arguing that what sets the computer apart from all other teaching devices is its potential for interactivity, this paper examines the concept of interactivity and explores ways in which its power can be harnessed and put to work. A discussion of interactivity in human-to-human communication sets a context within which to view human/computer…

Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C.

PubMed

Chattopadhyay, Debasish; Swingle, Mark R; Salter, Edward A; Wood, Eric; D'Arcy, Brandon; Zivanov, Catherine; Abney, Kevin; Musiyenko, Alla; Rusin, Scott F; Kettenbach, Arminja; Yet, Larry; Schroeder, Chad E; Golden, Jennifer E; Dunham, Wade H; Gingras, Anne-Claude; Banerjee, Surajit; Forbes, David; Wierzbicki, Andrzej; Honkanen, Richard E

2016-06-01

Cantharidin is a natural toxin and an active constituent in a traditional Chinese medicine used to treat tumors. Cantharidin acts as a semi-selective inhibitor of PPP-family ser/thr protein phosphatases. Despite sharing a common catalytic mechanism and marked structural similarity with PP1C, PP2AC and PP5C, human PP4C was found to be insensitive to the inhibitory activity of cantharidin. To explore the molecular basis for this selectivity, we synthesized and tested novel C5/C6-derivatives designed from quantum-based modeling of the interactions revealed in the co-crystal structures of PP5C in complex with cantharidin. Structure-activity relationship studies and analysis of high-resolution (1.25Å) PP5C-inhibitor co-crystal structures reveal close contacts between the inhibitor bridgehead oxygen and both a catalytic metal ion and a non-catalytic phenylalanine residue, the latter of which is substituted by tryptophan in PP4C. Quantum chemistry calculations predicted that steric clashes with the bulkier tryptophan side chain in PP4C would force all cantharidin-based inhibitors into an unfavorable binding mode, disrupting the strong coordination of active site metal ions observed in the PP5C co-crystal structures, thereby rendering PP4C insensitive to the inhibitors. This prediction was confirmed by inhibition studies employing native human PP4C. Mutation of PP5C (F446W) and PP1C (F257W), to mimic the PP4C active site, resulted in markedly suppressed sensitivity to cantharidin. These observations provide insight into the structural basis for the natural selectivity of cantharidin and provide an avenue for PP4C deselection. The novel crystal structures also provide insight into interactions that provide increased selectivity of the C5/C6 modifications for PP5C versus other PPP-family phosphatases. Copyright © 2016 Elsevier Inc. All rights reserved.

A Framework and Implementation of User Interface and Human-Computer Interaction Instruction

ERIC Educational Resources Information Center

Peslak, Alan

2005-01-01

Researchers have suggested that up to 50 % of the effort in development of information systems is devoted to user interface development (Douglas, Tremaine, Leventhal, Wills, & Manaris, 2002; Myers & Rosson, 1992). Yet little study has been performed on the inclusion of important interface and human-computer interaction topics into a current…

A Project-Based Learning Setting to Human-Computer Interaction for Teenagers

ERIC Educational Resources Information Center

Geyer, Cornelia; Geisler, Stefan

2012-01-01

Knowledge of fundamentals of human-computer interaction resp. usability engineering is getting more and more important in technical domains. However this interdisciplinary field of work and corresponding degree programs are not broadly known. Therefore at the Hochschule Ruhr West, University of Applied Sciences, a program was developed to give…

Fabrication of DNA/Hydroxyapatite nanocomposites by simulated body fluid for gene delivery

NASA Astrophysics Data System (ADS)

Takeshita, Takayuki; Okamoto, Masami

2015-05-01

The hydroxyapatite (HA) formation on the surface of DNA molecules in simulated body fluid (SBF) was examined. The osteoconductivity is estimated using SBF having ion concentrations approximately equal to those of human blood plasma. After immersion for 4 weeks in SBF at 36.5 °C, the HA crystallites possessing 1-14 micrometer in diameter grew on the surface of DNA molecules. The leaf flake-like and spherical shapes morphologies were observed through scanning electron microscopy analysis. Original peaks of both of DNA and HA were characterized by fourier transform infrared spectroscopy. The Ca/P ratio (1.1-1.5) in HA was estimated by energy dispersive X-ray analysis. After biomineralization, the calculated weight ratio of DNA/HA was 18/82 by thermogravimetry/differential thermal analysis. The molecular orbital computer simulation has been used to probe the interaction of DNA with two charge-balancing ions, CaOH+ and C a H2P O4+ . The adsorption enthalpy of the two ions on DNA having negative value was the evidence for the interface in mineralization of HA in SBF.

Identity of the segment of human complement C8 recognized by complement regulatory protein CD59.

PubMed

Lockert, D H; Kaufman, K M; Chang, C P; Hüsler, T; Sodetz, J M; Sims, P J

1995-08-25

CD59 antigen is a membrane glycoprotein that inhibits the activity of the C5b-9 membrane attack complex (MAC), thereby protecting human cells from lysis by human complement. The inhibitory function of CD59 derives from its capacity to interact with both the C8 and C9 components of MAC, preventing assembly of membrane-inserted C9 polymer. MAC-inhibitory activity of CD59 is species-selective and is most effective when both C8 and C9 derive from human or other primate plasma. Rabbit C8 and C9, which can substitute for human C8 and C9 in MAC, mediate virtually unrestricted lysis of human cells expressing CD59. In order to identify the segment of human C8 that is recognized by CD59, recombinant peptides containing human or rabbit C8 sequence were expressed in Escherichia coli and purified. CD59 was found to specifically bind to a peptide corresponding to residues 334-385 of the human C8 alpha-subunit, and to require a disulfide bond between Cys345 and Cys369. No specific binding was observed to the corresponding sequence from rabbit C8 alpha (residues 334-386). To obtain functional evidence that this segment of human C8 alpha is selectively recognized by CD59, recombinant C8 proteins were prepared by co-transfecting COS-7 cells with human/rabbit chimeras of the C8 alpha cDNA, and cDNAs encoding the C8 beta and C8 gamma chains. Hemolytic activity of MAC formed with chimeric C8 was analyzed using target cells reconstituted with CD59. These experiments confirmed that CD59 recognizes a conformationally sensitive epitope that is within a segment of human C8 alpha internal to residues 320-415. Our data also suggest that optimal interaction of CD59 with this segment of human C8 alpha is influenced by N-terminal flanking sequence in C8 alpha and by human C8 beta, but is unaffected by C8 gamma.

Development of viable TAP-tagged dengue virus for investigation of host-virus interactions in viral replication.

PubMed

Poyomtip, Teera; Hodge, Kenneth; Matangkasombut, Ponpan; Sakuntabhai, Anavaj; Pisitkun, Trairak; Jirawatnotai, Siwanon; Chimnaronk, Sarin

2016-03-01

Dengue virus (DENV) is a mosquito-borne flavivirus responsible for life-threatening dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). The viral replication machinery containing the core non-structural protein 5 (NS5) is implicated in severe dengue symptoms but molecular details remain obscure. To date, studies seeking to catalogue and characterize interaction networks between viral NS5 and host proteins have been limited to the yeast two-hybrid system, computational prediction and co-immunoprecipitation (IP) of ectopically expressed NS5. However, these traditional approaches do not reproduce a natural course of infection in which a number of DENV NS proteins colocalize and tightly associate during the replication process. Here, we demonstrate the development of a recombinant DENV that harbours a TAP tag in NS5 to study host-virus interactions in vivo. We show that our engineered DENV was infective in several human cell lines and that the tags were stable over multiple viral passages, suggesting negligible structural and functional disturbance of NS5. We further provide proof-of-concept for the use of rationally tagged virus by revealing a high confidence NS5 interaction network in human hepatic cells. Our analysis uncovered previously unrecognized hnRNP complexes and several low-abundance fatty acid metabolism genes, which have been implicated in the viral life cycle. This study sets a new standard for investigation of host-flavivirus interactions.

A novel approach based on KATZ measure to predict associations of human microbiota with non-infectious diseases.

PubMed

Chen, Xing; Huang, Yu-An; You, Zhu-Hong; Yan, Gui-Ying; Wang, Xue-Song

2017-03-01

Accumulating clinical observations have indicated that microbes living in the human body are closely associated with a wide range of human noninfectious diseases, which provides promising insights into the complex disease mechanism understanding. Predicting microbe-disease associations could not only boost human disease diagnostic and prognostic, but also improve the new drug development. However, little efforts have been attempted to understand and predict human microbe-disease associations on a large scale until now. In this work, we constructed a microbe-human disease association network and further developed a novel computational model of KATZ measure for Human Microbe-Disease Association prediction (KATZHMDA) based on the assumption that functionally similar microbes tend to have similar interaction and non-interaction patterns with noninfectious diseases, and vice versa. To our knowledge, KATZHMDA is the first tool for microbe-disease association prediction. The reliable prediction performance could be attributed to the use of KATZ measurement, and the introduction of Gaussian interaction profile kernel similarity for microbes and diseases. LOOCV and k-fold cross validation were implemented to evaluate the effectiveness of this novel computational model based on known microbe-disease associations obtained from HMDAD database. As a result, KATZHMDA achieved reliable performance with average AUCs of 0.8130 ± 0.0054, 0.8301 ± 0.0033 and 0.8382 in 2-fold and 5-fold cross validation and LOOCV framework, respectively. It is anticipated that KATZHMDA could be used to obtain more novel microbes associated with important noninfectious human diseases and therefore benefit drug discovery and human medical improvement. Matlab codes and dataset explored in this work are available at http://dwz.cn/4oX5mS . xingchen@amss.ac.cn or zhuhongyou@gmail.com or wangxuesongcumt@163.com. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Reciprocity in computer-human interaction: source-based, norm-based, and affect-based explanations.

PubMed

Lee, Seungcheol Austin; Liang, Yuhua Jake

2015-04-01

Individuals often apply social rules when they interact with computers, and this is known as the Computers Are Social Actors (CASA) effect. Following previous work, one approach to understand the mechanism responsible for CASA is to utilize computer agents and have the agents attempt to gain human compliance (e.g., completing a pattern recognition task). The current study focuses on three key factors frequently cited to influence traditional notions of compliance: evaluations toward the source (competence and warmth), normative influence (reciprocity), and affective influence (mood). Structural equation modeling assessed the effects of these factors on human compliance with computer request. The final model shows that norm-based influence (reciprocity) increased the likelihood of compliance, while evaluations toward the computer agent did not significantly influence compliance.

Are Children with Autism More Responsive to Animated Characters? A Study of Interactions with Humans and Human-Controlled Avatars

ERIC Educational Resources Information Center

Carter, Elizabeth J.; Williams, Diane L.; Hodgins, Jessica K.; Lehman, Jill F.

2014-01-01

Few direct comparisons have been made between the responsiveness of children with autism to computer-generated or animated characters and their responsiveness to humans. Twelve 4-to 8-year-old children with autism interacted with a human therapist; a human-controlled, interactive avatar in a theme park; a human actor speaking like the avatar; and…

Information visualization: Beyond traditional engineering

NASA Technical Reports Server (NTRS)

Thomas, James J.

1995-01-01

This presentation addresses a different aspect of the human-computer interface; specifically the human-information interface. This interface will be dominated by an emerging technology called Information Visualization (IV). IV goes beyond the traditional views of computer graphics, CADS, and enables new approaches for engineering. IV specifically must visualize text, documents, sound, images, and video in such a way that the human can rapidly interact with and understand the content structure of information entities. IV is the interactive visual interface between humans and their information resources.

Augmentation of Antitumor T-Cell Responses by Increasing APC T-Cell C5a/C3a-C5aR/C3aR Interactions

DTIC Science & Technology

2013-03-01

the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. The Journal of experimental medicine . 1984;160(5...cell immunity. The Journal of experimental medicine . 2005;201(10):1523-30. PubMed PMID: 15883171. 3. Vogel CW, Wilkie SD, Morgan AC. In vivo studies...with covalent conjugates of cobra venom factor and monoclonal antibodies to human tumors. Haematology and blood transfusion. 1985;29:514- 7. Epub

From Specific Information Extraction to Inferences: A Hierarchical Framework of Graph Comprehension

DTIC Science & Technology

2004-09-01

The skill to interpret the information displayed in graphs is so important to have, the National Council of Teachers of Mathematics has created...guidelines to ensure that students learn these skills ( NCTM : Standards for Mathematics , 2003). These guidelines are based primarily on the extraction of...graphical perception. Human Computer Interaction, 8, 353-388. NCTM : Standards for Mathematics . (2003, 2003). Peebles, D., & Cheng, P. C.-H. (2002

Human-computer interaction: psychological aspects of the human use of computing.

PubMed

Olson, Gary M; Olson, Judith S

2003-01-01

Human-computer interaction (HCI) is a multidisciplinary field in which psychology and other social sciences unite with computer science and related technical fields with the goal of making computing systems that are both useful and usable. It is a blend of applied and basic research, both drawing from psychological research and contributing new ideas to it. New technologies continuously challenge HCI researchers with new options, as do the demands of new audiences and uses. A variety of usability methods have been developed that draw upon psychological principles. HCI research has expanded beyond its roots in the cognitive processes of individual users to include social and organizational processes involved in computer usage in real environments as well as the use of computers in collaboration. HCI researchers need to be mindful of the longer-term changes brought about by the use of computing in a variety of venues.

Applications of airborne ultrasound in human-computer interaction.

PubMed

Dahl, Tobias; Ealo, Joao L; Bang, Hans J; Holm, Sverre; Khuri-Yakub, Pierre

2014-09-01

Airborne ultrasound is a rapidly developing subfield within human-computer interaction (HCI). Touchless ultrasonic interfaces and pen tracking systems are part of recent trends in HCI and are gaining industry momentum. This paper aims to provide the background and overview necessary to understand the capabilities of ultrasound and its potential future in human-computer interaction. The latest developments on the ultrasound transducer side are presented, focusing on capacitive micro-machined ultrasonic transducers, or CMUTs. Their introduction is an important step toward providing real, low-cost multi-sensor array and beam-forming options. We also provide a unified mathematical framework for understanding and analyzing algorithms used for ultrasound detection and tracking for some of the most relevant applications. Copyright © 2014. Published by Elsevier B.V.

Identification of a Conserved Interface of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Vifs with Cullin 5.

PubMed

Gu, Qinyong; Zhang, Zeli; Gertzen, Christoph G W; Häussinger, Dieter; Gohlke, Holger; Münk, Carsten

2018-03-15

Members of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3 [A3]) family of DNA cytidine deaminases are intrinsic restriction factors against retroviruses. In felids such as the domestic cat ( Felis catus ), the A3 genes encode the A3Z2, A3Z3, and A3Z2Z3 antiviral cytidine deaminases. Only A3Z3 and A3Z2Z3 inhibit viral infectivity factor (Vif)-deficient feline immunodeficiency virus (FIV). The FIV Vif protein interacts with Cullin (CUL), Elongin B (ELOB), and Elongin C (ELOC) to form an E3 ubiquitination complex to induce the degradation of feline A3s. However, the functional domains in FIV Vif for the interaction with Cullin are poorly understood. Here, we found that the expression of dominant negative CUL5 prevented the degradation of feline A3s by FIV Vif, while dominant negative CUL2 had no influence on the degradation of A3. In coimmunoprecipitation assays, FIV Vif bound to CUL5 but not CUL2. To identify the CUL5 interaction site in FIV Vif, the conserved amino acids from positions 47 to 160 of FIV Vif were mutated, but these mutations did not impair the binding of Vif to CUL5. By focusing on a potential zinc-binding motif (K175-C161-C184-C187) of FIV Vif, we found a conserved hydrophobic region (174IR175) that is important for the CUL5 interaction. Mutation of this region also impaired the FIV Vif-induced degradation of feline A3s. Based on a structural model of the FIV Vif-CUL5 interaction, the 52LW53 region in CUL5 was identified as mediating binding to FIV Vif. By comparing our results to the human immunodeficiency virus type 1 (HIV-1) Vif-CUL5 interaction surface (120IR121, a hydrophobic region that is localized in the zinc-binding motif), we suggest that the CUL5 interaction surface in the diverse HIV-1 and FIV Vifs is evolutionarily conserved, indicating a strong structural constraint. However, the FIV Vif-CUL5 interaction is zinc independent, which contrasts with the zinc dependence of HIV-1 Vif. IMPORTANCE Feline immunodeficiency virus (FIV), which is similar to human immunodeficiency virus type 1 (HIV-1), replicates in its natural host in T cells and macrophages that express the antiviral restriction factor APOBEC3 (A3). To escape A3s, FIV and HIV induce the degradation of these proteins by building a ubiquitin ligase complex using the viral protein Vif to connect to cellular proteins, including Cullin 5. Here, we identified the protein residues that regulate this interaction in FIV Vif and Cullin 5. While our structural model suggests that the diverse FIV and HIV-1 Vifs use conserved residues for Cullin 5 binding, FIV Vif binds Cullin 5 independently of zinc, in contrast to HIV-1 Vif. Copyright © 2018 American Society for Microbiology.

Brain-Computer Interfaces: A Neuroscience Paradigm of Social Interaction? A Matter of Perspective

PubMed Central

Mattout, Jérémie

2012-01-01

A number of recent studies have put human subjects in true social interactions, with the aim of better identifying the psychophysiological processes underlying social cognition. Interestingly, this emerging Neuroscience of Social Interactions (NSI) field brings up challenges which resemble important ones in the field of Brain-Computer Interfaces (BCI). Importantly, these challenges go beyond common objectives such as the eventual use of BCI and NSI protocols in the clinical domain or common interests pertaining to the use of online neurophysiological techniques and algorithms. Common fundamental challenges are now apparent and one can argue that a crucial one is to develop computational models of brain processes relevant to human interactions with an adaptive agent, whether human or artificial. Coupled with neuroimaging data, such models have proved promising in revealing the neural basis and mental processes behind social interactions. Similar models could help BCI to move from well-performing but offline static machines to reliable online adaptive agents. This emphasizes a social perspective to BCI, which is not limited to a computational challenge but extends to all questions that arise when studying the brain in interaction with its environment. PMID:22675291

Structure and ligand-binding site characteristics of the human P2Y11 nucleotide receptor deduced from computational modelling and mutational analysis

PubMed Central

Zylberg, Jacques; Ecke, Denise; Fischer, Bilha; Reiser, Georg

2007-01-01

The P2Y11-R (P2Y11 receptor) is a less explored drug target. We computed an hP2Y11-R (human P2Y11) homology model with two templates, bovine-rhodopsin (2.6 Å resolution; 1 Å=0.1 nm) and a hP2Y1–ATP complex model. The hP2Y11-R model was refined using molecular dynamics calculations and validated by virtual screening methods, with an enrichment factor of 5. Furthermore, mutational analyses of Arg106, Glu186, Arg268, Arg307 and Ala313 confirmed the adequacy of our hP2Y11-R model and the computed ligand recognition mode. The E186A and R268A mutants reduced the potency of ATP by one and three orders of magnitude respectively. The R106A and R307A mutants were functionally inactive. We propose that residues Arg106, Arg268, Arg307 and Glu186 are involved in ionic interactions with the phosphate moiety of ATP. Arg307 is possibly also H-bonded to N6 of ATP via the backbone carbonyl. Activity of ATP at the F109I mutant revealed that the proposed π-stacking of Phe109 with the adenine ring is a minor interaction. The mutation A313N, which is part of a hydrophobic pocket in the vicinity of the ATP C-2 position, partially explains the high activity of 2-MeS-ATP at P2Y1-R as compared with the negligible activity at the P2Y11-R. Inactivity of ATP at the Y261A mutant implies that Tyr261 acts as a molecular switch, as in other G-protein-coupled receptors. Moreover, analysis of cAMP responses seen with the mutants showed that the efficacy of coupling of the P2Y11-R with Gs is more variable than coupling with Gq. Our model also indicates that Ser206 forms an H-bond with Pγ (the γ-phosphate of the triphosphate chain of ATP) and Met310 interacts with the adenine moiety. PMID:17338680

Human computer confluence applied in healthcare and rehabilitation.

PubMed

Viaud-Delmon, Isabelle; Gaggioli, Andrea; Ferscha, Alois; Dunne, Stephen

2012-01-01

Human computer confluence (HCC) is an ambitious research program studying how the emerging symbiotic relation between humans and computing devices can enable radically new forms of sensing, perception, interaction, and understanding. It is an interdisciplinary field, bringing together researches from horizons as various as pervasive computing, bio-signals processing, neuroscience, electronics, robotics, virtual & augmented reality, and provides an amazing potential for applications in medicine and rehabilitation.

Human-technology interaction for standoff IED detection

NASA Astrophysics Data System (ADS)

Zhang, Evan; Zou, Yiyang; Zachrich, Liping; Fulton, Jack

2011-03-01

IEDs kill our soldiers and innocent people every day. Lessons learned from Iraq and Afghanistan clearly indicated that IEDs cannot be detected/defeated by technology alone; human-technology interaction must be engaged. In most cases, eye is the best detector, brain is the best computer, and technologies are tools, they must be used by human being properly then can achieve full functionality. In this paper, a UV Raman/fluorescence, CCD and LWIR 3 sensor fusion system for standoff IED detection and a handheld fusion system for close range IED detection are developed and demonstrated. We must train solders using their eyes or CCD/LWIR cameras to do wide area search while on the move to find small suspected area first then use the spectrometer because the laser spot is too small, to scan a one-mile long and 2-meter wide road needs 185 days although our fusion system can detect the IED in 30m with 1s interrogating time. Even if the small suspected area (e.g., 0.5mx0.5m) is found, human eyes still cannot detect the IED, soldiers must use or interact with the technology - laser based spectrometer to scan the area then they are able to detect and identify the IED in 10 minutes not 185 days. Therefore, the human-technology interaction approach will be the best solution for IED detection.

C-Terminal DxD-Containing Sequences within Paramyxovirus Nucleocapsid Proteins Determine Matrix Protein Compatibility and Can Direct Foreign Proteins into Budding Particles

PubMed Central

Ray, Greeshma; Schmitt, Phuong Tieu

2016-01-01

ABSTRACT Paramyxovirus particles are formed by a budding process coordinated by viral matrix (M) proteins. M proteins coalesce at sites underlying infected cell membranes and induce other viral components, including viral glycoproteins and viral ribonucleoprotein complexes (vRNPs), to assemble at these locations from which particles bud. M proteins interact with the nucleocapsid (NP or N) components of vRNPs, and these interactions enable production of infectious, genome-containing virions. For the paramyxoviruses parainfluenza virus 5 (PIV5) and mumps virus, M-NP interaction also contributes to efficient production of virus-like particles (VLPs) in transfected cells. A DLD sequence near the C-terminal end of PIV5 NP protein was previously found to be necessary for M-NP interaction and efficient VLP production. Here, we demonstrate that 15-residue-long, DLD-containing sequences derived from either the PIV5 or Nipah virus nucleocapsid protein C-terminal ends are sufficient to direct packaging of a foreign protein, Renilla luciferase, into budding VLPs. Mumps virus NP protein harbors DWD in place of the DLD sequence found in PIV5 NP protein, and consequently, PIV5 NP protein is incompatible with mumps virus M protein. A single amino acid change converting DLD to DWD within PIV5 NP protein induced compatibility between these proteins and allowed efficient production of mumps VLPs. Our data suggest a model in which paramyxoviruses share an overall common strategy for directing M-NP interactions but with important variations contained within DLD-like sequences that play key roles in defining M/NP protein compatibilities. IMPORTANCE Paramyxoviruses are responsible for a wide range of diseases that affect both humans and animals. Paramyxovirus pathogens include measles virus, mumps virus, human respiratory syncytial virus, and the zoonotic paramyxoviruses Nipah virus and Hendra virus. Infectivity of paramyxovirus particles depends on matrix-nucleocapsid protein interactions which enable efficient packaging of encapsidated viral RNA genomes into budding virions. In this study, we have defined regions near the C-terminal ends of paramyxovirus nucleocapsid proteins that are important for matrix protein interaction and that are sufficient to direct a foreign protein into budding particles. These results advance our basic understanding of paramyxovirus genome packaging interactions and also have implications for the potential use of virus-like particles as protein delivery tools. PMID:26792745

C-Terminal DxD-Containing Sequences within Paramyxovirus Nucleocapsid Proteins Determine Matrix Protein Compatibility and Can Direct Foreign Proteins into Budding Particles.

PubMed

Ray, Greeshma; Schmitt, Phuong Tieu; Schmitt, Anthony P

2016-01-20

Paramyxovirus particles are formed by a budding process coordinated by viral matrix (M) proteins. M proteins coalesce at sites underlying infected cell membranes and induce other viral components, including viral glycoproteins and viral ribonucleoprotein complexes (vRNPs), to assemble at these locations from which particles bud. M proteins interact with the nucleocapsid (NP or N) components of vRNPs, and these interactions enable production of infectious, genome-containing virions. For the paramyxoviruses parainfluenza virus 5 (PIV5) and mumps virus, M-NP interaction also contributes to efficient production of virus-like particles (VLPs) in transfected cells. A DLD sequence near the C-terminal end of PIV5 NP protein was previously found to be necessary for M-NP interaction and efficient VLP production. Here, we demonstrate that 15-residue-long, DLD-containing sequences derived from either the PIV5 or Nipah virus nucleocapsid protein C-terminal ends are sufficient to direct packaging of a foreign protein, Renilla luciferase, into budding VLPs. Mumps virus NP protein harbors DWD in place of the DLD sequence found in PIV5 NP protein, and consequently, PIV5 NP protein is incompatible with mumps virus M protein. A single amino acid change converting DLD to DWD within PIV5 NP protein induced compatibility between these proteins and allowed efficient production of mumps VLPs. Our data suggest a model in which paramyxoviruses share an overall common strategy for directing M-NP interactions but with important variations contained within DLD-like sequences that play key roles in defining M/NP protein compatibilities. Paramyxoviruses are responsible for a wide range of diseases that affect both humans and animals. Paramyxovirus pathogens include measles virus, mumps virus, human respiratory syncytial virus, and the zoonotic paramyxoviruses Nipah virus and Hendra virus. Infectivity of paramyxovirus particles depends on matrix-nucleocapsid protein interactions which enable efficient packaging of encapsidated viral RNA genomes into budding virions. In this study, we have defined regions near the C-terminal ends of paramyxovirus nucleocapsid proteins that are important for matrix protein interaction and that are sufficient to direct a foreign protein into budding particles. These results advance our basic understanding of paramyxovirus genome packaging interactions and also have implications for the potential use of virus-like particles as protein delivery tools. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Inhibition of human alcohol and aldehyde dehydrogenases by cimetidine and assessment of its effects on ethanol metabolism.

PubMed

Lai, Ching-Long; Li, Yeung-Pin; Liu, Chiu-Ming; Hsieh, Hsiu-Shan; Yin, Shih-Jiun

2013-02-25

Previous studies have reported that cimetidine, an H2-receptor antagonist used to treat gastric and duodenal ulcers, can inhibit alcohol dehydrogenases (ADHs) and ethanol metabolism. Human alcohol dehydrogenases and aldehyde dehydrogenases (ALDHs), the principal enzymes responsible for metabolism of ethanol, are complex enzyme families that exhibit functional polymorphisms among ethnic groups and distinct tissue distributions. We investigated the inhibition by cimetidine of alcohol oxidation by recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and aldehyde oxidation by ALDH1A1 and ALDH2 at pH 7.5 and a cytosolic NAD(+) concentration. Cimetidine acted as competitive or noncompetitive inhibitors for the ADH and ALDH isozymes/allozymes with near mM inhibition constants. The metabolic interactions between cimetidine and ethanol/acetaldehyde were assessed by computer simulation using the inhibition equations and the determined kinetic constants. At therapeutic drug levels (0.015 mM) and physiologically relevant concentrations of ethanol (10 mM) and acetaldehyde (10 μM) in target tissues, cimetidine could weakly inhibit (<5%) the activities of ADH1B2 and ADH1B3 in liver, ADH2 in liver and small intestine, ADH4 in stomach, and ALDH1A1 in the three tissues, but not significantly affect ADH1A, ADH1B1, ADH1C1/2, or ALDH2. At higher drug levels, which may accumulate in cells (0.2 mM), the activities of the weakly-inhibited enzymes may be decreased more significantly. The quantitative effects of cimetidine on metabolism of ethanol and other physiological substrates of ADHs need further investigation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Interactions among human behavior, social networks, and societal infrastructures: A Case Study in Computational Epidemiology

NASA Astrophysics Data System (ADS)

Barrett, Christopher L.; Bisset, Keith; Chen, Jiangzhuo; Eubank, Stephen; Lewis, Bryan; Kumar, V. S. Anil; Marathe, Madhav V.; Mortveit, Henning S.

Human behavior, social networks, and the civil infrastructures are closely intertwined. Understanding their co-evolution is critical for designing public policies and decision support for disaster planning. For example, human behaviors and day to day activities of individuals create dense social interactions that are characteristic of modern urban societies. These dense social networks provide a perfect fabric for fast, uncontrolled disease propagation. Conversely, people’s behavior in response to public policies and their perception of how the crisis is unfolding as a result of disease outbreak can dramatically alter the normally stable social interactions. Effective planning and response strategies must take these complicated interactions into account. In this chapter, we describe a computer simulation based approach to study these issues using public health and computational epidemiology as an illustrative example. We also formulate game-theoretic and stochastic optimization problems that capture many of the problems that we study empirically.

Human Adenovirus Infection Causes Cellular E3 Ubiquitin Ligase MKRN1 Degradation Involving the Viral Core Protein pVII.

PubMed

Inturi, Raviteja; Mun, Kwangchol; Singethan, Katrin; Schreiner, Sabrina; Punga, Tanel

2018-02-01

Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein, VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. Here we report the identification of several cellular proteins interacting with the precursor pVII protein. We show that the cellular E3 ubiquitin ligase MKRN1 is a novel precursor pVII-interacting protein in HAdV-C5-infected cells. Surprisingly, the endogenous MKRN1 protein underwent proteasomal degradation during the late phase of HAdV-C5 infection in various human cell lines. MKRN1 protein degradation occurred independently of the HAdV E1B55K and E4orf6 proteins. We provide experimental evidence that the precursor pVII protein binding enhances MKRN1 self-ubiquitination, whereas the processed mature VII protein is deficient in this function. Based on these data, we propose that the pVII protein binding promotes MKRN1 self-ubiquitination, followed by proteasomal degradation of the MKRN1 protein, in HAdV-C5-infected cells. In addition, we show that measles virus and vesicular stomatitis virus infections reduce the MKRN1 protein accumulation in the recipient cells. Taken together, our results expand the functional repertoire of the HAdV-C5 precursor pVII protein in lytic virus infection and highlight MKRN1 as a potential common target during different virus infections. IMPORTANCE Human adenoviruses (HAdVs) are common pathogens causing a wide range of diseases. To achieve pathogenicity, HAdVs have to counteract a variety of host cell antiviral defense systems, which would otherwise hamper virus replication. In this study, we show that the HAdV-C5 histone-like core protein pVII binds to and promotes self-ubiquitination of a cellular E3 ubiquitin ligase named MKRN1. This mutual interaction between the pVII and MKRN1 proteins may prime MKRN1 for proteasomal degradation, because the MKRN1 protein is efficiently degraded during the late phase of HAdV-C5 infection. Since MKRN1 protein accumulation is also reduced in measles virus- and vesicular stomatitis virus-infected cells, our results signify the general strategy of viruses to target MKRN1. Copyright © 2018 American Society for Microbiology.

Social robots as embedded reinforcers of social behavior in children with autism.

PubMed

Kim, Elizabeth S; Berkovits, Lauren D; Bernier, Emily P; Leyzberg, Dan; Shic, Frederick; Paul, Rhea; Scassellati, Brian

2013-05-01

In this study we examined the social behaviors of 4- to 12-year-old children with autism spectrum disorders (ASD; N = 24) during three tradic interactions with an adult confederate and an interaction partner, where the interaction partner varied randomly among (1) another adult human, (2) a touchscreen computer game, and (3) a social dinosaur robot. Children spoke more in general, and directed more speech to the adult confederate, when the interaction partner was a robot, as compared to a human or computer game interaction partner. Children spoke as much to the robot as to the adult interaction partner. This study provides the largest demonstration of social human-robot interaction in children with autism to date. Our findings suggest that social robots may be developed into useful tools for social skills and communication therapies, specifically by embedding social interaction into intrinsic reinforcers and motivators.

Learning, Interactional, and Motivational Outcomes in One-to-One Synchronous Computer-Mediated versus Face-to-Face Tutoring

ERIC Educational Resources Information Center

Siler, Stephanie Ann; VanLehn, Kurt

2009-01-01

Face-to-face (FTF) human-human tutoring has ranked among the most effective forms of instruction. However, because computer-mediated (CM) tutoring is becoming increasingly common, it is instructive to evaluate its effectiveness relative to face-to-face tutoring. Does the lack of spoken, face-to-face interaction affect learning gains and…

Interacting with a Computer-Simulated Pet: Factors Influencing Children's Humane Attitudes and Empathy

ERIC Educational Resources Information Center

Tsai, Yueh-Feng; Kaufman, David

2014-01-01

Previous research by Tsai and Kaufman (2010a, 2010b) has suggested that computer-simulated virtual pet dogs can be used as a potential medium to enhance children's development of empathy and humane attitudes toward animals. To gain a deeper understanding of how and why interacting with a virtual pet dog might influence children's social and…

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 study of early human embryos using interactive 3-dimensional computer reconstructions.

PubMed

Scarborough, J; Aiton, J F; McLachlan, J C; Smart, S D; Whiten, S C

1997-07-01

Tracings of serial histological sections from 4 human embryos at different Carnegie stages were used to create 3-dimensional (3D) computer models of the developing heart. The models were constructed using commercially available software developed for graphic design and the production of computer generated virtual reality environments. They are available as interactive objects which can be downloaded via the World Wide Web. This simple method of 3D reconstruction offers significant advantages for understanding important events in morphological sciences.

Estimation and Mapping of Clouds and Rainfall Areas with an Interactive Computer.

DTIC Science & Technology

1982-12-01

test. C . TEST PROCEDURES The following lis1t is the set of procedures for this test of the SPADS Cloud Model. The steps taken were to: 1. Capture...12, 1640-1648. 121 0 APPENDIX4 SPADS CLOUD MlDEL COMPUTER PROGrRArt C CLOY) -IS DRIVER/IMAIN PROGRAIM C T41S PROC.RAM ANALYZES VIS AND IR. TOGETHEI TO...NITH AN INTERACTIVE COMPUTER(U) NAYAL POSTGRADUATE SCHOOL MONTEREY CA C A NELSON DEC 92 UNLSSIFIED F/G 9/2 NUC MENOMONE NONI smhhhhhhhhohh

Why E-Business Must Evolve beyond Market Orientation: Applying Human Interaction Models to Computer-Mediated Corporate Communications.

ERIC Educational Resources Information Center

Johnston, Kevin McCullough

2001-01-01

Considers the design of corporate communications for electronic business and discusses the increasing importance of corporate interaction as companies work in virtual environments. Compares sociological and psychological theories of human interaction and relationship formation with organizational interaction theories of corporate relationship…

Multifunctional gold nanocomposites designed for targeted CT/MR/optical trimodal imaging of human non-small cell lung cancer cells

NASA Astrophysics Data System (ADS)

Chen, Jingwen; Sun, Yingqi; Chen, Qian; Wang, Le; Wang, Suhe; Tang, Yun; Shi, Xiangyang; Wang, Han

2016-07-01

Multifunctional gold nanocomposites, which were designed as dendrimer-entrapped gold nanoparticles functionalized with gadolinium, cyanine dye (Cy5.5), and folic acid, were synthesized to be used as the first dendrimer-based clinical nanoprobes for targeted X-ray computed tomography/magnetic resonance/optical trimodal imaging in vitro and in vivo of human non-small cell cancer cells.Multifunctional gold nanocomposites, which were designed as dendrimer-entrapped gold nanoparticles functionalized with gadolinium, cyanine dye (Cy5.5), and folic acid, were synthesized to be used as the first dendrimer-based clinical nanoprobes for targeted X-ray computed tomography/magnetic resonance/optical trimodal imaging in vitro and in vivo of human non-small cell cancer cells. Electronic supplementary information (ESI) available: Synthesis and characterization data of the nanoprobes; biocompatibility results; confirmation of the tumor cell uptake of the nanoprobes in vitro and in vivo; biodistribution results in vivo. See DOI: 10.1039/c6nr03143a

Russian and Chinese Information Warfare: Theory and Practice

DTIC Science & Technology

2004-06-01

Integral neurolinguistic programming •Placing essential programs into the conscious or sub- conscious mind •Subconscious suggestions that modify human...Generators of special rays •Optical systems • Neurolinguistic programming •Computer psychotechnology •The mass media •Audiovisual effects •Special effects...Information Warfare: Theory and Practice 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e

TAE+ 5.2 - TRANSPORTABLE APPLICATIONS ENVIRONMENT PLUS, VERSION 5.2 (HP9000 SERIES 700/800 VERSION)

NASA Technical Reports Server (NTRS)

TAE SUPPORT OFFICE

1994-01-01

TAE (Transportable Applications Environment) Plus is an integrated, portable environment for developing and running interactive window, text, and graphical object-based application systems. The program allows both programmers and non-programmers to easily construct their own custom application interface and to move that interface and application to different machine environments. TAE Plus makes both the application and the machine environment transparent, with noticeable improvements in the learning curve. The main components of TAE Plus are as follows: (1) the WorkBench, a What You See Is What You Get (WYSIWYG) tool for the design and layout of a user interface; (2) the Window Programming Tools Package (WPT), a set of callable subroutines that control an application's user interface; and (3) TAE Command Language (TCL), an easy-to-learn command language that provides an easy way to develop an executable application prototype with a run-time interpreted language. The WorkBench tool allows the application developer to interactively construct the layout of an application's display screen by manipulating a set of interaction objects including input items such as buttons, icons, and scrolling text lists. User interface interactive objects include data-driven graphical objects such as dials, thermometers, and strip charts as well as menubars, option menus, file selection items, message items, push buttons, and color loggers. The WorkBench user specifies the windows and interaction objects that will make up the user interface, then specifies the sequence of the user interface dialogue. The description of the designed user interface is then saved into resource files. For those who desire to develop the designed user interface into an operational application, the WorkBench tool also generates source code (C, C++, Ada, and TCL) which fully controls the application's user interface through function calls to the WPTs. The WPTs are the runtime services used by application programs to display and control the user interfaces. Since the WPTs access the workbench-generated resource files during each execution, details such as color, font, location, and object type remain independent from the application code, allowing changes to the user interface without recompiling and relinking. In addition to WPTs, TAE Plus can control interaction of objects from the interpreted TAE Command Language. TCL provides a means for the more experienced developer to quickly prototype an application's use of TAE Plus interaction objects and add programming logic without the overhead of compiling or linking. TAE Plus requires MIT's X Window System and the Open Software Foundation's Motif. The HP 9000 Series 700/800 version of TAE 5.2 requires Version 11 Release 5 of the X Window System. All other machine versions of TAE 5.2 require Version 11, Release 4 of the X Window System. The Workbench and WPTs are written in C++ and the remaining code is written in C. TAE Plus is available by license for an unlimited time period. The licensed program product includes the TAE Plus source code and one set of supporting documentation. Additional documentation may be purchased separately at the price indicated below. The amount of disk space required to load the TAE Plus tar format tape is between 35Mb and 67Mb depending on the machine version. The recommended minimum memory is 12Mb. Each TAE Plus platform delivery tape includes pre-built libraries and executable binary code for that particular machine, as well as source code, so users do not have to do an installation. Users wishing to recompile the source will need both a C compiler and either GNU's C++ Version 1.39 or later, or a C++ compiler based on AT&T 2.0 cfront. TAE Plus was developed in 1989 and version 5.2 was released in 1993. TAE Plus 5.2 is available on media suitable for five different machine platforms: (1) IBM RS/6000 series workstations running AIX (.25 inch tape cartridge in UNIX tar format), (2) DEC RISC workstations running ULTRIX (TK50 cartridge in UNIX tar format), (3) HP9000 Series 700/800 computers running HP-UX 9.x and X11/R5 (HP 4mm DDS DAT tape cartridge in UNIX tar format), (4) Sun4 (SPARC) series computers running SunOS (.25 inch tape cartridge in UNIX tar format), and (5) SGI Indigo computers running IRIX (.25 inch IRIS tape cartridge in UNIX tar format). Please contact COSMIC to obtain detailed information about the supported operating system and OSF/Motif releases required for each of these machine versions. An optional Motif Object Code License is available for the Sun4 version of TAE Plus 5.2. Version 5.1 of TAE Plus remains available for DEC VAX computers running VMS, HP9000 Series 300/400 computers running HP-UX, and HP 9000 Series 700/800 computers running HP-UX 8.x and X11/R4. Please contact COSMIC for details on these versions of TAE Plus.

TAE+ 5.2 - TRANSPORTABLE APPLICATIONS ENVIRONMENT PLUS, VERSION 5.2 (IBM RS/6000 VERSION)

NASA Technical Reports Server (NTRS)

TAE SUPPORT OFFICE

1994-01-01

TAE (Transportable Applications Environment) Plus is an integrated, portable environment for developing and running interactive window, text, and graphical object-based application systems. The program allows both programmers and non-programmers to easily construct their own custom application interface and to move that interface and application to different machine environments. TAE Plus makes both the application and the machine environment transparent, with noticeable improvements in the learning curve. The main components of TAE Plus are as follows: (1) the WorkBench, a What You See Is What You Get (WYSIWYG) tool for the design and layout of a user interface; (2) the Window Programming Tools Package (WPT), a set of callable subroutines that control an application's user interface; and (3) TAE Command Language (TCL), an easy-to-learn command language that provides an easy way to develop an executable application prototype with a run-time interpreted language. The WorkBench tool allows the application developer to interactively construct the layout of an application's display screen by manipulating a set of interaction objects including input items such as buttons, icons, and scrolling text lists. User interface interactive objects include data-driven graphical objects such as dials, thermometers, and strip charts as well as menubars, option menus, file selection items, message items, push buttons, and color loggers. The WorkBench user specifies the windows and interaction objects that will make up the user interface, then specifies the sequence of the user interface dialogue. The description of the designed user interface is then saved into resource files. For those who desire to develop the designed user interface into an operational application, the WorkBench tool also generates source code (C, C++, Ada, and TCL) which fully controls the application's user interface through function calls to the WPTs. The WPTs are the runtime services used by application programs to display and control the user interfaces. Since the WPTs access the workbench-generated resource files during each execution, details such as color, font, location, and object type remain independent from the application code, allowing changes to the user interface without recompiling and relinking. In addition to WPTs, TAE Plus can control interaction of objects from the interpreted TAE Command Language. TCL provides a means for the more experienced developer to quickly prototype an application's use of TAE Plus interaction objects and add programming logic without the overhead of compiling or linking. TAE Plus requires MIT's X Window System and the Open Software Foundation's Motif. The HP 9000 Series 700/800 version of TAE 5.2 requires Version 11 Release 5 of the X Window System. All other machine versions of TAE 5.2 require Version 11, Release 4 of the X Window System. The Workbench and WPTs are written in C++ and the remaining code is written in C. TAE Plus is available by license for an unlimited time period. The licensed program product includes the TAE Plus source code and one set of supporting documentation. Additional documentation may be purchased separately at the price indicated below. The amount of disk space required to load the TAE Plus tar format tape is between 35Mb and 67Mb depending on the machine version. The recommended minimum memory is 12Mb. Each TAE Plus platform delivery tape includes pre-built libraries and executable binary code for that particular machine, as well as source code, so users do not have to do an installation. Users wishing to recompile the source will need both a C compiler and either GNU's C++ Version 1.39 or later, or a C++ compiler based on AT&T 2.0 cfront. TAE Plus was developed in 1989 and version 5.2 was released in 1993. TAE Plus 5.2 is available on media suitable for five different machine platforms: (1) IBM RS/6000 series workstations running AIX (.25 inch tape cartridge in UNIX tar format), (2) DEC RISC workstations running ULTRIX (TK50 cartridge in UNIX tar format), (3) HP9000 Series 700/800 computers running HP-UX 9.x and X11/R5 (HP 4mm DDS DAT tape cartridge in UNIX tar format), (4) Sun4 (SPARC) series computers running SunOS (.25 inch tape cartridge in UNIX tar format), and (5) SGI Indigo computers running IRIX (.25 inch IRIS tape cartridge in UNIX tar format). Please contact COSMIC to obtain detailed information about the supported operating system and OSF/Motif releases required for each of these machine versions. An optional Motif Object Code License is available for the Sun4 version of TAE Plus 5.2. Version 5.1 of TAE Plus remains available for DEC VAX computers running VMS, HP9000 Series 300/400 computers running HP-UX, and HP 9000 Series 700/800 computers running HP-UX 8.x and X11/R4. Please contact COSMIC for details on these versions of TAE Plus.

TAE+ 5.2 - TRANSPORTABLE APPLICATIONS ENVIRONMENT PLUS, VERSION 5.2 (SUN4 VERSION WITH MOTIF)

NASA Technical Reports Server (NTRS)

TAE SUPPORT OFFICE

1994-01-01

TAE (Transportable Applications Environment) Plus is an integrated, portable environment for developing and running interactive window, text, and graphical object-based application systems. The program allows both programmers and non-programmers to easily construct their own custom application interface and to move that interface and application to different machine environments. TAE Plus makes both the application and the machine environment transparent, with noticeable improvements in the learning curve. The main components of TAE Plus are as follows: (1) the WorkBench, a What You See Is What You Get (WYSIWYG) tool for the design and layout of a user interface; (2) the Window Programming Tools Package (WPT), a set of callable subroutines that control an application's user interface; and (3) TAE Command Language (TCL), an easy-to-learn command language that provides an easy way to develop an executable application prototype with a run-time interpreted language. The WorkBench tool allows the application developer to interactively construct the layout of an application's display screen by manipulating a set of interaction objects including input items such as buttons, icons, and scrolling text lists. User interface interactive objects include data-driven graphical objects such as dials, thermometers, and strip charts as well as menubars, option menus, file selection items, message items, push buttons, and color loggers. The WorkBench user specifies the windows and interaction objects that will make up the user interface, then specifies the sequence of the user interface dialogue. The description of the designed user interface is then saved into resource files. For those who desire to develop the designed user interface into an operational application, the WorkBench tool also generates source code (C, C++, Ada, and TCL) which fully controls the application's user interface through function calls to the WPTs. The WPTs are the runtime services used by application programs to display and control the user interfaces. Since the WPTs access the workbench-generated resource files during each execution, details such as color, font, location, and object type remain independent from the application code, allowing changes to the user interface without recompiling and relinking. In addition to WPTs, TAE Plus can control interaction of objects from the interpreted TAE Command Language. TCL provides a means for the more experienced developer to quickly prototype an application's use of TAE Plus interaction objects and add programming logic without the overhead of compiling or linking. TAE Plus requires MIT's X Window System and the Open Software Foundation's Motif. The HP 9000 Series 700/800 version of TAE 5.2 requires Version 11 Release 5 of the X Window System. All other machine versions of TAE 5.2 require Version 11, Release 4 of the X Window System. The Workbench and WPTs are written in C++ and the remaining code is written in C. TAE Plus is available by license for an unlimited time period. The licensed program product includes the TAE Plus source code and one set of supporting documentation. Additional documentation may be purchased separately at the price indicated below. The amount of disk space required to load the TAE Plus tar format tape is between 35Mb and 67Mb depending on the machine version. The recommended minimum memory is 12Mb. Each TAE Plus platform delivery tape includes pre-built libraries and executable binary code for that particular machine, as well as source code, so users do not have to do an installation. Users wishing to recompile the source will need both a C compiler and either GNU's C++ Version 1.39 or later, or a C++ compiler based on AT&T 2.0 cfront. TAE Plus was developed in 1989 and version 5.2 was released in 1993. TAE Plus 5.2 is available on media suitable for five different machine platforms: (1) IBM RS/6000 series workstations running AIX (.25 inch tape cartridge in UNIX tar format), (2) DEC RISC workstations running ULTRIX (TK50 cartridge in UNIX tar format), (3) HP9000 Series 700/800 computers running HP-UX 9.x and X11/R5 (HP 4mm DDS DAT tape cartridge in UNIX tar format), (4) Sun4 (SPARC) series computers running SunOS (.25 inch tape cartridge in UNIX tar format), and (5) SGI Indigo computers running IRIX (.25 inch IRIS tape cartridge in UNIX tar format). Please contact COSMIC to obtain detailed information about the supported operating system and OSF/Motif releases required for each of these machine versions. An optional Motif Object Code License is available for the Sun4 version of TAE Plus 5.2. Version 5.1 of TAE Plus remains available for DEC VAX computers running VMS, HP9000 Series 300/400 computers running HP-UX, and HP 9000 Series 700/800 computers running HP-UX 8.x and X11/R4. Please contact COSMIC for details on these versions of TAE Plus.

TAE+ 5.2 - TRANSPORTABLE APPLICATIONS ENVIRONMENT PLUS, VERSION 5.2 (SILICON GRAPHICS VERSION)

NASA Technical Reports Server (NTRS)

TAE SUPPORT OFFICE

1994-01-01

TAE (Transportable Applications Environment) Plus is an integrated, portable environment for developing and running interactive window, text, and graphical object-based application systems. The program allows both programmers and non-programmers to easily construct their own custom application interface and to move that interface and application to different machine environments. TAE Plus makes both the application and the machine environment transparent, with noticeable improvements in the learning curve. The main components of TAE Plus are as follows: (1) the WorkBench, a What You See Is What You Get (WYSIWYG) tool for the design and layout of a user interface; (2) the Window Programming Tools Package (WPT), a set of callable subroutines that control an application's user interface; and (3) TAE Command Language (TCL), an easy-to-learn command language that provides an easy way to develop an executable application prototype with a run-time interpreted language. The WorkBench tool allows the application developer to interactively construct the layout of an application's display screen by manipulating a set of interaction objects including input items such as buttons, icons, and scrolling text lists. User interface interactive objects include data-driven graphical objects such as dials, thermometers, and strip charts as well as menubars, option menus, file selection items, message items, push buttons, and color loggers. The WorkBench user specifies the windows and interaction objects that will make up the user interface, then specifies the sequence of the user interface dialogue. The description of the designed user interface is then saved into resource files. For those who desire to develop the designed user interface into an operational application, the WorkBench tool also generates source code (C, C++, Ada, and TCL) which fully controls the application's user interface through function calls to the WPTs. The WPTs are the runtime services used by application programs to display and control the user interfaces. Since the WPTs access the workbench-generated resource files during each execution, details such as color, font, location, and object type remain independent from the application code, allowing changes to the user interface without recompiling and relinking. In addition to WPTs, TAE Plus can control interaction of objects from the interpreted TAE Command Language. TCL provides a means for the more experienced developer to quickly prototype an application's use of TAE Plus interaction objects and add programming logic without the overhead of compiling or linking. TAE Plus requires MIT's X Window System and the Open Software Foundation's Motif. The HP 9000 Series 700/800 version of TAE 5.2 requires Version 11 Release 5 of the X Window System. All other machine versions of TAE 5.2 require Version 11, Release 4 of the X Window System. The Workbench and WPTs are written in C++ and the remaining code is written in C. TAE Plus is available by license for an unlimited time period. The licensed program product includes the TAE Plus source code and one set of supporting documentation. Additional documentation may be purchased separately at the price indicated below. The amount of disk space required to load the TAE Plus tar format tape is between 35Mb and 67Mb depending on the machine version. The recommended minimum memory is 12Mb. Each TAE Plus platform delivery tape includes pre-built libraries and executable binary code for that particular machine, as well as source code, so users do not have to do an installation. Users wishing to recompile the source will need both a C compiler and either GNU's C++ Version 1.39 or later, or a C++ compiler based on AT&T 2.0 cfront. TAE Plus was developed in 1989 and version 5.2 was released in 1993. TAE Plus 5.2 is available on media suitable for five different machine platforms: (1) IBM RS/6000 series workstations running AIX (.25 inch tape cartridge in UNIX tar format), (2) DEC RISC workstations running ULTRIX (TK50 cartridge in UNIX tar format), (3) HP9000 Series 700/800 computers running HP-UX 9.x and X11/R5 (HP 4mm DDS DAT tape cartridge in UNIX tar format), (4) Sun4 (SPARC) series computers running SunOS (.25 inch tape cartridge in UNIX tar format), and (5) SGI Indigo computers running IRIX (.25 inch IRIS tape cartridge in UNIX tar format). Please contact COSMIC to obtain detailed information about the supported operating system and OSF/Motif releases required for each of these machine versions. An optional Motif Object Code License is available for the Sun4 version of TAE Plus 5.2. Version 5.1 of TAE Plus remains available for DEC VAX computers running VMS, HP9000 Series 300/400 computers running HP-UX, and HP 9000 Series 700/800 computers running HP-UX 8.x and X11/R4. Please contact COSMIC for details on these versions of TAE Plus.

TAE+ 5.2 - TRANSPORTABLE APPLICATIONS ENVIRONMENT PLUS, VERSION 5.2 (SUN4 VERSION)

NASA Technical Reports Server (NTRS)

TAE SUPPORT OFFICE

1994-01-01

TAE (Transportable Applications Environment) Plus is an integrated, portable environment for developing and running interactive window, text, and graphical object-based application systems. The program allows both programmers and non-programmers to easily construct their own custom application interface and to move that interface and application to different machine environments. TAE Plus makes both the application and the machine environment transparent, with noticeable improvements in the learning curve. The main components of TAE Plus are as follows: (1) the WorkBench, a What You See Is What You Get (WYSIWYG) tool for the design and layout of a user interface; (2) the Window Programming Tools Package (WPT), a set of callable subroutines that control an application's user interface; and (3) TAE Command Language (TCL), an easy-to-learn command language that provides an easy way to develop an executable application prototype with a run-time interpreted language. The WorkBench tool allows the application developer to interactively construct the layout of an application's display screen by manipulating a set of interaction objects including input items such as buttons, icons, and scrolling text lists. User interface interactive objects include data-driven graphical objects such as dials, thermometers, and strip charts as well as menubars, option menus, file selection items, message items, push buttons, and color loggers. The WorkBench user specifies the windows and interaction objects that will make up the user interface, then specifies the sequence of the user interface dialogue. The description of the designed user interface is then saved into resource files. For those who desire to develop the designed user interface into an operational application, the WorkBench tool also generates source code (C, C++, Ada, and TCL) which fully controls the application's user interface through function calls to the WPTs. The WPTs are the runtime services used by application programs to display and control the user interfaces. Since the WPTs access the workbench-generated resource files during each execution, details such as color, font, location, and object type remain independent from the application code, allowing changes to the user interface without recompiling and relinking. In addition to WPTs, TAE Plus can control interaction of objects from the interpreted TAE Command Language. TCL provides a means for the more experienced developer to quickly prototype an application's use of TAE Plus interaction objects and add programming logic without the overhead of compiling or linking. TAE Plus requires MIT's X Window System and the Open Software Foundation's Motif. The HP 9000 Series 700/800 version of TAE 5.2 requires Version 11 Release 5 of the X Window System. All other machine versions of TAE 5.2 require Version 11, Release 4 of the X Window System. The Workbench and WPTs are written in C++ and the remaining code is written in C. TAE Plus is available by license for an unlimited time period. The licensed program product includes the TAE Plus source code and one set of supporting documentation. Additional documentation may be purchased separately at the price indicated below. The amount of disk space required to load the TAE Plus tar format tape is between 35Mb and 67Mb depending on the machine version. The recommended minimum memory is 12Mb. Each TAE Plus platform delivery tape includes pre-built libraries and executable binary code for that particular machine, as well as source code, so users do not have to do an installation. Users wishing to recompile the source will need both a C compiler and either GNU's C++ Version 1.39 or later, or a C++ compiler based on AT&T 2.0 cfront. TAE Plus was developed in 1989 and version 5.2 was released in 1993. TAE Plus 5.2 is available on media suitable for five different machine platforms: (1) IBM RS/6000 series workstations running AIX (.25 inch tape cartridge in UNIX tar format), (2) DEC RISC workstations running ULTRIX (TK50 cartridge in UNIX tar format), (3) HP9000 Series 700/800 computers running HP-UX 9.x and X11/R5 (HP 4mm DDS DAT tape cartridge in UNIX tar format), (4) Sun4 (SPARC) series computers running SunOS (.25 inch tape cartridge in UNIX tar format), and (5) SGI Indigo computers running IRIX (.25 inch IRIS tape cartridge in UNIX tar format). Please contact COSMIC to obtain detailed information about the supported operating system and OSF/Motif releases required for each of these machine versions. An optional Motif Object Code License is available for the Sun4 version of TAE Plus 5.2. Version 5.1 of TAE Plus remains available for DEC VAX computers running VMS, HP9000 Series 300/400 computers running HP-UX, and HP 9000 Series 700/800 computers running HP-UX 8.x and X11/R4. Please contact COSMIC for details on these versions of TAE Plus.

TAE+ 5.2 - TRANSPORTABLE APPLICATIONS ENVIRONMENT PLUS, VERSION 5.2 (DEC RISC ULTRIX VERSION)

NASA Technical Reports Server (NTRS)

TAE SUPPORT OFFICE

1994-01-01

TAE (Transportable Applications Environment) Plus is an integrated, portable environment for developing and running interactive window, text, and graphical object-based application systems. The program allows both programmers and non-programmers to easily construct their own custom application interface and to move that interface and application to different machine environments. TAE Plus makes both the application and the machine environment transparent, with noticeable improvements in the learning curve. The main components of TAE Plus are as follows: (1) the WorkBench, a What You See Is What You Get (WYSIWYG) tool for the design and layout of a user interface; (2) the Window Programming Tools Package (WPT), a set of callable subroutines that control an application's user interface; and (3) TAE Command Language (TCL), an easy-to-learn command language that provides an easy way to develop an executable application prototype with a run-time interpreted language. The WorkBench tool allows the application developer to interactively construct the layout of an application's display screen by manipulating a set of interaction objects including input items such as buttons, icons, and scrolling text lists. User interface interactive objects include data-driven graphical objects such as dials, thermometers, and strip charts as well as menubars, option menus, file selection items, message items, push buttons, and color loggers. The WorkBench user specifies the windows and interaction objects that will make up the user interface, then specifies the sequence of the user interface dialogue. The description of the designed user interface is then saved into resource files. For those who desire to develop the designed user interface into an operational application, the WorkBench tool also generates source code (C, C++, Ada, and TCL) which fully controls the application's user interface through function calls to the WPTs. The WPTs are the runtime services used by application programs to display and control the user interfaces. Since the WPTs access the workbench-generated resource files during each execution, details such as color, font, location, and object type remain independent from the application code, allowing changes to the user interface without recompiling and relinking. In addition to WPTs, TAE Plus can control interaction of objects from the interpreted TAE Command Language. TCL provides a means for the more experienced developer to quickly prototype an application's use of TAE Plus interaction objects and add programming logic without the overhead of compiling or linking. TAE Plus requires MIT's X Window System and the Open Software Foundation's Motif. The HP 9000 Series 700/800 version of TAE 5.2 requires Version 11 Release 5 of the X Window System. All other machine versions of TAE 5.2 require Version 11, Release 4 of the X Window System. The Workbench and WPTs are written in C++ and the remaining code is written in C. TAE Plus is available by license for an unlimited time period. The licensed program product includes the TAE Plus source code and one set of supporting documentation. Additional documentation may be purchased separately at the price indicated below. The amount of disk space required to load the TAE Plus tar format tape is between 35Mb and 67Mb depending on the machine version. The recommended minimum memory is 12Mb. Each TAE Plus platform delivery tape includes pre-built libraries and executable binary code for that particular machine, as well as source code, so users do not have to do an installation. Users wishing to recompile the source will need both a C compiler and either GNU's C++ Version 1.39 or later, or a C++ compiler based on AT&T 2.0 cfront. TAE Plus was developed in 1989 and version 5.2 was released in 1993. TAE Plus 5.2 is available on media suitable for five different machine platforms: (1) IBM RS/6000 series workstations running AIX (.25 inch tape cartridge in UNIX tar format), (2) DEC RISC workstations running ULTRIX (TK50 cartridge in UNIX tar format), (3) HP9000 Series 700/800 computers running HP-UX 9.x and X11/R5 (HP 4mm DDS DAT tape cartridge in UNIX tar format), (4) Sun4 (SPARC) series computers running SunOS (.25 inch tape cartridge in UNIX tar format), and (5) SGI Indigo computers running IRIX (.25 inch IRIS tape cartridge in UNIX tar format). Please contact COSMIC to obtain detailed information about the supported operating system and OSF/Motif releases required for each of these machine versions. An optional Motif Object Code License is available for the Sun4 version of TAE Plus 5.2. Version 5.1 of TAE Plus remains available for DEC VAX computers running VMS, HP9000 Series 300/400 computers running HP-UX, and HP 9000 Series 700/800 computers running HP-UX 8.x and X11/R4. Please contact COSMIC for details on these versions of TAE Plus.

Determining electrically evoked compound action potential thresholds: a comparison of computer versus human analysis methods.

PubMed

Glassman, E Katelyn; Hughes, Michelle L

2013-01-01

Current cochlear implants (CIs) have telemetry capabilities for measuring the electrically evoked compound action potential (ECAP). Neural Response Telemetry (Cochlear) and Neural Response Imaging (Advanced Bionics [AB]) can measure ECAP responses across a range of stimulus levels to obtain an amplitude growth function. Software-specific algorithms automatically mark the leading negative peak, N1, and the following positive peak/plateau, P2, and apply linear regression to estimate ECAP threshold. Alternatively, clinicians may apply expert judgments to modify the peak markers placed by the software algorithms, or use visual detection to identify the lowest level yielding a measurable ECAP response. The goals of this study were to: (1) assess the variability between human and computer decisions for (a) marking N1 and P2 and (b) determining linear-regression threshold (LRT) and visual-detection threshold (VDT); and (2) compare LRT and VDT methods within and across human- and computer-decision methods. ECAP amplitude-growth functions were measured for three electrodes in each of 20 ears (10 Cochlear Nucleus® 24RE/CI512, and 10 AB CII/90K). LRT, defined as the current level yielding an ECAP with zero amplitude, was calculated for both computer- (C-LRT) and human-picked peaks (H-LRT). VDT, defined as the lowest level resulting in a measurable ECAP response, was also calculated for both computer- (C-VDT) and human-picked peaks (H-VDT). Because Neural Response Imaging assigns peak markers to all waveforms but does not include waveforms with amplitudes less than 20 μV in its regression calculation, C-VDT for AB subjects was defined as the lowest current level yielding an amplitude of 20 μV or more. Overall, there were significant correlations between human and computer decisions for peak-marker placement, LRT, and VDT for both manufacturers (r = 0.78-1.00, p < 0.001). For Cochlear devices, LRT and VDT correlated equally well for both computer- and human-picked peaks (r = 0.98-0.99, p < 0.001), which likely reflects the well-defined Neural Response Telemetry algorithm and the lower noise floor in the 24RE and CI512 devices. For AB devices, correlations between LRT and VDT for both peak-picker methods were weaker than for Cochlear devices (r = 0.69-0.85, p < 0.001), which likely reflect the higher noise floor of the system. Disagreement between computer and human decisions regarding the presence of an ECAP response occurred for 5 % of traces for Cochlear devices and 2.1 % of traces for AB devices. Results indicate that human and computer peak-picking methods can be used with similar accuracy for both Cochlear and AB devices. Either C-VDT or C-LRT can be used with equal confidence for Cochlear 24RE and CI512 recipients because both methods are strongly correlated with human decisions. However, for AB devices, greater variability exists between different threshold-determination methods. This finding should be considered in the context of using ECAP measures to assist with programming CIs.

Leveraging Human Insights by Combining Multi-Objective Optimization with Interactive Evolution

DTIC Science & Technology

2015-03-26

application, a program that used human selections to guide the evolution of insect -like images. He was able to demonstrate that humans provide key insights...LEVERAGING HUMAN INSIGHTS BY COMBINING MULTI-OBJECTIVE OPTIMIZATION WITH INTERACTIVE EVOLUTION THESIS Joshua R. Christman, Second Lieutenant, USAF...COMBINING MULTI-OBJECTIVE OPTIMIZATION WITH INTERACTIVE EVOLUTION THESIS Presented to the Faculty Department of Electrical and Computer Engineering

Nucleoside Inhibitors of Tick-Borne Encephalitis Virus

PubMed Central

Eyer, Luděk; Valdés, James J.; Gil, Victor A.; Nencka, Radim; Hřebabecký, Hubert; Šála, Michal; Salát, Jiří; Černý, Jiří; Palus, Martin; De Clercq, Erik

2015-01-01

Tick-borne encephalitis virus (TBEV) is a leading cause of human neuroinfections in Europe and Northeast Asia. There are no antiviral therapies for treating TBEV infection. A series of nucleoside analogues was tested for the ability to inhibit the replication of TBEV in porcine kidney cells and human neuroblastoma cells. The interactions of three nucleoside analogues with viral polymerase were simulated using advanced computational methods. The nucleoside analogues 7-deaza-2′-C-methyladenosine (7-deaza-2′-CMA), 2′-C-methyladenosine (2′-CMA), and 2′-C-methylcytidine (2′-CMC) inhibited TBEV replication. These compounds showed dose-dependent inhibition of TBEV-induced cytopathic effects, TBEV replication (50% effective concentrations [EC50]of 5.1 ± 0.4 μM for 7-deaza-2′-CMA, 7.1 ± 1.2 μM for 2′-CMA, and 14.2 ± 1.9 μM for 2′-CMC) and viral antigen production. Notably, 2′-CMC was relatively cytotoxic to porcine kidney cells (50% cytotoxic concentration [CC50] of ∼50 μM). The anti-TBEV effect of 2′-CMA in cell culture diminished gradually after day 3 posttreatment. 7-Deaza-2′-CMA showed no detectable cellular toxicity (CC50 > 50 μM), and the antiviral effect in culture was stable for >6 days posttreatment. Computational molecular analyses revealed that compared to the other two compounds, 7-deaza-2′-CMA formed a large cluster near the active site of the TBEV polymerase. High antiviral activity and low cytotoxicity suggest that 7-deaza-2′-CMA is a promising candidate for further investigation as a potential therapeutic agent in treating TBEV infection. PMID:26124166

Optimization of cryoprotectant loading into murine and human oocytes.

PubMed

Karlsson, Jens O M; Szurek, Edyta A; Higgins, Adam Z; Lee, Sang R; Eroglu, Ali

2014-02-01

Loading of cryoprotectants into oocytes is an important step of the cryopreservation process, in which the cells are exposed to potentially damaging osmotic stresses and chemical toxicity. Thus, we investigated the use of physics-based mathematical optimization to guide design of cryoprotectant loading methods for mouse and human oocytes. We first examined loading of 1.5 M dimethyl sulfoxide (Me(2)SO) into mouse oocytes at 23°C. Conventional one-step loading resulted in rates of fertilization (34%) and embryonic development (60%) that were significantly lower than those of untreated controls (95% and 94%, respectively). In contrast, the mathematically optimized two-step method yielded much higher rates of fertilization (85%) and development (87%). To examine the causes for oocyte damage, we performed experiments to separate the effects of cell shrinkage and Me(2)SO exposure time, revealing that neither shrinkage nor Me(2)SO exposure single-handedly impairs the fertilization and development rates. Thus, damage during one-step Me(2)SO addition appears to result from interactions between the effects of Me(2)SO toxicity and osmotic stress. We also investigated Me(2)SO loading into mouse oocytes at 30°C. At this temperature, fertilization rates were again lower after one-step loading (8%) in comparison to mathematically optimized two-step loading (86%) and untreated controls (96%). Furthermore, our computer algorithm generated an effective strategy for reducing Me(2)SO exposure time, using hypotonic diluents for cryoprotectant solutions. With this technique, 1.5 M Me(2)SO was successfully loaded in only 2.5 min, with 92% fertilizability. Based on these promising results, we propose new methods to load cryoprotectants into human oocytes, designed using our mathematical optimization approach. Copyright © 2013 Elsevier Inc. All rights reserved.

Optimization of Cryoprotectant Loading into Murine and Human Oocytes

PubMed Central

Karlsson, Jens O.M.; Szurek, Edyta A.; Higgins, Adam Z.; Lee, Sang R.; Eroglu, Ali

2014-01-01

Loading of cryoprotectants into oocytes is an important step of the cryopreservation process, in which the cells are exposed to potentially damaging osmotic stresses and chemical toxicity. Thus, we investigated the use of physics-based mathematical optimization to guide design of cryoprotectant loading methods for mouse and human oocytes. We first examined loading of 1.5 M dimethylsulfoxide (Me2SO) into mouse oocytes at 23°C. Conventional one-step loading resulted in rates of fertilization (34%) and embryonic development (60%) that were significantly lower than those of untreated controls (95% and 94%, respectively). In contrast, the mathematically optimized two-step method yielded much higher rates of fertilization (85%) and development (87%). To examine the causes for oocyte damage, we performed experiments to separate the effects of cell shrinkage and Me2SO exposure time, revealing that neither shrinkage nor Me2SO exposure single-handedly impairs the fertilization and development rates. Thus, damage during one-step Me2SO addition appears to result from interactions between the effects of Me2SO toxicity and osmotic stress. We also investigated Me2SO loading into mouse oocytes at 30°C. At this temperature, fertilization rates were again lower after one-step loading (8%) in comparison to mathematically optimized two-step loading (86%) and untreated controls (96%). Furthermore, our computer algorithm generated an effective strategy for reducing Me2SO exposure time, using hypotonic diluents for cryoprotectant solutions. With this technique, 1.5 M Me2SO was successfully loaded in only 2.5 min, with 92% fertilizability. Based on these promising results, we propose new methods to load cryoprotectants into human oocytes, designed using our mathematical optimization approach. PMID:24246951

Are Interactions between cis-Regulatory Variants Evidence for Biological Epistasis or Statistical Artifacts?

PubMed

Fish, Alexandra E; Capra, John A; Bush, William S

2016-10-06

The importance of epistasis-or statistical interactions between genetic variants-to the development of complex disease in humans has been controversial. Genome-wide association studies of statistical interactions influencing human traits have recently become computationally feasible and have identified many putative interactions. However, statistical models used to detect interactions can be confounded, which makes it difficult to be certain that observed statistical interactions are evidence for true molecular epistasis. In this study, we investigate whether there is evidence for epistatic interactions between genetic variants within the cis-regulatory region that influence gene expression after accounting for technical, statistical, and biological confounding factors. We identified 1,119 (FDR = 5%) interactions that appear to regulate gene expression in human lymphoblastoid cell lines, a tightly controlled, largely genetically determined phenotype. Many of these interactions replicated in an independent dataset (90 of 803 tested, Bonferroni threshold). We then performed an exhaustive analysis of both known and novel confounders, including ceiling/floor effects, missing genotype combinations, haplotype effects, single variants tagged through linkage disequilibrium, and population stratification. Every interaction could be explained by at least one of these confounders, and replication in independent datasets did not protect against some confounders. Assuming that the confounding factors provide a more parsimonious explanation for each interaction, we find it unlikely that cis-regulatory interactions contribute strongly to human gene expression, which calls into question the relevance of cis-regulatory interactions for other human phenotypes. We additionally propose several best practices for epistasis testing to protect future studies from confounding. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Antisense knockdown of sphingosine kinase 1 in human macrophages inhibits C5a receptor-dependent signal transduction, Ca2+ signals, enzyme release, cytokine production, and chemotaxis.

PubMed

Melendez, Alirio J; Ibrahim, Farazeela Bte Mohd

2004-08-01

The anaphylatoxin C5a is produced following the activation of the complement system and is associated with a variety of pathologies, including septic shock and adult respiratory distress syndrome, and with immune complex-dependent diseases such as rheumatoid arthritis. C5a has been shown to regulate inflammatory functions by interacting with its receptor, C5aR, which belong to the rhodopsin family of seven-transmembrane GPCRs. However, the intracellular signaling pathways triggered by C5aR on immune-effector cells are not well understood. In this report we present data showing that, in human monocyte-derived macrophages, C5aR uses the intracellular signaling molecule sphingosine kinase (SPHK)1 to trigger various physiological responses. Our data show that C5a rapidly stimulates the generation of sphingosine-1-phosphate, SPHK activity, and membrane translocation of SPHK1. Using an antisense oligonucleotide against SPHK1, we show that knockdown of SPHK1 abolishes the C5a-triggered intracellular Ca(2+) signals, degranulation, cytokine generation, and chemotaxis. Our study shows for the first time that SPHK1 not only plays a key role in the generation and release of proinflammatory mediators triggered by anaphylatoxins from human macrophages but is also involved in the process of immune cell motility, thus pointing out SPHK1 as a potential therapeutic target for the treatment of inflammatory and autoimmune diseases.

Quadcopter control in three-dimensional space using a noninvasive motor imagery based brain-computer interface

PubMed Central

LaFleur, Karl; Cassady, Kaitlin; Doud, Alexander; Shades, Kaleb; Rogin, Eitan; He, Bin

2013-01-01

Objective At the balanced intersection of human and machine adaptation is found the optimally functioning brain-computer interface (BCI). In this study, we report a novel experiment of BCI controlling a robotic quadcopter in three-dimensional physical space using noninvasive scalp EEG in human subjects. We then quantify the performance of this system using metrics suitable for asynchronous BCI. Lastly, we examine the impact that operation of a real world device has on subjects’ control with comparison to a two-dimensional virtual cursor task. Approach Five human subjects were trained to modulate their sensorimotor rhythms to control an AR Drone navigating a three-dimensional physical space. Visual feedback was provided via a forward facing camera on the hull of the drone. Individual subjects were able to accurately acquire up to 90.5% of all valid targets presented while travelling at an average straight-line speed of 0.69 m/s. Significance Freely exploring and interacting with the world around us is a crucial element of autonomy that is lost in the context of neurodegenerative disease. Brain-computer interfaces are systems that aim to restore or enhance a user’s ability to interact with the environment via a computer and through the use of only thought. We demonstrate for the first time the ability to control a flying robot in the three-dimensional physical space using noninvasive scalp recorded EEG in humans. Our work indicates the potential of noninvasive EEG based BCI systems to accomplish complex control in three-dimensional physical space. The present study may serve as a framework for the investigation of multidimensional non-invasive brain-computer interface control in a physical environment using telepresence robotics. PMID:23735712

Crystal structures of human 108V and 108M catechol O-methyltransferase

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

Rutherford, K.; Le Trong, I.; Stenkamp, R.E.

2008-08-01

Catechol O-methyltransferase (COMT) plays important roles in the metabolism of catecholamine neurotransmitters and catechol estrogens. The development of COMT inhibitors for use in the treatment of Parkinson's disease has been aided by crystallographic structures of the rat enzyme. However, the human and rat proteins have significantly different substrate specificities. Additionally, human COMT contains a common valine-methionine polymorphism at position 108. The methionine protein is less stable than the valine polymorph, resulting in decreased enzyme activity and protein levels in vivo. Here we describe the crystal structures of the 108V and 108M variants of the soluble form of human COMT boundmore » with S-adenosylmethionine (SAM) and a substrate analog, 3,5-dinitrocatechol. The polymorphic residue 108 is located in the {alpha}5-{beta}3 loop, buried in a hydrophobic pocket {approx}16 {angstrom} from the SAM-binding site. The 108V and 108M structures are very similar overall [RMSD of C{sup {alpha}} atoms between two structures (C{sup {alpha}} RMSD) = 0.2 {angstrom}], and the active-site residues are superposable, in accord with the observation that SAM stabilizes 108M COMT. However, the methionine side chain is packed more tightly within the polymorphic site and, consequently, interacts more closely with residues A22 ({alpha}2) and R78 ({alpha}4) than does valine. These interactions of the larger methionine result in a 0.7-{angstrom} displacement in the backbone structure near residue 108, which propagates along {alpha}1 and {alpha}5 toward the SAM-binding site. Although the overall secondary structures of the human and rat proteins are very similar (C{sup {alpha}} RMSD = 0.4 {angstrom}), several nonconserved residues are present in the SAM-(I89M, I91M, C95Y) and catechol- (C173V, R201M, E202K) binding sites. The human protein also contains three additional solvent-exposed cysteine residues (C95, C173, C188) that may contribute to intermolecular disulfide bond formation and protein aggregation.« less

Rethinking Visual Analytics for Streaming Data Applications

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

Crouser, R. Jordan; Franklin, Lyndsey; Cook, Kris

In the age of data science, the use of interactive information visualization techniques has become increasingly ubiquitous. From online scientific journals to the New York Times graphics desk, the utility of interactive visualization for both storytelling and analysis has become ever more apparent. As these techniques have become more readily accessible, the appeal of combining interactive visualization with computational analysis continues to grow. Arising out of a need for scalable, human-driven analysis, primary objective of visual analytics systems is to capitalize on the complementary strengths of human and machine analysis, using interactive visualization as a medium for communication between themore » two. These systems leverage developments from the fields of information visualization, computer graphics, machine learning, and human-computer interaction to support insight generation in areas where purely computational analyses fall short. Over the past decade, visual analytics systems have generated remarkable advances in many historically challenging analytical contexts. These include areas such as modeling political systems [Crouser et al. 2012], detecting financial fraud [Chang et al. 2008], and cybersecurity [Harrison et al. 2012]. In each of these contexts, domain expertise and human intuition is a necessary component of the analysis. This intuition is essential to building trust in the analytical products, as well as supporting the translation of evidence into actionable insight. In addition, each of these examples also highlights the need for scalable analysis. In each case, it is infeasible for a human analyst to manually assess the raw information unaided, and the communication overhead to divide the task between a large number of analysts makes simple parallelism intractable. Regardless of the domain, visual analytics tools strive to optimize the allocation of human analytical resources, and to streamline the sensemaking process on data that is massive, complex, incomplete, and uncertain in scenarios requiring human judgment.« less

Practice and Personhood in Professional Interaction: Social Identities and Information Needs.

ERIC Educational Resources Information Center

Mokros, Hartmut B.; And Others

1995-01-01

Explores the human aspect of information retrieval by examining the behavior and pronoun use of librarians in the course of communicating with patrons during online computer search interactions. Compares two studies on the conduct of librarians as intermediaries in naturally occurring online computer search interactions. (JMV)

Pilot interaction with automated airborne decision making systems

NASA Technical Reports Server (NTRS)

Rouse, W. B.; Chu, Y. Y.; Greenstein, J. S.; Walden, R. S.

1976-01-01

An investigation was made of interaction between a human pilot and automated on-board decision making systems. Research was initiated on the topic of pilot problem solving in automated and semi-automated flight management systems and attempts were made to develop a model of human decision making in a multi-task situation. A study was made of allocation of responsibility between human and computer, and discussed were various pilot performance parameters with varying degrees of automation. Optimal allocation of responsibility between human and computer was considered and some theoretical results found in the literature were presented. The pilot as a problem solver was discussed. Finally the design of displays, controls, procedures, and computer aids for problem solving tasks in automated and semi-automated systems was considered.

Overview Electrotactile Feedback for Enhancing Human Computer Interface

NASA Astrophysics Data System (ADS)

Pamungkas, Daniel S.; Caesarendra, Wahyu

2018-04-01

To achieve effective interaction between a human and a computing device or machine, adequate feedback from the computing device or machine is required. Recently, haptic feedback is increasingly being utilised to improve the interactivity of the Human Computer Interface (HCI). Most existing haptic feedback enhancements aim at producing forces or vibrations to enrich the user’s interactive experience. However, these force and/or vibration actuated haptic feedback systems can be bulky and uncomfortable to wear and only capable of delivering a limited amount of information to the user which can limit both their effectiveness and the applications they can be applied to. To address this deficiency, electrotactile feedback is used. This involves delivering haptic sensations to the user by electrically stimulating nerves in the skin via electrodes placed on the surface of the skin. This paper presents a review and explores the capability of electrotactile feedback for HCI applications. In addition, a description of the sensory receptors within the skin for sensing tactile stimulus and electric currents alsoseveral factors which influenced electric signal to transmit to the brain via human skinare explained.

SnapAnatomy, a computer-based interactive tool for independent learning of human anatomy.

PubMed

Yip, George W; Rajendran, Kanagasuntheram

2008-06-01

Computer-aided instruction materials are becoming increasing popular in medical education and particularly in the teaching of human anatomy. This paper describes SnapAnatomy, a new interactive program that the authors designed for independent learning of anatomy. SnapAnatomy is primarily tailored for the beginner student to encourage the learning of anatomy by developing a three-dimensional visualization of human structure that is essential to applications in clinical practice and the understanding of function. The program allows the student to take apart and to accurately put together body components in an interactive, self-paced and variable manner to achieve the learning outcome.

Human-Computer Interaction, Tourism and Cultural Heritage

NASA Astrophysics Data System (ADS)

Cipolla Ficarra, Francisco V.

We present a state of the art of the human-computer interaction aimed at tourism and cultural heritage in some cities of the European Mediterranean. In the work an analysis is made of the main problems deriving from training understood as business and which can derail the continuous growth of the HCI, the new technologies and tourism industry. Through a semiotic and epistemological study the current mistakes in the context of the interrelations of the formal and factual sciences will be detected and also the human factors that have an influence on the professionals devoted to the development of interactive systems in order to safeguard and boost cultural heritage.

What Machines Need to Learn to Support Human Problem-Solving

NASA Technical Reports Server (NTRS)

Vera, Alonso

2017-01-01

In the development of intelligent systems that interact with humans, there is often confusion between how the system functions with respect to the humans it interacts with and how it interfaces with those humans. The former is a much deeper challenge than the latter it requires a system-level understanding of evolving human roles as well as an understanding of what humans need to know (and when) in order to perform their tasks. This talk will focus on some of the challenges in getting this right as well as on the type of research and development that results in successful human-autonomy teaming. Brief Bio: Dr. Alonso Vera is Chief of the Human Systems Integration Division at NASA Ames Research Center. His expertise is in human-computer interaction, information systems, artificial intelligence, and computational human performance modeling. He has led the design, development and deployment of mission software systems across NASA robotic and human space flight missions, including Mars Exploration Rovers, Phoenix Mars Lander, ISS, Constellation, and Exploration Systems. Dr. Vera received a Bachelor of Science with First Class Honors from McGill University in 1985 and a Ph.D. from Cornell University in 1991. He went on to a Post-Doctoral Fellowship in the School of Computer Science at Carnegie Mellon University from 1990-93.

A Combined NMR-Computational Study of the Interaction between Influenza Virus Hemagglutinin and Sialic Derivatives from Human and Avian Receptors on the Surface of Transfected Cells.

PubMed

Vasile, Francesca; Panigada, Maddalena; Siccardi, Antonio; Potenza, Donatella; Tiana, Guido

2018-04-24

The development of small-molecule inhibitors of influenza virus Hemagglutinin could be relevant to the opposition of the diffusion of new pandemic viruses. In this work, we made use of Nuclear Magnetic Resonance (NMR) spectroscopy to study the interaction between two derivatives of sialic acid, Neu5Ac-α-(2,6)-Gal-β-(1⁻4)-GlcNAc and Neu5Ac-α-(2,3)-Gal-β-(1⁻4)-GlcNAc, and hemagglutinin directly expressed on the surface of recombinant human cells. We analyzed the interaction of these trisaccharides with 293T cells transfected with the H5 and H1 variants of hemagglutinin, which thus retain their native trimeric conformation in such a realistic environment. By exploiting the magnetization transfer between the protein and the ligand, we obtained evidence of the binding event, and identified the epitope. We analyzed the conformational features of the glycans with an approach combining NMR spectroscopy and data-driven molecular dynamics simulations, thus obtaining useful information for an efficient drug design.

Intelligent Context-Aware and Adaptive Interface for Mobile LBS

PubMed Central

Liu, Yanhong

2015-01-01

Context-aware user interface plays an important role in many human-computer Interaction tasks of location based services. Although spatial models for context-aware systems have been studied extensively, how to locate specific spatial information for users is still not well resolved, which is important in the mobile environment where location based services users are impeded by device limitations. Better context-aware human-computer interaction models of mobile location based services are needed not just to predict performance outcomes, such as whether people will be able to find the information needed to complete a human-computer interaction task, but to understand human processes that interact in spatial query, which will in turn inform the detailed design of better user interfaces in mobile location based services. In this study, a context-aware adaptive model for mobile location based services interface is proposed, which contains three major sections: purpose, adjustment, and adaptation. Based on this model we try to describe the process of user operation and interface adaptation clearly through the dynamic interaction between users and the interface. Then we show how the model applies users' demands in a complicated environment and suggested the feasibility by the experimental results. PMID:26457077

Real-time multiple human perception with color-depth cameras on a mobile robot.

PubMed

Zhang, Hao; Reardon, Christopher; Parker, Lynne E

2013-10-01

The ability to perceive humans is an essential requirement for safe and efficient human-robot interaction. In real-world applications, the need for a robot to interact in real time with multiple humans in a dynamic, 3-D environment presents a significant challenge. The recent availability of commercial color-depth cameras allow for the creation of a system that makes use of the depth dimension, thus enabling a robot to observe its environment and perceive in the 3-D space. Here we present a system for 3-D multiple human perception in real time from a moving robot equipped with a color-depth camera and a consumer-grade computer. Our approach reduces computation time to achieve real-time performance through a unique combination of new ideas and established techniques. We remove the ground and ceiling planes from the 3-D point cloud input to separate candidate point clusters. We introduce the novel information concept, depth of interest, which we use to identify candidates for detection, and that avoids the computationally expensive scanning-window methods of other approaches. We utilize a cascade of detectors to distinguish humans from objects, in which we make intelligent reuse of intermediary features in successive detectors to improve computation. Because of the high computational cost of some methods, we represent our candidate tracking algorithm with a decision directed acyclic graph, which allows us to use the most computationally intense techniques only where necessary. We detail the successful implementation of our novel approach on a mobile robot and examine its performance in scenarios with real-world challenges, including occlusion, robot motion, nonupright humans, humans leaving and reentering the field of view (i.e., the reidentification challenge), human-object and human-human interaction. We conclude with the observation that the incorporation of the depth information, together with the use of modern techniques in new ways, we are able to create an accurate system for real-time 3-D perception of humans by a mobile robot.

Toll like receptors TLR1/2, TLR6 and MUC5B as binding interaction partners with cytostatic proline rich polypeptide 1 in human chondrosarcoma.

PubMed

Galoian, Karina; Abrahamyan, Silva; Chailyan, Gor; Qureshi, Amir; Patel, Parthik; Metser, Gil; Moran, Alexandra; Sahakyan, Inesa; Tumasyan, Narine; Lee, Albert; Davtyan, Tigran; Chailyan, Samvel; Galoyan, Armen

2018-01-01

Metastatic chondrosarcoma is a bone malignancy not responsive to conventional therapies; new approaches and therapies are urgently needed. We have previously reported that mTORC1 inhibitor, antitumorigenic cytostatic proline rich polypeptide 1 (PRP-1), galarmin caused a significant upregulation of tumor suppressors including TET1/2 and SOCS3 (known to be involved in inflammatory processes), downregulation of oncoproteins and embryonic stem cell marker miR-302C and its targets Nanog, c-Myc and Bmi-1 in human chondrosarcoma. To understand better the mechanism of PRP-1 action it was very important to identify the receptor it binds to. Nuclear pathway receptor and GPCR assays indicated that PRP-1 receptors are not G protein coupled, neither do they belong to family of nuclear or orphan receptors. In the present study, we have demonstrated that PRP-1 binding interacting partners belong to innate immunity pattern recognition toll like receptors TLR1/2 and TLR6 and gel forming secreted mucin MUC5B. MUC5B was identified as PRP-1 receptor in human chondrosarcoma JJ012 cell line using Ligand-receptor capture technology. Toll like receptors TLR1/2 and TLR6 were identified as binding interaction partners with PRP-1 by western blot analysis in human chondrosarcoma JJ012 cell line lysates. Immunocytochemistry experiments confirmed the finding and indicated the localization of PRP-1 receptors in the tumor nucleus predominantly. TLR1/2, TLR6 and MUC5B were downregulated in human chondrosarcoma and upregulated in dose-response manner upon PRP-1 treatment. Experimental data indicated that in this cellular context the mentioned receptors had tumor suppressive function.

Toll like receptors TLR1/2, TLR6 and MUC5B as binding interaction partners with cytostatic proline rich polypeptide 1 in human chondrosarcoma

PubMed Central

Galoian, Karina; Abrahamyan, Silva; Chailyan, Gor; Qureshi, Amir; Patel, Parthik; Metser, Gil; Moran, Alexandra; Sahakyan, Inesa; Tumasyan, Narine; Lee, Albert; Davtyan, Tigran; Chailyan, Samvel; Galoyan, Armen

2018-01-01

Metastatic chondrosarcoma is a bone malignancy not responsive to conventional therapies; new approaches and therapies are urgently needed. We have previously reported that mTORC1 inhibitor, antitumorigenic cytostatic proline rich polypeptide 1 (PRP-1), galarmin caused a significant upregulation of tumor suppressors including TET1/2 and SOCS3 (known to be involved in inflammatory processes), downregulation of oncoproteins and embryonic stem cell marker miR-302C and its targets Nanog, c-Myc and Bmi-1 in human chondrosarcoma. To understand better the mechanism of PRP-1 action it was very important to identify the receptor it binds to. Nuclear pathway receptor and GPCR assays indicated that PRP-1 receptors are not G protein coupled, neither do they belong to family of nuclear or orphan receptors. In the present study, we have demonstrated that PRP-1 binding interacting partners belong to innate immunity pattern recognition toll like receptors TLR1/2 and TLR6 and gel forming secreted mucin MUC5B. MUC5B was identified as PRP-1 receptor in human chondrosarcoma JJ012 cell line using Ligand-receptor capture technology. Toll like receptors TLR1/2 and TLR6 were identified as binding interaction partners with PRP-1 by western blot analysis in human chondrosarcoma JJ012 cell line lysates. Immunocytochemistry experiments confirmed the finding and indicated the localization of PRP-1 receptors in the tumor nucleus predominantly. TLR1/2, TLR6 and MUC5B were downregulated in human chondrosarcoma and upregulated in dose-response manner upon PRP-1 treatment. Experimental data indicated that in this cellular context the mentioned receptors had tumor suppressive function. PMID:29138803

RPA physically interacts with the human DNA glycosylase NEIL1 to regulate excision of oxidative DNA base damage in primer-template structures.

PubMed

Theriot, Corey A; Hegde, Muralidhar L; Hazra, Tapas K; Mitra, Sankar

2010-06-04

The human DNA glycosylase NEIL1, activated during the S-phase, has been shown to excise oxidized base lesions in single-strand DNA substrates. Furthermore, our previous work demonstrating functional interaction of NEIL1 with PCNA and flap endonuclease 1 (FEN1) suggested its involvement in replication-associated repair. Here we show interaction of NEIL1 with replication protein A (RPA), the heterotrimeric single-strand DNA binding protein that is essential for replication and other DNA transactions. The NEIL1 immunocomplex isolated from human cells contains RPA, and its abundance in the complex increases after exposure to oxidative stress. NEIL1 directly interacts with the large subunit of RPA (K(d) approximately 20 nM) via the common interacting interface (residues 312-349) in NEIL1's disordered C-terminal region. RPA inhibits the base excision activity of both wild-type NEIL1 (389 residues) and its C-terminal deletion CDelta78 mutant (lacking the interaction domain) for repairing 5-hydroxyuracil (5-OHU) in a primer-template structure mimicking the DNA replication fork. This inhibition is reduced when the damage is located near the primer-template junction. Contrarily, RPA moderately stimulates wild-type NEIL1 but not the CDelta78 mutant when 5-OHU is located within the duplex region. While NEIL1 is inhibited by both RPA and Escherichia coli single-strand DNA binding protein, only inhibition by RPA is relieved by PCNA. These results showing modulation of NEIL1's activity on single-stranded DNA substrate by RPA and PCNA support NEIL1's involvement in repairing the replicating genome. Copyright 2010 Elsevier B.V. All rights reserved.

Inhibition of human alcohol and aldehyde dehydrogenases by acetaminophen: Assessment of the effects on first-pass metabolism of ethanol.

PubMed

Lee, Yung-Pin; Liao, Jian-Tong; Cheng, Ya-Wen; Wu, Ting-Lun; Lee, Shou-Lun; Liu, Jong-Kang; Yin, Shih-Jiun

2013-11-01

Acetaminophen is one of the most widely used over-the-counter analgesic, antipyretic medications. Use of acetaminophen and alcohol are commonly associated. Previous studies showed that acetaminophen might affect bioavailability of ethanol by inhibiting gastric alcohol dehydrogenase (ADH). However, potential inhibitions by acetaminophen of first-pass metabolism (FPM) of ethanol, catalyzed by the human ADH family and by relevant aldehyde dehydrogenase (ALDH) isozymes, remain undefined. ADH and ALDH both exhibit racially distinct allozymes and tissue-specific distribution of isozymes, and are principal enzymes responsible for ethanol metabolism in humans. In this study, we investigated acetaminophen inhibition of ethanol oxidation with recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and inhibition of acetaldehyde oxidation with recombinant human ALDH1A1 and ALDH2. The investigations were done at near physiological pH 7.5 and with a cytoplasmic coenzyme concentration of 0.5 mM NAD(+). Acetaminophen acted as a noncompetitive inhibitor for ADH enzymes, with the slope inhibition constants (Kis) ranging from 0.90 mM (ADH2) to 20 mM (ADH1A), and the intercept inhibition constants (Kii) ranging from 1.4 mM (ADH1C allozymes) to 19 mM (ADH1A). Acetaminophen exhibited noncompetitive inhibition for ALDH2 (Kis = 3.0 mM and Kii = 2.2 mM), but competitive inhibition for ALDH1A1 (Kis = 0.96 mM). The metabolic interactions between acetaminophen and ethanol/acetaldehyde were assessed by computer simulation using inhibition equations and the determined kinetic constants. At therapeutic to subtoxic plasma levels of acetaminophen (i.e., 0.2-0.5 mM) and physiologically relevant concentrations of ethanol (10 mM) and acetaldehyde (10 μm) in target tissues, acetaminophen could inhibit ADH1C allozymes (12-26%) and ADH2 (14-28%) in the liver and small intestine, ADH4 (15-31%) in the stomach, and ALDH1A1 (16-33%) and ALDH2 (8.3-19%) in all 3 tissues. The results suggest that inhibition by acetaminophen of hepatic and gastrointestinal FPM of ethanol through ADH and ALDH pathways might become significant at higher, subtoxic levels of acetaminophen. Copyright © 2013 Elsevier Inc. All rights reserved.

Steroid ligands bind human sex hormone-binding globulin in specific orientations and produce distinct changes in protein conformation.

PubMed

Grishkovskaya, Irina; Avvakumov, George V; Hammond, Geoffrey L; Catalano, Maria G; Muller, Yves A

2002-08-30

The amino-terminal laminin G-like domain of human sex hormone-binding globulin (SHBG) contains a single high affinity steroid-binding site. Crystal structures of this domain in complex with several different steroid ligands have revealed that estradiol occupies the SHBG steroid-binding site in an opposite orientation when compared with 5 alpha-dihydrotestosterone or C19 androgen metabolites (5 alpha-androstan-3 beta,17 beta-diol and 5 alpha-androstan-3 beta,17 alpha-diol) or the synthetic progestin levonorgestrel. Substitution of specific residues within the SHBG steroid-binding site confirmed that Ser(42) plays a key role in determining high affinity interactions by hydrogen bonding to functional groups at C3 of the androstanediols and levonorgestrel and the hydroxyl at C17 of estradiol. Among residues participating in the hydrogen bond network with hydroxy groups at C17 of C19 steroids or C3 of estradiol, Asp(65) appears to be the most important. The different binding mode of estradiol is associated with a difference in the position/orientation of residues (Leu(131) and Lys(134)) in the loop segment (Leu(131)-His(136)) that covers the steroid-binding site as well as others (Leu(171)-Lys(173) and Trp(84)) on the surface of human SHBG and may provide a basis for ligand-dependent interactions between SHBG and other macromolecules. These new crystal structures have also enabled us to construct a simple space-filling model that can be used to predict the characteristics of novel SHBG ligands.

Predicting PDZ domain mediated protein interactions from structure

PubMed Central

2013-01-01

Background PDZ domains are structural protein domains that recognize simple linear amino acid motifs, often at protein C-termini, and mediate protein-protein interactions (PPIs) in important biological processes, such as ion channel regulation, cell polarity and neural development. PDZ domain-peptide interaction predictors have been developed based on domain and peptide sequence information. Since domain structure is known to influence binding specificity, we hypothesized that structural information could be used to predict new interactions compared to sequence-based predictors. Results We developed a novel computational predictor of PDZ domain and C-terminal peptide interactions using a support vector machine trained with PDZ domain structure and peptide sequence information. Performance was estimated using extensive cross validation testing. We used the structure-based predictor to scan the human proteome for ligands of 218 PDZ domains and show that the predictions correspond to known PDZ domain-peptide interactions and PPIs in curated databases. The structure-based predictor is complementary to the sequence-based predictor, finding unique known and novel PPIs, and is less dependent on training–testing domain sequence similarity. We used a functional enrichment analysis of our hits to create a predicted map of PDZ domain biology. This map highlights PDZ domain involvement in diverse biological processes, some only found by the structure-based predictor. Based on this analysis, we predict novel PDZ domain involvement in xenobiotic metabolism and suggest new interactions for other processes including wound healing and Wnt signalling. Conclusions We built a structure-based predictor of PDZ domain-peptide interactions, which can be used to scan C-terminal proteomes for PDZ interactions. We also show that the structure-based predictor finds many known PDZ mediated PPIs in human that were not found by our previous sequence-based predictor and is less dependent on training–testing domain sequence similarity. Using both predictors, we defined a functional map of human PDZ domain biology and predict novel PDZ domain function. Users may access our structure-based and previous sequence-based predictors at http://webservice.baderlab.org/domains/POW. PMID:23336252

HIFiRE-1 Turbulent Shock Boundary Layer Interaction - Flight Data and Computations (Postprint)

DTIC Science & Technology

2015-06-01

tte rs on o n Se pt em be r 1, 2 01 5 | h ttp :// ar c. ai aa .o rg | D O I: 1 0. 25 14 /6 .2 01 5- 26 39...characteristics of a transitional interaction at about this time. D ow nl oa de d by A FR L D ’A zz o W ri gh t- Pa tte rs on o n Se pt em be r 1, 2 01 5...endoatmospheric. The remainder of the trajectory was exoatmospheric. D ow nl oa de d by A FR L D ’A zz o W

User-Computer Interactions: Some Problems for Human Factors Research

DTIC Science & Technology

1981-09-01

accessibility from the work place or home of R. information stored in major repositories. o Two-way real-time communication between broadcasting - facilities...Miller, and R.W. Pew (BBN Inc.) MDA 903-80-C-0551 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT, TASK AREA & WORK UNIT NUMBERS...average U.S. home has gone from about 10 in 1940 to about 100 in 1960 to a few thousand in 1930. Collectively, these trends represent an enormous

Usability and Utility of a Mobile Application for Marksmanship Training

DTIC Science & Technology

2015-01-01

Right of Canada, as represented by the Minister of National Defence, 2015 © Sa Majesté la Reine (en droit du Canada), telle que représentée par le...Empirical Evaluation of the System Usability Scale. International Journal of Human-Computer Interaction, 24(6), 574-594. BenMoussa, C. (2003). Workers on...Behavioral and Social Sciences. Jumisko-Pyykko, S., & Vainio, T. (2011). Framing the Context of Use for Mobile HCI. International Journal of Mobile

The Design of Hand Gestures for Human-Computer Interaction: Lessons from Sign Language Interpreters.

PubMed

Rempel, David; Camilleri, Matt J; Lee, David L

2015-10-01

The design and selection of 3D modeled hand gestures for human-computer interaction should follow principles of natural language combined with the need to optimize gesture contrast and recognition. The selection should also consider the discomfort and fatigue associated with distinct hand postures and motions, especially for common commands. Sign language interpreters have extensive and unique experience forming hand gestures and many suffer from hand pain while gesturing. Professional sign language interpreters (N=24) rated discomfort for hand gestures associated with 47 characters and words and 33 hand postures. Clear associations of discomfort with hand postures were identified. In a nominal logistic regression model, high discomfort was associated with gestures requiring a flexed wrist, discordant adjacent fingers, or extended fingers. These and other findings should be considered in the design of hand gestures to optimize the relationship between human cognitive and physical processes and computer gesture recognition systems for human-computer input.

The Murine Factor H-Related Protein FHR-B Promotes Complement Activation.

PubMed

Cserhalmi, Marcell; Csincsi, Ádám I; Mezei, Zoltán; Kopp, Anne; Hebecker, Mario; Uzonyi, Barbara; Józsi, Mihály

2017-01-01

Factor H-related (FHR) proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH). While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces. The aim of the current study was the functional characterization of a murine FHR, FHR-B. To this end, FHR-B was expressed in recombinant form. Recombinant FHR-B bound to human C3b and was able to compete with human FH for C3b binding. FHR-B supported the assembly of functionally active C3bBb alternative pathway C3 convertase via its interaction with C3b. This activity was confirmed by demonstrating C3 activation in murine serum. In addition, FHR-B bound to murine pentraxin 3 (PTX3), and this interaction resulted in murine C3 fragment deposition due to enhanced complement activation in mouse serum. FHR-B also induced C3 deposition on C-reactive protein, the extracellular matrix (ECM) extract Matrigel, and endothelial cell-derived ECM when exposed to mouse serum. Moreover, mouse C3 deposition was strongly enhanced on necrotic Jurkat T cells and the mouse B cell line A20 by FHR-B. FHR-B also induced lysis of sheep erythrocytes when incubated in mouse serum with FHR-B added in excess. Altogether, these data demonstrate that, similar to human FHR-1 and FHR-5, mouse FHR-B modulates complement activity by promoting complement activation via interaction with C3b and via competition with murine FH.

Application of a computational decision model to examine acute drug effects on human risk taking.

PubMed

Lane, Scott D; Yechiam, Eldad; Busemeyer, Jerome R

2006-05-01

In 3 previous experiments, high doses of alcohol, marijuana, and alprazolam acutely increased risky decision making by adult humans in a 2-choice (risky vs. nonrisky) laboratory task. In this study, a computational modeling analysis known as the expectancy valence model (J. R. Busemeyer & J. C. Stout, 2002) was applied to individual-participant data from these studies, for the highest administered dose of all 3 drugs and corresponding placebo doses, to determine changes in decision-making processes that may be uniquely engendered by each drug. The model includes 3 parameters: responsiveness to rewards and losses (valence or motivation); the rate of updating expectancies about the value of risky alternatives (learning/memory); and the consistency with which trial-by-trial choices match expected outcomes (sensitivity). Parameter estimates revealed 3 key outcomes: Alcohol increased responsiveness to risky rewards and decreased responsiveness to risky losses (motivation) but did not alter expectancy updating (learning/memory); both marijuana and alprazolam produced increases in risk taking that were related to learning/memory but not motivation; and alcohol and marijuana (but not alprazolam) produced more random response patterns that were less consistently related to expected outcomes on the 2 choices. No significant main effects of gender or dose by gender interactions were obtained, but 2 dose by gender interactions approached significance. These outcomes underscore the utility of using a computational modeling approach to deconstruct decision-making processes and thus better understand drug effects on risky decision making in humans.

Using Adaptive Automation to Increase Operator Performance and Decrease Stress in a Satellite Operations Environment

ERIC Educational Resources Information Center

Klein, David C.

2014-01-01

As advancements in automation continue to alter the systemic behavior of computer systems in a wide variety of industrial applications, human-machine interactions are increasingly becoming supervisory in nature, with less hands-on human involvement. This maturing of the human role within the human-computer relationship is relegating operations…

The C-terminus of the B-chain of human insulin-like peptide 5 is critical for cognate RXFP4 receptor activity.

PubMed

Patil, Nitin A; Bathgate, Ross A D; Kocan, Martina; Ang, Sheng Yu; Tailhades, Julien; Separovic, Frances; Summers, Roger; Grosse, Johannes; Hughes, Richard A; Wade, John D; Hossain, Mohammed Akhter

2016-04-01

Insulin-like peptide 5 (INSL5) is an orexigenic peptide hormone belonging to the relaxin family of peptides. It is expressed primarily in the L-cells of the colon and has a postulated key role in regulating food intake. Its G protein-coupled receptor, RXFP4, is a potential drug target for treating obesity and anorexia. We studied the effect of modification of the C-terminus of the A and B-chains of human INSL5 on RXFP4 binding and activation. Three variants of human INSL5 were prepared using solid phase peptide synthesis and subsequent sequential regioselective disulfide bond formation. The peptides were synthesized as C-terminal acids (both A- and B-chains with free C-termini, i.e., the native form), amides (both chains as the C-terminal amide) and one analog with the C-terminus of its A-chain as the amide and the C-terminus of the B-chain as the acid. The results showed that C-terminus of the B-chain is more important than that of the A-chain for RXFP4 binding and activity. Amidation of the A-chain C-terminus does not have any effect on the INSL5 activity. The difference in RXFP4 binding and activation between the three peptides is believed to be due to electrostatic interaction of the free carboxylate of INSL5 with a positively charged residue (s), either situated within the INSL5 molecule itself or in the receptor extracellular loops.

Role of the C-terminus in the activity, conformation, and stability of interleukin-6.

PubMed Central

Ward, L. D.; Hammacher, A.; Zhang, J. G.; Weinstock, J.; Yasukawa, K.; Morton, C. J.; Norton, R. S.; Simpson, R. J.

1993-01-01

Two murine interleukin-6 (mIL-6) variants were constructed using the polymerase chain reaction (PCR), one lacking the last five residues (183-187) at the C-terminus (pMC5) and another with the last five residues of mIL-6 substituted by the corresponding residues of human IL-6 (pMC5H). The growth stimulatory activity of pMC5 on the mouse hybridoma cell line 7TD1 was < 0.05% of mIL-6, whereas pMC5H and mIL-6 were equipotent. The loss of biological activity of pMC5 correlated with its negligible receptor binding affinity on 7TD1 cells, while the binding of pMC5H was comparable to that of mIL-6. Both pMC5 and pMC5H, like mIL-6, failed to interact with recombinant soluble human IL-6 receptor when assayed by surface plasmon resonance-based biosensor analysis. These studies suggest that the C-terminal seven amino acids of human IL-6, alone, do not define species specificity for receptor binding. A variety of biophysical techniques, as well as the binding of a conformational-specific monoclonal antibody, indicated that the global fold of the mIL-6 variants was similar to that of mIL-6, although small changes in the NMR spectra, particularly for pMC5, were observed. Some of these changes involved residues widely separated in the primary structure. For instance, interactions involving Tyr-22 were influenced by the C-terminal amino acids suggesting that the N- and C-termini of mIL-6 are in close proximity. Equilibrium unfolding experiments indicated that pMC5 was 0.8 kcal/mol less stable than mIL-6, whereas pMC5H was 1.4 kcal/mol more stable. These studies emphasize the structural importance of the C-terminal amino acids of IL-6 and suggest that truncation or mutation of this region could lead to small but significant alterations in other regions of the molecule. PMID:8401231

Metronidazole reduces the expression of cytochrome P450 enzymes in HepaRG cells and cryopreserved human hepatocytes.

PubMed

Kudo, Toshiyuki; Endo, Yumiko; Taguchi, Rina; Yatsu, Masami; Ito, Kiyomi

2015-05-01

1. Blood levels of S-warfarin have been reported to be increased by concomitant administration of metronidazole (MTZ), an antiprotozoal imidazole derivative. 2. To elucidate the mechanism of this interaction and to identify other possible drug-drug interactions, we conducted an in vitro study with the human hepatoma HepaRG cells and cryopreserved human hepatocytes on the ability of MTZ to reduce the expression of cytochrome P450 (CYP) as well as nuclear receptors that regulate the expression of these enzymes. 3. HepaRG cells and cryopreserved human hepatocytes were treated with MTZ (20 to 500 µM) and were then analyzed by real-time RT-PCR to determine mRNA levels of drug-metabolizing enzymes and nuclear receptors. 4. In both cells, the expressions of CYP2C8, CYP2C9, CYP3A4 and constitutive androstane receptor (CAR) were decreased by MTZ treatment. Particularly, in HepaRG cells, their mRNA levels were decreased by MTZ treatment in a concentration-dependent manner. 5. Our findings suggest that the interaction between MTZ and S-warfarin may be due to the MTZ-induced down-regulation of CYP2C9, the primary enzyme responsible for S-warfarin hydroxylation, and CAR, which regulates CYP2C9 expression. We also found that MTZ use may alter the disposition of drugs metabolized by the CYP isozymes investigated.

Sensor-based assessment of the in-situ quality of human computer interaction in the cars : final research report.

DOT National Transportation Integrated Search

2016-01-01

Human attention is a finite resource. When interrupted while performing a task, this : resource is split between two interactive tasks. People have to decide whether the benefits : from the interruptive interaction will be enough to offset the loss o...

Human-computer dialogue: Interaction tasks and techniques. Survey and categorization

NASA Technical Reports Server (NTRS)

Foley, J. D.

1983-01-01

Interaction techniques are described. Six basic interaction tasks, requirements for each task, requirements related to interaction techniques, and a technique's hardware prerequisites affective device selection are discussed.

Structural investigation of C4b-binding protein by molecular modeling: localization of putative binding sites.

PubMed

Villoutreix, B O; Härdig, Y; Wallqvist, A; Covell, D G; García de Frutos, P; Dahlbäck, B

1998-06-01

C4b-binding protein (C4BP) contributes to the regulation of the classical pathway of the complement system and plays an important role in blood coagulation. The main human C4BP isoform is composed of one beta-chain and seven alpha-chains essentially built from three and eight complement control protein (CCP) modules, respectively, followed by a nonrepeat carboxy-terminal region involved in polymerization of the chains. C4BP is known to interact with heparin, C4b, complement factor I, serum amyloid P component, streptococcal Arp and Sir proteins, and factor VIII/VIIIa via its alpha-chains and with protein S through its beta-chain. The principal aim of the present study was to localize regions of C4BP involved in the interaction with C4b, Arp, and heparin. For this purpose, a computer model of the 8 CCP modules of C4BP alpha-chain was constructed, taking into account data from previous electron microscopy (EM) studies. This structure was investigated in the context of known and/or new experimental data. Analysis of the alpha-chain model, together with monoclonal antibody studies and heparin binding experiments, suggests that a patch of positively charged residues, at the interface between the first and second CCP modules, plays an important role in the interaction between C4BP and C4b/Arp/Sir/heparin. Putative binding sites, secondary-structure prediction for the central core, and an overall reevaluation of the size of the C4BP molecule are also presented. An understanding of these intermolecular interactions should contribute to the rational design of potential therapeutic agents aiming at interfering specifically some of these protein-protein interactions.

Molecular interactions of agonist and inverse agonist ligands at serotonin 5-HT2C G protein-coupled receptors: computational ligand docking and molecular dynamics studies validated by experimental mutagenesis results

NASA Astrophysics Data System (ADS)

Córdova-Sintjago, Tania C.; Liu, Yue; Booth, Raymond G.

2015-02-01

To understand molecular determinants for ligand activation of the serotonin 5-HT2C G protein-coupled receptor (GPCR), a drug target for obesity and neuropsychiatric disorders, a 5-HT2C homology model was built according to an adrenergic β2 GPCR (β2AR) structure and validated using a 5-HT2B GPCR crystal structure. The models were equilibrated in a simulated phosphatidyl choline membrane for ligand docking and molecular dynamics studies. Ligands included (2S, 4R)-(-)-trans-4-(3'-bromo- and trifluoro-phenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalene-2-amine (3'-Br-PAT and 3'-CF3-PAT), a 5-HT2C agonist and inverse agonist, respectively. Distinct interactions of 3'-Br-PAT and 3'-CF3-PAT at the wild-type (WT) 5-HT2C receptor model were observed and experimental 5-HT2C receptor mutagenesis studies were undertaken to validate the modelling results. For example, the inverse agonist 3'-CF3-PAT docked deeper in the WT 5-HT2C binding pocket and altered the orientation of transmembrane helices (TM) 6 in comparison to the agonist 3'-Br-PAT, suggesting that changes in TM orientation that result from ligand binding impact function. For both PATs, mutation of 5-HT2C residues S3.36, T3.37, and F5.47 to alanine resulted in significantly decreased affinity, as predicted from modelling results. It was concluded that upon PAT binding, 5-HT2C residues T3.37 and F5.47 in TMs 3 and 5, respectively, engage in inter-helical interactions with TMs 4 and 6, respectively. The movement of TMs 5 and 6 upon agonist and inverse agonist ligand binding observed in the 5-HT2C receptor modelling studies was similar to movements reported for the activation and deactivation of the β2AR, suggesting common mechanisms among aminergic neurotransmitter GPCRs.

Employing Textual and Facial Emotion Recognition to Design an Affective Tutoring System

ERIC Educational Resources Information Center

Lin, Hao-Chiang Koong; Wang, Cheng-Hung; Chao, Ching-Ju; Chien, Ming-Kuan

2012-01-01

Emotional expression in Artificial Intelligence has gained lots of attention in recent years, people applied its affective computing not only in enhancing and realizing the interaction between computers and human, it also makes computer more humane. In this study, emotional expressions were applied into intelligent tutoring system, where learners'…

Packaging printed circuit boards: A production application of interactive graphics

NASA Technical Reports Server (NTRS)

Perrill, W. A.

1975-01-01

The structure and use of an Interactive Graphics Packaging Program (IGPP), conceived to apply computer graphics to the design of packaging electronic circuits onto printed circuit boards (PCB), were described. The intent was to combine the data storage and manipulative power of the computer with the imaginative, intuitive power of a human designer. The hardware includes a CDC 6400 computer and two CDC 777 terminals with CRT screens, light pens, and keyboards. The program is written in FORTRAN 4 extended with the exception of a few functions coded in COMPASS (assembly language). The IGPP performs four major functions for the designer: (1) data input and display, (2) component placement (automatic or manual), (3) conductor path routing (automatic or manual), and (4) data output. The most complex PCB packaged to date measured 16.5 cm by 19 cm and contained 380 components, two layers of ground planes and four layers of conductors mixed with ground planes.

Metabolic Pathway of Icotinib In Vitro: The Differential Roles of CYP3A4, CYP3A5, and CYP1A2 on Potential Pharmacokinetic Drug-Drug Interaction.

PubMed

Zhang, TianHong; Zhang, KeRong; Ma, Li; Li, Zheng; Wang, Juan; Zhang, YunXia; Lu, Chuang; Zhu, Mingshe; Zhuang, XiaoMei

2018-04-01

Icotinib is the first self-developed small molecule drug in China for targeted therapy of non-small cell lung cancer. To date, systematic studies on the pharmacokinetic drug-drug interaction of icotinib were limited. By identifying metabolite generated in human liver microsomes and revealing the contributions of major cytochromes P450 (CYPs) in the formation of major metabolites, the aim of the present work was to understand the mechanisms underlying pharmacokinetic and pharmacological variability in clinic. A liquid chromatography/UV/high-resolution mass spectrometer method was developed to characterize the icotinib metabolites. The formation of 6 major metabolites was studied in recombinant CYP isozymes and human liver microsomes with specific inhibitors to identify the CYPs responsible for icotinib metabolism. The metabolic pathways observed in vitro are consistent with those observed in human. Results demonstrated that the metabolites are predominantly catalyzed by CYP3A4 (77%∼87%), with a moderate contribution from CYP3A5 (5%∼15%) and CYP1A2 (3.7%∼7.5%). The contribution of CYP2C8, 2C9, 2C19, and 2D6 is insignificant. Based on our observations, to minimize drug-drug interaction risk in clinic, coprescription of icotinib with strong CYP3A inhibitors or inducers must be weighed. CYP1A2, a highly inducible enzyme in the smoking population, may also represent a determinant of pharmacokinetic and pharmacological variability of icotinib, especially in lung cancer patients with smoking history. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Interaction of an opportunistic fungus Purpureocillium lilacinum with human macrophages and dendritic cells.

PubMed

Peixoto, Mariana Lima Perazzini; Santos, Dilvani Oliveira; Souza, Ivy de Castro Campos de; Neri, Eloah Christina Lyrio; Sequeira, Danielly Correa Moreira de; De Luca, Paula Mello; Borba, Cíntia de Moraes

2014-01-01

Purpureocillium lilacinum is emerging as a causal agent of hyalohyphomycosis that is refractory to antifungal drugs; however, the pathogenic mechanisms underlying P. lilacinum infection are not understood. In this study, we investigated the interaction of P. lilacinum conidia with human macrophages and dendritic cells in vitro. Spores of a P. lilacinum clinical isolate were obtained by chill-heat shock. Mononuclear cells were isolated from eight healthy individuals. Monocytes were separated by cold aggregation and differentiated into macrophages by incubation for 7 to 10 days at 37°C or into dendritic cells by the addition of the cytokines human granulocyte-macrophage colony stimulating factor and interleukin-4. Conidial suspension was added to the human cells at 1:1, 2:1, and 5:1 (conidia:cells) ratios for 1h, 6h, and 24h, and the infection was evaluated by Giemsa staining and light microscopy. After 1h interaction, P. lilacinum conidia were internalized by human cells and after 6h contact, some conidia became inflated. After 24h interaction, the conidia produced germ tubes and hyphae, leading to the disruption of macrophage and dendritic cell membranes. The infection rate analyzed after 6h incubation of P. lilacinum conidia with cells at 2:1 and 1:1 ratios was 76.5% and 25.5%, respectively, for macrophages and 54.3% and 19.5%, respectively, for cultured dendritic cells. P. lilacinum conidia are capable of infecting and destroying both macrophages and dendritic cells, clearly demonstrating the ability of this pathogenic fungus to invade human phagocytic cells.

A high-resolution map of the three-dimensional chromatin interactome in human cells.

PubMed

Jin, Fulai; Li, Yan; Dixon, Jesse R; Selvaraj, Siddarth; Ye, Zhen; Lee, Ah Young; Yen, Chia-An; Schmitt, Anthony D; Espinoza, Celso A; Ren, Bing

2013-11-14

A large number of cis-regulatory sequences have been annotated in the human genome, but defining their target genes remains a challenge. One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C)-based techniques. However, previous studies lack either the resolution or coverage to permit a whole-genome, unbiased view of chromatin interactions. Here we report a comprehensive chromatin interaction map generated in human fibroblasts using a genome-wide 3C analysis method (Hi-C). We determined over one million long-range chromatin interactions at 5-10-kb resolution, and uncovered general principles of chromatin organization at different types of genomic features. We also characterized the dynamics of promoter-enhancer contacts after TNF-α signalling in these cells. Unexpectedly, we found that TNF-α-responsive enhancers are already in contact with their target promoters before signalling. Such pre-existing chromatin looping, which also exists in other cell types with different extracellular signalling, is a strong predictor of gene induction. Our observations suggest that the three-dimensional chromatin landscape, once established in a particular cell type, is relatively stable and could influence the selection or activation of target genes by a ubiquitous transcription activator in a cell-specific manner.

Polysaccharide peptides from Coriolus versicolor competitively inhibit tolbutamide 4-hydroxylation in specific human CYP2C9 isoform and pooled human liver microsomes.

PubMed

Yeung, John H K; Or, Penelope M Y

2011-10-15

Polysaccharide peptide (PSP), isolated from COV-1 strain of Coriolus versicolor, is commonly used as an adjunct in cancer chemotherapy in China. Previous studies have shown that PSP decreased antipyrine clearance and inhibited CYP2C11-mediated tolbutamide 4-hydroxylation in the rat both in vitro and in vivo. In this study, the effects of water extractable fraction of PSP on tolbutamide 4-hydroxylation was investigated in pooled human liver microsomes and in specific human CYP2C9 isoform. PSP (2.5-20μM) dose-dependently decreased the biotransformation of tolbutamide to 4-hydroxy-tolbutamide. Enzyme kinetics studies showed inhibition of tolbutamide 4-hydroxylase activity was competitive and concentration-dependent. In pooled human liver microsomes, PSP had a K(i) value of 14.2μM compared to sulfaphenazole, a human CYP2C9 inhibitor, showed a K(i) value of 0.32μM. In human CYP2C9 isoform, the K(i) value of PSP was 29.5μM and the K(i) value of sulfaphenazole was 0.04μM. This study demonstrated that PSP can competitively inhibit tolbutamide 4-hydroxylation in both pooled human liver microsomes and specific human CYP2C9 in vitro. This study compliments previous findings in the rat that PSP can inhibit human tolbutamide 4-hydroxylase, but the relatively high K(i) values in human CYP2C9 would suggest a low potential for PSP to cause herb-drug interaction. Copyright © 2011 Elsevier GmbH. All rights reserved.

TGA, Hirshfeld, Raman spectroscopy and computational studies of diethylammonium hexachloroplumbate [(C2H5)2NH2]2PbCl6

NASA Astrophysics Data System (ADS)

Ouasri, A.; El-Adel, L.; Zouihri, H.; Rhandour, A.; Jalbout, A. F.

2018-04-01

Diethylammonium hexachloroplumbate [(C2H5)2NH2]2PbCl6 was found to be monoclinic with P21/n (Z = 2) as space group at room temperature. The TGA analysis shows that this compound is slightly hygroscopic and presents moisture in itself. The Raman spectrum (50-4000 cm-1) of this compound recorded at room temperature was discussed on the basis of the factor group analysis using the structural data obtained recently [5]. The experimental frequencies are compared to those obtained by Density Functional Theory (DFT) by using the B3LYP functional and the 6-31G(d) (SDD) basis set. The thermodynamic properties and geometries of this compound have been determinated and characterized. The significant intermolecular interactions in the crystal structure are identified and analyzed using the Hirshfeld surface and fingerprint plots computational methods.

The Next Wave: Humans, Computers, and Redefining Reality

NASA Technical Reports Server (NTRS)

Little, William

2018-01-01

The Augmented/Virtual Reality (AVR) Lab at KSC is dedicated to " exploration into the growing computer fields of Extended Reality and the Natural User Interface (it is) a proving ground for new technologies that can be integrated into future NASA projects and programs." The topics of Human Computer Interface, Human Computer Interaction, Augmented Reality, Virtual Reality, and Mixed Reality are defined; examples of work being done in these fields in the AVR Lab are given. Current new and future work in Computer Vision, Speech Recognition, and Artificial Intelligence are also outlined.

Human Pacman: A Mobile Augmented Reality Entertainment System Based on Physical, Social, and Ubiquitous Computing

NASA Astrophysics Data System (ADS)

Cheok, Adrian David

This chapter details the Human Pacman system to illuminate entertainment computing which ventures to embed the natural physical world seamlessly with a fantasy virtual playground by capitalizing on infrastructure provided by mobile computing, wireless LAN, and ubiquitous computing. With Human Pacman, we have a physical role-playing computer fantasy together with real human-social and mobile-gaming that emphasizes on collaboration and competition between players in a wide outdoor physical area that allows natural wide-area human-physical movements. Pacmen and Ghosts are now real human players in the real world experiencing mixed computer graphics fantasy-reality provided by using the wearable computers on them. Virtual cookies and actual tangible physical objects are incorporated into the game play to provide novel experiences of seamless transitions between the real and virtual worlds. This is an example of a new form of gaming that anchors on physicality, mobility, social interaction, and ubiquitous computing.

The rational design of a novel potent analogue of the 5’-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity

PubMed Central

Machrouhi, Fouzia; Ouhamou, Nouara; Laderoute, Keith; Calaoagan, Joy; Bukhtiyarova, Marina; Ehrlich, Paula J.; Klon, Anthony E.

2010-01-01

We have designed and synthesized analogues of compound C, a non-specific inhibitor of 5’-AMP-activated protein kinase (AMPK), using a computational fragment-based drug design (FBDD) approach. Synthesizing only twenty-seven analogues yielded a compound that was equipotent to compound C in the inhibition of the human AMPK (hAMPK) α2 subunit in the heterotrimeric complex in vitro, exhibited significantly improved selectivity against a subset of relevant kinases, and demonstrated enhanced cellular inhibition of AMPK. PMID:20932747

High-performance biocomputing for simulating the spread of contagion over large contact networks

PubMed Central

2012-01-01

Background Many important biological problems can be modeled as contagion diffusion processes over interaction networks. This article shows how the EpiSimdemics interaction-based simulation system can be applied to the general contagion diffusion problem. Two specific problems, computational epidemiology and human immune system modeling, are given as examples. We then show how the graphics processing unit (GPU) within each compute node of a cluster can effectively be used to speed-up the execution of these types of problems. Results We show that a single GPU can accelerate the EpiSimdemics computation kernel by a factor of 6 and the entire application by a factor of 3.3, compared to the execution time on a single core. When 8 CPU cores and 2 GPU devices are utilized, the speed-up of the computational kernel increases to 9.5. When combined with effective techniques for inter-node communication, excellent scalability can be achieved without significant loss of accuracy in the results. Conclusions We show that interaction-based simulation systems can be used to model disparate and highly relevant problems in biology. We also show that offloading some of the work to GPUs in distributed interaction-based simulations can be an effective way to achieve increased intra-node efficiency. PMID:22537298

Functional expression of the 11 human Organic Anion Transporting Polypeptides in insect cells reveals that sodium fluorescein is a general OATP substrate.

PubMed

Patik, Izabel; Kovacsics, Daniella; Német, Orsolya; Gera, Melinda; Várady, György; Stieger, Bruno; Hagenbuch, Bruno; Szakács, Gergely; Özvegy-Laczka, Csilla

2015-12-15

Organic Anion Transporting Polypeptides (OATPs), encoded by genes of the Solute Carrier Organic Anion (SLCO) family, are transmembrane proteins involved in the uptake of various compounds of endogenous or exogenous origin. In addition to their physiological roles, OATPs influence the pharmacokinetics and drug-drug interactions of several clinically relevant compounds. To examine the function and molecular interactions of human OATPs, including several poorly characterized family members, we expressed all 11 human OATPs at high levels in the baculovirus-Sf9 cell system. We measured the temperature- and inhibitor-sensitive cellular accumulation of sodium fluorescein and fluorescein-methotrexate, two fluorescent substrates of the OATPs, OATP1B1 and 1B3. OATP1B1 and 1B3 were functional in Sf9 cells, showing rapid uptake (t1/2(fluorescein-methotrexate) 2.64 and 4.16 min, and t1/2(fluorescein) 6.71 and 5.58 min for OATP1B1 and 1B3, respectively) and high-affinity transport (Km(fluorescein-methotrexate) 0.23 and 0.53 μM, and Km(fluorescein) 25.73 and 38.55 μM for OATP1B1 and 1B3, respectively) of both substrates. We found that sodium fluorescein is a general substrate of all human OATPs: 1A2, 1B1, 1B3, 1C1, 2A1, 2B1, 3A1, 4A1, 4C1, 5A1 and 6A1, while fluorescein-methotrexate is only transported by 1B1, 1B3, 1A2 and 2B1. Acidic extracellular pH greatly facilitated fluorescein uptake by all OATPs, and new molecular interactions were detected (between OATP2B1 and Imatinib, OATP3A1, 5A1 and 6A1 and estradiol 17-β-d-glucuronide, and OATP1C1 and 4C1 and prostaglandin E2). These studies demonstrate, for the first time, that the insect cell system is suitable for the functional analysis of the entire human OATP family, and for drug-OATP interaction screening. Copyright © 2015 Elsevier Inc. All rights reserved.

Open-Box Muscle-Computer Interface: Introduction to Human-Computer Interactions in Bioengineering, Physiology, and Neuroscience Courses

ERIC Educational Resources Information Center

Landa-Jiménez, M. A.; González-Gaspar, P.; Pérez-Estudillo, C.; López-Meraz, M. L.; Morgado-Valle, C.; Beltran-Parrazal, L.

2016-01-01

A Muscle-Computer Interface (muCI) is a human-machine system that uses electromyographic (EMG) signals to communicate with a computer. Surface EMG (sEMG) signals are currently used to command robotic devices, such as robotic arms and hands, and mobile robots, such as wheelchairs. These signals reflect the motor intention of a user before the…

[An interactive three-dimensional model of the human body].

PubMed

Liem, S L

2009-01-01

Driven by advanced computer technology, it is now possible to show the human anatomy on a computer. On the internet, the Visible Body programme makes it possible to navigate in all directions through the anatomical structures of the human body, using mouse and keyboard. Visible Body is a wonderful tool to give insight in the human structures, body functions and organs.

Recent technology products from Space Human Factors research

NASA Technical Reports Server (NTRS)

Jenkins, James P.

1991-01-01

The goals of the NASA Space Human Factors program and the research carried out concerning human factors are discussed with emphasis given to the development of human performance models, data, and tools. The major products from this program are described, which include the Laser Anthropometric Mapping System; a model of the human body for evaluating the kinematics and dynamics of human motion and strength in microgravity environment; an operational experience data base for verifying and validating the data repository of manned space flights; the Operational Experience Database Taxonomy; and a human-computer interaction laboratory whose products are the display softaware and requirements and the guideline documents and standards for applications on human-computer interaction. Special attention is given to the 'Convoltron', a prototype version of a signal processor for synthesizing the head-related transfer functions.

Interaction between serotonin transporter and dopamine D2/D3 receptor radioligand measures is associated with harm avoidant symptoms in anorexia and bulimia nervosa.

PubMed

Bailer, Ursula F; Frank, Guido K; Price, Julie C; Meltzer, Carolyn C; Becker, Carl; Mathis, Chester A; Wagner, Angela; Barbarich-Marsteller, Nicole C; Bloss, Cinnamon S; Putnam, Karen; Schork, Nicholas J; Gamst, Anthony; Kaye, Walter H

2013-02-28

Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) have alterations of measures of serotonin (5-HT) and dopamine (DA) function, which persist after long-term recovery and are associated with elevated harm avoidance (HA), a measure of anxiety and behavioral inhibition. Based on theories that 5-HT is an aversive motivational system that may oppose a DA-related appetitive system, we explored interactions of positron emission tomography (PET) radioligand measures that reflect portions of these systems. Twenty-seven individuals recovered (REC) from eating disorders (EDs) (7 AN-BN, 11 AN, 9 BN) and nine control women (CW) were analyzed for correlations between [(11)C]McN5652 and [(11)C]raclopride binding. There was a significant positive correlation between [(11)C]McN5652 binding potential (BP(non displaceable(ND))) and [(11)C]Raclopride BP(ND) for the dorsal caudate, antero-ventral striatum (AVS), middle caudate, and ventral and dorsal putamen. No significant correlations were found in CW. [(11)C]Raclopride BP(ND), but not [(11)C]McN5652 BP(ND), was significantly related to HA in REC EDs. A linear regression analysis showed that the interaction between [(11)C]McN5652 BP(ND) and [(11)C]raclopride BP(ND) in the dorsal putamen significantly predicted HA. This is the first study using PET and the radioligands [(11)C]McN5652 and [(11)C]raclopride to show a direct relationship between 5-HT transporter and striatal DA D2/D3 receptor binding in humans, supporting the possibility that 5-HT and DA interactions contribute to HA behaviors in EDs. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Neo-Symbiosis: The Next Stage in the Evolution of Human Information Interaction

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

Griffith, Douglas; Greitzer, Frank L.

Abstract--The purpose of this paper is to re-address the vision of human-computer symbiosis as originally expressed by J.C.R. Licklider nearly a half-century ago. We describe this vision, place it in some historical context relating to the evolution of human factors research, and we observe that the field is now in the process of re-invigorating Licklider’s vision. We briefly assess the state of the technology within the context of contemporary theory and practice, and we describe what we regard as this emerging field of neo-symbiosis. We offer some initial thoughts on requirements to define functionality of neo-symbiotic systems and discuss researchmore » challenges associated with their development and evaluation.« less

A Dual-Mode Human Computer Interface Combining Speech and Tongue Motion for People with Severe Disabilities

PubMed Central

Huo, Xueliang; Park, Hangue; Kim, Jeonghee; Ghovanloo, Maysam

2015-01-01

We are presenting a new wireless and wearable human computer interface called the dual-mode Tongue Drive System (dTDS), which is designed to allow people with severe disabilities to use computers more effectively with increased speed, flexibility, usability, and independence through their tongue motion and speech. The dTDS detects users’ tongue motion using a magnetic tracer and an array of magnetic sensors embedded in a compact and ergonomic wireless headset. It also captures the users’ voice wirelessly using a small microphone embedded in the same headset. Preliminary evaluation results based on 14 able-bodied subjects and three individuals with high level spinal cord injuries at level C3–C5 indicated that the dTDS headset, combined with a commercially available speech recognition (SR) software, can provide end users with significantly higher performance than either unimodal forms based on the tongue motion or speech alone, particularly in completing tasks that require both pointing and text entry. PMID:23475380

Casein kinase 2 promotes interaction between Rad17 and the 9-1-1 complex through constitutive phosphorylation of the C-terminal tail of human Rad17.

PubMed

Fukumoto, Yasunori; Takahashi, Kazuaki; Suzuki, Noriyuki; Ogra, Yasumitsu; Nakayama, Yuji; Yamaguchi, Naoto

2018-06-15

An interaction between the Rad17-RFC2-5 and 9-1-1 complexes is essential for ATR-Chk1 signaling, which is one of the major DNA damage checkpoints. Recently, we showed that the polyanionic C-terminal tail of human Rad17 and the embedded conserved sequence iVERGE are important for the interaction with 9-1-1 complex. Here, we show that Rad17-S667 in the C-terminal tail is constitutively phosphorylated in vivo in a casein kinase 2-dependent manner, and the phosphorylation is important for 9-1-1 interaction. The serine phosphorylation of Rad17 could be seen in the absence of exogenous genotoxic stress, and was mostly abolished by S667A substitution. Rad17-S667 was also phosphorylated when the C-terminal tail was fused with EGFP, but the phosphorylation was inhibited by two casein kinase 2 inhibitors. Furthermore, interaction between Rad17 and the 9-1-1 complex was inhibited by the casein kinase 2 inhibitor CX-4945/Silmitasertib, and the effect was dependent on the Rad17-S667 residue, indicating that S667 phosphorylation is the only role of casein kinase 2 in the 9-1-1 interaction. Our data raise the possibility that the C-terminal tail of vertebrate Rad17 regulates ATR-Chk1 signaling through multi-site phosphorylation in the iVERGE. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Synthesis, characterization and computational study of the newly synthetized sulfonamide molecule

NASA Astrophysics Data System (ADS)

Murthy, P. Krishna; Suneetha, V.; Armaković, Stevan; Armaković, Sanja J.; Suchetan, P. A.; Giri, L.; Rao, R. Sreenivasa

2018-02-01

A new compound N-(2,5-dimethyl-4-nitrophenyl)-4-methylbenzenesulfonamide (NDMPMBS) has been derived from 2,5-dimethyl-4-nitroaniline and 4-methylbenzene-1-sulfonyl chloride. Structure was characterized by SCXRD studies and spectroscopic tools. Compound crystallized in the monoclinic crystal system with P21/c space group a = 10.0549, b = 18.967, c = 8.3087, β = 103.18 and Z = 4. Type and nature of intermolecular interaction in crystal state investigated by 3D-Hirshfeld surface and 2D-finger print plots revealed that title compound stabilized by several interactions. The structural and electronic properties of title compound have been calculated at DFT/B3LYP/6-311G++(d,p) level of theory. Computationally obtained spectral data was compared with experimental results, showing excellent mutual agreement. Assignment of each vibrational wave number was done on the basis of potential energy distribution (PED). Investigation of local reactivity descriptors encompassed visualization of molecular electrostatic potential (MEP) and average local ionization energy (ALIE) surfaces, visualization of Fukui functions, natural bond order (NBO) analysis, bond dissociation energies for hydrogen abstraction (H-BDE) and radial distribution functions (RDF) after molecular dynamics (MD) simulations. MD simulations were also used in order to investigate interaction of NDMPMBS molecule with 1WKR and 3ETT proteins protein.

Serum Albumin Domain Structures in Human Blood Serum by Mass Spectrometry and Computational Biology.

PubMed

Belsom, Adam; Schneider, Michael; Fischer, Lutz; Brock, Oliver; Rappsilber, Juri

2016-03-01

Chemical cross-linking combined with mass spectrometry has proven useful for studying protein-protein interactions and protein structure, however the low density of cross-link data has so far precluded its use in determining structures de novo. Cross-linking density has been typically limited by the chemical selectivity of the standard cross-linking reagents that are commonly used for protein cross-linking. We have implemented the use of a heterobifunctional cross-linking reagent, sulfosuccinimidyl 4,4'-azipentanoate (sulfo-SDA), combining a traditional sulfo-N-hydroxysuccinimide (sulfo-NHS) ester and a UV photoactivatable diazirine group. This diazirine yields a highly reactive and promiscuous carbene species, the net result being a greatly increased number of cross-links compared with homobifunctional, NHS-based cross-linkers. We present a novel methodology that combines the use of this high density photo-cross-linking data with conformational space search to investigate the structure of human serum albumin domains, from purified samples, and in its native environment, human blood serum. Our approach is able to determine human serum albumin domain structures with good accuracy: root-mean-square deviation to crystal structure are 2.8/5.6/2.9 Å (purified samples) and 4.5/5.9/4.8Å (serum samples) for domains A/B/C for the first selected structure; 2.5/4.9/2.9 Å (purified samples) and 3.5/5.2/3.8 Å (serum samples) for the best out of top five selected structures. Our proof-of-concept study on human serum albumin demonstrates initial potential of our approach for determining the structures of more proteins in the complex biological contexts in which they function and which they may require for correct folding. Data are available via ProteomeXchange with identifier PXD001692. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

An Affordance-Based Framework for Human Computation and Human-Computer Collaboration.

PubMed

Crouser, R J; Chang, R

2012-12-01

Visual Analytics is "the science of analytical reasoning facilitated by visual interactive interfaces". The goal of this field is to develop tools and methodologies for approaching problems whose size and complexity render them intractable without the close coupling of both human and machine analysis. Researchers have explored this coupling in many venues: VAST, Vis, InfoVis, CHI, KDD, IUI, and more. While there have been myriad promising examples of human-computer collaboration, there exists no common language for comparing systems or describing the benefits afforded by designing for such collaboration. We argue that this area would benefit significantly from consensus about the design attributes that define and distinguish existing techniques. In this work, we have reviewed 1,271 papers from many of the top-ranking conferences in visual analytics, human-computer interaction, and visualization. From these, we have identified 49 papers that are representative of the study of human-computer collaborative problem-solving, and provide a thorough overview of the current state-of-the-art. Our analysis has uncovered key patterns of design hinging on human and machine-intelligence affordances, and also indicates unexplored avenues in the study of this area. The results of this analysis provide a common framework for understanding these seemingly disparate branches of inquiry, which we hope will motivate future work in the field.

A model of cerebrocerebello-spinomuscular interaction in the sagittal control of human walking.

PubMed

Jo, Sungho; Massaquoi, Steve G

2007-03-01

A computationally developed model of human upright balance control (Jo and Massaquoi on Biol cybern 91:188-202, 2004) has been enhanced to describe biped walking in the sagittal plane. The model incorporates (a) non-linear muscle mechanics having activation level -dependent impedance, (b) scheduled cerebrocerebellar interaction for control of center of mass position and trunk pitch angle, (c) rectangular pulse-like feedforward commands from a brainstem/ spinal pattern generator, and (d) segmental reflex modulation of muscular synergies to refine inter-joint coordination. The model can stand when muscles around the ankle are coactivated. When trigger signals activate, the model transitions from standing still to walking at 1.5 m/s. Simulated natural walking displays none of seven pathological gait features. The model can simulate different walking speeds by tuning the amplitude and frequency in spinal pattern generator. The walking is stable against forward and backward pushes of up to 70 and 75 N, respectively, and with sudden changes in trunk mass of up to 18%. The sensitivity of the model to changes in neural parameters and the predicted behavioral results of simulated neural system lesions are examined. The deficit gait simulations may be useful to support the functional and anatomical correspondences of the model. The model demonstrates that basic human-like walking can be achieved by a hierarchical structure of stabilized-long loop feedback and synergy-mediated feedforward controls. In particular, internal models of body dynamics are not required.

Computer-assisted 3D design software for teaching neuro-ophthalmology of the oculomotor system and training new retinal surgery techniques

NASA Astrophysics Data System (ADS)

Glittenberg, Carl; Binder, Susanne

2004-07-01

Purpose: To create a more effective method of demonstrating complex subject matter in ophthalmology with the use of high end, 3-D, computer aided animation and interactive multimedia technologies. Specifically, to explore the possibilities of demonstrating the complex nature of the neuroophthalmological basics of the human oculomotor system in a clear and non confusing way, and to demonstrate new forms of retinal surgery in a manner that makes the procedures easier to understand for other retinal surgeons. Methods and Materials: Using Reflektions 4.3, Monzoom Pro 4.5, Cinema 4D XL 5.03, Cinema 4D XL 8 Studio Bundle, Mediator 4.0, Mediator Pro 5.03, Fujitsu-Siemens Pentium III and IV, Gericom Webgine laptop, M.G.I. Video Wave 1.0 and 5, Micrografix Picture Publisher 6.0 and 8, Amorphium 1.0, and Blobs for Windows, we created 3-D animations showing the origin, insertion, course, main direction of pull, and auxiliary direction of pull of the six extra-ocular eye muscles. We created 3-D animations that (a) show the intra-cranial path of the relevant oculomotor cranial nerves and which muscles are supplied by them, (b) show which muscles are active in each of the ten lines of sight, (c) demonstrate the various malfunctions of oculomotor systems, as well as (d) show the surgical techniques and the challenges in radial optic neurotomies and subretinal surgeries. Most of the 3-D animations were integrated in interactive multimedia teaching programs. Their effectiveness was compared to conventional teaching methods in a comparative study performed at the University of Vienna. We also performed a survey to examine the response of students being taught with the interactive programs. We are currently in the process of placing most of the animations in an interactive web site in order to make them freely available to everyone who is interested. Results: Although learning how to use complex 3-D computer animation and multimedia authoring software can be very time consuming and frustrating, we found that once the programs are mastered they can be used to create 3-D animations that drastically improve the quality of medical demonstrations. The comparative study showed a significant advantage of using these technologies over conventional teaching methods. The feedback from medical students, doctors, and retinal surgeons was overwhelmingly positive. A strong interest was expressed to have more subjects and techniques demonstrated in this fashion. Conclusion: 3-D computer technologies should be used in the demonstration of all complex medical subjects. More effort and resources need to be given to the development of these technologies that can improve the understanding of medicine for students, doctors, and patients alike.

Identification of conformational epitopes for human IgG on Chemotaxis inhibitory protein of Staphylococcus aureus

PubMed Central

Gustafsson, Erika; Haas, Pieter-Jan; Walse, Björn; Hijnen, Marcel; Furebring, Christina; Ohlin, Mats; van Strijp, Jos AG; van Kessel, Kok PM

2009-01-01

Background The Chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) blocks the Complement fragment C5a receptor (C5aR) and formylated peptide receptor (FPR) and is thereby a potent inhibitor of neutrophil chemotaxis and activation of inflammatory responses. The majority of the healthy human population has antibodies against CHIPS that have been shown to interfere with its function in vitro. The aim of this study was to define potential epitopes for human antibodies on the CHIPS surface. We also initiate the process to identify a mutated CHIPS molecule that is not efficiently recognized by preformed anti-CHIPS antibodies and retains anti-inflammatory activity. Results In this paper, we panned peptide displaying phage libraries against a pool of CHIPS specific affinity-purified polyclonal human IgG. The selected peptides could be divided into two groups of sequences. The first group was the most dominant with 36 of the 48 sequenced clones represented. Binding to human affinity-purified IgG was verified by ELISA for a selection of peptide sequences in phage format. For further analysis, one peptide was chemically synthesized and antibodies affinity-purified on this peptide were found to bind the CHIPS molecule as studied by ELISA and Surface Plasmon Resonance. Furthermore, seven potential conformational epitopes responsible for antibody recognition were identified by mapping phage selected peptide sequences on the CHIPS surface as defined in the NMR structure of the recombinant CHIPS31–121 protein. Mapped epitopes were verified by in vitro mutational analysis of the CHIPS molecule. Single mutations introduced in the proposed antibody epitopes were shown to decrease antibody binding to CHIPS. The biological function in terms of C5aR signaling was studied by flow cytometry. A few mutations were shown to affect this biological function as well as the antibody binding. Conclusion Conformational epitopes recognized by human antibodies have been mapped on the CHIPS surface and amino acid residues involved in both antibody and C5aR interaction could be defined. This information has implications for the development of an effective anti-inflammatory agent based on a functional CHIPS molecule with low interaction with human IgG. PMID:19284584

Computational design of protein antigens that interact with the CDR H3 loop of HIV broadly neutralizing antibody 2F5.

PubMed

Azoitei, M L; Ban, Y A; Kalyuzhny, O; Guenaga, J; Schroeter, A; Porter, J; Wyatt, R; Schief, William R

2014-10-01

Rational design of proteins with novel binding specificities and increased affinity is one of the major goals of computational protein design. Epitope-scaffolds are a new class of antigens engineered by transplanting viral epitopes of predefined structure to protein scaffolds, or by building protein scaffolds around such epitopes. Epitope-scaffolds are of interest as vaccine components to attempt to elicit neutralizing antibodies targeting the specified epitope. In this study we developed a new computational protocol, MultiGraft Interface, that transplants epitopes but also designs additional scaffold features outside the epitope to enhance antibody-binding specificity and potentially influence the specificity of elicited antibodies. We employed MultiGraft Interface to engineer novel epitope-scaffolds that display the known epitope of human immunodeficiency virus 1 (HIV-1) neutralizing antibody 2F5 and that also interact with the functionally important CDR H3 antibody loop. MultiGraft Interface generated an epitope-scaffold that bound 2F5 with subnanomolar affinity (K(D) = 400 pM) and that interacted with the antibody CDR H3 loop through computationally designed contacts. Substantial structural modifications were necessary to engineer this antigen, with the 2F5 epitope replacing a helix in the native scaffold and with 15% of the native scaffold sequence being modified in the design stage. This epitope-scaffold represents a successful example of rational protein backbone engineering and protein-protein interface design and could prove useful in the field of HIV vaccine design. MultiGraft Interface can be generally applied to engineer novel binding partners with altered specificity and optimized affinity. © 2014 Wiley Periodicals, Inc.

Projecting Grammatical Features in Nominals: Cognitive Processing Theory & Computational Implementation

DTIC Science & Technology

2010-03-01

functionality and plausibility distinguishes this research from most research in computational linguistics and computational psycholinguistics . The... Psycholinguistic Theory There is extensive psycholinguistic evidence that human language processing is essentially incremental and interactive...challenges of psycholinguistic research is to explain how humans can process language effortlessly and accurately given the complexity and ambiguity that is

Assessing the Purpose and Importance University Students Attribute to Current ICT Applications

ERIC Educational Resources Information Center

DiGiuseppe, Maurice; Partosoedarso, Elita

2014-01-01

In this study we surveyed students in a mid-sized university in Ontario, Canada to explore various aspects associated with their use of computer-based applications. For the purpose of analysis, the computer applications under study were categorized according to the Human-Computer-Human Interaction (HCHI) model of Desjardins (2005) in which…

Glucocorticoid receptor gene expression and promoter CpG modifications throughout the human brain.

PubMed

Cao-Lei, Lei; Suwansirikul, Songkiet; Jutavijittum, Prapan; Mériaux, Sophie B; Turner, Jonathan D; Muller, Claude P

2013-11-01

Glucocorticoids and the glucocorticoid (GR) and mineralocorticoid (MR) receptors have been implicated in many processes, particularly in negative feedback regulation of the hypothalamic-pituitary-adrenal axis. Epigenetically programmed GR alternative promoter usage underlies transcriptional control of GR levels, generation of GR 3' splice variants, and the overall GC response in the brain. No detailed analysis of GR first exons or GR transcript variants throughout the human brain has been reported. Therefore we investigated post mortem tissues from 28 brain regions of 5 individuals. GR first exons were expressed throughout the healthy human brain with no region-specific usage patterns. First exon levels were highly inter-correlated suggesting that they are co-regulated. GR 3' splice variants (GRα and GR-P) were equally distributed in all regions, and GRβ expression was always low. GR/MR ratios showed significant differences between the 28 tissues with the highest ratio in the pituitary gland. Modification levels of individual CpG dinucleotides, including 5-mC and 5-hmC, in promoters 1D, 1E, 1F, and 1H were low, and diffusely clustered; despite significant heterogeneity between the donors. In agreement with this clustering, sum modification levels rather than individual CpG modifications correlated with GR expression. Two-way ANOVA showed that this sum modification was both promoter and brain region specific, but that there was however no promoter*tissue interaction. The heterogeneity between donors may however hide such an interaction. In both promoters 1F and 1H modification levels correlated with GRα expression suggesting that 5-mC and 5-hmC play an important role in fine tuning GR expression levels throughout the brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Metabolism of a 5HT6 antagonist, 2-methyl-1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-benzo[d]imidazole (SAM-760): impact of sulfonamide metabolism on diminution of a ketoconazole mediated clinical drug-drug interaction.

PubMed

Sawant-Basak, Aarti; Obach, R Scott; Doran, Angela C; Lockwood, Peter; Schildknegt, Klaas; Gao, Hongying; Mancuso, Jessica; Tse, Susanna; Comery, Tom

2018-04-25

SAM-760, (2-methyl-1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-benzo[d]imidazole), a 5HT 6 antagonist, was investigated in humans for the treatment of Alzheimer's dementia. In liver microsomes and recombinant CYP450 isozymes, SAM-760 was predominantly metabolized by CYP3A (~85%). Based on these observations and an expectation of 5-fold magnitude of interaction with moderate to strong CYP3A inhibitors, a clinical DDI study was performed. In presence of ketoconazole, mean C max and AUC 0-inf of SAM-760 showed only a modest increase by 30% and 38%, respectively. In vitro investigation of this unexpectedly low interaction was undertaken using [ 14 C]SAM-760. Radiometric profiling in human hepatocytes, confirmed all oxidative metabolites observed previously with unlabeled SAM-760; however the pre-dominant radiometric peak was an unexpected polar metabolite which was insensitive to pan-CYP inhibitor, 1-aminobenzotriazole. In human hepatocytes, radiometric integration attributed 43% of total metabolism of SAM-760 to this non-CYP pathway. Using an authentic standard, this predominant metabolite was confirmed as benzenesulfinic acid. Additional investigation revealed that the benzenesulfinic acid metabolite may be a novel, non-enzymatic, thiol mediated reductive cleavage of aryl sulfonamide group of SAM-760. We also determined the relative contribution of P450 to metabolism of SAM-760 in human hepatocytes, by following the rate of formation of oxidative metabolites in presence and absence of P450 isoform specific inhibitors. P450 mediated oxidative metabolism of SAM-760 was still primarily attributed to CYP3A (33%), with minor contributions from CYP isoforms 2C19 and 2D6. Thus, disposition of [ 14 C]SAM-760 in human hepatocytes via novel sulfonamide metabolism and CYP3A verified the lower than expected clinical DDI when SAM-760 was co-administered with ketoconazole. The American Society for Pharmacology and Experimental Therapeutics.

Interaction of Human Cytomegalovirus Tegument Proteins ppUL35 and ppUL35A with Sorting Nexin 5 Regulates Glycoprotein B (gpUL55) Localization.

PubMed

Maschkowitz, Gregor; Gärtner, Sabine; Hofmann-Winkler, Heike; Fickenscher, Helmut; Winkler, Michael

2018-05-01

Human cytomegalovirus (HCMV) is a widespread human pathogen that causes asymptomatic infection in healthy individuals but poses a serious threat to immunocompromised patients. During the late phase of HCMV infection, the viral capsid is transported to the cytoplasmic viral assembly center (cVAC), where it is enclosed by the tegument protein layer and the viral envelope. The cVAC consists of circularly arranged vesicles from the trans -Golgi and endosomal networks. The HCMV gene UL35 encodes ppUL35 and its shorter form, ppUL35A. We have previously shown that the UL35 gene is involved in HCMV assembly, but it is unknown how UL35 proteins regulate viral assembly. Here we show that sorting nexin 5 (SNX5), a component of the retromer and part of the retrograde transport pathway, interacts with UL35 proteins. Expression of wild-type proteins but not mutants defective in SNX5 binding resulted in the cellular redistribution of the cation-independent mannose-6-phosphate receptor (CI-M6PR), indicating that UL35 proteins bind and negatively regulate SNX5 to modulate cellular transport pathways. Furthermore, binding of UL35 proteins to SNX5 was required for efficient viral replication and for transport of the most abundant HCMV glycoprotein B (gB; gpUL55) to the cVAC. These results indicate that ppUL35 and ppUL35A control the localization of the essential gB through the regulation of a retrograde transport pathway. Thus, this work is the first to define a molecular interaction between a tegument protein and a vesicular transport factor to regulate glycoprotein localization. IMPORTANCE Human cytomegalovirus is ubiquitously present in the healthy population, but reactivation or reinfection can cause serious, life-threatening infections in immunocompromised patients. For completion of its lytic cycle, human cytomegalovirus induces formation of an assembly center where mature virus particles are formed from multiple viral proteins. Viral glycoproteins use separate vesicular pathways for transport to the assembly center, which are incompletely understood. Our research identified a viral structural protein which affects the localization of one of the major glycoproteins. We could link this change in glycoprotein localization to an interaction of the structural protein with a cellular protein involved in regulation of vesicle transport. This increases our understanding of how the virus intersects into cellular regulatory pathways to enhance its own replication. Copyright © 2018 American Society for Microbiology.

Definition Of Touch-Sensitive Zones For Graphical Displays

NASA Technical Reports Server (NTRS)

Monroe, Burt L., III; Jones, Denise R.

1988-01-01

Touch zones defined simply by touching, while editing done automatically. Development of touch-screen interactive computing system, tedious task. Interactive Editor for Definition of Touch-Sensitive Zones computer program increases efficiency of human/machine communications by enabling user to define each zone interactively, minimizing redundancy in programming and eliminating need for manual computation of boundaries of touch areas. Information produced during editing process written to data file, to which access gained when needed by application program.

Intelligence for Human-Assistant Planetary Surface Robots

NASA Technical Reports Server (NTRS)

Hirsh, Robert; Graham, Jeffrey; Tyree, Kimberly; Sierhuis, Maarten; Clancey, William J.

2006-01-01

The central premise in developing effective human-assistant planetary surface robots is that robotic intelligence is needed. The exact type, method, forms and/or quantity of intelligence is an open issue being explored on the ERA project, as well as others. In addition to field testing, theoretical research into this area can help provide answers on how to design future planetary robots. Many fundamental intelligence issues are discussed by Murphy [2], including (a) learning, (b) planning, (c) reasoning, (d) problem solving, (e) knowledge representation, and (f) computer vision (stereo tracking, gestures). The new "social interaction/emotional" form of intelligence that some consider critical to Human Robot Interaction (HRI) can also be addressed by human assistant planetary surface robots, as human operators feel more comfortable working with a robot when the robot is verbally (or even physically) interacting with them. Arkin [3] and Murphy are both proponents of the hybrid deliberative-reasoning/reactive-execution architecture as the best general architecture for fully realizing robot potential, and the robots discussed herein implement a design continuously progressing toward this hybrid philosophy. The remainder of this chapter will describe the challenges associated with robotic assistance to astronauts, our general research approach, the intelligence incorporated into our robots, and the results and lessons learned from over six years of testing human-assistant mobile robots in field settings relevant to planetary exploration. The chapter concludes with some key considerations for future work in this area.

Potentiation of C1-esterase inhibitor by heparin and interactions with C1s protease as assessed by surface plasmon resonance.

PubMed

Rajabi, Mohsen; Struble, Evi; Zhou, Zhaohua; Karnaukhova, Elena

2012-01-01

Human C1-esterase inhibitor (C1-INH) is a multifunctional plasma protein with a wide range of inhibitory and non-inhibitory properties, mainly recognized as a key down-regulator of the complement and contact cascades. The potentiation of C1-INH by heparin and other glycosaminoglycans (GAGs) regulates a broad spectrum of C1-INH activities in vivo both in normal and disease states. SCOPE OF RESEARCH: We have studied the potentiation of human C1-INH by heparin using Surface Plasmon Resonance (SPR), circular dichroism (CD) and a functional assay. To advance a SPR for multiple-unit interaction studies of C1-INH we have developed a novel (consecutive double capture) approach exploring different immobilization and layout. Our SPR experiments conducted in three different design versions showed marked acceleration in C1-INH interactions with complement protease C1s as a result of potentiation of C1-INH by heparin (from 5- to 11-fold increase of the association rate). Far-UV CD studies suggested that heparin binding did not alter C1-INH secondary structure. Functional assay using chromogenic substrate confirmed that heparin does not affect the amidolytic activity of C1s, but does accelerate its consumption due to C1-INH potentiation. This is the first report that directly demonstrates a significant acceleration of the C1-INH interactions with C1s due to heparin by using a consecutive double capture SPR approach. The results of this study may be useful for further C-INH therapeutic development, ultimately for the enhancement of current C1-INH replacement therapies. Published by Elsevier B.V.

Insights into eukaryotic DNA priming from the structure and functional interactions of the 4Fe-4S cluster domain of human DNA primase

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

Vaithiyalingam, Sivaraja; Warren, Eric M.; Eichman, Brandt F.

2010-10-19

DNA replication requires priming of DNA templates by enzymes known as primases. Although DNA primase structures are available from archaea and bacteria, the mechanism of DNA priming in higher eukaryotes remains poorly understood in large part due to the absence of the structure of the unique, highly conserved C-terminal regulatory domain of the large subunit (p58C). Here, we present the structure of this domain determined to 1.7-{angstrom} resolution by X-ray crystallography. The p58C structure reveals a novel arrangement of an evolutionarily conserved 4Fe-4S cluster buried deeply within the protein core and is not similar to any known protein structure. Analysismore » of the binding of DNA to p58C by fluorescence anisotropy measurements revealed a strong preference for ss/dsDNA junction substrates. This approach was combined with site-directed mutagenesis to confirm that the binding of DNA occurs to a distinctively basic surface on p58C. A specific interaction of p58C with the C-terminal domain of the intermediate subunit of replication protein A (RPA32C) was identified and characterized by isothermal titration calorimetry and NMR. Restraints from NMR experiments were used to drive computational docking of the two domains and generate a model of the p58C-RPA32C complex. Together, our results explain functional defects in human DNA primase mutants and provide insights into primosome loading on RPA-coated ssDNA and regulation of primase activity.« less

Human computer interface guide, revision A

NASA Technical Reports Server (NTRS)

1993-01-01

The Human Computer Interface Guide, SSP 30540, is a reference document for the information systems within the Space Station Freedom Program (SSFP). The Human Computer Interface Guide (HCIG) provides guidelines for the design of computer software that affects human performance, specifically, the human-computer interface. This document contains an introduction and subparagraphs on SSFP computer systems, users, and tasks; guidelines for interactions between users and the SSFP computer systems; human factors evaluation and testing of the user interface system; and example specifications. The contents of this document are intended to be consistent with the tasks and products to be prepared by NASA Work Package Centers and SSFP participants as defined in SSP 30000, Space Station Program Definition and Requirements Document. The Human Computer Interface Guide shall be implemented on all new SSFP contractual and internal activities and shall be included in any existing contracts through contract changes. This document is under the control of the Space Station Control Board, and any changes or revisions will be approved by the deputy director.

Quadcopter control in three-dimensional space using a noninvasive motor imagery-based brain-computer interface

NASA Astrophysics Data System (ADS)

LaFleur, Karl; Cassady, Kaitlin; Doud, Alexander; Shades, Kaleb; Rogin, Eitan; He, Bin

2013-08-01

Objective. At the balanced intersection of human and machine adaptation is found the optimally functioning brain-computer interface (BCI). In this study, we report a novel experiment of BCI controlling a robotic quadcopter in three-dimensional (3D) physical space using noninvasive scalp electroencephalogram (EEG) in human subjects. We then quantify the performance of this system using metrics suitable for asynchronous BCI. Lastly, we examine the impact that the operation of a real world device has on subjects' control in comparison to a 2D virtual cursor task. Approach. Five human subjects were trained to modulate their sensorimotor rhythms to control an AR Drone navigating a 3D physical space. Visual feedback was provided via a forward facing camera on the hull of the drone. Main results. Individual subjects were able to accurately acquire up to 90.5% of all valid targets presented while travelling at an average straight-line speed of 0.69 m s-1. Significance. Freely exploring and interacting with the world around us is a crucial element of autonomy that is lost in the context of neurodegenerative disease. Brain-computer interfaces are systems that aim to restore or enhance a user's ability to interact with the environment via a computer and through the use of only thought. We demonstrate for the first time the ability to control a flying robot in 3D physical space using noninvasive scalp recorded EEG in humans. Our work indicates the potential of noninvasive EEG-based BCI systems for accomplish complex control in 3D physical space. The present study may serve as a framework for the investigation of multidimensional noninvasive BCI control in a physical environment using telepresence robotics.

Quadcopter control in three-dimensional space using a noninvasive motor imagery-based brain-computer interface.

PubMed

LaFleur, Karl; Cassady, Kaitlin; Doud, Alexander; Shades, Kaleb; Rogin, Eitan; He, Bin

2013-08-01

At the balanced intersection of human and machine adaptation is found the optimally functioning brain-computer interface (BCI). In this study, we report a novel experiment of BCI controlling a robotic quadcopter in three-dimensional (3D) physical space using noninvasive scalp electroencephalogram (EEG) in human subjects. We then quantify the performance of this system using metrics suitable for asynchronous BCI. Lastly, we examine the impact that the operation of a real world device has on subjects' control in comparison to a 2D virtual cursor task. Five human subjects were trained to modulate their sensorimotor rhythms to control an AR Drone navigating a 3D physical space. Visual feedback was provided via a forward facing camera on the hull of the drone. Individual subjects were able to accurately acquire up to 90.5% of all valid targets presented while travelling at an average straight-line speed of 0.69 m s(-1). Freely exploring and interacting with the world around us is a crucial element of autonomy that is lost in the context of neurodegenerative disease. Brain-computer interfaces are systems that aim to restore or enhance a user's ability to interact with the environment via a computer and through the use of only thought. We demonstrate for the first time the ability to control a flying robot in 3D physical space using noninvasive scalp recorded EEG in humans. Our work indicates the potential of noninvasive EEG-based BCI systems for accomplish complex control in 3D physical space. The present study may serve as a framework for the investigation of multidimensional noninvasive BCI control in a physical environment using telepresence robotics.

Interpersonal Biocybernetics: Connecting Through Social Psychophysiology

NASA Technical Reports Server (NTRS)

Pope, Alan T.; Stephens, Chad L.

2012-01-01

One embodiment of biocybernetic adaptation is a human-computer interaction system designed such that physiological signals modulate the effect that control of a task by other means, usually manual control, has on performance of the task. Such a modulation system enables a variety of human-human interactions based upon physiological self-regulation performance. These interpersonal interactions may be mixes of competition and cooperation for simulation training and/or videogame entertainment

An Empirical Study of User Experience on Touch Mice

ERIC Educational Resources Information Center

Chou, Jyh Rong

2016-01-01

The touch mouse is a new type of computer mouse that provides users with a new way of touch-based environment to interact with computers. For more than a decade, user experience (UX) has grown into a core concept of human-computer interaction (HCI), describing a user's perceptions and responses that result from the use of a product in a particular…

Binding of ring-substituted indole-3-acetic acids to human serum albumin.

PubMed

Soskić, Milan; Magnus, Volker

2007-07-01

The plant hormone, indole-3-acetic acid (IAA), and its ring-substituted derivatives have recently attracted attention as promising pro-drugs in cancer therapy. Here we present relative binding constants to human serum albumin for IAA and 34 of its derivatives, as obtained using the immobilized protein bound to a support suitable for high-performance liquid chromatography. We also report their octanol-water partition coefficients (logK(ow)) computed from retention data on a C(18) coated silica gel column. A four-parameter QSPR (quantitative structure-property relationships) model, based on physico-chemical properties, is put forward, which accounts for more than 96% of the variations in the binding affinities of these compounds. The model confirms the importance of lipophilicity as a global parameter governing interaction with serum albumin, but also assigns significant roles to parameters specifically related to the molecular topology of ring-substituted IAAs. Bulky substituents at ring-position 6 increase affinity, those at position 2 obstruct binding, while no steric effects were noted at other ring-positions. Electron-withdrawing substituents at position 5 enhance binding, but have no obvious effect at other ring positions.

Getting seamless care right from the beginning - integrating computers into the human interaction.

PubMed

Pearce, Christopher; Kumarpeli, Pushpa; de Lusignan, Simon

2010-01-01

The digital age is coming to the health space, behind many other fields of society. In part this is because health remains heavily reliant on human interaction. The doctor-patient relationship remains a significant factor in determining patient outcomes. Whilst there are many benefits to E-Health, there are also significant risks if computers are not adequately integrated into this interaction and accurate data are consequently not available on the patient's journey through the health system. Video analysis of routine clinical consultations in Australian and UK primary care. We analyzed 308 consultations (141+167 respectively) from these systems, with an emphasis on how the consultation starts. Australian consultations have a mean duration of 12.7 mins, UK 11.8 mins. In both countries around 7% of consultations are computer initiated. Where doctors engaged with computer use the patient observed the computer screen much more and better records were produced. However, there was suboptimal engagement and poor records and no coding in around 20% of consultations. How the computer is used at the start of the consultation can set the scene for an effective interaction or reflect disengagement from technology and creation of poor records.

A roadmap to computational social neuroscience.

PubMed

Tognoli, Emmanuelle; Dumas, Guillaume; Kelso, J A Scott

2018-02-01

To complement experimental efforts toward understanding human social interactions at both neural and behavioral levels, two computational approaches are presented: (1) a fully parameterizable mathematical model of a social partner, the Human Dynamic Clamp which, by virtue of experimentally controlled interactions between Virtual Partners and real people, allows for emergent behaviors to be studied; and (2) a multiscale neurocomputational model of social coordination that enables exploration of social self-organization at all levels-from neuronal patterns to people interacting with each other. These complementary frameworks and the cross product of their analysis aim at understanding the fundamental principles governing social behavior.

Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human cells

NASA Technical Reports Server (NTRS)

Wiese, Claudia; Collins, David W.; Albala, Joanna S.; Thompson, Larry H.; Kronenberg, Amy; Schild, David; Chatterjee, A. (Principal Investigator)

2002-01-01

Homologous recombinational repair of DNA double-strand breaks and crosslinks in human cells is likely to require Rad51 and the five Rad51 paralogs (XRCC2, XRCC3, Rad51B/Rad51L1, Rad51C/Rad51L2 and Rad51D/Rad51L3), as has been shown in chicken and rodent cells. Previously, we reported on the interactions among these proteins using baculovirus and two- and three-hybrid yeast systems. To test for interactions involving XRCC3 and Rad51C, stable human cell lines have been isolated that express (His)6-tagged versions of XRCC3 or Rad51C. Ni2+-binding experiments demonstrate that XRCC3 and Rad51C interact in human cells. In addition, we find that Rad51C, but not XRCC3, interacts directly or indirectly with Rad51B, Rad51D and XRCC2. These results argue that there are at least two complexes of Rad51 paralogs in human cells (Rad51C-XRCC3 and Rad51B-Rad51C-Rad51D-XRCC2), both containing Rad51C. Moreover, Rad51 is not found in these complexes. X-ray treatment did not alter either the level of any Rad51 paralog or the observed interactions between paralogs. However, the endogenous level of Rad51C is moderately elevated in the XRCC3-overexpressing cell line, suggesting that dimerization between these proteins might help stabilize Rad51C.

A computer program incorporating Pitzer's equations for calculation of geochemical reactions in brines

USGS Publications Warehouse

Plummer, Niel; Parkhurst, D.L.; Fleming, G.W.; Dunkle, S.A.

1988-01-01

The program named PHRQPITZ is a computer code capable of making geochemical calculations in brines and other electrolyte solutions to high concentrations using the Pitzer virial-coefficient approach for activity-coefficient corrections. Reaction-modeling capabilities include calculation of (1) aqueous speciation and mineral-saturation index, (2) mineral solubility, (3) mixing and titration of aqueous solutions, (4) irreversible reactions and mineral water mass transfer, and (5) reaction path. The computed results for each aqueous solution include the osmotic coefficient, water activity , mineral saturation indices, mean activity coefficients, total activity coefficients, and scale-dependent values of pH, individual-ion activities and individual-ion activity coeffients , and scale-dependent values of pH, individual-ion activities and individual-ion activity coefficients. A data base of Pitzer interaction parameters is provided at 25 C for the system: Na-K-Mg-Ca-H-Cl-SO4-OH-HCO3-CO3-CO2-H2O, and extended to include largely untested literature data for Fe(II), Mn(II), Sr, Ba, Li, and Br with provision for calculations at temperatures other than 25C. An extensive literature review of published Pitzer interaction parameters for many inorganic salts is given. Also described is an interactive input code for PHRQPITZ called PITZINPT. (USGS)

Assessing collaborative computing: development of the Collaborative-Computing Observation Instrument (C-COI)

NASA Astrophysics Data System (ADS)

Israel, Maya; Wherfel, Quentin M.; Shehab, Saadeddine; Ramos, Evan A.; Metzger, Adam; Reese, George C.

2016-07-01

This paper describes the development, validation, and uses of the Collaborative Computing Observation Instrument (C-COI), a web-based analysis instrument that classifies individual and/or collaborative behaviors of students during computing problem-solving (e.g. coding, programming). The C-COI analyzes data gathered through video and audio screen recording software that captures students' computer screens as they program, and their conversations with their peers or adults. The instrument allows researchers to organize and quantify these data to track behavioral patterns that could be further analyzed for deeper understanding of persistence and/or collaborative interactions. The article provides a rationale for the C-COI including the development of a theoretical framework for measuring collaborative interactions in computer-mediated environments. This theoretical framework relied on the computer-supported collaborative learning literature related to adaptive help seeking, the joint problem-solving space in which collaborative computing occurs, and conversations related to outcomes and products of computational activities. Instrument development and validation also included ongoing advisory board feedback from experts in computer science, collaborative learning, and K-12 computing as well as classroom observations to test out the constructs in the C-COI. These processes resulted in an instrument with rigorous validation procedures and a high inter-rater reliability.

Evolving technologies for Space Station Freedom computer-based workstations

NASA Technical Reports Server (NTRS)

Jensen, Dean G.; Rudisill, Marianne

1990-01-01

Viewgraphs on evolving technologies for Space Station Freedom computer-based workstations are presented. The human-computer computer software environment modules are described. The following topics are addressed: command and control workstation concept; cupola workstation concept; Japanese experiment module RMS workstation concept; remote devices controlled from workstations; orbital maneuvering vehicle free flyer; remote manipulator system; Japanese experiment module exposed facility; Japanese experiment module small fine arm; flight telerobotic servicer; human-computer interaction; and workstation/robotics related activities.

Computer-assisted visual interactive recognition and its prospects of implementation over the Internet

NASA Astrophysics Data System (ADS)

Zou, Jie; Gattani, Abhishek

2005-01-01

When completely automated systems don't yield acceptable accuracy, many practical pattern recognition systems involve the human either at the beginning (pre-processing) or towards the end (handling rejects). We believe that it may be more useful to involve the human throughout the recognition process rather than just at the beginning or end. We describe a methodology of interactive visual recognition for human-centered low-throughput applications, Computer Assisted Visual InterActive Recognition (CAVIAR), and discuss the prospects of implementing CAVIAR over the Internet. The novelty of CAVIAR is image-based interaction through a domain-specific parameterized geometrical model, which reduces the semantic gap between humans and computers. The user may interact with the computer anytime that she considers its response unsatisfactory. The interaction improves the accuracy of the classification features by improving the fit of the computer-proposed model. The computer makes subsequent use of the parameters of the improved model to refine not only its own statistical model-fitting process, but also its internal classifier. The CAVIAR methodology was applied to implement a flower recognition system. The principal conclusions from the evaluation of the system include: 1) the average recognition time of the CAVIAR system is significantly shorter than that of the unaided human; 2) its accuracy is significantly higher than that of the unaided machine; 3) it can be initialized with as few as one training sample per class and still achieve high accuracy; and 4) it demonstrates a self-learning ability. We have also implemented a Mobile CAVIAR system, where a pocket PC, as a client, connects to a server through wireless communication. The motivation behind a mobile platform for CAVIAR is to apply the methodology in a human-centered pervasive environment, where the user can seamlessly interact with the system for classifying field-data. Deploying CAVIAR to a networked mobile platform poses the challenge of classifying field images and programming under constraints of display size, network bandwidth, processor speed, and memory size. Editing of the computer-proposed model is performed on the handheld while statistical model fitting and classification take place on the server. The possibility that the user can easily take several photos of the object poses an interesting information fusion problem. The advantage of the Internet is that the patterns identified by different users can be pooled together to benefit all peer users. When users identify patterns with CAVIAR in a networked setting, they also collect training samples and provide opportunities for machine learning from their intervention. CAVIAR implemented over the Internet provides a perfect test bed for, and extends, the concept of Open Mind Initiative proposed by David Stork. Our experimental evaluation focuses on human time, machine and human accuracy, and machine learning. We devoted much effort to evaluating the use of our image-based user interface and on developing principles for the evaluation of interactive pattern recognition system. The Internet architecture and Mobile CAVIAR methodology have many applications. We are exploring in the directions of teledermatology, face recognition, and education.

What is consciousness, and could machines have it?

PubMed

Dehaene, Stanislas; Lau, Hakwan; Kouider, Sid

2017-10-27

The controversial question of whether machines may ever be conscious must be based on a careful consideration of how consciousness arises in the only physical system that undoubtedly possesses it: the human brain. We suggest that the word "consciousness" conflates two different types of information-processing computations in the brain: the selection of information for global broadcasting, thus making it flexibly available for computation and report (C1, consciousness in the first sense), and the self-monitoring of those computations, leading to a subjective sense of certainty or error (C2, consciousness in the second sense). We argue that despite their recent successes, current machines are still mostly implementing computations that reflect unconscious processing (C0) in the human brain. We review the psychological and neural science of unconscious (C0) and conscious computations (C1 and C2) and outline how they may inspire novel machine architectures. Copyright © 2017, American Association for the Advancement of Science.

A Human Factors Framework for Payload Display Design

NASA Technical Reports Server (NTRS)

Dunn, Mariea C.; Hutchinson, Sonya L.

1998-01-01

During missions to space, one charge of the astronaut crew is to conduct research experiments. These experiments, referred to as payloads, typically are controlled by computers. Crewmembers interact with payload computers by using visual interfaces or displays. To enhance the safety, productivity, and efficiency of crewmember interaction with payload displays, particular attention must be paid to the usability of these displays. Enhancing display usability requires adoption of a design process that incorporates human factors engineering principles at each stage. This paper presents a proposed framework for incorporating human factors engineering principles into the payload display design process.

The Design of Hand Gestures for Human-Computer Interaction: Lessons from Sign Language Interpreters

PubMed Central

Rempel, David; Camilleri, Matt J.; Lee, David L.

2015-01-01

The design and selection of 3D modeled hand gestures for human-computer interaction should follow principles of natural language combined with the need to optimize gesture contrast and recognition. The selection should also consider the discomfort and fatigue associated with distinct hand postures and motions, especially for common commands. Sign language interpreters have extensive and unique experience forming hand gestures and many suffer from hand pain while gesturing. Professional sign language interpreters (N=24) rated discomfort for hand gestures associated with 47 characters and words and 33 hand postures. Clear associations of discomfort with hand postures were identified. In a nominal logistic regression model, high discomfort was associated with gestures requiring a flexed wrist, discordant adjacent fingers, or extended fingers. These and other findings should be considered in the design of hand gestures to optimize the relationship between human cognitive and physical processes and computer gesture recognition systems for human-computer input. PMID:26028955

Object and Facial Recognition in Augmented and Virtual Reality: Investigation into Software, Hardware and Potential Uses

NASA Technical Reports Server (NTRS)

Schulte, Erin

2017-01-01

As augmented and virtual reality grows in popularity, and more researchers focus on its development, other fields of technology have grown in the hopes of integrating with the up-and-coming hardware currently on the market. Namely, there has been a focus on how to make an intuitive, hands-free human-computer interaction (HCI) utilizing AR and VR that allows users to control their technology with little to no physical interaction with hardware. Computer vision, which is utilized in devices such as the Microsoft Kinect, webcams and other similar hardware has shown potential in assisting with the development of a HCI system that requires next to no human interaction with computing hardware and software. Object and facial recognition are two subsets of computer vision, both of which can be applied to HCI systems in the fields of medicine, security, industrial development and other similar areas.

Antioxidant vitamins and magnesium and the risk of hearing loss in the US general population.

PubMed

Choi, Yoon-Hyeong; Miller, Josef M; Tucker, Katherine L; Hu, Howard; Park, Sung Kyun

2014-01-01

The protective effects of antioxidant vitamins on hearing loss are well established in animal studies but in few human studies. Recent animal studies suggest that magnesium intake along with antioxidants may act in synergy to prevent hearing loss. We examined associations between intake of antioxidant vitamins (daily β-carotene and vitamins C and E) and magnesium and hearing thresholds and explored their joint effects in US adults. We analyzed cross-sectional data from 2592 participants aged 20-69 y from NHANES 2001-2004. Hearing thresholds as pure tone averages (PTAs) at speech (0.5, 1, 2, and 4 kHz) and high frequencies (3, 4, and 6 kHz) were computed. When examined individually, modeled as quartiles, and after adjustment for potential confounders, higher intakes of β-carotene, vitamin C, and magnesium were associated with lower (better) PTAs at both speech and high frequencies. High intakes of β-carotene or vitamin C combined with high magnesium compared with low intakes of both nutrients were significantly associated with lower (better) PTAs at high frequencies (-14.82%; 95% CI: -20.50% to -8.74% for β-carotene + magnesium and -10.72%; 95% CI: -16.57% to -4.45% for vitamin C + magnesium). The estimated joint effects were borderline significantly larger than the sums of the individual effects [high β-carotene/low magnesium (-4.98%) and low β-carotene/high magnesium (-0.80%), P-interaction = 0.08; high vitamin C/low magnesium (-1.33%) and low vitamin C/high magnesium (2.13%), P-interaction = 0.09]. Dietary intakes of antioxidants and magnesium are associated with lower risks of hearing loss.

Unique membrane properties and enhanced signal processing in human neocortical neurons.

PubMed

Eyal, Guy; Verhoog, Matthijs B; Testa-Silva, Guilherme; Deitcher, Yair; Lodder, Johannes C; Benavides-Piccione, Ruth; Morales, Juan; DeFelipe, Javier; de Kock, Christiaan Pj; Mansvelder, Huibert D; Segev, Idan

2016-10-06

The advanced cognitive capabilities of the human brain are often attributed to our recently evolved neocortex. However, it is not known whether the basic building blocks of the human neocortex, the pyramidal neurons, possess unique biophysical properties that might impact on cortical computations. Here we show that layer 2/3 pyramidal neurons from human temporal cortex (HL2/3 PCs) have a specific membrane capacitance ( C m ) of ~0.5 µF/cm 2 , half of the commonly accepted 'universal' value (~1 µF/cm 2 ) for biological membranes. This finding was predicted by fitting in vitro voltage transients to theoretical transients then validated by direct measurement of C m in nucleated patch experiments. Models of 3D reconstructed HL2/3 PCs demonstrated that such low C m value significantly enhances both synaptic charge-transfer from dendrites to soma and spike propagation along the axon. This is the first demonstration that human cortical neurons have distinctive membrane properties, suggesting important implications for signal processing in human neocortex.

Toward Impactful Collaborations on Computing and Mental Health

PubMed Central

Dinakar, Karthik; Picard, Rosalind; Christensen, Helen; Torous, John

2018-01-01

We describe an initiative to bring mental health researchers, computer scientists, human-computer interaction researchers, and other communities together to address the challenges of the global mental ill health epidemic. Two face-to-face events and one special issue of the Journal of Medical Internet Research were organized. The works presented in these events and publication reflect key state-of-the-art research in this interdisciplinary collaboration. We summarize the special issue articles and contextualize them to present a picture of the most recent research. In addition, we describe a series of collaborative activities held during the second symposium and where the community identified 5 challenges and their possible solutions. PMID:29426812

An interactive human carbonic anhydrase-II (hCA-II) receptor--pharmacophore molecular model & anti-convulsant activity of the designed and synthesized 5-amino-1,3,4-thiadiazole-2-thiol conjugated imine derivatives.

PubMed

Yusuf, Mohammad; Khan, Riaz A; Khan, Maria; Ahmed, Bahar

2013-05-01

New imines, derived from aromatic aldehyde, chalcones and 5-amino-1,3,4-thiadiazole-2-thiol exhibited promising anti-convulsant activity which is explained through chemo-biological interactions at receptor site producing the inhibition of human Carbonic Anhydrase-II enzyme (hCA-II) through the proposed pharmacophore model at molecular levels as basis for pharmacological activity. The compounds 5-{1-(4-Chlorophenyl)-3-[4-(methoxy-phenyl)-prop-2-en-1-ylidene]amino}-1,3,4-thiadiazole-2-thiol (2b), 5-{[1-(4-chloro-phenyl)]-3-[4-(dimethyl-amino-phenyl)-prop-2-en-1-ylidene]amino}-1,3,4-thiadiazole-2-thiol (2c) and 5-{[1-(4-chloro-phenyl)]-3-[(4-amino-phenyl)-prop-2-en-1-ylidene]amino}-1,3,4-thiadiazole-2-thiol (2f) showed 100% activity in comparison with standard Acetazolamide, a known anti-convulsant drug. The compounds 2c, 2f also passed the Rotarod and Ethanol Potentiation tests which further confirmed them to be safe in motor coordination activity and safe from generating neurological toxicity. © 2013 John Wiley & Sons A/S.

Transportable Applications Environment Plus, Version 5.1

NASA Technical Reports Server (NTRS)

1994-01-01

Transportable Applications Environment Plus (TAE+) computer program providing integrated, portable programming environment for developing and running application programs based on interactive windows, text, and graphical objects. Enables both programmers and nonprogrammers to construct own custom application interfaces easily and to move interfaces and application programs to different computers. Used to define corporate user interface, with noticeable improvements in application developer's and end user's learning curves. Main components are; WorkBench, What You See Is What You Get (WYSIWYG) software tool for design and layout of user interface; and WPT (Window Programming Tools) Package, set of callable subroutines controlling user interface of application program. WorkBench and WPT's written in C++, and remaining code written in C.

Investigations in Computer-Aided Instruction and Computer-Aided Controls. Final Report.

ERIC Educational Resources Information Center

Rosenberg, R.C.; And Others

These research projects, designed to delve into certain relationships between humans and computers, are focused on computer-assisted instruction and on man-computer interaction. One study demonstrates that within the limits of formal engineering theory, a computer simulated laboratory (Dynamic Systems Laboratory) can be built in which freshmen…

Ethanol oxidation and the inhibition by drugs in human liver, stomach and small intestine: Quantitative assessment with numerical organ modeling of alcohol dehydrogenase isozymes.

PubMed

Chi, Yu-Chou; Lee, Shou-Lun; Lai, Ching-Long; Lee, Yung-Pin; Lee, Shiao-Pieng; Chiang, Chien-Ping; Yin, Shih-Jiun

2016-10-25

Alcohol dehydrogenase (ADH) is the principal enzyme responsible for metabolism of ethanol. Human ADH constitutes a complex isozyme family with striking variations in kinetic function and tissue distribution. Liver and gastrointestinal tract are the major sites for first-pass metabolism (FPM). Their relative contributions to alcohol FPM and degrees of the inhibitions by aspirin and its metabolite salicylate, acetaminophen and cimetidine remain controversial. To address this issue, mathematical organ modeling of ethanol-oxidizing activities in target tissues and that of the ethanol-drug interactions were constructed by linear combination of the corresponding numerical rate equations of tissue constituent ADH isozymes with the documented isozyme protein contents, kinetic parameters for ethanol oxidation and the drug inhibitions of ADH isozymes/allozymes that were determined in 0.1 M sodium phosphate at pH 7.5 and 25 °C containing 0.5 mM NAD(+). The organ simulations reveal that the ADH activities in mucosae of the stomach, duodenum and jejunum with ADH1C*1/*1 genotype are less than 1%, respectively, that of the ADH1B*1/*1-ADH1C*1/*1 liver at 1-200 mM ethanol, indicating that liver is major site of the FPM. The apparent hepatic KM and Vmax for ethanol oxidation are simulated to be 0.093 ± 0.019 mM and 4.0 ± 0.1 mmol/min, respectively. At 95% clearance in liver, the logarithmic average sinusoidal ethanol concentration is determined to be 0.80 mM in accordance with the flow-limited gradient perfusion model. The organ simulations indicate that higher therapeutic acetaminophen (0.5 mM) inhibits 16% of ADH1B*1/*1 hepatic ADH activity at 2-20 mM ethanol and that therapeutic salicylate (1.5 mM) inhibits 30-31% of the ADH1B*2/*2 activity, suggesting potential significant inhibitions of ethanol FPM in these allelotypes. The result provides systematic evaluations and predictions by computer simulation on potential ethanol FPM in target tissues and hepatic ethanol-drug interactions in the context of tissue ADH isozymes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of Ground Vibrations Induced by Military Noise Sources

DTIC Science & Technology

2006-08-01

1 Task 2—Determine the acoustic -to-seismic coupling coefficients C1 and C2 ...................... 1 Task 3—Computational modeling ...Determine the acoustic -to-seismic coupling coefficients C1 and C2 ....................45 Task 3—Computational modeling of acoustically induced ground...ground conditions. Task 3—Computational modeling of acoustically induced ground motion The simple model of blast sound interaction with the

Interactions of Human Nucleotide Excision Repair Protein XPA with DNA and RPA70 Delta c327: Chemical Shift Mapping and N-15 NMR Relaxation Studies

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

Buchko, Garry W.; Daughdrill, Gary W.; De Lorimier, Robert

1999-12-28

Human XPA is an essential component in the multienzyme nucleotide excision repair (NER) pathway. The solution structure of the minimal DNA binding domain of XPA (XPA-MBD: M98-F219) was recently determined [Buchko et al. (1998) Nucleic Acids Res. 26, 2779-2788, Ikegami et al (1998) Nat. Struct. Biol. 5, 701-706] and shown to consist of a compact zinc-binding core and a loop-rich C-terminal subdomain connected by a linker sequence.

Effective intermolecular potential and critical point for C60 molecule

NASA Astrophysics Data System (ADS)

Ramos, J. Eloy

2017-07-01

The approximate nonconformal (ANC) theory is applied to the C60 molecule. A new binary potential function is developed for C60, which has three parameters only and is obtained by averaging the site-site carbon interactions on the surface of two C60 molecules. It is shown that the C60 molecule follows, to a good approximation, the corresponding states principle with n-C8H18, n-C4F10 and n-C5F12. The critical point of C60 is estimated in two ways: first by applying the corresponding states principle under the framework of the ANC theory, and then by using previous computer simulations. The critical parameters obtained by applying the corresponding states principle, although very different from those reported in the literature, are consistent with the previous results of the ANC theory. It is shown that the Girifalco potential does not correspond to an average of the site-site carbon-carbon interaction.

TAE+ 5.1 - TRANSPORTABLE APPLICATIONS ENVIRONMENT PLUS, VERSION 5.1 (HP9000 SERIES 300/400 VERSION)

NASA Technical Reports Server (NTRS)

TAE SUPPORT OFFICE

1994-01-01

TAE (Transportable Applications Environment) Plus is an integrated, portable environment for developing and running interactive window, text, and graphical object-based application systems. The program allows both programmers and non-programmers to easily construct their own custom application interface and to move that interface and application to different machine environments. TAE Plus makes both the application and the machine environment transparent, with noticeable improvements in the learning curve. The main components of TAE Plus are as follows: (1) the WorkBench, a What You See Is What You Get (WYSIWYG) tool for the design and layout of a user interface; (2) the Window Programming Tools Package (WPT), a set of callable subroutines that control an application's user interface; and (3) TAE Command Language (TCL), an easy-to-learn command language that provides an easy way to develop an executable application prototype with a run-time interpreted language. The WorkBench tool allows the application developer to interactively construct the layout of an application's display screen by manipulating a set of interaction objects including input items such as buttons, icons, and scrolling text lists. User interface interactive objects include data-driven graphical objects such as dials, thermometers, and strip charts as well as menubars, option menus, file selection items, message items, push buttons, and color loggers. The WorkBench user specifies the windows and interaction objects that will make up the user interface, then specifies the sequence of the user interface dialogue. The description of the designed user interface is then saved into resource files. For those who desire to develop the designed user interface into an operational application, the WorkBench tool also generates source code (C, C++, Ada, and TCL) which fully controls the application's user interface through function calls to the WPTs. The WPTs are the runtime services used by application programs to display and control the user interfaces. Since the WPTs access the workbench-generated resource files during each execution, details such as color, font, location, and object type remain independent from the application code, allowing changes to the user interface without recompiling and relinking. In addition to WPTs, TAE Plus can control interaction of objects from the interpreted TAE Command Language. TCL provides a means for the more experienced developer to quickly prototype an application's use of TAE Plus interaction objects and add programming logic without the overhead of compiling or linking. TAE Plus requires MIT's X Window System, Version 11 Release 4, and the Open Software Foundation's Motif. The Workbench and WPTs are written in C++ and the remaining code is written in C. TAE Plus is available by license for an unlimited time period. The licensed program product includes the TAE Plus source code and one set of supporting documentation. Additional documentation may be purchased separately at the price indicated below. The amount of disk space required to load the TAE Plus tar format tape is between 35Mb and 67Mb depending on the machine version. The recommended minimum memory is 12Mb. Each TAE Plus platform delivery tape includes pre-built libraries and executable binary code for that particular machine, as well as source code, so users do not have to do an installation. Users wishing to recompile the source will need both a C compiler and either GNU's C++ Version 1.39 or later, or a C++ compiler based on AT&T 2.0 cfront. TAE Plus was developed in 1989 and version 5.2 was released in 1993. TAE Plus 5.2 is expected to be available on media suitable for seven different machine platforms: 1) DEC VAX computers running VMS (TK50 cartridge in VAX BACKUP format), 2) IBM RS/6000 series workstations running AIX (.25 inch tape cartridge in UNIX tar format), 3) DEC RISC workstations running ULTRIX (TK50 cartridge in UNIX tar format), 4) HP9000 Series 300/400 computers running HP-UX (.25 inch HP-preformatted tape cartridge in UNIX tar format), 5) HP9000 Series 700 computers running HP-UX (HP 4mm DDS DAT tape cartridge in UNIX tar format), 6) Sun4 (SPARC) series computers running SunOS (.25 inch tape cartridge in UNIX tar format), and 7) SGI Indigo computers running IRIX (.25 inch IRIS tape cartridge in UNIX tar format). Please contact COSMIC to obtain detailed information about the supported operating system and OSF/Motif releases required for each of these machine versions. An optional Motif Object Code License is available for the Sun4 version of TAE Plus 5.2.

TAE+ 5.1 - TRANSPORTABLE APPLICATIONS ENVIRONMENT PLUS, VERSION 5.1 (VAX VMS VERSION)

NASA Technical Reports Server (NTRS)

TAE SUPPORT OFFICE

1994-01-01

TAE (Transportable Applications Environment) Plus is an integrated, portable environment for developing and running interactive window, text, and graphical object-based application systems. The program allows both programmers and non-programmers to easily construct their own custom application interface and to move that interface and application to different machine environments. TAE Plus makes both the application and the machine environment transparent, with noticeable improvements in the learning curve. The main components of TAE Plus are as follows: (1) the WorkBench, a What You See Is What You Get (WYSIWYG) tool for the design and layout of a user interface; (2) the Window Programming Tools Package (WPT), a set of callable subroutines that control an application's user interface; and (3) TAE Command Language (TCL), an easy-to-learn command language that provides an easy way to develop an executable application prototype with a run-time interpreted language. The WorkBench tool allows the application developer to interactively construct the layout of an application's display screen by manipulating a set of interaction objects including input items such as buttons, icons, and scrolling text lists. User interface interactive objects include data-driven graphical objects such as dials, thermometers, and strip charts as well as menubars, option menus, file selection items, message items, push buttons, and color loggers. The WorkBench user specifies the windows and interaction objects that will make up the user interface, then specifies the sequence of the user interface dialogue. The description of the designed user interface is then saved into resource files. For those who desire to develop the designed user interface into an operational application, the WorkBench tool also generates source code (C, C++, Ada, and TCL) which fully controls the application's user interface through function calls to the WPTs. The WPTs are the runtime services used by application programs to display and control the user interfaces. Since the WPTs access the workbench-generated resource files during each execution, details such as color, font, location, and object type remain independent from the application code, allowing changes to the user interface without recompiling and relinking. In addition to WPTs, TAE Plus can control interaction of objects from the interpreted TAE Command Language. TCL provides a means for the more experienced developer to quickly prototype an application's use of TAE Plus interaction objects and add programming logic without the overhead of compiling or linking. TAE Plus requires MIT's X Window System, Version 11 Release 4, and the Open Software Foundation's Motif. The Workbench and WPTs are written in C++ and the remaining code is written in C. TAE Plus is available by license for an unlimited time period. The licensed program product includes the TAE Plus source code and one set of supporting documentation. Additional documentation may be purchased separately at the price indicated below. The amount of disk space required to load the TAE Plus tar format tape is between 35Mb and 67Mb depending on the machine version. The recommended minimum memory is 12Mb. Each TAE Plus platform delivery tape includes pre-built libraries and executable binary code for that particular machine, as well as source code, so users do not have to do an installation. Users wishing to recompile the source will need both a C compiler and either GNU's C++ Version 1.39 or later, or a C++ compiler based on AT&T 2.0 cfront. TAE Plus was developed in 1989 and version 5.2 was released in 1993. TAE Plus 5.2 is expected to be available on media suitable for seven different machine platforms: 1) DEC VAX computers running VMS (TK50 cartridge in VAX BACKUP format), 2) IBM RS/6000 series workstations running AIX (.25 inch tape cartridge in UNIX tar format), 3) DEC RISC workstations running ULTRIX (TK50 cartridge in UNIX tar format), 4) HP9000 Series 300/400 computers running HP-UX (.25 inch HP-preformatted tape cartridge in UNIX tar format), 5) HP9000 Series 700 computers running HP-UX (HP 4mm DDS DAT tape cartridge in UNIX tar format), 6) Sun4 (SPARC) series computers running SunOS (.25 inch tape cartridge in UNIX tar format), and 7) SGI Indigo computers running IRIX (.25 inch IRIS tape cartridge in UNIX tar format). Please contact COSMIC to obtain detailed information about the supported operating system and OSF/Motif releases required for each of these machine versions. An optional Motif Object Code License is available for the Sun4 version of TAE Plus 5.2.

'Tagger' - a Mac OS X Interactive Graphical Application for Data Inference and Analysis of N-Dimensional Datasets in the Natural Physical Sciences.

NASA Astrophysics Data System (ADS)

Morse, P. E.; Reading, A. M.; Lueg, C.

2014-12-01

Pattern-recognition in scientific data is not only a computational problem but a human-observer problem as well. Human observation of - and interaction with - data visualization software can augment, select, interrupt and modify computational routines and facilitate processes of pattern and significant feature recognition for subsequent human analysis, machine learning, expert and artificial intelligence systems.'Tagger' is a Mac OS X interactive data visualisation tool that facilitates Human-Computer interaction for the recognition of patterns and significant structures. It is a graphical application developed using the Quartz Composer framework. 'Tagger' follows a Model-View-Controller (MVC) software architecture: the application problem domain (the model) is to facilitate novel ways of abstractly representing data to a human interlocutor, presenting these via different viewer modalities (e.g. chart representations, particle systems, parametric geometry) to the user (View) and enabling interaction with the data (Controller) via a variety of Human Interface Devices (HID). The software enables the user to create an arbitrary array of tags that may be appended to the visualised data, which are then saved into output files as forms of semantic metadata. Three fundamental problems that are not strongly supported by conventional scientific visualisation software are addressed:1] How to visually animate data over time, 2] How to rapidly deploy unconventional parametrically driven data visualisations, 3] How to construct and explore novel interaction models that capture the activity of the end-user as semantic metadata that can be used to computationally enhance subsequent interrogation. Saved tagged data files may be loaded into Tagger, so that tags may be tagged, if desired. Recursion opens up the possibility of refining or overlapping different types of tags, tagging a variety of different POIs or types of events, and of capturing different types of specialist observations of important or noticeable events. Other visualisations and modes of interaction will also be demonstrated, with the aim of discovering knowledge in large datasets in the natural, physical sciences. Fig.1 Wave height data from an oceanographic Wave Rider Buoy. Colors/radii are driven by wave height data.

Atomic Structure of GRK5 Reveals Distinct Structural Features Novel for G Protein-coupled Receptor Kinases.

PubMed

Komolov, Konstantin E; Bhardwaj, Anshul; Benovic, Jeffrey L

2015-08-21

G protein-coupled receptor kinases (GRKs) are members of the protein kinase A, G, and C families (AGC) and play a central role in mediating G protein-coupled receptor phosphorylation and desensitization. One member of the family, GRK5, has been implicated in several human pathologies, including heart failure, hypertension, cancer, diabetes, and Alzheimer disease. To gain mechanistic insight into GRK5 function, we determined a crystal structure of full-length human GRK5 at 1.8 Å resolution. GRK5 in complex with the ATP analog 5'-adenylyl β,γ-imidodiphosphate or the nucleoside sangivamycin crystallized as a monomer. The C-terminal tail (C-tail) of AGC kinase domains is a highly conserved feature that is divided into three segments as follows: the C-lobe tether, the active-site tether (AST), and the N-lobe tether (NLT). This domain is fully resolved in GRK5 and reveals novel interactions with the nucleotide and N-lobe. Similar to other AGC kinases, the GRK5 AST is an integral part of the nucleotide-binding pocket, a feature not observed in other GRKs. The AST also mediates contact between the kinase N- and C-lobes facilitating closure of the kinase domain. The GRK5 NLT is largely displaced from its previously observed position in other GRKs. Moreover, although the autophosphorylation sites in the NLT are >20 Å away from the catalytic cleft, they are capable of rapid cis-autophosphorylation suggesting high mobility of this region. In summary, we provide a snapshot of GRK5 in a partially closed state, where structural elements of the kinase domain C-tail are aligned to form novel interactions to the nucleotide and N-lobe not previously observed in other GRKs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

C-terminal, endoplasmic reticulum-lumenal domain of prosurfactant protein C - structural features and membrane interactions.

PubMed

Casals, Cristina; Johansson, Hanna; Saenz, Alejandra; Gustafsson, Magnus; Alfonso, Carlos; Nordling, Kerstin; Johansson, Jan

2008-02-01

Surfactant protein C (SP-C) constitutes the transmembrane part of prosurfactant protein C (proSP-C) and is alpha-helical in its native state. The C-terminal part of proSP-C (CTC) is localized in the endoplasmic reticulum lumen and binds to misfolded (beta-strand) SP-C, thereby preventing its aggregation and amyloid fibril formation. In this study, we investigated the structure of recombinant human CTC and the effects of CTC-membrane interaction on protein structure. CTC forms noncovalent trimers and supratrimeric oligomers. It contains two intrachain disulfide bridges, and its secondary structure is significantly affected by urea or heat only after disulfide reduction. The postulated Brichos domain of CTC, with homologs found in proteins associated with amyloid and proliferative disease, is up to 1000-fold more protected from limited proteolysis than the rest of CTC. The protein exposes hydrophobic surfaces, as determined by CTC binding to the environment-sensitive fluorescent probe 1,1'-bis(4-anilino-5,5'-naphthalenesulfonate). Fluorescence energy transfer experiments further reveal close proximity between bound 1,1'-bis(4-anilino-5,5'-naphthalenesulfonate) and tyrosine residues in CTC, some of which are conserved in all Brichos domains. CTC binds to unilamellar phospholipid vesicles with low micromolar dissociation constants, and differential scanning calorimetry and CD analyses indicate that membrane-bound CTC is less structurally ordered than the unbound protein. The exposed hydrophobic surfaces and the structural disordering that result from interactions with phospholipid membranes suggest a mechanism whereby CTC binds to misfolded SP-C in the endoplasmic reticulum membrane.

GENOME-WIDE GENETIC INTERACTION ANALYSIS OF GLAUCOMA USING EXPERT KNOWLEDGE DERIVED FROM HUMAN PHENOTYPE NETWORKS

PubMed Central

HU, TING; DARABOS, CHRISTIAN; CRICCO, MARIA E.; KONG, EMILY; MOORE, JASON H.

2014-01-01

The large volume of GWAS data poses great computational challenges for analyzing genetic interactions associated with common human diseases. We propose a computational framework for characterizing epistatic interactions among large sets of genetic attributes in GWAS data. We build the human phenotype network (HPN) and focus around a disease of interest. In this study, we use the GLAUGEN glaucoma GWAS dataset and apply the HPN as a biological knowledge-based filter to prioritize genetic variants. Then, we use the statistical epistasis network (SEN) to identify a significant connected network of pairwise epistatic interactions among the prioritized SNPs. These clearly highlight the complex genetic basis of glaucoma. Furthermore, we identify key SNPs by quantifying structural network characteristics. Through functional annotation of these key SNPs using Biofilter, a software accessing multiple publicly available human genetic data sources, we find supporting biomedical evidences linking glaucoma to an array of genetic diseases, proving our concept. We conclude by suggesting hypotheses for a better understanding of the disease. PMID:25592582

Inhibitory effects of cytostatically active 6-aminobenzo[c]phenanthridines on cytochrome P450 enzymes in human hepatic microsomes.

PubMed

Zebothsen, Inga; Kunze, Thomas; Clement, Bernd

2006-07-01

Besides assays for the evaluation of efficacy new drug candidates have to undergo extensive testings for enhancement of pharmaceutical drug safety and optimization of application. The objective of the present work was to investigate the pharmacokinetic drug drug interaction potential for the cytostatically active 6-aminobenzo[c]phenanthridines BP-11 (6-amino-11,12-dihydro-11-(4-hydroxy-3,5-dimethoxyphenyl)benzo[c]phenanthridine) and BP-D7 (6-amino-11-(3,4,5-trimethoxyphenyl)benzo[c]phenanthridine) in vitro through incubation with human hepatic microsomes and marker substrates. For these studies the cytochrome P-450 isoenzymes and corresponding marker substrates recommended by the EMEA (The European Agency for the Evaluation of Medicinal Products) were chosen. In detail these selective substrates were caffeine (CYP1A2), coumarin (CYP2A6), tolbutamide (CYP2C9), S-(+)-mephenytoin (CYP2C19), dextromethorphane (CYP2D6), chlorzoxazone (CYP2E1) and testosterone (CYP3A4). Incubations with each substrate were carried out without a possible inhibitor and in the presence of a benzo[c]phenanthridine or a selective inhibitor at varying concentrations. Marker activities were determined by HPLC (high performance liquid chromatography). For the isoenzymes showing more than 50% inhibition by the addition of 20 microM BP-11 or BP-D7 additional concentrations of substrate and inhibitor were tested for a characterization of the inhibition. The studies showed a moderate risk for BP-11 for interactions with the cytochrome P-450 isoenzymes CYP1A2, CYP2C9, CYP2D6 and CYP3A4. BP-D7, the compound with the highest cytotstatic efficacy, showed only a moderate risk for interactions with drugs, also metabolized by CYP3A4.

Computational and experimental study of the interactions between ionic liquids and volatile organic compounds.

PubMed

Gao, Tingting; Andino, Jean M; Alvarez-Idaboy, J Raul

2010-09-07

Computational chemistry calculations were performed to investigate the interactions of ionic liquids with different classes of volatile organic compounds (VOCs), including alcohols, aldehydes, ketones, alkanes, alkenes, alkynes and aromatic compounds. At least one VOC was studied to represent each class. Initially, 1-butyl-3-methylimindazolium chloride (abbreviated as C(4)mimCl) was used as the test ionic liquid compound. Calculated interaction lengths between atoms in the ionic liquid and the VOC tested as well as thermodynamic data suggest that C(4)mimCl preferentially interacts with alcohols as compared to other classes of volatile organic compounds. The interactions of methanol with different kinds of ionic liquids, specifically 1-butyl-3-methylimidazolium bromine (C(4)mimBr) and 1-butyl-3-methylimidazolium tetrafluoroborate (C(4)mimBF(4)) were also studied. In comparing C(4)mimCl, C(4)mimBr, and C(4)mimBF(4), the computational results suggest that C(4)mimCl is more likely to interact with methanol. Laboratory experiments were performed to provide further evidence for the interaction between C(4)mimCl and different classes of VOCs. Fourier transform infrared spectroscopy was used to probe the ionic liquid surface before and after exposure to the VOCs that were tested. New spectral features were detected after exposure of C(4)mimCl to various alcohols. The new features are characteristic of the alcohols tested. No new IR features were detected after exposure of the C(4)mimCl to the aldehyde, ketone, alkane, alkene, alkyne or aromatic compounds studied. In addition, after exposing the C(4)mimCl to a multi-component mixture of various classes of compounds (including an alcohol), the only new peaks that were detected were characteristic of the alcohol that was tested. These experimental results demonstrated that C(4)mimCl is selective to alcohols, even in complex mixtures. The findings in this work provide information for future gas-phase alcohol sensor design.

TangibleCubes — Implementation of Tangible User Interfaces through the Usage of Microcontroller and Sensor Technology

NASA Astrophysics Data System (ADS)

Setscheny, Stephan

The interaction between human beings and technology builds a central aspect in human life. The most common form of this human-technology interface is the graphical user interface which is controlled through the mouse and the keyboard. In consequence of continuous miniaturization and the increasing performance of microcontrollers and sensors for the detection of human interactions, developers receive new possibilities for realising innovative interfaces. As far as this movement is concerned, the relevance of computers in the common sense and graphical user interfaces is decreasing. Especially in the area of ubiquitous computing and the interaction through tangible user interfaces a highly impact of this technical evolution can be seen. Apart from this, tangible and experience able interaction offers users the possibility of an interactive and intuitive method for controlling technical objects. The implementation of microcontrollers for control functions and sensors enables the realisation of these experience able interfaces. Besides the theories about tangible user interfaces, the consideration about sensors and the Arduino platform builds a main aspect of this work.

A truly human interface: interacting face-to-face with someone whose words are determined by a computer program

PubMed Central

Corti, Kevin; Gillespie, Alex

2015-01-01

We use speech shadowing to create situations wherein people converse in person with a human whose words are determined by a conversational agent computer program. Speech shadowing involves a person (the shadower) repeating vocal stimuli originating from a separate communication source in real-time. Humans shadowing for conversational agent sources (e.g., chat bots) become hybrid agents (“echoborgs”) capable of face-to-face interlocution. We report three studies that investigated people’s experiences interacting with echoborgs and the extent to which echoborgs pass as autonomous humans. First, participants in a Turing Test spoke with a chat bot via either a text interface or an echoborg. Human shadowing did not improve the chat bot’s chance of passing but did increase interrogators’ ratings of how human-like the chat bot seemed. In our second study, participants had to decide whether their interlocutor produced words generated by a chat bot or simply pretended to be one. Compared to those who engaged a text interface, participants who engaged an echoborg were more likely to perceive their interlocutor as pretending to be a chat bot. In our third study, participants were naïve to the fact that their interlocutor produced words generated by a chat bot. Unlike those who engaged a text interface, the vast majority of participants who engaged an echoborg did not sense a robotic interaction. These findings have implications for android science, the Turing Test paradigm, and human–computer interaction. The human body, as the delivery mechanism of communication, fundamentally alters the social psychological dynamics of interactions with machine intelligence. PMID:26042066

In silico design of novel hERG-neutral sildenafil-like PDE5 inhibitors.

PubMed

Kayık, Gülru; Tüzün, Nurcan Ş; Durdagi, Serdar

2017-10-01

Cyclic nucleotide phosphodiesterase enzymes (PDEs) have functions in regulating the levels of intracellular second messengers, 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP), via hydrolysis and decomposing mechanisms in cells. They take essential roles in modulating various cellular activities such as memory and smooth muscle functions. PDE type 5 (PDE5) inhibitors enhance the vasodilatory effects of cGMP in the corpus cavernosum and they are used to treat erectile dysfunction. Patch clamp experiments showed that the IC 50 values of the human ether-à-go-go-related gene (hERG1) potassium (K) ion channel blocking affinity of PDE5 inhibitors sildenafil, vardenafil, and tadalafil as 33, 12, and 100 μM, respectively. hERG1 channel is responsible for the regulation of the action potential of human ventricular myocyte by contributing the rapid component of delayed rectifier K + current (I Kr ) component of the cardiac action potential. In this work, interaction patterns and binding affinity predictions of selected PDE5 inhibitors against the hERG1 channel are studied. It is attempted to develop PDE5 inhibitor analogs with lower binding affinity to hERG1 ion channel while keeping their pharmacological activity against their principal target PDE5 using in silico methods. Based on detailed analyses of docking poses and predicted interaction energies, novel analogs of PDE5 inhibitors with lower predicted binding affinity to hERG1 channels without loosing their principal target activity were proposed. Moreover, molecular dynamics (MD) simulations and post-processing MD analyses (i.e. Molecular Mechanics/Generalized Born Surface Area calculations) were performed. Detailed analysis of molecular simulations helped us to better understand the PDE5 inhibitor-target binding interactions in the atomic level. Results of this study can be useful for designing of novel and safe PDE5 inhibitors with enhanced activity and other tailored properties.

Semisynthesis, cytotoxicity, antiviral activity, and drug interaction liability of 7-O-methylated analogues of flavonolignans from milk thistle.

PubMed

Althagafy, Hanan S; Graf, Tyler N; Sy-Cordero, Arlene A; Gufford, Brandon T; Paine, Mary F; Wagoner, Jessica; Polyak, Stephen J; Croatt, Mitchell P; Oberlies, Nicholas H

2013-07-01

Silymarin, an extract of the seeds of milk thistle (Silybum marianum), is used as an herbal remedy, particularly for hepatoprotection. The main chemical constituents in silymarin are seven flavonolignans. Recent studies explored the non-selective methylation of one flavonolignan, silybin B, and then tested those analogues for cytotoxicity and inhibition of both cytochrome P450 (CYP) 2C9 activity in human liver microsomes and hepatitis C virus infection in a human hepatoma (Huh7.5.1) cell line. In general, enhanced bioactivity was observed with the analogues. To further probe the biological consequences of methylation of the seven major flavonolignans, a series of 7-O-methylflavonolignans were generated. Optimization of the reaction conditions permitted selective methylation at the phenol in the 7-position in the presence of each metabolite's 4-5 other phenolic and/or alcoholic positions without the use of protecting groups. These 7-O-methylated analogues, in parallel with the corresponding parent compounds, were evaluated for cytotoxicity against Huh7.5.1 cells; in all cases the monomethylated analogues were more cytotoxic than the parent compounds. Moreover, parent compounds that were relatively non-toxic and inactive or weak inhibitors of hepatitis C virus infection had enhanced cytotoxicity and anti-HCV activity upon 7-O-methylation. Also, the compounds were tested for inhibition of major drug metabolizing enzymes (CYP2C9, CYP3A4/5, UDP-glucuronsyltransferases) in pooled human liver or intestinal microsomes. Methylation of flavonolignans differentially modified inhibitory potency, with compounds demonstrating both increased and decreased potency depending upon the compound tested and the enzyme system investigated. In total, these data indicated that monomethylation modulates the cytotoxic, antiviral, and drug interaction potential of silymarin flavonolignans. Copyright © 2013 Elsevier Ltd. All rights reserved.

Kenny Gruchalla | NREL

Science.gov Websites

feature extraction, human-computer interaction, and physics-based modeling. Professional Experience 2009 ., computer science, University of Colorado at Boulder M.S., computer science, University of Colorado at Boulder B.S., computer science, New Mexico Institute of Mining and Technology

Computer simulations suggest direct and stable tip to tip interaction between the outer membrane channel TolC and the isolated docking domain of the multidrug RND efflux transporter AcrB.

PubMed

Schmidt, Thomas H; Raunest, Martin; Fischer, Nadine; Reith, Dirk; Kandt, Christian

2016-07-01

One way by which bacteria achieve antibiotics resistance is preventing drug access to its target molecule for example through an overproduction of multi-drug efflux pumps of the resistance nodulation division (RND) protein super family of which AcrAB-TolC in Escherichia coli is a prominent example. Although representing one of the best studied efflux systems, the question of how AcrB and TolC interact is still unclear as the available experimental data suggest that either both proteins interact in a tip to tip manner or do not interact at all but are instead connected by a hexamer of AcrA molecules. Addressing the question of TolC-AcrB interaction, we performed a series of 100 ns - 1 µs-molecular dynamics simulations of membrane-embedded TolC in presence of the isolated AcrB docking domain (AcrB(DD)). In 5/6 simulations we observe direct TolC-AcrB(DD) interaction that is only stable on the simulated time scale when both proteins engage in a tip to tip manner. At the same time we find TolC opening and closing freely on extracellular side while remaining closed at the inner periplasmic bottleneck region, suggesting that either the simulated time is too short or additional components are required to unlock TolC. Copyright © 2016 Elsevier B.V. All rights reserved.

Can Machines Think? Interaction and Perspective Taking with Robots Investigated via fMRI

PubMed Central

Krach, Sören; Hegel, Frank; Wrede, Britta; Sagerer, Gerhard; Binkofski, Ferdinand; Kircher, Tilo

2008-01-01

Background When our PC goes on strike again we tend to curse it as if it were a human being. Why and under which circumstances do we attribute human-like properties to machines? Although humans increasingly interact directly with machines it remains unclear whether humans implicitly attribute intentions to them and, if so, whether such interactions resemble human-human interactions on a neural level. In social cognitive neuroscience the ability to attribute intentions and desires to others is being referred to as having a Theory of Mind (ToM). With the present study we investigated whether an increase of human-likeness of interaction partners modulates the participants' ToM associated cortical activity. Methodology/Principal Findings By means of functional magnetic resonance imaging (subjects n = 20) we investigated cortical activity modulation during highly interactive human-robot game. Increasing degrees of human-likeness for the game partner were introduced by means of a computer partner, a functional robot, an anthropomorphic robot and a human partner. The classical iterated prisoner's dilemma game was applied as experimental task which allowed for an implicit detection of ToM associated cortical activity. During the experiment participants always played against a random sequence unknowingly to them. Irrespective of the surmised interaction partners' responses participants indicated having experienced more fun and competition in the interaction with increasing human-like features of their partners. Parametric modulation of the functional imaging data revealed a highly significant linear increase of cortical activity in the medial frontal cortex as well as in the right temporo-parietal junction in correspondence with the increase of human-likeness of the interaction partner (computer

Can machines think? Interaction and perspective taking with robots investigated via fMRI.

PubMed

Krach, Sören; Hegel, Frank; Wrede, Britta; Sagerer, Gerhard; Binkofski, Ferdinand; Kircher, Tilo

2008-07-09

When our PC goes on strike again we tend to curse it as if it were a human being. Why and under which circumstances do we attribute human-like properties to machines? Although humans increasingly interact directly with machines it remains unclear whether humans implicitly attribute intentions to them and, if so, whether such interactions resemble human-human interactions on a neural level. In social cognitive neuroscience the ability to attribute intentions and desires to others is being referred to as having a Theory of Mind (ToM). With the present study we investigated whether an increase of human-likeness of interaction partners modulates the participants' ToM associated cortical activity. By means of functional magnetic resonance imaging (subjects n = 20) we investigated cortical activity modulation during highly interactive human-robot game. Increasing degrees of human-likeness for the game partner were introduced by means of a computer partner, a functional robot, an anthropomorphic robot and a human partner. The classical iterated prisoner's dilemma game was applied as experimental task which allowed for an implicit detection of ToM associated cortical activity. During the experiment participants always played against a random sequence unknowingly to them. Irrespective of the surmised interaction partners' responses participants indicated having experienced more fun and competition in the interaction with increasing human-like features of their partners. Parametric modulation of the functional imaging data revealed a highly significant linear increase of cortical activity in the medial frontal cortex as well as in the right temporo-parietal junction in correspondence with the increase of human-likeness of the interaction partner (computer

Implicit prosody mining based on the human eye image capture technology

NASA Astrophysics Data System (ADS)

Gao, Pei-pei; Liu, Feng

2013-08-01

The technology of eye tracker has become the main methods of analyzing the recognition issues in human-computer interaction. Human eye image capture is the key problem of the eye tracking. Based on further research, a new human-computer interaction method introduced to enrich the form of speech synthetic. We propose a method of Implicit Prosody mining based on the human eye image capture technology to extract the parameters from the image of human eyes when reading, control and drive prosody generation in speech synthesis, and establish prosodic model with high simulation accuracy. Duration model is key issues for prosody generation. For the duration model, this paper put forward a new idea for obtaining gaze duration of eyes when reading based on the eye image capture technology, and synchronous controlling this duration and pronunciation duration in speech synthesis. The movement of human eyes during reading is a comprehensive multi-factor interactive process, such as gaze, twitching and backsight. Therefore, how to extract the appropriate information from the image of human eyes need to be considered and the gaze regularity of eyes need to be obtained as references of modeling. Based on the analysis of current three kinds of eye movement control model and the characteristics of the Implicit Prosody reading, relative independence between speech processing system of text and eye movement control system was discussed. It was proved that under the same text familiarity condition, gaze duration of eyes when reading and internal voice pronunciation duration are synchronous. The eye gaze duration model based on the Chinese language level prosodic structure was presented to change previous methods of machine learning and probability forecasting, obtain readers' real internal reading rhythm and to synthesize voice with personalized rhythm. This research will enrich human-computer interactive form, and will be practical significance and application prospect in terms of disabled assisted speech interaction. Experiments show that Implicit Prosody mining based on the human eye image capture technology makes the synthesized speech has more flexible expressions.

Integrated computer-aided design using minicomputers

NASA Technical Reports Server (NTRS)

Storaasli, O. O.

1980-01-01

Computer-Aided Design/Computer-Aided Manufacturing (CAD/CAM), a highly interactive software, has been implemented on minicomputers at the NASA Langley Research Center. CAD/CAM software integrates many formerly fragmented programs and procedures into one cohesive system; it also includes finite element modeling and analysis, and has been interfaced via a computer network to a relational data base management system and offline plotting devices on mainframe computers. The CAD/CAM software system requires interactive graphics terminals operating at a minimum of 4800 bits/sec transfer rate to a computer. The system is portable and introduces 'interactive graphics', which permits the creation and modification of models interactively. The CAD/CAM system has already produced designs for a large area space platform, a national transonic facility fan blade, and a laminar flow control wind tunnel model. Besides the design/drafting element analysis capability, CAD/CAM provides options to produce an automatic program tooling code to drive a numerically controlled (N/C) machine. Reductions in time for design, engineering, drawing, finite element modeling, and N/C machining will benefit productivity through reduced costs, fewer errors, and a wider range of configuration.

Eye Tracking Based Control System for Natural Human-Computer Interaction

PubMed Central

Lin, Shu-Fan

2017-01-01

Eye movement can be regarded as a pivotal real-time input medium for human-computer communication, which is especially important for people with physical disability. In order to improve the reliability, mobility, and usability of eye tracking technique in user-computer dialogue, a novel eye control system with integrating both mouse and keyboard functions is proposed in this paper. The proposed system focuses on providing a simple and convenient interactive mode by only using user's eye. The usage flow of the proposed system is designed to perfectly follow human natural habits. Additionally, a magnifier module is proposed to allow the accurate operation. In the experiment, two interactive tasks with different difficulty (searching article and browsing multimedia web) were done to compare the proposed eye control tool with an existing system. The Technology Acceptance Model (TAM) measures are used to evaluate the perceived effectiveness of our system. It is demonstrated that the proposed system is very effective with regard to usability and interface design. PMID:29403528

Eye Tracking Based Control System for Natural Human-Computer Interaction.

PubMed

Zhang, Xuebai; Liu, Xiaolong; Yuan, Shyan-Ming; Lin, Shu-Fan

2017-01-01

Eye movement can be regarded as a pivotal real-time input medium for human-computer communication, which is especially important for people with physical disability. In order to improve the reliability, mobility, and usability of eye tracking technique in user-computer dialogue, a novel eye control system with integrating both mouse and keyboard functions is proposed in this paper. The proposed system focuses on providing a simple and convenient interactive mode by only using user's eye. The usage flow of the proposed system is designed to perfectly follow human natural habits. Additionally, a magnifier module is proposed to allow the accurate operation. In the experiment, two interactive tasks with different difficulty (searching article and browsing multimedia web) were done to compare the proposed eye control tool with an existing system. The Technology Acceptance Model (TAM) measures are used to evaluate the perceived effectiveness of our system. It is demonstrated that the proposed system is very effective with regard to usability and interface design.

Making intelligent systems team players: Additional case studies

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Schreckenghost, Debra L.; Rhoads, Ron W.

1993-01-01

Observations from a case study of intelligent systems are reported as part of a multi-year interdisciplinary effort to provide guidance and assistance for designers of intelligent systems and their user interfaces. A series of studies were conducted to investigate issues in designing intelligent fault management systems in aerospace applications for effective human-computer interaction. The results of the initial study are documented in two NASA technical memoranda: TM 104738 Making Intelligent Systems Team Players: Case Studies and Design Issues, Volumes 1 and 2; and TM 104751, Making Intelligent Systems Team Players: Overview for Designers. The objective of this additional study was to broaden the investigation of human-computer interaction design issues beyond the focus on monitoring and fault detection in the initial study. The results of this second study are documented which is intended as a supplement to the original design guidance documents. These results should be of interest to designers of intelligent systems for use in real-time operations, and to researchers in the areas of human-computer interaction and artificial intelligence.

Human/computer control of undersea teleoperators

NASA Technical Reports Server (NTRS)

Sheridan, T. B.; Verplank, W. L.; Brooks, T. L.

1978-01-01

The potential of supervisory controlled teleoperators for accomplishment of manipulation and sensory tasks in deep ocean environments is discussed. Teleoperators and supervisory control are defined, the current problems of human divers are reviewed, and some assertions are made about why supervisory control has potential use to replace and extend human diver capabilities. The relative roles of man and computer and the variables involved in man-computer interaction are next discussed. Finally, a detailed description of a supervisory controlled teleoperator system, SUPERMAN, is presented.

Electron interaction with phosphate cytidine oligomer dCpdC: base-centered radical anions and their electronic spectra.

PubMed

Gu, Jiande; Wang, Jing; Leszczynski, Jerzy

2014-01-30

Computational chemistry approach was applied to explore the nature of electron attachment to cytosine-rich DNA single strands. An oligomer dinucleoside phosphate deoxycytidylyl-3',5'-deoxycytidine (dCpdC) was selected as a model system for investigations by density functional theory. Electron distribution patterns for the radical anions of dCpdC in aqueous solution were explored. The excess electron may reside on the nucleobase at the 5' position (dC(•-)pdC) or at the 3' position (dCpdC(•-)). From comparison with electron attachment to the cytosine related DNA fragments, the electron affinity for the formation of the cytosine-centered radical anion in DNA is estimated to be around 2.2 eV. Electron attachment to cytosine sites in DNA single strands might cause perturbations of local structural characteristics. Visible absorption spectroscopy may be applied to validate computational results and determine experimentally the existence of the base-centered radical anion. The time-dependent DFT study shows the absorption around 550-600 nm for the cytosine-centered radical anions of DNA oligomers. This indicates that if such species are detected experimentally they would be characterized by a distinctive color.

“Doctor” or “darling”? Decoding the communication partner from ECoG of the anterior temporal lobe during non-experimental, real-life social interaction

PubMed Central

Derix, Johanna; Iljina, Olga; Schulze-Bonhage, Andreas; Aertsen, Ad; Ball, Tonio

2012-01-01

Human brain processes underlying real-life social interaction in everyday situations have been difficult to study and have, until now, remained largely unknown. Here, we investigated whether electrocorticography (ECoG) recorded for pre-neurosurgical diagnostics during the daily hospital life of epilepsy patients could provide a way to elucidate the neural correlates of non-experimental social interaction. We identified time periods in which patients were involved in conversations with either their respective life partners (Condition 1; C1) or attending physicians (Condition 2; C2). These two conditions can be expected to differentially involve subfunctions of social interaction which have been associated with activity in the anterior temporal lobe (ATL), including the temporal pole (TP). Therefore, we specifically focused on ECoG recordings from this brain region and investigated spectral power modulations in the alpha (8–12 Hz) and theta (3–5 Hz) frequency ranges, which have been previously assumed to play an important role in the processing of social interaction. We hypothesized that brain activity in this region might be sensitive to differences in the two interaction situations and tested whether these differences can be detected by single-trial decoding. Condition-specific effects in both theta and alpha bands were observed: the left and right TP exclusively showed increased power in C1 compared to C2, whereas more posterior parts of the ATL exhibited similar (C1 > C2) and also contrary (C2 > C1) effects. Single-trial decoding accuracies for classification of these effects were highly above chance. Our findings demonstrate that it is possible to study the neural correlates of human social interaction in non-experimental conditions. Decoding the identity of the communication partner and adjusting the speech output accordingly may be useful in the emerging field of brain-machine interfacing for restoration of expressive speech. PMID:22973215

An Overview of Computer-Based Natural Language Processing.

ERIC Educational Resources Information Center

Gevarter, William B.

Computer-based Natural Language Processing (NLP) is the key to enabling humans and their computer-based creations to interact with machines using natural languages (English, Japanese, German, etc.) rather than formal computer languages. NLP is a major research area in the fields of artificial intelligence and computational linguistics. Commercial…

Introduction to This Special Issue on Context-Aware Computing.

ERIC Educational Resources Information Center

Moran, Thomas P.; Dourish, Paul

2001-01-01

Discusses pervasive, or ubiquitous, computing; explains the notion of context; and defines context-aware computing as the key to disperse and enmesh computation into our lives. Considers context awareness in human-computer interaction and describes the broad topic areas of the essays included in this special issue. (LRW)

Developing the human-computer interface for Space Station Freedom

NASA Technical Reports Server (NTRS)

Holden, Kritina L.

1991-01-01

For the past two years, the Human-Computer Interaction Laboratory (HCIL) at the Johnson Space Center has been involved in prototyping and prototype reviews of in support of the definition phase of the Space Station Freedom program. On the Space Station, crew members will be interacting with multi-monitor workstations where interaction with several displays at one time will be common. The HCIL has conducted several experiments to begin to address design issues for this complex system. Experiments have dealt with design of ON/OFF indicators, the movement of the cursor across multiple monitors, and the importance of various windowing capabilities for users performing multiple tasks simultaneously.

Novel 3-D Computer Model Can Help Predict Pathogens’ Roles in Cancer | Poster

Cancer.gov

To understand how bacterial and viral infections contribute to human cancers, four NCI at Frederick scientists turned not to the lab bench, but to a computer. The team has created the world’s first—and currently, only—3-D computational approach for studying interactions between pathogen proteins and human proteins based on a molecular adaptation known as interface mimicry.

Supervised learning from human performance at the computationally hard problem of optimal traffic signal control on a network of junctions

PubMed Central

Box, Simon

2014-01-01

Optimal switching of traffic lights on a network of junctions is a computationally intractable problem. In this research, road traffic networks containing signallized junctions are simulated. A computer game interface is used to enable a human ‘player’ to control the traffic light settings on the junctions within the simulation. A supervised learning approach, based on simple neural network classifiers can be used to capture human player's strategies in the game and thus develop a human-trained machine control (HuTMaC) system that approaches human levels of performance. Experiments conducted within the simulation compare the performance of HuTMaC to two well-established traffic-responsive control systems that are widely deployed in the developed world and also to a temporal difference learning-based control method. In all experiments, HuTMaC outperforms the other control methods in terms of average delay and variance over delay. The conclusion is that these results add weight to the suggestion that HuTMaC may be a viable alternative, or supplemental method, to approximate optimization for some practical engineering control problems where the optimal strategy is computationally intractable. PMID:26064570

Supervised learning from human performance at the computationally hard problem of optimal traffic signal control on a network of junctions.

PubMed

Box, Simon

2014-12-01

Optimal switching of traffic lights on a network of junctions is a computationally intractable problem. In this research, road traffic networks containing signallized junctions are simulated. A computer game interface is used to enable a human 'player' to control the traffic light settings on the junctions within the simulation. A supervised learning approach, based on simple neural network classifiers can be used to capture human player's strategies in the game and thus develop a human-trained machine control (HuTMaC) system that approaches human levels of performance. Experiments conducted within the simulation compare the performance of HuTMaC to two well-established traffic-responsive control systems that are widely deployed in the developed world and also to a temporal difference learning-based control method. In all experiments, HuTMaC outperforms the other control methods in terms of average delay and variance over delay. The conclusion is that these results add weight to the suggestion that HuTMaC may be a viable alternative, or supplemental method, to approximate optimization for some practical engineering control problems where the optimal strategy is computationally intractable.

Insulin receptor substrate proteins create a link between the tyrosine phosphorylation cascade and the Ca2+-ATPases in muscle and heart.

PubMed

Algenstaedt, P; Antonetti, D A; Yaffe, M B; Kahn, C R

1997-09-19

Following phosphorylation by the insulin receptor kinase, the insulin receptor substrates (IRS)-1 and IRS-2 bind to and activate several Src homology 2 (SH2) domain proteins. To identify novel proteins that interact with IRS proteins in muscle, a human skeletal muscle cDNA expression library was created in the lambdaEXlox system and probed with baculovirus-produced and tyrosine-phosphorylated human IRS-1. One clone of the 10 clones which was positive through three rounds of screening represented the C terminus of the human homologue of the adult fast twitch skeletal muscle Ca2+-ATPase (SERCA1) including the cytoplasmic tail and part of transmembrane region 10. Western blot analysis of extracts of rat muscle demonstrated co-immunoprecipitation of both IRS-1 and IRS-2 with the skeletal muscle Ca2+-ATPase (SERCA1) and the cardiac muscle isoform (SERCA2). In both cases, injection of insulin stimulated a 2- to 6-fold increase in association of which was maximal within 5 min. In primary cultures of aortic smooth muscle cells and C2C12 cells, the insulin-stimulated interaction between IRS proteins and SERCA1 and -2 was dose-dependent with a maximum induction at 100 nM insulin. This interaction was confirmed in a "pull down" experiment using a glutathione S-transferase fusion protein containing the C terminus of the human SERCA isoform and phosphorylated IRS-1 in vitro and could be blocked by a FLVRES-like domain peptide present in the human SERCA sequence. Affinity chromatography of phosphopeptide libraries using the glutathione S-transferase fusion protein of the C terminus of SERCA1 indicated a consensus sequence for binding of XpYGSS; this is identical to potential tyrosine phosphorylation sites at position 431 of human IRS-1 and at position 500 of human IRS-2. In streptozotocin diabetic rats the interaction between IRS proteins and SERCA1 in skeletal muscle and SERCA2 in cardiac muscle was significantly reduced. Taken together, these results indicate that the IRS proteins bind to the Ca2+-ATPase of the sarcoplasmic reticulum in an insulin-regulated fashion, thus creating a potential link between the tyrosine phosphorylation cascade and effects of insulin on calcium.

Comparison of Interactive Computer-Based and Classroom Training on Human Rights Awareness in Persons with Intellectual Disabilities

ERIC Educational Resources Information Center

Tardif-Williams, Christine Y.; Owen, Frances; Feldman, Maurice; Tarulli, Donato; Griffiths, Dorothy; Sales, Carol; McQueen-Fuentes, Glenys; Stoner, Karen

2007-01-01

We tested the effectiveness of an interactive, video CD-ROM in teaching persons with intellectual disabilities (ID) about their human rights. Thirty-nine participants with ID were trained using both a classroom activity-based version of the training program and the interactive CD-ROM in a counterbalanced presentation. All individuals were pre- and…

Characterisation of 5-HT3C, 5-HT3D and 5-HT3E receptor subunits: evolution, distribution and function.

PubMed

Holbrook, Joanna D; Gill, Catherine H; Zebda, Noureddine; Spencer, Jon P; Leyland, Rebecca; Rance, Kim H; Trinh, Han; Balmer, Gemma; Kelly, Fiona M; Yusaf, Shahnaz P; Courtenay, Nicola; Luck, Jane; Rhodes, Andrew; Modha, Sundip; Moore, Stephen E; Sanger, Gareth J; Gunthorpe, Martin J

2009-01-01

The 5-HT(3) receptor is a member of the 'Cys-loop' family of ligand-gated ion channels that mediate fast excitatory and inhibitory transmission in the nervous system. Current evidence points towards native 5-HT(3) receptors originating from homomeric assemblies of 5-HT(3A) or heteromeric assembly of 5-HT(3A) and 5-HT(3B). Novel genes encoding 5-HT(3C), 5-HT(3D), and 5-HT(3E) have recently been described but the functional importance of these proteins is unknown. In the present study, in silico analysis (confirmed by partial cloning) indicated that 5-HT(3C), 5-HT(3D), and 5-HT(3E) are not human-specific as previously reported: they are conserved in multiple mammalian species but are absent in rodents. Expression profiles of the novel human genes indicated high levels in the gastrointestinal tract but also in the brain, Dorsal Root Ganglion (DRG) and other tissues. Following the demonstration that these subunits are expressed at the cell membrane, the functional properties of the recombinant human subunits were investigated using patch clamp electrophysiology. 5-HT(3C), 5-HT(3D), and 5-HT(3E) were all non-functional when expressed alone. Co-transfection studies to determine potential novel heteromeric receptor interactions with 5-HT(3A) demonstrated that the expression or function of the receptor was modified by 5-HT(3C) and 5-HT(3E), but not 5-HT(3D). The lack of distinct effects on current rectification, kinetics or pharmacology of 5-HT(3A) receptors does not however provide unequivocal evidence to support a direct contribution of 5-HT(3C) or 5-HT(3E) to the lining of the ion channel pore of novel heteromeric receptors. The functional and pharmacological contributions of these novel subunits to human biology and diseases such as irritable bowel syndrome for which 5-HT(3) receptor antagonists have major clinical usage, therefore remains to be fully determined.

[Characteristics of autonomic status in employees working with computers].

PubMed

Vlasova, E M; Zaĭtseva, N V; Maliutina, N N

2011-01-01

Human evolution is accompanied by "sensible thoughts" spread to all spheres of occupational activities. One can hardly find an industrial enterprise without computers. In contemporary industry, health care in conditions of humans and computers interaction and evaluation of harm in computer users remain topical. Social and occupational environment is not always comfortable for human body. Changes is occupational conditions, with wide use of computer technologies, decrease role of manual labour and increase role of intellectual work from the one hand, but from the other hand, chasing economic profit alters individual "comfort zone" due to constant psychoemotional stress and causes "burnout". Being healthy in constant stress is impossible.

A New Continent of Ideas

NASA Technical Reports Server (NTRS)

1990-01-01

While a new technology called 'virtual reality' is still at the 'ground floor' level, one of its basic components, 3D computer graphics is already in wide commercial use and expanding. Other components that permit a human operator to 'virtually' explore an artificial environment and to interact with it are being demonstrated routinely at Ames and elsewhere. Virtual reality might be defined as an environment capable of being virtually entered - telepresence, it is called - or interacted with by a human. The Virtual Interface Environment Workstation (VIEW) is a head-mounted stereoscopic display system in which the display may be an artificial computer-generated environment or a real environment relayed from remote video cameras. Operator can 'step into' this environment and interact with it. The DataGlove has a series of fiber optic cables and sensors that detect any movement of the wearer's fingers and transmit the information to a host computer; a computer generated image of the hand will move exactly as the operator is moving his gloved hand. With appropriate software, the operator can use the glove to interact with the computer scene by grasping an object. The DataSuit is a sensor equipped full body garment that greatly increases the sphere of performance for virtual reality simulations.

Design of a compact low-power human-computer interaction equipment for hand motion

NASA Astrophysics Data System (ADS)

Wu, Xianwei; Jin, Wenguang

2017-01-01

Human-Computer Interaction (HCI) raises demand of convenience, endurance, responsiveness and naturalness. This paper describes a design of a compact wearable low-power HCI equipment applied to gesture recognition. System combines multi-mode sense signals: the vision sense signal and the motion sense signal, and the equipment is equipped with the depth camera and the motion sensor. The dimension (40 mm × 30 mm) and structure is compact and portable after tight integration. System is built on a module layered framework, which contributes to real-time collection (60 fps), process and transmission via synchronous confusion with asynchronous concurrent collection and wireless Blue 4.0 transmission. To minimize equipment's energy consumption, system makes use of low-power components, managing peripheral state dynamically, switching into idle mode intelligently, pulse-width modulation (PWM) of the NIR LEDs of the depth camera and algorithm optimization by the motion sensor. To test this equipment's function and performance, a gesture recognition algorithm is applied to system. As the result presents, general energy consumption could be as low as 0.5 W.

Cytotoxic 3,4,5-trimethoxychalcones as mitotic arresters and cell migration inhibitors

PubMed Central

Salum, Lívia B.; Altei, Wanessa F.; Chiaradia, Louise D.; Cordeiro, Marlon N.S.; Canevarolo, Rafael R.; Melo, Carolina P.S.; Winter, Evelyn; Mattei, Bruno; Daghestani, Hikmat N.; Santos-Silva, Maria Cláudia; Creczynski-Pasa, Tânia B.; Yunes, Rosendo A.; Yunes, José A.; Andricopulo, Adriano D.; Day, Billy W.; Nunes, Ricardo J.; Vogt, Andreas

2013-01-01

Based on classical colchicine site ligands and a computational model of the colchicine binding site on beta tubulin, two classes of chalcone derivatives were designed, synthesized and evaluated for inhibition of tubulin assembly and toxicity in human cancer cell lines. Docking studies suggested that the chalcone scaffold could fit the colchicine site on tubulin in an orientation similar to that of the natural product. In particular, a 3,4,5-trimethoxyphenyl ring adjacent to the carbonyl group appeared to benefit the ligand-tubulin interaction, occupying the same subcavity as the corresponding moiety in colchicine. Consistent with modeling predictions, several 3,4,5-trimethoxychalcones showed improved cytotoxicity to murine acute lymphoblastic leukemia cells compared with a previously described parent compound, and inhibited tubulin assembly in vitro as potently as colchicine. The most potent chalcones inhibited the growth of human leukemia cell lines at nanomolar concentrations, caused microtubule destabilization and mitotic arrest in human cervical cancer cells, and inhibited human breast cancer cell migration in scratch wound and Boyden chamber assays. PMID:23524161

An Effective-Hamiltonian Approach to CH5+, Using Ideas from Atomic Spectroscopy

NASA Astrophysics Data System (ADS)

Hougen, Jon T.

2016-06-01

In this talk we present the first steps in the design of an effective Hamiltonian for the vibration-rotation energy levels of CH5+. Such a Hamiltonian would allow calculation of energy level patterns anywhere along the path travelled by a hypothetical CH5+ (or CD5+) molecule as it passes through various coupling cases, and might thus provide some hints for assigning the observed high-resolution spectra. The steps discussed here, which have not yet addressed computational problems, focus on mapping the vibration-rotation problem in CH5+ onto the five-electron problem in the boron atom, using ideas and mathematical machinery from Condon and Shortley's book on atomic spectroscopy. The mapping ideas are divided into: (i) a mapping of particles, (ii) a mapping of coordinates (i.e., mathematical degrees of freedom), and (iii) a mapping of quantum mechanical interaction terms. The various coupling cases along the path correspond conceptually to: (i) the analog of a free-rotor limit, where the H atoms see the central C atom but do not see each other, (ii) the low-barrier and high-barrier tunneling regimes, and (iii) the rigid-molecule limit, where the H atoms remain locked in some fixed molecular geometry. Since the mappings considered here often involve significant changes in mathematics, a number of interesting qualitative changes occur in the basic ideas when passing from B to CH5+, particularly in discussions of: (i) antisymmetrization and symmetrization ideas, (ii) n,l,ml,ms or n,l,j,mj quantum numbers, and (iii) Russell-Saunders computations and energy level patterns. Some of the mappings from B to CH5+ to be discussed are as follows. Particles: the atomic nucleus is replaced by the C atom, the electrons are replaced by protons, and the empty space between particles is replaced by an "electron soup." Coordinates: the radial coordinates of the electrons map onto the five local C-H stretching modes, the angular coordinates of the electrons map onto three rotational degrees of freedom and seven bending vibrational degrees of freedom. The half-integral electron spins map onto half-integral proton spins or onto integral deuterium spins (for CD5+). Interactions: the Coulomb attraction between nucleus and electrons maps onto a Morse-oscillator C-H stretching potential, spin-orbit interaction maps onto proton-spin-overall-rotation interaction, and Coulomb repulsion between electrons maps onto some kind of proton repulsion that leads to the equilibrium geometry.

An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L↑N↑L PR mutant

NASA Astrophysics Data System (ADS)

Sanusi, Zainab K.; Govender, Thavendran; Maguire, Glenn E. M.; Maseko, Sibusiso B.; Lin, Johnson; Kruger, Hendrik G.; Honarparvar, Bahareh

2018-03-01

The aspartate protease of the human immune deficiency type-1 virus (HIV-1) has become a crucial antiviral target in which many useful antiretroviral inhibitors have been developed. However, it seems the emergence of new HIV-1 PR mutations enhances drug resistance, hence, the available FDA approved drugs show less activity towards the protease. A mutation and insertion designated L38L↑N↑L PR was recently reported from subtype of C-SA HIV-1. An integrated two-layered ONIOM (QM:MM) method was employed in this study to examine the binding affinities of the nine HIV PR inhibitors against this mutant. The computed binding free energies as well as experimental data revealed a reduced inhibitory activity towards the L38L↑N↑L PR in comparison with subtype C-SA HIV-1 PR. This observation suggests that the insertion and mutations significantly affect the binding affinities or characteristics of the HIV PIs and/or parent PR. The same trend for the computational binding free energies was observed for eight of the nine inhibitors with respect to the experimental binding free energies. The outcome of this study shows that ONIOM method can be used as a reliable computational approach to rationalize lead compounds against specific targets. The nature of the intermolecular interactions in terms of the host-guest hydrogen bond interactions is discussed using the atoms in molecules (AIM) analysis. Natural bond orbital analysis was also used to determine the extent of charge transfer between the QM region of the L38L↑N↑L PR enzyme and FDA approved drugs. AIM analysis showed that the interaction between the QM region of the L38L↑N↑L PR and FDA approved drugs are electrostatic dominant, the bond stability computed from the NBO analysis supports the results from the AIM application. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to provide information that will aid in the design of much improved HIV-1 PR antiviral drugs.

Inhibition of Human Papillomavirus Type 16 Infection Using an RNA Aptamer.

PubMed

Valencia-Reséndiz, Diana Gabriela; Palomino-Vizcaino, Giovanni; Tapia-Vieyra, Juana Virginia; Benítez-Hess, María Luisa; Leija-Montoya, Ana Gabriela; Alvarez-Salas, Luis Marat

2018-04-01

Human papillomavirus type 16 (HPV16) DNA has been found in ∼50% of cervical tumors worldwide. HPV infection starts with the binding of the virus capsid to heparan sulfate (HS) receptors exposed on the surface of epithelial basal layer keratinocytes. Previously, our group isolated a high-affinity RNA aptamer (Sc5c3) specific for HPV16 L1 virus-like particles (VLPs). In this study, we report the inhibition of HPV16 infection by Sc5c3 in a pseudovirus (PsVs) model. 293TT cells were infected by HPV16 PsVs containing the yellow fluorescent protein (YFP) as reporter gene. Incubation of HPV16 PsVs with Sc5c3 before infection resulted in a dose-dependent decrease in YFP fluorescence, suggesting infection inhibition. Aptamer degradation by RNase A restored PsVs infectivity, supporting the previous observation that Sc5c3 aptamer can inhibit infection. VLP mutants with removed HS binding sites were used in binding assays to elucidate the Sc5c3 blocking mechanism; however, no binding difference was observed between wild-type and mutant VLPs, suggesting that pseudoinfection inhibition relies on mechanisms additional to electrostatic HS binding site interaction. A DNA/RNA Sc5c3 version also inhibited HPV PsVs infection, suggesting that a modified, nuclease-resistant Sc5c3 may be used to inhibit HPV16 infection in vivo.

A prisoner's dilemma experiment on cooperation with people and human-like computers.

PubMed

Kiesler, S; Sproull, L; Waters, K

1996-01-01

The authors investigated basic properties of social exchange and interaction with technology in an experiment on cooperation with a human-like computer partner or a real human partner. Talking with a computer partner may trigger social identity feelings or commitment norms. Participants played a prisoner's dilemma game with a confederate or a computer partner. Discussion, inducements to make promises, and partner cooperation varied across trials. On Trial 1, after discussion, most participants proposed cooperation. They kept their promises as much with a text-only computer as with a person, but less with a more human-like computer. Cooperation dropped sharply when any partner avoided discussion. The strong impact of discussion fits a social contract explanation of cooperation following discussion. Participants broke their promises to a computer more than to a person, however, indicating that people make heterogeneous commitments.

Th-Based Endohedral Metallofullerenes: Anomalous Metal Position and Significant Metal-Cage Covalent Interactions with the Involvement of Th 5f Orbitals.

PubMed

Li, Ying; Yang, Le; Liu, Chang; Hou, Qinghua; Jin, Peng; Lu, Xing

2018-05-29

Endohedral metallofullerenes (EMFs) containing actinides are rather intriguing due to potential 5f-orbital participation in the metal-metal or metal-cage bonding. In this work, density functional theory calculations first characterized the structure of recently synthesized ThC 74 as Th@ D 3 h (14246)-C 74 . We found that the thorium atom adopts an unusual off-axis position inside cage due to small metal ion size and the requirement of large coordination number, which phenomenon was further extended to other Th-based EMFs. Significantly, besides the strong metal-cage electrostatic attractions, topological and orbital analysis revealed that all the investigated Th-based EMFs exhibit obvious covalent interactions between metal and cage with substantial contribution from the Th 5f orbitals. The encapsulation by fullerenes is thus proposed as a practical pathway toward the f-orbital covalency for thorium. Interestingly, the anomalous internal position of Th led to a novel three-dimensional metal trajectory at elevated temperatures in the D 3 h -C 74 cavity, as elucidated by the static computations and molecular dynamic simulations.

An ab initio study of the C3(+) cation using multireference methods

NASA Technical Reports Server (NTRS)

Taylor, Peter R.; Martin, J. M. L.; Francois, J. P.; Gijbels, R.

1991-01-01

The energy difference between the linear 2 sigma(sup +, sub u) and cyclic 2B(sub 2) structures of C3(+) has been investigated using large (5s3p2d1f) basis sets and multireference electron correlation treatments, including complete active space self consistent fields (CASSCF), multireference configuration interaction (MRCI), and averaged coupled-pair functional (ACPF) methods, as well as the single-reference quadratic configuration interaction (QCISD(T)) method. Our best estimate, including a correction for basis set incompleteness, is that the linear form lies above the cyclic from by 5.2(+1.5 to -1.0) kcal/mol. The 2 sigma(sup +, sub u) state is probably not a transition state, but a local minimum. Reliable computation of the cyclic/linear energy difference in C3(+) is extremely demanding of the electron correlation treatment used: of the single-reference methods previously considered, CCSD(T) and QCISD(T) perform best. The MRCI + Q(0.01)/(4s2p1d) energy separation of 1.68 kcal/mol should provide a comparison standard for other electron correlation methods applied to this system.

Making It Real

ERIC Educational Resources Information Center

McCartney, Robert; Tenenberg, Josh

2008-01-01

Some have proposed that realistic problem situations are better for learning. This issue contains two articles that examine the effects of "making it real" in computer architecture and human-computer interaction.

Different Conformations of 2'-Deoxycytidine in the Gas and Solid Phases: Competition between Intra- and Intermolecular Hydrogen Bonds.

PubMed

Ling, Sanliang; Gutowski, Maciej

2016-10-06

Computational results have been reported for 2'-deoxycytidine (dC), its gas phase isomers, tautomers, and their conformers, as well as for the crystalline phase. In addition to the neutral gas phase molecules, we have also considered associated radical anions and cations. The structural calculations were performed at the density functional and MP2 levels of theory. Vertical electron ionization energies and excess electron binding energies were determined using electron propagator theory. The α-anomer proved to be more stable by a fraction of kcal/mol than the biologically relevant canonical β-anomer. The conformational space of canonical dC has been systematically probed. dC in the crystalline phase or DNA structures favors canonical anti conformations. These structures were used in past computational studies to model gas phase characteristics of dC. Our findings indicate, however, that the gas phase dC favors syn conformations. It has repercussions for earlier interpretations of gas phase experimental results based on these computational results. The thermodynamic dominance of syn conformations results from the formation of an intramolecular O5'-H13···O2 hydrogen bond. The IR spectra of the most stable syn and anti canonical conformers differ markedly in the region of frequencies corresponding to NH/OH stretching modes. The MP2 value of deprotonation enthalpy of dC of 1411.7 kJ/mol is in very good agreement with the experimental value of 1409 ± 2.5 kJ/mol. The most stable valence anions are characterized by electron vertical detachment energies (VDE) in the 0.8-1.0 eV range, in good agreement with the experimental VDE of 0.87 eV. The barrier for the glycosidic bond cleavage is significant in the neutral canonical dC, 40.0 kcal/mol, and it is reduced to 22 and 16 kcal/mol for the anionic and cationic radicals of dC, respectively. The cleavage reaction is exothermic by 4 kcal/mol for dC - and endothermic by 7 and 9 kcal/mol for dC + and dC, respectively. We decomposed the crystal cohesive energy into repulsive one-body terms associated with the syn-anti conformational changes, and the attractive intermolecular interaction term. We exposed that the syn-anti conformational changes are very favorable for intermolecular interactions; in particular they make the imino-amino side of the cytosine residue accessible to intermolecular interactions.

Designing Social Presence in e-Learning Environments: Testing the Effect of Interactivity on Children

ERIC Educational Resources Information Center

Tung, Fang-Wu; Deng, Yi-Shin

2006-01-01

The "computers are social actors" paradigm asserts that human-to-computer interactions are fundamentally social responses. Earlier research has shown that effective management of the social presence in user interface design can improve user engagement and motivation. Much of this research has focused on adult subjects. This study…

A Kinect-Based Assessment System for Smart Classroom

ERIC Educational Resources Information Center

Kumara, W. G. C. W.; Wattanachote, Kanoksak; Battulga, Batbaatar; Shih, Timothy K.; Hwang, Wu-Yuin

2015-01-01

With the advancements of the human computer interaction field, nowadays it is possible for the users to use their body motions, such as swiping, pushing and moving, to interact with the content of computers or smart phones without traditional input devices like mouse and keyboard. With the introduction of gesture-based interface Kinect from…

Spectral, optical, thermal, Hirshfeld, antimicrobial studies and computational calculations of a new organic crystal, 1H-benzo[d]imidazol-3-ium-3,5-dinitrobenzoate

NASA Astrophysics Data System (ADS)

Sathya, K.; Dhamodharan, P.; Dhandapani, M.

2017-06-01

Single crystals of 1H-benzo[d]imidazol-3-ium-3,5-dinitrobenzoate (BDNB) were grown by reacting 3,5-dinitrobenzoic acid and benzimidazole by slow evaporation method. UV-Vis-NIR spectral studies of the BDNB show that the crystal is excellently transparent in entire visible region. Chemically and magnetically equivalent protons in BDNB were identified by 1H NMR technique. The carbon frame work of the molecule was established by 13C NMR spectroscopy. Proton transfer mechanism was confirmed by the presence of N+H group in BDNB by FT-IR spectroscopic technique. TG/DTA analyses confirmed that the crystal is stable up to172 °C. Single crystal XRD analysis was carried out to ascertain the molecular structure and the crystal belongs to monoclinic system with space group P21/c. Computational studies that include optimization of molecular geometry, natural bond analysis, Mulliken population analysis and HOMO-LUMO analysis were performed using B3LYP method at 6-31 g level. The low HOMO-LUMO energy gap of BDNB confirms high reactivity of BDNB. Hirshfeld analysis expose that O⋯H/H⋯O interactions are the prominent interactions. Theoretical calculations indicate that first order hyperpolarizability is 16 times greater than urea. The results show that the BDNB may be used for opto-electronic applications. The antimicrobial and antioxidant analyses shows concentration of the compound increases inhibition activity also increases.

Enrichment of Human-Computer Interaction in Brain-Computer Interfaces via Virtual Environments

PubMed Central

Víctor Rodrigo, Mercado-García

2017-01-01

Tridimensional representations stimulate cognitive processes that are the core and foundation of human-computer interaction (HCI). Those cognitive processes take place while a user navigates and explores a virtual environment (VE) and are mainly related to spatial memory storage, attention, and perception. VEs have many distinctive features (e.g., involvement, immersion, and presence) that can significantly improve HCI in highly demanding and interactive systems such as brain-computer interfaces (BCI). BCI is as a nonmuscular communication channel that attempts to reestablish the interaction between an individual and his/her environment. Although BCI research started in the sixties, this technology is not efficient or reliable yet for everyone at any time. Over the past few years, researchers have argued that main BCI flaws could be associated with HCI issues. The evidence presented thus far shows that VEs can (1) set out working environmental conditions, (2) maximize the efficiency of BCI control panels, (3) implement navigation systems based not only on user intentions but also on user emotions, and (4) regulate user mental state to increase the differentiation between control and noncontrol modalities. PMID:29317861

Cynicism, anger and cardiovascular reactivity during anger recall and human-computer interaction.

PubMed

Why, Yong Peng; Johnston, Derek W

2008-06-01

Cynicism moderated by interpersonal anger has been found to be related to cardiovascular reactivity. This paper reports two studies; Study 1 used an Anger Recall task, which aroused interpersonal anger, while participants in Study 2 engaged in a multitasking computer task, which aroused non-interpersonal anger via systematic manipulation of the functioning of the computer mouse. The Cynicism by State Anger interaction was significant for blood pressure arousal in Study 2 but not for Study 1: in Study 2, when State Anger was high, cynicism was positively related to blood pressure arousal but when State Anger was low, cynicism was negatively related to blood pressure arousal. For both studies, when State Anger was low, cynicism was positively related to cardiac output arousal and negatively related to vascular arousal. The results suggest that Cynicism-State Anger interaction can be generalised to non-social anger-arousing situations for hemodynamic processes but blood pressure reactivity is task-dependent. The implication for the role of job control and cardiovascular health during human-computer interactions is discussed.

Usability characteristics of self-administered computer-assisted interviewing in the emergency department: factors affecting ease of use, efficiency, and entry error.

PubMed

Herrick, D B; Nakhasi, A; Nelson, B; Rice, S; Abbott, P A; Saber Tehrani, A S; Rothman, R E; Lehmann, H P; Newman-Toker, D E

2013-01-01

Self-administered computer-assisted interviewing (SACAI) gathers accurate information from patients and could facilitate Emergency Department (ED) diagnosis. As part of an ongoing research effort whose long-range goal is to develop automated medical interviewing for diagnostic decision support, we explored usability attributes of SACAI in the ED. Cross-sectional study at two urban, academic EDs. Convenience sample recruited daily over six weeks. Adult, non-level I trauma patients were eligible. We collected data on ease of use (self-reported difficulty, researcher documented need for help), efficiency (mean time-per-click on a standardized interview segment), and error (self-report age mismatched with age derived from electronic health records) when using SACAI on three different instruments: Elo TouchSystems ESY15A2 (finger touch), Toshiba M200 (with digitizer pen), and Motion C5 (with digitizer pen). We calculated descriptive statistics and used regression analysis to evaluate the impact of patient and computer factors on time-per-click. 841 participants completed all SACAI questions. Few (<1%) thought using the touch computer to ascertain medical information was difficult. Most (86%) required no assistance. Participants needing help were older (54 ± 19 vs. 40 ± 15 years, p<0.001) and more often lacked internet at home (13.4% vs. 7.3%, p = 0.004). On multivariate analysis, female sex (p<0.001), White (p<0.001) and other (p = 0.05) race (vs. Black race), younger age (p<0.001), internet access at home (p<0.001), high school graduation (p = 0.04), and touch screen entry (vs. digitizer pen) (p = 0.01) were independent predictors of decreased time-per-click. Participant misclick errors were infrequent, but, in our sample, occurred only during interviews using a digitizer pen rather than a finger touch-screen interface (1.9% vs. 0%, p = 0.09). Our results support the facility of interactions between ED patients and SACAI. Demographic factors associated with need for assistance or slower interviews could serve as important triggers to offering human support for SACAI interviews during implementation. Understanding human-computer interactions in real-world clinical settings is essential to implementing automated interviewing as means to a larger long-term goal of enhancing clinical care, diagnostic accuracy, and patient safety.

Usability Characteristics of Sel-Fadministered Computer-Assisted Interviewing in the Emergency Department

PubMed Central

Herrick, D. B.; Nakhasi, A.; Nelson, B.; Rice, S.; Abbott, P. A.; Saber Tehrani, A. S.; Rothman, R. E.; Lehmann, H. P.; Newman-Toker, D. E.

2013-01-01

Objective Self-administered computer-assisted interviewing (SACAI) gathers accurate information from patients and could facilitate Emergency Department (ED) diagnosis. As part of an ongoing research effort whose long-range goal is to develop automated medical interviewing for diagnostic decision support, we explored usability attributes of SACAI in the ED. Methods Cross-sectional study at two urban, academic EDs. Convenience sample recruited daily over six weeks. Adult, non-level I trauma patients were eligible. We collected data on ease of use (self-reported difficulty, researcher documented need for help), efficiency (mean time-per-click on a standardized interview segment), and error (self-report age mismatched with age derived from electronic health records) when using SACAI on three different instruments: Elo TouchSystems ESY15A2 (finger touch), Toshiba M200 (with digitizer pen), and Motion C5 (with digitizer pen). We calculated descriptive statistics and used regression analysis to evaluate the impact of patient and computer factors on time-per-click. Results 841 participants completed all SACAI questions. Few (<1%) thought using the touch computer to ascertain medical information was difficult. Most (86%) required no assistance. Participants needing help were older (54 ± 19 vs. 40 ± 15 years, p<0.001) and more often lacked internet at home (13.4% vs. 7.3%, p = 0.004). On multivariate analysis, female sex (p<0.001), White (p<0.001) and other (p = 0.05) race (vs. Black race), younger age (p<0.001), internet access at home (p<0.001), high school graduation (p = 0.04), and touch screen entry (vs. digitizer pen) (p = 0.01) were independent predictors of decreased time-per-click. Participant misclick errors were infrequent, but, in our sample, occurred only during interviews using a digitizer pen rather than a finger touch-screen interface (1.9% vs. 0%, p = 0.09). Discussion Our results support the facility of interactions between ED patients and SACAI. Demographic factors associated with need for assistance or slower interviews could serve as important triggers to offering human support for SACAI interviews during implementation. Conclusion Understanding human-computer interactions in real-world clinical settings is essential to implementing automated interviewing as means to a larger long-term goal of enhancing clinical care, diagnostic accuracy, and patient safety. PMID:23874364

Characterization of the conformational probability of N-acetyl-phenylalanyl-NH2 by RHF, DFT, and MP2 computation and AIM analyses, confirmed by jet-cooled infrared data.

PubMed

Chass, Gregory A; Mirasol, Rei S; Setiadi, David H; Tang, Ting-Hua; Chin, Wutharath; Mons, Michel; Dimicoli, Iliana; Dognon, Jean-Pierre; Viskolcz, Bela; Lovas, Sandor; Penke, Botond; Csizmadia, Imre G

2005-06-23

Computational and experimental determinations were carried out in parallel on the conformational probability of N-Acetyl-Phenylalanine-NH2 (NAPA). Ab initio computations were completed at the BLYP/6-311G(df,p), B3LYP/6-31G(d), B3LYP/6-31G(d,p), and B3LYP/6-31+G(d) levels of theory, labeled L/61fp, B/6, B/6p, and B/6+, respectively. Three experimentally identified conformers were compared with theoretical data, confirming their identities as the betaLanti, gammaLgauche+, and gammaLgauche- (BACKBONESIDECHAIN) conformers. Evidence comes from matching experimental and theoretical data for all three constituent N-H stretches of NAPA, with a Delta(Experimental-Theoretical) = approximately 1-3 cm(-1), approximately 0-5 cm(-1), and approximately 1-6 cm(-1), at the L/61fp and B/6+ levels, respectively. Corrected-ZPE relative energies were computed to be 0.14, 0.00, 0.26 and 0.00, 0.67, 0.57 (kcal*mol(-1)) for the betaLanti, gammaLgauche+, and gamma(Lgauche- conformers, respectively, at the L/61fp and B/6+ levels, respectively. The MP2/6-31+G(d) level of theory was subsequently found to give similar relative energies. Characterization of the intramolecular interactions responsible for red and blue shifting of the N-H stretches showed the existence of the following intramolecular interactions: C=O[i]- - -HN[i], (Ar[i])-Cgamma- - -HN[i+1], (Ar[i])-Cdelta-H- - -O=C[i-1] for betaLanti; C=O[i-1]- - -HN[i+1], (Ar[i])-Cgamma- - -HN[i+1], (Ar[i])-C-H- - -O=C[i] for gammaLgauche+; and C=O[i-1]- - -HN[i+1] for gammaLgauche-. Each of these interactions were further investigated and subsequently characterized by orbital population and Atoms-In-Molecules (AIM) analyses, with the identity of overlap and bond critical points (BCP) serving as 'scoring criteria', respectively. Experimental and theoretical carbonyl stretches were also compared and showed good agreement, adding further strength to the synergy between experiment and theory.

Distinct T cell interactions with HLA class II tetramers characterize a spectrum of TCR affinities in the human antigen-specific T cell response.

PubMed

Reichstetter, S; Ettinger, R A; Liu, A W; Gebe, J A; Nepom, G T; Kwok, W W

2000-12-15

The polyclonal nature of T cells expanding in an ongoing immune response results in a range of disparate affinities and activation potential. Recently developed human class II tetramers provide a means to analyze this diversity by direct characterization of the trimolecular TCR-peptide-MHC interaction in live cells. Two HSV-2 VP16(369-379)-specific, DQA1*0102/DQB1*0602 (DQ0602)-restricted T cell clones were compared by means of T cell proliferation assay and HLA-DQ0602 tetramer staining. These two clones were obtained from the same subject, but show different TCR gene usage. Clone 48 was 10-fold more sensitive to VP16(369-379) peptide stimulation than clone 5 as assayed by proliferation assays, correlating with differences in MHC tetramer binding. Clone 48 gave positive staining with the DQ0602/VP16(369-379) tetramer at either 23 or 37 degrees C. Weak staining was also observed at 4 degrees C. Clone 5 showed weaker staining compared with clone 48 at 37 degrees C, and no staining was observed at 23 degrees C or on ice. Receptor internalization was not required for positive staining. Competitive binding indicates that the cell surface TCR of clone 48 has higher affinity for the DQ0602/VP16(369-379) complex than clone 5. The higher binding affinity of clone 48 for the peptide-MHC complex also correlates with a slower dissociation rate compared with clone 5.

Learning by Communicating in Natural Language with Conversational Agents

ERIC Educational Resources Information Center

Graesser, Arthur; Li, Haiying; Forsyth, Carol

2014-01-01

Learning is facilitated by conversational interactions both with human tutors and with computer agents that simulate human tutoring and ideal pedagogical strategies. In this article, we describe some intelligent tutoring systems (e.g., AutoTutor) in which agents interact with students in natural language while being sensitive to their cognitive…

Biophysical Characterization of the Dimer and Tetramer Interface Interactions of the Human Cytosolic Malic Enzyme

PubMed Central

Murugan, Sujithkumar; Hung, Hui-Chih

2012-01-01

The cytosolic NADP+-dependent malic enzyme (c-NADP-ME) has a dimer-dimer quaternary structure in which the dimer interface associates more tightly than the tetramer interface. In this study, the urea-induced unfolding process of the c-NADP-ME interface mutants was monitored using fluorescence and circular dichroism spectroscopy, analytical ultracentrifugation and enzyme activities. Here, we demonstrate the differential protein stability between dimer and tetramer interface interactions of human c-NADP-ME. Our data clearly demonstrate that the protein stability of c-NADP-ME is affected predominantly by disruptions at the dimer interface rather than at the tetramer interface. First, during thermal stability experiments, the melting temperatures of the wild-type and tetramer interface mutants are 8–10°C higher than those of the dimer interface mutants. Second, during urea denaturation experiments, the thermodynamic parameters of the wild-type and tetramer interface mutants are almost identical. However, for the dimer interface mutants, the first transition of the urea unfolding curves shift towards a lower urea concentration, and the unfolding intermediate exist at a lower urea concentration. Third, for tetrameric WT c-NADP-ME, the enzyme is first dissociated from a tetramer to dimers before the 2 M urea treatment, and the dimers then dissociated into monomers before the 2.5 M urea treatment. With a dimeric tetramer interface mutant (H142A/D568A), the dimer completely dissociated into monomers after a 2.5 M urea treatment, while for a dimeric dimer interface mutant (H51A/D90A), the dimer completely dissociated into monomers after a 1.5 M urea treatment, indicating that the interactions of c-NADP-ME at the dimer interface are truly stronger than at the tetramer interface. Thus, this study provides a reasonable explanation for why malic enzymes need to assemble as a dimer of dimers. PMID:23284632

Artificial Intelligence and the Teaching of Reading and Writing by Computers.

ERIC Educational Resources Information Center

Balajthy, Ernest

1985-01-01

Discusses how computers can "converse" with students for teaching purposes, demonstrates how these interactions are becoming more complex, and explains how the computer's role is becoming more "human" in giving intelligent responses to students. (HOD)

The Interactive Electronic Technical Manual: Requirements, Current Status, and Implementation. Strategy Considerations.

DTIC Science & Technology

1991-07-01

authoring systems. Concurrently, great strides in computer-aided design and computer-aided maintenance have contributed to this capability. 12 Junod ...J.; William A. Nugent; and L. John Junod . Plan for the Navy/Air Force Test of the Interactive Electronic Technical Manual (IETM) at Cecil Field...AFHRL Logistics and Human Factors Division, WPAFB. Aug 1990. 12. Junod , John L. PY90 Interactive Electronic Technical Manual (IETM) Portable Delivery

The Pendulum Swing of User Instruction and Interaction: The Resurrection of "How to Use" Technology to Learn in the 21st Century

ERIC Educational Resources Information Center

Ramsay, Judith; Terras, Melody M.

2015-01-01

The use of technology to support learning is well recognised. One generation ago a major strand of human--computer interaction research focussed on the development of forms of instruction in how to interact with computers. Today, however, the advanced usability of modern technologies has all but removed the presence of many user manuals. Learners,…

Integrated microRNA and mRNA network analysis of the human myometrial transcriptome in the transition from quiescence to labor.

PubMed

Ackerman, William E; Buhimschi, Irina A; Brubaker, Douglas; Maxwell, Sean; Rood, Kara M; Chance, Mark R; Jing, Hongwu; Mesiano, Sam; Buhimschi, Catalin S

2018-02-13

We conducted integrated transcriptomics network analyses of miRNA and mRNA interactions in human myometrium to identify novel molecular candidates potentially involved in human parturition. Myometrial biopsies were collected from women undergoing primary Cesarean deliveries in well-characterized clinical scenarios: 1) spontaneous term labor (TL, n = 5); 2) term non-labor (TNL, n = 5); 3) spontaneous preterm birth (PTB) with histologic chorioamnionitis (PTB-HCA, n = 5); and 4) indicated PTB non-labor (PTB-NL, n = 5). MicroRNAs and long RNAs were profiled using RNA sequencing, and miRNA-target interaction networks were mined for key discriminatory subnetworks. Forty miRNAs differed between TL and TNL myometrium while seven miRNAs differed between PTB-HCA vs. PTB-NL specimens; six of these miRNAs were cross-validated using quantitative PCR. Based on the combined sequencing data, unsupervised clustering revealed two non-overlapping cohorts that differed primarily by absence or presence of uterine quiescence, rather than gestational age or original clinical cohort. The intersection of differentially expressed miRNAs and their mRNA targets predicted 22 subnetworks with enriched representation of miR-146b-5p, miR-223-3p, and miR-150-5p among miRNAs, and of myocyte enhancer factor-2C (MEF2C) among mRNAs. Of four known MEF2 transcription factors, decreased MEF2A and MEF2C expression in women with uterine non-quiescence was observed in the transcriptome profiling data, and validated in a second cohort by quantitative PCR. Immunohistochemistry localized MEF2A and MEF2C to myometrial smooth muscle cells and confirmed decreased abundance with labor. Collectively, these results suggest that repression of MEF2 expression may represent a previously unrecognized process through which miRNAs contribute to the phenotypic switch from quiescence to labor in human myometrium. © The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of HCM cTnI Mutation R145G on Troponin Structure and Modulation by PKA Phosphorylation Elucidated by Molecular Dynamics Simulations

PubMed Central

Lindert, Steffen; Cheng, Yuanhua; Kekenes-Huskey, Peter; Regnier, Michael; McCammon, J. Andrew

2015-01-01

Cardiac troponin (cTn) is a key molecule in the regulation of human cardiac muscle contraction. The N-terminal cardiac-specific peptide of the inhibitory subunit of troponin, cTnI (cTnI1-39), is a target for phosphorylation by protein kinase A (PKA) during β-adrenergic stimulation. We recently presented evidence indicating that this peptide interacts with the inhibitory peptide (cTnl137–147) when S23 and S24 are phosphorylated. The inhibitory peptide is also the target of the point mutation cTnI-R145G, which is associated with hypertrophic cardiomyopathy (HCM), a disease associated with sudden death in apparently healthy young adults. It has been shown that both phosphorylation and this mutation alter the cTnC-cTnI (C-I) interaction, which plays a crucial role in modulating contractile activation. However, little is known about the molecular-level events underlying this modulation. Here, we computationally investigated the effects of the cTnI-R145G mutation on the dynamics of cTn, cTnC Ca2+ handling, and the C-I interaction. Comparisons were made with the cTnI-R145G/S23D/S24D phosphomimic mutation, which has been used both experimentally and computationally to study the cTnI N-terminal specific effects of PKA phosphorylation. Additional comparisons between the phosphomimic mutations and the real phosphorylations were made. For this purpose, we ran triplicate 150 ns molecular dynamics simulations of cTnI-R145G Ca2+-bound cTnC1-161-cTnI1-172-cTnT236-285, cTnI-R145G/S23D/S24D Ca2+-bound cTnC1-161-cTnI1-172-cTnT236-285, and cTnI-R145G/PS23/PS24 Ca2+-bound cTnC1-161-cTnI1-172-cTnT236-285, respectively. We found that the cTnI-R145G mutation did not impact the overall dynamics of cTn, but stabilized crucial Ca2+-coordinating interactions. However, the phosphomimic mutations increased overall cTn fluctuations and destabilized Ca2+ coordination. Interestingly, cTnI-R145G blunted the intrasubunit interactions between the cTnI N-terminal extension and the cTnI inhibitory peptide, which have been suggested to play a crucial role in modulating troponin function during β-adrenergic stimulation. These findings offer a molecular-level explanation for how the HCM mutation cTnI-R145G reduces the modulation of cTn by phosphorylation of S23/S24 during β-adrenergic stimulation. PMID:25606687

Effects of HCM cTnI mutation R145G on troponin structure and modulation by PKA phosphorylation elucidated by molecular dynamics simulations.

PubMed

Lindert, Steffen; Cheng, Yuanhua; Kekenes-Huskey, Peter; Regnier, Michael; McCammon, J Andrew

2015-01-20

Cardiac troponin (cTn) is a key molecule in the regulation of human cardiac muscle contraction. The N-terminal cardiac-specific peptide of the inhibitory subunit of troponin, cTnI (cTnI(1-39)), is a target for phosphorylation by protein kinase A (PKA) during β-adrenergic stimulation. We recently presented evidence indicating that this peptide interacts with the inhibitory peptide (cTnl(137-147)) when S23 and S24 are phosphorylated. The inhibitory peptide is also the target of the point mutation cTnI-R145G, which is associated with hypertrophic cardiomyopathy (HCM), a disease associated with sudden death in apparently healthy young adults. It has been shown that both phosphorylation and this mutation alter the cTnC-cTnI (C-I) interaction, which plays a crucial role in modulating contractile activation. However, little is known about the molecular-level events underlying this modulation. Here, we computationally investigated the effects of the cTnI-R145G mutation on the dynamics of cTn, cTnC Ca(2+) handling, and the C-I interaction. Comparisons were made with the cTnI-R145G/S23D/S24D phosphomimic mutation, which has been used both experimentally and computationally to study the cTnI N-terminal specific effects of PKA phosphorylation. Additional comparisons between the phosphomimic mutations and the real phosphorylations were made. For this purpose, we ran triplicate 150 ns molecular dynamics simulations of cTnI-R145G Ca(2+)-bound cTnC(1-161)-cTnI(1-172)-cTnT(236-285), cTnI-R145G/S23D/S24D Ca(2+)-bound cTnC(1-161)-cTnI(1-172)-cTnT(236-285), and cTnI-R145G/PS23/PS24 Ca(2+)-bound cTnC(1-161)-cTnI(1-172)-cTnT(236-285), respectively. We found that the cTnI-R145G mutation did not impact the overall dynamics of cTn, but stabilized crucial Ca(2+)-coordinating interactions. However, the phosphomimic mutations increased overall cTn fluctuations and destabilized Ca(2+) coordination. Interestingly, cTnI-R145G blunted the intrasubunit interactions between the cTnI N-terminal extension and the cTnI inhibitory peptide, which have been suggested to play a crucial role in modulating troponin function during β-adrenergic stimulation. These findings offer a molecular-level explanation for how the HCM mutation cTnI-R145G reduces the modulation of cTn by phosphorylation of S23/S24 during β-adrenergic stimulation. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder.

PubMed Central

Deyashiki, Y; Ogasawara, A; Nakayama, T; Nakanishi, M; Miyabe, Y; Sato, K; Hara, A

1994-01-01

Human liver contains two dihydrodiol dehydrogenases, DD2 and DD4, associated with 3 alpha-hydroxysteroid dehydrogenase activity. We have raised polyclonal antibodies that cross-reacted with the two enzymes and isolated two 1.2 kb cDNA clones (C9 and C11) for the two enzymes from a human liver cDNA library using the antibodies. The clones of C9 and C11 contained coding sequences corresponding to 306 and 321 amino acid residues respectively, but lacked 5'-coding regions around the initiation codon. Sequence analyses of several peptides obtained by enzymic and chemical cleavages of the two purified enzymes verified that the C9 and C11 clones encoded DD2 and DD4 respectively, and further indicated that the sequence of DD2 had at least additional 16 residues upward from the N-terminal sequence deduced from the cDNA. There was 82% amino acid sequence identity between the two enzymes, indicating that the enzymes are genetic isoenzymes. A computer-based comparison of the cDNAs of the isoenzymes with the DNA sequence database revealed that the nucleotide and amino acid sequences of DD2 and DD4 are virtually identical with those of human bile-acid binder and human chlordecone reductase cDNAs respectively. Images Figure 1 PMID:8172617

The Relative Effectiveness of Human Tutoring, Intelligent Tutoring Systems, and Other Tutoring Systems

ERIC Educational Resources Information Center

VanLehn, Kurt

2011-01-01

This article is a review of experiments comparing the effectiveness of human tutoring, computer tutoring, and no tutoring. "No tutoring" refers to instruction that teaches the same content without tutoring. The computer tutoring systems were divided by their granularity of the user interface interaction into answer-based, step-based, and…

Mind, Brain, and Education in the Digital Era

ERIC Educational Resources Information Center

Battro, Antonio M.; Fischer, Kurt W.

2012-01-01

Computers are everywhere, and they are transforming the human world. The technology of computers and the Internet is radically changing the ways that people learn and communicate. In the midst of this technology-driven revolution people need to examine the changes to analyze how they are altering interaction and human culture. The changes have…

Loyalty to Computer Terminals: Is it Anthropomorphism or Consistency?

ERIC Educational Resources Information Center

Sundar, S. Shyam

2004-01-01

The psychological tendency to behave socially with a computer is quite well documented in the literature. But does the short-term socialness of human-computer interaction extend over to long-term social relationships with computers? In particular, do we show loyalty to particular computer terminals over a period of time? An electronic observation…

Advances in Human-Computer Interaction: Graphics and Animation Components for Interface Design

NASA Astrophysics Data System (ADS)

Cipolla Ficarra, Francisco V.; Nicol, Emma; Cipolla-Ficarra, Miguel; Richardson, Lucy

We present an analysis of communicability methodology in graphics and animation components for interface design, called CAN (Communicability, Acceptability and Novelty). This methodology has been under development between 2005 and 2010, obtaining excellent results in cultural heritage, education and microcomputing contexts. In studies where there is a bi-directional interrelation between ergonomics, usability, user-centered design, software quality and the human-computer interaction. We also present the heuristic results about iconography and layout design in blogs and websites of the following countries: Spain, Italy, Portugal and France.

An automatic eye detection and tracking technique for stereo video sequences

NASA Astrophysics Data System (ADS)

Paduru, Anirudh; Charalampidis, Dimitrios; Fouts, Brandon; Jovanovich, Kim

2009-05-01

Human-computer interfacing (HCI) describes a system or process with which two information processors, namely a human and a computer, attempt to exchange information. Computer-to-human (CtH) information transfer has been relatively effective through visual displays and sound devices. On the other hand, the human-tocomputer (HtC) interfacing avenue has yet to reach its full potential. For instance, the most common HtC communication means are the keyboard and mouse, which are already becoming a bottleneck in the effective transfer of information. The solution to the problem is the development of algorithms that allow the computer to understand human intentions based on their facial expressions, head motion patterns, and speech. In this work, we are investigating the feasibility of a stereo system to effectively determine the head position, including the head rotation angles, based on the detection of eye pupils.

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

Takeshita, Takayuki; Okamoto, Masami

The hydroxyapatite (HA) formation on the surface of DNA molecules in simulated body fluid (SBF) was examined. The osteoconductivity is estimated using SBF having ion concentrations approximately equal to those of human blood plasma. After immersion for 4 weeks in SBF at 36.5 °C, the HA crystallites possessing 1-14 micrometer in diameter grew on the surface of DNA molecules. The leaf flake-like and spherical shapes morphologies were observed through scanning electron microscopy analysis. Original peaks of both of DNA and HA were characterized by fourier transform infrared spectroscopy. The Ca/P ratio (1.1-1.5) in HA was estimated by energy dispersive X-raymore » analysis. After biomineralization, the calculated weight ratio of DNA/HA was 18/82 by thermogravimetry/differential thermal analysis. The molecular orbital computer simulation has been used to probe the interaction of DNA with two charge-balancing ions, CaOH{sup +} and CaH{sub 2}PO{sub 4}{sup +}. The adsorption enthalpy of the two ions on DNA having negative value was the evidence for the interface in mineralization of HA in SBF.« less

Probabilistic simulation of the human factor in structural reliability

NASA Astrophysics Data System (ADS)

Chamis, Christos C.; Singhal, Surendra N.

1994-09-01

The formal approach described herein computationally simulates the probable ranges of uncertainties for the human factor in probabilistic assessments of structural reliability. Human factors such as marital status, professional status, home life, job satisfaction, work load, and health are studied by using a multifactor interaction equation (MFIE) model to demonstrate the approach. Parametric studies in conjunction with judgment are used to select reasonable values for the participating factors (primitive variables). Subsequently performed probabilistic sensitivity studies assess the suitability of the MFIE as well as the validity of the whole approach. Results show that uncertainties range from 5 to 30 percent for the most optimistic case, assuming 100 percent for no error (perfect performance).

Probabilistic Simulation of the Human Factor in Structural Reliability

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Singhal, Surendra N.

1994-01-01

The formal approach described herein computationally simulates the probable ranges of uncertainties for the human factor in probabilistic assessments of structural reliability. Human factors such as marital status, professional status, home life, job satisfaction, work load, and health are studied by using a multifactor interaction equation (MFIE) model to demonstrate the approach. Parametric studies in conjunction with judgment are used to select reasonable values for the participating factors (primitive variables). Subsequently performed probabilistic sensitivity studies assess the suitability of the MFIE as well as the validity of the whole approach. Results show that uncertainties range from 5 to 30 percent for the most optimistic case, assuming 100 percent for no error (perfect performance).

BaffleText: a Human Interactive Proof

NASA Astrophysics Data System (ADS)

Chew, Monica; Baird, Henry S.

2003-01-01

Internet services designed for human use are being abused by programs. We present a defense against such attacks in the form of a CAPTCHA (Completely Automatic Public Turing test to tell Computers and Humans Apart) that exploits the difference in ability between humans and machines in reading images of text. CAPTCHAs are a special case of 'human interactive proofs,' a broad class of security protocols that allow people to identify themselves over networks as members of given groups. We point out vulnerabilities of reading-based CAPTCHAs to dictionary and computer-vision attacks. We also draw on the literature on the psychophysics of human reading, which suggests fresh defenses available to CAPTCHAs. Motivated by these considerations, we propose BaffleText, a CAPTCHA which uses non-English pronounceable words to defend against dictionary attacks, and Gestalt-motivated image-masking degradations to defend against image restoration attacks. Experiments on human subjects confirm the human legibility and user acceptance of BaffleText images. We have found an image-complexity measure that correlates well with user acceptance and assists in engineering the generation of challenges to fit the ability gap. Recent computer-vision attacks, run independently by Mori and Jitendra, suggest that BaffleText is stronger than two existing CAPTCHAs.

Computer simulations of the interaction of human immunodeficiency virus (HIV) aspartic protease with spherical gold nanoparticles: implications in acquired immunodeficiency syndrome (AIDS)

NASA Astrophysics Data System (ADS)

Whiteley, Chris G.; Lee, Duu-Jong

2016-09-01

The interaction of gold nanoparticles (AuNP) with human immune-deficiency virus aspartic protease (HIVPR) is modelled using a regime of molecular dynamics simulations. The simulations of the ‘docking’, first as a rigid-body complex, and eventually through flexible-fit analysis, creates 36 different complexes from four initial orientations of the nanoparticle strategically positioned around the surface of the enzyme. The structural deviations of the enzymes from the initial x-ray crystal structure during each docking simulation are assessed by comparative analysis of secondary structural elements, root mean square deviations, B-factors, interactive bonding energies, dihedral angles, radius of gyration (R g), circular dichroism (CD), volume occupied by C α , electrostatic potentials, solvation energies and hydrophobicities. Normalisation of the data narrows the selection from the initial 36 to one ‘final’ probable structure. It is concluded that, after computer simulations on each of the 36 initial complexes incorporating the 12 different biophysical techniques, the top five complexes are the same no matter which technique is explored. The significance of the present work is an expansion of an earlier study on the molecular dynamic simulation for the interaction of HIVPR with silver nanoparticles. This work is supported by experimental evidence since the initial ‘orientation’ of the AgNP with the enzyme is the same as the ‘final’ AuNP-HIVPR complex generated in the present study. The findings will provide insight into the forces of the binding of the HIVPR to AuNP. It is anticipated that the protocol developed in this study will act as a standard process for the interaction of any nanoparticle with any biomedical target.

Computer simulations of the interaction of human immunodeficiency virus (HIV) aspartic protease with spherical gold nanoparticles: implications in acquired immunodeficiency syndrome (AIDS).

PubMed

Whiteley, Chris G; Lee, Duu-Jong

2016-09-09

The interaction of gold nanoparticles (AuNP) with human immune-deficiency virus aspartic protease (HIVPR) is modelled using a regime of molecular dynamics simulations. The simulations of the 'docking', first as a rigid-body complex, and eventually through flexible-fit analysis, creates 36 different complexes from four initial orientations of the nanoparticle strategically positioned around the surface of the enzyme. The structural deviations of the enzymes from the initial x-ray crystal structure during each docking simulation are assessed by comparative analysis of secondary structural elements, root mean square deviations, B-factors, interactive bonding energies, dihedral angles, radius of gyration (R g), circular dichroism (CD), volume occupied by C α , electrostatic potentials, solvation energies and hydrophobicities. Normalisation of the data narrows the selection from the initial 36 to one 'final' probable structure. It is concluded that, after computer simulations on each of the 36 initial complexes incorporating the 12 different biophysical techniques, the top five complexes are the same no matter which technique is explored. The significance of the present work is an expansion of an earlier study on the molecular dynamic simulation for the interaction of HIVPR with silver nanoparticles. This work is supported by experimental evidence since the initial 'orientation' of the AgNP with the enzyme is the same as the 'final' AuNP-HIVPR complex generated in the present study. The findings will provide insight into the forces of the binding of the HIVPR to AuNP. It is anticipated that the protocol developed in this study will act as a standard process for the interaction of any nanoparticle with any biomedical target.

Crystal Structures of the Novel Cytosolic 5′-Nucleotidase IIIB Explain Its Preference for m7GMP

PubMed Central

Monecke, Thomas; Buschmann, Juliane; Neumann, Piotr; Wahle, Elmar; Ficner, Ralf

2014-01-01

5′-nucleotidases catalyze the hydrolytic dephosphorylation of nucleoside monophosphates. As catabolic enzymes they contribute significantly to the regulation of cellular nucleotide levels; misregulation of nucleotide metabolism and nucleotidase deficiencies are associated with a number of diseases. The seven human 5′-nucleotidases differ with respect to substrate specificity and cellular localization. Recently, the novel cytosolic 5′-nucleotidase III-like protein, or cN-IIIB, has been characterized in human and Drosophila. cN-IIIB exhibits a strong substrate preference for the modified nucleotide 7-methylguanosine monophosphate but the structural reason for this preference was unknown. Here, we present crystal structures of cN-IIIB from Drosophila melanogaster bound to the reaction products 7-methylguanosine or cytidine. The structural data reveal that the cytosine- and 7-methylguanine moieties of the products are stacked between two aromatic residues in a coplanar but off-centered position. 7-methylguanosine is specifically bound through π-π interactions and distinguished from unmodified guanosine by additional cation-π coulomb interactions between the aromatic side chains and the positively charged 7-methylguanine. Notably, the base is further stabilized by T-shaped edge-to-face stacking of an additional tryptophan packing perpendicularly against the purine ring and forming, together with the other aromates, an aromatic slot. The structural data in combination with site-directed mutagenesis experiments reveal the molecular basis for the broad substrate specificity of cN-IIIB but also explain the substrate preference for 7-methylguanosine monophosphate. Analyzing the substrate specificities of cN-IIIB and the main pyrimidine 5′-nucleotidase cN-IIIA by mutagenesis studies, we show that cN-IIIA dephosphorylates the purine m7GMP as well, hence redefining its substrate spectrum. Docking calculations with cN-IIIA and m7GMP as well as biochemical data reveal that Asn69 does not generally exclude the turnover of purine substrates thus correcting previous suggestions. PMID:24603684

Synthesis, crystal structure, spectroscopic characterization, docking simulation and density functional studies of 1-(3,4-dimethoxyphenyl) -3-(4-flurophenyl)-propan-1-one

NASA Astrophysics Data System (ADS)

Khamees, Hussien Ahmed; Jyothi, Mahima; Khanum, Shaukath Ara; Madegowda, Mahendra

2018-06-01

The compound 1-(3,4-dimethoxyphenyl)-3-(4-flurophenyl)-propan-1-one (DFPO) was synthesized by Claisen-Schmidt condensation reaction and the single crystals were obtained by slow evaporation method. Three-dimensional structure was confirmed by single crystal X-ray diffraction method and exhibiting the triclinic crystal system with space group P-1. The crystal structure is stabilized by Csbnd H⋯O intermolecular and weak interactions. Computed molecular geometry has been obtained by density functional theory (DFT) and compared with experimental results. The spectra of both FT-IR in the range (4000-400 cm-1) and FT- Raman (3500-50 cm-1) of DFPO were recorded experimentally and computed by (DFT) using B3LYP/6-311G (d,p) as basis sets. Intramolecular charge transfer has been scanned using natural bond orbital (NBO) analysis and revealed the various contribution of bonding and lone pair to the stabilization of molecule. Nonlinear optical activity (NLO) of the title compound has been determined by second harmonic generation (SHG) and computed using DFT method. Hyperpolarizability, HOMO-LUMO energy gap, hardness, softness electronegativity and others Global reactivity descriptors of DFPO has been calculated and revealed complete picture of chemical reactivity of DFPO. Hirshfeld surface analyses were applied to investigate the intermolecular interactions and revealed that more than two-thirds of the inter contacts are associated with O⋯H, C⋯H and H⋯H interactions. Docking studies of DFPO showed inhibition of Vascular endothelial growth Factor human receptor (VEGFR-2) signalling pathway, which indicates DFPO as anti-angiogenesis, that play pivotal role in cancer, so we suggest it for clinical studies to evaluate its potential to treat human cancers.

Dose Range Evaluation of Mycograb C28Y Variant, a Human Recombinant Antibody Fragment to Heat Shock Protein 90, in Combination with Amphotericin B-Desoxycholate for Treatment of Murine Systemic Candidiasis ▿

PubMed Central

Louie, Arnold; Stein, Daniel S.; Zack, Julia Z.; Liu, Weiguo; Conde, Haley; Fregeau, Christine; VanScoy, Brian D.; Drusano, George L.

2011-01-01

Systemic candidiasis causes significant mortality in patients despite amphotericin B (AMB) therapy. Mycograb C28Y variant, a human recombinant antibody fragment to heat shock protein 90, is closely related to Mycograb, which showed a survival advantage in combination with AMB in a phase III human trial. The Mycograb C28Y variant could potentially increase the antifungal effect of AMB. In our study, the interaction between AMB-desoxycholate (DAMB) and the Mycograb C28Y variant was characterized in vitro by using a checkerboard method. Quantitative cultures of kidneys, livers, and spleens of neutropenic mice with systemic Candida albicans infections were used to assess the in vivo interaction between 1.4 mg/kg of body weight/day of DAMB and 0.15, 1.5, and 15 mg/kg/day of the Mycograb C28Y variant after 1, 3, and 5 days of therapy. DAMB and Mycograb C28Y variant monotherapies, vehicle, and a no-treatment arm served as controls. Also, single- and multidose pharmacokinetics for the Mycograb C28Y variant were determined. Indifference or synergy between DAMB and the Mycograb C28Y variant was seen in two trials by the checkerboard method. The pharmacokinetics of the Mycograb C28Y variant was best described by a 2-compartment model with a median serum t1/2α of ∼0.198 h and a t1/2β of ∼1.77 h. In mice, DAMB together with the Mycograb C28Y variant was no more effective than AMB alone (P > 0.05 by analysis of variance). The Mycograb C28Y variant alone had no antifungal activity. We therefore conclude that the Mycograb C28Y variant in combination with DAMB offered no benefit over DAMB monotherapy in a neutropenic murine model of systemic candidiasis. PMID:21502626

Development of an Interactive Computer Program to Produce Body Description Data

DTIC Science & Technology

1983-07-01

arbitrary and has varied over the time that the CVS Program and the ATB Model have been in existence. Program GOOD produces data describing an upper torso...N NN NfU NJ JANNJ NN N5~SA NJN N a~mn ain itn ft atK 0 ,0 9a fK C ca I n k0 rC 91 01 tol s 6, -Inb v v P w Dvf 4oa 0 0 0 IS t. faa 0 o In - v - allT...NAMES/ SUSTYP(4),-SEGLAB(1 5)*J.JTLA9C¶14),PLTSY4!(29), 014NIN(-1 :31 )PTTLEPUNlITS( 3,-1:1) REAL MEAN(C:lp2:3)p STDEVCO:lp2: 3) CHARACTER SU83TYP*20

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

Gilchrist, Michael J.; Sobral, Daniel; Khoueiry, Pierre

Genome-wide resources, such as collections of cDNA clones encoding for complete proteins (full-ORF clones), are crucial tools for studying the evolution of gene function and genetic interactions. Non-model organisms, in particular marine organisms, provide a rich source of functional diversity. Marine organism genomes are, however, frequently highly polymorphic and encode proteins that diverge significantly from those of well-annotated model genomes. The construction of full-ORF clone collections from non-model organisms is hindered by the difficulty of predicting accurately the N-terminal ends of proteins, and distinguishing recent paralogs from highly polymorphic alleles. We also report a computational strategy that overcomes these difficulties,more » and allows for accurate gene level clustering of transcript data followed by the automated identification of full-ORFs with correct 5'- and 3'-ends. It is robust to polymorphism, includes paralog calling and does not require evolutionary proximity to well annotated model organisms. Here, we developed this pipeline for the ascidian Ciona intestinalis, a highly polymorphic member of the divergent sister group of the vertebrates, emerging as a powerful model organism to study chordate gene function, Gene Regulatory Networks and molecular mechanisms underlying human pathologies. Furthermore, using this pipeline we have generated the first full-ORF collection for a highly polymorphic marine invertebrate. It contains 19,163 full-ORF cDNA clones covering 60% of Ciona coding genes, and full-ORF orthologs for approximately half of curated human disease-associated genes.« less

Computational study of C(sp3)-O bond formation at a PdIV centre.

PubMed

Canty, Allan J; Ariafard, Alireza; Camasso, Nicole M; Higgs, Andrew T; Yates, Brian F; Sanford, Melanie S

2017-03-14

This report describes a computational study of C(sp 3 )-OR bond formation from Pd IV complexes of general structure Pd IV (CH 2 CMe 2 -o-C 6 H 4 -C,C')(F)(OR)(bpy-N,N') (bpy = 2,2'-bipyridine). Dissociation of - OR from the different octahedral Pd IV starting materials results in a common square-pyramidal Pd IV cation. An S N 2-type attack by - OR ( - OR = phenoxide, acetate, difluoroacetate, and nitrate) then leads to C(sp 3 )-OR bond formation. In contrast, when - OR = triflate, concerted C(sp 3 )-C(sp 2 ) bond-forming reductive elimination takes place, and the calculations indicate this outcome is the result of thermodynamic rather than kinetic control. The energy requirements for the dissociation and S N 2 steps with different - OR follow opposing trends. The S N 2 transition states exhibit "PdCO" angles in a tight range of 151.5 to 153.0°, resulting from steric interactions between the oxygen atom and the gem-dimethyl group of the ligand. Conformational effects for various OR ligands and isomerisation of the complexes were also examined as components of the solution dynamics in these systems. In all cases, the trends observed computationally agree with those observed experimentally.

Kinematics and dynamics of a solitary wave interacting with varying bathymetry and/or a vertical wall

NASA Astrophysics Data System (ADS)

Papoutsellis, Christos; Athanassoulis, Gerassimos; Charalampopoulos, Alexis-Tzianni

2017-04-01

In this work, we investigate the transformations that solitary surface waves undergo during their interaction with uneven seabed and/or fully reflective vertical boundaries. This is accomplished by performing simulations using a non-local Hamiltonian formulation, taking into account full nonlinearity and dispersion, in the presence of variable seabed [1]. This formulation is based on an exact coupled-mode representation of the velocity potential, leading to efficient and accurate computations of the Dirichlet to Neumann operator, required in Zakharov/Craig-Sulem formulation [2], [3]. In addition, it allows for the efficient computation of wave kinematics (velocity, acceleration) and the pressure field, in the time-dependent fluid domain, up to its physical boundaries. Such computations are performed for the case of high-amplitude solitary waves interacting with varying bathymetry and/or a vertical wall, shedding light to their kinematics and dynamics. More specifically, we first consider two benchmark cases, namely the transformation of solitary waves over a plane beach [4], and the reflection of solitary waves on a vertical wall [5]. As a further step, results on the scattering/reflection of a solitary wave due to an undulating seabed, and on the disintegration of a solitary wave travelling form shallow to deep water are also presented. References:[1] G.A. Athanassoulis. & Ch.E. Papoutsellis, in Volume 7: Ocean Engineering, ASME, OMAE2015-41452, p. V007T06A029 (2015)[2] W. Craig, C. Sulem, J. Comp. Phys. 108, 73-83 (1993) [3] V. Zakharov, J. Appl. Mech. Tech. Phys 9, 86-94 (1968)[4] S. Grilli, R. Subramanya, T. Svendsen. & J. Veeramony, J. Waterway, Port, Coastal, Ocean Eng. 120(6), 609-628. (1994)[5] Y.Y. Chen, C. Kharif , J.H. Yang, H.C. Hsu, J. Touboul & J. Chambarel, Eur. J. Mech B-Fluid 49, 20-28 (2015)

Visual Environments for CFD Research

NASA Technical Reports Server (NTRS)

Watson, Val; George, Michael W. (Technical Monitor)

1994-01-01

This viewgraph presentation gives an overview of the visual environments for computational fluid dynamics (CFD) research. It includes details on critical needs from the future computer environment, features needed to attain this environment, prospects for changes in and the impact of the visualization revolution on the human-computer interface, human processing capabilities, limits of personal environment and the extension of that environment with computers. Information is given on the need for more 'visual' thinking (including instances of visual thinking), an evaluation of the alternate approaches for and levels of interactive computer graphics, a visual analysis of computational fluid dynamics, and an analysis of visualization software.

A State Cyber Hub Operations Framework

DTIC Science & Technology

2016-06-01

to communicate and sense or interact with their internal states or the external environment. Machine Learning: A type of artificial intelligence that... artificial intelligence , and computational linguistics concerned with the interactions between computers and human (natural) languages. Patching: A piece...formalizing a proof of concept for cyber initiatives and developed frameworks for operationalizing the data and intelligence produced across state

Visual Debugging of Object-Oriented Systems With the Unified Modeling Language

DTIC Science & Technology

2004-03-01

to be “the systematic and imaginative use of the technology of interactive computer graphics and the disciplines of graphic design , typography ... Graphics volume 23 no 6, pp893-901, 1999. [SHN98] Shneiderman, B. Designing the User Interface. Strategies for Effective Human-Computer Interaction...System Design Objectives ................................................................................ 44 3.3 System Architecture

Complement Interaction with Trypanosomatid Promastigotes in Normal Human Serum

PubMed Central

Domínguez, Mercedes; Moreno, Inmaculada; López-Trascasa, Margarita; Toraño, Alfredo

2002-01-01

In normal human serum (NHS), axenic promastigotes of Crithidia, Phytomonas, and Leishmania trigger complement activation, and from 1.2 to 1.8 × 105 C3 molecules are deposited per promastigote within 2.5 min. In Leishmania, promastigote C3 binding capacity remains constant during in vitro metacyclogenesis. C3 deposition on promastigotes activated through the classical complement pathway reaches a 50% maximum after ∼50 s, and represents >85% of total C3 bound. In C1q- and C2-deficient human sera, promastigotes cannot activate the classical pathway (CP) unless purified C1q or C2 factors, respectively, are supplemented, demonstrating a requirement for CP factor in promastigote C3 opsonization. NHS depleted of natural anti-Leishmania antibodies cannot trigger promastigote CP activation, but IgM addition restores C3 binding. Furthermore, Leishmania binds natural antibodies in ethylenediaminetetracetic acid (EDTA)-treated NHS; after EDTA removal, promastigote-bound IgM triggers C3 deposition in natural antibody-depleted NHS. Serum collectins and pentraxins thus do not participate significantly in NHS promastigote C3 opsonization. Real-time kinetic analysis of promastigote CP-mediated lysis indicates that between 85–95% of parasites are killed within 2.5 min of serum contact. These data indicate that successful Leishmania infection in man must immediately follow promastigote transmission, and that Leishmania evasion strategies are shaped by the selective pressure exerted by complement. PMID:11854358

The crystal structure of sulfamethoxazole, interaction with DNA, DFT calculation, and molecular docking studies

NASA Astrophysics Data System (ADS)

Das, Dipankar; Sahu, Nilima; Roy, Suman; Dutta, Paramita; Mondal, Sudipa; Torres, Elena L.; Sinha, Chittaranjan

2015-02-01

Sulfamethoxazole (SMX) [4-amino-N-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide] is structurally established by single crystal X-ray diffraction measurement. The crystal packing shows H-bonded 2D polymer through N(7)sbnd H(7A)---O(2), N(7)sbnd H(7B)---O(3), N(1)sbnd H(1)---N(2), C(5)sbnd H(5)---O(3)sbnd S(1) and N(7)sbnd (H7A)---O(2)sbnd S(1). Density Functional Theory (DFT) and Time Dependent-DFT (TD-DFT) computations of optimized structure of SMX determine the electronic structure and has explained the electronic spectral transitions. The interaction of SMX with CT-DNA has been studied by absorption spectroscopy and the binding constant (Kb) is 4.37 × 104 M-1. The in silico test of SMX with DHPS from Escherichia coli and Streptococcus pneumoniae helps to understand drug metabolism and accounts the drug-molecule interactions. The molecular docking of SMX-DNA also helps to predict the interaction feature.

Synthesis, spectroscopic characterization and in vitro cytotoxicities of new organometallic palladium complexes with biologically active β-diketones; Biological evaluation probing of the interaction mechanism with DNA/Protein and molecular docking

NASA Astrophysics Data System (ADS)

Karami, Kazem; Rafiee, Mina; Lighvan, Zohreh Mehri; Zakariazadeh, Mostafa; Faal, Ali Yeganeh; Esmaeili, Seyed-Alireza; Momtazi-Borojeni, Amir Abbas

2018-02-01

[Pd{(C,N)sbnd C6H4CH (CH3)NH}(CUR)] (3) and [Pd2{(C,N)sbnd C6H4CH(CH3)NH2}2(μ-N3CS2)] (4) [cur = 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dion] novel organometallic complexes with biologically active ligands have been prepared and characterized via elemental analysis, multinuclear spectroscopic techniques (1H, and 13C NMR and IR) and their biological activities, including antitumoral activity and DNA-protein interactions have been investigated. Fluorescence spectroscopy used to study the interaction of the complexes with BSA have shown the affinity of the complexes for these proteins with relatively high binding constant values and the changed secondary structure of BSA in the presence of the complexes. In the meantime, spectroscopy and competitive titration have been applied to investigate the interaction of complexes with Warfarin and Ibuprofen site markers for sites I and II, respectively, with BSA. The results have suggested that the locations of complexes 3 and 4 are sites II and I, respectively. UV-Vis spectroscopy, emission titration and helix melting methods have been used to study the interaction of these complexes with CT-DNA, indicating that complexes are bound to CT-DNA by intercalation binding mode. In addition, good cytotoxic activity against MCF-7 (human breast cancer) and JURKAT (human leukemia) cell line has been shown by both complexes whereas low cytotoxicity was exerted on normal peripheral blood mononuclear cells.

Enhancing Hi-C data resolution with deep convolutional neural network HiCPlus.

PubMed

Zhang, Yan; An, Lin; Xu, Jie; Zhang, Bo; Zheng, W Jim; Hu, Ming; Tang, Jijun; Yue, Feng

2018-02-21

Although Hi-C technology is one of the most popular tools for studying 3D genome organization, due to sequencing cost, the resolution of most Hi-C datasets are coarse and cannot be used to link distal regulatory elements to their target genes. Here we develop HiCPlus, a computational approach based on deep convolutional neural network, to infer high-resolution Hi-C interaction matrices from low-resolution Hi-C data. We demonstrate that HiCPlus can impute interaction matrices highly similar to the original ones, while only using 1/16 of the original sequencing reads. We show that the models learned from one cell type can be applied to make predictions in other cell or tissue types. Our work not only provides a computational framework to enhance Hi-C data resolution but also reveals features underlying the formation of 3D chromatin interactions.

77 FR 62216 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-12

... NIST researchers to study human-computer interactions and help establish guidelines and standards for more effective and efficient interactions. Affected Public: Individual or households; State, Local or...

Adaptive allocation of decisionmaking responsibility between human and computer in multitask situations

NASA Technical Reports Server (NTRS)

Chu, Y.-Y.; Rouse, W. B.

1979-01-01

As human and computer come to have overlapping decisionmaking abilities, a dynamic or adaptive allocation of responsibilities may be the best mode of human-computer interaction. It is suggested that the computer serve as a backup decisionmaker, accepting responsibility when human workload becomes excessive and relinquishing responsibility when workload becomes acceptable. A queueing theory formulation of multitask decisionmaking is used and a threshold policy for turning the computer on/off is proposed. This policy minimizes event-waiting cost subject to human workload constraints. An experiment was conducted with a balanced design of several subject runs within a computer-aided multitask flight management situation with different task demand levels. It was found that computer aiding enhanced subsystem performance as well as subjective ratings. The queueing model appears to be an adequate representation of the multitask decisionmaking situation, and to be capable of predicting system performance in terms of average waiting time and server occupancy. Server occupancy was further found to correlate highly with the subjective effort ratings.

Population of 224 realistic human subject-based computational breast phantoms

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

Erickson, David W.; Wells, Jered R., E-mail: jered.wells@duke.edu; Sturgeon, Gregory M.

Purpose: To create a database of highly realistic and anatomically variable 3D virtual breast phantoms based on dedicated breast computed tomography (bCT) data. Methods: A tissue classification and segmentation algorithm was used to create realistic and detailed 3D computational breast phantoms based on 230 + dedicated bCT datasets from normal human subjects. The breast volume was identified using a coarse three-class fuzzy C-means segmentation algorithm which accounted for and removed motion blur at the breast periphery. Noise in the bCT data was reduced through application of a postreconstruction 3D bilateral filter. A 3D adipose nonuniformity (bias field) correction was thenmore » applied followed by glandular segmentation using a 3D bias-corrected fuzzy C-means algorithm. Multiple tissue classes were defined including skin, adipose, and several fractional glandular densities. Following segmentation, a skin mask was produced which preserved the interdigitated skin, adipose, and glandular boundaries of the skin interior. Finally, surface modeling was used to produce digital phantoms with methods complementary to the XCAT suite of digital human phantoms. Results: After rejecting some datasets due to artifacts, 224 virtual breast phantoms were created which emulate the complex breast parenchyma of actual human subjects. The volume breast density (with skin) ranged from 5.5% to 66.3% with a mean value of 25.3% ± 13.2%. Breast volumes ranged from 25.0 to 2099.6 ml with a mean value of 716.3 ± 386.5 ml. Three breast phantoms were selected for imaging with digital compression (using finite element modeling) and simple ray-tracing, and the results show promise in their potential to produce realistic simulated mammograms. Conclusions: This work provides a new population of 224 breast phantoms based on in vivo bCT data for imaging research. Compared to previous studies based on only a few prototype cases, this dataset provides a rich source of new cases spanning a wide range of breast types, volumes, densities, and parenchymal patterns.« less

Population of 224 realistic human subject-based computational breast phantoms

PubMed Central

Erickson, David W.; Wells, Jered R.; Sturgeon, Gregory M.; Dobbins, James T.; Segars, W. Paul; Lo, Joseph Y.

2016-01-01

Purpose: To create a database of highly realistic and anatomically variable 3D virtual breast phantoms based on dedicated breast computed tomography (bCT) data. Methods: A tissue classification and segmentation algorithm was used to create realistic and detailed 3D computational breast phantoms based on 230 + dedicated bCT datasets from normal human subjects. The breast volume was identified using a coarse three-class fuzzy C-means segmentation algorithm which accounted for and removed motion blur at the breast periphery. Noise in the bCT data was reduced through application of a postreconstruction 3D bilateral filter. A 3D adipose nonuniformity (bias field) correction was then applied followed by glandular segmentation using a 3D bias-corrected fuzzy C-means algorithm. Multiple tissue classes were defined including skin, adipose, and several fractional glandular densities. Following segmentation, a skin mask was produced which preserved the interdigitated skin, adipose, and glandular boundaries of the skin interior. Finally, surface modeling was used to produce digital phantoms with methods complementary to the XCAT suite of digital human phantoms. Results: After rejecting some datasets due to artifacts, 224 virtual breast phantoms were created which emulate the complex breast parenchyma of actual human subjects. The volume breast density (with skin) ranged from 5.5% to 66.3% with a mean value of 25.3% ± 13.2%. Breast volumes ranged from 25.0 to 2099.6 ml with a mean value of 716.3 ± 386.5 ml. Three breast phantoms were selected for imaging with digital compression (using finite element modeling) and simple ray-tracing, and the results show promise in their potential to produce realistic simulated mammograms. Conclusions: This work provides a new population of 224 breast phantoms based on in vivo bCT data for imaging research. Compared to previous studies based on only a few prototype cases, this dataset provides a rich source of new cases spanning a wide range of breast types, volumes, densities, and parenchymal patterns. PMID:26745896

Effect of serine-type protease of Candida spp. isolated from linear gingival erythema of HIV-positive children: critical factors in the colonization.

PubMed

Portela, Maristela B; Souza, Ivete P R; Abreu, Celina M; Bertolini, Martinna; Holandino, Carla; Alviano, Celuta S; Santos, André L S; Soares, Rosangela M A

2010-11-01

  There are several kinds of oral soft tissue lesions that are common manifestations observed in human immunodeficiency virus (HIV)-infected children; for example, linear gingival erythema (LGE) that is a distinctive fiery red band along the margin of the gingivae. The etiology and pathogenesis of LGE are questionable, but a candidal origin has been suggested. Proteases are key virulence attributes produced by a variety of pathogenic fungi, including Candida. The objective of the present study is to identify the protease production in Candida species including, C. albicans (n=5), C. dubliniensis (n=1) and C. tropicalis (n=1), isolated directly from typical LGE lesions observed in six HIV-positive children, and also to test the effect of a serine protease inhibitor on the interaction of Candida spp. and epithelial cells in vitro. The ability of Candida strains to release proteases in the culture supernatant fluids was visualized by gelatin-SDS-PAGE. Gel strips containing 30-fold concentrated supernatant (1.5×10(8) yeasts) were incubated at 37°C for 48 h in 50 mM sodium phosphate buffer, pH 5.5. The concentrated supernatants were also incubated with fibronectin, laminin, immunoglobulin G, bovine serum albumin and human serum albumin. The effect of serine protease inhibitor on the interaction of Candida spp. and epithelial cells (MA 104) was measured after pre-treatment of fungi with the inhibitor (phenylmethylsulphonyl fluoride, PMSF). All the extracellular proteases were completely inhibited by PMSF, identifying these activities as serine-type proteases. Interestingly, a common 62-kDa serine protease was observed in all Candida strains. The culture supernatants, rich in serine protease activities, cleaved several soluble proteinaceous substrates. Additionally, we demonstrated that pre-treatment of C. albicans, C. dubliniensis and C. tropicalis with PMSF diminished the interaction with epithelial cells. Collectively, our results show that Candida spp. isolated from LGE lesions produced and secreted serine proteases and these enzymes may be involved in the initial colonization events. © 2010 John Wiley & Sons A/S.

A Novel Computer-Based Set-Up to Study Movement Coordination in Human Ensembles

PubMed Central

Alderisio, Francesco; Lombardi, Maria; Fiore, Gianfranco; di Bernardo, Mario

2017-01-01

Existing experimental works on movement coordination in human ensembles mostly investigate situations where each subject is connected to all the others through direct visual and auditory coupling, so that unavoidable social interaction affects their coordination level. Here, we present a novel computer-based set-up to study movement coordination in human groups so as to minimize the influence of social interaction among participants and implement different visual pairings between them. In so doing, players can only take into consideration the motion of a designated subset of the others. This allows the evaluation of the exclusive effects on coordination of the structure of interconnections among the players in the group and their own dynamics. In addition, our set-up enables the deployment of virtual computer players to investigate dyadic interaction between a human and a virtual agent, as well as group synchronization in mixed teams of human and virtual agents. We show how this novel set-up can be employed to study coordination both in dyads and in groups over different structures of interconnections, in the presence as well as in the absence of virtual agents acting as followers or leaders. Finally, in order to illustrate the capabilities of the architecture, we describe some preliminary results. The platform is available to any researcher who wishes to unfold the mechanisms underlying group synchronization in human ensembles and shed light on its socio-psychological aspects. PMID:28649217

Plasmin cleaves fibrinogen and the human complement proteins C3b and C5 in the presence of Leptospira interrogans proteins: A new role of LigA and LigB in invasion and complement immune evasion.

PubMed

Castiblanco-Valencia, Mónica Marcela; Fraga, Tatiana Rodrigues; Pagotto, Ana Helena; Serrano, Solange Maria de Toledo; Abreu, Patricia Antonia Estima; Barbosa, Angela Silva; Isaac, Lourdes

2016-05-01

Plasminogen is a single-chain glycoprotein found in human plasma as the inactive precursor of plasmin. When converted to proteolytically active plasmin, plasmin(ogen) regulates both complement and coagulation cascades, thus representing an important target for pathogenic microorganisms. Leptospira interrogans binds plasminogen, which is converted to active plasmin. Leptospiral immunoglobulin-like (Lig) proteins are surface exposed molecules that interact with extracellular matrix components and complement regulators, including proteins of the FH family and C4BP. In this work, we demonstrate that these multifunctional molecules also bind plasminogen through both N- and C-terminal domains. These interactions are dependent on lysine residues and are affected by ionic strength. Competition assays suggest that plasminogen does not share binding sites with C4BP or FH on Lig proteins at physiological molar ratios. Plasminogen bound to Lig proteins is converted to proteolytic active plasmin in the presence of urokinase-type plasminogen activator (uPA). Lig-bound plasmin is able to cleave the physiological substrates fibrinogen and the complement proteins C3b and C5. Taken together, our data point to a new role of LigA and LigB in leptospiral invasion and complement immune evasion. Plasmin(ogen) acquisition by these versatile proteins may contribute to Leptospira infection, favoring bacterial survival and dissemination inside the host. Copyright © 2016. Published by Elsevier GmbH.

Design Guidelines and Criteria for User/Operator Transactions with Battlefield Automated Systems. Volume 2. Technical Discussion

DTIC Science & Technology

1981-02-01

Continue on tevetee «Id* If necemtery mid Identify br black number) Battlefield automated systems Human- computer interaction. Design criteria System...Report (this report) In-Depth Analyses of Individual Systems A. Tactical Fire Direction System (TACFIRE) (RP 81-26) B. Tactical Computer Terminal...select the design features and operating procedures of the human- computer Interface which best match the require- ments and capabilities of anticipated

Computational Insights into the Interactions between Calmodulin and the c/nSH2 Domains of p85α Regulatory Subunit of PI3Kα: Implication for PI3Kα Activation by Calmodulin.

PubMed

Ni, Duan; Liu, Dingyu; Zhang, Jian; Lu, Shaoyong

2018-01-04

Calmodulin (CaM) and phosphatidylinositide-3 kinase (PI3Kα) are well known for their multiple roles in a series of intracellular signaling pathways and in the progression of several human cancers. Crosstalk between CaM and PI3Kα has been an area of intensive research. Recent experiments have shown that in adenocarcinoma, K-Ras4B is involved in the CaM-PI3Kα crosstalk. Based on experimental results, we have recently put forward a hypothesis that the coordination of CaM and PI3Kα with K-Ras4B forms a CaM-PI3Kα-K-Ras4B ternary complex, which leads to the formation of pancreatic ductal adenocarcinoma. However, the mechanism for the CaM-PI3Kα crosstalk is unresolved. Based on molecular modeling and molecular dynamics simulations, here we explored the potential interactions between CaM and the c/nSH2 domains of p85α subunit of PI3Kα. We demonstrated that CaM can interact with the c/nSH2 domains and the interaction details were unraveled. Moreover, the possible modes for the CaM-cSH2 and CaM-nSH2 interactions were uncovered and we used them to construct a complete CaM-PI3Kα complex model. The structural model of CaM-PI3Kα interaction not only offers a support for our previous ternary complex hypothesis, but also is useful for drug design targeted at CaM-PI3Kα protein-protein interactions.

Neural correlate of human reciprocity in social interactions

PubMed Central

Sakaiya, Shiro; Shiraito, Yuki; Kato, Junko; Ide, Hiroko; Okada, Kensuke; Takano, Kouji; Kansaku, Kenji

2013-01-01

Reciprocity plays a key role maintaining cooperation in society. However, little is known about the neural process that underpins human reciprocity during social interactions. Our neuroimaging study manipulated partner identity (computer, human) and strategy (random, tit-for-tat) in repeated prisoner's dilemma games and investigated the neural correlate of reciprocal interaction with humans. Reciprocal cooperation with humans but exploitation of computers by defection was associated with activation in the left amygdala. Amygdala activation was also positively and negatively correlated with a preference change for human partners following tit-for-tat and random strategies, respectively. The correlated activation represented the intensity of positive feeling toward reciprocal and negative feeling toward non-reciprocal partners, and so reflected reciprocity in social interaction. Reciprocity in social interaction, however, might plausibly be misinterpreted and so we also examined the neural coding of insight into the reciprocity of partners. Those with and without insight revealed differential brain activation across the reward-related circuitry (i.e., the right middle dorsolateral prefrontal cortex and dorsal caudate) and theory of mind (ToM) regions [i.e., ventromedial prefrontal cortex (VMPFC) and precuneus]. Among differential activations, activation in the precuneus, which accompanied deactivation of the VMPFC, was specific to those without insight into human partners who were engaged in a tit-for-tat strategy. This asymmetric (de)activation might involve specific contributions of ToM regions to the human search for reciprocity. Consequently, the intensity of emotion attached to human reciprocity was represented in the amygdala, whereas insight into the reciprocity of others was reflected in activation across the reward-related and ToM regions. This suggests the critical role of mentalizing, which was not equated with reward expectation during social interactions. PMID:24381534

Neural correlate of human reciprocity in social interactions.

PubMed

Sakaiya, Shiro; Shiraito, Yuki; Kato, Junko; Ide, Hiroko; Okada, Kensuke; Takano, Kouji; Kansaku, Kenji

2013-01-01

Reciprocity plays a key role maintaining cooperation in society. However, little is known about the neural process that underpins human reciprocity during social interactions. Our neuroimaging study manipulated partner identity (computer, human) and strategy (random, tit-for-tat) in repeated prisoner's dilemma games and investigated the neural correlate of reciprocal interaction with humans. Reciprocal cooperation with humans but exploitation of computers by defection was associated with activation in the left amygdala. Amygdala activation was also positively and negatively correlated with a preference change for human partners following tit-for-tat and random strategies, respectively. The correlated activation represented the intensity of positive feeling toward reciprocal and negative feeling toward non-reciprocal partners, and so reflected reciprocity in social interaction. Reciprocity in social interaction, however, might plausibly be misinterpreted and so we also examined the neural coding of insight into the reciprocity of partners. Those with and without insight revealed differential brain activation across the reward-related circuitry (i.e., the right middle dorsolateral prefrontal cortex and dorsal caudate) and theory of mind (ToM) regions [i.e., ventromedial prefrontal cortex (VMPFC) and precuneus]. Among differential activations, activation in the precuneus, which accompanied deactivation of the VMPFC, was specific to those without insight into human partners who were engaged in a tit-for-tat strategy. This asymmetric (de)activation might involve specific contributions of ToM regions to the human search for reciprocity. Consequently, the intensity of emotion attached to human reciprocity was represented in the amygdala, whereas insight into the reciprocity of others was reflected in activation across the reward-related and ToM regions. This suggests the critical role of mentalizing, which was not equated with reward expectation during social interactions.

Origin of the SN2 benzylic effect.

PubMed

Galabov, Boris; Nikolova, Valia; Wilke, Jeremiah J; Schaefer, Henry F; Allen, Wesley D

2008-07-30

The S N2 identity exchange reactions of the fluoride ion with benzyl fluoride and 10 para-substituted derivatives (RC6H 4CH 2F, R = CH3, OH, OCH 3, NH2, F, Cl, CCH, CN, COF, and NO2) have been investigated by both rigorous ab initio methods and carefully calibrated density functional theory. Groundbreaking focal-point computations were executed for the C6H5CH 2F + F (-) and C 6H 5CH2Cl + Cl (-) SN2 reactions at the highest possible levels of electronic structure theory, employing complete basis set (CBS) extrapolations of aug-cc-pV XZ (X = 2-5) Hartree-Fock and MP2 energies, and including higher-order electron correlation via CCSD/aug-cc-pVQZ and CCSD(T)/aug-cc-pVTZ coupled cluster wave functions. Strong linear dependences are found between the computed electrostatic potential at the reaction-center carbon atom and the effective SN2 activation energies within the series of para-substituted benzyl fluorides. An activation strain energy decomposition indicates that the SN2 reactivity of these benzylic compounds is governed by the intrinsic electrostatic interaction between the reacting fragments. The delocalization of nucleophilic charge into the aromatic ring in the SN2 transition states is quite limited and should not be considered the origin of benzylic acceleration of SN2 reactions. Our rigorous focal-point computations validate the benzylic effect by establishing SN2 barriers for (F (-), Cl (-)) identity exchange in (C6H5CH2F, C6H 5CH2Cl) that are lower than those of (CH3F, CH3Cl) by (3.8, 1.6) kcal mol (-1), in order.

Visualization of metabolic interaction networks in microbial communities using VisANT 5.0

DOE PAGES

Granger, Brian R.; Chang, Yi -Chien; Wang, Yan; ...

2016-04-15

Here, the complexity of metabolic networks in microbial communities poses an unresolved visualization and interpretation challenge. We address this challenge in the newly expanded version of a software tool for the analysis of biological networks, VisANT 5.0. We focus in particular on facilitating the visual exploration of metabolic interaction between microbes in a community, e.g. as predicted by COMETS (Computation of Microbial Ecosystems in Time and Space), a dynamic stoichiometric modeling framework. Using VisANT's unique meta-graph implementation, we show how one can use VisANT 5.0 to explore different time-dependent ecosystem-level metabolic networks. In particular, we analyze the metabolic interaction networkmore » between two bacteria previously shown to display an obligate cross-feeding interdependency. In addition, we illustrate how a putative minimal gut microbiome community could be represented in our framework, making it possible to highlight interactions across multiple coexisting species. We envisage that the "symbiotic layout" of VisANT can be employed as a general tool for the analysis of metabolism in complex microbial communities as well as heterogeneous human tissues.« less

Critical chemical features in trans-acting-responsive RNA are required for interaction with human immunodeficiency virus type 1 Tat protein.

PubMed Central

Sumner-Smith, M; Roy, S; Barnett, R; Reid, L S; Kuperman, R; Delling, U; Sonenberg, N

1991-01-01

The human immunodeficiency virus type 1 Tat protein binds to an RNA stem-loop structure called TAR which is present at the 5' end of all human immunodeficiency virus type 1 transcripts. This binding is centered on a bulge within the stem of TAR and is an essential step in the trans-activation process which results in a dramatic increase in viral gene expression. By analysis of a series of TAR derivatives produced by transcription or direct chemical synthesis, we determined the structural and chemical requirements for Tat binding. Tat binds well to structures which have a bulge of two to at least five unpaired bases bounded on both sides by a double-stranded RNA stem. This apparent flexibility in bulge size is in contrast to an absolute requirement for an unpaired uridine (U) in the 5'-most position of the bulge (+23). Substitution of the U with either natural bases or chemical analogs demonstrated that the imido group at the N-3 position and, possibly, the carbonyl group at the C-4 position of U are critical for Tat binding. Cytosine (C), which differs from U at only these positions, is not an acceptable substitute. Furthermore, methylation at N-3 abolishes binding. While methylation of U at the C-5 position has little effect on binding, fluorination reduces it, possibly because of its effects on relative tautomer stability at the N-3 and C-4 positions. Thus, we have identified key moieties in the U residue that are of importance for the binding of Tat to TAR RNA. We hypothesize that the invariant U is involved in hydrogen bond interactions with either another part of TAR or the TAR-binding domain in Tat. Images PMID:1895380

Virtual Reality Anatomy: Is It Comparable with Traditional Methods in the Teaching of Human Forearm Musculoskeletal Anatomy?

ERIC Educational Resources Information Center

Codd, Anthony M.; Choudhury, Bipasha

2011-01-01

The use of cadavers to teach anatomy is well established, but limitations with this approach have led to the introduction of alternative teaching methods. One such method is the use of three-dimensional virtual reality computer models. An interactive, three-dimensional computer model of human forearm anterior compartment musculoskeletal anatomy…

Quantitative framework for ordered degradation of APC/C substrates.

PubMed

Lu, Dan; Girard, Juliet R; Li, Weihan; Mizrak, Arda; Morgan, David O

2015-11-16

During cell-cycle progression, substrates of a single master regulatory enzyme can be modified in a specific order. Here, we used experimental and computational approaches to dissect the quantitative mechanisms underlying the ordered degradation of the substrates of the ubiquitin ligase APC/C(Cdc20), a key regulator of chromosome segregation in mitosis. We show experimentally that the rate of catalysis varies with different substrates of APC/C(Cdc20). Using a computational model based on multi-step ubiquitination, we then show how changes in the interaction between a single substrate and APC/C(Cdc20) can alter the timing of degradation onset relative to APC/C(Cdc20) activation, while ensuring a fast degradation rate. Degradation timing and dynamics depend on substrate affinity for the enzyme as well as the catalytic rate at which the substrate is modified. When two substrates share the same pool of APC/C(Cdc20), their relative enzyme affinities and rates of catalysis influence the partitioning of APC/C(Cdc20) among substrates, resulting in substrate competition. Depending on how APC/C(Cdc20) is partitioned among its substrates, competition can have minor or major effects on the degradation of certain substrates. We show experimentally that increased expression of the early APC/C(Cdc20) substrate Clb5 does not delay the degradation of the later substrate securin, arguing against a role for competition with Clb5 in establishing securin degradation timing. The degradation timing of APC/C(Cdc20) substrates depends on the multi-step nature of ubiquitination, differences in substrate-APC/C(Cdc20) interactions, and competition among substrates. Our studies provide a conceptual framework for understanding how ordered modification can be established among substrates of the same regulatory enzyme, and facilitate our understanding of how precise temporal control is achieved by a small number of master regulators to ensure a successful cell division cycle.

An Interactive Computer Aided Design and Analysis Package.

DTIC Science & Technology

1986-03-01

Al-A167 114 AN INTERACTIVE COMPUTER AIDED DESIGN MUD ANAILYSIS 1/𔃼 PACKAGE(U) NAVAL POSTGRADUATE SCHOOL NONTEREY CA T L EUALD "AR 86 UNCLSSIFIED F... SCHOOL Monterey, California DTIC .LECTE MAYOS THESIS AN INTERACTIVE COMPUTER AIDED DESIGN AND ANALYSIS PACKAGE by Terrence L. Ewald March 1986 jThesis...ORGANIZATION Naval Postgraduate School (if dAp90h81111) Naval Postgraduate School . 62A 6C. ADDRESS (0ty. State, and ZIP Code) 7b. ADDRESS (City State. and

Geometric Computation of Human Gyrification Indexes from Magnetic Resonance Images

DTIC Science & Technology

2009-04-01

GEOMETRIC COMPUTATION OF HUMAN GYRIFICATION INDEXES FROM MAGNETIC RESONANCE IMAGES By Shu Su Tonya White Marcus Schmidt Chiu-Yen Kao and Guillermo...00-2009 to 00-00-2009 4. TITLE AND SUBTITLE Geometric Computation of Human Gyrification Indexes from Magnetic Resonance Images 5a. CONTRACT NUMBER... Geometric Computation of Gyrification Indexes Chiu-Yen Kao 1 Geometric Computation of Human Gyrification

Influence of aggregate size on the binding and activation of the first component of human complement by soluble IgG aggregates.

PubMed Central

Doekes, G; Vanes, L A; Daha, M R

1982-01-01

The interaction between small aggregates of human IgG and the first component of human complement was studied. Stabilized soluble IgG aggregates of restricted size were prepared by heat aggregation of human IgG, followed by sucrose-density ultracentrifugation. Human C1 was isolated in its precursor form by euglobulin precipitation, followed by gel filtration and immunoadsorption. A C1 preparation was obtained of which more than 90% was still in its unactivated form. Soluble aggregates containing 20, 10 or 5 molecules IgG, and monomeric IgG were tested for their ability to bind and to activate C1. The binding of C1 was determined by C1 consumption, whereas the activation of C1 was measured as the increased ability of the C1 preparation to consume purified human C4 after the incubation with the aggregates. The three aggregates tested and monomeric IgG were all able to bind and to activate C1, but the efficiency of both processes markedly increased with increasing aggregate-size. Furthermore, it was found that all four preparations activated an appreciable amount of C1 at concentrations that did not result in any detectable C1 fixation. These results confirm earlier suggestion that C1 can be activated during a short, transient binding to small aggregates or immune complexes that have a low avidity for C1, after which the activated form, C1, is released into the medium. PMID:7068172

Program Predicts Time Courses of Human/Computer Interactions

NASA Technical Reports Server (NTRS)

Vera, Alonso; Howes, Andrew

2005-01-01

CPM X is a computer program that predicts sequences of, and amounts of time taken by, routine actions performed by a skilled person performing a task. Unlike programs that simulate the interaction of the person with the task environment, CPM X predicts the time course of events as consequences of encoded constraints on human behavior. The constraints determine which cognitive and environmental processes can occur simultaneously and which have sequential dependencies. The input to CPM X comprises (1) a description of a task and strategy in a hierarchical description language and (2) a description of architectural constraints in the form of rules governing interactions of fundamental cognitive, perceptual, and motor operations. The output of CPM X is a Program Evaluation Review Technique (PERT) chart that presents a schedule of predicted cognitive, motor, and perceptual operators interacting with a task environment. The CPM X program allows direct, a priori prediction of skilled user performance on complex human-machine systems, providing a way to assess critical interfaces before they are deployed in mission contexts.

Interaction studies reveal specific recognition of an anti-inflammatory polyphosphorhydrazone dendrimer by human monocytes

NASA Astrophysics Data System (ADS)

Ledall, Jérémy; Fruchon, Séverine; Garzoni, Matteo; Pavan, Giovanni M.; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Blanzat, Muriel; Poupot, Rémy

2015-10-01

Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes.Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03884g

Evidence Report: Risk of Inadequate Human-Computer Interaction

NASA Technical Reports Server (NTRS)

Holden, Kritina; Ezer, Neta; Vos, Gordon

2013-01-01

Human-computer interaction (HCI) encompasses all the methods by which humans and computer-based systems communicate, share information, and accomplish tasks. When HCI is poorly designed, crews have difficulty entering, navigating, accessing, and understanding information. HCI has rarely been studied in an operational spaceflight context, and detailed performance data that would support evaluation of HCI have not been collected; thus, we draw much of our evidence from post-spaceflight crew comments, and from other safety-critical domains like ground-based power plants, and aviation. Additionally, there is a concern that any potential or real issues to date may have been masked by the fact that crews have near constant access to ground controllers, who monitor for errors, correct mistakes, and provide additional information needed to complete tasks. We do not know what types of HCI issues might arise without this "safety net". Exploration missions will test this concern, as crews may be operating autonomously due to communication delays and blackouts. Crew survival will be heavily dependent on available electronic information for just-in-time training, procedure execution, and vehicle or system maintenance; hence, the criticality of the Risk of Inadequate HCI. Future work must focus on identifying the most important contributing risk factors, evaluating their contribution to the overall risk, and developing appropriate mitigations. The Risk of Inadequate HCI includes eight core contributing factors based on the Human Factors Analysis and Classification System (HFACS): (1) Requirements, policies, and design processes, (2) Information resources and support, (3) Allocation of attention, (4) Cognitive overload, (5) Environmentally induced perceptual changes, (6) Misperception and misinterpretation of displayed information, (7) Spatial disorientation, and (8) Displays and controls.

Designing Interactions for Learning: Physicality, Interactivity, and Interface Effects in Digital Environments

ERIC Educational Resources Information Center

Hoffman, Daniel L.

2013-01-01

The purpose of the study is to better understand the role of physicality, interactivity, and interface effects in learning with digital content. Drawing on work in cognitive science, human-computer interaction, and multimedia learning, the study argues that interfaces that promote physical interaction can provide "conceptual leverage"…

Automated social skills training with audiovisual information.

PubMed

Tanaka, Hiroki; Sakti, Sakriani; Neubig, Graham; Negoro, Hideki; Iwasaka, Hidemi; Nakamura, Satoshi

2016-08-01

People with social communication difficulties tend to have superior skills using computers, and as a result computer-based social skills training systems are flourishing. Social skills training, performed by human trainers, is a well-established method to obtain appropriate skills in social interaction. Previous works have attempted to automate one or several parts of social skills training through human-computer interaction. However, while previous work on simulating social skills training considered only acoustic and linguistic features, human social skills trainers take into account visual features (e.g. facial expression, posture). In this paper, we create and evaluate a social skills training system that closes this gap by considering audiovisual features regarding ratio of smiling, yaw, and pitch. An experimental evaluation measures the difference in effectiveness of social skill training when using audio features and audiovisual features. Results showed that the visual features were effective to improve users' social skills.

Dehydrophenylnitrenes: matrix isolation and photochemical rearrangements.

PubMed

Sander, Wolfram; Winkler, Michael; Cakir, Bayram; Grote, Dirk; Bettinger, Holger F

2007-02-02

The photochemistry of 3-iodo-2,4,5,6-tetrafluorophenyl azide 8 and 3,5-diiodo-2,4,6-trifluorophenyl azide 9 was studied by IR and EPR spectroscopy in cryogenic argon and neon matrices. Both compounds form the corresponding nitrenes as primary photoproducts in photostationary equilibria with their azirine and ketenimine isomers. In contrast to fluorinated phenylnitrenes, ring-opened products are obtained upon short-wavelength irradiation of the iodine-containing systems, indicative of C-I bond cleavage in the nitrenes or didehydroazepines under these conditions. Neither 3-dehydrophenylnitrene 6 nor 3,5-didehydrophenylnitrene 7 could be detected directly. The structures of the acyclic photoproducts were identified by extensive comparison with DFT calculated spectra. Mechanistic aspects of the rearrangements leading to the observed products and the electronic properties of the title intermediates are discussed on the basis of DFT as well as high-level ab initio calculations. The computations indicate strong through-bond coupling of the exocyclic orbital in the meta position with the singly occupied in-plane nitrene orbital in the monoradical nitrenes. In contrast to the ortho or para isomers, this interaction results in low-spin ground states for meta nitrene radicals and a weakening of the C1-C2 bond causing the kinetic instability of these species even under low-temperature conditions. 3,5-Didehydrophenylnitrenes, on the other hand, in which a strong C3-C5 interaction reduces coupling of the radical sites with the nitrene unit, might be accessible synthetic targets if the intermediate formation of labile monoradicals could be circumvented.

Linguistic Analysis of Natural Language Communication with Computers.

ERIC Educational Resources Information Center

Thompson, Bozena Henisz

Interaction with computers in natural language requires a language that is flexible and suited to the task. This study of natural dialogue was undertaken to reveal those characteristics which can make computer English more natural. Experiments were made in three modes of communication: face-to-face, terminal-to-terminal, and human-to-computer,…

ARC: An open-source library for calculating properties of alkali Rydberg atoms

NASA Astrophysics Data System (ADS)

Šibalić, N.; Pritchard, J. D.; Adams, C. S.; Weatherill, K. J.

2017-11-01

We present an object-oriented Python library for the computation of properties of highly-excited Rydberg states of alkali atoms. These include single-body effects such as dipole matrix elements, excited-state lifetimes (radiative and black-body limited) and Stark maps of atoms in external electric fields, as well as two-atom interaction potentials accounting for dipole and quadrupole coupling effects valid at both long and short range for arbitrary placement of the atomic dipoles. The package is cross-referenced to precise measurements of atomic energy levels and features extensive documentation to facilitate rapid upgrade or expansion by users. This library has direct application in the field of quantum information and quantum optics which exploit the strong Rydberg dipolar interactions for two-qubit gates, robust atom-light interfaces and simulating quantum many-body physics, as well as the field of metrology using Rydberg atoms as precise microwave electrometers. Program Files doi:http://dx.doi.org/10.17632/hm5n8w628c.1 Licensing provisions: BSD-3-Clause Programming language: Python 2.7 or 3.5, with C extension External Routines: NumPy [1], SciPy [1], Matplotlib [2] Nature of problem: Calculating atomic properties of alkali atoms including lifetimes, energies, Stark shifts and dipole-dipole interaction strengths using matrix elements evaluated from radial wavefunctions. Solution method: Numerical integration of radial Schrödinger equation to obtain atomic wavefunctions, which are then used to evaluate dipole matrix elements. Properties are calculated using second order perturbation theory or exact diagonalisation of the interaction Hamiltonian, yielding results valid even at large external fields or small interatomic separation. Restrictions: External electric field fixed to be parallel to quantisation axis. Supplementary material: Detailed documentation (.html), and Jupyter notebook with examples and benchmarking runs (.html and .ipynb). [1] T.E. Oliphant, Comput. Sci. Eng. 9, 10 (2007). http://www.scipy.org/. [2] J.D. Hunter, Comput. Sci. Eng. 9, 90 (2007). http://matplotlib.org/.

Fourth Annual Workshop on Space Operations Applications and Research (SOAR 90)

NASA Technical Reports Server (NTRS)

Savely, Robert T. (Editor)

1991-01-01

The papers from the symposium are presented. Emphasis is placed on human factors engineering and space environment interactions. The technical areas covered in the human factors section include: satellite monitoring and control, man-computer interfaces, expert systems, AI/robotics interfaces, crew system dynamics, and display devices. The space environment interactions section presents the following topics: space plasma interaction, spacecraft contamination, space debris, and atomic oxygen interaction with materials. Some of the above topics are discussed in relation to the space station and space shuttle.

E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis

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

Pruneda, Jonathan N.; Smith, F. Donelson; Daurie, Angela

Pathogenic bacteria introduce effector proteins directly into the cytosol of eukaryotic cells to promote invasion and colonization. OspG, a Shigella spp. effector kinase, plays a role in this process by helping to suppress the host inflammatory response. OspG has been reported to bind host E2 ubiquitin-conjugating enzymes activated with ubiquitin (E2~Ub), a key enzyme complex in ubiquitin transfer pathways. A cocrystal structure of the OspG/UbcH5c~Ub complex reveals that complex formation has important ramifications for the activity of both OspG and the UbcH5c~Ub conjugate. OspG is a minimal kinase domain containing only essential elements required for catalysis. UbcH5c~Ub binding stabilizes anmore » active conformation of the kinase, greatly enhancing OspG kinase activity. In contrast, interaction with OspG stabilizes an extended, less reactive form of UbcH5c~Ub. Recognizing conserved E2 features, OspG can interact with at least ten distinct human E2s~Ub. Mouse oral infection studies indicate that E2~Ub conjugates act as novel regulators of OspG effector kinase function in eukaryotic host cells.« less

Situated Computing: The Next Frontier for HCI Research

DTIC Science & Technology

2002-01-01

population works and lives with information. Most individuals interact with information through a single portal: a personal desktop or laptop...of single devices, nor will one person necessarily own each device. This leap of imagination requires that human-computer interaction (HCI...wireless technologies, including Bluetooth [16], IrDA [22] (Infrared Data Association- standards for infrared communications) and HomeRF TM [21

The Impact of Epithelial-Stromal Interactions on Human Breast Tumor Heterogeneity

DTIC Science & Technology

2015-10-01

Heterogeneity 5b. GRANT NUMBER W81XWH-13-1-0357 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Dr. Crista Thompson 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail...2005;120:483‐95.   17.   Mateescu B, Batista L,  Cardon  M, et al. miR‐141 and miR‐200a act on ovarian  tumorigenesis by  controlling oxidative stress

Interactions with Virtual People: Do Avatars Dream of Digital Sheep?. Chapter 6

NASA Technical Reports Server (NTRS)

Slater, Mel; Sanchez-Vives, Maria V.

2007-01-01

This paper explores another form of artificial entity, ones without physical embodiment. We refer to virtual characters as the name for a type of interactive object that have become familiar in computer games and within virtual reality applications. We refer to these as avatars: three-dimensional graphical objects that are in more-or-less human form which can interact with humans. Sometimes such avatars will be representations of real-humans who are interacting together within a shared networked virtual environment, other times the representations will be of entirely computer generated characters. Unlike other authors, who reserve the term agent for entirely computer generated characters and avatars for virtual embodiments of real people; the same term here is used for both. This is because avatars and agents are on a continuum. The question is where does their behaviour originate? At the extremes the behaviour is either completely computer generated or comes only from tracking of a real person. However, not every aspect of a real person can be tracked every eyebrow move, every blink, every breath rather real tracking data would be supplemented by inferred behaviours which are programmed based on the available information as to what the real human is doing and her/his underlying emotional and psychological state. Hence there is always some programmed behaviour it is only a matter of how much. In any case the same underlying problem remains how can the human character be portrayed in such a manner that its actions are believable and have an impact on the real people with whom it interacts? This paper has three main parts. In the first part we will review some evidence that suggests that humans react with appropriate affect in their interactions with virtual human characters, or with other humans who are represented as avatars. This is so in spite of the fact that the representational fidelity is relatively low. Our evidence will be from the realm of psychotherapy, where virtual social situations are created that do test whether people react appropriately within these situations. We will also consider some experiments on face-to-face virtual communications between people in the same shared virtual environments. The second part will try to give some clues about why this might happen, taking into account modern theories of perception from neuroscience. The third part will include some speculations about the future developments of the relationship between people and virtual people. We will suggest that a more likely scenario than the world becoming populated by physically embodied virtual people (robots, androids) is that in the relatively near future we will interact more and more in our everyday lives with virtual people- bank managers, shop assistants, instructors, and so on. What is happening in the movies with computer graphic generated individuals and entire crowds may move into the space of everyday life.

A conjugate of decyltriphenylphosphonium with plastoquinone can carry cyclic adenosine monophosphate, but not cyclic guanosine monophosphate, across artificial and natural membranes.

PubMed

Firsov, Alexander M; Rybalkina, Irina G; Kotova, Elena A; Rokitskaya, Tatyana I; Tashlitsky, Vadim N; Korshunova, Galina A; Rybalkin, Sergei D; Antonenko, Yuri N

2018-02-01

The present study demonstrated for the first time the interaction between adenosine 3',5'-cyclic monophosphate (cAMP), one of the most important signaling compounds in living organisms, and the mitochondria-targeted antioxidant plastoquinonyl-decyltriphenylphosphonium (SkQ1). The data obtained on model liquid membranes and human platelets revealed the ability of SkQ1 to selectively transport cAMP, but not guanosine 3',5'-cyclic monophosphate (cGMP), across both artificial and natural membranes. In particular, SkQ1 elicited translocation of cAMP from the source to the receiving phase of a Pressman-type cell, while showing low activity with cGMP. Importantly, only conjugate with plastoquinone, but not dodecyl-triphenylphosphonium, was effective in carrying cAMP. In human platelets, SkQ1 also appeared to serve as a carrier of cAMP, but not cGMP, from outside to inside the cell, as measured by phosphorylation of the vasodilator stimulated phosphoprotein. The SkQ1-induced transfer of cAMP across the plasma membrane found here can be tentatively suggested to interfere with cAMP signaling pathways in living cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Determination of cyclic guanosine- and cyclic adenosine monophosphate (cGMP and cAMP) in human plasma and animal tissues by solid phase extraction on silica and liquid chromatography-triple quadrupole mass spectrometry.

PubMed

Van Damme, Thomas; Zhang, Yanhua; Lynen, Frédéric; Sandra, Pat

2012-11-15

3',5'-Cyclic guanosine monophosphate (cGMP) and 3',5'-cyclic adenosine monophosphate (cAMP) are essential second messenger molecules. They are involved in signal transduction within cells, in physiological functions such as neurotransmission and in the modulation of cell growth and differentiation of organisms, respectively. A quantitative solid phase extraction method (SPE) based on hydrophilic interaction on silica was developed and applied to both plasma and tissue samples. The stable isotope-labeled internal standards ²D₁, ¹⁵N₃-3',5'-cGMP and ¹³C₁₀, ¹⁵N₅-3',5'-cAMP were added prior to the sample preparation to ensure high precision and accuracy. The samples were analyzed by reversed-phase liquid chromatography (RP-LC). Negative electrospray (ESI)-MS/MS was used to selectively monitor several transitions of each metabolite. The method for the analysis of 3',5'-cAMP and 3',5'-cGMP in plasma was validated in the range of 0.15-20 ng/mL (R²=0.9996 and 0.9994 for 3',5'-cAMP and 3',5'-cGMP, respectively). Basal plasma concentrations for fifteen healthy human patients determined with this method varied between 4.66-9.20 ng/mL for 3',5'-cAMP and between 0.30-1.20 ng/mL for 3',5'-cGMP, with precisions better than 9.1%. 3',5'-cGMP and 3',5'-cAMP together with their 2',3'-isomers were also determined in a semi quantitative way in animal tissues. The structures of the isomers were confirmed by analysis with LC-high resolution time-of-flight MS and subsequently by comparison of retention times with standards. Copyright © 2012 Elsevier B.V. All rights reserved.

The interaction between ketamine and some crown ethers in common organic solvents studied by NMR: The effect of donating atoms and ligand structure

NASA Astrophysics Data System (ADS)

Chekin, Fereshteh; Bordbar, Maryam; Fathollahi, Yaghoub; Alizadeh, Naader

2006-02-01

1H NMR spectroscopy was used to investigate the stoichiometry and stability of the drug ketamine cation complexes with some crown ethers, such as 15-crown-5 (15C5), aza-15-crown-5 (A15C5), 18-crown-6 (18C6), aza-18-crown-6 (A18C6), diaza-18-crown-6 (DA18C6), dibenzyl-diaza-18-crown-6 (DBzDA18C6) and cryptant [2,2,2] (C222) in acetonitrile (AN), dimethylsulfoxide (DMSO) and methanol (MeOH) at 27 °C. In order to evaluate the formation constants of the ketamine cation complexes, the CH 3 protons chemical shift (on the nitrogen atom of ketamine) was measured as function of ligand/ketamine mole ratio. The formation constant of resulting complexes were calculated by the computer fitting of chemical shift versus mole ratio data to appropriate equations. A significant chemical shift variation was not observed for 15C5 and 18C6. The stoichiometry of the mono aza and diaza ligands are 1:1 and 1:2 (ligand/ketamine), respectively. In all of the solvents studied, DA18C6 formed more stable complexes than other ligands. The solvent effect on the stability of these complexes is discussed.

HYPERCLIPS

NASA Technical Reports Server (NTRS)

Hill, R. W.

1994-01-01

The integration of CLIPS into HyperCard combines the intuitive, interactive user interface of the Macintosh with the powerful symbolic computation of an expert system interpreter. HyperCard is an excellent environment for quickly developing the front end of an application with buttons, dialogs, and pictures, while the CLIPS interpreter provides a powerful inference engine for complex problem solving and analysis. In order to understand the benefit of integrating HyperCard and CLIPS, consider the following: HyperCard is an information storage and retrieval system which exploits the use of the graphics and user interface capabilities of the Apple Macintosh computer. The user can easily define buttons, dialog boxes, information templates, pictures, and graphic displays through the use of the HyperCard tools and scripting language. What is generally lacking in this environment is a powerful reasoning engine for complex problem solving, and this is where CLIPS plays a role. CLIPS 5.0 (C Language Integrated Production System, v5.0) was developed at the Johnson Space Center Software Technology Branch to allow artificial intelligence research, development, and delivery on conventional computers. CLIPS 5.0 supports forward chaining rule systems, object-oriented language, and procedural programming for the construction of expert systems. It features incremental reset, seven conflict resolution stategies, truth maintenance, and user-defined external functions. Since CLIPS is implemented in the C language it is highly portable; in addition, it is embeddable as a callable routine from a program written in another language such as Ada or Fortran. By integrating HyperCard and CLIPS the advantages and uses of both packages are made available for a wide range of applications: rapid prototyping of knowledge-based expert systems, interactive simulations of physical systems and intelligent control of hypertext processes, to name a few. HyperCLIPS 2.0 is written in C-Language (54%) and Pascal (46%) for Apple Macintosh computers running Macintosh System 6.0.2 or greater. HyperCLIPS requires HyperCard 1.2 or higher and at least 2Mb of RAM are recommended to run. An executable is provided. To compile the source code, the Macintosh Programmer's Workshop (MPW) version 3.0, CLIPS 5.0 (MSC-21927), and the MPW C-Language compiler are also required. NOTE: Installing this program under Macintosh System 7 requires HyperCard v2.1. This program is distributed on a 3.5 inch Macintosh format diskette. A copy of the program documentation is included on the diskette, but may be purchased separately. HyperCLIPS was developed in 1990 and version 2.0 was released in 1991. HyperCLIPS is a copyrighted work with all copyright vested in NASA. Apple, Macintosh, MPW, and HyperCard are registered trademarks of Apple Computer, Inc.

Thermal mapping on male genital and skin tissues of laptop thermal sources and electromagnetic interaction.

PubMed

Safari, Mahdi; Mosleminiya, Navid; Abdolali, Ali

2017-10-01

Since the development of communication devices and expansion of their applications, there have been concerns about their harmful health effects. The main aim of this study was to investigate laptop thermal effects caused by exposure to electromagnetic fields and thermal sources simultaneously; propose a nondestructive, replicable process that is less expensive than clinical measurements; and to study the effects of positioning any new device near the human body in steady state conditions to ensure safety by U.S. and European standard thresholds. A computer simulation was designed to obtain laptop heat flux from SolidWorks flow simulation. Increase in body temperature due to heat flux was calculated, and antenna radiation was calculated using Computer Simulation Technology (CST) Microwave Studio software. Steady state temperature and specific absorption rate (SAR) distribution in user's body, and heat flux beneath the laptop, were obtained from simulations. The laptop in its high performance mode caused 420 (W/m 2 ) peak two-dimensional heat flux beneath it. The cumulative effect of laptop in high performance mode and 1 W antenna radiation resulted in temperatures of 42.9, 38.1, and 37.2 °C in lap skin, scrotum, and testis, that is, 5.6, 2.1, and 1.4 °C increase in temperature, respectively. Also, 1 W antenna radiation caused 0.37 × 10 -3 and 0.13 × 10 -1 (W/kg) peak three-dimensional SAR at 2.4 and 5 GHz, respectively, which could be ignored in reference to standards and temperature rise due to laptop use. Bioelectromagnetics. 38:550-558, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Decision making and problem solving with computer assistance

NASA Technical Reports Server (NTRS)

Kraiss, F.

1980-01-01

In modern guidance and control systems, the human as manager, supervisor, decision maker, problem solver and trouble shooter, often has to cope with a marginal mental workload. To improve this situation, computers should be used to reduce the operator from mental stress. This should not solely be done by increased automation, but by a reasonable sharing of tasks in a human-computer team, where the computer supports the human intelligence. Recent developments in this area are summarized. It is shown that interactive support of operator by intelligent computer is feasible during information evaluation, decision making and problem solving. The applied artificial intelligence algorithms comprehend pattern recognition and classification, adaptation and machine learning as well as dynamic and heuristic programming. Elementary examples are presented to explain basic principles.

The interaction of C.I. acid red 27 with human hemoglobin in solution.

PubMed

Wang, Yan-Qing; Zhang, Hong-Mei; Tang, Bo-Ping

2010-08-02

The nature of the interaction between human hemoglobin and C.I. acid red 27 was investigated systematically by ultraviolet-vis absorbance, circular dichroism, fluorescence, synchronous fluorescence, and three-dimensional fluorescence spectra techniques at pH 7.40. The quenching mechanism, binding constants, and the number of binding sites were determined by the quenching of human hemoglobin fluorescence in presence of C.I. acid red 27. The results showed that the nature of the quenching was of static type and the process of binding acid red 27 on human hemoglobin was a spontaneous molecular interaction procedure. The electrostatic and hydrophobic interactions played a major role in stabilizing the complex; The distance r between donor and acceptor was obtained to be 4.40 nm according to Förster's theory; The effect of acid red 27 on the conformation of human hemoglobin was analyzed using synchronous fluorescence, circular dichroism and three-dimensional fluorescence spectra. 2010 Elsevier B.V. All rights reserved.

Enhanced Prediction of Src Homology 2 (SH2) Domain Binding Potentials Using a Fluorescence Polarization-derived c-Met, c-Kit, ErbB, and Androgen Receptor Interactome*

PubMed Central

Leung, Kin K.; Hause, Ronald J.; Barkinge, John L.; Ciaccio, Mark F.; Chuu, Chih-Pin; Jones, Richard B.

2014-01-01

Many human diseases are associated with aberrant regulation of phosphoprotein signaling networks. Src homology 2 (SH2) domains represent the major class of protein domains in metazoans that interact with proteins phosphorylated on the amino acid residue tyrosine. Although current SH2 domain prediction algorithms perform well at predicting the sequences of phosphorylated peptides that are likely to result in the highest possible interaction affinity in the context of random peptide library screens, these algorithms do poorly at predicting the interaction potential of SH2 domains with physiologically derived protein sequences. We employed a high throughput interaction assay system to empirically determine the affinity between 93 human SH2 domains and phosphopeptides abstracted from several receptor tyrosine kinases and signaling proteins. The resulting interaction experiments revealed over 1000 novel peptide-protein interactions and provided a glimpse into the common and specific interaction potentials of c-Met, c-Kit, GAB1, and the human androgen receptor. We used these data to build a permutation-based logistic regression classifier that performed considerably better than existing algorithms for predicting the interaction potential of several SH2 domains. PMID:24728074

Regulation of Viral RNA Synthesis by the V Protein of Parainfluenza Virus 5

PubMed Central

Yang, Yang; Zengel, James; Sun, Minghao; Sleeman, Katrina; Timani, Khalid Amine; Aligo, Jason; Rota, Paul

2015-01-01

ABSTRACT Paramyxoviruses include many important animal and human pathogens. The genome of parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, encodes a V protein that inhibits viral RNA synthesis. In this work, the mechanism of inhibition was investigated. Using mutational analysis and a minigenome system, we identified regions in the N and C termini of the V protein that inhibit viral RNA synthesis: one at the very N terminus of V and the second at the C terminus of V. Furthermore, we determined that residues L16 and I17 are critical for the inhibitory function of the N-terminal region of the V protein. Both regions interact with the nucleocapsid protein (NP), an essential component of the viral RNA genome complex (RNP). Mutations at L16 and I17 abolished the interaction between NP and the N-terminal domain of V. This suggests that the interaction between NP and the N-terminal domain plays a critical role in V inhibition of viral RNA synthesis by the N-terminal domain. Both the N- and C-terminal regions inhibited viral RNA replication. The C terminus inhibited viral RNA transcription, while the N-terminal domain enhanced viral RNA transcription, suggesting that the two domains affect viral RNA through different mechanisms. Interestingly, V also inhibited the synthesis of the RNA of other paramyxoviruses, such as Nipah virus (NiV), human parainfluenza virus 3 (HPIV3), measles virus (MeV), mumps virus (MuV), and respiratory syncytial virus (RSV). This suggests that a common host factor may be involved in the replication of these paramyxoviruses. IMPORTANCE We identified two regions of the V protein that interact with NP and determined that one of these regions enhances viral RNA transcription via its interaction with NP. Our data suggest that a common host factor may be involved in the regulation of paramyxovirus replication and could be a target for broad antiviral drug development. Understanding the regulation of paramyxovirus replication will enable the rational design of vaccines and potential antiviral drugs. PMID:26378167

A Guide for Developing Human-Robot Interaction Experiments in the Robotic Interactive Visualization and Experimentation Technology (RIVET) Simulation

DTIC Science & Technology

2016-05-01

research, Kunkler (2006) suggested that the similarities between computer simulation tools and robotic surgery systems (e.g., mechanized feedback...distribution is unlimited. 49 Davies B. A review of robotics in surgery . Proceedings of the Institution of Mechanical Engineers, Part H: Journal...ARL-TR-7683 ● MAY 2016 US Army Research Laboratory A Guide for Developing Human- Robot Interaction Experiments in the Robotic

Internal proton transfer and H2 rotations in the H5(+) cluster: a marked influence on its thermal equilibrium state.

PubMed

de Tudela, Ricardo Pérez; Barragán, Patricia; Prosmiti, Rita; Villarreal, Pablo; Delgado-Barrio, Gerardo

2011-03-31

Classical and path integral Monte Carlo (CMC, PIMC) "on the fly" calculations are carried out to investigate anharmonic quantum effects on the thermal equilibrium structure of the H5(+) cluster. The idea to follow in our computations is based on using a combination of the above-mentioned nuclear classical and quantum statistical methods, and first-principles density functional (DFT) electronic structure calculations. The interaction energies are computed within the DFT framework using the B3(H) hybrid functional, specially designed for hydrogen-only systems. The global minimum of the potential is predicted to be a nonplanar configuration of C(2v) symmetry, while the next three low-lying stationary points on the surface correspond to extremely low-energy barriers for the internal proton transfer and to the rotation of the H2 molecules, around the C2 axis of H5(+), connecting the symmetric C(2v) minima in the planar and nonplanar orientations. On the basis of full-dimensional converged PIMC calculations, results on the quantum vibrational zero-point energy (ZPE) and state of H5(+) are reported at a low temperature of 10 K, and the influence of the above-mentioned topological features of the surface on its probability distributions is clearly demonstrated.

Evaluation of an Adaptive Automation Trigger Based on Task Performance, Priority, and Frequency

DTIC Science & Technology

2013-06-01

with dual Intel ® Xeon ® CPU x5550 processors @ 2.67 GHz each, 12.0 GB RAM, and a 1.5 GB PCIe nVidia Quadro FX 4800 graphics card (Microsoft...Cole Publishing Company . Miller, C. A., & Parasuraman, R. (2007). Designing for flexible interaction between humans and automation: Delegation

Computational prediction of virus-human protein-protein interactions using embedding kernelized heterogeneous data.

PubMed

Nourani, Esmaeil; Khunjush, Farshad; Durmuş, Saliha

2016-05-24

Pathogenic microorganisms exploit host cellular mechanisms and evade host defense mechanisms through molecular pathogen-host interactions (PHIs). Therefore, comprehensive analysis of these PHI networks should be an initial step for developing effective therapeutics against infectious diseases. Computational prediction of PHI data is gaining increasing demand because of scarcity of experimental data. Prediction of protein-protein interactions (PPIs) within PHI systems can be formulated as a classification problem, which requires the knowledge of non-interacting protein pairs. This is a restricting requirement since we lack datasets that report non-interacting protein pairs. In this study, we formulated the "computational prediction of PHI data" problem using kernel embedding of heterogeneous data. This eliminates the abovementioned requirement and enables us to predict new interactions without randomly labeling protein pairs as non-interacting. Domain-domain associations are used to filter the predicted results leading to 175 novel PHIs between 170 human proteins and 105 viral proteins. To compare our results with the state-of-the-art studies that use a binary classification formulation, we modified our settings to consider the same formulation. Detailed evaluations are conducted and our results provide more than 10 percent improvements for accuracy and AUC (area under the receiving operating curve) results in comparison with state-of-the-art methods.

Evaluation of an automated ultraviolet-C light disinfection device and patient hand hygiene for reduction of pathogen transfer from interactive touchscreen computer kiosks.

PubMed

Alhmidi, Heba; Cadnum, Jennifer L; Piedrahita, Christina T; John, Amrita R; Donskey, Curtis J

2018-04-01

Touchscreens are a potential source of pathogen transmission. In our facility, patients and visitors rarely perform hand hygiene after using interactive touchscreen computer kiosks. An automated ultraviolet-C touchscreen disinfection device was effective in reducing bacteriophage MS2, bacteriophage ϕX174, methicillin-resistant Staphylococcus aureus, and Clostridium difficile spores inoculated onto a touchscreen. In simulations, an automated ultraviolet-C touchscreen disinfection device alone or in combination with hand hygiene reduced transfer of the viruses from contaminated touchscreens to fingertips. Published by Elsevier Inc.

ILLIAC IV Applications Research

DTIC Science & Technology

1974-12-31

Reducino a Real Matrix to the Unper-Hessenbern Form," CAC Document Ko . 11: Center for Advanced Computation, Pniversitv of Illinois at Urbana...Complex for small-scale interactive imane analysis; (4) The APPA Network for decentrali7ed user access Ko t.hp system; -11- APPA FINAL REPORT (5...Grossman David M. Grothe Bruce P. Hanna Bruce M. Hannon James H. Hansen David C. Healy Steven F, Holmgren Dorothy J. Hopkin Robert J. Husby Renato

Adenovirus type 5 E1A and E6 proteins of low-risk cutaneous beta-human papillomaviruses suppress cell transformation through interaction with FOXK1/K2 transcription factors.

PubMed

Komorek, Jessica; Kuppuswamy, Mohan; Subramanian, T; Vijayalingam, S; Lomonosova, Elena; Zhao, Ling-Jun; Mymryk, Joe S; Schmitt, Kimberly; Chinnadurai, G

2010-03-01

The adenovirus (Adv) oncoprotein E1A stimulates cell proliferation and inhibits differentiation. These activities are primarily linked to the N-terminal region (exon 1) of E1A, which interacts with multiple cellular protein complexes. The C terminus (exon 2) of E1A antagonizes these processes, mediated in part through interaction with C-terminal binding proteins 1 and 2 (CtBP1/2). To identify additional cellular E1A targets that are involved in the modulation of E1A C-terminus-mediated activities, we undertook tandem affinity purification of E1A-associated proteins. Through mass spectrometric analysis, we identified several known E1A-interacting proteins as well as novel E1A targets, such as the forkhead transcription factors, FOXK1/K2. We identified a Ser/Thr-containing sequence motif in E1A that mediated interaction with FOXK1/K2. We demonstrated that the E6 proteins of two beta-human papillomaviruses (HPV14 and HPV21) associated with epidermodysplasia verruciformis also interacted with FOXK1/K2 through a motif similar to that of E1A. The E1A mutants deficient in interaction with FOXK1/K2 induced enhanced cell proliferation and oncogenic transformation. The hypertransforming activity of the mutant E1A was suppressed by HPV21 E6. An E1A-E6 chimeric protein containing the Ser/Thr domain of the E6 protein in E1A interacted efficiently with FOXK1/K2 and inhibited cell transformation. Our results suggest that targeting FOXK1/K2 may be a common mechanism for certain beta-HPVs and Adv5. E1A exon 2 mutants deficient in interaction with the dual-specificity kinases DYRK1A/1B and their cofactor HAN11 also induced increased cell proliferation and transformation. Our results suggest that the E1A C-terminal region may suppress cell proliferation and oncogenic transformation through interaction with three different cellular protein complexes: FOXK1/K2, DYRK(1A/1B)/HAN11, and CtBP1/2.

LCR 5' hypersensitive site specificity for globin gene activation within the active chromatin hub.

PubMed

Peterson, Kenneth R; Fedosyuk, Halyna; Harju-Baker, Susanna

2012-12-01

The DNaseI hypersensitive sites (HSs) of the human β-globin locus control region (LCR) may function as part of an LCR holocomplex within a larger active chromatin hub (ACH). Differential activation of the globin genes during development may be controlled in part by preferential interaction of each gene with specific individual HSs during globin gene switching, a change in conformation of the LCR holocomplex, or both. To distinguish between these possibilities, human β-globin locus yeast artificial chromosome (β-YAC) lines were produced in which the ε-globin gene was replaced with a second marked β-globin gene (β(m)), coupled to an intact LCR, a 5'HS3 complete deletion (5'ΔHS3) or a 5'HS3 core deletion (5'ΔHS3c). The 5'ΔHS3c mice expressed β(m)-globin throughout development; γ-globin was co-expressed in the embryonic yolk sac, but not in the fetal liver; and wild-type β-globin was co-expressed in adult mice. Although the 5'HS3 core was not required for β(m)-globin expression, previous work showed that the 5'HS3 core is necessary for ε-globin expression during embryonic erythropoiesis. A similar phenotype was observed in 5'HS complete deletion mice, except β(m)-globin expression was higher during primitive erythropoiesis and γ-globin expression continued into fetal definitive erythropoiesis. These data support a site specificity model of LCR HS-globin gene interaction.

Integrating autonomous distributed control into a human-centric C4ISR environment

NASA Astrophysics Data System (ADS)

Straub, Jeremy

2017-05-01

This paper considers incorporating autonomy into human-centric Command, Control, Communications, Computers, Intelligence, Surveillance and Reconnaissance (C4ISR) environments. Specifically, it focuses on identifying ways that current autonomy technologies can augment human control and the challenges presented by additive autonomy. Three approaches to this challenge are considered, stemming from prior work in two converging areas. In the first, the problem is approached as augmenting what humans currently do with automation. In the alternate approach, the problem is approached as treating humans as actors within a cyber-physical system-of-systems (stemming from robotic distributed computing). A third approach, combines elements of both of the aforementioned.

Time-dependent inhibition (TDI) of CYP3A4 and CYP2C9 by noscapine potentially explains clinical noscapine-warfarin interaction.

PubMed

Fang, Zhong-Ze; Zhang, Yan-Yan; Ge, Guang-Bo; Huo, Hong; Liang, Si-Cheng; Yang, Ling

2010-02-01

To investigate the inhibition potential and kinetic information of noscapine to seven CYP isoforms and extrapolate in vivo noscapine-warfarin interaction magnitude from in vitro data. The activities of seven CYP isoforms (CYP3A4, CYP1A2, CYP2A6, CYP2E1, CYP2D6, CYP2C9, CYP2C8) in human liver microsomes were investigated following co- or preincubation with noscapine. A two-step incubation method was used to examine in vitro time-dependent inhibition (TDI) of noscapine. Reversible and TDI prediction equations were employed to extrapolate in vivo noscapine-warfarin interaction magnitude from in vitro data. Among seven CYP isoforms tested, the activities of CYP3A4 and CYP2C9 were strongly inhibited with an IC(50) of 10.8 +/- 2.5 microm and 13.3 +/- 1.2 microm. Kinetic analysis showed that inhibition of CYP2C9 by noscapine was best fit to a noncompetitive type with K(i) value of 8.8 microm, while inhibition of CYP3A4 by noscapine was best fit to a competitive manner with K(i) value of 5.2 microm. Noscapine also exhibited TDI to CYP3A4 and CYP2C9. The inactivation parameters (K(I) and k(inact)) were calculated to be 9.3 microm and 0.06 min(-1) for CYP3A4 and 8.9 microm and 0.014 min(-1) for CYP2C9, respectively. The AUC of (S)-warfarin and (R)-warfarin was predicted to increase 1.5% and 1.1% using C(max) or 0.5% and 0.4% using unbound C(max) with reversible inhibition prediction equation, while the AUC of (S)-warfarin and (R)-warfarin was estimated to increase by 110.9% and 48.9% using C(max) or 41.8% and 32.7% using unbound C(max) with TDI prediction equation. TDI of CYP3A4 and CYP2C9 by noscapine potentially explains clinical noscapine-warfarin interaction.

Identification of DNA-binding proteins that interact with the 5'-flanking region of the human D-amino acid oxidase gene by pull-down assay coupled with two-dimensional gel electrophoresis and mass spectrometry.

PubMed

Tran, Diem Hong; Shishido, Yuji; Chung, Seong Pil; Trinh, Huong Thi Thanh; Yorita, Kazuko; Sakai, Takashi; Fukui, Kiyoshi

2015-12-10

D-Amino acid oxidase (DAO) is a flavoenzyme that metabolizes D-amino acids and is expected to be a promising therapeutic target of schizophrenia and glioblastoma. The study of DNA-binding proteins has yielded much information in the regulation of transcription and other biological processes. However, proteins interacting with DAO gene have not been elucidated. Our assessment of human DAO promoter activity using luciferase reporter system indicated the 5'-flanking region of this gene (-4289 bp from transcription initiation site) has a regulatory sequence for gene expression, which is regulated by multi-protein complexes interacting with this region. By using pull-down assay coupled with two-dimensional gel electrophoresis and mass spectrometry, we identified six proteins binding to the 5'-flanking region of the human DAO gene (zinc finger C2HC domain-containing protein 1A; histidine-tRNA ligase, cytoplasmic; molybdenum cofactor biosynthesis protein; 60S ribosomal protein L37; calponin-1; calmodulin binding protein and heterogeneous nuclear ribonucleoprotein A2/B1). These preliminary results will contribute to the advance in the understanding of the potential factors associated with the regulatory mechanism of DAO expression. Copyright © 2015 Elsevier B.V. All rights reserved.

Testing the nature of reaction coordinate describing interaction of H2 with carbonyl carbon, activated by Lewis acid complexation, and the Lewis basic solvent: A Born-Oppenheimer molecular dynamics study with explicit solvent

NASA Astrophysics Data System (ADS)

Heshmat, Mojgan; Privalov, Timofei

2017-09-01

Using Born-Oppenheimer molecular dynamics (BOMD), we explore the nature of interactions between H2 and the activated carbonyl carbon, C(carbonyl), of the acetone-B(C6F5)3 adduct surrounded by an explicit solvent (1,4-dioxane). BOMD simulations at finite (non-zero) temperature with an explicit solvent produced long-lasting instances of significant vibrational perturbation of the H—H bond and H2-polarization at C(carbonyl). As far as the characteristics of H2 are concerned, the dynamical transient state approximates the transition-state of the heterolytic H2-cleavage. The culprit is the concerted interactions of H2 with C(carbonyl) and a number of Lewis basic solvent molecules—i.e., the concerted C(carbonyl)⋯H2⋯solvent interactions. On one hand, the results presented herein complement the mechanistic insight gained from our recent transition-state calculations, reported separately from this article. But on the other hand, we now indicate that an idea of the sufficiency of just one simple reaction coordinate in solution-phase reactions can be too simplistic and misleading. This article goes in the footsteps of the rapidly strengthening approach of investigating molecular interactions in large molecular systems via "computational experimentation" employing, primarily, ab initio molecular dynamics describing reactants-interaction without constraints of the preordained reaction coordinate and/or foreknowledge of the sampling order parameters.

Human factors in computing systems: focus on patient-centered health communication at the ACM SIGCHI conference.

PubMed

Wilcox, Lauren; Patel, Rupa; Chen, Yunan; Shachak, Aviv

2013-12-01

Health Information Technologies, such as electronic health records (EHR) and secure messaging, have already transformed interactions among patients and clinicians. In addition, technologies supporting asynchronous communication outside of clinical encounters, such as email, SMS, and patient portals, are being increasingly used for follow-up, education, and data reporting. Meanwhile, patients are increasingly adopting personal tools to track various aspects of health status and therapeutic progress, wishing to review these data with clinicians during consultations. These issues have drawn increasing interest from the human-computer interaction (HCI) community, with special focus on critical challenges in patient-centered interactions and design opportunities that can address these challenges. We saw this community presenting and interacting at the ACM SIGCHI 2013, Conference on Human Factors in Computing Systems, (also known as CHI), held April 27-May 2nd, 2013 at the Palais de Congrès de Paris in France. CHI 2013 featured many formal avenues to pursue patient-centered health communication: a well-attended workshop, tracks of original research, and a lively panel discussion. In this report, we highlight these events and the main themes we identified. We hope that it will help bring the health care communication and the HCI communities closer together. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A pipeline for the systematic identification of non-redundant full-ORF cDNAs for polymorphic and evolutionary divergent genomes: Application to the ascidian Ciona intestinalis

DOE PAGES

Gilchrist, Michael J.; Sobral, Daniel; Khoueiry, Pierre; ...

2015-05-27

Genome-wide resources, such as collections of cDNA clones encoding for complete proteins (full-ORF clones), are crucial tools for studying the evolution of gene function and genetic interactions. Non-model organisms, in particular marine organisms, provide a rich source of functional diversity. Marine organism genomes are, however, frequently highly polymorphic and encode proteins that diverge significantly from those of well-annotated model genomes. The construction of full-ORF clone collections from non-model organisms is hindered by the difficulty of predicting accurately the N-terminal ends of proteins, and distinguishing recent paralogs from highly polymorphic alleles. We also report a computational strategy that overcomes these difficulties,more » and allows for accurate gene level clustering of transcript data followed by the automated identification of full-ORFs with correct 5'- and 3'-ends. It is robust to polymorphism, includes paralog calling and does not require evolutionary proximity to well annotated model organisms. Here, we developed this pipeline for the ascidian Ciona intestinalis, a highly polymorphic member of the divergent sister group of the vertebrates, emerging as a powerful model organism to study chordate gene function, Gene Regulatory Networks and molecular mechanisms underlying human pathologies. Furthermore, using this pipeline we have generated the first full-ORF collection for a highly polymorphic marine invertebrate. It contains 19,163 full-ORF cDNA clones covering 60% of Ciona coding genes, and full-ORF orthologs for approximately half of curated human disease-associated genes.« less

After-effects of human-computer interaction indicated by P300 of the event-related brain potential.

PubMed

Trimmel, M; Huber, R

1998-05-01

After-effects of human-computer interaction (HCI) were investigated by using the P300 component of the event-related brain potential (ERP). Forty-nine subjects (naive non-users, beginners, experienced users, programmers) completed three paper/pencil tasks (text editing, solving intelligence test items, filling out a questionnaire on sensation seeking) and three HCI tasks (text editing, executing a tutor program or programming, playing Tetris). The sequence of 7-min tasks was randomized between subjects and balanced between groups. After each experimental condition ERPs were recorded during an acoustic discrimination task at F3, F4, Cz, P3 and P4. Data indicate that: (1) mental after-effects of HCI can be detected by P300 of the ERP; (2) HCI showed in general a reduced amplitude; (3) P300 amplitude varied also with type of task, mainly at F4 where it was smaller after cognitive tasks (intelligence test/programming) and larger after emotion-based tasks (sensation seeking/Tetris); (4) cognitive tasks showed shorter latencies; (5) latencies were widely location-independent (within the range of 356-358 ms at F3, F4, P3 and P4) after executing the tutor program or programming; and (6) all observed after-effects were independent of the user's experience in operating computers and may therefore reflect short-term after-effects only and no structural changes of information processing caused by HCI.

Computational model of in vivo human energy metabolism during semi-starvation and re-feeding

PubMed Central

Hall, Kevin D.

2008-01-01

Changes of body weight and composition are the result of complex interactions among metabolic fluxes contributing to macronutrient balances. To better understand these interactions, a mathematical model was constructed that used the measured dietary macronutrient intake during semi-starvation and re-feeding as model inputs and computed whole-body energy expenditure, de novo lipogenesis, gluconeogenesis, as well as turnover and oxidation of carbohydrate, fat and protein. Published in vivo human data provided the basis for the model components which were integrated by fitting a few unknown parameters to the classic Minnesota human starvation experiment. The model simulated the measured body weight and fat mass changes during semi-starvation and re-feeding and predicted the unmeasured metabolic fluxes underlying the body composition changes. The resting metabolic rate matched the experimental measurements and required a model of adaptive thermogenesis. Re-feeding caused an elevation of de novo lipogenesis which, along with increased fat intake, resulted in a rapid repletion and overshoot of body fat. By continuing the computer simulation with the pre-starvation diet and physical activity, the original body weight and composition was eventually restored, but body fat mass was predicted to take more than one additional year to return to within 5% of its original value. The model was validated by simulating a recently published short-term caloric restriction experiment without changing the model parameters. The predicted changes of body weight, fat mass, resting metabolic rate, and nitrogen balance matched the experimental measurements thereby providing support for the validity of the model. PMID:16449298

Intelligent control system based on ARM for lithography tool

NASA Astrophysics Data System (ADS)

Chen, Changlong; Tang, Xiaoping; Hu, Song; Wang, Nan

2014-08-01

The control system of traditional lithography tool is based on PC and MCU. The PC handles the complex algorithm, human-computer interaction, and communicates with MCU via serial port; The MCU controls motors and electromagnetic valves, etc. This mode has shortcomings like big volume, high power consumption, and wasting of PC resource. In this paper, an embedded intelligent control system of lithography tool, based on ARM, is provided. The control system used S5PV210 as processor, completing the functions of PC in traditional lithography tool, and provided a good human-computer interaction by using LCD and capacitive touch screen. Using Android4.0.3 as operating system, the equipment provided a cool and easy UI which made the control more user-friendly, and implemented remote control and debug, pushing video information of product by network programming. As a result, it's convenient for equipment vendor to provide technical support for users. Finally, compared with traditional lithography tool, this design reduced the PC part, making the hardware resources efficiently used and reducing the cost and volume. Introducing embedded OS and the concepts in "The Internet of things" into the design of lithography tool can be a development trend.

Yeast-2-Hybrid data file showing progranulin interactions in human fetal brain and bone marrow libraries.

PubMed

Tegeder, Irmgard

2016-12-01

Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech). This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016) [1].

Computational Modeling of Laser-Cell Biochemical Interactions

DTIC Science & Technology

2010-12-31

San Antonio, TX 78228 Jeffrey W. Oliver. Ph.D. Human Effectiveness Directorate Directed Energy Bioeffects Division Optical Radiation Branch...Affairs Case No. 11-080 Air Force Research Laboratory 711 Human Performance Wing Human Effectiveness Directorate Directed Energy Bioeffects...Directed Energy Bioeffects Division Human Effectiveness Directorate 711 Human Performance Wing Air Force Research Laboratory This report is

Homologous species restriction of the complement-mediated killing of nucleated cells.

PubMed Central

Yamamoto, H; Blaas, P; Nicholson-Weller, A; Hänsch, G M

1990-01-01

The homologous restriction of complement (C) lysis is attributed to membrane proteins: decay-accelerating factor (DAF), C8 binding protein (C8bp) and P18/CD59. Since these proteins are also expressed on peripheral blood cells, species restriction was tested for in the complement-mediated killing of antibody-coated human leucocytes by human or rabbit complement. Killing was more efficient when rabbit complement was used. Preincubation of cells with an antibody to DAF abolished the difference. When C1-7 sites were first attached to the cells and either rabbit or human C8, C9 were added, the killing of monocytes and lymphocytes was equally efficient; only in polymorphonuclear neutrophils was a higher efficiency of rabbit C8, C9 seen. Thus, in contrast to haemolysis, restriction occurred predominantly at the C3 level and the action of the terminal complement components was not inhibited. Since C8bp isolated from peripheral blood cells showed essentially similar characteristics as the erythrocyte-derived C8bp, the failure of C8bp to inhibit the action of the terminal components on nucleated cells might reflect differences of the complement membrane interactions between erythrocytes or nucleated cells, respectively. Images Figure 5 PMID:1697561

Computed secondary-particle energy spectra following nonelastic neutron interactions with C-12 for E(n) between 15 and 60 MeV: Comparisons of results from two calculational methods

NASA Astrophysics Data System (ADS)

Dickens, J. K.

1991-04-01

The organic scintillation detector response code SCINFUL has been used to compute secondary-particle energy spectra, d(sigma)/dE, following nonelastic neutron interactions with C-12 for incident neutron energies between 15 and 60 MeV. The resulting spectra are compared with published similar spectra computed by Brenner and Prael who used an intranuclear cascade code, including alpha clustering, a particle pickup mechanism, and a theoretical approach to sequential decay via intermediate particle-unstable states. The similarities of and the differences between the results of the two approaches are discussed.

Real-time 3D human capture system for mixed-reality art and entertainment.

PubMed

Nguyen, Ta Huynh Duy; Qui, Tran Cong Thien; Xu, Ke; Cheok, Adrian David; Teo, Sze Lee; Zhou, ZhiYing; Mallawaarachchi, Asitha; Lee, Shang Ping; Liu, Wei; Teo, Hui Siang; Thang, Le Nam; Li, Yu; Kato, Hirokazu

2005-01-01

A real-time system for capturing humans in 3D and placing them into a mixed reality environment is presented in this paper. The subject is captured by nine cameras surrounding her. Looking through a head-mounted-display with a camera in front pointing at a marker, the user can see the 3D image of this subject overlaid onto a mixed reality scene. The 3D images of the subject viewed from this viewpoint are constructed using a robust and fast shape-from-silhouette algorithm. The paper also presents several techniques to produce good quality and speed up the whole system. The frame rate of our system is around 25 fps using only standard Intel processor-based personal computers. Besides a remote live 3D conferencing and collaborating system, we also describe an application of the system in art and entertainment, named Magic Land, which is a mixed reality environment where captured avatars of human and 3D computer generated virtual animations can form an interactive story and play with each other. This system demonstrates many technologies in human computer interaction: mixed reality, tangible interaction, and 3D communication. The result of the user study not only emphasizes the benefits, but also addresses some issues of these technologies.

Eyetracking Methodology in SCMC: A Tool for Empowering Learning and Teaching

ERIC Educational Resources Information Center

Stickler, Ursula; Shi, Lijing

2017-01-01

Computer-assisted language learning, or CALL, is an interdisciplinary area of research, positioned between science and social science, computing and education, linguistics and applied linguistics. This paper argues that by appropriating methods originating in some areas of CALL-related research, for example human-computer interaction (HCI) or…

Bergamottin contribution to the grapefruit juice-felodipine interaction and disposition in humans.

PubMed

Goosen, Theunis C; Cillié, Doré; Bailey, David G; Yu, Chongwoo; He, Kan; Hollenberg, Paul F; Woster, Patrick M; Cohen, Lucinda; Williams, J Andrew; Rheeders, Malie; Dijkstra, H Paul

2004-12-01

Our objectives were to evaluate the contribution of bergamottin to the grapefruit juice-felodipine interaction and to characterize bergamottin disposition. In this study 250 mL grapefruit juice; 2-, 6-, or 12-mg capsules of bergamottin plus water; or water was administered with 5 mg extended-release felodipine to 11 volunteers in a partially randomized, 5-way crossover study. Plasma concentrations of felodipine, its primary metabolite (dehydrofelodipine), bergamottin, and 6',7'-dihydroxybergamottin were determined. Grapefruit juice (containing 1.7 mg bergamottin) increased peak plasma concentration (C max ) and area under the plasma concentration-time curve (AUC) of felodipine by 89% (P < .025) and 54% (P < .025), respectively, compared with water. With 2 mg bergamottin, felodipine C max increased by 33% (P < .05). The increase by bergamottin was markedly variable among individuals (range, -33% to 125%). With 6 mg bergamottin, felodipine C max was enhanced by 35% (P < .025), and with 12 mg bergamottin, felodipine C max increased by 40% (P < .05) and AUC increased by 37% (P < .05) compared with water. Bergamottin measured in plasma after administration of 6 and 12 mg produced C max values of 2.1 and 5.9 ng/mL, respectively, and times to reach C max of 0.8 and 1.1 hours, respectively. The bergamottin metabolite 6',7'-dihydroxybergamottin was detected in plasma of some subjects after bergamottin administration. Bergamottin enhanced the oral bioavailability of felodipine and may cause a clinically relevant drug interaction in susceptible individuals. Grapefruit juice-drug interactions likely also involve other furanocoumarins, possibly acting in combination by additive or synergistic mechanisms. Bergamottin has systemic availability and is metabolized in vivo to 6',7'-dihydroxybergamottin.

HExpoChem: a systems biology resource to explore human exposure to chemicals.

PubMed

Taboureau, Olivier; Jacobsen, Ulrik Plesner; Kalhauge, Christian; Edsgärd, Daniel; Rigina, Olga; Gupta, Ramneek; Audouze, Karine

2013-05-01

Humans are exposed to diverse hazardous chemicals daily. Although an exposure to these chemicals is suspected to have adverse effects on human health, mechanistic insights into how they interact with the human body are still limited. Therefore, acquisition of curated data and development of computational biology approaches are needed to assess the health risks of chemical exposure. Here we present HExpoChem, a tool based on environmental chemicals and their bioactivities on human proteins with the objective of aiding the qualitative exploration of human exposure to chemicals. The chemical-protein interactions have been enriched with a quality-scored human protein-protein interaction network, a protein-protein association network and a chemical-chemical interaction network, thus allowing the study of environmental chemicals through formation of protein complexes and phenotypic outcomes enrichment. HExpoChem is available at http://www.cbs.dtu.dk/services/HExpoChem-1.0/.

Rational design of biaryl pharmacophore inserted noscapine derivatives as potent tubulin binding anticancer agents.

PubMed

Santoshi, Seneha; Manchukonda, Naresh Kumar; Suri, Charu; Sharma, Manya; Sridhar, Balasubramanian; Joseph, Silja; Lopus, Manu; Kantevari, Srinivas; Baitharu, Iswar; Naik, Pradeep Kumar

2015-03-01

We have strategically designed a series of noscapine derivatives by inserting biaryl pharmacophore (a major structural constituent of many of the microtubule-targeting natural anticancer compounds) onto the scaffold structure of noscapine. Molecular interaction of these derivatives with α,β-tubulin heterodimer was investigated by molecular docking, molecular dynamics simulation, and binding free energy calculation. The predictive binding affinity indicates that the newly designed noscapinoids bind to tubulin with a greater affinity. The predictive binding free energy (ΔG(bind, pred)) of these derivatives (ranging from -5.568 to -5.970 kcal/mol) based on linear interaction energy (LIE) method with a surface generalized Born (SGB) continuum solvation model showed improved binding affinity with tubulin compared to the lead compound, natural α-noscapine (-5.505 kcal/mol). Guided by the computational findings, these new biaryl type α-noscapine congeners were synthesized from 9-bromo-α-noscapine using optimized Suzuki reaction conditions for further experimental evaluation. The derivatives showed improved inhibition of the proliferation of human breast cancer cells (MCF-7), human cervical cancer cells (HeLa) and human lung adenocarcinoma cells (A549), compared to natural noscapine. The cell cycle analysis in MCF-7 further revealed that these compounds alter the cell cycle profile and cause mitotic arrest at G2/M phase more strongly than noscapine. Tubulin binding assay revealed higher binding affinity to tubulin, as suggested by dissociation constant (Kd) of 126 ± 5.0 µM for 5a, 107 ± 5.0 µM for 5c, 70 ± 4.0 µM for 5d, and 68 ± 6.0 µM for 5e compared to noscapine (Kd of 152 ± 1.0 µM). In fact, the experimentally determined value of ΔG(bind, expt) (calculated from the Kd value) are consistent with the predicted value of ΔG(bind, pred) calculated based on LIE-SGB. Based on these results, one of the derivative 5e of this series was used for further toxicological evaluation. Treatment of mice with a daily dose of 300 mg/kg and a single dose of 600 mg/kg indicates that the compound does not induce detectable pathological abnormalities in normal tissues. Also there were no significant differences in hematological parameters between the treated and untreated groups. Hence, the newly designed noscapinoid, 5e is an orally bioavailable, safe and effective anticancer agent with a potential for the treatment of cancer and might be a candidate for clinical evaluation.

Rational design of biaryl pharmacophore inserted noscapine derivatives as potent tubulin binding anticancer agents

NASA Astrophysics Data System (ADS)

Santoshi, Seneha; Manchukonda, Naresh Kumar; Suri, Charu; Sharma, Manya; Sridhar, Balasubramanian; Joseph, Silja; Lopus, Manu; Kantevari, Srinivas; Baitharu, Iswar; Naik, Pradeep Kumar

2015-03-01

We have strategically designed a series of noscapine derivatives by inserting biaryl pharmacophore (a major structural constituent of many of the microtubule-targeting natural anticancer compounds) onto the scaffold structure of noscapine. Molecular interaction of these derivatives with α,β-tubulin heterodimer was investigated by molecular docking, molecular dynamics simulation, and binding free energy calculation. The predictive binding affinity indicates that the newly designed noscapinoids bind to tubulin with a greater affinity. The predictive binding free energy (ΔGbind, pred) of these derivatives (ranging from -5.568 to -5.970 kcal/mol) based on linear interaction energy (LIE) method with a surface generalized Born (SGB) continuum solvation model showed improved binding affinity with tubulin compared to the lead compound, natural α-noscapine (-5.505 kcal/mol). Guided by the computational findings, these new biaryl type α-noscapine congeners were synthesized from 9-bromo-α-noscapine using optimized Suzuki reaction conditions for further experimental evaluation. The derivatives showed improved inhibition of the proliferation of human breast cancer cells (MCF-7), human cervical cancer cells (HeLa) and human lung adenocarcinoma cells (A549), compared to natural noscapine. The cell cycle analysis in MCF-7 further revealed that these compounds alter the cell cycle profile and cause mitotic arrest at G2/M phase more strongly than noscapine. Tubulin binding assay revealed higher binding affinity to tubulin, as suggested by dissociation constant (Kd) of 126 ± 5.0 µM for 5a, 107 ± 5.0 µM for 5c, 70 ± 4.0 µM for 5d, and 68 ± 6.0 µM for 5e compared to noscapine (Kd of 152 ± 1.0 µM). In fact, the experimentally determined value of ΔGbind, expt (calculated from the Kd value) are consistent with the predicted value of ΔGbind, pred calculated based on LIE-SGB. Based on these results, one of the derivative 5e of this series was used for further toxicological evaluation. Treatment of mice with a daily dose of 300 mg/kg and a single dose of 600 mg/kg indicates that the compound does not induce detectable pathological abnormalities in normal tissues. Also there were no significant differences in hematological parameters between the treated and untreated groups. Hence, the newly designed noscapinoid, 5e is an orally bioavailable, safe and effective anticancer agent with a potential for the treatment of cancer and might be a candidate for clinical evaluation.

Role of a disulfide-bonded peptide loop within human complement C9 in the species-selectivity of complement inhibitor CD59.

PubMed

Husler, T; Lockert, D H; Sims, P J

1996-03-12

CD59 antigen is a membrane glycoprotein that inhibits the activity of the C9 component of the C5b-9 membrane attack complex (MAC), thereby protecting human cells from lysis by human complement. The complement-inhibitory activity of CD59 is species-selective, and is most effective toward C9 derived from human or other primate plasma. The species-selective activity of CD59 was recently used to map the segment of human C9 that is recognized by this MAC inhibitor, using recombinant rabbit/human C9 chimeras that retain lytic function within the MAC [Husler, T., Lockert, D. H., Kaufman, K. M., Sodetz, J. M., & Sims, P. J. (1995) J. Biol. Chem. 270,3483-3486]. These experiments suggested that the CD59 recognition domain was contained between residues 334 and 415 in human C9. By analyzing the species-selective lytic activity of recombinant C9 with chimeric substitutions internal to this segment, we now demonstrate that the site in human C9 uniquely recognized by CD59 is centered on those residues contained between C9 Cys359/Cys384, with an additional contribution by residues C-terminal to this segment. Consistent with its role as a CD59 recognition domain, CD59 specifically bound a human C9-derived peptide corresponding to residues 359-384, and antibody (Fab) raised against this C9-derived peptide inhibited the lytic activity of human MAC. Mutant human C9 in which Ala was substituted for Cys359/384 was found to express normal lytic activity and to be fully inhibited by CD59. This suggests that the intrachain Cys359/Cys384 disulfide bond within C9 is not required to maintain the conformation of this segment of C9 for interaction with CD59.

Inhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized extract and constituents.

PubMed

Ramasamy, Seetha; Kiew, Lik Voon; Chung, Lip Yong

2014-02-24

Bacopa monnieri and the constituents of this plant, especially bacosides, possess various neuropharmacological properties. Like drugs, some herbal extracts and the constituents of their extracts alter cytochrome P450 (CYP) enzymes, causing potential herb-drug interactions. The effects of Bacopa monnieri standardized extract and the bacosides from the extract on five major CYP isoforms in vitro were analyzed using a luminescent CYP recombinant human enzyme assay. B. monnieri extract exhibited non-competitive inhibition of CYP2C19 (IC50/Ki = 23.67/9.5 µg/mL), CYP2C9 (36.49/12.5 µg/mL), CYP1A2 (52.20/25.1 µg/mL); competitive inhibition of CYP3A4 (83.95/14.5 µg/mL) and weak inhibition of CYP2D6 (IC50 = 2061.50 µg/mL). However, the bacosides showed negligible inhibition of the same isoforms. B. monnieri, which is orally administered, has a higher concentration in the gut than the liver; therefore, this herb could exhibit stronger inhibition of intestinal CYPs than hepatic CYPs. At an estimated gut concentration of 600 µg/mL (based on a daily dosage of 300 mg/day), B. monnieri reduced the catalytic activities of CYP3A4, CYP2C9 and CYP2C19 to less than 10% compared to the total activity (without inhibitor = 100%). These findings suggest that B. monnieri extract could contribute to herb-drug interactions when orally co-administered with drugs metabolized by CYP1A2, CYP3A4, CYP2C9 and CYP2C19.

Trust and Trustworthiness in Human-Robot Interaction: A Formal Conceptualization

DTIC Science & Technology

2016-05-11

AFRL-AFOSR-VA-TR-2016-0198 Trust and Trustworthiness in Human- Robot Interaction: A formal conceptualization Alan Wagner GEORGIA TECH APPLIED RESEARCH...27/2013-03/31/2016 4. TITLE AND SUBTITLE Trust and Trustworthiness in Human- Robot Interaction: A formal conceptualization 5a. CONTRACT NUMBER 5b...evaluated algorithms for characterizing trust during interactions between a robot and a human and employed strategies for repairing trust during emergency

Synthesis and chemistry of the open-cage cobaltaheteroborane cluster [{(η(5)-C5Me5)Co}2B2H2Se2]: a combined experimental and theoretical study.

PubMed

Barik, Subrat Kumar; Dorcet, Vincent; Roisnel, Thierry; Halet, Jean-François; Ghosh, Sundargopal

2015-08-28

Reaction of [(η(5)-C5Me5)CoCl]2 with a two-fold excess of [LiBH4·thf] followed by heating with an excess of Se powder produces the dicobaltaselenaborane species [{(η(5)-C5Me5)Co}2B2H2Se2], , in good yield. The geometry of resembles a nido pentagonal [Co2B2Se2] bipyramid with a missing equatorial vertex. It can alternatively be seen as an open cage triple-decker cluster. Isolation of permits its reaction with [Fe2(CO)9] to give heterometallic diselenametallaborane [{(η(5)-C5Me5)Co}Fe(CO)3B2H2Se2], . The geometry of is similar to that of with one of the [(η(5)-C5Me5)Co] groups replaced by the isolobal, two-electron fragment [Fe(CO)3]. Both new compounds have been characterized by mass spectrometry, and by (1)H, (11)B and (13)C NMR spectroscopy. The structural architectures have been unequivocally established by crystallographic analysis. In addition, density functional theory calculations were performed to investigate the bonding and electronic properties. The large HOMO-LUMO gaps computed for both clusters are consistent with their thermodynamic stability. Natural bond order calculations predict the absence of metal-metal bonding interaction.

Towards a Computational Model of Sketching

DTIC Science & Technology

2000-01-01

interaction that sketching provides in human-to- human communication , multimodal research will rely heavily upon, and even drive, AI research . This...can. Dimensions of sketching The power of sketching in human communication arises from the high bandwidth it provides [21] . There is high perceptual

Probing the interaction between cHAVc3 peptide and the EC1 domain of E-cadherin using NMR and molecular dynamics simulations.

PubMed

Alaofi, Ahmed; Farokhi, Elinaz; Prasasty, Vivitri D; Anbanandam, Asokan; Kuczera, Krzysztof; Siahaan, Teruna J

2017-01-01

The goal of this work is to probe the interaction between cyclic cHAVc3 peptide and the EC1 domain of human E-cadherin protein. Cyclic cHAVc3 peptide (cyclo(1,6)Ac-CSHAVC-NH 2 ) binds to the EC1 domain as shown by chemical shift perturbations in the 2D 1 H,- 15 N-HSQC NMR spectrum. The molecular dynamics (MD) simulations of the EC1 domain showed folding of the C-terminal tail region into the main head region of the EC1 domain. For cHAVc3 peptide, replica exchange molecular dynamics (REMD) simulations generated five structural clusters of cHAVc3 peptide. Representative structures of cHAVc3 and the EC1 structure from MD simulations were used in molecular docking experiments with NMR constraints to determine the binding site of the peptide on EC1. The results suggest that cHAVc3 binds to EC1 around residues Y36, S37, I38, I53, F77, S78, H79, and I94. The dissociation constants (K d values) of cHAVc3 peptide to EC1 were estimated using the NMR chemical shifts data and the estimated K d s are in the range of .5 × 10 -5 -7.0 × 10 -5  M.

Numerical simulation of stress amplification induced by crack interaction in human femur bone

NASA Astrophysics Data System (ADS)

Alia, Noor; Daud, Ruslizam; Ramli, Mohammad Fadzli; Azman, Wan Zuki; Faizal, Ahmad; Aisyah, Siti

2015-05-01

This research is about numerical simulation using a computational method which study on stress amplification induced by crack interaction in human femur bone. Cracks in human femur bone usually occur because of large load or stress applied on it. Usually, the fracture takes longer time to heal itself. At present, the crack interaction is still not well understood due to bone complexity. Thus, brittle fracture behavior of bone may be underestimated and inaccurate. This study aims to investigate the geometrical effect of double co-planar edge cracks on stress intensity factor (K) in femur bone. This research focuses to analyze the amplification effect on the fracture behavior of double co-planar edge cracks, where numerical model is developed using computational method. The concept of fracture mechanics and finite element method (FEM) are used to solve the interacting cracks problems using linear elastic fracture mechanics (LEFM) theory. As a result, this study has shown the identification of the crack interaction limit (CIL) and crack unification limit (CUL) exist in the human femur bone model developed. In future research, several improvements will be made such as varying the load, applying thickness on the model and also use different theory or method in calculating the stress intensity factor (K).

Synthesis of novel anthraquinones: Molecular structure, molecular chemical reactivity descriptors and interactions with DNA as antibiotic and anti-cancer drugs

NASA Astrophysics Data System (ADS)

Al-Otaibi, Jamelah S.; EL Gogary, Tarek M.

2017-02-01

Anthraquinones are well-known anticancer drugs. Anthraquinones anticancer drugs carry out their cytotoxic activities through their interaction with DNA, and inhibition of topoisomerase II activity. Anthraquinones (AQ5 and AQ5H) were synthesized and studied with 1,5-DAAQ by computational and experimental tools. The purpose of this study is to shade more light on mechanism of interaction between anthraquinone DNA affinic agents and different types of DNA. This study will lead to gain of information useful for drug design and development. Molecular structures were optimized using DFT B3LYP/6-31 + G(d). Depending on intramolecular hydrogen bonding interactions four conformers of AQ5 were detected within the range of about 42 kcal/mol. Molecular reactivity of the anthraquinone compounds was explored using global and condensed descriptors (electrophilicity and Fukui functions). NMR and UV-VIS electronic absorption spectra of anthraquinones/DNA were investigated at the physiological pH. The interaction of the anthraquinones (AQ5 and AQ5H) were studied with different DNA namely, calf thymus DNA, (Poly[dA].Poly[dT]) and (Poly[dG].Poly[dC]). UV-VIS electronic absorption spectral data were employed to measure the affinity constants of drug/DNA binding using Scatchard analysis. NMR study confirms qualitatively the drug/DNA interaction in terms of peak shift and broadening.

The H/ACA RNP assembly factor SHQ1 functions as an RNA mimic.

PubMed

Walbott, Hélène; Machado-Pinilla, Rosario; Liger, Dominique; Blaud, Magali; Réty, Stéphane; Grozdanov, Petar N; Godin, Kate; van Tilbeurgh, Herman; Varani, Gabriele; Meier, U Thomas; Leulliot, Nicolas

2011-11-15

SHQ1 is an essential assembly factor for H/ACA ribonucleoproteins (RNPs) required for ribosome biogenesis, pre-mRNA splicing, and telomere maintenance. SHQ1 binds dyskerin/NAP57, the catalytic subunit of human H/ACA RNPs, and this interaction is modulated by mutations causing X-linked dyskeratosis congenita. We report the crystal structure of the C-terminal domain of yeast SHQ1, Shq1p, and its complex with yeast dyskerin/NAP57, Cbf5p, lacking its catalytic domain. The C-terminal domain of Shq1p interacts with the RNA-binding domain of Cbf5p and, through structural mimicry, uses the RNA-protein-binding sites to achieve a specific protein-protein interface. We propose that Shq1p operates as a Cbf5p chaperone during RNP assembly by acting as an RNA placeholder, thereby preventing Cbf5p from nonspecific RNA binding before association with an H/ACA RNA and the other core RNP proteins.

The H/ACA RNP assembly factor SHQ1 functions as an RNA mimic

PubMed Central

Walbott, Hélène; Machado-Pinilla, Rosario; Liger, Dominique; Blaud, Magali; Réty, Stéphane; Grozdanov, Petar N.; Godin, Kate; van Tilbeurgh, Herman; Varani, Gabriele; Meier, U. Thomas; Leulliot, Nicolas

2011-01-01

SHQ1 is an essential assembly factor for H/ACA ribonucleoproteins (RNPs) required for ribosome biogenesis, pre-mRNA splicing, and telomere maintenance. SHQ1 binds dyskerin/NAP57, the catalytic subunit of human H/ACA RNPs, and this interaction is modulated by mutations causing X-linked dyskeratosis congenita. We report the crystal structure of the C-terminal domain of yeast SHQ1, Shq1p, and its complex with yeast dyskerin/NAP57, Cbf5p, lacking its catalytic domain. The C-terminal domain of Shq1p interacts with the RNA-binding domain of Cbf5p and, through structural mimicry, uses the RNA–protein-binding sites to achieve a specific protein–protein interface. We propose that Shq1p operates as a Cbf5p chaperone during RNP assembly by acting as an RNA placeholder, thereby preventing Cbf5p from nonspecific RNA binding before association with an H/ACA RNA and the other core RNP proteins. PMID:22085966

Quizzing and Feedback in Computer-Based and Book-Based Training for Workplace Safety and Health

ERIC Educational Resources Information Center

Rohlman, Diane S.; Eckerman, David A.; Ammerman, Tammara A.; Fercho, Heather L.; Lundeen, Christine A.; Blomquist, Carrie; Anger, W. Kent

2005-01-01

Participants received different amounts of information in either a cTRAIN computer-based instruction (CBI) program or in a booklet format, presented before or concurrently with interactive questions about the information. An interactive CBI presentation that required an overt response during training produced equivalent acquisition and retention…

The Bayesian reader: explaining word recognition as an optimal Bayesian decision process.

PubMed

Norris, Dennis

2006-04-01

This article presents a theory of visual word recognition that assumes that, in the tasks of word identification, lexical decision, and semantic categorization, human readers behave as optimal Bayesian decision makers. This leads to the development of a computational model of word recognition, the Bayesian reader. The Bayesian reader successfully simulates some of the most significant data on human reading. The model accounts for the nature of the function relating word frequency to reaction time and identification threshold, the effects of neighborhood density and its interaction with frequency, and the variation in the pattern of neighborhood density effects seen in different experimental tasks. Both the general behavior of the model and the way the model predicts different patterns of results in different tasks follow entirely from the assumption that human readers approximate optimal Bayesian decision makers. ((c) 2006 APA, all rights reserved).

NOX5 in Human Spermatozoa

PubMed Central

Musset, Boris; Clark, Robert A.; DeCoursey, Thomas E.; Petheo, Gabor L.; Geiszt, Miklos; Chen, Yumin; Cornell, John E.; Eddy, Carlton A.; Brzyski, Robert G.; El Jamali, Amina

2012-01-01

Physiological and pathological processes in spermatozoa involve the production of reactive oxygen species (ROS), but the identity of the ROS-producing enzyme system(s) remains a matter of speculation. We provide the first evidence that NOX5 NADPH oxidase is expressed and functions in human spermatozoa. Immunofluorescence microscopy detected NOX5 protein in both the flagella/neck region and the acrosome. Functionally, spermatozoa exposed to calcium ionophore, phorbol ester, or H2O2 exhibited superoxide anion production, which was blocked by addition of superoxide dismutase, a Ca2+ chelator, or inhibitors of either flavoprotein oxidases (diphenylene iododonium) or NOX enzymes (GKT136901). Consistent with our previous overexpression studies, we found that H2O2-induced superoxide production by primary sperm cells was mediated by the non-receptor tyrosine kinase c-Abl. Moreover, the HV1 proton channel, which was recently implicated in spermatozoa motility, was required for optimal superoxide production by spermatozoa. Immunoprecipitation experiments suggested an interaction among NOX5, c-Abl, and HV1. H2O2 treatment increased the proportion of motile sperm in a NOX5-dependent manner. Statistical analyses showed a pH-dependent correlation between superoxide production and enhanced sperm motility. Collectively, our findings show that NOX5 is a major source of ROS in human spermatozoa and indicate a role for NOX5-dependent ROS generation in human spermatozoa motility. PMID:22291013

Initial Progress Toward Development of a Voice-Based Computer-Delivered Motivational Intervention for Heavy Drinking College Students: An Experimental Study

PubMed Central

Lechner, William J; MacGlashan, James; Wray, Tyler B; Littman, Michael L

2017-01-01

Background Computer-delivered interventions have been shown to be effective in reducing alcohol consumption in heavy drinking college students. However, these computer-delivered interventions rely on mouse, keyboard, or touchscreen responses for interactions between the users and the computer-delivered intervention. The principles of motivational interviewing suggest that in-person interventions may be effective, in part, because they encourage individuals to think through and speak aloud their motivations for changing a health behavior, which current computer-delivered interventions do not allow. Objective The objective of this study was to take the initial steps toward development of a voice-based computer-delivered intervention that can ask open-ended questions and respond appropriately to users’ verbal responses, more closely mirroring a human-delivered motivational intervention. Methods We developed (1) a voice-based computer-delivered intervention that was run by a human controller and that allowed participants to speak their responses to scripted prompts delivered by speech generation software and (2) a text-based computer-delivered intervention that relied on the mouse, keyboard, and computer screen for all interactions. We randomized 60 heavy drinking college students to interact with the voice-based computer-delivered intervention and 30 to interact with the text-based computer-delivered intervention and compared their ratings of the systems as well as their motivation to change drinking and their drinking behavior at 1-month follow-up. Results Participants reported that the voice-based computer-delivered intervention engaged positively with them in the session and delivered content in a manner consistent with motivational interviewing principles. At 1-month follow-up, participants in the voice-based computer-delivered intervention condition reported significant decreases in quantity, frequency, and problems associated with drinking, and increased perceived importance of changing drinking behaviors. In comparison to the text-based computer-delivered intervention condition, those assigned to voice-based computer-delivered intervention reported significantly fewer alcohol-related problems at the 1-month follow-up (incident rate ratio 0.60, 95% CI 0.44-0.83, P=.002). The conditions did not differ significantly on perceived importance of changing drinking or on measures of drinking quantity and frequency of heavy drinking. Conclusions Results indicate that it is feasible to construct a series of open-ended questions and a bank of responses and follow-up prompts that can be used in a future fully automated voice-based computer-delivered intervention that may mirror more closely human-delivered motivational interventions to reduce drinking. Such efforts will require using advanced speech recognition capabilities and machine-learning approaches to train a program to mirror the decisions made by human controllers in the voice-based computer-delivered intervention used in this study. In addition, future studies should examine enhancements that can increase the perceived warmth and empathy of voice-based computer-delivered intervention, possibly through greater personalization, improvements in the speech generation software, and embodying the computer-delivered intervention in a physical form. PMID:28659259

Analysis of nucleoside-binding proteins by ligand-specific elution from dye resin: application to Mycobacterium tuberculosis aldehyde dehydrogenases.

PubMed

Kim, Chang-Yub; Webster, Cecelia; Roberts, Justin K M; Moon, Jin Ho; Alipio Lyon, Emily Z; Kim, Heungbok; Yu, Minmin; Hung, Li-Wei; Terwilliger, Thomas C

2009-12-01

We show that Cibacron Blue F3GA dye resin chromatography can be used to identify ligands that specifically interact with proteins from Mycobacterium tuberculosis, and that the identification of these ligands can facilitate structure determination by enhancing the quality of crystals. Four native Mtb proteins of the aldehyde dehydrogenase (ALDH) family were previously shown to be specifically eluted from a Cibacron Blue F3GA dye resin with nucleosides. In this study we characterized the nucleoside-binding specificity of one of these ALDH isozymes (recombinant Mtb Rv0223c) and compared these biochemical results with co-crystallization experiments with different Rv0223c-nucleoside pairings. We found that the strongly interacting ligands (NAD and NADH) aided formation of high-quality crystals, permitting solution of the first Mtb ALDH (Rv0223c) structure. Other nucleoside ligands (AMP, FAD, adenosine, GTP and NADP) exhibited weaker binding to Rv0223c, and produced co-crystals diffracting to lower resolution. Difference electron density maps based on crystals of Rv0223c with various nucleoside ligands show most share the binding site where the natural ligand NAD binds. From the high degree of similarity of sequence and structure compared to human mitochondrial ALDH-2 (BLAST Z-score = 53.5 and RMSD = 1.5 A), Rv0223c appears to belong to the ALDH-2 class. An altered oligomerization domain in the Rv0223c structure seems to keep this protein as monomer whereas native human ALDH-2 is a multimer.

Information Interaction: Providing a Framework for Information Architecture.

ERIC Educational Resources Information Center

Toms, Elaine G.

2002-01-01

Discussion of information architecture focuses on a model of information interaction that bridges the gap between human and computer and between information behavior and information retrieval. Illustrates how the process of information interaction is affected by the user, the system, and the content. (Contains 93 references.) (LRW)

Understanding Teachers' Routines to Inform Classroom Technology Design

ERIC Educational Resources Information Center

An, Pengcheng; Bakker, Saskia; Eggen, Berry

2017-01-01

Secondary school teachers have quite busy and complex routines in their classrooms. However, present classroom technologies usually require focused attention from teachers while being interacted with, which restricts their use in teachers' daily routines. Peripheral interaction is a human-computer interaction style that aims to enable interaction…

Genome-wide analysis of epistasis in body mass index using multiple human populations.

PubMed

Wei, Wen-Hua; Hemani, Gib; Gyenesei, Attila; Vitart, Veronique; Navarro, Pau; Hayward, Caroline; Cabrera, Claudia P; Huffman, Jennifer E; Knott, Sara A; Hicks, Andrew A; Rudan, Igor; Pramstaller, Peter P; Wild, Sarah H; Wilson, James F; Campbell, Harry; Hastie, Nicholas D; Wright, Alan F; Haley, Chris S

2012-08-01

We surveyed gene-gene interactions (epistasis) in human body mass index (BMI) in four European populations (n<1200) via exhaustive pair-wise genome scans where interactions were computed as F ratios by testing a linear regression model fitting two single-nucleotide polymorphisms (SNPs) with interactions against the one without. Before the association tests, BMI was corrected for sex and age, normalised and adjusted for relatedness. Neither single SNPs nor SNP interactions were genome-wide significant in either cohort based on the consensus threshold (P=5.0E-08) and a Bonferroni corrected threshold (P=1.1E-12), respectively. Next we compared sub genome-wide significant SNP interactions (P<5.0E-08) across cohorts to identify common epistatic signals, where SNPs were annotated to genes to test for gene ontology (GO) enrichment. Among the epistatic genes contributing to the commonly enriched GO terms, 19 were shared across study cohorts of which 15 are previously published genome-wide association loci, including CDH13 (cadherin 13) associated with height and SORCS2 (sortilin-related VPS10 domain containing receptor 2) associated with circulating insulin-like growth factor 1 and binding protein 3. Interactions between the 19 shared epistatic genes and those involving BMI candidate loci (P<5.0E-08) were tested across cohorts and found eight replicated at the SNP level (P<0.05) in at least one cohort, which were further tested and showed limited replication in a separate European population (n>5000). We conclude that genome-wide analysis of epistasis in multiple populations is an effective approach to provide new insights into the genetic regulation of BMI but requires additional efforts to confirm the findings.

A scientific workflow framework for (13)C metabolic flux analysis.

PubMed

Dalman, Tolga; Wiechert, Wolfgang; Nöh, Katharina

2016-08-20

Metabolic flux analysis (MFA) with (13)C labeling data is a high-precision technique to quantify intracellular reaction rates (fluxes). One of the major challenges of (13)C MFA is the interactivity of the computational workflow according to which the fluxes are determined from the input data (metabolic network model, labeling data, and physiological rates). Here, the workflow assembly is inevitably determined by the scientist who has to consider interacting biological, experimental, and computational aspects. Decision-making is context dependent and requires expertise, rendering an automated evaluation process hardly possible. Here, we present a scientific workflow framework (SWF) for creating, executing, and controlling on demand (13)C MFA workflows. (13)C MFA-specific tools and libraries, such as the high-performance simulation toolbox 13CFLUX2, are wrapped as web services and thereby integrated into a service-oriented architecture. Besides workflow steering, the SWF features transparent provenance collection and enables full flexibility for ad hoc scripting solutions. To handle compute-intensive tasks, cloud computing is supported. We demonstrate how the challenges posed by (13)C MFA workflows can be solved with our approach on the basis of two proof-of-concept use cases. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibition of thrombin by functionalized C60 nanoparticles revealed via in vitro assays and in silico studies.

PubMed

Liu, Yanyan; Fu, Jianjie; Pan, Wenxiao; Xue, Qiao; Liu, Xian; Zhang, Aiqian

2018-01-01

The studies on the human toxicity of nanoparticles (NPs) are far behind the rapid development of engineered functionalized NPs. Fullerene has been widely used as drug carrier skeleton due to its reported low risk. However, different from other kinds of NPs, fullerene-based NPs (C 60 NPs) have been found to have an anticoagulation effect, although the potential target is still unknown. In the study, both experimental and computational methods were adopted to gain mechanistic insight into the modulation of thrombin activity by nine kinds of C 60 NPs with diverse surface chemistry properties. In vitro enzyme activity assays showed that all tested surface-modified C 60 NPs exhibited thrombin inhibition ability. Kinetic studies coupled with competitive testing using 3 known inhibitors indicated that six of the C 60 NPs, of greater hydrophobicity and hydrogen bond (HB) donor acidity or acceptor basicity, acted as competitive inhibitors of thrombin by directly interacting with the active site of thrombin. A simple quantitative nanostructure-activity relationship model relating the surface substituent properties to the inhibition potential was then established for the six competitive inhibitors. Molecular docking analysis revealed that the intermolecular HB interactions were important for the specific binding of C 60 NPs to the active site canyon, while the additional stability provided by the surface groups through van der Waals interaction also play a key role in the thrombin binding affinity of the NPs. Our results suggest that thrombin is a possible target of the surface-functionalized C 60 NPs relevant to their anticoagulation effect. Copyright © 2017. Published by Elsevier B.V.

Peptide ligands specific to the oxidized form of escherichia coli thioredoxin.

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

Scholle, M. D.; Banach, B. S.; Hamdan, S. M.

Thioredoxin (Trx) is a highly conserved redox protein involved in several essential cellular processes. In this study, our goal was to isolate peptide ligands to Escherichia coli Trx that mimic protein-protein interactions, specifically the T7 polymerase-Trx interaction. To do this, we subjected Trx to affinity selection against a panel of linear and cysteine-constrained peptides using M13 phage display. A novel cyclized conserved peptide sequence, with a motif of C(D/N/S/T/G)D(S/T)-hydrophobic-C-X-hydrophobic-P, was isolated to Trx. These peptides bound specifically to the E. coli Trx when compared to the human and spirulina homologs. An alanine substitution of the active site cysteines (CGPC) resultedmore » in a significant loss of peptide binding affinity to the Cys-32 mutant. The peptides were also characterized in the context of Trx's role as a processivity factor of the T7 DNA polymerase (gp5). As the interaction between gp5 and Trx normally takes place under reducing conditions, which might interfere with the conformation of the disulfide-bridged peptides, we made use of a 22 residue deletion mutant of gp5 in the thioredoxin binding domain (gp5{Delta}22) that bypassed the requirements of reducing conditions to interact with Trx. A competition study revealed that the peptide selectively inhibits the interaction of gp5{Delta}22 with Trx, under oxidizing conditions, with an IC50 of {approx} 10 {micro}M.« less

Molecular Determinants of the Human α2C-Adrenergic Receptor Temperature-Sensitive Intracellular Traffic

PubMed Central

Pullikuth, Ashok K.; Guidry, Jessie J.

2015-01-01

The human α2C-adrenergic receptor (α2C-AR) is localized intracellularly at physiologic temperature. Decreasing the environmental temperature strongly stimulates the receptor transport to the cell surface. In contrast, rat and mouse α2C-AR plasma membrane levels are less sensitive to decrease in temperature, whereas the opossum α2C-AR cell surface levels are not changed in these conditions. Structural analysis demonstrated that human α2C-AR has a high number of arginine residues in the third intracellular loop and in the C-terminus, organized as putative RXR motifs. Although these motifs do not affect the receptor subcellular localization at 37°C, deletion of the arginine clusters significantly enhanced receptor plasma membrane levels at reduced temperature. We found that this exaggerated transport of the human receptor is mediated by two functional arginine clusters, one in the third intracellular loop and one in the C-terminus. This effect is mediated by interactions with COPI vesicles, but not by 14-3-3 proteins. In rat α2C-AR, the arginine cluster from the third intracellular loop is shifted to the left due to three missing residues. Reinsertion of these residues in the rat α2C-AR restored the same temperature sensitivity as in the human receptor. Proteomic and coimmunoprecipitation experiments identified pontin as a molecule having stronger interactions with human α2C-AR compared with rat α2C-AR. Inhibition of pontin activity enhanced human receptor plasma membrane levels and signaling at 37°C. Our results demonstrate that human α2C-AR has a unique temperature-sensitive traffic pattern within the G protein–coupled receptor class due to interactions with different molecular chaperones, mediated in part by strict spatial localization of specific arginine residues. PMID:25680754

Analysis of context dependence in social interaction networks of a massively multiplayer online role-playing game.

PubMed

Son, Seokshin; Kang, Ah Reum; Kim, Hyun-chul; Kwon, Taekyoung; Park, Juyong; Kim, Huy Kang

2012-01-01

Rapid advances in modern computing and information technology have enabled millions of people to interact online via various social network and gaming services. The widespread adoption of such online services have made possible analysis of large-scale archival data containing detailed human interactions, presenting a very promising opportunity to understand the rich and complex human behavior. In collaboration with a leading global provider of Massively Multiplayer Online Role-Playing Games (MMORPGs), here we present a network science-based analysis of the interplay between distinct types of user interaction networks in the virtual world. We find that their properties depend critically on the nature of the context-interdependence of the interactions, highlighting the complex and multilayered nature of human interactions, a robust understanding of which we believe may prove instrumental in the designing of more realistic future virtual arenas as well as provide novel insights to the science of collective human behavior.

Human-computer interaction for alert warning and attention allocation systems of the multimodal watchstation

NASA Astrophysics Data System (ADS)

Obermayer, Richard W.; Nugent, William A.

2000-11-01

The SPAWAR Systems Center San Diego is currently developing an advanced Multi-Modal Watchstation (MMWS); design concepts and software from this effort are intended for transition to future United States Navy surface combatants. The MMWS features multiple flat panel displays and several modes of user interaction, including voice input and output, natural language recognition, 3D audio, stylus and gestural inputs. In 1999, an extensive literature review was conducted on basic and applied research concerned with alerting and warning systems. After summarizing that literature, a human computer interaction (HCI) designer's guide was prepared to support the design of an attention allocation subsystem (AAS) for the MMWS. The resultant HCI guidelines are being applied in the design of a fully interactive AAS prototype. An overview of key findings from the literature review, a proposed design methodology with illustrative examples, and an assessment of progress made in implementing the HCI designers guide are presented.

Human-computer interface including haptically controlled interactions

DOEpatents

Anderson, Thomas G.

2005-10-11

The present invention provides a method of human-computer interfacing that provides haptic feedback to control interface interactions such as scrolling or zooming within an application. Haptic feedback in the present method allows the user more intuitive control of the interface interactions, and allows the user's visual focus to remain on the application. The method comprises providing a control domain within which the user can control interactions. For example, a haptic boundary can be provided corresponding to scrollable or scalable portions of the application domain. The user can position a cursor near such a boundary, feeling its presence haptically (reducing the requirement for visual attention for control of scrolling of the display). The user can then apply force relative to the boundary, causing the interface to scroll the domain. The rate of scrolling can be related to the magnitude of applied force, providing the user with additional intuitive, non-visual control of scrolling.

Development and Validation of the Total HUman Model for Safety (THUMS) Toward Further Understanding of Occupant Injury Mechanisms in Precrash and During Crash.

PubMed

Iwamoto, Masami; Nakahira, Yuko; Kimpara, Hideyuki

2015-01-01

Active safety devices such as automatic emergency brake (AEB) and precrash seat belt have the potential to accomplish further reduction in the number of the fatalities due to automotive accidents. However, their effectiveness should be investigated by more accurate estimations of their interaction with human bodies. Computational human body models are suitable for investigation, especially considering muscular tone effects on occupant motions and injury outcomes. However, the conventional modeling approaches such as multibody models and detailed finite element (FE) models have advantages and disadvantages in computational costs and injury predictions considering muscular tone effects. The objective of this study is to develop and validate a human body FE model with whole body muscles, which can be used for the detailed investigation of interaction between human bodies and vehicular structures including some safety devices precrash and during a crash with relatively low computational costs. In this study, we developed a human body FE model called THUMS (Total HUman Model for Safety) with a body size of 50th percentile adult male (AM50) and a sitting posture. The model has anatomical structures of bones, ligaments, muscles, brain, and internal organs. The total number of elements is 281,260, which would realize relatively low computational costs. Deformable material models were assigned to all body parts. The muscle-tendon complexes were modeled by truss elements with Hill-type muscle material and seat belt elements with tension-only material. The THUMS was validated against 35 series of cadaver or volunteer test data on frontal, lateral, and rear impacts. Model validations for 15 series of cadaver test data associated with frontal impacts are presented in this article. The THUMS with a vehicle sled model was applied to investigate effects of muscle activations on occupant kinematics and injury outcomes in specific frontal impact situations with AEB. In the validations using 5 series of cadaver test data, force-time curves predicted by the THUMS were quantitatively evaluated using correlation and analysis (CORA), which showed good or acceptable agreement with cadaver test data in most cases. The investigation of muscular effects showed that muscle activation levels and timing had significant effects on occupant kinematics and injury outcomes. Although further studies on accident injury reconstruction are needed, the THUMS has the potential for predictions of occupant kinematics and injury outcomes considering muscular tone effects with relatively low computational costs.

Modulation of Human Leukocyte Antigen-C by Human Cytomegalovirus Stimulates KIR2DS1 Recognition by Natural Killer Cells

PubMed Central

van der Ploeg, Kattria; Chang, Chiwen; Ivarsson, Martin A.; Moffett, Ashley; Wills, Mark R.; Trowsdale, John

2017-01-01

The interaction of inhibitory killer cell Ig-like receptors (KIRs) with human leukocyte antigen (HLA) class I molecules has been characterized in detail. By contrast, activating members of the KIR family, although closely related to inhibitory KIRs, appear to interact weakly, if at all, with HLA class I. KIR2DS1 is the best studied activating KIR and it interacts with C2 group HLA-C (C2-HLA-C) in some assays, but not as strongly as KIR2DL1. We used a mouse 2B4 cell reporter system, which carries NFAT-green fluorescent protein with KIR2DS1 and a modified DAP12 adaptor protein. KIR2DS1 reporter cells were not activated upon coculture with 721.221 cells transfected with different HLA-C molecules, or with interferon-γ stimulated primary dermal fibroblasts. However, KIR2DS1 reporter cells and KIR2DS1+ primary natural killer (NK) cells were activated by C2-HLA-C homozygous human fetal foreskin fibroblasts (HFFFs) but only after infection with specific clones of a clinical strain of human cytomegalovirus (HCMV). Active viral gene expression was required for activation of both cell types. Primary NKG2A−KIR2DS1+ NK cell subsets degranulated after coculture with HCMV-infected HFFFs. The W6/32 antibody to HLA class I blocked the KIR2DS1 reporter cell interaction with its ligand on HCMV-infected HFFFs but did not block interaction with KIR2DL1. This implies a differential recognition of HLA-C by KIR2DL1 and KIR2DS1. The data suggest that modulation of HLA-C by HCMV is required for a potent KIR2DS1-mediated NK cell activation. PMID:28424684

A multimodal dataset for authoring and editing multimedia content: The MAMEM project.

PubMed

Nikolopoulos, Spiros; Petrantonakis, Panagiotis C; Georgiadis, Kostas; Kalaganis, Fotis; Liaros, Georgios; Lazarou, Ioulietta; Adam, Katerina; Papazoglou-Chalikias, Anastasios; Chatzilari, Elisavet; Oikonomou, Vangelis P; Kumar, Chandan; Menges, Raphael; Staab, Steffen; Müller, Daniel; Sengupta, Korok; Bostantjopoulou, Sevasti; Katsarou, Zoe; Zeilig, Gabi; Plotnik, Meir; Gotlieb, Amihai; Kizoni, Racheli; Fountoukidou, Sofia; Ham, Jaap; Athanasiou, Dimitrios; Mariakaki, Agnes; Comanducci, Dario; Sabatini, Edoardo; Nistico, Walter; Plank, Markus; Kompatsiaris, Ioannis

2017-12-01

We present a dataset that combines multimodal biosignals and eye tracking information gathered under a human-computer interaction framework. The dataset was developed in the vein of the MAMEM project that aims to endow people with motor disabilities with the ability to edit and author multimedia content through mental commands and gaze activity. The dataset includes EEG, eye-tracking, and physiological (GSR and Heart rate) signals collected from 34 individuals (18 able-bodied and 16 motor-impaired). Data were collected during the interaction with specifically designed interface for web browsing and multimedia content manipulation and during imaginary movement tasks. The presented dataset will contribute towards the development and evaluation of modern human-computer interaction systems that would foster the integration of people with severe motor impairments back into society.

Investigation of Molecule-Surface Interactions With Overtone Absorption Spectroscopy and Computational Methods

DTIC Science & Technology

2010-11-01

method at a fraction of the computational cost . The overtone frequency serves as the bridge between the molecule-surface interaction model and...the computational cost of utilizing higher levels of theory such as MP2. The second task is the calculation of absorption frequencies as a function...the methyl C-H bonds, and n\\ and inn are the carbon and hydrogen atomic masses, respectively. The calculation of the fundamental and overtone

State-Dependent Cross-Brain Information Flow in Borderline Personality Disorder.

PubMed

Bilek, Edda; Stößel, Gabriela; Schäfer, Axel; Clement, Laura; Ruf, Matthias; Robnik, Lydia; Neukel, Corinne; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas

2017-09-01

Although borderline personality disorder (BPD)-one of the most common, burdensome, and costly psychiatric conditions-is characterized by repeated interpersonal conflict and instable relationships, the neurobiological mechanism of social interactive deficits remains poorly understood. To apply recent advancements in the investigation of 2-person human social interaction to investigate interaction difficulties among people with BPD. Cross-brain information flow in BPD was examined from May 25, 2012, to December 4, 2015, in pairs of participants studied in 2 linked functional magnetic resonance imaging scanners in a university setting. Participants performed a joint attention task. Each pair included a healthy control individual (HC) and either a patient currently fulfilling DSM-IV criteria for BPD (cBPD) (n = 23), a patient in remission for 2 years or more (rBPD) (n = 17), or a second HC (n = 20). Groups were matched for age and educational level. A measure of cross-brain neural coupling was computed following previously published work to indicate synchronized flow between right temporoparietal junction networks (previously shown to host neural coupling abilities in health). This measure is derived from an independent component analysis contrasting the time courses of components between pairs of truly interacting participants compared with bootstrapped control pairs. In the sample including 23 women with cBPD (mean [SD] age, 26.8 [5.7] years), 17 women with rBPD (mean [SD] age, 28.5 [4.3] years), and 80 HCs (mean [SD] age, 24.0 [3.4] years]) investigated as dyads, neural coupling was found to be associated with disorder state (η2 = 0.17; P = .007): while HC-HC pairs showed synchronized neural responses, cBPD-HC pairs exhibited significantly lower neural coupling just above permutation-based data levels (η2 = 0.16; P = .009). No difference was found between neural coupling in rBPD-HC and HC-HC pairs. The neural coupling in patients was significantly associated with childhood adversity (T = 2.3; P = .03). This study provides a neural correlate for a core diagnostic and clinical feature of BPD. Results indicate that hyperscanning may deliver state-associated biomarkers for clinical social neuroscience. In addition, at least some neural deficits of BPD may be more reversible than is currently assumed for personality disorders.

Using Three-Dimensional Interactive Graphics To Teach Equipment Procedures.

ERIC Educational Resources Information Center

Hamel, Cheryl J.; Ryan-Jones, David L.

1997-01-01

Focuses on how three-dimensional graphical and interactive features of computer-based instruction can enhance learning and support human cognition during technical training of equipment procedures. Presents guidelines for using three-dimensional interactive graphics to teach equipment procedures based on studies of the effects of graphics, motion,…

Comparison of Classification Methods for Detecting Emotion from Mandarin Speech

NASA Astrophysics Data System (ADS)

Pao, Tsang-Long; Chen, Yu-Te; Yeh, Jun-Heng

It is said that technology comes out from humanity. What is humanity? The very definition of humanity is emotion. Emotion is the basis for all human expression and the underlying theme behind everything that is done, said, thought or imagined. Making computers being able to perceive and respond to human emotion, the human-computer interaction will be more natural. Several classifiers are adopted for automatically assigning an emotion category, such as anger, happiness or sadness, to a speech utterance. These classifiers were designed independently and tested on various emotional speech corpora, making it difficult to compare and evaluate their performance. In this paper, we first compared several popular classification methods and evaluated their performance by applying them to a Mandarin speech corpus consisting of five basic emotions, including anger, happiness, boredom, sadness and neutral. The extracted feature streams contain MFCC, LPCC, and LPC. The experimental results show that the proposed WD-MKNN classifier achieves an accuracy of 81.4% for the 5-class emotion recognition and outperforms other classification techniques, including KNN, MKNN, DW-KNN, LDA, QDA, GMM, HMM, SVM, and BPNN. Then, to verify the advantage of the proposed method, we compared these classifiers by applying them to another Mandarin expressive speech corpus consisting of two emotions. The experimental results still show that the proposed WD-MKNN outperforms others.

Raman Spectroscopic Signature Markers of Dopamine-Human Dopamine Transporter Interaction in Living Cells.

PubMed

Silwal, Achut P; Yadav, Rajeev; Sprague, Jon E; Lu, H Peter

2017-07-19

Dopamine (DA) controls many psychological and behavioral activities in the central nervous system (CNS) through interactions with the human dopamine transporter (hDAT) and dopamine receptors. The roles of DA in the function of the CNS are affected by the targeted binding of drugs to hDAT; thus, hDAT plays a critical role in neurophysiology and neuropathophysiology. An effective experimental method is necessary to study the DA-hDAT interaction and effects of variety of drugs like psychostimulants and antidepressants that are dependent on this interaction. In searching for obtaining and identifying the Raman spectral signatures, we have used surface enhanced Raman scattering (SERS) spectroscopy to record SERS spectra from DA, human embryonic kidney 293 cells (HEK293), hDAT-HEK293, DA-HEK293, and DA-hDAT-HEK293. We have demonstrated a specific 2D-distribution SERS spectral analytical approach to analyze DA-hDAT interaction. Our study shows that the Raman modes at 807, 839, 1076, 1090, 1538, and 1665 cm -1 are related to DA-hDAT interaction, where Raman shifts at 807 and 1076 cm -1 are the signature markers for the bound state of DA to probe DA-hDAT interaction. On the basis of density function theory (DFT) calculation, Raman shift of the bound state of DA at 807 cm -1 is related to combination of bending modes α(C3-O10-H21), α(C2-O11-H22), α(C7-C8-H18), α(C6-C4-H13), α(C7-C8-H19), and α(C7-C8-N9), and Raman shift at 1076 cm -1 is related to combination of bending modes α(H19-N9-C8), γ(N9-H19), γ(C8-H19), γ(N9-H20), γ(C8-H18), and α(C7-C8-H18). These findings demonstrate that protein-ligand interactions can be confirmed by probing change in Raman shift of ligand molecules, which could be crucial to understanding molecular interactions between neurotransmitters and their receptors or transporters.

Structural and computational analysis of intermolecular interactions in a new 2-thiouracil polymorph.

PubMed

Fabijanić, Ivana; Matković-Čalogović, Dubravka; Pilepić, Viktor; Sanković, Krešimir

2017-12-01

The crystallization and characterization of a new polymorph of 2-thiouracil by single-crystal X-ray diffraction, Hirshfeld surface analysis and periodic density functional theory (DFT) calculations are described. The previously published polymorph (A) crystallizes in the triclinic space group P\\overline{1}, while that described herein (B) crystallizes in the monoclinic space group P2 1 /c. Periodic DFT calculations showed that the energies of polymorphs A and B, compared to the gas-phase geometry, were -108.8 and -29.4 kJ mol -1 , respectively. The two polymorphs have different intermolecular contacts that were analyzed and are discussed in detail. Significant differences in the molecular structure were found only in the bond lengths and angles involving heteroatoms that are involved in hydrogen bonds. Decomposition of the Hirshfeld fingerprint plots revealed that O...H and S...H contacts cover over 50% of the noncovalent contacts in both of the polymorphs; however, they are quite different in strength. Hydrogen bonds of the N-H...O and N-H...S types were found in polymorph A, whereas in polymorph B, only those of the N-H...O type are present, resulting in a different packing in the unit cell. QTAIM (quantum theory of atoms in molecules) computational analysis showed that the interaction energies for these weak-to-medium strength hydrogen bonds with a noncovalent or mixed interaction character were estimated to fall within the ranges 5.4-10.2 and 4.9-9.2 kJ mol -1 for polymorphs A and B, respectively. Also, the NCI (noncovalent interaction) plots revealed weak stacking interactions. The interaction energies for these interactions were in the ranges 3.5-4.1 and 3.1-5.5 kJ mol -1 for polymorphs A and B, respectively, as shown by QTAIM analysis.

Side-chain to backbone interactions dictate the conformational preferences of a cyclopentane arginine analogue

PubMed Central

Revilla-López, Guillem; Torras, Juan; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos

2009-01-01

The intrinsic conformational preferences of the non-proteinogenic amino acids constructed by incorporating the arginine side chain in the β position of 1-aminocyclopentane-1-carboxylic acid (either in a cis or a trans orientation relative to the amino group) have been investigated using computational methods. These compounds may be considered as constrained analogues of arginine (denoted as c5Arg) in which the orientation of the side chain is fixed by the cyclopentane moiety. Specifically, the N-acetyl-N′-methylamide derivatives of cis and trans-c5Arg have been examined in the gas phase and in solution using B3LYP/6-311+G(d,p) calculations and Molecular Dynamics simulations. Results indicate that the conformational space available to these compounds is highly restricted, their conformational preferences being dictated by the ability of the guanidinium group in the side chain to establish hydrogen-bond interactions with the backbone. A comparison with the behavior previously described for the analogous phenylalanine derivatives is presented. PMID:19236034

Mistaking Identities: Challenging Representations of Language, Gender, and Race in High Tech Television Programs.

ERIC Educational Resources Information Center

Voithofer, R. J.

Television programs are increasingly featuring information technologies like computers as significant narrative devices, including the use of computer-based technologies as virtual worlds or environments in which characters interact, the use of computers as tools in problem solving and confronting conflict, and characters that are part human, part…

01010000 01001100 01000001 01011001: Play Elements in Computer Programming

ERIC Educational Resources Information Center

Breslin, Samantha

2013-01-01

This article explores the role of play in human interaction with computers in the context of computer programming. The author considers many facets of programming including the literary practice of coding, the abstract design of programs, and more mundane activities such as testing, debugging, and hacking. She discusses how these incorporate the…

Introduction to Social Network Analysis

NASA Astrophysics Data System (ADS)

Zaphiris, Panayiotis; Ang, Chee Siang

Social Network analysis focuses on patterns of relations between and among people, organizations, states, etc. It aims to describe networks of relations as fully as possible, identify prominent patterns in such networks, trace the flow of information through them, and discover what effects these relations and networks have on people and organizations. Social network analysis offers a very promising potential for analyzing human-human interactions in online communities (discussion boards, newsgroups, virtual organizations). This Tutorial provides an overview of this analytic technique and demonstrates how it can be used in Human Computer Interaction (HCI) research and practice, focusing especially on Computer Mediated Communication (CMC). This topic acquires particular importance these days, with the increasing popularity of social networking websites (e.g., youtube, myspace, MMORPGs etc.) and the research interest in studying them.

Computer-generated forces in distributed interactive simulation

NASA Astrophysics Data System (ADS)

Petty, Mikel D.

1995-04-01

Distributed Interactive Simulation (DIS) is an architecture for building large-scale simulation models from a set of independent simulator nodes communicating via a common network protocol. DIS is most often used to create a simulated battlefield for military training. Computer Generated Forces (CGF) systems control large numbers of autonomous battlefield entities in a DIS simulation using computer equipment and software rather than humans in simulators. CGF entities serve as both enemy forces and supplemental friendly forces in a DIS exercise. Research into various aspects of CGF systems is ongoing. Several CGF systems have been implemented.

An inhibitory interaction of human cortical responses to stimuli preferentially exciting Aδ or C fibers

PubMed Central

Tran, Tuan D.; Matre, Dagfinn; Casey, Kenneth L.

2008-01-01

Finely myelinated (type Aδ) and unmyelinated (type C) fibers are the major afferent inputs to spinothalamic tract neurons mediating sensory and reflex responses to noxious and thermal stimuli. These two fiber types differ in their sensory and biophysical properties, raising questions about the interaction of their supraspinal responses. Therefore, we investigated the interaction of cortical responses to stimuli that preferentially excite these fibers in human subjects using evoked potential recordings in a paired conditioning stimulation (CS) and test stimulation (TS) paradigm. There were two experiments, one with Aδ as CS and C as TS (Aδ-C) and another with these stimuli reversed (C-Aδ). We used intra-epidermal electrical pulses applied to the dorsal left hand at 2 and 1 × pinprick threshold (pp) for the preferential stimulation of Aδ fibers and 37 – 50°C contact heat pulses applied to the left or right thenar and left hypothenar eminences for the preferential stimulation of C fibers. We found that the cortical response to preferential Aδ or C fiber stimulation was attenuated whenever either cortical response preceded the other. Standardized values of peak and integrated amplitudes were < 1 in all paring conditions and in all subjects in both experiments. The suppressive effect varied in magnitude with the intensity of the conditioning stimulus in both Aδ-C and C-Aδ experiments. Furthermore, intra-segmental interaction was differentially effective for Aδ conditioning, (peak amplitude, p < 0.008; ANOVA). Our experiments provide the first neurophysiological evidence for a somatotopically distributed, mutually suppressive interaction between cortical responses to preferentially activated Aδ and C afferents in humans. This suppressive interaction of cortical responses suggests contrasting and possibly mutually exclusive sensori-motor functions mediated through the Aδ and C fiber afferent channels. PMID:18308475

Extra virgin olive oil aroma release after interaction with human saliva from individuals with different body mass index.

PubMed

Genovese, Alessandro; Rispoli, Tiziana; Sacchi, Raffaele

2018-07-01

The interindividual variability observed in saliva characteristics raises the question of its relationship with variability in fat sensory perception, particularly in aroma compounds. In the present study, which aimed to measure aroma release from different individuals, eleven key aroma compounds of extra virgin olive oil (EVOO) were monitored and quantified in dynamic headspace after an in vitro interaction between EVOO and human saliva. Therefore, 60 individuals were studied from those who were normal weight (NW), overweight (OW) and obese (O). OW and O demonstrate a higher release of C 6 compounds compared to NW. By contrast, NW have a higher release of C 5 compounds. Pentanal and hexanal also increased after saliva interaction in a refined olive oil that is free from volatiles. Among the saliva samples with a higher release in NW individuals, only pentanal was different. However, the low levels of these lipid oxidation end-products do not appear to be very important with respect to increasing odorous fat sensitivity. The results obtained in the present study demonstrate the important role of saliva in the aroma release of EVOO, indicating that humans can perceive it differently in relation to their body mass index. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.