Sample records for transfer function specification

  1. 5 CFR 351.302 - Transfer of employees.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... is not identified with an operating function specifically authorized at the time of transfer to... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Transfer of employees. 351.302 Section... FORCE Transfer of Function § 351.302 Transfer of employees. (a) Before a reduction in force is made in...

  2. 5 CFR 351.302 - Transfer of employees.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... is not identified with an operating function specifically authorized at the time of transfer to... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Transfer of employees. 351.302 Section... FORCE Transfer of Function § 351.302 Transfer of employees. (a) Before a reduction in force is made in...

  3. 5 CFR 351.302 - Transfer of employees.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... is not identified with an operating function specifically authorized at the time of transfer to... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Transfer of employees. 351.302 Section... FORCE Transfer of Function § 351.302 Transfer of employees. (a) Before a reduction in force is made in...

  4. 5 CFR 351.302 - Transfer of employees.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... is not identified with an operating function specifically authorized at the time of transfer to... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Transfer of employees. 351.302 Section... FORCE Transfer of Function § 351.302 Transfer of employees. (a) Before a reduction in force is made in...

  5. 5 CFR 351.302 - Transfer of employees.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... is not identified with an operating function specifically authorized at the time of transfer to... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Transfer of employees. 351.302 Section... FORCE Transfer of Function § 351.302 Transfer of employees. (a) Before a reduction in force is made in...

  6. Friendly Extensible Transfer Tool Beta Version

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

    Collins, William P.; Gutierrez, Kenneth M.; McRee, Susan R.

    2016-04-15

    Often data transfer software is designed to meet specific requirements or apply to specific environments. Frequently, this requires source code integration for added functionality. An extensible data transfer framework is needed to more easily incorporate new capabilities, in modular fashion. Using FrETT framework, functionality may be incorporated (in many cases without need of source code) to handle new platform capabilities: I/O methods (e.g., platform specific data access), network transport methods, data processing (e.g., data compression.).

  7. Semantic layers for illustrative volume rendering.

    PubMed

    Rautek, Peter; Bruckner, Stefan; Gröller, Eduard

    2007-01-01

    Direct volume rendering techniques map volumetric attributes (e.g., density, gradient magnitude, etc.) to visual styles. Commonly this mapping is specified by a transfer function. The specification of transfer functions is a complex task and requires expert knowledge about the underlying rendering technique. In the case of multiple volumetric attributes and multiple visual styles the specification of the multi-dimensional transfer function becomes more challenging and non-intuitive. We present a novel methodology for the specification of a mapping from several volumetric attributes to multiple illustrative visual styles. We introduce semantic layers that allow a domain expert to specify the mapping in the natural language of the domain. A semantic layer defines the mapping of volumetric attributes to one visual style. Volumetric attributes and visual styles are represented as fuzzy sets. The mapping is specified by rules that are evaluated with fuzzy logic arithmetics. The user specifies the fuzzy sets and the rules without special knowledge about the underlying rendering technique. Semantic layers allow for a linguistic specification of the mapping from attributes to visual styles replacing the traditional transfer function specification.

  8. Accounting for substitution and spatial heterogeneity in a labelled choice experiment.

    PubMed

    Lizin, S; Brouwer, R; Liekens, I; Broeckx, S

    2016-10-01

    Many environmental valuation studies using stated preferences techniques are single-site studies that ignore essential spatial aspects, including possible substitution effects. In this paper substitution effects are captured explicitly in the design of a labelled choice experiment and the inclusion of different distance variables in the choice model specification. We test the effect of spatial heterogeneity on welfare estimates and transfer errors for minor and major river restoration works, and the transferability of river specific utility functions, accounting for key variables such as site visitation, spatial clustering and income. River specific utility functions appear to be transferable, resulting in low transfer errors. However, ignoring spatial heterogeneity increases transfer errors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Persistence, immune specificity, and functional ability of murine mutant ras epitope-specific CD4(+) and CD8(+) T lymphocytes following in vivo adoptive transfer.

    PubMed

    Bristol, J A; Schlom, J; Abrams, S I

    1999-05-25

    Adoptive T-cell transfer has been shown to be a potentially effective strategy for cellular immunotherapy in some murine models of disease. However, several issues remain unresolved regarding some of the basic features involved in effective adoptive transfer, such as the influence of specific peptide antigen (Ag) boost after T-cell transfer, the addition of IL-2 post-T-cell transfer, the trafficking of transferred T cells to lymphoid and nonlymphoid tissues, and the functional stability of recoverable CD4(+) and CD8(+) T cells. We investigated several of these parameters, particularly as they relate to the persistence and maintenance of effector functions of murine CD4(+) and/or CD8(+) T lymphocytes after adoptive cellular transfer into partially gamma-irradiated syngeneic hosts. Our laboratory previously identified murine (H-2(d)) immunogenic CD4(+) and CD8(+) T-cell peptide epitopes reflecting codon 12 ras mutations as tumor-specific Ag. Therefore, the model system chosen here employed epitope-specific MHC class II-restricted CD4(+) T cells and MHC class I-restricted CD8(+) T cells produced from previously immunized BALB/c mice. Between 2 and 7 days after T-cell transfer, recipient mice received various combinations of peptide boosts and/or IL-2 treatments. At different times after the T-cell transfer, spleen and lung tissues were analyzed phenotypically to monitor the persistence of the immune T cells and functionally (via proliferation or cytotoxicity assays) to assess the maintenance of peptide specificity. The results showed that immune donor T lymphocytes (uncultured immune T cells or cloned T cells) were recoverable from the spleens and lungs of recipient mice after transfer. The recovery of Ag-specific T-cell responses was greatest from recipient mice that received peptide boosts and IL-2 treatment. However, mice that received a peptide boost without IL-2 treatment responded nearly as well, which suggested that including a peptide boost after T-cell transfer was more obligatory than exogenous IL-2 treatment to sustain adoptively transferred T cells in vivo. Ag-specific T-cell responses were weak in mice that either received IL-2 alone or did not receive the cognate peptide boost after T-cell transfer. The T-cell clones were also monitored by flow cytometry or RT-PCR based on expression of the T-cell receptor Vbeta-chain, which was previously characterized. Ag-specific T cells were recovered from both spleens and lungs of recipient mice, demonstrating that the T-cell clones could localize to both lymphoid and nonlymphoid tissues. This study demonstrates that both uncultured and in vitro-cloned T lymphocytes can migrate to lymphoid tissues and nonlymphoid (e.g., lung) tissues in recipient hosts and that their functional activities can be maintained at these sites after transfer, if they are exposed to peptide Ag in vivo. Copyright 1999 Academic Press.

  10. Use of localized performance-based functions for the specification and correction of hybrid imaging systems

    NASA Astrophysics Data System (ADS)

    Lisson, Jerold B.; Mounts, Darryl I.; Fehniger, Michael J.

    1992-08-01

    Localized wavefront performance analysis (LWPA) is a system that allows the full utilization of the system optical transfer function (OTF) for the specification and acceptance of hybrid imaging systems. We show that LWPA dictates the correction of wavefront errors with the greatest impact on critical imaging spatial frequencies. This is accomplished by the generation of an imaging performance map-analogous to a map of the optic pupil error-using a local OTF. The resulting performance map a function of transfer function spatial frequency is directly relatable to the primary viewing condition of the end-user. In addition to optimizing quality for the viewer it will be seen that the system has the potential for an improved matching of the optical and electronic bandpass of the imager and for the development of more realistic acceptance specifications. 1. LOCAL WAVEFRONT PERFORMANCE ANALYSIS The LWPA system generates a local optical quality factor (LOQF) in the form of a map analogous to that used for the presentation and evaluation of wavefront errors. In conjunction with the local phase transfer function (LPTF) it can be used for maximally efficient specification and correction of imaging system pupil errors. The LOQF and LPTF are respectively equivalent to the global modulation transfer function (MTF) and phase transfer function (PTF) parts of the OTF. The LPTF is related to difference of the average of the errors in separated regions of the pupil. Figure

  11. Ostracod-inferred conductivity transfer function and its utility in palaeo-conductivity reconstruction in Tibetan Lakes

    NASA Astrophysics Data System (ADS)

    Peng, P.; Zhu, L.; Guo, Y.; Wang, J.; Fürstenberg, S.; Ju, J.; Wang, Y.; Frenzel, P.

    2016-12-01

    Ostracod, was used as a sensitive monitor in palaeo-environmental change research. Ostracod transfer function was developing as a quantitate indicator in palaeo-limnology research. Plenty of lakes scattered on the Tibetan Plateau supplied sediments for analyzing indexes of environment in past climate change research. This application was research on samples of sub-fossil ostracod and its habitat condition, including water sample and water parameters, to produce a database for a forward transfer function based on gradient analyses. This transfer function was used for environment reconstruction of Tibetan lakes to preview past climate changes. In our research, twelve species belonging to ten genus were documented from 114 studied samples in 34 lakes. This research illustrated a specific conductivity gradient gradually increased by L.sinensis-L.dorsotuberosa-C.xizangensis, L.dorsotuberosa-L.inopinata and L.inopinata to indicate fresh-lightly brackish, brackish, brine water condition, respectively. Gradient analysis revealed that specific conductivity was the most important variable drove the distribution of sub-fossil Ostracods. A specific conductivity transfer function using a weighted averaging partial least squares (WA-PLS) model was set up to reconstruct palaeo-specific conductivity. The model presented a good correlation of measured and estimated specific conductivity (R2=0.67), a relative low root mean squared error of prediction (RMSEP=0.47). Multi-proxies, including ostracod assemblages, ostracod-inferred lake level and specific conductivity, mean grain size, total organic carbon and total inorganic carbon of sediment from core of Tibetan Lakes, inferred the palaeo-climate change history of the research area. The environmental change probably was an adaption to the weakening activities of India monsoon since mid-Holocene inferred from the comparable climatic change records from the Tibetan Plateau and relative monsoonal areas.

  12. System and method for characterizing synthesizing and/or canceling out acoustic signals from inanimate sound sources

    DOEpatents

    Holzrichter, John F.; Burnett, Greg C.; Ng, Lawrence C.

    2003-01-01

    A system and method for characterizing, synthesizing, and/or canceling out acoustic signals from inanimate sound sources is disclosed. Propagating wave electromagnetic sensors monitor excitation sources in sound producing systems, such as machines, musical instruments, and various other structures. Acoustical output from these sound producing systems is also monitored. From such information, a transfer function characterizing the sound producing system is generated. From the transfer function, acoustical output from the sound producing system may be synthesized or canceled. The methods disclosed enable accurate calculation of matched transfer functions relating specific excitations to specific acoustical outputs. Knowledge of such signals and functions can be used to effect various sound replication, sound source identification, and sound cancellation applications.

  13. Characterizing, synthesizing, and/or canceling out acoustic signals from sound sources

    DOEpatents

    Holzrichter, John F [Berkeley, CA; Ng, Lawrence C [Danville, CA

    2007-03-13

    A system for characterizing, synthesizing, and/or canceling out acoustic signals from inanimate and animate sound sources. Electromagnetic sensors monitor excitation sources in sound producing systems, such as animate sound sources such as the human voice, or from machines, musical instruments, and various other structures. Acoustical output from these sound producing systems is also monitored. From such information, a transfer function characterizing the sound producing system is generated. From the transfer function, acoustical output from the sound producing system may be synthesized or canceled. The systems disclosed enable accurate calculation of transfer functions relating specific excitations to specific acoustical outputs. Knowledge of such signals and functions can be used to effect various sound replication, sound source identification, and sound cancellation applications.

  14. System and method for characterizing, synthesizing, and/or canceling out acoustic signals from inanimate sound sources

    DOEpatents

    Holzrichter, John F; Burnett, Greg C; Ng, Lawrence C

    2013-05-21

    A system and method for characterizing, synthesizing, and/or canceling out acoustic signals from inanimate sound sources is disclosed. Propagating wave electromagnetic sensors monitor excitation sources in sound producing systems, such as machines, musical instruments, and various other structures. Acoustical output from these sound producing systems is also monitored. From such information, a transfer function characterizing the sound producing system is generated. From the transfer function, acoustical output from the sound producing system may be synthesized or canceled. The methods disclosed enable accurate calculation of matched transfer functions relating specific excitations to specific acoustical outputs. Knowledge of such signals and functions can be used to effect various sound replication, sound source identification, and sound cancellation applications.

  15. System and method for characterizing, synthesizing, and/or canceling out acoustic signals from inanimate sound sources

    DOEpatents

    Holzrichter, John F.; Burnett, Greg C.; Ng, Lawrence C.

    2007-10-16

    A system and method for characterizing, synthesizing, and/or canceling out acoustic signals from inanimate sound sources is disclosed. Propagating wave electromagnetic sensors monitor excitation sources in sound producing systems, such as machines, musical instruments, and various other structures. Acoustical output from these sound producing systems is also monitored. From such information, a transfer function characterizing the sound producing system is generated. From the transfer function, acoustical output from the sound producing system may be synthesized or canceled. The methods disclosed enable accurate calculation of matched transfer functions relating specific excitations to specific acoustical outputs. Knowledge of such signals and functions can be used to effect various sound replication, sound source identification, and sound cancellation applications.

  16. Transference and countertransference to medication and its implications for ego function.

    PubMed

    Marcus, Eric R

    2007-01-01

    Transference to medication can provide important information about specific ego dysfunction in sicker patients who often need medication. Whether positive or negative or both in content, the organization of the experience provides one example of the illness' effect on the patients' ego and can therefore be a specific diagnostic assessment strategy. Early resistances to medication may reveal the nature of resistances to the therapeutic alliance and to higher-level ego function. Understanding this can guide verbal and pharmacological interventions to strengthen ego function. Countertransference can similarly be helpful because it, too, can be a highly specific diagnostic indicator.

  17. Graphic design of pinhole cameras

    NASA Technical Reports Server (NTRS)

    Edwards, H. B.; Chu, W. P.

    1979-01-01

    The paper describes a graphic technique for the analysis and optimization of pinhole size and focal length. The technique is based on the use of the transfer function of optical elements described by Scott (1959) to construct the transfer function of a circular pinhole camera. This transfer function is the response of a component or system to a pattern of lines having a sinusoidally varying radiance at varying spatial frequencies. Some specific examples of graphic design are presented.

  18. Guiding Future Research on the Community College Transfer Function: Summary of a National Seminar (Washington, D.C., September 21-22, 1992).

    ERIC Educational Resources Information Center

    Ludwig, Meredith J.; Palmer, James C.

    1993-01-01

    In September 1992, a small group of experienced researchers met to identify areas of research and specific research hypotheses to guide further inquiry into transfer. Specifically, participants examined transfer as it relates to institutional mission, institutional organization, and access to education and identified various premises upon which…

  19. Restoration of Viral Immunity in Immunodeficient Humans by the Adoptive Transfer of T Cell Clones

    NASA Astrophysics Data System (ADS)

    Riddell, Stanley R.; Watanabe, Kathe S.; Goodrich, James M.; Li, Cheng R.; Agha, Mounzer E.; Greenberg, Philip D.

    1992-07-01

    The adoptive transfer of antigen-specific T cells to establish immunity is an effective therapy for viral infections and tumors in animal models. The application of this approach to human disease would require the isolation and in vitro expansion of human antigen-specific T cells and evidence that such T cells persist and function in vivo after transfer. Cytomegalovirus-specific CD8^+ cytotoxic T cell (CTL) clones could be isolated from bone marrow donors, propagated in vitro, and adoptively transferred to immunodeficient bone marrow transplant recipients. No toxicity developed and the clones provided persistent reconstitution of CD8^+ cytomegalovirus-specific CTL responses.

  20. The influence of a wall function on turbine blade heat transfer prediction

    NASA Technical Reports Server (NTRS)

    Whitaker, Kevin W.

    1989-01-01

    The second phase of a continuing investigation to improve the prediction of turbine blade heat transfer coefficients was completed. The present study specifically investigated how a numeric wall function in the turbulence model of a two-dimensional boundary layer code, STAN5, affected heat transfer prediction capabilities. Several sources of inaccuracy in the wall function were identified and then corrected or improved. Heat transfer coefficient predictions were then obtained using each one of the modifications to determine its effect. Results indicated that the modifications made to the wall function can significantly affect the prediction of heat transfer coefficients on turbine blades. The improvement in accuracy due the modifications is still inconclusive and is still being investigated.

  1. Improving Articulation and Transfer Relationships. New Directions for Community Colleges, Number 39.

    ERIC Educational Resources Information Center

    Kintzer, Frederick C., Ed.

    1982-01-01

    With the intent of revitalizing the study of educational articulation and transfer, this collection of essays describes and assesses the current status of transfer education, points to particular problems and concerns, and highlights specific techniques, activities, and practices. The volume includes "The Transfer Function--One of Many,"…

  2. Assessing the California Transfer Function: The Transfer Rate and Its Measurement. Conclusions of the Data Needs Task Force.

    ERIC Educational Resources Information Center

    Intersegmental Coordinating Council, Sacramento, CA.

    In the fall of 1989, the Intersegmental Coordinating Council organized the Data Needs Task Force (DNTF) to determine the feasibility of establishing a transfer rate definition. Specifically, the DNTF was charged with defining the information needed to strengthen intersegmental transfer programs, establishing common definitions (including…

  3. Assessing gene function in the ruminant placenta.

    PubMed

    Anthony, R V; Cantlon, J D; Gates, K C; Purcell, S H; Clay, C M

    2010-01-01

    The placenta provides the means for nutrient transfer from the mother to the fetus, waste transfer from the fetus to the mother, protection of the fetus from the maternal immune system, and is an active endocrine organ. While many placental functions have been defined and investigated, assessing the function of specific genes expressed by the placenta has been problematic, since classical ablation-replacement methods are not feasible with the placenta. The pregnant sheep has been a long-standing animal model for assessing in vivo physiology during pregnancy, since surgical placement of indwelling catheters into both maternal and fetal vasculature has allowed the assessment of placental nutrient transfer and utilization, as well as placental hormone secretion, under unanesthetized-unstressed steady state sampling conditions. However, in ruminants the lack of well-characterized trophoblast cell lines and the inefficiency of creating transgenic pregnancies in ruminants have inhibited our ability to assess specific gene function. Recently, sheep and cattle primary trophoblast cell lines have been reported, and may further our ability to investigate trophoblast function and transcriptional regulation of genes expressed by the placenta. Furthermore, viral infection of the trophoectoderm layer of hatched blastocysts, as a means for placenta-specific transgenesis, holds considerable potential to assess gene function in the ruminant placenta. This approach has been used successfully to "knockdown" gene expression in the developing sheep conceptus, and has the potential for gain-of-function experiments as well. While this technology is still being developed, it may provide an efficient approach to assess specific gene function in the ruminant placenta.

  4. T-cell receptor transfer for boosting HIV-1-specific T-cell immunity in HIV-1-infected patients.

    PubMed

    Mummert, Christiane; Hofmann, Christian; Hückelhoven, Angela G; Bergmann, Silke; Mueller-Schmucker, Sandra M; Harrer, Ellen G; Dörrie, Jan; Schaft, Niels; Harrer, Thomas

    2016-09-10

    Strategies to cure HIV-1 infection require the eradication of viral reservoirs. An innovative approach for boosting the cytotoxic T-lymphocyte response is the transfer of T-cell receptors (TCRs). Previously, we have shown that electroporation of TCR-encoding mRNA is able to reprogram CD8 T cells derived from healthy donors. So far, it is unknown whether the transfer of HIV-1-specific TCRs is capable to reprogram CD8 T cells of HIV-1-infected patients. To assess the efficiency of TCR-transfer by mRNA electroporation and the functionality of reprogramed T cells in HIV-1-infected patients, we performed an in-vitro analysis of TCR-transfer into T cells from HIV-1-infected patients in various stages of disease and from healthy controls. Peripheral blood mononuclear cells from 16 HIV-1-infected patients (nine HLA-A02-positive, seven HLA-A02-negative) and from five healthy controls were electroporated with mRNA-constructs encoding TCRs specific for the HLA-A02/HIV-1-gag p17 epitope SLYNTVATL (SL9). Functionality of the TCRs was measured by γIFN-ELISpot assays. SL9/TCR transfection into peripheral blood mononuclear cells from both HLA-A02-positive and HLA-A02-negative HIV-1-infected patients and from healthy blood donors reprogramed T cells for recognition of SL9-presenting HLA-A02-positive cells in γIFN-ELISpot assays. SL9/TCR-transfer into T cells from an immunodeficient AIDS patient could induce recognition of SL9-expressing target cells only after reversion of T-cell dysfunction by antiretroviral therapy. The transfer of HIV-1-p17-specific TCRs into T cells is functional both in HIV-1-infected patients as well as in healthy blood donors. TCR-transfer is a promising method to boost the immune system against HIV-1.

  5. Sensitive and Specific Guest Recognition through Pyridinium-Modification in Spindle-Like Coordination Containers.

    PubMed

    Bhuvaneswari, Nagarajan; Dai, Feng-Rong; Chen, Zhong-Ning

    2018-05-02

    An elaborately designed pyridinium-functionalized octanuclear zinc(II) coordination container 1-Zn was prepared through the self-assembly of Zn 2+ , p-tert-butylsulfonylcalix[4]arene, and pyridinium-functionalized angular flexible dicarboxylate linker (H 2 BrL1). The structure was determined by a single-crystal X-ray diffractometer. 1-Zn displays highly sensitive and specific recognition to 2-picolylamine as revealed by drastic blueshifts of the absorption and emission spectra, ascribed to the decrease of intramolecular charge transfer (ICT) character of the container and the occurrence of intermolecular charge transfer between the host and guest molecules. The intramolecular charge transfer plays a key role in the modulation of the electronic properties and is tunable through endo-encapsulation of specific guest molecules. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Effect of fascicle composition on ulnar to musculocutaneous nerve transfer (Oberlin transfer) in neonatal brachial plexus palsy.

    PubMed

    Smith, Brandon W; Chulski, Nicholas J; Little, Ann A; Chang, Kate W C; Yang, Lynda J S

    2018-06-01

    OBJECTIVE Neonatal brachial plexus palsy (NBPP) continues to be a problematic occurrence impacting approximately 1.5 per 1000 live births in the United States, with 10%-40% of these infants experiencing permanent disability. These children lose elbow flexion, and one surgical option for recovering it is the Oberlin transfer. Published data support the use of the ulnar nerve fascicle that innervates the flexor carpi ulnaris as the donor nerve in adults, but no analogous published data exist for infants. This study investigated the association of ulnar nerve fascicle choice with functional elbow flexion outcome in NBPP. METHODS The authors conducted a retrospective study of 13 cases in which infants underwent ulnar to musculocutaneous nerve transfer for NBPP at a single institution. They collected data on patient demographics, clinical characteristics, active range of motion (AROM), and intraoperative neuromonitoring (IONM) (using 4 ulnar nerve index muscles). Standard statistical analysis compared pre- and postoperative motor function improvement between specific fascicle transfer (1-2 muscles for either wrist flexion or hand intrinsics) and nonspecific fascicle transfer (> 2 muscles for wrist flexion and hand intrinsics) groups. RESULTS The patients' average age at initial clinic visit was 2.9 months, and their average age at surgical intervention was 7.4 months. All NBPPs were unilateral; the majority of patients were female (61%), were Caucasian (69%), had right-sided NBPP (61%), and had Narakas grade I or II injuries (54%). IONM recordings for the fascicular dissection revealed a donor fascicle with nonspecific innervation in 6 (46%) infants and specific innervation in the remaining 7 (54%) patients. At 6-month follow-up, the AROM improvement in elbow flexion in adduction was 38° in the specific fascicle transfer group versus 36° in the nonspecific fascicle transfer group, with no statistically significant difference (p = 0.93). CONCLUSIONS Both specific and nonspecific fascicle transfers led to functional recovery, but that the composition of the donor fascicle had no impact on early outcomes. In young infants, ulnar nerve fascicular dissection places the ulnar nerve at risk for iatrogenic damage. The data from this study suggest that the use of any motor fascicle, specific or nonspecific, produces similar results and that the Oberlin transfer can be performed with less intrafascicular dissection, less time of surgical exposure, and less potential for donor site morbidity.

  7. Network Interface Specification for the T1 Microprocessor

    DTIC Science & Technology

    1994-05-01

    features data transfer directly to/from processor registers, hardware dispatch directly to Active Message handlers (along with limited context...Implementation Choices 9 3.1 Overview .................................... 9 3.2 Context ..................................... 10 3.3 Data Transfer...details of the data transfer functional units, interconnect structure, and network operation. Application Layer Communication Model Communication

  8. Advanced Materials by Atom Transfer Radical Polymerization.

    PubMed

    Matyjaszewski, Krzysztof

    2018-06-01

    Atom transfer radical polymerization (ATRP) has been successfully employed for the preparation of various advanced materials with controlled architecture. New catalysts with strongly enhanced activity permit more environmentally benign ATRP procedures using ppm levels of catalyst. Precise control over polymer composition, topology, and incorporation of site specific functionality enables synthesis of well-defined gradient, block, comb copolymers, polymers with (hyper)branched structures including stars, densely grafted molecular brushes or networks, as well as inorganic-organic hybrid materials and bioconjugates. Examples of specific applications of functional materials include thermoplastic elastomers, nanostructured carbons, surfactants, dispersants, functionalized surfaces, and biorelated materials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Matrix Transfer Function Design for Flexible Structures: An Application

    NASA Technical Reports Server (NTRS)

    Brennan, T. J.; Compito, A. V.; Doran, A. L.; Gustafson, C. L.; Wong, C. L.

    1985-01-01

    The application of matrix transfer function design techniques to the problem of disturbance rejection on a flexible space structure is demonstrated. The design approach is based on parameterizing a class of stabilizing compensators for the plant and formulating the design specifications as a constrained minimization problem in terms of these parameters. The solution yields a matrix transfer function representation of the compensator. A state space realization of the compensator is constructed to investigate performance and stability on the nominal and perturbed models. The application is made to the ACOSSA (Active Control of Space Structures) optical structure.

  10. A randomized controlled trial of an activity specific exercise program for individuals with Alzheimer disease in long-term care settings.

    PubMed

    Roach, Kathryn E; Tappen, Ruth M; Kirk-Sanchez, Neva; Williams, Christine L; Loewenstein, David

    2011-01-01

    To determine whether an activity specific exercise program could improve ability to perform basic mobility activities in long-term care residents with Alzheimer disease (AD). Randomized, controlled, single-blinded clinical trial. Residents of 7 long-term care facilities. Eighty-two long-term care residents with mild to severe AD. An activity specific exercise program was compared to a walking program and to an attention control. Ability to perform bed mobility and transfers was assessed using the subscales of the Acute Care Index of Function; functional mobility was measured using the 6-Minute Walk test. Subjects receiving the activity specific exercise program improved in ability to perform transfers, whereas subjects in the other 2 groups declined.

  11. On the Relationship Between Transfer Function-derived Response Times and Hydrograph Analysis Timing Parameters: Are there Similarities?

    NASA Astrophysics Data System (ADS)

    Bansah, S.; Ali, G.; Haque, M. A.; Tang, V.

    2017-12-01

    The proportion of precipitation that becomes streamflow is a function of internal catchment characteristics - which include geology, landscape characteristics and vegetation - and influence overall storage dynamics. The timing and quantity of water discharged by a catchment are indeed embedded in event hydrographs. Event hydrograph timing parameters, such as the response lag and time of concentration, are important descriptors of how long it takes the catchment to respond to input precipitation and how long it takes the latter to filter through the catchment. However, the extent to which hydrograph timing parameters relate to average response times derived from fitting transfer functions to annual hydrographs is unknown. In this study, we used a gamma transfer function to determine catchment average response times as well as event-specific hydrograph parameters across a network of eight nested watersheds ranging from 0.19 km2 to 74.6 km2 prairie catchments located in south central Manitoba (Canada). Various statistical analyses were then performed to correlate average response times - estimated using the parameters of the fitted gamma transfer function - to event-specific hydrograph parameters. Preliminary results show significant interannual variations in response times and hydrograph timing parameters: the former were in the order of a few hours to days, while the latter ranged from a few days to weeks. Some statistically significant relationships were detected between response times and event-specific hydrograph parameters. Future analyses will involve the comparison of statistical distributions of event-specific hydrograph parameters with that of runoff response times and baseflow transit times in order to quantity catchment storage dynamics across a range of temporal scales.

  12. Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells.

    PubMed

    Bryniarski, Krzysztof; Ptak, Wlodzimierz; Martin, Emilia; Nazimek, Katarzyna; Szczepanik, Marian; Sanak, Marek; Askenase, Philip W

    2015-01-01

    Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA) is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.

  13. Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells

    PubMed Central

    Bryniarski, Krzysztof; Ptak, Wlodzimierz; Martin, Emilia; Nazimek, Katarzyna; Szczepanik, Marian; Sanak, Marek; Askenase, Philip W.

    2015-01-01

    Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA) is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases. PMID:25923429

  14. Bottom-up and top-down influences at untrained conditions determine perceptual learning specificity and transfer

    PubMed Central

    Xiong, Ying-Zi; Zhang, Jun-Yun; Yu, Cong

    2016-01-01

    Perceptual learning is often orientation and location specific, which may indicate neuronal plasticity in early visual areas. However, learning specificity diminishes with additional exposure of the transfer orientation or location via irrelevant tasks, suggesting that the specificity is related to untrained conditions, likely because neurons representing untrained conditions are neither bottom-up stimulated nor top-down attended during training. To demonstrate these top-down and bottom-up contributions, we applied a “continuous flash suppression” technique to suppress the exposure stimulus into sub-consciousness, and with additional manipulations to achieve pure bottom-up stimulation or top-down attention with the transfer condition. We found that either bottom-up or top-down influences enabled significant transfer of orientation and Vernier discrimination learning. These results suggest that learning specificity may result from under-activations of untrained visual neurons due to insufficient bottom-up stimulation and/or top-down attention during training. High-level perceptual learning thus may not functionally connect to these neurons for learning transfer. DOI: http://dx.doi.org/10.7554/eLife.14614.001 PMID:27377357

  15. Higher-order Brain Areas Associated with Real-time Functional MRI Neurofeedback Training of the Somato-motor Cortex.

    PubMed

    Auer, Tibor; Dewiputri, Wan Ilma; Frahm, Jens; Schweizer, Renate

    2018-05-15

    Neurofeedback (NFB) allows subjects to learn self-regulation of neuronal brain activation based on information about the ongoing activation. The implementation of real-time functional magnetic resonance imaging (rt-fMRI) for NFB training now facilitates the investigation into underlying processes. Our study involved 16 control and 16 training right-handed subjects, the latter performing an extensive rt-fMRI NFB training using motor imagery. A previous analysis focused on the targeted primary somato-motor cortex (SMC). The present study extends the analysis to the supplementary motor area (SMA), the next higher brain area within the hierarchy of the motor system. We also examined transfer-related functional connectivity using a whole-volume psycho-physiological interaction (PPI) analysis to reveal brain areas associated with learning. The ROI analysis of the pre- and post-training fMRI data for motor imagery without NFB (transfer) resulted in a significant training-specific increase in the SMA. It could also be shown that the contralateral SMA exhibited a larger increase than the ipsilateral SMA in the training and the transfer runs, and that the right-hand training elicited a larger increase in the transfer runs than the left-hand training. The PPI analysis revealed a training-specific increase in transfer-related functional connectivity between the left SMA and frontal areas as well as the anterior midcingulate cortex (aMCC) for right- and left-hand trainings. Moreover, the transfer success was related with training-specific increase in functional connectivity between the left SMA and the target area SMC. Our study demonstrates that NFB training increases functional connectivity with non-targeted brain areas. These are associated with the training strategy (i.e., SMA) as well as with learning the NFB skill (i.e., aMCC and frontal areas). This detailed description of both the system to be trained and the areas involved in learning can provide valuable information for further optimization of NFB trainings. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Functional relevance of interindividual differences in temporal lobe callosal pathways: a DTI tractography study.

    PubMed

    Westerhausen, René; Grüner, Renate; Specht, Karsten; Hugdahl, Kenneth

    2009-06-01

    The midsagittal corpus callosum is topographically organized, that is, with regard to their cortical origin several subtracts can be distinguished within the corpus callosum that belong to specific functional brain networks. Recent diffusion tensor tractography studies have also revealed remarkable interindividual differences in the size and exact localization of these tracts. To examine the functional relevance of interindividual variability in callosal tracts, 17 right-handed male participants underwent structural and diffusion tensor magnetic resonance imaging. Probabilistic tractography was carried out to identify the callosal subregions that interconnect left and right temporal lobe auditory processing areas, and the midsagittal size of this tract was seen as indicator of the (anatomical) strength of this connection. Auditory information transfer was assessed applying an auditory speech perception task with dichotic presentations of consonant-vowel syllables (e.g., /ba-ga/). The frequency of correct left ear reports in this task served as a functional measure of interhemispheric transfer. Statistical analysis showed that a stronger anatomical connection between the superior temporal lobe areas supports a better information transfer. This specific structure-function association in the auditory modality supports the general notion that interindividual differences in callosal topography possess functional relevance.

  17. Normalized power transmission between ABP and ICP in TBI.

    PubMed

    Shahsavari, S; Hallen, T; McKelvey, T; Ritzen, C; Rydenhag, B

    2009-01-01

    A new approach to study the pulse transmission between the cerebrovascular bed and the intracranial space is presented. In the proposed approach, the normalized power transmission between ABP and ICP has got the main attention rather than the actual power transmission. Evaluating the gain of the proposed transfer function at any single frequency can reveal how the percentage of contribution of that specific frequency component has been changed through the cerebrospinal system. The gain of the new transfer function at the fundamental cardiac frequency was utilized to evaluate the state of the brain in three TBI patients. Results were assessed using the reference evaluations achieved by a novel CT scan-based scoring scheme. In all three study cases, the gain of the transfer function showed a good capability to follow the trend of the CT scores and describe the brain state. Comparing the new transfer function with the traditional one and also the index of compensatory reserve, the proposed transfer function was found more informative about the state of the brain in the patients under study.

  18. Small-molecule inhibitors of phosphatidylcholine transfer protein/StarD2 identified by high-throughput screening.

    PubMed

    Wagle, Neil; Xian, Jun; Shishova, Ekaterina Y; Wei, Jie; Glicksman, Marcie A; Cuny, Gregory D; Stein, Ross L; Cohen, David E

    2008-12-01

    Phosphatidylcholine transfer protein (PC-TP, also referred to as StarD2) is a highly specific intracellular lipid-binding protein that catalyzes the transfer of phosphatidylcholines between membranes in vitro. Recent studies have suggested that PC-TP in vivo functions to regulate fatty acid and glucose metabolism, possibly via interactions with selected other proteins. To begin to address the relationship between activity in vitro and biological function, we undertook a high-throughput screen to identify small-molecule inhibitors of the phosphatidylcholine transfer activity of PC-TP. After adapting a fluorescence quench assay to measure phosphatidylcholine transfer activity, we screened 114,752 compounds of a small-molecule library. The high-throughput screen identified 14 potential PC-TP inhibitors. Of these, 6 compounds exhibited characteristics consistent with specific inhibition of PC-TP activity, with IC(50) values that ranged from 4.1 to 95.0muM under conditions of the in vitro assay. These compounds should serve as valuable reagents to elucidate the biological function of PC-TP. Because mice with homozygous disruption of the PC-TP gene (Pctp) are sensitized to insulin action and relatively resistant to the development of atherosclerosis, these inhibitors may also prove to be of value in the management of diabetes and atherosclerotic cardiovascular diseases.

  19. Alternative ground states enable pathway switching in biological electron transfer

    DOE PAGES

    Abriata, Luciano A.; Alvarez-Paggi, Damian; Ledesma, Gabirela N.; ...

    2012-10-10

    Electron transfer is the simplest chemical reaction and constitutes the basis of a large variety of biological processes, such as photosynthesis and cellular respiration. Nature has evolved specific proteins and cofactors for these functions. The mechanisms optimizing biological electron transfer have been matter of intense debate, such as the role of the protein milieu between donor and acceptor sites. Here we propose a mechanism regulating long-range electron transfer in proteins. Specifically, we report a spectroscopic, electrochemical, and theoretical study on WT and single-mutant CuA redox centers from Thermus thermophilus, which shows that thermal fluctuations may populate two alternative ground-state electronicmore » wave functions optimized for electron entry and exit, respectively, through two different and nearly perpendicular pathways. In conclusion, these findings suggest a unique role for alternative or “invisible” electronic ground states in directional electron transfer. Moreover, it is shown that this energy gap and, therefore, the equilibrium between ground states can be fine-tuned by minor perturbations, suggesting alternative ways through which protein–protein interactions and membrane potential may optimize and regulate electron–proton energy transduction.« less

  20. ChemTrove: enabling a generic ELN to support chemistry through the use of transferable plug-ins and online data sources.

    PubMed

    Day, Aileen E; Coles, Simon J; Bird, Colin L; Frey, Jeremy G; Whitby, Richard J; Tkachenko, Valery E; Williams, Antony J

    2015-03-23

    In designing an Electronic Lab Notebook (ELN), there is a balance to be struck between keeping it as general and multidisciplinary as possible for simplicity of use and maintenance and introducing more domain-specific functionality to increase its appeal to target research areas. Here, we describe the results of a collaboration between the Royal Society of Chemistry (RSC) and the University of Southampton, guided by the aims of the Dial-a-Molecule Grand Challenge, intended to achieve the best of both worlds and augment a discipline-agnostic ELN, LabTrove, with chemistry-specific functionality and using data provided by the ChemSpider platform. This has been done using plug-in technology to ensure maximum transferability with minimal effort of the chemistry functionality to other ELNs and equally other subject-specific functionality to LabTrove. The resulting product, ChemTrove, has undergone a usability trial by selected academics, and the resulting feedback will guide the future development of the underlying ELN technology.

  1. A Randomized Controlled Trial of an Activity Specific Exercise Program for Individuals With Alzheimer Disease in Long-term Care Settings

    PubMed Central

    Roach, Kathryn E.; Tappen, Ruth M.; Kirk-Sanchez, Neva; Williams, Christine L.; Loewenstein, David

    2011-01-01

    Objective To determine whether an activity specific exercise program could improve ability to perform basic mobility activities in long-term care residents with Alzheimer disease (AD). Design Randomized, controlled, single-blinded clinical trial. Setting Residents of 7 long-term care facilities. Participants Eighty-two long-term care residents with mild to severe AD. Intervention An activity specific exercise program was compared to a walking program and to an attention control. Measurements Ability to perform bed mobility and transfers were assessed using the subscales of the Acute Care Index of Function; functional mobility was measured using the 6-Minute Walk test. Results Subjects receiving the activity specific exercise program improved in ability to perform transfers, whereas subjects in the other 2 groups declined. PMID:21937893

  2. Site Transfer Functions of Three-Component Ground Motion in Western Turkey

    NASA Astrophysics Data System (ADS)

    Ozgur Kurtulmus, Tevfik; Akyol, Nihal; Camyildiz, Murat; Gungor, Talip

    2015-04-01

    Because of high seismicity accommodating crustal deformation and deep graben structures, on which have, urbanized and industrialized large cities in western Turkey, the importance of site-specific seismic hazard assessments becomes more crucial. Characterizing source, site and path effects is important for both assessing the seismic hazard in a specific region and generation of the building codes/or renewing previous ones. In this study, we evaluated three-component recordings for micro- and moderate-size earthquakes with local magnitudes ranging between 2.0 and 5.6. This dataset is used for site transfer function estimations, utilizing two different spectral ratio approaches 'Standard Spectral Ratio-(SSR)' and 'Horizontal to Vertical Spectral Ratio-(HVSR)' and a 'Generalized Inversion Technique-(GIT)' to highlight site-specific seismic hazard potential of deep basin structures of the region. Obtained transfer functions revealed that the sites located near the basin edges are characterized by broader HVSR curves. Broad HVSR peaks could be attributed to the complexity of wave propagation related to significant 2D/3D velocity variations at the sediment-bedrock interface near the basin edges. Comparison of HVSR and SSR estimates for the sites located on the grabens showed that SSR estimates give larger values at lower frequencies which could be attributed to lateral variations in regional velocity and attenuation values caused by basin geometry and edge effects. However, large amplitude values of vertical component GIT site transfer functions were observed at varying frequency ranges for some of the stations. These results imply that vertical component of ground motion is not amplification free. Contamination of HVSR site transfer function estimates at different frequency bands could be related to complexities in the wave field caused by deep or shallow heterogeneities in the region such as differences in the basin geometries, fracturing and fluid saturation along different propagation paths. The results also show that, even if the site is located on a horst, the presence of weathered zones near the surface could cause moderate frequency dependent site effects.

  3. Customized acoustic transform functions and their accuracy at predicting real-ear hearing aid performance.

    PubMed

    Munro, K J; Hatton, N

    2000-02-01

    The purpose of the study was to evaluate the validity of predicting the real-ear aided response by adding customized acoustic transform functions to the performance of a hearing aid in a 2-cc coupler. The real-ear hearing aid response, the real-ear-to-coupler difference (RECD/HA2), and field to behind-the-ear microphone transfer functions were measured in both ears of 24 normally hearing subjects using probe-tube microphone equipment. The RECD/HA2 transform function was obtained using both insert earphones and with the hearing aid/ pressure comparison method. An RECD/HA2 transfer function was also obtained with a customized earmold, ER-3A foam tip, and an oto-admittance tip. Validity estimates were calculated as the difference between the derived and measured real-ear response. The derived response was generally within 5 dB of the measured real-ear response when it incorporated an RECD/HA2 transform function obtained with a customized earmold for the specific ear in question. Discrepancies increased when the RECD/HA2 transfer function was obtained from the same subject but the opposite ear. There were significant differences between the RECD/HA2 transform function obtained with customized and temporary earmolds. As a result, the derived response incorporating these transforms differed significantly from the measured real-ear response obtained with the customized earmold. The insert earphone and the hearing aid RECD/HA2 transfer function were equally valid. The derived response may be used as a substitute for in situ hearing aid response procedures when it incorporates acoustic transform functions obtained with a customized earmold from the specific ear in question.

  4. Transfer of training between distinct motor tasks after stroke: implications for task-specific approaches to upper-extremity neurorehabilitation.

    PubMed

    Schaefer, Sydney Y; Patterson, Chavelle B; Lang, Catherine E

    2013-09-01

    Although task-specific training is emerging as a viable approach for recovering motor function after stroke, there is little evidence for whether the effects of such training transfer to other functional motor tasks not directly practiced in therapy. The purpose of the current study was to test whether training on one motor task in individuals with chronic hemiparesis poststroke would transfer to untrained tasks that were either spatiotemporally similar or different. In all, 11 participants with chronic mild to moderate hemiparesis following stroke completed 5 days of supervised massed practice of a feeding task with their affected side. Performance on the feeding task, along with 2 other untrained functional upper-extremity motor tasks (sorting, dressing) was assessed before and after training. Performance of all 3 tasks improved significantly after training exclusively on 1 motor task. The amount of improvement in the untrained tasks was comparable and was not dependent on the degree of similarity to the trained task. Because the number and type of tasks that can be practiced are often limited within standard stroke rehabilitation, results from this study will be useful for designing task-specific training plans to maximize therapy benefits.

  5. A comparison of hemisphere-specific training pattern in Inter-limb Learning Transfer (ILT) for stroke patients with hemiparesis.

    PubMed

    Yoo, In-gyu; Jung, Min-ye; Yoo, Eun-young; Park, Ji-hyuk; Kang, Dae-hyuk; Lee, Jin

    2014-01-01

    Stroke patients have major problems with impaired upper-extremity function. Unfortunately, many patients do not experience a full recovery from movement deficits in the upper extremities. The purpose of this study was to compare the effectiveness of inter-limb learning transfer (ILT) to the contralateral upper limb after both hemisphere-specific and -unspecific ipsilateral upper limb training for stroke patients with hemiparesis. Twenty-four stroke patients with hemiparesis participated. The hemisphere-specific training group performed reaching movements in a customized training setting in which non-dominant limb training participants began from a single starting location and proceeded to one of three target locations (1S3T condition); the dominant limb training participants started from one of three starting locations and proceeded to a single target location (3S1T condition). The hemisphere-unspecific training group performed these movements starting under reverse-start and target conditions. The non-dominant to dominant limb transfer, the hemisphere-specific training group performance time decreased significantly as compared with the pre-training session (p < 0.05). Also, the isolation contraction ratio was decreased significantly from that of the pre-training session in the biceps brachii muscles and increased significantly in the upper trapezius muscles (p < 0.05). And, dominant to non-dominant limb transfer in the hemisphere-specific training group significantly increased RMS amplitudes from the pre-training session in the biceps brachii and triceps muscles (p < 0.05). Also, the isolation contraction ratio was increased significantly from that of the pre-training session in the biceps brachii muscles and decreased significantly in the upper trapezius muscles (p < 0.05). However, the hemisphere-unspecific training group showed no significant differences in inter-limb learning transfer (ILT). The transfer of hemisphere-specific training from one arm to the other had a more positive influence on functional recovery than did hemisphere-unspecific training for patients with stroke and hemiparesis.

  6. Transfer functions for protein signal transduction: application to a model of striatal neural plasticity.

    PubMed

    Scheler, Gabriele

    2013-01-01

    We present a novel formulation for biochemical reaction networks in the context of protein signal transduction. The model consists of input-output transfer functions, which are derived from differential equations, using stable equilibria. We select a set of "source" species, which are interpreted as input signals. Signals are transmitted to all other species in the system (the "target" species) with a specific delay and with a specific transmission strength. The delay is computed as the maximal reaction time until a stable equilibrium for the target species is reached, in the context of all other reactions in the system. The transmission strength is the concentration change of the target species. The computed input-output transfer functions can be stored in a matrix, fitted with parameters, and even recalled to build dynamical models on the basis of state changes. By separating the temporal and the magnitudinal domain we can greatly simplify the computational model, circumventing typical problems of complex dynamical systems. The transfer function transformation of biochemical reaction systems can be applied to mass-action kinetic models of signal transduction. The paper shows that this approach yields significant novel insights while remaining a fully testable and executable dynamical model for signal transduction. In particular we can deconstruct the complex system into local transfer functions between individual species. As an example, we examine modularity and signal integration using a published model of striatal neural plasticity. The modularizations that emerge correspond to a known biological distinction between calcium-dependent and cAMP-dependent pathways. Remarkably, we found that overall interconnectedness depends on the magnitude of inputs, with higher connectivity at low input concentrations and significant modularization at moderate to high input concentrations. This general result, which directly follows from the properties of individual transfer functions, contradicts notions of ubiquitous complexity by showing input-dependent signal transmission inactivation.

  7. 32 CFR 2001.30 - Automatic declassification.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... transferred in conjunction with a transfer of functions, and not merely for storage, the receiving agency... contamination by a hazardous substance; and (iii) Electronic media if the media is subject to issues of software... the automatic declassification of a specific series of records as defined in section 6.1(r) of the...

  8. 32 CFR 2001.30 - Automatic declassification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... transferred in conjunction with a transfer of functions, and not merely for storage, the receiving agency... contamination by a hazardous substance; and (iii) Electronic media if the media is subject to issues of software... the automatic declassification of a specific series of records as defined in section 6.1(r) of the...

  9. 32 CFR 2001.30 - Automatic declassification.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... transferred in conjunction with a transfer of functions, and not merely for storage, the receiving agency... contamination by a hazardous substance; and (iii) Electronic media if the media is subject to issues of software... the automatic declassification of a specific series of records as defined in section 6.1(r) of the...

  10. 32 CFR 2001.30 - Automatic declassification.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... transferred in conjunction with a transfer of functions, and not merely for storage, the receiving agency... contamination by a hazardous substance; and (iii) Electronic media if the media is subject to issues of software... the automatic declassification of a specific series of records as defined in section 6.1(r) of the...

  11. 32 CFR 2001.30 - Automatic declassification.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... transferred in conjunction with a transfer of functions, and not merely for storage, the receiving agency... contamination by a hazardous substance; and (iii) Electronic media if the media is subject to issues of software... the automatic declassification of a specific series of records as defined in section 6.1(r) of the...

  12. Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors.

    PubMed

    Xin, Gang; Schauder, David M; Jing, Weiqing; Jiang, Aimin; Joshi, Nikhil S; Johnson, Bryon; Cui, Weiguo

    2017-01-24

    Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a bacterial antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice. The dual-specific CD8 T cells expanded vigorously, migrated to tumor sites, and robustly eradicated primary tumors. The mice cured from ReACT also developed immunological memory against tumor rechallenge. Mechanistically, we have found that this combined approach reverts the immunosuppressive TME and recruits CD8 T cells with an increased number and killing ability to the tumors.

  13. Phosphatidylserine Stimulates Ceramide 1-Phosphate (C1P) Intermembrane Transfer by C1P Transfer Proteins.

    PubMed

    Zhai, Xiuhong; Gao, Yong-Guang; Mishra, Shrawan K; Simanshu, Dhirendra K; Boldyrev, Ivan A; Benson, Linda M; Bergen, H Robert; Malinina, Lucy; Mundy, John; Molotkovsky, Julian G; Patel, Dinshaw J; Brown, Rhoderick E

    2017-02-10

    Genetic models for studying localized cell suicide that halt the spread of pathogen infection and immune response activation in plants include Arabidopsis accelerated-cell-death 11 mutant ( acd11 ). In this mutant, sphingolipid homeostasis is disrupted via depletion of ACD11, a lipid transfer protein that is specific for ceramide 1-phosphate (C1P) and phyto-C1P. The C1P binding site in ACD11 and in human ceramide-1-phosphate transfer protein (CPTP) is surrounded by cationic residues. Here, we investigated the functional regulation of ACD11 and CPTP by anionic phosphoglycerides and found that 1-palmitoyl-2-oleoyl-phosphatidic acid or 1-palmitoyl-2-oleoyl-phosphatidylglycerol (≤15 mol %) in C1P source vesicles depressed C1P intermembrane transfer. By contrast, replacement with 1-palmitoyl-2-oleoyl-phosphatidylserine stimulated C1P transfer by ACD11 and CPTP. Notably, "soluble" phosphatidylserine (dihexanoyl-phosphatidylserine) failed to stimulate C1P transfer. Also, none of the anionic phosphoglycerides affected transfer action by human glycolipid lipid transfer protein (GLTP), which is glycolipid-specific and has few cationic residues near its glycolipid binding site. These findings provide the first evidence for a potential phosphoglyceride headgroup-specific regulatory interaction site(s) existing on the surface of any GLTP-fold and delineate new differences between GLTP superfamily members that are specific for C1P versus glycolipid. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. High-level user interfaces for transfer function design with semantics.

    PubMed

    Salama, Christof Rezk; Keller, Maik; Kohlmann, Peter

    2006-01-01

    Many sophisticated techniques for the visualization of volumetric data such as medical data have been published. While existing techniques are mature from a technical point of view, managing the complexity of visual parameters is still difficult for non-expert users. To this end, this paper presents new ideas to facilitate the specification of optical properties for direct volume rendering. We introduce an additional level of abstraction for parametric models of transfer functions. The proposed framework allows visualization experts to design high-level transfer function models which can intuitively be used by non-expert users. The results are user interfaces which provide semantic information for specialized visualization problems. The proposed method is based on principal component analysis as well as on concepts borrowed from computer animation.

  15. Ultrafast Charge Transfer of a Valence Double Hole in Glycine Driven Exclusively by Nuclear Motion

    NASA Astrophysics Data System (ADS)

    Li, Zheng; Vendrell, Oriol; Santra, Robin

    2015-10-01

    We explore theoretically the ultrafast transfer of a double electron hole between the functional groups of glycine after K -shell ionization and subsequent Auger decay. Although a large energy gap of about 15 eV initially exists between the two electronic states involved and coherent electronic dynamics play no role in the hole transfer, we find that the double hole is transferred within 3 to 4 fs between both functional ends of the glycine molecule driven solely by specific nuclear displacements and non-Born-Oppenheimer effects. The nuclear displacements along specific vibrational modes are of the order of 15% of a typical chemical bond between carbon, oxygen, and nitrogen atoms and about 30% for bonds involving hydrogen atoms. The time required for the hole transfer corresponds to less than half a vibrational period of the involved nuclear modes. This finding challenges the common wisdom that nuclear dynamics of the molecular skeleton are unimportant for charge transfer processes at the few-femtosecond time scale and shows that they can even play a prominent role. It also indicates that in x-ray imaging experiments, in which ionization is unavoidable, valence electron redistribution caused by nuclear dynamics might be much faster than previously anticipated. Thus, non-Born-Oppenheimer effects may affect the apparent electron densities extracted from such measurements.

  16. Ultrafast Charge Transfer of a Valence Double Hole in Glycine Driven Exclusively by Nuclear Motion.

    PubMed

    Li, Zheng; Vendrell, Oriol; Santra, Robin

    2015-10-02

    We explore theoretically the ultrafast transfer of a double electron hole between the functional groups of glycine after K-shell ionization and subsequent Auger decay. Although a large energy gap of about 15 eV initially exists between the two electronic states involved and coherent electronic dynamics play no role in the hole transfer, we find that the double hole is transferred within 3 to 4 fs between both functional ends of the glycine molecule driven solely by specific nuclear displacements and non-Born-Oppenheimer effects. The nuclear displacements along specific vibrational modes are of the order of 15% of a typical chemical bond between carbon, oxygen, and nitrogen atoms and about 30% for bonds involving hydrogen atoms. The time required for the hole transfer corresponds to less than half a vibrational period of the involved nuclear modes. This finding challenges the common wisdom that nuclear dynamics of the molecular skeleton are unimportant for charge transfer processes at the few-femtosecond time scale and shows that they can even play a prominent role. It also indicates that in x-ray imaging experiments, in which ionization is unavoidable, valence electron redistribution caused by nuclear dynamics might be much faster than previously anticipated. Thus, non-Born-Oppenheimer effects may affect the apparent electron densities extracted from such measurements.

  17. Dynamics driving function: new insights from electron transferring flavoproteins and partner complexes.

    PubMed

    Toogood, Helen S; Leys, David; Scrutton, Nigel S

    2007-11-01

    Electron transferring flavoproteins (ETFs) are soluble heterodimeric FAD-containing proteins that function primarily as soluble electron carriers between various flavoprotein dehydrogenases. ETF is positioned at a key metabolic branch point, responsible for transferring electrons from up to 10 primary dehydrogenases to the membrane-bound respiratory chain. Clinical mutations of ETF result in the often fatal disease glutaric aciduria type II. Structural and biophysical studies of ETF in complex with partner proteins have shown that ETF partitions the functions of partner binding and electron transfer between (a) a 'recognition loop', which acts as a static anchor at the ETF-partner interface, and (b) a highly mobile redox-active FAD domain. Together, this enables the FAD domain of ETF to sample a range of conformations, some compatible with fast interprotein electron transfer. This 'conformational sampling' enables ETF to recognize structurally distinct partners, whilst also maintaining a degree of specificity. Complex formation triggers mobility of the FAD domain, an 'induced disorder' mechanism contrasting with the more generally accepted models of protein-protein interaction by induced fit mechanisms. We discuss the implications of the highly dynamic nature of ETFs in biological interprotein electron transfer. ETF complexes point to mechanisms of electron transfer in which 'dynamics drive function', a feature that is probably widespread in biology given the modular assembly and flexible nature of biological electron transfer systems.

  18. How to precisely measure the volume velocity transfer function of physical vocal tract models by external excitation

    PubMed Central

    Mainka, Alexander; Kürbis, Steffen; Birkholz, Peter

    2018-01-01

    Recently, 3D printing has been increasingly used to create physical models of the vocal tract with geometries obtained from magnetic resonance imaging. These printed models allow measuring the vocal tract transfer function, which is not reliably possible in vivo for the vocal tract of living humans. The transfer functions enable the detailed examination of the acoustic effects of specific articulatory strategies in speaking and singing, and the validation of acoustic plane-wave models for realistic vocal tract geometries in articulatory speech synthesis. To measure the acoustic transfer function of 3D-printed models, two techniques have been described: (1) excitation of the models with a broadband sound source at the glottis and measurement of the sound pressure radiated from the lips, and (2) excitation of the models with an external source in front of the lips and measurement of the sound pressure inside the models at the glottal end. The former method is more frequently used and more intuitive due to its similarity to speech production. However, the latter method avoids the intricate problem of constructing a suitable broadband glottal source and is therefore more effective. It has been shown to yield a transfer function similar, but not exactly equal to the volume velocity transfer function between the glottis and the lips, which is usually used to characterize vocal tract acoustics. Here, we revisit this method and show both, theoretically and experimentally, how it can be extended to yield the precise volume velocity transfer function of the vocal tract. PMID:29543829

  19. Influenza virus-specific TCR-transduced T cells as a model for adoptive immunotherapy

    PubMed Central

    Berdien, Belinda; Reinhard, Henrike; Meyer, Sabrina; Spöck, Stefanie; Kröger, Nicolaus; Atanackovic, Djordje; Fehse, Boris

    2013-01-01

    Adoptive transfer of T lymphocytes equipped with tumor-antigen specific T-cell receptors (TCRs) represents a promising strategy in cancer immunotherapy, but the approach remains technically demanding. Using influenza virus (Flu)-specific T-cell responses as a model system we compared different methods for the generation of T-cell clones and isolation of antigen-specific TCRs. Altogether, we generated 12 CD8+ T-cell clones reacting to the Flu matrix protein (Flu-M) and 6 CD4+ T-cell clones reacting to the Flu nucleoprotein (Flu-NP) from 4 healthy donors. IFN-γ-secretion-based enrichment of antigen-specific cells, optionally combined with tetramer staining, was the most efficient way for generating T-cell clones. In contrast, the commonly used limiting dilution approach was least efficient. TCR genes were isolated from T-cell clones and cloned into both a previously used gammaretroviral LTR-vector, MP91 and the novel lentiviral self-inactivating vector LeGO-MP that contains MP91-derived promotor and regulatory elements. To directly compare their functional efficiencies, we in parallel transduced T-cell lines and primary T cells with the two vectors encoding identical TCRs. Transduction efficiencies were approximately twice higher with the gammaretroviral vector. Secretion of high amounts of IFN-γ, IL-2 and TNF-α by transduced cells after exposure to the respective influenza target epitope proved efficient specificity transfer of the isolated TCRs to primary T-cells for both vectors, at the same time indicating superior functionality of MP91-transduced cells. In conclusion, we have developed optimized strategies to obtain and transfer antigen-specific TCRs as well as designed a novel lentiviral vector for TCR-gene transfer. Our data may help to improve adoptive T-cell therapies. PMID:23428899

  20. Making perceptual learning practical to improve visual functions.

    PubMed

    Polat, Uri

    2009-10-01

    Task-specific improvement in performance after training is well established. The finding that learning is stimulus-specific and does not transfer well between different stimuli, between stimulus locations in the visual field, or between the two eyes has been used to support the notion that neurons or assemblies of neurons are modified at the earliest stage of cortical processing. However, a debate regarding the proposed mechanism underlying perceptual learning is an ongoing issue. Nevertheless, generalization of a trained task to other functions is an important key, for both understanding the neural mechanisms and the practical value of the training. This manuscript describes a structured perceptual learning method that previously used (amblyopia, myopia) and a novel technique and results that were applied for presbyopia. In general, subjects were trained for contrast detection of Gabor targets under lateral masking conditions. Training improved contrast sensitivity and diminished the lateral suppression when it existed (amblyopia). The improvement was transferred to unrelated functions such as visual acuity. The new results of presbyopia show substantial improvement of the spatial and temporal contrast sensitivity, leading to improved processing speed of target detection as well as reaction time. Consequently, the subjects, who were able to eliminate the need for reading glasses, benefited. Thus, here we show that the transfer of functions indicates that the specificity of improvement in the trained task can be generalized by repetitive practice of target detection, covering a sufficient range of spatial frequencies and orientations, leading to an improvement in unrelated visual functions. Thus, perceptual learning can be a practical method to improve visual functions in people with impaired or blurred vision.

  1. Distinct Transfer Effects of Training Different Facets of Working Memory Capacity

    ERIC Educational Resources Information Center

    von Bastian, Claudia C.; Oberauer, Klaus

    2013-01-01

    The impact of working memory training on a broad set of transfer tasks was examined. Each of three groups of participants trained one specific functional category of working memory capacity: storage and processing, relational integration, and supervision. A battery comprising tests to measure working memory, task shifting, inhibition, and…

  2. Smooth-muscle-specific gene transfer with the human maxi-k channel improves erectile function and enhances sexual behavior in atherosclerotic cynomolgus monkeys.

    PubMed

    Christ, George J; Andersson, Karl-Erik; Williams, Koudy; Zhao, Weixin; D'Agostino, Ralph; Kaplan, Jay; Aboushwareb, Tamer; Yoo, James; Calenda, Giulia; Davies, Kelvin P; Sellers, Rani S; Melman, Arnold

    2009-12-01

    Despite the advent of effective oral therapies for erectile dysfunction (ED), many patients are not successfully treated, and side effects have been documented. To further evaluate the potential utility of naked DNA-based gene transfer as an attractive treatment option for ED. The effects of gene transfer on erectile function and sexual behavior were evaluated in eight male cynomolgus monkeys with ED secondary to moderately severe, diet-induced atherosclerosis. Following establishment of baseline characteristics, animals were subjected to intracavernous injection of a smooth-muscle-specific gene transfer vector (pSMAA-hSlo) encoding the pore-forming subunit of the human large-conductance, calcium-sensitive potassium channel (Maxi-K). For the sexual behavior studies, 2 wk of baseline data were obtained, and then animals were placed in the presence of estrogen-implanted females (n=2) three times per week for 30 min, and sexual behavior was recorded. The intracavernous pressure response to papaverine injection was also monitored. Dramatic changes in erectile function and sexual behavior were observed after intracorporal gene transfer. The frequency of partial (6±2 to 10±2) and full (2±1.5 to 5±1.4) erections were significantly increased, with a parallel 2-3-fold increase in the duration of the observed erections. The frequency and latency of ejaculation were increased and decreased, respectively. Frequency and duration of grooming by the female were increased, and the latency decreased. Increased latency and decreased frequency of body contact was also observed, and this is characteristic of the typical drop in consort intimacy that occurs after mating in most macaque species. In addition, an increased responsiveness to intracavernous papaverine injection was observed. The data indicate that intracorporal Maxi-K-channel gene transfer enhances erectile capacity and sexual behavior; the data imply that increased erectile function per se may lead to increased sexual function.

  3. Transfer of training between distinct motor tasks after stroke: Implications for task- specific approaches to upper extremity neurorehabilitation

    PubMed Central

    Schaefer, Sydney Y.; Patterson, Chavelle B.; Lang, Catherine E.

    2013-01-01

    Background Although task-specific training is emerging as a viable approach for recovering motor function after stroke, there is little evidence for whether the effects of such training transfer to other functional motor tasks not directly practiced in therapy. Objective The purpose of the current study was to test whether training on one motor task would transfer to untrained tasks that were either spatiotemporally similar or different in individuals with chronic hemiparesis post-stroke. Methods Eleven participants with chronic mild-to-moderate hemiparesis following stroke completed five days of supervised massed practice of a feeding task with their affected side. Performance on the feeding task, along with two other untrained functional upper extremity motor tasks (sorting, dressing) was assessed before and after training. Results Performance of all three tasks improved significantly after training exclusively on one motor task. The amount of improvement in the untrained tasks was comparable, and was not dependent on the degree of similarity to the trained task. Conclusions Because the number and type of tasks that can be practiced are often limited within standard stroke rehabilitation, results from this study will be useful for designing task-specific training plans to maximize therapy benefits. PMID:23549521

  4. Charge Transfer Directed Radical Substitution Enables para-Selective C–H Functionalization

    PubMed Central

    Boursalian, Gregory B.; Ham, Won Seok; Mazzotti, Anthony R.; Ritter, Tobias

    2016-01-01

    Efficient C–H functionalization requires selectivity for specific C–H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho- and meta- selectivity, but a general strategy for para-selective C–H functionalization has remained elusive. Herein, we introduce a previously unappreciated concept which enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit areneto-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate that the selectivity is predictable by a simple theoretical tool and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of charge transfer directed radical substitution could serve as the basis for the development of new, highly selective C–H functionalization reactions. PMID:27442288

  5. Charge-transfer-directed radical substitution enables para-selective C-H functionalization

    NASA Astrophysics Data System (ADS)

    Boursalian, Gregory B.; Ham, Won Seok; Mazzotti, Anthony R.; Ritter, Tobias

    2016-08-01

    Efficient C-H functionalization requires selectivity for specific C-H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho and meta selectivity, but a general strategy for para-selective C-H functionalization has remained elusive. Herein we introduce a previously unappreciated concept that enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit arene-to-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate with a simple theoretical tool that the selectivity is predictable and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of radical substitution directed by charge transfer could serve as the basis for the development of new, highly selective C-H functionalization reactions.

  6. Analysis of the transfer function for layered piezoelectric ultrasonic sensors

    NASA Astrophysics Data System (ADS)

    Gutiérrrez-Reyes, E.; García-Segundo, C.; García-Valenzuela, A.; Reyes-Ramírez, B.; Gutiérrez-Juárez, G.; Guadarrama-Santana, A.

    2017-06-01

    We model theoretically the voltage response to an acoustic pulse of a multilayer system forming a low noise capacitive sensor including a Polyvinylidene Fluoride piezoelectric film. First we model a generic piezoelectric detector consisting of a piezoelectric film between two metallic electrodes that are the responsible to convert the acoustic signal into a voltage signal. Then we calculate the pressure-to-voltage transfer function for a N-layer piezo-electric capacitor detector, allowing to study the effects of the electrode and protective layers thickness in typical layered piezoelectric sensors. The derived transfer function, when multiplied by the Fourier transform of the incident acoustic pulse, gives the voltage electric response in the frequency domain. An important concern regarding the transfer function is that it may have zeros at specific frequencies, and thus inverting the voltage Fourier transform of the pulse to recover the pressure signal in the time domain is not always, in principle, possible. Our formulas can be used to predict the existence and locations of such zeroes. We illustrate the use of the transfer function by predicting the electric signal generated at a multilayer piezoelectric sensor to an ultrasonic pulse generated photoacoustically by a laser pulse at a three media system with impedance mismatch. This theoretical calculations are compared with our own experimental measurements.

  7. Innate Functions of Immunoglobulin M Lessen Liver Gene Transfer with Helper-Dependent Adenovirus

    PubMed Central

    Unzu, Carmen; Morales-Kastresana, Aizea; Sampedro, Ana; Serrano-Mendioroz, Irantzu; Azpilikueta, Arantza; Ochoa, María Carmen; Dubrot, Juan; Martínez-Ansó, Eduardo

    2014-01-01

    The immune system poses obstacles to viral vectors, even in the first administration to preimmunized hosts. We have observed that the livers of B cell-deficient mice were more effectively transduced by a helper-dependent adenovirus serotype-5 (HDA) vector than those of WT mice. This effect was T-cell independent as shown in athymic mice. Passive transfer of the serum from adenovirus-naïve WT to Rag1KO mice resulted in a reduction in gene transfer that was traced to IgM purified from serum of adenovirus-naïve mice. To ascribe the gene transfer inhibition activity to either adenoviral antigen-specific or antigen-unspecific functions of IgM, we used a monoclonal IgM antibody of unrelated specificity. Both the polyclonal and the irrelevant monoclonal IgM inhibited gene transfer by the HDA vector to either cultured hepatocellular carcinoma cells or to the liver of mice in vivo. Adsorption of polyclonal or monoclonal IgMs to viral capsids was revealed by ELISAs on adenovirus-coated plates. These observations indicate the existence of an inborn IgM mechanism deployed against a prevalent virus to reduce early post-infection viremia. In conclusion, innate IgM binding to adenovirus serotype-5 capsids restrains gene-transfer and offers a mechanism to be targeted for optimization of vector dosage in gene therapy with HDA vectors. PMID:24465560

  8. 78 FR 956 - Statement of Organization, Functions and Delegations of Authority

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-07

    ... Management (RB4) and Office of Information Technology (RB5). Specifically, this notice: (1) Transfers the records management function from the Office of Management (RB4) to the Office of Information Technology (RB5); (2) updates the functional statement for the Office of Management (RB4) and the Office of the...

  9. Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors

    PubMed Central

    Xin, Gang; Schauder, David M.; Jing, Weiqing; Jiang, Aimin; Joshi, Nikhil S.; Johnson, Bryon; Cui, Weiguo

    2017-01-01

    Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a bacterial antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice. The dual-specific CD8 T cells expanded vigorously, migrated to tumor sites, and robustly eradicated primary tumors. The mice cured from ReACT also developed immunological memory against tumor rechallenge. Mechanistically, we have found that this combined approach reverts the immunosuppressive TME and recruits CD8 T cells with an increased number and killing ability to the tumors. PMID:28069963

  10. OPTICAL INFORMATION PROCESSING: Modulation—spectral analysis of an image transmitted across a distorting medium

    NASA Astrophysics Data System (ADS)

    Zubov, Vladimir A.; Mironova, T. V.

    1998-05-01

    The task of simultaneous determination of the structure and characteristics of a two-dimensional amplitude—phase signal and a two-dimensional complex transfer or instrumental function is considered. The solution is based on determination of four independent intensity distributions of spectral representations of the signal Isr(ωx, ωy) subjected to the action of the transfer function, of the signal Ismr(ωx, ωy which) has experienced additional modulation applied in a certain manner and the action of the transfer function, of the signal Isrn(ωx, ωy) representing the signal Isr(ωx, ωy) with certain additional modulation at the output, and of the signal Ismrn(ωx, ωy) which is the signal Ismr(ωx, ωy) with certain additional modulation at the output. These intensity distributions make it possible to calculate the amplitude and phase components of the image being analysed and of the transfer function. Additional modulations should in some way ensure visualisation of the phase information. A specific type of additional spatial modulation, in the form of linear amplitude, is discussed.

  11. Cell intrinsic abrogation of TGFβ signaling delays but does not prevent dysfunction of self/tumor specific CD8 T cells in a murine model of autochthonous prostate cancer

    PubMed Central

    Chou, Cassie K.; Schietinger, Andrea; Liggitt, H. Denny; Tan, Xiaoxia; Funk, Sarah; Freeman, Gordon J.; Ratliff, Timothy L.; Greenberg, Norman M.; Greenberg, Philip D.

    2012-01-01

    Adoptive T cell therapy (ACT) for the treatment of established cancers is actively being pursued in clinical trials. However, poor in vivo persistence and maintenance of anti-tumor activity of transferred T cells remain major problems. Transforming growth factor beta (TGFβ) is a potent immunosuppressive cytokine that is often expressed at high levels within the tumor microenvironment, potentially limiting T cell mediated anti-tumor activity. Here, we used a model of autochthonous murine prostate cancer to evaluate the effect of cell intrinsic abrogation of TGFβ signaling in self/tumor specific CD8 T cells used in ACT to target the tumor in situ. We found that persistence and anti-tumor activity of adoptively transferred effector T cells deficient in TGFβ signaling was significantly improved in the cancerous prostate. However, over time, despite persistence in peripheral lymphoid organs, the numbers of transferred cells in the prostate decreased and the residual prostate infiltrating T cells were no longer functional. These findings reveal that TGFβ negatively regulates the accumulation and effector function of transferred self/tumor specific CD8 T cells and highlight that, when targeting a tumor antigen that is also expressed as a self-protein, additional substantive obstacles are operative within the tumor microenvironment, potentially hampering the success of ACT for solid tumors. PMID:22984076

  12. Plasmids foster diversification and adaptation of bacterial populations in soil.

    PubMed

    Heuer, Holger; Smalla, Kornelia

    2012-11-01

    It is increasingly being recognized that the transfer of conjugative plasmids across species boundaries plays a vital role in the adaptability of bacterial populations in soil. There are specific driving forces and constraints of plasmid transfer within bacterial communities in soils. Plasmid-mediated genetic variation allows bacteria to respond rapidly with adaptive responses to challenges such as irregular antibiotic or metal concentrations, or opportunities such as the utilization of xenobiotic compounds. Cultivation-independent detection and capture of plasmids from soil bacteria, and complete sequencing have provided new insights into the role and ecology of plasmids. Broad host range plasmids such as those belonging to IncP-1 transfer a wealth of accessory functions which are carried by similar plasmid backbones. Plasmids with a narrower host range can be more specifically adapted to particular species and often transfer genes which complement chromosomally encoded functions. Plasmids seem to be an ancient and successful strategy to ensure survival of a soil population in spatial and temporal heterogeneous conditions with various environmental stresses or opportunities that occur irregularly or as a novel challenge in soil. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  13. 42 CFR 37.42 - Chest radiograph specifications-digital radiography systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... resolution, modulation transfer function (MTF), image signal-to-noise and detective quantum efficiency must... Information Object Definitions, sections: Computed Radiography Image Information Object Definition; Digital X...

  14. The transfer of Cfunc contextual control through equivalence relations.

    PubMed

    Perez, William F; Fidalgo, Adriana P; Kovac, Roberta; Nico, Yara C

    2015-05-01

    Derived relational responding is affected by contextual stimuli (Cfunc) that select specific stimulus functions. The present study investigated the transfer of Cfunc contextual control through equivalence relations by evaluating both (a) the maintenance of Cfunc contextual control after the expansion of a relational network, and (b) the establishment of novel contextual stimuli by the transfer of Cfunc contextual control through equivalence relations. Initially, equivalence relations were established and contingencies were arranged so that colors functioned as Cfunc stimuli controlling participants' key-pressing responses in the presence of any stimulus from a three-member equivalence network. To investigate the first research question, the three-member equivalence relations were expanded to five members and the novel members were presented with the Cfunc stimuli in the key-pressing task. To address the second goal of this study, the colors (Cfunc) were established as equivalent to certain line patterns. The transfer of contextual cue function (Cfunc) was tested replacing the colored backgrounds with line patterns in the key-pressing task. Results suggest that the Cfunc contextual control was transferred to novel stimuli that were added to the relational network. In addition, the line patterns indirectly acquired the contextual cue function (Cfunc) initially established for the colored backgrounds. The conceptual and applied implications of Cfunc contextual control are discussed. © Society for the Experimental Analysis of Behavior.

  15. Predator and prey biodiversity relationship and its consequences on marine ecosystem functioning-interplay between nanoflagellates and bacterioplankton.

    PubMed

    Yang, Jinny Wu; Wu, Wenxue; Chung, Chih-Ching; Chiang, Kuo-Ping; Gong, Gwo-Ching; Hsieh, Chih-Hao

    2018-06-01

    The importance of biodiversity effects on ecosystem functioning across trophic levels, especially via predatory-prey interactions, is receiving increased recognition. However, this topic has rarely been explored for marine microbes, even though microbial biodiversity contributes significantly to marine ecosystem function and energy flows. Here we examined diversity and biomass of bacteria (prey) and nanoflagellates (predators), as well as their effects on trophic transfer efficiency in the East China Sea. Specifically, we investigated: (i) predator diversity effects on prey biomass and trophic transfer efficiency (using the biomass ratio of predator/prey as a proxy), (ii) prey diversity effects on predator biomass and trophic transfer efficiency, and (iii) the relationship between predator and prey diversity. We found higher prey diversity enhanced both diversity and biomass of predators, as well as trophic transfer efficiency, which may arise from more balanced diet and/or enhanced niche complementarity owing to higher prey diversity. By contrast, no clear effect was detected for predator diversity on prey biomass and transfer efficiency. Notably, we found prey diversity effects on predator-prey interactions; whereas, we found no significant diversity effect on biomass within the same trophic level. Our findings highlight the importance of considering multi-trophic biodiversity effects on ecosystem functioning in natural ecosystems.

  16. Cytokines affecting CD4+T regulatory cells in transplant tolerance. II. Interferon gamma (IFN-γ) promotes survival of alloantigen-specific CD4+T regulatory cells.

    PubMed

    Nomura, Masaru; Hodgkinson, Suzanne J; Tran, Giang T; Verma, Nirupama D; Robinson, Catherine; Plain, Karren M; Boyd, Rochelle; Hall, Bruce M

    2017-06-01

    CD4 + T cells that transfer alloantigen-specific transplant tolerance are short lived in culture unless stimulated with specific-donor alloantigen and lymphocyte derived cytokines. Here, we examined if IFN-γ maintained survival of tolerance transferring CD4 + T cells. Alloantigen-specific transplant tolerance was induced in DA rats with heterotopic adult PVG heart allografts by a short course of immunosuppression and these grafts functioned for >100days with no further immunosuppression. In previous studies, we found the CD4 + T cells from tolerant rats that transfer tolerance to an irradiated DA host grafted with a PVG heart, lose their tolerance transferring ability after 3days of culture, either with or without donor alloantigen, and effect rejection of specific-donor grafts. If cultures with specific-donor alloantigen are supplemented by supernatant from ConA activated lymphocytes the tolerance transferring cells survive, suggesting these cells depend on cytokines for their survival. In this study, we found addition of rIFN-γ to MLC with specific-donor alloantigen maintained the capacity of tolerant CD4 + T cells to transfer alloantigen-specific tolerance and their ability to suppress PVG allograft rejection mediated by co-administered naïve CD4 + T cells. IFN-γ suppressed the in vitro proliferation of tolerant CD4 + T cells. Tolerant CD4 + CD25 + T cells did not proliferate in MLC to PVG stimulator cells with no cytokine added, but did when IFN-γ was present. IFN-γ did not alter proliferation of tolerant CD4 + CD25 + T cells to third-party Lewis. Tolerant CD4 + CD25 + T cells' expression of IFN-γ receptor (IFNGR) was maintained in culture when IFN-γ was present. This study suggested that IFN-γ maintained tolerance mediating alloantigen-specific CD4 + CD25 + T cells. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  17. Learning and Motivational Processes Contributing to Pavlovian-Instrumental Transfer and Their Neural Bases: Dopamine and Beyond.

    PubMed

    Corbit, Laura H; Balleine, Bernard W

    2016-01-01

    Pavlovian stimuli exert a range of effects on behavior from simple conditioned reflexes, such as salivation, to altering the vigor and direction of instrumental actions. It is currently accepted that these distinct behavioral effects stem from two sources (i) the various associative connections between predictive stimuli and the component features of the events that these stimuli predict and (ii) the distinct motivational and cognitive functions served by cues, particularly their arousing and informational effects on the selection and performance of specific actions. Here, we describe studies that have assessed these latter phenomena using a paradigm that has come to be called Pavlovian-instrumental transfer. We focus first on behavioral experiments that have described distinct sources of stimulus control derived from the general affective and outcome-specific predictions of conditioned stimuli, referred to as general transfer and specific transfer, respectively. Subsequently, we describe research efforts attempting to establish the neural bases of these transfer effects, largely in the afferent and efferent connections of the nucleus accumbens (NAc) core and shell. Finally, we examine the role of predictive cues in examples of aberrant stimulus control associated with psychiatric disorders and addiction.

  18. Automated Transfer Vehicle Proximity Flight Safety Overview

    NASA Astrophysics Data System (ADS)

    Cornier, Dominique; Berthelier, David; Requiston, Helene; Zekri, Eric; Chase, Richard

    2005-12-01

    The European Automated Transfer Vehicle (ATV) is an unmanned transportation spacecraft designed to contribute to the logistic servicing of the ISS. The ATV will be launched by ARIANE 5 and, after phasing and rendezvous maneuvers, it autonomously docks to the International Space Station (ISS).The ATV control is nominally handled by the Guidance, Navigation and Control (GNC) function using computers, software, sensors and actuators. During rendezvous operations, in order to cover the extreme situations where the GNC function fails to ensure a safe trajectory with respect to the ISS, a segregated Proximity Flight Safety (PFS) function is activated : this function will initiate a collision avoidance maneuver which will place the ATV on a trajectory ensuring safety with respect to the ISS. The PFS function relies on segregated computers, the Monitoring and Safing Units (MSUs) running specific software, on four dedicated thrusters, on dedicated batteries and on specific interfaces with ATV gyrometers.The PFS function being the ultimate protection to ensure ISS safety in case of ATV malfunction, specific rules have been applied to its implementation, in particular for the development of the MSU software, which is critical since any failure of this software may result in catastrophic consequences.This paper provides an overview of the ATV Proximity Flight Safety function. After a short description of the overall ATV avionics architecture and its rationale, the second part of the paper presents more details on the PFS function both in terms of hardware and software implementation. The third part of the paper is dedicated to the MSU software validation method that is specific considering its criticality. The last part of the paper provides information on the different operations related to the use of the PFS function during an ATV flight.

  19. Are videogame training gains specific or general?

    PubMed

    Oei, Adam C; Patterson, Michael D

    2014-01-01

    Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames (AVGs). Playing action games (e.g., Call of Duty, Medal of Honor) is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the AVGs because the AVGs and laboratory tasks contain similar demands. We review studies of action and non-AVGs to show support for the latter proposal. To explain transfer in AVGs, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking (MOT), rapid attentional switches, and peripheral vision). In non-AVGs, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g., Tetris). In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning). Thus, the "common demands" hypothesis of transfer not only characterizes transfer effects in AVGs, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements.

  20. Are videogame training gains specific or general?

    PubMed Central

    Patterson, Michael D.

    2014-01-01

    Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames (AVGs). Playing action games (e.g., Call of Duty, Medal of Honor) is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the AVGs because the AVGs and laboratory tasks contain similar demands. We review studies of action and non-AVGs to show support for the latter proposal. To explain transfer in AVGs, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking (MOT), rapid attentional switches, and peripheral vision). In non-AVGs, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g., Tetris). In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning). Thus, the “common demands” hypothesis of transfer not only characterizes transfer effects in AVGs, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements. PMID:24782722

  1. Mass transfer resistance in ASFF reactors for waste water treatment.

    PubMed

    Ettouney, H M; Al-Haddad, A A; Abu-Irhayem, T M

    1996-01-01

    Analysis of mass transfer resistances was performed for an aerated submerged fixed-film reactor (ASFF) for the treatment of waste water containing a mixture of sucrose and ammonia. Both external and internal mass transfer resistances were considered in the analysis, and characterized as a function of feed flow-rate and concentration. Results show that, over a certain operating regime, external mass transfer resistance in the system was greater for sucrose removal than ammonia. This is because the reaction rates for carbon removal were much larger than those of nitrogen. As a result, existence of any form of mass transfer resistance caused by inadequate mixing or diffusion limitations, strongly affects the overall removal rates of carbon more than nitrogen. Effects of the internal måss transfer resistance were virtually non-existent for ammonia removal. This behaviour was found over two orders of magnitude range for the effective diffusivity for ammonia, and one order of magnitude for the film specific surface area. However, over the same parameters' range, it is found that sucrose removal was strongly affected upon lowering its effective diffusivity and increasing the film specific surface area.

  2. Transfer of location-specific control to untrained locations.

    PubMed

    Weidler, Blaire J; Bugg, Julie M

    2016-11-01

    Recent research highlights a seemingly flexible and automatic form of cognitive control that is triggered by potent contextual cues, as exemplified by the location-specific proportion congruence effect--reduced compatibility effects in locations associated with a high as compared to low likelihood of conflict. We investigated just how flexible location-specific control is by examining whether novel locations effectively cue control for congruency-unbiased stimuli. In two experiments, biased (mostly compatible or mostly incompatible) training stimuli appeared in distinct locations. During a final block, unbiased (50% compatible) stimuli appeared in novel untrained locations spatially linked to biased locations. The flanker compatibly effect was reduced for unbiased stimuli in novel locations linked to a mostly incompatible compared to a mostly compatible location, indicating transfer. Transfer was observed when stimuli appeared along a linear function (Experiment 1) or in rings of a bullseye (Experiment 2). The novel transfer effects imply that location-specific control is more flexible than previously reported and further counter the complex stimulus-response learning account of location-specific proportion congruence effects. We propose that the representation and retrieval of control settings in untrained locations may depend on environmental support and the presentation of stimuli in novel locations that fall within the same categories of space as trained locations.

  3. Biointerfacial Property of Plasma-Treated Single-Walled Carbon Nanotube Film Electrodes for Electrochemical Biosensors

    NASA Astrophysics Data System (ADS)

    Kim, Joon Hyub; Lee, Jun-Yong; Jin, Joon-Hyung; Park, Eun Jin; Min, Nam Ki

    2013-01-01

    The single-walled carbon nanotube (SWCNT)-based thin film was spray-coated on the Pt support and functionalized using O2 plasma. The effects of plasma treatment on the biointerfacial properties of the SWCNT films were analyzed by cyclic voltammogram (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). The plasma-functionalized (pf) SWCNT electrodes modified with Legionella pneumophila-specific probe DNA strands showed a much higher peak current and a smaller peak separation in differential pulse voltammetry and a lower charge transfer resistance, compared to the untreated samples. These results suggest that the pf-SWCNT films have a better electrocatalytic character and an electron transfer capability faster than the untreated SWCNTs, due to the fact that the oxygen-containing functional groups promote direct electron transfer in the biointerfacial region of the electrocatalytic activity of redox-active biomolecules.

  4. Surfactant effects on alpha-factors in aeration systems.

    PubMed

    Rosso, Diego; Stenstrom, Michael K

    2006-04-01

    Aeration in wastewater treatment processes accounts for the largest fraction of plant energy costs. Aeration systems function by shearing the surface (surface aerators) or releasing bubbles at the bottom of the tank (coarse- or fine-bubble aerators). Surfactant accumulation on gas-liquid interfaces reduces mass transfer rates, and this reduction in general is larger for fine-bubble aerators. This study evaluates mass transfer effects on the characterization and specification of aeration systems in clean and process water conditions. Tests at different interfacial turbulence regimes show higher gas transfer depression for lower turbulence regimes. Contamination effects can be offset at the expense of operating efficiency, which is characteristic of surface aerators and coarse-bubble diffusers. Results describe the variability of alpha-factors measured at small scale, due to uncontrolled energy density. Results are also reported in dimensionless empirical correlations describing mass transfer as a function of physiochemical and geometrical characteristics of the aeration process.

  5. Cumulant generating function formula of heat transfer in ballistic systems with lead-lead coupling

    NASA Astrophysics Data System (ADS)

    Li, Huanan; Agarwalla, Bijay Kumar; Wang, Jian-Sheng

    2012-10-01

    Based on a two-time observation protocol, we consider heat transfer in a given time interval tM in a lead-junction-lead system taking coupling between the leads into account. In view of the two-time observation, consistency conditions are carefully verified in our specific family of quantum histories. Furthermore, its implication is briefly explored. Then using the nonequilibrium Green's function method, we obtain an exact formula for the cumulant generating function for heat transfer between the two leads, valid in both transient and steady-state regimes. Also, a compact formula for the cumulant generating function in the long-time limit is derived, for which the Gallavotti-Cohen fluctuation symmetry is explicitly verified. In addition, we briefly discuss Di Ventra's repartitioning trick regarding whether the repartitioning procedure of the total Hamiltonian affects the nonequilibrium steady-state current fluctuation. All kinds of properties of nonequilibrium current fluctuations, such as the fluctuation theorem in different time regimes, could be readily given according to these exact formulas.

  6. Outcome Following Spinal Accessory to Suprascapular (Spinoscapular) Nerve Transfer in Infants with Brachial Plexus Birth Injuries

    PubMed Central

    Ruchelsman, David E.; Ramos, Lorna E.; Alfonso, Israel; Price, Andrew E.; Grossman, Agatha

    2009-01-01

    The purpose of this study is to evaluate the value of distal spinal accessory nerve (SAN) transfer to the suprascapular nerve (SSN) in children with brachial plexus birth injuries in order to better define the application and outcome of this transfer in these infants. Over a 3-year period, 34 infants with brachial plexus injuries underwent transfer of the SAN to the SSN as part of the primary surgical reconstruction. Twenty-five patients (direct repair, n = 20; interposition graft, n = 5) achieved a minimum follow-up of 24 months. Fourteen children underwent plexus reconstruction with SAN-to-SSN transfer at less than 9 months of age, and 11 underwent surgical reconstruction at the age of 9 months or older. Mean age at the time of nerve transfer was 11.6 months (range, 5–30 months). At latest follow-up, active shoulder external rotation was measured in the arm abducted position and confirmed by review of videos. The Gilbert and Miami shoulder classification scores were utilized to report shoulder-specific functional outcomes. The effects of patient age at the time of nerve transfer and the use of interpositional nerve graft were analyzed. Overall mean active external rotation measured 69.6°; mean Gilbert score was 4.1 and the mean Miami score was 7.1, corresponding to overall good shoulder functional outcomes. Similar clinical and shoulder-specific functional outcomes were obtained in patients undergoing early (<9 months of age, n = 14) and late (>9 months of age, n = 11) SAN-to-SSN transfer and primary plexus reconstruction. Nine patients (27%) were lost to follow-up and are not included in the analysis. Optimum results were achieved following direct transfer (n = 20). Results following the use of an interpositional graft (n = 5) were rated satisfactory. No patient required a secondary shoulder procedure during the study period. There were no postoperative complications. Distal SAN-to-SSN (spinoscapular) nerve transfer is a reliable option for shoulder reinnervation in infants with brachial plexus birth injuries. Direct transfer seems to be the optimum method. The age of the patient does not seem to significantly impact on outcome. PMID:19882190

  7. CRIMEtoYHU: a new web tool to develop yeast-based functional assays for characterizing cancer-associated missense variants.

    PubMed

    Mercatanti, Alberto; Lodovichi, Samuele; Cervelli, Tiziana; Galli, Alvaro

    2017-12-01

    Evaluation of the functional impact of cancer-associated missense variants is more difficult than for protein-truncating mutations and consequently standard guidelines for the interpretation of sequence variants have been recently proposed. A number of algorithms and software products were developed to predict the impact of cancer-associated missense mutations on protein structure and function. Importantly, direct assessment of the variants using high-throughput functional assays using simple genetic systems can help in speeding up the functional evaluation of newly identified cancer-associated variants. We developed the web tool CRIMEtoYHU (CTY) to help geneticists in the evaluation of the functional impact of cancer-associated missense variants. Humans and the yeast Saccharomyces cerevisiae share thousands of protein-coding genes although they have diverged for a billion years. Therefore, yeast humanization can be helpful in deciphering the functional consequences of human genetic variants found in cancer and give information on the pathogenicity of missense variants. To humanize specific positions within yeast genes, human and yeast genes have to share functional homology. If a mutation in a specific residue is associated with a particular phenotype in humans, a similar substitution in the yeast counterpart may reveal its effect at the organism level. CTY simultaneously finds yeast homologous genes, identifies the corresponding variants and determines the transferability of human variants to yeast counterparts by assigning a reliability score (RS) that may be predictive for the validity of a functional assay. CTY analyzes newly identified mutations or retrieves mutations reported in the COSMIC database, provides information about the functional conservation between yeast and human and shows the mutation distribution in human genes. CTY analyzes also newly found mutations and aborts when no yeast homologue is found. Then, on the basis of the protein domain localization and functional conservation between yeast and human, the selected variants are ranked by the RS. The RS is assigned by an algorithm that computes functional data, type of mutation, chemistry of amino acid substitution and the degree of mutation transferability between human and yeast protein. Mutations giving a positive RS are highly transferable to yeast and, therefore, yeast functional assays will be more predictable. To validate the web application, we have analyzed 8078 cancer-associated variants located in 31 genes that have a yeast homologue. More than 50% of variants are transferable to yeast. Incidentally, 88% of all transferable mutations have a reliability score >0. Moreover, we analyzed by CTY 72 functionally validated missense variants located in yeast genes at positions corresponding to the human cancer-associated variants. All these variants gave a positive RS. To further validate CTY, we analyzed 3949 protein variants (with positive RS) by the predictive algorithm PROVEAN. This analysis shows that yeast-based functional assays will be more predictable for the variants with positive RS. We believe that CTY could be an important resource for the cancer research community by providing information concerning the functional impact of specific mutations, as well as for the design of functional assays useful for decision support in precision medicine. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Tumor-targeting CTL expressing a single-chain Fv specific for VEGFR2.

    PubMed

    Kanagawa, Naoko; Yanagawa, Tatsuya; Mukai, Yohei; Yoshioka, Yasuo; Okada, Naoki; Nakagawa, Shinsaku

    2010-03-26

    Cytotoxic T lymphocytes (CTL) are critical effector cells in tumor immunity. Adoptive transfer therapy with in vitro-expanded tumor-specific CTL is a promising approach for preventing cancer metastasis and recurrence. Transferred CTL are not effective in clinical trials, however, due to inadequate tumor-infiltration. Therefore, the development of functionally modified CTL, such as tumor-targeting CTL, is widely desired. Here, we designed the tumor-targeting CTL expressing a single-chain antibody fragment (scFv-CTL) specific for vascular endothelial growth factor receptor 2 (VEGFR2/flk1) by transducing the CTL with a retroviral vector. The scFv-CTL bound to VEGFR2/flk1-expressing cells and retained their cytotoxic activity against tumor cells. In addition, adoptive transfer of scFv-CTL into tumor-bearing mice effectively suppressed tumor growth due to the augmented accumulation of the transferred CTL in the tumor tissue. These findings indicate that the creation of CTL capable of targeting tumor vascular endothelial cells by scFv-expression technique is considerably promising for improvement of efficacy in adoptive immunotherapy. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  9. Cumulant generating function formula of heat transfer in ballistic systems with lead-lead coupling and general nonlinear systems

    NASA Astrophysics Data System (ADS)

    Li, Huanan

    2013-03-01

    Based on a two-time observation protocol, we consider heat transfer in a given time interval tM in a lead-junction-lead system taking coupling between the leads into account. In view of the two-time observation, consistency conditions are carefully verified in our specific family of quantum histories. Furthermore, its implication is briefly explored. Then using the nonequilibrium Green's function method, we obtain an exact formula for the cumulant generating function for heat transfer between the two leads, valid in both transient and steady-state regimes. Also, a compact formula for the cumulant generating function in the long-time limit is derived, for which the Gallavotti-Cohen fluctuation symmetry is explicitly verified. In addition, we briefly discuss Di Ventra's repartitioning trick regarding whether the repartitioning procedure of the total Hamiltonian affects the nonequilibrium steady-state current fluctuation. All kinds of properties of nonequilibrium current fluctuations, such as the fluctuation theorem in different time regimes, could be readily given according to these exact formulas. Finally a practical formalism dealing with cumulants of heat transfer across general nonlinear quantum systems is established based on field theoretical/algebraic method.

  10. Acoustic radiation from weakly wrinkled premixed flames

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

    Lieuwen, Tim; Mohan, Sripathi; Rajaram, Rajesh

    2006-01-01

    This paper describes a theoretical analysis of acoustic radiation from weakly wrinkled (i.e., u'/S{sub L}<1) premixed flames. Specifically, it determines the transfer function relating the spectrum of the acoustic pressure oscillations, P'({omega}), to that of the turbulent velocity fluctuations in the approach flow, U'({omega}). In the weakly wrinkled limit, this transfer function is local in frequency space; i.e., velocity fluctuations at a frequency {omega} distort the flame and generate sound at the same frequency. This transfer function primarily depends upon the flame Strouhal number St (based on mean flow velocity and flame length) and the correlation length, {lambda}, of themore » flow fluctuations. For cases where the ratio of the correlation length and duct radius {lambda}/a>>1, the acoustic pressure and turbulent velocity power spectra are related by P'({omega})-{omega}{sup 2}U'({omega}) and P'({omega})-U'({omega}) for St<<1 and St>>1, respectively. For cases where {lambda}/a<<1, the transfer functions take the form P'({omega})-{omega}{sup 2}({lambda}/a){sup 2}U'({omega}) and P'({omega})-{omega}{sup 2}({lambda}/a){sup 2}({psi}-{delta}ln({lambda}/a))U'({omega}) for St<<1 and St>>1, respectively, where (PS) and {delta} are constants. The latter result demonstrates that this transfer function does not exhibit a simple power law relationship in the high frequency region of the spectra. The simultaneous dependence of this pressure-velocity transfer function upon the Strouhal number and correlation length suggests a mechanism for the experimentally observed maximum in acoustic spectra and provides some insight into the controversy in the literature over how this peak should scale with the flame Strouhal number.« less

  11. Transfer of Learning Relates to Intrinsic Connectivity between Hippocampus, Ventromedial Prefrontal Cortex, and Large-Scale Networks

    PubMed Central

    Gerraty, Raphael T.; Davidow, Juliet Y.; Wimmer, G. Elliott; Kahn, Itamar

    2014-01-01

    An important aspect of adaptive learning is the ability to flexibly use past experiences to guide new decisions. When facing a new decision, some people automatically leverage previously learned associations, while others do not. This variability in transfer of learning across individuals has been demonstrated repeatedly and has important implications for understanding adaptive behavior, yet the source of these individual differences remains poorly understood. In particular, it is unknown why such variability in transfer emerges even among homogeneous groups of young healthy participants who do not vary on other learning-related measures. Here we hypothesized that individual differences in the transfer of learning could be related to relatively stable differences in intrinsic brain connectivity, which could constrain how individuals learn. To test this, we obtained a behavioral measure of memory-based transfer outside of the scanner and on a separate day acquired resting-state functional MRI images in 42 participants. We then analyzed connectivity across independent component analysis-derived brain networks during rest, and tested whether intrinsic connectivity in learning-related networks was associated with transfer. We found that individual differences in transfer were related to intrinsic connectivity between the hippocampus and the ventromedial prefrontal cortex, and between these regions and large-scale functional brain networks. Together, the findings demonstrate a novel role for intrinsic brain dynamics in flexible learning-guided behavior, both within a set of functionally specific regions known to be important for learning, as well as between these regions and the default and frontoparietal networks, which are thought to serve more general cognitive functions. PMID:25143610

  12. Item-Specific and Generalization Effects on Brain Activation when Learning Chinese Characters

    ERIC Educational Resources Information Center

    Deng, Yuan; Booth, James R.; Chou, Tai-Li; Ding, Guo-Sheng; Peng, Dan-Ling

    2008-01-01

    Neural changes related to learning of the meaning of Chinese characters in English speakers were examined using functional magnetic resonance imaging (fMRI). We examined item specific learning effects for trained characters, but also the generalization of semantic knowledge to novel transfer characters that shared a semantic radical (part of a…

  13. Lunar ash flow with heat transfer.

    NASA Technical Reports Server (NTRS)

    Pai, S. I.; Hsieh, T.; O'Keefe, J. A.

    1972-01-01

    The most important heat-transfer process in the ash flow under consideration is heat convection. Besides the four important nondimensional parameters of isothermal ash flow (Pai et al., 1972), we have three additional important nondimensional parameters: the ratio of the specific heat of the gas, the ratio of the specific heat of the solid particles to that of gas, and the Prandtl number. We reexamine the one dimensional steady ash flow discussed by Pai et al. (1972) by including the effects of heat transfer. Numerical results for the pressure, temperature, density of the gas, velocities of gas and solid particles, and volume fraction of solid particles as function of altitude for various values of the Jeffreys number, initial velocity ratio, and two different gas species (steam and hydrogen) are presented.

  14. Comparison of Commercial Electromagnetic Interface Test Techniques to NASA Electromagnetic Interference Test Techniques

    NASA Astrophysics Data System (ADS)

    Smith, V.

    2000-11-01

    This report documents the development of analytical techniques required for interpreting and comparing space systems electromagnetic interference test data with commercial electromagnetic interference test data using NASA Specification SSP 30237A "Space Systems Electromagnetic Emission and Susceptibility Requirements for Electromagnetic Compatibility." The PSpice computer simulation results and the laboratory measurements for the test setups under study compare well. The study results, however, indicate that the transfer function required to translate test results of one setup to another is highly dependent on cables and their actual layout in the test setup. Since cables are equipment specific and are not specified in the test standards, developing a transfer function that would cover all cable types (random, twisted, or coaxial), sizes (gauge number and length), and layouts (distance from the ground plane) is not practical.

  15. Comparison of Commercial Electromagnetic Interface Test Techniques to NASA Electromagnetic Interference Test Techniques

    NASA Technical Reports Server (NTRS)

    Smith, V.; Minor, J. L. (Technical Monitor)

    2000-01-01

    This report documents the development of analytical techniques required for interpreting and comparing space systems electromagnetic interference test data with commercial electromagnetic interference test data using NASA Specification SSP 30237A "Space Systems Electromagnetic Emission and Susceptibility Requirements for Electromagnetic Compatibility." The PSpice computer simulation results and the laboratory measurements for the test setups under study compare well. The study results, however, indicate that the transfer function required to translate test results of one setup to another is highly dependent on cables and their actual layout in the test setup. Since cables are equipment specific and are not specified in the test standards, developing a transfer function that would cover all cable types (random, twisted, or coaxial), sizes (gauge number and length), and layouts (distance from the ground plane) is not practical.

  16. Charge-transfer-based terbium MOF nanoparticles as fluorescent pH sensor for extreme acidity.

    PubMed

    Qi, Zewan; Chen, Yang

    2017-01-15

    Newly emerged metal organic frameworks (MOFs) have aroused the great interest in designing functional materials by means of its flexible structure and component. In this study, we used lanthanide Tb 3+ ions and small molecular ligands to design and assemble a kind of pH-sensitive MOF nanoparticle based on intramolecular-charge-transfer effect. This kind of made-to-order MOF nanoparticle for H + is highly specific and sensitive and could be used to fluorescently indicate pH value of strong acidic solution via preset mechanism through luminescence of Tb 3+ . The long luminescence lifetime of Tb 3+ allows eliminating concomitant non-specific fluorescence by time-revised fluorescence techniques, processing an advantage in sensing H + in biological media with strong autofluorescence. Our method showed a great potential of MOF structures in designing and constructing sensitive sensing materials for specific analytes directly via the assembly of functional ions/ligands. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Treatment alternatives of congenital hand differences with thumb hypoplasia involvement.

    PubMed

    Papadogeorgou, Ellada V; Soucacos, Panayotis N

    2008-01-01

    Congenital thumb hypoplasia is a complex and heterogeneous congenital difference that is detrimental to hand function. Apart from its' classic form, which is now considered to be part of radial dysplasia, it can occur as part of other congenital anomalies including, syndactyly, symbrachydactyly, atypical cleft hand, bifid thumb, triphalangeal thumb, mirror hand, constriction band syndrome, as well as generalized anomalies and syndromes. Management is aimed primarily at restoring basic hand function, specifically, power grasp and precision pinch, and secondarily to improve cosmoses, which inevitably is going to be impaired. Several treatment alternatives have been proposed to manage the specific disabling condition and include, 1st web space reconstruction and opponensplasty, pollicization, toe-to-hand transfer, distraction lengthening, free toe phalangeal transfer or the use of allograft, stabilization of the metacarpophalangeal joint, and surgery of "spare parts." The purpose of this study is to evaluate the various alternatives available today and propose an algorithm applicable for the appropriate management of thumb deficiency, based on their specific characteristics. Copyright 2008 Wiley-Liss, Inc. Microsurgery, 2008.

  18. MICOS and phospholipid transfer by Ups2-Mdm35 organize membrane lipid synthesis in mitochondria.

    PubMed

    Aaltonen, Mari J; Friedman, Jonathan R; Osman, Christof; Salin, Bénédicte; di Rago, Jean-Paul; Nunnari, Jodi; Langer, Thomas; Tatsuta, Takashi

    2016-06-06

    Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochondrial membrane, promotes mitochondrial PE synthesis via two pathways. First, Ups2-Mdm35 complexes (SLMO2-TRIAP1 in humans) serve as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial intermembrane space, allowing formation of PE by Psd1 in the inner membrane. Second, Psd1 decarboxylates PS in the outer membrane in trans, independently of PS transfer by Ups2-Mdm35. This latter pathway requires close apposition between both mitochondrial membranes and the mitochondrial contact site and cristae organizing system (MICOS). In MICOS-deficient cells, limiting PS transfer by Ups2-Mdm35 and reducing mitochondrial PE accumulation preserves mitochondrial respiration and cristae formation. These results link mitochondrial PE metabolism to MICOS, combining functions in protein and lipid homeostasis to preserve mitochondrial structure and function. © 2016 Aaltonen et al.

  19. A generic archive protocol and an implementation

    NASA Technical Reports Server (NTRS)

    Jordan, J. M.; Jennings, D. G.; Mcglynn, T. A.; Ruggiero, N. G.; Serlemitsos, T. A.

    1992-01-01

    Archiving vast amounts of data has become a major part of every scientific space mission today. The Generic Archive/Retrieval Services Protocol (GRASP) addresses the question of how to archive the data collected in an environment where the underlying hardware archives may be rapidly changing. GRASP is a device independent specification defining a set of functions for storing and retrieving data from an archive, as well as other support functions. GRASP is divided into two levels: the Transfer Interface and the Action Interface. The Transfer Interface is computer/archive independent code while the Action Interface contains code which is dedicated to each archive/computer addressed. Implementations of the GRASP specification are currently available for DECstations running Ultrix, Sparcstations running SunOS, and microVAX/VAXstation 3100's. The underlying archive is assumed to function as a standard Unix or VMS file system. The code, written in C, is a single suite of files. Preprocessing commands define the machine unique code sections in the device interface. The implementation was written, to the greatest extent possible, using only ANSI standard C functions.

  20. Polarity inversion of bioanode for biocathodic reduction of aromatic pollutants.

    PubMed

    Yun, Hui; Liang, Bin; Kong, De-Yong; Cheng, Hao-Yi; Li, Zhi-Ling; Gu, Ya-Bing; Yin, Hua-Qun; Wang, Ai-Jie

    2017-06-05

    The enrichment of specific pollutant-reducing consortium is usually required prior to the startup of biocathode bioelectrochemical system (BES) and the whole process is time consuming. To rapidly establish a non-specific functional biocathode, direct polar inversion from bioanode to biocathode is proposed in this study. Based on the diverse reductases and electron transfer related proteins of anode-respiring bacteria (ARB), the acclimated electrochemically active biofilm (EAB) may catalyze reduction of different aromatic pollutants. Within approximately 12 d, the acclimated bioanodes were directly employed as biocathodes for nitroaromatic nitrobenzene (NB) and azo dye acid orange 7 (AO7) reduction. Our results indicated that the established biocathode significantly accelerated the reduction of NB to aniline (AN) and AO7 to discolored products compared with the abiotic cathode and open circuit controls. Several microbes possessing capabilities of nitroaromatic/azo dye reduction and bidirectional electron transfer were maintained or enriched in the biocathode communities. Cyclic voltammetry highlighted the decreased over-potentials and enhanced electron transfer of biocathode as well as demonstrated the ARB Geobacter containing cytochrome c involved in the backward electron transfer from electrode to NB. This study offers new insights into the rapid establishment and modularization of functional biocathodes for the potential treatment of complicated electron acceptors-coexisting wastewaters. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Is tibialis anterior tendon transfer effective for recurrent clubfoot?

    PubMed

    Gray, Kelly; Burns, Joshua; Little, David; Bellemore, Michael; Gibbons, Paul

    2014-02-01

    Tibialis anterior tendon transfer surgery forms a part of Ponseti management for children with congenital talipes equinovarus who, after initial correction, present with residual dynamic supination. Although retrospective studies support good outcomes, prospective longitudinal studies in this population are lacking. We assessed strength, plantar loading, ROM, foot alignment, function, satisfaction, and quality of life in patients with clubfoot that recurred after Ponseti casting who met indications for tibialis anterior tendon transfer surgery, and compared them with a group of patients with clubfoot treated with casting but whose deformity did not recur (therefore who were not indicated for tibialis anterior tendon transfer surgery). Twenty children with idiopathic congenital talipes equinovarus indicated for tibialis anterior tendon transfer surgery were recruited. Assessment at baseline (before surgery), and 3, 6, and 12 months (after surgery) included strength (hand-held dynamometry), plantar loading (capacitance transducer matrix platform), ROM (Dimeglio scale), foot alignment (Foot Posture Index(©)), function and satisfaction (disease-specific instrument for clubfoot), and quality of life (Infant Toddler Quality of Life Questionnaire™). Outcomes were compared with those of 12 age-matched children with congenital talipes equinovarus not indicated for tibialis anterior tendon transfer surgery. Followup was 100% in the control group and 95% (19 of 20) in the tibialis anterior transfer group. At baseline, the tibialis anterior tendon transfer group had a significantly worse eversion-to-inversion strength ratio, plantar loading, ROM, foot alignment, and function and satisfaction. At 3 months after surgery, eversion-to-inversion strength, plantar loading, and function and satisfaction were no longer different between groups. Improvements were maintained at 12 months after surgery (eversion-to-inversion strength mean difference, 8% body weight; 95% CI, -26% to 11%; p = 0.412; plantar loading, p > 0.251; function and satisfaction, p = 0.076). ROM remained less and foot alignment more supinated in the tibialis anterior tendon transfer group between baseline and followup (p < 0.001, p < 0.001). Tibialis anterior tendon transfer surgery was an effective procedure, which at 12-month followup restored the balance of eversion-to-inversion strength and resulted in plantar loading and function and satisfaction outcomes similar to those of age-matched children with congenital talipes equinovarus who after Ponseti casting were not indicated for tibialis anterior tendon transfer.

  2. Rapid Covalent Fluorescence Labeling of Membrane Proteins on Live Cells via Coiled-Coil Templated Acyl Transfer.

    PubMed

    Reinhardt, Ulrike; Lotze, Jonathan; Mörl, Karin; Beck-Sickinger, Annette G; Seitz, Oliver

    2015-10-21

    Fluorescently labeled proteins enable the microscopic imaging of protein localization and function in live cells. In labeling reactions targeted against specific tag sequences, the size of the fluorophore-tag is of major concern. The tag should be small to prevent interference with protein function. Furthermore, rapid and covalent labeling methods are desired to enable the analysis of fast biological processes. Herein, we describe the development of a method in which the formation of a parallel coiled coil triggers the transfer of a fluorescence dye from a thioester-linked coil peptide conjugate onto a cysteine-modified coil peptide. This labeling method requires only small tag sequences (max 23 aa) and occurs with high tag specificity. We show that size matching of the coil peptides and a suitable thioester reactivity allow the acyl transfer reaction to proceed within minutes (rather than hours). We demonstrate the versatility of this method by applying it to the labeling of different G-protein coupled membrane receptors including the human neuropeptide Y receptors 1, 2, 4, 5, the neuropeptide FF receptors 1 and 2, and the dopamine receptor 1. The labeled receptors are fully functional and able to bind the respective ligand with high affinity. Activity is not impaired as demonstrated by activation, internalization, and recycling experiments.

  3. Real-time colouring and filtering with graphics shaders

    NASA Astrophysics Data System (ADS)

    Vohl, D.; Fluke, C. J.; Barnes, D. G.; Hassan, A. H.

    2017-11-01

    Despite the popularity of the Graphics Processing Unit (GPU) for general purpose computing, one should not forget about the practicality of the GPU for fast scientific visualization. As astronomers have increasing access to three-dimensional (3D) data from instruments and facilities like integral field units and radio interferometers, visualization techniques such as volume rendering offer means to quickly explore spectral cubes as a whole. As most 3D visualization techniques have been developed in fields of research like medical imaging and fluid dynamics, many transfer functions are not optimal for astronomical data. We demonstrate how transfer functions and graphics shaders can be exploited to provide new astronomy-specific explorative colouring methods. We present 12 shaders, including four novel transfer functions specifically designed to produce intuitive and informative 3D visualizations of spectral cube data. We compare their utility to classic colour mapping. The remaining shaders highlight how common computation like filtering, smoothing and line ratio algorithms can be integrated as part of the graphics pipeline. We discuss how this can be achieved by utilizing the parallelism of modern GPUs along with a shading language, letting astronomers apply these new techniques at interactive frame rates. All shaders investigated in this work are included in the open source software shwirl (Vohl 2017).

  4. The Simulation of Daily Temperature Time Series from GCM Output. Part II: Sensitivity Analysis of an Empirical Transfer Function Methodology.

    NASA Astrophysics Data System (ADS)

    Winkler, Julie A.; Palutikof, Jean P.; Andresen, Jeffrey A.; Goodess, Clare M.

    1997-10-01

    Empirical transfer functions have been proposed as a means for `downscaling' simulations from general circulation models (GCMs) to the local scale. However, subjective decisions made during the development of these functions may influence the ensuing climate scenarios. This research evaluated the sensitivity of a selected empirical transfer function methodology to 1) the definition of the seasons for which separate specification equations are derived, 2) adjustments for known departures of the GCM simulations of the predictor variables from observations, 3) the length of the calibration period, 4) the choice of function form, and 5) the choice of predictor variables. A modified version of the Climatological Projection by Model Statistics method was employed to generate control (1 × CO2) and perturbed (2 × CO2) scenarios of daily maximum and minimum temperature for two locations with diverse climates (Alcantarilla, Spain, and Eau Claire, Michigan). The GCM simulations used in the scenario development were from the Canadian Climate Centre second-generation model (CCC GCMII).Variations in the downscaling methodology were found to have a statistically significant impact on the 2 × CO2 climate scenarios, even though the 1 × CO2 scenarios for the different transfer function approaches were often similar. The daily temperature scenarios for Alcantarilla and Eau Claire were most sensitive to the decision to adjust for deficiencies in the GCM simulations, the choice of predictor variables, and the seasonal definitions used to derive the functions (i.e., fixed seasons, floating seasons, or no seasons). The scenarios were less sensitive to the choice of function form (i.e., linear versus nonlinear) and to an increase in the length of the calibration period.The results of Part I, which identified significant departures of the CCC GCMII simulations of two candidate predictor variables from observations, together with those presented here in Part II, 1) illustrate the importance of detailed comparisons of observed and GCM 1 × CO2 series of candidate predictor variables as an initial step in impact analysis, 2) demonstrate that decisions made when developing the transfer functions can have a substantial influence on the 2 × CO2 scenarios and their interpretation, 3) highlight the uncertainty in the appropriate criteria for evaluating transfer function approaches, and 4) suggest that automation of empirical transfer function methodologies is inappropriate because of differences in the performance of transfer functions between sites and because of spatial differences in the GCM's ability to adequately simulate the predictor variables used in the functions.

  5. Genetic code expansion for multiprotein complex engineering.

    PubMed

    Koehler, Christine; Sauter, Paul F; Wawryszyn, Mirella; Girona, Gemma Estrada; Gupta, Kapil; Landry, Jonathan J M; Fritz, Markus Hsi-Yang; Radic, Ksenija; Hoffmann, Jan-Erik; Chen, Zhuo A; Zou, Juan; Tan, Piau Siong; Galik, Bence; Junttila, Sini; Stolt-Bergner, Peggy; Pruneri, Giancarlo; Gyenesei, Attila; Schultz, Carsten; Biskup, Moritz Bosse; Besir, Hueseyin; Benes, Vladimir; Rappsilber, Juri; Jechlinger, Martin; Korbel, Jan O; Berger, Imre; Braese, Stefan; Lemke, Edward A

    2016-12-01

    We present a baculovirus-based protein engineering method that enables site-specific introduction of unique functionalities in a eukaryotic protein complex recombinantly produced in insect cells. We demonstrate the versatility of this efficient and robust protein production platform, 'MultiBacTAG', (i) for the fluorescent labeling of target proteins and biologics using click chemistries, (ii) for glycoengineering of antibodies, and (iii) for structure-function studies of novel eukaryotic complexes using single-molecule Förster resonance energy transfer as well as site-specific crosslinking strategies.

  6. Submolecular Gates Self-Assemble for Hot-Electron Transfer in Proteins.

    PubMed

    Filip-Granit, Neta; Goldberg, Eran; Samish, Ilan; Ashur, Idan; van der Boom, Milko E; Cohen, Hagai; Scherz, Avigdor

    2017-07-27

    Redox reactions play key roles in fundamental biological processes. The related spatial organization of donors and acceptors is assumed to undergo evolutionary optimization facilitating charge mobilization within the relevant biological context. Experimental information from submolecular functional sites is needed to understand the organization strategies and driving forces involved in the self-development of structure-function relationships. Here we exploit chemically resolved electrical measurements (CREM) to probe the atom-specific electrostatic potentials (ESPs) in artificial arrays of bacteriochlorophyll (BChl) derivatives that provide model systems for photoexcited (hot) electron donation and withdrawal. On the basis of computations we show that native BChl's in the photosynthetic reaction center (RC) self-assemble at their ground-state as aligned gates for functional charge transfer. The combined computational and experimental results further reveal how site-specific polarizability perpendicular to the molecular plane enhances the hot-electron transport. Maximal transport efficiency is predicted for a specific, ∼5 Å, distance above the center of the metalized BChl, which is in remarkably close agreement with the distance and mutual orientation of corresponding native cofactors. These findings provide new metrics and guidelines for analysis of biological redox centers and for designing charge mobilizing machines such as artificial photosynthesis.

  7. Cerebrovascular and cardiovascular variability interactions investigated through conditional joint transfer entropy in subjects prone to postural syncope.

    PubMed

    Bari, Vlasta; De Maria, Beatrice; Mazzucco, Claudio Enrico; Rossato, Gianluca; Tonon, Davide; Nollo, Giandomenico; Faes, Luca; Porta, Alberto

    2017-05-01

    A model-based conditional transfer entropy approach was exploited to quantify the information transfer in cerebrovascular (CBV) and cardiovascular (CV) systems in subjects prone to develop postural syncope. Spontaneous beat-to-beat variations of mean cerebral blood flow velocity (MCBFV) derived from a transcranial Doppler device, heart period (HP) derived from surface electrocardiogram, mean arterial pressure (MAP) and systolic arterial pressure (SAP) derived from finger plethysmographic arterial pressure device were monitored at rest in supine position (REST) and during 60° head-up tilt (TILT) in 13 individuals (age mean  ±  standard deviation: 28  ±  9 years, min-max range: 18-44 years, 5 males) with a history of recurrent episodes of syncope (SYNC) and in 13 age- and gender-matched controls (NonSYNC). Respiration (R) obtained from a thoracic belt was acquired as well and considered as a conditioning signal in transfer entropy assessment. Synchronous sequences of 250 consecutive MCBFV, HP, MAP, SAP and R values were utilized to estimate the information genuinely transferred from MAP to MCBFV (i.e. disambiguated from R influences) and vice versa. Analogous indexes were computed from SAP to HP and vice versa. Traditional time and frequency domain analyses were carried out as well. SYNC subjects showed an increased genuine information transfer from MAP to MCBFV during TILT, while they did not exhibit the expected rise of the genuine information transfer from SAP to HP. We conclude that SYNC individuals featured an impaired cerebral autoregulation visible during TILT and were unable to activate cardiac baroreflex to cope with the postural challenge. Traditional frequency domain markers based on transfer function modulus, phase and coherence functions were less powerful or less specific in typifying the CBV and CV controls of SYNC individuals. Conditional transfer entropy approach can identify the impairment of CBV and CV controls and provide specific clues to identify subjects prone to develop postural syncope.

  8. Dynamic reconfiguration of human brain functional networks through neurofeedback.

    PubMed

    Haller, Sven; Kopel, Rotem; Jhooti, Permi; Haas, Tanja; Scharnowski, Frank; Lovblad, Karl-Olof; Scheffler, Klaus; Van De Ville, Dimitri

    2013-11-01

    Recent fMRI studies demonstrated that functional connectivity is altered following cognitive tasks (e.g., learning) or due to various neurological disorders. We tested whether real-time fMRI-based neurofeedback can be a tool to voluntarily reconfigure brain network interactions. To disentangle learning-related from regulation-related effects, we first trained participants to voluntarily regulate activity in the auditory cortex (training phase) and subsequently asked participants to exert learned voluntary self-regulation in the absence of feedback (transfer phase without learning). Using independent component analysis (ICA), we found network reconfigurations (increases in functional network connectivity) during the neurofeedback training phase between the auditory target region and (1) the auditory pathway; (2) visual regions related to visual feedback processing; (3) insula related to introspection and self-regulation and (4) working memory and high-level visual attention areas related to cognitive effort. Interestingly, the auditory target region was identified as the hub of the reconfigured functional networks without a-priori assumptions. During the transfer phase, we again found specific functional connectivity reconfiguration between auditory and attention network confirming the specific effect of self-regulation on functional connectivity. Functional connectivity to working memory related networks was no longer altered consistent with the absent demand on working memory. We demonstrate that neurofeedback learning is mediated by widespread changes in functional connectivity. In contrast, applying learned self-regulation involves more limited and specific network changes in an auditory setup intended as a model for tinnitus. Hence, neurofeedback training might be used to promote recovery from neurological disorders that are linked to abnormal patterns of brain connectivity. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Transfer factor - hypotheses for its structure and function.

    PubMed

    Shifrine, M; Scibienski, R

    1975-01-01

    Transfer factor (TF) is a dialyzable extract from primed lymphocytes that is able to transfer specific delayed hypersensitivity from one animal to another. On the basis of available data we suggest that TF is a polypeptide with a molecular weight below 15,000 daltons. We hypothesize that TF is the variable light or heavy chain domain of immunoglobulin: such a molecule conforms with the accepted properties of TF and also has the necessary specificity requirements. We also hypothesize that TF is part of a receptor site. beta-2-microglobulin, a molecule that is an integral part of cell surfaces, could be the anchor for TF. beta-2-microglobulin has homologies with the constant portion of immunoglobulin light or heavy chain and thus would combine with the variable domain (TF) to form a complete receptor site for a specific antigen. The properties of TF suggest its mode of action, which is discussed in detail in the text. The biologic advantages of TF is its ability to confer immediate (immunologie specific) protection while the 'normal' immune response develops.

  10. Ferritin light-chain subunits: key elements for the electron transfer across the protein cage.

    PubMed

    Carmona, Unai; Li, Le; Zhang, Lianbing; Knez, Mato

    2014-12-18

    The first specific functionality of the light-chain (L-chain) subunit of the universal iron storage protein ferritin was identified. The electrons released during iron-oxidation were transported across the ferritin cage specifically through the L-chains and the inverted electron transport through the L-chains also accelerated the demineralization of ferritin.

  11. Ultrafast electronic dynamics driven by nuclear motion

    NASA Astrophysics Data System (ADS)

    Vendrell, Oriol

    2016-05-01

    The transfer of electrical charge on a microscopic scale plays a fundamental role in chemistry, in biology, and in technological applications. In this contribution, we will discuss situations in which nuclear motion plays a central role in driving the electronic dynamics of photo-excited or photo-ionized molecular systems. In particular, we will explore theoretically the ultrafast transfer of a double electron hole between the functional groups of glycine after K-shell ionization and subsequent Auger decay. Although a large energy gap of about 15 eV initially exists between the two electronic states involved and coherent electronic dynamics play no role in the hole transfer, we will illustrate how the double hole can be transferred within 3 to 4 fs between both functional ends of the glycine molecule driven solely by specific nuclear displacements and non-Born-Oppenheimer effects. This finding challenges the common wisdom that nuclear dynamics of the molecular skeleton are unimportant for charge transfer processes at the few-femtosecond time scale and shows that they can even play a prominent role. We thank the Hamburg Centre for Ultrafast Imaging and the Volkswagen Foundation for financial support.

  12. Transfer of learning relates to intrinsic connectivity between hippocampus, ventromedial prefrontal cortex, and large-scale networks.

    PubMed

    Gerraty, Raphael T; Davidow, Juliet Y; Wimmer, G Elliott; Kahn, Itamar; Shohamy, Daphna

    2014-08-20

    An important aspect of adaptive learning is the ability to flexibly use past experiences to guide new decisions. When facing a new decision, some people automatically leverage previously learned associations, while others do not. This variability in transfer of learning across individuals has been demonstrated repeatedly and has important implications for understanding adaptive behavior, yet the source of these individual differences remains poorly understood. In particular, it is unknown why such variability in transfer emerges even among homogeneous groups of young healthy participants who do not vary on other learning-related measures. Here we hypothesized that individual differences in the transfer of learning could be related to relatively stable differences in intrinsic brain connectivity, which could constrain how individuals learn. To test this, we obtained a behavioral measure of memory-based transfer outside of the scanner and on a separate day acquired resting-state functional MRI images in 42 participants. We then analyzed connectivity across independent component analysis-derived brain networks during rest, and tested whether intrinsic connectivity in learning-related networks was associated with transfer. We found that individual differences in transfer were related to intrinsic connectivity between the hippocampus and the ventromedial prefrontal cortex, and between these regions and large-scale functional brain networks. Together, the findings demonstrate a novel role for intrinsic brain dynamics in flexible learning-guided behavior, both within a set of functionally specific regions known to be important for learning, as well as between these regions and the default and frontoparietal networks, which are thought to serve more general cognitive functions. Copyright © 2014 the authors 0270-6474/14/3411297-07$15.00/0.

  13. Genetic Engineering of the Phosphocarrier Protein NPr of the Escherichia coli Phosphotransferase System Selectively Improves Sugar Uptake Activity*

    PubMed Central

    Lopez-de los Santos, Yossef; Chan, Henry; Cantu, Vito A.; Rettner, Rachael; Sanchez, Filiberto; Zhang, Zhongge; Saier, Milton H.; Soberon, Xavier

    2012-01-01

    The Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system (PTS) in prokaryotes mediates the uptake and phosphorylation of its numerous substrates through a phosphoryl transfer chain where a phosphoryl transfer protein, HPr, transfers its phosphoryl group to any of several sugar-specific Enzyme IIA proteins in preparation for sugar transport. A phosphoryl transfer protein of the PTS, NPr, homologous to HPr, functions to regulate nitrogen metabolism and shows virtually no enzymatic cross-reactivity with HPr. Here we describe the genetic engineering of a “chimeric” HPr/NPr protein, termed CPr14 because 14 amino acid residues of the interface were replaced. CPr14 shows decreased activity with most PTS permeases relative to HPr, but increases activity with the broad specificity mannose permease. The results lead to the proposal that HPr is not optimal for most PTS permeases but instead represents a compromise with suboptimal activity for most PTS permeases. The evolutionary implications are discussed. PMID:22767600

  14. Receptor-mediated gene transfer vectors: progress towards genetic pharmaceuticals.

    PubMed

    Molas, M; Gómez-Valadés, A G; Vidal-Alabró, A; Miguel-Turu, M; Bermudez, J; Bartrons, R; Perales, J C

    2003-10-01

    Although specific delivery to tissues and unique cell types in vivo has been demonstrated for many non-viral vectors, current methods are still inadequate for human applications, mainly because of limitations on their efficiencies. All the steps required for an efficient receptor-mediated gene transfer process may in principle be exploited to enhance targeted gene delivery. These steps are: DNA/vector binding, internalization, subcellular trafficking, vesicular escape, nuclear import, and unpacking either for transcription or other functions (i.e., antisense, RNA interference, etc.). The large variety of vector designs that are currently available, usually aimed at improving the efficiency of these steps, has complicated the evaluation of data obtained from specific derivatives of such vectors. The importance of the structure of the final vector and the consequences of design decisions at specific steps on the overall efficiency of the vector will be discussed in detail. We emphasize in this review that stability in serum and thus, proper bioavailability of vectors to their specific receptors may be the single greatest limiting factor on the overall gene transfer efficiency in vivo. We discuss current approaches to overcome the intrinsic instability of synthetic vectors in the blood. In this regard, a summary of the structural features of the vectors obtained from current protocols will be presented and their functional characteristics evaluated. Dissecting information on molecular conjugates obtained by such methodologies, when carefully evaluated, should provide important guidelines for the creation of effective, targeted and safe DNA therapeutics.

  15. Band Alignment and Charge Transfer in Complex Oxide Interfaces

    NASA Astrophysics Data System (ADS)

    Zhong, Zhicheng; Hansmann, Philipp

    2017-01-01

    The synthesis of transition metal heterostructures is currently one of the most vivid fields in the design of novel functional materials. In this paper, we propose a simple scheme to predict band alignment and charge transfer in complex oxide interfaces. For semiconductor heterostructures, band-alignment rules like the well-known Anderson or Schottky-Mott rule are based on comparison of the work function or electron affinity of the bulk components. This scheme breaks down for oxides because of the invalidity of a single work-function approximation as recently shown in [Phys. Rev. B 93, 235116 (2016), 10.1103/PhysRevB.93.235116; Adv. Funct. Mater. 26, 5471 (2016), 10.1002/adfm.201600243]. Here, we propose a new scheme that is built on a continuity condition of valence states originating in the compounds' shared network of oxygen. It allows for the prediction of sign and relative amplitude of the intrinsic charge transfer, taking as input only information about the bulk properties of the components. We support our claims by numerical density functional theory simulations as well as (where available) experimental evidence. Specific applications include (i) controlled doping of SrTiO3 layers with the use of 4 d and 5 d transition metal oxides and (ii) the control of magnetic ordering in manganites through tuned charge transfer.

  16. Loop transfer recovery for general nonminimum phase discrete time systems. I - Analysis

    NASA Technical Reports Server (NTRS)

    Chen, Ben M.; Saberi, Ali; Sannuti, Peddapullaiah; Shamash, Yacov

    1992-01-01

    A complete analysis of loop transfer recovery (LTR) for general nonstrictly proper, not necessarily minimum phase discrete time systems is presented. Three different observer-based controllers, namely, `prediction estimator' and full or reduced-order type `current estimator' based controllers, are used. The analysis corresponding to all these three controllers is unified into a single mathematical framework. The LTR analysis given here focuses on three fundamental issues: (1) the recoverability of a target loop when it is arbitrarily given, (2) the recoverability of a target loop while taking into account its specific characteristics, and (3) the establishment of necessary and sufficient conditions on the given system so that it has at least one recoverable target loop transfer function or sensitivity function. Various differences that arise in LTR analysis of continuous and discrete systems are pointed out.

  17. Sensitivity function analysis of gravitational wave detection with single-laser and large-momentum-transfer atomic sensors

    NASA Astrophysics Data System (ADS)

    Tang, Biao; Zhang, Bao-Cheng; Zhou, Lin; Wang, Jin; Zhan, Ming-Sheng

    2015-03-01

    Recently, a configuration using atomic interferometers (AIs) had been suggested for the detection of gravitational waves. A new AI with some additional laser pulses for implementing large momentum transfer was also put forward, in order to reduce the effect of shot noise and laser frequency noise. We use a sensitivity function to analyze all possible configurations of the new AI and to distinguish how many momenta are transferred in a specific configuration. By analyzing the new configuration, we further explore a detection scheme for gravitational waves, in particular, that ameliorates laser frequency noise. We find that the amelioration occurs in such a scheme, but novelly, in some cases, the frequency noise can be canceled completely by using a proper data processing method. Supported by the National Natural Science Foundation of China.

  18. Information thermodynamics of near-equilibrium computation

    NASA Astrophysics Data System (ADS)

    Prokopenko, Mikhail; Einav, Itai

    2015-06-01

    In studying fundamental physical limits and properties of computational processes, one is faced with the challenges of interpreting primitive information-processing functions through well-defined information-theoretic as well as thermodynamic quantities. In particular, transfer entropy, characterizing the function of computational transmission and its predictability, is known to peak near critical regimes. We focus on a thermodynamic interpretation of transfer entropy aiming to explain the underlying critical behavior by associating information flows intrinsic to computational transmission with particular physical fluxes. Specifically, in isothermal systems near thermodynamic equilibrium, the gradient of the average transfer entropy is shown to be dynamically related to Fisher information and the curvature of system's entropy. This relationship explicitly connects the predictability, sensitivity, and uncertainty of computational processes intrinsic to complex systems and allows us to consider thermodynamic interpretations of several important extreme cases and trade-offs.

  19. Donor and host photoreceptors engage in material transfer following transplantation of post-mitotic photoreceptor precursors

    PubMed Central

    Pearson, R. A.; Gonzalez-Cordero, A.; West, E. L.; Ribeiro, J. R.; Aghaizu, N.; Goh, D.; Sampson, R. D.; Georgiadis, A.; Waldron, P. V.; Duran, Y.; Naeem, A.; Kloc, M.; Cristante, E.; Kruczek, K.; Warre-Cornish, K.; Sowden, J. C.; Smith, A. J.; Ali, R. R.

    2016-01-01

    Photoreceptor replacement by transplantation is proposed as a treatment for blindness. Transplantation of healthy photoreceptor precursor cells into diseased murine eyes leads to the presence of functional photoreceptors within host retinae that express an array of donor-specific proteins. The resulting improvement in visual function was understood to be due to donor cells integrating within host retinae. Here, however, we show that while integration occurs the majority of donor-reporter-labelled cells in the host arises as a result of material transfer between donor and host photoreceptors. Material transfer does not involve permanent donor–host nuclear or cell–cell fusion, or the uptake of free protein or nucleic acid from the extracellular environment. Instead, RNA and/or protein are exchanged between donor and host cells in vivo. These data require a re-evaluation of the mechanisms underlying rescue by photoreceptor transplantation and raise the possibility of material transfer as a strategy for the treatment of retinal disorders. PMID:27701378

  20. A direct approach to the design of linear multivariable systems

    NASA Technical Reports Server (NTRS)

    Agrawal, B. L.

    1974-01-01

    Design of multivariable systems is considered and design procedures are formulated in the light of the most recent work on model matching. The word model matching is used exclusively to mean matching the input-output behavior of two systems. The term is used in the frequency domain to indicate the comparison of two transfer matrices containing transfer functions as elements. Design methods where non-interaction is not used as a criteria were studied. Two design methods are considered. The first method of design is based solely upon the specification of generalized error coefficients for each individual transfer function of the overall system transfer matrix. The second design method is called the pole fixing method because all the system poles are fixed at preassigned positions. The zeros of terms either above or below the diagonal are partially fixed via steady state error coefficients. The advantages and disadvantages of each method are discussed and an example is worked to demonstrate their uses. The special cases of triangular decoupling and minimum constraints are discussed.

  1. Regressed relations for forced convection heat transfer in a direct injection stratified charge rotary engine

    NASA Technical Reports Server (NTRS)

    Lee, Chi M.; Schock, Harold J.

    1988-01-01

    Currently, the heat transfer equation used in the rotary combustion engine (RCE) simulation model is taken from piston engine studies. These relations have been empirically developed by the experimental input coming from piston engines whose geometry differs considerably from that of the RCE. The objective of this work was to derive equations to estimate heat transfer coefficients in the combustion chamber of an RCE. This was accomplished by making detailed temperature and pressure measurements in a direct injection stratified charge (DISC) RCE under a range of conditions. For each specific measurement point, the local gas velocity was assumed equal to the local rotor tip speed. Local physical properties of the fluids were then calculated. Two types of correlation equations were derived and are described in this paper. The first correlation expresses the Nusselt number as a function of the Prandtl number, Reynolds number, and characteristic temperature ratio; the second correlation expresses the forced convection heat transfer coefficient as a function of fluid temperature, pressure and velocity.

  2. Transferring the entatic-state principle to copper photochemistry

    NASA Astrophysics Data System (ADS)

    Dicke, B.; Hoffmann, A.; Stanek, J.; Rampp, M. S.; Grimm-Lebsanft, B.; Biebl, F.; Rukser, D.; Maerz, B.; Göries, D.; Naumova, M.; Biednov, M.; Neuber, G.; Wetzel, A.; Hofmann, S. M.; Roedig, P.; Meents, A.; Bielecki, J.; Andreasson, J.; Beyerlein, K. R.; Chapman, H. N.; Bressler, C.; Zinth, W.; Rübhausen, M.; Herres-Pawlis, S.

    2018-03-01

    The entatic state denotes a distorted coordination geometry of a complex from its typical arrangement that generates an improvement to its function. The entatic-state principle has been observed to apply to copper electron-transfer proteins and it results in a lowering of the reorganization energy of the electron-transfer process. It is thus crucial for a multitude of biochemical processes, but its importance to photoactive complexes is unexplored. Here we study a copper complex—with a specifically designed constraining ligand geometry—that exhibits metal-to-ligand charge-transfer state lifetimes that are very short. The guanidine-quinoline ligand used here acts on the bis(chelated) copper(I) centre, allowing only small structural changes after photoexcitation that result in very fast structural dynamics. The data were collected using a multimethod approach that featured time-resolved ultraviolet-visible, infrared and X-ray absorption and optical emission spectroscopy. Through supporting density functional calculations, we deliver a detailed picture of the structural dynamics in the picosecond-to-nanosecond time range.

  3. High-order solution methods for grey discrete ordinates thermal radiative transfer

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

    Maginot, Peter G., E-mail: maginot1@llnl.gov; Ragusa, Jean C., E-mail: jean.ragusa@tamu.edu; Morel, Jim E., E-mail: morel@tamu.edu

    This work presents a solution methodology for solving the grey radiative transfer equations that is both spatially and temporally more accurate than the canonical radiative transfer solution technique of linear discontinuous finite element discretization in space with implicit Euler integration in time. We solve the grey radiative transfer equations by fully converging the nonlinear temperature dependence of the material specific heat, material opacities, and Planck function. The grey radiative transfer equations are discretized in space using arbitrary-order self-lumping discontinuous finite elements and integrated in time with arbitrary-order diagonally implicit Runge–Kutta time integration techniques. Iterative convergence of the radiation equation ismore » accelerated using a modified interior penalty diffusion operator to precondition the full discrete ordinates transport operator.« less

  4. High-order solution methods for grey discrete ordinates thermal radiative transfer

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

    Maginot, Peter G.; Ragusa, Jean C.; Morel, Jim E.

    This paper presents a solution methodology for solving the grey radiative transfer equations that is both spatially and temporally more accurate than the canonical radiative transfer solution technique of linear discontinuous finite element discretization in space with implicit Euler integration in time. We solve the grey radiative transfer equations by fully converging the nonlinear temperature dependence of the material specific heat, material opacities, and Planck function. The grey radiative transfer equations are discretized in space using arbitrary-order self-lumping discontinuous finite elements and integrated in time with arbitrary-order diagonally implicit Runge–Kutta time integration techniques. Iterative convergence of the radiation equation ismore » accelerated using a modified interior penalty diffusion operator to precondition the full discrete ordinates transport operator.« less

  5. High-order solution methods for grey discrete ordinates thermal radiative transfer

    DOE PAGES

    Maginot, Peter G.; Ragusa, Jean C.; Morel, Jim E.

    2016-09-29

    This paper presents a solution methodology for solving the grey radiative transfer equations that is both spatially and temporally more accurate than the canonical radiative transfer solution technique of linear discontinuous finite element discretization in space with implicit Euler integration in time. We solve the grey radiative transfer equations by fully converging the nonlinear temperature dependence of the material specific heat, material opacities, and Planck function. The grey radiative transfer equations are discretized in space using arbitrary-order self-lumping discontinuous finite elements and integrated in time with arbitrary-order diagonally implicit Runge–Kutta time integration techniques. Iterative convergence of the radiation equation ismore » accelerated using a modified interior penalty diffusion operator to precondition the full discrete ordinates transport operator.« less

  6. Neurophysiological evidence for transfer appropriate processing of memory: processing versus feature similarity.

    PubMed

    Schendan, Haune E; Kutas, Malra

    2007-08-01

    Transfer appropriate processing (TAP) accounts propose that memory is a function of the degree to which the same neural processes transfer appropriately from the study experience to the memory test. However, in prior research, study and test stimuli were often similar physically. In two experiments, event-related brain potentials (ERPs) were recorded to fragmented objects during an indirect memory test to isolate transfer of a specific perceptual process from overlap of physical features between experiences. An occipitotemporoparietal P2(00) at 200 msec showed implicit memory effects only when similar perceptual grouping processes of good continuation were repeatedly engaged-despite physical feature differences--as TAP accounts hypothesize. This result provides direct neurophysiological evidence for the critical role of process transfer across experiences for memory.

  7. Activating Developmental Reserve Capacity Via Cognitive Training or Non-invasive Brain Stimulation: Potentials for Promoting Fronto-Parietal and Hippocampal-Striatal Network Functions in Old Age

    PubMed Central

    Passow, Susanne; Thurm, Franka; Li, Shu-Chen

    2017-01-01

    Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate short- and long-term cognitive and brain plasticity in old age. PMID:28280465

  8. Regression of experimental medulloblastoma following transfer of HER2-specific T cells.

    PubMed

    Ahmed, Nabil; Ratnayake, Maheshika; Savoldo, Barbara; Perlaky, Laszlo; Dotti, Gianpietro; Wels, Winfried S; Bhattacharjee, Meenakshi B; Gilbertson, Richard J; Shine, H David; Weiss, Heidi L; Rooney, Cliona M; Heslop, Helen E; Gottschalk, Stephen

    2007-06-15

    Medulloblastoma is a common malignant brain tumor of childhood. Human epidermal growth factor receptor 2 (HER2) is expressed by 40% of medulloblastomas and is a risk factor for poor outcome with current aggressive multimodal therapy. In contrast to breast cancer, HER2 is expressed only at low levels in medulloblastomas, rendering monoclonal antibodies ineffective. We determined if T cells grafted with a HER2-specific chimeric antigen receptor (CAR; HER2-specific T cells) recognized and killed HER2-positive medulloblastomas. Ex vivo, stimulation of HER2-specific T cells with HER2-positive medulloblastomas resulted in T-cell proliferation and secretion of IFN-gamma and interleukin 2 (IL-2) in a HER2-dependent manner. HER2-specific T cells killed autologous HER2-positive primary medulloblastoma cells and medulloblastoma cell lines in cytotoxicity assays, whereas HER2-negative tumor cells were not killed. No functional difference was observed between HER2-specific T cells generated from medulloblastoma patients and healthy donors. In vivo, the adoptive transfer of HER2-specific T cells resulted in sustained regression of established medulloblastomas in an orthotopic, xenogenic severe combined immunodeficiency model. In contrast, delivery of nontransduced T cells did not change the tumor growth pattern. Adoptive transfer of HER2-specific T cells may represent a promising immunotherapeutic approach for medulloblastoma.

  9. Interfamily Transfer of Dual NB-LRR Genes Confers Resistance to Multiple Pathogens

    PubMed Central

    Narusaka, Mari; Kubo, Yasuyuki; Hatakeyama, Katsunori; Imamura, Jun; Ezura, Hiroshi; Nanasato, Yoshihiko; Tabei, Yutaka; Takano, Yoshitaka; Shirasu, Ken; Narusaka, Yoshihiro

    2013-01-01

    A major class of disease resistance (R) genes which encode nucleotide binding and leucine rich repeat (NB-LRR) proteins have been used in traditional breeding programs for crop protection. However, it has been difficult to functionally transfer NB-LRR-type R genes in taxonomically distinct families. Here we demonstrate that a pair of Arabidopsis (Brassicaceae) NB-LRR-type R genes, RPS4 and RRS1, properly function in two other Brassicaceae, Brassica rapa and Brassica napus, but also in two Solanaceae, Nicotiana benthamiana and tomato (Solanum lycopersicum). The solanaceous plants transformed with RPS4/RRS1 confer bacterial effector-specific immunity responses. Furthermore, RPS4 and RRS1, which confer resistance to a fungal pathogen Colletotrichum higginsianum in Brassicaceae, also protect against Colletotrichum orbiculare in cucumber (Cucurbitaceae). Importantly, RPS4/RRS1 transgenic plants show no autoimmune phenotypes, indicating that the NB-LRR proteins are tightly regulated. The successful transfer of two R genes at the family level implies that the downstream components of R genes are highly conserved. The functional interfamily transfer of R genes can be a powerful strategy for providing resistance to a broad range of pathogens. PMID:23437080

  10. Excitation energy transfer in the photosystem I

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

    Webber, Andrew N

    2012-09-25

    Photosystem I is a multimeric pigment protein complex in plants, green alage and cyanobacteria that functions in series with Photosystem II to use light energy to oxidize water and reduce carbon dioxide. The Photosystem I core complex contains 96 chlorophyll a molecules and 22 carotenoids that are involved in light harvesting and electron transfer. In eucaryotes, PSI also has a peripheral light harvesting complex I (LHCI). The role of specific chlorophylls in excitation and electron transfer are still unresolved. In particular, the role of so-called bridging chlorophylls, located between the bulk antenna and the core electron transfer chain, in themore » transfer of excitation energy to the reaction center are unknown. During the past funding period, site directed mutagenesis has been used to create mutants that effect the physical properties of these key chlorophylls, and to explore how this alters the function of the photosystem. Studying these mutants using ultrafast absorption spectroscopy has led to a better understanding of the process by which excitation energy is transferred from the antenna chlorophylls to the electron transfer chain chlorophylls, and what the role of connecting chlorophylls and A_0 chlorophylls is in this process. We have also used these mutants to investigate whch of the central group of six chlorophylls are involved in the primary steps of charge separation and electron transfer.« less

  11. Horizontal Transfers and Gene Losses in the Phospholipid Pathway of Bartonella Reveal Clues about Early Ecological Niches

    PubMed Central

    Zhu, Qiyun; Kosoy, Michael; Olival, Kevin J.; Dittmar, Katharina

    2014-01-01

    Bartonellae are mammalian pathogens vectored by blood-feeding arthropods. Although of increasing medical importance, little is known about their ecological past, and host associations are underexplored. Previous studies suggest an influence of horizontal gene transfers in ecological niche colonization by acquisition of host pathogenicity genes. We here expand these analyses to metabolic pathways of 28 Bartonella genomes, and experimentally explore the distribution of bartonellae in 21 species of blood-feeding arthropods. Across genomes, repeated gene losses and horizontal gains in the phospholipid pathway were found. The evolutionary timing of these patterns suggests functional consequences likely leading to an early intracellular lifestyle for stem bartonellae. Comparative phylogenomic analyses discover three independent lineage-specific reacquisitions of a core metabolic gene—NAD(P)H-dependent glycerol-3-phosphate dehydrogenase (gpsA)—from Gammaproteobacteria and Epsilonproteobacteria. Transferred genes are significantly closely related to invertebrate Arsenophonus-, and Serratia-like endosymbionts, and mammalian Helicobacter-like pathogens, supporting a cellular association with arthropods and mammals at the base of extant Bartonella spp. Our studies suggest that the horizontal reacquisitions had a key impact on bartonellae lineage specific ecological and functional evolution. PMID:25106622

  12. Insights into functional bacterial diversity and its effects on Alpine bog ecosystem functioning.

    PubMed

    Bragina, Anastasia; Berg, Christian; Müller, Henry; Moser, Daniel; Berg, Gabriele

    2013-01-01

    Plant-associated bacteria are important for the growth and health of their host, but little is known about its functional diversity and impact on ecosystem functioning. We studied bacterial nitrogen fixation and methane oxidation from indicator Sphagnum mosses in Alpine bogs to test a hypothesis that the plant microbiome contained different functional patterns depending on their functions within the ecosystem. A high abundance and diversity of nitrogenase genes were detected, mostly specific for each Sphagnum. In contrast, methanotrophs formed highly similar patterns despite a high abundance and diversity of methane monooxygenase genes. Our hypothesis was supported by these contrasting functional patterns together with the result that the Sphagnum sporophyte contained a high proportion of specific diazotrophs (45.5%) but no potential methanotrophs. While essential for plant growth under nutrient-limited conditions, nitrogen-fixing bacteria were highly specific and transferred with the sporophyte unlike the ubiquitous methanotrophs which are important for the climate-relevant ecosystem itself.

  13. Two-Dimensional Magnetotelluric Modelling of Ore Deposits: Improvements in Model Constraints by Inclusion of Borehole Measurements

    NASA Astrophysics Data System (ADS)

    Kalscheuer, Thomas; Juhojuntti, Niklas; Vaittinen, Katri

    2017-12-01

    A combination of magnetotelluric (MT) measurements on the surface and in boreholes (without metal casing) can be expected to enhance resolution and reduce the ambiguity in models of electrical resistivity derived from MT surface measurements alone. In order to quantify potential improvement in inversion models and to aid design of electromagnetic (EM) borehole sensors, we considered two synthetic 2D models containing ore bodies down to 3000 m depth (the first with two dipping conductors in resistive crystalline host rock and the second with three mineralisation zones in a sedimentary succession exhibiting only moderate resistivity contrasts). We computed 2D inversion models from the forward responses based on combinations of surface impedance measurements and borehole measurements such as (1) skin-effect transfer functions relating horizontal magnetic fields at depth to those on the surface, (2) vertical magnetic transfer functions relating vertical magnetic fields at depth to horizontal magnetic fields on the surface and (3) vertical electric transfer functions relating vertical electric fields at depth to horizontal magnetic fields on the surface. Whereas skin-effect transfer functions are sensitive to the resistivity of the background medium and 2D anomalies, the vertical magnetic and electric field transfer functions have the disadvantage that they are comparatively insensitive to the resistivity of the layered background medium. This insensitivity introduces convergence problems in the inversion of data from structures with strong 2D resistivity contrasts. Hence, we adjusted the inversion approach to a three-step procedure, where (1) an initial inversion model is computed from surface impedance measurements, (2) this inversion model from surface impedances is used as the initial model for a joint inversion of surface impedances and skin-effect transfer functions and (3) the joint inversion model derived from the surface impedances and skin-effect transfer functions is used as the initial model for the inversion of the surface impedances, skin-effect transfer functions and vertical magnetic and electric transfer functions. For both synthetic examples, the inversion models resulting from surface and borehole measurements have higher similarity to the true models than models computed exclusively from surface measurements. However, the most prominent improvements were obtained for the first example, in which a deep small-sized ore body is more easily distinguished from a shallow main ore body penetrated by a borehole and the extent of the shadow zone (a conductive artefact) underneath the main conductor is strongly reduced. Formal model error and resolution analysis demonstrated that predominantly the skin-effect transfer functions improve model resolution at depth below the sensors and at distance of ˜ 300-1000 m laterally off a borehole, whereas the vertical electric and magnetic transfer functions improve resolution along the borehole and in its immediate vicinity. Furthermore, we studied the signal levels at depth and provided specifications of borehole magnetic and electric field sensors to be developed in a future project. Our results suggest that three-component SQUID and fluxgate magnetometers should be developed to facilitate borehole MT measurements at signal frequencies above and below 1 Hz, respectively.

  14. Relationships between the decoupled and coupled transfer functions: Theoretical studies and experimental validation

    NASA Astrophysics Data System (ADS)

    Wang, Zengwei; Zhu, Ping; Liu, Zhao

    2018-01-01

    A generalized method for predicting the decoupled transfer functions based on in-situ transfer functions is proposed. The method allows predicting the decoupled transfer functions using coupled transfer functions, without disassembling the system. Two ways to derive relationships between the decoupled and coupled transfer functions are presented. Issues related to immeasurability of coupled transfer functions are also discussed. The proposed method is validated by numerical and experimental case studies.

  15. In vivo programming of tumor antigen-specific T lymphocytes from pluripotent stem cells to promote cancer immunosurveillance.

    PubMed

    Lei, Fengyang; Zhao, Baohua; Haque, Rizwanul; Xiong, Xiaofang; Budgeon, Lynn; Christensen, Neil D; Wu, Yuzhang; Song, Jianxun

    2011-07-15

    Adoptive T-cell immunotherapy has garnered wide attention, but its effective use is limited by the need of multiple ex vivo manipulations and infusions that are complex and expensive. In this study, we show how highly reactive antigen (Ag)-specific CTLs can be generated from induced pluripotent stem (iPS) cells to provide an unlimited source of functional CTLs for adoptive immunotherapy. iPS cell-derived T cells can offer the advantages of avoiding possible immune rejection and circumventing ethical and practical issues associated with other stem cell types. iPS cells can be differentiated into progenitor T cells in vitro by stimulation with the Notch ligand Delta-like 1 (DL1) overexpressed on bone marrow stromal cells, with complete maturation occurring upon adoptive transfer into Rag1-deficient mice. Here, we report that these iPS cells can be differentiated in vivo into functional CTLs after overexpression of MHC I-restricted Ag-specific T-cell receptors (TCR). In this study, we generated murine iPS cells genetically modified with ovalbumin (OVA)-specific and MHC-I restricted TCR (OT-I) by retrovirus-mediated transduction. After their adoptive transfer into recipient mice, the majority of OT-I/iPS cells underwent differentiation into CD8+ CTLs. TCR-transduced iPS cells developed in vivo responded in vitro to peptide stimulation by secreting interleukin 2 and IFN-γ. Most importantly, adoptive transfer of TCR-transduced iPS cells triggered infiltration of OVA-reactive CTLs into tumor tissues and protected animals from tumor challenge. Taken together, our findings offer proof of concept for a potentially more efficient approach to generate Ag-specific T lymphocytes for adoptive immunotherapy. ©2011 AACR.

  16. Differences in perceptual learning transfer as a function of training task.

    PubMed

    Green, C Shawn; Kattner, Florian; Siegel, Max H; Kersten, Daniel; Schrater, Paul R

    2015-01-01

    A growing body of research--including results from behavioral psychology, human structural and functional imaging, single-cell recordings in nonhuman primates, and computational modeling--suggests that perceptual learning effects are best understood as a change in the ability of higher-level integration or association areas to read out sensory information in the service of particular decisions. Work in this vein has argued that, depending on the training experience, the "rules" for this read-out can either be applicable to new contexts (thus engendering learning generalization) or can apply only to the exact training context (thus resulting in learning specificity). Here we contrast learning tasks designed to promote either stimulus-specific or stimulus-general rules. Specifically, we compare learning transfer across visual orientation following training on three different tasks: an orientation categorization task (which permits an orientation-specific learning solution), an orientation estimation task (which requires an orientation-general learning solution), and an orientation categorization task in which the relevant category boundary shifts on every trial (which lies somewhere between the two tasks above). While the simple orientation-categorization training task resulted in orientation-specific learning, the estimation and moving categorization tasks resulted in significant orientation learning generalization. The general framework tested here--that task specificity or generality can be predicted via an examination of the optimal learning solution--may be useful in building future training paradigms with certain desired outcomes.

  17. WLCG Transfers Dashboard: a Unified Monitoring Tool for Heterogeneous Data Transfers

    NASA Astrophysics Data System (ADS)

    Andreeva, J.; Beche, A.; Belov, S.; Kadochnikov, I.; Saiz, P.; Tuckett, D.

    2014-06-01

    The Worldwide LHC Computing Grid provides resources for the four main virtual organizations. Along with data processing, data distribution is the key computing activity on the WLCG infrastructure. The scale of this activity is very large, the ATLAS virtual organization (VO) alone generates and distributes more than 40 PB of data in 100 million files per year. Another challenge is the heterogeneity of data transfer technologies. Currently there are two main alternatives for data transfers on the WLCG: File Transfer Service and XRootD protocol. Each LHC VO has its own monitoring system which is limited to the scope of that particular VO. There is a need for a global system which would provide a complete cross-VO and cross-technology picture of all WLCG data transfers. We present a unified monitoring tool - WLCG Transfers Dashboard - where all the VOs and technologies coexist and are monitored together. The scale of the activity and the heterogeneity of the system raise a number of technical challenges. Each technology comes with its own monitoring specificities and some of the VOs use several of these technologies. This paper describes the implementation of the system with particular focus on the design principles applied to ensure the necessary scalability and performance, and to easily integrate any new technology providing additional functionality which might be specific to that technology.

  18. Evaluation of Hose in Hose Transfer Line Service Life for Hanfords Interim Stabilization Program

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

    TORRES, T.D.

    RPP-6153, Engineering Task Plan for Hose-in-Hose Transfer System for the Interim Stabilization Program (Torres, 2000a), defines the programmatic goals, functional requirements, and technical criteria for the development and subsequent installation of waste transfer line equipment to support Hanford's Interim Stabilization Program. RPP-6028, Specification for Hose in Hose Transfer Lines for Hanford's Interim Stabilization Program (Torres, 2000b), has been issued to define the specific requirements for the design, manufacture, and verification of transfer line assemblies for specific waste transfer applications associated with Interim Stabilization. Included in RPP-6028 are tables defining the chemical constituents of concern to which transfer lines will bemore » exposed. Current Interim Stabilization Program planning forecasts that the at-grade transfer lines will be required to convey pumpable waste for as much as three years after commissioning, RPP-6028 Section 3.2.7. Performance Incentive Number ORP-05 requires that all the Single Shell Tanks be Interim Stabilized by September 30, 2003. The Tri-Party Agreement (TPA) milestone M-41-00, enforced by a federal consent decree, requires all the Single Shell Tanks to be Interim stabilized by September 30, 2004. By meeting the Performance Incentive the TPA milestone is met. Prudent engineering dictates that the equipment used to transfer waste have a life in excess of the forecasted operational time period, with some margin to allow for future adjustments to the planned schedule. This document evaluates the effective service life of the Hose-in-Hose Transfer Lines, based on information submitted by the manufacturer, published literature and calculations. The effective service life of transfer line assemblies is a function of several factors. Foremost among these are the hose material's resistance to the harmful effects of process fluid characteristics, ambient environmental conditions, exposure to ionizing radiation and the manufacturer's stated shelf life. In order to determine the transfer line service life this evaluation examines the certification of shelf life, the certification of chemical compatibility with waste, catalog information of ambient ratings and published literature on the effects of exposure to ionizing radiation on the mechanical properties of elastomeric materials. During initial hose procurements, the hose-in-hose transfer line vendor River Bend Hose Specialty (RBHS) submitted a letter, dated 6/8/00, which recommended the service and shelf life of the hose to be seven years. In submittals for later hose procurements, RBHS submitted a letter, dated 11/6/00, which recommended the service life of the hose to be three years. This submittal was followed by documentation, on 2/14/01, which submitted new storage requirements and restated the seven year shelf life. RBHS revised their original hose service life estimate to a more conservative three years due to concerns over the effects of chemicals in transferred waste. The above mentioned submittals from RBHS are the primary drivers of the three year service life limit established by this document.« less

  19. Development of endosperm transfer cells in barley.

    PubMed

    Thiel, Johannes

    2014-01-01

    Endosperm transfer cells (ETCs) are positioned at the intersection of maternal and filial tissues in seeds of cereals and represent a bottleneck for apoplasmic transport of assimilates into the endosperm. Endosperm cellularization starts at the maternal-filial boundary and generates the highly specialized ETCs. During differentiation barley ETCs develop characteristic flange-like wall ingrowths to facilitate effective nutrient transfer. A comprehensive morphological analysis depicted distinct developmental time points in establishment of transfer cell (TC) morphology and revealed intracellular changes possibly associated with cell wall metabolism. Embedded inside the grain, ETCs are barely accessible by manual preparation. To get tissue-specific information about ETC specification and differentiation, laser microdissection (LM)-based methods were used for transcript and metabolite profiling. Transcriptome analysis of ETCs at different developmental stages by microarrays indicated activated gene expression programs related to control of cell proliferation and cell shape, cell wall and carbohydrate metabolism reflecting the morphological changes during early ETC development. Transporter genes reveal distinct expression patterns suggesting a switch from active to passive modes of nutrient uptake with the onset of grain filling. Tissue-specific RNA-seq of the differentiating ETC region from the syncytial stage until functionality in nutrient transfer identified a high number of novel transcripts putatively involved in ETC differentiation. An essential role for two-component signaling (TCS) pathways in ETC development of barley emerged from this analysis. Correlative data provide evidence for abscisic acid and ethylene influences on ETC differentiation and hint at a crosstalk between hormone signal transduction and TCS phosphorelays. Collectively, the data expose a comprehensive view on ETC development, associated pathways and identified candidate genes for ETC specification.

  20. Development of endosperm transfer cells in barley

    PubMed Central

    Thiel, Johannes

    2014-01-01

    Endosperm transfer cells (ETCs) are positioned at the intersection of maternal and filial tissues in seeds of cereals and represent a bottleneck for apoplasmic transport of assimilates into the endosperm. Endosperm cellularization starts at the maternal-filial boundary and generates the highly specialized ETCs. During differentiation barley ETCs develop characteristic flange-like wall ingrowths to facilitate effective nutrient transfer. A comprehensive morphological analysis depicted distinct developmental time points in establishment of transfer cell (TC) morphology and revealed intracellular changes possibly associated with cell wall metabolism. Embedded inside the grain, ETCs are barely accessible by manual preparation. To get tissue-specific information about ETC specification and differentiation, laser microdissection (LM)-based methods were used for transcript and metabolite profiling. Transcriptome analysis of ETCs at different developmental stages by microarrays indicated activated gene expression programs related to control of cell proliferation and cell shape, cell wall and carbohydrate metabolism reflecting the morphological changes during early ETC development. Transporter genes reveal distinct expression patterns suggesting a switch from active to passive modes of nutrient uptake with the onset of grain filling. Tissue-specific RNA-seq of the differentiating ETC region from the syncytial stage until functionality in nutrient transfer identified a high number of novel transcripts putatively involved in ETC differentiation. An essential role for two-component signaling (TCS) pathways in ETC development of barley emerged from this analysis. Correlative data provide evidence for abscisic acid and ethylene influences on ETC differentiation and hint at a crosstalk between hormone signal transduction and TCS phosphorelays. Collectively, the data expose a comprehensive view on ETC development, associated pathways and identified candidate genes for ETC specification. PMID:24723929

  1. 78 FR 42089 - Statement of Organization, Functions and Delegations of Authority

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-15

    ... related to external media relations and internal employee communications including those for the..., visual, and multimedia activities in support of communications efforts through multiple media formats... of Communications and the Office of Management. Specifically, this notice: (1) Transfers the Freedom...

  2. Long-term effects of transference interpretation in dynamic psychotherapy of personality disorders.

    PubMed

    Høglend, P; Dahl, H-S; Hersoug, A G; Lorentzen, S; Perry, J C

    2011-10-01

    Only a few treatment studies of personality disorders (PD) patients are on longer-term psychotherapy, general outcome measures are used, and follow-up periods are usually short. More studies of long-term therapies, using outcome measures of core psychopathology, are needed. This study is a dismantling randomized controlled clinical trial, specifically designed to study long-term effects of transference interpretation. Forty-six patients with mainly cluster C personality disorders were randomly assigned to 1 year of dynamic psychotherapy with or without transference interpretations. The outcome measures were remission from PD, improvement in interpersonal functioning, and use of mental health resources in the 3-year period after treatment termination. After therapy with transference interpretation PD-patients improved significantly more in core psychopathology and interpersonal functioning, the drop-out rate was reduced to zero, and use of health services was reduced to 50%, compared to therapy without this ingredient. Three years after treatment termination, 73% no longer met diagnostic criteria for any PD in the transference group, compared to 44% in the comparison group. PD-patients with co-morbid disorders improved in both treatment arms in this study. However, transference interpretation improved outcome substantially more. Long-term psychotherapy that includes transference interpretation is an effective treatment for cluster C personality disorders and milder cluster B personality disorders. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  3. Identification and characterization of an oocyte factor required for development of porcine nuclear transfer embryos

    PubMed Central

    Miyamoto, Kei; Nagai, Kouhei; Kitamura, Naoya; Nishikawa, Tomoaki; Ikegami, Haruka; Binh, Nguyen T.; Tsukamoto, Satoshi; Matsumoto, Mai; Tsukiyama, Tomoyuki; Minami, Naojiro; Yamada, Masayasu; Ariga, Hiroyoshi; Miyake, Masashi; Kawarasaki, Tatsuo; Matsumoto, Kazuya; Imai, Hiroshi

    2011-01-01

    Nuclear reprogramming of differentiated cells can be induced by oocyte factors. Despite numerous attempts, these factors and mechanisms responsible for successful reprogramming remain elusive. Here, we identify one such factor, necessary for the development of nuclear transfer embryos, using porcine oocyte extracts in which some reprogramming events are recapitulated. After incubating somatic nuclei in oocyte extracts from the metaphase II stage, the oocyte proteins that were specifically and abundantly incorporated into the nuclei were identified by mass spectrometry. Among 25 identified proteins, we especially focused on a multifunctional protein, DJ-1. DJ-1 is present at a high concentration in oocytes from the germinal vesicle stage until embryos at the four-cell stage. Inhibition of DJ-1 function compromises the development of nuclear transfer embryos but not that of fertilized embryos. Microarray analysis of nuclear transfer embryos in which DJ-1 function is inhibited shows perturbed expression of P53 pathway components. In addition, embryonic arrest of nuclear transfer embryos injected with anti–DJ-1 antibody is rescued by P53 inhibition. We conclude that DJ-1 is an oocyte factor that is required for development of nuclear transfer embryos. This study presents a means for identifying natural reprogramming factors in mammalian oocytes and a unique insight into the mechanisms underlying reprogramming by nuclear transfer. PMID:21482765

  4. Implications of Mycobacterium Major Facilitator Superfamily for Novel Measures against Tuberculosis.

    PubMed

    Wang, Rui; Zhang, Zhen; Xie, Longxiang; Xie, Jianping

    2015-01-01

    Major facilitator superfamily (MFS) is an important secondary membrane transport protein superfamily conserved from prokaryotes to eukaryotes. The MFS proteins are widespread among bacteria and are responsible for the transfer of substrates. Pathogenic Mycobacterium MFS transporters, their distribution, function, phylogeny, and predicted crystal structures were studied to better understand the function of MFS and to discover specific inhibitors of MFS for better tuberculosis control.

  5. Characterization of adaptive statistical iterative reconstruction (ASIR) in low contrast helical abdominal imaging via a transfer function based method

    NASA Astrophysics Data System (ADS)

    Zhang, Da; Li, Xinhua; Liu, Bob

    2012-03-01

    Since the introduction of ASiR, its potential in noise reduction has been reported in various clinical applications. However, the influence of different scan and reconstruction parameters on the trade off between ASiR's blurring effect and noise reduction in low contrast imaging has not been fully studied. Simple measurements on low contrast images, such as CNR or phantom scores could not explore the nuance nature of this problem. We tackled this topic using a method which compares the performance of ASiR in low contrast helical imaging based on an assumed filter layer on top of the FBP reconstruction. Transfer functions of this filter layer were obtained from the noise power spectra (NPS) of corresponding FBP and ASiR images that share the same scan and reconstruction parameters. 2D transfer functions were calculated as sqrt[NPSASiR(u, v)/NPSFBP(u, v)]. Synthesized ACR phantom images were generated by filtering the FBP images with the transfer functions of specific (FBP, ASiR) pairs, and were compared with the ASiR images. It is shown that the transfer functions could predict the deterministic blurring effect of ASiR on low contrast objects, as well as the degree of noise reductions. Using this method, the influence of dose, scan field of view (SFOV), display field of view (DFOV), ASiR level, and Recon Mode on the behavior of ASiR in low contrast imaging was studied. It was found that ASiR level, dose level, and DFOV play more important roles in determining the behavior of ASiR than the other two parameters.

  6. Short-term perceptual learning in visual conjunction search.

    PubMed

    Su, Yuling; Lai, Yunpeng; Huang, Wanyi; Tan, Wei; Qu, Zhe; Ding, Yulong

    2014-08-01

    Although some studies showed that training can improve the ability of cross-dimension conjunction search, less is known about the underlying mechanism. Specifically, it remains unclear whether training of visual conjunction search can successfully bind different features of separated dimensions into a new function unit at early stages of visual processing. In the present study, we utilized stimulus specificity and generalization to provide a new approach to investigate the mechanisms underlying perceptual learning (PL) in visual conjunction search. Five experiments consistently showed that after 40 to 50 min of training of color-shape/orientation conjunction search, the ability to search for a certain conjunction target improved significantly and the learning effects did not transfer to a new target that differed from the trained target in both color and shape/orientation features. However, the learning effects were not strictly specific. In color-shape conjunction search, although the learning effect could not transfer to a same-shape different-color target, it almost completely transferred to a same-color different-shape target. In color-orientation conjunction search, the learning effect partly transferred to a new target that shared same color or same orientation with the trained target. Moreover, the sum of transfer effects for the same color target and the same orientation target in color-orientation conjunction search was algebraically equivalent to the learning effect for trained target, showing an additive transfer effect. The different transfer patterns in color-shape and color-orientation conjunction search learning might reflect the different complexity and discriminability between feature dimensions. These results suggested a feature-based attention enhancement mechanism rather than a unitization mechanism underlying the short-term PL of color-shape/orientation conjunction search.

  7. Is the self a higher-order or fundamental function of the brain? The "basis model of self-specificity" and its encoding by the brain's spontaneous activity.

    PubMed

    Northoff, Georg

    2016-01-01

    What is the self? This is a question that has long been discussed in (Western) philosophy where the self is traditionally conceived a higher-order function at the apex or pinnacle of all functions. This tradition has been transferred to recent neuroscience where the self is often considered to be a higher-order cognitive function reflected in memory and other high-level judgements. However, other lines of research demonstrate a close and intimate relationship between self-specificity and more basic functions like perceptions, emotions and reward. This paper focuses on the relationship between self-specificity and other basic functions relating to emotions, reward and perception. I propose the basis model that conceives self-specificity as a fundamental feature of the brain's spontaneous activity. This is supported by recent findings showing rest-self overlap in midline regions as well as findings demonstrating that the resting state can predict subsequent degrees of self-specificity. I conclude that such self-specificity in the brain's spontaneous activity may be central in linking the self to either internal or external stimuli. This may also provide the basis for coding the self as subject in relation to internal (i.e., self-consciousness) or external (i.e., phenomenal consciousness) mental events.

  8. Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells

    PubMed Central

    Herrmann, Andreas; Kortylewski, Marcin; Kujawski, Maciej; Zhang, Chunyan; Reckamp, Karen; Armstrong, Brian; Wang, Lin; Kowolik, Claudia; Deng, Jiehui; Robert, Figlin; Yu, Hua

    2010-01-01

    Improving effector T cell functions is highly desirable for preventive or therapeutic interventions of diverse diseases. Stat3 in the myeloid compartment constrains Th-1 type immunity, dampening natural and induced antitumor immune responses. We have recently developed an in vivo siRNA delivery platform by conjugating a TLR9 agonist with siRNA that efficiently targets myeloid and B cells. Here we show that either ablating the Stat3 alleles in the myeloid compartment and B cells combined with CpG triggering or administrating the CpG-Stat3siRNA conjugates drastically augments effector functions of adoptively transferred CD8+ T cells. Specifically, we demonstrate that both approaches are capable of increasing dendritic cell and CD8+ T cell engagement in tumor draining lymph nodes. Furthermore, both approaches can significantly activate the transferred CD8+ T cells in vivo, upregulating effector molecules such as perforin, granzyme B and IFN-γ. Intravital multiphoton microscopy reveals that Stat3 silencing combined with CpG triggering greatly increases killing activity and tumor infiltration of transferred T cells. These results suggest the use of CpG-Stat3siRNA, and possibly other Stat3 inhibitors, as a potent adjuvant to improve T cell therapies. PMID:20841481

  9. [Nuclear transfer and therapeutic cloning].

    PubMed

    Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

    2005-03-01

    Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

  10. Hydroxide diffuses slower than hydronium in water because its solvated structure inhibits correlated proton transfer

    NASA Astrophysics Data System (ADS)

    Chen, Mohan; Zheng, Lixin; Santra, Biswajit; Ko, Hsin-Yu; DiStasio, Robert A., Jr.; Klein, Michael L.; Car, Roberto; Wu, Xifan

    2018-03-01

    Proton transfer via hydronium and hydroxide ions in water is ubiquitous. It underlies acid-base chemistry, certain enzyme reactions, and even infection by the flu. Despite two centuries of investigation, the mechanism underlying why hydroxide diffuses slower than hydronium in water is still not well understood. Herein, we employ state-of-the-art density-functional-theory-based molecular dynamics—with corrections for non-local van der Waals interactions, and self-interaction in the electronic ground state—to model water and hydrated water ions. At this level of theory, we show that structural diffusion of hydronium preserves the previously recognized concerted behaviour. However, by contrast, proton transfer via hydroxide is less temporally correlated, due to a stabilized hypercoordination solvation structure that discourages proton transfer. Specifically, the latter exhibits non-planar geometry, which agrees with neutron-scattering results. Asymmetry in the temporal correlation of proton transfer leads to hydroxide diffusing slower than hydronium.

  11. SXT/R391 Integrative and Conjugative Elements (ICEs) Encode a Novel 'Trap-Door' Strategy for Mobile Element Escape.

    PubMed

    Ryan, Michael P; Armshaw, Patricia; Pembroke, J Tony

    2016-01-01

    Integrative conjugative elements (ICEs) are a class of bacterial mobile elements that have the ability to mediate their own integration, excision, and transfer from one host genome to another by a mechanism of site-specific recombination, self-circularisation, and conjugative transfer. Members of the SXT/R391 ICE family of enterobacterial mobile genetic elements display an unusual UV-inducible sensitization function which results in stress induced killing of bacterial cells harboring the ICE. This sensitization has been shown to be associated with a stress induced overexpression of a mobile element encoded conjugative transfer gene, orf43, a traV homolog. This results in cell lysis and release of a circular form of the ICE. Induction of this novel system may allow transfer of an ICE, enhancing its survival potential under conditions not conducive to conjugative transfer.

  12. Interluekin-12 enhances the function and anti-tumor activity in murine and human CD8+ T cells

    PubMed Central

    Rubinstein, Mark P.; Su, Ee Wern; Suriano, Samantha; Cloud, Colleen A.; Andrijauskaite, Kristina; Kesarwani, Pravin; Schwartz, Kristina M.; Williams, Katelyn; Johnson, C. Bryce; Li, Mingli; Scurti, Gina M.; Salem, Mohamed L.; Paulos, Chrystal M.; Garrett-Mayer, Elizabeth; Mehrotra, Shikhar; Cole, David J.

    2016-01-01

    Mouse CD8+ T cells conditioned with Interleukin (IL)-12 ex vivo mediate the potent regression of established melanoma when transferred into lymphodepleted mice. However, the quantitative and qualitative changes induced by IL-12 in the responding mouse CD8+ T cells have not been well defined. Moreover, the mechanisms by which IL-12-conditioning impacts human CD8+ T cells, and how such cells might be expanded prior to infusion into patients is not known. We found that ex vivo IL-12-conditioning of mouse CD8+ T cells led to a 10- to 100-fold increase in persistence and anti-tumor efficacy upon adoptive transfer into lymphodepleted mice. The enhancing effect of IL-12 was associated with maintenance of functional avidity. Importantly, in the context of ongoing ACT clinical trials, human CD8+ T cells genetically modified with a tyrosinase-specific T-cell receptor exhibited significantly enhanced functional activity when conditioned with IL-12 as indicated by heightened granzyme B expression and elevated peptide-specific CD107a degranulation. This effect was sustainable despite the 20 days of in vitro cellular expansion required to expand cells over 1,000-fold allowing adequate cell numbers for administration to cancer patients. Overall, these findings support the efficacy and feasibility of ex vivo IL-12-conditioning of TCR-modified human CD8+ T cells for adoptive transfer and cancer therapy. PMID:25676709

  13. The mechanism and control of DNA transfer by the conjugative relaxase of resistance plasmid pCU1

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

    Nash, Rebekah Potts; Habibi, Sohrab; Cheng, Yuan

    2010-11-15

    Bacteria expand their genetic diversity, spread antibiotic resistance genes, and obtain virulence factors through the highly coordinated process of conjugative plasmid transfer (CPT). A plasmid-encoded relaxase enzyme initiates and terminates CPT by nicking and religating the transferred plasmid in a sequence-specific manner. We solved the 2.3 {angstrom} crystal structure of the relaxase responsible for the spread of the resistance plasmid pCU1 and determined its DNA binding and nicking capabilities. The overall fold of the pCU1 relaxase is similar to that of the F plasmid and plasmid R388 relaxases. However, in the pCU1 structure, the conserved tyrosine residues (Y18,19,26,27) that aremore » required for DNA nicking and religation were displaced up to 14 {angstrom} out of the relaxase active site, revealing a high degree of mobility in this region of the enzyme. In spite of this flexibility, the tyrosines still cleaved the nic site of the plasmid's origin of transfer, and did so in a sequence-specific, metal-dependent manner. Unexpectedly, the pCU1 relaxase lacked the sequence-specific DNA binding previously reported for the homologous F and R388 relaxase enzymes, despite its high sequence and structural similarity with both proteins. In summary, our work outlines novel structural and functional aspects of the relaxase-mediated conjugative transfer of plasmid pCU1.« less

  14. Dynamic analysis of patterns of renal sympathetic nerve activity: implications for renal function.

    PubMed

    DiBona, Gerald F

    2005-03-01

    Methods of dynamic analysis are used to provide additional understanding of the renal sympathetic neural control of renal function. The concept of functionally specific subgroups of renal sympathetic nerve fibres conveying information encoded in the frequency domain is presented. Analog pulse modulation and pseudorandom binary sequence stimulation patterns are used for the determination of renal vascular frequency response. Transfer function analysis is used to determine the effects of non-renal vasoconstrictor and vasoconstrictor intensities of renal sympathetic nerve activity on dynamic autoregulation of renal blood flow.

  15. Electrical resistance behavior of oxyfluorinated graphene under oxidizing and reducing gas exposure.

    PubMed

    Im, Ji Sun; Bae, Tae-Sung; Shin, Eunjeong; Lee, Young-Seak

    2014-03-01

    The electrical resistance behavior of graphene was studied under oxidizing and reducing gas exposure. The graphene surface was modified via oxyfluorination to obtain a specific surface area and oxygen functional groups. Fluorine radicals provided improved pore structure and introduction of an oxygen functional group. A high-performance gas sensor was obtained based on enlarged target gas adsorption sites and an enhanced electron charge transfer between the target gas and carbon surface via improved pore structure and the introduction of oxygen functional groups, respectively.

  16. A maize resistance gene functions against bacterial streak disease in rice

    PubMed Central

    Zhao, Bingyu; Lin, Xinghua; Poland, Jesse; Trick, Harold; Leach, Jan; Hulbert, Scot

    2005-01-01

    Although cereal crops all belong to the grass family (Poacea), most of their diseases are specific to a particular species. Thus, a given cereal species is typically resistant to diseases of other grasses, and this nonhost resistance is generally stable. To determine the feasibility of transferring nonhost resistance genes (R genes) between distantly related grasses to control specific diseases, we identified a maize R gene that recognizes a rice pathogen, Xanthomonas oryzae pv. oryzicola, which causes bacterial streak disease. Bacterial streak is an important disease of rice in Asia, and no simply inherited sources of resistance have been identified in rice. Although X. o. pv. oryzicola does not cause disease on maize, we identified a maize gene, Rxo1, that conditions a resistance reaction to a diverse collection of pathogen strains. Surprisingly, Rxo1 also controls resistance to the unrelated pathogen Burkholderia andropogonis, which causes bacterial stripe of sorghum and maize. The same gene thus controls resistance reactions to both pathogens and nonpathogens of maize. Rxo1 has a nucleotide-binding site-leucine-rich repeat structure, similar to many previously identified R genes. Most importantly, Rxo1 functions after transfer as a transgene to rice, demonstrating the feasibility of nonhost R gene transfer between cereals and providing a valuable tool for controlling bacterial streak disease. PMID:16230639

  17. A maize resistance gene functions against bacterial streak disease in rice.

    PubMed

    Zhao, Bingyu; Lin, Xinghua; Poland, Jesse; Trick, Harold; Leach, Jan; Hulbert, Scot

    2005-10-25

    Although cereal crops all belong to the grass family (Poacea), most of their diseases are specific to a particular species. Thus, a given cereal species is typically resistant to diseases of other grasses, and this nonhost resistance is generally stable. To determine the feasibility of transferring nonhost resistance genes (R genes) between distantly related grasses to control specific diseases, we identified a maize R gene that recognizes a rice pathogen, Xanthomonas oryzae pv. oryzicola, which causes bacterial streak disease. Bacterial streak is an important disease of rice in Asia, and no simply inherited sources of resistance have been identified in rice. Although X. o. pv. oryzicola does not cause disease on maize, we identified a maize gene, Rxo1, that conditions a resistance reaction to a diverse collection of pathogen strains. Surprisingly, Rxo1 also controls resistance to the unrelated pathogen Burkholderia andropogonis, which causes bacterial stripe of sorghum and maize. The same gene thus controls resistance reactions to both pathogens and nonpathogens of maize. Rxo1 has a nucleotide-binding site-leucine-rich repeat structure, similar to many previously identified R genes. Most importantly, Rxo1 functions after transfer as a transgene to rice, demonstrating the feasibility of nonhost R gene transfer between cereals and providing a valuable tool for controlling bacterial streak disease.

  18. Concentration specific and tunable photoresponse of bismuth vanadate functionalized hexagonal ZnO nanocrystals based photoanodes for photoelectrochemical application

    NASA Astrophysics Data System (ADS)

    Singh, Sonal; Ruhela, Aakansha; Rani, Sanju; Khanuja, Manika; Sharma, Rishabh

    2018-02-01

    In the present work, dual layer BiVO4/ZnO photoanode is instigated for photo-electrochemical (PEC) water splitting applications. Two different photocatalytic layers ZnO and BiVO4, reduces charge carrier recombination and charge transfer resistance at photoanode/electrolyte junction. The concentration-specific, tunable and without 'spike and overshoot' features, photocurrent density response is originated by varying BiVO4 concentration in the BiVO4/ZnO photoanode. The crystal structure of ZnO (hexagonal wurtzite structure) and BiVO4 (monoclinic scheelite structure) is confirmed by X-ray diffraction studies. The band gap of BiVO4/ZnO was estimated to be ca. 2.42 eV through Kubler-Munk function F(R∞) using diffuse reflectance spectroscopy. Electrochemical behavior of samples was analyzed with photocurrent measurements, electrochemical impedance, Mott-Schottky plots, bulk separation efficiency and surface transfer efficiency. The maximum photocurrent density of BiVO4/ZnO photoanode was found to be 2.3 times higher than pristine ZnO sample.0.038 M BiVO4/ZnO exhibited the highest separation efficiency of 72% and surface transfer efficiency of 64.7% at +1.23 V vs. RHE. Mott-Schottky study revealed the maximum charge carrier density in the same sample.

  19. Shifts of Gamma Phase across Primary Visual Cortical Sites Reflect Dynamic Stimulus-Modulated Information Transfer.

    PubMed

    Besserve, Michel; Lowe, Scott C; Logothetis, Nikos K; Schölkopf, Bernhard; Panzeri, Stefano

    2015-01-01

    Distributed neural processing likely entails the capability of networks to reconfigure dynamically the directionality and strength of their functional connections. Yet, the neural mechanisms that may allow such dynamic routing of the information flow are not yet fully understood. We investigated the role of gamma band (50-80 Hz) oscillations in transient modulations of communication among neural populations by using measures of direction-specific causal information transfer. We found that the local phase of gamma-band rhythmic activity exerted a stimulus-modulated and spatially-asymmetric directed effect on the firing rate of spatially separated populations within the primary visual cortex. The relationships between gamma phases at different sites (phase shifts) could be described as a stimulus-modulated gamma-band wave propagating along the spatial directions with the largest information transfer. We observed transient stimulus-related changes in the spatial configuration of phases (compatible with changes in direction of gamma wave propagation) accompanied by a relative increase of the amount of information flowing along the instantaneous direction of the gamma wave. These effects were specific to the gamma-band and suggest that the time-varying relationships between gamma phases at different locations mark, and possibly causally mediate, the dynamic reconfiguration of functional connections.

  20. Shifts of Gamma Phase across Primary Visual Cortical Sites Reflect Dynamic Stimulus-Modulated Information Transfer

    PubMed Central

    Besserve, Michel; Lowe, Scott C.; Logothetis, Nikos K.; Schölkopf, Bernhard; Panzeri, Stefano

    2015-01-01

    Distributed neural processing likely entails the capability of networks to reconfigure dynamically the directionality and strength of their functional connections. Yet, the neural mechanisms that may allow such dynamic routing of the information flow are not yet fully understood. We investigated the role of gamma band (50–80 Hz) oscillations in transient modulations of communication among neural populations by using measures of direction-specific causal information transfer. We found that the local phase of gamma-band rhythmic activity exerted a stimulus-modulated and spatially-asymmetric directed effect on the firing rate of spatially separated populations within the primary visual cortex. The relationships between gamma phases at different sites (phase shifts) could be described as a stimulus-modulated gamma-band wave propagating along the spatial directions with the largest information transfer. We observed transient stimulus-related changes in the spatial configuration of phases (compatible with changes in direction of gamma wave propagation) accompanied by a relative increase of the amount of information flowing along the instantaneous direction of the gamma wave. These effects were specific to the gamma-band and suggest that the time-varying relationships between gamma phases at different locations mark, and possibly causally mediate, the dynamic reconfiguration of functional connections. PMID:26394205

  1. Influence of the type of training task on intermanual transfer effects in upper-limb prosthesis training: A randomized pre-posttest study.

    PubMed

    Romkema, Sietske; Bongers, Raoul M; van der Sluis, Corry K

    2017-01-01

    Intermanual transfer, the transfer of motor skills from the trained hand to the untrained hand, can be used to train upper limb prosthesis skills. The aim of this study was to determine the relation between the magnitude of the intermanual transfer effect and the type of training task. The used tasks were based on different aspects of prosthetic handling: reaching, grasping, grip-force production and functional tasks. A single-blinded clinical trial, with a pre-posttest design was executed. Seventy-one able-bodied, right-handed participants were randomly assigned to four training and two control groups. The training groups performed a training program with an upper-limb prosthesis simulator. One control group performed a sham training (a dummy training without the prosthesis simulator) and another control group received no training at all. The training groups and sham group trained on five consecutive days. To determine the improvement in skills, a test was administered before, immediately after, and one week after the training. Training was performed with the 'unaffected' arm; tests were performed with the 'affected' arm, with the latter resembling the amputated limb. In this study half of the participants trained with the dominant hand, while the other half trained with the non-dominant hand. Participants executed four tests that corresponded to the different training tasks. The tests measured the reaching (movement time and symmetry ratio), grasping (opening time, duration of maximum hand opening, and closing time), grip-force production (deviation of asked grip-force) and functional (movement time) performance. Half of the participants were tested with their dominant arm and half of the participants with their non-dominant arm. Intermanual transfer effects were not found for reaching, grasping or functional tasks. However, we did find intermanual transfer effects for grip-force production tasks. Possibly, the study design contributed to the negative results due to the duration of the training sessions and test sessions. The positive results of the grip-force production might be an effect of the specificity of the training, that was totally focused on training grip-force production. When using intermanual transfer training in novice amputees, specific training should be devoted to grip-force.

  2. Influence of the type of training task on intermanual transfer effects in upper-limb prosthesis training: A randomized pre-posttest study

    PubMed Central

    Romkema, Sietske; Bongers, Raoul M.; van der Sluis, Corry K.

    2017-01-01

    Intermanual transfer, the transfer of motor skills from the trained hand to the untrained hand, can be used to train upper limb prosthesis skills. The aim of this study was to determine the relation between the magnitude of the intermanual transfer effect and the type of training task. The used tasks were based on different aspects of prosthetic handling: reaching, grasping, grip-force production and functional tasks. A single-blinded clinical trial, with a pre-posttest design was executed. Seventy-one able-bodied, right-handed participants were randomly assigned to four training and two control groups. The training groups performed a training program with an upper-limb prosthesis simulator. One control group performed a sham training (a dummy training without the prosthesis simulator) and another control group received no training at all. The training groups and sham group trained on five consecutive days. To determine the improvement in skills, a test was administered before, immediately after, and one week after the training. Training was performed with the ‘unaffected’ arm; tests were performed with the ‘affected’ arm, with the latter resembling the amputated limb. In this study half of the participants trained with the dominant hand, while the other half trained with the non-dominant hand. Participants executed four tests that corresponded to the different training tasks. The tests measured the reaching (movement time and symmetry ratio), grasping (opening time, duration of maximum hand opening, and closing time), grip-force production (deviation of asked grip-force) and functional (movement time) performance. Half of the participants were tested with their dominant arm and half of the participants with their non-dominant arm. Intermanual transfer effects were not found for reaching, grasping or functional tasks. However, we did find intermanual transfer effects for grip-force production tasks. Possibly, the study design contributed to the negative results due to the duration of the training sessions and test sessions. The positive results of the grip-force production might be an effect of the specificity of the training, that was totally focused on training grip-force production. When using intermanual transfer training in novice amputees, specific training should be devoted to grip-force. PMID:29190727

  3. HAL/S-FC compiler system functional specification

    NASA Technical Reports Server (NTRS)

    1974-01-01

    Compiler organization is discussed, including overall compiler structure, internal data transfer, compiler development, and code optimization. The user, system, and SDL interfaces are described, along with compiler system requirements. Run-time software support package and restrictions and dependencies are also considered of the HAL/S-FC system.

  4. Transferable Output ASCII Data (TOAD) editor version 1.0 user's guide

    NASA Technical Reports Server (NTRS)

    Bingel, Bradford D.; Shea, Anne L.; Hofler, Alicia S.

    1991-01-01

    The Transferable Output ASCII Data (TOAD) editor is an interactive software tool for manipulating the contents of TOAD files. The TOAD editor is specifically designed to work with tabular data. Selected subsets of data may be displayed to the user's screen, sorted, exchanged, duplicated, removed, replaced, inserted, or transferred to and from external files. It also offers a number of useful features including on-line help, macros, a command history, an 'undo' option, variables, and a full compliment of mathematical functions and conversion factors. Written in ANSI FORTRAN 77 and completely self-contained, the TOAD editor is very portable and has already been installed on SUN, SGI/IRIS, and CONVEX hosts.

  5. Photosensitive function of encapsulated dye in carbon nanotubes.

    PubMed

    Yanagi, Kazuhiro; Iakoubovskii, Konstantin; Matsui, Hiroyuki; Matsuzaki, Hiroyuki; Okamoto, Hiroshi; Miyata, Yasumitsu; Maniwa, Yutaka; Kazaoui, Said; Minami, Nobutsugu; Kataura, Hiromichi

    2007-04-25

    Single-wall carbon nanotubes (SWCNTs) exhibit resonant absorption localized in specific spectral regions. To expand the light spectrum that can be utilized by SWCNTs, we have encapsulated squarylium dye into SWCNTs and clarified its microscopic structure and photosensitizing function. X-ray diffraction and polarization-resolved optical absorption measurements revealed that the encapsulated dye molecules are located at an off center position inside the tubes and aligned to the nanotube axis. Efficient energy transfer from the encapsulated dye to SWCNTs was clearly observed in the photoluminescence spectra. Enhancement of transient absorption saturation in the S1 state of the semiconducting SWCNTs was detected after the photoexcitation of the encapsulated dye, which indicates that ultrafast (<190 fs) energy transfer occurred from the dye to the SWCNTs.

  6. Interosseous nerve transfers for tibialis anterior muscle paralysis (foot drop): a human cadaver-based feasibility study.

    PubMed

    Pirela-Cruz, Miguel A; Hansen, Uel; Terreros, Daniel A; Rossum, Alfred; West, Priscilla

    2009-03-01

    This study explored the anatomical feasibility of using an interosseous nerve transfer (routed between the tibia and fibula) to restore motor function to the tibialis anterior (TA) muscle, following injury to the common peroneal nerve (resulting in a foot drop). The specific nerve branches evaluated as possible donor nerves included the nerves to the medial gastrocnemius, the lateral gastrocnemius, and the soleus muscles. All nerve transfers were accomplished using a direct interosseous route and a direct repair (one medial gastrocnemius transfer did require interpositional grafting). The distance from the repair site to the TA muscle was shortest for the transfer using the nerve branch to the soleus. Histologically, the nerve branch to the soleus was most similar to the branch to the TA for both axonal count and cross-sectional area. A two-incision surgical approach using a fibular window (mobilizing a fibular segment after double osteotomy) and interosseous routing of the transfer is proposed.

  7. Working memory at work: how the updating process alters the nature of working memory transfer.

    PubMed

    Zhang, Yanmin; Verhaeghen, Paul; Cerella, John

    2012-01-01

    In three N-Back experiments, we investigated components of the process of working memory (WM) updating, more specifically access to items stored outside the focus of attention and transfer from the focus to the region of WM outside the focus. We used stimulus complexity as a marker. We found that when WM transfer occurred under full attention, it was slow and highly sensitive to stimulus complexity, much more so than WM access. When transfer occurred in conjunction with access, however, it was fast and no longer sensitive to stimulus complexity. Thus the updating context altered the nature of WM processing: The dual-task situation (transfer in conjunction with access) drove memory transfer into a more efficient mode, indifferent to stimulus complexity. In contrast, access times consistently increased with complexity, unaffected by the processing context. This study reinforces recent reports that retrieval is a (perhaps the) key component of working memory functioning. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Working Memory at Work: How the Updating Process Alters the Nature of Working Memory Transfer

    PubMed Central

    Zhang, Yanmin; Verhaeghen, Paul; Cerella, John

    2011-01-01

    In three N-Back experiments, we investigated components of the process of working memory (WM) updating, more specifically access to items stored outside the focus of attention and transfer from the focus to the region of WM outside the focus. We used stimulus complexity as a marker. We found that when WM transfer occurred under full attention, it was slow and highly sensitive to stimulus complexity, much more so than WM access. When transfer occurred in conjunction with access, however, it was fast and no longer sensitive to stimulus complexity. Thus the updating context altered the nature of WM processing: The dual-task situation (transfer in conjunction with access) drove memory transfer into a more efficient mode, indifferent to stimulus complexity. In contrast, access times consistently increased with complexity, unaffected by the processing context. This study reinforces recent reports that retrieval is a (perhaps the) key component of working memory functioning. PMID:22105718

  9. Effects of transference work in the context of therapeutic alliance and quality of object relations.

    PubMed

    Høglend, Per; Hersoug, Anne Grete; Bøgwald, Kjell-Petter; Amlo, Svein; Marble, Alice; Sørbye, Øystein; Røssberg, Jan Ivar; Ulberg, Randi; Gabbard, Glen O; Crits-Christoph, Paul

    2011-10-01

    Transference interpretation is considered as a core active ingredient in dynamic psychotherapy. In common clinical theory, it is maintained that more mature relationships, as well as a strong therapeutic alliance, may be prerequisites for successful transference work. In this study, the interaction between quality of object relations, transference interpretation, and alliance is estimated. One hundred outpatients seeking psychotherapy for depression, anxiety, and personality disorders were randomly assigned to 1 year of weekly sessions of dynamic psychotherapy with transference interpretation or to the same type and duration of treatment, but without the use of transference interpretation. Quality of Object Relations (QOR)-lifelong pattern was evaluated before treatment (P. Høglend, 1994). The Working Alliance Inventory (A. O. Horvath & L. S. Greenberg, 1989; T. J. Tracey & A. M. Kokotovic, 1989) was rated in Session 7. The primary outcome variable was the Psychodynamic Functioning Scales (P. Høglend et al., 2000), measured at pretreatment, posttreatment, and 1 year after treatment termination. A significant Treatment Group × Quality of Object Relations × Alliance interaction was present, indicating that alliance had a significantly different impact on effects of transference interpretation, depending on the level of QOR. The impact of transference interpretation on psychodynamic functioning was more positive within the context of a weak therapeutic alliance for patients with low quality of object relations. For patients with more mature object relations and high alliance, the authors observed a negative effect of transference work. The specific effects of transference work was influenced by the interaction of object relations and alliance, but in the direct opposite direction of what is generally maintained in mainstream clinical theory.

  10. Immediate toe-to-hand transfer in acute hand injuries: overall results, compared with results for elective cases.

    PubMed

    Woo, Sang-Hyun; Kim, Joo-Sung; Seul, Jung-Hyun

    2004-03-01

    In the past 5 years, 25 mutilated digits were reconstructed with immediate toe-to-hand transfers after acute hand injuries, for 21 patients. The overall results of the immediate toe-to-hand transfers were evaluated and compared with the results of 65 elective procedures performed during the same period by the same surgeon. There were 15 cases of great toe-to-hand transfer for thumb reconstruction, two cases of second toe transfer for index finger reconstruction, and four cases of simultaneous two-toe transfer for reconstruction of multiple-digit amputations. Two cases (two of 25 cases, 8 percent) were successfully salvaged with emergency reexploration. The incidences of emergency reexploration and postoperative infection were not significantly different from those for elective toe-to-hand transfer cases. The duration of industrial insurance coverage was much shorter than for elective cases, averaging 225 days (p < 0.001). Approximately 44 percent of the patients maintained their original jobs after immediate toe-to-hand transfer. The subjective satisfaction self-assessment scores of aesthetic appearance and function for the newly reconstructed thumb averaged 80 and 88 (of a total score of 100), respectively. Although satisfaction was lower than for elective reconstruction (p < 0.001), it was higher than for reconstruction of other digits. The donor-site appearance after great toe harvesting was mostly unsatisfactory. Immediate toe-to-hand transfer provides many advantages over the elective procedure in acute hand injuries, including single-stage reconstruction, shortened convalescence, early return to work, and socioeconomic efficiency. Because there were no significant differences in the success rates, frequencies of complications, or ultimate functional results, immediate toe-to-hand transfer is a safe and reliable procedure that is indicated for specific cases of acute digital amputation.

  11. Outer Membrane Protein Folding and Topology from a Computational Transfer Free Energy Scale.

    PubMed

    Lin, Meishan; Gessmann, Dennis; Naveed, Hammad; Liang, Jie

    2016-03-02

    Knowledge of the transfer free energy of amino acids from aqueous solution to a lipid bilayer is essential for understanding membrane protein folding and for predicting membrane protein structure. Here we report a computational approach that can calculate the folding free energy of the transmembrane region of outer membrane β-barrel proteins (OMPs) by combining an empirical energy function with a reduced discrete state space model. We quantitatively analyzed the transfer free energies of 20 amino acid residues at the center of the lipid bilayer of OmpLA. Our results are in excellent agreement with the experimentally derived hydrophobicity scales. We further exhaustively calculated the transfer free energies of 20 amino acids at all positions in the TM region of OmpLA. We found that the asymmetry of the Gram-negative bacterial outer membrane as well as the TM residues of an OMP determine its functional fold in vivo. Our results suggest that the folding process of an OMP is driven by the lipid-facing residues in its hydrophobic core, and its NC-IN topology is determined by the differential stabilities of OMPs in the asymmetrical outer membrane. The folding free energy is further reduced by lipid A and assisted by general depth-dependent cooperativities that exist between polar and ionizable residues. Moreover, context-dependency of transfer free energies at specific positions in OmpLA predict regions important for protein function as well as structural anomalies. Our computational approach is fast, efficient and applicable to any OMP.

  12. Spectrometry: Report of panel

    NASA Technical Reports Server (NTRS)

    Farmer, C. Barney; Murcray, David G.; Abreu, Vincent; Gille, John C.; Hanel, Rudolph A.; Hoell, James M., Jr.; Jamieson, John A.; Zwick, Harold

    1987-01-01

    Spectroscopic measurements are required to define the spectral background and provide the detailed spectral information that is essential for the design of species-specific systems and the analysis of data obtained from them. This function of spectroscopic measurements is expected to be an important part of any tropospheric remote-sensing program, and both emission and absorption spectroscopy are relevant in this context. The data from such observations are of value to tropospheric science in their own right, during the initial phases while species-specific techniques and instruments are under development. In addition, there are a number of unresolved problems in tropospheric radiative transfer and spectroscopy which presently limit the accuracy and reliability of all remote sensing methods. Only through a supporting program of spectroscopic measurements can progress be made in improving the understanding of these aspects of radiative transfer and ultimately reaching the desired confidence in the accuracy to species-specific monitoring techniques.

  13. Improvement of Ohmic contacts on Ga 2O 3 through use of ITO-interlayers

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

    Carey, Patrick H.; Yang, Jiancheng; Ren, Fan

    In this work, the use of ITO interlayers between Ga 2O 3 and Ti/Au metallization is shown to produce Ohmic contacts after annealing in the range of 500–600 °C. Without the ITO, similar anneals do not lead to linear current–voltage characteristics. Transmission line measurements were used to extract the specific contact resistance of the Au/Ti/ITO/Ga 2O 3 stacks as a function of annealing temperature. Sheet, specific contact, and transfer resistances all decreased sharply from as-deposited values with annealing. The minimum transfer resistance and specific contact resistance of 0.60 Ω mm and 6.3 × 10 -5 Ω cm 2 were achievedmore » after 600 °C annealing, respectively. Lastly, the conduction band offset between ITO and Ga 2O 3 is 0.32 eV and is consistent with the improved electron transport across the heterointerface.« less

  14. A Novel Leu92 Mutant of HIV-1 Reverse Transcriptase with a Selective Deficiency in Strand Transfer Causes a Loss of Viral Replication.

    PubMed

    Herzig, Eytan; Voronin, Nickolay; Kucherenko, Nataly; Hizi, Amnon

    2015-08-01

    The process of reverse transcription (RTN) in retroviruses is essential to the viral life cycle. This key process is catalyzed exclusively by the viral reverse transcriptase (RT) that copies the viral RNA into DNA by its DNA polymerase activity, while concomitantly removing the original RNA template by its RNase H activity. During RTN, the combination between DNA synthesis and RNA hydrolysis leads to strand transfers (or template switches) that are critical for the completion of RTN. The balance between these RT-driven activities was considered to be the sole reason for strand transfers. Nevertheless, we show here that a specific mutation in HIV-1 RT (L92P) that does not affect the DNA polymerase and RNase H activities abolishes strand transfer. There is also a good correlation between this complete loss of the RT's strand transfer to the loss of the DNA clamp activity of the RT, discovered recently by us. This finding indicates a mechanistic linkage between these two functions and that they are both direct and unique functions of the RT (apart from DNA synthesis and RNA degradation). Furthermore, when the RT's L92P mutant was introduced into an infectious HIV-1 clone, it lost viral replication, due to inefficient intracellular strand transfers during RTN, thus supporting the in vitro data. As far as we know, this is the first report on RT mutants that specifically and directly impair RT-associated strand transfers. Therefore, targeting residue Leu92 may be helpful in selectively blocking this RT activity and consequently HIV-1 infectivity and pathogenesis. Reverse transcription in retroviruses is essential for the viral life cycle. This multistep process is catalyzed by viral reverse transcriptase, which copies the viral RNA into DNA by its DNA polymerase activity (while concomitantly removing the RNA template by its RNase H activity). The combination and balance between synthesis and hydrolysis lead to strand transfers that are critical for reverse transcription completion. We show here for the first time that a single mutation in HIV-1 reverse transcriptase (L92P) selectively abolishes strand transfers without affecting the enzyme's DNA polymerase and RNase H functions. When this mutation was introduced into an infectious HIV-1 clone, viral replication was lost due to an impaired intracellular strand transfer, thus supporting the in vitro data. Therefore, finding novel drugs that target HIV-1 reverse transcriptase Leu92 may be beneficial for developing new potent and selective inhibitors of retroviral reverse transcription that will obstruct HIV-1 infectivity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Functional transferred DNA within extracellular vesicles

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

    Cai, Jin; Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province; Wu, Gengze

    Extracellular vesicles (EVs) are small membrane vesicles including exosomes and shedding vesicles that mediated a cell-to-cell communication. EVs are released from almost all cell types under both physiological and pathological conditions and incorporate nuclear and cytoplasmic molecules for intercellular delivery. Besides protein, mRNA, and microRNA of these molecules, as recent studies show, specific DNA are prominently packaged into EVs. It appears likely that some of exosomes or shedding vesicles, bearing nuclear molecules are released upon bubble-like blebs. Specific interaction of EVs with susceptible recipients performs the uptake of EVs into the target cells, discharging their cargo including nuclear and cytoplasmicmore » macromolecules into the cytosol. These findings expand the nucleic acid content of EVs to include increased levels of specific DNA. Thus, EVs contain a repertoire of genetic information available for horizontal gene transfer and potential use as blood biomarkers for cancer and atherosclerosis. In this review, the focus is on the characteristics, biological functions, and roles in diseases of DNA within EVs. - Highlights: • This review is focused on the DNA within EVs including its characteristics, biological functions, and roles in diseases. • It is clear that DNA within EVs might have important physiological and pathological roles in various diseases. • Knowledge in this area may provides us alternative methods for disease diagnosis or therapy in the future.« less

  16. Gene Duplication and Transference of Function in the paleoAP3 Lineage of Floral Organ Identity Genes

    PubMed Central

    Galimba, Kelsey D.; Martínez-Gómez, Jesús; Di Stilio, Verónica S.

    2018-01-01

    The floral organ identity gene APETALA3 (AP3) is a MADS-box transcription factor involved in stamen and petal identity that belongs to the B-class of the ABC model of flower development. Thalictrum (Ranunculaceae), an emerging model in the non-core eudicots, has AP3 homologs derived from both ancient and recent gene duplications. Prior work has shown that petals have been lost repeatedly and independently in Ranunculaceae in correlation with the loss of a specific AP3 paralog, and Thalictrum represents one of these instances. The main goal of this study was to conduct a functional analysis of the three AP3 orthologs present in Thalictrum thalictroides, representing the paleoAP3 gene lineage, to determine the degree of redundancy versus divergence after gene duplication. Because Thalictrum lacks petals, and has lost the petal-specific AP3, we also asked whether heterotopic expression of the remaining AP3 genes contributes to the partial transference of petal function to the first whorl found in insect-pollinated species. To address these questions, we undertook functional characterization by virus-induced gene silencing (VIGS), protein–protein interaction and binding site analyses. Our results illustrate partial redundancy among Thalictrum AP3s, with deep conservation of B-class function in stamen identity and a novel role in ectopic petaloidy of sepals. Certain aspects of petal function of the lost AP3 locus have apparently been transferred to the other paralogs. A novel result is that the protein products interact not only with each other, but also as homodimers. Evidence presented here also suggests that expression of the different ThtAP3 paralogs is tightly integrated, with an apparent disruption of B function homeostasis upon silencing of one of the paralogs that codes for a truncated protein. To explain this result, we propose two testable alternative scenarios: that the truncated protein is a dominant negative mutant or that there is a compensational response as part of a back-up circuit. The evidence for promiscuous protein–protein interactions via yeast two-hybrid combined with the detection of AP3 specific binding motifs in all B-class gene promoters provide partial support for these hypotheses. PMID:29628932

  17. Mechanism of energy conversion and transfer in bioluminescence. Final report. [Sea pansy Renilla reniformis

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

    Cormier, M.J.

    1979-01-01

    Bioluminescence in the sea pansy, Renilla reniformis, a marine anthozoan coelenterate, is a complex process involving the participation of three proteins specific to anthozoan coelenterate-type systems. These are: (1) the luciferin binding protein, (2) the enzyme luciferase, and (3) the green-fluorescent protein. Each of these have been purified and characterized and the structure of luciferin has been confirmed by synthesis. Luciferin binding protein (BP-LH/sub 2/) is a specific substrate binding protein which binds one molecule of coelenterate-type luciferin per molecule of protein and which then releases luciferin in the presence of Ca/sup + +/. Luciferase is the enzyme which catalyzesmore » oxidation (by O/sub 2/) of coelenterate-type luciferin, leading to the production of CO/sub 2/ and enzyme-bound, excited-state oxyluciferin. Oxyluciferin may then emit blue light by a direct de-excitation pathway or may transfer excitation energy to the green-fluorescent protein (GFP). GFP is a non-catalytic accessory protein which accepts excitation energy from oxyluciferin, by radiationless energy transfer, and then emits green bioluminescence. The Renilla bioluminescence system is thus the first radiationless energy transfer system the individual components of which have been purified to homogeneity, characterized, and then reassembled in vitro with restoration of the energy transfer function.« less

  18. Improvements in hip flexibility do not transfer to mobility in functional movement patterns.

    PubMed

    Moreside, Janice M; McGill, Stuart M

    2013-10-01

    The purpose of this study was to analyze the transference of increased passive hip range of motion (ROM) and core endurance to functional movement. Twenty-four healthy young men with limited hip mobility were randomly assigned to 4 intervention groups: group 1, stretching; group 2, stretching plus hip/spine disassociation exercises; group 3, core endurance; and group 4, control. Previous work has documented the large increase in passive ROM and core endurance that was attained over the 6-week interventions, but whether these changes transferred to functional activities was unclear. Four dynamic activities were analyzed before and after the 6-week interventions: active standing hip extension, lunge, a standing twist/reach maneuver, and exercising on an elliptical trainer. A Vicon motion capture system collected body segment kinematics, with hip and lumbar spine angles subsequently calculated in Visual 3D. Repeated measures analyses of variance determined group effects on various hip and spine angles, with paired t-tests on specific pre/post pairs. Despite the large increases in passive hip ROM, there was no evidence of increased hip ROM used during functional movement testing. Similarly, the only significant change in lumbar motion was a reduction in lumbar rotation during the active hip extension maneuver (p < 0.05). These results indicate that changes in passive ROM or core endurance do not automatically transfer to changes in functional movement patterns. This implies that training and rehabilitation programs may benefit from an additional focus on 'grooving' new motor patterns if newfound movement range is to be used.

  19. Pirating conserved phage mechanisms promotes promiscuous staphylococcal pathogenicity island transfer.

    PubMed

    Bowring, Janine; Neamah, Maan M; Donderis, Jorge; Mir-Sanchis, Ignacio; Alite, Christian; Ciges-Tomas, J Rafael; Maiques, Elisa; Medmedov, Iltyar; Marina, Alberto; Penadés, José R

    2017-08-08

    Targeting conserved and essential processes is a successful strategy to combat enemies. Remarkably, the clinically important Staphylococcus aureus pathogenicity islands (SaPIs) use this tactic to spread in nature. SaPIs reside passively in the host chromosome, under the control of the SaPI-encoded master repressor, Stl. It has been assumed that SaPI de-repression is effected by specific phage proteins that bind to Stl, initiating the SaPI cycle. Different SaPIs encode different Stl repressors, so each targets a specific phage protein for its de-repression. Broadening this narrow vision, we report here that SaPIs ensure their promiscuous transfer by targeting conserved phage mechanisms. This is accomplished because the SaPI Stl repressors have acquired different domains to interact with unrelated proteins, encoded by different phages, but in all cases performing the same conserved function. This elegant strategy allows intra- and inter-generic SaPI transfer, highlighting these elements as one of nature's most fascinating subcellular parasites.

  20. Skill transfer specificity shapes perception and action under varying environmental constraints.

    PubMed

    Seifert, Ludovic; Wattebled, Léo; Orth, Dominic; L'Hermette, Maxime; Boulanger, Jérémie; Davids, Keith

    2016-08-01

    Using an ecological dynamics framework, this study investigated the generality and specificity of skill transfer processes in organisation of perception and action using climbing as a task vehicle. Fluency of hip trajectory and orientation was assessed using normalized jerk coefficients exhibited by participants as they adapted perception and action under varying environmental constraints. Twelve recreational climbers were divided into two groups: one completing a 10-m high route on an indoor climbing wall; a second undertaking a 10-m high route on an icefall in a top-rope condition. We maintained the same level of difficulty between these two performance environments. An inertial measurement unit was attached each climber's hips to collect 3D acceleration and 3D orientation data to compute jerk coefficient values. Video footage was used to record the ratio of exploratory/performatory movements. Results showed higher jerk coefficient values and number of exploratory movements for performance on the icefall route, perhaps due to greater functional complexity in perception and action required when climbing icefalls, which involves use of specific tools for anchorage. Findings demonstrated how individuals solve different motor problems, exploiting positive general transfer processes enabling participants to explore the pick-up of information for the perception of affordances specific to icefall climbing. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Shared function knowledge: infants' attention to function information in communicative contexts.

    PubMed

    Träuble, Birgit; Bätz, Johannes

    2014-08-01

    Humans are specifically adapted to knowledge acquisition and transfer by social communication. According to natural pedagogy theory, infants are highly sensitive to signals that indicate a teacher's communicative intention and are biased to interpret communicative contexts as conveying relevant and generalizable knowledge that is also shared by other conspecifics. We investigated whether infants as young as 12 months interpret ostensively communicated object-directed emotion expressions as generalizable and shareable with others. Given that young infants pay particular attention to information about objects' functions, we were interested in whether the shareability assumption also holds for emotional attitudes toward functional features of unfamiliar objects. The results suggest that 12-month-olds (N=80) flexibly interpret another person's emotion displays toward unfamiliar artifacts either as object-centered and generalizable attitudes or as person-centered subjective attitudes, depending on the communicative characteristics of the learning context. Furthermore, the transfer of ostensively communicated information about the artifacts depended on their functional usability, which is consistent with infants' early sensitivity to function information in various areas of cognitive development. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Data base management system configuration specification. [computer storage devices

    NASA Technical Reports Server (NTRS)

    Neiers, J. W.

    1979-01-01

    The functional requirements and the configuration of the data base management system are described. Techniques and technology which will enable more efficient and timely transfer of useful data from the sensor to the user, extraction of information by the user, and exchange of information among the users are demonstrated.

  3. Memory and Study Strategies for Optimal Learning.

    ERIC Educational Resources Information Center

    Hamachek, Alice L.

    Study strategies are those specific reading skills that increase understanding, memory storage, and retrieval. Memory techniques are crucial to effective studying, and to subsequent performance in class and on written examinations. A major function of memory is to process information. Stimuli are picked up by sensory receptors and transferred to…

  4. Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells

    PubMed Central

    2013-01-01

    Introduction Malignant pleural mesothelioma (MPM) is an incurable malignant disease, which results from chronic exposition to asbestos in at least 70% of the cases. Fibroblast activation protein (FAP) is predominantly expressed on the surface of reactive tumor-associated fibroblasts as well as on particular cancer types. Because of its expression on the cell surface, FAP is an attractive target for adoptive T cell therapy. T cells can be re-directed by retroviral transfer of chimeric antigen receptors (CAR) against tumor-associated antigens (TAA) and therefore represent a therapeutic strategy of adoptive immunotherapy. Methods To evaluate FAP expression immunohistochemistry was performed in tumor tissue from MPM patients. CD8+ human T cells were retrovirally transduced with an anti-FAP-F19-∆CD28/CD3ζ-CAR. T cell function was evaluated in vitro by cytokine release and cytotoxicity assays. In vivo function was tested with an intraperitoneal xenograft tumor model in immunodeficient mice. Results FAP was found to be expressed in all subtypes of MPM. Additionally, FAP expression was evaluated in healthy adult tissue samples and was only detected in specific areas in the pancreas, the placenta and very weakly for cervix and uterus. Expression of the anti-FAP-F19-∆CD28/CD3ζ-CAR in CD8+ T cells resulted in antigen-specific IFNγ release. Additionally, FAP-specific re-directed T cells lysed FAP positive mesothelioma cells and inflammatory fibroblasts in an antigen-specific manner in vitro. Furthermore, FAP-specific re-directed T cells inhibited the growth of FAP positive human tumor cells in the peritoneal cavity of mice and significantly prolonged survival of mice. Conclusion FAP re-directed CD8+ T cells showed antigen-specific functionality in vitro and in vivo. Furthermore, FAP expression was verified in all MPM histotypes. Therefore, our data support performing a phase I clinical trial in which MPM patients are treated with adoptively transferred FAP-specific re-directed T cells. PMID:23937772

  5. Copolymers of poly-L-lysine with serine and tryptophan form stable DNA vectors: implications for receptor-mediated gene transfer.

    PubMed

    Gómez-Valadés, A G; Molas, M; Vidal-Alabró, A; Bermúdez, J; Bartrons, R; Perales, J C

    2005-01-20

    Inefficient gene transfer and poor stability in physiological medium are important shortcomings for receptor-mediated gene transfer vectors. Here, we evaluate vectors formulated with random copolymers of L-lysine/L-serine (3:1) and L-lysine/L-tryptophan (4:1), focusing on both their biophysical and functional characterization. By means of dynamic light scattering (DLS) and transmission electron microscopy (TEM), we demonstrate that poly-L-lysine (pK), poly-L-lysine-L-tryptophan (pKW) and poly-L-lysine-L-serine (pKS) are able to form compacted, small particles when mixed with plasmid DNA in the absence of salt. Upon dilution in physiological medium, copolymers of both lys/ser and lys/trp do not aggregate, in contrast with poly-L-lysine DNA complexes as determined by scattering, DLS and TEM measurements. Tight packing, as demonstrated by resistance to heparin, SDS and trypsin treatments, is also featured in tryptophan-containing complexes. Successful receptor-mediated endocytosis gene transfer using galactosylated copolymers into cells expressing the asiagloglycoprotein receptor correlated with lack of aggregation. Particles obtained using galactosylated poly-L-lysine-L-tryptophan (Gal-pKW) copolymer demonstrated specific receptor-mediated gene transfer since reporter gene activity dropped in the presence of an excess ligand in the culture medium during transfection. Although copolymers of galactosylated poly-L-lysine-L-serine (Gal-pKS) do not aggregate in the presence of salt, they are not able to internalize in a specific receptor-mediated endocytosis fashion. The introduction of bulky aromatic/hydrophobic (tryptophan) or hydrophillic (serine) moieties into the positively charged vectors allows the compacted particles to disperse into salt-containing medium avoiding salt-induced aggregation. Moreover, tryptophan-containing particles are able to mediate specific gene transfer via receptor-mediated endocytosis.

  6. Horizontally transferred genes in the genome of Pacific white shrimp, Litopenaeus vannamei

    PubMed Central

    2013-01-01

    Background In recent years, as the development of next-generation sequencing technology, a growing number of genes have been reported as being horizontally transferred from prokaryotes to eukaryotes, most of them involving arthropods. As a member of the phylum Arthropoda, the Pacific white shrimp Litopenaeus vannamei has to adapt to the complex water environments with various symbiotic or parasitic microorganisms, which provide a platform for horizontal gene transfer (HGT). Results In this study, we analyzed the genome-wide HGT events in L. vannamei. Through homology search and phylogenetic analysis, followed by experimental PCR confirmation, 14 genes with HGT event were identified: 12 of them were transferred from bacteria and two from fungi. Structure analysis of these genes showed that the introns of the two fungi-originated genes were substituted by shrimp DNA fragment, two genes transferred from bacteria had shrimp specific introns inserted in them. Furthermore, around other three bacteria-originated genes, there were three large DNA segments inserted into the shrimp genome. One segment was a transposon that fully transferred, and the other two segments contained only coding regions of bacteria. Functional prediction of these 14 genes showed that 6 of them might be related to energy metabolism, and 4 others related to defense of the organism. Conclusions HGT events from bacteria or fungi were happened in the genome of L. vannamei, and these horizontally transferred genes can be transcribed in shrimp. This is the first time to report the existence of horizontally transferred genes in shrimp. Importantly, most of these genes are exposed to a negative selection pressure and appeared to be functional. PMID:23914989

  7. Thermo-responsive cell culture carriers based on poly(vinyl methyl ether)—the effect of biomolecular ligands to balance cell adhesion and stimulated detachment

    NASA Astrophysics Data System (ADS)

    Teichmann, Juliane; Nitschke, Mirko; Pette, Dagmar; Valtink, Monika; Gramm, Stefan; Härtel, Frauke V.; Noll, Thomas; Funk, Richard H. W.; Engelmann, Katrin; Werner, Carsten

    2015-08-01

    Two established material systems for thermally stimulated detachment of adherent cells were combined in a cross-linked polymer blend to merge favorable properties. Through this approach poly(N-isopropylacrylamide) (PNiPAAm) with its superior switching characteristic was paired with a poly(vinyl methyl ether)-based composition that allows adjusting physico-chemical and biomolecular properties in a wide range. Beyond pure PNiPAAm, the proposed thermo-responsive coating provides thickness, stiffness and swelling behavior, as well as an apposite density of reactive sites for biomolecular functionalization, as effective tuning parameters to meet specific requirements of a particular cell type regarding initial adhesion and ease of detachment. To illustrate the strength of this approach, the novel cell culture carrier was applied to generate transplantable sheets of human corneal endothelial cells (HCEC). Sheets were grown, detached, and transferred onto planar targets. Cell morphology, viability and functionality were analyzed by immunocytochemistry and determination of transepithelial electrical resistance (TEER) before and after sheet detachment and transfer. HCEC layers showed regular morphology with appropriate TEER. Cells were positive for function-associated marker proteins ZO-1, Na+/K+-ATPase, and paxillin, and extracellular matrix proteins fibronectin, laminin and collagen type IV before and after transfer. Sheet detachment and transfer did not impair cell viability. Subsequently, a potential application in ophthalmology was demonstrated by transplantation onto de-endothelialized porcine corneas in vitro. The novel thermo-responsive cell culture carrier facilitates the generation and transfer of functional HCEC sheets. This paves the way to generate tissue engineered human corneal endothelium as an alternative transplant source for endothelial keratoplasty.

  8. Thermo-responsive cell culture carriers based on poly(vinyl methyl ether)-the effect of biomolecular ligands to balance cell adhesion and stimulated detachment.

    PubMed

    Teichmann, Juliane; Nitschke, Mirko; Pette, Dagmar; Valtink, Monika; Gramm, Stefan; Härtel, Frauke V; Noll, Thomas; Funk, Richard H W; Engelmann, Katrin; Werner, Carsten

    2015-08-01

    Two established material systems for thermally stimulated detachment of adherent cells were combined in a cross-linked polymer blend to merge favorable properties. Through this approach poly( N -isopropylacrylamide) (PNiPAAm) with its superior switching characteristic was paired with a poly(vinyl methyl ether)-based composition that allows adjusting physico-chemical and biomolecular properties in a wide range. Beyond pure PNiPAAm, the proposed thermo-responsive coating provides thickness, stiffness and swelling behavior, as well as an apposite density of reactive sites for biomolecular functionalization, as effective tuning parameters to meet specific requirements of a particular cell type regarding initial adhesion and ease of detachment. To illustrate the strength of this approach, the novel cell culture carrier was applied to generate transplantable sheets of human corneal endothelial cells (HCEC). Sheets were grown, detached, and transferred onto planar targets. Cell morphology, viability and functionality were analyzed by immunocytochemistry and determination of transepithelial electrical resistance (TEER) before and after sheet detachment and transfer. HCEC layers showed regular morphology with appropriate TEER. Cells were positive for function-associated marker proteins ZO-1, Na + /K + -ATPase, and paxillin, and extracellular matrix proteins fibronectin, laminin and collagen type IV before and after transfer. Sheet detachment and transfer did not impair cell viability. Subsequently, a potential application in ophthalmology was demonstrated by transplantation onto de-endothelialized porcine corneas in vitro . The novel thermo-responsive cell culture carrier facilitates the generation and transfer of functional HCEC sheets. This paves the way to generate tissue engineered human corneal endothelium as an alternative transplant source for endothelial keratoplasty.

  9. Thermo-responsive cell culture carriers based on poly(vinyl methyl ether)—the effect of biomolecular ligands to balance cell adhesion and stimulated detachment

    PubMed Central

    Teichmann, Juliane; Nitschke, Mirko; Pette, Dagmar; Valtink, Monika; Gramm, Stefan; Härtel, Frauke V; Noll, Thomas; Funk, Richard H W; Engelmann, Katrin; Werner, Carsten

    2015-01-01

    Two established material systems for thermally stimulated detachment of adherent cells were combined in a cross-linked polymer blend to merge favorable properties. Through this approach poly(N-isopropylacrylamide) (PNiPAAm) with its superior switching characteristic was paired with a poly(vinyl methyl ether)-based composition that allows adjusting physico-chemical and biomolecular properties in a wide range. Beyond pure PNiPAAm, the proposed thermo-responsive coating provides thickness, stiffness and swelling behavior, as well as an apposite density of reactive sites for biomolecular functionalization, as effective tuning parameters to meet specific requirements of a particular cell type regarding initial adhesion and ease of detachment. To illustrate the strength of this approach, the novel cell culture carrier was applied to generate transplantable sheets of human corneal endothelial cells (HCEC). Sheets were grown, detached, and transferred onto planar targets. Cell morphology, viability and functionality were analyzed by immunocytochemistry and determination of transepithelial electrical resistance (TEER) before and after sheet detachment and transfer. HCEC layers showed regular morphology with appropriate TEER. Cells were positive for function-associated marker proteins ZO-1, Na+/K+-ATPase, and paxillin, and extracellular matrix proteins fibronectin, laminin and collagen type IV before and after transfer. Sheet detachment and transfer did not impair cell viability. Subsequently, a potential application in ophthalmology was demonstrated by transplantation onto de-endothelialized porcine corneas in vitro. The novel thermo-responsive cell culture carrier facilitates the generation and transfer of functional HCEC sheets. This paves the way to generate tissue engineered human corneal endothelium as an alternative transplant source for endothelial keratoplasty. PMID:27877823

  10. Transcript Profiling Identifies Gene Cohorts Controlled by Each Signal Regulating Trans-Differentiation of Epidermal Cells of Vicia faba Cotyledons to a Transfer Cell Phenotype

    PubMed Central

    Zhang, Hui-Ming; Wheeler, Simon L.; Xia, Xue; Colyvas, Kim; Offler, Christina E.; Patrick, John W.

    2017-01-01

    Transfer cells (TCs) support high rates of membrane transport of nutrients conferred by a plasma membrane area amplified by lining a wall labyrinth comprised of an uniform wall layer (UWL) upon which intricate wall ingrowth (WI) papillae are deposited. A signal cascade of auxin, ethylene, extracellular hydrogen peroxide (H2O2) and cytosolic Ca2+ regulates wall labyrinth assembly. To identify gene cohorts regulated by each signal, a RNA- sequencing study was undertaken using Vicia faba cotyledons. When cotyledons are placed in culture, their adaxial epidermal cells spontaneously undergo trans-differentiation to epidermal TCs (ETCs). Expressed genes encoding proteins central to wall labyrinth formation (signaling, intracellular organization, cell wall) and TC function of nutrient transport were assembled. Transcriptional profiles identified 9,742 annotated ETC-specific differentially expressed genes (DEGs; Log2fold change > 1; FDR p ≤ 0.05) of which 1,371 belonged to signaling (50%), intracellular organization (27%), cell wall (15%) and nutrient transporters (9%) functional categories. Expression levels of 941 ETC-specific DEGs were found to be sensitive to the known signals regulating ETC trans-differentiation. Significantly, signals acting alone, or in various combinations, impacted similar numbers of ETC-specific DEGs across the four functional gene categories. Amongst the signals acting alone, H2O2 exerted most influence affecting expression levels of 56% of the ETC-specific DEGs followed by Ca2+ (21%), auxin (18%) and ethylene (5%). The dominance by H2O2 was evident across all functional categories, but became more attenuated once trans-differentiation transitioned into WI papillae formation. Amongst the eleven signal combinations, H2O2/Ca2+ elicited the greatest impact across all functional categories accounting for 20% of the ETC-specific DEG cohort. The relative influence of the other signals acting alone, or in various combinations, varied across the four functional categories and two phases of wall labyrinth construction. These transcriptome data provide a powerful information platform from which to examine signal transduction pathways and how these regulate expression of genes encoding proteins engaged in intracellular organization, cell wall construction and nutrient transport. PMID:29234338

  11. Transcript Profiling Identifies Gene Cohorts Controlled by Each Signal Regulating Trans-Differentiation of Epidermal Cells of Vicia faba Cotyledons to a Transfer Cell Phenotype.

    PubMed

    Zhang, Hui-Ming; Wheeler, Simon L; Xia, Xue; Colyvas, Kim; Offler, Christina E; Patrick, John W

    2017-01-01

    Transfer cells (TCs) support high rates of membrane transport of nutrients conferred by a plasma membrane area amplified by lining a wall labyrinth comprised of an uniform wall layer (UWL) upon which intricate wall ingrowth (WI) papillae are deposited. A signal cascade of auxin, ethylene, extracellular hydrogen peroxide (H 2 O 2 ) and cytosolic Ca 2+ regulates wall labyrinth assembly. To identify gene cohorts regulated by each signal, a RNA- sequencing study was undertaken using Vicia faba cotyledons. When cotyledons are placed in culture, their adaxial epidermal cells spontaneously undergo trans -differentiation to epidermal TCs (ETCs). Expressed genes encoding proteins central to wall labyrinth formation (signaling, intracellular organization, cell wall) and TC function of nutrient transport were assembled. Transcriptional profiles identified 9,742 annotated ETC-specific differentially expressed genes (DEGs; Log 2 fold change > 1; FDR p ≤ 0.05) of which 1,371 belonged to signaling (50%), intracellular organization (27%), cell wall (15%) and nutrient transporters (9%) functional categories. Expression levels of 941 ETC-specific DEGs were found to be sensitive to the known signals regulating ETC trans -differentiation. Significantly, signals acting alone, or in various combinations, impacted similar numbers of ETC-specific DEGs across the four functional gene categories. Amongst the signals acting alone, H 2 O 2 exerted most influence affecting expression levels of 56% of the ETC-specific DEGs followed by Ca 2+ (21%), auxin (18%) and ethylene (5%). The dominance by H 2 O 2 was evident across all functional categories, but became more attenuated once trans -differentiation transitioned into WI papillae formation. Amongst the eleven signal combinations, H 2 O 2 /Ca 2+ elicited the greatest impact across all functional categories accounting for 20% of the ETC-specific DEG cohort. The relative influence of the other signals acting alone, or in various combinations, varied across the four functional categories and two phases of wall labyrinth construction. These transcriptome data provide a powerful information platform from which to examine signal transduction pathways and how these regulate expression of genes encoding proteins engaged in intracellular organization, cell wall construction and nutrient transport.

  12. Functional mixed effects spectral analysis

    PubMed Central

    KRAFTY, ROBERT T.; HALL, MARTICA; GUO, WENSHENG

    2011-01-01

    SUMMARY In many experiments, time series data can be collected from multiple units and multiple time series segments can be collected from the same unit. This article introduces a mixed effects Cramér spectral representation which can be used to model the effects of design covariates on the second-order power spectrum while accounting for potential correlations among the time series segments collected from the same unit. The transfer function is composed of a deterministic component to account for the population-average effects and a random component to account for the unit-specific deviations. The resulting log-spectrum has a functional mixed effects representation where both the fixed effects and random effects are functions in the frequency domain. It is shown that, when the replicate-specific spectra are smooth, the log-periodograms converge to a functional mixed effects model. A data-driven iterative estimation procedure is offered for the periodic smoothing spline estimation of the fixed effects, penalized estimation of the functional covariance of the random effects, and unit-specific random effects prediction via the best linear unbiased predictor. PMID:26855437

  13. Retrospective Cost Adaptive Control with Concurrent Closed-Loop Identification

    NASA Astrophysics Data System (ADS)

    Sobolic, Frantisek M.

    Retrospective cost adaptive control (RCAC) is a discrete-time direct adaptive control algorithm for stabilization, command following, and disturbance rejection. RCAC is known to work on systems given minimal modeling information which is the leading numerator coefficient and any nonminimum-phase (NMP) zeros of the plant transfer function. This information is normally needed a priori and is key in the development of the filter, also known as the target model, within the retrospective performance variable. A novel approach to alleviate the need for prior modeling of both the leading coefficient of the plant transfer function as well as any NMP zeros is developed. The extension to the RCAC algorithm is the use of concurrent optimization of both the target model and the controller coefficients. Concurrent optimization of the target model and controller coefficients is a quadratic optimization problem in the target model and controller coefficients separately. However, this optimization problem is not convex as a joint function of both variables, and therefore nonconvex optimization methods are needed. Finally, insights within RCAC that include intercalated injection between the controller numerator and the denominator, unveil the workings of RCAC fitting a specific closed-loop transfer function to the target model. We exploit this interpretation by investigating several closed-loop identification architectures in order to extract this information for use in the target model.

  14. 5 CFR 351.303 - Identification of positions with a transferring function.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... transferring function. 351.303 Section 351.303 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Transfer of Function § 351.303 Identification of positions with a transferring function. (a) The competitive area losing the function is responsible for identifying the...

  15. 5 CFR 351.303 - Identification of positions with a transferring function.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... transferring function. 351.303 Section 351.303 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS REDUCTION IN FORCE Transfer of Function § 351.303 Identification of positions with a transferring function. (a) The competitive area losing the function is responsible for identifying the...

  16. Infralimbic prefrontal cortex interacts with nucleus accumbens shell to unmask expression of outcome-selective Pavlovian-to-instrumental transfer

    PubMed Central

    Keistler, Colby; Barker, Jacqueline M.

    2015-01-01

    Although several studies have examined the subcortical circuitry underlying Pavlovian-to-instrumental transfer (PIT), the role of medial prefrontal cortex in this behavior is largely unknown. Elucidating the cortical contributions to PIT will be key for understanding how reward-paired cues control behavior in both adaptive and maladaptive context (i.e., addiction). Here we use bilateral lesions in a rat model to show that infralimbic prefrontal cortex (ilPFC) is necessary for appropriate expression of PIT. Further, we show that ilPFC mediates this effect via functional connectivity with nucleus accumbens shell (NAcS). Together, these data provide the first demonstration that a specific cortico-striatal circuit is necessary for cue-invigorated reward seeking during specific PIT. PMID:26373829

  17. Integrated flight/propulsion control - Subsystem specifications for performance

    NASA Technical Reports Server (NTRS)

    Neighbors, W. K.; Rock, Stephen M.

    1993-01-01

    A procedure is presented for calculating multiple subsystem specifications given a number of performance requirements on the integrated system. This procedure applies to problems where the control design must be performed in a partitioned manner. It is based on a structured singular value analysis, and generates specifications as magnitude bounds on subsystem uncertainties. The performance requirements should be provided in the form of bounds on transfer functions of the integrated system. This form allows the expression of model following, command tracking, and disturbance rejection requirements. The procedure is demonstrated on a STOVL aircraft design.

  18. Well-defined single polymer nanoparticles for the antibody-targeted delivery of chemotherapeutic agents.

    PubMed

    Lane, D D; Chiu, D Y; Su, F Y; Srinivasan, S; Kern, H B; Press, O W; Stayton, P S; Convertine, A J

    2015-02-28

    Aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization was employed to prepare a series of linear copolymers of N,N-dimethylacrylamide (DMA) and 2-hydroxyethylacrylamide (HEAm) with narrow Đ values over a molecular weight range spanning three orders of magnitude (10 3 to 10 6 Da). Trithiocarbonate-based RAFT chain transfer agents (CTAs) were grafted onto these scaffolds using carbodiimide chemistry catalyzed with DMAP. The resultant graft chain transfer agent (gCTA) was subsequently employed to synthesize polymeric brushes with a number of important vinyl monomer classes including acrylamido, methacrylamido, and methacrylate. Brush polymerization kinetics were evaluated for the aqueous RAFT polymerization of DMA from a 10 arm gCTA. Polymeric brushes containing hydroxyl functionality were further functionalized in order to prepare 2nd generation gCTAs which were subsequently employed to prepare polymers with a brushed-brush architecture with molecular weights in excess of 10 6 Da. These resultant single particle nanoparticles (SNPs) were employed as drug delivery vehicles for the anthracycline-based drug doxorubicin via copolymerization of DMA with a protected carbazate monomer (bocSMA). Cell-specific targeting functionality was also introduced via copolymerization with a biotin-functional monomer (bioHEMA). Drug release of the hydrazone linked doxorubicin was evaluated as function of pH and serum and chemotherapeutic activity was evaluated in SKOV3 ovarian cancer cells.

  19. Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy: role of CD62L.

    PubMed

    Díaz-Montero, C Marcela; Zidan, Abdel-Aziz; Pallin, Maria F; Anagnostopoulos, Vasileios; Salem, Mohamed L; Wieder, Eric; Komanduri, Krishna; Montero, Alberto J; Lichtenheld, Mathias G

    2013-12-01

    CD62L governs the circulation of CD8(+) T cells between lymph nodes and peripheral tissues, whereby the expression of CD62L by CD8(+) T cells promotes their recirculation through lymph nodes. As such, CD62L participates in the fate of adoptively transferred CD8(+) T cells and may control their effectiveness for cancer immunotherapy, including settings in which host preconditioning results in the acute lymphopenia-induced proliferation of the transferred cells. Indeed, previous studies correlated CD62L expression by donor CD8(+) cells with the success rate of adoptive cell therapy (ACT). Here, we analyzed the functions and fate of ex vivo-activated, tumor-specific CD62L(-/-) CD8(+) T cells in a mouse melanoma model for ACT. Unexpectedly, we observed that CD62L(-/-) CD8(+) T cells were functionally indistinguishable from CD62L(+/+) CD8(+) T cells, i.e., both greatly expanded in cyclophosphamide preconditioned animals, controlled subcutaneously and hematogenously spreading tumors, and generated anti-tumor-specific CD8(+) T cell memory. Moreover, even in hosts with rudimentary secondary lymphoid organs (LT(-/-) animals), CD8(+) T cells with and without CD62L expanded equivalently to those adoptively transferred into wild-type animals. These results put into question the utility of CD62L as a predictive biomarker for the efficacy of ex vivo-expanded T cells after ACT in lymphopenic conditions and also offer new insights into the homing, engraftment, and memory generation of adoptively transferred ex vivo-activated CD8(+) T cells.

  20. Preparation of fluorescent tocopherols for use in protein binding and localization with the alpha-tocopherol transfer protein.

    PubMed

    Nava, Phillip; Cecchini, Matt; Chirico, Sara; Gordon, Heather; Morley, Samantha; Manor, Danny; Atkinson, Jeffrey

    2006-06-01

    Sixteen fluorescent analogues of the lipid-soluble antioxidant vitamin alpha-tocopherol were prepared incorporating fluorophores at the terminus of omega-functionalized 2-n-alkyl-substituted chromanols (1a-d and 4a-d) that match the methylation pattern of alpha-tocopherol, the most biologically active form of vitamin E. The fluorophores used include 9-anthroyloxy (AO), 7-nitrobenz-2-oxa-1,3-diazole (NBD), N-methyl anthranilamide (NMA), and dansyl (DAN). The compounds were designed to function as fluorescent reporter ligands for protein-binding and lipid transfer assays. The fluorophores were chosen to maximize the fluorescence changes observed upon moving from an aqueous environment (low fluorescence intensity) to an hydrophobic environment such as a protein's binding site (high fluorescence intensity). Compounds 9d (anthroyloxy) and 10d (nitrobenzoxadiazole), having a C9-carbon chain between the chromanol and the fluorophore, were shown to bind specifically and reversibly to recombinant human tocopherol transfer protein (alpha-TTP) with dissociation constants of approximately 280 and 60 nM, respectively, as compared to 25 nM for the natural ligand 2R,4'R,8'R-alpha-tocopherol. Thus, compounds have been prepared that allow the investigation of the rate of alpha-TTP-mediated inter-membrane transfer of alpha-tocopherol and to investigate the mechanism of alpha-TTP function at membranes of different composition.

  1. Optimal Experiment Design for Thermal Characterization of Functionally Graded Materials

    NASA Technical Reports Server (NTRS)

    Cole, Kevin D.

    2003-01-01

    The purpose of the project was to investigate methods to accurately verify that designed , materials meet thermal specifications. The project involved heat transfer calculations and optimization studies, and no laboratory experiments were performed. One part of the research involved study of materials in which conduction heat transfer predominates. Results include techniques to choose among several experimental designs, and protocols for determining the optimum experimental conditions for determination of thermal properties. Metal foam materials were also studied in which both conduction and radiation heat transfer are present. Results of this work include procedures to optimize the design of experiments to accurately measure both conductive and radiative thermal properties. Detailed results in the form of three journal papers have been appended to this report.

  2. The heat-transfer method: a versatile low-cost, label-free, fast, and user-friendly readout platform for biosensor applications.

    PubMed

    van Grinsven, Bart; Eersels, Kasper; Peeters, Marloes; Losada-Pérez, Patricia; Vandenryt, Thijs; Cleij, Thomas J; Wagner, Patrick

    2014-08-27

    In recent years, biosensors have become increasingly important in various scientific domains including medicine, biology, and pharmacology, resulting in an increased demand for fast and effective readout techniques. In this Spotlight on Applications, we report on the recently developed heat-transfer method (HTM) and illustrate the use of the technique by zooming in on four established bio(mimetic) sensor applications: (i) mutation analysis in DNA sequences, (ii) cancer cell identification through surface-imprinted polymers, (iii) detection of neurotransmitters with molecularly imprinted polymers, and (iv) phase-transition analysis in lipid vesicle layers. The methodology is based on changes in heat-transfer resistance at a functionalized solid-liquid interface. To this extent, the device applies a temperature gradient over this interface and monitors the temperature underneath and above the functionalized chip in time. The heat-transfer resistance can be obtained by dividing this temperature gradient by the power needed to achieve a programmed temperature. The low-cost, fast, label-free and user-friendly nature of the technology in combination with a high degree of specificity, selectivity, and sensitivity makes HTM a promising sensor technology.

  3. Redox reaction characteristics of riboflavin: a fluorescence spectroelectrochemical analysis and density functional theory calculation.

    PubMed

    Chen, Wei; Chen, Jie-Jie; Lu, Rui; Qian, Chen; Li, Wen-Wei; Yu, Han-Qing

    2014-08-01

    Riboflavin (RF), the primary redox active component of flavin, is involved in many redox processes in biogeochemical systems. Despite of its wide distribution and important roles in environmental remediation, its redox behaviors and reaction mechanisms in hydrophobic sites remain unclear yet. In this study, spectroelectrochemical analysis and density functional theory (DFT) calculation were integrated to explore the redox behaviors of RF in dimethyl sulfoxide (DMSO), which was used to create a hydrophobic environment. Specifically, cyclic voltafluorometry (CVF) and derivative cyclic voltafluorometry (DCVF) were employed to track the RF concentration changing profiles. It was found that the reduction contained a series of proton-coupled electron transfers dependent of potential driving force. In addition to the electron transfer-chemical reaction-electron transfer process, a disproportionation (DISP1) process was also identified to be involved in the reduction. The redox potential and free energy of each step obtained from the DFT calculations further confirmed the mechanisms proposed based on the experimental results. The combination of experimental and theoretical approaches yields a deep insight into the characteristics of RF in environmental remediation and better understanding about the proton-coupled electron transfer mechanisms. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Mechanism to support generic collective communication across a variety of programming models

    DOEpatents

    Almasi, Gheorghe [Ardsley, NY; Dozsa, Gabor [Ardsley, NY; Kumar, Sameer [White Plains, NY

    2011-07-19

    A system and method for supporting collective communications on a plurality of processors that use different parallel programming paradigms, in one aspect, may comprise a schedule defining one or more tasks in a collective operation, an executor that executes the task, a multisend module to perform one or more data transfer functions associated with the tasks, and a connection manager that controls one or more connections and identifies an available connection. The multisend module uses the available connection in performing the one or more data transfer functions. A plurality of processors that use different parallel programming paradigms can use a common implementation of the schedule module, the executor module, the connection manager and the multisend module via a language adaptor specific to a parallel programming paradigm implemented on a processor.

  5. Modeling of Atmospheric Turbulence as Disturbances for Control Design and Evaluation of High Speed Propulsion Systems

    NASA Technical Reports Server (NTRS)

    Kopasakis, George

    2010-01-01

    Atmospheric turbulence models are necessary for the design of both inlet/engine and flight controls, as well as for studying integrated couplings between the propulsion and the vehicle structural dynamics for supersonic vehicles. Models based on the Kolmogorov spectrum have been previously utilized to model atmospheric turbulence. In this paper, a more accurate model is developed in its representative fractional order form, typical of atmospheric disturbances. This is accomplished by first scaling the Kolmogorov spectral to convert them into finite energy von Karman forms. Then a generalized formulation is developed in frequency domain for these scale models that approximates the fractional order with the products of first order transfer functions. Given the parameters describing the conditions of atmospheric disturbances and utilizing the derived formulations, the objective is to directly compute the transfer functions that describe these disturbances for acoustic velocity, temperature, pressure and density. Utilizing these computed transfer functions and choosing the disturbance frequencies of interest, time domain simulations of these representative atmospheric turbulences can be developed. These disturbance representations are then used to first develop considerations for disturbance rejection specifications for the design of the propulsion control system, and then to evaluate the closed-loop performance.

  6. Multi-domain training in healthy old age: Hotel Plastisse as an iPad-based serious game to systematically compare multi-domain and single-domain training.

    PubMed

    Binder, Julia C; Zöllig, Jacqueline; Eschen, Anne; Mérillat, Susan; Röcke, Christina; Schoch, Sarah F; Jäncke, Lutz; Martin, Mike

    2015-01-01

    Finding effective training interventions for declining cognitive abilities in healthy aging is of great relevance, especially in view of the demographic development. Since it is assumed that transfer from the trained to untrained domains is more likely to occur when training conditions and transfer measures share a common underlying process, multi-domain training of several cognitive functions should increase the likelihood of such an overlap. In the first part, we give an overview of the literature showing that cognitive training using complex tasks, such as video games, leisure activities, or practicing a series of cognitive tasks, has shown promising results regarding transfer to a number of cognitive functions. These studies, however, do not allow direct inference about the underlying functions targeted by these training regimes. Custom-designed serious games allow to design training regimes according to specific cognitive functions and a target population's need. In the second part, we introduce the serious game Hotel Plastisse as an iPad-based training tool for older adults that allows the comparison of the simultaneous training of spatial navigation, visuomotor function, and inhibition to the training of each of these functions separately. Hotel Plastisse not only defines the cognitive functions of the multi-domain training clearly, but also implements training in an interesting learning environment including adaptive difficulty and feedback. We propose this novel training tool with the goal of furthering our understanding of how training regimes should be designed in order to affect cognitive functioning of older adults most broadly.

  7. Multi-domain training in healthy old age: Hotel Plastisse as an iPad-based serious game to systematically compare multi-domain and single-domain training

    PubMed Central

    Binder, Julia C.; Zöllig, Jacqueline; Eschen, Anne; Mérillat, Susan; Röcke, Christina; Schoch, Sarah F.; Jäncke, Lutz; Martin, Mike

    2015-01-01

    Finding effective training interventions for declining cognitive abilities in healthy aging is of great relevance, especially in view of the demographic development. Since it is assumed that transfer from the trained to untrained domains is more likely to occur when training conditions and transfer measures share a common underlying process, multi-domain training of several cognitive functions should increase the likelihood of such an overlap. In the first part, we give an overview of the literature showing that cognitive training using complex tasks, such as video games, leisure activities, or practicing a series of cognitive tasks, has shown promising results regarding transfer to a number of cognitive functions. These studies, however, do not allow direct inference about the underlying functions targeted by these training regimes. Custom-designed serious games allow to design training regimes according to specific cognitive functions and a target population's need. In the second part, we introduce the serious game Hotel Plastisse as an iPad-based training tool for older adults that allows the comparison of the simultaneous training of spatial navigation, visuomotor function, and inhibition to the training of each of these functions separately. Hotel Plastisse not only defines the cognitive functions of the multi-domain training clearly, but also implements training in an interesting learning environment including adaptive difficulty and feedback. We propose this novel training tool with the goal of furthering our understanding of how training regimes should be designed in order to affect cognitive functioning of older adults most broadly. PMID:26257643

  8. The functional transfer of genes from the mitochondria to the nucleus: the effects of selection, mutation, population size and rate of self-fertilization.

    PubMed

    Brandvain, Yaniv; Wade, Michael J

    2009-08-01

    The transfer of mitochondrial genes to the nucleus is a recurrent and consistent feature of eukaryotic genome evolution. Although many theories have been proposed to explain such transfers, little relevant data exist. The observation that clonal and self-fertilizing plants transfer more mitochondrial genes to their nuclei than do outcrossing plants contradicts predictions of major theories based on nuclear recombination and leaves a gap in our conceptual understanding how the observed pattern of gene transfer could arise. Here, with a series of deterministic and stochastic simulations, we show how epistatic selection and relative mutation rates of mitochondrial and nuclear genes influence mitochondrial-to-nuclear gene transfer. Specifically, we show that when there is a benefit to having a mitochondrial gene present in the nucleus, but absent in the mitochondria, self-fertilization dramatically increases both the rate and the probability of gene transfer. However, absent such a benefit, when mitochondrial mutation rates exceed those of the nucleus, self-fertilization decreases the rate and probability of transfer. This latter effect, however, is much weaker than the former. Our results are relevant to understanding the probabilities of fixation when loci in different genomes interact.

  9. A new way to generate cytolytic tumor-specific T cells: electroporation of RNA coding for a T cell receptor into T lymphocytes.

    PubMed

    Schaft, Niels; Dörrie, Jan; Müller, Ina; Beck, Verena; Baumann, Stefanie; Schunder, Tanja; Kämpgen, Eckhart; Schuler, Gerold

    2006-09-01

    Effective T cell receptor (TCR) transfer until now required stable retroviral transduction. However, retroviral transduction poses the threat of irreversible genetic manipulation of autologous cells. We, therefore, used optimized RNA transfection for transient manipulation. The transfection efficiency, using EGFP RNA, was >90%. The electroporation of primary T cells, isolated from blood, with TCR-coding RNA resulted in functional cytotoxic T lymphocytes (CTLs) (>60% killing at an effector to target ratio of 20:1) with the same HLA-A2/gp100-specificity as the parental CTL clone. The TCR-transfected T cells specifically recognized peptide-pulsed T2 cells, or dendritic cells electroporated with gp100-coding RNA, in an IFNgamma-secretion assay and retained this ability, even after cryopreservation, over 3 days. Most importantly, we show here for the first time that the electroporated T cells also displayed cytotoxicity, and specifically lysed peptide-loaded T2 cells and HLA-A2+/gp100+ melanoma cells over a period of at least 72 h. Peptide-titration studies showed that the lytic efficiency of the RNA-transfected T cells was similar to that of retrovirally transduced T cells, and approximated that of the parental CTL clone. Functional TCR transfer by RNA electroporation is now possible without the disadvantages of retroviral transduction, and forms a new strategy for the immunotherapy of cancer.

  10. Inflammatory impact of IFN-γ in CD8+ T cell-mediated lung injury is mediated by both Stat1-dependent and -independent pathways

    PubMed Central

    Ramana, Chilakamarti V.; DeBerge, Matthew P.; Kumar, Aseem; Alia, Christopher S.; Durbin, Joan E.

    2015-01-01

    Influenza infection results in considerable pulmonary pathology, a significant component of which is mediated by CD8+ T cell effector functions. To isolate the specific contribution of CD8+ T cells to lung immunopathology, we utilized a nonviral murine model in which alveolar epithelial cells express an influenza antigen and injury is initiated by adoptive transfer of influenza-specific CD8+ T cells. We report that IFN-γ production by adoptively transferred influenza-specific CD8+ T cells is a significant contributor to acute lung injury following influenza antigen recognition, in isolation from its impact on viral clearance. CD8+ T cell production of IFN-γ enhanced lung epithelial cell expression of chemokines and the subsequent recruitment of inflammatory cells into the airways. Surprisingly, Stat1 deficiency in the adoptive-transfer recipients exacerbated the lung injury that was mediated by the transferred influenza-specific CD8+ T cells but was still dependent on IFN-γ production by these cells. Loss of Stat1 resulted in sustained activation of Stat3 signaling, dysregulated chemokine expression, and increased infiltration of the airways by inflammatory cells. Taken together, these data identify important roles for IFN-γ signaling and Stat1-independent IFN-γ signaling in regulating CD8+ T cell-mediated acute lung injury. This is the first study to demonstrate an anti-inflammatory effect of Stat1 on CD8+ T cell-mediated lung immunopathology without the complication of differences in viral load. PMID:25617378

  11. Optically coded nanocrystal taggants and optical frequency IDs

    NASA Astrophysics Data System (ADS)

    Williams, George M., Jr.; Allen, Thomas; Dupuy, Charles; Novet, Thomas; Schut, David

    2010-04-01

    A series of nanocrystal and nanocrystal quantum dot taggant technologies were developed for covertly tagging and tracking objects of interest. Homogeneous and heterogeneous nanocrystal taggant designs were developed and optimized for ultraviolet through infrared emissions, utilizing either Dexter energy transfer or Förster resonant energy transfer (FRET) between specific absorbing and emitting functionalities. The conversion efficiency, target-specific identification, and adhesion properties of the taggants were engineered by means of various surface ligand chemistries. The ability to engineer poly-functional ligands was shown effective in the detection of a biological agent simulant, detected through a NC photoluminescence that is altered in the presence of the agent of interest; the technique has broad potential applicability to chemical, biological, and explosive (CBE) agent detection. The NC photoluminescence can be detected by a remote LIDAR system; the performance of a taggant system has been modeled and subsequently verified in a series of controlled field tests. LIDAR detection of visible-emitting taggants was shown to exceed 2.8 km in calibrated field tests, and from these field data and calibrated laboratory measurements we predict >5 km range in the covert shortwavelength infrared (SWIR) spectral region.

  12. Structures and functions of proteins and nucleic acids in protein biosynthesis

    NASA Astrophysics Data System (ADS)

    Miyazawa, Tatsuo; Yokoyama, Shigeyuki

    Infrared and Raman spectroscopy is useful for studying helical conformations of polypeptides, which are determined by molecular structure parameters. Nuclear magnetic resonance spectroscopy, as well as X-ray analysis, is now established to be important for conformation studies of proteins and nucleic acids in solution. This article is mainly concerned with the conformational aspect and function regulation in protein biosynthesis. The strict recognition of transfer ribonucleic acid (tRNA) by aminoacyl-tRNA synthetase (ARS) is achieved by multi-step mutual adaptation. The conformations of ARS-bound amino acids have been elucidated by transferred nuclear Overhauser effect analysis. Aminoacyl-tRNA takes the 3‧-isomeric form in the polypeptide chain elongation cycle. The regulation of codon recognition by post-transcriptional modification is achieved by conversion of the conformational characteristic of the anticodon of tRNA. The cytidine → lysidine modification of the anticodon of minor isoleucine tRNA concurrently converts the amino acid specificity and the codon specificity. As novel protein engineering, a basic strategy has been established for in vivo biosynthesis of proteins that are substituted with unnatural amino acids (alloproteins).

  13. B′-protein phosphatase 2A is a functional binding partner of delta-retroviral integrase

    PubMed Central

    Maertens, Goedele N.

    2016-01-01

    To establish infection, a retrovirus must insert a DNA copy of its RNA genome into host chromatin. This reaction is catalysed by the virally encoded enzyme integrase (IN) and is facilitated by viral genus-specific host factors. Herein, cellular serine/threonine protein phosphatase 2A (PP2A) is identified as a functional IN binding partner exclusive to δ-retroviruses, including human T cell lymphotropic virus type 1 and 2 (HTLV-1 and HTLV-2) and bovine leukaemia virus (BLV). PP2A is a heterotrimer composed of a scaffold, catalytic and one of any of four families of regulatory subunits, and the interaction is specific to the B′ family of the regulatory subunits. B′-PP2A and HTLV-1 IN display nuclear co-localization, and the B′ subunit stimulates concerted strand transfer activity of δ-retroviral INs in vitro. The protein–protein interaction interface maps to a patch of highly conserved residues on B′, which when mutated render B′ incapable of binding to and stimulating HTLV-1 and -2 IN strand transfer activity. PMID:26657642

  14. 454 Transcriptome sequencing suggests a role for two-component signalling in cellularization and differentiation of barley endosperm transfer cells.

    PubMed

    Thiel, Johannes; Hollmann, Julien; Rutten, Twan; Weber, Hans; Scholz, Uwe; Weschke, Winfriede

    2012-01-01

    Cell specification and differentiation in the endosperm of cereals starts at the maternal-filial boundary and generates the endosperm transfer cells (ETCs). Besides the importance in assimilate transfer, ETCs are proposed to play an essential role in the regulation of endosperm differentiation by affecting development of proximate endosperm tissues. We attempted to identify signalling elements involved in early endosperm differentiation by using a combination of laser-assisted microdissection and 454 transcriptome sequencing. 454 sequencing of the differentiating ETC region from the syncytial state until functionality in transfer processes captured a high proportion of novel transcripts which are not available in existing barley EST databases. Intriguingly, the ETC-transcriptome showed a high abundance of elements of the two-component signalling (TCS) system suggesting an outstanding role in ETC differentiation. All components and subfamilies of the TCS, including distinct kinds of membrane-bound receptors, have been identified to be expressed in ETCs. The TCS system represents an ancient signal transduction system firstly discovered in bacteria and has previously been shown to be co-opted by eukaryotes, like fungi and plants, whereas in animals and humans this signalling route does not exist. Transcript profiling of TCS elements by qRT-PCR suggested pivotal roles for specific phosphorelays activated in a coordinated time flow during ETC cellularization and differentiation. ETC-specificity of transcriptionally activated TCS phosphorelays was assessed for early differentiation and cellularization contrasting to an extension of expression to other grain tissues at the beginning of ETC maturation. Features of candidate genes of distinct phosphorelays and transcriptional activation of genes putatively implicated in hormone signalling pathways hint at a crosstalk of hormonal influences, putatively ABA and ethylene, and TCS signalling. Our findings suggest an integral function for the TCS in ETC differentiation possibly coupled to sequent hormonal regulation by ABA and ethylene.

  15. 454 Transcriptome Sequencing Suggests a Role for Two-Component Signalling in Cellularization and Differentiation of Barley Endosperm Transfer Cells

    PubMed Central

    Thiel, Johannes; Hollmann, Julien; Rutten, Twan; Weber, Hans; Scholz, Uwe; Weschke, Winfriede

    2012-01-01

    Background Cell specification and differentiation in the endosperm of cereals starts at the maternal-filial boundary and generates the endosperm transfer cells (ETCs). Besides the importance in assimilate transfer, ETCs are proposed to play an essential role in the regulation of endosperm differentiation by affecting development of proximate endosperm tissues. We attempted to identify signalling elements involved in early endosperm differentiation by using a combination of laser-assisted microdissection and 454 transcriptome sequencing. Principal Findings 454 sequencing of the differentiating ETC region from the syncytial state until functionality in transfer processes captured a high proportion of novel transcripts which are not available in existing barley EST databases. Intriguingly, the ETC-transcriptome showed a high abundance of elements of the two-component signalling (TCS) system suggesting an outstanding role in ETC differentiation. All components and subfamilies of the TCS, including distinct kinds of membrane-bound receptors, have been identified to be expressed in ETCs. The TCS system represents an ancient signal transduction system firstly discovered in bacteria and has previously been shown to be co-opted by eukaryotes, like fungi and plants, whereas in animals and humans this signalling route does not exist. Transcript profiling of TCS elements by qRT-PCR suggested pivotal roles for specific phosphorelays activated in a coordinated time flow during ETC cellularization and differentiation. ETC-specificity of transcriptionally activated TCS phosphorelays was assessed for early differentiation and cellularization contrasting to an extension of expression to other grain tissues at the beginning of ETC maturation. Features of candidate genes of distinct phosphorelays and transcriptional activation of genes putatively implicated in hormone signalling pathways hint at a crosstalk of hormonal influences, putatively ABA and ethylene, and TCS signalling. Significance Our findings suggest an integral function for the TCS in ETC differentiation possibly coupled to sequent hormonal regulation by ABA and ethylene. PMID:22848641

  16. Simulation-Based Approach to Determining Electron Transfer Rates Using Square-Wave Voltammetry.

    PubMed

    Dauphin-Ducharme, Philippe; Arroyo-Currás, Netzahualcóyotl; Kurnik, Martin; Ortega, Gabriel; Li, Hui; Plaxco, Kevin W

    2017-05-09

    The efficiency with which square-wave voltammetry differentiates faradic and charging currents makes it a particularly sensitive electroanalytical approach, as evidenced by its ability to measure nanomolar or even picomolar concentrations of electroactive analytes. Because of the relative complexity of the potential sweep it uses, however, the extraction of detailed kinetic and mechanistic information from square-wave data remains challenging. In response, we demonstrate here a numerical approach by which square-wave data can be used to determine electron transfer rates. Specifically, we have developed a numerical approach in which we model the height and the shape of voltammograms collected over a range of square-wave frequencies and amplitudes to simulated voltammograms as functions of the heterogeneous rate constant and the electron transfer coefficient. As validation of the approach, we have used it to determine electron transfer kinetics in both freely diffusing and diffusionless surface-tethered species, obtaining electron transfer kinetics in all cases in good agreement with values derived using non-square-wave methods.

  17. Transfer molding processes for nanoscale patterning of poly-L-lactic acid (PLLA) films

    NASA Astrophysics Data System (ADS)

    Dhakal, Rabin; Peer, Akshit; Biswas, Rana; Kim, Jaeyoun

    2016-03-01

    Nanoscale patterned structures composed of biomaterials exhibit great potential for the fabrication of functional biostructures. In this paper, we report cost-effective, rapid, and highly reproducible soft lithographic transfer-molding techniques for creating periodic micro- and nano-scale textures on poly (L-lactic acid) (PLLA) surface. These artificial textures can increase the overall surface area and change the release dynamics of the therapeutic agents coated on it. Specifically, we use the double replication technique in which the master pattern is first transferred to the PDMS mold and the pattern on PDMS is then transferred to the PLLA films through drop-casting as well as nano-imprinting. The ensuing comparison studies reveal that the drop-cast PLLA allows pattern transfer at higher levels of fidelity, enabling the realization of nano-hole and nano-cone arrays with pitch down to ~700 nm. The nano-patterned PLLA film was then coated with rapamycin to make it drug-eluting.

  18. Testate amoeba transfer function performance along localised hydrological gradients.

    PubMed

    Tsyganov, Andrey N; Mityaeva, Olga A; Mazei, Yuri A; Payne, Richard J

    2016-09-01

    Testate amoeba transfer functions are widely used for reconstruction of palaeo-hydrological regime in peatlands. However, the limitations of this approach have become apparent with increasing attention to validation and assessing sources of uncertainty. This paper investigates effects of peatland type and sampling depth on the performance of a transfer function using an independent test-set from four Sphagnum-dominated sites in European Russia (Penza Region). We focus on transfer function performance along localised hydrological gradients, which is a useful analogue for predictive ability through time. The performance of the transfer function with the independent test-set was generally weaker than for the leave-one-out or bootstrap cross-validations. However, the transfer function was robust for the reconstruction of relative changes in water-table depth, provided the presence of good modern analogues and overlap in water-table depth ranges. When applied to subsurface samples, the performance of the transfer function was reduced due to selective decomposition, the presence of deep-dwelling taxa or vertical transfer of shells. Our results stress the importance of thorough testing of transfer functions, and highlight the role of taphonomic processes in determining results. Further studies of stratification, taxonomy and taphonomy of testate amoebae will be needed to improve the robustness of transfer function output. Copyright © 2015 Elsevier GmbH. All rights reserved.

  19. Surface Redox Chemistry of Immobilized Nanodiamond: Effects of Particle Size and Electrochemical Environment

    NASA Astrophysics Data System (ADS)

    Gupta, S.; McDonald, B.; Carrizosa, S. B.

    2017-07-01

    The size of the diamond particle is tailored to nanoscale (nanodiamond, ND), and the ND surface is engineered targeting specific (electrochemical and biological) applications. In this work, we investigated the complex surface redox chemistry of immobilized ND layer on conductive boron-doped diamond electrode with a broad experimental parameter space such as particle size (nano versus micron), scan rate, pH (cationic/acidic versus anionic/basic), electrolyte KCl concentration (four orders of magnitude), and redox agents (neutral and ionic). We reported on the significant enhancement of ionic currents while recording reversible oxidation of neutral ferrocene methanol (FcMeOH) by almost one order of magnitude than traditional potassium ferricyanide (K3Fe(CN)6) redox agent. The current enhancement is inversely related to ND particle diameter in the following order: 1 μm << 1000 nm < 100 nm < 10 nm ≤ 5 nm < 2 nm. We attribute the current enhancement to concurrent electrocatalytic processes, i.e. the electron transfer between redox probes and electroactive surface functional (e.g. hydroxyl, carboxyl, epoxy) moieties and the electron transfer mediated by adsorbed FcMeOH+ (or Fe(CN) 6 3+ ) ions onto ND surface. The first process is pH dependent since it depends upon ND surface functionalities for which the electron transfer is coupled to proton transfer. The adsorption mediated process is observed most apparently at slower scan rates owing to self-exchange between adsorbed FcMeOH+ ions and FcMeOH redox agent molecules in diffusion-limited bulk electrolyte solution. Alternatively, it is hypothesized that the surface functionality and defect sites ( sp 2-bonded C shell and unsaturated bonds) give rise to surface electronic states with energies within the band gap (midgap states) in undoped ND. These surface states serve as electron donors (and acceptors) depending upon their bonding (and antibonding) character and, therefore, they can support electrocatalytic redox processes in the presence of specific redox-active molecules via feedback mechanism. Apparently, FcMeOH+ tended to have electrostatic affinity for negatively charged ND surface functionalities, corroborated by present experiments. We also attempted to study biocatalytic process using model metalloprotein (cytochrome c; Cyt c) immobilized on ND particles for investigating interfacial electron transfer kinetics and compared with those of functionalized graphene (graphene oxide; GO and reduced GO). The findings are discussed in terms of interplay of sp 3-bonded C (ND core) and sp 2-bonded C (ND shell and graphene-based systems).

  20. Heat and Mass Transfer in the Over-Shower Zone of a Cooling Tower with Flow Rotation

    NASA Astrophysics Data System (ADS)

    Kashani, M. M. Hemmasian; Dobrego, K. V.

    2013-11-01

    The influence of flow rotation in the over-shower zone of a natural draft wet cooling tower (NDCT) on heat and mass transfer in this zone is investigated numerically. The 3D geometry of an actual NDCT and three models of the induced rotation velocity fields are utilized for calculations. Two phases (liquid and gaseous) and three components are taken into consideration. The interphase heat exchange, heat transfer to the walls, condensation-evaporation intensity field, and other parameters are investigated as functions of the induced rotation intensity (the inclination of the velocity vector at the periphery). It is shown that the induced flow rotation intensifies the heat and mass transfer in the over-shower zone of an NDCT. Flow rotation leads to specific redistribution of evaporation-condensation areas in an NDCT and stimulates water condensation near its walls.

  1. Wireless power using magnetic resonance coupling for neural sensing applications

    NASA Astrophysics Data System (ADS)

    Yoon, Hargsoon; Kim, Hyunjung; Choi, Sang H.; Sanford, Larry D.; Geddis, Demetris; Lee, Kunik; Kim, Jaehwan; Song, Kyo D.

    2012-04-01

    Various wireless power transfer systems based on electromagnetic coupling have been investigated and applied in many biomedical applications including functional electrical stimulation systems and physiological sensing in humans and animals. By integrating wireless power transfer modules with wireless communication devices, electronic systems can deliver data and control system operation in untethered freely-moving conditions without requiring access through the skin, a potential source of infection. In this presentation, we will discuss a wireless power transfer module using magnetic resonance coupling that is specifically designed for neural sensing systems and in-vivo animal models. This research presents simple experimental set-ups and circuit models of magnetic resonance coupling modules and discusses advantages and concerns involved in positioning and sizing of source and receiver coils compared to conventional inductive coupling devices. Furthermore, the potential concern of tissue heating in the brain during operation of the wireless power transfer systems will also be addressed.

  2. Transfer function characteristics of super resolving systems

    NASA Technical Reports Server (NTRS)

    Milster, Tom D.; Curtis, Craig H.

    1992-01-01

    Signal quality in an optical storage device greatly depends on the optical system transfer function used to write and read data patterns. The problem is similar to analysis of scanning optical microscopes. Hopkins and Braat have analyzed write-once-read-many (WORM) optical data storage devices. Herein, transfer function analysis of magnetooptic (MO) data storage devices is discussed with respect to improving transfer-function characteristics. Several authors have described improving the transfer function as super resolution. However, none have thoroughly analyzed the MO optical system and effects of the medium. Both the optical system transfer function and effects of the medium of this development are discussed.

  3. Integrated controls and health monitoring for chemical transfer propulsion

    NASA Technical Reports Server (NTRS)

    Millis, Marc G.; Binder, Michael P.

    1990-01-01

    NASA is reviewing various propulsion technologies for exploring space. The requirements are examined for one enabling propulsion technology: Integrated Controls and Health Monitoring (ICHM) for Chemical Transfer Propulsion (CTP). Functional requirements for a CTP-ICHM system are proposed from tentative mission scenarios, vehicle configurations, CTP specifications, and technical feasibility. These CTP-ICHM requirements go beyond traditional reliable operation and emergency shutoff control to include: (1) enhanced mission flexibility; (2) continuously variable throttling; (3) tank-head start control; (4) automated prestart and post-shutoff engine check; (5) monitoring of space exposure degradation; and (6) product evolution flexibility. Technology development plans are also discussed.

  4. Interlayer‐State‐Coupling Dependent Ultrafast Charge Transfer in MoS2/WS2 Bilayers

    PubMed Central

    Zhang, Jin; Hong, Hao; Lian, Chao; Ma, Wei; Xu, Xiaozhi; Zhou, Xu; Fu, Huixia

    2017-01-01

    Light‐induced interlayer ultrafast charge transfer in 2D heterostructures provides a new platform for optoelectronic and photovoltaic applications. The charge separation process is generally hypothesized to be dependent on the interlayer stackings and interactions, however, the quantitative characteristic and detailed mechanism remain elusive. Here, a systematical study on the interlayer charge transfer in model MoS2/WS2 bilayer system with variable stacking configurations by time‐dependent density functional theory methods is demonstrated. The results show that the slight change of interlayer geometry can significantly modulate the charge transfer time from 100 fs to 1 ps scale. Detailed analysis further reveals that the transfer rate in MoS2/WS2 bilayers is governed by the electronic coupling between specific interlayer states, rather than the interlayer distances, and follows a universal dependence on the state‐coupling strength. The results establish the interlayer stacking as an effective freedom to control ultrafast charge transfer dynamics in 2D heterostructures and facilitate their future applications in optoelectronics and light harvesting. PMID:28932669

  5. An expanded ostracod-based conductivity transfer function for climate reconstruction in the Levant

    NASA Astrophysics Data System (ADS)

    Mischke, Steffen; Almogi-Labin, Ahuva; Al-Saqarat, Bety; Rosenfeld, Arik; Elyashiv, Hadar; Boomer, Ian; Stein, Mordechai; Lev, Lilach; Ito, Emi

    2014-06-01

    We present the first modern calibration dataset linking ostracod assemblage composition to water chemistry, and other site-specific variables, in the hydrologically and geopolitically sensitive southern Levant region. A total of 42 ostracod taxa were recorded from the 178 sampled sites in Israel and Jordan. Ilyocypris spp., Heterocypris salina and Cypridopsis vidua are the most abundant taxa. Species strictly confined to freshwater conditions are Prionocypris zenkeri, Gomphocythere ortali and Prionocypris olivaceus. In contrast, H. salina, Bradleytriebella lineata and Cyprideis torosa show high frequencies in brackish waters (waters with higher conductivity). Humphcypris subterranea, G. ortali, P. olivaceus and Cypridopsis elongata apparently prefer flowing waters. Specific conductivity optima and tolerance ranges were calculated for the recorded ostracod species and may be used for the palaeoenvironmental assessment of fossil ostracod assemblages. In addition, a transfer-function for quantitative specific conductivity estimation based on 141 samples was established with weighted averaging partial least squares regression (WA-PLS). The resulting coefficient of determination r2 between observed and predicted conductivity values (0.72) and the root-mean-square error of prediction (RMSEP) in % gradient length (13.1) indicate that conductivity may be reliably estimated from ostracod assemblage data. The transfer function was first applied to last glacial ostracod assemblage data from an archaeological trench in the Sea of Galilee (northern Israel). Relatively large conductivity fluctuations between ca 1 and 7 mS cm-1 were inferred for the period 24-20 cal ka BP. In addition, four episodes of freshwater influx near the site of the trench were identified from the presence of shells of freshwater and stream-dwelling species intermingled with very abundant shells of Cyprideis torosa. The results of our study allow a better use of Quaternary ostracods from the Levant as palaeoenvironmental indicators of water-body types and past conductivity levels and will contribute to a better understanding of Quaternary environmental and climate change in the Levant.

  6. Efficient patient modeling for visuo-haptic VR simulation using a generic patient atlas.

    PubMed

    Mastmeyer, Andre; Fortmeier, Dirk; Handels, Heinz

    2016-08-01

    This work presents a new time-saving virtual patient modeling system by way of example for an existing visuo-haptic training and planning virtual reality (VR) system for percutaneous transhepatic cholangio-drainage (PTCD). Our modeling process is based on a generic patient atlas to start with. It is defined by organ-specific optimized models, method modules and parameters, i.e. mainly individual segmentation masks, transfer functions to fill the gaps between the masks and intensity image data. In this contribution, we show how generic patient atlases can be generalized to new patient data. The methodology consists of patient-specific, locally-adaptive transfer functions and dedicated modeling methods such as multi-atlas segmentation, vessel filtering and spline-modeling. Our full image volume segmentation algorithm yields median DICE coefficients of 0.98, 0.93, 0.82, 0.74, 0.51 and 0.48 regarding soft-tissue, liver, bone, skin, blood and bile vessels for ten test patients and three selected reference patients. Compared to standard slice-wise manual contouring time saving is remarkable. Our segmentation process shows out efficiency and robustness for upper abdominal puncture simulation systems. This marks a significant step toward establishing patient-specific training and hands-on planning systems in a clinical environment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Self-optimizing charge-transfer energy phenomena in metallosupramolecular complexes by dynamic constitutional self-sorting.

    PubMed

    Legrand, Yves-Marie; van der Lee, Arie; Barboiu, Mihail

    2007-11-12

    In this paper we report an extended series of 2,6-(iminoarene)pyridine-type ZnII complexes [(Lii)2Zn]II, which were surveyed for their ability to self-exchange both their ligands and their aromatic arms and to form different homoduplex and heteroduplex complexes in solution. The self-sorting of heteroduplex complexes is likely to be the result of geometric constraints. Whereas the imine-exchange process occurs quantitatively in 1:1 mixtures of [(Lii)2Zn]II complexes, the octahedral coordination process around the metal ion defines spatial-frustrated exchanges that involve the selective formation of heterocomplexes of two, by two different substituents; the bulkiest ones (pyrene in principle) specifically interact with the pseudoterpyridine core, sterically hindering the least bulky ones, which are intermolecularly stacked with similar ligands of neighboring molecules. Such a self-sorting process defined by the specific self-constitution of the ligands exchanging their aromatic substituents is self-optimized by a specific control over their spatial orientation around a metal center within the complex. They ultimately show an improved charge-transfer energy function by virtue of the dynamic amplification of self-optimized heteroduplex architectures. These systems therefore illustrate the convergence of the combinatorial self-sorting of the dynamic combinatorial libraries (DCLs) strategy and the constitutional self-optimized function.

  8. [Patient-centered approaches to understanding, transformation and solution of team conflicts in the psychiatric clinic within the scope of the Balint group concept].

    PubMed

    Drees, A

    1987-08-01

    The working climate and therapeutic possibilities in a hospital are determined, among other factors, by emotional processes in everyday ward routine. Team conflicts and their solution are not infrequently reflections of the open-mindedness of a hospital towards the complexity of these processes. However, the complex interlocking of transference processes with rôle-specific and personality-conditioned behaviour patterns makes it more difficult to understand and make use of these emotional processes within the team. We present a specific attempt to working up emotional conflicts in a patient-centred approach via focussing on self-rating of the team workers in respect of mood, feeling tone and imagination. Specific internal Balint groups are the fulcrum. To distinguish this method from the theory of object-directed transference of emotions and constructions of relations, the theoretical basis of this group method is seen in the systemic paradigm with which patient-focussed solution functions are obtained in respect of process orientation and instrumental part functions of the team workers. In this connection it was explored to what extent the following factors can be interpreted as patient-induced phenomena: therapeutic and rôle behaviour, hospital structures and administrative squabbles, internal and external walls of a mental hospital.

  9. Development of a new pan-European testate amoeba transfer function for reconstructing peatland palaeohydrology

    NASA Astrophysics Data System (ADS)

    Amesbury, Matthew J.; Swindles, Graeme T.; Bobrov, Anatoly; Charman, Dan J.; Holden, Joseph; Lamentowicz, Mariusz; Mallon, Gunnar; Mazei, Yuri; Mitchell, Edward A. D.; Payne, Richard J.; Roland, Thomas P.; Turner, T. Edward; Warner, Barry G.

    2016-11-01

    In the decade since the first pan-European testate amoeba-based transfer function for peatland palaeohydrological reconstruction was published, a vast amount of additional data collection has been undertaken by the research community. Here, we expand the pan-European dataset from 128 to 1799 samples, spanning 35° of latitude and 55° of longitude. After the development of a new taxonomic scheme to permit compilation of data from a wide range of contributors and the removal of samples with high pH values, we developed ecological transfer functions using a range of model types and a dataset of ∼1300 samples. We rigorously tested the efficacy of these models using both statistical validation and independent test sets with associated instrumental data. Model performance measured by statistical indicators was comparable to other published models. Comparison to test sets showed that taxonomic resolution did not impair model performance and that the new pan-European model can therefore be used as an effective tool for palaeohydrological reconstruction. Our results question the efficacy of relying on statistical validation of transfer functions alone and support a multi-faceted approach to the assessment of new models. We substantiated recent advice that model outputs should be standardised and presented as residual values in order to focus interpretation on secure directional shifts, avoiding potentially inaccurate conclusions relating to specific water-table depths. The extent and diversity of the dataset highlighted that, at the taxonomic resolution applied, a majority of taxa had broad geographic distributions, though some morphotypes appeared to have restricted ranges.

  10. Function Transfer in Human Operant Experiments: The Role of Stimulus Pairings

    ERIC Educational Resources Information Center

    Tonneau, Francois; Gonzalez, Carmen

    2004-01-01

    Although function transfer often has been studied in complex operant procedures (such as matching to sample), whether operant reinforcement actually produces function transfer in such settings has not been established. The present experiments, with high school students as subjects, suggest that stimulus pairings can promote function transfer in…

  11. A DCM study of spectral asymmetries in feedforward and feedback connections between visual areas V1 and V4 in the monkey.

    PubMed

    Bastos, A M; Litvak, V; Moran, R; Bosman, C A; Fries, P; Friston, K J

    2015-03-01

    This paper reports a dynamic causal modeling study of electrocorticographic (ECoG) data that addresses functional asymmetries between forward and backward connections in the visual cortical hierarchy. Specifically, we ask whether forward connections employ gamma-band frequencies, while backward connections preferentially use lower (beta-band) frequencies. We addressed this question by modeling empirical cross spectra using a neural mass model equipped with superficial and deep pyramidal cell populations-that model the source of forward and backward connections, respectively. This enabled us to reconstruct the transfer functions and associated spectra of specific subpopulations within cortical sources. We first established that Bayesian model comparison was able to discriminate between forward and backward connections, defined in terms of their cells of origin. We then confirmed that model selection was able to identify extrastriate (V4) sources as being hierarchically higher than early visual (V1) sources. Finally, an examination of the auto spectra and transfer functions associated with superficial and deep pyramidal cells confirmed that forward connections employed predominantly higher (gamma) frequencies, while backward connections were mediated by lower (alpha/beta) frequencies. We discuss these findings in relation to current views about alpha, beta, and gamma oscillations and predictive coding in the brain. Copyright © 2015. Published by Elsevier Inc.

  12. Symbolic Regression for the Estimation of Transfer Functions of Hydrological Models

    NASA Astrophysics Data System (ADS)

    Klotz, D.; Herrnegger, M.; Schulz, K.

    2017-11-01

    Current concepts for parameter regionalization of spatially distributed rainfall-runoff models rely on the a priori definition of transfer functions that globally map land surface characteristics (such as soil texture, land use, and digital elevation) into the model parameter space. However, these transfer functions are often chosen ad hoc or derived from small-scale experiments. This study proposes and tests an approach for inferring the structure and parametrization of possible transfer functions from runoff data to potentially circumvent these difficulties. The concept uses context-free grammars to generate possible proposition for transfer functions. The resulting structure can then be parametrized with classical optimization techniques. Several virtual experiments are performed to examine the potential for an appropriate estimation of transfer function, all of them using a very simple conceptual rainfall-runoff model with data from the Austrian Mur catchment. The results suggest that a priori defined transfer functions are in general well identifiable by the method. However, the deduction process might be inhibited, e.g., by noise in the runoff observation data, often leading to transfer function estimates of lower structural complexity.

  13. First-and Second-Order Displacement Transfer Functions for Structural Shape Calculations Using Analytically Predicted Surface Strains

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Fleischer, Van Tran

    2012-01-01

    New first- and second-order displacement transfer functions have been developed for deformed shape calculations of nonuniform cross-sectional beam structures such as aircraft wings. The displacement transfer functions are expressed explicitly in terms of beam geometrical parameters and surface strains (uniaxial bending strains) obtained at equally spaced strain stations along the surface of the beam structure. By inputting the measured or analytically calculated surface strains into the displacement transfer functions, one could calculate local slopes, deflections, and cross-sectional twist angles of the nonuniform beam structure for mapping the overall structural deformed shapes for visual display. The accuracy of deformed shape calculations by the first- and second-order displacement transfer functions are determined by comparing these values to the analytically predicted values obtained from finite element analyses. This comparison shows that the new displacement transfer functions could quite accurately calculate the deformed shapes of tapered cantilever tubular beams with different tapered angles. The accuracy of the present displacement transfer functions also are compared to those of the previously developed displacement transfer functions.

  14. Multiple functionalization of fluorescent nanoparticles for specific biolabeling and drug delivery of dopamine

    NASA Astrophysics Data System (ADS)

    Malvindi, Maria Ada; di Corato, Riccardo; Curcio, Annalisa; Melisi, Daniela; Rimoli, Maria Grazia; Tortiglione, Claudia; Tino, Angela; George, Chandramohan; Brunetti, Virgilio; Cingolani, Roberto; Pellegrino, Teresa; Ragusa, Andrea

    2011-12-01

    The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release.The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release. Electronic supplementary information (ESI) available: TEM images, absorption and emission spectra, ζ-potential and DLS graphics, gel electrophoresis images, cyclic voltammograms, western blot and RT-PCR data. See DOI: 10.1039/c1nr10797f

  15. Recombinational Cloning Using Gateway and In-Fusion Cloning Schemes

    PubMed Central

    Throop, Andrea L.; LaBaer, Joshua

    2015-01-01

    The comprehensive study of protein structure and function, or proteomics, depends on the obtainability of full-length cDNAs in species-specific expression vectors and subsequent functional analysis of the expressed protein. Recombinational cloning is a universal cloning technique based on site-specific recombination that is independent of the insert DNA sequence of interest, which differentiates this method from the classical restriction enzyme-based cloning methods. Recombinational cloning enables rapid and efficient parallel transfer of DNA inserts into multiple expression systems. This unit summarizes strategies for generating expression-ready clones using the most popular recombinational cloning technologies, including the commercially available Gateway® (Life Technologies) and In-Fusion® (Clontech) cloning technologies. PMID:25827088

  16. 10 CFR 70.39 - Specific licenses for the manufacture or initial transfer of calibration or reference sources.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Specific licenses for the manufacture or initial transfer... manufacture or initial transfer of calibration or reference sources. (a) An application for a specific license to manufacture or initially transfer calibration or reference sources containing plutonium, for...

  17. Fusion of GFP to the M.EcoKI DNA methyltransferase produces a new probe of Type I DNA restriction and modification enzymes

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

    Chen, Kai; Roberts, Gareth A.; Stephanou, Augoustinos S.

    2010-07-23

    Research highlights: {yields} Successful fusion of GFP to M.EcoKI DNA methyltransferase. {yields} GFP located at C-terminal of sequence specificity subunit does not later enzyme activity. {yields} FRET confirms structural model of M.EcoKI bound to DNA. -- Abstract: We describe the fusion of enhanced green fluorescent protein to the C-terminus of the HsdS DNA sequence-specificity subunit of the Type I DNA modification methyltransferase M.EcoKI. The fusion expresses well in vivo and assembles with the two HsdM modification subunits. The fusion protein functions as a sequence-specific DNA methyltransferase protecting DNA against digestion by the EcoKI restriction endonuclease. The purified enzyme shows Foerstermore » resonance energy transfer to fluorescently-labelled DNA duplexes containing the target sequence and to fluorescently-labelled ocr protein, a DNA mimic that binds to the M.EcoKI enzyme. Distances determined from the energy transfer experiments corroborate the structural model of M.EcoKI.« less

  18. The sacroiliac joint: an overview of its anatomy, function and potential clinical implications

    PubMed Central

    Vleeming, A; Schuenke, M D; Masi, A T; Carreiro, J E; Danneels, L; Willard, F H

    2012-01-01

    This article focuses on the (functional) anatomy and biomechanics of the pelvic girdle and specifically the sacroiliac joints (SIJs). The SIJs are essential for effective load transfer between the spine and legs. The sacrum, pelvis and spine, and the connections to the arms, legs and head, are functionally interrelated through muscular, fascial and ligamentous interconnections. A historical overview is presented on pelvic and especially SIJ research, followed by a general functional anatomical overview of the pelvis. In specific sections, the development and maturation of the SIJ is discussed, and a description of the bony anatomy and sexual morphism of the pelvis and SIJ is debated. The literature on the SIJ ligaments and innervation is discussed, followed by a section on the pathology of the SIJ. Pelvic movement studies are investigated and biomechanical models for SIJ stability analyzed, including examples of insufficient versus excessive sacroiliac force closure. PMID:22994881

  19. SPICODYN: A Toolbox for the Analysis of Neuronal Network Dynamics and Connectivity from Multi-Site Spike Signal Recordings.

    PubMed

    Pastore, Vito Paolo; Godjoski, Aleksandar; Martinoia, Sergio; Massobrio, Paolo

    2018-01-01

    We implemented an automated and efficient open-source software for the analysis of multi-site neuronal spike signals. The software package, named SPICODYN, has been developed as a standalone windows GUI application, using C# programming language with Microsoft Visual Studio based on .NET framework 4.5 development environment. Accepted input data formats are HDF5, level 5 MAT and text files, containing recorded or generated time series spike signals data. SPICODYN processes such electrophysiological signals focusing on: spiking and bursting dynamics and functional-effective connectivity analysis. In particular, for inferring network connectivity, a new implementation of the transfer entropy method is presented dealing with multiple time delays (temporal extension) and with multiple binary patterns (high order extension). SPICODYN is specifically tailored to process data coming from different Multi-Electrode Arrays setups, guarantying, in those specific cases, automated processing. The optimized implementation of the Delayed Transfer Entropy and the High-Order Transfer Entropy algorithms, allows performing accurate and rapid analysis on multiple spike trains from thousands of electrodes.

  20. Nonparametric Transfer Function Models

    PubMed Central

    Liu, Jun M.; Chen, Rong; Yao, Qiwei

    2009-01-01

    In this paper a class of nonparametric transfer function models is proposed to model nonlinear relationships between ‘input’ and ‘output’ time series. The transfer function is smooth with unknown functional forms, and the noise is assumed to be a stationary autoregressive-moving average (ARMA) process. The nonparametric transfer function is estimated jointly with the ARMA parameters. By modeling the correlation in the noise, the transfer function can be estimated more efficiently. The parsimonious ARMA structure improves the estimation efficiency in finite samples. The asymptotic properties of the estimators are investigated. The finite-sample properties are illustrated through simulations and one empirical example. PMID:20628584

  1. Neural network processing of microbial fuel cell signals for the identification of chemicals present in water.

    PubMed

    Feng, Yinghua; Barr, William; Harper, W F

    2013-05-15

    Biosensing is emerging as an important element of water quality monitoring. This research demonstrated that microbial fuel cell (MFC)-based biosensing can be integrated with artificial neural networks (ANNs) to identify specific chemicals present in water samples. The non-fermentable substrates, acetate and butyrate, induced peak areas (PA) and peak heights (PH) that were generally larger than those caused by the injection of fermentable substrates, glucose and corn starch. The ANN successfully identified peaks associated with these four chemicals under a variety of experimental conditions and for two MFCs that had different levels of sensitivity. ANNs that employ the hyperbolic tangent sigmoid transfer function performed better than those using non-continuous transfer functions. ANNs should be integrated into water quality monitoring efforts for smart biosensing. Published by Elsevier Ltd.

  2. Localized electron transfer rates and microelectrode-based enrichment of microbial communities within a phototrophic microbial mat.

    PubMed

    Babauta, Jerome T; Atci, Erhan; Ha, Phuc T; Lindemann, Stephen R; Ewing, Timothy; Call, Douglas R; Fredrickson, James K; Beyenal, Haluk

    2014-01-01

    Phototrophic microbial mats frequently exhibit sharp, light-dependent redox gradients that regulate microbial respiration on specific electron acceptors as a function of depth. In this work, a benthic phototrophic microbial mat from Hot Lake, a hypersaline, epsomitic lake located near Oroville in north-central Washington, was used to develop a microscale electrochemical method to study local electron transfer processes within the mat. To characterize the physicochemical variables influencing electron transfer, we initially quantified redox potential, pH, and dissolved oxygen gradients by depth in the mat under photic and aphotic conditions. We further demonstrated that power output of a mat fuel cell was light-dependent. To study local electron transfer processes, we deployed a microscale electrode (microelectrode) with tip size ~20 μm. To enrich a subset of microorganisms capable of interacting with the microelectrode, we anodically polarized the microelectrode at depth in the mat. Subsequently, to characterize the microelectrode-associated community and compare it to the neighboring mat community, we performed amplicon sequencing of the V1-V3 region of the 16S gene. Differences in Bray-Curtis beta diversity, illustrated by large changes in relative abundance at the phylum level, suggested successful enrichment of specific mat community members on the microelectrode surface. The microelectrode-associated community exhibited substantially reduced alpha diversity and elevated relative abundances of Prosthecochloris, Loktanella, Catellibacterium, other unclassified members of Rhodobacteraceae, Thiomicrospira, and Limnobacter, compared with the community at an equivalent depth in the mat. Our results suggest that local electron transfer to an anodically polarized microelectrode selected for a specific microbial population, with substantially more abundance and diversity of sulfur-oxidizing phylotypes compared with the neighboring mat community.

  3. Localized electron transfer rates and microelectrode-based enrichment of microbial communities within a phototrophic microbial mat

    PubMed Central

    Babauta, Jerome T.; Atci, Erhan; Ha, Phuc T.; Lindemann, Stephen R.; Ewing, Timothy; Call, Douglas R.; Fredrickson, James K.; Beyenal, Haluk

    2014-01-01

    Phototrophic microbial mats frequently exhibit sharp, light-dependent redox gradients that regulate microbial respiration on specific electron acceptors as a function of depth. In this work, a benthic phototrophic microbial mat from Hot Lake, a hypersaline, epsomitic lake located near Oroville in north-central Washington, was used to develop a microscale electrochemical method to study local electron transfer processes within the mat. To characterize the physicochemical variables influencing electron transfer, we initially quantified redox potential, pH, and dissolved oxygen gradients by depth in the mat under photic and aphotic conditions. We further demonstrated that power output of a mat fuel cell was light-dependent. To study local electron transfer processes, we deployed a microscale electrode (microelectrode) with tip size ~20 μm. To enrich a subset of microorganisms capable of interacting with the microelectrode, we anodically polarized the microelectrode at depth in the mat. Subsequently, to characterize the microelectrode-associated community and compare it to the neighboring mat community, we performed amplicon sequencing of the V1–V3 region of the 16S gene. Differences in Bray-Curtis beta diversity, illustrated by large changes in relative abundance at the phylum level, suggested successful enrichment of specific mat community members on the microelectrode surface. The microelectrode-associated community exhibited substantially reduced alpha diversity and elevated relative abundances of Prosthecochloris, Loktanella, Catellibacterium, other unclassified members of Rhodobacteraceae, Thiomicrospira, and Limnobacter, compared with the community at an equivalent depth in the mat. Our results suggest that local electron transfer to an anodically polarized microelectrode selected for a specific microbial population, with substantially more abundance and diversity of sulfur-oxidizing phylotypes compared with the neighboring mat community. PMID:24478768

  4. Localized electron transfer rates and microelectrode-based enrichment of microbial communities within a phototrophic microbial mat

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

    Babauta, Jerome T.; Atci, Erhan; Ha, Phuc T.

    2014-01-01

    Phototrophic microbial mats frequently exhibit sharp, light-dependent redox gradients that regulate microbial respiration on specific electron acceptors as a function of depth. In this work, a benthic phototrophic microbial mat from Hot Lake, a hypersaline, epsomitic lake located near Oroville in north-central Washington, was used to develop a microscale electrochemical method to study local electron transfer processes within the mat. To characterize the physicochemical variables influencing electron transfer, we initially quantified redox potential, pH, and dissolved oxygen gradients by depth in the mat under photic and aphotic conditions. We further demonstrated that power output of a mat fuel cell wasmore » light-dependent. To study local electron transfer processes, we deployed a microscale electrode (microelectrode) with tip size ~20 μm. To enrich a subset of microorganisms capable of interacting with the microelectrode, we anodically polarized the microelectrode at depth in the mat. Subsequently, to characterize the microelectrode- associated community and compare it to the neighboring mat community, we performed amplicon sequencing of the V1-V3 region of the 16S gene. Differences in Bray-Curtis beta diversity, illustrated by large changes in relative abundance at the phylum level, suggested successful enrichment of specific mat community members on the microelectrode surface. The microelectrode-associated community exhibited substantially reduced alpha diversity and elevated relative abundances of Prosthecochloris, Loktanella, Catellibacterium, other unclassified members of Rhodobacteraceae, Thiomicrospira, and Limnobacter, compared with the community at an equivalent depth in the mat. Our results suggest that local electron transfer to an anodically polarized microelectrode selected for a specific microbial population, with substantially more abundance and diversity of sulfur-oxidizing phylotypes compared with the neighboring mat community.« less

  5. Learning-Related Translocation of δ-Opioid Receptors on Ventral Striatal Cholinergic Interneurons Mediates Choice between Goal-Directed Actions

    PubMed Central

    Bertran-Gonzalez, Jesus; Laurent, Vincent; Chieng, Billy C.; Christie, MacDonald J.

    2013-01-01

    The ability of animals to extract predictive information from the environment to inform their future actions is a critical component of decision-making. This phenomenon is studied in the laboratory using the pavlovian–instrumental transfer protocol in which a stimulus predicting a specific pavlovian outcome biases choice toward those actions earning the predicted outcome. It is well established that this transfer effect is mediated by corticolimbic afferents on the nucleus accumbens shell (NAc-S), and recent evidence suggests that δ-opioid receptors (DORs) play an essential role in this effect. In DOR-eGFP knock-in mice, we show a persistent, learning-related plasticity in the translocation of DORs to the somatic plasma membrane of cholinergic interneurons (CINs) in the NAc-S during the encoding of the specific stimulus–outcome associations essential for pavlovian–instrumental transfer. We found that increased membrane DOR expression reflected both stimulus-based predictions of reward and the degree to which these stimuli biased choice during the pavlovian–instrumental transfer test. Furthermore, this plasticity altered the firing pattern of CINs increasing the variance of action potential activity, an effect that was exaggerated by DOR stimulation. The relationship between the induction of membrane DOR expression in CINs and both pavlovian conditioning and pavlovian–instrumental transfer provides a highly specific function for DOR-related modulation in the NAc-S, and it is consistent with an emerging role for striatal CIN activity in the processing of predictive information. Therefore, our results reveal evidence of a long-term, experience-dependent plasticity in opioid receptor expression on striatal modulatory interneurons critical for the cognitive control of action. PMID:24107940

  6. Charge-transfer optical absorption mechanism of DNA:Ag-nanocluster complexes

    NASA Astrophysics Data System (ADS)

    Longuinhos, R.; Lúcio, A. D.; Chacham, H.; Alexandre, S. S.

    2016-05-01

    Optical properties of DNA:Ag-nanoclusters complexes have been successfully applied experimentally in Chemistry, Physics, and Biology. Nevertheless, the mechanisms behind their optical activity remain unresolved. In this work, we present a time-dependent density functional study of optical absorption in DNA:Ag4. In all 23 different complexes investigated, we obtain new absorption peaks in the visible region that are not found in either the isolated Ag4 or isolated DNA base pairs. Absorption from red to green are predominantly of charge-transfer character, from the Ag4 to the DNA fragment, while absorption in the blue-violet range are mostly associated to electronic transitions of a mixed character, involving either DNA-Ag4 hybrid orbitals or intracluster orbitals. We also investigate the role of exchange-correlation functionals in the calculated optical spectra. Significant differences are observed between the calculations using the PBE functional (without exact exchange) and the CAM-B3LYP functional (which partly includes exact exchange). Specifically, we observe a tendency of charge-transfer excitations to involve purines bases, and the PBE spectra error is more pronounced in the complexes where the Ag cluster is bound to the purines. Finally, our results also highlight the importance of adding both the complementary base pair and the sugar-phosphate backbone in order to properly characterize the absorption spectrum of DNA:Ag complexes.

  7. Charge-transfer optical absorption mechanism of DNA:Ag-nanocluster complexes.

    PubMed

    Longuinhos, R; Lúcio, A D; Chacham, H; Alexandre, S S

    2016-05-01

    Optical properties of DNA:Ag-nanoclusters complexes have been successfully applied experimentally in Chemistry, Physics, and Biology. Nevertheless, the mechanisms behind their optical activity remain unresolved. In this work, we present a time-dependent density functional study of optical absorption in DNA:Ag_{4}. In all 23 different complexes investigated, we obtain new absorption peaks in the visible region that are not found in either the isolated Ag_{4} or isolated DNA base pairs. Absorption from red to green are predominantly of charge-transfer character, from the Ag_{4} to the DNA fragment, while absorption in the blue-violet range are mostly associated to electronic transitions of a mixed character, involving either DNA-Ag_{4} hybrid orbitals or intracluster orbitals. We also investigate the role of exchange-correlation functionals in the calculated optical spectra. Significant differences are observed between the calculations using the PBE functional (without exact exchange) and the CAM-B3LYP functional (which partly includes exact exchange). Specifically, we observe a tendency of charge-transfer excitations to involve purines bases, and the PBE spectra error is more pronounced in the complexes where the Ag cluster is bound to the purines. Finally, our results also highlight the importance of adding both the complementary base pair and the sugar-phosphate backbone in order to properly characterize the absorption spectrum of DNA:Ag complexes.

  8. Structural basis of sterol recognition and nonvesicular transport by lipid transfer proteins anchored at membrane contact sites.

    PubMed

    Tong, Junsen; Manik, Mohammad Kawsar; Im, Young Jun

    2018-01-30

    Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential for many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains [StARkin domain (SD)] and multiple targeting modules to specific membrane organelles. Elucidating the structural mechanisms of targeting and ligand recognition by LAMs is important for understanding the interorganelle communication and exchange at MCSs. Here, we determined the crystal structures of the yeast Lam6 pleckstrin homology (PH)-like domain and the SDs of Lam2 and Lam4 in the apo form and in complex with ergosterol. The Lam6 PH-like domain displays a unique PH domain fold with a conserved N-terminal α-helix. The Lam6 PH-like domain lacks the basic surface for phosphoinositide binding, but contains hydrophobic patches on its surface, which are critical for targeting to endoplasmic reticulum (ER)-mitochondrial contacts. Structures of the LAM SDs display a helix-grip fold with a hydrophobic cavity and a flexible Ω1-loop as a lid. Ergosterol is bound to the pocket in a head-down orientation, with its hydrophobic acyl group located in the tunnel entrance. The Ω1-loop in an open conformation is essential for ergosterol binding by direct hydrophobic interaction. Structural comparison suggested that the sterol binding mode of the Lam2 SD2 is likely conserved among the sterol transfer proteins of the StARkin superfamily. Structural models of full-length Lam2 correlated with the sterol transport function at the membrane contact sites.

  9. Surfactant-free Colloidal Particles with Specific Binding Affinity

    PubMed Central

    2017-01-01

    Colloidal particles with specific binding affinity are essential for in vivo and in vitro biosensing, targeted drug delivery, and micrometer-scale self-assembly. Key to these techniques are surface functionalizations that provide high affinities to specific target molecules. For stabilization in physiological environments, current particle coating methods rely on adsorbed surfactants. However, spontaneous desorption of these surfactants typically has an undesirable influence on lipid membranes. To address this issue and create particles for targeting molecules in lipid membranes, we present here a surfactant-free coating method that combines high binding affinity with stability at physiological conditions. After activating charge-stabilized polystyrene microparticles with EDC/Sulfo-NHS, we first coat the particles with a specific protein and subsequently covalently attach a dense layer of poly(ethyelene) glycol. This polymer layer provides colloidal stability at physiological conditions as well as antiadhesive properties, while the protein coating provides the specific affinity to the targeted molecule. We show that NeutrAvidin-functionalized particles bind specifically to biotinylated membranes and that Concanavalin A-functionalized particles bind specifically to the glycocortex of Dictyostelium discoideum cells. The affinity of the particles changes with protein density, which can be tuned during the coating procedure. The generic and surfactant-free coating method reported here transfers the high affinity and specificity of a protein onto colloidal polystyrene microparticles. PMID:28847149

  10. Closed-loop spontaneous baroreflex transfer function is inappropriate for system identification of neural arc but partly accurate for peripheral arc: predictability analysis

    PubMed Central

    Kamiya, Atsunori; Kawada, Toru; Shimizu, Shuji; Sugimachi, Masaru

    2011-01-01

    Abstract Although the dynamic characteristics of the baroreflex system have been described by baroreflex transfer functions obtained from open-loop analysis, the predictability of time-series output dynamics from input signals, which should confirm the accuracy of system identification, remains to be elucidated. Moreover, despite theoretical concerns over closed-loop system identification, the accuracy and the predictability of the closed-loop spontaneous baroreflex transfer function have not been evaluated compared with the open-loop transfer function. Using urethane and α-chloralose anaesthetized, vagotomized and aortic-denervated rabbits (n = 10), we identified open-loop baroreflex transfer functions by recording renal sympathetic nerve activity (SNA) while varying the vascularly isolated intracarotid sinus pressure (CSP) according to a binary random (white-noise) sequence (operating pressure ± 20 mmHg), and using a simplified equation to calculate closed-loop-spontaneous baroreflex transfer function while matching CSP with systemic arterial pressure (AP). Our results showed that the open-loop baroreflex transfer functions for the neural and peripheral arcs predicted the time-series SNA and AP outputs from measured CSP and SNA inputs, with r2 of 0.8 ± 0.1 and 0.8 ± 0.1, respectively. In contrast, the closed-loop-spontaneous baroreflex transfer function for the neural arc was markedly different from the open-loop transfer function (enhanced gain increase and a phase lead), and did not predict the time-series SNA dynamics (r2; 0.1 ± 0.1). However, the closed-loop-spontaneous baroreflex transfer function of the peripheral arc partially matched the open-loop transfer function in gain and phase functions, and had limited but reasonable predictability of the time-series AP dynamics (r2, 0.7 ± 0.1). A numerical simulation suggested that a noise predominantly in the neural arc under resting conditions might be a possible mechanism responsible for our findings. Furthermore, the predictabilities of the neural arc transfer functions obtained in open-loop and closed-loop conditions were validated by closed-loop pharmacological (phenylephrine and nitroprusside infusions) pressure interventions. Time-series SNA responses to drug-induced AP changes predicted by the open-loop transfer function matched closely the measured responses (r2, 0.9 ± 0.1), whereas SNA responses predicted by closed-loop-spontaneous transfer function deviated greatly and were the inverse of measured responses (r, −0.8 ± 0.2). These results indicate that although the spontaneous baroreflex transfer function obtained by closed-loop analysis has been believed to represent the neural arc function, it is inappropriate for system identification of the neural arc but is essentially appropriate for the peripheral arc under resting conditions, when compared with open-loop analysis. PMID:21486839

  11. Automated Transfer Vehicle (ATV) Critical Safety Software Overview

    NASA Astrophysics Data System (ADS)

    Berthelier, D.

    2002-01-01

    The European Automated Transfer Vehicle is an unmanned transportation system designed to dock to International Space Station (ISS) and to contribute to the logistic servicing of the ISS. Concisely, ATV control is realized by a nominal flight control function (using computers, softwares, sensors, actuators). In order to cover the extreme situations where this nominal chain can not ensure safe trajectory with respect to ISS, a segregated proximity flight safety function is activated, where unsafe free drift trajectories can be encountered. This function relies notably on a segregated computer, the Monitoring and Safing Unit (MSU) ; in case of major ATV malfunction detection, ATV is then controlled by MSU software. Therefore, this software is critical because a MSU software failure could result in catastrophic consequences. This paper provides an overview both of this software functions and of the software development and validation method which is specific considering its criticality. First part of the paper describes briefly the proximity flight safety chain. Second part deals with the software functions. Indeed, MSU software is in charge of monitoring nominal computers and ATV corridors, using its own navigation algorithms, and, if an abnormal situation is detected, it is in charge of the ATV control during the Collision Avoidance Manoeuvre (CAM) consisting in an attitude controlled braking boost, followed by a Post-CAM manoeuvre : a Sun-pointed ATV attitude control during up to 24 hours on a safe trajectory. Monitoring, navigation and control algorithms principles are presented. Third part of this paper describes the development and validation process : algorithms functional studies , ADA coding and unit validations ; algorithms ADA code integration and validation on a specific non real-time MATLAB/SIMULINK simulator ; global software functional engineering phase, architectural design, unit testing, integration and validation on target computer.

  12. Characterizing 3D sensors using the 3D modulation transfer function

    NASA Astrophysics Data System (ADS)

    Kellner, Timo; Breitbarth, Andreas; Zhang, Chen; Notni, Gunther

    2018-03-01

    The fields of optical 3D measurement system applications are continuously expanding and becoming more and more diverse. To evaluate appropriate systems for various measurement tasks, comparable parameters are necessary, whereas the 3D modulation transfer function (3D-MTF) has been established as a further criterion. Its aim is the determination of the system response between the measurement of a straight, sharp-edged cube and its opposite ideal calculated one. Within the scope of this work simulations and practical investigations regarding the 3D-MTF’s influences and its main issues are specifically investigated. Therefore, different determined edge radii representing the high-frequency spectra lead to various decreasing 3D-MTF characteristics. Furthermore, rising sampling frequencies improve its maximum transfer value to a saturation point in dependence of the radius. To approve these results of previous simulations, three fringe projection scanners were selected to determine the diversity. As the best 3D-MTF characteristic, a saturated transfer value of H_3D( f_N, 3D) = 0.79 has been identified at a sufficient sampling frequency, which is reached at four times the Nyquist limit. This high 3D resolution can mainly be achieved due to an improved camera projector interaction. Additionally, too small sampling ratios lead to uncertainties in the edge function determination, while higher ratios do not show major improvements. In conclusion, the 3D-MTF algorithm has thus been practically verified and its repeatability as well as its robustness have been confirmed.

  13. Transferred interbacterial antagonism genes augment eukaryotic innate immune function.

    PubMed

    Chou, Seemay; Daugherty, Matthew D; Peterson, S Brook; Biboy, Jacob; Yang, Youyun; Jutras, Brandon L; Fritz-Laylin, Lillian K; Ferrin, Michael A; Harding, Brittany N; Jacobs-Wagner, Christine; Yang, X Frank; Vollmer, Waldemar; Malik, Harmit S; Mougous, Joseph D

    2015-02-05

    Horizontal gene transfer allows organisms to rapidly acquire adaptive traits. Although documented instances of horizontal gene transfer from bacteria to eukaryotes remain rare, bacteria represent a rich source of new functions potentially available for co-option. One benefit that genes of bacterial origin could provide to eukaryotes is the capacity to produce antibacterials, which have evolved in prokaryotes as the result of eons of interbacterial competition. The type VI secretion amidase effector (Tae) proteins are potent bacteriocidal enzymes that degrade the cell wall when delivered into competing bacterial cells by the type VI secretion system. Here we show that tae genes have been transferred to eukaryotes on at least six occasions, and that the resulting domesticated amidase effector (dae) genes have been preserved for hundreds of millions of years through purifying selection. We show that the dae genes acquired eukaryotic secretion signals, are expressed within recipient organisms, and encode active antibacterial toxins that possess substrate specificity matching extant Tae proteins of the same lineage. Finally, we show that a dae gene in the deer tick Ixodes scapularis limits proliferation of Borrelia burgdorferi, the aetiologic agent of Lyme disease. Our work demonstrates that a family of horizontally acquired toxins honed to mediate interbacterial antagonism confers previously undescribed antibacterial capacity to eukaryotes. We speculate that the selective pressure imposed by competition between bacteria has produced a reservoir of genes encoding diverse antimicrobial functions that are tailored for co-option by eukaryotic innate immune systems.

  14. Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia

    PubMed Central

    Paszkiewicz, Paulina J.; Fräßle, Simon P.; Srivastava, Shivani; Sommermeyer, Daniel; Hudecek, Michael; Sadelain, Michel; Liu, Lingfeng; Jensen, Michael C.; Riddell, Stanley R.; Busch, Dirk H.

    2016-01-01

    The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface. Here, we show that targeting EGFRt with the IgG1 monoclonal antibody cetuximab eliminates CD19 CAR T cells both early and late after adoptive transfer in mice, resulting in complete and permanent recovery of normal functional B cells, without tumor relapse. EGFRt can be incorporated into many clinical applications to regulate the survival of gene-engineered cells. These results support the concept that EGFRt represents a promising approach to improve safety of cell-based therapies. PMID:27760047

  15. Corazonin Signaling Is Required in the Male for Sperm Transfer in the Oriental Fruit Fly Bactrocera dorsalis

    PubMed Central

    Hou, Qiu-Li; Chen, Er-Hu; Jiang, Hong-Bo; Yu, Shuai-Feng; Yang, Pei-Jin; Liu, Xiao-Qiang; Park, Yoonseong; Wang, Jin-Jun; Smagghe, Guy

    2018-01-01

    Corazonin (Crz) is a widely distributed neuropeptide (or neurohormone) in insects with diverse physiological functions. The present study aimed to reveal the functions of Crz and its receptor (CrzR) in the regulation of sexual behavior and fertility in male Bactrocera dorsalis. Tissue-specific expression analyses showed that the BdCrz transcript was most abundant in the central nervous system (CNS), and the BdCrzR transcript was most abundant in both the fat body and CNS. Immunochemical localization confirmed that three pairs of Crz-immunoreactive neurons are located in the dorsolateral protocerebrum region of male adult brain. Importantly, RNAi-mediated Crz knockdown lengthened mating duration in males, and knockdown of Crz or CrzR strongly decreased male fertility in the following 3 days, while the courtship behavior and mating efficiency were not affected. The reduced number of sperm in the reproductive organs of mated females indicated that Crz knockdown in males reduced sperm transfer. The findings of this study indicate that Crz contributes to the reproductive physiology of the oriental fruit fly B. dorsalis by regulating sperm transfer in male adults.

  16. Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia.

    PubMed

    Paszkiewicz, Paulina J; Fräßle, Simon P; Srivastava, Shivani; Sommermeyer, Daniel; Hudecek, Michael; Drexler, Ingo; Sadelain, Michel; Liu, Lingfeng; Jensen, Michael C; Riddell, Stanley R; Busch, Dirk H

    2016-11-01

    The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface. Here, we show that targeting EGFRt with the IgG1 monoclonal antibody cetuximab eliminates CD19 CAR T cells both early and late after adoptive transfer in mice, resulting in complete and permanent recovery of normal functional B cells, without tumor relapse. EGFRt can be incorporated into many clinical applications to regulate the survival of gene-engineered cells. These results support the concept that EGFRt represents a promising approach to improve safety of cell-based therapies.

  17. Corazonin Signaling Is Required in the Male for Sperm Transfer in the Oriental Fruit Fly Bactrocera dorsalis.

    PubMed

    Hou, Qiu-Li; Chen, Er-Hu; Jiang, Hong-Bo; Yu, Shuai-Feng; Yang, Pei-Jin; Liu, Xiao-Qiang; Park, Yoonseong; Wang, Jin-Jun; Smagghe, Guy

    2018-01-01

    Corazonin (Crz) is a widely distributed neuropeptide (or neurohormone) in insects with diverse physiological functions. The present study aimed to reveal the functions of Crz and its receptor (CrzR) in the regulation of sexual behavior and fertility in male Bactrocera dorsalis . Tissue-specific expression analyses showed that the BdCrz transcript was most abundant in the central nervous system (CNS), and the BdCrzR transcript was most abundant in both the fat body and CNS. Immunochemical localization confirmed that three pairs of Crz-immunoreactive neurons are located in the dorsolateral protocerebrum region of male adult brain. Importantly, RNAi-mediated Crz knockdown lengthened mating duration in males, and knockdown of Crz or CrzR strongly decreased male fertility in the following 3 days, while the courtship behavior and mating efficiency were not affected. The reduced number of sperm in the reproductive organs of mated females indicated that Crz knockdown in males reduced sperm transfer. The findings of this study indicate that Crz contributes to the reproductive physiology of the oriental fruit fly B. dorsalis by regulating sperm transfer in male adults.

  18. Development of a large commercial camel embryo transfer program: 20 years of scientific research.

    PubMed

    Anouassi, Abdelhaq; Tibary, Ahmed

    2013-01-10

    Embryo transfer in camels was initiated to respond to demand from the camel industry particularly in the United Arab Emirates since 1990. This paper reviews the research performed in critical areas of reproductive physiology and reproductive function evaluation that constitute a pre-requisite for a successful embryo transfer program. A description of donor and recipient management as well as a retrospective evaluation of calf production in the embryo transfer program at Sweihan, UAE is provided. The program utilized two management systems for donors, with and without ovarian superstimulation. Non-stimulated donors are flushed every 14-15 days with a mean embryo production per year per female of 8.5±3.1 (mean±SEM). Response to gonadotropin stimulation is extremely variable. FSH doses and frequency of administration is often adjusted to a specific female. In the period of 1990-2010, 11,477 embryos were transferred to recipients. Transfers from 1990 to 2009 (n=10,600) resulted in 2858 weaned calves, representing an overall efficiency (% weaned calves/transfer) of 27%. Pregnancy rates at 60 days post transfer varied from 19 to 44%. Pregnancy length following transfer is extremely variable. A major challenge in a large embryo transfer program is finding good quality recipients. Causes of pregnancy and neonatal losses are under study. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits

    PubMed Central

    Niwa, Minae; Kamiya, Atsushi; Murai, Rina; Kubo, Ken-ichiro; Gruber, Aaron J; Tomita, Kenji; Lu, Lingling; Tomisato, Shuta; Jaaro-Peled, Hanna; Seshadri, Saurav; Hiyama, Hideki; Huang, Beverly; Kohda, Kazuhisa; Noda, Yukihiro; O’Donnell, Patricio; Nakajima, Kazunori; Sawa, Akira; Nabeshima, Toshitaka

    2011-01-01

    SUMMARY Adult brain function and behavior are influenced by neuronal network formation during development. Genetic susceptibility factors for adult psychiatric illnesses, such as Neuregulin-1 and Disrupted-in-Schizophrenia-1 (DISC1), influence adult high brain functions, including cognition and information processing. These factors have roles during neurodevelopment and are likely to cooperate, forming “pathways” or “signalosomes.” Here we report the potential to generate an animal model via in utero gene transfer in order to address an important question of how nonlethal deficits in early development may affect postnatal brain maturation and high brain functions in adulthood, which are impaired in various psychiatric illnesses, such as schizophrenia. We show that transient knockdown of DISC1 in the pre- and peri-natal stages, specifically in a lineage of pyramidal neurons mainly in the prefrontal cortex, leads to selective abnormalities in postnatal mesocortical dopaminergic maturation and behavioral abnormalities associated with disturbed cortical neurocircuitry after puberty. PMID:20188653

  20. Towards a theoretical clarification of biomimetics using conceptual tools from engineering design.

    PubMed

    Drack, M; Limpinsel, M; de Bruyn, G; Nebelsick, J H; Betz, O

    2017-12-13

    Many successful examples of biomimetic products are available, and most research efforts in this emerging field are directed towards the development of specific applications. The theoretical and conceptual underpinnings of the knowledge transfer between biologists, engineers and architects are, however, poorly investigated. The present article addresses this gap. We use a 'technomorphic' approach, i.e. the application of conceptual tools derived from engineering design, to better understand the processes operating during a typical biomimetic research project. This helps to elucidate the formal connections between functions, working principles and constructions (in a broad sense)-because the 'form-function-relationship' is a recurring issue in biology and engineering. The presented schema also serves as a conceptual framework that can be implemented for future biomimetic projects. The concepts of 'function' and 'working principle' are identified as the core elements in the biomimetic knowledge transfer towards applications. This schema not only facilitates the development of a common language in the emerging science of biomimetics, but also promotes the interdisciplinary dialogue among its subdisciplines.

  1. Inflammatory Monocytes Mediate Early and Organ-Specific Innate Defense During Systemic Candidiasis

    PubMed Central

    Ngo, Lisa Y.; Kasahara, Shinji; Kumasaka, Debra K.; Knoblaugh, Sue E.; Jhingran, Anupam; Hohl, Tobias M.

    2014-01-01

    Candida albicans is a commensal fungus that can cause systemic disease in patients with breaches in mucosal integrity, indwelling catheters, and defects in phagocyte function. Although circulating human and murine monocytes bind C. albicans and promote inflammation, it remains unclear whether C-C chemokine receptor 2 (CCR2)– and Ly6C-expressing inflammatory monocytes exert a protective or a deleterious function during systemic infection. During murine systemic candidiasis, interruption of CCR2-dependent inflammatory monocyte trafficking into infected kidneys impaired fungal clearance and decreased murine survival. Depletion of CCR2-expressing cells led to uncontrolled fungal growth in the kidneys and brain and demonstrated an essential antifungal role for inflammatory monocytes and their tissue-resident derivatives in the first 48 hours postinfection. Adoptive transfer of purified inflammatory monocytes in depleted hosts reversed the defect in fungal clearance to a substantial extent, indicating a compartmentally and temporally restricted protective function that can be transferred to enhance systemic innate antifungal immunity. PMID:23922372

  2. Spatial Data Transfer Standard (SDTS)

    USGS Publications Warehouse

    ,

    1995-01-01

    The Spatial Data Transfer Standard (SOTS) is a mechanism for the transfer of spatial data between dissimilar computer systems. The SOTS specifies exchange constructs, addressing formats, structure, and content for spatially referenced vector and raster (including gridded) data. SOTS components are a conceptual model, specifications for a quality report, transfer module specifications, data dictionary specifications, and definitions of spatial features and attributes.

  3. Occupational Rhinoconjunctivitis due to Maize in a Snack Processor: A Cross-Reactivity Study Between Lipid Transfer Proteins From Different Cereals and Peach.

    PubMed

    Guillen, Daiana; Barranco, Pilar; Palacín, Arantxa; Quirce, Santiago

    2014-09-01

    We report the case of a snack processor who developed occupational rhinoconjunctivitis due to maize brand exposure during the extrusion process, and who experienced abdominal pain upon drinking beer. The allergens implicated and the cross-reactivity between non-specific lipid transfer proteins (LTPs) from different cereals and peach were investigated. Skin prick tests and specific IgE to cereal flours, pulmonary functions tests and specific conjunctival and inhalation challenges to maize extract were performed. In vitro studies included IgE immunoblotting and ELISA inhibition assays. Skin prick tests with maize flour, maize brand and wheat flour extracts were positive, whereas serum specific IgE was positive only to maize flour. Specific inhalation challenge (SIC) to maize flour did not elicit an asthmatic reaction; however, conjunctival challenge test with the same extract was positive. Patient's serum recognized IgE-binding bands in the maize and beer extracts corresponding to LTPs. In the ELISA inhibition assays, a significant degree of allergenic cross-reactivity was found between maize and beer LTPs, whereas no cross-reactivity was observed between maize LTP and wheat and peach LTPs.

  4. Versatile Gene-Specific Sequence Tags for Arabidopsis Functional Genomics: Transcript Profiling and Reverse Genetics Applications

    PubMed Central

    Hilson, Pierre; Allemeersch, Joke; Altmann, Thomas; Aubourg, Sébastien; Avon, Alexandra; Beynon, Jim; Bhalerao, Rishikesh P.; Bitton, Frédérique; Caboche, Michel; Cannoot, Bernard; Chardakov, Vasil; Cognet-Holliger, Cécile; Colot, Vincent; Crowe, Mark; Darimont, Caroline; Durinck, Steffen; Eickhoff, Holger; de Longevialle, Andéol Falcon; Farmer, Edward E.; Grant, Murray; Kuiper, Martin T.R.; Lehrach, Hans; Léon, Céline; Leyva, Antonio; Lundeberg, Joakim; Lurin, Claire; Moreau, Yves; Nietfeld, Wilfried; Paz-Ares, Javier; Reymond, Philippe; Rouzé, Pierre; Sandberg, Goran; Segura, Maria Dolores; Serizet, Carine; Tabrett, Alexandra; Taconnat, Ludivine; Thareau, Vincent; Van Hummelen, Paul; Vercruysse, Steven; Vuylsteke, Marnik; Weingartner, Magdalena; Weisbeek, Peter J.; Wirta, Valtteri; Wittink, Floyd R.A.; Zabeau, Marc; Small, Ian

    2004-01-01

    Microarray transcript profiling and RNA interference are two new technologies crucial for large-scale gene function studies in multicellular eukaryotes. Both rely on sequence-specific hybridization between complementary nucleic acid strands, inciting us to create a collection of gene-specific sequence tags (GSTs) representing at least 21,500 Arabidopsis genes and which are compatible with both approaches. The GSTs were carefully selected to ensure that each of them shared no significant similarity with any other region in the Arabidopsis genome. They were synthesized by PCR amplification from genomic DNA. Spotted microarrays fabricated from the GSTs show good dynamic range, specificity, and sensitivity in transcript profiling experiments. The GSTs have also been transferred to bacterial plasmid vectors via recombinational cloning protocols. These cloned GSTs constitute the ideal starting point for a variety of functional approaches, including reverse genetics. We have subcloned GSTs on a large scale into vectors designed for gene silencing in plant cells. We show that in planta expression of GST hairpin RNA results in the expected phenotypes in silenced Arabidopsis lines. These versatile GST resources provide novel and powerful tools for functional genomics. PMID:15489341

  5. The potential of multiparametric MRI of the breast

    PubMed Central

    Pinker, Katja; Helbich, Thomas H

    2017-01-01

    MRI is an essential tool in breast imaging, with multiple established indications. Dynamic contrast-enhanced MRI (DCE-MRI) is the backbone of any breast MRI protocol and has an excellent sensitivity and good specificity for breast cancer diagnosis. DCE-MRI provides high-resolution morphological information, as well as some functional information about neoangiogenesis as a tumour-specific feature. To overcome limitations in specificity, several other functional MRI parameters have been investigated and the application of these combined parameters is defined as multiparametric MRI (mpMRI) of the breast. MpMRI of the breast can be performed at different field strengths (1.5–7 T) and includes both established (diffusion-weighted imaging, MR spectroscopic imaging) and novel MRI parameters (sodium imaging, chemical exchange saturation transfer imaging, blood oxygen level-dependent MRI), as well as hybrid imaging with positron emission tomography (PET)/MRI and different radiotracers. Available data suggest that multiparametric imaging using different functional MRI and PET parameters can provide detailed information about the underlying oncogenic processes of cancer development and progression and can provide additional specificity. This article will review the current and emerging functional parameters for mpMRI of the breast for improved diagnostic accuracy in breast cancer. PMID:27805423

  6. Uncertainty of Monetary Valued Ecosystem Services – Value Transfer Functions for Global Mapping

    PubMed Central

    Schmidt, Stefan; Manceur, Ameur M.; Seppelt, Ralf

    2016-01-01

    Growing demand of resources increases pressure on ecosystem services (ES) and biodiversity. Monetary valuation of ES is frequently seen as a decision-support tool by providing explicit values for unconsidered, non-market goods and services. Here we present global value transfer functions by using a meta-analytic framework for the synthesis of 194 case studies capturing 839 monetary values of ES. For 12 ES the variance of monetary values could be explained with a subset of 93 study- and site-specific variables by utilizing boosted regression trees. This provides the first global quantification of uncertainties and transferability of monetary valuations. Models explain from 18% (water provision) to 44% (food provision) of variance and provide statistically reliable extrapolations for 70% (water provision) to 91% (food provision) of the terrestrial earth surface. Although the application of different valuation methods is a source of uncertainty, we found evidence that assuming homogeneity of ecosystems is a major error in value transfer function models. Food provision is positively correlated with better life domains and variables indicating positive conditions for human well-being. Water provision and recreation service show that weak ownerships affect valuation of other common goods negatively (e.g. non-privately owned forests). Furthermore, we found support for the shifting baseline hypothesis in valuing climate regulation. Ecological conditions and societal vulnerability determine valuation of extreme event prevention. Valuation of habitat services is negatively correlated with indicators characterizing less favorable areas. Our analysis represents a stepping stone to establish a standardized integration of and reporting on uncertainties for reliable and valid benefit transfer as an important component for decision support. PMID:26938447

  7. Sharpening coarse-to-fine stereo vision by perceptual learning: asymmetric transfer across the spatial frequency spectrum

    PubMed Central

    Tran, Truyet T.; Craven, Ashley P.; Leung, Tsz-Wing; Chat, Sandy W.; Levi, Dennis M.

    2016-01-01

    Neurons in the early visual cortex are finely tuned to different low-level visual features, forming a multi-channel system analysing the visual image formed on the retina in a parallel manner. However, little is known about the potential ‘cross-talk’ among these channels. Here, we systematically investigated whether stereoacuity, over a large range of target spatial frequencies, can be enhanced by perceptual learning. Using narrow-band visual stimuli, we found that practice with coarse (low spatial frequency) targets substantially improves performance, and that the improvement spreads from coarse to fine (high spatial frequency) three-dimensional perception, generalizing broadly across untrained spatial frequencies and orientations. Notably, we observed an asymmetric transfer of learning across the spatial frequency spectrum. The bandwidth of transfer was broader when training was at a high spatial frequency than at a low spatial frequency. Stereoacuity training is most beneficial when trained with fine targets. This broad transfer of stereoacuity learning contrasts with the highly specific learning reported for other basic visual functions. We also revealed strategies to boost learning outcomes ‘beyond-the-plateau’. Our investigations contribute to understanding the functional properties of the network subserving stereovision. The ability to generalize may provide a key principle for restoring impaired binocular vision in clinical situations. PMID:26909178

  8. Transfer of function and prior derived-relations testing.

    PubMed

    Doughty, Adam H; Best, Lauren

    2017-10-01

    This experiment assessed transfer of function through equivalence relations with and without prior derived-stimulus-relations (DSR) testing. In a DSR-Testing Group, eight college students learned A-B and A-C discriminations in baseline. They then derived the B-C and C-B equivalence relations before being exposed to a transfer-of-function manipulation and test. Eight participants in a No-DSR Testing Group were exposed to the transfer-of-function manipulation and test immediately after learning the baseline discriminations (i.e., B-C and C-B testing were omitted). In the transfer-of-function manipulation, participants learned to respond differently in the presence of B1 and B2 to avoid money loss. In the transfer-of-function test, responding in the presence of C1 and C2 was measured in the absence of differential consequences. Transfer of function occurred reliably only in the DSR-Testing Group (i.e., participants responding to C1 and C2 in the manner they learned to respond to B1 and B2, respectively). These findings support the notion that prior DSR testing can be critical to observing transfer of function. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. System and method of active vibration control for an electro-mechanically cooled device

    DOEpatents

    Lavietes, Anthony D.; Mauger, Joseph; Anderson, Eric H.

    2000-01-01

    A system and method of active vibration control of an electro-mechanically cooled device is disclosed. A cryogenic cooling system is located within an environment. The cooling system is characterized by a vibration transfer function, which requires vibration transfer function coefficients. A vibration controller generates the vibration transfer function coefficients in response to various triggering events. The environments may differ by mounting apparatus, by proximity to vibration generating devices, or by temperature. The triggering event may be powering on the cooling system, reaching an operating temperature, or a reset action. A counterbalance responds to a drive signal generated by the vibration controller, based on the vibration signal and the vibration transfer function, which adjusts vibrations. The method first places a cryogenic cooling system within a first environment and then generates a first set of vibration transfer function coefficients, for a vibration transfer function of the cooling system. Next, the cryogenic cooling system is placed within a second environment and a second set of vibration transfer function coefficients are generated. Then, a counterbalance is driven, based on the vibration transfer function, to reduce vibrations received by a vibration sensitive element.

  10. Central blood pressure in children and adolescents: non-invasive development and testing of novel transfer functions.

    PubMed

    Cai, T Y; Qasem, A; Ayer, J G; Butlin, M; O'Meagher, S; Melki, C; Marks, G B; Avolio, A; Celermajer, D S; Skilton, M R

    2017-12-01

    Central blood pressure can be estimated from peripheral pulses in adults using generalised transfer functions (TF). We sought to create and test age-specific non-invasively developed TFs in children, with comparison to a pre-existing adult TF. We studied healthy children from two sites at two time points, 8 and 14 years of age, split by site into development and validation groups. Radial and carotid pressure waveforms were obtained by applanation tonometry. Central systolic pressure was derived from carotid waveforms calibrated to brachial mean and diastolic pressures. Age-specific TFs created in the development groups (n=50) were tested in the validation groups aged 8 (n=137) and 14 years (n=85). At 8 years of age, the age-specific TF estimated 82, 99 and 100% of central systolic pressure values within 5, 10 and 15 mm Hg of their measured values, respectively. This TF overestimated central systolic pressure by 2.2 (s.d. 3.7) mm Hg, compared to being underestimated by 5.6 (s.d. 3.9) mm Hg with the adult TF. At 14 years of age, the age-specific TF estimated 60, 87 and 95% of values within 5, 10 and 15 mm Hg of their measured values, respectively. This TF underestimated central systolic pressure by 0.5 (s.d. 6.7) mm Hg, while the adult TF underestimated it by 6.8 (s.d. 6.0) mm Hg. In conclusion, age-specific TFs more accurately predict central systolic pressure measured at the carotid artery in children than an existing adult TF.

  11. Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity

    PubMed Central

    Nazimek, Katarzyna; Bryniarski, Krzysztof; Askenase, Philip W.

    2016-01-01

    Extracellular vesicles, such as exosomes, are newly recognized intercellular conveyors of functional molecular mechanisms. Notably, they transfer RNAs and proteins between cells in general, that then can participate, as described herein, in the complex pathogenesis of allergic and related hypersensitivity responses and disease mechanisms. This review highlights this important new appreciation of the in vivo participation of such extracellular vesicles in the interactions between allergy-mediating cells, taking into account paracrine epigenetic exchanges mediated by surrounding stromal cells and the endocrine receipt of exosomes from distant cells via the circulation. Exosomes are natural ancient nanoparticles of life. They are made by all cells and in some form by all species down to fungi and bacteria, and are present in all fluids. Besides a new focus on their role in the transmission of genetic regulation, exosome transfer of allergens was recently shown to induce allergic inflammation. Importantly, regulatory and tolerogenic exosomes can potently inhibit allergy and hypersensitivity responses, usually acting non-specifically, but also can proceed in an antigen-specific manner due to coating of the exosome surface with antibodies. Deep analysis of processes mediated by exosomes should result in development of early diagnostic biomarkers, as well as allergen-specific, preventive and therapeutic strategies. These likely will significantly diminish the risks of current allergen specific parenteral desensitization procedures, and of the use of systemic immunosuppressive drugs. Since extracellular vesicles are physiological, they can be fashioned for specific delivery of therapeutic molecular instructions through easily tolerated, non-invasive routes, such as oral ingestion, nasal administration, and perhaps even inhalation. PMID:27820941

  12. CMV-Specific CD8 T Cell Differentiation and Localization: Implications for Adoptive Therapies.

    PubMed

    Smith, Corinne J; Quinn, Michael; Snyder, Christopher M

    2016-01-01

    Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection and, thus, is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8 + T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization, and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8 + T cell immunity. The aim of this review is to briefly summarize the role of these T cell subsets in CMV immunity and to describe how current adoptive immunotherapy practices might affect their reconstitution in patients. The bulk of the CMV-specific CD8 + T cell population is made up of terminally differentiated effector T cells with immediate effector function and a short life span. Self-renewing memory T cells within the CMV-specific population retain the capacity to expand and differentiate upon challenge and are important for the long-term persistence of the CD8 + T cell response. Finally, mucosal organs, which are frequent sites of CMV reactivation, are primarily inhabited by tissue-resident memory T cells, which do not recirculate. Future work on adoptive transfer strategies may need to focus on striking a balance between the formation of these subsets to ensure the development of long lasting and protective immune responses that can access the organs affected by CMV disease.

  13. Transfer Function Identification Using Orthogonal Fourier Transform Modeling Functions

    NASA Technical Reports Server (NTRS)

    Morelli, Eugene A.

    2013-01-01

    A method for transfer function identification, including both model structure determination and parameter estimation, was developed and demonstrated. The approach uses orthogonal modeling functions generated from frequency domain data obtained by Fourier transformation of time series data. The method was applied to simulation data to identify continuous-time transfer function models and unsteady aerodynamic models. Model fit error, estimated model parameters, and the associated uncertainties were used to show the effectiveness of the method for identifying accurate transfer function models from noisy data.

  14. Multiconfiguration Pair-Density Functional Theory Outperforms Kohn-Sham Density Functional Theory and Multireference Perturbation Theory for Ground-State and Excited-State Charge Transfer.

    PubMed

    Ghosh, Soumen; Sonnenberger, Andrew L; Hoyer, Chad E; Truhlar, Donald G; Gagliardi, Laura

    2015-08-11

    The correct description of charge transfer in ground and excited states is very important for molecular interactions, photochemistry, electrochemistry, and charge transport, but it is very challenging for Kohn-Sham (KS) density functional theory (DFT). KS-DFT exchange-correlation functionals without nonlocal exchange fail to describe both ground- and excited-state charge transfer properly. We have recently proposed a theory called multiconfiguration pair-density functional theory (MC-PDFT), which is based on a combination of multiconfiguration wave function theory with a new type of density functional called an on-top density functional. Here we have used MC-PDFT to study challenging ground- and excited-state charge-transfer processes by using on-top density functionals obtained by translating KS exchange-correlation functionals. For ground-state charge transfer, MC-PDFT performs better than either the PBE exchange-correlation functional or CASPT2 wave function theory. For excited-state charge transfer, MC-PDFT (unlike KS-DFT) shows qualitatively correct behavior at long-range with great improvement in predicted excitation energies.

  15. Small-molecule control of protein function through Staudinger reduction

    NASA Astrophysics Data System (ADS)

    Luo, Ji; Liu, Qingyang; Morihiro, Kunihiko; Deiters, Alexander

    2016-11-01

    Using small molecules to control the function of proteins in live cells with complete specificity is highly desirable, but challenging. Here we report a small-molecule switch that can be used to control protein activity. The approach uses a phosphine-mediated Staudinger reduction to activate protein function. Genetic encoding of an ortho-azidobenzyloxycarbonyl amino acid using a pyrrolysyl transfer RNA synthetase/tRNACUA pair in mammalian cells enables the site-specific introduction of a small-molecule-removable protecting group into the protein of interest. Strategic placement of this group renders the protein inactive until deprotection through a bioorthogonal Staudinger reduction delivers the active wild-type protein. This developed methodology was applied to the conditional control of several cellular processes, including bioluminescence (luciferase), fluorescence (enhanced green fluorescent protein), protein translocation (nuclear localization sequence), DNA recombination (Cre) and gene editing (Cas9).

  16. The relation between the cell-mediated immunological response and the induction of circulating antibodies to collagen in guinea-pigs.

    PubMed Central

    Gentner, G J; Adelmann, B C

    1976-01-01

    Cutaneous delayed hypersensitivity reactions to collagen in guinea-pigs were partially but specifically suppressed if the animals had been pretreated with collagen and Freund's incomplete adjuvant. Such animals responded normally to skin-reactive factor prepared with ovalbumin. Lymphoid cells from animals with normal delayed hypersensitivity to collagen functioned normally in animals with suppressed skin reactivity. Cells from animals with suppressed delayed hypersensitivity were specifically, functionally impaired since they transferred delayed hypersensitivity into neutral recipients efficiently for PPD but not for collagen. Suppression could be induced in Cy-treated animals, and it persisted for at least 143 days. It is concluded that guinea-pigs with depressed delayed hypersensitivity to collagen are functionally impaired with respect to those T cells normally generated by induction of delayed hypersensitivity. PMID:1088420

  17. Classifying the molecular functions of Rab GTPases in membrane trafficking using deep convolutional neural networks.

    PubMed

    Le, Nguyen-Quoc-Khanh; Ho, Quang-Thai; Ou, Yu-Yen

    2018-06-13

    Deep learning has been increasingly used to solve a number of problems with state-of-the-art performance in a wide variety of fields. In biology, deep learning can be applied to reduce feature extraction time and achieve high levels of performance. In our present work, we apply deep learning via two-dimensional convolutional neural networks and position-specific scoring matrices to classify Rab protein molecules, which are main regulators in membrane trafficking for transferring proteins and other macromolecules throughout the cell. The functional loss of specific Rab molecular functions has been implicated in a variety of human diseases, e.g., choroideremia, intellectual disabilities, cancer. Therefore, creating a precise model for classifying Rabs is crucial in helping biologists understand the molecular functions of Rabs and design drug targets according to such specific human disease information. We constructed a robust deep neural network for classifying Rabs that achieved an accuracy of 99%, 99.5%, 96.3%, and 97.6% for each of four specific molecular functions. Our approach demonstrates superior performance to traditional artificial neural networks. Therefore, from our proposed study, we provide both an effective tool for classifying Rab proteins and a basis for further research that can improve the performance of biological modeling using deep neural networks. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Computer method for identification of boiler transfer functions

    NASA Technical Reports Server (NTRS)

    Miles, J. H.

    1971-01-01

    An iterative computer method is described for identifying boiler transfer functions using frequency response data. An objective penalized performance measure and a nonlinear minimization technique are used to cause the locus of points generated by a transfer function to resemble the locus of points obtained from frequency response measurements. Different transfer functions can be tried until a satisfactory empirical transfer function to the system is found. To illustrate the method, some examples and some results from a study of a set of data consisting of measurements of the inlet impedance of a single tube forced flow boiler with inserts are given.

  19. Impacts of leguminous shrub encroachment on neighboring grasses include transfer of fixed nitrogen.

    PubMed

    Zhang, Hai-Yang; Yu, Qiang; Lü, Xiao-Tao; Trumbore, Susan E; Yang, Jun-Jie; Han, Xing-Guo

    2016-04-01

    Shrub encroachment induced by global change and human disturbance strongly affects ecosystem structure and function. In this study, we explore the degree to which invading leguminous shrubs affected neighboring grasses, including via the transfer of fixed nitrogen (N). We measured N concentrations and natural abundance (15)N of shoot tissues from three dominant grasses from different plant functional groups across seven distances along a local transect (up to 500 cm) to the leguminous shrub, Caragana microphylla. C. microphylla did transfer fixed N to neighboring grasses, but the amount and distance of N transferred were strongly species-specific. Shoot N concentrations decreased significantly with distance from C. microphylla, for a rhizomatous grass, Leymus chinensis, and a bunchgrass, Achnatherum sibiricum. However, N concentrations of another bunchgrass, Stipa grandis, were higher only directly underneath the shrub canopy. Shoot δ(15)N values of L. chinensis were enriched up to 500 cm from the shrub, but for S. grandis were enriched only below the shrub canopy. In contrast, δ(15)N of A. sibiricum did not change along the 500-cm transect. Our results indicated the rhizomatous grass transferred fixed N over long distances while bunchgrasses did not. The presence of C. microphylla increased the shoot biomass of L. chinensis but decreased that of S. grandis and A. sibiricum. These findings highlight the potential role of nutrient-acquisition strategies of neighboring grasses in moderating the interspecific variation of fixed N transfer from the leguminous shrub. Overall, leguminous shrubs have either positive or negative effects on the neighboring grasses and dramatically affect plant community composition and structure.

  20. Conjugative DNA Transfer Is Enhanced by Plasmid R1 Partitioning Proteins

    PubMed Central

    Gruber, Christian J.; Lang, Silvia; Rajendra, Vinod K. H.; Nuk, Monika; Raffl, Sandra; Schildbach, Joel F.; Zechner, Ellen L.

    2016-01-01

    Bacterial conjugation is a form of type IV secretion used to transport protein and DNA directly to recipient bacteria. The process is cell contact-dependent, yet the mechanisms enabling extracellular events to trigger plasmid transfer to begin inside the cell remain obscure. In this study of plasmid R1 we investigated the role of plasmid proteins in the initiation of gene transfer. We find that TraI, the central regulator of conjugative DNA processing, interacts physically, and functionally with the plasmid partitioning proteins ParM and ParR. These interactions stimulate TraI catalyzed relaxation of plasmid DNA in vivo and in vitro and increase ParM ATPase activity. ParM also binds the coupling protein TraD and VirB4-like channel ATPase TraC. Together, these protein-protein interactions probably act to co-localize the transfer components intracellularly and promote assembly of the conjugation machinery. Importantly these data also indicate that the continued association of ParM and ParR at the conjugative pore is necessary for plasmid transfer to start efficiently. Moreover, the conjugative pilus and underlying secretion machinery assembled in the absence of Par proteins mediate poor biofilm formation and are completely dysfunctional for pilus specific R17 bacteriophage uptake. Thus, functional integration of Par components at the interface of relaxosome, coupling protein, and channel ATPases appears important for an optimal conformation and effective activation of the transfer machinery. We conclude that low copy plasmid R1 has evolved an active segregation system that optimizes both its vertical and lateral modes of dissemination. PMID:27486582

  1. The three principles of action: a Pavlovian-instrumental transfer hypothesis

    PubMed Central

    Cartoni, Emilio; Puglisi-Allegra, Stefano; Baldassarre, Gianluca

    2013-01-01

    Pavlovian conditioned stimuli can influence instrumental responding, an effect called Pavlovian-instrumental transfer (PIT). During the last decade, PIT has been subdivided into two types: specific PIT and general PIT, each having its own neural substrates. Specific PIT happens when a conditioned stimulus (CS) associated with a reward enhances an instrumental response directed to the same reward. Under general PIT, instead, the CS enhances a response directed to a different reward. While important progress has been made into identifying the neural substrates, the function of specific and general PIT and how they interact with instrumental responses are still not clear. In the experimental paradigm that distinguishes specific and general PIT an effect of PIT inhibition has also been observed and is waiting for an explanation. Here we propose an hypothesis that links these three PIT effects (specific PIT, general PIT and PIT inhibition) to three aspects of action evaluation. These three aspects, which we call “principles of action”, are: context, efficacy, and utility. In goal-directed behavior, an agent has to evaluate if the context is suitable to accomplish the goal, the efficacy of his action in getting the goal, and the utility of the goal itself: we suggest that each of the three PIT effects is related to one of these aspects of action evaluation. In particular, we link specific PIT with the estimation of efficacy, general PIT with the evaluation of utility, and PIT inhibition with the adequacy of context. We also provide a latent cause Bayesian computational model that exemplifies this hypothesis. This hypothesis and the model provide a new framework and new predictions to advance knowledge about PIT functioning and its role in animal adaptation. PMID:24312025

  2. Electronic Excitations in Solution: The Interplay between State Specific Approaches and a Time-Dependent Density Functional Theory Description.

    PubMed

    Guido, Ciro A; Jacquemin, Denis; Adamo, Carlo; Mennucci, Benedetta

    2015-12-08

    We critically analyze the performances of continuum solvation models when coupled to time-dependent density functional theory (TD-DFT) to predict solvent effects on both absorption and emission energies of chromophores in solution. Different polarization schemes of the polarizable continuum model (PCM), such as linear response (LR) and three different state specific (SS) approaches, are considered and compared. We show the necessity of introducing a SS model in cases where large electron density rearrangements are involved in the excitations, such as charge-transfer transitions in both twisted and quadrupolar compounds, and underline the very delicate interplay between the selected polarization method and the chosen exchange-correlation functional. This interplay originates in the different descriptions of the transition and ground/excited state multipolar moments by the different functionals. As a result, the choice of both the DFT functional and the solvent polarization scheme has to be consistent with the nature of the studied electronic excitation.

  3. Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells.

    PubMed

    Gonzalez, Gaëlle; Vituret, Cyrielle; Di Pietro, Attilio; Chanson, Marc; Boulanger, Pierre; Hong, Saw-See

    2012-01-01

    Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins.

  4. Intergenerational private transfers: Portugal in the European context.

    PubMed

    Albuquerque, Paula C

    2014-12-01

    Intergenerational private transfers should be made important as a common occurrence in familialistic societies when establishing the identity of Southern European welfare state regimes. They function as a safety net and as a way of reinforcing the bonds amongst elements in a family. Although Portugal is undoubtedly a Southern European country, it is frequently ignored in comparative studies, and is assumed to share the characteristics of Spain and Italy. But do these countries really belong to a common, distinctive model? Portugal was included in the fourth wave of the survey of health, ageing and retirement in Europe, which provides a large sample for the study of intergenerational private transfers in this country. It also enables comparison with what happens elsewhere in Europe. We examine the upward and downward flows between generations and identify several important determinants of each type of transfers. Additionally, we show that the different types and directions of transfers are positively correlated, pointing to a self-reinforcement of transfer behaviour in families. We find that Portugal has an especially low probability of private transfers of time and money. After taking into consideration the household-level characteristics, none of the countries included in this study has a significantly lower probability of occurrence of any type of transfer than that of Portugal. A Southern European specific pattern of family transfers is only partially confirmed, yet Portugal and Spain do share the same model.

  5. Manufacturing Technology Information Analysis Center: Knowledge Is Strength

    NASA Technical Reports Server (NTRS)

    Safar, Michal

    1992-01-01

    The Center's primary function is to facilitate technology transfer within DoD, other government agencies and industry. The DoD has recognized the importance of technology transfer, not only to support specific weapon system manufacture, but to strengthen the industrial base that sustains DoD. MTIAC uses an experienced technical staff of engineers and information specialists to acquire, analyze, and disseminate technical information. Besides ManTech project data, MTIAC collects manufacturing technology from other government agencies, commercial publications, proceedings, and various international sources. MTIAC has various means of disseminating this information. Much of the technical data is on user accessible data bases. The Center researches and writes a number of technical reports each year and publishes a newsletter monthly. Customized research is performed in response to specific inquiries from government and industry. MTIAC serves as a link between Government and Industry to strengthen the manufacturing technology base through the dissemination of advanced manufacturing information.

  6. Fins effectiveness and efficiency with position function of rhombus sectional area in unsteady condition

    NASA Astrophysics Data System (ADS)

    Nugroho, Tito Dwi; Purwadi, P. K.

    2017-01-01

    The function of the fin is to extend surfaces so that objects fitted with fin can remove the heat to the surrounding environment so that the cooling process can take place more quickly. The purpose of this study is to calculate and determine the effect of (a) the convective heat transfer coefficient of fluid on the value of the fin on the efficiency and effectiveness of non-steady state, and (b) the fin material to the value of the fins on the efficiency and effectiveness of non-steady state. The studied fins are in the form of straight fins with rhombus sectional area which is a function of position x with the short diagonal length of D1 and D2 as long diagonal length, L as fin's length and α as fin's tilt angle. Research solved numerical computation, using a finite difference method on the explicit way. At first, the fin has the same initial temperature with essentially temperature Ti = Tb, then abruptly fin conditioned on fluid temperature environment T∞. Fin's material is assumed with uniform properties, does not change with changes in temperature, and fin does not change the shape and volume during the process. The temperature of the fluid around the fins and the value of the convective heat transfer coefficient are permanently constant, and there is no energy generation in the fin. Fin's heat transfer conduction only take place in one direction, namely in the direction perpendicular to the fin base (or x-direction). The entire surface of the fin makes the process of heat transfer to a fluid environment around the fins. The results show that (a) the greater the value of heat transfer coefficient of convection h, the smaller the efficiency fin and effectiveness fins (b) In circumstances of unsteady state, the efficiency and effectivity influenced by the value of density, specific heat, heat transfer coefficient of conduction and thermal diffusivity fin material.

  7. 41 CFR 302-3.206 - If I am re-employed after a separation by reduction in force or transfer of functions, may my...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false If I am re-employed... allowance? 302-3.206 Section 302-3.206 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of...

  8. 41 CFR 302-3.206 - If I am re-employed after a separation by reduction in force or transfer of functions, may my...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 41 Public Contracts and Property Management 4 2014-07-01 2014-07-01 false If I am re-employed... allowance? 302-3.206 Section 302-3.206 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of...

  9. 41 CFR 302-3.206 - If I am re-employed after a separation by reduction in force or transfer of functions, may my...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 41 Public Contracts and Property Management 4 2012-07-01 2012-07-01 false If I am re-employed... allowance? 302-3.206 Section 302-3.206 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of...

  10. 41 CFR 302-3.206 - If I am re-employed after a separation by reduction in force or transfer of functions, may my...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 41 Public Contracts and Property Management 4 2011-07-01 2011-07-01 false If I am re-employed... allowance? 302-3.206 Section 302-3.206 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of...

  11. Design of Solid-Gas Interfaces for Enhanced Thermal Transfer

    DTIC Science & Technology

    2015-09-28

    modifications. Specifically, for metal surfaces modified with organic self - assembled monolayers (SAMs), both TAC and MAC are close to its theoretical...we designed solid surfaces functionalized with organic self - assembled monolayers (SAMs) and demonstrated associated significant improvement of the...at solid-gas interfaces by self - assembled monolayers ” Applied Physics Letters 102, 061907 (2013). 2. Zhi Liang, William Evans, and Pawel Keblinski

  12. Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity

    PubMed Central

    Sun, Weijia; Zhao, Chenyang; Li, Yuheng; Wang, Liang; Nie, Guangjun; Peng, Jiang; Wang, Aiyuan; Zhang, Pengfei; Tian, Weiming; Li, Qi; Song, Jinping; Wang, Cheng; Xu, Xiaolong; Tian, Yanhua; Zhao, Dingsheng; Xu, Zi; Zhong, Guohui; Han, Bingxing; Ling, Shukuan; Chang, Yan-Zhong; Li, Yingxian

    2016-01-01

    MicroRNAs have an important role in bone homeostasis. However, the detailed mechanism of microRNA-mediated intercellular communication between bone cells remains elusive. Here, we report that osteoclasts secrete microRNA-enriched exosomes, by which miR-214 is transferred into osteoblasts to inhibit their function. In a coculture system, inhibition of exosome formation and secretion prevented miR-214 transportation. Exosomes specifically recognized osteoblasts through the interaction between ephrinA2 and EphA2. In osteoclast-specific miR-214 transgenic mice, exosomes were secreted into the serum, and miR-214 and ephrinA2 levels were elevated. Therefore, these exosomes have an inhibitory role in osteoblast activity. miR-214 and ephrinA2 levels in serum exosomes from osteoporotic patients and mice were upregulated substantially. These exosomes may significantly inhibit osteoblast activity. Inhibition of exosome secretion via Rab27a small interfering RNA prevented ovariectomized-induced osteoblast dysfunction in vivo. Taken together, these findings suggest that exosome-mediated transfer of microRNA plays an important role in the regulation of osteoblast activity. Circulating miR-214 in exosomes not only represents a biomarker for bone loss but could selectively regulate osteoblast function. PMID:27462462

  13. Quantifying electron transfer reactions in biological systems: what interactions play the major role?

    NASA Astrophysics Data System (ADS)

    Sjulstok, Emil; Olsen, Jógvan Magnus Haugaard; Solov'Yov, Ilia A.

    2015-12-01

    Various biological processes involve the conversion of energy into forms that are usable for chemical transformations and are quantum mechanical in nature. Such processes involve light absorption, excited electronic states formation, excitation energy transfer, electrons and protons tunnelling which for example occur in photosynthesis, cellular respiration, DNA repair, and possibly magnetic field sensing. Quantum biology uses computation to model biological interactions in light of quantum mechanical effects and has primarily developed over the past decade as a result of convergence between quantum physics and biology. In this paper we consider electron transfer in biological processes, from a theoretical view-point; namely in terms of quantum mechanical and semi-classical models. We systematically characterize the interactions between the moving electron and its biological environment to deduce the driving force for the electron transfer reaction and to establish those interactions that play the major role in propelling the electron. The suggested approach is seen as a general recipe to treat electron transfer events in biological systems computationally, and we utilize it to describe specifically the electron transfer reactions in Arabidopsis thaliana cryptochrome-a signaling photoreceptor protein that became attractive recently due to its possible function as a biological magnetoreceptor.

  14. INCA- INTERACTIVE CONTROLS ANALYSIS

    NASA Technical Reports Server (NTRS)

    Bauer, F. H.

    1994-01-01

    The Interactive Controls Analysis (INCA) program was developed to provide a user friendly environment for the design and analysis of linear control systems, primarily feedback control systems. INCA is designed for use with both small and large order systems. Using the interactive graphics capability, the INCA user can quickly plot a root locus, frequency response, or time response of either a continuous time system or a sampled data system. The system configuration and parameters can be easily changed, allowing the INCA user to design compensation networks and perform sensitivity analysis in a very convenient manner. A journal file capability is included. This stores an entire sequence of commands, generated during an INCA session into a file which can be accessed later. Also included in INCA are a context-sensitive help library, a screen editor, and plot windows. INCA is robust to VAX-specific overflow problems. The transfer function is the basic unit of INCA. Transfer functions are automatically saved and are available to the INCA user at any time. A powerful, user friendly transfer function manipulation and editing capability is built into the INCA program. The user can do all transfer function manipulations and plotting without leaving INCA, although provisions are made to input transfer functions from data files. By using a small set of commands, the user may compute and edit transfer functions, and then examine these functions by using the ROOT_LOCUS, FREQUENCY_RESPONSE, and TIME_RESPONSE capabilities. Basic input data, including gains, are handled as single-input single-output transfer functions. These functions can be developed using the function editor or by using FORTRAN- like arithmetic expressions. In addition to the arithmetic functions, special functions are available to 1) compute step, ramp, and sinusoid functions, 2) compute closed loop transfer functions, 3) convert from S plane to Z plane with optional advanced Z transform, and 4) convert from Z plane to W plane and back. These capabilities allow the INCA user to perform block diagram algebraic manipulations quickly for functions in the S, Z, and W domains. Additionally, a versatile digital control capability has been included in INCA. Special plane transformations allow the user to easily convert functions from one domain to another. Other digital control capabilities include: 1) totally independent open loop frequency response analyses on a continuous plant, discrete control system with a delay, 2) advanced Z-transform capability for systems with delays, and 3) multirate sampling analyses. The current version of INCA includes Dynamic Functions (which change when a parameter changes), standard filter generation, PD and PID controller generation, incorporation of the QZ-algorithm (function addition, inverse Laplace), and describing functions that allow the user to calculate the gain and phase characteristics of a nonlinear device. The INCA graphic modes provide the user with a convenient means to document and study frequency response, time response, and root locus analyses. General graphics features include: 1) zooming and dezooming, 2) plot documentation, 3) a table of analytic computation results, 4) multiple curves on the same plot, and 5) displaying frequency and gain information for a specific point on a curve. Additional capabilities in the frequency response mode include: 1) a full complement of graphical methods Bode magnitude, Bode phase, Bode combined magnitude and phase, Bode strip plots, root contour plots, Nyquist, Nichols, and Popov plots; 2) user selected plot scaling; and 3) gain and phase margin calculation and display. In the time response mode, additional capabilities include: 1) support for inverse Laplace and inverse Z transforms, 2) support for various input functions, 3) closed loop response evaluation, 4) loop gain sensitivity analyses, 5) intersample time response for discrete systems using the advanced Z transform, and 6) closed loop time response using mixed plane (S, Z, W) operations with delay. A Graphics mode command was added to the current version of INCA, version 3.13, to produce Metafiles (graphic files) of the currently displayed plot. The metafile can be displayed and edited using the QPLOT Graphics Editor and Replotter for Metafiles (GERM) program included with the INCA package. The INCA program is written in Pascal and FORTRAN for interactive or batch execution and has been implemented on a DEC VAX series computer under VMS. Both source code and executable code are supplied for INCA. Full INCA graphics capabilities are supported for various Tektronix 40xx and 41xx terminals; DEC VT graphics terminals; many PC and Macintosh terminal emulators; TEK014 hardcopy devices such as the LN03 Laserprinter; and bit map graphics external hardcopy devices. Also included for the TEK4510 rasterizer users are a multiple copy feature, a wide line feature, and additional graphics fonts. The INCA program was developed in 1985, Version 2.04 was released in 1986, Version 3.00 was released in 1988, and Version 3.13 was released in 1989. An INCA version 2.0X conversion program is included.

  15. Consistent Parameter and Transfer Function Estimation using Context Free Grammars

    NASA Astrophysics Data System (ADS)

    Klotz, Daniel; Herrnegger, Mathew; Schulz, Karsten

    2017-04-01

    This contribution presents a method for the inference of transfer functions for rainfall-runoff models. Here, transfer functions are defined as parametrized (functional) relationships between a set of spatial predictors (e.g. elevation, slope or soil texture) and model parameters. They are ultimately used for estimation of consistent, spatially distributed model parameters from a limited amount of lumped global parameters. Additionally, they provide a straightforward method for parameter extrapolation from one set of basins to another and can even be used to derive parameterizations for multi-scale models [see: Samaniego et al., 2010]. Yet, currently an actual knowledge of the transfer functions is often implicitly assumed. As a matter of fact, for most cases these hypothesized transfer functions can rarely be measured and often remain unknown. Therefore, this contribution presents a general method for the concurrent estimation of the structure of transfer functions and their respective (global) parameters. Note, that by consequence an estimation of the distributed parameters of the rainfall-runoff model is also undertaken. The method combines two steps to achieve this. The first generates different possible transfer functions. The second then estimates the respective global transfer function parameters. The structural estimation of the transfer functions is based on the context free grammar concept. Chomsky first introduced context free grammars in linguistics [Chomsky, 1956]. Since then, they have been widely applied in computer science. But, to the knowledge of the authors, they have so far not been used in hydrology. Therefore, the contribution gives an introduction to context free grammars and shows how they can be constructed and used for the structural inference of transfer functions. This is enabled by new methods from evolutionary computation, such as grammatical evolution [O'Neill, 2001], which make it possible to exploit the constructed grammar as a search space for equations. The parametrization of the transfer functions is then achieved through a second optimization routine. The contribution explores different aspects of the described procedure through a set of experiments. These experiments can be divided into three categories: (1) The inference of transfer functions from directly measurable parameters; (2) The estimation of global parameters for given transfer functions from runoff data; and (3) The estimation of sets of completely unknown transfer functions from runoff data. The conducted tests reveal different potentials and limits of the procedure. In concrete it is shown that example (1) and (2) work remarkably well. Example (3) is much more dependent on the setup. In general, it can be said that in that case much more data is needed to derive transfer function estimations, even for simple models and setups. References: - Chomsky, N. (1956): Three Models for the Description of Language. IT IRETr. 2(3), p 113-124 - O'Neil, M. (2001): Grammatical Evolution. IEEE ToEC, Vol.5, No. 4 - Samaniego, L.; Kumar, R.; Attinger, S. (2010): Multiscale parameter regionalization of a grid-based hydrologic model at the mesoscale. WWR, Vol. 46, W05523, doi:10.1029/2008WR007327

  16. A 'user friendly' geographic information system in a color interactive digital image processing system environment

    NASA Technical Reports Server (NTRS)

    Campbell, W. J.; Goldberg, M.

    1982-01-01

    NASA's Eastern Regional Remote Sensing Applications Center (ERRSAC) has recognized the need to accommodate spatial analysis techniques in its remote sensing technology transfer program. A computerized Geographic Information System to incorporate remotely sensed data, specifically Landsat, with other relevant data was considered a realistic approach to address a given resource problem. Questions arose concerning the selection of a suitable available software system to demonstrate, train, and undertake demonstration projects with ERRSAC's user community. The very specific requirements for such a system are discussed. The solution found involved the addition of geographic information processing functions to the Interactive Digital Image Manipulation System (IDIMS). Details regarding the functions of the new integrated system are examined along with the characteristics of the software.

  17. Towards a functional model of mental disorders incorporating the laws of thermodynamics.

    PubMed

    Murray, George C; McKenzie, Karen

    2013-05-01

    The current paper presents the hypothesis that the understanding of mental disorders can be advanced by incorporating the laws of thermodynamics, specifically relating to energy conservation and energy transfer. These ideas, along with the introduction of the notion that entropic activities are symptomatic of inefficient energy transfer or disorder, were used to propose a model of understanding mental ill health as resulting from the interaction of entropy, capacity and work (environmental demands). The model was applied to Attention Deficit Hyperactivity Disorder, and was shown to be compatible with current thinking about this condition, as well as emerging models of mental disorders as complex networks. A key implication of the proposed model is that it argues that all mental disorders require a systemic functional approach, with the advantage that it offers a number of routes into the assessment, formulation and treatment for mental health problems. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Tunneling of heat: Beyond linear response regime

    NASA Astrophysics Data System (ADS)

    Walczak, Kamil; Saroka, David

    2018-02-01

    We examine nanoscale processes of heat (energy) transfer as carried by electrons tunneling via potential barriers and molecular interconnects between two heat reservoirs (thermal baths). For that purpose, we use Landauer-type formulas to calculate thermal conductance and quadratic correction to heat flux flowing via quantum systems. As an input, we implement analytical expressions for transmission functions related to simple potential barriers and atomic bridges. Our results are discussed with respect to energy of tunneling electrons, temperature, the presence of resonant states, and specific parameters characterizing potential barriers as well as heat carriers. The simplicity of semi-analytical models developed by us allows to fit experimental data and extract crucial information about the values of model parameters. Further investigations are expected for more realistic transmission functions, while time-dependent aspects of nanoscale heat transfer may be addressed by using the concept of wave packets scattered on potential barriers and point-like defects within regular (periodic) nanostructures.

  19. Aerogel Hybrid Composite Materials: Designs and Testing for Multifunctional Applications

    NASA Technical Reports Server (NTRS)

    Williams, Martha K.; Fesmire, James E.

    2016-01-01

    This webinar will introduce the broad spectrum of aerogel composites and their diverse performance properties such as reduced heat transfer to energy storage, and expands specifically on the aerogel/fiber laminate systems and testing methodologies. The multi-functional laminate composite system, AeroFiber, and its construction is designed by varying the type of fiber (e.g. polyester, carbon, Kevlar®, Spectra® or Innegral(TradeMark) and combinations thereof), the aerogel panel type and thickness, and overall layup configuration. The combination and design of materials may be customized and tailored to achieve a range of desired properties in the resulting laminate system. Multi-functional properties include structural strength, impact resistance, reduction in heat transfer, increased fire resistance, mechanical energy absorption, and acoustic energy dampening. Applications include aerospace, aircraft, automotive, boating, building and construction, lightweight portable structures, liquefied natural gas, cryogenics, transportation and energy, sporting equipment, and military protective gear industries.

  20. Amine-functionalized lanthanide-doped zirconia nanoparticles: optical spectroscopy, time-resolved fluorescence resonance energy transfer biodetection, and targeted imaging.

    PubMed

    Liu, Yongsheng; Zhou, Shanyong; Tu, Datao; Chen, Zhuo; Huang, Mingdong; Zhu, Haomiao; Ma, En; Chen, Xueyuan

    2012-09-12

    Ultrasmall inorganic oxide nanoparticles doped with trivalent lanthanide ions (Ln(3+)), a new and huge family of luminescent bioprobes, remain nearly untouched. Currently it is a challenge to synthesize biocompatible ultrasmall oxide bioprobes. Herein, we report a new inorganic oxide bioprobe based on sub-5 nm amine-functionalized tetragonal ZrO(2)-Ln(3+) nanoparticles synthesized via a facile solvothermal method and ligand exchange. By utilizing the long-lived luminescence of Ln(3+), we demonstrate its application as a sensitive time-resolved fluorescence resonance energy transfer (FRET) bioprobe to detect avidin with a record-low detection limit of 3.0 nM. The oxide nanoparticles also exhibit specific recognition of cancer cells overexpressed with urokinase plasminogen activator receptor (uPAR, an important marker of tumor biology and metastasis) and thus may have great potentials in targeted bioimaging.

  1. A visual approach to efficient analysis and quantification of ductile iron and reinforced sprayed concrete.

    PubMed

    Fritz, Laura; Hadwiger, Markus; Geier, Georg; Pittino, Gerhard; Gröller, M Eduard

    2009-01-01

    This paper describes advanced volume visualization and quantification for applications in non-destructive testing (NDT), which results in novel and highly effective interactive workflows for NDT practitioners. We employ a visual approach to explore and quantify the features of interest, based on transfer functions in the parameter spaces of specific application scenarios. Examples are the orientations of fibres or the roundness of particles. The applicability and effectiveness of our approach is illustrated using two specific scenarios of high practical relevance. First, we discuss the analysis of Steel Fibre Reinforced Sprayed Concrete (SFRSpC). We investigate the orientations of the enclosed steel fibres and their distribution, depending on the concrete's application direction. This is a crucial step in assessing the material's behavior under mechanical stress, which is still in its infancy and therefore a hot topic in the building industry. The second application scenario is the designation of the microstructure of ductile cast irons with respect to the contained graphite. This corresponds to the requirements of the ISO standard 945-1, which deals with 2D metallographic samples. We illustrate how the necessary analysis steps can be carried out much more efficiently using our system for 3D volumes. Overall, we show that a visual approach with custom transfer functions in specific application domains offers significant benefits and has the potential of greatly improving and optimizing the workflows of domain scientists and engineers.

  2. Artificial Neural Network with Hardware Training and Hardware Refresh

    NASA Technical Reports Server (NTRS)

    Duong, Tuan A. (Inventor)

    2003-01-01

    A neural network circuit is provided having a plurality of circuits capable of charge storage. Also provided is a plurality of circuits each coupled to at least one of the plurality of charge storage circuits and constructed to generate an output in accordance with a neuron transfer function. Each of a plurality of circuits is coupled to one of the plurality of neuron transfer function circuits and constructed to generate a derivative of the output. A weight update circuit updates the charge storage circuits based upon output from the plurality of transfer function circuits and output from the plurality of derivative circuits. In preferred embodiments, separate training and validation networks share the same set of charge storage circuits and may operate concurrently. The validation network has a separate transfer function circuits each being coupled to the charge storage circuits so as to replicate the training network s coupling of the plurality of charge storage to the plurality of transfer function circuits. The plurality of transfer function circuits may be constructed each having a transconductance amplifier providing differential currents combined to provide an output in accordance with a transfer function. The derivative circuits may have a circuit constructed to generate a biased differential currents combined so as to provide the derivative of the transfer function.

  3. Functional and Evolutionary Characterization of a Gene Transfer Agent’s Multilocus “Genome”

    PubMed Central

    Hynes, Alexander P.; Shakya, Migun; Mercer, Ryan G.; Grüll, Marc P.; Bown, Luke; Davidson, Fraser; Steffen, Ekaterina; Matchem, Heidi; Peach, Mandy E.; Berger, Tim; Grebe, Katherine; Zhaxybayeva, Olga; Lang, Andrew S.

    2016-01-01

    Gene transfer agents (GTAs) are phage-like particles that can package and transfer a random piece of the producing cell’s genome, but are unable to transfer all the genes required for their own production. As such, GTAs represent an evolutionary conundrum: are they selfish genetic elements propagating through an unknown mechanism, defective viruses, or viral structures “repurposed” by cells for gene exchange, as their name implies? In Rhodobacter capsulatus, production of the R. capsulatus GTA (RcGTA) particles is associated with a cluster of genes resembling a small prophage. Utilizing transcriptomic, genetic and biochemical approaches, we report that the RcGTA “genome” consists of at least 24 genes distributed across five distinct loci. We demonstrate that, of these additional loci, two are involved in cell recognition and binding and one in the production and maturation of RcGTA particles. The five RcGTA “genome” loci are widespread within Rhodobacterales, but not all loci have the same evolutionary histories. Specifically, two of the loci have been subject to frequent, probably virus-mediated, gene transfer events. We argue that it is unlikely that RcGTA is a selfish genetic element. Instead, our findings are compatible with the scenario that RcGTA is a virus-derived element maintained by the producing organism due to a selective advantage of within-population gene exchange. The modularity of the RcGTA “genome” is presumably a result of selection on the host organism to retain GTA functionality. PMID:27343288

  4. Synergy of brief activation of CD8 T-cells in the presence of IL-12 and adoptive transfer into lymphopenic hosts promotes tumor clearance and anti-tumor memory

    PubMed Central

    Díaz-Montero, C Marcela; Naga, Osama; Zidan, Abdel-Aziz A; Salem, Mohamed L; Pallin, Maria; Parmigiani, Anita; Walker, Gail; Wieder, Eric; Komanduri, Krishna; Cole, David J; Montero, Alberto J; Lichtenheld, Mathias G

    2011-01-01

    Adoptive T-cell therapy holds great promise for the treatment of metastatic melanoma. However, prohibitive costs associated with current technology required for culture and expansion of tumor-reactive T-cells, the need for intense preconditioning regimens to induce lymphopenia, and the unpredictable anti-tumor effect of adoptively transferred T-cells remain significant impediments for its clinical implementation. Here we report a simplified combinatorial approach that involves short activation of CD8+ T cells in the presence of IL-12 followed by adoptive transfer into tumor bearing animals after a single injection of cyclophosphamide. This approach resulted in complete eradication of B16 melanoma, and the establishment of long term immunological memory capable of fully protecting mice after a second B16 melanoma challenge. The activated donor cells were unique because they simultaneously exhibited traits for cytotoxic effector function, central memory-like, homing, and senescence. After tumor eradication and within three months after transfer, CD8+ cells exhibited a conventional memory CTL phenotype. Moreover, these memory CTLs acquired functional attributes characteristic of memory stem cells, including the ability to resist chemotherapy-induced toxicity. Our results suggest that short-term T-cell receptor signaling in the presence of IL-12 promotes promiscuous qualities in naïve CTL which - upon transfer into lymphopenic hosts- are sufficient to eradicate tumors and generate life-long tumor-specific memory. PMID:21915391

  5. Spatial Data Transfer Standard (SDTS), part 1 : logical specifications

    DOT National Transportation Integrated Search

    1997-11-20

    This document contains a specification of the Spatial Data Transfer Standard (SDTS), that will serve as a national spatial data transfer mechanism for the United States. As such it is designed to transfer a wide variety of data structures that are us...

  6. Identification of boiler inlet transfer functions and estimation of system parameters

    NASA Technical Reports Server (NTRS)

    Miles, J. H.

    1972-01-01

    An iterative computer method is described for identifying boiler transfer functions using frequency response data. An objective penalized performance measure and a nonlinear minimization technique are used to cause the locus of points generated by a transfer function to resemble the locus of points obtained from frequency response measurements. Different transfer functions can be tried until a satisfactory empirical transfer function of the system is found. To illustrate the method, some examples and some results from a study of a set of data consisting of measurements of the inlet impedance of a single tube forced flow boiler with inserts are given.

  7. On the design of decoupling controllers for advanced rotorcraft in the hover case

    NASA Technical Reports Server (NTRS)

    Fan, M. K. H.; Tits, A.; Barlow, J.; Tsing, N. K.; Tischler, M.; Takahashi, M.

    1991-01-01

    A methodology for design of helicopter control systems is proposed that can account for various types of concurrent specifications: stability, decoupling between longitudinal and lateral motions, handling qualities, and physical limitations of the swashplate motions. This is achieved by synergistic use of analytical techniques (Q-parameterization of all stabilizing controllers, transfer function interpolation) and advanced numerical optimization techniques. The methodology is used to design a controller for the UH-60 helicopter in hover. Good results are achieved for decoupling and handling quality specifications.

  8. Spatial Data Transfer Standard (SDTS)

    USGS Publications Warehouse

    ,

    1999-01-01

    The American National Standards Institute?s (ANSI) Spatial Data Transfer Standard (SDTS) is a mechanism for archiving and transferring of spatial data (including metadata) between dissimilar computer systems. The SDTS specifies exchange constructs, such as format, structure, and content, for spatially referenced vector and raster (including gridded) data. The SDTS includes a flexible conceptual model, specifications for a quality report, transfer module specifications, data dictionary specifications, and definitions of spatial features and attributes.

  9. Enhanced Imaging of Specific Cell-Surface Glycosylation Based on Multi-FRET.

    PubMed

    Yuan, Baoyin; Chen, Yuanyuan; Sun, Yuqiong; Guo, Qiuping; Huang, Jin; Liu, Jianbo; Meng, Xiangxian; Yang, Xiaohai; Wen, Xiaohong; Li, Zenghui; Li, Lie; Wang, Kemin

    2018-05-15

    Cell-surface glycosylation contains abundant biological information that reflects cell physiological state, and it is of great value to image cell-surface glycosylation to elucidate its functions. Here we present a hybridization chain reaction (HCR)-based multifluorescence resonance energy transfer (multi-FRET) method for specific imaging of cell-surface glycosylation. By installing donors through metabolic glycan labeling and acceptors through aptamer-tethered nanoassemblies on the same glycoconjugate, intramolecular multi-FRET occurs due to near donor-acceptor distance. Benefiting from amplified effect and spatial flexibility of the HCR nanoassemblies, enhanced multi-FRET imaging of specific cell-surface glycosylation can be obtained. With this HCR-based multi-FRET method, we achieved obvious contrast in imaging of protein-specific GalNAcylation on 7211 cell surfaces. In addition, we demonstrated the general applicability of this method by visualizing the protein-specific sialylation on CEM cell surfaces. Furthermore, the expression changes of CEM cell-surface protein-specific sialylation under drug treatment was accurately monitored. This developed imaging method may provide a powerful tool in researching glycosylation functions, discovering biomarkers, and screening drugs.

  10. Computer method for identification of boiler transfer functions

    NASA Technical Reports Server (NTRS)

    Miles, J. H.

    1972-01-01

    Iterative computer aided procedure was developed which provides for identification of boiler transfer functions using frequency response data. Method uses frequency response data to obtain satisfactory transfer function for both high and low vapor exit quality data.

  11. Proceedings and findings of the 1976 Workshop on Ride Quality. [passenger acceptance of transportation systems

    NASA Technical Reports Server (NTRS)

    Kuhlthau, A. R. (Editor)

    1976-01-01

    The workshop was organized around the study of the three basic transfer functions required to evaluate and/or predict passenger acceptance of transportation systems: These are the vehicle, passenger, and value transfer functions. For the purpose of establishing working groups corresponding to the basic transfer functions, it was decided to split the vehicle transfer function into two distinct groups studying surface vehicles and air/marine vehicles, respectively.

  12. Unraveling the evolutionary history of the phosphoryl-transfer chain of the phosphoenolpyruvate:phosphotransferase system through phylogenetic analyses and genome context

    PubMed Central

    2008-01-01

    Background The phosphoenolpyruvate phosphotransferase system (PTS) plays a major role in sugar transport and in the regulation of essential physiological processes in many bacteria. The PTS couples solute transport to its phosphorylation at the expense of phosphoenolpyruvate (PEP) and it consists of general cytoplasmic phosphoryl transfer proteins and specific enzyme II complexes which catalyze the uptake and phosphorylation of solutes. Previous studies have suggested that the evolution of the constituents of the enzyme II complexes has been driven largely by horizontal gene transfer whereas vertical inheritance has been prevalent in the general phosphoryl transfer proteins in some bacterial groups. The aim of this work is to test this hypothesis by studying the evolution of the phosphoryl transfer proteins of the PTS. Results We have analyzed the evolutionary history of the PTS phosphoryl transfer chain (PTS-ptc) components in 222 complete genomes by combining phylogenetic methods and analysis of genomic context. Phylogenetic analyses alone were not conclusive for the deepest nodes but when complemented with analyses of genomic context and functional information, the main evolutionary trends of this system could be depicted. Conclusion The PTS-ptc evolved in bacteria after the divergence of early lineages such as Aquificales, Thermotogales and Thermus/Deinococcus. The subsequent evolutionary history of the PTS-ptc varied in different bacterial lineages: vertical inheritance and lineage-specific gene losses mainly explain the current situation in Actinobacteria and Firmicutes whereas horizontal gene transfer (HGT) also played a major role in Proteobacteria. Most remarkably, we have identified a HGT event from Firmicutes or Fusobacteria to the last common ancestor of the Enterobacteriaceae, Pasteurellaceae, Shewanellaceae and Vibrionaceae. This transfer led to extensive changes in the metabolic and regulatory networks of these bacteria including the development of a novel carbon catabolite repression system. Hence, this example illustrates that HGT can drive major physiological modifications in bacteria. PMID:18485189

  13. Computer task performance by subjects with Duchenne muscular dystrophy.

    PubMed

    Malheiros, Silvia Regina Pinheiro; da Silva, Talita Dias; Favero, Francis Meire; de Abreu, Luiz Carlos; Fregni, Felipe; Ribeiro, Denise Cardoso; de Mello Monteiro, Carlos Bandeira

    2016-01-01

    Two specific objectives were established to quantify computer task performance among people with Duchenne muscular dystrophy (DMD). First, we compared simple computational task performance between subjects with DMD and age-matched typically developing (TD) subjects. Second, we examined correlations between the ability of subjects with DMD to learn the computational task and their motor functionality, age, and initial task performance. The study included 84 individuals (42 with DMD, mean age of 18±5.5 years, and 42 age-matched controls). They executed a computer maze task; all participants performed the acquisition (20 attempts) and retention (five attempts) phases, repeating the same maze. A different maze was used to verify transfer performance (five attempts). The Motor Function Measure Scale was applied, and the results were compared with maze task performance. In the acquisition phase, a significant decrease was found in movement time (MT) between the first and last acquisition block, but only for the DMD group. For the DMD group, MT during transfer was shorter than during the first acquisition block, indicating improvement from the first acquisition block to transfer. In addition, the TD group showed shorter MT than the DMD group across the study. DMD participants improved their performance after practicing a computational task; however, the difference in MT was present in all attempts among DMD and control subjects. Computational task improvement was positively influenced by the initial performance of individuals with DMD. In turn, the initial performance was influenced by their distal functionality but not their age or overall functionality.

  14. Modeling collision energy transfer in APCI/CID mass spectra of PAHs using thermal-like post-collision internal energy distributions

    NASA Astrophysics Data System (ADS)

    Solano, Eduardo A.; Mohamed, Sabria; Mayer, Paul M.

    2016-10-01

    The internal energy transferred when projectile molecular ions of naphthalene collide with argon gas atoms was extracted from the APCI-CID (atmospheric-pressure chemical ionization collision-induced dissociation) mass spectra acquired as a function of collision energy. Ion abundances were calculated by microcanonical integration of the differential rate equations using the Rice-Ramsperger-Kassel-Marcus rate constants derived from a UB3LYP/6-311G+(3df,2p)//UB3LYP/6-31G(d) fragmentation mechanism and thermal-like vibrational energy distributions p M (" separators=" E , T char ) . The mean vibrational energy excess of the ions was characterized by the parameter Tchar ("characteristic temperature"), determined by fitting the theoretical ion abundances to the experimental breakdown graph (a plot of relative abundances of the ions as a function of kinetic energy) of activated naphthalene ions. According to these results, the APCI ion source produces species below Tchar = 1457 K, corresponding to 3.26 eV above the vibrational ground state. Subsequent collisions heat the ions up further, giving rise to a sigmoid curve of Tchar as a function of Ecom (center-of-mass-frame kinetic energy). The differential internal energy absorption per kinetic energy unit (dEvib/dEcom) changes with Ecom according to a symmetric bell-shaped function with a maximum at 6.38 ± 0.32 eV (corresponding to 6.51 ± 0.27 eV of vibrational energy excess), and a half-height full width of 6.30 ± 1.15 eV. This function imposes restrictions on the amount of energy that can be transferred by collisions, such that a maximum is reached as kinetic energy is increased. This behavior suggests that the collisional energy transfer exhibits a pronounced increase around some specific value of energy. Finally, the model is tested against the CID mass spectra of anthracene and pyrene ions and the corresponding results are discussed.

  15. Modeling collision energy transfer in APCI/CID mass spectra of PAHs using thermal-like post-collision internal energy distributions.

    PubMed

    Solano, Eduardo A; Mohamed, Sabria; Mayer, Paul M

    2016-10-28

    The internal energy transferred when projectile molecular ions of naphthalene collide with argon gas atoms was extracted from the APCI-CID (atmospheric-pressure chemical ionization collision-induced dissociation) mass spectra acquired as a function of collision energy. Ion abundances were calculated by microcanonical integration of the differential rate equations using the Rice-Ramsperger-Kassel-Marcus rate constants derived from a UB3LYP/6-311G+(3df,2p)//UB3LYP/6-31G(d) fragmentation mechanism and thermal-like vibrational energy distributions p M E,T char . The mean vibrational energy excess of the ions was characterized by the parameter T char ("characteristic temperature"), determined by fitting the theoretical ion abundances to the experimental breakdown graph (a plot of relative abundances of the ions as a function of kinetic energy) of activated naphthalene ions. According to these results, the APCI ion source produces species below T char = 1457 K, corresponding to 3.26 eV above the vibrational ground state. Subsequent collisions heat the ions up further, giving rise to a sigmoid curve of T char as a function of E com (center-of-mass-frame kinetic energy). The differential internal energy absorption per kinetic energy unit (dE vib /dE com ) changes with E com according to a symmetric bell-shaped function with a maximum at 6.38 ± 0.32 eV (corresponding to 6.51 ± 0.27 eV of vibrational energy excess), and a half-height full width of 6.30 ± 1.15 eV. This function imposes restrictions on the amount of energy that can be transferred by collisions, such that a maximum is reached as kinetic energy is increased. This behavior suggests that the collisional energy transfer exhibits a pronounced increase around some specific value of energy. Finally, the model is tested against the CID mass spectra of anthracene and pyrene ions and the corresponding results are discussed.

  16. Nerve transfers in tetraplegia I: Background and technique

    PubMed Central

    Brown, Justin M.

    2011-01-01

    Background: The recovery of hand function is consistently rated as the highest priority for persons with tetraplegia. Recovering even partial arm and hand function can have an enormous impact on independence and quality of life of an individual. Currently, tendon transfers are the accepted modality for improving hand function. In this procedure, the distal end of a functional muscle is cut and reattached at the insertion site of a nonfunctional muscle. The tendon transfer sacrifices the function at a lesser location to provide function at a more important location. Nerve transfers are conceptually similar to tendon transfers and involve cutting and connecting a healthy but less critical nerve to a more important but paralyzed nerve to restore its function. Methods: We present a case of a 28-year-old patient with a C5-level ASIA B (international classification level 1) injury who underwent nerve transfers to restore arm and hand function. Intact peripheral innervation was confirmed in the paralyzed muscle groups corresponding to finger flexors and extensors, wrist flexors and extensors, and triceps bilaterally. Volitional control and good strength were present in the biceps and brachialis muscles, the deltoid, and the trapezius. The patient underwent nerve transfers to restore finger flexion and extension, wrist flexion and extension, and elbow extension. Intraoperative motor-evoked potentials and direct nerve stimulation were used to identify donor and recipient nerve branches. Results: The patient tolerated the procedure well, with a preserved function in both elbow flexion and shoulder abduction. Conclusions: Nerve transfers are a technically feasible means of restoring the upper extremity function in tetraplegia in cases that may not be amenable to tendon transfers. PMID:21918736

  17. [Institutional psychotherapy, caring for patients and the place of care].

    PubMed

    Drogoul, Frank

    2013-01-01

    Institutional psychotherapy was developed in the specific context of the "assassination" of the Spanish revolution. There are two distinct movements or two periods. The first, based around Georges Daumézon and Henri Ey gave birth to the sector. The second, around FrançoisTosquelles and Jean Oury emphasised the asylum as the place of care. The function of institutional psychotherapy is to care not only for the patients but also the place of treatment. To fulfil this function, it has a tool box: transfer, the fight against the overvaluation of hierarchy as well as the function of the therapeutic club.

  18. Transfer function concept for ultrasonic characterization of material microstructures

    NASA Technical Reports Server (NTRS)

    Vary, A.; Kautz, H. E.

    1986-01-01

    The approach given depends on treating material microstructures as elastomechanical filters that have analytically definable transfer functions. These transfer functions can be defined in terms of the frequency dependence of the ultrasonic attenuation coefficient. The transfer function concept provides a basis for synthesizing expressions that characterize polycrystalline materials relative to microstructural factors such as mean grain size, grain-size distribution functions, and grain boundary energy transmission. Although the approach is nonrigorous, it leads to a rational basis for combining the previously mentioned diverse and fragmented equations for ultrasonic attenuation coefficients.

  19. The nitric-oxide reductase from Paracoccus denitrificans uses a single specific proton pathway.

    PubMed

    ter Beek, Josy; Krause, Nils; Reimann, Joachim; Lachmann, Peter; Ädelroth, Pia

    2013-10-18

    The NO reductase from Paracoccus denitrificans reduces NO to N2O (2NO + 2H(+) + 2e(-) → N2O + H2O) with electrons donated by periplasmic cytochrome c (cytochrome c-dependent NO reductase; cNOR). cNORs are members of the heme-copper oxidase superfamily of integral membrane proteins, comprising the O2-reducing, proton-pumping respiratory enzymes. In contrast, although NO reduction is as exergonic as O2 reduction, there are no protons pumped in cNOR, and in addition, protons needed for NO reduction are derived from the periplasmic solution (no contribution to the electrochemical gradient is made). cNOR thus only needs to transport protons from the periplasm into the active site without the requirement to control the timing of opening and closing (gating) of proton pathways as is needed in a proton pump. Based on the crystal structure of a closely related cNOR and molecular dynamics simulations, several proton transfer pathways were suggested, and in principle, these could all be functional. In this work, we show that residues in one of the suggested pathways (denoted pathway 1) are sensitive to site-directed mutation, whereas residues in the other proposed pathways (pathways 2 and 3) could be exchanged without severe effects on turnover activity with either NO or O2. We further show that electron transfer during single-turnover reduction of O2 is limited by proton transfer and can thus be used to study alterations in proton transfer rates. The exchange of residues along pathway 1 showed specific slowing of this proton-coupled electron transfer as well as changes in its pH dependence. Our results indicate that only pathway 1 is used to transfer protons in cNOR.

  20. A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy

    PubMed Central

    Spielmann, Guillaume; Bollard, Catherine M.; Kunz, Hawley; Hanley, Patrick J.; Simpson, Richard J.

    2016-01-01

    Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5), and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy. PMID:27181409

  1. A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy.

    PubMed

    Spielmann, Guillaume; Bollard, Catherine M; Kunz, Hawley; Hanley, Patrick J; Simpson, Richard J

    2016-05-16

    Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5), and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy.

  2. Improving accuracy and power with transfer learning using a meta-analytic database.

    PubMed

    Schwartz, Yannick; Varoquaux, Gaël; Pallier, Christophe; Pinel, Philippe; Poline, Jean-Baptiste; Thirion, Bertrand

    2012-01-01

    Typical cohorts in brain imaging studies are not large enough for systematic testing of all the information contained in the images. To build testable working hypotheses, investigators thus rely on analysis of previous work, sometimes formalized in a so-called meta-analysis. In brain imaging, this approach underlies the specification of regions of interest (ROIs) that are usually selected on the basis of the coordinates of previously detected effects. In this paper, we propose to use a database of images, rather than coordinates, and frame the problem as transfer learning: learning a discriminant model on a reference task to apply it to a different but related new task. To facilitate statistical analysis of small cohorts, we use a sparse discriminant model that selects predictive voxels on the reference task and thus provides a principled procedure to define ROIs. The benefits of our approach are twofold. First it uses the reference database for prediction, i.e., to provide potential biomarkers in a clinical setting. Second it increases statistical power on the new task. We demonstrate on a set of 18 pairs of functional MRI experimental conditions that our approach gives good prediction. In addition, on a specific transfer situation involving different scanners at different locations, we show that voxel selection based on transfer learning leads to higher detection power on small cohorts.

  3. Item-specific and generalization effects on brain activation when learning Chinese characters

    PubMed Central

    Deng, Yuan; Booth, James R.; Chou, Tai-Li; Ding, Guo-Sheng; Peng, Dan-Ling

    2009-01-01

    Neural changes related to learning of the meaning of Chinese characters in English speakers were examined using functional magnetic resonance imaging (fMRI). We examined item specific learning effects for trained characters, but also the generalization of semantic knowledge to novel transfer characters that shared a semantic radical (part of a character that gives a clue to word meaning, e.g. water for lake) with trained characters. Behavioral results show that acquired semantic knowledge improves performance for both trained and transfer characters. Neuroimaging results show that the left fusiform gyrus plays a central role in the visual processing of orthographic information in characters. The left superior parietal cortex seems to play a crucial role in learning the visual–spatial aspects of the characters because it shows learning related decreases for trained characters, is correlated with behavioral improvement from early to late in learning for the trained characters, and is correlated with better long-term retention for the transfer characters. The inferior frontal gyrus seems to be associated with the efficiency of retrieving and manipulating semantic representations because there are learning related decreases for trained characters and this decrease is correlated with greater behavioral improvement from early to late in learning. PMID:18514678

  4. Using viral vectors as gene transfer tools (Cell Biology and Toxicology Special Issue: ETCS-UK 1 day meeting on genetic manipulation of cells).

    PubMed

    Howarth, Joanna L; Lee, Youn Bok; Uney, James B

    2010-02-01

    In recent years, the development of powerful viral gene transfer techniques has greatly facilitated the study of gene function. This review summarises some of the viral delivery systems routinely used to mediate gene transfer into cell lines, primary cell cultures and in whole animal models. The systems described were originally discussed at a 1-day European Tissue Culture Society (ETCS-UK) workshop that was held at University College London on 1st April 2009. Recombinant-deficient viral vectors (viruses that are no longer able to replicate) are used to transduce dividing and post-mitotic cells, and they have been optimised to mediate regulatable, powerful, long-term and cell-specific expression. Hence, viral systems have become very widely used, especially in the field of neurobiology. This review introduces the main categories of viral vectors, focusing on their initial development and highlighting modifications and improvements made since their introduction. In particular, the use of specific promoters to restrict expression, translational enhancers and regulatory elements to boost expression from a single virion and the development of regulatable systems is described.

  5. VALIDATION OF BENEFIT-TRANSFER FUNCTIONS

    EPA Science Inventory

    1. Identification of benefit-transfer functions that are the most credible. 2. Identification of benefit-transfer issues that are related to transfer method and those related to data limitations. 3. Clarification of issues t...

  6. The recalibration of tactile perception during tool use is body-part specific

    PubMed Central

    Cawley-Bennett, Andrew; Longo, Matthew R.; Saygin, Ayse P.

    2018-01-01

    Two decades of research have demonstrated that using a tool modulates spatial representations of the body. Whether this embodiment is specific to representations of the tool-using limb or extends to representations of other body parts has received little attention. Several studies of other perceptual phenomena have found that modulations to the primary somatosensory representation of the hand transfers to the face, due in part to their close proximity in primary somatosensory cortex. In the present study, we investigated whether tool-induced recalibration of tactile perception on the hand transfers to the cheek. Participants verbally estimated the distance between two tactile points applied to either their hand or face, before and after using a hand-shaped tool. Tool use recalibrated tactile distance perception on the hand—in line with previous findings—but left perception on the cheek unchanged. This finding provides support for the idea that embodiment is body-part specific. Furthermore, it suggests that tool-induced perceptual recalibration occurs at a level of somatosensory processing, where representations of the hand and face have become functionally disentangled. PMID:28702834

  7. A high molecular weight-melanoma associated antigen-specific chimeric antigen receptor redirects lymphocytes to target human melanomas

    PubMed Central

    Burns, William R.; Zhao, Yangbing; Frankel, Timothy L.; Hinrichs, Christian S.; Zheng, Zhili; Xu, Hui; Feldman, Steven A.; Ferrone, Soldano; Rosenberg, Steven A.; Morgan, Richard A.

    2011-01-01

    Immunotherapy, particularly the adoptive cell transfer (ACT) of tumor infiltrating lymphocytes (TIL), is a very promising therapy for metastatic melanoma. Some patients unable to receive TIL have been successfully treated with autologous peripheral blood lymphocytes (PBL), genetically modified to express HLA class I antigen restricted, melanoma antigen-reactive T-cell receptors; however, substantial numbers of patients remain ineligible due to the lack of expression of the restricting HLA class I allele. We sought to overcome this limitation by designing a non-MHC-restricted, chimeric antigen receptor (CAR) targeting the high molecular weight-melanoma associated antigen (HMW-MAA), which is highly expressed on over 90% of human melanomas but has a restricted distribution in normal tissues. HMW-MAA-specific CARs containing an antigen recognition domain based on variations of the HMW-MAA-specific monoclonal antibody (mAb) 225.28S and a T-cell activation domain based on combinations of CD28, 4-1BB, and CD3ζ activation motifs were constructed within a retroviral vector to allow stable gene transfer into cells and their progeny. Following optimization of the HMW-MAA-specific CAR for expression and function in human PBL, these gene-modified T cells secreted cytokines, were cytolytic, and proliferated in response to HMW-MAA expressing cell lines. Furthermore, the receptor functioned in both CD4+ and CD8+ cells, was non-MHC-restricted, and reacted against explanted human melanomas. To evaluate this HMW-MAA-specific CAR in patients with metastatic melanoma, we developed a clinical-grade retroviral packaging line. This may represent a novel means to treat the majority of patients with advanced melanoma, most notably those unable to receive current ACT therapies. PMID:20395199

  8. 41 CFR 302-3.206 - If I am re-employed after a separation by reduction in force or transfer of functions, may my...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 4 2013-07-01 2012-07-01 true If I am re-employed after... allowance? 302-3.206 Section 302-3.206 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES RELOCATION ALLOWANCES 3-RELOCATION ALLOWANCE BY SPECIFIC TYPE Types of...

  9. Lentiviral Protein Transfer Vectors Are an Efficient Vaccine Platform and Induce a Strong Antigen-Specific Cytotoxic T Cell Response

    PubMed Central

    Uhlig, Katharina M.; Schülke, Stefan; Scheuplein, Vivian A. M.; Malczyk, Anna H.; Reusch, Johannes; Kugelmann, Stefanie; Muth, Anke; Koch, Vivian; Hutzler, Stefan; Bodmer, Bianca S.; Schambach, Axel; Buchholz, Christian J.; Waibler, Zoe; Scheurer, Stephan

    2015-01-01

    ABSTRACT To induce and trigger innate and adaptive immune responses, antigen-presenting cells (APCs) take up and process antigens. Retroviral particles are capable of transferring not only genetic information but also foreign cargo proteins when they are genetically fused to viral structural proteins. Here, we demonstrate the capacity of lentiviral protein transfer vectors (PTVs) for targeted antigen transfer directly into APCs and thereby induction of cytotoxic T cell responses. Targeting of lentiviral PTVs to APCs can be achieved analogously to gene transfer vectors by pseudotyping the particles with truncated wild-type measles virus (MV) glycoproteins (GPs), which use human SLAM (signaling lymphocyte activation molecule) as a main entry receptor. SLAM is expressed on stimulated lymphocytes and APCs, including dendritic cells. SLAM-targeted PTVs transferred the reporter protein green fluorescent protein (GFP) or Cre recombinase with strict receptor specificity into SLAM-expressing CHO and B cell lines, in contrast to broadly transducing vesicular stomatitis virus G protein (VSV-G) pseudotyped PTVs. Primary myeloid dendritic cells (mDCs) incubated with targeted or nontargeted ovalbumin (Ova)-transferring PTVs stimulated Ova-specific T lymphocytes, especially CD8+ T cells. Administration of Ova-PTVs into SLAM-transgenic and control mice confirmed the observed predominant induction of antigen-specific CD8+ T cells and demonstrated the capacity of protein transfer vectors as suitable vaccines for the induction of antigen-specific immune responses. IMPORTANCE This study demonstrates the specificity and efficacy of antigen transfer by SLAM-targeted and nontargeted lentiviral protein transfer vectors into antigen-presenting cells to trigger antigen-specific immune responses in vitro and in vivo. The observed predominant activation of antigen-specific CD8+ T cells indicates the suitability of SLAM-targeted and also nontargeted PTVs as a vaccine for the induction of cytotoxic immune responses. Since cytotoxic CD8+ T lymphocytes are a mainstay of antitumoral immune responses, PTVs could be engineered for the transfer of specific tumor antigens provoking tailored antitumoral immunity. Therefore, PTVs can be used as safe and efficient alternatives to gene transfer vectors or live attenuated replicating vector platforms, avoiding genotoxicity or general toxicity in highly immunocompromised patients, respectively. Thereby, the potential for easy envelope exchange allows the circumventing of neutralizing antibodies, e.g., during repeated boost immunizations. PMID:26085166

  10. Mitochondrial Retroprocessing Promoted Functional Transfers of rpl5 to the Nucleus in Grasses.

    PubMed

    Wu, Zhiqiang; Sloan, Daniel B; Brown, Colin W; Rosenblueth, Mónica; Palmer, Jeffrey D; Ong, Han Chuan

    2017-09-01

    Functional gene transfers from the mitochondrion to the nucleus are ongoing in angiosperms and have occurred repeatedly for all 15 ribosomal protein genes, but it is not clear why some of these genes are transferred more often than others nor what the balance is between DNA- and RNA-mediated transfers. Although direct insertion of mitochondrial DNA into the nucleus occurs frequently in angiosperms, case studies of functional mitochondrial gene transfer have implicated an RNA-mediated mechanism that eliminates introns and RNA editing sites, which would otherwise impede proper expression of mitochondrial genes in the nucleus. To elucidate the mechanisms that facilitate functional gene transfers and the evolutionary dynamics of the coexisting nuclear and mitochondrial gene copies that are established during these transfers, we have analyzed rpl5 genes from 90 grasses (Poaceae) and related monocots. Multiple lines of evidence indicate that rpl5 has been functionally transferred to the nucleus at least three separate times in the grass family and that at least seven species have intact and transcribed (but not necessarily functional) copies in both the mitochondrion and nucleus. In two grasses, likely functional nuclear copies of rpl5 have been subject to recent gene conversion events via secondarily transferred mitochondrial copies in what we believe are the first described cases of mitochondrial-to-nuclear gene conversion. We show that rpl5 underwent a retroprocessing event within the mitochondrial genome early in the evolution of the grass family, which we argue predisposed the gene towards successful, DNA-mediated functional transfer by generating a "pre-edited" sequence. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. The sacroiliac joint: an overview of its anatomy, function and potential clinical implications.

    PubMed

    Vleeming, A; Schuenke, M D; Masi, A T; Carreiro, J E; Danneels, L; Willard, F H

    2012-12-01

    This article focuses on the (functional) anatomy and biomechanics of the pelvic girdle and specifically the sacroiliac joints (SIJs). The SIJs are essential for effective load transfer between the spine and legs. The sacrum, pelvis and spine, and the connections to the arms, legs and head, are functionally interrelated through muscular, fascial and ligamentous interconnections. A historical overview is presented on pelvic and especially SIJ research, followed by a general functional anatomical overview of the pelvis. In specific sections, the development and maturation of the SIJ is discussed, and a description of the bony anatomy and sexual morphism of the pelvis and SIJ is debated. The literature on the SIJ ligaments and innervation is discussed, followed by a section on the pathology of the SIJ. Pelvic movement studies are investigated and biomechanical models for SIJ stability analyzed, including examples of insufficient versus excessive sacroiliac force closure. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

  12. DBATE: database of alternative transcripts expression.

    PubMed

    Bianchi, Valerio; Colantoni, Alessio; Calderone, Alberto; Ausiello, Gabriele; Ferrè, Fabrizio; Helmer-Citterich, Manuela

    2013-01-01

    The use of high-throughput RNA sequencing technology (RNA-seq) allows whole transcriptome analysis, providing an unbiased and unabridged view of alternative transcript expression. Coupling splicing variant-specific expression with its functional inference is still an open and difficult issue for which we created the DataBase of Alternative Transcripts Expression (DBATE), a web-based repository storing expression values and functional annotation of alternative splicing variants. We processed 13 large RNA-seq panels from human healthy tissues and in disease conditions, reporting expression levels and functional annotations gathered and integrated from different sources for each splicing variant, using a variant-specific annotation transfer pipeline. The possibility to perform complex queries by cross-referencing different functional annotations permits the retrieval of desired subsets of splicing variant expression values that can be visualized in several ways, from simple to more informative. DBATE is intended as a novel tool to help appreciate how, and possibly why, the transcriptome expression is shaped. DATABASE URL: http://bioinformatica.uniroma2.it/DBATE/.

  13. PiggyBac-mediated Cancer Immunotherapy Using EBV-specific Cytotoxic T-cells Expressing HER2-specific Chimeric Antigen Receptor

    PubMed Central

    Nakazawa, Yozo; Huye, Leslie E; Salsman, Vita S; Leen, Ann M; Ahmed, Nabil; Rollins, Lisa; Dotti, Gianpietro; Gottschalk, Stephen M; Wilson, Matthew H; Rooney, Cliona M

    2011-01-01

    Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) can be modified to function as heterologous tumor directed effector cells that survive longer in vivo than tumor directed T cells without virus specificity, due to chronic stimulation by viral antigens expressed during persistent infection in seropositive individuals. We evaluated the nonviral piggyBac (PB) transposon system as a platform for modifying EBV-CTLs to express a functional human epidermal growth factor receptor 2-specific chimeric antigen receptor (HER2-CAR) thereby directing virus-specific, gene modified CTLs towards HER2-positive cancer cells. Peripheral blood mononuclear cells (PBMCs) were nucleofected with transposons encoding a HER2-CAR and a truncated CD19 molecule for selection followed by specific activation and expansion of EBV-CTLs. HER2-CAR was expressed in ~40% of T cells after CD19 selection with retention of immunophenotype, polyclonality, and function. HER2-CAR-modified EBV-CTLs (HER2-CTLs) killed HER2-positive brain tumor cell lines in vitro, exhibited transient and reversible increases in HER2-CAR expression following antigen-specific stimulation, and stably expressed HER2-CAR beyond 120 days. Adoptive transfer of PB-modified HER2-CTLs resulted in tumor regression in a murine xenograft model. Our results demonstrate that PB can be used to redirect virus-specific CTLs to tumor targets, which should prolong tumor-specific T cell survival in vivo producing more efficacious immunotherapy. PMID:21772253

  14. PiggyBac-mediated cancer immunotherapy using EBV-specific cytotoxic T-cells expressing HER2-specific chimeric antigen receptor.

    PubMed

    Nakazawa, Yozo; Huye, Leslie E; Salsman, Vita S; Leen, Ann M; Ahmed, Nabil; Rollins, Lisa; Dotti, Gianpietro; Gottschalk, Stephen M; Wilson, Matthew H; Rooney, Cliona M

    2011-12-01

    Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) can be modified to function as heterologous tumor directed effector cells that survive longer in vivo than tumor directed T cells without virus specificity, due to chronic stimulation by viral antigens expressed during persistent infection in seropositive individuals. We evaluated the nonviral piggyBac (PB) transposon system as a platform for modifying EBV-CTLs to express a functional human epidermal growth factor receptor 2-specific chimeric antigen receptor (HER2-CAR) thereby directing virus-specific, gene modified CTLs towards HER2-positive cancer cells. Peripheral blood mononuclear cells (PBMCs) were nucleofected with transposons encoding a HER2-CAR and a truncated CD19 molecule for selection followed by specific activation and expansion of EBV-CTLs. HER2-CAR was expressed in ~40% of T cells after CD19 selection with retention of immunophenotype, polyclonality, and function. HER2-CAR-modified EBV-CTLs (HER2-CTLs) killed HER2-positive brain tumor cell lines in vitro, exhibited transient and reversible increases in HER2-CAR expression following antigen-specific stimulation, and stably expressed HER2-CAR beyond 120 days. Adoptive transfer of PB-modified HER2-CTLs resulted in tumor regression in a murine xenograft model. Our results demonstrate that PB can be used to redirect virus-specific CTLs to tumor targets, which should prolong tumor-specific T cell survival in vivo producing more efficacious immunotherapy.

  15. Fast computation of the electrolyte-concentration transfer function of a lithium-ion cell model

    NASA Astrophysics Data System (ADS)

    Rodríguez, Albert; Plett, Gregory L.; Trimboli, M. Scott

    2017-08-01

    One approach to creating physics-based reduced-order models (ROMs) of battery-cell dynamics requires first generating linearized Laplace-domain transfer functions of all cell internal electrochemical variables of interest. Then, the resulting infinite-dimensional transfer functions can be reduced by various means in order to find an approximate low-dimensional model. These methods include Padé approximation or the Discrete-Time Realization algorithm. In a previous article, Lee and colleagues developed a transfer function of the electrolyte concentration for a porous-electrode pseudo-two-dimensional lithium-ion cell model. Their approach used separation of variables and Sturm-Liouville theory to compute an infinite-series solution to the transfer function, which they then truncated to a finite number of terms for reasons of practicality. Here, we instead use a variation-of-parameters approach to arrive at a different representation of the identical solution that does not require a series expansion. The primary benefits of the new approach are speed of computation of the transfer function and the removal of the requirement to approximate the transfer function by truncating the number of terms evaluated. Results show that the speedup of the new method can be more than 3800.

  16. The transfer functions of cardiac tissue during stochastic pacing.

    PubMed

    de Lange, Enno; Kucera, Jan P

    2009-01-01

    The restitution properties of cardiac action potential duration (APD) and conduction velocity (CV) are important factors in arrhythmogenesis. They determine alternans, wavebreak, and the patterns of reentrant arrhythmias. We developed a novel approach to characterize restitution using transfer functions. Transfer functions relate an input and an output quantity in terms of gain and phase shift in the complex frequency domain. We derived an analytical expression for the transfer function of interbeat intervals (IBIs) during conduction from one site (input) to another site downstream (output). Transfer functions can be efficiently obtained using a stochastic pacing protocol. Using simulations of conduction and extracellular mapping of strands of neonatal rat ventricular myocytes, we show that transfer functions permit the quantification of APD and CV restitution slopes when it is difficult to measure APD directly. We find that the normally positive CV restitution slope attenuates IBI variations. In contrast, a negative CV restitution slope (induced by decreasing extracellular [K(+)]) amplifies IBI variations with a maximum at the frequency of alternans. Hence, it potentiates alternans and renders conduction unstable, even in the absence of APD restitution. Thus, stochastic pacing and transfer function analysis represent a powerful strategy to evaluate restitution and the stability of conduction.

  17. Does inhibitory control training transfer?: behavioral and neural effects on an untrained emotion regulation task.

    PubMed

    Beauchamp, Kathryn G; Kahn, Lauren E; Berkman, Elliot T

    2016-09-01

    Inhibitory control (IC) is a critical neurocognitive skill for successfully navigating challenges across domains. Several studies have attempted to use training to improve neurocognitive skills such as IC, but few have found that training generalizes to performance on non-trained tasks. We used functional magnetic resonance imaging (fMRI) to investigate the effect of IC training on a related but untrained emotion regulation (ER) task with the goal of clarifying how training alters brain function and why its effects typically do not transfer across tasks. We suggest hypotheses for training-related changes in activation relevant to transfer effects: the strength model and several plausible alternatives (shifting priorities, stimulus-response automaticity, scaffolding). Sixty participants completed three weeks of IC training and underwent fMRI scanning before and after. The training produced pre- to post-training changes in neural activation during the ER task in the absence of behavioral changes. Specifically, individuals in the training group demonstrated reduced activation during ER in the left inferior frontal gyrus and supramarginal gyrus, key regions in the IC neural network. This result is less consistent with the strength model and more consistent with a motivational account. Implications for future work aiming to further pinpoint mechanisms of training transfer are discussed. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  18. Topology-function conservation in protein-protein interaction networks.

    PubMed

    Davis, Darren; Yaveroğlu, Ömer Nebil; Malod-Dognin, Noël; Stojmirovic, Aleksandar; Pržulj, Nataša

    2015-05-15

    Proteins underlay the functioning of a cell and the wiring of proteins in protein-protein interaction network (PIN) relates to their biological functions. Proteins with similar wiring in the PIN (topology around them) have been shown to have similar functions. This property has been successfully exploited for predicting protein functions. Topological similarity is also used to guide network alignment algorithms that find similarly wired proteins between PINs of different species; these similarities are used to transfer annotation across PINs, e.g. from model organisms to human. To refine these functional predictions and annotation transfers, we need to gain insight into the variability of the topology-function relationships. For example, a function may be significantly associated with specific topologies, while another function may be weakly associated with several different topologies. Also, the topology-function relationships may differ between different species. To improve our understanding of topology-function relationships and of their conservation among species, we develop a statistical framework that is built upon canonical correlation analysis. Using the graphlet degrees to represent the wiring around proteins in PINs and gene ontology (GO) annotations to describe their functions, our framework: (i) characterizes statistically significant topology-function relationships in a given species, and (ii) uncovers the functions that have conserved topology in PINs of different species, which we term topologically orthologous functions. We apply our framework to PINs of yeast and human, identifying seven biological process and two cellular component GO terms to be topologically orthologous for the two organisms. © The Author 2015. Published by Oxford University Press.

  19. Music training and inhibitory control: a multidimensional model.

    PubMed

    Moreno, Sylvain; Farzan, Faranak

    2015-03-01

    Training programs aimed to improve cognitive skills have either yielded mixed results or remain to be validated. The limited benefits of such regimens are largely attributable to weak understanding of (1) how (and which) interventions provide the most cognitive improvements; and (2) how brain networks and neural mechanisms that underlie specific cognitive abilities can be modified selectively. Studies indicate that music training leads to robust and long-lasting benefits to behavior. Importantly, behavioral advantages conferred by music extend beyond perceptual abilities to even nonauditory functions, such as inhibitory control (IC) and its neural correlates. Alternative forms of arts engagement or brain training do not appear to yield such enhancements, which suggests that music uniquely taps into brain networks subserving a variety of auditory as well as domain-general mechanisms such as IC. To account for such widespread benefits of music training, we propose a framework of transfer effects characterized by three dimensions: level of processing, nature of the transfer, and involvement of executive functions. We suggest that transfer of skills is mediated through modulation of general cognitive processes, in particular IC. We believe that this model offers a viable framework to test the extent and limitations of music-related changes. © 2014 New York Academy of Sciences.

  20. Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity.

    PubMed

    Nazimek, Katarzyna; Bryniarski, Krzysztof; Askenase, Philip W

    2016-01-01

    Extracellular vesicles, such as exosomes, are newly recognized intercellular conveyors of functional molecular mechanisms. Notably, they transfer RNAs and proteins between different cells that can then participate in the complex pathogenesis of allergic and related hypersensitivity responses and disease mechanisms, as described herein. This review highlights this important new appreciation of the in vivo participation of such extracellular vesicles in the interactions between allergy-mediating cells. We take into account paracrine epigenetic exchanges mediated by surrounding stromal cells and the endocrine receipt of exosomes from distant cells via the circulation. Exosomes are natural ancient nanoparticles of life. They are made by all cells and in some form by all species down to fungi and bacteria, and are present in all fluids. Besides a new focus on their role in the transmission of genetic regulation, exosome transfer of allergens was recently shown to induce allergic inflammation. Importantly, regulatory and tolerogenic exosomes can potently inhibit allergy and hypersensitivity responses, usually acting nonspecifically, but can also proceed in an antigen-specific manner due to the coating of the exosome surface with antibodies. Deep analysis of processes mediated by exosomes should result in the development of early diagnostic biomarkers, as well as allergen-specific, preventive and therapeutic strategies. These will likely significantly diminish the risks of current allergen-specific parenteral desensitization procedures, and of the use of systemic immunosuppressive drugs. Since extracellular vesicles are physiological, they can be fashioned for the specific delivery of therapeutic molecular instructions through easily tolerated, noninvasive routes, such as oral ingestion, nasal administration, and perhaps even inhalation. © 2016 S. Karger AG, Basel.

  1. Carbohydrate Recognition Specificity of Trans-sialidase Lectin Domain from Trypanosoma congolense

    PubMed Central

    Waespy, Mario; Gbem, Thaddeus T.; Elenschneider, Leroy; Jeck, André-Philippe; Day, Christopher J.; Hartley-Tassell, Lauren; Bovin, Nicolai; Tiralongo, Joe; Haselhorst, Thomas; Kelm, Sørge

    2015-01-01

    Fourteen different active Trypanosoma congolense trans-sialidases (TconTS), 11 variants of TconTS1 besides TconTS2, TconTS3 and TconTS4, have been described. Notably, the specific transfer and sialidase activities of these TconTS differ by orders of magnitude. Surprisingly, phylogenetic analysis of the catalytic domains (CD) grouped each of the highly active TconTS together with the less active enzymes. In contrast, when aligning lectin-like domains (LD), the highly active TconTS grouped together, leading to the hypothesis that the LD of TconTS modulates its enzymatic activity. So far, little is known about the function and ligand specificity of these LDs. To explore their carbohydrate-binding potential, glycan array analysis was performed on the LD of TconTS1, TconTS2, TconTS3 and TconTS4. In addition, Saturation Transfer Difference (STD) NMR experiments were done on TconTS2-LD for a more detailed analysis of its lectin activity. Several mannose-containing oligosaccharides, such as mannobiose, mannotriose and higher mannosylated glycans, as well as Gal, GalNAc and LacNAc containing oligosaccharides were confirmed as binding partners of TconTS1-LD and TconTS2-LD. Interestingly, terminal mannose residues are not acceptor substrates for TconTS activity. This indicates a different, yet unknown biological function for TconTS-LD, including specific interactions with oligomannose-containing glycans on glycoproteins and GPI anchors found on the surface of the parasite, including the TconTS itself. Experimental evidence for such a scenario is presented. PMID:26474304

  2. Adjustment of interaural time difference in head related transfer functions based on listeners' anthropometry and its effect on sound localization

    NASA Astrophysics Data System (ADS)

    Suzuki, Yôiti; Watanabe, Kanji; Iwaya, Yukio; Gyoba, Jiro; Takane, Shouichi

    2005-04-01

    Because the transfer functions governing subjective sound localization (HRTFs) show strong individuality, sound localization systems based on synthesis of HRTFs require suitable HRTFs for individual listeners. However, it is impractical to obtain HRTFs for all listeners based on measurements. Improving sound localization by adjusting non-individualized HRTFs to a specific listener based on that listener's anthropometry might be a practical method. This study first developed a new method to estimate interaural time differences (ITDs) using HRTFs. Then correlations between ITDs and anthropometric parameters were analyzed using the canonical correlation method. Results indicated that parameters relating to head size, and shoulder and ear positions are significant. Consequently, it was attempted to express ITDs based on listener's anthropometric data. In this process, the change of ITDs as a function of azimuth angle was parameterized as a sum of sine functions. Then the parameters were analyzed using multiple regression analysis, in which the anthropometric parameters were used as explanatory variables. The predicted or individualized ITDs were installed in the nonindividualized HRTFs to evaluate sound localization performance. Results showed that individualization of ITDs improved horizontal sound localization.

  3. The Role of Electronic and Phononic Excitation in the Optical Response of Monolayer WS 2 after Ultrafast Excitation

    DOE PAGES

    Ruppert, Claudia; Chernikov, Alexey; Hill, Heather M.; ...

    2017-01-06

    We study transient changes of the optical response of WS 2 monolayers by femtosecond broadband pump–probe spectroscopy. Time-dependent absorption spectra are analyzed by tracking the line width broadening, bleaching, and energy shift of the main exciton resonance as a function of time delay after the excitation. Two main sources for the pump-induced changes of the optical response are identified. Specifically, we find an interplay between modifications induced by many-body interactions from photoexcited carriers and by the subsequent transfer of the excitation to the phonon system followed by cooling of the material through the heat transfer to the substrate.

  4. The Role of Electronic and Phononic Excitation in the Optical Response of Monolayer WS 2 after Ultrafast Excitation

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

    Ruppert, Claudia; Chernikov, Alexey; Hill, Heather M.

    We study transient changes of the optical response of WS 2 monolayers by femtosecond broadband pump–probe spectroscopy. Time-dependent absorption spectra are analyzed by tracking the line width broadening, bleaching, and energy shift of the main exciton resonance as a function of time delay after the excitation. Two main sources for the pump-induced changes of the optical response are identified. Specifically, we find an interplay between modifications induced by many-body interactions from photoexcited carriers and by the subsequent transfer of the excitation to the phonon system followed by cooling of the material through the heat transfer to the substrate.

  5. A patient transfer apparatus between bed and stretcher.

    PubMed

    Wang, Hongbo; Kasagami, Fumio

    2008-02-01

    This paper presents a patient transfer apparatus between bed and stretcher. This apparatus makes it possible for the nurse to move weak, injured, or paralyzed patient from bed to stretcher, or vice versa, alone. Moreover, the suffering, stress, and uneasy feeling of the patient can be alleviated. This paper describes the specification, mechanical design, control system, and motion control of the apparatus. A special devised mechanism is developed, and a new servo system is used in this control system. The control principle and algorithm of the new servo system are proposed, and the motion-control method and safety function of the apparatus are described. The experimental results and evaluation indicated the effectiveness of this system.

  6. Characterization of the space shuttle reaction control system engine

    NASA Technical Reports Server (NTRS)

    Wilson, M. S.; Stechman, R. C.; Edelman, R. B.; Fortune, O. F.; Economos, C.

    1972-01-01

    A computer program was developed and written in FORTRAN 5 which predicts the transient and steady state performance and heat transfer characteristics of a pulsing GO2/GH2 rocket engine. This program predicts the dynamic flow and ignition characteristics which, when combined in a quasi-steady state manner with the combustion and mixing analysis program, will provide the thrust and specific impulse of the engine as a function of time. The program also predicts the transient and steady state heat transfer characteristics of the engine using various cooling concepts. The computer program, test case, and documentation are presented. The program is applicable to any system capable of utilizing the FORTRAN 4 or FORTRAN 5 language.

  7. Endogenous Phenazine Antibiotics Promote Anaerobic Survival of Pseudomonas aeruginosa via Extracellular Electron Transfer ▿

    PubMed Central

    Wang, Yun; Kern, Suzanne E.; Newman, Dianne K.

    2010-01-01

    Antibiotics are increasingly recognized as having other, important physiological functions for the cells that produce them. An example of this is the effect that phenazines have on signaling and community development for Pseudomonas aeruginosa (L. E. Dietrich, T. K. Teal, A. Price-Whelan, and D. K. Newman, Science 321:1203-1206, 2008). Here we show that phenazine-facilitated electron transfer to poised-potential electrodes promotes anaerobic survival but not growth of Pseudomonas aeruginosa PA14 under conditions of oxidant limitation. Other electron shuttles that are reduced but not made by PA14 do not facilitate survival, suggesting that the survival effect is specific to endogenous phenazines. PMID:19880596

  8. Improved functional status by comprehensive physical and psychosocial approach through right insula activation in poststroke vascular dementia.

    PubMed

    Tanaka, Naofumi; Meguro, Kenichi; Ishikawa, Hiroyasu; Yamaguchi, Satoshi

    2013-10-01

    The aim is to investigate the effect of a comprehensive physical and psychosocial approach on functional outcome and cerebral glucose metabolism in poststroke vascular dementia (PSVaD). Ten PSVaD patients participated in the study. They were diagnosed according to the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN) criteria and needed physical assistance in sit-to-stand transfer activities. Six were enrolled in a comprehensive program consisted of an individualized task-specific exercise regimen of transfer training and a psychosocial intervention program. The other 4 patients participated in the control group. The programs were undertaken over a period of 2 months. Outcomes were the scores on the Mini-Mental State Examination and the Functional Independence Measure (FIM), and on cerebral glucose metabolism determined by (18)F-fluorodeoxyglucose positron emission tomography performed before and at the end of the program. The score on the transfer mobility subscale of the FIM increased at the end of the program in all patients who received the comprehensive program. Regional glucose metabolism was increased in the right insular cortex at the end of the combined program. Control patients showed no change in FIM score or regional cerebral metabolism. A combined approach may be associated with an increase in glucose metabolism of the right insula cortex in PSVaD patients.

  9. Bilateral transfer phenomenon: A functional magnetic resonance imaging pilot study of healthy subjects.

    PubMed

    Uggetti, Carla; Ausenda, Carlo D; Squarza, Silvia; Cadioli, Marcello; Grimoldi, Ludovico; Cerri, Cesare; Cariati, Maurizio

    2016-08-01

    The bilateral transfer of a motor skill is a physiological phenomenon: the development of a motor skill with one hand can trigger the development of the same ability of the other hand. The purpose of this study was to verify whether bilateral transfer is associated with a specific brain activation pattern using functional magnetic resonance imaging (fMRI). The motor task was implemented as the execution of the Nine Hole Peg Test. Fifteen healthy subjects (10 right-handers and five left-handers) underwent two identical fMRI runs performing the motor task with the non-dominant hand. Between the first and the second run, each subject was intensively trained for five minutes to perform the same motor task with the dominant hand. Comparing the two functional scans across the pool of subjects, a change of the motor activation pattern was observed. In particular, we observed, in the second run, a change in the activation pattern both in the cerebellum and in the cerebral cortex. We found activations in cortical areas involved in somatosensory integration, areas involved in procedural memory. Our study shows, in a small group of healthy subjects, the modification of the fMRI activation pathway of a motor task performed by the non-dominant hand after intensive exercise performing the same task with the dominant hand. © The Author(s) 2016.

  10. Treatment of peroneal nerve injuries with simultaneous tendon transfer and nerve exploration.

    PubMed

    Ho, Bryant; Khan, Zubair; Switaj, Paul J; Ochenjele, George; Fuchs, Daniel; Dahl, William; Cederna, Paul; Kung, Theodore A; Kadakia, Anish R

    2014-08-06

    Common peroneal nerve palsy leading to foot drop is difficult to manage and has historically been treated with extended bracing with expectant waiting for return of nerve function. Peroneal nerve exploration has traditionally been avoided except in cases of known traumatic or iatrogenic injury, with tendon transfers being performed in a delayed fashion after exhausting conservative treatment. We present a new strategy for management of foot drop with nerve exploration and concomitant tendon transfer. We retrospectively reviewed a series of 12 patients with peroneal nerve palsies that were treated with tendon transfer from 2005 to 2011. Of these patients, seven were treated with simultaneous peroneal nerve exploration and repair at the time of tendon transfer. Patients with both nerve repair and tendon transfer had superior functional results with active dorsiflexion in all patients, compared to dorsiflexion in 40% of patients treated with tendon transfers alone. Additionally, 57% of patients treated with nerve repair and tendon transfer were able to achieve enough function to return to running, compared to 20% in patients with tendon transfer alone. No patient had full return of native motor function resulting in excessive dorsiflexion strength. The results of our limited case series for this rare condition indicate that simultaneous nerve repair and tendon transfer showed no detrimental results and may provide improved function over tendon transfer alone.

  11. Application of biomechanics to tendon transfers.

    PubMed

    Hoard, A S; Bell-Krotoski, J A; Mathews, R

    1995-01-01

    This article has focused on considerations important in the application of biomechanics to tendon transfers and has used an example protocol. Different surgeries require different protocols. What is most important is that specific protocols are used, and that they are both safe and effective. The communication among the therapist, surgeon, and patient is essential with the use of any protocol. As Brand has stated, "A hand is a very personal thing. It is the interface between the patient and his or her world. It is an emblem of strength, beauty, skill, sexuality, and sensibility. When it is damaged it becomes a symbol of the vulnerability of the whole person." For the patient who has damage from nerve palsy, paralysis, or injury resulting in a dysfunctional hand, a tendon transfer procedure may prove to be a viable option to restore balance and function, especially if the biomechanics of deformity and correction are considered.

  12. Training Attentional Control Improves Cognitive and Motor Task Performance.

    PubMed

    Ducrocq, Emmanuel; Wilson, Mark; Vine, Sam; Derakshan, Nazanin

    2016-10-01

    Attentional control is a necessary function for the regulation of goal-directed behavior. In three experiments we investigated whether training inhibitory control using a visual search task could improve task-specific measures of attentional control and performance. In Experiment 1 results revealed that training elicited a near-transfer effect, improving performance on a cognitive (antisaccade) task assessing inhibitory control. In Experiment 2 an initial far-transfer effect of training was observed on an index of attentional control validated for tennis. The principal aim of Experiment 3 was to expand on these findings by assessing objective gaze measures of inhibitory control during the performance of a tennis task. Training improved inhibitory control and performance when pressure was elevated, confirming the mechanisms by which cognitive anxiety impacts performance. These results suggest that attentional control training can improve inhibition and reduce taskspecific distractibility with promise of transfer to more efficient sporting performance in competitive contexts.

  13. Causal transfer function analysis to describe closed loop interactions between cardiovascular and cardiorespiratory variability signals.

    PubMed

    Faes, L; Porta, A; Cucino, R; Cerutti, S; Antolini, R; Nollo, G

    2004-06-01

    Although the concept of transfer function is intrinsically related to an input-output relationship, the traditional and widely used estimation method merges both feedback and feedforward interactions between the two analyzed signals. This limitation may endanger the reliability of transfer function analysis in biological systems characterized by closed loop interactions. In this study, a method for estimating the transfer function between closed loop interacting signals was proposed and validated in the field of cardiovascular and cardiorespiratory variability. The two analyzed signals x and y were described by a bivariate autoregressive model, and the causal transfer function from x to y was estimated after imposing causality by setting to zero the model coefficients representative of the reverse effects from y to x. The method was tested in simulations reproducing linear open and closed loop interactions, showing a better adherence of the causal transfer function to the theoretical curves with respect to the traditional approach in presence of non-negligible reverse effects. It was then applied in ten healthy young subjects to characterize the transfer functions from respiration to heart period (RR interval) and to systolic arterial pressure (SAP), and from SAP to RR interval. In the first two cases, the causal and non-causal transfer function estimates were comparable, indicating that respiration, acting as exogenous signal, sets an open loop relationship upon SAP and RR interval. On the contrary, causal and traditional transfer functions from SAP to RR were significantly different, suggesting the presence of a considerable influence on the opposite causal direction. Thus, the proposed causal approach seems to be appropriate for the estimation of parameters, like the gain and the phase lag from SAP to RR interval, which have a large clinical and physiological relevance.

  14. Nerve Transfers for Improved Hand Function Following Cervical Spinal Cord Injury

    DTIC Science & Technology

    the cervical spine resulting in diminished or complete loss of arm and/or hand function. Cervical SCI patients consistently rank hand function as the...most desired function above bowel and bladder function, sexual function, standing, and pain control. The overall goal of the proposed study is to...evaluate the efficacy of nerve transfers to treat patients with cervical SCIs. Over the last decade, nerve transfers have been used with increasing

  15. Anti-influenza Hyperimmune Immunoglobulin Enhances Fc-functional Antibody Immunity during Human Influenza Infection.

    PubMed

    Vanderven, Hillary A; Wragg, Kathleen; Ana-Sosa-Batiz, Fernanda; Kristensen, Anne B; Jegaskanda, Sinthujan; Wheatley, Adam K; Wentworth, Deborah; Wines, Bruce D; Hogarth, P Mark; Rockman, Steve; Kent, Stephen J

    2018-05-31

    New treatments for severe influenza are needed. Passive transfer of influenza-specific hyperimmune pooled immunoglobulin (Flu-IVIG) boosts neutralising antibody responses to past strains in influenza-infected subjects. The effect of Flu-IVIG on antibodies with Fc-mediated functions, which may target diverse influenza strains, is unclear. We studied the capacity of Flu-IVIG, relative to standard IVIG, to bind to Fc receptors and mediate antibody-dependent cellular cytotoxicity in vitro. The effect of Flu-IVIG infusion, compared to placebo infusion, was examined in serial plasma samples from 24 subjects with confirmed influenza infection in the INSIGHT FLU005 pilot study. Flu-IVIG contains higher concentrations of Fc-functional antibodies than IVIG against a diverse range of influenza hemagglutinins. Following infusion of Flu-IVIG into influenza-infected subjects, a transient increase in Fc-functional antibodies was present for 1-3 days against infecting and non-infecting strains of influenza. Flu-IVIG contains antibodies with Fc-mediated functions against influenza virus and passive transfer of Flu-IVIG increases anti-influenza Fc-functional antibodies in the plasma of influenza-infected subjects. Enhancement of Fc-functional antibodies to a diverse range of influenza strains suggests that Flu-IVIG infusion could prove useful in the context of novel influenza virus infections, when there may be minimal or no neutralising antibodies in the Flu-IVIG preparation.

  16. Influence of acoustic impedance of multilayer acoustic systems on the transfer function of ultrasonic airborne transducers.

    PubMed

    Gudra, Tadeusz; Opieliński, Krzysztof J

    2002-05-01

    In different solutions of ultrasonic transducers radiating acoustic energy into the air there occurs the problem of the proper selection of the acoustic impedance of one or more matching layers. The goal of this work was a computer analysis of the influence of acoustic impedance on the transfer function of piezoceramic transducers equipped with matching layers. Cases of resonance and non-resonance matching impedance in relation to the transfer function and the energy transmission coefficient for solid state-air systems were analysed. With stable thickness of matching layers the required shape of the transfer function can be obtained through proper choice of acoustic impedance were built (e.g. maximal flat function). The proper choice of acoustic impedance requires an elaboration of precise methods of synthesis of matching systems. Using the known matching criteria (Chebyshev's, DeSilets', Souquet's), the transfer function characteristics of transducers equipped with one, two, and three matching layers as well as the optimisation methods of the energy transmission coefficient were presented. The influence of the backside load of the transducer on the shape of transfer function was also analysed. The calculation results of this function for different loads of the transducer backside without and with the different matching layers were presented. The proper load selection allows us to obtain the desired shape of the transfer function, which determines the pulse shape generated by the transducer.

  17. Significance of a Recurring Function in Energy Transfer

    NASA Astrophysics Data System (ADS)

    Mishra, Subodha

    2017-05-01

    The appearance of a unique function in the energy transfer from one system to the other in different physical situations such as electrical, mechanical, optical, and quantum mechanical processes is established in this work. Though the laws governing the energy transformation and its transfer from system to system are well known, here we notice a unity in diversity; a unique function appears in various cases of energy transfer whether it is a classical or a quantum mechanical process. We consider four examples, well known in elementary physics, from the fields of electricity, mechanics, optics, and quantum mechanics. We find that this unique function is in fact the transfer function corresponding to all these physical situations, and the interesting and intriguing finding is that the inverse Laplace transform of this transfer function, which is the impulse-response function of the systems when multiplied by a factor of -½, is the solution of a linear differential equation for an "instantly forced critically damped harmonic oscillator." It is important to note that though the physical phenomena considered are quite distinct, the underlying process in the language of impulse-response of the system in the time domain is a unique one. To the best of our knowledge we have not seen anywhere the above analysis of determining the unique function or its description as a transfer function in literature.

  18. Using nerve transfer to restore prehension and grasp 12 years following spinal cord injury: a case report.

    PubMed

    Fox, Ida K; Novak, Christine B; Kahn, Lorna C; Mackinnon, Susan E; Ruvinskaya, Rimma; Juknis, Neringa

    2018-01-01

    Nerve transfers are used routinely for reconstruction of hand function following lower motor neuron lesions. In people with cervical spinal cord injury (SCI), this novel and alternate reconstruction option may be useful to restore prehension and grasp, and improve hand function. A 34-year-old male presented 12 years post-mid-cervical SCI. Pre-operative electrodiagnostic studies revealed intact lower motor neurons below the SCI level. He elected to undergo nerve transfer surgery to restore hand function. Intraoperative evaluation led to the transfer of a brachialis nerve to several median nerve recipient branches. Post surgery, he was discharged home and resumed activities of daily living. He achieved independent thumb and finger flexion function and continued to exhibit functional improvement at 4 years post surgery. These results should prompt referral for consideration of nerve transfer surgery-an exciting alternative to tendon transfer and neuroprostheses.

  19. Serum oestradiol and beta-HCG measurements after day 3 or 5 embryo transfers in interpreting pregnancy outcome.

    PubMed

    Kumbak, Banu; Oral, Engin; Karlikaya, Guvenc; Lacin, Selman; Kahraman, Semra

    2006-10-01

    The aim of this study was to assess the clinical value of serum oestradiol concentration 8 days after embryo transfer (D8E2) and beta-human chorionic gonadotrophin (HCG-beta) concentration 12 days after embryo transfer (D12HCG-beta) in the prediction of pregnancy and the outcome of pregnancy following assisted reproduction, taking into account the day of transfer, which was either day 3 (D3) or day 5 (D5). The objective was to improve patient counselling by giving quantitative and reliable predictive information instead of non-specific uncertainties. A total of 2035 embryo transfer cycles performed between January 2003 and June 2005 were analysed retrospectively. Biochemical pregnancy, ectopic pregnancy and first-trimester abortions were classified as non-viable pregnancies; pregnancies beyond 12 weeks gestation were classified as ongoing pregnancies (OP). Significantly higher D8E2 and D12HCG-beta were obtained in D5 transfers compared with D3 transfers with regard to pregnancy and OP (P

  20. Predicting multicellular function through multi-layer tissue networks

    PubMed Central

    Zitnik, Marinka; Leskovec, Jure

    2017-01-01

    Abstract Motivation: Understanding functions of proteins in specific human tissues is essential for insights into disease diagnostics and therapeutics, yet prediction of tissue-specific cellular function remains a critical challenge for biomedicine. Results: Here, we present OhmNet, a hierarchy-aware unsupervised node feature learning approach for multi-layer networks. We build a multi-layer network, where each layer represents molecular interactions in a different human tissue. OhmNet then automatically learns a mapping of proteins, represented as nodes, to a neural embedding-based low-dimensional space of features. OhmNet encourages sharing of similar features among proteins with similar network neighborhoods and among proteins activated in similar tissues. The algorithm generalizes prior work, which generally ignores relationships between tissues, by modeling tissue organization with a rich multiscale tissue hierarchy. We use OhmNet to study multicellular function in a multi-layer protein interaction network of 107 human tissues. In 48 tissues with known tissue-specific cellular functions, OhmNet provides more accurate predictions of cellular function than alternative approaches, and also generates more accurate hypotheses about tissue-specific protein actions. We show that taking into account the tissue hierarchy leads to improved predictive power. Remarkably, we also demonstrate that it is possible to leverage the tissue hierarchy in order to effectively transfer cellular functions to a functionally uncharacterized tissue. Overall, OhmNet moves from flat networks to multiscale models able to predict a range of phenotypes spanning cellular subsystems. Availability and implementation: Source code and datasets are available at http://snap.stanford.edu/ohmnet. Contact: jure@cs.stanford.edu PMID:28881986

  1. Visual information transfer. Part 1: Assessment of specific information needs. Part 2: Parameters of appropriate instrument scanning behavior

    NASA Technical Reports Server (NTRS)

    Comstock, J. R., Jr.; Kirby, R. H.; Coates, G. D.

    1985-01-01

    The present study explored eye scan behavior as a function of level of subject training. Oculometric (eye scan) measures were recorded from each of ten subjects during training trials on a CRT based flight simulation task. The task developed for the study incorporated subtasks representative of specific activities performed by pilots, but which could be performed at asymptotic levels within relatively short periods of training. Changes in eye scan behavior were examined as initially untrained subjects developed skill in the task. Eye scan predictors of performance on the task were found. Examination of eye scan in proximity to selected task events revealed differences in the distribution of looks at the instruments as a function of level of training.

  2. Technology transfer

    NASA Technical Reports Server (NTRS)

    Handley, Thomas

    1992-01-01

    The requirements for a successful technology transfer program and what such a program would look like are discussed. In particular, the issues associated with technology transfer in general, and within the Jet Propulsion Laboratory (JPL) environment specifically are addressed. The section on background sets the stage, identifies the barriers to successful technology transfer, and suggests actions to address the barriers either generally or specifically. The section on technology transfer presents a process with its supporting management plan that is required to ensure a smooth transfer process. Viewgraphs are also included.

  3. Nanostructured disposable impedimetric sensors as tools for specific biomolecular interactions: sensitive recognition of concanavalin A.

    PubMed

    Loaiza, Oscar A; Lamas-Ardisana, Pedro J; Jubete, Elena; Ochoteco, Estibalitz; Loinaz, Iraida; Cabañero, Germán; García, Isabel; Penadés, Soledad

    2011-04-15

    The development of sensors to detect specific weak biological interactions is still today a challenging topic. Characteristics of carbohydrate-protein (lectin) interactions include high specificity and low affinity. This work describes the development of nanostructured impedimetric sensors for the detection of concanavalin A (Con A) binding to immobilized thiolated carbohydrate derivatives (D-mannose or D-glucose) onto screen-printed carbon electrodes (SPCEs) modified with gold nanoparticles. Thiolated D-galactose derivative was employed as negative control to evaluate the selectivity of the proposed methodology. After binding the thiolated carbohydrate to the nanostructured SPCEs, different functionalized thiols were employed to form mixed self-assembled monolayers (SAM). Electrochemical impedance spectroscopy (EIS) was employed as a technique to evaluate the binding of Con A to selected carbohydrates through the increase of electron transfer resistance of the ferri/ferrocyanide redox probe at the differently SAM modified electrodes. Different variables of the assay protocol were studied in order to optimize the sensor performance. Selective Con A determinations were only achieved by the formation of mixed SAMs with adequate functionalized thiols. Important differences were obtained depending on the chain lengths and functional groups of these thiols. For the 3-mercapto-1-propanesulfonate mixed SAMs, the electron transfer resistance varied linearly with the Con A concentration in the 2.2-40.0 μg mL(-1) range for D-mannose and D-glucose modified sensors. Low detection limits (0.099 and 0.078 pmol) and good reproducibility (6.9 and 6.1%, n=10) were obtained for the D-glucose and D-mannose modified sensors, respectively, without any amplification strategy. © 2011 American Chemical Society

  4. Experimental Waterflow Determination of the Dynamic Hydraulic Transfer Function for the J-2X Oxidizer Turbopump. Part Two; Results and Interpretation

    NASA Technical Reports Server (NTRS)

    Zoladz, Tom; Patel, Sandeep; Lee, Erik; Karon, Dave

    2011-01-01

    Experimental results describing the hydraulic dynamic pump transfer matrix (Yp) for a cavitating J-2X oxidizer turbopump inducer+impeller tested in subscale waterflow are presented. The transfer function is required for integrated vehicle pogo stability analysis as well as optimization of local inducer pumping stability. Dynamic transfer functions across widely varying pump hydrodynamic inlet conditions are extracted from measured data in conjunction with 1D-model based corrections. Derived Dynamic transfer functions are initially interpreted relative to traditional Pogo pump equations. Water-to-liquid oxygen scaling of measured cavitation characteristics are discussed. Comparison of key dynamic transfer matrix terms derived from waterflow testing are made with those implemented in preliminary Ares Upper Stage Pogo stability modeling. Alternate cavitating pump hydraulic dynamic equations are suggested which better reflect frequency dependencies of measured transfer matrices.

  5. Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer-specific bioluminescence resonance energy transfer-based sensors

    PubMed Central

    Giner, Xavier C; Cotnoir-White, David; Mader, Sylvie; Lévesque, Daniel

    2017-01-01

    Retinoid X receptors (RXR) play a role as master regulators due to their capacity to form heterodimers with other nuclear receptors. Accordingly, retinoid signaling is involved in multiple biological processes, including development, cell differentiation, metabolism and cell death. However, the role and functions of RXR in different heterodimer complexes remain unsolved, mainly because most RXR drugs (called rexinoids) are not selective to specific heterodimer complexes. This also strongly limits the use of rexinoids for specific therapeutic approaches. In order to better characterize rexinoids at specific nuclear receptor complexes, we have developed and optimized luciferase protein complementation-based Bioluminescence Resonance Energy Transfer (BRET) assays, which can directly measure recruitment of a co-activator motif fused to yellow fluorescent protein (YFP) by specific nuclear receptor dimers. To validate the assays, we compared rexinoid modulation of co-activator recruitment by RXR homodimer, and heterodimers Nur77/RXR and Nurr1/RXR. Results reveal that some rexinoids display selective co-activator recruitment activities with homo- or hetero-dimer complexes. In particular, SR11237 (BMS649) has increased potency for recruitment of co-activator motif and transcriptional activity with the Nur77/RXR heterodimer compared to other complexes. This technology should prove useful to identify new compounds with specificity for individual dimeric species formed by nuclear receptors. PMID:26148973

  6. Development of a Dynamic Visco-elastic Vehicle-Soil Interaction Model for Rut Depth, and Power Determinations

    DTIC Science & Technology

    2011-09-06

    Presentation Outline A) Review of Soil Model governing equations B) Development of pedo -transfer functions (terrain database to engineering properties) C...lateral earth pressure) UNCLASSIFIED B) Development of pedo -transfer functions Engineering parameters needed by soil model - compression index - rebound...inches, RCI for fine- grained soils, CI for coarse-grained soils. UNCLASSIFIED Pedo -transfer function • Need to transfer existing terrain database

  7. Adaptive Same Frequency Repeater (SFR) Study

    DTIC Science & Technology

    1976-03-01

    Formulation 13 (2) Evaluation of the Steady State Weights!.’.’.’!.*!!."!! 21 (3) Evaluation of the Composite Transfer Function.... 2^ (4) Simplified...well as possible the amplitude and phase of the composite coupling path. Because the coupling paths have frequency-dependent transfer functions...34), (35) and the notch filter and channel transfer .’unctions (3fi) and (39). The composite transfer function Hc(f ’ ^’.f) is then found and

  8. Systems of meaning and transference: Implicit significant-other activation evokes shared reality.

    PubMed

    Przybylinski, Elizabeth; Andersen, Susan M

    2015-10-01

    Evidence shows that representations of significant others (SOs) are used in interpersonal relations-for example, in the social-cognitive process of transference (see Andersen & Chen, 2002), a process that is assumed to serve meaning-making functions (Glassman & Andersen, 1999b). Five studies tested the more specific notion that implicit activation of an SO representation in transference should indirectly activate the worldview shared with the SO, leading to its active pursuit, validation, and protection. Shared worldviews were assessed beforehand, both idiographically, as values (Studies 1 and 4), and nomothetically, as political ideology or religious beliefs (Studies 2, 3, and 5). In each experiment, participants learned about new persons, one subtly resembling their own SO. Transference was assessed (memory bias; positive evaluation; see Andersen, Reznik, & Manzella, 1996) and, crucially, as predicted, when considering the new person resembling their SO (vs. the control persons), participants showed faster response latencies in a lexical decision task to words reflecting the worldview shared with the SO (vs. held only personally, Studies 1-3, or only by the SO, Study 3). With this person, they also anticipated a more meaningful interaction and actively socially tuned to the SO-shared worldview, selecting conversation topics reflecting the SO-shared worldview (vs. personally held or SO-held topics, Studies 1-3). Finally, threatening the SO-shared worldview with this person (vs. threatening personally held, SO-held, or irrelevant worldviews) prompted goal activation to restore the disrupted meaning (Studies 4 and 5), assessed by response latency in a lexical decision task. Transference thus evokes shared meaning systems and serves epistemic functions. (c) 2015 APA, all rights reserved).

  9. Automatic spin-chain learning to explore the quantum speed limit

    NASA Astrophysics Data System (ADS)

    Zhang, Xiao-Ming; Cui, Zi-Wei; Wang, Xin; Yung, Man-Hong

    2018-05-01

    One of the ambitious goals of artificial intelligence is to build a machine that outperforms human intelligence, even if limited knowledge and data are provided. Reinforcement learning (RL) provides one such possibility to reach this goal. In this work, we consider a specific task from quantum physics, i.e., quantum state transfer in a one-dimensional spin chain. The mission for the machine is to find transfer schemes with the fastest speeds while maintaining high transfer fidelities. The first scenario we consider is when the Hamiltonian is time independent. We update the coupling strength by minimizing a loss function dependent on both the fidelity and the speed. Compared with a scheme proven to be at the quantum speed limit for the perfect state transfer, the scheme provided by RL is faster while maintaining the infidelity below 5 ×10-4 . In the second scenario where a time-dependent external field is introduced, we convert the state transfer process into a Markov decision process that can be understood by the machine. We solve it with the deep Q-learning algorithm. After training, the machine successfully finds transfer schemes with high fidelities and speeds, which are faster than previously known ones. These results show that reinforcement learning can be a powerful tool for quantum control problems.

  10. Applications of free-electron lasers to measurements of energy transfer in biopolymers and materials

    NASA Astrophysics Data System (ADS)

    Edwards, Glenn S.; Johnson, J. B.; Kozub, John A.; Tribble, Jerri A.; Wagner, Katrina

    1992-08-01

    Free-electron lasers (FELs) provide tunable, pulsed radiation in the infrared. Using the FEL as a pump beam, we are investigating the mechanisms for energy transfer between localized vibrational modes and between vibrational modes and lattice or phonon modes. Either a laser-Raman system or a Fourier transform infrared (FTIR) spectrometer will serve as the probe beam, with the attribute of placing the burden of detection on two conventional spectroscopic techniques that circumvent the limited response of infrared detectors. More specifically, the Raman effect inelastically shifts an exciting laser line, typically a visible frequency, by the energy of the vibrational mode; however, the shifted Raman lines also lie in the visible, allowing for detection with highly efficient visible detectors. With regards to FTIR spectroscopy, the multiplex advantage yields a distinct benefit for infrared detector response. Our group is investigating intramolecular and intermolecular energy transfer processes in both biopolymers and more traditional materials. For example, alkali halides contain a number of defect types that effectively transfer energy in an intermolecular process. Similarly, the functioning of biopolymers depends on efficient intramolecular energy transfer. Understanding these mechanisms will enhance our ability to modify biopolymers and materials with applications to biology, medecine, and materials science.

  11. Bidirectional Transfer between Metaphorical Related Domains in Implicit Learning of Form-Meaning Connections

    PubMed Central

    Yang, Zhiliang; Dienes, Zoltan

    2013-01-01

    People can implicitly learn a connection between linguistic forms and meanings, for example between specific determiners (e.g. this, that…) and the type of nouns to which they apply. Li et al (2013) recently found that transfer of form-meaning connections from a concrete domain (height) to an abstract domain (power) was achieved in a metaphor-consistent way without awareness, showing that unconscious knowledge can be abstract and flexibly deployed. The current study aims to determine whether people transfer knowledge of form-meaning connections not only from a concrete domain to an abstract one, but also vice versa, consistent with metaphor representation being bi-directional. With a similar paradigm as used by Li et al, participants learnt form- meaning connections of different domains (concrete vs. abstract) and then were tested on two kinds of generalizations (same and different domain generalization). As predicted, transfer of form-meaning connections occurred bidirectionally when structural knowledge was unconscious. Moreover, the present study also revealed that more transfer occurred between metaphorically related domains when judgment knowledge was conscious (intuition) rather than unconscious (guess). Conscious and unconscious judgment knowledge may have different functional properties. PMID:23844159

  12. Monitoring glycolipid transfer protein activity and membrane interaction with the surface plasmon resonance technique.

    PubMed

    Ohvo-Rekilä, Henna; Mattjus, Peter

    2011-01-01

    The glycolipid transfer protein (GLTP) is a protein capable of binding and transferring glycolipids. GLTP is cytosolic and it can interact through its FFAT-like (two phenylalanines in an acidic tract) motif with proteins localized on the surface of the endoplasmic reticulum. Previous in vitro work with GLTP has focused mainly on the complete transfer reaction of the protein, that is, binding and subsequent removal of the glycolipid from the donor membrane, transfer through the aqueous environment, and the final release of the glycolipid to an acceptor membrane. Using bilayer vesicles and surface plasmon resonance spectroscopy, we have now, for the first time, analyzed the binding and lipid removal capacity of GLTP with a completely label-free technique. This technique is focused on the initial steps in GLTP-mediated transfer and the parameters affecting these steps can be more precisely determined. We used the new approach for detailed structure-function studies of GLTP by examining the glycolipid transfer capacity of specific GLTP tryptophan mutants. Tryptophan 96 is crucial for the transfer activity of the protein and tryptophan 142 is an important part of the proteins membrane interacting domain. Further, we varied the composition of the used lipid vesicles and gained information on the effect of membrane properties on GLTP activity. GLTP prefers to interact with more tightly packed membranes, although GLTP-mediated transfer is faster from more fluid membranes. This technique is very useful for the study of membrane-protein interactions and lipid-transfer rates and it can easily be adapted to other membrane-interacting proteins. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Impact of kinetic mass transfer on free convection in a porous medium

    NASA Astrophysics Data System (ADS)

    Lu, Chunhui; Shi, Liangsheng; Chen, Yiming; Xie, Yueqing; Simmons, Craig T.

    2016-05-01

    We investigate kinetic mass transfer effects on unstable density-driven flow and transport processes by numerical simulations of a modified Elder problem. The first-order dual-domain mass transfer model coupled with a variable-density-flow model is employed to describe transport behavior in porous media. Results show that in comparison to the no-mass-transfer case, a higher degree of instability and more unstable system is developed in the mass transfer case due to the reduced effective porosity and correspondingly a larger Rayleigh number (assuming permeability is independent on the mobile porosity). Given a constant total porosity, the magnitude of capacity ratio (i.e., immobile porosity/mobile porosity) controls the macroscopic plume profile in the mobile domain, while the magnitude of mass transfer timescale (i.e., the reciprocal of the mass transfer rate coefficient) dominates its evolution rate. The magnitude of capacity ratio plays an important role on the mechanism driving the mass flux into the aquifer system. Specifically, for a small capacity ratio, solute loading is dominated by the density-driven transport, while with increasing capacity ratio local mass transfer dominated solute loading may occur at later times. At significantly large times, however, both mechanisms contribute comparably to solute loading. Sherwood Number could be a nonmonotonic function of mass transfer timescale due to complicated interactions of solute between source zone, mobile zone and immobile zone in the top boundary layer, resulting in accordingly a similar behavior of the total mass. The initial assessment provides important insights into unstable density-driven flow and transport in the presence of kinetic mass transfer.

  14. Image Processing, Coding, and Compression with Multiple-Point Impulse Response Functions.

    NASA Astrophysics Data System (ADS)

    Stossel, Bryan Joseph

    1995-01-01

    Aspects of image processing, coding, and compression with multiple-point impulse response functions are investigated. Topics considered include characterization of the corresponding random-walk transfer function, image recovery for images degraded by the multiple-point impulse response, and the application of the blur function to image coding and compression. It is found that although the zeros of the real and imaginary parts of the random-walk transfer function occur in continuous, closed contours, the zeros of the transfer function occur at isolated spatial frequencies. Theoretical calculations of the average number of zeros per area are in excellent agreement with experimental results obtained from computer counts of the zeros. The average number of zeros per area is proportional to the standard deviations of the real part of the transfer function as well as the first partial derivatives. Statistical parameters of the transfer function are calculated including the mean, variance, and correlation functions for the real and imaginary parts of the transfer function and their corresponding first partial derivatives. These calculations verify the assumptions required in the derivation of the expression for the average number of zeros. Interesting results are found for the correlations of the real and imaginary parts of the transfer function and their first partial derivatives. The isolated nature of the zeros in the transfer function and its characteristics at high spatial frequencies result in largely reduced reconstruction artifacts and excellent reconstructions are obtained for distributions of impulses consisting of 25 to 150 impulses. The multiple-point impulse response obscures original scenes beyond recognition. This property is important for secure transmission of data on many communication systems. The multiple-point impulse response enables the decoding and restoration of the original scene with very little distortion. Images prefiltered by the random-walk transfer function yield greater compression ratios than are obtained for the original scene. The multiple-point impulse response decreases the bit rate approximately 40-70% and affords near distortion-free reconstructions. Due to the lossy nature of transform-based compression algorithms, noise reduction measures must be incorporated to yield acceptable reconstructions after decompression.

  15. Hydrogen bonding in malonaldehyde: a density functional and reparametrized semiempirical approach

    NASA Astrophysics Data System (ADS)

    Kovačević, Goran; Hrenar, Tomica; Došlić, Nadja

    2003-08-01

    Intramolecular proton transfer in malonaldehyde (MA) has been investigated by density functional theory (DFT). The DFT results were used for the construction of a high quality semiempirical potential energy surface with a reparametrized PM3 Hamiltonian. A two-step reparameterization procedure is proposed in which (i) the PM3-MAIS core-core functions for the O-H and H-H interactions were used and a new functional form for the O-O correction function was proposed and (ii) a set of specific reaction parameters (SRP) has been obtained via genetic algorithm optimization. The quality of the reparametrized semiempirical potential energy surfaces was tested by calculating the tunneling splitting of vibrational levels and the anharmonic vibrational frequencies of the system. The applicability to multi-dimensional dynamics in large molecular systems is discussed.

  16. Description, Analysis and Simulation of a New Realization of Digital Filters.

    DTIC Science & Technology

    1987-09-01

    together with its staircase representation h,.(t) . ..... .. ... ... .. 79 6.3 The-RDC LPF transfer function when Td includes 2 zeroes of hc(t) 81 6.4 The...RDC LPF transfer function when Td includes 6 zeroes of hc(t) 82 6.5 The RDC LPF transfer function when Td includes 8 zeroes of h,(t) 83 6.6 The RDC LPF...transfer function when Td includes 6 zeroes of h,(t) and when rectangular and Hamming windows are used ........ ... 84 6.7 The input z(t) and its

  17. a Middle-Ear Reverse Transfer Function Computed from Vibration Measurements of Otoacoustic Emissions on the Ear Drum of the Guinea PIG

    NASA Astrophysics Data System (ADS)

    Dalhoff, Ernst; Turcanu, Diana; Gummer, Anthony W.

    2009-02-01

    Using distortion products measured as vibration of the umbo and as sound pressure in the ear canal of guinea pigs, we calculated the corresponding reverse transfer function. We compare the measurements with a middle-ear model taken from the literature and adapted to the guinea pig. A reasonable fit could be achieved. We conclude that the reverse transfer function will be useful to aid fitting a middle-ear model to measured transfer functions of human subjects.

  18. Transfer Function Bounds for Partial-unit-memory Convolutional Codes Based on Reduced State Diagram

    NASA Technical Reports Server (NTRS)

    Lee, P. J.

    1984-01-01

    The performance of a coding system consisting of a convolutional encoder and a Viterbi decoder is analytically found by the well-known transfer function bounding technique. For the partial-unit-memory byte-oriented convolutional encoder with m sub 0 binary memory cells and (k sub 0 m sub 0) inputs, a state diagram of 2(K) (sub 0) was for the transfer function bound. A reduced state diagram of (2 (m sub 0) +1) is used for easy evaluation of transfer function bounds for partial-unit-memory codes.

  19. Determining A Purely Symbolic Transfer Function from Symbol Streams: Theory and Algorithms

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

    Griffin, Christopher H

    Transfer function modeling is a \\emph{standard technique} in classical Linear Time Invariant and Statistical Process Control. The work of Box and Jenkins was seminal in developing methods for identifying parameters associated with classicalmore » $(r,s,k)$$ transfer functions. Discrete event systems are often \\emph{used} for modeling hybrid control structures and high-level decision problems. \\emph{Examples include} discrete time, discrete strategy repeated games. For these games, a \\emph{discrete transfer function in the form of} an accurate hidden Markov model of input-output relations \\emph{could be used to derive optimal response strategies.} In this paper, we develop an algorithm \\emph{for} creating probabilistic \\textit{Mealy machines} that act as transfer function models for discrete event dynamic systems (DEDS). Our models are defined by three parameters, $$(l_1, l_2, k)$ just as the Box-Jenkins transfer function models. Here $$l_1$$ is the maximal input history lengths to consider, $$l_2$$ is the maximal output history lengths to consider and $k$ is the response lag. Using related results, We show that our Mealy machine transfer functions are optimal in the sense that they maximize the mutual information between the current known state of the DEDS and the next observed input/output pair.« less

  20. Gene transfer with a vector expressing Maxi-K from a smooth muscle-specific promoter restores erectile function in the aging rat.

    PubMed

    Melman, A; Biggs, G; Davies, K; Zhao, W; Tar, M T; Christ, G J

    2008-03-01

    Previous reports have demonstrated that gene transfer with the alpha, or pore-forming, subunit of the human Maxi-K channel (hSlo) restores the decline in erectile capacity observed in established rat models of diabetes and aging. Preliminary data from a human clinical trial also showed safety and potential efficacy in 11 men treated with the same plasmid construct expressing the Maxi-K channel. In all instances, the original plasmid was driven by the heterologous cytomegalovirus promoter which is broadly active in a wide variety of cell and tissue types. To more precisely determine the contribution of the corporal myocyte to the observed physiological effects in vivo, we report here our initial work using a distinct vector (pSMAA-hSlo) in which hSlo gene expression was driven off the mouse smooth muscle alpha-actin (SMAA) promoter. Specifically, older rats, with diminished erectile capacity, were given a single intracorporal injection with either 100 mug pVAX-hSlo or 10, 100 or 1000 mug pSMAA-hSlo, or vector or vehicle alone. Significantly increased intracavernous pressure (ICP) responses to cavernous nerve stimulation were observed for all doses of both plasmids encoding hSlo, relative to control injections. These data confirm and extend previous observations to document that smooth muscle cell-specific expression of hSlo in corporal tissue is both necessary and sufficient to restore erectile function in aging rats.

  1. Identification of Candidate Transcriptional Regulators of Epidermal Transfer Cell Development in Vicia faba Cotyledons

    PubMed Central

    Arun-Chinnappa, Kiruba S.; McCurdy, David W.

    2016-01-01

    Transfer cells (TCs) are anatomically-specialized cells formed at apoplasmic-symplasmic bottlenecks in nutrient transport pathways in plants. TCs form invaginated wall ingrowths which provide a scaffold to amplify plasma membrane surface area and thus increase the density of nutrient transporters required to achieve enhanced nutrient flow across these bottlenecks. Despite their importance to nutrient transport in plants, little is known of the transcriptional regulation of wall ingrowth formation. Here, we used RNA-Seq to identify transcription factors putatively involved in regulating epidermal TC development in cotyledons of Vicia faba. Comparing cotyledons cultured for 0, 3, 9, and 24 h to induce trans-differentiation of epidermal TCs identified 43 transcription factors that showed either epidermal-specific or epidermal–enhanced expression, and 10 that showed epidermal-specific down regulation. Members of the WRKY and ethylene-responsive families were prominent in the cohort of transcription factors showing epidermal-specific or epidermal–enhanced expression, consistent with the initiation of TC development often representing a response to stress. Members of the MYB family were also prominent in these categories, including orthologs of MYB genes involved in localized secondary wall deposition in Arabidopsis thaliana. Among the group of transcription factors showing down regulation were various homeobox genes and members of the MADs-box and zinc-finger families of poorly defined functions. Collectively, this study identified several transcription factors showing expression characteristics and orthologous functions that indicate likely participation in transcriptional regulation of epidermal TC development in V. faba cotyledons. PMID:27252730

  2. A Case Study to Evaluate Balance Training with Movement Test Items and through Teaching Observation: Beyond Specificity and Transfer of Learning

    ERIC Educational Resources Information Center

    Kluwe, Margret; Miyahara, Motohide; Heveldt, Kate

    2012-01-01

    Background: Specificity and transfer of learning have been examined in experimental studies. However, their findings may not be relevant to practitioners because of the difference between the experiment conditions and teaching situations. This case study investigates the theoretical issue of specificity vs. transfer of learning by conducting…

  3. Digital control algorithms for microgravity isolation systems

    NASA Technical Reports Server (NTRS)

    Sinha, Alok; Wang, Yung-Peng

    1992-01-01

    New digital control algorithms were developed to achieve the desired acceleration transmissibility function. The attractive electromagnets have been taken as actuators. The relative displacement and the acceleration of the mass were used as feedback signals. Two approaches were developed to find that controller transfer function in Z-domain, which yields the desired transmissibility at each frequency. In the first approach, the controller transfer function is obtained by assuming that the desired transmissibility is known in Z-domain. Since the desired transmissibility H sub d(S) = 1/(tauS+1)(exp 2) is given in S-domain, the first task is to obtain the desired transmissibility in Z-domain. There are three methods to perform this task: bilinear transformation, and backward and forward rectangular rules. The bilinear transformation and backward rectangular rule lead to improper controller transfer functions, which are physically not realizable. The forward rectangular rule does lead to a physically realizable controller. However, this controller is found to be marginally stable because of a pole at Z=1. In order to eliminate this pole, a hybrid control structure is proposed. Here the control input is composed of two parts: analog and digital. The analog input simply represents the velocity (or the integral of acceleration) feedback; and the digital controller which uses only relative displacement signal, is then obtained to achieve the desired closed-loop transfer function. The stability analysis indicates that the controller transfer function is stable for typical values of sampling period. In the second approach, the aforementioned hybrid control structure is again used. First, an analog controller transfer function corresponding to relative displacement feedback is obtained to achieve the transmissibility as 1/(tauS+1)(exp 2). Then the transfer function for the digital control input is obtained by discretizing this analog controller transfer function via bilinear transformation. The stability of the resulting Z-domain closed loop system is analyzed. Also, the frequency response of the Z-domain closed-loop transfer function is determined to evaluate the performance of the control system.

  4. Vernier perceptual learning transfers to completely untrained retinal locations after double training: A “piggybacking” effect

    PubMed Central

    Wang, Rui; Zhang, Jun-Yun; Klein, Stanley A.; Levi, Dennis M.; Yu, Cong

    2014-01-01

    Perceptual learning, a process in which training improves visual discrimination, is often specific to the trained retinal location, and this location specificity is frequently regarded as an indication of neural plasticity in the retinotopic visual cortex. However, our previous studies have shown that “double training” enables location-specific perceptual learning, such as Vernier learning, to completely transfer to a new location where an irrelevant task is practiced. Here we show that Vernier learning can be actuated by less location-specific orientation or motion-direction learning to transfer to completely untrained retinal locations. This “piggybacking” effect occurs even if both tasks are trained at the same retinal location. However, piggybacking does not occur when the Vernier task is paired with a more location-specific contrast-discrimination task. This previously unknown complexity challenges the current understanding of perceptual learning and its specificity/transfer. Orientation and motion-direction learning, but not contrast and Vernier learning, appears to activate a global process that allows learning transfer to untrained locations. Moreover, when paired with orientation or motion-direction learning, Vernier learning may be “piggybacked” by the activated global process to transfer to other untrained retinal locations. How this task-specific global activation process is achieved is as yet unknown. PMID:25398974

  5. Rehabilitation, Using Guided Cerebral Plasticity, of a Brachial Plexus Injury Treated with Intercostal and Phrenic Nerve Transfers.

    PubMed

    Dahlin, Lars B; Andersson, Gert; Backman, Clas; Svensson, Hampus; Björkman, Anders

    2017-01-01

    Recovery after surgical reconstruction of a brachial plexus injury using nerve grafting and nerve transfer procedures is a function of peripheral nerve regeneration and cerebral reorganization. A 15-year-old boy, with traumatic avulsion of nerve roots C5-C7 and a non-rupture of C8-T1, was operated 3 weeks after the injury with nerve transfers: (a) terminal part of the accessory nerve to the suprascapular nerve, (b) the second and third intercostal nerves to the axillary nerve, and (c) the fourth to sixth intercostal nerves to the musculocutaneous nerve. A second operation-free contralateral gracilis muscle transfer directly innervated by the phrenic nerve-was done after 2 years due to insufficient recovery of the biceps muscle function. One year later, electromyography showed activation of the biceps muscle essentially with coughing through the intercostal nerves, and of the transferred gracilis muscle by deep breathing through the phrenic nerve. Voluntary flexion of the elbow elicited clear activity in the biceps/gracilis muscles with decreasing activity in intercostal muscles distal to the transferred intercostal nerves (i.e., corresponding to eighth intercostal), indicating cerebral plasticity, where neural control of elbow flexion is gradually separated from control of breathing. To restore voluntary elbow function after nerve transfers, the rehabilitation of patients operated with intercostal nerve transfers should concentrate on transferring coughing function, while patients with phrenic nerve transfers should focus on transferring deep breathing function.

  6. Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT.

    PubMed

    Neuenhahn, M; Albrecht, J; Odendahl, M; Schlott, F; Dössinger, G; Schiemann, M; Lakshmipathi, S; Martin, K; Bunjes, D; Harsdorf, S; Weissinger, E M; Menzel, H; Verbeek, M; Uharek, L; Kröger, N; Wagner, E; Kobbe, G; Schroeder, T; Schmitt, M; Held, G; Herr, W; Germeroth, L; Bonig, H; Tonn, T; Einsele, H; Busch, D H; Grigoleit, G U

    2017-10-01

    Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively the safety and efficacy of stem cell-donor- or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase I/IIa trial. Allo-HSCT patients with drug-refractory CMV infection and lacking virus-specific T cells were treated with a single dose of ex vivo major histocompatibility complex-Streptamer-isolated CMV epitope-specific donor T cells. Forty-four allo-HSCT patients receiving a T-cell-replete (D + repl; n=28) or T-cell-depleted (D + depl; n=16) graft from a CMV-seropositive donor were screened for CMV-specific T-cell immunity. Eight D + depl recipients received adoptive T-cell therapy from their stem cell donor. CMV epitope-specific T cells were well supported and became detectable in all treated patients. Complete and partial virological response rates were 62.5% and 25%, respectively. Owing to longsome third-party donor (TPD) identification, only 8 of the 57 CMV patients transplanted from CMV-seronegative donors (D - ) received antigen-specific T cells from partially human leukocyte antigen (HLA)-matched TPDs. In all but one, TPD-derived CMV-specific T cells remained undetectable. In summary, adoptive transfer correlated with functional virus-specific T-cell reconstitution in D + depl patients. Suboptimal HLA match may counteract expansion of TPD-derived virus-specific T cells in D - patients.

  7. Blockade of the interaction of leukotriene b4 with its receptor prevents development of autoimmune uveitis.

    PubMed

    Liao, Tianjiang; Ke, Yan; Shao, Wen-Hai; Haribabu, Bodduluri; Kaplan, Henry J; Sun, Deming; Shao, Hui

    2006-04-01

    To investigate the role of leukotriene B4 (LTB4) and its receptor BLT1 in the pathogenesis of mouse uveitis. Experimental autoimmune uveitis (EAU) was induced in B10RIII mice by immunization of interphotoreceptor retinoid binding protein (IRBP; peptide sequence 161-180) or in C57BL/6 (B6) mice by transfer of activated T cells specific for IRBP1-20. The animals were then treated with and without the BLT1 receptor antagonist, CP105696, at the disease onset after immunization or at day 0 or day 6 after T-cell transfer. EAU was also induced in wild-type B6 (WT) and BLT1-deficient (BLT1-/-) mice by reciprocal transfer of the T cells from B6 to BLT1-deficient mice and vise versa. Clinical signs of inflammation and ocular histology were compared. The chemotactic activity of LTB4 on naïve and IRBP-specific autoreactive T cells as well as effector leukocytes was examined. The treatment of CP105696, greatly reduced the intensity of ongoing disease. IRBP1-20-specific T cells derived from wild-type B6 mice induced only mild uveitis in syngeneic BLT1-deficient mice and that IRBP1-20-specific T cells derived from BLT1-/- mice induced milder disease in wild-type B6 mice than those derived from wild-type B6 mice, suggesting that expression of the LTB4 receptor on both activated autoreactive T cells and effector leukocytes was necessary for ocular inflammation to occur. Consistent with these data, transfer of autoreactive T cells from B6 mice to 5-lipoxygenase-deficient (5-LO-/-) mice, which have a functional defect in LTB4 expression, also failed to induce uveitis in the recipient mice. The results demonstrate a critical role for LTB4 in ocular inflammation and in the development and progression of EAU and suggest a new potential target for therapeutic intervention in this disease.

  8. Combustion and Heat Transfer Studies Utilizing Advanced Diagnostics: Combustion Studies

    DTIC Science & Technology

    1992-11-01

    Research Zone With Combustion," Turbulent Shear Flows. VoL 5. pp. 337- and Development Center, Aero Propulsion and Power 346, Springer Verlg, New ...200 words) A long-term goal of the Air Force is to develop near-stoichiometric gas turbine combustors that will burn broad-specification fuels, and...laboratory combustors. Two novel methods for CARS slit function were developed ; these made possible precise and unambiguous measurements of flame

  9. Satellite services system overview

    NASA Technical Reports Server (NTRS)

    Rysavy, G.

    1982-01-01

    The benefits of a satellite services system and the basic needs of the Space Transportation System to have improved satellite service capability are identified. Specific required servicing equipment are discussed in terms of their technology development status and their operative functions. Concepts include maneuverable television systems, extravehicular maneuvering unit, orbiter exterior lighting, satellite holding and positioning aid, fluid transfer equipment, end effectors for the remote manipulator system, teleoperator maneuvering system, and hand and power tools.

  10. Orbital operations study. Appendix A: Interactivity analysis

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Supplemental analyses conducted to verify that safe, feasible, design concepts exist for accomplishing the attendant interface activities of the orbital operations mission are presented. The data are primarily concerned with functions and concepts common to more than one of the interfacing activities or elements. Specific consideration is given to state vector update, payload deployment, communications links, jet plume impingement, attached element operations, docking and structural interface assessment, and propellant transfer.

  11. Modeling of the structure-specific kinetics of abiotic, dark reduction of Hg(II) complexed by O/N and S functional groups in humic acids while accounting for time-dependent structural rearrangement

    USDA-ARS?s Scientific Manuscript database

    Redox transformations involving electron transfer from natural organic matter (NOM) are important for the mercury (Hg) biogeochemical cycle. In the water column light drives the reduction of Hg(II) to Hg(0), whereas in soils and sediments dark reduction of Hg(II) is of greater importance. The object...

  12. Neural correlates of training and transfer effects in working memory in older adults.

    PubMed

    Heinzel, Stephan; Lorenz, Robert C; Pelz, Patricia; Heinz, Andreas; Walter, Henrik; Kathmann, Norbert; Rapp, Michael A; Stelzel, Christine

    2016-07-01

    As indicated by previous research, aging is associated with a decline in working memory (WM) functioning, related to alterations in fronto-parietal neural activations. At the same time, previous studies showed that WM training in older adults may improve the performance in the trained task (training effect), and more importantly, also in untrained WM tasks (transfer effects). However, neural correlates of these transfer effects that would improve understanding of its underlying mechanisms, have not been shown in older participants as yet. In this study, we investigated blood-oxygen-level-dependent (BOLD) signal changes during n-back performance and an untrained delayed recognition (Sternberg) task following 12sessions (45min each) of adaptive n-back training in older adults. The Sternberg task used in this study allowed to test for neural training effects independent of specific task affordances of the trained task and to separate maintenance from updating processes. Thirty-two healthy older participants (60-75years) were assigned either to an n-back training or a no-contact control group. Before (t1) and after (t2) training/waiting period, both the n-back task and the Sternberg task were conducted while BOLD signal was measured using functional Magnetic Resonance Imaging (fMRI) in all participants. In addition, neuropsychological tests were performed outside the scanner. WM performance improved with training and behavioral transfer to tests measuring executive functions, processing speed, and fluid intelligence was found. In the training group, BOLD signal in the right lateral middle frontal gyrus/caudal superior frontal sulcus (Brodmann area, BA 6/8) decreased in both the trained n-back and the updating condition of the untrained Sternberg task at t2, compared to the control group. fMRI findings indicate a training-related increase in processing efficiency of WM networks, potentially related to the process of WM updating. Performance gains in untrained tasks suggest that transfer to other cognitive tasks remains possible in aging. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Deficits in hippocampal-dependent transfer generalization learning accompany synaptic dysfunction in a mouse model of amyloidosis.

    PubMed

    Montgomery, Karienn S; Edwards, George; Levites, Yona; Kumar, Ashok; Myers, Catherine E; Gluck, Mark A; Setlow, Barry; Bizon, Jennifer L

    2016-04-01

    Elevated β-amyloid and impaired synaptic function in hippocampus are among the earliest manifestations of Alzheimer's disease (AD). Most cognitive assessments employed in both humans and animal models, however, are insensitive to this early disease pathology. One critical aspect of hippocampal function is its role in episodic memory, which involves the binding of temporally coincident sensory information (e.g., sights, smells, and sounds) to create a representation of a specific learning epoch. Flexible associations can be formed among these distinct sensory stimuli that enable the "transfer" of new learning across a wide variety of contexts. The current studies employed a mouse analog of an associative "transfer learning" task that has previously been used to identify risk for prodromal AD in humans. The rodent version of the task assesses the transfer of learning about stimulus features relevant to a food reward across a series of compound discrimination problems. The relevant feature that predicts the food reward is unchanged across problems, but an irrelevant feature (i.e., the context) is altered. Experiment 1 demonstrated that C57BL6/J mice with bilateral ibotenic acid lesions of hippocampus were able to discriminate between two stimuli on par with control mice; however, lesioned mice were unable to transfer or apply this learning to new problem configurations. Experiment 2 used the APPswe PS1 mouse model of amyloidosis to show that robust impairments in transfer learning are evident in mice with subtle β-amyloid-induced synaptic deficits in the hippocampus. Finally, Experiment 3 confirmed that the same transfer learning impairments observed in APPswePS1 mice were also evident in the Tg-SwDI mouse, a second model of amyloidosis. Together, these data show that the ability to generalize learned associations to new contexts is disrupted even in the presence of subtle hippocampal dysfunction and suggest that, across species, this aspect of hippocampal-dependent learning may be useful for early identification of AD-like pathology. © 2015 Wiley Periodicals, Inc.

  14. Perceptual learning modifies the functional specializations of visual cortical areas.

    PubMed

    Chen, Nihong; Cai, Peng; Zhou, Tiangang; Thompson, Benjamin; Fang, Fang

    2016-05-17

    Training can improve performance of perceptual tasks. This phenomenon, known as perceptual learning, is strongest for the trained task and stimulus, leading to a widely accepted assumption that the associated neuronal plasticity is restricted to brain circuits that mediate performance of the trained task. Nevertheless, learning does transfer to other tasks and stimuli, implying the presence of more widespread plasticity. Here, we trained human subjects to discriminate the direction of coherent motion stimuli. The behavioral learning effect substantially transferred to noisy motion stimuli. We used transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms underlying the transfer of learning. The TMS experiment revealed dissociable, causal contributions of V3A (one of the visual areas in the extrastriate visual cortex) and MT+ (middle temporal/medial superior temporal cortex) to coherent and noisy motion processing. Surprisingly, the contribution of MT+ to noisy motion processing was replaced by V3A after perceptual training. The fMRI experiment complemented and corroborated the TMS finding. Multivariate pattern analysis showed that, before training, among visual cortical areas, coherent and noisy motion was decoded most accurately in V3A and MT+, respectively. After training, both kinds of motion were decoded most accurately in V3A. Our findings demonstrate that the effects of perceptual learning extend far beyond the retuning of specific neural populations for the trained stimuli. Learning could dramatically modify the inherent functional specializations of visual cortical areas and dynamically reweight their contributions to perceptual decisions based on their representational qualities. These neural changes might serve as the neural substrate for the transfer of perceptual learning.

  15. Enhancements to the SSME transfer function modeling code

    NASA Technical Reports Server (NTRS)

    Irwin, R. Dennis; Mitchell, Jerrel R.; Bartholomew, David L.; Glenn, Russell D.

    1995-01-01

    This report details the results of a one year effort by Ohio University to apply the transfer function modeling and analysis tools developed under NASA Grant NAG8-167 (Irwin, 1992), (Bartholomew, 1992) to attempt the generation of Space Shuttle Main Engine High Pressure Turbopump transfer functions from time domain data. In addition, new enhancements to the transfer function modeling codes which enhance the code functionality are presented, along with some ideas for improved modeling methods and future work. Section 2 contains a review of the analytical background used to generate transfer functions with the SSME transfer function modeling software. Section 2.1 presents the 'ratio method' developed for obtaining models of systems that are subject to single unmeasured excitation sources and have two or more measured output signals. Since most of the models developed during the investigation use the Eigensystem Realization Algorithm (ERA) for model generation, Section 2.2 presents an introduction of ERA, and Section 2.3 describes how it can be used to model spectral quantities. Section 2.4 details the Residue Identification Algorithm (RID) including the use of Constrained Least Squares (CLS) and Total Least Squares (TLS). Most of this information can be found in the report (and is repeated for convenience). Section 3 chronicles the effort of applying the SSME transfer function modeling codes to the a51p394.dat and a51p1294.dat time data files to generate transfer functions from the unmeasured input to the 129.4 degree sensor output. Included are transfer function modeling attempts using five methods. The first method is a direct application of the SSME codes to the data files and the second method uses the underlying trends in the spectral density estimates to form transfer function models with less clustering of poles and zeros than the models obtained by the direct method. In the third approach, the time data is low pass filtered prior to the modeling process in an effort to filter out high frequency characteristics. The fourth method removes the presumed system excitation and its harmonics in order to investigate the effects of the excitation on the modeling process. The fifth method is an attempt to apply constrained RID to obtain better transfer functions through more accurate modeling over certain frequency ranges. Section 4 presents some new C main files which were created to round out the functionality of the existing SSME transfer function modeling code. It is now possible to go from time data to transfer function models using only the C codes; it is not necessary to rely on external software. The new C main files and instructions for their use are included. Section 5 presents current and future enhancements to the XPLOT graphics program which was delivered with the initial software. Several new features which have been added to the program are detailed in the first part of this section. The remainder of Section 5 then lists some possible features which may be added in the future. Section 6 contains the conclusion section of this report. Section 6.1 is an overview of the work including a summary and observations relating to finding transfer functions with the SSME code. Section 6.2 contains information relating to future work on the project.

  16. An integrated reweighting theory of perceptual learning

    PubMed Central

    Dosher, Barbara Anne; Jeter, Pamela; Liu, Jiajuan; Lu, Zhong-Lin

    2013-01-01

    Improvements in performance on visual tasks due to practice are often specific to a retinal position or stimulus feature. Many researchers suggest that specific perceptual learning alters selective retinotopic representations in early visual analysis. However, transfer is almost always practically advantageous, and it does occur. If perceptual learning alters location-specific representations, how does it transfer to new locations? An integrated reweighting theory explains transfer over retinal locations by incorporating higher level location-independent representations into a multilevel learning system. Location transfer is mediated through location-independent representations, whereas stimulus feature transfer is determined by stimulus similarity at both location-specific and location-independent levels. Transfer to new locations/positions differs fundamentally from transfer to new stimuli. After substantial initial training on an orientation discrimination task, switches to a new location or position are compared with switches to new orientations in the same position, or switches of both. Position switches led to the highest degree of transfer, whereas orientation switches led to the highest levels of specificity. A computational model of integrated reweighting is developed and tested that incorporates the details of the stimuli and the experiment. Transfer to an identical orientation task in a new position is mediated via more broadly tuned location-invariant representations, whereas changing orientation in the same position invokes interference or independent learning of the new orientations at both levels, reflecting stimulus dissimilarity. Consistent with single-cell recording studies, perceptual learning alters the weighting of both early and midlevel representations of the visual system. PMID:23898204

  17. LANDSAT-D investigations in snow hydrology

    NASA Technical Reports Server (NTRS)

    Dozier, J.

    1983-01-01

    The atmospheric radiative transfer calculation program (ATARD) and its supporting programs (setting up atmospheric profile, making Mie tables and an exponential-sum-fitting table) were completed. More sophisticated treatment of aerosol scattering (including angular phase function or asymmetric factor) and multichannel analysis of results from ATRAD are being developed. Some progress was made on a Monte Carlo program for examining two dimensional effects, specifically a surface boundary condition that varies across a scene. The MONTE program combines ATRAD and the Monte Carlo method together to produce an atmospheric point spread function. Currently the procedure passes monochromatic tests and the results are reasonable.

  18. Spacecraft Health Automated Reasoning Prototype (SHARP): The fiscal year 1989 SHARP portability evaluations task for NASA Solar System Exploration Division's Voyager project

    NASA Technical Reports Server (NTRS)

    Atkinson, David J.; Doyle, Richard J.; James, Mark L.; Kaufman, Tim; Martin, R. Gaius

    1990-01-01

    A Spacecraft Health Automated Reasoning Prototype (SHARP) portability study is presented. Some specific progress is described on the portability studies, plans for technology transfer, and potential applications of SHARP and related artificial intelligence technology to telescience operations. The application of SHARP to Voyager telecommunications was a proof-of-capability demonstration of artificial intelligence as applied to the problem of real time monitoring functions in planetary mission operations. An overview of the design and functional description of the SHARP system is also presented as it was applied to Voyager.

  19. Resonance energy transfer improves the biological function of bacteriorhodopsin within a hybrid material built from purple membranes and semiconductor quantum dots.

    PubMed

    Rakovich, Aliaksandra; Sukhanova, Alyona; Bouchonville, Nicolas; Lukashev, Evgeniy; Oleinikov, Vladimir; Artemyev, Mikhail; Lesnyak, Vladimir; Gaponik, Nikolai; Molinari, Michael; Troyon, Michel; Rakovich, Yury P; Donegan, John F; Nabiev, Igor

    2010-07-14

    Purple membrane (PM) from bacteria Halobacterium salinarum contains a photochromic protein bacteriorhodopsin (bR) arranged in a 2D hexagonal nanocrystalline lattice (Figure 1 ). Absorption of light by the protein-bound chromophore retinal results in pumping the protons through the PM creating an electrochemical gradient which is then used by the ATPases to energize the cellular processes. Energy conversion, photochromism, and photoelectrism are the inherent effects which are employed in many bR technical applications. bR, along with the other photosensitive proteins, is not able to deal with the excess energy of photons in UV and blue spectral region and utilizes less than 0.5% of the energy from the available incident solar light for its biological function. Here, we proceed with optimization of bR functions through the engineering of a "nanoconverter" of solar energy based on semiconductor quantum dots (QDs) tagged with the PM. These nanoconverters are able to harvest light from deep-UV to the visible region and to transfer this additionally collected energy to bR via Förster resonance energy transfer (FRET). We show that specific nanobio-optical and spatial coupling of QDs (donor) and bR retinal (acceptor) provide a means to achieve FRET with efficiency approaching 100%. We have finally demonstrated that the integration of QDs within PM significantly increases the efficiency of light-driven transmembrane proton pumping, which is the main bR biological function. This new QD-PM hybrid material will have numerous optoelectronic, photonic, and photovoltaic applications based on its energy conversion, photochromism, and photoelectrism properties.

  20. Translational simulation: not 'where?' but 'why?' A functional view of in situ simulation.

    PubMed

    Brazil, Victoria

    2017-01-01

    Healthcare simulation has been widely adopted for health professional education at all stages of training and practice and across cognitive, procedural, communication and teamwork domains. Recent enthusiasm for in situ simulation-delivered in the real clinical environment-cites improved transfer of knowledge and skills into real-world practice, as well as opportunities to identify latent safety threats and other workplace-specific issues. However, describing simulation type according to place may not be helpful. Instead, I propose the term translational simulation as a functional term for how simulation may be connected directly with health service priorities and patient outcomes, through interventional and diagnostic functions, independent of the location of the simulation activity.

  1. Coherent exciton-vibrational dynamics and energy transfer in conjugated organics

    DOE PAGES

    Nelson, Tammie R.; Ondarse-Alvarez, Dianelys; Oldani, Nicolas; ...

    2018-06-13

    Coherence, signifying concurrent electron-vibrational dynamics in complex natural and man-made systems, is currently a subject of intense study. Understanding this phenomenon is important when designing carrier transport in optoelectronic materials. Here, excited state dynamics simulations reveal a ubiquitous pattern in the evolution of photoexcitations for a broad range of molecular systems. Symmetries of the wavefunctions define a specific form of the non-adiabatic coupling that drives quantum transitions between excited states, leading to a collective asymmetric vibrational excitation coupled to the electronic system. This promotes periodic oscillatory evolution of the wavefunctions, preserving specific phase and amplitude relations across the ensemble ofmore » trajectories. The simple model proposed here explains the appearance of coherent exciton-vibrational dynamics due to non-adiabatic transitions, which is universal across multiple molecular systems. The observed relationships between electronic wavefunctions and the resulting functionalities allows us to understand, and potentially manipulate, excited state dynamics and energy transfer in molecular materials.« less

  2. Coherent exciton-vibrational dynamics and energy transfer in conjugated organics

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

    Nelson, Tammie R.; Ondarse-Alvarez, Dianelys; Oldani, Nicolas

    Coherence, signifying concurrent electron-vibrational dynamics in complex natural and man-made systems, is currently a subject of intense study. Understanding this phenomenon is important when designing carrier transport in optoelectronic materials. Here, excited state dynamics simulations reveal a ubiquitous pattern in the evolution of photoexcitations for a broad range of molecular systems. Symmetries of the wavefunctions define a specific form of the non-adiabatic coupling that drives quantum transitions between excited states, leading to a collective asymmetric vibrational excitation coupled to the electronic system. This promotes periodic oscillatory evolution of the wavefunctions, preserving specific phase and amplitude relations across the ensemble ofmore » trajectories. The simple model proposed here explains the appearance of coherent exciton-vibrational dynamics due to non-adiabatic transitions, which is universal across multiple molecular systems. The observed relationships between electronic wavefunctions and the resulting functionalities allows us to understand, and potentially manipulate, excited state dynamics and energy transfer in molecular materials.« less

  3. An interface for simulating radiative transfer in and around volcanic plumes with the Monte Carlo radiative transfer model McArtim

    USGS Publications Warehouse

    Kern, Christoph

    2016-03-23

    This report describes two software tools that, when used as front ends for the three-dimensional backward Monte Carlo atmospheric-radiative-transfer model (RTM) McArtim, facilitate the generation of lookup tables of volcanic-plume optical-transmittance characteristics in the ultraviolet/visible-spectral region. In particular, the differential optical depth and derivatives thereof (that is, weighting functions), with regard to a change in SO2 column density or aerosol optical thickness, can be simulated for a specific measurement geometry and a representative range of plume conditions. These tables are required for the retrieval of SO2 column density in volcanic plumes, using the simulated radiative-transfer/differential optical-absorption spectroscopic (SRT-DOAS) approach outlined by Kern and others (2012). This report, together with the software tools published online, is intended to make this sophisticated SRT-DOAS technique available to volcanologists and gas geochemists in an operational environment, without the need for an indepth treatment of the underlying principles or the low-level interface of the RTM McArtim.

  4. Surfactant effects on alpha factors in full-scale wastewater aeration systems.

    PubMed

    Rosso, D; Larson, L E; Stenstrom, M K

    2006-01-01

    Aeration is an essential process in the majority of wastewater treatment processes, and accounts for the largest fraction of plant energy costs. Aeration systems can achieve wastewater oxygenation by shearing the surface (surface aerators) or releasing bubbles at the bottom of the tank (coarse- or fine-bubble aerators). Surfactants accumulate on gas-liquid interfaces and reduce mass transfer rates. This reduction in general is larger for fine-bubble aerators. This study was conducted to evaluate mass transfer effects on the characterization and specification of aeration systems in clean and process water conditions. Tests at different interfacial turbulence regimes were analysed, showing higher gas transfer depression for lower turbulence regimes. Higher turbulence regimes can offset contamination effects, at the expense of operating efficiency. This phenomenon is characteristic of surface aerators and coarse bubble diffusers and is here discussed. The results explain the variability of alpha factors measured at small scale, due to uncontrolled energy density. Results are also reported in dimensionless empirical correlations that describe mass transfer as a function of physiochemical and geometrical characteristics of the aeration process.

  5. Temporal Organization of Sound Information in Auditory Memory.

    PubMed

    Song, Kun; Luo, Huan

    2017-01-01

    Memory is a constructive and organizational process. Instead of being stored with all the fine details, external information is reorganized and structured at certain spatiotemporal scales. It is well acknowledged that time plays a central role in audition by segmenting sound inputs into temporal chunks of appropriate length. However, it remains largely unknown whether critical temporal structures exist to mediate sound representation in auditory memory. To address the issue, here we designed an auditory memory transferring study, by combining a previously developed unsupervised white noise memory paradigm with a reversed sound manipulation method. Specifically, we systematically measured the memory transferring from a random white noise sound to its locally temporal reversed version on various temporal scales in seven experiments. We demonstrate a U-shape memory-transferring pattern with the minimum value around temporal scale of 200 ms. Furthermore, neither auditory perceptual similarity nor physical similarity as a function of the manipulating temporal scale can account for the memory-transferring results. Our results suggest that sounds are not stored with all the fine spectrotemporal details but are organized and structured at discrete temporal chunks in long-term auditory memory representation.

  6. SAR Processing Based On Two-Dimensional Transfer Function

    NASA Technical Reports Server (NTRS)

    Chang, Chi-Yung; Jin, Michael Y.; Curlander, John C.

    1994-01-01

    Exact transfer function, ETF, is two-dimensional transfer function that constitutes basis of improved frequency-domain-convolution algorithm for processing synthetic-aperture-radar, SAR data. ETF incorporates terms that account for Doppler effect of motion of radar relative to scanned ground area and for antenna squint angle. Algorithm based on ETF outperforms others.

  7. Kill: boosting HIV-specific immune responses.

    PubMed

    Trautmann, Lydie

    2016-07-01

    Increasing evidence suggests that purging the latent HIV reservoir in virally suppressed individuals will require both the induction of viral replication from its latent state and the elimination of these reactivated HIV-infected cells ('Shock and Kill' strategy). Boosting potent HIV-specific CD8 T cells is a promising way to achieve an HIV cure. Recent studies provided the rationale for developing immune interventions to increase the numbers, function and location of HIV-specific CD8 T cells to purge HIV reservoirs. Multiple approaches are being evaluated including very early suppression of HIV replication in acute infection, adoptive cell transfer, therapeutic vaccination or use of immunomodulatory molecules. New assays to measure the killing and antiviral function of induced HIV-specific CD8 T cells have been developed to assess the efficacy of these new approaches. The strategies combining HIV reactivation and immunobased therapies to boost HIV-specific CD8 T cells can be tested in in-vivo and in-silico models to accelerate the design of new clinical trials. New immunobased strategies are explored to boost HIV-specific CD8 T cells able to purge the HIV-infected cells with the ultimate goal of achieving spontaneous control of viral replication without antiretroviral treatment.

  8. Probing the rate-limiting step for intramolecular transfer of a transcription factor between specific sites on the same DNA molecule by (15)Nz-exchange NMR spectroscopy.

    PubMed

    Ryu, Kyoung-Seok; Tugarinov, Vitali; Clore, G Marius

    2014-10-15

    The kinetics of translocation of the homeodomain transcription factor HoxD9 between specific sites of the same or opposite polarities on the same DNA molecule have been studied by (15)Nz-exchange NMR spectroscopy. We show that exchange occurs by two facilitated diffusion mechanisms: a second-order intermolecular exchange reaction between specific sites located on different DNA molecules without the protein dissociating into free solution that predominates at high concentrations of free DNA, and a first-order intramolecular process involving direct transfer between specific sites located on the same DNA molecule. Control experiments using a mixture of two DNA molecules, each possessing only a single specific site, indicate that transfer between specific sites by full dissociation of HoxD9 into solution followed by reassociation is too slow to measure by z-exchange spectroscopy. Intramolecular transfer with comparable rate constants occurs between sites of the same and opposing polarity, indicating that both rotation-coupled sliding and hopping/flipping (analogous to geminate recombination) occur. The half-life for intramolecular transfer (0.5-1 s) is many orders of magnitude larger than the calculated transfer time (1-100 μs) by sliding, leading us to conclude that the intramolecular transfer rates measured by z-exchange spectroscopy represent the rate-limiting step for a one-base-pair shift from the specific site to the immediately adjacent nonspecific site. At zero concentration of added salt, the intramolecular transfer rate constants between sites of opposing polarity are smaller than those between sites of the same polarity, suggesting that hopping/flipping may become rate-limiting at very low salt concentrations.

  9. Propagation of eigenmodes and transfer functions in waveguide WDM structures

    NASA Astrophysics Data System (ADS)

    Mashkov, Vladimir A.; Francoeur, S.; Geuss, U.; Neiser, K.; Temkin, Henryk

    1998-02-01

    A method of propagation functions and transfer amplitudes suitable for the design of integrated optical circuits is presented. The method is based on vectorial formulation of electrodynamics: the distributions and propagation of electromagnetic fields in optical circuits is described by equivalent surface sources. This approach permits a division of complex optical waveguide structures into sets of primitive blocks and to separately calculate the transfer function and the transfer amplitude for each block. The transfer amplitude of the entire optical system is represented by a convolution of transfer amplitudes of its primitive blocks. The eigenvalues and eigenfunctions of arbitrary waveguide structure are obtained in the WKB approximation and compared with other methods. The general approach is illustrated with the transfer amplitude calculations for Dragone's star coupler and router.

  10. A caveat regarding diatom-inferred nitrogen concentrations in oligotrophic lakes

    USGS Publications Warehouse

    Arnett, Heather A.; Saros, Jasmine E.; Mast, M. Alisa

    2012-01-01

    Atmospheric deposition of reactive nitrogen (Nr) has enriched oligotrophic lakes with nitrogen (N) in many regions of the world and elicited dramatic changes in diatom community structure. The lakewater concentrations of nitrate that cause these community changes remain unclear, raising interest in the development of diatom-based transfer functions to infer nitrate. We developed a diatom calibration set using surface sediment samples from 46 high-elevation lakes across the Rocky Mountains of the western US, a region spanning an N deposition gradient from very low to moderate levels (<1 to 3.2 kg Nr ha−1 year−1 in wet deposition). Out of the fourteen measured environmental variables for these 46 lakes, ordination analysis identified that nitrate, specific conductance, total phosphorus, and hypolimnetic water temperature were related to diatom distributions. A transfer function was developed for nitrate and applied to a sedimentary diatom profile from Heart Lake in the central Rockies. The model coefficient of determination (bootstrapping validation) of 0.61 suggested potential for diatom-inferred reconstructions of lakewater nitrate concentrations over time, but a comparison of observed versus diatom-inferred nitrate values revealed the poor performance of this model at low nitrate concentrations. Resource physiology experiments revealed that nitrogen requirements of two key taxa were opposite to nitrate optima defined in the transfer function. Our data set reveals two underlying ecological constraints that impede the development of nitrate transfer functions in oligotrophic lakes: (1) even in lakes with nitrate concentrations below quantification (<1 μg L−1), diatom assemblages were already dominated by species indicative of moderate N enrichment; (2) N-limited oligotrophic lakes switch to P limitation after receiving only modest inputs of reactive N, shifting the controls on diatom species changes along the length of the nitrate gradient. These constraints suggest that quantitative inferences of nitrate from diatom assemblages will likely require experimental approaches.

  11. Optical analysis of electro-optical systems by MTF calculus

    NASA Astrophysics Data System (ADS)

    Barbarini, Elisa Signoreto; Dos Santos, Daniel, Jr.; Stefani, Mário Antonio; Yasuoka, Fátima Maria Mitsue; Castro Neto, Jarbas C.; Rodrigues, Evandro Luís Linhari

    2011-08-01

    One of the widely used methods for performance analysis of an optical system is the determination of the Modulation Transfer Function (MTF). The MTF represents a quantitative and direct measure of image quality, and, besides being an objective test, it can be used on concatenated optical system. This paper presents the application of software called SMTF (software modulation transfer function), built in C++ and Open CV platforms for MTF calculation on electro-optical system. Through this technique, it is possible to develop specific method to measure the real time performance of a digital fundus camera, an infrared sensor and an ophthalmological surgery microscope. Each optical instrument mentioned has a particular device to measure the MTF response, which is being developed. Then the MTF information assists the analysis of the optical system alignment, and also defines its resolution limit by the MTF graphic. The result obtained from the implemented software is compared with the theoretical MTF curve from the analyzed systems.

  12. User's Manual: Routines for Radiative Heat Transfer and Thermometry

    NASA Technical Reports Server (NTRS)

    Risch, Timothy K.

    2016-01-01

    Determining the intensity and spectral distribution of radiation emanating from a heated surface has applications in many areas of science and engineering. Areas of research in which the quantification of spectral radiation is used routinely include thermal radiation heat transfer, infrared signature analysis, and radiation thermometry. In the analysis of radiation, it is helpful to be able to predict the radiative intensity and the spectral distribution of the emitted energy. Presented in this report is a set of routines written in Microsoft Visual Basic for Applications (VBA) (Microsoft Corporation, Redmond, Washington) and incorporating functions specific to Microsoft Excel (Microsoft Corporation, Redmond, Washington) that are useful for predicting the radiative behavior of heated surfaces. These routines include functions for calculating quantities of primary importance to engineers and scientists. In addition, the routines also provide the capability to use such information to determine surface temperatures from spectral intensities and for calculating the sensitivity of the surface temperature measurements to unknowns in the input parameters.

  13. The Total Synthesis Problem of linear multivariable control. II - Unity feedback and the design morphism

    NASA Technical Reports Server (NTRS)

    Sain, M. K.; Antsaklis, P. J.; Gejji, R. R.; Wyman, B. F.; Peczkowski, J. L.

    1981-01-01

    Zames (1981) has observed that there is, in general, no 'separation principle' to guarantee optimality of a division between control law design and filtering of plant uncertainty. Peczkowski and Sain (1978) have solved a model matching problem using transfer functions. Taking into consideration this investigation, Peczkowski et al. (1979) proposed the Total Synthesis Problem (TSP), wherein both the command/output-response and command/control-response are to be synthesized, subject to the plant constraint. The TSP concept can be subdivided into a Nominal Design Problem (NDP), which is not dependent upon specific controller structures, and a Feedback Synthesis Problem (FSP), which is. Gejji (1980) found that NDP was characterized in terms of the plant structural matrices and a single, 'good' transfer function matrix. Sain et al. (1981) have extended this NDP work. The present investigation is concerned with a study of FSP for the unity feedback case. NDP, together with feedback synthesis, is understood as a Total Synthesis Problem.

  14. Protonation-state-Coupled Conformational Dynamics in Reaction Mechanisms of Channel and Pump Rhodopsins

    DOE PAGES

    Bondar, Ana-Nicoleta; Smith, Jeremy C.

    2017-07-25

    Channel and pump rhodopsins use energy from light absorbed by a covalently bound retinal chromophore to transport ions across membranes of microbial cells. Ion transfer steps, including proton transfer, can couple to changes in protein conformational dynamics and water positions. Although general principles of how microbial rhodopsins function are largely understood, key issues pertaining to reaction mechanisms remain unclear. Here, we compare the protonation-coupled dynamics of pump and channelrhodopsins, highlighting the roles that water dynamics, protein electrostatics and protein flexibility can have in ion transport mechanisms. We discuss observations supporting important functional roles of inter- and intra-helical carboxylate/hydroxyl hydrogen-bonding motifs.more » Specifically, we use the proton pump bacteriorhodopsin, the sodium pump KR2, channelrhodopsins and Anabaena sensory rhodopsin. We outline the usefulness of theoretic biophysics approaches to the study of retinal proteins, challenges in studying the hydrogen-bond dynamics of rhodopsin active sites, and implications for conformational coupling in membrane transporters.« less

  15. Fishing for biodiversity: Novel methanopterin-linked C1 transfergenes deduced from the Sargasso Sea metagenome

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

    Kalyuzhnaya, Marina G.; Nercessian, Olivier; Lapidus, Alla

    2004-07-01

    The recently generated database of microbial genes from anoligotrophic environment populated by a calculated 1,800 of major phylotypes (the Sargasso Sea metagenome) presents a great source for expanding local databases of genes indicative of a specific function. In this paper we analyze the Sargasso Sea metagenome in terms of the presence of methanopterin-linked C1 transfer genes that are signature for methylotrophy. We conclude that more than 10 phylotypes possessing genes of interest are present in this environment, and a few of these are relatively abundant species. The sequences representative of the major phylotypes do not appear to belong to anymore » known microbial group capable of methanopterin-linked C1 transfer. Instead, they separate from all known sequences on phylogenetic trees, pointing towards their affiliation with a novel microbial phylum. These data imply a broader distribution of methanopterin-linked functions in the microbial world than previously known.« less

  16. Protonation-state-Coupled Conformational Dynamics in Reaction Mechanisms of Channel and Pump Rhodopsins

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

    Bondar, Ana-Nicoleta; Smith, Jeremy C.

    Channel and pump rhodopsins use energy from light absorbed by a covalently bound retinal chromophore to transport ions across membranes of microbial cells. Ion transfer steps, including proton transfer, can couple to changes in protein conformational dynamics and water positions. Although general principles of how microbial rhodopsins function are largely understood, key issues pertaining to reaction mechanisms remain unclear. Here, we compare the protonation-coupled dynamics of pump and channelrhodopsins, highlighting the roles that water dynamics, protein electrostatics and protein flexibility can have in ion transport mechanisms. We discuss observations supporting important functional roles of inter- and intra-helical carboxylate/hydroxyl hydrogen-bonding motifs.more » Specifically, we use the proton pump bacteriorhodopsin, the sodium pump KR2, channelrhodopsins and Anabaena sensory rhodopsin. We outline the usefulness of theoretic biophysics approaches to the study of retinal proteins, challenges in studying the hydrogen-bond dynamics of rhodopsin active sites, and implications for conformational coupling in membrane transporters.« less

  17. Spatially Controlled Noncovalent Functionalization of 2D Materials Based on Molecular Architecture.

    PubMed

    Bang, Jae Jin; Porter, Ashlin G; Davis, Tyson C; Hayes, Tyler R; Claridge, Shelley A

    2018-05-15

    Polymerizable amphiphiles can be assembled into lying-down phases on 2D materials such as graphite and graphene to create chemically orthogonal surface patterns at 5-10 nm scales, locally modulating functionality of the 2D basal plane. Functionalization can be carried out through Langmuir-Schaefer conversion, in which a subset of molecules is transferred out of a standing phase film on water onto the 2D substrate. Here, we leverage differences in molecular structure to spatially control transfer at both nanoscopic and microscopic scales. We compare transfer properties of five different single- and dual-chain amphiphiles, demonstrating that those with strong lateral interactions (e.g., hydrogen-bonding networks) exhibit the lowest transfer efficiencies. Since molecular structures also influence microscopic domain morphologies in Langmuir films, we show that it is possible to transfer such microscale patterns, taking advantage of variations in the local transfer rates based on the structural heterogeneity in Langmuir films. Nanoscale domain morphologies also vary in ways that are consistent with predicted relative transfer and diffusion rates. These results suggest strategies to tailor noncovalent functionalization of 2D substrates through controlled LS transfer.

  18. pH-regulated metal-ligand switching in the HM loop of ATP7A: a new paradigm for metal transfer chemistry.

    PubMed

    Kline, Chelsey D; Gambill, Benjamin F; Mayfield, Mary; Lutsenko, Svetlana; Blackburn, Ninian J

    2016-08-01

    Cuproproteins such as PHM and DBM mature in late endosomal vesicles of the mammalian secretory pathway where changes in vesicle pH are employed for sorting and post-translational processing. Colocation with the P1B-type ATPase ATP7A suggests that the latter is the source of copper and supports a mechanism where selectivity in metal transfer is achieved by spatial colocation of partner proteins in their specific organelles or vesicles. In previous work we have suggested that a lumenal loop sequence located between trans-membrane helices TM1 and TM2 of the ATPase, and containing five histidines and four methionines, acts as an organelle-specific chaperone for metallation of the cuproproteins. The hypothesis posits that the pH of the vesicle regulates copper ligation and loop conformation via a mechanism which involves His to Met ligand switching induced by histidine protonation. Here we report the effect of pH on the HM loop copper coordination using X-ray absorption spectroscopy (XAS), and show via selenium substitution of the Met residues that the HM loop undergoes similar conformational switching to that found earlier for its partner PHM. We hypothesize that in the absence of specific chaperones, HM motifs provide a template for building a flexible, pH-sensitive transfer site whose structure and function can be regulated to accommodate the different active site structural elements and pH environments of its partner proteins.

  19. Performance of Frozen Density Embedding for Modeling Hole Transfer Reactions.

    PubMed

    Ramos, Pablo; Papadakis, Markos; Pavanello, Michele

    2015-06-18

    We have carried out a thorough benchmark of the frozen density-embedding (FDE) method for calculating hole transfer couplings. We have considered 10 exchange-correlation functionals, 3 nonadditive kinetic energy functionals, and 3 basis sets. Overall, we conclude that with a 7% mean relative unsigned error, the PBE and PW91 functionals coupled with the PW91k nonadditive kinetic energy functional and a TZP basis set constitute the most stable and accurate levels of theory for hole transfer coupling calculations. The FDE-ET method is found to be an excellent tool for computing diabatic couplings for hole transfer reactions.

  20. Improved Displacement Transfer Functions for Structure Deformed Shape Predictions Using Discretely Distributed Surface Strains

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Fleischer, Van Tran

    2012-01-01

    In the formulations of earlier Displacement Transfer Functions for structure shape predictions, the surface strain distributions, along a strain-sensing line, were represented with piecewise linear functions. To improve the shape-prediction accuracies, Improved Displacement Transfer Functions were formulated using piecewise nonlinear strain representations. Through discretization of an embedded beam (depth-wise cross section of a structure along a strain-sensing line) into multiple small domains, piecewise nonlinear functions were used to describe the surface strain distributions along the discretized embedded beam. Such piecewise approach enabled the piecewise integrations of the embedded beam curvature equations to yield slope and deflection equations in recursive forms. The resulting Improved Displacement Transfer Functions, written in summation forms, were expressed in terms of beam geometrical parameters and surface strains along the strain-sensing line. By feeding the surface strains into the Improved Displacement Transfer Functions, structural deflections could be calculated at multiple points for mapping out the overall structural deformed shapes for visual display. The shape-prediction accuracies of the Improved Displacement Transfer Functions were then examined in view of finite-element-calculated deflections using different tapered cantilever tubular beams. It was found that by using the piecewise nonlinear strain representations, the shape-prediction accuracies could be greatly improved, especially for highly-tapered cantilever tubular beams.

  1. Derived Manding in Children with Autism: Synthesizing Skinner's Verbal Behavior with Relational Frame Theory

    PubMed Central

    2005-01-01

    Mand functions for two stimuli (A1 and A2) were trained for 3 children with autism and were then incorporated into two related conditional discriminations (A1-B1/A2 -B2 and B1-C1/B2-C2). Tests were conducted to probe for a derived transfer of mand response functions from A1 and A2 to C1 and C2, respectively. When 1 participant failed to demonstrate derived transfer of mand response functions, transfer training using exemplars was conducted. When participants had demonstrated derived transfer of mand functions, the X1 and X2 tokens that were employed as reinforcers for mand responses were incorporated into two conditional discriminations (X1-Y1/X2-Y2 and Y1-Z1/Y2-Z2). Tests were conducted for derived transfer of reinforcing functions. Finally, tests were conducted to determine if the participants would demonstrate derived manding for the derived reinforcers (present C1 and C2 to mand for Z1 and Z2, respectively). Derived transfer of functions was observed when the sequence of training and testing was reversed (i.e., training and testing reinforcing functions before mand response functions) and when only minimal instructions were provided. PMID:16463526

  2. How do CARs work?

    PubMed Central

    Davila, Marco L.; Brentjens, Renier; Wang, Xiuyan; Rivière, Isabelle; Sadelain, Michel

    2012-01-01

    Second-generation chimeric antigen receptors (CARs) are powerful tools to redirect antigen-specific T cells independently of HLA-restriction. Recent clinical studies evaluating CD19-targeted T cells in patients with B-cell malignancies demonstrate the potency of CAR-engineered T cells. With results from 28 subjects enrolled by five centers conducting studies in patients with chronic lymphocytic leukemia (CLL) or lymphoma, some insights into the parameters that determine T-cell function and clinical outcome of CAR-based approaches are emerging. These parameters involve CAR design, T-cell production methods, conditioning chemotherapy as well as patient selection. Here, we discuss the potential relevance of these findings and in particular the interplay between the adoptive transfer of T cells and pre-transfer patient conditioning. PMID:23264903

  3. Non-equilibrium reaction rates in chemical kinetic equations

    NASA Astrophysics Data System (ADS)

    Gorbachev, Yuriy

    2018-05-01

    Within the recently proposed asymptotic method for solving the Boltzmann equation for chemically reacting gas mixture, the chemical kinetic equations has been derived. Corresponding one-temperature non-equilibrium reaction rates are expressed in terms of specific heat capacities of the species participate in the chemical reactions, bracket integrals connected with the internal energy transfer in inelastic non-reactive collisions and energy transfer coefficients. Reactions of dissociation/recombination of homonuclear and heteronuclear diatomic molecules are considered. It is shown that all reaction rates are the complex functions of the species densities, similarly to the unimolecular reaction rates. For determining the rate coefficients it is recommended to tabulate corresponding bracket integrals, additionally to the equilibrium rate constants. Correlation of the obtained results with the irreversible thermodynamics is established.

  4. A method to model latent heat for transient analysis using NASTRAN

    NASA Technical Reports Server (NTRS)

    Harder, R. L.

    1982-01-01

    A sample heat transfer analysis is demonstrated which includes the heat of fusion. The method can be used to analyze a system with nonconstant specific heat. The enthalpy is introduced as an independent degree of freedom at each node. The user input consists of a curve of temperature as a function of enthalpy, which may include a constant temperature phase change. The basic NASTRAN heat transfer capability is used to model the effects of latent heat with existing direct matrix output and nonlinear load data cards. Although some user care is required, the numerical stability of the integration is quite good when the given recommendations are followed. The theoretical equations used and the NASTRAN techniques are shown.

  5. Cell-Specific Multifunctional Processing of Heterogeneous Cell Systems in a Single Laser Pulse Treatment

    PubMed Central

    Lukianova-Hleb, Ekaterina Y.; Mutonga, Martin B. G.; Lapotko, Dmitri O.

    2012-01-01

    Current methods of cell processing for gene and cell therapies use several separate procedures for gene transfer and cell separation or elimination, because no current technology can offer simultaneous multi-functional processing of specific cell sub-sets in highly heterogeneous cell systems. Using the cell-specific generation of plasmonic nanobubbles of different sizes around cell-targeted gold nanoshells and nanospheres, we achieved simultaneous multifunctional cell-specific processing in a rapid single 70 ps laser pulse bulk treatment of heterogeneous cell suspension. This method supported the detection of cells, delivery of external molecular cargo to one type of cells and the concomitant destruction of another type of cells without damaging other cells in suspension, and real-time guidance of the two above cellular effects. PMID:23167546

  6. General and specific factors in the intersensory transfer of form.

    NASA Technical Reports Server (NTRS)

    Clark, J. L.; Warm, J. S.; Schumsky, D. A.

    1972-01-01

    This study assessed the relative contributions of specific and nonspecific components to intersensory transfer between vision and touch. A paired-associate paradigm was used in which visual metric figures and their tactual analogs served as stimuli, and familiar adjectives were the responses. Positive intersensory transfer, characterized by symmetry across modalities was obtained. The contribution of nonspecific learning to this effect was negligible. Intersensory transfer was found to be less efficient than the empirically determined maximum level of intrasensory transfer possible in this task.

  7. High Throughput Engineering to Revitalize a Vestigial Electron Transfer Pathway in Bacterial Photosynthetic Reaction Centers*

    PubMed Central

    Faries, Kaitlyn M.; Kressel, Lucas L.; Wander, Marc J.; Holten, Dewey; Laible, Philip D.; Kirmaier, Christine; Hanson, Deborah K.

    2012-01-01

    Photosynthetic reaction centers convert light energy into chemical energy in a series of transmembrane electron transfer reactions, each with near 100% yield. The structures of reaction centers reveal two symmetry-related branches of cofactors (denoted A and B) that are functionally asymmetric; purple bacterial reaction centers use the A pathway exclusively. Previously, site-specific mutagenesis has yielded reaction centers capable of transmembrane charge separation solely via the B branch cofactors, but the best overall electron transfer yields are still low. In an attempt to better realize the architectural and energetic factors that underlie the directionality and yields of electron transfer, sites within the protein-cofactor complex were targeted in a directed molecular evolution strategy that implements streamlined mutagenesis and high throughput spectroscopic screening. The polycistronic approach enables efficient construction and expression of a large number of variants of a heteroligomeric complex that has two intimately regulated subunits with high sequence similarity, common features of many prokaryotic and eukaryotic transmembrane protein assemblies. The strategy has succeeded in the discovery of several mutant reaction centers with increased efficiency of the B pathway; they carry multiple substitutions that have not been explored or linked using traditional approaches. This work expands our understanding of the structure-function relationships that dictate the efficiency of biological energy-conversion reactions, concepts that will aid the design of bio-inspired assemblies capable of both efficient charge separation and charge stabilization. PMID:22247556

  8. Feedback Specificity, Information Processing, and Transfer of Training

    ERIC Educational Resources Information Center

    Goodman, Jodi S.; Wood, Robert E.; Chen, Zheng

    2011-01-01

    This study examines the effects of feedback specificity on transfer of training and the mechanisms through which feedback can enhance or inhibit transfer. We used concurrent verbal protocol methodology to elicit and operationalize the explicit information processing activities used by 48 trainees performing the Furniture Factory computer…

  9. Engineering tumor cell targeting in nanoscale amyloidal materials

    NASA Astrophysics Data System (ADS)

    Unzueta, Ugutz; Seras-Franzoso, Joaquin; Virtudes Céspedes, María; Saccardo, Paolo; Cortés, Francisco; Rueda, Fabián; Garcia-Fruitós, Elena; Ferrer-Miralles, Neus; Mangues, Ramon; Vázquez, Esther; Villaverde, Antonio

    2017-01-01

    Bacterial inclusion bodies are non-toxic, mechanically stable and functional protein amyloids within the nanoscale size range that are able to naturally penetrate into mammalian cells, where they deliver the embedded protein in a functional form. The potential use of inclusion bodies in protein delivery or protein replacement therapies is strongly impaired by the absence of specificity in cell binding and penetration, thus preventing targeting. To address this issue, we have here explored whether the genetic fusion of two tumor-homing peptides, the CXCR4 ligands R9 and T22, to an inclusion body-forming green fluorescent protein (GFP), would keep the interaction potential and the functionality of the fused peptides and then confer CXCR4 specificity in cell binding and further uptake of the materials. The fusion proteins have been well produced in Escherichia coli in their full-length form, keeping the potential for fluorescence emission of the partner GFP. By using specific inhibitors of CXCR4 binding, we have demonstrated that the engineered protein particles are able to penetrate CXCR4+ cells, in a receptor-mediated way, without toxicity or visible cytopathic effects, proving the availability of the peptide ligands on the surface of inclusion bodies. Since no further modification is required upon their purification, the biological production of genetically targeted inclusion bodies opens a plethora of cost-effective possibilities in the tissue-specific intracellular transfer of functional proteins through the use of structurally and functionally tailored soft materials.

  10. Conserved phosphoryl transfer mechanisms within kinase families and the role of the C8 proton of ATP in the activation of phosphoryl transfer

    PubMed Central

    2012-01-01

    Background The kinome is made up of a large number of functionally diverse enzymes, with the classification indicating very little about the extent of the conserved kinetic mechanisms associated with phosphoryl transfer. It has been demonstrated that C8-H of ATP plays a critical role in the activity of a range of kinase and synthetase enzymes. Results A number of conserved mechanisms within the prescribed kinase fold families have been identified directly utilizing the C8-H of ATP in the initiation of phosphoryl transfer. These mechanisms are based on structurally conserved amino acid residues that are within hydrogen bonding distance of a co-crystallized nucleotide. On the basis of these conserved mechanisms, the role of the nucleotide C8-H in initiating the formation of a pentavalent intermediate between the γ-phosphate of the ATP and the substrate nucleophile is defined. All reactions can be clustered into two mechanisms by which the C8-H is induced to be labile via the coordination of a backbone carbonyl to C6-NH2 of the adenyl moiety, namely a "push" mechanism, and a "pull" mechanism, based on the protonation of N7. Associated with the "push" mechanism and "pull" mechanisms are a series of proton transfer cascades, initiated from C8-H, via the tri-phosphate backbone, culminating in the formation of the pentavalent transition state between the γ-phosphate of the ATP and the substrate nucleophile. Conclusions The "push" mechanism and a "pull" mechanism are responsible for inducing the C8-H of adenyl moiety to become more labile. These mechanisms and the associated proton transfer cascades achieve the proton transfer via different family-specific conserved sets of amino acids. Each of these mechanisms would allow for the regulation of the rate of formation of the pentavalent intermediate between the ATP and the substrate nucleophile. Phosphoryl transfer within kinases is therefore a specific event mediated and regulated via the coordination of the adenyl moiety of ATP and the C8-H of the adenyl moiety. PMID:22397702

  11. Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy

    PubMed Central

    Powell, Daniel J.; Dudley, Mark E.; Robbins, Paul F.; Rosenberg, Steven A.

    2007-01-01

    In humans, the pathways of memory T-cell differentiation remain poorly defined. Recently, adoptive cell transfer (ACT) of tumor-reactive T lymphocytes to metastatic melanoma patients after nonmyeloablative chemotherapy has resulted in persistence of functional, tumor-reactive lymphocytes, regression of disease, and induction of melanocyte-directed autoimmunity in some responding patients. In the current study, longitudinal phenotypic analysis was performed on melanoma antigen–specific CD8+ T cells during their transition from in vitro cultured effector cells to long-term persistent memory cells following ACT to 6 responding patients. Tumor-reactive T cells used for therapy were generally late-stage effector cells with a CD27Lo CD28Lo CD45RA− CD62 ligand− (CD62L−) CC chemokine receptor 7− (CCR7−) interleukin-7 receptor αLo (IL-7RαLo) phenotype. After transfer, rapid up-regulation and continued expression of IL-7Rα in vivo suggested an important role for IL-7R in immediate and long-term T-cell survival. Although the tumor antigen–specific T-cell population contracted between 1 and 4 weeks after transfer, stable numbers of CD27+ CD28+ tumor-reactive T cells were maintained, demonstrating their contribution to the development of long-term, melanoma-reactive memory CD8+ T cells in vivo. At 2 months after transfer, melanoma-reactive T cells persisted at high levels and displayed an effector memory phenotype, including a CD27+ CD28+ CD62L− CCR7− profile, which may explain in part their ability to mediate tumor destruction. PMID:15345595

  12. Coarse-Grained Theory of Biological Charge Transfer with Spatially and Temporally Correlated Noise.

    PubMed

    Liu, Chaoren; Beratan, David N; Zhang, Peng

    2016-04-21

    System-environment interactions are essential in determining charge-transfer (CT) rates and mechanisms. We developed a computationally accessible method, suitable to simulate CT in flexible molecules (i.e., DNA) with hundreds of sites, where the system-environment interactions are explicitly treated with numerical noise modeling of time-dependent site energies and couplings. The properties of the noise are tunable, providing us a flexible tool to investigate the detailed effects of correlated thermal fluctuations on CT mechanisms. The noise is parametrizable by molecular simulation and quantum calculation results of specific molecular systems, giving us better molecular resolution in simulating the system-environment interactions than sampling fluctuations from generic spectral density functions. The spatially correlated thermal fluctuations among different sites are naturally built-in in our method but are not readily incorporated using approximate spectral densities. Our method has quantitative accuracy in systems with small redox potential differences (

  13. Single-Molecule Interfacial Electron Transfer

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

    Lu, H. Peter

    This project is focused on the use of single-molecule high spatial and temporal resolved techniques to study molecular dynamics in condensed phase and at interfaces, especially, the complex reaction dynamics associated with electron and energy transfer rate processes. The complexity and inhomogeneity of the interfacial ET dynamics often present a major challenge for a molecular level comprehension of the intrinsically complex systems, which calls for both higher spatial and temporal resolutions at ultimate single-molecule and single-particle sensitivities. Combined single-molecule spectroscopy and electrochemical atomic force microscopy approaches are unique for heterogeneous and complex interfacial electron transfer systems because the static andmore » dynamic inhomogeneities can be identified and characterized by studying one molecule at a specific nanoscale surface site at a time. The goal of our project is to integrate and apply these spectroscopic imaging and topographic scanning techniques to measure the energy flow and electron flow between molecules and substrate surfaces as a function of surface site geometry and molecular structure. We have been primarily focusing on studying interfacial electron transfer under ambient condition and electrolyte solution involving both single crystal and colloidal TiO 2 and related substrates. The resulting molecular level understanding of the fundamental interfacial electron transfer processes will be important for developing efficient light harvesting systems and broadly applicable to problems in fundamental chemistry and physics. We have made significant advancement on deciphering the underlying mechanism of the complex and inhomogeneous interfacial electron transfer dynamics in dyesensitized TiO 2 nanoparticle systems that strongly involves with and regulated by molecule-surface interactions. We have studied interfacial electron transfer on TiO 2 nanoparticle surfaces by using ultrafast single-molecule spectroscopy and electrochemical AFM metal tip scanning microscopy, focusing on understanding the interfacial electron transfer dynamics at specific nanoscale electron transfer sites with high-spatially and temporally resolved topographic-and-spectroscopic characterization at individual molecule basis, characterizing single-molecule rate processes, reaction driving force, and molecule-substrate electronic coupling. One of the most significant characteristics of our new approach is that we are able to interrogate the complex interfacial electron transfer dynamics by actively pin-point energetic manipulation of the surface interaction and electronic couplings, beyond the conventional excitation and observation.« less

  14. Antigen-specific T-cell lines transfer protective immunity against Trichinella spiralis in vivo.

    PubMed Central

    Riedlinger, J; Grencis, R K; Wakelin, D

    1986-01-01

    T-cell lines specific for infective muscle larvae antigens of the intestinal nematode Trichinella spiralis have been generated in vitro. These antigen-specific T-cell lines express the L3T4+ Ly2- phenotype and secrete the lymphokines IL-2, IL-3 and gamma-IFN. They are stable in culture for up to 15 weeks and are protective when adoptively transferred into naive recipients. As few as 2 x 10(5) T. spiralis-specific tract. In addition, intestinal mastocytosis and peripheral blood eosinophilia were accelerated after adoptive transfer of T. spiralis-specific T-cell lines. PMID:2423438

  15. On the role of covarying functions in stimulus class formation and transfer of function.

    PubMed Central

    Markham, Rebecca G; Markham, Michael R

    2002-01-01

    This experiment investigated whether directly trained covarying functions are necessary for stimulus class formation and transfer of function in humans. Initial class training was designed to establish two respondent-based stimulus classes by pairing two visual stimuli with shock and two other visual stimuli with no shock. Next, two operant discrimination functions were trained to one stimulus of each putative class. The no-shock group received the same training and testing in all phases, except no stimuli were ever paired with shock. The data indicated that skin conductance response conditioning did not occur for the shock groups or for the no-shock group. Tests showed transfer of the established discriminative functions, however, only for the shock groups, indicating the formation of two stimulus classes only for those participants who received respondent class training. The results suggest that transfer of function does not depend on first covarying the stimulus class functions. PMID:12507017

  16. Performance considerations for high-definition head-mounted displays

    NASA Technical Reports Server (NTRS)

    Edwards, Oliver J.; Larimer, James; Gille, Jennifer

    1992-01-01

    Design image-optimization for helmet-mounted displays (HMDs) for military systems is presently discussed within the framework of a systems-engineering approach that encompasses (1) a description of natural targets in the field; (2) the characteristics of human visual perception; and (3) device specifications that directly relate to these ecological and human-factors parameters. Attention is given to target size and contrast and the relationship of the modulation transfer function to image resolution.

  17. Automatic transfer function design for medical visualization using visibility distributions and projective color mapping.

    PubMed

    Cai, Lile; Tay, Wei-Liang; Nguyen, Binh P; Chui, Chee-Kong; Ong, Sim-Heng

    2013-01-01

    Transfer functions play a key role in volume rendering of medical data, but transfer function manipulation is unintuitive and can be time-consuming; achieving an optimal visualization of patient anatomy or pathology is difficult. To overcome this problem, we present a system for automatic transfer function design based on visibility distribution and projective color mapping. Instead of assigning opacity directly based on voxel intensity and gradient magnitude, the opacity transfer function is automatically derived by matching the observed visibility distribution to a target visibility distribution. An automatic color assignment scheme based on projective mapping is proposed to assign colors that allow for the visual discrimination of different structures, while also reflecting the degree of similarity between them. When our method was tested on several medical volumetric datasets, the key structures within the volume were clearly visualized with minimal user intervention. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Redox active molecules cytochrome c and vitamin C enhance heme-enzyme peroxidations by serving as non-specific agents for redox relay

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

    Gade, Sudeep Kumar; Bhattacharya, Subarna; Manoj, Kelath Murali, E-mail: satyamjayatu@yahoo.com

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer At low concentrations, cytochrome c/vitamin C do not catalyze peroxidations. Black-Right-Pointing-Pointer But low levels of cytochrome c/vitamin C enhance diverse heme peroxidase activities. Black-Right-Pointing-Pointer Enhancement positively correlates to the concentration of peroxide in reaction. Black-Right-Pointing-Pointer Reducible additives serve as non-specific agents for redox relay in the system. Black-Right-Pointing-Pointer Insight into electron transfer processes in routine and oxidative-stress states. -- Abstract: We report that incorporation of very low concentrations of redox protein cytochrome c and redox active small molecule vitamin C impacted the outcome of one-electron oxidations mediated by structurally distinct plant/fungal heme peroxidases. Evidence suggests that cytochrome cmore » and vitamin C function as a redox relay for diffusible reduced oxygen species in the reaction system, without invoking specific or affinity-based molecular interactions for electron transfers. The findings provide novel perspectives to understanding - (1) the promiscuous role of cytochrome b{sub 5} in the metabolism mediated by liver microsomal xenobiotic metabolizing systems and (2) the roles of antioxidant molecules in affording relief from oxidative stress.« less

  19. Discovering cultural differences (and similarities) in facial expressions of emotion.

    PubMed

    Chen, Chaona; Jack, Rachael E

    2017-10-01

    Understanding the cultural commonalities and specificities of facial expressions of emotion remains a central goal of Psychology. However, recent progress has been stayed by dichotomous debates (e.g. nature versus nurture) that have created silos of empirical and theoretical knowledge. Now, an emerging interdisciplinary scientific culture is broadening the focus of research to provide a more unified and refined account of facial expressions within and across cultures. Specifically, data-driven approaches allow a wider, more objective exploration of face movement patterns that provide detailed information ontologies of their cultural commonalities and specificities. Similarly, a wider exploration of the social messages perceived from face movements diversifies knowledge of their functional roles (e.g. the 'fear' face used as a threat display). Together, these new approaches promise to diversify, deepen, and refine knowledge of facial expressions, and deliver the next major milestones for a functional theory of human social communication that is transferable to social robotics. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Sex-specific triacylglycerides are widely conserved in Drosophila and mediate mating behavior

    PubMed Central

    Chin, Jacqueline SR; Ellis, Shane R; Pham, Huong T; Blanksby, Stephen J; Mori, Kenji; Koh, Qi Ling; Etges, William J; Yew, Joanne Y

    2014-01-01

    Pheromones play an important role in the behavior, ecology, and evolution of many organisms. The structure of many insect pheromones typically consists of a hydrocarbon backbone, occasionally modified with various functional oxygen groups. Here we show that sex-specific triacylclyerides (TAGs) are broadly conserved across the subgenus Drosophila in 11 species and represent a novel class of pheromones that has been largely overlooked. In desert-adapted drosophilids, 13 different TAGs are secreted exclusively by males from the ejaculatory bulb, transferred to females during mating, and function synergistically to inhibit courtship from other males. Sex-specific TAGs are comprised of at least one short branched tiglic acid and a long linear fatty acyl component, an unusual structural motif that has not been reported before in other natural products. The diversification of chemical cues used by desert-adapted Drosophila as pheromones may be related to their specialized diet of fermenting cacti. DOI: http://dx.doi.org/10.7554/eLife.01751.001 PMID:24618898

  1. Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes.

    PubMed

    Dindar, Gülcin; Anger, Andreas M; Mehlhorn, Christine; Hake, Sandra B; Janzen, Christian J

    2014-11-12

    DOT1 enzymes are conserved methyltransferases that catalyse the methylation of lysine 79 on histone H3 (H3K79). Most eukaryotes contain one DOT1 enzyme, whereas African trypanosomes have two homologues, DOT1A and DOT1B, with different enzymatic activities. DOT1A mediates mono- and dimethylation of H3K76, the homologue of H3K79 in other organisms, whereas DOT1B additionally catalyses H3K76 trimethylation. However, it is unclear how these different enzymatic activities are achieved. Here we employ a trypanosomal nucleosome reconstitution system and structure-guided homology modelling to identify critical residues within and outside the catalytic centre that modulate product specificity. Exchange of these residues transfers the product specificity from one enzyme to the other, and reveals the existence of distinct regulatory domains adjacent to the catalytic centre. Our study provides the first evidence that a few crucial residues in DOT1 enzymes are sufficient to catalyse methyl-state-specific reactions. These results might also have far-reaching consequences for the functional understanding of homologous enzymes in higher eukaryotes.

  2. LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3

    DOE PAGES

    Golczak, Marcin; Sears, Avery E.; Kiser, Philip D.; ...

    2014-11-10

    Cellular uptake of vitamin A, production of visual chromophore and triglyceride homeostasis in adipocytes depend on two representatives of the vertebrate N1pC/P60 protein family, lecithin:retinol acyltransferase (LRAT) and HRAS-like tumor suppressor 3 (HRASLS3). Both proteins function as lipid-metabolizing enzymes but differ in their substrate preferences and dominant catalytic activity. The mechanism of this catalytic diversity is not understood. In this paper, by using a gain-of-function approach, we identified a specific sequence responsible for the substrate specificity of N1pC/P60 proteins. A 2.2-Å crystal structure of the HRASLS3-LRAT chimeric enzyme in a thioester catalytic intermediate state revealed a major structural rearrangement accompaniedmore » by three-dimensional domain swapping dimerization not observed in native HRASLS proteins. Structural changes affecting the active site environment contributed to slower hydrolysis of the catalytic intermediate, supporting efficient acyl transfer. Finally, these findings reveal structural adaptation that facilitates selective catalysis and mechanism responsible for diverse substrate specificity within the LRAT-like enzyme family.« less

  3. Evaluation of UDP-GlcN derivatives for selective labeling of 5-(hydroxymethyl)cytosine.

    PubMed

    Dai, Nan; Bitinaite, Jurate; Chin, Hang-Gyeong; Pradhan, Sriharsa; Corrêa, Ivan R

    2013-11-04

    5-(hydroxymethyl)cytosine (5-hmC) is a newly identified oxidative product of 5-methylcytosine (5-mC) in the mammalian genome, and is believed to be an important epigenetic marker influencing a variety of biological processes. In addition to its relatively low abundance, the fluctuation of 5-hmC levels over time during cell development poses a formidable challenge for its accurate mapping and quantification. Here we describe a specific chemoenzymatic approach to 5-hmC detection in DNA samples by using new uridine 5'-diphosphoglucosamine (UDP-GlcN) probes. Our approach requires modification of the glucose moiety of UDP-Glc with small amino groups and transfer of these glucose derivatives to the hydroxy moiety of 5-hmC by using T4 phage glucosyltransferases. We evaluated the transfer efficiencies of three glucosyltransferases (wild-type α- and β-GTs and a Y261L mutant β-GT) with five different UDP-Glc derivatives containing functionalized groups for subsequent bioconjugation and detection. Our results indicate that UDP-6-N3 -Glc, UDP-6-GlcN, and UDP-2-GlcN can be transferred by β-GT with efficiencies similar to that seen with the native UDP-Glc cofactor. 6-N3 -Glc- and 6-GlcN-containing oligonucleotides were selectively labeled with reactive fluorescent probes. In addition, a 2 kb DNA fragment modified with 2-GlcN groups was specifically detected by use of a commercially available antiglucosamine antibody. Alternative substrates for β-GT and correlated glycosyltransferases might prove useful for the study of the function and dynamics of 5-hmC and other modified nucleotides, as well as for multiplex analysis. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Transfer of allogeneic CD4+ T cells rescues CD8+ T cells in anti-PD-L1–resistant tumors leading to tumor eradication

    PubMed Central

    Arina, Ainhoa; Karrison, Theodore; Galka, Eva; Schreiber, Karin; Weichselbaum, Ralph R.; Schreiber, Hans

    2017-01-01

    Adoptively transferred CD8+ T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell–mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule Kb needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8+ T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months. Escape was associated with reduced numbers of circulating 2C cells. Tumor-infiltrating 2C cells produced significantly less TNFα and expressed more of the “exhaustion” markers PD-1 and Tim-3 than T cells from lymphoid organs. High-dose local ionizing radiation, depletion of myeloid-derived suppressor cells, infusions of additional 2C cells, and antibodies blocking PD-L1 did not prevent tumor escape. In contrast, adoptive transfer of allogeneic CD4+ T cells restored the numbers of circulating Ag-specific CD8+ T cells and their intratumoral function, resulting in tumor eradication. These CD4+ T cells had no antitumor effects in the absence of CD8+ T cells and recognized the alloantigen cross-presented on tumor stroma. CD4+ T cells might also be effective in cancer patients when PD1/PD-L1 blockade does not rescue intratumoral CD8+ T-cell function and tumors persist. PMID:28077434

  5. Rehabilitation of executive functioning in patients with frontal lobe brain damage with goal management training.

    PubMed

    Levine, Brian; Schweizer, Tom A; O'Connor, Charlene; Turner, Gary; Gillingham, Susan; Stuss, Donald T; Manly, Tom; Robertson, Ian H

    2011-01-01

    Executive functioning deficits due to brain disease affecting frontal lobe functions cause significant real-life disability, yet solid evidence in support of executive functioning interventions is lacking. Goal Management Training (GMT), an executive functioning intervention that draws upon theories concerning goal processing and sustained attention, has received empirical support in studies of patients with traumatic brain injury, normal aging, and case studies. GMT promotes a mindful approach to complex real-life tasks that pose problems for patients with executive functioning deficits, with a main goal of periodically stopping ongoing behavior to monitor and adjust goals. In this controlled trial, an expanded version of GMT was compared to an alternative intervention, Brain Health Workshop that was matched to GMT on non-specific characteristics that can affect intervention outcome. Participants included 19 individuals in the chronic phase of recovery from brain disease (predominantly stroke) affecting frontal lobe function. Outcome data indicated specific effects of GMT on the Sustained Attention to Response Task as well as the Tower Test, a visuospatial problem-solving measure that reflected far transfer of training effects. There were no significant effects on self-report questionnaires, likely owing to the complexity of these measures in this heterogeneous patient sample. Overall, these data support the efficacy of GMT in the rehabilitation of executive functioning deficits.

  6. Evaluation of nerve transfer options for treating total brachial plexus avulsion injury: a retrospective study of 73 participants

    PubMed Central

    Gao, Kai-ming; Hu, Jing-jing; Lao, Jie; Zhao, Xin

    2018-01-01

    Despite recent great progress in diagnosis and microsurgical repair, the prognosis in total brachial plexus-avulsion injury remains unfavorable. Insufficient number of donors and unreasonable use of donor nerves might be key factors. To identify an optimal treatment strategy for this condition, we conducted a retrospective review. Seventy-three patients with total brachial plexus avulsion injury were followed up for an average of 7.3 years. Our analysis demonstrated no significant difference in elbow-flexion recovery between phrenic nerve-transfer (25 cases), phrenic nerve-graft (19 cases), intercostal nerve (17 cases), or contralateral C7-transfer (12 cases) groups. Restoration of shoulder function was attempted through anterior accessory nerve (27 cases), posterior accessory nerve (10 cases), intercostal nerve (5 cases), or accessory + intercostal nerve transfer (31 cases). Accessory nerve + intercostal nerve transfer was the most effective method. A significantly greater amount of elbow extension was observed in patients with intercostal nerve transfer (25 cases) than in those with contralateral C7 transfer (10 cases). Recovery of median nerve function was noticeably better for those who received entire contralateral C7 transfer (33 cases) than for those who received partial contralateral C7 transfer (40 cases). Wrist and finger extension were reconstructed by intercostal nerve transfer (31 cases). Overall, the recommended surgical treatment for total brachial plexus-avulsion injury is phrenic nerve transfer for elbow flexion, accessory nerve + intercostal nerve transfer for shoulder function, intercostal nerves transfer for elbow extension, entire contralateral C7 transfer for median nerve function, and intercostal nerve transfer for finger extension. The trial was registered at ClinicalTrials.gov (identifier: NCT03166033). PMID:29623932

  7. Evaluation of nerve transfer options for treating total brachial plexus avulsion injury: A retrospective study of 73 participants.

    PubMed

    Gao, Kai-Ming; Hu, Jing-Jing; Lao, Jie; Zhao, Xin

    2018-03-01

    Despite recent great progress in diagnosis and microsurgical repair, the prognosis in total brachial plexus-avulsion injury remains unfavorable. Insufficient number of donors and unreasonable use of donor nerves might be key factors. To identify an optimal treatment strategy for this condition, we conducted a retrospective review. Seventy-three patients with total brachial plexus avulsion injury were followed up for an average of 7.3 years. Our analysis demonstrated no significant difference in elbow-flexion recovery between phrenic nerve-transfer (25 cases), phrenic nerve-graft (19 cases), intercostal nerve (17 cases), or contralateral C 7 -transfer (12 cases) groups. Restoration of shoulder function was attempted through anterior accessory nerve (27 cases), posterior accessory nerve (10 cases), intercostal nerve (5 cases), or accessory + intercostal nerve transfer (31 cases). Accessory nerve + intercostal nerve transfer was the most effective method. A significantly greater amount of elbow extension was observed in patients with intercostal nerve transfer (25 cases) than in those with contralateral C 7 transfer (10 cases). Recovery of median nerve function was noticeably better for those who received entire contralateral C 7 transfer (33 cases) than for those who received partial contralateral C 7 transfer (40 cases). Wrist and finger extension were reconstructed by intercostal nerve transfer (31 cases). Overall, the recommended surgical treatment for total brachial plexus-avulsion injury is phrenic nerve transfer for elbow flexion, accessory nerve + intercostal nerve transfer for shoulder function, intercostal nerves transfer for elbow extension, entire contralateral C 7 transfer for median nerve function, and intercostal nerve transfer for finger extension. The trial was registered at ClinicalTrials.gov (identifier: NCT03166033).

  8. Delayed excitatory and inhibitory feedback shape neural information transmission

    NASA Astrophysics Data System (ADS)

    Chacron, Maurice J.; Longtin, André; Maler, Leonard

    2005-11-01

    Feedback circuitry with conduction and synaptic delays is ubiquitous in the nervous system. Yet the effects of delayed feedback on sensory processing of natural signals are poorly understood. This study explores the consequences of delayed excitatory and inhibitory feedback inputs on the processing of sensory information. We show, through numerical simulations and theory, that excitatory and inhibitory feedback can alter the firing frequency response of stochastic neurons in opposite ways by creating dynamical resonances, which in turn lead to information resonances (i.e., increased information transfer for specific ranges of input frequencies). The resonances are created at the expense of decreased information transfer in other frequency ranges. Using linear response theory for stochastically firing neurons, we explain how feedback signals shape the neural transfer function for a single neuron as a function of network size. We also find that balanced excitatory and inhibitory feedback can further enhance information tuning while maintaining a constant mean firing rate. Finally, we apply this theory to in vivo experimental data from weakly electric fish in which the feedback loop can be opened. We show that it qualitatively predicts the observed effects of inhibitory feedback. Our study of feedback excitation and inhibition reveals a possible mechanism by which optimal processing may be achieved over selected frequency ranges.

  9. Medicago truncatula Mtha1-2 mutants loose metabolic responses to mycorrhizal colonization.

    PubMed

    Hubberten, Hans-Michael; Sieh, Daniela; Zöller, Daniela; Hoefgen, Rainer; Krajinski, Franziska

    2015-01-01

    Bidirectional nutrient transfer is one of the key features of the arbuscular mycorrhizal symbiosis. Recently we were able to identify a Medicago truncatula mutant (mtha1-2) that is defective in the uptake of phosphate from the periarbuscular space due to a lack of the energy providing proton gradient provided by the symbiosis specific proton ATPase MtHA1 In order to further characterize the impact of fungal colonization on the plant metabolic status, without the beneficial aspect of improved mineral nutrition, we performed leaf ion analyses in mutant and wildtype plants with and without fungal colonization. Although frequency of fungal colonization was unaltered, the mutant did not show a positive growth response to mycorrhizal colonization. This indicates that nutrient transfer into the plant cell fails in the truncated arbuscules due to lacking expression of a functional MtHA1 protein. The leaves of wildtype plants showed clear metabolic responses to root mycorrhizal colonization, whereas no changes of leaf metabolite levels of mycorrhizal mtha1-2 plants were detected, even though they were colonized. These results show that MtHa1 is indispensable for a functional mycorrhizal symbiosis and, moreover, suggest that fungal root colonization per se does not depend on nutrient transfer to the plant host.

  10. Numerical investigations in three-dimensional internal flows

    NASA Astrophysics Data System (ADS)

    Rose, William C.

    1988-08-01

    An investigation into the use of computational fluid dynamics (CFD) was performed to examine the expected heat transfer rates that will occur within the NASA-Ames 100 megawatt arc heater nozzle. This nozzle was tentatively designed and identified to provide research for a directly connected combustion experiment specifically related to the National Aerospace Plane Program (NASP) aircraft, and is expected to simulate the flow field entering the combustor section. It was found that extremely fine grids, that is very small mesh spacing near the wall, are required to accurately model the heat transfer process and, in fact, must contain a point within the laminar sublayer if results are to be taken directly from a numerical simulation code. In the present study, an alternative to this very fine mesh and its attendant increase in computational time was invoked and is based on a wall-function method. It was shown that solutions could be obtained that give accurate indications of surface heat transfer rate throughout the nozzle in approximately 1/100 of the computer time required to do the simulation directly without the use of the wall-function implementation. Finally, a maximum heating value in the throat region of the proposed slit nozzle for the 100 megawatt arc heater was shown to be approximately 6 MW per square meter.

  11. Coupling the Multizone Airflow and Contaminant Transport Software CONTAM with EnergyPlus Using Co-Simulation.

    PubMed

    Dols, W Stuart; Emmerich, Steven J; Polidoro, Brian J

    2016-08-01

    Building modelers need simulation tools capable of simultaneously considering building energy use, airflow and indoor air quality (IAQ) to design and evaluate the ability of buildings and their systems to meet today's demanding energy efficiency and IAQ performance requirements. CONTAM is a widely-used multizone building airflow and contaminant transport simulation tool that requires indoor temperatures as input values. EnergyPlus is a prominent whole-building energy simulation program capable of performing heat transfer calculations that require interzone and infiltration airflows as input values. On their own, each tool is limited in its ability to account for thermal processes upon which building airflow may be significantly dependent and vice versa. This paper describes the initial phase of coupling of CONTAM with EnergyPlus to capture the interdependencies between airflow and heat transfer using co-simulation that allows for sharing of data between independently executing simulation tools. The coupling is accomplished based on the Functional Mock-up Interface (FMI) for Co-simulation specification that provides for integration between independently developed tools. A three-zone combined heat transfer/airflow analytical BESTEST case was simulated to verify the co-simulation is functioning as expected, and an investigation of a two-zone, natural ventilation case designed to challenge the coupled thermal/airflow solution methods was performed.

  12. Human mitochondrial disease-like symptoms caused by a reduced tRNA aminoacylation activity in flies

    PubMed Central

    Guitart, Tanit; Picchioni, Daria; Piñeyro, David; Ribas de Pouplana, Lluís

    2013-01-01

    The translation of genes encoded in the mitochondrial genome requires specific machinery that functions in the organelle. Among the many mutations linked to human disease that affect mitochondrial translation, several are localized to nuclear genes coding for mitochondrial aminoacyl-transfer RNA synthetases. The molecular significance of these mutations is poorly understood, but it is expected to be similar to that of the mutations affecting mitochondrial transfer RNAs. To better understand the molecular features of diseases caused by these mutations, and to improve their diagnosis and therapeutics, we have constructed a Drosophila melanogaster model disrupting the mitochondrial seryl-tRNA synthetase by RNA interference. At the molecular level, the knockdown generates a reduction in transfer RNA serylation, which correlates with the severity of the phenotype observed. The silencing compromises viability, longevity, motility and tissue development. At the cellular level, the knockdown alters mitochondrial morphology, biogenesis and function, and induces lactic acidosis and reactive oxygen species accumulation. We report that administration of antioxidant compounds has a palliative effect of some of these phenotypes. In conclusion, the fly model generated in this work reproduces typical characteristics of pathologies caused by mutations in the mitochondrial aminoacylation system, and can be useful to assess therapeutic approaches. PMID:23677612

  13. Specificity and Transfer in Learning How to Follow Navigation Instructions

    NASA Technical Reports Server (NTRS)

    Healy, Alice F.; Schneider, Vivian L.; Barshi, Immanuel

    2012-01-01

    We report a series of experiments that use a navigation task in which instructions for navigating in a space displayed as grids on a computer screen are given to subjects who then attempt to follow them by mouse clicking on the grids. The navigation task was broken down into component dimensions (e.g., presentation mode of the instructions, length of the instructions, characteristics of the display, size of the grids, response type). For each task dimension, one condition was used at training and the same or another condition was used at test. Each task dimension was examined in terms of two measures. One measure provided an index of transfer (i.e., better performance at test than at training when test and training involved different conditions), and the other provided an index of specificity (i.e., better performance at test when training and test conditions were the same than when training and test conditions were different). By and large, these two indices were complementary, so there was evidence of either transfer or specificity but not both. For one dimension transfer but no specificity was evident, and for another dimension specificity but no transfer was evident. For the remaining dimensions, however, there was asymmetrical transfer, with transfer evident for some conditions and specificity evident for others. The findings are interpreted within the procedural reinstatement framework. They have practical implications concerning how to optimize training and how much fidelity to the testing situation is necessary when training.

  14. Probing membrane protein structure using water polarization transfer solid-state NMR.

    PubMed

    Williams, Jonathan K; Hong, Mei

    2014-10-01

    Water plays an essential role in the structure and function of proteins, lipid membranes and other biological macromolecules. Solid-state NMR heteronuclear-detected (1)H polarization transfer from water to biomolecules is a versatile approach for studying water-protein, water-membrane, and water-carbohydrate interactions in biology. We review radiofrequency pulse sequences for measuring water polarization transfer to biomolecules, the mechanisms of polarization transfer, and the application of this method to various biological systems. Three polarization transfer mechanisms, chemical exchange, spin diffusion and NOE, manifest themselves at different temperatures, magic-angle-spinning frequencies, and pulse irradiations. Chemical exchange is ubiquitous in all systems examined so far, and spin diffusion plays the key role in polarization transfer within the macromolecule. Tightly bound water molecules with long residence times are rare in proteins at ambient temperature. The water polarization-transfer technique has been used to study the hydration of microcrystalline proteins, lipid membranes, and plant cell wall polysaccharides, and to derive atomic-resolution details of the kinetics and mechanism of ion conduction in channels and pumps. Using this approach, we have measured the water polarization transfer to the transmembrane domain of the influenza M2 protein to obtain information on the structure of this tetrameric proton channel. At short mixing times, the polarization transfer rates are site-specific and depend on the pH, labile protons, sidechain conformation, as well as the radial position of the residues in this four-helix bundle. Despite the multiple dependences, the initial transfer rates reflect the periodic nature of the residue positions from the water-filled pore, thus this technique provides a way of gleaning secondary structure information, helix tilt angle, and the oligomeric structure of membrane proteins. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. AMICAL: An aid for architectural synthesis and exploration of control circuits

    NASA Astrophysics Data System (ADS)

    Park, Inhag

    AMICAL is an architectural synthesis system for control flow dominated circuits. A behavioral finite state machine specification, where the scheduling and register allocation were performed, is presented. An abstract architecture specification that may feed existing silicon compilers acting at the logic and register transfer levels is described. AMICAL consists of five main functions allowing automatic, interactive and manual synthesis, as well as the combination of these methods. These functions are a synthesizer, a graphics editor, a verifier, an evaluator, and a documentor. Automatic synthesis is achieved by algorithms that allocate both functional units, stored in an expandable user defined library, and connections. AMICAL also allows the designer to interrupt the synthesis process at any stage and make interactive modifications via a specially designed graphics editor. The user's modifications are verified and evaluated to ensure that no design rules are broken and that any imposed constraints are still met. A documentor provides the designer with status and feedback reports from the synthesis process.

  16. Performance of SEM scintillation detector evaluated by modulation transfer function and detective quantum efficiency function.

    PubMed

    Bok, Jan; Schauer, Petr

    2014-01-01

    In the paper, the SEM detector is evaluated by the modulation transfer function (MTF) which expresses the detector's influence on the SEM image contrast. This is a novel approach, since the MTF was used previously to describe only the area imaging detectors, or whole imaging systems. The measurement technique and calculation of the MTF for the SEM detector are presented. In addition, the measurement and calculation of the detective quantum efficiency (DQE) as a function of the spatial frequency for the SEM detector are described. In this technique, the time modulated e-beam is used in order to create well-defined input signal for the detector. The MTF and DQE measurements are demonstrated on the Everhart-Thornley scintillation detector. This detector was alternated using the YAG:Ce, YAP:Ce, and CRY18 single-crystal scintillators. The presented MTF and DQE characteristics show good imaging properties of the detectors with the YAP:Ce or CRY18 scintillator, especially for a specific type of the e-beam scan. The results demonstrate the great benefit of the description of SEM detectors using the MTF and DQE. In addition, point-by-point and continual-sweep e-beam scans in SEM were discussed and their influence on the image quality was revealed using the MTF. © 2013 Wiley Periodicals, Inc.

  17. Alterations in blood-brain barrier function following acute hypertension: comparison of the blood-to-brain transfer of horseradish peroxidase with that of alpha-aminisobutyric acid

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

    Ellison, M.D.B.

    The blood-brain barrier (BBB) selectively restricts the blood-to-brain passage of many solutes owing to unique properties of cerebrovascular endothelial cell membranes. To date, experimental study of the BBB has been accomplished primarily through the use of two different methodological approaches. Morphological studies have mostly employed large molecular weight (MW) tracers to detect morphological alterations underlying increased permeability. Physiological studies, employing smaller, more physiologic tracers have successfully described, quantitatively, certain functional aspects of blood-to-brain transfer. The current work attempts to merge these two approaches and to consider barrier function/dysfunction from both a morphological and a functional perspective. Specifically, the study comparesmore » in rats, following acute hypertension, the cerebrovascular passage of /sup 14/C-alpha-aminoisobutyric acid (AIB) and that of horseradish peroxidase (HRP). The blood-to-brain passage of AIB and HRP were compared following acute hypertension, with regard to both the distributions of the tracer extravasation patterns and the magnitude of tracer extravasation. The results of this study suggest that traditional morphological barrier studies alone do not reveal all aspects of altered barrier status and that multiple mechanisms underlying increased BBB permeability may operate simultaneously during BBB dysfunction.« less

  18. Treatment of adolescents with depression: the effect of transference interventions in a randomized controlled study of dynamic psychotherapy

    PubMed Central

    2012-01-01

    Background Depression in adolescents seems to be a growing problem that causes mental suffering and prevents young people from joining the workforce. There is also a high risk of relapse during adult life. There is emerging evidence for the effect of psychodynamic psychotherapy in adolescents. In-session relational intervention (that is, transference intervention) is a key component of psychodynamic psychotherapy. However, whether depressed adolescents profit most from psychodynamic psychotherapy with or without transference interventions has not been stated. Object The effect of transference interventions in depressed adolescents and the moderator moderating effect of quality of object relations, personality disorder and gender will be explored. Methods and study design The First Experimental Study of Transference Work–In Teenagers (FEST–IT) will be a randomized clinical trial with a dismantling design. The study is aimed to explore the effects of transference work in psychodynamic psychotherapy for adolescents with depression. One hundred patients ages 16 to 18 years old will be randomized to one of two treatment groups, in both of which general psychodynamic techniques will be used. The patients will be treated over 28 weeks with either a moderate level of transference intervention or no transference intervention. Follow-up will be at 1 year after treatment termination. The outcome measures will be the Psychodynamic Functioning Scales (PFS), Inventory of Interpersonal Problems–Circumplex Version (IIP-C), Global Assessment of Functioning (GAF), and the total mean score of Symptom Checklist–90 (Global Severity Index; GSI), Beck Depression Inventory (BDI), and Montgomery Åsberg Rating Scale (MADRS). The quality of adolescents’ relationships will be a central focus of the study, and the Adolescent Relationship Scales (ARS) and Differentiation–Relatedness Scale (DRS) will also be used. Change will be assessed using linear-mixed models. Gender personality disorder (PD) and quality of object relations (QOR) will be the preselected putative moderators. Discussion The object of this clinical trial is to explore the effect of transference interventions in psychodynamic psychotherapy in adolescents with a major depressive disorder. Using a randomized and dismantling design, we hope that the study will add more specific knowledge to the evidence base. Trial registration ClinicalTrials.gov Identifier: NCT01531101 First Experimental Study of Transference work Work–In Teenagers (FEST-IT) PMID:22950546

  19. Treatment of adolescents with depression: the effect of transference interventions in a randomized controlled study of dynamic psychotherapy.

    PubMed

    Ulberg, Randi; Hersoug, Anne Grete; Høglend, Per

    2012-09-06

    Depression in adolescents seems to be a growing problem that causes mental suffering and prevents young people from joining the workforce. There is also a high risk of relapse during adult life. There is emerging evidence for the effect of psychodynamic psychotherapy in adolescents. In-session relational intervention (that is, transference intervention) is a key component of psychodynamic psychotherapy. However, whether depressed adolescents profit most from psychodynamic psychotherapy with or without transference interventions has not been stated. The effect of transference interventions in depressed adolescents and the moderator moderating effect of quality of object relations, personality disorder and gender will be explored. The First Experimental Study of Transference Work-In Teenagers (FEST-IT) will be a randomized clinical trial with a dismantling design. The study is aimed to explore the effects of transference work in psychodynamic psychotherapy for adolescents with depression. One hundred patients ages 16 to 18 years old will be randomized to one of two treatment groups, in both of which general psychodynamic techniques will be used. The patients will be treated over 28 weeks with either a moderate level of transference intervention or no transference intervention. Follow-up will be at 1 year after treatment termination. The outcome measures will be the Psychodynamic Functioning Scales (PFS), Inventory of Interpersonal Problems-Circumplex Version (IIP-C), Global Assessment of Functioning (GAF), and the total mean score of Symptom Checklist-90 (Global Severity Index; GSI), Beck Depression Inventory (BDI), and Montgomery Åsberg Rating Scale (MADRS). The quality of adolescents' relationships will be a central focus of the study, and the Adolescent Relationship Scales (ARS) and Differentiation-Relatedness Scale (DRS) will also be used. Change will be assessed using linear-mixed models. Gender personality disorder (PD) and quality of object relations (QOR) will be the preselected putative moderators. The object of this clinical trial is to explore the effect of transference interventions in psychodynamic psychotherapy in adolescents with a major depressive disorder. Using a randomized and dismantling design, we hope that the study will add more specific knowledge to the evidence base. ClinicalTrials.gov Identifier: NCT01531101First Experimental Study of Transference work Work-In Teenagers (FEST-IT).

  20. Tunable magnetotransport in Fe/hBN/graphene/hBN/Pt(Fe) epitaxial multilayers

    NASA Astrophysics Data System (ADS)

    Magnus Ukpong, Aniekan

    2018-03-01

    Theoretical and computational analysis of the magnetotransport properties and spin-transfer torque field-induced switching of magnetization density in vertically-stacked multilayers is presented. Using epitaxially-capped free layers of Pt and Fe, atom-resolved magnetic moments and spin-transfer torques are computed at finite bias. The calculations are performed within linear response approximation to the spin-density reformulation of the van der Waals density functional theory. Dynamical spin excitations are computed as a function of a spin-transfer torque induced magnetic field along the magnetic easy axis, and the corresponding spin polarization perpendicular to the easy axis is obtained. Bias-dependent giant anisotropic magnetoresistance of up to 3200% is obtained in the nonmagnetic-metal-capped Fe/hBN/graphene/hBN/Pt multilayer architecture. Since this specific heterostructure is not yet fabricated and characterized, the predicted high performance has not been demonstrated experimentally. Nevertheless, similar calculations performed on the Fe/hBN/Co stack show that the tunneling magnetoresistance obtained at the Fermi-level is in excellent agreement with results of recent magnetotransport measurements on magnetic tunnel junctions that contain the monolayer hBN tunnel region. The magnitude of the spin-transfer torque is found to increase as the tunneling spin current increases, and this activates the magnetization switching process due to increased charge accumulation. This mechanism causes substantial spin backflow, which manifests as rapid undulations in the bias-dependent tunneling spin currents. The implication of these findings on the design of nanoscale spintronic devices with spin-transfer torque tunable magnetization density is discussed. Insights derived from this study are expected to enhance the prospects for developing and integrating artificially assembled van der Waals multilayer heterostructures as the preferred material platform for efficient engineering of spin switches for spintronic applications.

  1. Social insect colony as a biological regulatory system: modelling information flow in dominance networks.

    PubMed

    Nandi, Anjan K; Sumana, Annagiri; Bhattacharya, Kunal

    2014-12-06

    Social insects provide an excellent platform to investigate flow of information in regulatory systems since their successful social organization is essentially achieved by effective information transfer through complex connectivity patterns among the colony members. Network representation of such behavioural interactions offers a powerful tool for structural as well as dynamical analysis of the underlying regulatory systems. In this paper, we focus on the dominance interaction networks in the tropical social wasp Ropalidia marginata-a species where behavioural observations indicate that such interactions are principally responsible for the transfer of information between individuals about their colony needs, resulting in a regulation of their own activities. Our research reveals that the dominance networks of R. marginata are structurally similar to a class of naturally evolved information processing networks, a fact confirmed also by the predominance of a specific substructure-the 'feed-forward loop'-a key functional component in many other information transfer networks. The dynamical analysis through Boolean modelling confirms that the networks are sufficiently stable under small fluctuations and yet capable of more efficient information transfer compared to their randomized counterparts. Our results suggest the involvement of a common structural design principle in different biological regulatory systems and a possible similarity with respect to the effect of selection on the organization levels of such systems. The findings are also consistent with the hypothesis that dominance behaviour has been shaped by natural selection to co-opt the information transfer process in such social insect species, in addition to its primal function of mediation of reproductive competition in the colony. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  2. Quantitative Analysis of the Effective Functional Structure in Yeast Glycolysis

    PubMed Central

    De la Fuente, Ildefonso M.; Cortes, Jesus M.

    2012-01-01

    The understanding of the effective functionality that governs the enzymatic self-organized processes in cellular conditions is a crucial topic in the post-genomic era. In recent studies, Transfer Entropy has been proposed as a rigorous, robust and self-consistent method for the causal quantification of the functional information flow among nonlinear processes. Here, in order to quantify the functional connectivity for the glycolytic enzymes in dissipative conditions we have analyzed different catalytic patterns using the technique of Transfer Entropy. The data were obtained by means of a yeast glycolytic model formed by three delay differential equations where the enzymatic rate equations of the irreversible stages have been explicitly considered. These enzymatic activity functions were previously modeled and tested experimentally by other different groups. The results show the emergence of a new kind of dynamical functional structure, characterized by changing connectivity flows and a metabolic invariant that constrains the activity of the irreversible enzymes. In addition to the classical topological structure characterized by the specific location of enzymes, substrates, products and feedback-regulatory metabolites, an effective functional structure emerges in the modeled glycolytic system, which is dynamical and characterized by notable variations of the functional interactions. The dynamical structure also exhibits a metabolic invariant which constrains the functional attributes of the enzymes. Finally, in accordance with the classical biochemical studies, our numerical analysis reveals in a quantitative manner that the enzyme phosphofructokinase is the key-core of the metabolic system, behaving for all conditions as the main source of the effective causal flows in yeast glycolysis. PMID:22393350

  3. Toll-like receptor-2 agonist-allergen coupling efficiently redirects Th2 cell responses and inhibits allergic airway eosinophilia.

    PubMed

    Krishnaswamy, Jayendra Kumar; Jirmo, Adan Chari; Baru, Abdul Mannan; Ebensen, Thomas; Guzmán, Carlos A; Sparwasser, Tim; Behrens, Georg M N

    2012-12-01

    Toll-like receptor (TLR) agonists beneficially modulate allergic airway inflammation. However, the efficiency of TLR agonists varies considerably, and their exact cellular mechanisms (especially of TLR 2/6 agonists) are incompletely understood. We investigated at a cellular level whether the administration of the pharmacologically improved TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPP) conjugated to antigenic peptide (BPP-OVA) could divert an existing Th2 response and influence airway eosinophilia. The effects of BPP-OVA on airway inflammation were assessed in a classic murine sensitization/challenge model and an adoptive transfer model, which involved the adoptive transfer of in vitro differentiated ovalbumin (OVA)-specific Th2 cells. Functional T-cell stimulation by lung dendritic cells (DCs) was determined both in vitro and in vivo, combined with a cytokine secretion analysis. A single mucosal application of BPP-OVA efficiently delivered antigen, led to TLR2-mediated DC activation, and resulted in OVA-specific T-cell proliferation via lung DCs in vivo. In alternative models of allergic airway disease, a single administration of BPP-OVA before OVA challenge (but not BPP alone) significantly reduced airway eosinophilia, most likely through altered antigen-specific T-cell stimulation via DCs. Analyses of adoptively transferred Th2-biased cells after BPP-OVA administration in vivo suggested that BPP-OVA guides antigen-specific Th2 cells to produce significantly higher amounts of IFN-γ upon allergen challenge. In conclusion, our data show for the first time that a single mucosal administration of a TLR 2/6 agonist-allergen conjugate can provoke IFN-γ responses in Th2-biased cells and alleviate allergic airway inflammation.

  4. Unzippers, Resolvers and Sensors: A Structural and Functional Biochemistry Tale of RNA Helicases

    PubMed Central

    Leitão, Ana Lúcia; Costa, Marina C.; Enguita, Francisco J.

    2015-01-01

    The centrality of RNA within the biological world is an irrefutable fact that currently attracts increasing attention from the scientific community. The panoply of functional RNAs requires the existence of specific biological caretakers, RNA helicases, devoted to maintain the proper folding of those molecules, resolving unstable structures. However, evolution has taken advantage of the specific position and characteristics of RNA helicases to develop new functions for these proteins, which are at the interface of the basic processes for transference of information from DNA to proteins. RNA helicases are involved in many biologically relevant processes, not only as RNA chaperones, but also as signal transducers, scaffolds of molecular complexes, and regulatory elements. Structural biology studies during the last decade, founded in X-ray crystallography, have characterized in detail several RNA-helicases. This comprehensive review summarizes the structural knowledge accumulated in the last two decades within this family of proteins, with special emphasis on the structure-function relationships of the most widely-studied families of RNA helicases: the DEAD-box, RIG-I-like and viral NS3 classes. PMID:25622248

  5. Transfer of Motor Learning Is More Pronounced in Proximal Compared to Distal Effectors in Upper Extremities

    PubMed Central

    Aune, Tore K.; Aune, Morten A.; Ingvaldsen, Rolf P.; Vereijken, Beatrix

    2017-01-01

    The current experiment investigated generalizability of motor learning in proximal versus distal effectors in upper extremities. Twenty-eight participants were divided into three groups: training proximal effectors, training distal effectors, and no training control group (CG). Performance was tested pre- and post-training for specific learning and three learning transfer conditions: (1) bilateral learning transfer between homologous effectors, (2) lateral learning transfer between non-homologous effectors, and (3) bilateral learning transfer between non-homologous effectors. With respect to specific learning, both training groups showed significant, similar improvement for the trained proximal and distal effectors, respectively. In addition, there was significant learning transfer to all three transfer conditions, except for bilateral learning transfer between non-homologous effectors for the distal training group. Interestingly, the proximal training group showed significantly larger learning transfer to other effectors compared to the distal training group. The CG did not show significant improvements from pre- to post-test. These results show that learning is partly effector independent and generalizable to different effectors, even though transfer is suboptimal compared to specific learning. Furthermore, there is a proximal-distal gradient in generalizability, in that learning transfer from trained proximal effectors is larger than from trained distal effectors, which is consistent with neuroanatomical differences in activation of proximal and distal muscles. PMID:28943857

  6. 5 CFR 630.212 - Use of annual leave to establish initial eligibility for retirement or continuation of health...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... decline relocation (including transfer of function). (b)(1) Annual leave that may be used for the purposes... transfer of function) and annual leave earned by an employee while in a paid leave status after the effective date of the reduction in force or relocation (including transfer of function). (2) Annual leave...

  7. Dispersion relations of elastic waves in one-dimensional piezoelectric/piezomagnetic phononic crystal with functionally graded interlayers.

    PubMed

    Guo, Xiao; Wei, Peijun; Lan, Man; Li, Li

    2016-08-01

    The effects of functionally graded interlayers on dispersion relations of elastic waves in a one-dimensional piezoelectric/piezomagnetic phononic crystal are studied in this paper. First, the state transfer equation of the functionally graded interlayer is derived from the motion equation by the reduction of order (from second order to first order). The transfer matrix of the functionally graded interlayer is obtained by solving the state transfer equation with the spatial-varying coefficient. Based on the transfer matrixes of the piezoelectric slab, the piezomagnetic slab and the functionally graded interlayers, the total transfer matrix of a single cell is obtained. Further, the Bloch theorem is used to obtain the resultant dispersion equations of in-plane and anti-plane Bloch waves. The dispersion equations are solved numerically and the numerical results are shown graphically. Five kinds of profiles of functionally graded interlayers between a piezoelectric slab and a piezomagnetic slab are considered. It is shown that the functionally graded interlayers have evident influences on the dispersion curves and the band gaps. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Variable-Domain Displacement Transfer Functions for Converting Surface Strains into Deflections for Structural Deformed Shape Predictions

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Fleischer, Van Tran

    2015-01-01

    Variable-Domain Displacement Transfer Functions were formulated for shape predictions of complex wing structures, for which surface strain-sensing stations must be properly distributed to avoid jointed junctures, and must be increased in the high strain gradient region. Each embedded beam (depth-wise cross section of structure along a surface strain-sensing line) was discretized into small variable domains. Thus, the surface strain distribution can be described with a piecewise linear or a piecewise nonlinear function. Through discretization, the embedded beam curvature equation can be piece-wisely integrated to obtain the Variable-Domain Displacement Transfer Functions (for each embedded beam), which are expressed in terms of geometrical parameters of the embedded beam and the surface strains along the strain-sensing line. By inputting the surface strain data into the Displacement Transfer Functions, slopes and deflections along each embedded beam can be calculated for mapping out overall structural deformed shapes. A long tapered cantilever tubular beam was chosen for shape prediction analysis. The input surface strains were analytically generated from finite-element analysis. The shape prediction accuracies of the Variable- Domain Displacement Transfer Functions were then determined in light of the finite-element generated slopes and deflections, and were fofound to be comparable to the accuracies of the constant-domain Displacement Transfer Functions

  9. Modified Displacement Transfer Functions for Deformed Shape Predictions of Slender Curved Structures with Varying Curvatives

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Fleischer, Van Tran

    2014-01-01

    To eliminate the need to use finite-element modeling for structure shape predictions, a new method was invented. This method is to use the Displacement Transfer Functions to transform the measured surface strains into deflections for mapping out overall structural deformed shapes. The Displacement Transfer Functions are expressed in terms of rectilinearly distributed surface strains, and contain no material properties. This report is to apply the patented method to the shape predictions of non-symmetrically loaded slender curved structures with different curvatures up to a full circle. Because the measured surface strains are not available, finite-element analysis had to be used to analytically generate the surface strains. Previously formulated straight-beam Displacement Transfer Functions were modified by introducing the curvature-effect correction terms. Through single-point or dual-point collocations with finite-elementgenerated deflection curves, functional forms of the curvature-effect correction terms were empirically established. The resulting modified Displacement Transfer Functions can then provide quite accurate shape predictions. Also, the uniform straight-beam Displacement Transfer Function was applied to the shape predictions of a section-cut of a generic capsule (GC) outer curved sandwich wall. The resulting GC shape predictions are quite accurate in partial regions where the radius of curvature does not change sharply.

  10. A Non-parametric Approach to Constrain the Transfer Function in Reverberation Mapping

    NASA Astrophysics Data System (ADS)

    Li, Yan-Rong; Wang, Jian-Min; Bai, Jin-Ming

    2016-11-01

    Broad emission lines of active galactic nuclei stem from a spatially extended region (broad-line region, BLR) that is composed of discrete clouds and photoionized by the central ionizing continuum. The temporal behaviors of these emission lines are blurred echoes of continuum variations (I.e., reverberation mapping, RM) and directly reflect the structures and kinematic information of BLRs through the so-called transfer function (also known as the velocity-delay map). Based on the previous works of Rybicki and Press and Zu et al., we develop an extended, non-parametric approach to determine the transfer function for RM data, in which the transfer function is expressed as a sum of a family of relatively displaced Gaussian response functions. Therefore, arbitrary shapes of transfer functions associated with complicated BLR geometry can be seamlessly included, enabling us to relax the presumption of a specified transfer function frequently adopted in previous studies and to let it be determined by observation data. We formulate our approach in a previously well-established framework that incorporates the statistical modeling of continuum variations as a damped random walk process and takes into account long-term secular variations which are irrelevant to RM signals. The application to RM data shows the fidelity of our approach.

  11. Nominal and functional task difficulty in skill acquisition: Effects on performance in two tests of transfer.

    PubMed

    Sanli, Elizabeth A; Lee, Timothy D

    2015-06-01

    The influence of nominal and functional task difficulty during the acquisition of a motor skill was examined in two tests of transfer of learning. The task involved a ballistic, target-directed, finger action. Nominal task difficulty was defined as the distance of the target from the home position. Functional task difficulty was created by manipulating the progression of target distances during practice. Based on the challenge point framework (Guadagnoli & Lee, 2004), we predicted that practice with a set of targets farther away from the performer would benefit from less functional task difficulty, while practice with a closer set of targets would benefit from more functional task difficulty. In single-task transfer tests, learners who practiced using the high nominal task difficulty targets benefitted in terms of persistence of performance over time. In dual-task transfer tests, groups with an intermediate combined (nominal and functional) task difficulty performed with greater persistence over time on tests of transfer than those who practiced with the highest or lowest combined difficulty. Together these findings suggest that the influences of nominal and functional task difficulty during acquisition are weighted differentially depending upon the transfer test context. The challenge point framework does not accurately capture this complex relationship in its current form. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. The importance of momentum transfer in collision-induced breakups in low Earth orbit

    NASA Technical Reports Server (NTRS)

    Reynolds, Robert C.; Lillie, Brian J.

    1991-01-01

    Although there is adequate information on larger objects in low Earth orbit, specifically those objects larger than about 10 cm in diameter, there is little direct information on objects from this size down to 1 mm. Yet, this is the sized regime where objects acting as projectiles represent the ability to seriously damage or destroy a functioning spacecraft if they collide with it. The observed consequences of known collisional breakups in orbit indicates no significant momentum transfer in the resulting debris cloud. The position taken in this paper is that this is an observational selection effect: what is seen in these events is an explosion-like breakup of the target structure arising from shock waves introduced into the structure by the collision, but one that occurs significantly after the collision processes are completed; the collision cloud, in which there is momentum transfer, consists of small, unobserved fragments. Preliminary computations of the contribution of one known collisional breakup, Solwind at 500 km in 1985, and Cosmos 1275 in 1981, assume no momentum transfer on breakup and indicate that these two events are the dominant contributors to the current millimeter and centimeter population. A different story would emerge if momentum transfer was taken into account. The topics covered include: (1) observation of on-orbit collisional breakups; (2) a model for momentum transfer; and (3) velocity space representation of breakup clouds.

  13. Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex.

    PubMed

    Toogood, Helen S; van Thiel, Adam; Basran, Jaswir; Sutcliffe, Mike J; Scrutton, Nigel S; Leys, David

    2004-07-30

    The crystal structure of the human electron transferring flavoprotein (ETF).medium chain acyl-CoA dehydrogenase (MCAD) complex reveals a dual mode of protein-protein interaction, imparting both specificity and promiscuity in the interaction of ETF with a range of structurally distinct primary dehydrogenases. ETF partitions the functions of partner binding and electron transfer between (i) the recognition loop, which acts as a static anchor at the ETF.MCAD interface, and (ii) the highly mobile redox active FAD domain. Together, these enable the FAD domain of ETF to sample a range of conformations, some compatible with fast interprotein electron transfer. Disorders in amino acid or fatty acid catabolism can be attributed to mutations at the protein-protein interface. Crucially, complex formation triggers mobility of the FAD domain, an induced disorder that contrasts with general models of protein-protein interaction by induced fit mechanisms. The subsequent interfacial motion in the MCAD.ETF complex is the basis for the interaction of ETF with structurally diverse protein partners. Solution studies using ETF and MCAD with mutations at the protein-protein interface support this dynamic model and indicate ionic interactions between MCAD Glu(212) and ETF Arg alpha(249) are likely to transiently stabilize productive conformations of the FAD domain leading to enhanced electron transfer rates between both partners.

  14. Artificial neural network and classical least-squares methods for neurotransmitter mixture analysis.

    PubMed

    Schulze, H G; Greek, L S; Gorzalka, B B; Bree, A V; Blades, M W; Turner, R F

    1995-02-01

    Identification of individual components in biological mixtures can be a difficult problem regardless of the analytical method employed. In this work, Raman spectroscopy was chosen as a prototype analytical method due to its inherent versatility and applicability to aqueous media, making it useful for the study of biological samples. Artificial neural networks (ANNs) and the classical least-squares (CLS) method were used to identify and quantify the Raman spectra of the small-molecule neurotransmitters and mixtures of such molecules. The transfer functions used by a network, as well as the architecture of a network, played an important role in the ability of the network to identify the Raman spectra of individual neurotransmitters and the Raman spectra of neurotransmitter mixtures. Specifically, networks using sigmoid and hyperbolic tangent transfer functions generalized better from the mixtures in the training data set to those in the testing data sets than networks using sine functions. Networks with connections that permit the local processing of inputs generally performed better than other networks on all the testing data sets. and better than the CLS method of curve fitting, on novel spectra of some neurotransmitters. The CLS method was found to perform well on noisy, shifted, and difference spectra.

  15. Learning better by repetition or variation? Is transfer at odds with task specific training?

    PubMed

    Bonney, Emmanuel; Jelsma, Lemke Dorothee; Ferguson, Gillian D; Smits-Engelsman, Bouwien C M

    2017-01-01

    Transfer of motor skills is the ultimate goal of motor training in rehabilitation practice. In children with Developmental Coordination Disorder (DCD), very little is known about how skills are transferred from training situations to real life contexts. In this study we examined the influence of two types of practice on transfer of motor skills acquired in a virtual reality (VR) environment. One hundred and eleven children with DCD and their typically developing (TD) peers, aged 6-10 years (M = 8.0 SD = 1.0) were randomly assigned to either variable (n = 56) or repetitive practice (n = 55). Participants in the repetitive practice played the same exergame (ski slalom) twice weekly for 20 minutes, over a period of 5 weeks, while those in the variable group played 10 different games. Motor skills such as balance tasks (hopping), running and agility tasks, ball skills and functional activities were evaluated before and after 5 weeks of training. ANOVA repeated measures indicated that both DCD and TD children demonstrated transfer effects to real life skills with identical and non-identical elements at exactly the same rate, irrespective of the type of practice they were assigned to. Based on these findings, we conclude that motor skills acquired in the VR environment, transfers to real world contexts in similar proportions for both TD and DCD children. The type of practice adopted does not seem to influence children's ability to transfer skills acquired in an exergame to life situations but the number of identical elements does.

  16. A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells.

    PubMed

    Schulein, Ralf; Guye, Patrick; Rhomberg, Thomas A; Schmid, Michael C; Schröder, Gunnar; Vergunst, Annette C; Carena, Ilaria; Dehio, Christoph

    2005-01-18

    Bacterial type IV secretion (T4S) systems mediate the transfer of macromolecular substrates into various target cells, e.g., the conjugative transfer of DNA into bacteria or the transfer of virulence proteins into eukaryotic host cells. The T4S apparatus VirB of the vascular tumor-inducing pathogen Bartonella henselae causes subversion of human endothelial cell (HEC) function. Here we report the identification of multiple protein substrates of VirB, which, upon translocation into HEC, mediate all known VirB-dependent cellular changes. These Bartonella-translocated effector proteins (Beps) A-G are encoded together with the VirB system and the T4S coupling protein VirD4 on a Bartonella-specific pathogenicity island. The Beps display a modular architecture, suggesting an evolution by extensive domain duplication and reshuffling. The C terminus of each Bep harbors at least one copy of the Bep-intracellular delivery domain and a short positively charged tail sequence. This biparte C terminus constitutes a transfer signal that is sufficient to mediate VirB/VirD4-dependent intracellular delivery of reporter protein fusions. The Bep-intracellular delivery domain is also present in conjugative relaxases of bacterial conjugation systems. We exemplarily show that the C terminus of such a conjugative relaxase mediates protein transfer through the Bartonella henselae VirB/VirD4 system into HEC. Conjugative relaxases may thus represent the evolutionary origin of the here defined T4S signal for protein transfer into human cells.

  17. Toe-to-hand transfer in symbrachydactyly.

    PubMed

    Richardson, Philip W F; Johnstone, Bruce R; Coombs, Christopher J

    2004-07-01

    Symbrachydactyly, or central atypical cleft, is classified as a failure of formation. For the adactylous or monodactylous forms, free toe transfer is the treatment of choice. We present 18 free toe transfers in 13 patients for symbrachydactyly. Despite abnormal anatomy, the functional building blocks have always been available and transfer technically possible. The result has been improved function and high levels of parental satisfaction.

  18. DISTRIBUTED RC NETWORKS WITH RATIONAL TRANSFER FUNCTIONS,

    DTIC Science & Technology

    A distributed RC circuit analogous to a continuously tapped transmission line can be made to have a rational short-circuit transfer admittance and...one rational shortcircuit driving-point admittance. A subcircuit of the same structure has a rational open circuit transfer impedance and one rational ...open circuit driving-point impedance. Hence, rational transfer functions may be obtained while considering either generator impedance or load

  19. Mission analysis for cross-site transfer

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

    Riesenweber, S.D.; Fritz, R.L.; Shipley, L.E.

    1995-11-01

    The Mission Analysis Report describes the requirements and constraints associated with the Transfer Waste Function as necessary to support the Manage Tank Waste, Retrieve Waste, and Process Tank Waste Functions described in WHC-SD-WM-FRD-020, Tank Waste Remediation System (TWRS) Functions and Requirements Document and DOE/RL-92-60, Revision 1, TWRS Functions and Requirements Document, March 1994. It further assesses the ability of the ``initial state`` (or current cross-site transfer system) to meet the requirements and constraints.

  20. Thunder-induced ground motions: 1. Observations

    NASA Astrophysics Data System (ADS)

    Lin, Ting-L.; Langston, Charles A.

    2009-04-01

    Acoustic pressure from thunder and its induced ground motions were investigated using a small array consisting of five three-component short-period surface seismometers, a three-component borehole seismometer, and five infrasound microphones. We used the array to constrain wave parameters of the incident acoustic and seismic waves. The incident slowness differences between acoustic pressure and ground motions suggest that ground reverberations were first initiated somewhat away from the array. Using slowness inferred from ground motions is preferable to obtain the seismic source parameters. We propose a source equalization procedure for acoustic/seismic deconvolution to generate the time domain transfer function, a procedure similar to that of obtaining teleseismic earthquake receiver functions. The time domain transfer function removes the incident pressure time history from the seismogram. An additional vertical-to-radial ground motion transfer function was used to identify the Rayleigh wave propagation mode of induced seismic waves complementing that found using the particle motions and amplitude variations in the borehole. The initial motions obtained by the time domain transfer functions suggest a low Poisson's ratio for the near-surface layer. The acoustic-to-seismic transfer functions show a consistent reverberation series at frequencies near 5 Hz. This gives an empirical measure of site resonance that depends on the ratio of the layer velocity to layer thickness for earthquake P and S waves. The time domain transfer function approach by transferring a spectral division into the time domain provides an alternative method for studying acoustic-to-seismic coupling.

  1. Functional Latissimus Dorsi Transfer for Upper-Extremity Reconstruction: A Case Report and Review of the Literature.

    PubMed

    Sood, Aditya; Therattil, Paul J; Russo, Gerardo; Lee, Edward S

    2017-01-01

    Objective: The latissimus dorsi flap is a workhorse for plastic surgeons, being used for many years for soft-tissue coverage of the upper extremity as well as for functional reconstruction to restore motion to the elbow and shoulder. The authors present a case of functional latissimus dorsi transfer for restoration of elbow flexion and review the literature on technique and outcomes. Methods: A literature review was performed using MEDLINE and the Cochrane Collaboration Library for primary research articles on functional latissimus dorsi flap transfer. Data related to surgical techniques and outcomes were extracted. Results: The literature search yielded 13 relevant studies, with a total of 52 patients who received pedicled, functional latissimus dorsi flaps for upper-extremity reconstruction. The most common etiology requiring reconstruction was closed brachial plexus injury (n = 13). After flap transfer, 98% of patients were able to flex the elbow against gravity and 82.3% were able to flex against resistance. In the presented case, a 77-year-old man underwent resection of myxofibrosarcoma of the upper arm with elbow prosthesis placement and functional latissimus dorsi transfer. The patient was able to actively flex against gravity at 3-month follow-up. Conclusions: A review of the literature shows that nearly all patients undergoing functional latissimus dorsi transfer for upper-extremity reconstruction regain at least motion against gravity whereas a large proportion regain motion against resistance. Considerations when planning for functional latissimus dorsi transfer include patient positioning, appropriate tensioning of the muscle, safe inset, polarity, management of other affected upper-extremity joints, and educating patients on the expected outcomes.

  2. Functional Latissimus Dorsi Transfer for Upper-Extremity Reconstruction: A Case Report and Review of the Literature

    PubMed Central

    Therattil, Paul J.; Russo, Gerardo; Lee, Edward S.

    2017-01-01

    Objective: The latissimus dorsi flap is a workhorse for plastic surgeons, being used for many years for soft-tissue coverage of the upper extremity as well as for functional reconstruction to restore motion to the elbow and shoulder. The authors present a case of functional latissimus dorsi transfer for restoration of elbow flexion and review the literature on technique and outcomes. Methods: A literature review was performed using MEDLINE and the Cochrane Collaboration Library for primary research articles on functional latissimus dorsi flap transfer. Data related to surgical techniques and outcomes were extracted. Results: The literature search yielded 13 relevant studies, with a total of 52 patients who received pedicled, functional latissimus dorsi flaps for upper-extremity reconstruction. The most common etiology requiring reconstruction was closed brachial plexus injury (n = 13). After flap transfer, 98% of patients were able to flex the elbow against gravity and 82.3% were able to flex against resistance. In the presented case, a 77-year-old man underwent resection of myxofibrosarcoma of the upper arm with elbow prosthesis placement and functional latissimus dorsi transfer. The patient was able to actively flex against gravity at 3-month follow-up. Conclusions: A review of the literature shows that nearly all patients undergoing functional latissimus dorsi transfer for upper-extremity reconstruction regain at least motion against gravity whereas a large proportion regain motion against resistance. Considerations when planning for functional latissimus dorsi transfer include patient positioning, appropriate tensioning of the muscle, safe inset, polarity, management of other affected upper-extremity joints, and educating patients on the expected outcomes. PMID:28293330

  3. Transient, Inducible, Placenta-Specific Gene Expression in Mice

    PubMed Central

    Fan, Xiujun; Petitt, Matthew; Gamboa, Matthew; Huang, Mei; Dhal, Sabita; Druzin, Maurice L.; Wu, Joseph C.

    2012-01-01

    Molecular understanding of placental functions and pregnancy disorders is limited by the absence of methods for placenta-specific gene manipulation. Although persistent placenta-specific gene expression has been achieved by lentivirus-based gene delivery methods, developmentally and physiologically important placental genes have highly stage-specific functions, requiring controllable, transient expression systems for functional analysis. Here, we describe an inducible, placenta-specific gene expression system that enables high-level, transient transgene expression and monitoring of gene expression by live bioluminescence imaging in mouse placenta at different stages of pregnancy. We used the third generation tetracycline-responsive tranactivator protein Tet-On 3G, with 10- to 100-fold increased sensitivity to doxycycline (Dox) compared with previous versions, enabling unusually sensitive on-off control of gene expression in vivo. Transgenic mice expressing Tet-On 3G were created using a new integrase-based, site-specific approach, yielding high-level transgene expression driven by a ubiquitous promoter. Blastocysts from these mice were transduced with the Tet-On 3G-response element promoter-driving firefly luciferase using lentivirus-mediated placenta-specific gene delivery and transferred into wild-type pseudopregnant recipients for placenta-specific, Dox-inducible gene expression. Systemic Dox administration at various time points during pregnancy led to transient, placenta-specific firefly luciferase expression as early as d 5 of pregnancy in a Dox dose-dependent manner. This system enables, for the first time, reliable pregnancy stage-specific induction of gene expression in the placenta and live monitoring of gene expression during pregnancy. It will be widely applicable to studies of both placental development and pregnancy, and the site-specific Tet-On G3 mouse will be valuable for studies in a broad range of tissues. PMID:23011919

  4. Triggering Avoidance: Dissociable Influences of Aversive Pavlovian Conditioned Stimuli on Human Instrumental Behavior.

    PubMed

    Garofalo, Sara; Robbins, Trevor W

    2017-01-01

    The present study investigates human aversive Pavlovian-to-Instrumental Transfer (PIT) and possible influences of outcome devaluation and instrumental overtraining on this effect. PIT measures the extent to which a Pavlovian conditioned stimulus (CS) can increase instrumental responses independently paired with the same (outcome-specific transfer) or a different (general transfer) reinforcer. Two measures of PIT were obtained: the percentage of instrumental responses and the vigor of such responses. Thirty-eight volunteers performed a standard PIT task sequence. Results showed a double dissociation between outcome-specific and general transfer: the first selectively expressed in the amount of responses, the second in the vigor measure solely. Furthermore, outcome-specific transfer was enhanced by overtraining, but not affected by devaluation. General transfer, on the other hand, was affected by neither overtraining, nor devaluation. A positive correlation between general transfer and sensitivity to punishments was found. Findings are discussed in terms of hypothetically different underlying neurobehavioral mechanisms and their relations to habits and goal-directed behavior.

  5. Optimization of a gene electrotransfer procedure for efficient intradermal immunization with an hTERT-based DNA vaccine in mice

    PubMed Central

    Calvet, Christophe Y; Thalmensi, Jessie; Liard, Christelle; Pliquet, Elodie; Bestetti, Thomas; Huet, Thierry; Langlade-Demoyen, Pierre; Mir, Lluis M

    2014-01-01

    DNA vaccination consists in administering an antigen-encoding plasmid in order to trigger a specific immune response. This specific vaccine strategy is of particular interest to fight against various infectious diseases and cancer. Gene electrotransfer is the most efficient and safest non-viral gene transfer procedure and specific electrical parameters have been developed for several target tissues. Here, a gene electrotransfer protocol into the skin has been optimized in mice for efficient intradermal immunization against the well-known telomerase tumor antigen. First, the luciferase reporter gene was used to evaluate gene electrotransfer efficiency into the skin as a function of the electrical parameters and electrodes, either non-invasive or invasive. In a second time, these parameters were tested for their potency to generate specific cellular CD8 immune responses against telomerase epitopes. These CD8 T-cells were fully functional as they secreted IFNγ and were endowed with specific cytotoxic activity towards target cells. This simple and optimized procedure for efficient gene electrotransfer into the skin using the telomerase antigen is to be used in cancer patients for the phase 1 clinical evaluation of a therapeutic cancer DNA vaccine called INVAC-1. PMID:26015983

  6. Th1-like Plasmodium-Specific Memory CD4+ T Cells Support Humoral Immunity.

    PubMed

    Zander, Ryan A; Vijay, Rahul; Pack, Angela D; Guthmiller, Jenna J; Graham, Amy C; Lindner, Scott E; Vaughan, Ashley M; Kappe, Stefan H I; Butler, Noah S

    2017-11-14

    Effector T cells exhibiting features of either T helper 1 (Th1) or T follicular helper (Tfh) populations are essential to control experimental Plasmodium infection and are believed to be critical for resistance to clinical malaria. To determine whether Plasmodium-specific Th1- and Tfh-like effector cells generate memory populations that contribute to protection, we developed transgenic parasites that enable high-resolution study of anti-malarial memory CD4 T cells in experimental models. We found that populations of both Th1- and Tfh-like Plasmodium-specific memory CD4 T cells persist. Unexpectedly, Th1-like memory cells exhibit phenotypic and functional features of Tfh cells during recall and provide potent B cell help and protection following transfer, characteristics that are enhanced following ligation of the T cell co-stimulatory receptor OX40. Our findings delineate critical functional attributes of Plasmodium-specific memory CD4 T cells and identify a host-specific factor that can be targeted to improve resolution of acute malaria and provide durable, long-term protection against Plasmodium parasite re-exposure. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Deconstructing thermodynamic parameters of a coupled system from site-specific observables.

    PubMed

    Chowdhury, Sandipan; Chanda, Baron

    2010-11-02

    Cooperative interactions mediate information transfer between structural domains of a protein molecule and are major determinants of protein function and modulation. The prevalent theories to understand the thermodynamic origins of cooperativity have been developed to reproduce the complex behavior of a global thermodynamic observable such as ligand binding or enzyme activity. However, in most cases the measurement of a single global observable cannot uniquely define all the terms that fully describe the energetics of the system. Here we establish a theoretical groundwork for analyzing protein thermodynamics using site-specific information. Our treatment involves extracting a site-specific parameter (defined as χ value) associated with a structural unit. We demonstrate that, under limiting conditions, the χ value is related to the direct interaction terms associated with the structural unit under observation and its intrinsic activation energy. We also introduce a site-specific interaction energy term (χ(diff)) that is a function of the direct interaction energy of that site with every other site in the system. When combined with site-directed mutagenesis and other molecular level perturbations, analyses of χ values of site-specific observables may provide valuable insights into protein thermodynamics and structure.

  8. Nerve Transfers to Restore Shoulder Function.

    PubMed

    Leechavengvongs, Somsak; Malungpaishorpe, Kanchai; Uerpairojkit, Chairoj; Ng, Chye Yew; Witoonchart, Kiat

    2016-05-01

    The restoration of shoulder function after brachial plexus injury represents a significant challenge facing the peripheral nerve surgeons. This is owing to a combination of the complex biomechanics of the shoulder girdle, the multitude of muscles and nerves that could be potentially injured, and a limited number of donor options. In general, nerve transfer is favored over tendon transfer, because the biomechanics of the musculotendinous units are not altered. This article summarizes the surgical techniques and clinical results of nerve transfers for restoration of shoulder function. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Technology utilization office data base analysis and design

    NASA Technical Reports Server (NTRS)

    Floyd, Stephen A.

    1993-01-01

    NASA Headquarters is placing a high priority on the transfer of NASA and NASA contractor developed technologies and expertise to the private sector and to other federal, state and local government organizations. The ultimate objective of these efforts is positive economic impact, an improved quality of life, and a more competitive U.S. posture in international markets. The Technology Utilization Office (TUO) currently serves seven states with its technology transfer efforts. Since 1989, the TUO has handled over one-thousand formal requests for NASA related technologies assistance. The technology transfer process requires promoting public awareness of NASA related soliciting requests for assistance, matching technologies to specific needs, assuring appropriate technology transfer, and monitoring and evaluating the process. Each of these activities have one very important aspect in common: the success of each is dissemination of appropriate high quality information. The purpose of the research was to establish the requirements and develop a preliminary design for a database system to increase the effectiveness and efficiency of the TUO's technology transfer function. The research was conducted following the traditional systems development life cycle methodology and was supported through the use of modern structured analysis techniques. The next section will describe the research and findings as conducted under the life cycle approach.

  10. Gap junctions modulate glioma invasion by direct transfer of microRNA.

    PubMed

    Hong, Xiaoting; Sin, Wun Chey; Harris, Andrew L; Naus, Christian C

    2015-06-20

    The invasiveness of high-grade glioma is the primary reason for poor survival following treatment. Interaction between glioma cells and surrounding astrocytes are crucial to invasion. We investigated the role of gap junction mediated miRNA transfer in this context. By manipulating gap junctions with a gap junction inhibitor, siRNAs, and a dominant negative connexin mutant, we showed that functional glioma-glioma gap junctions suppress glioma invasion while glioma-astrocyte and astrocyte-astrocyte gap junctions promote it in an in vitro transwell invasion assay. After demonstrating that glioma-astrocyte gap junctions are permeable to microRNA, we compared the microRNA profiles of astrocytes before and after co-culture with glioma cells, identifying specific microRNAs as candidates for transfer through gap junctions from glioma cells to astrocytes. Further analysis showed that transfer of miR-5096 from glioma cells to astrocytes is through gap junctions; this transfer is responsible, in part, for the pro-invasive effect. Our results establish a role for glioma-astrocyte gap junction mediated microRNA signaling in modulation of glioma invasive behavior, and that gap junction coupling among astrocytes magnifies the pro-invasive signaling. Our findings reveal the potential for therapeutic interventions based on abolishing alteration of stromal cells by tumor cells via manipulation of microRNA and gap junction channel activity.

  11. Gap junctions modulate glioma invasion by direct transfer of microRNA

    PubMed Central

    Hong, Xiaoting; Sin, Wun Chey; Harris, Andrew L.; Naus, Christian C.

    2015-01-01

    The invasiveness of high-grade glioma is the primary reason for poor survival following treatment. Interaction between glioma cells and surrounding astrocytes are crucial to invasion. We investigated the role of gap junction mediated miRNA transfer in this context. By manipulating gap junctions with a gap junction inhibitor, siRNAs, and a dominant negative connexin mutant, we showed that functional glioma-glioma gap junctions suppress glioma invasion while glioma-astrocyte and astrocyte-astrocyte gap junctions promote it in an in vitro transwell invasion assay. After demonstrating that glioma-astrocyte gap junctions are permeable to microRNA, we compared the microRNA profiles of astrocytes before and after co-culture with glioma cells, identifying specific microRNAs as candidates for transfer through gap junctions from glioma cells to astrocytes. Further analysis showed that transfer of miR-5096 from glioma cells to astrocytes is through gap junctions; this transfer is responsible, in part, for the pro-invasive effect. Our results establish a role for glioma-astrocyte gap junction mediated microRNA signaling in modulation of glioma invasive behavior, and that gap junction coupling among astrocytes magnifies the pro-invasive signaling. Our findings reveal the potential for therapeutic interventions based on abolishing alteration of stromal cells by tumor cells via manipulation of microRNA and gap junction channel activity. PMID:25978028

  12. Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies.

    PubMed

    Tardivel, Meryem; Bégard, Séverine; Bousset, Luc; Dujardin, Simon; Coens, Audrey; Melki, Ronald; Buée, Luc; Colin, Morvane

    2016-11-04

    A given cell makes exchanges with its neighbors through a variety of means ranging from diffusible factors to vesicles. Cells use also tunneling nanotubes (TNTs), filamentous-actin-containing membranous structures that bridge and connect cells. First described in immune cells, TNTs facilitate HIV-1 transfer and are found in various cell types, including neurons. We show that the microtubule-associated protein Tau, a key player in Alzheimer's disease, is a bona fide constituent of TNTs. This is important because Tau appears beside filamentous actin and myosin 10 as a specific marker of these fine protrusions of membranes and cytosol that are difficult to visualize. Furthermore, we observed that exogenous Tau species increase the number of TNTs established between primary neurons, thereby facilitating the intercellular transfer of Tau fibrils. In conclusion, Tau may contribute to the formation and function of the highly dynamic TNTs that may be involved in the prion-like propagation of Tau assemblies.

  13. Structural and mechanistic insights into phospholipid transfer by Ups1-Mdm35 in mitochondria

    NASA Astrophysics Data System (ADS)

    Watanabe, Yasunori; Tamura, Yasushi; Kawano, Shin; Endo, Toshiya

    2015-08-01

    Eukaryotic cells are compartmentalized into membrane-bounded organelles whose functions rely on lipid trafficking to achieve membrane-specific compositions of lipids. Here we focused on the Ups1-Mdm35 system, which mediates phosphatidic acid (PA) transfer between the outer and inner mitochondrial membranes, and determined the X-ray structures of Mdm35 and Ups1-Mdm35 with and without PA. The Ups1-Mdm35 complex constitutes a single domain that has a deep pocket and flexible Ω-loop lid. Structure-based mutational analyses revealed that a basic residue at the pocket bottom and the Ω-loop lid are important for PA extraction from the membrane following Ups1 binding. Ups1 binding to the membrane is enhanced by the dissociation of Mdm35. We also show that basic residues around the pocket entrance are important for Ups1 binding to the membrane and PA extraction. These results provide a structural basis for understanding the mechanism of PA transfer between mitochondrial membranes.

  14. Identification of another module involved in the horizontal transfer of the Haemophilus genomic island ICEHin1056.

    PubMed

    Juhas, Mario; Dimopoulou, Ioanna; Robinson, Esther; Elamin, Abdel; Harding, Rosalind; Hood, Derek; Crook, Derrick

    2013-09-01

    A significant part of horizontal gene transfer is facilitated by genomic islands. Haemophilus influenzae genomic island ICEHin1056 is an archetype of a genomic island that accounts for pandemic spread of antibiotics resistance. ICEHin1056 has modular structure and harbors modules involved in type IV secretion and integration. Previous studies have shown that ICEHin1056 encodes a functional type IV secretion system; however, other modules have not been characterized yet. Here we show that the module on the 5' extremity of ICEHin1056 consists of 15 genes that are well conserved in a number of related genomic islands. Furthermore by disrupting six genes of the investigated module of ICEHin1056 by site-specific mutagenesis we demonstrate that in addition to type IV secretion system module, the investigated module is also important for the successful conjugal transfer of ICEHin1056 from donor to recipient cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Intrinsic Tryptophan Fluorescence in the Detection and Analysis of Proteins: A Focus on Förster Resonance Energy Transfer Techniques

    PubMed Central

    Ghisaidoobe, Amar B. T.; Chung, Sang J.

    2014-01-01

    Förster resonance energy transfer (FRET) occurs when the distance between a donor fluorophore and an acceptor is within 10 nm, and its application often necessitates fluorescent labeling of biological targets. However, covalent modification of biomolecules can inadvertently give rise to conformational and/or functional changes. This review describes the application of intrinsic protein fluorescence, predominantly derived from tryptophan (λEX ∼ 280 nm, λEM ∼ 350 nm), in protein-related research and mainly focuses on label-free FRET techniques. In terms of wavelength and intensity, tryptophan fluorescence is strongly influenced by its (or the protein’s) local environment, which, in addition to fluorescence quenching, has been applied to study protein conformational changes. Intrinsic Förster resonance energy transfer (iFRET), a recently developed technique, utilizes the intrinsic fluorescence of tryptophan in conjunction with target-specific fluorescent probes as FRET donors and acceptors, respectively, for real time detection of native proteins. PMID:25490136

  16. 10 CFR 32.22 - Self-luminous products containing tritium, krypton-85 or promethium-147: Requirements for license...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... promethium-147: Requirements for license to manufacture, process, produce, or initially transfer. 32.22 Section 32.22 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER..., or initially transfer. (a) An application for a specific license to manufacture, process, or produce...

  17. 10 CFR 32.14 - Certain items containing byproduct material; requirements for license to apply or initially...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... for license to apply or initially transfer. 32.14 Section 32.14 Energy NUCLEAR REGULATORY COMMISSION SPECIFIC DOMESTIC LICENSES TO MANUFACTURE OR TRANSFER CERTAIN ITEMS CONTAINING BYPRODUCT MATERIAL Exempt... or initially transfer. An application for a specific license to apply byproduct material to, or to...

  18. Elements of the cellular metabolic structure

    PubMed Central

    De la Fuente, Ildefonso M.

    2015-01-01

    A large number of studies have demonstrated the existence of metabolic covalent modifications in different molecular structures, which are able to store biochemical information that is not encoded by DNA. Some of these covalent mark patterns can be transmitted across generations (epigenetic changes). Recently, the emergence of Hopfield-like attractor dynamics has been observed in self-organized enzymatic networks, which have the capacity to store functional catalytic patterns that can be correctly recovered by specific input stimuli. Hopfield-like metabolic dynamics are stable and can be maintained as a long-term biochemical memory. In addition, specific molecular information can be transferred from the functional dynamics of the metabolic networks to the enzymatic activity involved in covalent post-translational modulation, so that determined functional memory can be embedded in multiple stable molecular marks. The metabolic dynamics governed by Hopfield-type attractors (functional processes), as well as the enzymatic covalent modifications of specific molecules (structural dynamic processes) seem to represent the two stages of the dynamical memory of cellular metabolism (metabolic memory). Epigenetic processes appear to be the structural manifestation of this cellular metabolic memory. Here, a new framework for molecular information storage in the cell is presented, which is characterized by two functionally and molecularly interrelated systems: a dynamic, flexible and adaptive system (metabolic memory) and an essentially conservative system (genetic memory). The molecular information of both systems seems to coordinate the physiological development of the whole cell. PMID:25988183

  19. Multifunctional Cytochrome c: Learning New Tricks from an Old Dog.

    PubMed

    Alvarez-Paggi, Damián; Hannibal, Luciana; Castro, María A; Oviedo-Rouco, Santiago; Demicheli, Veronica; Tórtora, Veronica; Tomasina, Florencia; Radi, Rafael; Murgida, Daniel H

    2017-11-08

    Cytochrome c (cyt c) is a small soluble heme protein characterized by a relatively flexible structure, particularly in the ferric form, such that it is able to sample a broad conformational space. Depending on the specific conditions, interactions, and cellular localization, different conformations may be stabilized, which differ in structure, redox properties, binding affinities, and enzymatic activity. The primary function is electron shuttling in oxidative phosphorylation, and is exerted by the so-called native cyt c in the intermembrane mitochondrial space of healthy cells. Under pro-apoptotic conditions, however, cyt c gains cardiolipin peroxidase activity, translocates into the cytosol to engage in the intrinsic apoptotic pathway, and enters the nucleus where it impedes nucleosome assembly. Other reported functions include cytosolic redox sensing and involvement in the mitochondrial oxidative folding machinery. Moreover, post-translational modifications such as nitration, phosphorylation, and sulfoxidation of specific amino acids induce alternative conformations with differential properties, at least in vitro. Similar structural and functional alterations are elicited by biologically significant electric fields and by naturally occurring mutations of human cyt c that, along with mutations at the level of the maturation system, are associated with specific diseases. Here, we summarize current knowledge and recent advances in understanding the different structural, dynamic, and thermodynamic factors that regulate the primary electron transfer function, as well as alternative functions and conformations of cyt c. Finally, we present recent technological applications of this moonlighting protein.

  20. Completion processing for data communications instructions

    DOEpatents

    Blocksome, Michael A.; Kumar, Sameer; Parker, Jeffrey J.

    2014-06-03

    Completion processing of data communications instructions in a distributed computing environment, including receiving, in an active messaging interface (`AMI`) data communications instructions, at least one instruction specifying a callback function; injecting into an injection FIFO buffer of a data communication adapter, an injection descriptor, each slot in the injection FIFO buffer having a corresponding slot in a pending callback list; listing in the pending callback list any callback function specified by an instruction, incrementing a pending callback counter for each listed callback function; transferring payload data as per each injection descriptor, incrementing a transfer counter upon completion of each transfer; determining from counter values whether the pending callback list presently includes callback functions whose data transfers have been completed; calling by the AMI any such callback functions from the pending callback list, decrementing the pending callback counter for each callback function called.

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