Science.gov

Sample records for correcting potential human

  1. Structured methods for identifying and correcting potential human errors in aviation operations

    SciTech Connect

    Nelson, W.R.

    1997-10-01

    Human errors have been identified as the source of approximately 60% of the incidents and accidents that occur in commercial aviation. It can be assumed that a very large number of human errors occur in aviation operations, even though in most cases the redundancies and diversities built into the design of aircraft systems prevent the errors from leading to serious consequences. In addition, when it is acknowledged that many system failures have their roots in human errors that occur in the design phase, it becomes apparent that the identification and elimination of potential human errors could significantly decrease the risks of aviation operations. This will become even more critical during the design of advanced automation-based aircraft systems as well as next-generation systems for air traffic management. Structured methods to identify and correct potential human errors in aviation operations have been developed and are currently undergoing testing at the Idaho National Engineering and Environmental Laboratory (INEEL).

  2. Exemplar-based human action pose correction.

    PubMed

    Shen, Wei; Deng, Ke; Bai, Xiang; Leyvand, Tommer; Guo, Baining; Tu, Zhuowen

    2014-07-01

    The launch of Xbox Kinect has built a very successful computer vision product and made a big impact on the gaming industry. This sheds lights onto a wide variety of potential applications related to action recognition. The accurate estimation of human poses from the depth image is universally a critical step. However, existing pose estimation systems exhibit failures when facing severe occlusion. In this paper, we propose an exemplar-based method to learn to correct the initially estimated poses. We learn an inhomogeneous systematic bias by leveraging the exemplar information within a specific human action domain. Furthermore, as an extension, we learn a conditional model by incorporation of pose tags to further increase the accuracy of pose correction. In the experiments, significant improvements on both joint-based skeleton correction and tag prediction are observed over the contemporary approaches, including what is delivered by the current Kinect system. Our experiments for the facial landmark correction also illustrate that our algorithm can improve the accuracy of other detection/estimation systems. PMID:24058046

  3. Exemplar-based human action pose correction.

    PubMed

    Shen, Wei; Deng, Ke; Bai, Xiang; Leyvand, Tommer; Guo, Baining; Tu, Zhuowen

    2014-07-01

    The launch of Xbox Kinect has built a very successful computer vision product and made a big impact on the gaming industry. This sheds lights onto a wide variety of potential applications related to action recognition. The accurate estimation of human poses from the depth image is universally a critical step. However, existing pose estimation systems exhibit failures when facing severe occlusion. In this paper, we propose an exemplar-based method to learn to correct the initially estimated poses. We learn an inhomogeneous systematic bias by leveraging the exemplar information within a specific human action domain. Furthermore, as an extension, we learn a conditional model by incorporation of pose tags to further increase the accuracy of pose correction. In the experiments, significant improvements on both joint-based skeleton correction and tag prediction are observed over the contemporary approaches, including what is delivered by the current Kinect system. Our experiments for the facial landmark correction also illustrate that our algorithm can improve the accuracy of other detection/estimation systems.

  4. 75 FR 21508 - Health and Human Services Acquisition Regulation; Corrections

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... HUMAN SERVICES 48 CFR Chapter 3 Health and Human Services Acquisition Regulation; Corrections AGENCY: Department of Health and Human Services. ACTION: Correcting amendments. SUMMARY: This action corrects minor errors, inconsistencies and omissions in the final rule, which revised the Health and Human...

  5. The Human Potential Movement.

    ERIC Educational Resources Information Center

    Tamashiro, Roy T.

    The advent of the human potential movement has generated the expectation that educators unleash the intellectual, emotional, physical, and spiritual talents of students. This movement is characterized by its focus on (1) the person as a total being, (2) the needs and concerns of students, (3) phenomenology, (4) personal values and goals, and (5)…

  6. Loop corrections to the antibrane potential

    NASA Astrophysics Data System (ADS)

    Bena, Iosif; Blåbäck, Johan; Turton, David

    2016-07-01

    Antibranes provide some of the most generic ways to uplift Anti-de Sitter flux compactifications to de Sitter, and there is a growing body of evidence that antibranes placed in long warped throats such as the Klebanov-Strassler warped deformed conifold solution have a brane-brane-repelling tachyon. This tachyon was first found in the regime of parameters in which the backreaction of the antibranes is large, and its existence was inferred from a highly nontrivial cancellation of certain terms in the inter-brane potential. We use a brane effective action approach, similar to that proposed by Michel, Mintun, Polchinski, Puhm and Saad in [29], to analyze antibranes in Klebanov-Strassler when their backreaction is small, and find a regime of parameters where all perturbative contributions to the action can be computed explicitly. We find that the cancellation found at strong coupling is also present in the weak-coupling regime, and we establish its existence to all loops. Our calculation indicates that the spectrum of the antibrane worldvolume theory is not gapped, and may generically have a tachyon. Hence uplifting mechanisms involving antibranes remain questionable even when backreaction is small.

  7. 77 FR 51579 - Meetings of Humanities Panel; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-24

    ..., at (202) 606-8322. Correction In the Federal Register of August 14, 2012, in FR Doc. 2012-19899, on... ARTS AND THE HUMANITIES Meetings of Humanities Panel; Correction AGENCY: National Endowment for the Humanities, National Foundation on the Arts and the Humanities. ACTION: Notice of meetings;...

  8. Alternate corrections for estimating actual wetland evapotranspiration from potential evapotranspiration

    USGS Publications Warehouse

    Barclay, Shoemaker W.; Sumner, D.M.

    2006-01-01

    Corrections can be used to estimate actual wetland evapotranspiration (AET) from potential evapotranspiration (PET) as a means to define the hydrology of wetland areas. Many alternate parameterizations for correction coefficients for three PET equations are presented, covering a wide range of possible data-availability scenarios. At nine sites in the wetland Everglades of south Florida, USA, the relatively complex PET Penman equation was corrected to daily total AET with smaller standard errors than the PET simple and Priestley-Taylor equations. The simpler equations, however, required less data (and thus less funding for instrumentation), with the possibility of being corrected to AET with slightly larger, comparable, or even smaller standard errors. Air temperature generally corrected PET simple most effectively to wetland AET, while wetland stage and humidity generally corrected PET Priestley-Taylor and Penman most effectively to wetland AET. Stage was identified for PET Priestley-Taylor and Penman as the data type with the most correction ability at sites that are dry part of each year or dry part of some years. Finally, although surface water generally was readily available at each monitoring site, AET was not occurring at potential rates, as conceptually expected under well-watered conditions. Apparently, factors other than water availability, such as atmospheric and stomata resistances to vapor transport, also were limiting the PET rate. ?? 2006, The Society of Wetland Scientists.

  9. Better band gaps with asymptotically corrected local exchange potentials

    DOE PAGES

    Singh, Prashant; Harbola, Manoj K.; Hemanadhan, M.; Mookerjee, Abhijit; Johnson, D. D.

    2016-02-22

    In this study, we formulate a spin-polarized van Leeuwen and Baerends (vLB) correction to the local density approximation (LDA) exchange potential [R. van Leeuwen and E. J. Baerends, Phys. Rev. A 49, 2421 (1994)] that enforces the ionization potential (IP) theorem following T. Stein et al. [Phys. Rev. Lett. 105, 266802 (2010)]. For electronic-structure problems, the vLB correction replicates the behavior of exact-exchange potentials, with improved scaling and well-behaved asymptotics, but with the computational cost of semilocal functionals. The vLB + IP correction produces a large improvement in the eigenvalues over those from the LDA due to correct asymptotic behaviormore » and atomic shell structures, as shown in rare-gas, alkaline-earth, zinc-based oxides, alkali halides, sulfides, and nitrides. In half-Heusler alloys, this asymptotically corrected LDA reproduces the spin-polarized properties correctly, including magnetism and half-metallicity. We also consider finite-sized systems [e.g., ringed boron nitride (B12N12) and graphene (C24)] to emphasize the wide applicability of the method.« less

  10. Calibration and temperature correction of heat dissipation matric potential sensors

    USGS Publications Warehouse

    Flint, A.L.; Campbell, G.S.; Ellett, K.M.; Calissendorff, C.

    2002-01-01

    This paper describes how heat dissipation sensors, used to measure soil water matric potential, were analyzed to develop a normalized calibration equation and a temperature correction method. Inference of soil matric potential depends on a correlation between the variable thermal conductance of the sensor's porous ceramic and matric poten-tial. Although this correlation varies among sensors, we demonstrate a normalizing procedure that produces a single calibration relationship. Using sensors from three sources and different calibration methods, the normalized calibration resulted in a mean absolute error of 23% over a matric potential range of -0.01 to -35 MPa. Because the thermal conductivity of variably saturated porous media is temperature dependent, a temperature correction is required for application of heat dissipation sensors in field soils. A temperature correction procedure is outlined that reduces temperature dependent errors by 10 times, which reduces the matric potential measurement errors by more than 30%. The temperature dependence is well described by a thermal conductivity model that allows for the correction of measurements at any temperature to measurements at the calibration temperature.

  11. Developing Human Resources through Actualizing Human Potential

    ERIC Educational Resources Information Center

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  12. The Performance Diagnostic Checklist-Human Services: a Correction.

    PubMed

    Carr, James E; Wilder, David A

    2016-03-01

    The Performance Diagnostic Checklist (PDC) has been used in a number of investigations to assess the environmental determinants of substandard employee performance. Carr et al. (2013) revised the PDC to explicitly assess the performance of employees in human-service settings who are responsible for providing care to others: the Performance Diagnostic Checklist-Human Services (PDC-HS). The originally published PDC-HS contained three minor scoring errors, which have been corrected in the present version. PMID:27606231

  13. The Performance Diagnostic Checklist-Human Services: a Correction.

    PubMed

    Carr, James E; Wilder, David A

    2016-03-01

    The Performance Diagnostic Checklist (PDC) has been used in a number of investigations to assess the environmental determinants of substandard employee performance. Carr et al. (2013) revised the PDC to explicitly assess the performance of employees in human-service settings who are responsible for providing care to others: the Performance Diagnostic Checklist-Human Services (PDC-HS). The originally published PDC-HS contained three minor scoring errors, which have been corrected in the present version.

  14. The Complete Correctional Officer: Human Service and the Human Environment of Prison.

    ERIC Educational Resources Information Center

    Johnson, Robert; Price, Shelley

    1981-01-01

    Examines the correctional officer role in relation to possibilities for the delivery of human services to inmates with problems and adjustment crises. Describes aspects of this approach to the correctional officer's role including building resilient prison environments, and a more human community. Discusses implications for officer support and…

  15. Correcting for Purifying Selection: An Improved Human Mitochondrial Molecular Clock

    PubMed Central

    Soares, Pedro; Ermini, Luca; Thomson, Noel; Mormina, Maru; Rito, Teresa; Röhl, Arne; Salas, Antonio; Oppenheimer, Stephen; Macaulay, Vincent; Richards, Martin B.

    2009-01-01

    There is currently no calibration available for the whole human mtDNA genome, incorporating both coding and control regions. Furthermore, as several authors have pointed out recently, linear molecular clocks that incorporate selectable characters are in any case problematic. We here confirm a modest effect of purifying selection on the mtDNA coding region and propose an improved molecular clock for dating human mtDNA, based on a worldwide phylogeny of > 2000 complete mtDNA genomes and calibrating against recent evidence for the divergence time of humans and chimpanzees. We focus on a time-dependent mutation rate based on the entire mtDNA genome and supported by a neutral clock based on synonymous mutations alone. We show that the corrected rate is further corroborated by archaeological dating for the settlement of the Canary Islands and Remote Oceania and also, given certain phylogeographic assumptions, by the timing of the first modern human settlement of Europe and resettlement after the Last Glacial Maximum. The corrected rate yields an age of modern human expansion in the Americas at ∼15 kya that—unlike the uncorrected clock—matches the archaeological evidence, but continues to indicate an out-of-Africa dispersal at around 55–70 kya, 5–20 ky before any clear archaeological record, suggesting the need for archaeological research efforts focusing on this time window. We also present improved rates for the mtDNA control region, and the first comprehensive estimates of positional mutation rates for human mtDNA, which are essential for defining mutation models in phylogenetic analyses. PMID:19500773

  16. Correction.

    PubMed

    2015-11-01

    In the article by Heuslein et al, which published online ahead of print on September 3, 2015 (DOI: 10.1161/ATVBAHA.115.305775), a correction was needed. Brett R. Blackman was added as the penultimate author of the article. The article has been corrected for publication in the November 2015 issue. PMID:26490278

  17. Radioactive smart probe for potential corrected matrix metalloproteinase imaging.

    PubMed

    Huang, Chiun-Wei; Li, Zibo; Conti, Peter S

    2012-11-21

    Although various activatable optical probes have been developed to visualize metalloproteinase (MMP) activities in vivo, precise quantification of the enzyme activity is limited due to the inherent scattering and attenuation (limited depth penetration) properties of optical imaging. In this investigation, a novel activatable peptide probe (64)Cu-BBQ650-PLGVR-K(Cy5.5)-E-K(DOTA)-OH was constructed to detect tumor MMP activity in vivo. This agent is optically quenched in its native form, but releases strong fluorescence upon cleavage by selected enzymes. MMP specificity was confirmed both in vitro and in vivo by fluorescent imaging studies. The use of a single modality to image biomarkers/processes may lead to erroneous interpretation of imaging data. The introduction of a quantitative imaging modality, such as PET, would make it feasible to correct the enzyme activity determined from optical imaging. In this proof of principle report, we demonstrated the feasibility of correcting the activatable optical imaging data through the PET signal. This approach provides an attractive new strategy for accurate imaging of MMP activity, which may also be applied for other protease imaging. PMID:23025637

  18. On the correctness of cosmology from quantum potential

    NASA Astrophysics Data System (ADS)

    Lashin, E. I.

    2016-02-01

    We examine in detail the cosmology based on quantal (Bohmian) trajectories as suggested in a recent study [A. F. Ali and S. Das, Phys. Lett. B 741, 276 (2014)]. We disagree with the conclusions regarding predicting the value of the cosmological constant Λ and evading the Big Bang singularity. Furthermore, we show that the approach of using a quantum corrected Raychaudhuri equation (QRE), as suggested in A. F. Ali and S. Das, Phys. Lett. B 741, 276 (2014), is unsatisfactory, because, essentially, it uses the Raychaudhuri equation (RE), which is a kinematical equation, in order to predict dynamics. In addition, even within this inconsistent framework, the authors have adopted unjustified assumptions and carried out incorrect steps leading to doubtful conclusions.

  19. Potential of software-based scatter corrections in cone-beam volume CT

    NASA Astrophysics Data System (ADS)

    Bertram, Matthias; Wiegert, Jens; Rose, Georg

    2005-04-01

    This study deals with a systematic assessment of the potential of different schemes for computerized scatter correction in flat detector based cone-beam X-ray computed tomography. The analysis is based on simulated scatter of a CT image of a human head. Using a Monte-Carlo cone-beam CT simulator, the spatial distribution of scattered radiation produced by this object has been calculated with high accuracy for the different projected views of a circular tomographic scan. Using this data and, as a reference, a scatter-free forward projection of the phantom, the potential of different schemes for scatter correction has been evaluated. In particular, the ideally achievable degree of accuracy of schemes based on estimating a constant scatter level in each projection was compared to approaches aiming at estimation of a more complex spatial shape of the scatter distribution. For each scheme, remaining cupping artifacts in the reconstructed volumetric image were quantified and analyzed. It was found that already accurate estimation of a constant scatter level for each projection allows for comparatively accurate compensation of scatter-caused artifacts.

  20. Corrections

    NASA Astrophysics Data System (ADS)

    2012-09-01

    The feature article "Material advantage?" on the effects of technology and rule changes on sporting performance (July pp28-30) stated that sprinters are less affected by lower oxygen levels at high altitudes because they run "aerobically". They run anaerobically. The feature about the search for the Higgs boson (August pp22-26) incorrectly gave the boson's mass as roughly 125 MeV it is 125 GeV, as correctly stated elsewhere in the issue. The article also gave a wrong value for the intended collision energy of the Superconducting Super Collider, which was designed to collide protons with a total energy of 40 TeV.

  1. Correction.

    PubMed

    2015-05-22

    The Circulation Research article by Keith and Bolli (“String Theory” of c-kitpos Cardiac Cells: A New Paradigm Regarding the Nature of These Cells That May Reconcile Apparently Discrepant Results. Circ Res. 2015:116:1216-1230. doi: 10.1161/CIRCRESAHA.116.305557) states that van Berlo et al (2014) observed that large numbers of fibroblasts and adventitial cells, some smooth muscle and endothelial cells, and rare cardiomyocytes originated from c-kit positive progenitors. However, van Berlo et al reported that only occasional fibroblasts and adventitial cells derived from c-kit positive progenitors in their studies. Accordingly, the review has been corrected to indicate that van Berlo et al (2014) observed that large numbers of endothelial cells, with some smooth muscle cells and fibroblasts, and more rarely cardiomyocytes, originated from c-kit positive progenitors in their murine model. The authors apologize for this error, and the error has been noted and corrected in the online version of the article, which is available at http://circres.ahajournals.org/content/116/7/1216.full ( PMID:25999426

  2. Human Potential Education and Public Schooling.

    ERIC Educational Resources Information Center

    Fletcher, Jerry L.

    The human potential movement the encourages growth beyond the conventional definitions of a normal or successful life. This movement is entering into a new phase characterized by carefully integrated sequences of the best human potential exercises, put together in a program that enables individuals to take a deep, personal look at their lives.…

  3. Correction of human. beta. sup S -globin gene by gene targeting

    SciTech Connect

    Shesely, E.G.; Hyungsuk Kim; Shehee, W.R.; Smithies, O. ); Papayannopoulou, T. ); Popovich, B.W. )

    1991-05-15

    As a step toward using gene targeting for gene therapy, the authors have corrected a human {beta}{sup S}-globin gene to the normal {beta}{sup A} allele by homologous recombination in the mouse-human hybrid cell line BSM. BSM is derived from a mouse erythroleukemia cell line and carries a single human chromosome 11 with the {beta}{sup S}-globin allele. A {beta}{sup A}-globin targeting construct containing a unique oligomer and a neomycin-resistance gene was electroporated into the BSM cells, which were then placed under G418 selection. Then 126 resulting pools containing a total {approx}29,000 G418-resistant clones were screened by PCR for the presence of a targeted recombinant: 3 positive pools were identified. A targeted clone was isolated by replating one of the positive pools into smaller pools and rescreening by PCR, followed by dilution cloning. Southern blot analysis demonstrated that the isolated clone had been targeted as planned. The correction of the {beta}{sup S} allele to {beta}{sup A} was confirmed both by allele-specific PCR and by allele-specific antibodies. Expression studies comparing the uninduced and induced RNA levels in unmodified BSM cells and in the targeted clone showed no significant alteration in the ability of the targeted clone to undergo induction, despite the potentially disrupting presence of a transcriptionally active neomycin gene 5{prime} to the human {beta}{sup A}-globin gene. Thus gene targeting can correct a {beta}{sup S} allele to {beta}{sup A}, and the use of a selectable helper gene need not significantly interfere with the induction of the corrected gene.

  4. Correction.

    PubMed

    1992-05-15

    In the 24 April "Inside AAAS" article "AAAS organizes more meetings of the mind" (p. 548), it is stated incorrectly that Paul Berg of Stanford University will be giving the keynote address and that Helen Donis-Keller of Washington University will be presenting a paper at the Science Innovation '92 meeting in San Francisco (21 to 25 July 1992). The Science Innovation '92 program was tentative at the time the article was written. Joseph Martin of the University of California, San Francisco, will deliver the keynote address on one of the major themes of the meeting, "Mapping the Human Brain." Helen Donis-Keller and Paul Berg were invited to speak but will not be on the program this year.

  5. 76 FR 3134 - Human Studies Review Board; Notice of Public Meeting; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-19

    ..., in FR Doc. 2011-625, on page 2107, in the title, correct the ``Docket ID No.'' to read EPA- HQ-ORD... AGENCY Human Studies Review Board; Notice of Public Meeting; Correction AGENCY: Environmental Protection... meeting of the Human Studies Review Board. The document contained incorrect Docket ID Number. FOR...

  6. Allometric Scaling of Therapeutic Monoclonal Antibodies Using Antigen Concentration as a Correction Factor: Application to the Human Clearance Prediction.

    PubMed

    Wang, Lei; Qiang, Wei; Cheng, Zeneng

    2016-03-01

    Allometric scaling has been widely used for predictions of human pharmacokinetic (PK) parameters in the development of monoclonal antibody (mAb) drugs, and some correction factors have been proposed to improve the estimations. However, classic correction factors fail to offer a complete explanation of the additional differences among species besides the body weight and, thus, lack enough power to further improve the predictions. In this study, the antigen concentration was initially set as a new correction factor to predict the human clearance (CL) of mAbs. Bevacizumab was intravenously injected into 2 animal species and humans to obtain PK data to predict human CL from the animal data. Additionally, a new approach was also validated with data from 3 other mAbs which were collected through a literature review of published work. Accordingly, allometric scaling with a correction factor of the antigen concentration generated accurate estimations of the human CL of 4 mAbs, which were superior to the results obtained by other classic scaling methods. More importantly, the proposed method also achieved good predictions of individual human CL of bevacizumab. In conclusion, the potential of this method as a powerful tool for human PK estimation of mAbs in species translation has been demonstrated. PMID:26886347

  7. Generalized gradient approximation exchange energy functional with correct asymptotic behavior of the corresponding potential.

    PubMed

    Carmona-Espíndola, Javier; Gázquez, José L; Vela, Alberto; Trickey, S B

    2015-02-01

    A new non-empirical exchange energy functional of the generalized gradient approximation (GGA) type, which gives an exchange potential with the correct asymptotic behavior, is developed and explored. In combination with the Perdew-Burke-Ernzerhof (PBE) correlation energy functional, the new CAP-PBE (CAP stands for correct asymptotic potential) exchange-correlation functional gives heats of formation, ionization potentials, electron affinities, proton affinities, binding energies of weakly interacting systems, barrier heights for hydrogen and non-hydrogen transfer reactions, bond distances, and harmonic frequencies on standard test sets that are fully competitive with those obtained from other GGA-type functionals that do not have the correct asymptotic exchange potential behavior. Distinct from them, the new functional provides important improvements in quantities dependent upon response functions, e.g., static and dynamic polarizabilities and hyperpolarizabilities. CAP combined with the Lee-Yang-Parr correlation functional gives roughly equivalent results. Consideration of the computed dynamical polarizabilities in the context of the broad spectrum of other properties considered tips the balance to the non-empirical CAP-PBE combination. Intriguingly, these improvements arise primarily from improvements in the highest occupied and lowest unoccupied molecular orbitals, and not from shifts in the associated eigenvalues. Those eigenvalues do not change dramatically with respect to eigenvalues from other GGA-type functionals that do not provide the correct asymptotic behavior of the potential. Unexpected behavior of the potential at intermediate distances from the nucleus explains this unexpected result and indicates a clear route for improvement.

  8. Human intestinal potential difference: recording method and biophysical implications.

    PubMed Central

    Gustke, R F; McCormick, P; Ruppin, H; Soergel, K H; Whalen, G E; Wood, C M

    1981-01-01

    1. The transmural electrical potential difference (PD) of the intact human small intestine was recorded with close attention to electrical symmetry, shielding from electro-magnetic waves and correction for junction potentials. 2. The PD is -12 mV (mucosa-negative) in the fasting jejunum and ileum and does not change during perfusion with isotonic NaCl. 3. Absorption of Na and Cl appears to be non-electrogenic and the 'resting' PD is probably generated by active anion secretion of fasting intestinal contents. 4. Diffusion potentials during isotonic D-mannitol perfusion indicated higher cation selectivity in the ileum than in the jejunum. 5. The calculated contribution of a free-solution path to total paracellular permeability is 55% in the jejunum but only 15% in the ileum. 6. No 'streaming' potential was detected during osmotic water flow, suggesting that the cation-selectivity of the channels is temporarily inactivated during dilatation of the lateral intercellular space. PMID:6802960

  9. Moving Away From Error-Related Potentials to Achieve Spelling Correction in P300 Spellers

    PubMed Central

    Mainsah, Boyla O.; Morton, Kenneth D.; Collins, Leslie M.; Sellers, Eric W.; Throckmorton, Chandra S.

    2016-01-01

    P300 spellers can provide a means of communication for individuals with severe neuromuscular limitations. However, its use as an effective communication tool is reliant on high P300 classification accuracies (>70%) to account for error revisions. Error-related potentials (ErrP), which are changes in EEG potentials when a person is aware of or perceives erroneous behavior or feedback, have been proposed as inputs to drive corrective mechanisms that veto erroneous actions by BCI systems. The goal of this study is to demonstrate that training an additional ErrP classifier for a P300 speller is not necessary, as we hypothesize that error information is encoded in the P300 classifier responses used for character selection. We perform offline simulations of P300 spelling to compare ErrP and non-ErrP based corrective algorithms. A simple dictionary correction based on string matching and word frequency significantly improved accuracy (35–185%), in contrast to an ErrP-based method that flagged, deleted and replaced erroneous characters (−47 – 0%). Providing additional information about the likelihood of characters to a dictionary-based correction further improves accuracy. Our Bayesian dictionary-based correction algorithm that utilizes P300 classifier confidences performed comparably (44–416%) to an oracle ErrP dictionary-based method that assumed perfect ErrP classification (43–433%). PMID:25438320

  10. 75 FR 5536 - Pipeline Safety: Control Room Management/Human Factors, Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-03

    ... Safety: Control Room Management/Human Factors, Correction AGENCY: Pipeline and Hazardous Materials Safety... Regulations to address human factors and other aspects of control room management for pipelines where... 63310) entitled ``Pipeline Safety: Control Room Management/Human Factors.'' This final rule...

  11. Student Human Potential: Going beyond the Basics.

    ERIC Educational Resources Information Center

    White, Sylvia Ann

    The expansion of human potential and the accompanying increase in self-esteem and self-actualization is the key to emotional and physical health, social relations, learning problems, self-discipline, and future survival. Self-knowledge, obtained through such measures as keeping records of moods and through biomechanical devices, can enable…

  12. Ionization potential of {sup 9}Be calculated including nuclear motion and relativistic corrections

    SciTech Connect

    Stanke, Monika; Kedziera, Dariusz; Bubin, Sergiy; Adamowicz, Ludwik

    2007-05-15

    Variational calculations employing explicitly correlated Gaussian functions have been performed for the ground states of {sup 9}Be and {sup 9}Be{sup +} including the nuclear motion [i.e., without assuming the Born-Oppenheimer (BO) approximation]. An approach based on the analytical energy gradient calculated with respect to the Gaussian exponential parameters was employed, leading to energies of the two systems noticeably improved over those found in the recent paper of Pachucki and Komasa [Phys. Rev. A 73, 052502 (2006)]. The non-BO wave functions were used to calculate the {alpha}{sup 2} relativistic corrections ({alpha}=e{sup 2}/({Dirac_h}/2{pi})c). With those corrections and the {alpha}{sup 3} and {alpha}{sup 4} corrections taken from Pachucki and Komasa, a new value of the ionization potential (IP) of {sup 9}Be was determined. It agrees very well with the most recent experimental IP.

  13. Evaluating sedimentary basins for geothermal power production potential and bottom-hole temperature corrections

    NASA Astrophysics Data System (ADS)

    Crowell, Anna M.

    At present, the risks and costs associated with geothermal energy wildcat exploration are prohibitive. With improved technology, the future may be brighter, and a play fairway analysis, for geothermal exploration can guide development. Comparing geophysical data with geothermal gradient allows identification of potentially economic areas of interest. The play fairway analysis is a common tool used by the petroleum industry to identify areas for potential exploration. The analysis identifies areas in the Denver, Illinois, Michigan, and Williston Basins with the highest development potential. A great deal of data have potential for a play fairway analysis, but data quality is problematic due to systematic errors in bottom-hole temperatures (BHTs). Corrections to bottom-hole temperatures are necessary due to the perturbation of temperature caused by the drilling mud, and can range from 5 to 30 °C. Correction schemes for bottom-hole temperatures can be applied to both the energy-in-place estimates and play fairway analyses. The Harrison equation is the most accurate for basins less than 4.5 km deep. The Kehle correction is the most accurate for basins deeper than 4.5 km. Chapter II explains why BHTs grouped by depth are more statistically robust than those grouped by geochronological unit. Chapter III demonstrates why the Harrison Equation is the best correction method to use for BHTs. Chapters IV and V give the volumetric energy-in-place for the Denver, Illinois, and Michigan Basins for discrete temperature ranges, and Chapter 6 provides the final Play Fairway Favorability maps.

  14. piggyBac transposons expressing full-length human dystrophin enable genetic correction of dystrophic mesoangioblasts.

    PubMed

    Loperfido, Mariana; Jarmin, Susan; Dastidar, Sumitava; Di Matteo, Mario; Perini, Ilaria; Moore, Marc; Nair, Nisha; Samara-Kuko, Ermira; Athanasopoulos, Takis; Tedesco, Francesco Saverio; Dickson, George; Sampaolesi, Maurilio; VandenDriessche, Thierry; Chuah, Marinee K

    2016-01-29

    Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder caused by the absence of dystrophin. We developed a novel gene therapy approach based on the use of the piggyBac (PB) transposon system to deliver the coding DNA sequence (CDS) of either full-length human dystrophin (DYS: 11.1 kb) or truncated microdystrophins (MD1: 3.6 kb; MD2: 4 kb). PB transposons encoding microdystrophins were transfected in C2C12 myoblasts, yielding 65±2% MD1 and 66±2% MD2 expression in differentiated multinucleated myotubes. A hyperactive PB (hyPB) transposase was then deployed to enable transposition of the large-size PB transposon (17 kb) encoding the full-length DYS and green fluorescence protein (GFP). Stable GFP expression attaining 78±3% could be achieved in the C2C12 myoblasts that had undergone transposition. Western blot analysis demonstrated expression of the full-length human DYS protein in myotubes. Subsequently, dystrophic mesoangioblasts from a Golden Retriever muscular dystrophy dog were transfected with the large-size PB transposon resulting in 50±5% GFP-expressing cells after stable transposition. This was consistent with correction of the differentiated dystrophic mesoangioblasts following expression of full-length human DYS. These results pave the way toward a novel non-viral gene therapy approach for DMD using PB transposons underscoring their potential to deliver large therapeutic genes.

  15. piggyBac transposons expressing full-length human dystrophin enable genetic correction of dystrophic mesoangioblasts

    PubMed Central

    Loperfido, Mariana; Jarmin, Susan; Dastidar, Sumitava; Di Matteo, Mario; Perini, Ilaria; Moore, Marc; Nair, Nisha; Samara-Kuko, Ermira; Athanasopoulos, Takis; Tedesco, Francesco Saverio; Dickson, George; Sampaolesi, Maurilio; VandenDriessche, Thierry; Chuah, Marinee K.

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder caused by the absence of dystrophin. We developed a novel gene therapy approach based on the use of the piggyBac (PB) transposon system to deliver the coding DNA sequence (CDS) of either full-length human dystrophin (DYS: 11.1 kb) or truncated microdystrophins (MD1: 3.6 kb; MD2: 4 kb). PB transposons encoding microdystrophins were transfected in C2C12 myoblasts, yielding 65±2% MD1 and 66±2% MD2 expression in differentiated multinucleated myotubes. A hyperactive PB (hyPB) transposase was then deployed to enable transposition of the large-size PB transposon (17 kb) encoding the full-length DYS and green fluorescence protein (GFP). Stable GFP expression attaining 78±3% could be achieved in the C2C12 myoblasts that had undergone transposition. Western blot analysis demonstrated expression of the full-length human DYS protein in myotubes. Subsequently, dystrophic mesoangioblasts from a Golden Retriever muscular dystrophy dog were transfected with the large-size PB transposon resulting in 50±5% GFP-expressing cells after stable transposition. This was consistent with correction of the differentiated dystrophic mesoangioblasts following expression of full-length human DYS. These results pave the way toward a novel non-viral gene therapy approach for DMD using PB transposons underscoring their potential to deliver large therapeutic genes. PMID:26682797

  16. Vascular Potential of Human Pluripotent Stem Cells

    PubMed Central

    Iacobas, Ionela; Vats, Archana; Hirschi, Karen K.

    2010-01-01

    Cardiovascular disease is the number one cause of death and disability in the US. Understanding the biological activity of stem and progenitor cells, and their ability to contribute to the repair, regeneration and remodeling of the heart and blood vessels affected by pathologic processes is an essential part of the paradigm in enabling us to achieve a reduction in related deaths. Both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are promising sources of cells for clinical cardiovascular therapies. Additional in vitro studies are needed, however, to understand their relative phenotypes and molecular regulation toward cardiovascular cell fates. Further studies in translational animal models are also needed to gain insights into the potential and function of both human ES- and iPS-derived cardiovascular cells, and enable translation from experimental and pre-clinical studies to human trials. PMID:20453170

  17. Potential human health effects of acid rain

    SciTech Connect

    Not Available

    1984-01-01

    Adverse human health effects, namely acute and chronic respiratory effects, can occur from the pre-deposition phase of the acid rain phenomenon due to inhalation of acidic particles and gases. State-of-the-art methodology to evaluate these effects is just now being applied to this question. The major post-deposition effect of the acid rain phenomenon is to acidify water, increasing solubility and subsequent human exposure to mercury, lead, cadmium, and aluminum. Acidification increases bioconversion of mercury to methylmercury, a highly toxic compound, which accumulates in fish, increasing the risk to toxicity in people who eat fish. Increase in water and soil content of lead and cadmium increases human exposure to these metals which become additive to other sources presently under regulatory control. The potential adverse health effects of increased human exposure to aluminum is not known at the present time. Deficiencies in the identification of the contribution of pre-deposition of air pollutants and post-deposition mobilization of toxic metals to the recognized potential health effects of the involved toxic substances is due to the fact that scientists have not addressed these specific questions. 113 references, 4 figures, 2 tables.

  18. Influence of sociodemographic characteristics on human mobility [corrected].

    PubMed

    Lenormand, Maxime; Louail, Thomas; Cantú-Ros, Oliva G; Picornell, Miguel; Herranz, Ricardo; Arias, Juan Murillo; Barthelemy, Marc; Miguel, Maxi San; Ramasco, José J

    2015-01-01

    Human mobility has been traditionally studied using surveys that deliver snapshots of population displacement patterns. The growing accessibility to ICT information from portable digital media has recently opened the possibility of exploring human behavior at high spatio-temporal resolutions. Mobile phone records, geolocated tweets, check-ins from Foursquare or geotagged photos, have contributed to this purpose at different scales, from cities to countries, in different world areas. Many previous works lacked, however, details on the individuals' attributes such as age or gender. In this work, we analyze credit-card records from Barcelona and Madrid and by examining the geolocated credit-card transactions of individuals living in the two provinces, we find that the mobility patterns vary according to gender, age and occupation. Differences in distance traveled and travel purpose are observed between younger and older people, but, curiously, either between males and females of similar age. While mobility displays some generic features, here we show that sociodemographic characteristics play a relevant role and must be taken into account for mobility and epidemiological modelization.

  19. Potential shift correction in multivariate curve resolution of voltammetric data. General formulation and application to some experimental systems.

    PubMed

    Alberich, Arístides; Díaz-Cruz, José Manuel; Ariño, Cristina; Esteban, Miquel

    2008-01-01

    A new mathematical algorithm is proposed to correct the progressive potential shift of some voltammetric signals that decrease the linearity of the data. The corrected data matrix can be further analysed by Multivariate Curve Resolution by Alternating Least Squares (MCR-ALS) and the vector including the potential shift corrections can be fitted to specific equations such as that by DeFord-Hume. A detailed discussion is given on the different cases of potential shift correction, and, in some of them, mathematical simulation is made or experimental systems [Cd(ii)-glutathione and Zn(ii)-glycine] are analysed.

  20. Humanizing Prisons with Animals: A Closer Look at "Cell Dogs" and Horse Programs in Correctional Institutions

    ERIC Educational Resources Information Center

    Deaton, Christiane

    2005-01-01

    If correctional education aims to transform individuals and bring about change, we need to consider the whole person who comes with human needs, emotions and attitudes. In order to expand our approach, alternative programs should be explored. A somewhat unusual but very promising approach to address offenders' human needs is the use of animals in …

  1. Stimulation artifact correction method for estimation of early cortico-cortical evoked potentials

    PubMed Central

    Trebaul, Lena; Rudrauf, David; Job, Anne-Sophie; Mălîia, Mihai Dragos; Popa, Irina; Barborica, Andrei; Minotti, Lorella; Mîndruţă, Ioana; Kahane, Philippe; David, Olivier

    2016-01-01

    Background Effective connectivity can be explored using direct electrical stimulations in patients suffering from drug-resistant focal epilepsies and investigated with intracranial electrodes. Responses to brief electrical pulses mimic the physiological propagation of signals and manifest as cortico-cortical evoked potentials (CCEP). The first CCEP component is believed to reflect direct connectivity with the stimulated region but the stimulation artifact, a sharp deflection occurring during a few milliseconds, frequently contaminates it. New method In order to recover the characteristics of early CCEP responses, we developed an artifact correction method based on electrical modeling of the electrode–tissue interface. The biophysically motivated artifact templates are then regressed out of the recorded data as in any classical template-matching removal artifact methods. Results Our approach is able to make the distinction between the physiological responses time-locked to the stimulation pulses and the non-physiological component. We tested the correction on simulated CCEP data in order to quantify its efficiency for different stimulation and recording parameters. We demonstrated the efficiency of the new correction method on simulations of single trial recordings for early responses contaminated with the stimulation artifact. The results highlight the importance of sampling frequency for an accurate analysis of CCEP. We then applied the approach to experimental data. Comparison with existing method The model-based template removal was compared to a correction based on the subtraction of the averaged artifact. Conclusions This new correction method of stimulation artifact will enable investigators to better analyze early CCEP components and infer direct effective connectivity in future CCEP studies. PMID:26952846

  2. The Therapeutic Potential of Brown Adipocytes in Humans.

    PubMed

    Porter, Craig; Chondronikola, Maria; Sidossis, Labros S

    2015-01-01

    Obesity and its metabolic consequences represent a significant clinical problem. From a thermodynamic standpoint, obesity results from a discord in energy intake and expenditure. To date, lifestyle interventions based on reducing energy intake and/or increasing energy expenditure have proved ineffective in the prevention and/or treatment of obesity, owing to poor long-term adherence to such interventions. Thus, an effective strategy to prevent or correct obesity is currently lacking. As the combustion engines of our cells, mitochondria play a critical role in energy expenditure. At a whole-body level, approximately 80% of mitochondrial membrane potential generated by fuel oxidation is used to produce ATP, and the remaining 20% is lost through heat-producing uncoupling reactions. The coupling of mitochondrial respiration to ATP production represents an important component in whole-body energy expenditure. Brown adipose tissue (BAT) is densely populated with mitochondria containing the inner mitochondrial proton carrier uncoupling protein 1 (UCP1). UCP1 uncouples oxidative phosphorylation, meaning that mitochondrial membrane potential is dissipated as heat. The recent rediscovery of BAT depots in adult humans has rekindled scientific interest in the manipulation of mitochondrial uncoupling reactions as a means to increase metabolic rate, thereby counteracting obesity and its associated metabolic phenotype. In this article, we discuss the evidence for the role BAT plays in metabolic rate and glucose and lipid metabolism in humans and the potential for UCP1 recruitment in the white adipose tissue of humans. While the future holds much promise for a therapeutic role of UCP1 expressing adipocytes in human energy metabolism, particularly in the context of obesity, tissue-specific strategies that activate or recruit UCP1 in human adipocytes represent an obligatory translational step for this early promise to be realized. PMID:26528238

  3. The Therapeutic Potential of Brown Adipocytes in Humans

    PubMed Central

    Porter, Craig; Chondronikola, Maria; Sidossis, Labros S.

    2015-01-01

    Obesity and its metabolic consequences represent a significant clinical problem. From a thermodynamic standpoint, obesity results from a discord in energy intake and expenditure. To date, lifestyle interventions based on reducing energy intake and/or increasing energy expenditure have proved ineffective in the prevention and/or treatment of obesity, owing to poor long-term adherence to such interventions. Thus, an effective strategy to prevent or correct obesity is currently lacking. As the combustion engines of our cells, mitochondria play a critical role in energy expenditure. At a whole-body level, approximately 80% of mitochondrial membrane potential generated by fuel oxidation is used to produce ATP, and the remaining 20% is lost through heat-producing uncoupling reactions. The coupling of mitochondrial respiration to ATP production represents an important component in whole-body energy expenditure. Brown adipose tissue (BAT) is densely populated with mitochondria containing the inner mitochondrial proton carrier uncoupling protein 1 (UCP1). UCP1 uncouples oxidative phosphorylation, meaning that mitochondrial membrane potential is dissipated as heat. The recent rediscovery of BAT depots in adult humans has rekindled scientific interest in the manipulation of mitochondrial uncoupling reactions as a means to increase metabolic rate, thereby counteracting obesity and its associated metabolic phenotype. In this article, we discuss the evidence for the role BAT plays in metabolic rate and glucose and lipid metabolism in humans and the potential for UCP1 recruitment in the white adipose tissue of humans. While the future holds much promise for a therapeutic role of UCP1 expressing adipocytes in human energy metabolism, particularly in the context of obesity, tissue-specific strategies that activate or recruit UCP1 in human adipocytes represent an obligatory translational step for this early promise to be realized. PMID:26528238

  4. Attenuation correction for the large non-human primate brain imaging using microPET.

    PubMed

    Naidoo-Variawa, S; Lehnert, W; Kassiou, M; Banati, R; Meikle, S R

    2010-04-21

    Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a (57)Co transmission point source with a 4% energy window. The optimal energy window for a (68)Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for (57)Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [(18)F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass (57)Co (4% energy window) or (68)Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

  5. Attenuation correction for the large non-human primate brain imaging using microPET

    NASA Astrophysics Data System (ADS)

    Naidoo-Variawa, S.; Lehnert, W.; Kassiou, M.; Banati, R.; Meikle, S. R.

    2010-04-01

    Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a 57Co transmission point source with a 4% energy window. The optimal energy window for a 68Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for 57Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [18F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass 57Co (4% energy window) or 68Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

  6. [Music-Acoustic Signals Controlled by Subject's Brain Potentials in the Correction of Unfavorable Functional States].

    PubMed

    Fedotchev, A I; Bondar, A T; Bakhchina, A V; Parin, S B; Polevaya, S A; Radchenko, G S

    2016-01-01

    Literature review and the results of own studies on the development and experimental testing of musical EEG neurofeedback technology are presented. The technology is based on exposure of subjects to music or music-like signals that are organized in strict accordance with the current values of brain potentials of the patient. The main attention is paid to the analysis of the effectiveness of several versions of the technology, using specific and meaningful for the individual narrow-frequency EEG oscillators during the correction of unfavorable changes of the functional state. PMID:27149824

  7. Time transients in the quantum corrected Newtonian potential induced by a massless nonminimally coupled scalar field

    SciTech Connect

    Marunovic, Anja; Prokopec, Tomislav

    2011-05-15

    We calculate the one-loop graviton vacuum polarization induced by a massless, nonminimally coupled scalar field on Minkowski background. We make use of the Schwinger-Keldysh formalism, which allows us to study time dependent phenomena. As an application we compute the leading quantum correction to the Newtonian potential of a point particle. The novel aspect of the calculation is the use of the Schwinger-Keldysh formalism, within which we calculate the time transients induced by switching on the graviton-scalar coupling.

  8. [Music-Acoustic Signals Controlled by Subject's Brain Potentials in the Correction of Unfavorable Functional States].

    PubMed

    Fedotchev, A I; Bondar, A T; Bakhchina, A V; Parin, S B; Polevaya, S A; Radchenko, G S

    2016-01-01

    Literature review and the results of own studies on the development and experimental testing of musical EEG neurofeedback technology are presented. The technology is based on exposure of subjects to music or music-like signals that are organized in strict accordance with the current values of brain potentials of the patient. The main attention is paid to the analysis of the effectiveness of several versions of the technology, using specific and meaningful for the individual narrow-frequency EEG oscillators during the correction of unfavorable changes of the functional state.

  9. Derivation of the correct waveform of the human electrocardiogram by Willem Einthoven, 1890-1895.

    PubMed

    Kligfield, Paul

    2010-01-01

    In the period 1890 to 1895, Willem Einthoven greatly improved the quality of tracings that could be directly obtained with the capillary electrometer. He then introduced an ingenious correction for the poor frequency response of these instruments, using differential equations. This method allowed him to predict the correct form of the human electrocardiogram, as subsequently revealed by the new string galvanometer that he introduced in 1902. For Einthoven, who won the Nobel Prize for the development of the electrocardiogram in 1924, one of the most rewarding aspects of the high fidelity recording of the human electrocardiogram was its validation of his earlier theoretical predictions regarding the electrical activity of the heart. PMID:20104469

  10. Does Human Milk Modulate Body Composition in Late Preterm Infants at Term-Corrected Age?

    PubMed Central

    Giannì, Maria Lorella; Consonni, Dario; Liotto, Nadia; Roggero, Paola; Morlacchi, Laura; Piemontese, Pasqua; Menis, Camilla; Mosca, Fabio

    2016-01-01

    (1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at  term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content(β = −47.9, 95% confidence interval (CI) = −95.7; −0.18; p = 0.049; β = −89.6, 95% CI = −131.5; −47.7; p < 0.0001; β = −104.1, 95% CI = −151.4; −56.7, p < 0.0001); (4) Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants. PMID:27782098

  11. Quantification of regenerative potential in primary human mammary epithelial cells

    PubMed Central

    Linnemann, Jelena R.; Miura, Haruko; Meixner, Lisa K.; Irmler, Martin; Kloos, Uwe J.; Hirschi, Benjamin; Bartsch, Harald S.; Sass, Steffen; Beckers, Johannes; Theis, Fabian J.; Gabka, Christian; Sotlar, Karl; Scheel, Christina H.

    2015-01-01

    We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49fhi/EpCAM− population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis. PMID:26071498

  12. Quantification of regenerative potential in primary human mammary epithelial cells.

    PubMed

    Linnemann, Jelena R; Miura, Haruko; Meixner, Lisa K; Irmler, Martin; Kloos, Uwe J; Hirschi, Benjamin; Bartsch, Harald S; Sass, Steffen; Beckers, Johannes; Theis, Fabian J; Gabka, Christian; Sotlar, Karl; Scheel, Christina H

    2015-09-15

    We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49f(hi)/EpCAM(-) population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis.

  13. Formal Analysis of Human Automation Interaction: The Problem of Display Correctness

    NASA Technical Reports Server (NTRS)

    Degani, Asaf; Heymann, Michael; Austin, David; Shafto, Michael; Remington, Roger (Technical Monitor)

    1998-01-01

    This presentation attempted to develop a quantitative method for evaluating the effectiveness of autoflight displays. Researchers sought to develop a methodology for evaluation of display correctness and develop a methodology for display synthesis. Topics covered included: mode awareness, industry/research contributions, human-machine interface analysis, research objectives, modeling, flight guidance project and evaluation.

  14. The correction of the distortion of human face based on three-dimensional modeling methods

    NASA Astrophysics Data System (ADS)

    Ye, Qingmin; Chen, Kuo; Feng, Huajun; Xu, Zhihai; Li, Qi

    2015-08-01

    When the human face is on the edge of field of the camera which has a large view, serious deformation will be captured. To correct the distortion of the human face, we present an approach based on setting up a 3D model. Firstly, we construct 3D target face modeling by using the data and depth information of the standard human face, which is set up by the three-dimensional model with three-dimensional Gaussian function with sectional type. According to the size of the face in the image and the parameters of the camera, we can obtain the information of relative position and depth of the human face. Then by translating the virtual camera axis to the center of the face, we can achieve the goal to correct the distortion of the face based on the theory of three-dimensional imaging. Finally, we have made a lot of experiments, and we study the influence of parameters of the 3D model of human face. The result indicates that the method presented by this paper can play an effective role in correcting the distortion of the face in the edge of the view, and we can get better results if the model appreciates the real human face.

  15. Deoxynivalenol: toxicology and potential effects on humans.

    PubMed

    Pestka, James J; Smolinski, Alexa T

    2005-01-01

    Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereal-based foods worldwide. At the molecular level, DON disrupts normal cell function by inhibiting protein synthesis via binding to the ribosome and by activating critical cellular kinases involved in signal transduction related to proliferation, differentiation, and apoptosis. Relative to toxicity, there are marked species differences, with the pig being most sensitive to DON, followed by rodent > dog > cat > poultry > ruminants. The physiologic parameter that is most sensitive to low-level DON exposure is the emetic response, with as little as 0.05 to 0.1 mg/kg body weight (bw) inducing vomiting in swine and dogs. Chinese epidemiological studies suggest that DON may also produce emetic effects in humans. With respect to chronic effects, growth (anorexia and decreased nutritional efficiency), immune function, (enhancement and suppression), and reproduction (reduced litter size) are also adversely affected by DON in animals, whereas incidence of neoplasia is not affected. When hazard evaluations were conducted using existing chronic toxicity data and standard safety factors employed for anthropogenic additives/contaminants in foods, tolerable daily intakes (TDIs) ranging from 1 to 5 microg/kg bw have been generated. Given that critical data gaps still exist regarding the potential health effects of DON, additional research is needed to improve capacity for assessing adverse health effects of this mycotoxin. Critical areas for future DON research include molecular mechanisms underlying toxicity, sensitivity of human cells/tissues relative to other species, emetic effects in primates, epidemiological association with gastroenteritis and chronic disease in humans, and surveillance in cereal crops worldwide.

  16. Correction: Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguy&Ecirtil; N. Thi&Cmb. B. Dot; Kim

    2016-02-01

    Correction for `Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents' by Roxanne Hachani et al., Nanoscale, 2015, DOI: 10.1039/c5nr03867g.

  17. Correction: Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents.

    PubMed

    Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguyen Thi Kim

    2016-02-21

    Correction for 'Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents' by Roxanne Hachani et al., Nanoscale, 2015, DOI: 10.1039/c5nr03867g. PMID:26823197

  18. Human-induced pluripotent stem cells: potential for neurodegenerative diseases.

    PubMed

    Ross, Christopher A; Akimov, Sergey S

    2014-09-15

    The cell biology of human neurodegenerative diseases has been difficult to study till recently. The development of human induced pluripotent stem cell (iPSC) models has greatly enhanced our ability to model disease in human cells. Methods have recently been improved, including increasing reprogramming efficiency, introducing non-viral and non-integrating methods of cell reprogramming, and using novel gene editing techniques for generating genetically corrected lines from patient-derived iPSCs, or for generating mutations in control cell lines. In this review, we highlight accomplishments made using iPSC models to study neurodegenerative disorders such as Huntington's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, Fronto-Temporal Dementia, Alzheimer's disease, Spinomuscular Atrophy and other polyglutamine diseases. We review disease-related phenotypes shown in patient-derived iPSCs differentiated to relevant neural subtypes, often with stressors or cell "aging", to enhance disease-specific phenotypes. We also discuss prospects for the future of using of iPSC models of neurodegenerative disorders, including screening and testing of therapeutic compounds, and possibly of cell transplantation in regenerative medicine. The new iPSC models have the potential to greatly enhance our understanding of pathogenesis and to facilitate the development of novel therapeutics.

  19. Field of view extension and truncation correction for MR-based human attenuation correction in simultaneous MR/PET imaging

    SciTech Connect

    Blumhagen, Jan O. Ladebeck, Ralf; Fenchel, Matthias; Braun, Harald; Quick, Harald H.; Faul, David; Scheffler, Klaus

    2014-02-15

    Purpose: In quantitative PET imaging, it is critical to accurately measure and compensate for the attenuation of the photons absorbed in the tissue. While in PET/CT the linear attenuation coefficients can be easily determined from a low-dose CT-based transmission scan, in whole-body MR/PET the computation of the linear attenuation coefficients is based on the MR data. However, a constraint of the MR-based attenuation correction (AC) is the MR-inherent field-of-view (FoV) limitation due to static magnetic field (B{sub 0}) inhomogeneities and gradient nonlinearities. Therefore, the MR-based human AC map may be truncated or geometrically distorted toward the edges of the FoV and, consequently, the PET reconstruction with MR-based AC may be biased. This is especially of impact laterally where the patient arms rest beside the body and are not fully considered. Methods: A method is proposed to extend the MR FoV by determining an optimal readout gradient field which locally compensates B{sub 0} inhomogeneities and gradient nonlinearities. This technique was used to reduce truncation in AC maps of 12 patients, and the impact on the PET quantification was analyzed and compared to truncated data without applying the FoV extension and additionally to an established approach of PET-based FoV extension. Results: The truncation artifacts in the MR-based AC maps were successfully reduced in all patients, and the mean body volume was thereby increased by 5.4%. In some cases large patient-dependent changes in SUV of up to 30% were observed in individual lesions when compared to the standard truncated attenuation map. Conclusions: The proposed technique successfully extends the MR FoV in MR-based attenuation correction and shows an improvement of PET quantification in whole-body MR/PET hybrid imaging. In comparison to the PET-based completion of the truncated body contour, the proposed method is also applicable to specialized PET tracers with little uptake in the arms and might

  20. Latency correction of event-related potentials between different experimental protocols

    NASA Astrophysics Data System (ADS)

    Iturrate, I.; Chavarriaga, R.; Montesano, L.; Minguez, J.; Millán, JdR

    2014-06-01

    Objective. A fundamental issue in EEG event-related potentials (ERPs) studies is the amount of data required to have an accurate ERP model. This also impacts the time required to train a classifier for a brain-computer interface (BCI). This issue is mainly due to the poor signal-to-noise ratio and the large fluctuations of the EEG caused by several sources of variability. One of these sources is directly related to the experimental protocol or application designed, and may affect the amplitude or latency of ERPs. This usually prevents BCI classifiers from generalizing among different experimental protocols. In this paper, we analyze the effect of the amplitude and the latency variations among different experimental protocols based on the same type of ERP. Approach. We present a method to analyze and compensate for the latency variations in BCI applications. The algorithm has been tested on two widely used ERPs (P300 and observation error potentials), in three experimental protocols in each case. We report the ERP analysis and single-trial classification. Main results. The results obtained show that the designed experimental protocols significantly affect the latency of the recorded potentials but not the amplitudes. Significance. These results show how the use of latency-corrected data can be used to generalize the BCIs, reducing the calibration time when facing a new experimental protocol.

  1. Intensity inhomogeneity correction for magnetic resonance imaging of human brain at 7T

    SciTech Connect

    Uwano, Ikuko; Yamashita, Fumio; Higuchi, Satomi; Ito, Kenji; Sasaki, Makoto; Kudo, Kohsuke Goodwin, Jonathan; Harada, Taisuke; Ogawa, Akira

    2014-02-15

    Purpose: To evaluate the performance and efficacy for intensity inhomogeneity correction of various sequences of the human brain in 7T MRI using the extended version of the unified segmentation algorithm. Materials: Ten healthy volunteers were scanned with four different sequences (2D spin echo [SE], 3D fast SE, 2D fast spoiled gradient echo, and 3D time-of-flight) by using a 7T MRI system. Intensity inhomogeneity correction was performed using the “New Segment” module in SPM8 with four different values (120, 90, 60, and 30 mm) of full width at half maximum (FWHM) in Gaussian smoothness. The uniformity in signals in the entire white matter was evaluated using the coefficient of variation (CV); mean signal intensities between the subcortical and deep white matter were compared, and contrast between subcortical white matter and gray matter was measured. The length of the lenticulostriate (LSA) was measured on maximum intensity projection (MIP) images in the original and corrected images. Results: In all sequences, the CV decreased as the FWHM value decreased. The differences of mean signal intensities between subcortical and deep white matter also decreased with smaller FWHM values. The contrast between white and gray matter was maintained at all FWHM values. LSA length was significantly greater in corrected MIP than in the original MIP images. Conclusions: Intensity inhomogeneity in 7T MRI can be successfully corrected using SPM8 for various scan sequences.

  2. Gene transfer corrects acute GM2 gangliosidosis--potential therapeutic contribution of perivascular enzyme flow.

    PubMed

    Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2012-08-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity-as opposed to tremor-ataxia-were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue-long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system. PMID:22453766

  3. Gene Transfer Corrects Acute GM2 Gangliosidosis—Potential Therapeutic Contribution of Perivascular Enzyme Flow

    PubMed Central

    Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2012-01-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay–Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity—as opposed to tremor-ataxia—were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue—long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system. PMID:22453766

  4. Gray matter myelination of 1555 human brains using partial volume corrected MRI images

    PubMed Central

    Shafee, Rebecca; Buckner, Randy L.; Fischl, Bruce

    2014-01-01

    The myelin content of the cortex changes over the human lifetime and aberrant cortical myelination is associated with diseases such as schizophrenia and multiple sclerosis. Recently magnetic resonance imaging (MRI) techniques have shown potential in differentiating between myeloarchitectonically distinct cortical regions in vivo. Here we introduce a new algorithm for correcting partial volume effects present in mm-scale MRI images which was used to investigate the myelination pattern of the cerebral cortex in 1555 clinically normal subjects using the ratio of T1-weighted (T1w) and T2-weighted (T2w) MRI images. A significant linear cross-sectional age increase in T1w/T2w estimated myelin was detected across an 18 to 35 year age span (highest value of ~ 1%/year compared to mean T1w/T2w myelin value at 18 years). The cortex was divided at mid-thickness and the value of T1w/T2w myelin calculated for the inner and the outer layers separately. The increase in T1w/T2w estimated myelin occurs predominantly in the inner layer for most cortical regions. The ratio of the inner and outer layer T1w/T12w myelin was further validated using high-resolution in vivo MRI scans and also a high-resolution MRI scan of a postmortem brain. Additionally, the relationships between cortical thickness, curvature and T1w/T2w estimated myelin were found to be significant, although the relationships varied across the cortex. We discuss these observations as well as limitations of using the T1w/T2w ratio as an estimate of cortical myelin. PMID:25449739

  5. Correction for human head motion in helical x-ray CT

    NASA Astrophysics Data System (ADS)

    Kim, J.-H.; Sun, T.; Alcheikh, A. R.; Kuncic, Z.; Nuyts, J.; Fulton, R.

    2016-02-01

    Correction for rigid object motion in helical CT can be achieved by reconstructing from a modified source-detector orbit, determined by the object motion during the scan. This ensures that all projections are consistent, but it does not guarantee that the projections are complete in the sense of being sufficient for exact reconstruction. We have previously shown with phantom measurements that motion-corrected helical CT scans can suffer from data-insufficiency, in particular for severe motions and at high pitch. To study whether such data-insufficiency artefacts could also affect the motion-corrected CT images of patients undergoing head CT scans, we used an optical motion tracking system to record the head movements of 10 healthy volunteers while they executed each of the 4 different types of motion (‘no’, slight, moderate and severe) for 60 s. From these data we simulated 354 motion-affected CT scans of a voxelized human head phantom and reconstructed them with and without motion correction. For each simulation, motion-corrected (MC) images were compared with the motion-free reference, by visual inspection and with quantitative similarity metrics. Motion correction improved similarity metrics in all simulations. Of the 270 simulations performed with moderate or less motion, only 2 resulted in visible residual artefacts in the MC images. The maximum range of motion in these simulations would encompass that encountered in the vast majority of clinical scans. With severe motion, residual artefacts were observed in about 60% of the simulations. We also evaluated a new method of mapping local data sufficiency based on the degree to which Tuy’s condition is locally satisfied, and observed that areas with high Tuy values corresponded to the locations of residual artefacts in the MC images. We conclude that our method can provide accurate and artefact-free MC images with most types of head motion likely to be encountered in CT imaging, provided that the motion can

  6. Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

    SciTech Connect

    Kyle, J.W.; Vogler, C.; Hoffmann, J.W.; Sly, W.S. ); Birkenmeier, E.H.; Gwynn, B. )

    1990-05-01

    The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.

  7. Adaptive Optics Analysis of Visual Benefit with Higher-order Aberrations Correction of Human Eye - Poster Paper

    NASA Astrophysics Data System (ADS)

    Xue, Lixia; Dai, Yun; Rao, Xuejun; Wang, Cheng; Hu, Yiyun; Liu, Qian; Jiang, Wenhan

    2008-01-01

    Higher-order aberrations correction can improve visual performance of human eye to some extent. To evaluate how much visual benefit can be obtained with higher-order aberrations correction we developed an adaptive optics vision simulator (AOVS). Dynamic real time optimized modal compensation was used to implement various customized higher-order ocular aberrations correction strategies. The experimental results indicate that higher-order aberrations correction can improve visual performance of human eye comparing with only lower-order aberration correction but the improvement degree and higher-order aberration correction strategy are different from each individual. Some subjects can acquire great visual benefit when higher-order aberrations were corrected but some subjects acquire little visual benefit even though all higher-order aberrations were corrected. Therefore, relative to general lower-order aberrations correction strategy, customized higher-order aberrations correction strategy is needed to obtain optimal visual improvement for each individual. AOVS provides an effective tool for higher-order ocular aberrations optometry for customized ocular aberrations correction.

  8. The impact of highly correlated potential energy surfaces on the anharmonically corrected IR spectrum of acetonitrile.

    PubMed

    Lutz, Oliver M D; Rode, Bernd M; Bonn, Günther K; Huck, Christian W

    2014-10-15

    This paper discusses the quality and feasibility of highly correlated ab initio techniques in a vibrational self-consistent field (VSCF) approach using acetonitrile as a model system. The topical renormalized coupled-cluster technique exploiting the similarity-transformed Hamiltonian's left eigenstates (i.e. CR-CC(2,3)) is investigated alongside the well-known Hartree-Fock (HF), Møller-Plesset second-order perturbation theory (MP2) and coupled cluster (CCSD(T)) methods. The inclusion of mode triple interactions is discussed and it is found that the use of an effective core potential (ECP) serves as a viable compromise during the highly demanding task of computing such contributions, thus enabling a grid-based evaluation of three mode interaction terms with coupled cluster techniques also for larger molecules. In this context, a previously proposed reduced coupling scheme [1] is investigated, confirming the applicability of this technique to a system exhibiting a rather complex electronic structure. A combination of Ahlrichs' triple-ζ valence polarized (TZVP) basis set with Dunning's set of core-valence correlation functions is found to deliver results in good agreement with experiment while being computationally very feasible. Since CH3CN exhibits four degenerate vibrational degrees of freedom, it serves as an ideal model system for critically assessing the qualities of the degenerate second-order perturbation theory corrected (DPT2) VSCF technique. Besides fundamental vibrations, a thorough investigation of overtone transitions and combination bands is conducted by means of comparing the results to both available and newly recorded experimental data.

  9. The impact of highly correlated potential energy surfaces on the anharmonically corrected IR spectrum of acetonitrile

    NASA Astrophysics Data System (ADS)

    Lutz, Oliver M. D.; Rode, Bernd M.; Bonn, Günther K.; Huck, Christian W.

    2014-10-01

    This paper discusses the quality and feasibility of highly correlated ab initio techniques in a vibrational self-consistent field (VSCF) approach using acetonitrile as a model system. The topical renormalized coupled-cluster technique exploiting the similarity-transformed Hamiltonian's left eigenstates (i.e. CR-CC(2,3)) is investigated alongside the well-known Hartree-Fock (HF), Møller-Plesset second-order perturbation theory (MP2) and coupled cluster (CCSD(T)) methods. The inclusion of mode triple interactions is discussed and it is found that the use of an effective core potential (ECP) serves as a viable compromise during the highly demanding task of computing such contributions, thus enabling a grid-based evaluation of three mode interaction terms with coupled cluster techniques also for larger molecules. In this context, a previously proposed reduced coupling scheme [1] is investigated, confirming the applicability of this technique to a system exhibiting a rather complex electronic structure. A combination of Ahlrichs' triple-ζ valence polarized (TZVP) basis set with Dunning's set of core-valence correlation functions is found to deliver results in good agreement with experiment while being computationally very feasible. Since CH3CN exhibits four degenerate vibrational degrees of freedom, it serves as an ideal model system for critically assessing the qualities of the degenerate second-order perturbation theory corrected (DPT2) VSCF technique. Besides fundamental vibrations, a thorough investigation of overtone transitions and combination bands is conducted by means of comparing the results to both available and newly recorded experimental data.

  10. Rovibrational spectra of ammonia. I. Unprecedented accuracy of a potential energy surface used with nonadiabatic corrections

    NASA Astrophysics Data System (ADS)

    Huang, Xinchuan; Schwenke, David W.; Lee, Timothy J.

    2011-01-01

    In this work, we build upon our previous work on the theoretical spectroscopy of ammonia, NH3. Compared to our 2008 study, we include more physics in our rovibrational calculations and more experimental data in the refinement procedure, and these enable us to produce a potential energy surface (PES) of unprecedented accuracy. We call this the HSL-2 PES. The additional physics we include is a second-order correction for the breakdown of the Born-Oppenheimer approximation, and we find it to be critical for improved results. By including experimental data for higher rotational levels in the refinement procedure, we were able to greatly reduce our systematic errors for the rotational dependence of our predictions. These additions together lead to a significantly improved total angular momentum (J) dependence in our computed rovibrational energies. The root-mean-square error between our predictions using the HSL-2 PES and the reliable energy levels from the HITRAN database for J = 0-6 and J = 7/8 for 14NH3 is only 0.015 cm-1 and 0.020/0.023 cm-1, respectively. The root-mean-square errors for the characteristic inversion splittings are approximately 1/3 smaller than those for energy levels. The root-mean-square error for the 6002 J = 0-8 transition energies is 0.020 cm-1. Overall, for J = 0-8, the spectroscopic data computed with HSL-2 is roughly an order of magnitude more accurate relative to our previous best ammonia PES (denoted HSL-1). These impressive numbers are eclipsed only by the root-mean-square error between our predictions for purely rotational transition energies of 15NH3 and the highly accurate Cologne database (CDMS): 0.00034 cm-1 (10 MHz), in other words, 2 orders of magnitude smaller. In addition, we identify a deficiency in the 15NH3 energy levels determined from a model of the experimental data .

  11. Rovibrational spectra of ammonia. I. Unprecedented accuracy of a potential energy surface used with nonadiabatic corrections.

    PubMed

    Huang, Xinchuan; Schwenke, David W; Lee, Timothy J

    2011-01-28

    In this work, we build upon our previous work on the theoretical spectroscopy of ammonia, NH(3). Compared to our 2008 study, we include more physics in our rovibrational calculations and more experimental data in the refinement procedure, and these enable us to produce a potential energy surface (PES) of unprecedented accuracy. We call this the HSL-2 PES. The additional physics we include is a second-order correction for the breakdown of the Born-Oppenheimer approximation, and we find it to be critical for improved results. By including experimental data for higher rotational levels in the refinement procedure, we were able to greatly reduce our systematic errors for the rotational dependence of our predictions. These additions together lead to a significantly improved total angular momentum (J) dependence in our computed rovibrational energies. The root-mean-square error between our predictions using the HSL-2 PES and the reliable energy levels from the HITRAN database for J = 0-6 and J = 7∕8 for (14)NH(3) is only 0.015 cm(-1) and 0.020∕0.023 cm(-1), respectively. The root-mean-square errors for the characteristic inversion splittings are approximately 1∕3 smaller than those for energy levels. The root-mean-square error for the 6002 J = 0-8 transition energies is 0.020 cm(-1). Overall, for J = 0-8, the spectroscopic data computed with HSL-2 is roughly an order of magnitude more accurate relative to our previous best ammonia PES (denoted HSL-1). These impressive numbers are eclipsed only by the root-mean-square error between our predictions for purely rotational transition energies of (15)NH(3) and the highly accurate Cologne database (CDMS): 0.00034 cm(-1) (10 MHz), in other words, 2 orders of magnitude smaller. In addition, we identify a deficiency in the (15)NH(3) energy levels determined from a model of the experimental data. PMID:21280738

  12. TALEN-mediated generation and genetic correction of disease-specific human induced pluripotent stem cells.

    PubMed

    Ramalingam, Sivaprakash; Annaluru, Narayana; Kandavelou, Karthikeyan; Chandrasegaran, Srinivasan

    2014-01-01

    Generation and precise genetic correction of patient-derived hiPSCs have great potential in regenerative medicine. Such targeted genetic manipulations can now be achieved using gene-editing nucleases. Here, we report generation of cystic fibrosis (CF) and Gaucher's disease (GD) hiPSCs respectively from CF (homozygous for CFTRΔF508 mutation) and Type II GD [homozygous for β-glucocerebrosidase (GBA) 1448T>C mutation] patient fibroblasts, using CCR5- specific TALENs. Site-specific addition of loxP-flanked Oct4/Sox2/Klf4/Lin28/Nanog/eGFP gene cassette at the endogenous CCR5 site of patient-derived disease-specific primary fibroblasts induced reprogramming, giving rise to both monoallele (heterozygous) and biallele CCR5-modified hiPSCs. Subsequent excision of the donor cassette was done by treating CCR5-modified CF and GD hiPSCs with Cre. We also demonstrate site-specific correction of sickle cell disease (SCD) mutations at the endogenous HBB locus of patient-specific hiPSCs [TNC1 line that is homozygous for mutated β- globin alleles (βS/βS)], using HBB-specific TALENs. SCD-corrected hiPSC lines showed gene conversion of the mutated βS to the wild-type βA in one of the HBB alleles, while the other allele remained a mutant phenotype. After excision of the loxP-flanked DNA cassette from the SCD-corrected hiPSC lines using Cre, we obtained secondary heterozygous βS/βA hiPSCs, which express the wild-type (βA) transcript to 30-40% level as compared to uncorrected (βS/βS) SCD hiPSCs when differentiated into erythroid cells. Furthermore, we also show that TALEN-mediated generation and genetic correction of disease-specific hiPSCs did not induce any off-target mutations at closely related sites.

  13. In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases.

    PubMed

    Sebastiano, Vittorio; Maeder, Morgan L; Angstman, James F; Haddad, Bahareh; Khayter, Cyd; Yeo, Dana T; Goodwin, Mathew J; Hawkins, John S; Ramirez, Cherie L; Batista, Luis F Z; Artandi, Steven E; Wernig, Marius; Joung, J Keith

    2011-11-01

    The combination of induced pluripotent stem cell (iPSC) technology and targeted gene modification by homologous recombination (HR) represents a promising new approach to generate genetically corrected, patient-derived cells that could be used for autologous transplantation therapies. This strategy has several potential advantages over conventional gene therapy including eliminating the need for immunosuppression, avoiding the risk of insertional mutagenesis by therapeutic vectors, and maintaining expression of the corrected gene by endogenous control elements rather than a constitutive promoter. However, gene targeting in human pluripotent cells has remained challenging and inefficient. Recently, engineered zinc finger nucleases (ZFNs) have been shown to substantially increase HR frequencies in human iPSCs, raising the prospect of using this technology to correct disease causing mutations. Here, we describe the generation of iPSC lines from sickle cell anemia patients and in situ correction of the disease causing mutation using three ZFN pairs made by the publicly available oligomerized pool engineering method (OPEN). Gene-corrected cells retained full pluripotency and a normal karyotype following removal of reprogramming factor and drug-resistance genes. By testing various conditions, we also demonstrated that HR events in human iPSCs can occur as far as 82 bps from a ZFN-induced break. Our approach delineates a roadmap for using ZFNs made by an open-source method to achieve efficient, transgene-free correction of monogenic disease mutations in patient-derived iPSCs. Our results provide an important proof of principle that ZFNs can be used to produce gene-corrected human iPSCs that could be used for therapeutic applications.

  14. Effect of the corrected ionization potential and spatial distribution on the angular and energy distribution in tunnel ionization

    NASA Astrophysics Data System (ADS)

    Petrović, V. M.; Miladinović, T. B.

    2016-05-01

    Within the framework of the Ammosov-Delone-Krainov theory, we consider the angular and energy distribution of outgoing electrons due to ionization by a circularly polarized electromagnetic field. A correction of the ground ionization potential by the ponderomotive and Stark shift is incorporated in both distributions. Spatial dependence is analyzed.

  15. Pacesetter potential of the human gastroduodenal junction

    PubMed Central

    Duthie, H. L.; Kwong, N. K.; Brown, B. H.; Whittaker, G. E.

    1971-01-01

    The pacesetter potential of the gastric antrum and proximal duodenum has been recorded in man by electrodes placed under the serosal coat of the gut. The typical 3 cycle/min of the stomach was found to be conducted across the pylorus into the first part of the duodenum at a rate (2 cm/sec) about four times as fast as its conduction in the more proximal antrum (0·5 cm/sec). A 3 cycle/min pacesetter potential could be detected as far distally in the duodenum as 10 cm from the pylorus. ImagesFig. 3Fig. 5Fig. 7 PMID:5574794

  16. Highest Resolution In Vivo Human Brain MRI Using Prospective Motion Correction.

    PubMed

    Stucht, Daniel; Danishad, K Appu; Schulze, Peter; Godenschweger, Frank; Zaitsev, Maxim; Speck, Oliver

    2015-01-01

    High field MRI systems, such as 7 Tesla (T) scanners, can deliver higher signal to noise ratio (SNR) than lower field scanners and thus allow for the acquisition of data with higher spatial resolution, which is often demanded by users in the fields of clinical and neuroscientific imaging. However, high resolution scans may require long acquisition times, which in turn increase the discomfort for the subject and the risk of subject motion. Even with a cooperative and trained subject, involuntary motion due to heartbeat, swallowing, respiration and changes in muscle tone can cause image artifacts that reduce the effective resolution. In addition, scanning with higher resolution leads to increased sensitivity to even very small movements. Prospective motion correction (PMC) at 3T and 7T has proven to increase image quality in case of subject motion. Although the application of prospective motion correction is becoming more popular, previous articles focused on proof of concept studies and technical descriptions, whereas this paper briefly describes the technical aspects of the optical tracking system, marker fixation and cross calibration and focuses on the application of PMC to very high resolution imaging without intentional motion. In this study we acquired in vivo MR images at 7T using prospective motion correction during long acquisitions. As a result, we present images among the highest, if not the highest resolution of in vivo human brain MRI ever acquired. PMID:26226146

  17. Highest Resolution In Vivo Human Brain MRI Using Prospective Motion Correction

    PubMed Central

    Stucht, Daniel; Danishad, K. Appu; Schulze, Peter; Godenschweger, Frank; Zaitsev, Maxim; Speck, Oliver

    2015-01-01

    High field MRI systems, such as 7 Tesla (T) scanners, can deliver higher signal to noise ratio (SNR) than lower field scanners and thus allow for the acquisition of data with higher spatial resolution, which is often demanded by users in the fields of clinical and neuroscientific imaging. However, high resolution scans may require long acquisition times, which in turn increase the discomfort for the subject and the risk of subject motion. Even with a cooperative and trained subject, involuntary motion due to heartbeat, swallowing, respiration and changes in muscle tone can cause image artifacts that reduce the effective resolution. In addition, scanning with higher resolution leads to increased sensitivity to even very small movements. Prospective motion correction (PMC) at 3T and 7T has proven to increase image quality in case of subject motion. Although the application of prospective motion correction is becoming more popular, previous articles focused on proof of concept studies and technical descriptions, whereas this paper briefly describes the technical aspects of the optical tracking system, marker fixation and cross calibration and focuses on the application of PMC to very high resolution imaging without intentional motion. In this study we acquired in vivo MR images at 7T using prospective motion correction during long acquisitions. As a result, we present images among the highest, if not the highest resolution of in vivo human brain MRI ever acquired. PMID:26226146

  18. The osteogenic potential of human bone callus

    PubMed Central

    Han, Weiqi; He, Wei; Yang, Wanlei; Li, Jianlei; Yang, Zhifan; Lu, Xuanyuan; Qin, An; Qian, Yu

    2016-01-01

    Bone callus, generated during fracture healing, is commonly discarded during surgical procedures. The aim of this study was to investigate the osteogenic potential of bone callus and its possible use as autograft material for patients needing bone grafts. Histology, immunohistochemistry, micro-computed tomography, and biomechanics were performed to examine osteogenic cells, osteoinductive factors, and the osteoconductive structure of bone callus. Alkaline phosphatase-positive osteoblasts, osteoinductive factors (including BMP2, FGF2, TGFB1, and IGF1), and a porous structure were found in bone callus. Early-stage callus (within 3 months after fracture) presented significantly improved osteogenic properties compared to medium- (3–9 months) and late-stage (longer than 9 months) callus. The results revealed that bone callus induced new bone formation in a nude mouse model. Early-stage callus showed better performance to medium- and late-stage callus in the induction of new bone formation at both 8 and 12 weeks. These findings indicated that bone callus, especially early-stage callus, possesses osteogenic potential and can potentially serve as an alternative source of material for bone grafts. PMID:27796345

  19. Corrective transduction of human epidermal stem cells in laminin-5-dependent junctional epidermolysis bullosa.

    PubMed

    Dellambra, E; Vailly, J; Pellegrini, G; Bondanza, S; Golisano, O; Macchia, C; Zambruno, G; Meneguzzi, G; De Luca, M

    1998-06-10

    Laminin-5 is composed of three distinct polypeptides, alpha3, beta3, and gamma2, which are encoded by three different genes, LAMA3, LAMB3, and LAMC2, respectively. We have isolated epidermal keratinocytes from a patient presenting with a lethal form of junctional epidermolysis bullosa characterized by a homozygous mutation of the LAMB3 gene, which led to complete absence of the beta3 polypeptide. In vitro, beta3-null keratinocytes were unable to synthesize laminin-5 and to assemble hemidesmosomes, maintained the impairment of their adhesive properties, and displayed a decrease of their colony-forming ability. A retroviral construct expressing a human beta3 cDNA was used to transduce primary beta3-null keratinocytes. Clonogenic beta3-null keratinocytes were transduced with an efficiency of 100%. Beta3-transduced keratinocytes were able to synthesize and secrete mature heterotrimeric laminin-5. Gene correction fully restored the keratinocyte adhesion machinery, including the capacity of proper hemidesmosomal assembly, and prevented the loss of the colony-forming ability, suggesting a direct link between adhesion to laminin-5 and keratinocyte proliferative capacity. Clonal analysis demonstrated that holoclones expressed the transgene permanently, suggesting stable correction of epidermal stem cells. Because cultured keratinocytes are used routinely to make autologous grafts for patients suffering from large skin or mucosal defects, the full phenotypic reversion of primary human epidermal stem cells defective for a structural protein opens new perspectives in the long-term treatment of genodermatoses. PMID:9650620

  20. Functional requirements for the man-vehicle systems research facility. [identifying and correcting human errors during flight simulation

    NASA Technical Reports Server (NTRS)

    Clement, W. F.; Allen, R. W.; Heffley, R. K.; Jewell, W. F.; Jex, H. R.; Mcruer, D. T.; Schulman, T. M.; Stapleford, R. L.

    1980-01-01

    The NASA Ames Research Center proposed a man-vehicle systems research facility to support flight simulation studies which are needed for identifying and correcting the sources of human error associated with current and future air carrier operations. The organization of research facility is reviewed and functional requirements and related priorities for the facility are recommended based on a review of potentially critical operational scenarios. Requirements are included for the experimenter's simulation control and data acquisition functions, as well as for the visual field, motion, sound, computation, crew station, and intercommunications subsystems. The related issues of functional fidelity and level of simulation are addressed, and specific criteria for quantitative assessment of various aspects of fidelity are offered. Recommendations for facility integration, checkout, and staffing are included.

  1. Potential of bias correction for downscaling passive microwave and soil moisture data

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Passive microwave satellites such as SMOS (Soil Moisture and Ocean Salinity) or SMAP (Soil Moisture Active Passive) observe brightness temperature (TB) and retrieve soil moisture at a spatial resolution greater than most hydrological processes. Bias correction is proposed as a simple method to disag...

  2. Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures.

    PubMed

    Amano, Tomokazu; Jeffries, Emiko; Amano, Misa; Ko, Akihiro C; Yu, Hong; Ko, Minoru S H

    2015-10-01

    Aneuploidy, an abnormal number of chromosomes, has previously been considered irremediable. Here, we report findings that euploid cells increased among cultured aneuploid cells after exposure to the protein ZSCAN4, encoded by a mammalian-specific gene that is ordinarily expressed in preimplantation embryos and occasionally in stem cells. For footprint-free delivery of ZSCAN4 to cells, we developed ZSCAN4 synthetic mRNAs and Sendai virus vectors that encode human ZSCAN4. Applying the ZSCAN4 biologics to established cultures of mouse embryonic stem cells, most of which had become aneuploid and polyploid, dramatically increased the number of euploid cells within a few days. We then tested the biologics on non-immortalized primary human fibroblast cells derived from four individuals with Down syndrome—the most frequent autosomal trisomy of chromosome 21. Within weeks after ZSCAN4 application to the cells in culture, fluorescent in situ hybridization with a chromosome 21-specific probe detected the emergence of up to 24% of cells with only two rather than three copies. High-resolution G-banded chromosomes further showed up to 40% of cells with a normal karyotype. These findings were confirmed by whole-exome sequencing. Similar results were obtained for cells with the trisomy 18 of Edwards syndrome. Thus a direct, efficient correction of aneuploidy in human fibroblast cells seems possible in vitro using human ZSCAN4. PMID:26324424

  3. Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures

    PubMed Central

    Amano, Tomokazu; Jeffries, Emiko; Amano, Misa; Ko, Akihiro C.; Yu, Hong; Ko, Minoru S. H.

    2015-01-01

    Aneuploidy, an abnormal number of chromosomes, has previously been considered irremediable. Here, we report findings that euploid cells increased among cultured aneuploid cells after exposure to the protein ZSCAN4, encoded by a mammalian-specific gene that is ordinarily expressed in preimplantation embryos and occasionally in stem cells. For footprint-free delivery of ZSCAN4 to cells, we developed ZSCAN4 synthetic mRNAs and Sendai virus vectors that encode human ZSCAN4. Applying the ZSCAN4 biologics to established cultures of mouse embryonic stem cells, most of which had become aneuploid and polyploid, dramatically increased the number of euploid cells within a few days. We then tested the biologics on non-immortalized primary human fibroblast cells derived from four individuals with Down syndrome—the most frequent autosomal trisomy of chromosome 21. Within weeks after ZSCAN4 application to the cells in culture, fluorescent in situ hybridization with a chromosome 21-specific probe detected the emergence of up to 24% of cells with only two rather than three copies. High-resolution G-banded chromosomes further showed up to 40% of cells with a normal karyotype. These findings were confirmed by whole-exome sequencing. Similar results were obtained for cells with the trisomy 18 of Edwards syndrome. Thus a direct, efficient correction of aneuploidy in human fibroblast cells seems possible in vitro using human ZSCAN4. PMID:26324424

  4. A New, Self-Contained Asymptotic Correction Scheme To Exchange-Correlation Potentials For Time-Dependent Density Functional Theory

    SciTech Connect

    Hirata, So; Zhan, Chang-Guo; Apra, Edoardo; Windus, Theresa L.; Dixon, David A.

    2003-11-07

    By combining the asymptotic correction scheme of Casida and Salahub to exchange cor-relation potentials and the phenomenological linear correlation between experimental ionization potentials and highest occupied Kohn–Sham (KS) orbital energies found by Zhan, Nichols, and Dixon, we propose a new, expedient, and self-contained asymptotic correction to exchange-correlation potentials in KS density functional theory (DFT) for use in time-dependent density functional theory (TDDFT) that does not require an ionization potential as an external parameter from a separate calculation. The asymptotically-corrected (TD)DFT is implemented in the quan-tum chemistry program suite NWChem for both sequential and massively parallel execution. The method is shown to be well balanced for both valence- and Rydberg-type transitions with average errors in excitation energies of CO, N2, CH2O, and C2H4 being smaller than those of uncorrected BLYP and B3LYP TDDFT by a factor of 4 and 2, respectively. We demonstrate the general ap-plicability and accuracy of the method for the Rydberg excited states of mono- to tetra-fluorinated methanes, the valence and Rydberg excited states of benzene, and the Q, B, N, and L band posi-tions of free-base porphin.

  5. Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells

    NASA Astrophysics Data System (ADS)

    Bershteyn, Marina; Hayashi, Yohei; Desachy, Guillaume; Hsiao, Edward C.; Sami, Salma; Tsang, Kathryn M.; Weiss, Lauren A.; Kriegstein, Arnold R.; Yamanaka, Shinya; Wynshaw-Boris, Anthony

    2014-03-01

    Ring chromosomes are structural aberrations commonly associated with birth defects, mental disabilities and growth retardation. Rings form after fusion of the long and short arms of a chromosome, and are sometimes associated with large terminal deletions. Owing to the severity of these large aberrations that can affect multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have been proposed. During cell division, ring chromosomes can exhibit unstable behaviour leading to continuous production of aneuploid progeny with low viability and high cellular death rate. The overall consequences of this chromosomal instability have been largely unexplored in experimental model systems. Here we generated human induced pluripotent stem cells (iPSCs) from patient fibroblasts containing ring chromosomes with large deletions and found that reprogrammed cells lost the abnormal chromosome and duplicated the wild-type homologue through the compensatory uniparental disomy (UPD) mechanism. The karyotypically normal iPSCs with isodisomy for the corrected chromosome outgrew co-existing aneuploid populations, enabling rapid and efficient isolation of patient-derived iPSCs devoid of the original chromosomal aberration. Our results suggest a fundamentally different function for cellular reprogramming as a means of `chromosome therapy' to reverse combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures. In addition, our work provides an experimentally tractable human cellular system for studying mechanisms of chromosomal number control, which is of critical relevance to human development and disease.

  6. Efficient genomic correction methods in human iPS cells using CRISPR-Cas9 system.

    PubMed

    Li, Hongmei Lisa; Gee, Peter; Ishida, Kentaro; Hotta, Akitsu

    2016-05-15

    Precise gene correction using the CRISPR-Cas9 system in human iPS cells holds great promise for various applications, such as the study of gene functions, disease modeling, and gene therapy. In this review article, we summarize methods for effective editing of genomic sequences of iPS cells based on our experiences correcting dystrophin gene mutations with the CRISPR-Cas9 system. Designing specific sgRNAs as well as having efficient transfection methods and proper detection assays to assess genomic cleavage activities are critical for successful genome editing in iPS cells. In addition, because iPS cells are fragile by nature when dissociated into single cells, a step-by-step confirmation during the cell recovery process is recommended to obtain an adequate number of genome-edited iPS cell clones. We hope that the techniques described here will be useful for researchers from diverse backgrounds who would like to perform genome editing in iPS cells.

  7. Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease.

    PubMed

    Zou, Jizhong; Mali, Prashant; Huang, Xiaosong; Dowey, Sarah N; Cheng, Linzhao

    2011-10-27

    Human induced pluripotent stem cells (iPSCs) bearing monogenic mutations have great potential for modeling disease phenotypes, screening candidate drugs, and cell replacement therapy provided the underlying disease-causing mutation can be corrected. Here, we report a homologous recombination-based approach to precisely correct the sickle cell disease (SCD) mutation in patient-derived iPSCs with 2 mutated β-globin alleles (β(s)/β(s)). Using a gene-targeting plasmid containing a loxP-flanked drug-resistant gene cassette to assist selection of rare targeted clones and zinc finger nucleases engineered to specifically stimulate homologous recombination at the β(s) locus, we achieved precise conversion of 1 mutated β(s) to the wild-type β(A) in SCD iPSCs. However, the resulting co-integration of the selection gene cassette into the first intron suppressed the corrected allele transcription. After Cre recombinase-mediated excision of this loxP-flanked selection gene cassette, we obtained "secondary" gene-corrected β(s)/β(A) heterozygous iPSCs that express at 25% to 40% level of the wild-type transcript when differentiated into erythrocytes. These data demonstrate that single nucleotide substitution in the human genome is feasible using human iPSCs. This study also provides a new strategy for gene therapy of monogenic diseases using patient-specific iPSCs, even if the underlying disease-causing mutation is not expressed in iPSCs.

  8. Phospholipids in Human Milk and Infant Formulas: Benefits and Needs for Correct Infant Nutrition.

    PubMed

    Cilla, Antonio; Diego Quintaes, Késia; Barberá, Reyes; Alegría, Amparo

    2016-08-17

    The composition of human milk has served as a basis for the development of infant formulas, which are used when breastfeeding is not possible. Among the human milk nutrients, 50% of the total energetic value corresponds to fat, with a high level of fatty acids and 0.2-2.0% present in the form of phospholipids (PLs). The PL contents and fatty acid distribution in PL species have been investigated as bioactive elements for the production of infant formulas, since they offer potential benefits for the optimum growth and health of the newborn infant. The differences in the amount of PLs and in fatty acid distribution in PL species between human milk and infant formulas can imply biologically significant differences for newborn infants fed with infant formulas versus human milk-mainly due to the greater proportion of sphingomyelin with respect to phosphatidylcholine in infant formulas. The limited information referred to the characterization of fatty acid distribution in PL species in infant formulas or in ingredients used to enrich them merits further research in order to obtain products with benefits similar to those of human milk in terms of infant growth, visual acuity, and neurological development. The present review establishes the scientific basis for helping to adjust formulations to the requirements of infant nutrition.

  9. Phospholipids in Human Milk and Infant Formulas: Benefits and Needs for Correct Infant Nutrition.

    PubMed

    Cilla, Antonio; Diego Quintaes, Késia; Barberá, Reyes; Alegría, Amparo

    2016-08-17

    The composition of human milk has served as a basis for the development of infant formulas, which are used when breastfeeding is not possible. Among the human milk nutrients, 50% of the total energetic value corresponds to fat, with a high level of fatty acids and 0.2-2.0% present in the form of phospholipids (PLs). The PL contents and fatty acid distribution in PL species have been investigated as bioactive elements for the production of infant formulas, since they offer potential benefits for the optimum growth and health of the newborn infant. The differences in the amount of PLs and in fatty acid distribution in PL species between human milk and infant formulas can imply biologically significant differences for newborn infants fed with infant formulas versus human milk-mainly due to the greater proportion of sphingomyelin with respect to phosphatidylcholine in infant formulas. The limited information referred to the characterization of fatty acid distribution in PL species in infant formulas or in ingredients used to enrich them merits further research in order to obtain products with benefits similar to those of human milk in terms of infant growth, visual acuity, and neurological development. The present review establishes the scientific basis for helping to adjust formulations to the requirements of infant nutrition. PMID:26075805

  10. [Correction of anemia in chronic kidney failure with lyophilized recombinant human erythropoietin using a subcutaneous approach].

    PubMed

    Amar, M; Cendoroglo Neto, M; Canziani, M E; Nadaletto, M A; Ajzen, H; Draibe, S A

    1994-01-01

    The recombinant human erythropoietin (rHuEPO) by subcutaneous route has been considered the drug of choice for the correction of the anemia of chronic renal patients. PURPOSE--To evaluate the efficacy of a new preparation of rHuEPO in the correction of the anemia of chronic renal patients maintained by haemodialysis, exclusively administered by subcutaneous route, studying the adverse effects and searching for predictive factors for the response to this medication. METHODS--Twelve patients in regular haemodialysis were treated with freeze-dried rHuEPO by subcutaneous route during 18 months with initial doses of 20U/kg/dialysis. They were submitted to a careful clinical and laboratory monitoring for all this study. RESULTS--Eleven patients ended the study reaching the target hematocrit (Htc) of 30% and keeping it during the whole period of the study. The mean correction and maintenance doses of rHuEPO were 65U/kg/dialysis and 51U/kg/dialysis respectively. At the 12th week of the study a significative increase of Htc (18.4 +/- 3.5% vs. 25.4% +/- 3.8%, p < 0.05) was demonstrated. An increase of the erythrocytes and hemoglobin was concomitantly observed. Leucocytes and platelets increased significantly from the 24th week and kept steadily until the end of study. Just potassium increased in the biochemistry analysis of the patients at the 4th and the 12th week of the study returning to the basal values at the 24th week. The evolution of the iron metabolism parameters demonstrated an intermitent and statistically significant decrease of transferrin saturation at the 1st, 12th and 24th week, returning to the basal levels at the end of study. The serum ferritin did not change (582.7 +/- 700, 9ng/mL vs. 700.0 +/- 651, 6ng/nL). The weight and the blood pressure did not change either, although 2 normotensive patients became hypertensive and 2 others with controlled hypertension needed drug rearrange for blood pressure control (36%). A patient had a seizure episode with a full

  11. [Dietary phytoestrogen and its potential benefits in adult human health].

    PubMed

    Garrido, Argelia; de la Maza, María Pía; Valladares, Luis

    2003-11-01

    Human diet contains a series of bioactive vegetal compounds that can improve human health. Among these, there has been a special interest for phytoestrogens. This article reviews the evidence about the potential benefits of phytoestrogens for human health. Forty eight manuscripts were selected for their study design and relevance to human health. The cell growth inhibitory effects of phytoestrogens and their implication in breast cancer are reviewed. Also the effects of these compounds on serum lipid levels and the effectiveness of a phytoestrogen derivate, ipriflavone, on the prevention of osteoporosis are analyzed. Although these compounds have a great potential for improving health, there is still not enough evidence to recommend the routine use of phytoestrogens.

  12. One-loop quantum electrodynamic correction to the gravitational potentials on de Sitter spacetime

    NASA Astrophysics Data System (ADS)

    Wang, C. L.; Woodard, R. P.

    2015-10-01

    We compute the one-loop photon contribution to the graviton self-energy on a de Sitter background and use it to solve the linearized Einstein equation for a point mass. Our results show that a comoving observer sees a logarithmic spatial running Newton's constant. Equivalently, a static observer reports a secular suppression of the Newtonian potential.

  13. Specific gravity and creatinine as corrections for variation in urine concentration in humans, gorillas, and woolly monkeys.

    PubMed

    White, Brent C; Jamison, Keri M; Grieb, Cassie; Lally, Drew; Luckett, Cloe; Kramer, Katie S; Phillips, Justin

    2010-12-01

    Hormones excreted in the urine are widely used to assess the physiological and psychological condition of unrestrained animals. In order to control for variation in the water concentration of urine samples, the hormone concentration is often indexed to the concentration of creatinine. Because there are several problems with using creatinine, we have investigated the efficacy of specific gravity as an alternative basis for adjusting the hormone concentration in humans, gorillas, and woolly monkeys. In an experimental manipulation of human urine hydration, ten volunteers drank a water load proportional to body weight, and provided complete urine collection and saliva samples for four consecutive 20 min intervals. From the urine, we measured cortisol (radioimmunoassay), creatinine (colorimetric assay), and specific gravity (refractometer). Only cortisol was assayed from saliva. During 80 min following water ingestion, cortisol, creatinine, and specific gravity declined as urine became diluted; however, total cortisol excretion remained constant. Only cortisol concentration indexed to specific gravity accurately reflected the consistent cortisol excretion. Specific gravity and creatinine-corrected cortisol values were highly correlated but were significantly different. Salivary cortisol provided evidence for the relative stability of serum cortisol. To determine the utility of these corrections in other primates, we compared specific gravity- and creatinine-corrected cortisol in urine samples from captive gorillas (N=16) and woolly monkeys (N=8). As with the human study, the two corrections were strongly correlated in each species, but the means were different. Specific gravity correction was superior in revealing the circadian variation in cortisol.

  14. Surface-wave potential for triggering tectonic (nonvolcanic) tremor-corrected

    USGS Publications Warehouse

    Hill, David P.

    2012-01-01

    Source processes commonly posed to explain instances of remote dynamic triggering of tectonic (nonvolcanic) tremor by surface waves include frictional failure and various modes of fluid activation. The relative potential for Love- and Rayleigh-wave dynamic stresses to trigger tectonic tremor through failure on critically stressed thrust and vertical strike-slip faults under the Coulomb-Griffith failure criteria as a function of incidence angle are anticorrelated over the 15- to 30-km-depth range that hosts tectonic tremor. Love-wave potential is high for strike-parallel incidence on low-angle reverse faults and null for strike-normal incidence; the opposite holds for Rayleigh waves. Love-wave potential is high for both strike-parallel and strike-normal incidence on vertical, strike-slip faults and minimal for ~45° incidence angles. The opposite holds for Rayleigh waves. This pattern is consistent with documented instances of tremor triggered by Love waves incident on the Cascadia megathrust and the San Andreas fault (SAF) in central California resulting from shear failure on weak faults (apparent friction is μ* ≤ 0:2). Documented instances of tremor triggered by surface waves with strike-parallel incidence along the Nankai megathrust beneath Shikoku, Japan, however, are associated primarily with Rayleigh waves. This is consistent with the tremor bursts resulting from mixed-mode failure (crack opening and shear failure) facilitated by near-lithostatic ambient pore pressure, low differential stress, with a moderate friction coefficient (μ ~ 0:6) on the Nankai subduction interface. Rayleigh-wave dilatational stress is relatively weak at tectonic tremor source depths and seems unlikely to contribute significantly to the triggering process, except perhaps for an indirect role on the SAF in sustaining tremor into the Rayleigh-wave coda that was initially triggered by Love waves.

  15. Convective available potential energy in the environment of oceanic and continental clouds: Correction and comments

    NASA Technical Reports Server (NTRS)

    Lucas, Christopher; Zipser, Edward J.; Lemone, Margaret A.

    1994-01-01

    In 1980, Zipser and LeMone estimated the convective available potential energy (CAPE) for the Thunderstorm Project cumulonimbus environment to be about 3000 J per kg. By assuming the most adiabat reported by Byers and Braham (1949) to be that of an undilute parcel rather than a reference moist adiabat, a significant error was introduced. On the basis of recent calculations made under similar conditions in Oklahoma and Florida, CAPE is now estimated to be considerably lower. These lower CAPE estimates shed doubt on the suggestion that differences in CAPE account for differences in the vertical velocities in convective updrafts over land and over the ocean.

  16. Influence and Correction from the Human Body on the Measurement of a Power-Frequency Electric Field Sensor.

    PubMed

    Xiao, Dongping; Liu, Huaitong; Zhou, Qiang; Xie, Yutong; Ma, Qichao

    2016-06-10

    According to the operating specifications of existing electric field measuring instruments, measuring technicians must be located far from the instruments to eliminate the influence of the human body occupancy on a spatial electric field. Nevertheless, in order to develop a portable safety protection instrument with an effective electric field warning function for working staff in a high-voltage environment, it is necessary to study the influence of an approaching human body on the measurement of an electric field and to correct the measurement results. A single-shaft electric field measuring instrument called the Type LP-2000, which was developed by our research team, is used as the research object in this study. First, we explain the principle of electric field measurement and describe the capacitance effect produced by the human body. Through a theoretical analysis, we show that the measured electric field value decreases as a human body approaches. Their relationship is linearly proportional. Then, the ratio is identified as a correction coefficient to correct for the influence of human body proximity. The conclusion drawn from the theoretical analysis is proved via simulation. The correction coefficient kb = 1.8010 is obtained on the basis of the linear fitting of simulated data. Finally, a physical experiment is performed. When no human is present, we compare the results from the Type LP-2000 measured with Narda EFA-300 and the simulated value to verify the accuracy of the Type LP-2000. For the case of an approaching human body, the correction coefficient kb* = 1.9094 is obtained by comparing the data measured with the Type LP-2000 to the simulated value. The correction coefficient obtained from the experiment (i.e., kb*) is highly consistent with that obtained from the simulation (i.e., kb). Two experimental programs are set; under these programs, the excitation voltages and distance measuring points are regulated to produce different electric field

  17. Influence and Correction from the Human Body on the Measurement of a Power-Frequency Electric Field Sensor

    PubMed Central

    Xiao, Dongping; Liu, Huaitong; Zhou, Qiang; Xie, Yutong; Ma, Qichao

    2016-01-01

    According to the operating specifications of existing electric field measuring instruments, measuring technicians must be located far from the instruments to eliminate the influence of the human body occupancy on a spatial electric field. Nevertheless, in order to develop a portable safety protection instrument with an effective electric field warning function for working staff in a high-voltage environment, it is necessary to study the influence of an approaching human body on the measurement of an electric field and to correct the measurement results. A single-shaft electric field measuring instrument called the Type LP-2000, which was developed by our research team, is used as the research object in this study. First, we explain the principle of electric field measurement and describe the capacitance effect produced by the human body. Through a theoretical analysis, we show that the measured electric field value decreases as a human body approaches. Their relationship is linearly proportional. Then, the ratio is identified as a correction coefficient to correct for the influence of human body proximity. The conclusion drawn from the theoretical analysis is proved via simulation. The correction coefficient kb = 1.8010 is obtained on the basis of the linear fitting of simulated data. Finally, a physical experiment is performed. When no human is present, we compare the results from the Type LP-2000 measured with Narda EFA-300 and the simulated value to verify the accuracy of the Type LP-2000. For the case of an approaching human body, the correction coefficient kb* = 1.9094 is obtained by comparing the data measured with the Type LP-2000 to the simulated value. The correction coefficient obtained from the experiment (i.e., kb*) is highly consistent with that obtained from the simulation (i.e., kb). Two experimental programs are set; under these programs, the excitation voltages and distance measuring points are regulated to produce different electric field

  18. Measurement of Myocardial T1ρ with a Motion Corrected, Parametric Mapping Sequence in Humans

    PubMed Central

    Shahid, Mohammed; Han, Yuchi; Witschey, Walter R. T.

    2016-01-01

    Purpose To develop a robust T1ρ magnetic resonance imaging (MRI) sequence for assessment of myocardial disease in humans. Materials and Methods We developed a breath-held T1ρ mapping method using a single-shot, T1ρ-prepared balanced steady-state free-precession (bSSFP) sequence. The magnetization trajectory was simulated to identify sources of T1ρ error. To limit motion artifacts, an optical flow-based image registration method was used to align T1ρ images. The reproducibility and accuracy of these methods was assessed in phantoms and 10 healthy subjects. Results are shown in 1 patient with pre-ventricular contractions (PVCs), 1 patient with chronic myocardial infarction (MI) and 2 patients with hypertrophic cardiomyopathy (HCM). Results In phantoms, the mean bias was 1.0 ± 2.7 msec (100 msec phantom) and 0.9 ± 0.9 msec (60 msec phantom) at 60 bpm and 2.2 ± 3.2 msec (100 msec) and 1.4 ± 0.9 msec (60 msec) at 80 bpm. The coefficient of variation (COV) was 2.2 (100 msec) and 1.3 (60 msec) at 60 bpm and 2.6 (100 msec) and 1.4 (60 msec) at 80 bpm. Motion correction improved the alignment of T1ρ images in subjects, as determined by the increase in Dice Score Coefficient (DSC) from 0.76 to 0.88. T1ρ reproducibility was high (COV < 0.05, intra-class correlation coefficient (ICC) = 0.85–0.97). Mean myocardial T1ρ value in healthy subjects was 63.5 ± 4.6 msec. There was good correspondence between late-gadolinium enhanced (LGE) MRI and increased T1ρ relaxation times in patients. Conclusion Single-shot, motion corrected, spin echo, spin lock MRI permits 2D T1ρ mapping in a breath-hold with good accuracy and precision. PMID:27003184

  19. MOLECULAR ANALYSIS OF HUMAN SPERMATOZOA: POTENTIAL FOR INFERTILITY RESEARCH

    EPA Science Inventory

    Gordon Research Conference: Mammalian Gametogenesis and Embryogenesis
    New London, CT, July 1-6, 2000

    Molecular Analysis of Human Spermatozoa:
    Potential for Infertility Research

    David Miller 1, David Dix2, Robert Reid 3, Stephen A Krawetz 3
    1Reproductive ...

  20. The Human Potential Movement: Body/Movement/Non-Verbal Experiencing.

    ERIC Educational Resources Information Center

    Caldwell, Stratton F.

    A social, humanistic movement focusing on the needs and concerns of more advantaged, affluent persons has emerged, called the "Human Potential Movement." The emphasis of the movement centers around group processes, small group experiences, and the search for personal, interpersonal, and organizational growth. The development and emergence of…

  1. Saccade-related brain potentials during reading correct and incorrect versions of proverbs.

    PubMed

    Marton, M; Szirtes, J

    1988-11-01

    Using a reading task, the present study investigated saccade-related brain potentials (SRPs) accompanying the perception of the final words of proverbs, i.e. of sentences where the context allows a strong anticipation of the final word. The sentences were presented one at a time on a TV monitor. The proverbs appeared either in their original form or with their final word changed to be incongruous with the sentence context. SRPs to the two types of final words were recorded from 4 scalp areas. The onset of the saccade leading to the final word was used to trigger the averaging of SRPs. Incongruent and congruent brain responses were also compared by means of difference waveforms. The results showed that a difference between SRPs to congruous vs incongruous final words of proverbs already appeared simultaneously with the SRP component indicating the analysis of the visual pattern of the word. This finding supports an interactive model of word perception.

  2. Increasing the applicability of density functional theory. V. X-ray absorption spectra with ionization potential corrected exchange and correlation potentials

    NASA Astrophysics Data System (ADS)

    Verma, Prakash; Bartlett, Rodney J.

    2016-07-01

    Core excitation energies are computed with time-dependent density functional theory (TD-DFT) using the ionization energy corrected exchange and correlation potential QTP(0,0). QTP(0,0) provides C, N, and O K-edge spectra to about an electron volt. A mean absolute error (MAE) of 0.77 and a maximum error of 2.6 eV is observed for QTP(0,0) for many small molecules. TD-DFT based on QTP (0,0) is then used to describe the core-excitation spectra of the 22 amino acids. TD-DFT with conventional functionals greatly underestimates core excitation energies, largely due to the significant error in the Kohn-Sham occupied eigenvalues. To the contrary, the ionization energy corrected potential, QTP(0,0), provides excellent approximations (MAE of 0.53 eV) for core ionization energies as eigenvalues of the Kohn-Sham equations. As a consequence, core excitation energies are accurately described with QTP(0,0), as are the core ionization energies important in X-ray photoionization spectra or electron spectroscopy for chemical analysis.

  3. Synthetic Biology and Human Health: Potential Applications for Spaceflight

    NASA Technical Reports Server (NTRS)

    Karouia, Fathi; Carr, Christopher; Cai, Yizhi; Chen, Y.; Grenon, Marlene; Larios-Sanz, Maia; Jones, Jeffrey A.; Santos, Orlando

    2011-01-01

    Human space travelers experience a unique environment that affects homeostasis and physiologic adaptation. Spaceflight-related changes have been reported in the musculo-skeletal, cardiovascular, neurovestibular, endocrine, and immune systems. The spacecraft environment further subjects the traveler to noise and gravitational forces, as well as airborne chemical, microbiological contaminants, and radiation exposure. As humans prepare for longer duration missions effective countermeasures must be developed, verified, and implemented to ensure mission success. Over the past ten years, synthetic biology has opened new avenues for research and development in areas such as biological control, biomaterials, sustainable energy production, bioremediation, and biomedical therapies. The latter in particular is of great interest to the implementation of long-duration human spaceflight capabilities. This article discusses the effects of spaceflight on humans, and reviews current capabilities and potential needs associated with the health of the astronauts where synthetic biology could play an important role in the pursuit of space exploration.

  4. The effect of local perturbation fields on human DTI: Characterisation, measurement and correction

    PubMed Central

    Mohammadi, Siawoosh; Nagy, Zoltan; Möller, Harald E.; Symms, Mark R.; Carmichael, David W.; Josephs, Oliver; Weiskopf, Nikolaus

    2012-01-01

    Indices derived from diffusion tensor imaging (DTI) data, including the mean diffusivity (MD) and fractional anisotropy (FA), are often used to better understand the microstructure of the brain. DTI, however, is susceptible to imaging artefacts, which can bias these indices. The most important sources of artefacts in DTI include eddy currents, nonuniformity and mis-calibration of gradients. We modelled these and other artefacts using a local perturbation field (LPF) approach. LPFs during the diffusion-weighting period describe the local mismatches between the effective and the expected diffusion gradients resulting in a spatially varying error in the diffusion weighting B matrix and diffusion tensor estimation. We introduced a model that makes use of phantom measurements to provide a robust estimation of the LPF in DTI without requiring any scanner-hardware-specific information or special MRI sequences. We derived an approximation of the perturbed diffusion tensor in the isotropic-diffusion limit that can be used to identify regions in any DTI index map that are affected by LPFs. Using these models, we simulated and measured LPFs and characterised their effect on human DTI for three different clinical scanners. The small FA values found in grey matter were biased towards greater anisotropy leading to lower grey-to-white matter contrast (up to 10%). Differences in head position due to e.g. repositioning produced errors of up to 10% in the MD, reducing comparability in multi-centre or longitudinal studies. We demonstrate the importance of the proposed correction by showing improved consistency across scanners, different head positions and an increased FA contrast between grey and white matter. PMID:22197741

  5. Sorghum phytochemicals and their potential impact on human health.

    PubMed

    Awika, Joseph M; Rooney, Lloyd W

    2004-05-01

    Sorghum is a rich source of various phytochemicals including tannins, phenolic acids, anthocyanins, phytosterols and policosanols. These phytochemicals have potential to significantly impact human health. Sorghum fractions possess high antioxidant activity in vitro relative to other cereals or fruits. These fractions may offer similar health benefits commonly associated with fruits. Available epidemiological evidence suggests that sorghum consumption reduces the risk of certain types of cancer in humans compared to other cereals. The high concentration of phytochemicals in sorghum may be partly responsible. Sorghums containing tannins are widely reported to reduce caloric availability and hence weight gain in animals. This property is potentially useful in helping reduce obesity in humans. Sorghum phytochemicals also promote cardiovascular health in animals. Such properties have not been reported in humans and require investigation, since cardiovascular disease is currently the leading killer in the developed world. This paper reviews available information on sorghum phytochemicals, how the information relates to current phytonutrient research and how it has potential to combat common nutrition-related diseases including cancer, cardiovascular disease and obesity.

  6. Clinical evaluation of the computed tomography attenuation correction map for myocardial perfusion imaging: the potential for incidental pathology detection.

    PubMed

    Tootell, Andrew; Vinjamuri, Sobhan; Elias, Mark; Hogg, Peter

    2012-11-01

    The benefits of hybrid imaging in nuclear medicine have been proven to increase the diagnostic accuracy and sensitivity of many procedures by localizing or characterizing lesions or by correcting emission data to more accurately represent radiopharmaceutical distribution. Single-photon emission computed tomography/computed tomography (SPECT/CT) has a significant role in the diagnosis and follow-up of ischaemic heart disease with attenuation correction data being obtained on an integrated CT scanner. Initially, the CT component of hybrid SPECT/CT systems was what could be described as low specification utilizing fixed output parameters. As technology has progressed, the CT component of newer systems has specifications that are identical to that of stand-alone diagnostic systems. Irrespective of the type of scanner used, the computed tomography attenuation correction (CTAC) for myocardial perfusion imaging produces low-quality, limited-range CT images of the chest that include the mediastinum, lung fields and surrounding soft tissues. The diagnostic potential of this data set is unclear; yet, examples exist whereby significant pathology can be identified and investigated further. Despite guidance from a number of professional bodies suggesting that evaluation of the resulting images for every medical exposure be carried out, there is no indication as to whether this should include the evaluation of CTAC images. This review aims to initiate discussion by examining the ethical, legal, financial and practical issues (e.g. CT specification and image quality) surrounding the clinical evaluation of the CTAC for myocardial perfusion imaging images. Reference to discussions that have taken place, and continue to take place, in other modalities, current European and UK legislations, and guidelines and research in the field will be made.

  7. 3D cultures of human neural progenitor cells: dopaminergic differentiation and genetic modification. [corrected].

    PubMed

    Brito, Catarina; Simão, Daniel; Costa, Inês; Malpique, Rita; Pereira, Cristina I; Fernandes, Paulo; Serra, Margarida; Schwarz, Sigrid C; Schwarz, Johannes; Kremer, Eric J; Alves, Paula M

    2012-03-01

    therapeutic potential within human neural cell populations, thus enabling the introduction of specific therapeutic genes for treatment of CNS pathologies; to study the fate and effect of delivered therapeutic genes; to study toxicological effects. Furthermore these methodologies may be extended to other sources of human neural stem cells, such as human pluripotent stem cells, including patient-derived induced pluripotent stem cells. PMID:22433395

  8. 3D cultures of human neural progenitor cells: dopaminergic differentiation and genetic modification. [corrected].

    PubMed

    Brito, Catarina; Simão, Daniel; Costa, Inês; Malpique, Rita; Pereira, Cristina I; Fernandes, Paulo; Serra, Margarida; Schwarz, Sigrid C; Schwarz, Johannes; Kremer, Eric J; Alves, Paula M

    2012-03-01

    therapeutic potential within human neural cell populations, thus enabling the introduction of specific therapeutic genes for treatment of CNS pathologies; to study the fate and effect of delivered therapeutic genes; to study toxicological effects. Furthermore these methodologies may be extended to other sources of human neural stem cells, such as human pluripotent stem cells, including patient-derived induced pluripotent stem cells.

  9. Potentiation by caffeine of potentially lethal fast-neutron damage in cultured human cells

    SciTech Connect

    Schroy, C.B.; Furcinitti, P.S.; Todd, P.; Kukulinsky, N.E.

    1980-11-01

    Caffeine was found to potentiate single-dose fast-neutron-induced killing of human T-1 cells when present at 2 mM for 60 hr or more after (and 10 hr before) irradiation. Analyses of survival curves of cells treated with neutrons or X rays with and without caffeine indicate that only the linear, low-dose portion of survival curves is modified. Potentiation of lethality by caffeine is attributed mainly to its effects on single-hit potentially lethal lesions, possibly certain DNA double-strand breaks.

  10. Confocal Raman microspectroscopy on excised human skin: uncertainties in depth profiling and mathematical correction applied to dermatological drug permeation.

    PubMed

    Tfayli, A; Piot, O; Manfait, M

    2008-05-01

    Confocal Raman microspectroscopy represents the advantage of giving structural and conformational information on samples without any destructive treatment. Recently, several studies were achieved to study the skin hydration, endogenous and exogenous molecules repartition in the skin using the confocal feature of this technique. Meanwhile, when working through a material boundary with a different refractive index, the main limitation remains the spatial precision, especially the distortion in the depth and the depth resolution. Recently, several authors described mathematical models to correct the depth and the resolution values. In this study, we combined theoretical approaches, proposed by different authors with experimental measurements to try to find out the most appropriate approach for correction. We then applied the corrections on in-depth profiles tracking the penetration of Metronidazole, a drug produced by Galderma for rosacea treatment, through excised human skin. PMID:19343645

  11. Confocal Raman microspectroscopy on excised human skin: uncertainties in depth profiling and mathematical correction applied to dermatological drug permeation.

    PubMed

    Tfayli, A; Piot, O; Manfait, M

    2008-05-01

    Confocal Raman microspectroscopy represents the advantage of giving structural and conformational information on samples without any destructive treatment. Recently, several studies were achieved to study the skin hydration, endogenous and exogenous molecules repartition in the skin using the confocal feature of this technique. Meanwhile, when working through a material boundary with a different refractive index, the main limitation remains the spatial precision, especially the distortion in the depth and the depth resolution. Recently, several authors described mathematical models to correct the depth and the resolution values. In this study, we combined theoretical approaches, proposed by different authors with experimental measurements to try to find out the most appropriate approach for correction. We then applied the corrections on in-depth profiles tracking the penetration of Metronidazole, a drug produced by Galderma for rosacea treatment, through excised human skin.

  12. Potentiators exert distinct effects on human, murine, and Xenopus CFTR.

    PubMed

    Cui, Guiying; Khazanov, Netaly; Stauffer, Brandon B; Infield, Daniel T; Imhoff, Barry R; Senderowitz, Hanoch; McCarty, Nael A

    2016-08-01

    VX-770 (Ivacaftor) has been approved for clinical usage in cystic fibrosis patients with several CFTR mutations. Yet the binding site(s) on CFTR for this compound and other small molecule potentiators are unknown. We hypothesize that insight into this question could be gained by comparing the effect of potentiators on CFTR channels from different origins, e.g., human, mouse, and Xenopus (frog). In the present study, we combined this comparative molecular pharmacology approach with that of computer-aided drug discovery to identify and characterize new potentiators of CFTR and to explore possible mechanism of action. Our results demonstrate that 1) VX-770, NPPB, GlyH-101, P1, P2, and P3 all exhibited ortholog-specific behavior in that they potentiated hCFTR, mCFTR, and xCFTR with different efficacies; 2) P1, P2, and P3 potentiated hCFTR in excised macropatches in a manner dependent on the degree of PKA-mediated stimulation; 3) P1 and P2 did not have additive effects, suggesting that these compounds might share binding sites. Also 4) using a pharmacophore modeling approach, we identified three new potentiators (IOWH-032, OSSK-2, and OSSK-3) that have structures similar to GlyH-101 and that also exhibit ortholog-specific potentiation of CFTR. These could potentially serve as lead compounds for development of new drugs for the treatment of cystic fibrosis. The ortholog-specific behavior of these compounds suggest that a comparative pharmacology approach, using cross-ortholog chimeras, may be useful for identification of binding sites on human CFTR. PMID:27288484

  13. Toxic phytochemicals and their potential risks for human cancer

    PubMed Central

    Bode, Ann M.; Dong, Zigang

    2014-01-01

    Consuming plants for their presumed health benefits has occurred since early civilizations. Phytochemicals are found in various plants that are frequently included in the human diet and are generally thought to be safe for consumption because they are produced naturally. However, this is not always the case and in fact many natural compounds found in several commonly consumed plants are potential carcinogens or tumor promoters and should be avoided. PMID:25348854

  14. Toxic phytochemicals and their potential risks for human cancer.

    PubMed

    Bode, Ann M; Dong, Zigang

    2015-01-01

    Consuming plants for their presumed health benefits has occurred since early civilizations. Phytochemicals are found in various plants that are frequently included in the human diet and are generally thought to be safe for consumption because they are produced naturally. However, this is not always the case and in fact many natural compounds found in several commonly consumed plants are potential carcinogens or tumor promoters and should be avoided.

  15. Potential applications of keratinocytes derived from human embryonic stem cells.

    PubMed

    Movahednia, Mohammad M; Kidwai, Fahad K; Jokhun, Doorgesh S; Squier, Christopher A; Toh, Wei Seong; Cao, Tong

    2016-01-01

    Although skin grafting is one of the most advanced cell therapy technique, wide application of skin substitutes is hampered by the difficulty in securing sufficient amount of epidermal substitute. Additionally, in understanding the progression of skin aging and disease, and in screening the cosmetic and pharmaceutical products, there is lack of a satisfactory human skin-specific in vitro model. Recently, human embryonic stem cells (hESCs) have been proposed as an unlimited and reliable cell source to obtain almost all cell types present in the human body. This review focuses on the potential off-the-shelf use of hESC-derived keratinocytes for future clinical applications as well as a powerful in vitro skin model to study skin function and integrity, host-pathogen interactions and disease pathogenesis. Furthermore, we discuss the industrial applications of hESC-derived keratinized multi-layer epithelium which provides a human-like test platform for understanding disease pathogenesis, evaluation of new therapeutic modalities and assessment of the safety and efficacy of skin cosmetics and therapeutics. Overall, we conclude that the hESC-derived keratinocytes have great potential for clinical, research and industrial applications. PMID:26663861

  16. "It's doom alone that counts": can international human rights law be an effective source of rights in correctional conditions litigation?

    PubMed

    Perlin, Michael L; Dlugacz, Henry A

    2009-01-01

    Over the past three decades, the U.S. judiciary has grown increasingly less receptive to claims by convicted felons as to the conditions of their confinement while in prison. Although courts have not articulated a return to the "hands off" policy of the 1950s, it is clear that it has become significantly more difficult for prisoners to prevail in constitutional correctional litigation. The passage and aggressive implementation of the Prison Litigation Reform Act has been a powerful disincentive to such litigation in many areas of prisoners' rights law. From the perspective of the prisoner, the legal landscape is more hopeful in matters that relate to mental health care and treatment. Here, in spite of a general trend toward more stringent applications of standards of proof and a reluctance to order sweeping, intrusive remedies, some courts have aggressively protected prisoners' rights to be free from "deliberate indifference" to serious medical needs, and to be free from excessive force on the part of prison officials. A mostly hidden undercurrent in some prisoners' rights litigation has been the effort on the part of some plaintiffs' lawyers to look to international human rights doctrines as a potential source of rights, an effort that has met with some modest success. It receives support by the inclination of other courts to turn to international human rights conventions-even in nations where such conventions have not been ratified-as a kind of "best practice" in the area. The recent publication and subsequent ratification (though not, as of yet, by the United States) of the UN Convention on the Rights of Persons with Disabilities (CRPD) may add new support to those using international human rights documents as a basis for litigating prisoners' rights claims. To the best of our knowledge, there has, as of yet, been no scholarly literature on the question of the implications of the CRPD on the state of prisoners' rights law in a U.S. domestic context. In this

  17. Relaxin Enhances the Oncogenic Potential of Human Thyroid Carcinoma Cells

    PubMed Central

    Hombach-Klonisch, Sabine; Bialek, Joanna; Trojanowicz, Bogusz; Weber, Ekkehard; Holzhausen, Hans-Jürgen; Silvertown, Josh D.; Summerlee, Alastair J.; Dralle, Henning; Hoang-Vu, Cuong; Klonisch, Thomas

    2006-01-01

    The role of members of the insulin-like superfamily in human thyroid carcinoma is primarily unknown. Here we demonstrate the presence of RLN2 relaxin and relaxin receptor LGR7 in human papillary, follicular, and undifferentiated anaplastic thyroid carcinoma suggesting a specific involvement of relaxin-LGR7 signaling in thyroid carcinoma. Stable transfectants of the LGR7-positive human follicular thyroid carcinoma cell lines FTC-133 and FTC-238 that secrete bioactive proRLN2 revealed this hormone to act as a multifunctional endocrine factor in thyroid carcinoma cells. Although RLN2 did not act as a mitogen, it acted as an autocrine/paracrine factor and significantly increased anchorage-independent growth and thyroid carcinoma cell motility and invasiveness through elastin matrices. Suppression of LGR7 expression by LGR7-siRNA abolished the RLN2-mediated accelerated tumor cell motility. The increased elastinolytic activity correlated with enhanced production and secretion of the lysosomal proteinases cathepsin-D (cath-D) and cath-L forms hereby identified as new RLN2 target molecules in human neoplastic thyrocytes. We found the intracellular distribution of procath-L specifically altered in RLN2 transfectants, providing first evidence for selective actions of relaxin on the powerful elastinolytic cath-L production, storage, and secretion in thyroid carcinoma cells. Thus, relaxin enhances the oncogenic potential and acts as novel endocrine modulator of invasiveness in human thyroid carcinoma cells. PMID:16877360

  18. Relaxin enhances the oncogenic potential of human thyroid carcinoma cells.

    PubMed

    Hombach-Klonisch, Sabine; Bialek, Joanna; Trojanowicz, Bogusz; Weber, Ekkehard; Holzhausen, Hans-Jürgen; Silvertown, Josh D; Summerlee, Alastair J; Dralle, Henning; Hoang-Vu, Cuong; Klonisch, Thomas

    2006-08-01

    The role of members of the insulin-like superfamily in human thyroid carcinoma is primarily unknown. Here we demonstrate the presence of RLN2 relaxin and relaxin receptor LGR7 in human papillary, follicular, and undifferentiated anaplastic thyroid carcinoma suggesting a specific involvement of relaxin-LGR7 signaling in thyroid carcinoma. Stable transfectants of the LGR7-positive human follicular thyroid carcinoma cell lines FTC-133 and FTC-238 that secrete bioactive proRLN2 revealed this hormone to act as a multifunctional endocrine factor in thyroid carcinoma cells. Although RLN2 did not act as a mitogen, it acted as an autocrine/paracrine factor and significantly increased anchorage-independent growth and thyroid carcinoma cell motility and invasiveness through elastin matrices. Suppression of LGR7 expression by LGR7-siRNA abolished the RLN2-mediated accelerated tumor cell motility. The increased elastinolytic activity correlated with enhanced production and secretion of the lysosomal proteinases cathepsin-D (cath-D) and cath-L forms hereby identified as new RLN2 target molecules in human neoplastic thyrocytes. We found the intracellular distribution of procath-L specifically altered in RLN2 transfectants, providing first evidence for selective actions of relaxin on the powerful elastinolytic cath-L production, storage, and secretion in thyroid carcinoma cells. Thus, relaxin enhances the oncogenic potential and acts as novel endocrine modulator of invasiveness in human thyroid carcinoma cells.

  19. CRISPR/Cas9-Mediated Correction of the Sickle Mutation in Human CD34+ cells.

    PubMed

    Hoban, Megan D; Lumaquin, Dianne; Kuo, Caroline Y; Romero, Zulema; Long, Joseph; Ho, Michelle; Young, Courtney S; Mojadidi, Michelle; Fitz-Gibbon, Sorel; Cooper, Aaron R; Lill, Georgia R; Urbinati, Fabrizia; Campo-Fernandez, Beatriz; Bjurstrom, Carmen F; Pellegrini, Matteo; Hollis, Roger P; Kohn, Donald B

    2016-09-01

    Targeted genome editing technology can correct the sickle cell disease mutation of the β-globin gene in hematopoietic stem cells. This correction supports production of red blood cells that synthesize normal hemoglobin proteins. Here, we demonstrate that Transcription Activator-Like Effector Nucleases (TALENs) and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease system can target DNA sequences around the sickle-cell mutation in the β-globin gene for site-specific cleavage and facilitate precise correction when a homologous donor template is codelivered. Several pairs of TALENs and multiple CRISPR guide RNAs were evaluated for both on-target and off-target cleavage rates. Delivery of the CRISPR/Cas9 components to CD34+ cells led to over 18% gene modification in vitro. Additionally, we demonstrate the correction of the sickle cell disease mutation in bone marrow derived CD34+ hematopoietic stem and progenitor cells from sickle cell disease patients, leading to the production of wild-type hemoglobin. These results demonstrate correction of the sickle mutation in patient-derived CD34+ cells using CRISPR/Cas9 technology.

  20. Effect of correction of aberration dynamics on chaos in human ocular accommodation.

    PubMed

    Hampson, Karen M; Cufflin, Matthew P; Mallen, Edward A H

    2013-11-15

    We used adaptive optics to determine the effect of monochromatic aberration dynamics on the level of chaos in the accommodation control system. Four participants viewed a stationary target while the dynamics of their aberrations were either left uncorrected, defocus was corrected, or all aberrations except defocus were corrected. Chaos theory analysis was used to discern changes in the accommodative microfluctuations. We found a statistically significant reduction in the chaotic nature of the accommodation microfluctuations during correction of defocus, but not when all aberrations except defocus were corrected. The Lyapunov exponent decreased from 0.71 ± 0.07 D/s (baseline) to 0.55 ± 0.03 D/s (correction of defocus fluctuations). As the reduction of chaos in physiological signals is indicative of stress to the system, the results indicate that for the participants included in this study, fluctuations in defocus have a more profound effect than those of the other aberrations. There were no changes in the power spectrum between experimental conditions. Hence chaos theory analysis is a more subtle marker of changes in the accommodation control system and will be of value in the study of myopia onset and progression. PMID:24322122

  1. Nanomaterials in Humans: Identification, Characteristics, and Potential Damage

    PubMed Central

    Song, Yuguo; Li, Xue; Wang, Liying; Rojanasakul, Yon; Castranova, Vincent; Li, Huiling; Ma, Jing

    2016-01-01

    Nanomaterials are increasingly being used for commercial purposes. However, concerns about the potential risks of exposure to humans have been raised. We previously reported unusual pulmonary disease and death in a group of patients with occupational exposure to spray paint. However, the nanoparticle and chemical composition of the exposure was not fully described. The present study aimed to isolate and identify the nanoparticles observed in the patients’ biopsies and report the potential deleterious effects to human lungs using electron microscopy. Using electron microscopy and energy dispersive x-ray analysis, silica nanoparticles were identified and characterized mainly in macrophages, pulmonary microvessels, vascular endothelial cells, microlymphatic vessels, pleural effusions, and a few in alveolar epithelial cells and pulmonary interstitial tissue (with no microscale particles present). Notably, damage to alveolar epithelial cells, macrophages, vascular endothelial cells, and the blood–gas barrier was observed. Given the well-documented toxicity of microscale silica, it is possible that these silica nanoparticles may have contributed in part to the illness reported in these workers. Such a possibility supports the adoption of controls and prevention strategies to minimize inhalation of nanoparticles by workers, and it highlights the urgent need and the importance of the nanosafety study in humans. PMID:21768271

  2. Human sperm chromatin epigenetic potential: genomics, proteomics, and male infertility

    PubMed Central

    Castillo, Judit; Estanyol, Josep Maria; Ballescà, Josep Lluis; Oliva, Rafael

    2015-01-01

    The classical idea about the function of the mammalian sperm chromatin is that it serves to transmit a highly protected and transcriptionally inactive paternal genome, largely condensed by protamines, to the next generation. In addition, recent sperm chromatin genome-wide dissection studies indicate the presence of a differential distribution of the genes and repetitive sequences in the protamine-condensed and histone-condensed sperm chromatin domains, which could be potentially involved in regulatory roles after fertilization. Interestingly, recent proteomic studies have shown that sperm chromatin contains many additional proteins, in addition to the abundant histones and protamines, with specific modifications and chromatin affinity features which are also delivered to the oocyte. Both gene and protein signatures seem to be altered in infertile patients and, as such, are consistent with the potential involvement of the sperm chromatin landscape in early embryo development. This present work reviews the available information on the composition of the human sperm chromatin and its epigenetic potential, with a particular focus on recent results derived from high-throughput genomic and proteomic studies. As a complement, we provide experimental evidence for the detection of phosphorylations and acetylations in human protamine 1 using a mass spectrometry approach. The available data indicate that the sperm chromatin is much more complex than what it was previously thought, raising the possibility that it could also serve to transmit crucial paternal epigenetic information to the embryo. PMID:25926607

  3. Mapping human brain networks with cortico-cortical evoked potentials

    PubMed Central

    Keller, Corey J.; Honey, Christopher J.; Mégevand, Pierre; Entz, Laszlo; Ulbert, Istvan; Mehta, Ashesh D.

    2014-01-01

    The cerebral cortex forms a sheet of neurons organized into a network of interconnected modules that is highly expanded in humans and presumably enables our most refined sensory and cognitive abilities. The links of this network form a fundamental aspect of its organization, and a great deal of research is focusing on understanding how information flows within and between different regions. However, an often-overlooked element of this connectivity regards a causal, hierarchical structure of regions, whereby certain nodes of the cortical network may exert greater influence over the others. While this is difficult to ascertain non-invasively, patients undergoing invasive electrode monitoring for epilepsy provide a unique window into this aspect of cortical organization. In this review, we highlight the potential for cortico-cortical evoked potential (CCEP) mapping to directly measure neuronal propagation across large-scale brain networks with spatio-temporal resolution that is superior to traditional neuroimaging methods. We first introduce effective connectivity and discuss the mechanisms underlying CCEP generation. Next, we highlight how CCEP mapping has begun to provide insight into the neural basis of non-invasive imaging signals. Finally, we present a novel approach to perturbing and measuring brain network function during cognitive processing. The direct measurement of CCEPs in response to electrical stimulation represents a potentially powerful clinical and basic science tool for probing the large-scale networks of the human cerebral cortex. PMID:25180306

  4. Reconstruction of a geometrically correct diffusion tensor image of a moving human fetal brain

    NASA Astrophysics Data System (ADS)

    Kim, Kio; Habas, Piotr A.; Rousseau, Francois; Glenn, Orit A.; Barkovich, A. J.; Koob, Meriam; Dietemann, Jean-Louis; Robinson, Ashley J.; Poskitt, Kenneth J.; Miller, Steven P.; Studholme, Colin

    2010-03-01

    Recent studies reported the development of methods for rigid registration of 2D fetal brain imaging data to correct for unconstrained fetal and maternal motion, and allow the formation of a true 3D image of conventional fetal brain anatomy from conventional MRI. Diffusion tensor imaging provides additional valuable insight into the developing brain anatomy, however the correction of motion artifacts in clinical fetal diffusion imaging is still a challenging problem. This is due to the challenging problem of matching lower signal-to-noise ratio diffusion weighted EPI slice data to recover between-slice motion, compounded by the presence of possible geometric distortions in the EPI data. In addition, the problem of estimating a diffusion model (such as a tensor) on a regular grid that takes into account the inconsistent spatial and orientation sampling of the diffusion measurements needs to be solved in a robust way. Previous methods have used slice to volume registration within the diffusion dataset. In this work, we describe an alternative approach that makes use of an alignment of diffusion weighted EPI slices to a conventional structural MRI scan which provides a geometrically correct reference image. After spatial realignment of each diffusion slice, a tensor field representing the diffusion profile is estimated by weighted least squared fitting. By qualitative and quantitative evaluation of the results, we confirm the proposed algorithm successfully corrects the motion and reconstructs the diffusion tensor field.

  5. Nutritional Evaluation of Australian Microalgae as Potential Human Health Supplements

    PubMed Central

    Kent, Megan; Welladsen, Heather M.; Mangott, Arnold; Li, Yan

    2015-01-01

    This study investigated the biochemical suitability of Australian native microalgal species Scenedesmus sp., Nannochloropsis sp., Dunaliella sp., and a chlorophytic polyculture as nutritional supplements for human health. The four microalgal cultures were harvested during exponential growth, lyophilized, and analysed for proximate composition (moisture, ash, lipid, carbohydrates, and protein), pigments, and amino acid and fatty acid profiles. The resulting nutritional value, based on biochemical composition, was compared to commercial Spirulina and Chlorella products. The Australian native microalgae exhibited similar, and in several cases superior, organic nutritional properties relative to the assessed commercial products, with biochemical profiles rich in high-quality protein, nutritious polyunsaturated fats (such as α-linolenic acid, arachidonic acid, and eicosapentaenoic acid), and antioxidant pigments. These findings indicate that the microalgae assessed have great potential as multi-nutrient human health supplements. PMID:25723496

  6. Decade of the Brain 1990--2000: Maximizing human potential

    SciTech Connect

    Not Available

    1991-04-01

    The US Decade of the Brain offers scientists throughout the Federal Government a unique opportunity to advance and apply scientific knowledge about the brain and nervous system. During the next 10 years, scientists hope to maximize human potential through studies of human behavior, senses and communication, learning and memory, genetic/chemical alterations, and environmental interactions. Progress in these areas should lead to reductions in mortality from brain and nervous system disorders and to improvements in the quality of life. This report identifies nine research areas that could form the basis of an integrated program in the brain and behavioral sciences. A chart summarizing the Federal activities in these nine areas may be found at the back of the report. In addition, three areas that span the nine research areas -- basic research, technology and international activities -- are considered.

  7. Nutritional evaluation of Australian microalgae as potential human health supplements.

    PubMed

    Kent, Megan; Welladsen, Heather M; Mangott, Arnold; Li, Yan

    2015-01-01

    This study investigated the biochemical suitability of Australian native microalgal species Scenedesmus sp., Nannochloropsis sp., Dunaliella sp., and a chlorophytic polyculture as nutritional supplements for human health. The four microalgal cultures were harvested during exponential growth, lyophilized, and analysed for proximate composition (moisture, ash, lipid, carbohydrates, and protein), pigments, and amino acid and fatty acid profiles. The resulting nutritional value, based on biochemical composition, was compared to commercial Spirulina and Chlorella products. The Australian native microalgae exhibited similar, and in several cases superior, organic nutritional properties relative to the assessed commercial products, with biochemical profiles rich in high-quality protein, nutritious polyunsaturated fats (such as α-linolenic acid, arachidonic acid, and eicosapentaenoic acid), and antioxidant pigments. These findings indicate that the microalgae assessed have great potential as multi-nutrient human health supplements. PMID:25723496

  8. Beyond abortion: the potential reach of a human life amendment.

    PubMed

    Westfall, D

    1982-01-01

    In Roe v. Wade, the Supreme Court held that the constitutionally protected right to privacy includes a woman's right to terminate pregnancy. Following the decision, anti-abortion groups turned to Congress to limit or negate that right. As a result of their efforts, several "human life" statutes and constitutional amendments have been proposed. This Article focuses on the implications of proposed amendments that seek to ban or limit the availability of abortions indirectly by broadening the definition of "person" to include unborn individuals. The Article discusses the potentially serious effects such an amendment would have in areas unrelated to abortion. It finds that the resulting chaos and uncertainty would have great social costs, and concludes that if abortions are to be banned or restricted, a human life amendment that directly deals with abortion is preferable to one that defines "person" to include the unborn.

  9. Beyond abortion: the potential reach of a human life amendment.

    PubMed

    Westfall, D

    1982-01-01

    In Roe v. Wade, the Supreme Court held that the constitutionally protected right to privacy includes a woman's right to terminate pregnancy. Following the decision, anti-abortion groups turned to Congress to limit or negate that right. As a result of their efforts, several "human life" statutes and constitutional amendments have been proposed. This Article focuses on the implications of proposed amendments that seek to ban or limit the availability of abortions indirectly by broadening the definition of "person" to include unborn individuals. The Article discusses the potentially serious effects such an amendment would have in areas unrelated to abortion. It finds that the resulting chaos and uncertainty would have great social costs, and concludes that if abortions are to be banned or restricted, a human life amendment that directly deals with abortion is preferable to one that defines "person" to include the unborn. PMID:7148834

  10. Potential misinterpretation of the nutritional value of dietary fiber: correcting fiber digestibility values for nondietary gut-interfering material.

    PubMed

    Montoya, Carlos A; Henare, Sharon J; Rutherfurd, Shane M; Moughan, Paul J

    2016-08-01

    The aim of this review is to identify the origin and implications of a nondietary material present in digesta and feces that interferes with the determination of dietary fiber in gastrointestinal contents. Negative values for ileal and fecal digestibility of dietary fiber are commonly reported in the literature for monogastric animal species, including humans. As negative values are not possible physiologically, this suggests the existence of a nondietary material in the gastrointestinal contents and feces that interferes with the accurate determination of dietary fiber digestibility when conventional methods of fiber determination are applied. To date, little attention has been given to this nondietary interfering material, which appears to be influenced by the type and concentration of fiber in the diet. Interestingly, estimates of dietary fiber digestibility increase substantially when corrected for the nondietary interfering material, which suggests that currently reported values underestimate the digestibility of dietary fiber and may misrepresent where, in the digestive tract, fermentation of fiber occurs. A new perspective of dietary fiber digestion in the gastrointestinal tract is developing, leading to a better understanding of the contribution of dietary fiber to health.

  11. Experimental demonstration of passive acoustic imaging in the human skull cavity using CT-based aberration corrections

    PubMed Central

    Jones, Ryan M.; O’Reilly, Meaghan A.; Hynynen, Kullervo

    2015-01-01

    Purpose: Experimentally verify a previously described technique for performing passive acoustic imaging through an intact human skull using noninvasive, computed tomography (CT)-based aberration corrections Jones et al. [Phys. Med. Biol. 58, 4981–5005 (2013)]. Methods: A sparse hemispherical receiver array (30 cm diameter) consisting of 128 piezoceramic discs (2.5 mm diameter, 612 kHz center frequency) was used to passively listen through ex vivo human skullcaps (n = 4) to acoustic emissions from a narrow-band fixed source (1 mm diameter, 516 kHz center frequency) and from ultrasound-stimulated (5 cycle bursts, 1 Hz pulse repetition frequency, estimated in situ peak negative pressure 0.11–0.33 MPa, 306 kHz driving frequency) Definity™ microbubbles flowing through a thin-walled tube phantom. Initial in vivo feasibility testing of the method was performed. The performance of the method was assessed through comparisons to images generated without skull corrections, with invasive source-based corrections, and with water-path control images. Results: For source locations at least 25 mm from the inner skull surface, the modified reconstruction algorithm successfully restored a single focus within the skull cavity at a location within 1.25 mm from the true position of the narrow-band source. The results obtained from imaging single bubbles are in good agreement with numerical simulations of point source emitters and the authors’ previous experimental measurements using source-based skull corrections O’Reilly et al. [IEEE Trans. Biomed. Eng. 61, 1285–1294 (2014)]. In a rat model, microbubble activity was mapped through an intact human skull at pressure levels below and above the threshold for focused ultrasound-induced blood–brain barrier opening. During bursts that led to coherent bubble activity, the location of maximum intensity in images generated with CT-based skull corrections was found to deviate by less than 1 mm, on average, from the position

  12. Targeted gene addition in human CD34(+) hematopoietic cells for correction of X-linked chronic granulomatous disease.

    PubMed

    De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H; Chan, Andy; Pearl, Jocelynn R; Paschon, David E; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A; Zarember, Kol A; Peshwa, Madhusudan V; Gregory, Philip D; Urnov, Fyodor D; Malech, Harry L

    2016-04-01

    Gene therapy with genetically modified human CD34(+) hematopoietic stem and progenitor cells (HSPCs) may be safer using targeted integration (TI) of transgenes into a genomic 'safe harbor' site rather than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno-associated virus (AAV) 6 delivery of donor constructs in human HSPCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus(+) HSPCs with 6-16% human cell marking were observed following engraftment into mice. In HSPCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 resulted in ∼15% gp91phox expression and increased NADPH oxidase activity in ex vivo-derived neutrophils. In mice transplanted with corrected HSPCs, 4-11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases.

  13. Targeted gene addition in human CD34(+) hematopoietic cells for correction of X-linked chronic granulomatous disease.

    PubMed

    De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H; Chan, Andy; Pearl, Jocelynn R; Paschon, David E; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A; Zarember, Kol A; Peshwa, Madhusudan V; Gregory, Philip D; Urnov, Fyodor D; Malech, Harry L

    2016-04-01

    Gene therapy with genetically modified human CD34(+) hematopoietic stem and progenitor cells (HSPCs) may be safer using targeted integration (TI) of transgenes into a genomic 'safe harbor' site rather than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno-associated virus (AAV) 6 delivery of donor constructs in human HSPCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus(+) HSPCs with 6-16% human cell marking were observed following engraftment into mice. In HSPCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 resulted in ∼15% gp91phox expression and increased NADPH oxidase activity in ex vivo-derived neutrophils. In mice transplanted with corrected HSPCs, 4-11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases. PMID:26950749

  14. Climate Change in the US: Potential Consequences for Human Health

    NASA Technical Reports Server (NTRS)

    Maynard, Nancy G.

    2001-01-01

    The U.S. National Assessment identified five major areas of consequences of climate change in the United States: temperature-related illnesses and deaths, health effects related to extreme weather events, air pollution-related health effects, water- and food-borne diseases, and insect-, tick-, and rodent-borne diseases. The U.S. National Assessment final conclusions about these potential health effects will be described. In addition, a summary of some of the new tools for studying human health aspects of climate change as well as environment-health linkages through remotely sensed data and observations will be provided.

  15. Human auditory evoked potentials. II - Effects of attention

    NASA Technical Reports Server (NTRS)

    Picton, T. W.; Hillyard, S. A.

    1974-01-01

    Attention directed toward auditory stimuli, in order to detect an occasional fainter 'signal' stimulus, caused a substantial increase in the N1 (83 msec) and P2 (161 msec) components of the auditory evoked potential without any change in preceding components. This evidence shows that human auditory attention is not mediated by a peripheral gating mechanism. The evoked response to the detected signal stimulus also contained a large P3 (450 msec) wave that was topographically distinct from the preceding components. This late positive wave could also be recorded in response to a detected omitted stimulus in a regular train and therefore seemed to index a stimulus-independent perceptual decision process.

  16. ATSDR evaluation of potential for human exposure to zinc.

    PubMed

    Roney, Nickolette; Osier, Mark; Paikoff, Sari J; Smith, Cassandra V; Williams, Malcolm; De Rosa, Christopher T

    2007-01-01

    As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of portions of the toxicological profile for zinc. The primary purpose of this article is to provide interested individuals with environmental information on zinc that includes production data, environmental fate, potential for human exposure, analytical methods and a listing of regulations and advisories. PMID:18386523

  17. ATSDR evaluation of potential for human exposure to benzene.

    PubMed

    Wilbur, S; Wohlers, D; Paikoff, S; Keith, L S; Faroon, O

    2008-01-01

    As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of portions of the toxicological profile for benzene. The primary purpose of this article is to provide interested individuals with environmental information on benzene that includes production data, environmental fate, potential for human exposure, analytical methods, and a listing of regulations and advisories. PMID:19022881

  18. Validation of Correction Algorithms for Near-IR Analysis of Human Milk in an Independent Sample Set-Effect of Pasteurization.

    PubMed

    Kotrri, Gynter; Fusch, Gerhard; Kwan, Celia; Choi, Dasol; Choi, Arum; Al Kafi, Nisreen; Rochow, Niels; Fusch, Christoph

    2016-03-01

    Commercial infrared (IR) milk analyzers are being increasingly used in research settings for the macronutrient measurement of breast milk (BM) prior to its target fortification. These devices, however, may not provide reliable measurement if not properly calibrated. In the current study, we tested a correction algorithm for a Near-IR milk analyzer (Unity SpectraStar, Brookfield, CT, USA) for fat and protein measurements, and examined the effect of pasteurization on the IR matrix and the stability of fat, protein, and lactose. Measurement values generated through Near-IR analysis were compared against those obtained through chemical reference methods to test the correction algorithm for the Near-IR milk analyzer. Macronutrient levels were compared between unpasteurized and pasteurized milk samples to determine the effect of pasteurization on macronutrient stability. The correction algorithm generated for our device was found to be valid for unpasteurized and pasteurized BM. Pasteurization had no effect on the macronutrient levels and the IR matrix of BM. These results show that fat and protein content can be accurately measured and monitored for unpasteurized and pasteurized BM. Of additional importance is the implication that donated human milk, generally low in protein content, has the potential to be target fortified. PMID:26927169

  19. Validation of Correction Algorithms for Near-IR Analysis of Human Milk in an Independent Sample Set-Effect of Pasteurization.

    PubMed

    Kotrri, Gynter; Fusch, Gerhard; Kwan, Celia; Choi, Dasol; Choi, Arum; Al Kafi, Nisreen; Rochow, Niels; Fusch, Christoph

    2016-03-01

    Commercial infrared (IR) milk analyzers are being increasingly used in research settings for the macronutrient measurement of breast milk (BM) prior to its target fortification. These devices, however, may not provide reliable measurement if not properly calibrated. In the current study, we tested a correction algorithm for a Near-IR milk analyzer (Unity SpectraStar, Brookfield, CT, USA) for fat and protein measurements, and examined the effect of pasteurization on the IR matrix and the stability of fat, protein, and lactose. Measurement values generated through Near-IR analysis were compared against those obtained through chemical reference methods to test the correction algorithm for the Near-IR milk analyzer. Macronutrient levels were compared between unpasteurized and pasteurized milk samples to determine the effect of pasteurization on macronutrient stability. The correction algorithm generated for our device was found to be valid for unpasteurized and pasteurized BM. Pasteurization had no effect on the macronutrient levels and the IR matrix of BM. These results show that fat and protein content can be accurately measured and monitored for unpasteurized and pasteurized BM. Of additional importance is the implication that donated human milk, generally low in protein content, has the potential to be target fortified.

  20. Human neural tuning estimated from compound action potentials in normal hearing human volunteers

    NASA Astrophysics Data System (ADS)

    Verschooten, Eric; Desloovere, Christian; Joris, Philip X.

    2015-12-01

    The sharpness of cochlear frequency tuning in humans is debated. Evoked otoacoustic emissions and psychophysical measurements suggest sharper tuning in humans than in laboratory animals [15], but this is disputed based on comparisons of behavioral and electrophysiological measurements across species [14]. Here we used evoked mass potentials to electrophysiologically quantify tuning (Q10) in humans. We combined a notched noise forward masking paradigm [9] with the recording of trans tympanic compound action potentials (CAP) from masked probe tones in awake human and anesthetized monkey (Macaca mulatta). We compare our results to data obtained with the same paradigm in cat and chinchilla [16], and find that CAP-Q10values in human are ˜1.6x higher than in cat and chinchilla and ˜1.3x higher than in monkey. To estimate frequency tuning of single auditory nerve fibers (ANFs) in humans, we derive conversion functions from ANFs in cat, chinchilla, and monkey and apply these to the human CAP measurements. The data suggest that sharp cochlear tuning is a feature of old-world primates.

  1. Human leader and robot follower team: correcting leader's position from follower's heading

    NASA Astrophysics Data System (ADS)

    Borenstein, Johann; Thomas, David; Sights, Brandon; Ojeda, Lauro; Bankole, Peter; Fellars, Donald

    2010-04-01

    In multi-agent scenarios, there can be a disparity in the quality of position estimation amongst the various agents. Here, we consider the case of two agents - a leader and a follower - following the same path, in which the follower has a significantly better estimate of position and heading. This may be applicable to many situations, such as a robotic "mule" following a soldier. Another example is that of a convoy, in which only one vehicle (not necessarily the leading one) is instrumented with precision navigation instruments while all other vehicles use lower-precision instruments. We present an algorithm, called Follower-derived Heading Correction (FDHC), which substantially improves estimates of the leader's heading and, subsequently, position. Specifically, FHDC produces a very accurate estimate of heading errors caused by slow-changing errors (e.g., those caused by drift in gyros) of the leader's navigation system and corrects those errors.

  2. Human DNA Polymerase ν Catalyzes Correct and Incorrect DNA Synthesis with High Catalytic Efficiency.

    PubMed

    Gowda, A S Prakasha; Moldovan, George-Lucian; Spratt, Thomas E

    2015-06-26

    DNA polymerase ν (pol ν) is a low fidelity A-family polymerase with a putative role in interstrand cross-link repair and homologous recombination. We carried out pre-steady-state kinetic analysis to elucidate the kinetic mechanism of this enzyme. We found that the mechanism consists of seven steps, similar that of other A-family polymerases. pol ν binds to DNA with a Kd for DNA of 9.2 nm, with an off-rate constant of 0.013 s(-1)and an on-rate constant of 14 μm(-1) s(-1). dNTP binding is rapid with Kd values of 20 and 476 μm for the correct and incorrect dNTP, respectively. Pyrophosphorylation occurs with a Kd value for PPi of 3.7 mm and a maximal rate constant of 11 s(-1). Pre-steady-state kinetics, examination of the elemental effect using dNTPαS, and pulse-chase experiments indicate that a rapid phosphodiester bond formation step is flanked by slow conformational changes for both correct and incorrect base pair formation. These experiments in combination with computer simulations indicate that the first conformational change occurs with rate constants of 75 and 20 s(-1); rapid phosphodiester bond formation occurs with a Keq of 2.2 and 1.7, and the second conformational change occurs with rate constants of 2.1 and 0.5 s(-1), for correct and incorrect base pair formation, respectively. The presence of a mispair does not induce the polymerase to adopt a low catalytic conformation. pol ν catalyzes both correct and mispair formation with high catalytic efficiency.

  3. Correct folding of an α-helix and a β-hairpin using a polarized 2D torsional potential.

    PubMed

    Gao, Ya; Li, Yongxiu; Mou, Lirong; Lin, Bingbing; Zhang, John Z H; Mei, Ye

    2015-01-01

    A new modification to the AMBER force field that incorporates the coupled two-dimensional main chain torsion energy has been evaluated for the balanced representation of secondary structures. In this modified AMBER force field (AMBER03(2D)), the main chain torsion energy is represented by 2-dimensional Fourier expansions with parameters fitted to the potential energy surface generated by high-level quantum mechanical calculations of small peptides in solution. Molecular dynamics simulations are performed to study the folding of two model peptides adopting either α-helix or β-hairpin structures. Both peptides are successfully folded into their native structures using an AMBER03(2D) force field with the implementation of a polarization scheme (AMBER03(2D)p). For comparison, simulations using a standard AMBER03 force field with and without polarization, as well as AMBER03(2D) without polarization, fail to fold both peptides successfully. The correction to secondary structure propensity in the AMBER03 force field and the polarization effect are critical to folding Trpzip2; without these factors, a helical structure is obtained. This study strongly suggests that this new force field is capable of providing a more balanced preference for helical and extended conformations. The electrostatic polarization effect is shown to be indispensable to the growth of secondary structures. PMID:26039188

  4. 'Cebiche'--a potential source of human anisakiasis in Mexico?

    PubMed

    Laffon-Leal, S M; Vidal-Martínez, V M; Arjona-Torres, G

    2000-06-01

    Five fish species used for preparation of a popular dish (cebiche) made with raw fish flesh in Mexico were obtained from five localities of the coast of Yucatan. Lutjanus synagris, Gerres cinereus, Sphyraena barracuda, Epinephelus morio and Haemulon plumieriwere examined for the presence of larvae of anisakid nematodes, causative agents of human anisakiasis. The nematode Pseudoterranova sp. was found in E. morio and S. barracuda with a total prevalence of 83% and 6.5 +/- 6.2 worms per fish for E. morio, and a prevalence of 33% and 10.2 +/- 30.0 worms per fish for S. barracuda. Contracaecumsp. was found to infect G. cinereus with a prevalence of 57% and 7.6 +/- 11.4 worms per fish. The relatively high prevalence of Pseudoterranova sp. indicates that this parasite is a potential causal agent of anisakiasis on the coast of Yucatan. Although all larvae were found only in the mesentery of the fish host, their importance as a potential source of human infection cannot be excluded as larval migration to the muscles in dead fish is possible. PMID:10881286

  5. Bacteriophage and their potential roles in the human oral cavity.

    PubMed

    Edlund, Anna; Santiago-Rodriguez, Tasha M; Boehm, Tobias K; Pride, David T

    2015-01-01

    The human oral cavity provides the perfect portal of entry for viruses and bacteria in the environment to access new hosts. Hence, the oral cavity is one of the most densely populated habitats of the human body containing some 6 billion bacteria and potentially 35 times that many viruses. The role of these viral communities remains unclear; however, many are bacteriophage that may have active roles in shaping the ecology of oral bacterial communities. Other implications for the presence of such vast oral phage communities include accelerating the molecular diversity of their bacterial hosts as both host and phage mutate to gain evolutionary advantages. Additional roles include the acquisitions of new gene functions through lysogenic conversions that may provide selective advantages to host bacteria in response to antibiotics or other types of disturbances, and protection of the human host from invading pathogens by binding to and preventing pathogens from crossing oral mucosal barriers. Recent evidence suggests that phage may be more involved in periodontal diseases than were previously thought, as their compositions in the subgingival crevice in moderate to severe periodontitis are known to be significantly altered. However, it is unclear to what extent they contribute to dysbiosis or the transition of the microbial community into a state promoting oral disease. Bacteriophage communities are distinct in saliva compared to sub- and supragingival areas, suggesting that different oral biogeographic niches have unique phage ecology shaping their bacterial biota. In this review, we summarize what is known about phage communities in the oral cavity, the possible contributions of phage in shaping oral bacterial ecology, and the risks to public health oral phage may pose through their potential to spread antibiotic resistance gene functions to close contacts. PMID:25861745

  6. Bacteriophage and their potential roles in the human oral cavity

    PubMed Central

    Edlund, Anna; Santiago-Rodriguez, Tasha M.; Boehm, Tobias K.; Pride, David T.

    2015-01-01

    The human oral cavity provides the perfect portal of entry for viruses and bacteria in the environment to access new hosts. Hence, the oral cavity is one of the most densely populated habitats of the human body containing some 6 billion bacteria and potentially 35 times that many viruses. The role of these viral communities remains unclear; however, many are bacteriophage that may have active roles in shaping the ecology of oral bacterial communities. Other implications for the presence of such vast oral phage communities include accelerating the molecular diversity of their bacterial hosts as both host and phage mutate to gain evolutionary advantages. Additional roles include the acquisitions of new gene functions through lysogenic conversions that may provide selective advantages to host bacteria in response to antibiotics or other types of disturbances, and protection of the human host from invading pathogens by binding to and preventing pathogens from crossing oral mucosal barriers. Recent evidence suggests that phage may be more involved in periodontal diseases than were previously thought, as their compositions in the subgingival crevice in moderate to severe periodontitis are known to be significantly altered. However, it is unclear to what extent they contribute to dysbiosis or the transition of the microbial community into a state promoting oral disease. Bacteriophage communities are distinct in saliva compared to sub- and supragingival areas, suggesting that different oral biogeographic niches have unique phage ecology shaping their bacterial biota. In this review, we summarize what is known about phage communities in the oral cavity, the possible contributions of phage in shaping oral bacterial ecology, and the risks to public health oral phage may pose through their potential to spread antibiotic resistance gene functions to close contacts. PMID:25861745

  7. Mapping Resources Potential of the Lunar Surface for Human Exploration

    NASA Astrophysics Data System (ADS)

    Garvin, James

    2005-07-01

    We propose to use the ACS/HRC to delineate UV through visible color units at three test sites on the lunar surface for the purpose of identifying localized areas enriched in potential resources, including TiO2. This pathfinding experiment will make use of HST's unique high resolution imaging capabilities in the near UV. We will observe the Apollo 15 and 17 sites to establish an empirical calibration against sampled lunar soils. We will then observe the Aristarchus Plateau in search of regions enriched in TiO2 at levels that could permit in situ resources utilization activities that support sustained human exploration. Precision mapping of TiO2 abundance and other chemical proxies by virtue of HST's high angular resolution in near UV wavelengths will extend lower resolution Visible-NIR results obtained from orbit by Clementine, and set the stage for future orbital surveys later in the decade. Understanding whether there are lunar near-side sites with adequate resource potential to target human "sorties" and related robotic precursor missions represents an important decision point in NASA's implementation of the President's Vision for Space Exploration. The proposed HST ACS/HRC test data directly support near-term engineering trades associated with the optimal location for the first human return missions to the Moon. No past, current, or planned future lunar orbiting spacecraft will have the ability to investigate the near UV aspects of the lunar spectrum at such scales { 50m}, so the results of the proposed HST observations are unique and relevant to NASA's mission.

  8. The Human Potential Movement: Body/Nonverbal/Movement Approaches to Human Growth.

    ERIC Educational Resources Information Center

    Caldwell, Stratton F.

    This report briefly describes the recent search for personal and interpersonal growth which has been termed the "Human Potential Movement," and the institutions or "growth centers" which have evolved as a result of this movement. It presents a list of body, nonverbal, and movement experiences derived from descriptive literature of the growth…

  9. Memory Distortion and Its Avoidance: An Event-Related Potentials Study on False Recognition and Correct Rejection

    PubMed Central

    Beato, Maria Soledad

    2016-01-01

    Memory researchers have long been captivated by the nature of memory distortions and have made efforts to identify the neural correlates of true and false memories. However, the underlying mechanisms of avoiding false memories by correctly rejecting related lures remains underexplored. In this study, we employed a variant of the Deese/Roediger-McDermott paradigm to explore neural signatures of committing and avoiding false memories. ERP were obtained for True recognition, False recognition, Correct rejection of new items, and, more importantly, Correct rejection of related lures. With these ERP data, early-frontal, left-parietal, and late right-frontal old/new effects (associated with familiarity, recollection, and monitoring processes, respectively) were analysed. Results indicated that there were similar patterns for True and False recognition in all three old/new effects analysed in our study. Also, False recognition and Correct rejection of related lures activities seemed to share common underlying familiarity-based processes. The ERP similarities between False recognition and Correct rejection of related lures disappeared when recollection processes were examined because only False recognition presented a parietal old/new effect. This finding supported the view that actual false recollections underlie false memories, providing evidence consistent with previous behavioural research and with most ERP and neuroimaging studies. Later, with the onset of monitoring processes, False recognition and Correct rejection of related lures waveforms presented, again, clearly dissociated patterns. Specifically, False recognition and True recognition showed more positive going patterns than Correct rejection of related lures signal and Correct rejection of new items signature. Since False recognition and Correct rejection of related lures triggered familiarity-recognition processes, our results suggest that deciding which items are studied is based more on recollection

  10. Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells.

    PubMed

    Hoban, Megan D; Cost, Gregory J; Mendel, Matthew C; Romero, Zulema; Kaufman, Michael L; Joglekar, Alok V; Ho, Michelle; Lumaquin, Dianne; Gray, David; Lill, Georgia R; Cooper, Aaron R; Urbinati, Fabrizia; Senadheera, Shantha; Zhu, Allen; Liu, Pei-Qi; Paschon, David E; Zhang, Lei; Rebar, Edward J; Wilber, Andrew; Wang, Xiaoyan; Gregory, Philip D; Holmes, Michael C; Reik, Andreas; Hollis, Roger P; Kohn, Donald B

    2015-04-23

    Sickle cell disease (SCD) is characterized by a single point mutation in the seventh codon of the β-globin gene. Site-specific correction of the sickle mutation in hematopoietic stem cells would allow for permanent production of normal red blood cells. Using zinc-finger nucleases (ZFNs) designed to flank the sickle mutation, we demonstrate efficient targeted cleavage at the β-globin locus with minimal off-target modification. By co-delivering a homologous donor template (either an integrase-defective lentiviral vector or a DNA oligonucleotide), high levels of gene modification were achieved in CD34(+) hematopoietic stem and progenitor cells. Modified cells maintained their ability to engraft NOD/SCID/IL2rγ(null) mice and to produce cells from multiple lineages, although with a reduction in the modification levels relative to the in vitro samples. Importantly, ZFN-driven gene correction in CD34(+) cells from the bone marrow of patients with SCD resulted in the production of wild-type hemoglobin tetramers.

  11. Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells

    PubMed Central

    Hoban, Megan D.; Cost, Gregory J.; Mendel, Matthew C.; Romero, Zulema; Kaufman, Michael L.; Joglekar, Alok V.; Ho, Michelle; Lumaquin, Dianne; Gray, David; Lill, Georgia R.; Cooper, Aaron R.; Urbinati, Fabrizia; Senadheera, Shantha; Zhu, Allen; Liu, Pei-Qi; Paschon, David E.; Zhang, Lei; Rebar, Edward J.; Wilber, Andrew; Wang, Xiaoyan; Gregory, Philip D.; Holmes, Michael C.; Reik, Andreas; Hollis, Roger P.

    2015-01-01

    Sickle cell disease (SCD) is characterized by a single point mutation in the seventh codon of the β-globin gene. Site-specific correction of the sickle mutation in hematopoietic stem cells would allow for permanent production of normal red blood cells. Using zinc-finger nucleases (ZFNs) designed to flank the sickle mutation, we demonstrate efficient targeted cleavage at the β-globin locus with minimal off-target modification. By codelivering a homologous donor template (either an integrase-defective lentiviral vector or a DNA oligonucleotide), high levels of gene modification were achieved in CD34+ hematopoietic stem and progenitor cells. Modified cells maintained their ability to engraft NOD/SCID/IL2rγnull mice and to produce cells from multiple lineages, although with a reduction in the modification levels relative to the in vitro samples. Importantly, ZFN-driven gene correction in CD34+ cells from the bone marrow of patients with SCD resulted in the production of wild-type hemoglobin tetramers. PMID:25733580

  12. The therapeutic potential of human olfactory-derived stem cells.

    PubMed

    Marshall, C T; Lu, C; Winstead, W; Zhang, X; Xiao, M; Harding, G; Klueber, K M; Roisen, F J

    2006-06-01

    Stem cells from fetal and adult central nervous system have been isolated and characterized, providing populations for potential replacement therapy for traumatic injury repair and neurodegenerative diseases. The regenerative capacity of the olfactory system has attracted scientific interest. Studies focusing on animal and human olfactory bulb ensheathing cells (OECs) have heightened the expectations that OECs can enhance axonal regeneration and repair demyelinating diseases. Harvest of OECs from the olfactory bulb requires highly invasive surgery, which is a major obstacle. In contrast, olfactory epithelium (OE) has a unique regenerative capacity and is readily accessible from its location in the nasal cavity, allowing for harvest without lasting damage to the donor. Adult OE contains progenitors responsible for the normal life-long continuous replacement of neurons and supporting cells. Culture techniques have been established for human OE that generate populations of mitotically active neural progenitors that form neurospheres (Roisen et al., 2001; Winstead et al., 2005). The potential application of this technology includes autologous transplantation where minimal donor material can be isolated, expanded ex vivo, and lineage restricted to a desired phenotype prior to/or after re-implantation. Furthermore, these strategies circumvent the ethical issues that arise with embryonic or fetal tissues. The long term goal is to develop procedures through which a victim of a spinal cord injury or neurodegenerative condition would serve as a source of progenitors for his/her own regenerative grafts, avoiding the need for immunosuppression and ethical controversy. In addition, these cells can provide populations for pharmacological and/or diagnostic evaluation.

  13. Potential effects of gas hydrate on human welfare

    USGS Publications Warehouse

    Kvenvolden, K.A.

    1999-01-01

    For almost 30 years, serious interest has been directed toward natural gas hydrate, a crystalline solid composed of water and methane, as a potential (i) energy resource, (ii) factor in global climate change, and (iii) sub-marine geohazard. Although each of these issues can affect human welfare, only (iii) is considered to be of immediate importance. Assessments of gas hydrate as an energy resource have often been overly optimistic, based in part on its very high methane content and on its worldwide occurrence in continental margins. Although these attributes are attractive, geologic settings, reservoir properties, and phase-equilibria considerations diminish the energy resource potential of natural gas hydrate. The possible role of gas hydrate in global climate change has been often overstated. Although methane is a 'greenhouse' gas in the atmosphere, much methane from dissociated gas hydrate may never reach the atmosphere, but rather may be converted to carbon dioxide and sequestered by the hydrosphere/biosphere before reaching the atmosphere. Thus, methane from gas hydrate may have little opportunity to affect global climate change. However, submarine geohazards (such as sediment instabilities and slope failures on local and regional scales, leading to debris flows, slumps, slides, and possible tsunamis) caused by gas-hydrate dissociation are of immediate and increasing importance as humankind moves to exploit seabed resources in ever-deepening waters of coastal oceans. The vulnerability of gas hydrate to temperature and sea level changes enhances the instability of deep-water oceanic sediments, and thus human activities and installations in this setting can be affected.

  14. Potential effects of gas hydrate on human welfare

    PubMed Central

    Kvenvolden, Keith A.

    1999-01-01

    For almost 30 years. serious interest has been directed toward natural gas hydrate, a crystalline solid composed of water and methane, as a potential (i) energy resource, (ii) factor in global climate change, and (iii) submarine geohazard. Although each of these issues can affect human welfare, only (iii) is considered to be of immediate importance. Assessments of gas hydrate as an energy resource have often been overly optimistic, based in part on its very high methane content and on its worldwide occurrence in continental margins. Although these attributes are attractive, geologic settings, reservoir properties, and phase-equilibria considerations diminish the energy resource potential of natural gas hydrate. The possible role of gas hydrate in global climate change has been often overstated. Although methane is a “greenhouse” gas in the atmosphere, much methane from dissociated gas hydrate may never reach the atmosphere, but rather may be converted to carbon dioxide and sequestered by the hydrosphere/biosphere before reaching the atmosphere. Thus, methane from gas hydrate may have little opportunity to affect global climate change. However, submarine geohazards (such as sediment instabilities and slope failures on local and regional scales, leading to debris flows, slumps, slides, and possible tsunamis) caused by gas-hydrate dissociation are of immediate and increasing importance as humankind moves to exploit seabed resources in ever-deepening waters of coastal oceans. The vulnerability of gas hydrate to temperature and sea level changes enhances the instability of deep-water oceanic sediments, and thus human activities and installations in this setting can be affected. PMID:10097052

  15. Electromagnetic wave emitting products and "Kikoh" potentiate human leukocyte functions.

    PubMed

    Niwa, Y; Iizawa, O; Ishimoto, K; Jiang, X; Kanoh, T

    1993-09-01

    Tourmaline (electric stone, a type of granite stone), common granite stone, ceramic disks, hot spring water and human palmar energy (called "Kikoh" in Japan and China), all which emit electromagnetic radiation in the far infrared region (wavelength 4-14 microns). These materials were thus examined for effects on human leukocyte activity and on lipid peroxidation of unsaturated fatty acids. It was revealed that these materials significantly increased intracellular calcium ion concentration, phagocytosis, and generation of reactive oxygen species in neutrophils, and the blastogenetic response of lymphocytes to mitogens. Chemotactic activity by neutrophils was also enhanced by exposure to tourmaline and the palm of "Kikohshi" i.e., a person who heals professionally by the laying on of hands. Despite the increase in reactive oxygen species generated by neutrophils, lipid peroxidation from unsaturated fatty acid was markedly inhibited by these four materials. The results suggest that materials emitting electromagnetic radiation in the far infrared range, which are widely used in Japan for cosmetic, therapeutic, and preservative purposes, appear capable of potentiating leukocyte functions without promoting oxidative injury. PMID:8406976

  16. Electromagnetic wave emitting products and "Kikoh" potentiate human leukocyte functions.

    PubMed

    Niwa, Y; Iizawa, O; Ishimoto, K; Jiang, X; Kanoh, T

    1993-09-01

    Tourmaline (electric stone, a type of granite stone), common granite stone, ceramic disks, hot spring water and human palmar energy (called "Kikoh" in Japan and China), all which emit electromagnetic radiation in the far infrared region (wavelength 4-14 microns). These materials were thus examined for effects on human leukocyte activity and on lipid peroxidation of unsaturated fatty acids. It was revealed that these materials significantly increased intracellular calcium ion concentration, phagocytosis, and generation of reactive oxygen species in neutrophils, and the blastogenetic response of lymphocytes to mitogens. Chemotactic activity by neutrophils was also enhanced by exposure to tourmaline and the palm of "Kikohshi" i.e., a person who heals professionally by the laying on of hands. Despite the increase in reactive oxygen species generated by neutrophils, lipid peroxidation from unsaturated fatty acid was markedly inhibited by these four materials. The results suggest that materials emitting electromagnetic radiation in the far infrared range, which are widely used in Japan for cosmetic, therapeutic, and preservative purposes, appear capable of potentiating leukocyte functions without promoting oxidative injury.

  17. Human amniotic fluid stem cell preconditioning improves their regenerative potential.

    PubMed

    Rota, Cinzia; Imberti, Barbara; Pozzobon, Michela; Piccoli, Martina; De Coppi, Paolo; Atala, Anthony; Gagliardini, Elena; Xinaris, Christodoulos; Benedetti, Valentina; Fabricio, Aline S C; Squarcina, Elisa; Abbate, Mauro; Benigni, Ariela; Remuzzi, Giuseppe; Morigi, Marina

    2012-07-20

    Human amniotic fluid stem (hAFS) cells, a novel class of broadly multipotent stem cells that share characteristics of both embryonic and adult stem cells, have been regarded as promising candidate for cell therapy. Taking advantage by the well-established murine model of acute kidney injury (AKI), we studied the proregenerative effect of hAFS cells in immunodeficient mice injected with the nephrotoxic drug cisplatin. Infusion of hAFS cells in cisplatin mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. Human AFS cells engrafted injured kidney predominantly in peritubular region without acquiring tubular epithelial markers. Human AFS cells exerted antiapoptotic effect, activated Akt, and stimulated proliferation of tubular cells possibly via local release of factors, including interleukin-6, vascular endothelial growth factor, and stromal cell-derived factor-1, which we documented in vitro to be produced by hAFS cells. The therapeutic potential of hAFS cells was enhanced by cell pretreatment with glial cell line-derived neurotrophic factor (GDNF), which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartment. By in vitro studies, GDNF increased hAFS cell production of growth factors, motility, and expression of receptors involved in cell homing and survival. These findings indicate that hAFS cells can promote functional recovery and contribute to renal regeneration in AKI mice via local production of mitogenic and prosurvival factors. The effects of hAFS cells can be remarkably enhanced by GDNF preconditioning.

  18. Human Amniotic Fluid Stem Cell Preconditioning Improves Their Regenerative Potential

    PubMed Central

    Rota, Cinzia; Imberti, Barbara; Pozzobon, Michela; Piccoli, Martina; De Coppi, Paolo; Atala, Anthony; Gagliardini, Elena; Xinaris, Christodoulos; Benedetti, Valentina; Fabricio, Aline S.C.; Squarcina, Elisa; Abbate, Mauro; Benigni, Ariela; Remuzzi, Giuseppe

    2012-01-01

    Human amniotic fluid stem (hAFS) cells, a novel class of broadly multipotent stem cells that share characteristics of both embryonic and adult stem cells, have been regarded as promising candidate for cell therapy. Taking advantage by the well-established murine model of acute kidney injury (AKI), we studied the proregenerative effect of hAFS cells in immunodeficient mice injected with the nephrotoxic drug cisplatin. Infusion of hAFS cells in cisplatin mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. Human AFS cells engrafted injured kidney predominantly in peritubular region without acquiring tubular epithelial markers. Human AFS cells exerted antiapoptotic effect, activated Akt, and stimulated proliferation of tubular cells possibly via local release of factors, including interleukin-6, vascular endothelial growth factor, and stromal cell–derived factor-1, which we documented in vitro to be produced by hAFS cells. The therapeutic potential of hAFS cells was enhanced by cell pretreatment with glial cell line–derived neurotrophic factor (GDNF), which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartment. By in vitro studies, GDNF increased hAFS cell production of growth factors, motility, and expression of receptors involved in cell homing and survival. These findings indicate that hAFS cells can promote functional recovery and contribute to renal regeneration in AKI mice via local production of mitogenic and prosurvival factors. The effects of hAFS cells can be remarkably enhanced by GDNF preconditioning. PMID:22066606

  19. Under-correction of human myopia – Is it myopigenic?: A retrospective analysis of clinical refraction data

    PubMed Central

    Vasudevan, Balamurali; Esposito, Christina; Peterson, Cody; Coronado, Cory; Ciuffreda, Kenneth J.

    2014-01-01

    Purpose To investigate retrospectively, based on routine clinical records in an optometric office, the effect of refractive under-correction of the myopic spectacle prescription on myopic progression in children and young adults. Methods Patient records of children and young-adult myopes in a private optometric practice in Glendale, Arizona, USA, were initially reviewed to identify those that met the criteria. Information collected from the patient records included: age, gender, the dates and number of their visits (more than one visit was required for use of the data), final prescription, and non-cycloplegic subjective refraction. For each patient visit, the difference in spherical equivalent (SE) between the subjective refraction for maximum visual acuity and the final prescription was calculated for both the left and right eyes. Myopia progression was defined as the difference in SE between the final subjective refraction of the previous visit and that of the subsequent visit. Based on the study criteria, a total of 275 patient visits were obtained from the data collected in 76 patients. Results A significant positive correlation was found between the magnitude of under-correction of the refractive error and myopic progression (r = 0.301, p < 0.01); that is, the greater the under-correction, the greater the myopic progression. In addition, there was a significant positive correlation between myopia progression and subjective refraction (r = 0.166, p = 0.006); that is, the greater the degree of myopia, the greater the effect of under-correction. However, there was no significant correlation between myopia progression and either age (r = −0.11, p = 0.86) or gender (r = −0.82, p = 0.17). Conclusion Under-correction of myopia produced a small but progressively greater degree of myopic progression than did full correction. The present finding is consistent with earlier clinical trials and modeling of human myopia. PMID:25000870

  20. Gait curves for human recognition, backpack detection, and silhouette correction in a nighttime environment

    NASA Astrophysics Data System (ADS)

    DeCann, Brian; Ross, Arun

    2010-04-01

    The need for an automated surveillance system is pronounced at night when the capability of the human eye to detect anomalies is reduced. While there have been significant efforts in the classification of individuals using human metrology and gait, the majority of research assumes a day-time environment. The aim of this study is to move beyond traditional image acquisition modalities and explore the issues of object detection and human identification at night. To address these issues, a spatiotemporal gait curve that captures the shape dynamics of a moving human silhouette is employed. Initially proposed by Wang et al., this representation of the gait is expanded to incorporate modules for individual classification, backpack detection, and silhouette restoration. Evaluation of these algorithms is conducted on the CASIA Night Gait Database, which includes 10 video sequences for each of 153 unique subjects. The video sequences were captured using a low resolution thermal camera. Matching performance of the proposed algorithms is evaluated using a nearest neighbor classifier. The outcome of this work is an efficient algorithm for backpack detection and human identification, and a basis for further study in silhouette enhancement.

  1. Analysis of measured data of human body based on error correcting frequency

    NASA Astrophysics Data System (ADS)

    Jin, Aiyan; Peipei, Gao; Shang, Xiaomei

    2014-04-01

    Anthropometry is to measure all parts of human body surface, and the measured data is the basis of analysis and study of the human body, establishment and modification of garment size and formulation and implementation of online clothing store. In this paper, several groups of the measured data are gained, and analysis of data error is gotten by analyzing the error frequency and using analysis of variance method in mathematical statistics method. Determination of the measured data accuracy and the difficulty of measured parts of human body, further studies of the causes of data errors, and summarization of the key points to minimize errors possibly are also mentioned in the paper. This paper analyses the measured data based on error frequency, and in a way , it provides certain reference elements to promote the garment industry development.

  2. Acrolein environmental levels and potential for human exposure.

    PubMed

    Faroon, O; Roney, N; Taylor, J; Ashizawa, A; Lumpkin, M H; Plewak, D J

    2008-09-01

    This article provides environmental information on acrolein including environmental fate, potential for human exposure, analytical methods, and a listing of regulations and advisories. Acrolein may be released to the environment in emissions and effluents from its manufacturing and use facilities, in emissions from combustion processes (including cigarette smoking and combustion of petrochemical fuels), from direct application to water and waste water as a slimicide and aquatic herbicide, as a photooxidation product of various hydrocarbon pollutants found in air (including propylene and 1,3-butadiene), and from land disposal of some organic waste materials. Acrolein is a reactive compound and is unstable in the environment. The general population may be exposed to acrolein through inhalation of contaminated air and through ingestion of certain foods. Important sources of acrolein exposure are via inhalation of tobacco smoke and environmental tobacco smoke and via the overheating of fats contained in all living matter. There is potential for exposure to acrolein in many occupational settings as the result of its varied uses and its formation during the combustion and pyrolysis of materials such as wood, petrochemical fuels, and plastics. PMID:19039083

  3. The /A 1 Sigma +/ - /X 1 Sigma +/ system of the isotopic lithium hydrides - The molecular constants, potential energy curves, and their adiabatic corrections

    NASA Technical Reports Server (NTRS)

    Vidal, C. R.; Stwalley, W. C.

    1982-01-01

    The molecular constants and their adiabatic corrections have been determined for the (A 1 Sigma +) - (X 1 Sigma +) system of the isotopic lithium hydrides: (Li-6)H, (Li-7)H, (Li-6)D, and (Li-7)D. Using a fully quantum mechanical variational method, the potential energy curves (IPA potentials) are determined. Extending the variational method, we have obtained for the first time adiabatic corrections of potential energy curves from isotopic spectroscopic data. A significant difference between the potential energy curves of the lithium hydrides and the lithium deuterides has been observed. When Li-6 was replaced by Li-7, a significant difference was only observed for the (A 1 Sigma +) state, but not for the (X 1 Sigma +) state.

  4. The potential of bone marrow stem cells to correct liver dysfunction in a mouse model of Wilson's disease.

    PubMed

    Allen, Katrina J; Cheah, Daphne M Y; Lee, Xiao Ling; Pettigrew-Buck, Nicole E; Vadolas, Jim; Mercer, Julian F B; Ioannou, Panayiotis A; Williamson, Robert

    2004-01-01

    Metabolic liver diseases are excellent targets for correction using novel stem cell, hepatocyte, and gene therapies. In this study, the use of bone marrow stem cell transplantation to correct liver disease in the toxic milk (tx) mouse, a murine model for Wilson's disease, was evaluated. Preconditioning with sublethal irradiation, dietary copper loading, and the influence of cell transplantation sites were assessed. Recipient tx mice were sublethally irradiated (4 Gy) prior to transplantation with bone marrow stem cells harvested from normal congenic (DL) littermates. Of 46 transplanted tx mice, 11 demonstrated genotypic repopulation in the liver. Sublethal irradiation was found to be essential for donor cell engraftment and liver repopulation. Dietary copper loading did not improve cell engraftment and repopulation results. Both intravenously and intrasplenically transplanted cells produced similar repopulation successes. Direct evidence of functionality and disease correction following liver repopulation was observed in the 11 mice where liver copper levels were significantly reduced when compared with mice with no liver repopulation. The reversal of copper loading with bone marrow cells is similar to the level of correction seen when normal congenic liver cells are used. Transplantation of bone marrow cells partially corrects the metabolic phenotype in a mouse model for Wilson's disease.

  5. Massive transfusion: an overview of the main characteristics and potential risks associated with substances used for correction of a coagulopathy.

    PubMed

    Seghatchian, Jerard; Samama, Meyer Michel

    2012-10-01

    Massive transfusion (MT) is an empiric mode of treatment advocated for uncontrolled bleeding and massive haemorrhage, aiming at optimal resuscitation and aggressive correction of coagulopathy. Conventional guidelines recommend early administration of crystalloids and colloids in conjunction with red cells, where the red cell also plays a critical haemostatic function. Plasma and platelets are only used in patients with microvascular bleeding with PT/APTT values >1.5 times the normal values and if PLT counts are below 50×10(9)/L. Massive transfusion carries a significant mortality rate (40%), which increases with the number of volume expanders and blood components transfused. Controversies still exist over the optimal ratio of blood components with respect to overall clinical outcomes and collateral damage. While inadequate transfusion is believed to be associated with poor outcomes but empirical over transfusion results in unnecessary donor exposure with an increased rate of sepsis, transfusion overload and infusion of variable amounts of some biological response modifiers (BRMs), which have the potential to cause additional harm. Alternative strategies, such as early use of tranexamic acid are helpful. However in trauma settings the use of warm fresh whole blood (WFWB) instead of reconstituted components with a different ratio of stored components might be the most cost effective and safer option to improve the patient's survival rate and minimise collateral damage. This manuscript, after a brief summary of standard medical intervention in massive transfusion focuses on the main characteristics of various substances currently available to overcome massive transfusion coagulopathy. The relative levels of some BRMs in fresh and aged blood components of the same origin are highlighted and some myths and unresolved issues related to massive transfusion practice are discussed. In brief, the coagulopathy in MT is a complex phenomenon, often complicated by chronic

  6. Potential applications of gut microbiota to control human physiology.

    PubMed

    Umu, Ozgün Candan Onarman; Oostindjer, Marije; Pope, Phillip B; Svihus, Birger; Egelandsdal, Bjørg; Nes, Ingolf F; Diep, Dzung B

    2013-11-01

    The microorganisms living in our gut have been a black box to us for a long time. However, with the recent advances in high throughput DNA sequencing technologies, it is now possible to assess virtually all microorganisms in our gut including non-culturable ones. With the use of powerful bioinformatics tools to deal with multivariate analyses of huge amounts of data from metagenomics, metatranscriptomics, metabolomics, we now start to gain some important insights into these tiny gut inhabitants. Our knowledge is increasing about who they are, to some extent, what they do and how they affect our health. Gut microbiota have a broad spectrum of possible effects on health, from preventing serious diseases, improving immune system and gut health to stimulating the brain centers responsible for appetite and food intake control. Further, we may be on the verge of being capable of manipulating the gut microbiota by diet control to possibly improve our health. Diets consisting of different components that are fermentable by microbiota are substrates for different kinds of microbes in the gut. Thus, diet control can be used to favor the growth of some selected gut inhabitants. Nowadays, the gut microbiota is taken into account as a separate organ in human body and their activities and metabolites in gut have many physiological and neurological effects. In this mini-review, we discuss the diversity of gut microbiota, the technologies used to assess them, factors that affect microbial composition and metabolites that affect human physiology, and their potential applications in satiety control via the gut-brain axis.

  7. Short-term potentiation of breathing in humans.

    PubMed

    Fregosi, R F

    1991-09-01

    The purpose of this study was to determine if the increase in ventilation induced by hypoxic stimulation of the carotid bodies (CB) persists after cessation of the stimulus in humans. I reasoned that a short-term potentiation (STP) of breathing, sometimes called an "afterdischarge," could be unmasked by combining hypoxia with exercise, because ventilation increases synergistically under these conditions. Seven young healthy men performed mild bicycle exercise (30% peak power) while breathing O2 for 1.5 min ("control" state), and their CB were then stimulated by 1.5 min of hypoxic exercise (10% O2--balance N2). CB stimulation was then terminated by changing the inspirate back to O2 as exercise continued. Inspiratory and expiratory duration (TI and TE) and inspiratory flow and its time integral [tidal volume (VT)] were measured with a pneumotachometer. Inspired minute ventilation (VI) and mean inspiratory flow (VT/TI) declined exponentially after the cessation of CB stimulation, with first-order time constants of 28.6 +/- 6.7 and 24.6 +/- 1.6 (SD) s, respectively. The slow decay of VI was due primarily to potentiation of both TI and TE, although the effect on the latter predominated. Additional experiments in six subjects showed that brief intense CB stimulation with four to five breaths of N2 during mild exercise induced STP of similar magnitude to that observed in the hypoxic exercise experiments. Finally, the imposition of hyperoxia during air breathing exercise at a level of respiratory drive similar to that induced by the hypoxic exercise did not change VI significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1757326

  8. Crystal structure of human CRMP-4: correction of intensities for lattice-translocation disorder

    SciTech Connect

    Ponnusamy, Rajesh; Lebedev, Andrey A.; Pahlow, Steffen; Lohkamp, Bernhard

    2014-06-01

    Crystals of human CRMP-4 showed severe lattice-translocation disorder. Intensities were demodulated using the so-called lattice-alignment method and a new more general method with simplified parameterization, and the structure is presented. Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins that are mainly involved in neuronal cell development. In humans, the CRMP family comprises five members. Here, crystal structures of human CRMP-4 in a truncated and a full-length version are presented. The latter was determined from two types of crystals, which were either twinned or partially disordered. The crystal disorder was coupled with translational NCS in ordered domains and manifested itself with a rather sophisticated modulation of intensities. The data were demodulated using either the two-lattice treatment of lattice-translocation effects or a novel method in which demodulation was achieved by independent scaling of several groups of intensities. This iterative protocol does not rely on any particular parameterization of the modulation coefficients, but uses the current refined structure as a reference. The best results in terms of R factors and map correlation coefficients were obtained using this new method. The determined structures of CRMP-4 are similar to those of other CRMPs. Structural comparison allowed the confirmation of known residues, as well as the identification of new residues, that are important for the homo- and hetero-oligomerization of these proteins, which are critical to nerve-cell development. The structures provide further insight into the effects of medically relevant mutations of the DPYSL-3 gene encoding CRMP-4 and the putative enzymatic activities of CRMPs.

  9. Potential prognostic, diagnostic and therapeutic markers for human gastric cancer

    PubMed Central

    Tsai, Ming-Ming; Wang, Chia-Siu; Tsai, Chung-Ying; Chi, Hsiang-Cheng; Tseng, Yi-Hsin; Lin, Kwang-Huei

    2014-01-01

    The high incidence of gastric cancer (GC) and its consequent mortality rate severely threaten human health. GC is frequently not diagnosed until a relatively advanced stage. Surgery is the only potentially curative treatment. Thus, early screening and diagnosis are critical for improving prognoses in patients with GC. Gastroscopy with biopsy is an appropriate method capable of aiding the diagnosis of specific early GC tumor types; however, the stress caused by this method together with it being excessively expensive makes it difficult to use it as a routine method for screening for GC on a population basis. The currently used tumor marker assays for detecting GC are simple and rapid, but their use is limited by their low sensitivity and specificity. In recent years, several markers have been identified and tested for their clinical relevance in the management of GC. Here, we review the serum-based tumor markers for GC and their clinical significance, focusing on discoveries from microarray/proteomics research. We also review tissue-based GC tumor markers and their clinical application, focusing on discoveries from immunohistochemical research. This review provides a brief description of various tumor markers for the purposes of diagnosis, prognosis and therapeutics, and we include markers already in clinical practice and various forthcoming biomarkers. PMID:25320517

  10. Fat emulsion infusion potentiates coagulation activation during human endotoxemia.

    PubMed

    van der Poll, T; Coyle, S M; Levi, M; Boermeester, M A; Braxton, C C; Jansen, P M; Hack, C E; Lowry, S F

    1996-01-01

    Intravenous fat emulsions are frequently given to malnourished patients who are prone to suffer from infectious complications. As injection of low dose endotoxin represents a model to study the human response to acute infection, we sought to determine the effect of lipid emulsion infusion on endotoxin-induced activation of the hemostatic mechanism in man. Ten healthy men received a bolus intravenous injection of endotoxin (lot EC-5; 20 U/kg) midway through a 4-h infusion (125 ml/h) of either dextrose 5% (n = 5) or Intralipid 20% (n = 5). Lipid infusion potentiated endotoxin-induced coagulation activation, as indicated by higher plasma levels of the prothrombin fragment F1 + 2 and of thrombin-antithrombin III complexes (both p < 0.05 for the difference between groups). However, lipid infusion did not influence the fibrinolytic response to intravenous endotoxin, as reflected by similar increases in the levels of tissue-type plasminogen activator and plasmin-alpha 2-antiplasmin complexes in both groups. Endotoxin-induced appearance of plasminogen activator inhibitor type I was enhanced by lipid infusion (p < 0.05). These data suggest that fat emulsion infusion may enhance the tendency towards thrombotic complications in patients with infections.

  11. Therapeutic potential of perivascular cells from human pluripotent stem cells.

    PubMed

    Dar, Ayelet; Itskovitz-Eldor, Joseph

    2015-09-01

    Vascularization of injured tissues or artificial grafts is a major challenge in tissue engineering, stimulating a continued search for alternative sources for vasculogenic cells and the development of therapeutic strategies. Human pluripotent stem cells (hPSCs), either embryonic or induced, offer a plentiful platform for the derivation of large numbers of vasculogenic cells, as required for clinical transplantations. Various protocols for generation of vasculogenic smooth muscle cells (SMCs) from hPSCs have been described with considerably different SMC derivatives. In addition, we recently identified hPSC-derived pericytes, which are similar to their physiological counterparts, exhibiting unique features of blood vessel-residing perivascular cells, as well as multipotent mesenchymal precursors with therapeutic angiogenic potential. In this review we refer to methodologies for the development of a variety of perivascular cells from hPSCs with respect to developmental induction, differentiation capabilities, potency and their dual function as mesenchymal precursors. The therapeutic effect of hPSC-derived perivascular cells in experimental models of tissue engineering and regenerative medicine are described and compared to those of their native physiological counterparts.

  12. A method for potentiating Renshaw cell activity in humans.

    PubMed

    Mazzocchio, R; Rossi, A

    1997-12-01

    Owing to the introduction of a special electrophysiological method [3] it has been possible to study spinal recurrent inhibition in humans. The method, however, is indirect and, being based on an H reflex technique, can only be tested in motor nuclei from which a large monosynaptic response can be obtained. We have developed a complementary method by which pharmacological stimulation of Renshaw cells is obtained [6]. It exploits the central cholinergic properties of L-acetylcarnitine [18], a substance which most likely acts potentiating the synaptic drive of the motoneurone collaterals [7], known to be the main source of excitation of Renshaw cells [15,20]. The use of L-acetylcarnitine has allowed to establish the validity of the original methodology [6] and to confirm the presence of recurrent inhibition, tested either by the H reflex technique [11-13] or, if not possible, by the PSTH technique and/or rectified averaged EMG analysis [1,4], in many limb motor nuclei. Thus, it can be expected that L-acetylcarnitine may be used as an independent means for identifying changes in motoneuronal activity related or attributed to the influence of Renshaw cells.

  13. Perivascular Stromal Cells as a Potential Reservoir of Human Cytomegalovirus

    PubMed Central

    Soland, M. A.; Keyes, L. R.; Bayne, R.; Moon, J.; Porada, C. D.; St. Jeor, S.; Almeida-Porada, G.

    2014-01-01

    Human cytomegalovirus (HCMV) infection is an important cause of morbidity and mortality among both solid organ and hematopoietic stem cell transplant recipients. Identification of cells throughout the body that can potentially serve as a viral reservoir is essential to dissect mechanisms of cell tropism and latency and to develop novel therapies. Here, we tested and compared the permissivity of liver-, brain-, lung (LNG)- and bone marrow (BM)-derived perivascular mesenchymal stromal cells (MSC) to HCMV infection and their ability to propagate and produce infectious virus. Perivascular MSC isolated from the different organs have in common the expression of CD146 and Stro-1. While all these cells were permissive to HCMV infection, the highest rate of HCMV infection was seen with LNG-MSC, as determined by viral copy number and production of viral particles by these cells. In addition, we showed that, although the supernatants from each of the HCMV-infected cultures contained infectious virus, the viral copy number and the quantity and timing of virus production varied among the various organ-specific MSC. Furthermore, using quantitative polymerase chain reaction, we were able to detect HCMV DNA in BM-MSC isolated from 7 out of 19 healthy, HCMV-seropositive adults, suggesting that BM-derived perivascular stromal cells may constitute an unrecognized natural HCMV reservoir. PMID:24592822

  14. Oncogenic potential diverge among human papillomavirus type 16 natural variants

    SciTech Connect

    Sichero, Laura; Simao Sobrinho, Joao; Lina Villa, Luisa

    2012-10-10

    We compared E6/E7 protein properties of three different HPV-16 variants: AA, E-P and E-350G. Primary human foreskin keratinocytes (PHFK) were transduced with HPV-16 E6 and E7 and evaluated for proliferation and ability to grow in soft agar. E-P infected keratinocytes presented the lowest efficiency in colony formation. AA and E-350G keratinocytes attained higher capacity for in vitro transformation. We observed similar degradation of TP53 among HPV-16 variants. Furthermore, we accessed the expression profile in early (p5) and late passage (p30) transduced cells of 84 genes commonly involved in carcinogenesis. Most differences could be attributed to HPV-16 E6/E7 expression. In particular, we detected different expression of ITGA2 and CHEK2 in keratinocytes infected with AA and AA/E-350G late passage cells, respectively, and higher expression of MAP2K1 in E-350G transduced keratinocytes. Our results indicate differences among HPV-16 variants that could explain, at least in part, differences in oncogenic potential attributed to these variants.

  15. Stewardship and Accountability: Valued Elements in Maximising Human Potential.

    ERIC Educational Resources Information Center

    Todd, Sally M.

    1998-01-01

    Explains the application of five principles of stewardship to the education of gifted children: (1) teachers/parents teach correct principles; (2) students set their own goals in harmony with these principles; (3) teachers serve students as a source of help; (4) students ask for and receive help when needed; and (5) students give an accounting of…

  16. Motion correction of in vivo three-dimensional optical coherence tomography of human skin using a fiducial marker

    PubMed Central

    Liew, Yih Miin; McLaughlin, Robert A.; Wood, Fiona M.; Sampson, David D.

    2012-01-01

    This paper presents a novel method based on a fiducial marker for correction of motion artifacts in 3D, in vivo, optical coherence tomography (OCT) scans of human skin and skin scars. The efficacy of this method was compared against a standard cross-correlation intensity-based registration method. With a fiducial marker adhered to the skin, OCT scans were acquired using two imaging protocols: direct imaging from air into tissue; and imaging through ultrasound gel into tissue, which minimized the refractive index mismatch at the tissue surface. The registration methods were assessed with data from both imaging protocols and showed reduced distortion of skin features due to motion. The fiducial-based method was found to be more accurate and robust, with an average RMS error below 20 µm and success rate above 90%. In contrast, the intensity-based method had an average RMS error ranging from 36 to 45 µm, and a success rate from 50% to 86%. The intensity-based algorithm was found to be particularly confounded by corrugations in the skin. By contrast, tissue features did not affect the fiducial-based method, as the motion correction was based on delineation of the flat fiducial marker. The average computation time for the fiducial-based algorithm was approximately 21 times less than for the intensity-based algorithm. PMID:22876343

  17. Curcumin Suppresses Soluble Tau Dimers and Corrects Molecular Chaperone, Synaptic, and Behavioral Deficits in Aged Human Tau Transgenic Mice*

    PubMed Central

    Ma, Qiu-Lan; Zuo, Xiaohong; Yang, Fusheng; Ubeda, Oliver J.; Gant, Dana J.; Alaverdyan, Mher; Teng, Edmond; Hu, Shuxin; Chen, Ping-Ping; Maiti, Panchanan; Teter, Bruce; Cole, Greg M.; Frautschy, Sally A.

    2013-01-01

    The mechanisms underlying Tau-related synaptic and cognitive deficits and the interrelationships between Tau species, their clearance pathways, and synaptic impairments remain poorly understood. To gain insight into these mechanisms, we examined these interrelationships in aged non-mutant genomic human Tau mice, with established Tau pathology and neuron loss. We also examined how these interrelationships changed with an intervention by feeding mice either a control diet or one containing the brain permeable beta-amyloid and Tau aggregate binding molecule curcumin. Transgene-dependent elevations in soluble and insoluble phospho-Tau monomer and soluble Tau dimers accompanied deficits in behavior, hippocampal excitatory synaptic markers, and molecular chaperones (heat shock proteins (HSPs)) involved in Tau degradation and microtubule stability. In human Tau mice but not control mice, HSP70, HSP70/HSP72, and HSP90 were reduced in membrane-enriched fractions but not in cytosolic fractions. The synaptic proteins PSD95 and NR2B were reduced in dendritic fields and redistributed into perikarya, corresponding to changes observed by immunoblot. Curcumin selectively suppressed levels of soluble Tau dimers, but not of insoluble and monomeric phospho-Tau, while correcting behavioral, synaptic, and HSP deficits. Treatment increased PSD95 co-immunoprecipitating with NR2B and, independent of transgene, increased HSPs implicated in Tau clearance. It elevated HSP90 and HSC70 without increasing HSP mRNAs; that is, without induction of the heat shock response. Instead curcumin differentially impacted HSP90 client kinases, reducing Fyn without reducing Akt. In summary, curcumin reduced soluble Tau and elevated HSPs involved in Tau clearance, showing that even after tangles have formed, Tau-dependent behavioral and synaptic deficits can be corrected. PMID:23264626

  18. Early corrective reactions of the leg to perturbations at the torso during walking in humans.

    PubMed

    Misiaszek, J E; Stephens, M J; Yang, J F; Pearson, K G

    2000-04-01

    The contribution of afferent feedback to the regulation of locomotion in humans is not well understood. Animal experiments have suggested that loading of the leg during the stance phase may enhance the magnitude of extensor burst activity and delay the onset of swing phase. The aim of the present study was to determine whether transient loading of the leg at the end of stance would enhance extensor-muscle activity and delay the onset of swing in walking humans. To test this hypothesis, we applied loads to the hips of subjects so that the load was applied along the long axis of the leg at the end of stance (down-back unsupported, DBU). This resulted in an unexpectedly complex reaction characterised by rapid co-contraction of antagonist pairs of muscles around the ankle and knee and a prolongation of the stance phase. We speculated that the complexity of the reaction was, in part, due to a disturbance in equilibrium. To address this possibility, two additional perturbation paradigms were tested: (1) subjects held a rail during the loading paradigm (down-back supported, DBS), or (2) subjects received only a posteriorly directed perturbation of the hips, which added no additional load to the leg (backward unsupported, BU). As predicted, the DBS perturbation resulted in an enhancement of the ongoing soleus-muscle activity, and the unexpected tibialis anterior burst that was observed during the DBU paradigm was absent. Allowing the subjects to hold a rail substantially reduced the change in the timing of the step cycle observed in the DBU paradigm. The BU perturbation prolonged the stance phase duration and, as expected, resulted in a burst of activity in tibialis activity. This was usually accompanied by a reduction in the ongoing soleus activity. Two important conclusions are drawn from the present study. First, loading of the leg at the end of stance phase enhances the ongoing extensor-muscle activity. We suggest that afferent feedback responding to the increase load

  19. Constitutive Expression of Human Telomerase Enhances the Proliferation Potential of Human Mesenchymal Stem Cells

    PubMed Central

    Bischoff, David S.; Makhijani, Nalini S.

    2012-01-01

    Abstract Human mesenchymal stem cells (hMSCs) are highly desirable cells for bone engineering due to the inherent multipotent nature of the cells. Unfortunately, there is a high degree of variability, as primary hMSC cultures quickly undergo replicative senescence with loss of proliferative potential as they are continually propagated in cell culture. We sought to reduce the variability of these cells by insertion and expression of human telomerase reverse transcriptase (TERT) to immortalize the cell line. hMSCs were transduced with a lentivirus containing the human TERT gene. The resulting cell line has been propagated through more than 70 population-doubling level (PDL) to date and continues to grow exhibiting the characteristic fibroblastic hMSC phenotype. Expression of TERT mRNA and protein activity was confirmed in the TERT-transduced cells. Mock-transduced hMSCs had almost undetectable levels of TERT mRNA and protein activity and lost proliferation potential at PDL 14. The enhanced growth capacity of the hMSC TERT cells was due to increased cell proliferation and reduced cellular senescence rather than due to inhibition of apoptosis. The multipotent nature of the TERT cells was confirmed by differentiation toward the osteoblastic and adipogenic lineages in vitro. Osteoblastic differentiation was confirmed by both expression of alkaline phosphate and mineral deposition visualized by Alizarin Red staining. Adipogenic differentiation was confirmed by production of lipid droplets, which were detected by Oil Red-O staining. In summary, we have generated a stable hMSC line that can be continually propagated and retains both osteoblastic and adipogenic differentiation potential. PMID:23515239

  20. Bioinformatics approach for choosing the correct reference genes when studying gene expression in human keratinocytes.

    PubMed

    Beer, Lucian; Mlitz, Veronika; Gschwandtner, Maria; Berger, Tanja; Narzt, Marie-Sophie; Gruber, Florian; Brunner, Patrick M; Tschachler, Erwin; Mildner, Michael

    2015-10-01

    Reverse transcription polymerase chain reaction (qRT-PCR) has become a mainstay in many areas of skin research. To enable quantitative analysis, it is necessary to analyse expression of reference genes (RGs) for normalization of target gene expression. The selection of reliable RGs therefore has an important impact on the experimental outcome. In this study, we aimed to identify and validate the best suited RGs for qRT-PCR in human primary keratinocytes (KCs) over a broad range of experimental conditions using the novel bioinformatics tool 'RefGenes', which is based on a manually curated database of published microarray data. Expression of 6 RGs identified by RefGenes software and 12 commonly used RGs were validated by qRT-PCR. We assessed whether these 18 markers fulfilled the requirements for a valid RG by the comprehensive ranking of four bioinformatics tools and the coefficient of variation (CV). In an overall ranking, we found GUSB to be the most stably expressed RG, whereas the expression values of the commonly used RGs, GAPDH and B2M were significantly affected by varying experimental conditions. Our results identify RefGenes as a powerful tool for the identification of valid RGs and suggest GUSB as the most reliable RG for KCs. PMID:25980460

  1. Correction of defective protein kinesis of human P-glycoprotein mutants by substrates and modulators.

    PubMed

    Loo, T W; Clarke, D M

    1997-01-10

    There is growing evidence that abnormal protein folding or trafficking (protein kinesis) leads to diseases. We have used P-glycoprotein as a model protein to develop strategies to overcome defects in protein kinesis. Misprocessed mutants of the human P-glycoprotein are retained in the endoplasmic reticulum as core-glycosylated biosynthetic intermediates and rapidly degraded. Synthesis of the mutant proteins in the presence of drug substrates or modulators such as capsaicin, cyclosporin, vinblastine, or verapamil, however, resulted in the appearance of a fully glycosylated and functional protein at the cell surface. These effects were dose-dependent and occurred within a few hours after the addition of substrate. The ability to facilitate processing of the misfolded mutants appeared to be independent of the cell lines used and location of the mutation. P-glycoproteins with mutations in transmembrane segments, extracellular or cytoplasmic loops, the nucleotide-binding domains, or the linker region were processed to the fully mature form in the presence of these substrates. These drug substrates or modulators acted as specific chemical chaperones for P-glycoprotein because they were ineffective on the deltaF508 mutant of cystic fibrosis transmembrane conductance regulator. Therefore, one possible strategy to prevent protein misfolding is to carry out synthesis in the presence of specific substrates or modulators of the protein.

  2. CRISPR-mediated genotypic and phenotypic correction of a chronic granulomatous disease mutation in human iPS cells

    PubMed Central

    Flynn, Rowan; Grundmann, Alexander; Renz, Peter; Hänseler, Walther; James, William S.; Cowley, Sally A.; Moore, Michael D.

    2015-01-01

    Chronic granulomatous disease (CGD) is a rare genetic disease characterized by severe and persistent childhood infections. It is caused by the lack of an antipathogen oxidative burst, normally performed by phagocytic cells to contain and clear bacterial and fungal growth. Restoration of immune function can be achieved with heterologous bone marrow transplantation; however, autologous bone marrow transplantation would be a preferable option. Thus, a method is required to recapitulate the function of the diseased gene within the patient's own cells. Gene therapy approaches for CGD have employed randomly integrating viruses with concomitant issues of insertional mutagenesis, inaccurate gene dosage, and gene silencing. Here, we explore the potential of the recently described clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 site-specific nuclease system to encourage repair of the endogenous gene by enhancing the levels of homologous recombination. Using induced pluripotent stem cells derived from a CGD patient containing a single intronic mutation in the CYBB gene, we show that footprintless gene editing is a viable option to correct disease mutations. Gene correction results in restoration of oxidative burst function in iPS-derived phagocytes by reintroduction of a previously skipped exon in the cytochrome b-245 heavy chain (CYBB) protein. This study provides proof-of-principle for a gene therapy approach to CGD treatment using CRISPR-Cas9. PMID:26101162

  3. Reversible Femtosecond Laser-Assisted Myopia Correction: A Non-Human Primate Study of Lenticule Re-Implantation after Refractive Lenticule Extraction

    PubMed Central

    Chaurasia, Shyam S.; Lee, Wing S.; Tan, Donald T.; Mehta, Jodhbir S.

    2013-01-01

    LASIK (laser-assisted in situ keratomileusis) is a common laser refractive procedure for myopia and astigmatism, involving permanent removal of anterior corneal stromal tissue by excimer ablation beneath a hinged flap. Correction of refractive error is achieved by the resulting change in the curvature of the cornea and is limited by central corneal thickness, as a thin residual stromal bed may result in biomechanical instability of the cornea. A recently developed alternative to LASIK called Refractive Lenticule Extraction (ReLEx) utilizes solely a femtosecond laser (FSL) to incise an intrastromal refractive lenticule (RL), which results in reshaping the corneal curvature and correcting the myopia and/or astigmatism. As the RL is extracted intact in the ReLEx, we hypothesized that it could be cryopreserved and re-implanted at a later date to restore corneal stromal volume, in the event of keratectasia, making ReLEx a potentially reversible procedure, unlike LASIK. In this study, we re-implanted cryopreserved RLs in a non-human primate model of ReLEx. Mild intrastromal haze, noted during the first 2 weeks after re-implantation, subsided after 8 weeks. Refractive parameters including corneal thickness, anterior curvature and refractive error indices were restored to near pre-operative values after the re-implantation. Immunohistochemistry revealed no myofibroblast formation or abnormal collagen type I expression after 8 weeks, and a significant attenuation of fibronectin and tenascin expression from week 8 to 16 after re-implantation. In addition, keratocyte re-population could be found along the implanted RL interfaces. Our findings suggest that RL cryopreservation and re-implantation after ReLEx appears feasible, suggesting the possibility of potential reversibility of the procedure, and possible future uses of RLs in treating other corneal disorders and refractive errors. PMID:23826194

  4. Gene Editing in Human Pluripotent Stem Cells: Choosing the Correct Path

    PubMed Central

    Singh, Amar M.; Adjan Steffey, Valeriya V.; Yeshi, Tseten; Allison, Daniel W.

    2015-01-01

    The recent emergence of targeted nucleases has opened up new opportunities for performing genetic modifications with human pluripotent stem cells (hPSCs). These modifications can range from the creation of a routine knock-out to the more challenging single point-mutation. For both the new and established user, deciding on the best approach for the specific modification of interest can be an arduous task, as new and improved technologies are rapidly and continuously being developed. The choices between the reagents and methodologies depends entirely on the end-goal of the experiments and the locus to be modified. Investigators need to decide on the best nuclease to use for each experiment from among Zinc-Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 that would result in the highest likelihood of success with the fewest pitfalls. Furthermore, there have been significant improvements over the first-generation nucleases, such as the development of the dimeric CRISPR RNA-guided Fok1 nucleases (RFNs, marketed as NextGEN™ CRISPR) that reduces the “off-target” mutation rate, providing further options for investigators. Should researchers need to perform a point mutation, then considerations must be made between using single-stranded oligo-deoxynucleotides (ssODN) as the donor for homology-directed repair or utilizing a selection cassette within a donor vector in combination with an excision-only piggyBac™ transposase to leave a seamless edit. In this review, we will provide a general overview of the current technologies, along with methodologies for generating point mutations, while considering both their pros and cons. PMID:26702451

  5. Is there a relationship between dietary MSG and [corrected] obesity in animals or humans?

    PubMed

    Brosnan, John T; Drewnowski, Adam; Friedman, Mark I

    2014-09-01

    The sodium salt of glutamate (monosodium glutamate; MSG) imparts a savory/meaty taste to foods, and has been used as a flavoring agent for millennia. Past research on MSG/glutamate has evaluated its physiologic, metabolic and behavioral actions, and its safety. Ingested MSG has been found to be safe, and to produce no remarkable effects, except on taste. However, some recent epidemiologic and animal studies have associated MSG use with obesity and aberrations in fat metabolism. Reported effects are usually attributed to direct actions of ingested MSG in brain. As these observations conflict with past MSG research findings, a symposium was convened at the 13th International Congress on Amino Acids, Peptides and Proteins to discuss them. The principal conclusions were: (1) the proposed link between MSG intake and weight gain is likely explained by co-varying environmental factors (e.g., diet, physical activity) linked to the "nutrition transition" in developing Asian countries. (2) Controlled intervention studies adding MSG to the diet of animals and humans show no effect on body weight. (3) Hypotheses positing dietary MSG effects on body weight involve results from rodent MSG injection studies that link MSG to actions in brain not applicable to MSG ingestion studies. The fundamental reason is that glutamate is metabolically compartmentalized in the body, and generally does not passively cross biologic membranes. Hence, almost no ingested glutamate/MSG passes from gut into blood, and essentially none transits placenta from maternal to fetal circulation, or crosses the blood-brain barrier. Dietary MSG, therefore, does not gain access to brain. Overall, it appears that normal dietary MSG use is unlikely to influence energy intake, body weight or fat metabolism. PMID:24927698

  6. Political Correctness--Correct?

    ERIC Educational Resources Information Center

    Boase, Paul H.

    1993-01-01

    Examines the phenomenon of political correctness, its roots and objectives, and its successes and failures in coping with the conflicts and clashes of multicultural campuses. Argues that speech codes indicate failure in academia's primary mission to civilize and educate through talk, discussion, thought,166 and persuasion. (SR)

  7. The human CSB (ERCC6) gene corrects the transcription-coupled repair defect in the CHO cell mutant UV61.

    PubMed

    Orren, D K; Dianov, G L; Bohr, V A

    1996-09-01

    The human CSB gene, mutated in Cockayne's syndrome group B (partially defective in both repair and transcription) was previously cloned by virtue of its ability to correct the moderate UV sensitivity of the CHO mutant UV61. To determine whether the defect in UV61 is the hamster equivalent of Cockayne's syndrome, the RNA polymerase II transcription and DNA repair characteristics of a repair-proficient CHO cell line (AA8), UV61 and a CSB transfectant of UV61 were compared. In each cell line, formation and removal of UV-induced cyclobutane pyrimidine dimers (CPDs) were measured in the individual strands of the actively transcribed DHFR gene and in a transcriptionally inactive region downstream of DHFR. AA8 cells efficiently remove CPDs from the transcribed strand, but not from either the non-transcribed strand or the inactive region. There was no detectable repair of CPDs in any region of the genome in UV61. Transfection of the human CSB gene into UV61 restores the normal repair pattern (CPD removal in only the transcribed strand), demonstrating that the DNA repair defect in UV61 is homologous to that in Cockayne's syndrome (complementation group B) cells. However, we observe no significant deficiency in RNA polymerase II-mediated transcription in UV61, suggesting that the CSB protein has independent roles in DNA repair and RNA transcription pathways. PMID:8811084

  8. POTENTIAL FOR GULLS TO TRANSPORT BACTERIA FROM HUMAN WASTE SITES

    EPA Science Inventory

    This study was designed as a first step in assessing whether gulls visiting human waste sites can acquire human microorganisms and distribute them across the coastal landscape. Beaches, landfills, and a lagoon of treated wastewater located in a coastal Lake Michigan county were t...

  9. Environmental Epigenetics: Potential Application in Human Health Risk Assessment

    EPA Science Inventory

    Although previous studies have shown a significant involvement of epigenetic dysregulation in human diseases, the applicability of epigenetic data in the current human health risk assessment paradigm is unclear. The goals of this study are to compare the relative sensitivities of...

  10. A rigorous approach to facilitate and guarantee the correctness of the genetic testing management in human genome information systems

    PubMed Central

    2011-01-01

    Background Recent medical and biological technology advances have stimulated the development of new testing systems that have been providing huge, varied amounts of molecular and clinical data. Growing data volumes pose significant challenges for information processing systems in research centers. Additionally, the routines of genomics laboratory are typically characterized by high parallelism in testing and constant procedure changes. Results This paper describes a formal approach to address this challenge through the implementation of a genetic testing management system applied to human genome laboratory. We introduced the Human Genome Research Center Information System (CEGH) in Brazil, a system that is able to support constant changes in human genome testing and can provide patients updated results based on the most recent and validated genetic knowledge. Our approach uses a common repository for process planning to ensure reusability, specification, instantiation, monitoring, and execution of processes, which are defined using a relational database and rigorous control flow specifications based on process algebra (ACP). The main difference between our approach and related works is that we were able to join two important aspects: 1) process scalability achieved through relational database implementation, and 2) correctness of processes using process algebra. Furthermore, the software allows end users to define genetic testing without requiring any knowledge about business process notation or process algebra. Conclusions This paper presents the CEGH information system that is a Laboratory Information Management System (LIMS) based on a formal framework to support genetic testing management for Mendelian disorder studies. We have proved the feasibility and showed usability benefits of a rigorous approach that is able to specify, validate, and perform genetic testing using easy end user interfaces. PMID:22369688

  11. A Nucleotide-Analogue-Induced Gain of Function Corrects the Error-Prone Nature of Human DNA Polymerase iota

    SciTech Connect

    Ketkar, Amit; Zafar, Maroof K.; Banerjee, Surajit; Marquez, Victor E.; Egli, Martin; Eoff, Robert L.

    2012-10-25

    Y-family DNA polymerases participate in replication stress and DNA damage tolerance mechanisms. The properties that allow these enzymes to copy past bulky adducts or distorted template DNA can result in a greater propensity for them to make mistakes. Of the four human Y-family members, human DNA polymerase iota (hpol{iota}) is the most error-prone. In the current study, we elucidate the molecular basis for improving the fidelity of hpol{iota} through use of the fixed-conformation nucleotide North-methanocarba-2{prime}-deoxyadenosine triphosphate (N-MC-dATP). Three crystal structures were solved of hpol{iota} in complex with DNA containing a template 2{prime}-deoxythymidine (dT) paired with an incoming dNTP or modified nucleotide triphosphate. The ternary complex of hpol{iota} inserting N-MC-dATP opposite dT reveals that the adenine ring is stabilized in the anti orientation about the pseudo-glycosyl torsion angle, which mimics precisely the mutagenic arrangement of dGTP:dT normally preferred by hpol{iota}. The stabilized anti conformation occurs without notable contacts from the protein but likely results from constraints imposed by the bicyclo[3.1.0]hexane scaffold of the modified nucleotide. Unmodified dATP and South-MC-dATP each adopt syn glycosyl orientations to form Hoogsteen base pairs with dT. The Hoogsteen orientation exhibits weaker base-stacking interactions and is less catalytically favorable than anti N-MC-dATP. Thus, N-MC-dATP corrects the error-prone nature of hpol{iota} by preventing the Hoogsteen base-pairing mode normally observed for hpol{iota}-catalyzed insertion of dATP opposite dT. These results provide a previously unrecognized means of altering the efficiency and the fidelity of a human translesion DNA polymerase.

  12. Potential Therapy for Neisseria Gonorrhoeae Infections With Human Chorionic Gonadotropin.

    PubMed

    Rao, C V

    2015-12-01

    The scientific evidence suggests that Neisseria gonorrhoeae (NG) infects human fallopian tubes by molecular mimicry in which pathogens act like a ligand to bind to epithelial cell surface human chorionic gonadotrophin (hCG)/luteinizing hormone (LH) receptors. The hCG-like molecule has been identified as ribosomal protein L12 in NG coat surface. Human fallopian tube epithelial cells have been shown to contain functional hCG/LH receptors. As previously shown in human fallopian tube organ and cell culture studies, cellular invasion and infection can be prevented by exposing the cells to excess hCG, which would outnumber and outcompete NG for receptor binding. Based on these data, we suggest testing hCG in clinical trials on infected women.

  13. Giant viruses of amoebae as potential human pathogens.

    PubMed

    Colson, Philippe; La Scola, Bernard; Raoult, Didier

    2013-01-01

    Giant viruses infecting phagocytic protists are composed of mimiviruses, the record holders of particle and genome size amongst viruses, and marseilleviruses. Since the discovery in 2003 at our laboratory of the first of these giant viruses, the Mimivirus, a growing body of data has revealed that they are common inhabitants of our biosphere. Moreover, from the outset, the story of Mimivirus has been linked to that of patients exhibiting pneumonia and it was shown that patients developed antibodies to this amoebal pathogen. Since then, there have been several proven cases of human infection or colonization with giant viruses of amoebae, which are known to host several bacteria that are human pathogens. Mimiviruses and marseilleviruses represent a major challenge in human pathology, as virological procedures implemented to date have not used appropriate media to allow their culture, and molecular techniques have used filtration steps that likely prevented their detection. Nevertheless, there is an increasing body of evidence that mimiviruses might cause pneumonia and that humans carry marseilleviruses, and re-analyses of metagenomic databases have provided evidence that these giant viruses can be common in human samples. The proportion of human infections related to these giant mimiviruses and marseilleviruses and the precise short- and long-term consequences of these infections have been scarcely investigated so far and should be the subject of future works. PMID:24157884

  14. Giant viruses of amoebae as potential human pathogens.

    PubMed

    Colson, Philippe; La Scola, Bernard; Raoult, Didier

    2013-01-01

    Giant viruses infecting phagocytic protists are composed of mimiviruses, the record holders of particle and genome size amongst viruses, and marseilleviruses. Since the discovery in 2003 at our laboratory of the first of these giant viruses, the Mimivirus, a growing body of data has revealed that they are common inhabitants of our biosphere. Moreover, from the outset, the story of Mimivirus has been linked to that of patients exhibiting pneumonia and it was shown that patients developed antibodies to this amoebal pathogen. Since then, there have been several proven cases of human infection or colonization with giant viruses of amoebae, which are known to host several bacteria that are human pathogens. Mimiviruses and marseilleviruses represent a major challenge in human pathology, as virological procedures implemented to date have not used appropriate media to allow their culture, and molecular techniques have used filtration steps that likely prevented their detection. Nevertheless, there is an increasing body of evidence that mimiviruses might cause pneumonia and that humans carry marseilleviruses, and re-analyses of metagenomic databases have provided evidence that these giant viruses can be common in human samples. The proportion of human infections related to these giant mimiviruses and marseilleviruses and the precise short- and long-term consequences of these infections have been scarcely investigated so far and should be the subject of future works.

  15. Potential for portal detection of human chemical and biological contamination

    NASA Astrophysics Data System (ADS)

    Settles, Gary S.; McGann, William J.

    2001-08-01

    The walk-through metal-detection portal is a paradigm of non-intrusive passenger screening in aviation security. Modern explosive detection portals based on this paradigm will soon appear in airports. This paper suggests that the airborne trace detection technology developed for that purpose can also be adapted to human chemical and biological contamination. The waste heat of the human body produces a rising warm-air sheath of 50-80 liters/sec known as the human thermal plume. Contained within this plume are hundreds of bioeffluents from perspiration and breath, and millions of skin flakes. Since early medicine, the airborne human scent was used in the diagnosis of disease. Recent examples also include toxicity and substance abuse, but this approach has never been quantified. The appearance of new bioeffluents or subtle changes in the steady-state may signal the onset of a chemical/biological attack. Portal sampling of the human thermal plume is suggested, followed by a pre-concentration step and the detection of the attacking agent or the early human response. The ability to detect nanogram levels of explosive trace contamination this way was already demonstrated. Key advantages of the portal approach are its rapidity and non-intrusiveness, and the advantage that it does not require the traditional bodily fluid or tissue sampling.

  16. Potential exposure to human prescription pharmaceutical residues from wastewater

    EPA Science Inventory

    Pharmaceuticals in the environment (PiE) pose a complicated problem, involving multiple dissimilar compounds, multiple routes of potential exposure, and a range of potentially affected organisms that span the tree of life. Key uncertainties include not knowing which of the thous...

  17. Nephroprotective Potential of Human Albumin Infusion: A Narrative Review.

    PubMed

    Wiedermann, Christian J; Joannidis, Michael

    2015-01-01

    Albumin infusion improves renal function in cirrhosis; however, mechanisms are incompletely understood. In clinical practice, human albumin is used in various intensive care unit indications to deal with a wide range of problems, from volume replacement in hypovolemic shock, or sepsis, to treatment of ascites in patients with liver cirrhosis. Against the background of the results of recent studies on the use of human albumin in septic patients, the importance of the natural colloid in these critically ill patients is being redefined. In addition to the hemodynamic effects of administration of human albumin impacting on sympathetic tone, attention is being paid to other effects in which its pharmacodynamics is associated with the physiological importance of endogenous albumin. The morbidity and mortality data discussed in this paper support the importance of both the hemodynamic and the pharmacological effects of the administration of human albumin in various indications. The contribution that human albumin could make towards the maintenance of renal function in the course and treatment of severe sepsis and cirrhosis of the liver is the subject of this narrative review. PMID:26136776

  18. Potential treatments for genetic hearing loss in humans: current conundrums.

    PubMed

    Minoda, R; Miwa, T; Ise, M; Takeda, H

    2015-08-01

    Genetic defects are a major cause of hearing loss in newborns. Consequently, hearing loss has a profound negative impact on human daily living. Numerous causative genes for genetic hearing loss have been identified. However, presently, there are no truly curative treatments for this condition. There have been several recent reports on successful treatments in mice using embryonic gene therapy, neonatal gene therapy and neonatal antisense oligonucleotide therapy. Herein, we describe state-of-the-art research on genetic hearing loss treatment through gene therapy and discuss the obstacles to overcome in curative treatments of genetic hearing loss in humans.

  19. Extrahepatic sources of factor VIII potentially contribute to the coagulation cascade correcting the bleeding phenotype of mice with hemophilia A.

    PubMed

    Zanolini, Diego; Merlin, Simone; Feola, Maria; Ranaldo, Gabriella; Amoruso, Angela; Gaidano, Gianluca; Zaffaroni, Mauro; Ferrero, Alessandro; Brunelleschi, Sandra; Valente, Guido; Gupta, Sanjeev; Prat, Maria; Follenzi, Antonia

    2015-07-01

    A large fraction of factor VIII in blood originates from liver sinusoidal endothelial cells although extrahepatic sources also contribute to plasma factor VIII levels. Identification of cell-types other than endothelial cells with the capacity to synthesize and release factor VIII will be helpful for therapeutic approaches in hemophilia A. Recent cell therapy and bone marrow transplantation studies indicated that Küpffer cells, monocytes and mesenchymal stromal cells could synthesize factor VIII in sufficient amount to ameliorate the bleeding phenotype in hemophilic mice. To further establish the role of blood cells in expressing factor VIII, we studied various types of mouse and human hematopoietic cells. We identified factor VIII in cells isolated from peripheral and cord blood, as well as bone marrow. Co-staining for cell type-specific markers verified that factor VIII was expressed in monocytes, macrophages and megakaryocytes. We additionally verified that factor VIII was expressed in liver sinusoidal endothelial cells and endothelial cells elsewhere, e.g., in the spleen, lungs and kidneys. Factor VIII was well expressed in sinusoidal endothelial cells and Küpffer cells isolated from human liver, whereas by comparison isolated human hepatocytes expressed factor VIII at very low levels. After transplantation of CD34(+) human cord blood cells into NOD/SCIDγNull-hemophilia A mice, fluorescence activated cell sorting of peripheral blood showed >40% donor cells engrafted in the majority of mice. In these animals, plasma factor VIII activity 12 weeks after cell transplantation was up to 5% and nine of 12 mice survived after a tail clip-assay. In conclusion, hematopoietic cells, in addition to endothelial cells, express and secrete factor VIII: this information should offer further opportunities for understanding mechanisms of factor VIII synthesis and replenishment.

  20. Extrahepatic sources of factor VIII potentially contribute to the coagulation cascade correcting the bleeding phenotype of mice with hemophilia A.

    PubMed

    Zanolini, Diego; Merlin, Simone; Feola, Maria; Ranaldo, Gabriella; Amoruso, Angela; Gaidano, Gianluca; Zaffaroni, Mauro; Ferrero, Alessandro; Brunelleschi, Sandra; Valente, Guido; Gupta, Sanjeev; Prat, Maria; Follenzi, Antonia

    2015-07-01

    A large fraction of factor VIII in blood originates from liver sinusoidal endothelial cells although extrahepatic sources also contribute to plasma factor VIII levels. Identification of cell-types other than endothelial cells with the capacity to synthesize and release factor VIII will be helpful for therapeutic approaches in hemophilia A. Recent cell therapy and bone marrow transplantation studies indicated that Küpffer cells, monocytes and mesenchymal stromal cells could synthesize factor VIII in sufficient amount to ameliorate the bleeding phenotype in hemophilic mice. To further establish the role of blood cells in expressing factor VIII, we studied various types of mouse and human hematopoietic cells. We identified factor VIII in cells isolated from peripheral and cord blood, as well as bone marrow. Co-staining for cell type-specific markers verified that factor VIII was expressed in monocytes, macrophages and megakaryocytes. We additionally verified that factor VIII was expressed in liver sinusoidal endothelial cells and endothelial cells elsewhere, e.g., in the spleen, lungs and kidneys. Factor VIII was well expressed in sinusoidal endothelial cells and Küpffer cells isolated from human liver, whereas by comparison isolated human hepatocytes expressed factor VIII at very low levels. After transplantation of CD34(+) human cord blood cells into NOD/SCIDγNull-hemophilia A mice, fluorescence activated cell sorting of peripheral blood showed >40% donor cells engrafted in the majority of mice. In these animals, plasma factor VIII activity 12 weeks after cell transplantation was up to 5% and nine of 12 mice survived after a tail clip-assay. In conclusion, hematopoietic cells, in addition to endothelial cells, express and secrete factor VIII: this information should offer further opportunities for understanding mechanisms of factor VIII synthesis and replenishment. PMID:25911555

  1. The human microbiome and its potential importance to pediatrics.

    PubMed

    Johnson, Coreen L; Versalovic, James

    2012-05-01

    The human body is home to more than 1 trillion microbes, with the gastrointestinal tract alone harboring a diverse array of commensal microbes that are believed to contribute to host nutrition, developmental regulation of intestinal angiogenesis, protection from pathogens, and development of the immune response. Recent advances in genome sequencing technologies and metagenomic analysis are providing a broader understanding of these resident microbes and highlighting differences between healthy and disease states. The aim of this review is to provide a detailed summary of current pediatric microbiome studies in the literature, in addition to highlighting recent findings and advancements in studies of the adult microbiome. This review also seeks to elucidate the development of, and factors that could lead to changes in, the composition and function of the human microbiome.

  2. Potential applications of human saliva as diagnostic fluid.

    PubMed

    Castagnola, M; Picciotti, P M; Messana, I; Fanali, C; Fiorita, A; Cabras, T; Calò, L; Pisano, E; Passali, G C; Iavarone, F; Paludetti, G; Scarano, E

    2011-12-01

    The use of human saliva as a diagnostic and prognostic fluid has until recently been somewhat disregarded. Although sample collection is non-invasive, physiological and genetic variations were largely responsible for its infrequent application in the past. Recently, several proteomic studies contributed to partial elucidation of the salivary proteome (more than 2400 protein components have been characterized), both in terms of composition, contributions to whole saliva and genetic/physiological variability. On this basis, is not too optimistic to believe that in the near future human saliva could become a relevant diagnostic fluid. In this review, the characterization by proteomic approaches of new salivary markers in oncology, head and neck carcinoma (oral cavity, oropharynx, larynx, and salivary glands), breast and gastric cancers, salivary gland function and disease, Sjögren syndrome, systemic sclerosis, dental and gingival pathology, systemic, psychiatric and neurological diseases, is described.

  3. Human auditory evoked potentials. I - Evaluation of components

    NASA Technical Reports Server (NTRS)

    Picton, T. W.; Hillyard, S. A.; Krausz, H. I.; Galambos, R.

    1974-01-01

    Fifteen distinct components can be identified in the scalp recorded average evoked potential to an abrupt auditory stimulus. The early components occurring in the first 8 msec after a stimulus represent the activation of the cochlea and the auditory nuclei of the brainstem. The middle latency components occurring between 8 and 50 msec after the stimulus probably represent activation of both auditory thalamus and cortex but can be seriously contaminated by concurrent scalp muscle reflex potentials. The longer latency components occurring between 50 and 300 msec after the stimulus are maximally recorded over fronto-central scalp regions and seem to represent widespread activation of frontal cortex.

  4. Digital Anthropomorphic Phantoms of Non-Rigid Human Respiratory and Voluntary Body Motion for Investigating Motion Correction in Emission Imaging

    PubMed Central

    Könik, Arda; Connolly, Caitlin M; Johnson, Karen L; Dasari, Paul; Segars, Paul W; Pretorius, P H; Lindsay, Clifford; Dey, Joyoni; King, Michael A

    2014-01-01

    The development of methods for correcting patient motion in emission tomography has been receiving increased attention. Often performance of these methods is evaluated through simulations using digital anthropomorphic phantoms, such as the commonly used XCAT phantom, which models both respiratory and cardiac motion based on human studies. However, non-rigid body motion, which is frequently seen in clinical studies, is not present in the standard XCAT phantom. In addition, respiratory motion in the standard phantom is limited to a single generic trend. In this work, to obtain more realistic representation of motion, we developed a series of individual-specific XCAT phantoms modeling non-rigid respiratory and non-rigid body motions derived from the MRI acquisitions of volunteers. Acquisitions were performed in the sagittal orientation using the Navigator methodology. Baseline (no motion) acquisitions at end-expiration were obtained at the beginning of each imaging session for each volunteer. For the body motion studies, MRI was again acquired only at end-expiration for five body motion poses (shoulder stretch, shoulder twist, lateral bend, side roll, and axial slide). For the respiratory motion studies, MRI was acquired during free/regular breathing. The MR slices were then retrospectively sorted into 14 amplitude-binned respiratory states, end-expiration, end-inspiration, six intermediary states during inspiration, and six during expiration using the recorded Navigator signal. XCAT phantoms were then generated based on these MRI data by interactive alignment of the organ contours of the XCAT with the MRI slices using a GUI. Thus far we have created 5 body motion and 5 respiratory motion XCAT phantoms from MRI acquisitions of 6 healthy volunteers (3 males and 3 females). Non-rigid motion exhibited by the volunteers was reflected in both respiratory and body motion phantoms with a varying extent and character for each individual. In addition to these phantoms, we

  5. [Biofunctional age diagnosis in humans. Potentials and limits].

    PubMed

    Pöthig, D; Gerdes, W; Viol, M; Wagner, P; Simm, A

    2011-06-01

    The demand and requirements for valid, practicable, and reliable procedures for age diagnosis are increasing worldwide. In contrast, few studies and only a small number of procedures exist. The authors review the theoretical and methodological requirements for the development of models for age diagnostics. They describe the fundamentals for further studies, based on an analysis of current gerontological research in this area. A following publication will report the valid systems measuring vitality and biofunctional age(ing) of human beings. PMID:21505938

  6. Cylindrospermopsin: water-linked potential threat to human health in Europe.

    PubMed

    Poniedziałek, Barbara; Rzymski, Piotr; Kokociński, Mikołaj

    2012-11-01

    Cylindrospermopsin (CYN) is a secondary metabolite produced by several cyanobacteria species. Its potential effect on human health includes liver, kidneys, lungs, spleen and intestine injuries. CYN can be cyto- and genotoxic to a variety of cell types. Occurrence and expansion of species able to synthesize CYN in European water bodies has been recently reported and raised awareness of potential harm to human health. Therefore, surface water of different human use should be monitored for the presence of toxic species of blue-green algae. This paper aims to describe the distribution of CYN producers in Europe and the potential effects of the toxin on human health according to the current state of knowledge.

  7. Methanol clusters (CH3OH)n: putative global minimum-energy structures from model potentials and dispersion-corrected density functional theory.

    PubMed

    Kazachenko, Sergey; Bulusu, Satya; Thakkar, Ajit J

    2013-06-14

    Putative global minima are reported for methanol clusters (CH3OH)n with n ≤ 15. The predictions are based on global optimization of three intermolecular potential energy models followed by local optimization and single-point energy calculations using two variants of dispersion-corrected density functional theory. Recurring structural motifs include folded and/or twisted rings, folded rings with a short branch, and stacked rings. Many of the larger structures are stabilized by weak C-H···O bonds.

  8. GM-CSF production from human airway smooth muscle cells is potentiated by human serum.

    PubMed Central

    Sukkar, M B; Hughes, J M; Johnson, P R; Armour, C L

    2000-01-01

    Recent evidence suggests that airway smooth muscle cells (ASMC) actively participate in the airway inflammatory process in asthma. Interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) induce ASMC to release inflammatory mediators in vitro. ASMC mediator release in vivo, however, may be influenced by features of the allergic asthmatic phenotype. We determined whether; (1) allergic asthmatic serum (AAS) modulates ASMC mediator release in response to IL-1beta and TNF-alpha, and (2) IL-1beta/TNF-alpha prime ASMC to release mediators in response to AAS. IL-5 and GM-CSF were quantified by ELISA in culture supernatants of; (1) ASMC pre-incubated with either AAS, nonallergic non-asthmatic serum (NAS) or Monomed (a serum substitute) and subsequently stimulated with IL-1beta and TNF-alpha and (2) ASMC stimulated with IL-1beta/TNF-alpha and subsequently exposed to either AAS, NAS or Monomed. IL-1beta and TNF-alpha induced GM-CSF release in ASMC pre-incubated with AAS was not greater than that in ASMC pre-incubated with NAS or Monomed. IL-1beta and TNF-alpha, however, primed ASMC to release GM-CSF in response to human serum. GM-CSF production following IL-1beta/TNF-alpha and serum exposure (AAS or NAS) was significantly greater than that following IL-1beta/TNF-alpha and Monomed exposure or IL-1beta/TNF-alpha exposure only. Whilst the potentiating effects of human serum were not specific to allergic asthma, these findings suggest that the secretory capacity of ASMC may be up-regulated during exacerbations of asthma, where there is evidence of vascular leakage. PMID:11132773

  9. Brain potentials related to the human penile erection.

    PubMed

    Ponseti, J; Kropp, P; Bosinski, H A

    2009-01-01

    The aim of this study was to elucidate the brain processes preceding penile responses. Electroencephalographic (EEG) potentials and penile circumference were recorded simultaneously while male subjects were exposed to visual sexual stimuli (VSS). The trials were sorted by the penile response of the subjects (erection, maintenance or detumescence). The corresponding EEG recordings were then subjected to independent component analysis. We found that 200 ms after VSS onset brain potentials differ according to the genital response to follow. Whereas early posterior negativity (EPN) was predominantly related to erection and maintenance, P3-like activity was found to precede detumescence. EPN indicates a more 'emotional' processing state of the brain, whereas P3-like activity related to detumescence indicates a more 'cognitive' processing state. The latter is assumed to reflect activity of the locus coeruleus-norepinephrine system. Further research should evaluate the contribution of P3-related brain activity to psychogenic erectile dysfunction.

  10. Does implicit motor imagery ability predict reaching correction efficiency? A test of recent models of human motor control.

    PubMed

    Hyde, Christian; Wilmut, Kate; Fuelscher, Ian; Williams, Jacqueline

    2013-01-01

    Neurocomputational models of reaching indicate that efficient purposive correction of movement midflight (e.g., online control) depends on one's ability to generate and monitor an accurate internal (neural) movement representation. In the first study to test this empirically, the authors investigated the relationship between healthy young adults' implicit motor imagery performance and their capacity to correct their reaching trajectory. As expected, after controlling for general reaching speed, hierarchical regression demonstrated that imagery ability was a significant predictor of hand correction speed; that is, faster and more accurate imagery performance associated with faster corrections to reaching following target displacement at movement onset. They argue that these findings provide preliminary support for the view that a link exists between an individual's ability to represent movement mentally and correct movement online efficiently.

  11. A 40-Hz Auditory Potential Recorded from the Human Scalp

    NASA Astrophysics Data System (ADS)

    Galambos, Robert; Makeig, Scott; Talmachoff, Peter J.

    1981-04-01

    Computer techniques readily extract from the brainwaves an orderly sequence of brain potentials locked in time to sound stimuli. The potentials that appear 8 to 80 msec after the stimulus resemble 3 or 4 cycles of a 40-Hz sine wave; we show here that these waves combine to form a single, stable, composite wave when the sounds are repeated at rates around 40 per sec. This phenomenon, the 40-Hz event-related potential (ERP), displays several properties of theoretical and practical interest. First, it reportedly disappears with surgical anesthesia, and it resembles similar phenomena in the visual and olfactory system, facts which suggest that adequate processing of sensory information may require cyclical brain events in the 30- to 50-Hz range. Second, latency and amplitude measurements on the 40-Hz ERP indicate it may contain useful information on the number and basilar membrane location of the auditory nerve fibers a given tone excites. Third, the response is present at sound intensities very close to normal adult thresholds for the audiometric frequencies, a fact that could have application in clinical hearing testing.

  12. In vivo potential of recombinant granulysin against human tumors

    PubMed Central

    Al-Wasaby, Sameer; de Miguel, Diego; Aporta, Adriana; Naval, Javier; Conde, Blanca; Martínez-Lostao, Luis; Anel, Alberto

    2015-01-01

    9 kDa granulysin is a protein present in the granules of human CTL and NK cells, with cytolytic activity against microbes and tumors. Previous work from our group demonstrated that this granulysin isoform induced apoptosis in vitro on hematological tumor cells and on primary tumor cells from B-CLL patients. In the present work, recombinant 9 kDa granulysin was used as an anti-tumoral agent to study its in vivo effect on tumor development in athymic “nude” mice models bearing human breast adenocarcinoma MDA-MB-231 or multiple myeloma NCI-H929–derived xenografts. Granulysin prevented the in vivo development of detectable MDA-MB-231-derived tumors. In addition, recombinant granulysin was able to completely eradicate NCI-H929-derived tumors. All granulysin-treated tumors exhibited signs of apoptosis induction and an increased NK cell infiltration inside the tumor tissue comparing to control ones. Moreover, no in vivo deleterious effects of the recombinant 9 kDa granulysin doses used in this study were observed on the skin or on the internal organs of the animals. In conclusion, granulysin was able to inhibit the progression of MDA-MB-231-derived xenografts and also to eradicate multiple myeloma NCI-H929-derived xenografts. This work opens the door to the initiation of preclinical and possibly clinical studies for the use of 9 kDa granulysin as a new anti-tumoral treatment. PMID:26405603

  13. Leptospirosis in Mexico: Epidemiology and Potential Distribution of Human Cases

    PubMed Central

    Sánchez-Montes, Sokani; Espinosa-Martínez, Deborah V.; Ríos-Muñoz, César A.; Berzunza-Cruz, Miriam; Becker, Ingeborg

    2015-01-01

    Background Leptospirosis is widespread in Mexico, yet the potential distribution and risk of the disease remain unknown. Methodology/Principal Findings We analysed morbidity and mortality according to age and gender based on three sources of data reported by the Ministry of Health and the National Institute of Geography and Statics of Mexico, for the decade 2000–2010. A total of 1,547 cases were reported in 27 states, the majority of which were registered during the rainy season, and the most affected age group was 25–44 years old. Although leptospirosis has been reported as an occupational disease of males, analysis of morbidity in Mexico showed no male preference. A total number of 198 deaths were registered in 21 states, mainly in urban settings. Mortality was higher in males (61.1%) as compared to females (38.9%), and the case fatality ratio was also increased in males. The overall case fatality ratio in Mexico was elevated (12.8%), as compared to other countries. We additionally determined the potential disease distribution by examining the spatial epidemiology combined with spatial modeling using ecological niche modeling techniques. We identified regions where leptospirosis could be present and created a potential distribution map using bioclimatic variables derived from temperature and precipitation. Our data show that the distribution of the cases was more related to temperature (75%) than to precipitation variables. Ecological niche modeling showed predictive areas that were widely distributed in central and southern Mexico, excluding areas characterized by extreme climates. Conclusions/Significance In conclusion, an epidemiological surveillance of leptospirosis is recommended in Mexico, since 55.7% of the country has environmental conditions fulfilling the criteria that favor the presence of the disease. PMID:26207827

  14. The potential for new methods to assess human reproductive genotoxicity

    SciTech Connect

    Mendelsohn, M.L.

    1987-09-01

    The immediate prospects are not good for practical methods for measuring the human heritable mutation rate. The methods discussed here range from speculative to impractical, and at best are sensitive enough only for large numbers of subjects. Given the rapid development of DNA methods and the current status of two-dimensional gel electrophoresis, there is some hope that the intermediate prospects may be better. In contrast, the prospects for useful cellular-based male germinal methods seem more promising and immediate. Effective specific locus methods for sperm are already conceivable and may be practical in a few years. Obviously such methods will not predict heritable effects definitively, but they will provide direct information on reproductive genotoxicity and should contribute significantly to many current medical and environmental situations where genetic damage is suspected. 22 refs.

  15. The potential for a controlled human infection platform in Singapore

    PubMed Central

    Balasingam, Shobana; Horby, Peter; Wilder-Smith, Annelies

    2014-01-01

    For over 100 years, controlled human infection (CHI) studies have been performed to advance the understanding of the pathogenesis, treatment and prevention of infectious diseases. This methodology has seen a resurgence, as it offers an efficient model for selecting the most promising agents for further development from available candidates. CHI studies are utilised to bridge safety and immunogenicity testing and phase II/III efficacy studies. However, as this platform is not currently utilised in Asia, opportunities to study therapeutics and vaccines for infections that are important in Asia are missed. This review examines the regulatory differences for CHI studies between countries and summarises other regulatory differences in clinical trials as a whole. We found that the regulations that would apply to CHI studies in Singapore closely mirror those in the United Kingdom, and conclude that the regulatory and ethical guidelines in Singapore are compatible with the conduct of CHI studies. PMID:25273928

  16. The human urinary exosome as a potential metabolic effector cargo.

    PubMed

    Bruschi, Maurizio; Ravera, Silvia; Santucci, Laura; Candiano, Giovanni; Bartolucci, Martina; Calzia, Daniela; Lavarello, Chiara; Inglese, Elvira; Petretto, Andrea; Ghiggeri, Gianmarco; Panfoli, Isabella

    2015-08-01

    Exosomes are nanovesicles, derived from the endocytic pathway, released by most cell types and found in many body fluids, including urine. A variety of exosomal functions have been reported, including transfer of RNA, cell communication, control of apoptosis and protein lifespan. Exosomes from mesenchymal stem cells can rescue bioenergetics of injured cells. Here the urinary exosome proteome, non-urinary exosome proteome and urinome are compared. A consistent number of identified proteins cluster to metabolic functions. Cytoscape software analysis based on biological processes gene ontology database shows that metabolic pathways such as aerobic glycolysis and oxidative phosphorylation have a high probability (p ≤ 0.05) of being expressed and therefore functional. A metabolic function appears to be associated with human urinary exosomes, whose relevance experimental studies can assess. PMID:26186710

  17. The division of attention and the human auditory evoked potential

    NASA Technical Reports Server (NTRS)

    Hink, R. F.; Van Voorhis, S. T.; Hillyard, S. A.; Smith, T. S.

    1977-01-01

    The sensitivity of the scalp-recorded, auditory evoked potential to selective attention was examined while subjects responded to stimuli presented to one ear (focused attention) and to both ears (divided attention). The amplitude of the N1 component was found to be largest to stimuli in the ear upon which attention was to be focused, smallest to stimuli in the ear to be ignored, and intermediate to stimuli in both ears when attention was divided. The results are interpreted as supporting a capacity model of attention.

  18. Motion sickness potentiates core cooling during immersion in humans

    PubMed Central

    Mekjavic, Igor B; Tipton, Michael J; Gennser, Mikael; Eiken, Ola

    2001-01-01

    The present study tested the hypothesis that motion sickness affects thermoregulatory responses to cooling in humans. Ten healthy male volunteers underwent three separate head-out immersions in 28 °C water after different preparatory procedures. In the ‘control’ procedure immersion was preceded by a rest period. In the ‘motion sickness’ procedure immersion was preceded by provocation of motion sickness in a human centrifuge. This comprised rapid and repeated alterations of the gravitational (G-) stress in the head-to-foot direction, plus a standardized regimen of head movements at increased G-stress. In the ‘G-control’ procedure, the subjects were exposed to similar G-stress, but without the motion sickness provocation. During immersion mean skin temperature, rectal temperature, the difference in temperature between the forearm and 3rd digit of the right hand (ΔTforearm-fingertip), oxygen uptake and heart rate were recorded. Subjects provided ratings of temperature perception, thermal comfort and level of motion sickness discomfort at regular intervals. No differences were observed in any of the variables between control and G-control procedures. In the motion sickness procedure, the ΔTforearm-fingertip response was significantly attenuated, indicating a blunted vasoconstrictor response, and rectal temperature decreased at a faster rate. No other differences were observed. Motion sickness attenuates the vasoconstrictor response to skin and core cooling, thereby enhancing heat loss and the magnitude of the fall in deep body temperature. Motion sickness may predispose individuals to hypothermia, and have significant implications for survival time in maritime accidents. PMID:11533150

  19. Functional representation for the born-oppenheimer diagonal correction and born-huang adiabatic potential energy surfaces for isotopomers of H3.

    PubMed

    Mielke, Steven L; Schwenke, David W; Schatz, George C; Garrett, Bruce C; Peterson, Kirk A

    2009-04-23

    Multireference configuration interaction (MRCI) calculations of the Born-Oppenheimer diagonal correction (BODC) for H(3) were performed at 1397 symmetry-unique configurations using the Handy-Yamaguchi-Schaefer approach; isotopic substitution leads to 4041 symmetry-unique configurations for the DH(2) mass combination. These results were then fit to a functional form that permits calculation of the BODC for any combination of isotopes. Mean unsigned fitting errors on a test grid of configurations not included in the fitting process were 0.14, 0.12, and 0.65 cm(-1) for the H(3), DH(2), and MuH(2) isotopomers, respectively. This representation can be combined with any Born-Oppenheimer potential energy surface (PES) to yield Born-Huang (BH) PESs; herein, we choose the CCI potential energy surface, the uncertainties of which ( approximately 0.01 kcal/mol) are much smaller than the magnitude of the BODC. Fortran routines to evaluate these BH surfaces are provided. Variational transition state theory calculations are presented comparing thermal rate constants for reactions on the BO and BH surfaces to provide an initial estimate of the significance of the diagonal correction for the dynamics. PMID:19290604

  20. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    PubMed

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

    2015-09-01

    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  1. Endocannabinoids Measurement in Human Saliva as Potential Biomarker of Obesity

    PubMed Central

    Tabarin, Antoine; Clark, Samantha; Leste-Lasserre, Thierry; Marsicano, Giovanni; Piazza, Pier Vincenzo; Cota, Daniela

    2012-01-01

    Background The discovery of the endocannabinoid system and of its role in the regulation of energy balance has significantly advanced our understanding of the physiopathological mechanisms leading to obesity and type 2 diabetes. New knowledge on the role of this system in humans has been acquired by measuring blood endocannabinoids. Here we explored endocannabinoids and related N-acylethanolamines in saliva and verified their changes in relation to body weight status and in response to a meal or to body weight loss. Methodology/Principal Findings Fasting plasma and salivary endocannabinoids and N-acylethanolamines were measured through liquid mass spectrometry in 12 normal weight and 12 obese, insulin-resistant subjects. Salivary endocannabinoids and N-acylethanolamines were evaluated in the same cohort before and after the consumption of a meal. Changes in salivary endocannabinoids and N-acylethanolamines after body weight loss were investigated in a second group of 12 obese subjects following a 12-weeks lifestyle intervention program. The levels of mRNAs coding for enzymes regulating the metabolism of endocannabinoids, N-acylethanolamines and of cannabinoid type 1 (CB1) receptor, alongside endocannabinoids and N-acylethanolamines content, were assessed in human salivary glands. The endocannabinoids 2-arachidonoylglycerol (2-AG), N-arachidonoylethanolamide (anandamide, AEA), and the N-acylethanolamines (oleoylethanolamide, OEA and palmitoylethanolamide, PEA) were quantifiable in saliva and their levels were significantly higher in obese than in normal weight subjects. Fasting salivary AEA and OEA directly correlated with BMI, waist circumference and fasting insulin. Salivary endocannabinoids and N-acylethanolamines did not change in response to a meal. CB1 receptors, ligands and enzymes were expressed in the salivary glands. Finally, a body weight loss of 5.3% obtained after a 12-weeks lifestyle program significantly decreased salivary AEA levels. Conclusions

  2. Neonatal helper-dependent adenoviral vector gene therapy mediates correction of hemophilia A and tolerance to human factor VIII

    PubMed Central

    Cela, Racel G.; Suzuki, Masataka; Lee, Brendan; Lipshutz, Gerald S.

    2011-01-01

    Neonatal gene therapy is a promising strategy for treating a number of congenital diseases diagnosed shortly after birth as expression of therapeutic proteins during postnatal life may limit the pathologic consequences and result in a potential “cure.” Hemophilia A is often complicated by the development of antibodies to recombinant protein resulting in treatment failure. Neonatal administration of vectors may avoid inhibitory antibody formation to factor VIII (FVIII) by taking advantage of immune immaturity. A helper-dependent adenoviral vector expressing human factor VIII was administered i.v. to neonatal hemophilia A knockout mice. Three days later, mice produced high levels of FVIII. Levels declined rapidly with animal growth to 5 wk of age with stable factor VIII expression thereafter to >1 y of age. Decline in factor VIII expression was not related to cell-mediated or humoral responses with lack of development of antibodies to capsid or human factor VIII proteins. Subsequent readministration and augmentation of expression was possible as operational tolerance was established to factor VIII without development of inhibitors; however, protective immunity to adenovirus remained. PMID:21245323

  3. Paleopathology of human tuberculosis and the potential role of climate.

    PubMed

    Nerlich, Andreas G; Lösch, Sandra

    2009-01-01

    Both origin and evolution of tuberculosis and its pathogens (Mycobacterium tuberculosis complex) are not fully understood. The paleopathological investigation of human remains offers a unique insight into the molecular evolution and spread including correlative data of the environment. The molecular analysis of material from Egypt (3000-500 BC), Sudan (200-600 AD), Hungary (600-1700 AD), Latvia (1200-1600 AD), and South Germany (1400-1800 AD) urprisingly revealed constantly high frequencies of tuberculosis in all different time periods excluding significant environmental influence on tuberculosis spread. The typing of various mycobacteria strains provides evidence for ancestral M. tuberculosis strains in Pre- to early Egyptian dynastic material (3500-2650 BC), while typical M. africanum signatures were detected in a Middle Kingdom tomb (2050-1650 BC). Samples from the New Kingdom to Late Period (1500-500 BC) indicated modern M. tuberculosis strains. No evidence was seen for M. bovis in Egyptian material while M. bovis signatures were first identified in Siberian biomaterial dating 2000 years before present. These results contraindicates the theory that M. tuberculosis evolved from M. bovis during early domestication in the region of the "Fertile Crescent," but supports the scenario that M. tuberculosis probably derived from an ancestral progenitor strain. The environmental influence of this evolutionary scenario deserves continuing intense evaluation. PMID:19360109

  4. Paleopathology of Human Tuberculosis and the Potential Role of Climate

    PubMed Central

    Nerlich, Andreas G.; Lösch, Sandra

    2009-01-01

    Both origin and evolution of tuberculosis and its pathogens (Mycobacterium tuberculosis complex) are not fully understood. The paleopathological investigation of human remains offers a unique insight into the molecular evolution and spread including correlative data of the environment. The molecular analysis of material from Egypt (3000–500 BC), Sudan (200–600 AD), Hungary (600–1700 AD), Latvia (1200–1600 AD), and South Germany (1400–1800 AD) urprisingly revealed constantly high frequencies of tuberculosis in all different time periods excluding significant environmental influence on tuberculosis spread. The typing of various mycobacteria strains provides evidence for ancestral M. tuberculosis strains in Pre- to early Egyptian dynastic material (3500–2650 BC), while typical M. africanum signatures were detected in a Middle Kingdom tomb (2050–1650 BC). Samples from the New Kingdom to Late Period (1500–500 BC) indicated modern M. tuberculosis strains. No evidence was seen for M. bovis in Egyptian material while M. bovis signatures were first identified in Siberian biomaterial dating 2000 years before present. These results contraindicates the theory that M. tuberculosis evolved from M. bovis during early domestication in the region of the “Fertile Crescent,” but supports the scenario that M. tuberculosis probably derived from an ancestral progenitor strain. The environmental influence of this evolutionary scenario deserves continuing intense evaluation. PMID:19360109

  5. Cocoa Polyphenols and Their Potential Benefits for Human Health

    PubMed Central

    Andújar, I.; Recio, M. C.; Giner, R. M.; Ríos, J. L.

    2012-01-01

    This paper compiles the beneficial effects of cocoa polyphenols on human health, especially with regard to cardiovascular and inflammatory diseases, metabolic disorders, and cancer prevention. Their antioxidant properties may be responsible for many of their pharmacological effects, including the inhibition of lipid peroxidation and the protection of LDL-cholesterol against oxidation, and increase resistance to oxidative stress. The phenolics from cocoa also modify the glycemic response and the lipid profile, decreasing platelet function and inflammation along with diastolic and systolic arterial pressures, which, taken together, may reduce the risk of cardiovascular mortality. Cocoa polyphenols can also modulate intestinal inflammation through the reduction of neutrophil infiltration and expression of different transcription factors, which leads to decreases in the production of proinflammatory enzymes and cytokines. The phenolics from cocoa may thus protect against diseases in which oxidative stress is implicated as a causal or contributing factor, such as cancer. They also have antiproliferative, antimutagenic, and chemoprotective effects, in addition to their anticariogenic effects. PMID:23150750

  6. Potential role of human growth hormone in melanoma growth promotion.

    PubMed

    Handler, Marc Z; Ross, Andrew L; Shiman, Michael I; Elgart, George W; Grichnik, James M

    2012-10-01

    BACKGROUND Human growth hormone (HGH) and insulin-like growth factor-1 (IGF-1) have been shown to play a role in the malignant transformation and progression of a variety of cancers. HGH is also known to upregulate molecular signaling pathways implicated in the pathogenesis of melanoma. Although HGH has previously been implicated in promoting the clinical growth of both benign and malignant melanocytic neoplasms, to our knowledge there are no conclusive studies demonstrating an increased risk of melanoma following HGH therapy. Nevertheless, there are reports of melanoma developing subsequent to HGH coadministered with either other hormones or following irradiation. OBSERVATION A 49-year-old white man presented with a new pigmented papule that was diagnosed as melanoma. The patient reported using HGH for 3 months prior to the diagnosis. His 51-year-old wife, who also was white, had also been using exogenous HGH for 3 months and had been diagnosed as having a melanoma 2 weeks prior. CONCLUSIONS Given the unlikelihood of 2 unrelated people developing melanoma within a short time span, it is reasonable to assume that a common environmental component (HGH or other shared exposure) contributed to the development of both melanomas. Because of the increased use of exogenous HGH as an antiaging agent, it is important to be aware of the growth-promoting effects of this hormone. Until better data are available that determines the true risk of exogenous HGH, its use as an antiaging agent merits increased surveillance. PMID:23069955

  7. Human recombinant RNASET2: A potential anti-cancer drug

    PubMed Central

    Roiz, Levava; Smirnoff, Patricia; Lewin, Iris; Shoseyov, Oded; Schwartz, Betty

    2016-01-01

    The roles of cell motility and angiogenetic processes in metastatic spread and tumor aggressiveness are well established and must be simultaneously targeted to maximize antitumor drug potency. This work evaluated the antitumorigenic capacities of human recombinant RNASET2 (hrRNASET2), a homologue of the Aspergillus niger T2RNase ACTIBIND, which has been shown to display both antitumorigenic and antiangiogenic activities. hrRNASET2 disrupted intracellular actin filament and actin-rich extracellular extrusion organization in both CT29 colon cancer and A375SM melanoma cells and induced a significant dose-dependent inhibition of A375SM cell migration. hrRNASET2 also induced full arrest of angiogenin-induced tube formation and brought to a three-fold lower relative HT29 colorectal and A375SM melanoma tumor volume, when compared to Avastin-treated animals. In parallel, mean blood vessel counts were 36.9% lower in hrRNASET2-vs. Avastin-treated mice and survival rates of hrRNASET2-treated mice were 50% at 73 days post-treatment, while the median survival time for untreated animals was 22 days. Moreover, a 60-day hrRNASET2 treatment period reduced mean A375SM lung metastasis foci counts by three-fold when compared to untreated animals. Taken together, the combined antiangiogenic and antitumorigenic capacities of hrRNASET2, seemingly arising from its direct interaction with intercellular and extracellular matrices, render it an attractive anticancer therapy candidate. PMID:27014725

  8. Iterative scatter correction based on artifact assessment

    NASA Astrophysics Data System (ADS)

    Wiegert, Jens; Hohmann, Steffen; Bertram, Matthias

    2008-03-01

    In this paper we propose a novel scatter correction methodology for X-ray based cone-beam CT that allows to combine the advantages of projection-based and volume-based correction approaches. The basic idea is to use a potentially non-optimal projection-based scatter correction method and to iteratively optimize its performance by repeatedly assessing remaining scatter-induced artifacts in intermediately reconstructed volumes. The novel approach exploits the fact that due to the flatness of the scatter-background, compensation itself is most easily performed in the projection-domain, while the scatter-induced artifacts can be better observed in the reconstructed volume. The presented method foresees to evaluate the scatter correction efficiency after each iteration by means of a quantitative measure characterizing the amount of residual cupping and to adjust the parameters of the projection-based scatter correction for the next iteration accordingly. The potential of this iterative scatter correction approach is demonstrated using voxelized Monte Carlo scatter simulations as ground truth. Using the proposed iterative scatter correction method, remarkable scatter correction performance was achieved both using simple parametric heuristic techniques as well as by optimizing previously published scatter estimation schemes. For the human head, scatter induced artifacts were reduced from initially 148 HU to less than 8.1 HU to 9.1 HU for different studied methods, corresponding to an artifact reduction exceeding 93%.

  9. Immunoproteomic Analysis of Potential Serum Biomarker Candidates in Human Glaucoma

    PubMed Central

    Tezel, Gülgün; Thornton, Ivey L.; Tong, Melissa G.; Luo, Cheng; Yang, Xiangjun; Cai, Jian; Powell, David W.; Soltau, Joern B.; Liebmann, Jeffrey M.; Ritch, Robert

    2012-01-01

    Purpose. Evidence supporting the immune system involvement in glaucoma includes increased titers of serum antibodies to retina and optic nerve proteins, although their pathogenic importance remains unclear. This study using an antibody-based proteomics approach aimed to identify disease-related antigens as candidate biomarkers of glaucoma. Methods. Serum samples were collected from 111 patients with primary open-angle glaucoma and an age-matched control group of 49 healthy subjects without glaucoma. For high-throughput characterization of antigens, serum IgG was eluted from five randomly selected glaucomatous samples and analyzed by linear ion trap mass spectrometry (LC-MS/MS). Serum titers of selected biomarker candidates were then measured by specific ELISAs in the whole sample pool (including an additional control group of diabetic retinopathy). Results. LC-MS/MS analysis of IgG elutes revealed a complex panel of proteins, including those detectable only in glaucomatous samples. Interestingly, many of these antigens corresponded to upregulated retinal proteins previously identified in glaucomatous donors (or that exhibited increased methionine oxidation). Moreover, additional analysis detected a greater immunoreactivity of the patient sera to glaucomatous retinal proteins (or to oxidatively stressed cell culture proteins), thereby suggesting the importance of disease-related protein modifications in autoantibody production/reactivity. As a narrowing-down strategy for selection of initial biomarker candidates, we determined the serum proteins overlapping with the retinal proteins known to be up-regulated in glaucoma. Four of the selected 10 candidates (AIF, cyclic AMP-responsive element binding protein, ephrin type-A receptor, and huntingtin) exhibited higher ELISA titers in the glaucomatous sera. Conclusions. A number of serum proteins identified by this immunoproteomic study of human glaucoma may represent diseased tissue-related antigens and serve as candidate

  10. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential

    PubMed Central

    Colangelo, Donato; Gregoletto, Luca; Reano, Simone; Pietronave, Stefano; Merlin, Simone; Talmon, Maria; Novelli, Eugenio; Diena, Marco; Nicoletti, Carmine; Musarò, Antonio; Filigheddu, Nicoletta; Follenzi, Antonia; Prat, Maria

    2015-01-01

    A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol. PMID:26375957

  11. Cortically evoked potentials in the human subthalamic nucleus.

    PubMed

    Zwartjes, Daphne G M; Janssen, Marcus L F; Heida, Tjitske; Van Kranen-Mastenbroek, Vivianne; Bour, Lo J; Temel, Yasin; Visser-Vandewalle, Veerle; Veltink, Peter H

    2013-02-28

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor symptoms in Parkinson's disease (PD) patients. However, in a substantial number of patients the beneficial effects of STN DBS are overshadowed by psychiatric side effects. We hypothesize that stimulation of the STN motor area will provide the optimal effect on the motor symptoms without inducing these side effects, and expect that motor cortex stimulation (MCS) evokes a spatially specific response within the STN, which identifies the STN motor area. We previously showed that MCS evokes responses in the unit activity specifically within certain areas of the STN. Unit activity is generally considered a measure of the output activity. To gain more insight into the neuronal input into the STN, we describe the results of cortically evoked subthalamic local field potentials (LFPs). We show that the cortically evoked LFPs follow a certain temporal and spatial pattern. The significant peaks of the evoked LFPs coincide with the timing of some of the inhibitions and excitations present in the unit responses. The spatial resolution of responses measured in the LFP to MCS is not high enough to identify the STN motor region. However, we believe that optimizing targeting techniques and the development of novel DBS electrodes will improve STN DBS therapy for PD patients.

  12. Llama Nanoantibodies with Therapeutic Potential against Human Norovirus Diarrhea

    PubMed Central

    Garaicoechea, Lorena; Aguilar, Andrea; Parra, Gabriel I.; Bok, Marina; Sosnovtsev, Stanislav V.; Canziani, Gabriela; Green, Kim Y.; Bok, Karin; Parreño, Viviana

    2015-01-01

    Noroviruses are a major cause of acute gastroenteritis, but no vaccines or therapeutic drugs are available. Llama-derived single chain antibody fragments (also called VHH) are small, recombinant monoclonal antibodies of 15 kDa with several advantages over conventional antibodies. The aim of this study was to generate recombinant monoclonal VHH specific for the two major norovirus (NoV) genogroups (GI and GII) in order to investigate their potential as immunotherapy for the treatment of NoV diarrhea. To accomplish this objective, two llamas were immunized with either GI.1 (Norwalk-1968) or GII.4 (MD2004) VLPs. After immunization, peripheral blood lymphocytes were collected and used to generate two VHH libraries. Using phage display technology, 10 VHH clones specific for GI.1, and 8 specific for GII.4 were selected for further characterization. All VHH recognized conformational epitopes in the P domain of the immunizing VP1 capsid protein, with the exception of one GII.4 VHH that recognized a linear P domain epitope. The GI.1 VHHs were highly specific for the immunizing GI.1 genotype, with only one VHH cross-reacting with GI.3 genotype. The GII.4 VHHs reacted with the immunizing GII.4 strain and showed a varying reactivity profile among different GII genotypes. One VHH specific for GI.1 and three specific for GII.4 could block the binding of homologous VLPs to synthetic HBGA carbohydrates, saliva, and pig gastric mucin, and in addition, could inhibit the hemagglutination of red blood cells by homologous VLPs. The ability of Nov-specific VHHs to perform well in these surrogate neutralization assays supports their further development as immunotherapy for NoV treatment and immunoprophylaxis. PMID:26267898

  13. Llama nanoantibodies with therapeutic potential against human norovirus diarrhea.

    PubMed

    Garaicoechea, Lorena; Aguilar, Andrea; Parra, Gabriel I; Bok, Marina; Sosnovtsev, Stanislav V; Canziani, Gabriela; Green, Kim Y; Bok, Karin; Parreño, Viviana

    2015-01-01

    Noroviruses are a major cause of acute gastroenteritis, but no vaccines or therapeutic drugs are available. Llama-derived single chain antibody fragments (also called VHH) are small, recombinant monoclonal antibodies of 15 kDa with several advantages over conventional antibodies. The aim of this study was to generate recombinant monoclonal VHH specific for the two major norovirus (NoV) genogroups (GI and GII) in order to investigate their potential as immunotherapy for the treatment of NoV diarrhea. To accomplish this objective, two llamas were immunized with either GI.1 (Norwalk-1968) or GII.4 (MD2004) VLPs. After immunization, peripheral blood lymphocytes were collected and used to generate two VHH libraries. Using phage display technology, 10 VHH clones specific for GI.1, and 8 specific for GII.4 were selected for further characterization. All VHH recognized conformational epitopes in the P domain of the immunizing VP1 capsid protein, with the exception of one GII.4 VHH that recognized a linear P domain epitope. The GI.1 VHHs were highly specific for the immunizing GI.1 genotype, with only one VHH cross-reacting with GI.3 genotype. The GII.4 VHHs reacted with the immunizing GII.4 strain and showed a varying reactivity profile among different GII genotypes. One VHH specific for GI.1 and three specific for GII.4 could block the binding of homologous VLPs to synthetic HBGA carbohydrates, saliva, and pig gastric mucin, and in addition, could inhibit the hemagglutination of red blood cells by homologous VLPs. The ability of Nov-specific VHHs to perform well in these surrogate neutralization assays supports their further development as immunotherapy for NoV treatment and immunoprophylaxis. PMID:26267898

  14. A Study on Combination of Reliability-based Automatic Repeat reQuest with Error Potential-based Error Correction for Improving P300 Speller Performance

    NASA Astrophysics Data System (ADS)

    Takahashi, Hiromu; Yoshikawa, Tomohiro; Furuhashi, Takeshi

    Brain-computer interfaces (BCIs) are systems that translate one's thoughts into commands to restore control and communication to severely paralyzed people, and also appealing to healthy people. The P300 speller, one of the most renowned BCIs for communication, allows users to select letters just by thoughts. However, due to the low signal-to-noise ratio of the P300, signal averaging is often performed, which improves the spelling accuracy but degrades the spelling speed. The authors have proposed reliability-based automatic repeat request (RB-ARQ) to ease this problem. RB-ARQ could be enhanced when it is combined with the error correction based on the error-related potentials (ErrPs) that occur on erroneous feedbacks. Thus, this study aims to reveal the characteristics of the ErrPs in the P300 speller paradigm, and to combine RB-ARQ with the ErrP-based error correction to further improve the performance. The results show that the ErrPs observed in the current study resemble the previously reported ErrPs observed in a cursor control task using a BCI, and that the performance of the P300 speller could be improved by 35 percent on average.

  15. Reduction of coherence of the human brain electric potentials

    NASA Astrophysics Data System (ADS)

    Novik, Oleg; Smirnov, Fedor

    Plenty of technological processes are known to be damaged by magnetic storms. But technology is controlled by men and their functional systems may be damaged as well. We are going to consider the electro-neurophysiological aspect of the general problem: men surrounded by physical fields including ones of cosmic origination. Magnetic storms’ influence had been observed for a group of 13 students (practically healthy girls and boys from 18 to 23 years old, Moscow). To control the main functional systems of the examinees, their electroencephalograms (EEG) were being registered along with electrocardiograms, respiratory rhythms, arterial blood pressure and other characteristics during a year. All of these characteristics, save for the EEG, were within the normal range for all of the examinees during measurements. According to the EEG investigations by implementation of the computer proof-reading test in absence of magnetic storms, the values of the coherence function of time series of the theta-rhythm oscillations (f = 4 - 7.9 Hz, A = 20 μV) of electric potentials of the frontal-polar and occipital areas of the head belong to the interval [0.3, 0.8] for all of the students under investigation. (As the proof-reading test, it was necessary to choose given symbols from a random sequence of ones demonstrated at a monitor and to enter the number of the symbols discovered in a computer. Everyone was known that the time for determination of symbols is unlimited. On the other hand, nobody was known that the EEG and other registrations mentioned are connected with electromagnetic geophysical researches and geomagnetic storms). Let us formulate the main result: by implementation of the same test during a magnetic storm, 5 ≤ K ≤ 6, or no later then 24 hours after its beginning (different types of moderate magnetic storms occurred, the data of IZMIRAN were used), the values of the theta-rhythm frontal - occipital coherence function of all of the students of the group under

  16. Porphyrin Metabolisms in Human Skin Commensal Propionibacterium acnes Bacteria: Potential Application to Monitor Human Radiation Risk

    PubMed Central

    Shu, M.; Kuo, S.; Wang, Y.; Jiang, Y.; Liu, Y.-T.; Gallo, R.L.; Huang, C.-M.

    2013-01-01

    Propionibacterium acnes (P. acnes), a Gram-positive anaerobic bacterium, is a commensal organism in human skin. Like human cells, the bacteria produce porphyrins, which exhibit fluorescence properties and make bacteria visible with a Wood’s lamp. In this review, we compare the porphyrin biosynthesis in humans and P. acnes. Also, since P. acnes living on the surface of skin receive the same radiation exposure as humans, we envision that the changes in porphyrin profiles (the absorption spectra and/or metabolism) of P. acnes by radiation may mirror the response of human cells to radiation. The porphyrin profiles of P. acnes may be a more accurate reflection of radiation risk to the patient than other biodosimeters/biomarkers such as gene up-/down-regulation, which may be non-specific due to patient related factors such as autoimmune diseases. Lastly, we discuss the challenges and possible solutions for using the P. acnes response to predict the radiation risk. PMID:23231351

  17. Developmental potential of human oocytes reconstructed by transferring somatic cell nuclei into polyspermic zygote cytoplasm

    SciTech Connect

    Fan, Yong; Chen, Xinjie; Luo, Yumei; Chen, Xiaolin; Li, Shaoying; Huang, Yulin; Sun, Xiaofang

    2009-04-24

    The generation of patient-specific nuclear transfer embryonic stem cells holds huge promise in modern regenerative medicine and cell-based drug discovery. Since human in vivo matured oocytes are not readily available, human therapeutic cloning is developing slowly. Here, we investigated for the first time whether human polyspermic zygotes could support preimplantation development of cloned embryos. Our results showed that polyspermic zygotes could be used as recipients for human somatic cell nuclear transfer (SCNT). The preimplantation developmental potential of SCNT embryos from polyspermic zygotes was limited to the 8-cell stage. Since ES cell lines can be derived from single blastomeres, these results may have important significance for human ES cells derived by SCNT. In addition, confocal images demonstrated that all of the SCNT embryos that failed to cleave showed abnormal microtubule organization. The results of the present study suggest that polyspermic human zygotes could be used as a potential source of recipient cytoplasm for SCNT.

  18. Research Sees Potential to Make Bone, Muscle from Human Stem Cells

    MedlinePlus

    ... 159885.html Research Sees Potential to Make Bone, Muscle From Human Stem Cells Could be a major advance for regenerative medicine, ... and chemical signals needed to make bone, heart muscle and 10 other cells types from human stem cells within a matter of days. The researchers ...

  19. Identification of potentially human-pathogenic Enterocytozoon bieneusi genotypes in various birds.

    PubMed

    Lobo, Maria Luísa; Xiao, Lihua; Cama, Vitaliano; Magalhães, Nuno; Antunes, Francisco; Matos, Olga

    2006-11-01

    Enterocytozoon bieneusi was detected in 24 of 83 samples from birds of the orders Columbiformes, Passeriformes, and Psittaciformes. It was identical to or closely related to the Peru6 genotype, which was previously found in humans in Peru. Thus, various birds can be a significant source of environmental contamination by potentially human-pathogenic E. bieneusi.

  20. Identification of Potentially Human-Pathogenic Enterocytozoon bieneusi Genotypes in Various Birds▿

    PubMed Central

    Lobo, Maria Luísa ; Xiao, Lihua; Cama, Vitaliano; Magalhães, Nuno; Antunes, Francisco; Matos, Olga

    2006-01-01

    Enterocytozoon bieneusi was detected in 24 of 83 samples from birds of the orders Columbiformes, Passeriformes, and Psittaciformes. It was identical to or closely related to the Peru6 genotype, which was previously found in humans in Peru. Thus, various birds can be a significant source of environmental contamination by potentially human-pathogenic E. bieneusi. PMID:16936045

  1. Numerical human models for accident research and safety - potentials and limitations.

    PubMed

    Praxl, Norbert; Adamec, Jiri; Muggenthaler, Holger; von Merten, Katja

    2008-01-01

    The method of numerical simulation is frequently used in the area of automotive safety. Recently, numerical models of the human body have been developed for the numerical simulation of occupants. Different approaches in modelling the human body have been used: the finite-element and the multibody technique. Numerical human models representing the two modelling approaches are introduced and the potentials and limitations of these models are discussed.

  2. Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

    SciTech Connect

    Nozaki, Yumiko; Honda, Yayoi; Tsujimoto, Shinji; Watanabe, Hitoshi; Kunimatsu, Takeshi; Funabashi, Hitoshi

    2014-07-01

    Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min for 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I{sub Kr} blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans.

  3. Development of new versions of anti-human CD34 monoclonal antibodies with potentially reduced immunogenicity

    SciTech Connect

    Qian Weizhu; Wang Ling; Li Bohua; Wang Hao; Hou Sheng; Hong Xueyu; Zhang Dapeng; Guo Yajun

    2008-03-07

    Despite the widespread clinical use of CD34 antibodies for the purification of human hematopoietic stem/progenitor cells, all the current anti-human CD34 monoclonal antibodies (mAbs) are murine, which have the potential to elicit human antimouse antibody (HAMA) immune response. In the present study, we developed three new mouse anti-human CD34 mAbs which, respectively, belonged to class I, class II and class III CD34 epitope antibodies. In an attempt to reduce the immunogenicity of these three murine mAbs, their chimeric antibodies, which consisted of mouse antibody variable regions fused genetically to human antibody constant regions, were constructed and characterized. The anti-CD34 chimeric antibodies were shown to possess affinity and specificity similar to that of their respective parental murine antibodies. Due to the potentially better safety profiles, these chimeric antibodies might become alternatives to mouse anti-CD34 antibodies routinely used for clinical application.

  4. A potential model for methane in water describing correctly the solubility of the gas and the properties of the methane hydrate.

    PubMed

    Docherty, H; Galindo, A; Vega, C; Sanz, E

    2006-08-21

    We have obtained the excess chemical potential of methane in water, over a broad range of temperatures, from computer simulation. The methane molecules are described as simple Lennard-Jones interaction sites, while water is modeled by the recently proposed TIP4P/2005 model. We have observed that the experimental values of the chemical potential are not reproduced when using the Lorentz-Berthelot combining rules. However, we also noticed that the deviation is systematic, suggesting that this may be corrected. In fact, by introducing positive deviations from the energetic Lorentz-Berthelot rule to account indirectly for the polarization methane-water energy, we are able to describe accurately the excess chemical potential of methane in water. Thus, by using a model capable of describing accurately the density of pure water in a wide range of temperatures and by deviating from the Lorentz-Berthelot combining rules, it is possible to reproduce the properties of methane in water at infinite dilution. In addition, we have applied this methane-water potential to the study of the solid methane hydrate structure, commonly denoted as sI, and find that the model describes the experimental value of the unit cell of the hydrate with an error of about 0.2%. Moreover, we have considered the effect of the amount of methane contained in the hydrate. In doing so, we determine that the presence of methane increases slightly the value of the unit cell and decreases slightly the compressibility of the structure. We also note that the presence of methane increases greatly the range of pressures where the sI hydrate is mechanically stable. PMID:16942354

  5. A potential model for methane in water describing correctly the solubility of the gas and the properties of the methane hydrate.

    PubMed

    Docherty, H; Galindo, A; Vega, C; Sanz, E

    2006-08-21

    We have obtained the excess chemical potential of methane in water, over a broad range of temperatures, from computer simulation. The methane molecules are described as simple Lennard-Jones interaction sites, while water is modeled by the recently proposed TIP4P/2005 model. We have observed that the experimental values of the chemical potential are not reproduced when using the Lorentz-Berthelot combining rules. However, we also noticed that the deviation is systematic, suggesting that this may be corrected. In fact, by introducing positive deviations from the energetic Lorentz-Berthelot rule to account indirectly for the polarization methane-water energy, we are able to describe accurately the excess chemical potential of methane in water. Thus, by using a model capable of describing accurately the density of pure water in a wide range of temperatures and by deviating from the Lorentz-Berthelot combining rules, it is possible to reproduce the properties of methane in water at infinite dilution. In addition, we have applied this methane-water potential to the study of the solid methane hydrate structure, commonly denoted as sI, and find that the model describes the experimental value of the unit cell of the hydrate with an error of about 0.2%. Moreover, we have considered the effect of the amount of methane contained in the hydrate. In doing so, we determine that the presence of methane increases slightly the value of the unit cell and decreases slightly the compressibility of the structure. We also note that the presence of methane increases greatly the range of pressures where the sI hydrate is mechanically stable.

  6. Nonlinear time-varying potential bistable energy harvesting from human motion

    NASA Astrophysics Data System (ADS)

    Cao, Junyi; Wang, Wei; Zhou, Shengxi; Inman, Daniel J.; Lin, Jing

    2015-10-01

    A theoretical and experimental investigation into nonlinear bistable energy harvesting with time-varying potential energy is presented. The motivation for examining time-varying potentials comes from the desire to harvest energy from human motion. Time-varying potential energy function of bistable oscillator with respect to the swing angle are established to derive the governing electromechanical model for harvesting vibration energy from the swaying motion during human walking or running. Numerical simulations show good agreement with the experimental potential energy function under different swing angles. Various motion speed treadmill tests are performed to demonstrate the advantage of time-varying bistable harvesters over linear and monostable ones in harvesting energy from human motion.

  7. Targeted Gene Addition to a Safe Harbor locus in human CD34+ Hematopoietic Stem Cells for Correction of X-linked Chronic Granulomatous Disease

    PubMed Central

    De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H.; Chan, Andy; Pearl, Jocelynn R.; Paschon, David E.; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A.; Zarember, Kol A.; Peshwa, Madhusudan V.; Gregory, Philip D.; Urnov, Fyodor D.; Malech, Harry L.

    2016-01-01

    Gene therapy with genetically modified human CD34+ hematopoietic stem cells (HSCs) may be safer using targeted integration (TI) of transgenes into a genomic ‘safe harbor’ site than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno associated virus (AAV) 6 delivery of donor constructs in human HSCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus-positive HSCs with 6–16% human cell marking were observed following engraftment into mice. In HSCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 in resulted in ~15% gp91phox expression and increased NADPH oxidase activity in ex vivo–derived neutrophils. In mice transplanted with corrected HSCs, 4–11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases. PMID:26950749

  8. A Density Functional Theory Based Protocol to Compute the Redox Potential of Transition Metal Complex with the Correction of Pseudo-Counterion: General Theory and Applications.

    PubMed

    Matsui, Toru; Kitagawa, Yasutaka; Shigeta, Yasuteru; Okumura, Mitsutaka

    2013-07-01

    We propose an accurate scheme to evaluate the redox potential of a wide variety of transition metal complexes by adding a charge-dependent correction term for a counterion around the charged complexes, which is based on Generalized Born theory, to the solvation energy. The mean absolute error (MAE) toward experimental redox potentials of charged complexes is considerably reduced from 0.81 V (maximum error 1.22 V) to 0.22 V (maximum error 0.50 V). We found a remarkable exchange-correlation functional dependence on the results rather than the basis set ones. The combination of Wachters+f (for metal) and 6-31++G(d,p) (for other atoms) with the B3LYP functional gives the least MAE 0.15 V for the test complexes. This scheme is applicable to other solvents, and heavier transition metal complexes such as M1(CO)5(pycn) (M1 = Cr, Mo, W), M2(mnt)2 (M2 = Ni, Pd, Pt), and M3(bpy)3 (M3 = Fe, Ru, Os) with the same quality.

  9. Sequence specificity, statistical potentials, and three-dimensional structure prediction with self-correcting distance geometry calculations of beta-sheet formation in proteins.

    PubMed Central

    Zhu, H.; Braun, W.

    1999-01-01

    A statistical analysis of a representative data set of 169 known protein structures was used to analyze the specificity of residue interactions between spatial neighboring strands in beta-sheets. Pairwise potentials were derived from the frequency of residue pairs in nearest contact, second nearest and third nearest contacts across neighboring beta-strands compared to the expected frequency of residue pairs in a random model. A pseudo-energy function based on these statistical pairwise potentials recognized native beta-sheets among possible alternative pairings. The native pairing was found within the three lowest energies in 73% of the cases in the training data set and in 63% of beta-sheets in a test data set of 67 proteins, which were not part of the training set. The energy function was also used to detect tripeptides, which occur frequently in beta-sheets of native proteins. The majority of native partners of tripeptides were distributed in a low energy range. Self-correcting distance geometry (SECODG) calculations using distance constraints sets derived from possible low energy pairing of beta-strands uniquely identified the native pairing of the beta-sheet in pancreatic trypsin inhibitor (BPTI). These results will be useful for predicting the structure of proteins from their amino acid sequence as well as for the design of proteins containing beta-sheets. PMID:10048326

  10. Band-structure calculations of noble-gas and alkali halide solids using accurate Kohn-Sham potentials with self-interaction correction

    SciTech Connect

    Li, Y.; Krieger, J.B. ); Norman, M.R. ); Iafrate, G.J. )

    1991-11-15

    The optimized-effective-potential (OEP) method and a method developed recently by Krieger, Li, and Iafrate (KLI) are applied to the band-structure calculations of noble-gas and alkali halide solids employing the self-interaction-corrected (SIC) local-spin-density (LSD) approximation for the exchange-correlation energy functional. The resulting band gaps from both calculations are found to be in fair agreement with the experimental values. The discrepancies are typically within a few percent with results that are nearly the same as those of previously published orbital-dependent multipotential SIC calculations, whereas the LSD results underestimate the band gaps by as much as 40%. As in the LSD---and it is believed to be the case even for the exact Kohn-Sham potential---both the OEP and KLI predict valence-band widths which are narrower than those of experiment. In all cases, the KLI method yields essentially the same results as the OEP.

  11. Human eosinophils - potential pharmacological model applied in human histamine H4 receptor research.

    PubMed

    Grosicki, Marek; Kieć-Kononowicz, Katarzyna

    2015-01-01

    Histamine and histamine receptors are well known for their immunomodulatory role in inflammation. In this review we describe the role of histamine and histamine H4 receptor on human eosinophils. In the first part of article we provide short summary of histamine and histamine receptors role in physiology and histamine related therapeutics used in clinics. We briefly describe the human histamine receptor H4 and its ligands, as well as human eosinophils. In the second part of the review we provide detailed description of known histamine effects on eosinophils including: intracellular calcium concentration flux, actin polymerization, cellular shape change, upregulation of adhesion proteins and cellular chemotaxis. We provide proofs that these effects are mainly connected with the activation of histamine H4 receptor. When examining experimental data we discuss the controversial results and limitations of the studies performed on isolated eosinophils. In conclusion we believe that studies on histamine H4 receptor on human eosinophils can provide interesting new biomarkers that can be used in clinical studies of histamine receptors, that in future might result in the development of new strategies in the treatment of chronic inflammatory conditions like asthma or allergy, in which eosinophils are involved.

  12. Multipotent stromal stem cells from human placenta demonstrate high therapeutic potential.

    PubMed

    Nazarov, Igor; Lee, Jae W; Soupene, Eric; Etemad, Sara; Knapik, Derrick; Green, William; Bashkirova, Elizaveta; Fang, Xiaohui; Matthay, Michael A; Kuypers, Frans A; Serikov, Vladimir B

    2012-05-01

    We describe human chorionic mesenchymal stem cell (hCMSC) lines obtained from the chorion of human term placenta with high therapeutic potential in human organ pathology. hCMSCs propagated for more than 100 doublings without a decrease in telomere length and with no telomerase activity. Cells were highly positive for the embryonic stem cell markers OCT-4, NANOG, SSEA-3, and TRA-1-60. In vitro, cells could be differentiated into neuron-like cells (ectoderm), adipocytes, osteoblasts, endothelial-like cells (mesoderm), and hepatocytes (endoderm)-derivatives of all three germ layers. hCMSCs effectively facilitated repair of injured epithelium as demonstrated in an ex vivo-perfused human lung preparation injured by Escherichia coli endotoxin and in in vitro human lung epithelial cultures. We conclude that the chorion of human term placenta is an abundant source of multipotent stem cells that are promising candidates for cell-based therapies. PMID:23197815

  13. Multipotent Stromal Stem Cells from Human Placenta Demonstrate High Therapeutic Potential

    PubMed Central

    Nazarov, Igor; Lee, Jae W.; Soupene, Eric; Etemad, Sara; Knapik, Derrick; Green, William; Bashkirova, Elizaveta; Fang, Xiaohui; Matthay, Michael A.; Kuypers, Frans A.

    2012-01-01

    We describe human chorionic mesenchymal stem cell (hCMSC) lines obtained from the chorion of human term placenta with high therapeutic potential in human organ pathology. hCMSCs propagated for more than 100 doublings without a decrease in telomere length and with no telomerase activity. Cells were highly positive for the embryonic stem cell markers OCT-4, NANOG, SSEA-3, and TRA-1–60. In vitro, cells could be differentiated into neuron-like cells (ectoderm), adipocytes, osteoblasts, endothelial-like cells (mesoderm), and hepatocytes (endoderm)—derivatives of all three germ layers. hCMSCs effectively facilitated repair of injured epithelium as demonstrated in an ex vivo-perfused human lung preparation injured by Escherichia coli endotoxin and in in vitro human lung epithelial cultures. We conclude that the chorion of human term placenta is an abundant source of multipotent stem cells that are promising candidates for cell-based therapies. PMID:23197815

  14. Event-related potentials associated with performance monitoring in non-human primates.

    PubMed

    Phillips, Jessica M; Everling, Stefan

    2014-08-15

    The abilities to monitor performance outcomes and, when appropriate, impose strategic adjustments in behavior, are core features of the intact human cognitive control system. Errors committed in choice reaction time tasks are typically followed by two scalp potentials, the error negativity (Ne) and error positivity (Pe). These components are considered physiological signatures of the performance monitoring system. Several theories have been proposed to account for these error-related potentials and their functional and behavioral significance. These ideas were inspired by empirical data in humans and other mammalian species, and supported by the results of experiments in which performance monitoring, in humans and computational models, was investigated. However, an appropriate animal model is required to rigorously test the predictions that arise from these theories. Here, using a variant of the anti-saccade task, we demonstrate that event-related signals recorded from macaque monkeys, following errors in choice, resemble the human Ne and Pe. These components were modulated by cognitive variables, namely the degree of cognitive control associated with the applied rule, which implies the existence of hierarchical error processing systems in monkeys, and the degree of response control associated with the saccade. Error-related potential amplitudes were also correlated with remedial action, in a rule-dependent manner. These results demonstrate that error-related potentials in macaque monkeys and human subjects show important similarities, thus supporting the use of the macaque monkey as an animal model for the neurophysiological study of performance monitoring, and potentially, post-error adjustments.

  15. In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins.

    PubMed

    Liu, Hua; Kim, Yonghak; Sharkis, Saul; Marchionni, Luigi; Jang, Yoon-Young

    2011-05-11

    Human induced pluripotent stem cells (iPSCs) are a potential source of hepatocytes for liver transplantation to treat end-stage liver disease. In vitro differentiation of human iPSCs into hepatic cells has been achieved using a multistage differentiation protocol, but whether these cells are functional and capable of engrafting and regenerating diseased liver tissue is not clear. We show that human iPSC-derived hepatic cells at various differentiation stages can engraft the liver in a mouse transplantation model. Using the same differentiation and transplantation protocols, we also assessed the ability of human iPSCs derived from each of the three developmental germ layer tissues (that is, ectoderm, mesoderm, and endoderm) to regenerate mouse liver. These iPSC lines, with similar but distinct global DNA methylation patterns, differentiated into multistage hepatic cells with an efficiency similar to that of human embryonic stem cells. Human hepatic cells at various differentiation stages derived from iPSC lines of different origins successfully repopulated the liver tissue of mice with liver cirrhosis. They also secreted human-specific liver proteins into mouse blood at concentrations comparable to that of proteins secreted by human primary hepatocytes. Our results demonstrate the engraftment and liver regenerative capabilities of human iPSC-derived multistage hepatic cells in vivo and suggest that human iPSCs of distinct origins and regardless of their parental epigenetic memory can efficiently differentiate along the hepatic lineage.

  16. High volume hydraulic fracturing operations: potential impacts on surface water and human health.

    PubMed

    Mrdjen, Igor; Lee, Jiyoung

    2016-08-01

    High volume, hydraulic fracturing (HVHF) processes, used to extract natural gas and oil from underground shale deposits, pose many potential hazards to the environment and human health. HVHF can negatively affect the environment by contaminating soil, water, and air matrices with potential pollutants. Due to the relatively novel nature of the process, hazards to surface waters and human health are not well known. The purpose of this article is to link the impacts of HVHF operations on surface water integrity, with human health consequences. Surface water contamination risks include: increased structural failure rates of unconventional wells, issues with wastewater treatment, and accidental discharge of contaminated fluids. Human health risks associated with exposure to surface water contaminated with HVHF chemicals include increased cancer risk and turbidity of water, leading to increased pathogen survival time. Future research should focus on modeling contamination spread throughout the environment, and minimizing occupational exposure to harmful chemicals.

  17. Potential human health effects of acid rain: report of a workshop.

    PubMed

    Goyer, R A; Bachmann, J; Clarkson, T W; Ferris, B G; Graham, J; Mushak, P; Perl, D P; Rall, D P; Schlesinger, R; Sharpe, W

    1985-05-01

    This report summarizes the potential impact of the acid precipitation phenomenon on human health. There are two major components to this phenomenon: the predepositional phase, during which there is direct human exposure to acidic substances from ambient air, and the post-depositional phase, in which the deposition of acid materials on water and soil results in the mobilization, transport, and even chemical transformation of toxic metals. Acidification increases bioconversion of mercury to methylmercury, which accumulates in fish, increasing the risk to toxicity in people who eat fish. Increase in water and soil content of lead and cadmium increases human exposure to these metals which become additive to other sources presently under regulatory control. The potential adverse health effects of increased human exposure to aluminum is not known at the present time.

  18. Potential human health effects of acid rain: report of a workshop

    PubMed Central

    Goyer, Robert A.; Bachmann, John; Clarkson, Thomas W.; Ferris, Benjamin G.; Graham, Judith; Mushak, Paul; Perl, Daniel P.; Rall, David P.; Schlesinger, Richard; Sharpe, William; Wood, John M.

    1985-01-01

    This report summarizes the potential impact of the acid precipitation phenomenon on human health. There are two major components to this phenomenon: the predepositional phase, during which there is direct human exposure to acidic substances from ambient air, and the post-depositional phase, in which the deposition of acid materials on water and soil results in the mobilization, transport, and even chemical transformation of toxic metals. Acidification increases bioconversion of mercury to methylmercury, which accumulates in fish, increasing the risk to toxicity in people who eat fish. Increase in water and soil content of lead and cadmium increases human exposure to these metals which become additive to other sources presently under regulatory control. The potential adverse health effects of increased human exposure to aluminum is not known at the present time. PMID:3896772

  19. High volume hydraulic fracturing operations: potential impacts on surface water and human health.

    PubMed

    Mrdjen, Igor; Lee, Jiyoung

    2016-08-01

    High volume, hydraulic fracturing (HVHF) processes, used to extract natural gas and oil from underground shale deposits, pose many potential hazards to the environment and human health. HVHF can negatively affect the environment by contaminating soil, water, and air matrices with potential pollutants. Due to the relatively novel nature of the process, hazards to surface waters and human health are not well known. The purpose of this article is to link the impacts of HVHF operations on surface water integrity, with human health consequences. Surface water contamination risks include: increased structural failure rates of unconventional wells, issues with wastewater treatment, and accidental discharge of contaminated fluids. Human health risks associated with exposure to surface water contaminated with HVHF chemicals include increased cancer risk and turbidity of water, leading to increased pathogen survival time. Future research should focus on modeling contamination spread throughout the environment, and minimizing occupational exposure to harmful chemicals. PMID:26608711

  20. Induced Long-Range Attractive Potentials of Human Serum Albumin by Ligand Binding

    SciTech Connect

    Sato, Takaaki; Komatsu, Teruyuki; Nakagawa, Akito; Tsuchida, Eishun

    2007-05-18

    Small-angle x-ray scattering and dielectric spectroscopy investigation on the solutions of recombinant human serum albumin and its heme hybrid revealed that heme incorporation induces a specific long-range attractive potential between protein molecules. This is evidenced by the enhanced forward intensity upon heme binding, despite no hindrance to rotatory Brownian motion, unbiased colloid osmotic pressure, and discontiguous nearest-neighbor distance, confirming monodispersity of the proteins. The heme-induced potential may play a trigger role in recognition of the ligand-filled human serum albumins in the circulatory system.

  1. Force correcting atom centred potentials for generalised gradient approximated density functional theory: Approaching hybrid functional accuracy for geometries and harmonic frequencies in small chlorofluorocarbons

    NASA Astrophysics Data System (ADS)

    Anatole von Lilienfeld, O.

    2013-08-01

    Generalised gradient approximated (GGA) density functional theory (DFT) typically overestimates polarisability and bond-lengths, and underestimates force constants of covalent bonds. To overcome this problem we show that one can use empirical force correcting atom centred potentials (FCACPs), parametrised for every nuclear species. Parameters are obtained through minimisation of a penalty functional that explicitly encodes hybrid DFT forces and static polarisabilities of reference molecules. For hydrogen, fluorine, chlorine and carbon the respective reference molecules consist of H2, F2, Cl2 and CH4. The transferability of this approach is assessed for harmonic frequencies in a small set of chlorofluorocarbon molecules. Numerical evidence, gathered for CF4, CCl4, CCl3F, CCl2F2, CClF3, ClF, HF, HCl, CFH3, CF2H2, CF3H, CHCl3, CH2Cl2 and CH3Cl indicates that the GGA+FCACP level of theory yields harmonic frequencies that are significantly more consistent with hybrid DFT values, as well as slightly reduced molecular polarisability.

  2. H7N9 avian influenza A virus and the perpetual challenge of potential human pandemicity.

    PubMed

    Morens, David M; Taubenberger, Jeffery K; Fauci, Anthony S

    2013-07-09

    ABSTRACT The ongoing H7N9 influenza epizootic in China once again presents us questions about the origin of pandemics and how to recognize them in early stages of development. Over the past ~135 years, H7 influenza viruses have neither caused pandemics nor been recognized as having undergone human adaptation. Yet several unusual properties of these viruses, including their poultry epizootic potential, mammalian adaptation, and atypical clinical syndromes in rarely infected humans, suggest that they may be different from other avian influenza viruses, thus questioning any assurance that the likelihood of human adaptation is low. At the same time, the H7N9 epizootic provides an opportunity to learn more about the mammalian/human adaptational capabilities of avian influenza viruses and challenges us to integrate virologic and public health research and surveillance at the animal-human interface.

  3. New XDM-corrected potential energy surfaces for Ar–NO(X{sup 2}Π): A comparison with CCSD(T) calculations and experiments

    SciTech Connect

    Warehime, Michael; Johnson, Erin R.; Kłos, Jacek

    2015-01-14

    We report new potential energy surfaces for the ground state Ar–NO(X{sup 2}Π) van der Waals system calculated using the unrestricted Hartree-Fock (UHF) method with the addition of the Becke-Roussel correlation functional and exchange-hole dipole moment dispersion correction (XDM). We compare UHFBR-XDM surfaces and those previously reported by Alexander from coupled cluster CCSD(T) calculations [J. Chem. Phys. 111, 7426 (1999)]. The bound states of Ar–NO have been investigated with these new UHFBR-XDM surfaces, including relative energy-level spacing, adiabatic bender states and wave functions, and spectroscopic data. These results have been found to be in good agreement with calculations based on the CCSD(T) PESs. These new PESs are used to investigate the inelastic scattering of NO(X) by Ar. Full close-coupling integral cross sections at collision energies of 442 cm{sup −1}, 1774 cm{sup −1} and differential cross sections at collision energy of 530 cm{sup −1} were determined for transitions out of the lowest NO(X) rotational level (j = ω = 1/2,f). These cross sections are in good agreement with those calculated with CCSD(T) and accordingly in good agreement with the most recent initial and final state resolved experimental data. The UHFBR-XDM scheme yields high-quality potential surfaces with computational cost comparable to the Hartree-Fock method and our results may serve as a benchmark for application of this scheme to collisions between larger molecules.

  4. Electroweak Corrections

    NASA Astrophysics Data System (ADS)

    Barbieri, Riccardo

    2016-10-01

    The test of the electroweak corrections has played a major role in providing evidence for the gauge and the Higgs sectors of the Standard Model. At the same time the consideration of the electroweak corrections has given significant indirect information on the masses of the top and the Higgs boson before their discoveries and important orientation/constraints on the searches for new physics, still highly valuable in the present situation. The progression of these contributions is reviewed.

  5. Repair of x-ray-induced DNA double-strand breaks in specific Not I restriction fragments in human fibroblasts: joining of correct and incorrect ends

    NASA Technical Reports Server (NTRS)

    Lobrich, M.; Rydberg, B.; Cooper, P. K.; Chatterjee, A. (Principal Investigator)

    1995-01-01

    An assay that allows measurement of absolute induction frequencies for DNA double-strand breaks (dsbs) in defined regions of the genome and that quantitates rejoining of correct DNA ends has been used to study repair of dsbs in normal human fibroblasts after x-irradiation. The approach involves hybridization of single-copy DNA probes to Not I restriction fragments separated according to size by pulsed-field gel electrophoresis. Induction of dsbs is quantitated from the decrease in the intensity of the hybridizing restriction fragment and an accumulation of a smear below the band. Rejoining of dsbs results in reconstitution of the intact restriction fragment only if correct DNA ends are joined. By comparing results from this technique with results from a conventional electrophoresis assay that detects all rejoining events, it is possible to quantitate the misrejoining frequency. Three Not I fragments on the long arm of chromosome 21 were investigated with regard to dsb induction, yielding an identical induction rate of 5.8 X 10(-3) break per megabase pair per Gy. Correct dsb rejoining was measured for two of these Not I fragments after initial doses of 80 and 160 Gy. The misrejoining frequency was about 25% for both fragments and was independent of dose. This result appears to be representative for the whole genome as shown by analysis of the entire Not I fragment distribution. The correct rejoining events primarily occurred within the first 2 h, while the misrejoining kinetics included a much slower component, with about half of the events occurring between 2 and 24 h. These misrejoining kinetics are similar to those previously reported for production of exchange aberrations in interphase chromosomes.

  6. Numerical [corrected] analysis of the load capacity of the human spine fitted with L-rod instrumentation.

    PubMed

    Weiler, P J; Medley, J B; McNeice, G M

    1990-12-01

    L-rod procedures with sublaminar wiring have become widespread in orthopaedic practice, and serious mechanical problems involving fatigue failure, creep, and fixation have been reported. To address these problems, numerical [corrected] analysis was developed to provide estimates for the maximum bending stresses, approximately equal to maximum tensile stresses, in L-rods subject to various axial loads and postoperative Cobb angles. The superior load capacity of L-rods made from MP35N multiphase alloy compared with 316L stainless steel was demonstrated. Bending stresses in excess of the fatigue limit were predicted for eight patients with broken rods, suggesting that such failures might be prevented by prior analysis. This analytic approach provides a foundation for future studies of custom-designed L-rods and perhaps the successful use of L-rods without arthrodesis. PMID:2281372

  7. [Psychophysiological correlates of increasing the work ability of human operator owing to the programmable correction of the functional status].

    PubMed

    Tuzin, P S; Evdokimov, A V; Iznak, A F; Chaianov, N V

    1996-01-01

    There has been studied application of a complex approach to development of automated ways to gain contactless psychophysiological correction of functional status and improvement of performance of working up operators. The psychophysiological support of operator consisted in combined presentation of functional music, surf noise and pulsed dynamic green lighting under a special program built-up on the principle of biological feedback of heart and respiration rates. The individually adaptable audio and visual pulses on the programme showed a rather high efficiency as was confirmed by the change in the set of psychophysiological indices (heart rate, arterial pressure, cutaneogalvanic reaction, accommodation volume, critical rate of flicker fusion, electroencephalogram), and subjective SAM (self-feeling, activity, mood) estimates in the course of extended operator's activity.

  8. "Human Potential" and Progressive Pedagogy: A Long Cultural History of the Ambiguity of "Race" and "Intelligence"

    ERIC Educational Resources Information Center

    Oland, Trine

    2012-01-01

    This article examines the cultural constructs of progressive pedagogy in Danish school pedagogy and its emerging focus on the child's human potential from the 1920s to the 1950s. It draws on Foucault's notion of "dispositifs" and the "elements of history," encircling a complex transformation of continuity and discontinuity of progressive pedagogy.…

  9. Chapter 6: Ecotoxicology, Environmental Risk Assessment & Potential Impact on Human Health

    EPA Science Inventory

    This chapter examines potential risks posed by pharmaceuticals present in the aquatic environment to humans and aquatic life. We begin by describing the mechanisms by which pharmaceuticals enter the vertebrate body, produce effects and leave the body. Then we describe theoretical...

  10. MOLECULAR ANALYSIS OF HUMAN SPERMATOZOA: POTENTIAL FOR INFERTILITY RESEARCH AND SCREENING

    EPA Science Inventory

    Molecular Analysis of Human Spermatozoa: Potential for Infertility Research and Screening
    David Miller1, David Dix2, Robert Reid3, Susan Wykes3 and Stephen Krawetz3
    1Reproductive Biology Group, University of Leeds, UK
    2Reproductive Toxicology Division, U.S. Environmenta...

  11. ANALYSIS OR THE POTENTIAL SPERM BIOMARKER, SP22, IN HUMAN SEMEN

    EPA Science Inventory

    ANALYSIS OF THE POTENTIAL SPERM BIOMARKER SP22 IN HUMAN SEMEN
    Rebecca A. Morris Ph.D.1, Gary R. Klinefelter Ph.D.1, Naomi L. Roberts 1, Juan D. Suarez 1,
    Lillian F. Strader 1, Susan C. Jeffay 1 and Sally D. Perreault Ph.D.1

    1 U.S. EPA / ORD / National Health a...

  12. The Human Potential Movement: Forms of Body/Movement/Nonverbal Experiencing.

    ERIC Educational Resources Information Center

    Caldwell, Stratton F.

    A social, humanistic movement has emerged which focuses on the desire of many affluent and advantaged citizens for personal, interpersonal, transpersonal, and organizational growth. It has been termed the "Human Potential Movement." Growth centers, which emphasize the integrated totality of the person, have developed all over the United States and…

  13. Conditioned Fear Extinction and Reinstatement in a Human Fear-Potentiated Startle Paradigm

    ERIC Educational Resources Information Center

    Norrholm, Seth D.; Jovanovic, Tanja; Vervliet, Bram; Myers, Karyn M.; Davis, Michael; Rothbaum, Barbara O.; Duncan, Erica J.

    2006-01-01

    The purpose of this study was to analyze fear extinction and reinstatement in humans using fear-potentiated startle. Participants were fear conditioned using a simple discrimination procedure with colored lights as the conditioned stimuli (CSs) and an airblast to the throat as the unconditioned stimulus (US). Participants were extinguished 24 h…

  14. AN EVALUATION OF THE HUMAN CARCINOGENIC POTENTIAL OF ETHYLENE GLYCOL BUTYL ETHER (EGBE)

    EPA Science Inventory

    Background

    The position paper, An Evaluation of the Human Carcinogenic Potential of Ethylene Glycol Butyl Ether, was developed in support of the Agency's evaluation of a petition from the...

  15. We Are Each Like the Unicorn, Unique and Rare: Human Individual Potentialities.

    ERIC Educational Resources Information Center

    Kyrene Elementary School District 28, Tempe, AZ.

    The proposed gifted and talented program for grades K-8 of the Kyrene School District (Tempe, Arizona) is described. It is explained that the program is based on a philosophy emphasizing human individual potentialities. The curriculum is said to be personalized, utilizing a seminar-resource center approach. Characteristics of exceptionally…

  16. Cocaine exposure impairs multilineage hematopoiesis of human hematopoietic progenitor cells mediated by the sigma-1 receptor [corrected].

    PubMed

    Nixon, Christopher C; Schwartz, Brandon H; Dixit, Dhaval; Zack, Jerome A; Vatakis, Dimitrios N

    2015-01-01

    Prenatal exposure to cocaine is a significant source of fetal and neonatal developmental defects. While cocaine associated neurological and cardiac pathologies are well-documented, it is apparent that cocaine use has far more diverse physiological effects. It is known that in some cell types, the sigma-1 receptor mediates many of cocaine's cellular effects. Here we present a novel and concise investigation into the mechanism that underlies cocaine associated hematopoietic pathology. Indeed, this is the first examination of the effects of cocaine on hematopoiesis. We show that cocaine impairs multilineage hematopoiesis from human progenitors from multiple donors and tissue types. We go on to present the first demonstration of the expression of the sigma-1 receptor in human CD34 + human hematopoietic stem/progenitor cells. Furthermore, we demonstrate that these cocaine-induced hematopoietic defects can be reversed through sigma-1 receptor blockade. PMID:25728014

  17. Probiotic potential of Lactobacillus strains with antimicrobial activity against some human pathogenic strains.

    PubMed

    Shokryazdan, Parisa; Sieo, Chin Chin; Kalavathy, Ramasamy; Liang, Juan Boo; Alitheen, Noorjahan Banu; Faseleh Jahromi, Mohammad; Ho, Yin Wan

    2014-01-01

    The objective of this study was to isolate, identify, and characterize some lactic acid bacterial strains from human milk, infant feces, and fermented grapes and dates, as potential probiotics with antimicrobial activity against some human pathogenic strains. One hundred and forty bacterial strains were isolated and, after initial identification and a preliminary screening for acid and bile tolerance, nine of the best isolates were selected and further identified using 16 S rRNA gene sequences. The nine selected isolates were then characterized in vitro for their probiotic characteristics and their antimicrobial activities against some human pathogens. Results showed that all nine isolates belonged to the genus Lactobacillus. They were able to tolerate pH 3 for 3 h, 0.3% bile salts for 4 h, and 1.9 mg/mL pancreatic enzymes for 3 h. They exhibited good ability to attach to intestinal epithelial cells and were not resistant to the tested antibiotics. They also showed good antimicrobial activities against the tested pathogenic strains of humans, and most of them exhibited stronger antimicrobial activity than the reference strain L. casei Shirota. Thus, the nine Lactobacillus strains could be considered as potential antimicrobial probiotic strains against human pathogens and should be further studied for their human health benefits.

  18. Probiotic Potential of Lactobacillus Strains with Antimicrobial Activity against Some Human Pathogenic Strains

    PubMed Central

    Shokryazdan, Parisa; Sieo, Chin Chin; Kalavathy, Ramasamy; Liang, Juan Boo; Alitheen, Noorjahan Banu; Faseleh Jahromi, Mohammad; Ho, Yin Wan

    2014-01-01

    The objective of this study was to isolate, identify, and characterize some lactic acid bacterial strains from human milk, infant feces, and fermented grapes and dates, as potential probiotics with antimicrobial activity against some human pathogenic strains. One hundred and forty bacterial strains were isolated and, after initial identification and a preliminary screening for acid and bile tolerance, nine of the best isolates were selected and further identified using 16 S rRNA gene sequences. The nine selected isolates were then characterized in vitro for their probiotic characteristics and their antimicrobial activities against some human pathogens. Results showed that all nine isolates belonged to the genus Lactobacillus. They were able to tolerate pH 3 for 3 h, 0.3% bile salts for 4 h, and 1.9 mg/mL pancreatic enzymes for 3 h. They exhibited good ability to attach to intestinal epithelial cells and were not resistant to the tested antibiotics. They also showed good antimicrobial activities against the tested pathogenic strains of humans, and most of them exhibited stronger antimicrobial activity than the reference strain L. casei Shirota. Thus, the nine Lactobacillus strains could be considered as potential antimicrobial probiotic strains against human pathogens and should be further studied for their human health benefits. PMID:25105147

  19. Comparative transforming potential of different human papillomaviruses associated with non-melanoma skin cancer

    SciTech Connect

    Massimi, Paola; Thomas, Miranda; Bouvard, Veronique; Ruberto, Irene; Campo, M. Saveria; Tommasino, Massimo; Banks, Lawrence

    2008-02-20

    It is well established that high-risk human papillomaviruses (HPVs) that infect mucosal epithelia are the causative agents of cervical cancer. In contrast, the association of cutaneo-tropic HPV types with the development of non-melanoma skin cancer (NMSC) is less well defined. In this study, we have analysed the in vitro transforming potential of various cutaneous HPV types. Using oncogene cooperation assays with activated ras, we have shown that diverse cutaneous types, including 12, 14, 15, 24, 36 and 49, have significant transforming potential. Interestingly, most of this activity appears to be encoded by the E6 gene product. In contrast, the common HPV-10 exhibits no significant transforming potential in these assays. This difference may be a reflection of different patterns of cellular localization, with transforming E6s being nuclear and non-transforming being cytoplasmic. These results provide molecular support for a role of these viruses in the development of certain human malignancies.

  20. Potential impact of human mitochondrial replacement on global policy regarding germline gene modification.

    PubMed

    Ishii, Tetsuya

    2014-08-01

    Previous discussions regarding human germline gene modification led to a global consensus that no germline should undergo genetic modification. However, the UK Human Fertilisation and Embryology Authority, having conducted at the UK Government's request a scientific review and a wide public consultation, provided advice to the Government on the pros and cons of Parliament's lifting a ban on altering mitochondrial DNA content of human oocytes and embryos, so as to permit the prevention of maternal transmission of mitochondrial diseases. In this commentary, relevant ethical and biomedical issues are examined and requirements for proceeding with this novel procedure are suggested. Additionally, potentially significant impacts of the UK legalization on global policy concerning germline gene modification are discussed in the context of recent advances in genome-editing technology. It is concluded that international harmonization is needed, as well as further ethical and practical consideration, prior to the legalization of human mitochondrial replacement.

  1. Gene Therapy: The Potential Applicability of Gene Transfer Technology to the Human Germline

    PubMed Central

    2004-01-01

    The theoretical possibility of applying gene transfer methodologies to the human germline is explored. Transgenic methods for genetically manipulating embryos may in principle be applied to humans. In particular, microinjection of retroviral vector appears to hold the greatest promise, with transgenic primates already obtained from this approach. Sperm-mediated gene transfer offers potentially the easiest route to the human germline, however the requisite methodology is presently underdeveloped. Nuclear transfer (cloning) offers an alternative approach to germline genetic modification, however there are major health concerns associated with current nuclear transfer methods. It is concluded that human germline gene therapy remains for all practical purposes a future possibility that must await significant and important advances in gene transfer technology. PMID:15912200

  2. Potential impact of human mitochondrial replacement on global policy regarding germline gene modification.

    PubMed

    Ishii, Tetsuya

    2014-08-01

    Previous discussions regarding human germline gene modification led to a global consensus that no germline should undergo genetic modification. However, the UK Human Fertilisation and Embryology Authority, having conducted at the UK Government's request a scientific review and a wide public consultation, provided advice to the Government on the pros and cons of Parliament's lifting a ban on altering mitochondrial DNA content of human oocytes and embryos, so as to permit the prevention of maternal transmission of mitochondrial diseases. In this commentary, relevant ethical and biomedical issues are examined and requirements for proceeding with this novel procedure are suggested. Additionally, potentially significant impacts of the UK legalization on global policy concerning germline gene modification are discussed in the context of recent advances in genome-editing technology. It is concluded that international harmonization is needed, as well as further ethical and practical consideration, prior to the legalization of human mitochondrial replacement. PMID:24832374

  3. The N2-P3 complex of the evoked potential and human performance

    NASA Technical Reports Server (NTRS)

    Odonnell, Brian F.; Cohen, Ronald A.

    1988-01-01

    The N2-P3 complex and other endogenous components of human evoked potential provide a set of tools for the investigation of human perceptual and cognitive processes. These multidimensional measures of central nervous system bioelectrical activity respond to a variety of environmental and internal factors which have been experimentally characterized. Their application to the analysis of human performance in naturalistic task environments is just beginning. Converging evidence suggests that the N2-P3 complex reflects processes of stimulus evaluation, perceptual resource allocation, and decision making that proceed in parallel, rather than in series, with response generation. Utilization of these EP components may provide insights into the central nervous system mechanisms modulating task performance unavailable from behavioral measures alone. The sensitivity of the N2-P3 complex to neuropathology, psychopathology, and pharmacological manipulation suggests that these components might provide sensitive markers for the effects of environmental stressors on the human central nervous system.

  4. Restricting the above ground sink corrects the root/shoot ratio and substantially boosts the yield potential per panicle in field-grown rice (Oryza sativa L.).

    PubMed

    Nada, Reham M; Abogadallah, Gaber M

    2016-04-01

    Rice has shallow, weak roots, but it is unknown how much increase in yield potential could be achieved if the root/shoot ratio is corrected. Removing all tillers except the main one, in a japonica (Sakha 101) and an indica (IR64) rice cultivar, instantly increased the root/shoot ratio from 0.21 to 1.16 in Sakha 101 and from 0.16 to 1.46 in IR64. Over 30 days after detillering, the root/shoot ratios of the detillered plants decreased to 0.49 in Sakha 101 and 0.46 in IR64 but remained significantly higher than in the controls. The detillered plants showed two- or fourfold increase in the main tiller fresh weight, as a consequence of more positive midday leaf relative water content (RWC), and consistently higher rates of stomatal conductance and photosynthesis, but not transpiration, compared with the controls. The enhanced photosynthesis in Sakha 101 after detillering resulted from both improved water status and higher Rubisco contents whereas in IR64, increasing the Rubisco content did not contribute to improving photosynthesis. Detillering did not increase the carbohydrate contents of leaves but prevented starch depletion at the end of grain filling. The leaf protein content during vegetative and reproductive stages, the grain filling rate, the number of filled grains per panicle were greatly improved, bringing about 38.3 and 35.9% increase in the harvested grain dry weight per panicle in Sakha 101 and IR64, respectively. We provide evidence that improving the root performance by increasing the root/shoot ratio would eliminate the current limitations to photosynthesis and growth in rice. PMID:26296302

  5. Restricting the above ground sink corrects the root/shoot ratio and substantially boosts the yield potential per panicle in field-grown rice (Oryza sativa L.).

    PubMed

    Nada, Reham M; Abogadallah, Gaber M

    2016-04-01

    Rice has shallow, weak roots, but it is unknown how much increase in yield potential could be achieved if the root/shoot ratio is corrected. Removing all tillers except the main one, in a japonica (Sakha 101) and an indica (IR64) rice cultivar, instantly increased the root/shoot ratio from 0.21 to 1.16 in Sakha 101 and from 0.16 to 1.46 in IR64. Over 30 days after detillering, the root/shoot ratios of the detillered plants decreased to 0.49 in Sakha 101 and 0.46 in IR64 but remained significantly higher than in the controls. The detillered plants showed two- or fourfold increase in the main tiller fresh weight, as a consequence of more positive midday leaf relative water content (RWC), and consistently higher rates of stomatal conductance and photosynthesis, but not transpiration, compared with the controls. The enhanced photosynthesis in Sakha 101 after detillering resulted from both improved water status and higher Rubisco contents whereas in IR64, increasing the Rubisco content did not contribute to improving photosynthesis. Detillering did not increase the carbohydrate contents of leaves but prevented starch depletion at the end of grain filling. The leaf protein content during vegetative and reproductive stages, the grain filling rate, the number of filled grains per panicle were greatly improved, bringing about 38.3 and 35.9% increase in the harvested grain dry weight per panicle in Sakha 101 and IR64, respectively. We provide evidence that improving the root performance by increasing the root/shoot ratio would eliminate the current limitations to photosynthesis and growth in rice.

  6. An intact PDZ motif is essential for correct P2Y12 purinoceptor traffic in human platelets.

    PubMed

    Nisar, Shaista; Daly, Martina E; Federici, Augusto B; Artoni, Andrea; Mumford, Andrew D; Watson, Stephen P; Mundell, Stuart J

    2011-11-17

    The platelet P2Y(12) purinoceptor (P2Y(12)R), which plays a crucial role in hemostasis, undergoes internalization and subsequent recycling to maintain receptor responsiveness, processes that are essential for normal platelet function. Here, we observe that P2Y(12)R function is compromised after deletion or mutation of the 4 amino acids at the extreme C-terminus of this receptor (ETPM), a putative postsynaptic density 95/disc large/zonula occludens-1 (PDZ)-binding motif. In cell line models, removal of this sequence or mutation of one of its core residues (P341A), attenuates receptor internalization and receptor recycling back to the membrane, thereby blocking receptor resensitization. The physiologic significance of these findings in the regulation of platelet function is shown by identification of a patient with a heterozygous mutation in the PDZ binding sequence of their P2Y(12)R (P341A) that is associated with reduced expression of the P2Y(12)R on the cell surface. Importantly, platelets from this subject showed significantly compromised P2Y(12)R recycling, emphasizing the importance of the extreme C-terminus of this receptor to ensure correct receptor traffic. PMID:21937696

  7. Correction of human phospholamban R14del mutation associated with cardiomyopathy using targeted nucleases and combination therapy

    PubMed Central

    Karakikes, Ioannis; Stillitano, Francesca; Nonnenmacher, Mathieu; Tzimas, Christos; Sanoudou, Despina; Termglinchan, Vittavat; Kong, Chi-Wing; Rushing, Stephanie; Hansen, Jens; Ceholski, Delaine; Kolokathis, Fotis; Kremastinos, Dimitrios; Katoulis, Alexandros; Ren, Lihuan; Cohen, Ninette; Gho, Johannes M.I.H.; Tsiapras, Dimitrios; Vink, Aryan; Wu, Joseph C.; Asselbergs, Folkert W.; Li, Ronald A.; Hulot, Jean-Sebastien; Kranias, Evangelia G.; Hajjar, Roger J.

    2015-01-01

    A number of genetic mutations is associated with cardiomyopathies. A mutation in the coding region of the phospholamban (PLN) gene (R14del) is identified in families with hereditary heart failure. Heterozygous patients exhibit left ventricular dilation and ventricular arrhythmias. Here we generate induced pluripotent stem cells (iPSCs) from a patient harbouring the PLN R14del mutation and differentiate them into cardiomyocytes (iPSC-CMs). We find that the PLN R14del mutation induces Ca2+ handling abnormalities, electrical instability, abnormal cytoplasmic distribution of PLN protein and increases expression of molecular markers of cardiac hypertrophy in iPSC-CMs. Gene correction using transcription activator-like effector nucleases (TALENs) ameliorates the R14del-associated disease phenotypes in iPSC-CMs. In addition, we show that knocking down the endogenous PLN and simultaneously expressing a codon-optimized PLN gene reverses the disease phenotype in vitro. Our findings offer novel strategies for targeting the pathogenic mutations associated with cardiomyopathies. PMID:25923014

  8. Genesis & the Human Ribcage: An Opportunity to Correct a Misconception & Introduce an Evolution Lesson into the Anatomy Class

    ERIC Educational Resources Information Center

    Senter, Phil

    2013-01-01

    Many anatomy students begin the course with a misconception that human males and females do not have the same number of ribs. At the root of that misconception is Genesis 2:21-22, in which God removes a rib from Adam to make Eve. Removal of a body part is a surgical procedure, and one does not pass on the results of surgery to one's offspring. The…

  9. Vestibular evoked potentials with short and middle latencies recorded in humans.

    PubMed

    Leibner, E; Elidan, J; Freeman, S; Sela, M; Nitzan, M; Sohmer, H

    1990-01-01

    Following success in recording short latency vestibular evoked potentials in experimental animals, we have succeeded in our attempts to record such potentials in human subjects. The stimuli were repetitive, short steps of high intensity angular acceleration (10,000 degrees/sec2) with short rise times which would synchronously activate many neurons of the vestibular pathway. Stringent control procedures ensured that the recorded activity was not an artefact. Short latency vestibular evoked potentials were recorded in 10 normal subjects with peak latencies of 3.5, 6.0 and 8.4 msec and amplitudes of 0.5 microV. Middle latency potentials were also recorded with latencies of 8.8, 18.8 and 26.8 msec and amplitudes of 15 microV. These responses were absent in a cadaver and in patients with bilateral dead labyrinths. In normal subjects, these vestibular evoked potentials were not affected by white noise. In conclusion, short and middle latency vestibular evoked potentials were recorded in normal human subjects. PMID:2289418

  10. Human hormone-sensitive lipase (HSL): expression in white fat corrects the white adipose phenotype of HSL-deficient mice.

    PubMed

    Fortier, Mélanie; Soni, Krishnakant; Laurin, Nancy; Wang, Shu Pei; Mauriège, Pascale; Jirik, Frank R; Mitchell, Grant A

    2005-09-01

    In white adipose tissue (WAT), hormone-sensitive lipase (HSL) can mediate lipolysis, a central pathway in obesity and diabetes. Gene-targeted HSL-deficient (HSL-/-) mice with no detectable HSL peptide or activity (measured as cholesteryl esterase) have WAT abnormalities, including low mass, marked heterogeneity of cell diameter, increased diacylglycerol content, and low beta-adrenergic stimulation of adipocyte lipolysis. Three transgenic mouse strains preferentially expressing human HSL in WAT were bred to a HSL-/- background. One, HSL-/- N, expresses normal human HSL (41.3 +/- 9.1% of normal activity); two express a serine-to-alanine mutant (S554A) initially hypothesized to be constitutively active: HSL-/- ML, 50.3 +/- 12.3% of normal, and HSL-/- MH, 69.8 +/- 15.8% of normal. In WAT, HSL-/- N mice resembled HSL+/+ controls in WAT mass, histology, diacylglyceride content, and lipolytic response to beta-adrenergic agents. In contrast, HSL-/- ML and HSL-/- MH mice resembled nontransgenic HSL-/- mice, except that diacylglycerol content and perirenal and inguinal WAT masses approached normal in HSL-/- MH mice. Therefore, 1) WAT expression of normal human HSL markedly improves HSL-/- WAT biochemically, physiologically, and morphologically; 2) similar levels of S554A HSL have a low physiological effect despite being active in vitro; and 3) diacylglycerol accumulation is not essential for the development of the characteristic WAT pathology of HSL-/- mice.

  11. The potential for snow to supply human water demand in the present and future

    NASA Astrophysics Data System (ADS)

    Mankin, Justin S.; Viviroli, Daniel; Singh, Deepti; Hoekstra, Arjen Y.; Diffenbaugh, Noah S.

    2015-11-01

    Runoff from snowmelt is regarded as a vital water source for people and ecosystems throughout the Northern Hemisphere (NH). Numerous studies point to the threat global warming poses to the timing and magnitude of snow accumulation and melt. But analyses focused on snow supply do not show where changes to snowmelt runoff are likely to present the most pressing adaptation challenges, given sub-annual patterns of human water consumption and water availability from rainfall. We identify the NH basins where present spring and summer snowmelt has the greatest potential to supply the human water demand that would otherwise be unmet by instantaneous rainfall runoff. Using a multi-model ensemble of climate change projections, we find that these basins—which together have a present population of ∼2 billion people—are exposed to a 67% risk of decreased snow supply this coming century. Further, in the multi-model mean, 68 basins (with a present population of >300 million people) transition from having sufficient rainfall runoff to meet all present human water demand to having insufficient rainfall runoff. However, internal climate variability creates irreducible uncertainty in the projected future trends in snow resource potential, with about 90% of snow-sensitive basins showing potential for either increases or decreases over the near-term decades. Our results emphasize the importance of snow for fulfilling human water demand in many NH basins, and highlight the need to account for the full range of internal climate variability in developing robust climate risk management decisions.

  12. A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral

    PubMed Central

    Smith, Claire M.; Scott, Paul D.; O’Callaghan, Christopher; Easton, Andrew J.; Dimmock, Nigel J.

    2016-01-01

    Defective interfering (DI) viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8) was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1); it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral. PMID:27556481

  13. A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral.

    PubMed

    Smith, Claire M; Scott, Paul D; O'Callaghan, Christopher; Easton, Andrew J; Dimmock, Nigel J

    2016-01-01

    Defective interfering (DI) viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8) was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1); it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral. PMID:27556481

  14. PKC-mediated potentiation of morphine analgesia by St. John's Wort in rodents and humans.

    PubMed

    Galeotti, Nicoletta; Farzad, Mersedeh; Bianchi, Enrica; Ghelardini, Carla

    2014-01-01

    Our purpose was to combine the use of morphine with clinically available inhibitors of protein kinase C (PKC), finally potentiating morphine analgesia in humans. Thermal tests were performed in rodents and humans previously administered with acute or chronic morphine combined or not with increasing doses of the PKC-blocker St. John's Wort (SJW) or its main component hypericin. Phosphorylation of the γ subunit of PKC enzyme was assayed by western blotting in the periaqueductal grey matter (PAG) from rodents co-administered with morphine and hypericin and was prevented in rodent PAG by SJW or hypericin co-administration with morphine, inducing a potentiation of morphine analgesia in thermal pain. The score of pain assessment in healthy volunteers were decreased by 40% when morphine was co-administered with SJW at a dose largely below those used to obtain an antidepressant or analgesic effect in both rodents and humans. The SJW/hypericin potentiating effect lasted in time and preserved morphine analgesia in tolerant mice. Our findings indicate that, in clinical practice, SJW could reduce the dose of morphine obtaining the same analgesic effect. Therefore, SJW and one of its main components, hypericin, appear ideal to potentiate morphine-induced analgesia.

  15. Regenerative potential of human schneiderian membrane: progenitor cells and epithelial-mesenchymal transition.

    PubMed

    Derjac-Aramă, A I; Sarafoleanu, C; Manea, C M; Nicolescu, M I; Vrapciu, A D; Rusu, M C

    2015-12-01

    An innate osteogenic potential of the Schneiderian membrane (SM) is progressively assessed in studies ranging from non-human species to human subjects. It has relevance for endosteal placement and osseointegration. Nestin-expressing osteogenic progenitor cells are allegedly involved in bone formation and remodelling. Nestin phenotype was not assessed previously in human SM. We therefore aimed to fill that particular gap in the literature. Bioptic samples of human adult SM were obtained during surgery from eight adult patients, operated for non-malignant pathologies. Immunohistochemistry on paraffin-embedded tissue samples used primary antibodies against nestin, CD45, CD146, cytokeratin 7 (CK7), and alpha-smooth muscle actin (α-SMA). Nestin expression was consistently found in endothelial cells, and was scarcely encountered in pericytes, putative stromal stem/progenitor cells, as well as in glandular epithelial cells. Moreover, woven bone formation in the periosteal layer of the SM can also be regarded as evidence of the osteogenic potential of this membrane. Nestin and CD45 expression in cells of the primary bone supports the osteogenic potential of SM nestin-expressing cells and a possible involvement of hematopoietic stem cells in maxillary sinus floor remodeling. CD146, a known inducer of epithelial-mesenchymal transition (EMT), was expressed in epithelia, as was CK7. Isolated stromal cells were found expressing CD146, CK7 and α-SMA, suggesting that regenerative processes happening in the SM may also involve processes of EMT which generate stem/progenitor cells. This study provides additional evidence for the regenerative potential of the Schneiderian membrane and identifies potential roles for cells of its stem niche in osteogenesis. PMID:26414809

  16. Jitter Correction

    NASA Technical Reports Server (NTRS)

    Waegell, Mordecai J.; Palacios, David M.

    2011-01-01

    Jitter_Correct.m is a MATLAB function that automatically measures and corrects inter-frame jitter in an image sequence to a user-specified precision. In addition, the algorithm dynamically adjusts the image sample size to increase the accuracy of the measurement. The Jitter_Correct.m function takes an image sequence with unknown frame-to-frame jitter and computes the translations of each frame (column and row, in pixels) relative to a chosen reference frame with sub-pixel accuracy. The translations are measured using a Cross Correlation Fourier transformation method in which the relative phase of the two transformed images is fit to a plane. The measured translations are then used to correct the inter-frame jitter of the image sequence. The function also dynamically expands the image sample size over which the cross-correlation is measured to increase the accuracy of the measurement. This increases the robustness of the measurement to variable magnitudes of inter-frame jitter

  17. In vitro cardiomyogenic potential of human umbilical vein-derived mesenchymal stem cells

    SciTech Connect

    Kadivar, Mehdi; Khatami, Shohreh . E-mail: khatamibiochem@yahoo.com; Mortazavi, Yousef; Shokrgozar, Mohammad Ali; Taghikhani, Mohammad; Soleimani, Masoud

    2006-02-10

    Cardiomyocyte loss in the ischemically injured human heart often leads to irreversible defects in cardiac function. Recently, cellular cardiomyoplasty with mesenchymal stem cells, which are multipotent cells with the ability to differentiate into specialized cells under appropriate stimuli, has emerged as a new approach for repairing damaged myocardium. In the present study, the potential of human umbilical cord-derived mesenchymal stem cells to differentiate into cells with characteristics of cardiomyocyte was investigated. Mesenchymal stem cells were isolated from endothelial/subendothelial layers of the human umbilical cords using a method similar to that of human umbilical vein endothelial cell isolation. Isolated cells were characterized by transdifferentiation ability to adipocytes and osteoblasts, and also with flow cytometry analysis. After treatment with 5-azacytidine, the human umbilical cord-derived mesenchymal stem cells were morphologically transformed into cardiomyocyte-like cells and expressed cardiac differentiation markers. During the differentiation, cells were monitored by a phase contrast microscope and their morphological changes were demonstrated. Immunostaining of the differentiated cells for sarcomeric myosin (MF20), desmin, cardiac troponin I, and sarcomeric {alpha}-actinin was positive. RT-PCR analysis showed that these differentiated cells express cardiac-specific genes. Transmission electron microscopy revealed a cardiomyocyte-like ultrastructure and typical sarcomers. These observations confirm that human umbilical cord-derived mesenchymal stem cells can be chemically transformed into cardiomyocytes and can be considered as a source of cells for cellular cardiomyoplasty.

  18. Influence of the oxygen microenvironment on the proangiogenic potential of human endothelial colony forming cells.

    PubMed

    Decaris, Martin L; Lee, Chang I; Yoder, Mervin C; Tarantal, Alice F; Leach, J Kent

    2009-01-01

    Therapeutic angiogenesis is a promising strategy to promote the formation of new or collateral vessels for tissue regeneration and repair. Since changes in tissue oxygen concentrations are known to stimulate numerous cell functions, these studies have focused on the oxygen microenvironment and its role on the angiogenic potential of endothelial cells. We analyzed the proangiogenic potential of human endothelial colony-forming cells (hECFCs), a highly proliferative population of circulating endothelial progenitor cells, and compared outcomes to human dermal microvascular cells (HMVECs) under oxygen tensions ranging from 1% to 21% O2, representative of ischemic or healthy tissues and standard culture conditions. Compared to HMVECs, hECFCs (1) exhibited significantly greater proliferation in both ischemic conditions and ambient air; (2) demonstrated increased migration compared to HMVECs when exposed to chemotactic gradients in reduced oxygen; and (3) exhibited comparable or superior proangiogenic potential in reduced oxygen conditions when assessed using a vessel-forming assay. These data demonstrate that the angiogenic potential of both endothelial populations is influenced by the local oxygen microenvironment. However, hECFCs exhibit a robust angiogenic potential in oxygen conditions representative of physiologic, ischemic, or ambient air conditions, and these findings suggest that hECFCs may be a superior cell source for use in cell-based approaches for the neovascularization of ischemic or engineered tissues.

  19. In vitro fermentability and prebiotic potential of soyabean Okara by human faecal microbiota.

    PubMed

    Pérez-López, E; Cela, D; Costabile, A; Mateos-Aparicio, I; Rupérez, P

    2016-09-01

    At present, there is a huge interest in finding new prebiotics from agrofood industrial waste, such as the soyabean by-product Okara, rich in insoluble dietary fibre. A previous treatment of Okara with high hydrostatic pressure assisted by the food-grade enzyme Ultraflo ® L achieved a 58·2 % increment in its soluble dietary fibre (SDF) contents. Therefore, potential prebiotic effect of both treated and native Okara was assayed using 48 h, pH-controlled, anaerobic batch cultures inoculated with human faecal slurries, which simulate the human gut. Changes in faecal microbiota were evaluated using 16S rRNA-based fluorescence in situ hybridisation, whereas release of SCFA and lactic acid was assessed by HPLC. Both Okara samples exhibited potential prebiotic effects but Okara treated to maximise its SDF content showed higher SCFA plus lactic acid, better growth promotion of beneficial bacteria, including bifidobacteria after 4 and 48 h and lactobacilli after 4 h of fermentation, and a greater inhibition of potentially harmful bacterial groups such as clostridia and Bacteroides. Differences found between fructo-oligosaccharides and Okara substrates could be attributed to the great complexity of Okara's cell wall, which would need longer times to be fermented than other easily digested molecules, thus allowing an extended potential prebiotic effect. These results support an in vitro potential prebiotic effect of Okara.

  20. In vitro fermentability and prebiotic potential of soyabean Okara by human faecal microbiota.

    PubMed

    Pérez-López, E; Cela, D; Costabile, A; Mateos-Aparicio, I; Rupérez, P

    2016-09-01

    At present, there is a huge interest in finding new prebiotics from agrofood industrial waste, such as the soyabean by-product Okara, rich in insoluble dietary fibre. A previous treatment of Okara with high hydrostatic pressure assisted by the food-grade enzyme Ultraflo ® L achieved a 58·2 % increment in its soluble dietary fibre (SDF) contents. Therefore, potential prebiotic effect of both treated and native Okara was assayed using 48 h, pH-controlled, anaerobic batch cultures inoculated with human faecal slurries, which simulate the human gut. Changes in faecal microbiota were evaluated using 16S rRNA-based fluorescence in situ hybridisation, whereas release of SCFA and lactic acid was assessed by HPLC. Both Okara samples exhibited potential prebiotic effects but Okara treated to maximise its SDF content showed higher SCFA plus lactic acid, better growth promotion of beneficial bacteria, including bifidobacteria after 4 and 48 h and lactobacilli after 4 h of fermentation, and a greater inhibition of potentially harmful bacterial groups such as clostridia and Bacteroides. Differences found between fructo-oligosaccharides and Okara substrates could be attributed to the great complexity of Okara's cell wall, which would need longer times to be fermented than other easily digested molecules, thus allowing an extended potential prebiotic effect. These results support an in vitro potential prebiotic effect of Okara. PMID:27469454

  1. Potential impact of antimicrobial resistance in wildlife, environment and human health

    PubMed Central

    Radhouani, Hajer; Silva, Nuno; Poeta, Patrícia; Torres, Carmen; Correia, Susana; Igrejas, Gilberto

    2014-01-01

    Given the significant spatial and temporal heterogeneity in antimicrobial resistance distribution and the factors that affect its evolution, dissemination, and persistence, it is important to highlight that antimicrobial resistance must be viewed as an ecological problem. Monitoring the resistance prevalence of indicator bacteria such as Escherichia coli and enterococci in wild animals makes it possible to show that wildlife has the potential to serve as an environmental reservoir and melting pot of bacterial resistance. These researchers address the issue of antimicrobial-resistant microorganism proliferation in the environment and the related potential human health and environmental impact. PMID:24550896

  2. Prevalence and pathogenic potential of campylobacter isolates from free-living, human-commensal american crows.

    PubMed

    Weis, Allison M; Miller, Woutrina A; Byrne, Barbara A; Chouicha, Nadira; Boyce, Walter M; Townsend, Andrea K

    2014-03-01

    Recent studies have suggested a potential role for wild birds in zoonotic transmission of Campylobacter jejuni, the leading cause of gastroenteritis in humans worldwide. In this study, we detected Campylobacter spp. in 66.9% (85/127) of free-ranging American crows (Corvus brachyrhyncos) sampled in the Sacramento Valley of California in 2012 and 2013. Biochemical testing and sequence analysis of 16S rRNA revealed that 93% of isolates (n = 70) were C. jejuni, with cytolethal distending toxin (CDT) and flagellin A genes detected by PCR in 20% and 46% of the C. jejuni isolates (n = 59), respectively. The high prevalence of C. jejuni, coupled with the occurrence of known virulence markers CDT and flagellin A, demonstrates that crows shed Campylobacter spp. in their feces that are potentially pathogenic to humans. Crows are abundant in urban, suburban, and agricultural settings, and thus further study to determine their role in zoonotic transmission of Campylobacter will inform public health.

  3. Prevalence and Pathogenic Potential of Campylobacter Isolates from Free-Living, Human-Commensal American Crows

    PubMed Central

    Weis, Allison M.; Miller, Woutrina A.; Byrne, Barbara A.; Chouicha, Nadira; Boyce, Walter M.

    2014-01-01

    Recent studies have suggested a potential role for wild birds in zoonotic transmission of Campylobacter jejuni, the leading cause of gastroenteritis in humans worldwide. In this study, we detected Campylobacter spp. in 66.9% (85/127) of free-ranging American crows (Corvus brachyrhyncos) sampled in the Sacramento Valley of California in 2012 and 2013. Biochemical testing and sequence analysis of 16S rRNA revealed that 93% of isolates (n = 70) were C. jejuni, with cytolethal distending toxin (CDT) and flagellin A genes detected by PCR in 20% and 46% of the C. jejuni isolates (n = 59), respectively. The high prevalence of C. jejuni, coupled with the occurrence of known virulence markers CDT and flagellin A, demonstrates that crows shed Campylobacter spp. in their feces that are potentially pathogenic to humans. Crows are abundant in urban, suburban, and agricultural settings, and thus further study to determine their role in zoonotic transmission of Campylobacter will inform public health. PMID:24375131

  4. Robotic Reconnaissance Missions to Small Bodies and Their Potential Contributions to Human Exploration

    NASA Technical Reports Server (NTRS)

    Abell, P. A.; Rivkin, A. S.

    2015-01-01

    Introduction: Robotic reconnaissance missions to small bodies will directly address aspects of NASA's Asteroid Initiative and will contribute to future human exploration. The NASA Asteroid Initiative is comprised of two major components: the Grand Challenge and the Asteroid Mission. The first component, the Grand Challenge, focuses on protecting Earth's population from asteroid impacts by detecting potentially hazardous objects with enough warning time to either prevent them from impacting the planet, or to implement civil defense procedures. The Asteroid Mission involves sending astronauts to study and sample a near- Earth asteroid (NEA) prior to conducting exploration missions of the Martian system, which includes Phobos and Deimos. The science and technical data obtained from robotic precursor missions that investigate the surface and interior physical characteristics of an object will help identify the pertinent physical properties that will maximize operational efficiency and reduce mission risk for both robotic assets and crew operating in close proximity to, or at the surface of, a small body. These data will help fill crucial strategic knowledge gaps (SKGs) concerning asteroid physical characteristics that are relevant for human exploration considerations at similar small body destinations. Small Body Strategic Knowledge Gaps: For the past several years NASA has been interested in identifying the key SKGs related to future human destinations. These SKGs highlight the various unknowns and/or data gaps of targets that the science and engineering communities would like to have filled in prior to committing crews to explore the Solar System. An action team from the Small Bodies Assessment Group (SBAG) was formed specifically to identify the small body SKGs under the direction of the Human Exploration and Operations Missions Directorate (HEOMD), given NASA's recent interest in NEAs and the Martian moons as potential human destinations [1]. The action team

  5. Optimal humanization of 1B4, an anti-CD18 murine monoclonal antibody, is achieved by correct choice of human V-region framework sequences.

    PubMed

    Singer, I I; Kawka, D W; DeMartino, J A; Daugherty, B L; Elliston, K O; Alves, K; Bush, B L; Cameron, P M; Cuca, G C; Davies, P

    1993-04-01

    The murine anti-CD18 mAb 1B4 has been humanized using CDR grafting. Three VH (Gal, Jon, and New) and two VL (Rei and Len) human frameworks, whose selection was based exclusively on their sequence identity with m1B4, were used to construct five human gamma 4/kappa recombinant antibodies: Gal/Rei, Gal/Len, Jon/Rei, and New/Rei, and a "hemichimeric" antibody pairing the VH of m1B4 with grafted Rei. Each of these h1B4 constructs completely inhibited the binding of m1B4 to activated human leukocytes with avidities (IC50) ranging from 1.5 to 8.0 nM, compared to 0.5 nM for m1B4. Replacement of three VH residues in the best VH framework, Gal, with the corresponding m1B4 "packing" (nonsolvent exposed) residues gave an h1B4 (mutant Gal/Rei) with the same avidity as m1B4. Avidity correlated with overall percent identity between the human and murine VH frameworks and, in particular, with conservation of "packing" residues. Rei and Len VL frameworks proved to be interchangeable. Further characterization showed that the Gal/Rei prototype was equipotent to m1B4 in blocking adhesion of polymorphonuclear leukocytes and monocytes to human vascular endothelium in vitro, and polymorphonuclear leukocyte extravasation into C5a-injected rabbit or monkey skin sites. Dual-label immunofluorescence microscopy of bone marrow cells with Gal/Rei h1B4 and m1B4 demonstrated that the fine specificity of the combining sites had not been altered by humanization. Reduced immunogenicity was demonstrated in rhesus monkeys that tolerated weekly treatment with h1B4 for 6 wk, whereas m1B4 induced profound anaphylaxis at 3 wk. Anti-1B4 titers in h1B4-treated rhesus were 50 to 66% lower and developed 1 wk later than in m1B4-treated monkeys. Crucially, the anti-h1B4 antibodies were anti-idiotypic while the anti-m1B4 antibodies were directed against constant and framework regions. We conclude that sequence identity searches are sufficient to identify suitable human frameworks for CDR-grafting of m1B4

  6. Joining of correct and incorrect DNA ends at double-strand breaks produced by high-linear energy transfer radiation in human fibroblasts

    NASA Technical Reports Server (NTRS)

    Lobrich, M.; Cooper, P. K.; Rydberg, B.; Chatterjee, A. (Principal Investigator)

    1998-01-01

    DNA double-strand breaks (DSBs) were measured within a 3.2-Mbp NotI fragment on chromosome 21 of cells of a normal human fibroblast cell line. Correct rejoining of DSBs was followed by measuring reconstitution of the original-size NotI fragment, and this was compared to total rejoining as measured by a conventional pulsed-field gel electrophoresis technique (FAR assay). After 80 Gy of particle irradiations with LETs in the range of 7-150 keV/microm, it was found that the repair kinetics was generally slower after irradiation with high-LET particles compared to X irradiation and that a larger proportion of the breaks remained unrepaired after 24 h. On the other hand, the misrejoining frequency as measured by the difference between correct and total rejoining after 24 h did not change with LET, but was approximately the same for all radiations at this dose, equal to 25-30% of the initial breaks. This result is discussed in relation to formation of chromosomal aberrations, deletion mutations and other biological end points.

  7. Similarity of polygenic profiles limits the potential for elite human physical performance

    PubMed Central

    Williams, Alun G; Folland, Jonathan P

    2008-01-01

    Human physical capability is influenced by many environmental and genetic factors, and it is generally accepted that physical capability phenotypes are highly polygenic. However, the ways in which relevant polymorphisms combine to influence the physical capability of individuals and populations are unknown. Initially, the literature was searched to identify associations between 23 genetic polymorphisms and human endurance phenotypes. Next, typical genotype frequencies of those polymorphisms in the general population were obtained from suitable literature. Using probability calculations, we found only a 0.0005% chance of a single individual in the world having the ‘preferable’ form of all 23 polymorphisms. As the number of DNA variants shown to be associated with human endurance phenotypes continues to increase, the probability of any single individual possessing the ‘preferable’ form of each polymorphism will become even lower. However, with population turnover, the chance of such genetically gifted individuals existing increases. To examine the polygenic endurance potential of a human population, a ‘total genotype score’ (for the 23 polymorphisms) was calculated for each individual within a hypothetical population of 1000 000. There was considerable homogeneity in terms of genetic predisposition to high endurance potential, with 99% of people differing by no more than seven genotypes from the typical profile. Consequently, with population turnover world and Olympic records should improve even without further enhancement of environmental factors, as more ‘advantageous’ polygenic profiles occasionally, though rarely, emerge. More broadly, human potential appears limited by the similarity of polygenic profiles at both the ‘elite sport’ and ‘chronic disorder’ ends of the performance continuum. PMID:17901117

  8. Coupling Between Neuronal Firing, Field Potentials, and fMRI in Human Auditory Cortex

    NASA Astrophysics Data System (ADS)

    Mukamel, Roy; Gelbard, Hagar; Arieli, Amos; Hasson, Uri; Fried, Itzhak; Malach, Rafael

    2005-08-01

    Functional magnetic resonance imaging (fMRI) is an important tool for investigating human brain function, but the relationship between the hemodynamically based fMRI signals in the human brain and the underlying neuronal activity is unclear. We recorded single unit activity and local field potentials in auditory cortex of two neurosurgical patients and compared them with the fMRI signals of 11 healthy subjects during presentation of an identical movie segment. The predicted fMRI signals derived from single units and the measured fMRI signals from auditory cortex showed a highly significant correlation (r = 0.75, P < 10-47). Thus, fMRI signals can provide a reliable measure of the firing rate of human cortical neurons.

  9. Osteoinductive potential of human demineralised bone and a bioceramic in abdominal musculature of the rat.

    PubMed

    Nolan, P; Templeton, P; Mollan, R A; Wilson, D J

    1991-02-01

    Human demineralised cortical bone chips ('bank' bone) and a particulate bioceramic (20% hydroxyapatite: 80% tricalcium phosphate) were implanted into muscle pouches in the rat abdominal wall. Combined implants of both bone and bioceramic were also made. The implants were examined histologically at thirty day intervals over a three month period. The results showed that the hydroxyapatite: tricalcium phosphate bioceramic was not resorbed and did not induce bone formation when implanted alone or in combination with human demineralised bone. In contrast the bank bone was osteogenic but, even at three months, bone formation was sparse. These results are in accord with recent findings that the use of xenogeneic model systems to evaluate the osteogenic potential of human bone is limited.

  10. Characterization and Angiogenic Potential of Human Neonatal and Infant Thymus Mesenchymal Stromal Cells

    PubMed Central

    Wang, Shuyun; Mundada, Lakshmi; Johnson, Sean; Wong, Joshua; Witt, Russell; Ohye, Richard G.

    2015-01-01

    Resident mesenchymal stromal cells (MSCs) are involved in angiogenesis during thymus regeneration. We have previously shown that MSCs can be isolated from enzymatically digested human neonatal and infant thymus tissue that is normally discarded during pediatric cardiac surgical procedures. In this paper, we demonstrate that thymus MSCs can also be isolated by explant culture of discarded thymus tissue and that these cells share many of the characteristics of bone marrow MSCs. Human neonatal thymus MSCs are clonogenic, demonstrate exponential growth in nearly 30 population doublings, have a characteristic surface marker profile, and express pluripotency genes. Furthermore, thymus MSCs have potent proangiogenic behavior in vitro with sprout formation and angiogenic growth factor production. Thymus MSCs promote neoangiogenesis and cooperate with endothelial cells to form functional human blood vessels in vivo. These characteristics make thymus MSCs a potential candidate for use as an angiogenic cell therapeutic agent and for vascularizing engineered tissues in vitro. PMID:25713463

  11. Maximum recovery potential of human tumor cells may predict clinical outcome in radiotherapy

    SciTech Connect

    Weichselbaum, R.R.; Beckett, M.

    1987-05-01

    We studied inherent radiosensitivity/resistance (D0), ability to accumulate sublethal damage (n) and repair of potentially lethal damage (PLDR) in established human tumor cell lines as well as early passage human tumor cell lines derived from patients with known outcome following radiotherapy. Survival 24 hrs after treatment of human tumor cells with X rays in plateau phase cultures is a function of initial damage (D0, n), as well as recovery over 24 hrs (PLDR). A surviving fraction greater than .1 24 hrs following treatment with 7 Gy in plateau phase cultures is associated with tumor cell types (melanoma, osteosarcoma) with a high probability of radiotherapy failure or tumor cells derived from patients who actually failed radiotherapy. Therefore, total cellular recovery following radiation may be an important determinant of radiocurability. Accurate assays of radiotherapy outcome may need to account for all these radiobiological parameters.

  12. Characterization and angiogenic potential of human neonatal and infant thymus mesenchymal stromal cells.

    PubMed

    Wang, Shuyun; Mundada, Lakshmi; Johnson, Sean; Wong, Joshua; Witt, Russell; Ohye, Richard G; Si, Ming-Sing

    2015-04-01

    Resident mesenchymal stromal cells (MSCs) are involved in angiogenesis during thymus regeneration. We have previously shown that MSCs can be isolated from enzymatically digested human neonatal and infant thymus tissue that is normally discarded during pediatric cardiac surgical procedures. In this paper, we demonstrate that thymus MSCs can also be isolated by explant culture of discarded thymus tissue and that these cells share many of the characteristics of bone marrow MSCs. Human neonatal thymus MSCs are clonogenic, demonstrate exponential growth in nearly 30 population doublings, have a characteristic surface marker profile, and express pluripotency genes. Furthermore, thymus MSCs have potent proangiogenic behavior in vitro with sprout formation and angiogenic growth factor production. Thymus MSCs promote neoangiogenesis and cooperate with endothelial cells to form functional human blood vessels in vivo. These characteristics make thymus MSCs a potential candidate for use as an angiogenic cell therapeutic agent and for vascularizing engineered tissues in vitro.

  13. Potential antitumor therapeutic strategies of human amniotic membrane and amniotic fluid-derived stem cells.

    PubMed

    Kang, N-H; Hwang, K-A; Kim, S U; Kim, Y-B; Hyun, S-H; Jeung, E-B; Choi, K-C

    2012-08-01

    As stem cells are capable of self-renewal and can generate differentiated progenies for organ development, they are considered as potential source for regenerative medicine and tissue replacement after injury or disease. Along with this capacity, stem cells have the therapeutic potential for treating human diseases including cancers. According to the origins, stem cells are broadly classified into two types: embryonic stem cells (ESCs) and adult stem cells. In terms of differentiation potential, ESCs are pluripotent and adult stem cells are multipotent. Amnion, which is a membranous sac that contains the fetus and amniotic fluid and functions in protecting the developing embryo during gestation, is another stem cell source. Amnion-derived stem cells are classified as human amniotic membrane-derived epithelial stem cells, human amniotic membrane-derived mesenchymal stem cells and human amniotic fluid-derived stem cells. They are in an intermediate stage between pluripotent ESCs and lineage-restricted adult stem cells, non-tumorigenic, and contribute to low immunogenicity and anti-inflammation. Furthermore, they are easily available and do not cause any controversial issues in their recovery and applications. Not only are amnion-derived stem cells applicable in regenerative medicine, they have anticancer capacity. In non-engineered stem cells transplantation strategies, amnion-derived stem cells effectively target the tumor and suppressed the tumor growth by expressing cytotoxic cytokines. Additionally, they also have a potential as novel delivery vehicles transferring therapeutic genes to the cancer formation sites in gene-directed enzyme/prodrug combination therapy. Owing to their own advantageous properties, amnion-derived stem cells are emerging as a new candidate in anticancer therapy.

  14. Enhancement of the amplitude of somatosensory evoked potentials following magnetic pulse stimulation of the human brain.

    PubMed

    Seyal, M; Browne, J K; Masuoka, L K; Gabor, A J

    1993-01-01

    In this study we have demonstrated an enhancement of cortically generated wave forms of the somatosensory evoked potential (SEP) following magnetic pulse stimulation of the human brain. Subcortically generated activity was unaltered. The enhancement of SEP amplitude was greatest when the median nerve was stimulated 30-70 msec following magnetic pulse stimulation over the contralateral parietal scalp. We posit that the enhancement of the SEP is the result of synchronization of pyramidal cells in the sensorimotor cortex resulting from the magnetic pulse.

  15. Psychiatry and human rights: a difficult relationship, but with a growing potential.

    PubMed

    Jarab, Jan

    2015-01-01

    Persons with psychosocial disabilities (mental health problems) are under the protection of the new United Nations Convention on Rights of Persons with Disabilities (CRPD). The CRPD brings a human rights-based approach to disability: it challenges paternalistic views by emphasizing the person as a rights-holder, an active subject, and not just a passive object of care. It also represents a challenge to mainstream human rights movements and mechanisms who have long paid insufficient attention to human rights of persons with (psychosocial) disabilities. It is increasingly understood that human rights of persons with psychosocial disabilities (mental health problems) should not be seen in the narrow perspective, as if the only issue was the most controversial one, that is, deprivation of liberty. In many areas, reform-minded psychiatrists have themselves initiated human rights-friendly reforms. For instance, efforts to implement article 19 of the CRPD—independent living and inclusion in the community—are increasingly becoming part of the mainstream in mental health care. There is potential for further synergy between mental health professionals and human rights activists in looking at the whole range of civil, political, economic, and social rights listed in the Universal Declaration of Human Rights—realizing that all these rights apply also to persons with psychosocial disabilities, and working together towards removing real-life obstacles to their enjoyment.The building of bridges between the two different types of expertise should be encouraged. In this regard, psychiatry would benefit from more cooperation across borders as well as with international human rights bodies, non-governmental organizations and persons with psychosocial disabilities themselves PMID:26464182

  16. Psychiatry and human rights: a difficult relationship, but with a growing potential.

    PubMed

    Jarab, Jan

    2015-01-01

    Persons with psychosocial disabilities (mental health problems) are under the protection of the new United Nations Convention on Rights of Persons with Disabilities (CRPD). The CRPD brings a human rights-based approach to disability: it challenges paternalistic views by emphasizing the person as a rights-holder, an active subject, and not just a passive object of care. It also represents a challenge to mainstream human rights movements and mechanisms who have long paid insufficient attention to human rights of persons with (psychosocial) disabilities. It is increasingly understood that human rights of persons with psychosocial disabilities (mental health problems) should not be seen in the narrow perspective, as if the only issue was the most controversial one, that is, deprivation of liberty. In many areas, reform-minded psychiatrists have themselves initiated human rights-friendly reforms. For instance, efforts to implement article 19 of the CRPD—independent living and inclusion in the community—are increasingly becoming part of the mainstream in mental health care. There is potential for further synergy between mental health professionals and human rights activists in looking at the whole range of civil, political, economic, and social rights listed in the Universal Declaration of Human Rights—realizing that all these rights apply also to persons with psychosocial disabilities, and working together towards removing real-life obstacles to their enjoyment.The building of bridges between the two different types of expertise should be encouraged. In this regard, psychiatry would benefit from more cooperation across borders as well as with international human rights bodies, non-governmental organizations and persons with psychosocial disabilities themselves

  17. Potential of decursin to inhibit the human cytochrome P450 2J2 isoform.

    PubMed

    Lee, Boram; Wu, Zhexue; Sung, Sang Hyun; Lee, Taeho; Song, Kyung-Sik; Lee, Min Young; Liu, Kwang-Hyeon

    2014-08-01

    CYP2J2 enzyme is highly expressed in human tumors and carcinoma cell lines, and epoxyeicosatrienoic acids, CYP2J2-mediated metabolites, have been implicated in the pathologic development of human cancers. To identify a CYP2J2 inhibitor, 50 natural products obtained from plants were screened using astemizole as a CYP2J2 probe substrate in human liver microsomes. Of these, decursin noncompetitively inhibited CYP2J2-mediated astemizole O-demethylation and terfenadine hydroxylation activities with Ki values of 8.34 and 15.8μM, respectively. It also showed cytotoxic effects against human hepatoma HepG2 cells in a dose-dependent manner while it did not show cytotoxicity against mouse hepatocytes. The present data suggest that decursin is a potential candidate for further evaluation for its CYP2J2 targeting anti-cancer activities. Studies are currently underway to test decursin as a potential therapeutic agent for cancer. PMID:24788058

  18. White-tailed deer (Odocoileus virginianus) as a potential sentinel for human Lyme disease in Indiana.

    PubMed

    Raizman, E A; Holland, J D; Shukle, J T

    2013-05-01

    We assessed the potential of white-tailed deer (WTD) (Odocoileus virginianus) to be a sentinel for human cases of Lyme disease (LD) in Indiana using location data from a 3-year survey of approximately 3400 hunted deer with associated tick Ixodes scapularis and Borrelia burgdorferi (Bb) data. Data on human LD cases at the county level were obtained from the Indiana Department of Health. All data were assigned to county centroids to match the resolution of the LD data before creating optimized trend surfaces for LD incidence, hunted deer count, Ixodes scapularis and Bb prevalence. To determine whether LD was spatially associated with the areas of high densities of deer, deer with Ixodes scapularis and deer with ticks infected with Bb, we used spatial analysis with distance indices (SADIE). The SADIE analysis found significant spatial association between LD and the distribution of three organismal predictor variables, that is, WTD, Ixodes ticks and Bb. Lyme disease incident rate varied between 0.08 cases per 10,000 habitants (Johnson county) and 5.9 cases per 10,000 habitants (Warren county). In conclusion, WTD can be used as an accurate and cost-effective sentinel for human LD. This method will permit public health workers to identify potentially endemic areas independently of human case reports.

  19. Ground-nesting marine birds and potential for human disturbance in Glacier Bay National Park

    USGS Publications Warehouse

    Arimitsu, M.L.; Romano, Marc D.; Piatt, J.F.; Piatt, J.F.; Gende, S.M.

    2004-01-01

    Glacier Bay National Park and Preserve contains a diverse assemblage of marine birds that use the area for nesting, foraging and molting. The abundance and diversity of marine bird species in Glacier Bay is unmatched in the region, due in part to the geomorphic and successional characteristics that result in a wide array of habitat types (Robards and others, 2003). The opportunity for proactive management of these species is unique in Glacier Bay National Park because much of the suitable marine bird nesting habitat occurs in areas designated as wilderness. Ground-nesting marine birds are vulnerable to human disturbance wherever visitors can access nest sites during the breeding season. Human disturbance of nest sites can be significant because intense parental care is required for egg and hatchling survival, and repeated disturbance can result in reduced productivity (Leseberg and others, 2000). Temporary nest desertion by breeding birds in disturbed areas can lead to increased predation on eggs and hatchlings by conspecifics or other predators (Bolduc and Guillemette, 2003). Human disturbance of ground-nesting birds may also affect incubation time and adult foraging success, which in turn can alter breeding success (Verhulst and others, 2001). Furthermore, human activity can potentially cause colony failure when disturbance prevents the initiation of nesting (Hatch, 2002). There is management concern about the susceptibility of breeding birds to disturbance from human activities, but little historical data has been collected on the distribution of ground-nesting marine birds in Glacier Bay. This report summarizes results obtained during two years of a three-year study to determine the distribution of ground-nesting marine birds in Glacier Bay, and the potential for human disturbance of those nesting birds.

  20. Periodontitis promotes the proliferation and suppresses the differentiation potential of human periodontal ligament stem cells.

    PubMed

    Zheng, Wei; Wang, Shi; Wang, Jianguo; Jin, Fang

    2015-10-01

    The aim of the present study was to investigate the periodontitis-associated changes in the number, proliferation and differentiation potential of human periodontal ligament stem cells (PDLSCs). Cultures of human periodontal ligament cells (PDLCs) were established from healthy donors and donors with periodontitis. The numbers of stem cell were characterized using flow cytometry. PDLSCs were isolated from the PDLCs by immunomagnetic bead selection. Colony‑forming abilities, osteogenic and adipogenic potential, gene expression of cementoblast phenotype, alkaline phosphatase activity and in vivo differentiation capacities were then evaluated. Periodontitis caused an increase in the proliferation of PDLSCs and a decrease in the commitment to the osteoblast lineage. This is reflected by changes in the expression of osteoblast markers. When transplanted into immunocompromised mice, PDLSCs from the healthy donors exhibited the capacity to produce cementum PDL‑like structures, whereas, the inflammatory PDLSCs transplants predominantly formed connective tissues. In conclusion, the data from the present study suggest that periodontitis affects the proliferation and differentiation potential of human PDLSCs in vitro and in vivo.

  1. Fluoride-treated bio-resorbable synthetic nonceramic [corrected] hydroxyapatite promotes proliferation and differentiation of human osteoblastic MG-63 cells.

    PubMed

    Ohno, Motofumi; Kimoto, Kazunari; Toyoda, Toshihisa; Kawata, Kazushige; Arakawa, Hirohisa

    2013-04-01

    When resorbable hydroxyapatite (HA) granules, which are used as a bone supplement material, were treated in neutral 4% sodium fluoride (NaF) solution, formation of a reactant resembling calcium fluoride was observed on the surface of the granules. Immediate and slow release of fluoride from fluoridated HA (HA+F) granules was observed after immersion in culture fluid, and the concentration increased over time to 1.25 ± 0.05 ppm F at 0.5 hours, 1.57 ± 0.12 ppm F at 24 hours, and 1.73 ± 0.15 ppm F at 48 hours. On invasion assay, migration of human osteoblast-like MG-63 cells exposed to the released fluoride was confirmed in comparison to the cells incubated with a nonfluoridated control sample (P < .01). In addition, fluoride added to the medium increased MG-63 cell proliferation in a manner dependent on fluoride concentrations up to 2.0 ppm (P < .05). At 5.0 ppm, however, fluoride significantly inhibited cell proliferation (P < .005). Activity of the osteogenic differentiation marker, alkaline phosphatase (ALP), also increased with fluoride after exposure for 1 week, increasing significantly at 1.0 ppm (P < .05). The promotion of MG-63 cell migration and proliferation, as well as increased ALP activity, suggested that fluoride released from the surface of resorbable HA granules, which were fluoridated by prior treatment with neutral 4% NaF solution, can provide a superb method to supply fluoride and promote osteogenic cell differentiation.

  2. Potential human pathogenic bacteria in a mixed urban watershed as revealed by pyrosequencing.

    PubMed

    Ibekwe, A Mark; Leddy, Menu; Murinda, Shelton E

    2013-01-01

    Current microbial source tracking (MST) methods for water depend on testing for fecal indicator bacterial counts or specific marker gene sequences to identify fecal contamination where potential human pathogenic bacteria could be present. In this study, we applied 454 high-throughput pyrosequencing to identify bacterial pathogen DNA sequences, including those not traditionally monitored by MST and correlated their abundances to specific sources of contamination such as urban runoff and agricultural runoff from concentrated animal feeding operations (CAFOs), recreation park area, waste-water treatment plants, and natural sites with little or no human activities. Samples for pyrosequencing were surface water, and sediment collected from 19 sites. A total of 12,959 16S rRNA gene sequences with average length of ≤400 bp were obtained, and were assigned to corresponding taxonomic ranks using ribosomal database project (RDP), Classifier and Greengenes databases. The percent of total potential pathogens were highest in urban runoff water (7.94%), agricultural runoff sediment (6.52%), and Prado Park sediment (6.00%), respectively. Although the numbers of DNA sequence tags from pyrosequencing were very high for the natural site, corresponding percent potential pathogens were very low (3.78-4.08%). Most of the potential pathogenic bacterial sequences identified were from three major phyla, namely, Proteobacteria, Bacteroidetes, and Firmicutes. The use of deep sequencing may provide improved and faster methods for the identification of pathogen sources in most watersheds so that better risk assessment methods may be developed to enhance public health.

  3. Effects of osmotic challenges on membrane potential in human articular chondrocytes from healthy and osteoarthritic cartilage.

    PubMed

    Sánchez, Julio C; López-Zapata, Diego F

    2010-01-01

    Changes in external osmolarity arise from variations in mechanical loads on joints and may affect the homeostasis of chondrocytes, which are the only cell type responsible for matrix turnover. Accordingly, variations in membrane potential may affect cartilage production. The present study assessed the effects of variations in external osmolarity on membrane potential and the possible mechanisms responsible for this response. Membrane potential was measured by the patch clamp whole-cell technique using human articular chondrocytes freshly isolated from healthy and osteoarthritic cartilage. The membrane potential was -39±4 mV in articular human chondrocytes from healthy cartilage and -26±4 mV in those from osteoarthritic cartilage. Increasing the osmolarity produced a reversible hyperpolarization mediated by K+ efflux through BKCa channels in both groups of chondrocytes, but the response in osteoarthritic cells was significantly reduced; no other K+ pathways were involved in this effect. Alternatively, decreasing the osmolarity elicited depolarization in healthy chondrocytes but did not produce any response in chondrocytes from osteoarthritic cartilage. The depolarization was dependent on Na+ influx through Gd3+-sensitive stretch-activated cation channels and was independent of external Ca2+. The differential responses observed in chondrocytes from osteoarthritic cartilage suggest that disregulation on the responses to external osmolarity may be involved in the process that leads to the alterations in the cartilage structure observed in osteoarthritis.

  4. Screening workers for genetic hypersusceptibility: potential ethical, legal, and social implications from the Human Genome Project.

    PubMed

    Wicks, A C; Sever, L E; Harty, R; Gajewski, S W; Marcus-Smith, M

    1999-01-01

    One of the potential outcomes of the Human Genome Project will be the ability to identify individuals who are at increased risk of adverse health effects following exposure to hazardous substances in the workplace because of genetic hypersusceptibility. The ability to identify such individuals is likely to lead to the inclusion of genetic screening in worker protection programs. This technology and its applications will have a number of potential ethical, legal, and social implications. In this commentary, the authors examine five broad topics relating to the use of screening for genetic hypersusceptibility in the workplace: (1) issues of risk; (2) the rationale and legal basis for screening; (3) the privacy concerns of workers; (4) the confidentiality of test results; and (5) potential discrimination. The authors close by suggesting some guidelines for developing policies regarding genetic screening.

  5. An event-related potential component sensitive to images of the human body.

    PubMed

    Thierry, Guillaume; Pegna, Alan J; Dodds, Chris; Roberts, Mark; Basan, Sébastien; Downing, Paul

    2006-08-15

    One of the critical functions of vision is to provide information about other individuals. Neuroimaging experiments examining the cortical regions that analyze the appearance of other people have found partially overlapping networks that respond selectively to human faces and bodies. In event-related potential (ERP) studies, faces systematically elicit a negative component peaking 170 ms after presentation - the N170. To characterize the electrophysiological response to human bodies, we compared the ERPs elicited by faces, bodies and various control stimuli. In Experiment 1, a comparison of ERPs elicited by faces, bodies, objects and places showed that pictures of the human body (without the head) elicit a negative component peaking at 190 ms (an N190). While broadly similar to the N170, the N190 differs in both spatial distribution and amplitude from the N1 components elicited by faces, objects and scenes and peaks significantly later than the N170. The difference between N190 and N170 was further supported using topographic analyses of ERPs and source localization techniques. A unique, stable map topography was found to characterize human bodies between 130 and 230 ms. In Experiment 2, we tested the four conditions from Experiment 1, as well as intact and scrambled silhouettes and stick figures of the human body. We found that intact silhouettes and stick figures elicited significantly greater N190 amplitudes than their scrambled counterparts. Thus, the N190 generalizes to some degree to schematic depictions of the human form. Overall, our findings are consistent with intertwined, but functionally distinct, neural representations of the human face and body.

  6. The Influence of Aging on the Regenerative Potential of Human Adipose Derived Mesenchymal Stem Cells

    PubMed Central

    Marycz, Krzysztof; Henry, Brandon Michael

    2016-01-01

    Tissue regeneration using human adipose derived mesenchymal stem cells (hASCs) has significant potential as a novel treatment for many degenerative bone and joint diseases. Previous studies have established that age negatively affects the proliferation status and the osteogenic and chondrogenic differentiation potential of mesenchymal stem cells. The aim of this study was to assess the age-related maintenance of physiological function and differentiation potential of hASCs in vitro. hASCs were isolated from patients of four different age groups: (1) >20 years (n = 7), (2) >50 years (n = 7), (3) >60 years (n = 7), and (4) >70 years (n = 7). The hASCs were characterized according to the number of fibroblasts colony forming unit (CFU-F), proliferation rate, population doubling time (PDT), and quantified parameters of adipogenic, chondrogenic, and osteogenic differentiation. Compared to younger cells, aged hASCs had decreased proliferation rates, decreased chondrogenic and osteogenic potential, and increased senescent features. A shift in favor of adipogenic differentiation with increased age was also observed. As many bone and joint diseases increase in prevalence with age, it is important to consider the negative influence of age on hASCs viability, proliferation status, and multilineage differentiation potential when considering the potential therapeutic applications of hASCs. PMID:26941800

  7. The I' potential of the human auditory brainstem response to paired click stimuli.

    PubMed

    Davis-Gunter, M J; Löwenheim, H; Gopal, K V; Moore, E J

    2001-01-01

    When stimulated with an appropriate stimulus, the hair cells of the organ of Corti depolarize, causing the release of a neurotransmitter substance, which excites afferent VIIIth nerve dendrites. It is reasonable to hypothesize that excitatory postsynaptic potentials (EPSPs) generated by the dendrites of the auditory nerve in turn initiate a compound action potential (CAP). The EPSP is thought to be the generator potential for the CAP, and may be recorded in auditory brainstem responses (ABRs) as the I' potential. Determining the anatomical origin of I' may enhance the sensitivity of the ABR technique in hair cell/dendrite/auditory nerve evaluations. Whether I' is of sensory or of neural origin is equivocal, and therefore I' is not well understood. To investigate this dilemma, ABRs were recorded from human subjects using standard and paired-click stimuli, and using subtraction methods to generate a derived ABR. Two early peaks, designated as I degree and I', occurred before wave I in the derived ABR. It was hypothesized that peaks I degrees and I' represent the summating potential and the generator potential, generated by the cochlea and VIIIth nerve dendrites, respectively.

  8. HIV behind Bars: Human Immunodeficiency Virus Cluster Analysis and Drug Resistance in a Reference Correctional Unit from Southern Brazil

    PubMed Central

    Ikeda, Maria Letícia R.; Kuhleis, Daniele; Picon, Pedro D.; Jarczewski, Carla A.; Osório, Marta R.; Sánchez, Alexandra; Seuánez, Héctor N.; Larouzé, Bernard; Soares, Marcelo A.; Soares, Esmeralda A.

    2013-01-01

    People deprived of liberty in prisons are at higher risk of infection by the human immunodeficiency virus (HIV) due to their increased exposure through intravenous drug use, unprotected sexual activity, tattooing in prison and blood exposure in fights and rebellions. Yet, the contribution of intramural HIV transmission to the epidemic is scarcely known, especially in low- and middle-income settings. In this study, we surveyed 1,667 inmates incarcerated at Presídio Central de Porto Alegre, located in southern Brazil, for HIV infection and molecular characterization. The HIV seroprevalence was 6.6% (110/1,667). Further analyses were carried out on 40 HIV-seropositive inmates to assess HIV transmission clusters and drug resistance within the facility with the use of molecular and phylogenetic techniques. The molecular epidemiology of HIV-1 subtypes observed was similar to the one reported for the general population in southern Brazil, with the predominance of HIV-1 subtypes C, B, CRF31_BC and unique BC recombinants. In particular, the high rate (24%) of URF_BC found here may reflect multiple exposures of the population investigated to HIV infection. We failed to find HIV-infected inmates sharing transmission clusters with each other. Importantly, the analysis of HIV-1 pol genomic fragments evidenced high rates of HIV primary and secondary (acquired) drug resistance and an alarming proportion of virologic failure among patients under treatment, unveiling suboptimal access to antiretroviral therapy (ARV), low ARV adherence and dissemination of drug resistant HIV strains in primary infections. Our results call for immediate actions of public authority to implement preventive measures, serological screening and, for HIV-seropositive subjects, clinical and treatment follow-up in order to control HIV infection and limit the spread of drug resistance strains in Brazilian prisons. PMID:23874857

  9. Non-averaged human brain potentials in somatic attention: the short-latency cognition-related P40 component.

    PubMed Central

    Tomberg, C; Desmedt, J E

    1996-01-01

    1. Non-averaged scalp-recorded brain potentials were studied in humans during selective attention to randomly intermixed series of stimuli to fingers. Physiological tests were use for validating the presence or absence of the short-latency cognition-related P40 electrogeneses in parietal cortex in the response to a single-target stimulus (P40 signifies a positive polarity of about 40 ms peak latency). 2. To minimize interference from the electroencephalogram and noise we mapped single brain responses over the scalp and identified P40 topographies by an updated form of the numerical estimator Z for assessment of recorded potentials over time. We found that Z should exceed 0.96 for at least 15 ms for validation of the topographical congruity between the single P40 and an averaged P40 template. 3. Individual responses to 145 target finger stimuli correctly identified by the subject were analysed. P40 occurred only intermittently (34.5%) in a series of targets, but its voltage was unexpectedly large, exceeding the P40 voltage in averaged responses by a factor of about 10. 4. The usual assumption in the averaging method that the single brain responses combined in the average are stable but merely contaminated by unrelated noise was shown to be false for the cognition-related P40, which was considerably underestimated because of its intermittency in the averaged single trials. 5. The reaction time of the subject was on average 19% shorter in the trials in which a P40 was present, thus suggesting that P40 can influence subsequent perceptual processing by the brain in the same trial. 6. The feasibility of identifying specific cognition-related electrogeneses in single brain responses opens up the study of momentary shifts in brain processing strategies thereby allowing the neurophysiology of cognition to be based in real time. Images Figure 5 Figure 6 Figure 8 Figure 11 Figure 12 PMID:8910238

  10. Refraction corrections for surveying

    NASA Technical Reports Server (NTRS)

    Lear, W. M.

    1980-01-01

    Optical measurements of range and elevation angles are distorted by refraction of Earth's atmosphere. Theoretical discussion of effect, along with equations for determining exact range and elevation corrections, is presented in report. Potentially useful in optical site surveying and related applications, analysis is easily programmed on pocket calculator. Input to equation is measured range and measured elevation; output is true range and true elevation.

  11. Pleasant and Unpleasant Odors Influence Hedonic Evaluations of Human Faces: An Event-Related Potential Study

    PubMed Central

    Cook, Stephanie; Fallon, Nicholas; Wright, Hazel; Thomas, Anna; Giesbrecht, Timo; Field, Matt; Stancak, Andrej

    2015-01-01

    Odors can alter hedonic evaluations of human faces, but the neural mechanisms of such effects are poorly understood. The present study aimed to analyze the neural underpinning of odor-induced changes in evaluations of human faces in an odor-priming paradigm, using event-related potentials (ERPs). Healthy, young participants (N = 20) rated neutral faces presented after a 3 s pulse of a pleasant odor (jasmine), unpleasant odor (methylmercaptan), or no-odor control (clean air). Neutral faces presented in the pleasant odor condition were rated more pleasant than the same faces presented in the no-odor control condition, which in turn were rated more pleasant than faces in the unpleasant odor condition. Analysis of face-related potentials revealed four clusters of electrodes significantly affected by odor condition at specific time points during long-latency epochs (600−950 ms). In the 620−640 ms interval, two scalp-time clusters showed greater negative potential in the right parietal electrodes in response to faces in the pleasant odor condition, compared to those in the no-odor and unpleasant odor conditions. At 926 ms, face-related potentials showed greater positivity in response to faces in the pleasant and unpleasant odor conditions at the left and right lateral frontal-temporal electrodes, respectively. Our data shows that odor-induced shifts in evaluations of faces were associated with amplitude changes in the late (>600) and ultra-late (>900 ms) latency epochs. The observed amplitude changes during the ultra-late epoch are consistent with a left/right hemisphere bias towards pleasant/unpleasant odor effects. Odors alter evaluations of human faces, even when there is a temporal lag between presentation of odors and faces. Our results provide an initial understanding of the neural mechanisms underlying effects of odors on hedonic evaluations. PMID:26733843

  12. Potential environmental and human health impacts of rechargeable lithium batteries in electronic waste.

    PubMed

    Kang, Daniel Hsing Po; Chen, Mengjun; Ogunseitan, Oladele A

    2013-05-21

    Rechargeable lithium-ion (Li-ion) and lithium-polymer (Li-poly) batteries have recently become dominant in consumer electronic products because of advantages associated with energy density and product longevity. However, the small size of these batteries, the high rate of disposal of consumer products in which they are used, and the lack of uniform regulatory policy on their disposal means that lithium batteries may contribute substantially to environmental pollution and adverse human health impacts due to potentially toxic materials. In this research, we used standardized leaching tests, life-cycle impact assessment (LCIA), and hazard assessment models to evaluate hazardous waste classification, resource depletion potential, and toxicity potentials of lithium batteries used in cellphones. Our results demonstrate that according to U.S. federal regulations, defunct Li-ion batteries are classified hazardous due to their lead (Pb) content (average 6.29 mg/L; σ = 11.1; limit 5). However, according to California regulations, all lithium batteries tested are classified hazardous due to excessive levels of cobalt (average 163,544 mg/kg; σ = 62,897; limit 8000), copper (average 98,694 mg/kg; σ = 28,734; limit 2500), and nickel (average 9525 mg/kg; σ = 11,438; limit 2000). In some of the Li-ion batteries, the leached concentrations of chromium, lead, and thallium exceeded the California regulation limits. The environmental impact associated with resource depletion and human toxicity is mainly associated with cobalt, copper, nickel, thallium, and silver, whereas the ecotoxicity potential is primarily associated with cobalt, copper, nickel, thallium, and silver. However, the relative contribution of aluminum and lithium to human toxicity and ecotoxicity could not be estimated due to insufficient toxicity data in the models. These findings support the need for stronger government policy at the local, national, and international levels to encourage recovery, recycling, and

  13. Pleasant and Unpleasant Odors Influence Hedonic Evaluations of Human Faces: An Event-Related Potential Study.

    PubMed

    Cook, Stephanie; Fallon, Nicholas; Wright, Hazel; Thomas, Anna; Giesbrecht, Timo; Field, Matt; Stancak, Andrej

    2015-01-01

    Odors can alter hedonic evaluations of human faces, but the neural mechanisms of such effects are poorly understood. The present study aimed to analyze the neural underpinning of odor-induced changes in evaluations of human faces in an odor-priming paradigm, using event-related potentials (ERPs). Healthy, young participants (N = 20) rated neutral faces presented after a 3 s pulse of a pleasant odor (jasmine), unpleasant odor (methylmercaptan), or no-odor control (clean air). Neutral faces presented in the pleasant odor condition were rated more pleasant than the same faces presented in the no-odor control condition, which in turn were rated more pleasant than faces in the unpleasant odor condition. Analysis of face-related potentials revealed four clusters of electrodes significantly affected by odor condition at specific time points during long-latency epochs (600-950 ms). In the 620-640 ms interval, two scalp-time clusters showed greater negative potential in the right parietal electrodes in response to faces in the pleasant odor condition, compared to those in the no-odor and unpleasant odor conditions. At 926 ms, face-related potentials showed greater positivity in response to faces in the pleasant and unpleasant odor conditions at the left and right lateral frontal-temporal electrodes, respectively. Our data shows that odor-induced shifts in evaluations of faces were associated with amplitude changes in the late (>600) and ultra-late (>900 ms) latency epochs. The observed amplitude changes during the ultra-late epoch are consistent with a left/right hemisphere bias towards pleasant/unpleasant odor effects. Odors alter evaluations of human faces, even when there is a temporal lag between presentation of odors and faces. Our results provide an initial understanding of the neural mechanisms underlying effects of odors on hedonic evaluations. PMID:26733843

  14. Potential environmental and human health impacts of rechargeable lithium batteries in electronic waste.

    PubMed

    Kang, Daniel Hsing Po; Chen, Mengjun; Ogunseitan, Oladele A

    2013-05-21

    Rechargeable lithium-ion (Li-ion) and lithium-polymer (Li-poly) batteries have recently become dominant in consumer electronic products because of advantages associated with energy density and product longevity. However, the small size of these batteries, the high rate of disposal of consumer products in which they are used, and the lack of uniform regulatory policy on their disposal means that lithium batteries may contribute substantially to environmental pollution and adverse human health impacts due to potentially toxic materials. In this research, we used standardized leaching tests, life-cycle impact assessment (LCIA), and hazard assessment models to evaluate hazardous waste classification, resource depletion potential, and toxicity potentials of lithium batteries used in cellphones. Our results demonstrate that according to U.S. federal regulations, defunct Li-ion batteries are classified hazardous due to their lead (Pb) content (average 6.29 mg/L; σ = 11.1; limit 5). However, according to California regulations, all lithium batteries tested are classified hazardous due to excessive levels of cobalt (average 163,544 mg/kg; σ = 62,897; limit 8000), copper (average 98,694 mg/kg; σ = 28,734; limit 2500), and nickel (average 9525 mg/kg; σ = 11,438; limit 2000). In some of the Li-ion batteries, the leached concentrations of chromium, lead, and thallium exceeded the California regulation limits. The environmental impact associated with resource depletion and human toxicity is mainly associated with cobalt, copper, nickel, thallium, and silver, whereas the ecotoxicity potential is primarily associated with cobalt, copper, nickel, thallium, and silver. However, the relative contribution of aluminum and lithium to human toxicity and ecotoxicity could not be estimated due to insufficient toxicity data in the models. These findings support the need for stronger government policy at the local, national, and international levels to encourage recovery, recycling, and

  15. Soluble Epoxide Hydrolase as a Potential Key Factor for Human Prenatal Development.

    PubMed

    Cizkova, Katerina; Rajdova, Aneta; Ehrmann, Jiri

    2016-01-01

    Soluble epoxide hydrolase (sEH) converts highly active epoxyeicosatrienoic acids (EETs) generated by cytochrome P450 (CYP) epoxygenases from arachidonic acid to less active dihydroxyeicosatrienoic acids. Because of the role of EETs in processes potentially relevant to the development of organisms, EETs could be suggested as potential morphogens. Unfortunately, only little is known about sEH expression during human intrauterine development (IUD). We investigated the spatio-temporal expression pattern of sEH in human embryonic/foetal intestines, liver and kidney from the 6th to the 20th week of IUD by two-step immunohistochemistry. sEH was expressed during the whole tested period of prenatal development and its level of expression remained more or less the same during the estimated period of IUD. Distribution of CYP epoxygenases and sEH in the intestinal epithelium and the nephrogenic zone of the kidney suggests an influence of EETs on cell proliferation and differentiation and, consequently, on the development of intestines and kidney. Thus, alterations in the strict spatio-temporal pattern of expression of CYP epoxygenases and/or sEH during human prenatal development by xenobiotics could have a harmful impact for developing organisms. PMID:27144772

  16. Human induced pluripotent stem cells from basic research to potential clinical applications in cancer.

    PubMed

    Fernandez, Teresa de Souza; de Souza Fernandez, Cecilia; Mencalha, André Luiz

    2013-01-01

    The human induced pluripotent stem cells (hiPSCs) are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs' basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.

  17. Crystal structure of human esterase D: a potential genetic marker of retinoblastoma

    SciTech Connect

    Wu, Dong; Li, Yang; Song, Gaojie; Zhang, David; Shaw, Neil; Liu, Zhi-Jie

    2009-07-10

    Retinoblastoma (RB), a carcinoma of the retina, is caused by mutations in the long arm of chromosome 13, band 13q14. The esterase D (ESD) gene maps at a similar location as the RB gene locus and therefore serves as a potential marker for the prognosis of retinoblastoma. Because very little is known about the structure and function of ESD, we determined the 3-dimensional structure of the enzyme at 1.5 {angstrom} resolution using X-ray crystallography. ESD shows a single domain with an {alpha}/{beta}-hydrolase fold. A number of insertions are observed in the canonical {alpha}/{beta}-hydrolase fold. The active site is located in a positively charged, shallow cleft on the surface lined by a number of aromatic residues. Superimposition studies helped identify the typical catalytic triad residues -- Ser-153, His264, and Asp230 -- involved in catalysis. Mutagenesis of any of the catalytic triad residues to alanine abolished the enzyme activity. Backbone amides of Leu54 and Met150 are involved in the formation of the oxyanion hole. Interestingly, a M150A mutation increased the enzyme activity by 62%. The structure of human ESD determined in this study will aid the elucidation of the physiological role of the enzyme in the human body and will assist in the early diagnosis of retinoblastoma. Wu, D., Li, Y., Song, G., Zhang, D., Shaw, N., Liu, Z. J. Crystal structure of human esterase D: a potential genetic marker of retinoblastoma.

  18. Invariance of Firing Rate and Field Potential Dynamics to Stimulus Modulation Rate in Human Auditory Cortex

    PubMed Central

    Mukamel, Roy; Nir, Yuval; Harel, Michal; Arieli, Amos; Malach, Rafael; Fried, Itzhak

    2011-01-01

    The effect of stimulus modulation rate on the underlying neural activity in human auditory cortex is not clear. Human studies (using both invasive and noninvasive techniques) have demonstrated that at the population level, auditory cortex follows stimulus envelope. Here we examined the effect of stimulus modulation rate by using a rare opportunity to record both spiking activity and local field potentials (LFP) in auditory cortex of patients during repeated presentations of an audio-visual movie clip presented at normal, double, and quadruple speeds. Mean firing rate during evoked activity remained the same across speeds and the temporal response profile of firing rate modulations at increased stimulus speeds was a linearly scaled version of the response during slower speeds. Additionally, stimulus induced power modulation of local field potentials in the high gamma band (64–128 Hz) exhibited similar temporal scaling as the neuronal firing rate modulations. Our data confirm and extend previous studies in humans and anesthetized animals, supporting a model in which both firing rate, and high-gamma LFP power modulations in auditory cortex follow the temporal envelope of the stimulus across different modulation rates. PMID:20665720

  19. Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans

    PubMed Central

    Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S.; Kiso, Wendy K.; Schmitt, Dennis L.; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T.; Maley, Carlo C.; Schiffman, Joshua D.

    2016-01-01

    IMPORTANCE Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. OBJECTIVE To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). DESIGN, SETTING, AND PARTICIPANTS A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. EXPOSURES Ionizing radiation and doxorubicin. MAIN OUTCOMES AND MEASURES Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. RESULTS Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95%CI, 0%–5%]; African wild dog, 8%[95%CI, 0%–16%]; lion, 2%[95%CI, 0% –7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95%CI, 3.14%–6.49%), compared with humans, who have 11% to 25%cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain

  20. Assessing the Biohazard Potential of Putative Martian Organisms for Exploration Class Human Space Missions

    NASA Technical Reports Server (NTRS)

    Warmflash, David; Larios-Sanz, Maia; Jones, Jeffrey; Fox, George E.; McKay, David S.

    2007-01-01

    Exploration Class missions to Mars will require precautions against potential contamination by any native microorganisms that may be incidentally pathogenic to humans. While the results of NASA's Viking biology experiments of 1976 have been generally interpreted as inconclusive for surface organisms, the possibility of native surface life has never been ruled out and more recent studies suggest that the case for biological interpretation of the Viking Labeled Release data may now be stronger than it was when the experiments were originally conducted. It is possible that, prior to the first human landing on Mars, robotic craft and sample return missions will provide enough data to know with certainty whether or not future human landing sites harbor extant life forms. However, if native life is confirmed, it will be problematic to determine whether any of its species may present a medical risk to astronauts. Therefore, it will become necessary to assess empirically the risk that the planet contains pathogens based on terrestrial examples of pathogenicity and to take a reasonably cautious approach to bio-hazard protection. A survey of terrestrial pathogens was conducted with special emphasis on those pathogens whose evolution has not depended on the presence of animal hosts. The history of the development and implementation of Apollo anticontamination protocol and recent recommendations of the NRC Space Studies Board regarding Mars were reviewed. Organisms can emerge in nature in the absence of indigenous animal hosts and both infectious and non-infectious human pathogens are theoretically possible on Mars. The prospect of Martian surface life, together with the existence of a diversity of routes by which pathogenicity has emerged on Earth, suggests that the possibility of human pathogens on Mars, while low, is not zero. Since the discovery and study of Martian life can have long-term benefits for humanity, the risk that Martian life might include pathogens should not

  1. All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma.

    PubMed

    Alloussi, S H; Alkassar, M; Urbschat, S; Graf, N; Gärtner, B

    2011-09-01

    Reoviridae are non-human pathogenic viruses. The family of reoviridae consists of 4 different subtypes. Many studies have proven that the Dearing subtype 3 has oncolytic potential. This potential is related to the RAS protein expression in tumour cells. The aim of this study, was to investigate whether all reovirus subtypes have oncolytic potential and whether there are differences in their efficacy, in particular for high-grade glioma. To evaluate the oncolytic potential, we performed an in vitro head-to-head study for all reovirus subtypes in 5 primary cell cultures of high-grade gliomas. The oncolytic activity was determined using end-point titration with observation of the cytopathogenic effect. For measurement of RAS activity, we performed an immunofluorescent detection stain on all cell cultures. For quantification of the virus, an RT-PCR measurement for all subtypes was performed. All reovirus subtypes showed oncolytic activity in the observed glioma biopsies. These observations correlated with RAS overexpression in the observed cells. All glioma biopsies overexpressed the RAS protein. The quantitative oncolytic potential differed in relation to the single observed cell culture and in relation to the chosen reovirus subtype. To our knowledge, this is the first study showing oncolytic activity for all reovirus subtypes. We show the relationship and correlation between RAS protein overexpression and vulnerability of cells to reovirus. Efficacy of the different subtypes is interindividually different and cannot be forecast.

  2. Cigarette smoking hinders human periodontal ligament-derived stem cell proliferation, migration and differentiation potentials.

    PubMed

    Ng, Tsz Kin; Huang, Li; Cao, Di; Yip, Yolanda Wong-Ying; Tsang, Wai Ming; Yam, Gary Hin-Fai; Pang, Chi Pui; Cheung, Herman S

    2015-01-01

    Cigarette smoking contributes to the development of destructive periodontal diseases and delays its healing process. Our previous study demonstrated that nicotine, a major constituent in the cigarette smoke, inhibits the regenerative potentials of human periodontal ligament-derived stem cells (PDLSC) through microRNA (miRNA) regulation. In this study, we hypothesized that the delayed healing in cigarette smokers is caused by the afflicted regenerative potential of smoker PDLSC. We cultured PDLSC from teeth extracted from smokers and non-smokers. In smoker PDLSC, we found significantly reduced proliferation rate and retarded migration capabilities. Moreover, alkaline phosphatase activity, calcium deposition and acidic polysaccharide staining were reduced after BMP2-induced differentiation. In contrast, more lipid deposition was observed in adipogenic-induced smoker PDLSC. Furthermore, two nicotine-related miRNAs, hsa-miR-1305 (22.08 folds, p = 0.040) and hsa-miR-18b (15.56 folds, p = 0.018), were significantly upregulated in smoker PDLSC, suggesting these miRNAs might play an important role in the deteriorative effects on stem cells by cigarette smoke. Results of this study provide further evidences that cigarette smoking affects the regenerative potentials of human adult stem cells.

  3. Survival of Potentially Pathogenic Human-Associated Bacteria in the Rhizosphere of Hydroponically Grown Wheat

    NASA Technical Reports Server (NTRS)

    Morales, Anabelle; Garland, Jay L.; Lim, Daniel V.

    1996-01-01

    Plants may serve as reservoirs for human-associated bacteria (H-AB) in long-term space missions containing bioregenerative life support systems. The current study examined the abilities of five human-associated potential pathogens, Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli, to colonize and grow in the rhizosphere of hydroponically grown wheat, a candidate crop for life support. All of these bacteria have been recovered from past NASA missions and present potential problems for future missions. The abilities of these organisms to adhere to the roots of axenic five-day-old wheat (Triticum aestivum L. cv. Yecora rojo) were evaluated by enumeration of the attached organisms after a one hour incubation of roots in a suspension (approximately 10(exp 8 cu/ml)) of the H-AB. Results showed that a greater percentage of P. aeruginosa cells adhered to the wheat roots than the other four H-AB. Similarly incubated seedlings were also grown under attempted axenic conditions for seven days to examine the potential of each organism to proliferate in the rhizosphere (root colonization capacity). P. cepacia and P. aeruginosa showed considerable growth. E. coli and S. aureus showed no significant growth, and S. pyogenes died off in the wheat rhizosphere. Studies examining the effects of competition on the survival of these microorganisms indicated that P. aeruginosa was the only organism that survived in the rhizosphere of hydroponically grown wheat in the presence of different levels of microbial competition.

  4. Cleavage pattern predicts developmental potential of day 3 human embryos produced by IVF.

    PubMed

    Yang, S T; Shi, J X; Gong, F; Zhang, S P; Lu, C F; Tan, K; Leng, L Z; Hao, M; He, H; Gu, Y F; Lu, G X; Lin, G

    2015-06-01

    Time-lapse technique provides opportunities to observe the dynamic process of human early development. Previous studies have suggested several abnormal division patterns were associated with decreased developmental potential, but no systematic results are currently available. In this study, seven abnormal division patterns were observed during early cleavage, and these had different effects on the further development potential of daughter blastomeres. According to the severity and occurrence of abnormal division patterns during the initial three cleavages, an embryo hierarchical classification model was developed and day 3 embryos were classified into six grades (from A to F). The good-quality blastocyst formation rate for these grades decreased from 70.8-3.8% (P < 0.001). In a prospective observational study, 139 IVF cycles were recruited to assess the efficiency of this classification model. In the embryos that had confirmed implantation results, the implantation rate decreased from 67.0% (Grade A) to 0% (Grade D;P < 0.001). These results indicated that cleavage patterns can predict the developmental potential of day 3 human embryos. PMID:25892500

  5. Survival of potentially pathogenic human-associated bacteria in the rhizosphere of hydroponically grown wheat.

    PubMed

    Morales, A; Garland, J L; Lim, D V

    1996-07-01

    Plants may serve as reservoirs for human-associated bacteria (H-AB) in long-term space missions containing bioregenerative life support systems. The current study examined the abilities of five human-associated potential pathogens, Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Streptococcus pyogenes and Escherichia coli, to colonize and grow in the rhizosphere of hydroponically grown wheat, a candidate crop for life support. All of these bacteria have been recovered from past NASA missions and present potential problems for future missions. The abilities of these organisms to adhere to the roots of axenic five-day-old wheat (Triticum aestivum L. cv. Yecora rojo) were evaluated by enumeration of the attached organisms after a one hour incubation of roots in a suspension (approximately 10(8) cfu ml-1) of the H-AB. Results showed that a greater percentage of P. aeruginosa cells adhered to the wheat roots than the other four H-AB. Similarly incubated seedlings were also grown under attempted axenic conditions for seven days to examine the potential of each organism to proliferate in the rhizosphere (root colonization capacity). P. cepacia and P. aerogiunosa showed considerable growth, E. coli and S. aureus showed no significant growth, and S. pyogenes died off in the wheat rhizosphere. Studies examining the effects of competition on the survival of these microorganisms indicated that P. aeruginosa was the only organism that survived in the rhizosphere of hydroponically grown wheat in the presence of different levels of microbial competition.

  6. The Human Cathelicidin Antimicrobial Peptide LL-37 as a Potential Treatment for Polymicrobial Infected Wounds.

    PubMed

    Duplantier, Allen J; van Hoek, Monique L

    2013-01-01

    Diabetic patients often have ulcers on their lower-limbs that are infected by multiple biofilm-forming genera of bacteria, and the elimination of the biofilm has proven highly successful in resolving such wounds in patients. To that end, antimicrobial peptides have shown potential as a new anti-biofilm approach. The single human cathelicidin peptide LL-37 has been shown to have antimicrobial and anti-biofilm activity against multiple Gram-positive and Gram-negative human pathogens, and have wound-healing effects on the host. The combination of the anti-biofilm effect and wound-healing properties of LL-37 may make it highly effective in resolving polymicrobially infected wounds when topically applied. Such a peptide or its derivatives could be a platform from which to develop new therapeutic strategies to treat biofilm-mediated infections of wounds. This review summarizes known mechanisms that regulate the endogenous levels of LL-37 and discusses the anti-biofilm, antibacterial, and immunological effects of deficient vs. excessive concentrations of LL-37 within the wound environment. Here, we review recent advances in understanding the therapeutic potential of this peptide and other clinically advanced peptides as a potential topical treatment for polymicrobial infected wounds.

  7. Developmental potential of clinically discarded human embryos and associated chromosomal analysis

    PubMed Central

    Yao, Guidong; Xu, Jiawei; Xin, Zhimin; Niu, Wenbin; Shi, Senlin; Jin, Haixia; Song, Wenyan; Wang, Enyin; Yang, Qingling; Chen, Lei; Sun, Yingpu

    2016-01-01

    Clinically discarded human embryos, which are generated from both normal and abnormal fertilizations, have the potential of developing into blastocysts. A total of 1,649 discarded human embryos, including zygotes containing normal (2PN) and abnormal (0PN, 1PN, 3PN and ≥4PN) pronuclei and prematurely cleaved embryos (2Cell), were collected for in vitro culture to investigate their developmental potential and chromosomal constitution using an SNP array-based chromosomal analysis. We found that blastocyst formation rates were 63.8% (for 2Cell embryos), 22.6% (2PN), 16.7% (0PN), 11.2% (3PN) and 3.6% (1PN). SNP array-based chromosomal analysis of the resultant blastocysts revealed that the percentages of normal chromosomes were 55.2% (2Cell), 60.7% (2PN), 44.4% (0PN) and 47.4% (0PN). Compared with clinical preimplantation genetic diagnosis (PGD) data generated with clinically acceptable embryos, results of the SNP array-based chromosome analysis on blastocysts from clinically discarded embryos showed similar values for the frequency of abnormal chromosome occurrence, aberrant signal classification and chromosomal distribution. The present study is perhaps the first systematic analysis of the developmental potential of clinically discarded embryos and provides a basis for future studies. PMID:27045374

  8. The structure of the human peripherin gene (PRPH) and identification of potential regulatory elements

    SciTech Connect

    Foley, J.; Ley, C.A.; Parysek, L.M.

    1994-07-15

    The authors determined the complete nucleotide sequence of the coding region of the human peripherin gene (PRPH), as well as 742 bp 5{prime} to the cap site and 584 bp 3{prime} to the stop codon, and compared its structure and sequence to the rat and mouse genes. The overall structure of 9 exons separated by 8 introns is conserved among these three mammalian species. The nucleotide sequences of the human peripherin gene exons were 90% identical to the rat gene sequences, and the predicted human peripherin protein differed from rat peripherin at only 18 of 475 amino acid residues. Comparison of the 5{prime} flanking regions of the human peripherin gene and rodent genes revealed extensive areas of high homology. Additional conserved segments were found in introns 1 and 2. Within the 5{prime} region, potential regulatory sequences, including a nerve growth factor negative regulatory element, a Hox protein binding site, and a heat shock element, were identified in all peripherin genes. The positional conservation of each element suggests that they may be important in the tissue-specific, developmental-specific, and injury-specific expression of the peripherin gene. 24 refs., 2 figs., 1 tab.

  9. Population Bottlenecks as a Potential Major Shaping Force of Human Genome Architecture

    PubMed Central

    Teslovich, Tanya M; Stankiewicz, Pawel; Withers, Marjorie; Kashuk, Carl S; Chakravarti, Aravinda; Lupski, James R; Cutler, David J; Katsanis, Nicholas

    2007-01-01

    The modern synthetic view of human evolution proposes that the fixation of novel mutations is driven by the balance among selective advantage, selective disadvantage, and genetic drift. When considering the global architecture of the human genome, the same model can be applied to understanding the rapid acquisition and proliferation of exogenous DNA. To explore the evolutionary forces that might have morphed human genome architecture, we investigated the origin, composition, and functional potential of numts (nuclear mitochondrial pseudogenes), partial copies of the mitochondrial genome found abundantly in chromosomal DNA. Our data indicate that these elements are unlikely to be advantageous, since they possess no gross positional, transcriptional, or translational features that might indicate beneficial functionality subsequent to integration. Using sequence analysis and fossil dating, we also show a probable burst of integration of numts in the primate lineage that centers on the prosimian–anthropoid split, mimics closely the temporal distribution of Alu and processed pseudogene acquisition, and coincides with the major climatic change at the Paleocene–Eocene boundary. We therefore propose a model according to which the gross architecture and repeat distribution of the human genome can be largely accounted for by a population bottleneck early in the anthropoid lineage and subsequent effectively neutral fixation of repetitive DNA, rather than positive selection or unusual insertion pressures. PMID:17658953

  10. Mining the potential interrelationships between human health and ecological risk assessments of metal-contaminated sites

    SciTech Connect

    Appling, J.W.

    1994-12-31

    Conservative approaches to human health or ecological risk assessment often result in evaluations that indicate a risk at metal concentrations near or below background levels. This presents a complex dilemma to regulators, responsible parties, and the public: How can risk be more realistically estimated so that the public is not unnecessarily alarmed into thinking normal exposures pose abnormal risk, and site remediation can be responsible yet cost-effective? One answer is using-ecological and human health studies together to improve the quality of both types of assessments. Mammalian herbivores and roving children are good spatial and temporal integrators of exposure; biomarkers or Monte Carlo-based models of exposure to herbivores can support realistic estimates of exposure to children. Reduced bioavailability of metals in soils at mining sites is well recognized for many metals and is amenable to study in ecological species; such studies reduce the overestimate of risk to humans through direct contact or exposure via the food chain. Recent and current human health studies of lead and arsenic bioavailability also support ecological assessments. Mixtures of metals pose special challenges because of the potential for antagonistic, additive, or synergistic effects with respect to bioavailability, absorption, distribution, excretion, toxic effects and nutritional or physiological essentiality. Combining results from pharmacokinetic, mechanistic, and environmental studies of mixtures enhances the predictive abilities of risk assessments.

  11. The natural antibody repertoire of sharks and humans recognizes the potential universe of antigens.

    PubMed

    Adelman, Miranda K; Schluter, Samuel F; Marchalonis, John J

    2004-02-01

    In ancestral sharks, a rapid emergence in the evolution of the immune system occurred, giving jawed-vertebrates the necessary components for the combinatorial immune response (CIR). To compare the natural antibody (NAb) repertoires of the most divergent vertebrates with the capacity to produce antibodies, we isolated NAbs to the same set of antigens by affinity chromatography from two species of Carcharhine sharks and from human polyclonal IgG and IgM antibody preparations. The activities of the affinity-purified anti-T-cell receptor (anti-TCR) NAbs were compared with those of monoclonal anti-TCR NAbs that were generated from a systemic lupus erythematosus patient. We report that sharks and humans, representing the evolutionary extremes of vertebrate species sharing the CIR, have NAbs to human TCRs, Igs, the human senescent cell antigen, and to numerous retroviral antigens, indicating that essential features of the combinatorial repertoire and the capacity to recognize the potential universe of antigens is shared among all jawed-vertebrates.

  12. Probiotic lactobacilli: a potential prophylactic treatment for reducing pesticide absorption in humans and wildlife.

    PubMed

    Trinder, M; Bisanz, J E; Burton, J P; Reid, G

    2015-01-01

    Numerous pesticides are used in agriculture, gardening, and wildlife-control. Despite their intended toxicity to pests, these compounds can also cause harm to wildlife and humans due to their ability to potentially bioaccumulate, leach into soils, and persist in the environment. Humans and animals are commonly exposed to these compounds through agricultural practices and consumption of contaminated foods and water. Pesticides can cause a range of adverse effects in humans ranging from minor irritation, to endocrine or nervous system disruption, cancer, or even death. A convenient and cost-effective method to reduce unavoidable pesticide absorption in humans and wildlife could be the use of probiotic lactobacilli. Lactobacillus is a genus of Gram-positive gut commensal bacteria used in the production of functional foods, such as yoghurt, cheese, sauerkraut and pickles, as well as silage for animal feed. Preliminary in vitro experiments suggested that lactobacilli are able to degrade some pesticides. Probiotic Lactobacillus rhamnosus GR-1-supplemented yoghurt reduced the bioaccumulation of mercury and arsenic in pregnant women and children. A similar study is warranted to test if this approach can reduce pesticide absorption in vivo, given that the lactobacilli can also attenuate reactive oxygen production, enhance gastrointestinal barrier function, reduce inflammation, and modulate host xenobiotic metabolism. PMID:26123785

  13. Probiotic lactobacilli: a potential prophylactic treatment for reducing pesticide absorption in humans and wildlife.

    PubMed

    Trinder, M; Bisanz, J E; Burton, J P; Reid, G

    2015-01-01

    Numerous pesticides are used in agriculture, gardening, and wildlife-control. Despite their intended toxicity to pests, these compounds can also cause harm to wildlife and humans due to their ability to potentially bioaccumulate, leach into soils, and persist in the environment. Humans and animals are commonly exposed to these compounds through agricultural practices and consumption of contaminated foods and water. Pesticides can cause a range of adverse effects in humans ranging from minor irritation, to endocrine or nervous system disruption, cancer, or even death. A convenient and cost-effective method to reduce unavoidable pesticide absorption in humans and wildlife could be the use of probiotic lactobacilli. Lactobacillus is a genus of Gram-positive gut commensal bacteria used in the production of functional foods, such as yoghurt, cheese, sauerkraut and pickles, as well as silage for animal feed. Preliminary in vitro experiments suggested that lactobacilli are able to degrade some pesticides. Probiotic Lactobacillus rhamnosus GR-1-supplemented yoghurt reduced the bioaccumulation of mercury and arsenic in pregnant women and children. A similar study is warranted to test if this approach can reduce pesticide absorption in vivo, given that the lactobacilli can also attenuate reactive oxygen production, enhance gastrointestinal barrier function, reduce inflammation, and modulate host xenobiotic metabolism.

  14. Regenerative potential of human airway stem cells in lung epithelial engineering.

    PubMed

    Gilpin, Sarah E; Charest, Jonathan M; Ren, Xi; Tapias, Luis F; Wu, Tong; Evangelista-Leite, Daniele; Mathisen, Douglas J; Ott, Harald C

    2016-11-01

    Bio-engineered organs for transplantation may ultimately provide a personalized solution for end-stage organ failure, without the risk of rejection. Building upon the process of whole organ perfusion decellularization, we aimed to develop novel, translational methods for the recellularization and regeneration of transplantable lung constructs. We first isolated a proliferative KRT5(+)TP63(+) basal epithelial stem cell population from human lung tissue and demonstrated expansion capacity in conventional 2D culture. We then repopulated acellular rat scaffolds in ex vivo whole organ culture and observed continued cell proliferation, in combination with primary pulmonary endothelial cells. To show clinical scalability, and to test the regenerative capacity of the basal cell population in a human context, we then recellularized and cultured isolated human lung scaffolds under biomimetic conditions. Analysis of the regenerated tissue constructs confirmed cell viability and sustained metabolic activity over 7 days of culture. Tissue analysis revealed extensive recellularization with organized tissue architecture and morphology, and preserved basal epithelial cell phenotype. The recellularized lung constructs displayed dynamic compliance and rudimentary gas exchange capacity. Our results underline the regenerative potential of patient-derived human airway stem cells in lung tissue engineering. We anticipate these advances to have clinically relevant implications for whole lung bioengineering and ex vivo organ repair. PMID:27622532

  15. Reliability of directional information in unsorted spikes and local field potentials recorded in human motor cortex

    PubMed Central

    Perge, János A.; Zhang, Shaomin; Malik, Wasim Q.; Homer, Mark L.; Cash, Sydney; Friehs, Gerhard; Eskandar, Emad N.; Donoghue, John P.; Hochberg, Leigh R.

    2014-01-01

    Objective Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs along with action potentials a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. Approach We conducted intracortical multielectrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. Main results We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200–400Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70–400Hz), and increasing disparity with lower frequency bands (0–7, 10–40 and 50–65Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p=0.27[0.03]). Significance Field potentials provided comparable

  16. The Potential Economic Value of a Human Norovirus Vaccine for the United States

    PubMed Central

    Bartsch, Sarah M.; Lopman, Benjamin A.; Hall, Aron J.; Parashar, Umesh D.; Lee, Bruce Y.

    2012-01-01

    Vaccines against human norovirus are currently under development. We developed a simulation model to determine their potential economic value. Vaccination prevented 100–6,125 norovirus gastroenteritis cases per 10,000 vaccinees. Low vaccine cost (≤$50) garnered cost-savings and a more expensive vaccine led to costs per case averted comparable to other vaccines. In the US, vaccination could avert approximately 1.0–2.2 million cases (efficacy 50%, 12 month duration), costing an additional $400 million to $1.0 billion, but could save ≤$2.1 billion (48 month duration). Human norovirus vaccination can offer economic value while averting clinical outcomes, depending on price, efficacy, and protection duration. PMID:23026689

  17. Potential applications of atomic force microscopy of DNA to the human genome project

    NASA Astrophysics Data System (ADS)

    Hansma, Helen G.; Hansma, Paul K.

    1993-06-01

    A simple calculation shows that the information contained in the base sequence of the human genome could be recorded onto less than two compact discs. To read amounts of information comparable in size to the human genome, scanning probes are used routinely in both biology (i.e., living systems) and technology. The atomic force microscope (AFM) is a scanning probe that is now capable of imaging DNA routinely and reproducibly. The minimum size of structures seen reproducibly along DNA strands with the AFM is presently 2 to 3 nm, which is an order of magnitude less resolution than would be required to sequence DNA. At present, the AFM shows great potential for high-resolution mapping of DNA but is not capable of sequencing DNA without further improvements.

  18. Potential Use of Bacterial Community Succession in Decaying Human Bone for Estimating Postmortem Interval.

    PubMed

    Damann, Franklin E; Williams, Daniel E; Layton, Alice C

    2015-07-01

    Bacteria are taphonomic agents of human decomposition, potentially useful for estimating postmortem interval (PMI) in late-stage decomposition. Bone samples from 12 individuals and three soil samples were analyzed to assess the effects of decomposition and advancing time on bacterial communities. Results indicated that partially skeletonized remains maintained a presence of bacteria associated with the human gut, whereas bacterial composition of dry skeletal remains maintained a community profile similar to soil communities. Variation in the UniFrac distances was significantly greater between groups than within groups (p < 0.001) for the unweighted metric and not the weighted metric. The members of the bacterial communities were more similar within than between decomposition stages. The oligotrophic environment of bone relative to soft tissue and the physical protection of organic substrates may preclude bacterial blooms during the first years of skeletonization. Therefore, community membership (unweighted) may be better for estimating PMI from skeletonized remains than community structure (weighted).

  19. Potential Therapeutic Roles of Tanshinone IIA in Human Bladder Cancer Cells

    PubMed Central

    Chiu, Sheng-Chun; Huang, Sung-Ying; Chang, Shu-Fang; Chen, Shee-Ping; Chen, Chi-Cheng; Lin, Tien-Huang; Liu, Hsin-Ho; Tsai, Tsung-Hsun; Lee, Shang-Sen; Pang, Cheng-Yoong; Hsieh, Teng-Fu

    2014-01-01

    Tanshinone IIA (Tan-IIA), one of the major lipophilic components isolated from the root of Salviae Miltiorrhizae, has been found to exhibit anticancer activity in various cancer cells. We have demonstrated that Tan-IIA induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. Here we explored the anticancer effect of Tan-IIA in human bladder cancer cell lines. Our results showed that Tan-IIA caused bladder cancer cell death in a time- and dose-dependent manner. Tan-IIA induced apoptosis through the mitochondria-dependent pathway in these bladder cancer cells. Tan-IIA also suppressed the migration of bladder cancer cells as revealed by the wound healing and transwell assays. Finally, combination therapy of Tan-IIA with a lower dose of cisplatin successfully killed bladder cancer cells, suggesting that Tan-IIA can serve as a potential anti-cancer agent in bladder cancer. PMID:25192287

  20. Aviation human factors research in US universities: Potential contributions to national needs

    NASA Technical Reports Server (NTRS)

    Dismukes, R. Key

    1994-01-01

    Universities can and should make vital contributions to national needs in aviation human factors. However, to guide and utilize university research effectively we must understand what types of expertise and facilities universities can bring to bear on aviation problems. We should be aware of where relevant research is already underway and where untapped potential exists. How does the character of research in universities differ from and complement research in government and industry laboratories? What conditions would encourage universities to focus on national priorities and would promote high quality, relevant research? This paper attempts to address these issues. It is based on a survey conducted by the author, which included site visits to several universities, telephone interviews with faculty members at other universities, and a search of the aviation human factors research literature.

  1. Isolation of Mycobacterium mucogenicum from street-vended chili sauces: a potential source of human infection.

    PubMed

    Cerna-Cortés, Jorge F; Estrada-García, Teresa; González-y-Merchand, Jorge A

    2009-01-01

    Recently human illnesses due to nontuberculous mycobacteria (NTM) have increased worldwide, but the sources of transmission have not been well established. Street-vended food is widely consumed in Mexico, and chili sauces are the most typical dressings for this food. Thus, we examined street-vended chili sauces as a possible source for NTM. Fifty-one street-vended chili sauces were collected in different areas of Mexico City during the spring of 2007. NTM were recovered from 6% (3 of 51) of samples, and in all cases the identified species was Mycobacterium mucogenicum. This mycobacterium has been associated with human illness; therefore, street-vended chili sauces are a potential source of NTM infection.

  2. Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy.

    PubMed

    Clement, Omoshile O; Freeman, Clive M; Hartmann, Rolf W; Handratta, Venkatesh D; Vasaitis, Tadas S; Brodie, Angela M H; Njar, Vincent C O

    2003-06-01

    We report here a molecular modeling investigation of steroidal and nonsteroidal inhibitors of human cytochrome P450 17alpha-hydroxylase-17,20-lyase (CYP17). Using the pharmacophore perception technique, we have generated common-feature pharmacophore model(s) to explain the putative binding requirements for two classes of human CYP17 inhibitors. Common chemical features in the steroid and nonsteroid human CYP17 enzyme inhibitors, as deduced by the Catalyst/HipHop program, are one to two hydrogen bond acceptors (HBAs) and three hydrophobic groups. For azole-steroidal ligands, the 3beta-OH group of ring A and the N-3 of the azole ring attached to ring D at C-17 act as hydrogen bond acceptors. A model that permits hydrogen bond interaction between the azole functionality on ring D and the enzyme is consistent with experimental deductions for type II CYP17 inhibitors where a sixth ligating atom interacts with Fe(II) of heme. In general, pharmacophore models derived for steroid and nonsteroidal compounds bear striking similarities to all azole sites mapping the HBA functionality and to three hydrophobic features describing the hydrophobic interactions between the ligands and the enzyme. Using the pharmacophore model derived for azole-steroidal inhibitors as a 3D search query against several 3D multiconformational Catalyst formatted databases, we identified several steroidal compounds with potential inhibition of this enzyme. Biological testing of some of these compounds show low to high inhibitory potency against the human CYP17 enzyme. This shows the potential of our pharmacophore model in identifying new and potent CYP17 inhibitors. Further refinement of the model is in progress with a view to identifying and optimizing new leads. PMID:12773039

  3. Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy.

    PubMed

    Clement, Omoshile O; Freeman, Clive M; Hartmann, Rolf W; Handratta, Venkatesh D; Vasaitis, Tadas S; Brodie, Angela M H; Njar, Vincent C O

    2003-06-01

    We report here a molecular modeling investigation of steroidal and nonsteroidal inhibitors of human cytochrome P450 17alpha-hydroxylase-17,20-lyase (CYP17). Using the pharmacophore perception technique, we have generated common-feature pharmacophore model(s) to explain the putative binding requirements for two classes of human CYP17 inhibitors. Common chemical features in the steroid and nonsteroid human CYP17 enzyme inhibitors, as deduced by the Catalyst/HipHop program, are one to two hydrogen bond acceptors (HBAs) and three hydrophobic groups. For azole-steroidal ligands, the 3beta-OH group of ring A and the N-3 of the azole ring attached to ring D at C-17 act as hydrogen bond acceptors. A model that permits hydrogen bond interaction between the azole functionality on ring D and the enzyme is consistent with experimental deductions for type II CYP17 inhibitors where a sixth ligating atom interacts with Fe(II) of heme. In general, pharmacophore models derived for steroid and nonsteroidal compounds bear striking similarities to all azole sites mapping the HBA functionality and to three hydrophobic features describing the hydrophobic interactions between the ligands and the enzyme. Using the pharmacophore model derived for azole-steroidal inhibitors as a 3D search query against several 3D multiconformational Catalyst formatted databases, we identified several steroidal compounds with potential inhibition of this enzyme. Biological testing of some of these compounds show low to high inhibitory potency against the human CYP17 enzyme. This shows the potential of our pharmacophore model in identifying new and potent CYP17 inhibitors. Further refinement of the model is in progress with a view to identifying and optimizing new leads.

  4. Carbon monoxide effects on human ventricle action potential assessed by mathematical simulations

    PubMed Central

    Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne R.

    2013-01-01

    Carbon monoxide (CO) that is produced in a number of different mammalian tissues is now known to have significant effects on the cardiovascular system. These include: (i) vasodilation, (ii) changes in heart rate and strength of contractions, and (iii) modulation of autonomic nervous system input to both the primary pacemaker and the working myocardium. Excessive CO in the environment is toxic and can initiate or mediate life threatening cardiac rhythm disturbances. Recent reports link these ventricular arrhythmias to an increase in the slowly inactivating, or “late” component of the Na+ current in the mammalian heart. The main goal of this paper is to explore the basis of this pro-arrhythmic capability of CO by incorporating changes in CO-induced ion channel activity with intracellular signaling pathways in the mammalian heart. To do this, a quite well-documented mathematical model of the action potential and intracellular calcium transient in the human ventricular myocyte has been employed. In silico iterations based on this model provide a useful first step in illustrating the cellular electrophysiological consequences of CO that have been reported from mammalian heart experiments. Specifically, when the Grandi et al. model of the human ventricular action potential is utilized, and after the Na+ and Ca2+ currents in a single myocyte are modified based on the experimental literature, early after-depolarization (EAD) rhythm disturbances appear, and important elements of the underlying causes of these EADs are revealed/illustrated. Our modified mathematical model of the human ventricular action potential also provides a convenient digital platform for designing future experimental work and relating these changes in cellular cardiac electrophysiology to emerging clinical and epidemiological data on CO toxicity. PMID:24146650

  5. Peroxynitrite-mediated nitrosative stress decreases motility and mitochondrial membrane potential in human spermatozoa.

    PubMed

    Uribe, P; Boguen, R; Treulen, F; Sánchez, R; Villegas, J V

    2015-03-01

    Nitrosative stress is produced by high levels of reactive nitrogen species (RNS). The RNS include peroxynitrite, a highly reactive free radical produced from a diffusion-controlled reaction between nitric oxide and superoxide anion. Peroxynitrite causes nitration and oxidation of lipids, proteins and DNA, and is thus considered an important pathogenic mechanism in various diseases. Although high levels of peroxynitrite are associated with astenozoospermia, few reports exist regarding the in vitro effect of high levels of this RNS on human sperm. The aim of this study was to evaluate the in vitro effect of nitrosative stress caused by peroxynitrite on the viability, motility and mitochondrial membrane potential of human spermatozoa. To do this, human spermatozoa from healthy donors were exposed in vitro to 3-morpholinosydnonimine (SIN-1), a molecule that generates peroxynitrite. Incubations were done at 37°C for up to 4 h with SIN-1 concentrations between 0.2 and 1.0 mmol/l. Generation of peroxynitrite was confirmed using dihydrorhodamine 123 (DHR) by spectrophotometry and flow cytometry. Sperm viability was assessed by propidium iodide staining; sperm motility was analyzed by CASA, and the state of mitochondrial membrane potential (ΔΨm) by JC-1 staining. Viability and ΔΨm were measured by flow cytometry. The results showed an increase in DHR oxidation, demonstrating the generation of peroxynitrite through SIN-1. Peroxynitrite decreased progressive and total motility, as well as some sperm kinetic parameters. Mitochondrial membrane potential also decreased. These alterations occurred with no decrease in sperm viability. In conclusion, peroxynitrite-induced nitrosative stress impairs vital functions in the male gamete, possibly contributing to male infertility. PMID:25425609

  6. Potentially-lethal damage and radioprotection in human cells exposed to californium-252

    SciTech Connect

    Schroy, C.B.; Goud, S.N.; Magura, C.; Feola, J.M.; Maruyama, Y.

    1986-01-01

    Cultured human T-1E cells were irradiated with californium-252 neutrons and gamma rays. When 2 mm caffeine was present in the medium for 47 h after irradiation cell survival (assayed by colony formation) was decreased significantly. When 2 m dimethylsulfoxide was present during the irradiations radioprotection was observed using the same assay. The caffeine data indicate that potentially-lethal lesions exist in cells after californium exposure and that these lesions can be made lethal when they would otherwise be repaired. The DMSO data indicate that radioprotection from californium exposure can be achieved and that scanvengable free radicals play an important role in Cf-252 lethality.

  7. [ASSESSMENT OF POTENTIAL RISK FOR CONTAMINATION OF SURFACE WATER RESERVOIRS BY PATHOGENS OF HUMAN PARASITIC DISEASES].

    PubMed

    Khromenkova, E P; Dimidova, L L; Dumbadze, O S; Aidinov, G T; Shendo, G L; Agirov, A Kh; Batchaev, Kh Kh

    2015-01-01

    Sanitary and parasitological studies of the waste effluents and surface reservoir waters were conducted in the south of Russia. The efficiency of purification of waste effluents from the pathogens of parasitic diseases was investigated in the region's sewage-purification facilities. The water of the surface water reservoirs was found to contain helminthic eggs and larvae and intestinal protozoan cysts because of the poor purification and disinfection of service fecal sewage waters. The poor purification and disinvasion of waste effluents in the region determine the potential risk of contamination of the surface water reservoirs and infection of the population with the pathogens of human parasitic diseases.

  8. Potential of Cells and Cytokines/Chemokines to Regulate Tertiary Lymphoid Structures in Human Diseases

    PubMed Central

    Jing, Feifeng

    2016-01-01

    Tertiary lymphoid structures (TLS) are ectopic lymphoid tissues involved in chronic inflammation, autoimmune diseases, transplant rejection and cancer. They exhibit almost all the characteristics of secondary lymphoid organs (SLO), which are associated with adaptive immune responses; as such, they contain organized B-cell follicles with germinal centers, distinct areas containing T cells and dendritic cells, high endothelial venules, and lymphatics. In this review, we briefly describe the formation of SLO, and describe the cellular subsets and molecular cues involved in the formation and maintenance of TLS. Finally, we discuss the associations of TLS with human diseases, especially autoimmune diseases, and the potential for therapeutic targeting. PMID:27799872

  9. Remote detection of human electroencephalograms using ultrahigh input impedance electric potential sensors

    NASA Astrophysics Data System (ADS)

    Harland, C. J.; Clark, T. D.; Prance, R. J.

    2002-10-01

    In this letter, we demonstrate the use of very high performance, ultrahigh impedance, electric potential probes in the detection of electrical activity in the brain. We show that these sensors, requiring no electrical or physical contact with the body, can be used to monitor the human electroencephalogram (EEG) revealing, as examples, the α and β rhythms and the α blocking phenomenon. We suggest that the advantages offered by these sensors compared with the currently used contact (Ag/AgCl) electrodes may act to stimulate new developments in multichannel EEG monitoring and in real-time electrical imaging of the brain.

  10. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Ethylene Glycol.

    PubMed

    2004-01-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for ethylene glycol (EG) to cause adverse effects on reproduction and development in humans. EG was selected for evaluation due to recent toxicity and occupational exposure information and widespread exposure in the general public. EG is a small, hydroxy-substituted hydrocarbon used as a chemical intermediate in the production of polyester compounds. It is also found in automotive anti-freeze, industrial coolants, hydraulic fluids, and windshield deicer fluids. The results of this evaluation on EG are published in a NTP-CERHR monograph which includes: 1) the Expert Panel Report on the Reproductive and Developmental Toxicity of Ethylene Glycol, 2) the NTP Brief, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to EG on human development and reproduction based on the conclusions of the NTP-CERHR Expert Panel Report and the public comments received on that report. These conclusions concurred with those of the expert panel. First, although EG could possibly affect human development if exposures are sufficiently high, there is negligible concern for developmental effects in humans at current proposed/estimated exposure levels. There is no direct evidence that exposure of people to EG adversely affects reproduction or development, but studies reviewed by the expert panel show that oral exposure to high doses of EG can adversely affect development in mice and rats. These studies indicate doses that exceed saturation of the glycolic acid metabolism are needed to produce developmental toxicity. Proposed exposure scenarios constructed by the expert panel and current proposed/estimated exposure levels suggest that human exposures are at least 100- to 1000-fold lower than the dose expected to result in metabolic

  11. Potential Limitations of the NSG Humanized Mouse as a Model System to Optimize Engineered Human T cell Therapy for Cancer

    PubMed Central

    Alcantar-Orozco, Erik M.; Gornall, Hannah; Baldan, Vania; Hawkins, Robert E.

    2013-01-01

    Abstract The genetic modification of peripheral blood lymphocytes using retroviral vectors to redirect T cells against tumor cells has been recently used as a means to generate large numbers of antigen-specific T cells for adoptive cell therapy protocols. However, commonly used retroviral vector-based genetic modification requires T cells to be driven into cell division; this potent mitogenic stimulus is associated with the development of an effector phenotype that may adversely impact upon the long-term engraftment potential and subsequent antitumor effects of T cells. To investigate whether the cytokines used during culture impact upon the engraftment potential of gene-modified T cells, a humanized model employing T cells engrafted with a MART-1-specific T cell receptor adoptively transferred into NOD/Shi-scid IL-2rγ−/− (NSG) immune-deficient mice bearing established melanoma tumors was used to compare the effects of the common γ chain cytokines IL-2, IL-7, and IL-15 upon gene-modified T cell activity. MART-1-specific T cells cultured in IL-7 and IL-15 demonstrated greater relative in vitro proliferation and viability of T cells compared with the extensively used IL-2. Moreover, the IL-15 culture prolonged the survival of animals bearing melanoma tumors after adoptive transfer. However, the combination of IL-7 and IL-15 produced T cells with improved engraftment potential compared with IL-15 alone; however, a high rate of xenogeneic graft-versus-host disease prevented the identification of a clear improvement in antitumor effect of these T cells. These results clearly demonstrate modulation of gene-modified T cell engraftment in the NSG mouse, which supports the future testing of the combination of IL-7 and IL-15 in adoptive cell therapy protocols; however, this improved engraftment is also associated with the long-term maintenance of xenoreactive T cells, which limits the ultimate usefulness of the NSG mouse model in this situation. PMID:23931270

  12. Sulfidation of silver nanowires inside human alveolar epithelial cells: a potential detoxification mechanism

    NASA Astrophysics Data System (ADS)

    Chen, Shu; Goode, Angela E.; Sweeney, Sinbad; Theodorou, Ioannis G.; Thorley, Andrew J.; Ruenraroengsak, Pakatip; Chang, Yan; Gow, Andrew; Schwander, Stephan; Skepper, Jeremy; Zhang, Junfeng (Jim); Shaffer, Milo S.; Chung, Kian Fan; Tetley, Teresa D.; Ryan, Mary P.; Porter, Alexandra E.

    2013-09-01

    Silver nanowires (AgNWs) are being developed for use in optoelectronics. However before widespread usage, it is crucial to determine their potential effects on human health. It is accepted that Ag nanoparticles (AgNPs) exert toxic effects by releasing Ag+ ions, but much less is known about whether Ag+ reacts with compounds, or any downstream bioactive effects of transformed AgNPs. Analytical high-resolution transmission electron microscopy has been employed to elucidate cellular uptake and reactivity of AgNWs inside human alveolar epithelial type 1-like cells. AgNWs were observed in the cytoplasm and membrane-bound vesicles, and precipitation of Ag2S within the cell occurred after 1 h exposure. Cell viability studies showed no evidence of cytotoxicity and reactive oxygen species were not observed on exposure of cells to AgNWs. We suggest that Ag2S formation acts as a `trap' for free Ag+, significantly limiting short-term toxicological effects - with important consequences for the safety of Ag-nanomaterials to human health.Silver nanowires (AgNWs) are being developed for use in optoelectronics. However before widespread usage, it is crucial to determine their potential effects on human health. It is accepted that Ag nanoparticles (AgNPs) exert toxic effects by releasing Ag+ ions, but much less is known about whether Ag+ reacts with compounds, or any downstream bioactive effects of transformed AgNPs. Analytical high-resolution transmission electron microscopy has been employed to elucidate cellular uptake and reactivity of AgNWs inside human alveolar epithelial type 1-like cells. AgNWs were observed in the cytoplasm and membrane-bound vesicles, and precipitation of Ag2S within the cell occurred after 1 h exposure. Cell viability studies showed no evidence of cytotoxicity and reactive oxygen species were not observed on exposure of cells to AgNWs. We suggest that Ag2S formation acts as a `trap' for free Ag+, significantly limiting short-term toxicological effects

  13. NTP-CERHR monograph on the potential human reproductive and developmental effects of amphetamines.

    PubMed

    2005-07-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for amphetamines to cause adverse effects on reproduction and development in humans. Amphetamines evaluated were D- and D,L-amphetamine and methamphetamine. Amphetamine is approved by the U.S. Food and Drug Administration for the treatment of attention deficit hyperactivity disorder (ADHD) in persons over 3 years of age and narcolepsy; methamphetamine is approved for the treatment of ADHD in persons 6 years of age and older and for short-term treatment of obesity. Amphetamines were selected for evaluation because of 1) widespread usage in children, 2) availability of developmental studies in children and experimental animals, and 3) public concern about the effect of this stimulant on child development. The results of this evaluation on amphetamines are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Methylphenidate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to methylphenidate on human development and reproduction. First, there is some concern for developmental effects, specifically for potential neurobehavioral alterations, from prenatal amphetamine exposure in humans both in therapeutic and non-therapeutic settings. After prenatal exposure to therapeutic doses of amphetamine, rat pups demonstrated neurobehavioral alterations. Data from human and animal studies were judged insufficient for an evaluation of the effect of amphetamine exposure on growth and other related developmental effects. Second, there is concern for methamphetamine-induced adverse developmental effects, specifically on growth and neurobehavioral development, in therapeutic and non-therapeutic settings. This conclusion is based

  14. Host-defense peptides of the skin with therapeutic potential: From hagfish to human.

    PubMed

    Conlon, J Michael

    2015-05-01

    It is now well established that peptides that were first identified on the basis of their ability to inhibit growth of bacteria and fungi are multifunctional and so are more informatively described as host-defense peptides. In some cases, their role in protecting the organism against pathogenic microorganisms, although of importance, may be secondary. A previous article in the journal (Peptides 2014; 57:67-77) assessed the potential of peptides present in the skin secretions of frogs for development into anticancer, antiviral, immunomodulatory and antidiabetic drugs. This review aims to extend the scope of this earlier article by focusing upon therapeutic applications of host-defense peptides present in skin secretions and/or skin extracts of species belonging to other vertebrate classes (Agnatha, Elasmobranchii, Teleostei, Reptilia, and Mammalia as represented by the human) that supplement their potential role as anti-infectives for use against multidrug-resistant microorganisms.

  15. MicroRNAs as potential target in human bone and soft tissue sarcoma therapeutics

    PubMed Central

    Varshney, Jyotika; Subramanian, Subbaya

    2015-01-01

    Sarcomas are highly aggressive heterogeneous tumors that are mesenchymal in origin. There have been vast advancements on identifying diagnostic markers for sarcomas including chromosomal translocations, but very little progress has been made to identify targeted therapies against them. The tumor heterogeneity, genetic complexity and the lack of drug studies make it challenging to recognize the potential targets and also accounts for the inadequate treatments in sarcomas. In recent years, microRNAs that are a part of small non-coding RNAs have shown promising results as potential diagnostic and prognostic biomarkers in multiple sarcoma types. This review focuses on the current knowledge of the microRNAs that are deregulated in sarcomas, and an insight on the strategies to target these microRNAs that are essential for developing improved therapies for various human sarcomas. PMID:26137468

  16. Correction: Cecotti, H. and Rivet, B. Subject Combination and Electrode Selection in Cooperative Brain-Computer Interface Based on Event Related Potentials. Brain Sci. 2014, 4, 335–355

    PubMed Central

    Cecotti, Hubert; Rivet, Bertrand

    2014-01-01

    The authors wish to make the following correction to this paper (Cecotti, H.; Rivet, B. Subject Combination and Electrode Selection in Cooperative Brain-Computer Interface Based on Event Related Potentials. Brain Sci. 2014, 4, 335–355): Due to an internal error, the reference numbers in the original published paper were not shown, and the error was not due to the authors. The former main text should be replaced as below. PMID:25243772

  17. Robotic Missions to Small Bodies and Their Potential Contributions to Human Exploration and Planetary Defense

    NASA Technical Reports Server (NTRS)

    Abell, Paul A.; Rivkin, Andrew S.

    2015-01-01

    Introduction: Robotic missions to small bodies will directly address aspects of NASA's Asteroid Initiative and will contribute to future human exploration and planetary defense. The NASA Asteroid Initiative is comprised of two major components: the Grand Challenge and the Asteroid Mission. The first component, the Grand Challenge, focuses on protecting Earth's population from asteroid impacts by detecting potentially hazardous objects with enough warning time to either prevent them from impacting the planet, or to implement civil defense procedures. The Asteroid Mission involves sending astronauts to study and sample a near-Earth asteroid (NEA) prior to conducting exploration missions of the Martian system, which includes Phobos and Deimos. The science and technical data obtained from robotic precursor missions that investigate the surface and interior physical characteristics of an object will help identify the pertinent physical properties that will maximize operational efficiency and reduce mission risk for both robotic assets and crew operating in close proximity to, or at the surface of, a small body. These data will help fill crucial strategic knowledge gaps (SKGs) concerning asteroid physical characteristics that are relevant for human exploration considerations at similar small body destinations. These data can also be applied for gaining an understanding of pertinent small body physical characteristics that would also be beneficial for formulating future impact mitigation procedures. Small Body Strategic Knowledge Gaps: For the past several years NASA has been interested in identifying the key SKGs related to future human destinations. These SKGs highlight the various unknowns and/or data gaps of targets that the science and engineering communities would like to have filled in prior to committing crews to explore the Solar System. An action team from the Small Bodies Assessment Group (SBAG) was formed specifically to identify the small body SKGs under the

  18. Potential Human Pathogenic Bacteria in a Mixed Urban Watershed as Revealed by Pyrosequencing

    PubMed Central

    Ibekwe, A. Mark; Leddy, Menu; Murinda, Shelton E.

    2013-01-01

    Current microbial source tracking (MST) methods for water depend on testing for fecal indicator bacterial counts or specific marker gene sequences to identify fecal contamination where potential human pathogenic bacteria could be present. In this study, we applied 454 high-throughput pyrosequencing to identify bacterial pathogen DNA sequences, including those not traditionally monitored by MST and correlated their abundances to specific sources of contamination such as urban runoff and agricultural runoff from concentrated animal feeding operations (CAFOs), recreation park area, waste-water treatment plants, and natural sites with little or no human activities. Samples for pyrosequencing were surface water, and sediment collected from 19 sites. A total of 12,959 16S rRNA gene sequences with average length of ≤400 bp were obtained, and were assigned to corresponding taxonomic ranks using ribosomal database project (RDP), Classifier and Greengenes databases. The percent of total potential pathogens were highest in urban runoff water (7.94%), agricultural runoff sediment (6.52%), and Prado Park sediment (6.00%), respectively. Although the numbers of DNA sequence tags from pyrosequencing were very high for the natural site, corresponding percent potential pathogens were very low (3.78–4.08%). Most of the potential pathogenic bacterial sequences identified were from three major phyla, namely, Proteobacteria, Bacteroidetes, and Firmicutes. The use of deep sequencing may provide improved and faster methods for the identification of pathogen sources in most watersheds so that better risk assessment methods may be developed to enhance public health. PMID:24278139

  19. AHI-1: a novel signaling protein and potential therapeutic target in human leukemia and brain disorders

    PubMed Central

    Esmailzadeh, Sharmin; Jiang, Xiaoyan

    2011-01-01

    Progress in the understanding of the molecular and cellular mechanisms of human cancer, including human leukemia and lymphomas, has been spurred by cloning of fusion genes created by chromosomal translocations or by retroviral insertional mutagenesis; a number of oncogenes and tumor suppressors involved in development of a number of malignancies have been identified in this manner. The BCR-ABL fusion gene, originating in a multipotent hematopoietic stem cell, is the molecular signature of chronic myeloid leukemia (CML). Discovery of this fusion gene has led to the development of one of the first successful targeted molecular therapies for cancer (Imatinib). It illustrates the advances that can result from an understanding of the molecular basis of disease. However, there still remain many as yet unidentified mutations that may influence the initiation or progression of human diseases. Thus, identification and characterization of the mechanism of action of genes that contribute to human diseases is an important and opportune area of current research. One promising candidate as a potential therapeutic target is Abelson helper integration site-1(Ahi-1/AHI-1) that was identified by retroviral insertional mutagenesis in murine models of leukemia/lymphomas and is highly elevated in certain human lymphoma and leukemia stem/progenitor cells. It encodes a unique protein with a SH3 domain, multiple SH3 binding sites and a WD40-repeat domain, suggesting that the normal protein has novel signaling activities. A new AHI-1-BCR-ABL-JAK2 interaction complex has recently been identified and this complex regulates transforming activities and drug resistance in CML stem/progenitor cells. Importantly, AHI-1 has recently been identified as a susceptibility gene involved in a number of brain disorders, including Joubert syndrome. Therefore, understanding molecular functions of the AHI-1 gene could lead to important and novel insights into disease processes involved in specific types of

  20. Development of human cell models for assessing the carcinogenic potential of chemicals

    SciTech Connect

    Pang Yaqin; Li Wenxue; Ma Rulin; Ji Weidong; Wang Qing; Li Daochuan; Xiao Yongmei; Wei Qing; Lai Yandong; Yang Ping; Chen Liping; Tang Shifu; Lin Yuchun; Zhuang Zhixiong; Zheng Yuxin; Chen Wen

    2008-11-01

    To develop human cell models for assessing the carcinogenic potential of chemicals, we established transgenic human cell lines and tested the sensitivity of known carcinogens using a cell transformation assay. A retroviral vector encoding an oncogenic allele of H-Ras (HBER) or c-Myc (HBEM) was introduced into human bronchial epithelial cells (HBE) immortalized by SV40 large T (LT) antigen, leading to increased cell proliferation but failing to confer a transformed phenotype characterized by anchorage-independent cell growth and tumor formation of immunodeficient mice. When these pre-transformed cells were treated with nickel sulfate (NiSO{sub 4}), we found that it shortened the latency of malignant transformation at least by 19 wk in HBER cells or 16 wk in HBEM cells compared to vector control cells. Similarly, the latency of cell transformation was shorter by 15 wk in HBER cells or 9 wk in HBEM cells when cells were treated with benzo(a)pyrenediol epoxide (BPDE). HBER cells appeared to be more sensitive to TPA, NiSO{sub 4} or BPDE-induced cell transformation compared to human embryonic kidney cells expressing H-Ras (HEKR), implying that cell-type specificity is one of important factors determining the effectiveness of the assay. Using AFB{sub 1} and BaP as the representative pro-carcinogens, we also compared the efficiency of three different metabolic conditions in mediating cell transformation. Low dose chemical induction seems to be a prospective system used for metabolic activation of pro-carcinogens. Our findings provided direct evidence that a genetically modified human cell transformation model can be applied to the assessment of potent carcinogens.

  1. A CORRECTION.

    PubMed

    Johnson, D

    1940-03-22

    IN a recently published volume on "The Origin of Submarine Canyons" the writer inadvertently credited to A. C. Veatch an excerpt from a submarine chart actually contoured by P. A. Smith, of the U. S. Coast and Geodetic Survey. The chart in question is Chart IVB of Special Paper No. 7 of the Geological Society of America entitled "Atlantic Submarine Valleys of the United States and the Congo Submarine Valley, by A. C. Veatch and P. A. Smith," and the excerpt appears as Plate III of the volume fist cited above. In view of the heavy labor involved in contouring the charts accompanying the paper by Veatch and Smith and the beauty of the finished product, it would be unfair to Mr. Smith to permit the error to go uncorrected. Excerpts from two other charts are correctly ascribed to Dr. Veatch. PMID:17839404

  2. A CORRECTION.

    PubMed

    Johnson, D

    1940-03-22

    IN a recently published volume on "The Origin of Submarine Canyons" the writer inadvertently credited to A. C. Veatch an excerpt from a submarine chart actually contoured by P. A. Smith, of the U. S. Coast and Geodetic Survey. The chart in question is Chart IVB of Special Paper No. 7 of the Geological Society of America entitled "Atlantic Submarine Valleys of the United States and the Congo Submarine Valley, by A. C. Veatch and P. A. Smith," and the excerpt appears as Plate III of the volume fist cited above. In view of the heavy labor involved in contouring the charts accompanying the paper by Veatch and Smith and the beauty of the finished product, it would be unfair to Mr. Smith to permit the error to go uncorrected. Excerpts from two other charts are correctly ascribed to Dr. Veatch.

  3. The Impact of Biopsy on Human Embryo Developmental Potential during Preimplantation Genetic Diagnosis

    PubMed Central

    Cimadomo, Danilo; Capalbo, Antonio; Ubaldi, Filippo Maria; Scarica, Catello; Palagiano, Antonio; Canipari, Rita; Rienzi, Laura

    2016-01-01

    Preimplantation Genetic Diagnosis and Screening (PGD/PGS) for monogenic diseases and/or numerical/structural chromosomal abnormalities is a tool for embryo testing aimed at identifying nonaffected and/or euploid embryos in a cohort produced during an IVF cycle. A critical aspect of this technology is the potential detrimental effect that the biopsy itself can have upon the embryo. Different embryo biopsy strategies have been proposed. Cleavage stage blastomere biopsy still represents the most commonly used method in Europe nowadays, although this approach has been shown to have a negative impact on embryo viability and implantation potential. Polar body biopsy has been proposed as an alternative to embryo biopsy especially for aneuploidy testing. However, to date no sufficiently powered study has clarified the impact of this procedure on embryo reproductive competence. Blastocyst stage biopsy represents nowadays the safest approach not to impact embryo implantation potential. For this reason, as well as for the evidences of a higher consistency of the molecular analysis when performed on trophectoderm cells, blastocyst biopsy implementation is gradually increasing worldwide. The aim of this review is to present the evidences published to date on the impact of the biopsy at different stages of preimplantation development upon human embryos reproductive potential. PMID:26942198

  4. [Unconscious Acoustical Stimuli Effects on Event-related Potentials in Humans].

    PubMed

    Kopeikina, E A; Choroshich, V V; Aleksandrov, A Y; Ivanova, V Y

    2015-01-01

    Unconscious perception essentially affects human behavior. The main results in this area obtained in experiments with visual stimuli. However, the acoustical stimuli play not less important role in behavior. The main idea of this paper is the electroencephalographic investigation of unconscious acoustical stimulation effects on electro-physiological activity of the brain. For this purpose, the event-related potentials were acquired under unconscious stimulus priming paradigm. The one syllable, three letter length, Russian words and pseudo-words with single letter substitution were used as primes and targets. As a result, we find out that repetition and alternative priming similarly affects the event-related potential's component with 200 ms latency after target application in frontal parietal and temporal areas. Under alternative priming the direction of potential amplitude modification nearby 400 ms was altered for word and semi-word targets. Alternative priming reliably increase ERP's amplitude in 400 ms locality with pseudo-word targets and decrease it under word targets. Taking into account, that all participants were unable to distinguish the applied prime stimuli, we can assume that the event-related potential changes evoked by unconscious perception of acoustical stimuli. The ERP amplitude dynamics revealed in current investigation demonstrate the opportunity of subliminal acoustical stimuli to modulate the electrical activity evoked by verbal acoustical stimulation. PMID:26237945

  5. Human toxicity potentials for life-cycle assessment and toxics release inventory risk screening.

    PubMed

    Hertwich, E G; Mateles, S F; Pease, W S; McKone, T E

    2001-04-01

    The human toxicity potential (HTP), a calculated index that reflects the potential harm of a unit of chemical released into the environment, is based on both the inherent toxicity of a compound and its potential dose. It is used to weight emissions inventoried as part of a life-cycle assessment (LCA) or in the toxics release inventory (TRI) and to aggregate emissions in terms of a reference compound. Total emissions can be evaluated in terms of benzene equivalence (carcinogens) and toluene equivalents (noncarcinogens). The potential dose is calculated using a generic fate and exposure model, CalTOX, which determines the distribution of a chemical in a model environment and accounts for a number of exposure routes, including inhalation, ingestion of produce, fish, and meat, and dermal contact with water and soil. Toxicity is represented by the cancer potency q1* for carcinogens and the safe dose (RfD, RfC) for noncarcinogens. This article presents cancer and noncancer HTP values for air and surface-water emissions of 330 compounds. This list covers 258 chemicals listed in U.S. Environmental Protection Agency TRI, or 79 weight-% of the TRI releases to air reported in 1997.

  6. Entropic Corrections to Coulomb's Law

    NASA Astrophysics Data System (ADS)

    Hendi, S. H.; Sheykhi, A.

    2012-04-01

    Two well-known quantum corrections to the area law have been introduced in the literatures, namely, logarithmic and power-law corrections. Logarithmic corrections, arises from loop quantum gravity due to thermal equilibrium fluctuations and quantum fluctuations, while, power-law correction appears in dealing with the entanglement of quantum fields in and out the horizon. Inspired by Verlinde's argument on the entropic force, and assuming the quantum corrected relation for the entropy, we propose the entropic origin for the Coulomb's law in this note. Also we investigate the Uehling potential as a radiative correction to Coulomb potential in 1-loop order and show that for some value of distance the entropic corrections of the Coulomb's law is compatible with the vacuum-polarization correction in QED. So, we derive modified Coulomb's law as well as the entropy corrected Poisson's equation which governing the evolution of the scalar potential ϕ. Our study further supports the unification of gravity and electromagnetic interactions based on the holographic principle.

  7. Caring potentials in the shadows of power, correction, and discipline—Forensic psychiatric care in the light of the work of Michel Foucault

    PubMed Central

    Hörberg, Ulrica; Dahlberg, Karin

    2015-01-01

    The aim of this article is to shed light on contemporary forensic psychiatric care through a philosophical examination of the empirical results from two lifeworld phenomenological studies from the perspective of patients and carers, by using the French philosopher Michel Foucault's historical–philosophical work. Both empirical studies were conducted in a forensic psychiatric setting. The essential results of the two empirical studies were reexamined in a phenomenological meaning analysis to form a new general structure in accordance with the methodological principles of Reflective Lifeworld Research. This general structure shows how the caring on the forensic psychiatric wards appears to be contradictory, in that it is characterized by an unreflective (non-)caring attitude and contributes to an inconsistent and insecure existence. The caring appears to have a corrective approach and thus lacks a clear caring structure, a basic caring approach that patients in forensic psychiatric services have a great need of. To gain a greater understanding of forensic psychiatric caring, the new empirical results were further examined in the light of Foucault's historical–philosophical work. The philosophical examination is presented in terms of the three meaning constituents: Caring as correction and discipline, The existence of power, and Structures and culture in care. The philosophical examination illustrates new meaning nuances of the corrective and disciplinary nature of forensic psychiatric care, its power, and how this is materialized in caring, and what this does to the patients. The examination reveals embedded difficulties in forensic psychiatric care and highlights a need to revisit the aim of such care. PMID:26319100

  8. Caring potentials in the shadows of power, correction, and discipline - Forensic psychiatric care in the light of the work of Michel Foucault.

    PubMed

    Hörberg, Ulrica; Dahlberg, Karin

    2015-01-01

    The aim of this article is to shed light on contemporary forensic psychiatric care through a philosophical examination of the empirical results from two lifeworld phenomenological studies from the perspective of patients and carers, by using the French philosopher Michel Foucault's historical-philosophical work. Both empirical studies were conducted in a forensic psychiatric setting. The essential results of the two empirical studies were reexamined in a phenomenological meaning analysis to form a new general structure in accordance with the methodological principles of Reflective Lifeworld Research. This general structure shows how the caring on the forensic psychiatric wards appears to be contradictory, in that it is characterized by an unreflective (non-)caring attitude and contributes to an inconsistent and insecure existence. The caring appears to have a corrective approach and thus lacks a clear caring structure, a basic caring approach that patients in forensic psychiatric services have a great need of. To gain a greater understanding of forensic psychiatric caring, the new empirical results were further examined in the light of Foucault's historical-philosophical work. The philosophical examination is presented in terms of the three meaning constituents: Caring as correction and discipline, The existence of power, and Structures and culture in care. The philosophical examination illustrates new meaning nuances of the corrective and disciplinary nature of forensic psychiatric care, its power, and how this is materialized in caring, and what this does to the patients. The examination reveals embedded difficulties in forensic psychiatric care and highlights a need to revisit the aim of such care.

  9. Caring potentials in the shadows of power, correction, and discipline - Forensic psychiatric care in the light of the work of Michel Foucault.

    PubMed

    Hörberg, Ulrica; Dahlberg, Karin

    2015-01-01

    The aim of this article is to shed light on contemporary forensic psychiatric care through a philosophical examination of the empirical results from two lifeworld phenomenological studies from the perspective of patients and carers, by using the French philosopher Michel Foucault's historical-philosophical work. Both empirical studies were conducted in a forensic psychiatric setting. The essential results of the two empirical studies were reexamined in a phenomenological meaning analysis to form a new general structure in accordance with the methodological principles of Reflective Lifeworld Research. This general structure shows how the caring on the forensic psychiatric wards appears to be contradictory, in that it is characterized by an unreflective (non-)caring attitude and contributes to an inconsistent and insecure existence. The caring appears to have a corrective approach and thus lacks a clear caring structure, a basic caring approach that patients in forensic psychiatric services have a great need of. To gain a greater understanding of forensic psychiatric caring, the new empirical results were further examined in the light of Foucault's historical-philosophical work. The philosophical examination is presented in terms of the three meaning constituents: Caring as correction and discipline, The existence of power, and Structures and culture in care. The philosophical examination illustrates new meaning nuances of the corrective and disciplinary nature of forensic psychiatric care, its power, and how this is materialized in caring, and what this does to the patients. The examination reveals embedded difficulties in forensic psychiatric care and highlights a need to revisit the aim of such care. PMID:26319100

  10. Data from human salivary proteome – A resource of potential biomarkers for oral cancer

    PubMed Central

    Sivadasan, Priya; Kumar Gupta, Manoj; Sathe, Gajanan J.; Balakrishnan, Lavanya; Palit, Priyanka; Gowda, Harsha; Suresh, Amritha; Abraham Kuriakose, Moni; Sirdeshmukh, Ravi

    2015-01-01

    Salivary proteins are an important source for developing marker-based assays for oral cancers. To get an insight into the proteins present in human saliva, we applied multiple strategies involving affinity-based depletion of abundant proteins, fractionation of the resulting proteins or their tryptic peptides followed by LC–MS/MS analysis, using high resolution mass spectrometry. By integrating the protein identifications observed by us with those from similar workflows employed in earlier investigations, we compiled an updated salivary proteome. We have mapped the salivary proteome to the published data on differentially expressed proteins from oral cancer tissues and also for their secretory features using prediction tools, SignalP 4.1, TMHMM 2c and Exocarta. Proteotypic peptides for the subset of proteins implicated in oral cancer and mapped to any two of the prediction tools for secretory potential have been listed. The data here are related to the research article “Human saliva proteome – a resource of potential biomarkers for oral cancer” in the Journal of Proteomics [1]. PMID:26217819

  11. Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential

    PubMed Central

    Ishii, Tetsuya

    2014-01-01

    Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS) cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART) that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions. PMID:26237592

  12. ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs

    PubMed Central

    Lee, Michelle H.; Goralczyk, Anna G.; Kriszt, Rókus; Ang, Xiu Min; Badowski, Cedric; Li, Ying; Summers, Scott A.; Toh, Sue-Anne; Yassin, M. Shabeer; Shabbir, Asim; Sheppard, Allan; Raghunath, Michael

    2016-01-01

    Key to realizing the diagnostic and therapeutic potential of human brown/brite adipocytes is the identification of a renewable, easily accessible and safe tissue source of progenitor cells, and an efficacious in vitro differentiation protocol. We show that macromolecular crowding (MMC) facilitates brown adipocyte differentiation in adult human bone marrow mesenchymal stem cells (bmMSCs), as evidenced by substantially upregulating uncoupling protein 1 (UCP1) and uncoupled respiration. Moreover, MMC also induced ‘browning’ in bmMSC-derived white adipocytes. Mechanistically, MMC creates a 3D extracellular matrix architecture enshrouding maturing adipocytes in a collagen IV cocoon that is engaged by paxillin-positive focal adhesions also at the apical side of cells, without contact to the stiff support structure. This leads to an enhanced matrix-cell signaling, reflected by increased phosphorylation of ATF2, a key transcription factor in UCP1 regulation. Thus, tuning the dimensionality of the microenvironment in vitro can unlock a strong brown potential dormant in bone marrow. PMID:26883894

  13. Antitumor potential of three herbal extracts against human oral squamous cell lines.

    PubMed

    Chu, Qing; Satoh, Kazue; Kanamoto, Taisei; Terakubo, Shigemi; Nakashima, Hideki; Wang, Qintao; Sakagami, Hiroshi

    2009-08-01

    Three Chinese herbal extracts of Drynaria baronii, Angelica sinensis and Cornus officinalis Sieb. et Zucc (referred to as DB, AS, CO, respectively) were investigated for their antitumor potential. These extracts showed very weak cytotoxicity against all nine cultured human cells (normal and tumor cells), but with some tumor-specific cytotoxicity displayed by DB and CO. These extracts showed little or no growth stimulation effects at lower concentrations (so-called 'hormetic effect'). Human oral squamous cell carcinoma cell lines (HSC-2, NA) were relatively resistant to committing apoptosis, as compared with human promyelocytic leukemia HL-60 cells. Electron-spin resonance spectroscopy shows that DB and CO scavenged superoxide anion (generated by hypoxanthine and xanthine oxidase reaction) and hydroxyl radical (generated by Fenton reaction) more efficiently than AS. DB and CO, but not AS, produced broad radical peak(s) and enhanced the superoxide scavenging activity of vitamin C. However, none of the extracts clearly enhanced the cytotoxicity of mitoxantrone, an anthracycline antitumor antibiotic. DB, but not CO and AS, showed weak anti-HIV activity. These data demonstrate several unique antitumor properties of DB. PMID:19661337

  14. Human recombinant truncated RNASET2, devoid of RNase activity; A potential cancer therapeutic agent

    PubMed Central

    Nesiel-Nuttman, Liron; Schwartz, Betty; Shoseyov, Oded

    2014-01-01

    Human RNASET2 has been implicated in antitumorigenic and antiangiogenic activities, independent of its ribonuclease capacities. We constructed a truncated version of human RNASET2, starting at E50 (trT2-50) and devoid of ribonuclease activity. trT2-50 maintained its ability to bind actin and to inhibit angiogenesis and tumorigenesis. trT2-50 binds to cell surface actin and formed a complex with actin in vitro. The antiangiogenic effect of this protein was demonstrated in human umbilical vein endothelial cells (HUVECs) by its ability to arrest tube formation on Matrigel, induced by angiogenic factors. Immunofluorescence staining of HUVECs showed nuclear and cytosolic RNASET2 protein that was no longer detectable inside the cell following trT2-50 treatment. This effect was associated with disruption of the intracellular actin network. trT2-50 co-localized with angiogenin, suggesting that both molecules bind (or compete) for similar cellular epitopes. Moreover, trT2-50 led to a significant inhibition of tumor development. Histological analysis demonstrated abundant necrotic tissue and a substantial loss of endothelial structure in trT2-50-treated tumors. Collectively, the present results indicate that trT2-50, a molecule engineered to be deficient of its catalytic activity, still maintained its actin binding and anticancer-related biological activities. We therefore suggest that trT2-50 may serve as a potential cancer therapeutic agent. PMID:25426551

  15. Potential Applications for Radioisotope Power Systems in Support of Human Exploration Missions

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.; Colozza, Anthony J.; Schmitz, Paul C.

    2013-01-01

    Radioisotope power systems (RPS) for space applications have powered over 27 U.S. space systems, starting with Transit 4A and 4B in 1961, and more recently with the successful landing of the Mars Science Laboratory rover Curiosity in August 2012. RPS enable missions with destinations far from the Sun with faint solar flux, on planetary surfaces with dense or dusty atmospheres, and at places with long eclipse periods where solar array sizes and energy storage mass become impractical. RPS could also provide an enabling capability in support of human exploration activities. It is envisioned that with the higher power needs of most human mission concepts, a high efficiency thermal-to-electric technology would be required such as the Advanced Stirling Radioisotope generator (ASRG). The ASRG should be capable of a four-fold improvement in efficiency over traditional thermoelectric RPS. While it may be impractical to use RPS as a main power source, many other applications could be considered, such as crewed pressurized rovers, in-situ resource production of propellants, back-up habitat power, drilling, any mobile or remote activity from the main base habitat, etc. This paper will identify potential applications and provide concepts that could be a practical extension of the current ASRG design in providing for robust and flexible use of RPS on human exploration missions.

  16. Potential uses of human salivary protein and peptide analysis in the diagnosis of disease.

    PubMed

    Al Kawas, Sausan; Rahim, Zubaidah H A; Ferguson, David B

    2012-01-01

    Saliva is an important body fluid containing a complex mixture of proteins, peptides and other substances. These are not only important in maintaining the health of the oral cavity but also may yield information about oral and systemic disease. Comprehensive analysis and identification of the proteomic content of human saliva may contribute to the understanding of oral pathophysiology and provide a foundation for the recognition of potential biomarkers of human disease. The collection of saliva samples is non-invasive, safe, and inexpensive. It seems likely that testing methods can be developed which can be used in general medical or dental practice. However, it is important to realize that the collection of saliva must be carefully controlled. In this paper we review the progress in the analysis of the human salivary proteome and summarise the diagnostic possibilities that have been explored. The precautions in collecting saliva, and some of the factors which would have to be considered if a diagnostic test were to be generally adopted are discussed.

  17. Alterations of p53 in tumorigenic human bronchial epithelial cells correlate with metastatic potential

    NASA Technical Reports Server (NTRS)

    Piao, C. Q.; Willey, J. C.; Hei, T. K.; Hall, E. J. (Principal Investigator)

    1999-01-01

    The cellular and molecular mechanisms of radiation-induced lung cancer are not known. In the present study, alterations of p53 in tumorigenic human papillomavirus-immortalized human bronchial epithelial (BEP2D) cells induced by a single low dose of either alpha-particles or 1 GeV/nucleon (56)Fe were analyzed by PCR-single-stranded conformation polymorphism (SSCP) coupled with sequencing analysis and immunoprecipitation assay. A total of nine primary and four secondary tumor cell lines, three of which were metastatic, together with the parental BEP2D and primary human bronchial epithelial (NHBE) cells were studied. The immunoprecipitation assay showed overexpression of mutant p53 proteins in all the tumor lines but not in NHBE and BEP2D cells. PCR-SSCP and sequencing analysis found band shifts and gene mutations in all four of the secondary tumors. A G-->T transversion in codon 139 in exon 5 that replaced Lys with Asn was detected in two tumor lines. One mutation each, involving a G-->T transversion in codon 215 in exon 6 (Ser-->lle) and a G-->A transition in codon 373 in exon 8 (Arg-->His), was identified in the remaining two secondary tumors. These results suggest that p53 alterations correlate with tumorigenesis in the BEP2D cell model and that mutations in the p53 gene may be indicative of metastatic potential.

  18. Human BK Polyomavirus—The Potential for Head and Neck Malignancy and Disease

    PubMed Central

    Burger-Calderon, Raquel; Webster-Cyriaque, Jennifer

    2015-01-01

    Members of the human Polyomaviridae family are ubiquitous and pathogenic among immune-compromised individuals. While only Merkel cell polyomavirus (MCPyV) has conclusively been linked to human cancer, all members of the polyomavirus (PyV) family encode the oncoprotein T antigen and may be potentially carcinogenic. Studies focusing on PyV pathogenesis in humans have become more abundant as the number of PyV family members and the list of associated diseases has expanded. BK polyomavirus (BKPyV) in particular has emerged as a new opportunistic pathogen among HIV positive individuals, carrying harmful implications. Increasing evidence links BKPyV to HIV-associated salivary gland disease (HIVSGD). HIVSGD is associated with elevated risk of lymphoma formation and its prevalence has increased among HIV/AIDS patients. Determining the relationship between BKPyV, disease and tumorigenesis among immunosuppressed individuals is necessary and will allow for expanding effective anti-viral treatment and prevention options in the future. PMID:26184314

  19. Microcystin accumulation in freshwater bivalves from Lake Taihu, China, and the potential risk to human consumption.

    PubMed

    Chen, Jun; Xie, Ping

    2007-05-01

    The potential risk through ingestion of microcystins (MC) in contaminated mollusks has not been well studied. The present paper studied seasonal changes of MC content (determined by liquid chromatography-mass spectrometry) in various organs of three species of bivalves (Cristaria plicata, Hyriopsis cumingii, and Lamprotula leai) in Lake Taihu, China, where toxic cyanobacterial blooms occurred. Coinciding with peaks of seston MC (maximum, 5.7 microg/L) and MC in cyanobacterial blooms (maximum, 0.534 mg/g), most organs showed sharp MC peaks during the summer, indicating both fast uptake and fast depuration by bivalves. Because hepatopancreas and intestine had considerably higher MC content than other organs, they are the most dangerous for human consumption. Both the present and previous studies show that the hepatopancreatic MC and total tissue MC often are correlated in various aquatic invertebrates. During the peak of the cyanobacterial blooms, C. plicata had higher hepatopancreatic MC content than the other bivalves, whereas H. cumingii had higher intestinal MC content than the other bivalves. Estimated daily intakes for humans from the consumption of whole tissues of the three bivalves were 0.48 to 0.94 microg MC-LR equivalent/kg body weight (12- to 23.5-fold the tolerable daily intake value proposed by the World Health Organization), which indicates a high risk for humans consuming these bivalves.

  20. Human BK Polyomavirus-The Potential for Head and Neck Malignancy and Disease.

    PubMed

    Burger-Calderon, Raquel; Webster-Cyriaque, Jennifer

    2015-07-08

    Members of the human Polyomaviridae family are ubiquitous and pathogenic among immune-compromised individuals. While only Merkel cell polyomavirus (MCPyV) has conclusively been linked to human cancer, all members of the polyomavirus (PyV) family encode the oncoprotein T antigen and may be potentially carcinogenic. Studies focusing on PyV pathogenesis in humans have become more abundant as the number of PyV family members and the list of associated diseases has expanded. BK polyomavirus (BKPyV) in particular has emerged as a new opportunistic pathogen among HIV positive individuals, carrying harmful implications. Increasing evidence links BKPyV to HIV-associated salivary gland disease (HIVSGD). HIVSGD is associated with elevated risk of lymphoma formation and its prevalence has increased among HIV/AIDS patients. Determining the relationship between BKPyV, disease and tumorigenesis among immunosuppressed individuals is necessary and will allow for expanding effective anti-viral treatment and prevention options in the future.

  1. Invasive lionfish (Pterois volitans): a potential human health threat for ciguatera fish poisoning in tropical waters.

    PubMed

    Robertson, Alison; Garcia, Ana C; Quintana, Harold A Flores; Smith, Tyler B; Castillo, Bernard F; Reale-Munroe, Kynoch; Gulli, Joseph A; Olsen, David A; Hooe-Rollman, Jennifer I; Jester, Edward L E; Klimek, Brian J; Plakas, Steven M

    2013-12-27

    Invasive Indo-Pacific lionfish (Pterois volitans) have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP). More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 µg/kg C-CTX-1 equivalents was identified in fish from the U.S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas.

  2. Invasive Lionfish (Pterois volitans): A Potential Human Health Threat for Ciguatera Fish Poisoning in Tropical Waters

    PubMed Central

    Robertson, Alison; Garcia, Ana C.; Flores Quintana, Harold A.; Smith, Tyler B.; Castillo, Bernard F.; Reale-Munroe, Kynoch; Gulli, Joseph A.; Olsen, David A.; Hooe-Rollman, Jennifer I.; Jester, Edward L. E.; Klimek, Brian J.; Plakas, Steven M.

    2013-01-01

    Invasive Indo-Pacific lionfish (Pterois volitans) have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP). More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 µg/kg C-CTX-1 equivalents was identified in fish from the U.S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas. PMID:24378919

  3. Invasive lionfish (Pterois volitans): a potential human health threat for ciguatera fish poisoning in tropical waters.

    PubMed

    Robertson, Alison; Garcia, Ana C; Quintana, Harold A Flores; Smith, Tyler B; Castillo, Bernard F; Reale-Munroe, Kynoch; Gulli, Joseph A; Olsen, David A; Hooe-Rollman, Jennifer I; Jester, Edward L E; Klimek, Brian J; Plakas, Steven M

    2014-01-01

    Invasive Indo-Pacific lionfish (Pterois volitans) have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP). More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 µg/kg C-CTX-1 equivalents was identified in fish from the U.S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas. PMID:24378919

  4. [In vivo investigation of human brain networks by using cortico-cortical evoked potentials].

    PubMed

    Matsumoto, Riki; Kunieda, Takeharu; Ikeda, Akio

    2012-09-01

    A better understanding of seizure networks and the mechanisms underlying human higher cortical functions requires a detailed knowledge of neuronal connectivity. As it relates to higher cortical functions, such as language, in humans, studies performed in nonhuman primates are less relevant. By using subdural electrodes implanted for presurgical evaluation, we developed an in vivo electrical tract-tracing technique of cortico-cortical evoked potentials (CCEPs). Cortico-cortical connections could be traced by applying repetitive single-pulse electrical stimuli to a part of the cortices and recording evoked cortical potentials from adjacent and remote cortical regions by averaging electrocorticogram time-locked to stimulus onset. This technique has contributed to the understanding of human cortico-cortical networks involved in higher brain functions, such as language, praxis, and higher motor control. Establishing a CCEP connectivity map in the MNI standard space is also of academic importance, since a standardized CCEP connectivity map would provide a substantial reference for noninvasive network analyses. In addition to its importance in basic systems neuroscience, this method, in combination with conventional cortical mapping, could be used to clinically map functional brain systems by tracking cortico-cortical connections among functional cortical regions in individual patients. This approach may help identify the cortico-cortical network of a given function within the context of pathology and any resultant plasticity of brain systems. In relation to epileptogenicity, as CCEPs can be used as a measure of regional cortical excitability, stimulating the epileptic focus and recording CCEPs in adjacent areas could help evaluate cortical excitability at and around the focus.

  5. Circulating MicroRNAs: Potential and Emerging Biomarkers for Diagnosis of Human Infectious Diseases.

    PubMed

    Verma, Parmila; Pandey, Rajan K; Prajapati, Priyanka; Prajapati, Vijay K

    2016-01-01

    MicroRNAs (miRNAs) are evolutionary conserved, small non-coding RNA with size ranging from 19 to 24 nucleotides. They endogenously regulate the gene expression at the post transcriptional level either through translation repression or mRNA degradation. MiRNAs have shown the potential to be used as a biomarker for the diagnosis, prognosis, and therapy of infectious diseases. Many miRNAs have shown significantly altered expression during infection. The altered expression of miRNA level in an infected human can be identified by the use of advanced diagnostic tools. In this review, we have highlighted the use of miRNA as an emerging tool for the identification of the human infectious disease. Till date, several miRNAs have been reported as a molecular biomarker in infectious diseases, such as miRNA-150 and miRNA-146b-5p in human immunodeficiency virus (HIV); miRNA-122, miRNA-21, and miRNA-34a in hepatitis; miRNA-361-5p and miRNA-29c in tuberculosis; miRNA-16 and miRNA-451 in malaria and miRNA-181 in Helicobacter pylori infection. The diagnosis of infection with the help of a biomarker is a non-invasive tool that has shown to have a key role in early diagnosis of infection. The discovery of circulating miRNA in the blood of infected patients has the potential to become a powerful non-invasive biomarker in coming future. PMID:27574520

  6. Virtual impact: visualizing the potential effects of cosmic impact in human history

    SciTech Connect

    Masse, W Bruce; Janecky, David R; Forte, Maurizio; Barrientos, Gustavo

    2009-01-01

    Current models indicate that catastrophic impacts by asteroids and comets capable of killing more than one quarter of Earth's human population have occurred on average once every million years; smaller impacts, such the 1908 Tunguska impact that leveled more than 2,000 square km of Siberian forest, occur every 200-300 years. Therefore, cosmic impact likely significantly affected hominine evolution and conceivably played a role in Holocene period human culture history. Regrettably, few archaeologists are trained to appreciate the nature and potential effects of cosmic impact. We have developed a conceptual model for an extensible set of educational and research tools based on virtual reality collaborative environments to engage archaeologists and the general public on the topic of the role of cosmic impact in human history. Our initial focus is on two documented asteroid impacts in Argentina during the period of 4000 to 1000 B.C. Campo del Cicio resulted in an energy release of around 2-3 megatons (100-150 times the Hiroshima atomic weapon), and left several craters and a strewn field covering 493 km{sup 2} in northeastern Argentina. Rio Cuarto was likely more than 1000 megatons and may have devastated an area greater than 50,000 km{sup 2} in central Argentina. We are focusing on reconstructions of these events and their potential effects on contemporary hunter and gatherers. Our vinual reality tools also introduce interactive variables (e.g., impactor physical properties, climate, vegetation, topography, and social complexity) to allow researchers and students to better investigate and evaluate the factors that significantly influence cosmic impact effects.

  7. Circulating MicroRNAs: Potential and Emerging Biomarkers for Diagnosis of Human Infectious Diseases

    PubMed Central

    Verma, Parmila; Pandey, Rajan K.; Prajapati, Priyanka; Prajapati, Vijay K.

    2016-01-01

    MicroRNAs (miRNAs) are evolutionary conserved, small non-coding RNA with size ranging from 19 to 24 nucleotides. They endogenously regulate the gene expression at the post transcriptional level either through translation repression or mRNA degradation. MiRNAs have shown the potential to be used as a biomarker for the diagnosis, prognosis, and therapy of infectious diseases. Many miRNAs have shown significantly altered expression during infection. The altered expression of miRNA level in an infected human can be identified by the use of advanced diagnostic tools. In this review, we have highlighted the use of miRNA as an emerging tool for the identification of the human infectious disease. Till date, several miRNAs have been reported as a molecular biomarker in infectious diseases, such as miRNA-150 and miRNA-146b-5p in human immunodeficiency virus (HIV); miRNA-122, miRNA-21, and miRNA-34a in hepatitis; miRNA-361-5p and miRNA-29c in tuberculosis; miRNA-16 and miRNA-451 in malaria and miRNA-181 in Helicobacter pylori infection. The diagnosis of infection with the help of a biomarker is a non-invasive tool that has shown to have a key role in early diagnosis of infection. The discovery of circulating miRNA in the blood of infected patients has the potential to become a powerful non-invasive biomarker in coming future. PMID:27574520

  8. Early Detection of Human Epileptic Seizures Based on Intracortical Local Field Potentials.

    PubMed

    Park, Yun S; Hochberg, Leigh R; Eskandar, Emad N; Cash, Sydney S; Truccolo, Wilson

    2013-01-01

    The unpredictability of re-occurring seizures dramatically impacts the quality of life and autonomy of people with epilepsy. Reliable early seizure detection could open new therapeutic possibilities and thus substantially improve quality of life and autonomy. Though many seizure detection studies have shown the potential of scalp electroencephalogram (EEG) and intracranial EEG (iEEG) signals, reliable early detection of human seizures remains elusive in practice. Here, we examined the use of intracortical local field potentials (LFPs) recorded from 4×4-mm(2) 96-microelectrode arrays (MEA) for early detection of human epileptic seizures. We adopted a framework consisting of (1) sampling of intracortical LFPs; (2) denoising of LFPs with the Kalman filter; (3) spectral power estimation in specific frequency bands using 1-sec moving time windows; (4) extraction of statistical features, such as the mean, variance, and Fano factor (calculated across channels) of the power in each frequency band; and (5) cost-sensitive support vector machine (SVM) classification of ictal and interictal samples. We tested the framework in one-participant dataset, including 4 seizures and corresponding interictal recordings preceding each seizure. The participant was a 52-year-old woman suffering from complex partial seizures. LFPs were recorded from an MEA implanted in the participant's left middle temporal gyrus. In this participant, spectral power in 0.3-10 Hz, 20-55 Hz, and 125-250 Hz changed significantly between ictal and interictal epochs. The examined seizure detection framework provided an event-wise sensitivity of 100% (4/4) and only one 20-sec-long false positive event in interictal recordings (likely an undetected subclinical event under further visual inspection), and a detection latency of 4.35 ± 2.21 sec (mean ± std) with respect to iEEG-identified seizure onsets. These preliminary results indicate that intracortical MEA recordings may provide key signals to quickly and

  9. Advantages and limitations of the protein digestibility-corrected amino acid score (PDCAAS) as a method for evaluating protein quality in human diets.

    PubMed

    Schaafsma, Gertjan

    2012-08-01

    PDCAAS is a widely used assay for evaluating protein quality. It is a chemical score, which is derived from the ratio between the first limiting amino acid in a test protein and the corresponding amino acid in a reference amino acid pattern and corrected for true faecal N digestibility. Chemical scores exceeding 100 % are truncated to 100 %. The advantages of the PDCAAS are its simplicity and direct relationship to human protein requirements. The limitations are as follows: the reference pattern is based on the minimum amino acid requirements for tissue growth and maintenance and does not necessarily reflect the optimum intake. Truncated PDCAAS of high-quality proteins do not give any information about the power of these proteins to compensate, as a supplement, for low levels of dietary essential amino acids in low-quality proteins. It is likely that faecal N digestibility does not take into account the loss from the colon of indispensable amino acids that were not absorbed in the ileum. Anti-nutritional factors, such as lectins and trypsin inhibitors, in several plant protein sources can cause heightened endogenous losses of amino acids, an issue which is particularly relevant in animal feedstuffs. The assumption that amino acid supplementation can completely restore biological efficiency of the protein source is incorrect since the kinetics of digestion and absorption between supplemented free amino acids and amino acids present in dietary proteins, are different. PMID:23107546

  10. Acetaminophen potentiates staurosporine-induced death in a human neuroblastoma cell line

    PubMed Central

    Posadas, I; Vellecco, V; Santos, P; Prieto-Lloret, J; Ceña, V

    2007-01-01

    Background and purpose: Neuroblastoma is the most common solid tumour in infants characterized by a high resistance to apoptosis. Recently, the cyclo-oxygenase pathway has been considered a potential target in the treatment of different kinds of tumours. The aim of the present work was to investigate a possible relationship between cyclo-oxygenase pathway and stauroporine-induced apoptosis in the neuroblastoma cell line SH-SY5Y. Experimental approach: Cellular viability was measured by release of LDH. DNA fragmentation was visualized by electrophoresis on agarose gel containing ethidium bromide. Cyclo-oxygenase activity was measured in microsomal fractions obtained from cells by quantification of its final product PGE2 by RIA. Caspase-3 activity was measured fluorimetrically and Western blot analysis was performed to assess cytochrome c expression. Key results: We have found that staurosporine (500 nM) induced cellular death in a time-dependent manner in SH-SY5Y human neuroblastoma cells. Cyclo-oxygenase enzymatic activity was present in SH-SY5Y human neuroblastoma cells under basal conditions and pharmacological experiments using COX inhibitors indicate that cyclo-oxygenase-1 and cyclo-oxygenase-3 are the active isoforms in these cells. Co-incubation of SH-SY5Y cells with staurosporine (500 nM) and acetaminophen for 24 h potentiated staurosporine-mediated cellular death in a concentration-dependent manner. This process is mediated by an increase in cytochrome c release and caspase 3 activation and is prevented by N-acetylcysteine or the superoxide dismutase mimetic, MnTBAP. Conclusions and implications: Acetaminophen potentiates staurosporine-mediated neuroblastoma cell death. The mechanism of action of acetaminophen seems to be related to production of reactive oxygen species and decreased intracellular glutathione levels. PMID:17245372

  11. The Metastatic Potential and Chemoresistance of Human Pancreatic Cancer Stem Cells.

    PubMed

    Bhagwandin, Vikash J; Bishop, J Michael; Wright, Woodring E; Shay, Jerry W

    2016-01-01

    Cancer stem cells (CSCs) typically have the capacity to evade chemotherapy and may be the principal source of metastases. CSCs for human pancreatic ductal carcinoma (PDAC) have been identified, but neither the metastatic potential nor the chemoresistance of these cells has been adequately evaluated. We have addressed these issues by examining side-population (SP) cells isolated from the Panc-1 and BxPC3 lines of human PDAC cells, the oncogenotypes of which differ. SP cells could be isolated from monolayers of Panc-1, but only from spheroids of BxPC3. Using orthotopic xenografts into the severely immunocompromised NSG mouse, we found that SP cells isolated from both cell lines produced tumors that were highly metastatic, in contrast to previous experience with PDAC cell lines. SP cells derived from both cell lines expressed the ABCG2 transporter, which was demonstrably responsible for the SP phenotype. SP cells gave rise to non-SP (NSP) cells in vitro and in vivo, a transition that was apparently due to posttranslational inhibition of the ABCG2 transporter. Twenty-two other lines of PDAC cells also expressed ABCG2. The sensitivity of PDAC SP cells to the vinca alkaloid vincristine could be greatly increased by verapamil, a general inhibitor of transporters. In contrast, verapamil had no effect on the killing of PDAC cells by gemcitabine, the current first-line therapeutic for PDAC. We conclude that the isolation of SP cells can be a convenient and effective tool for the study of PDAC CSCs; that CSCs may be the principal progenitors of metastasis by human PDAC; that the ABCG2 transporter is responsible for the SP phenotype in human PDAC cells, and may be a ubiquitous source of drug-resistance in PDAC, but does not confer resistance to gemcitabine; and that inhibition of ABCG2 might offer a useful adjunct in a therapeutic attack on the CSCs of PDAC. PMID:26859746

  12. Neurotoxic potential and cellular uptake of T-2 toxin in human astrocytes in primary culture.

    PubMed

    Weidner, Maria; Lenczyk, Marlies; Schwerdt, Gerald; Gekle, Michael; Humpf, Hans-Ulrich

    2013-03-18

    The trichothecene mycotoxin T-2 toxin, which is produced by fungi of the Fusarium species, is a worldwide occurring contaminant of cereal based food and feed. The cytotoxic properties of T-2 toxin are already well described with apoptosis being a major mechanism of action in various cell lines as well as in primary cells of different origin. However, only few data on neurotoxic properties of T-2 toxin are reported so far, but in vivo studies showed different effects of T-2 toxin on behavior as well as on levels of brain amines in animals. To further investigate the cytotoxic properties of T-2 toxin on cells derived from brain tissue, normal human astrocytes in primary culture (NHA) were used in this study. Besides studies of cytotoxicity, apoptosis (caspase-3-activation, Annexin V) and necrosis (LDH-release), the cellular uptake and metabolism of T-2 toxin in NHA was analyzed and compared to the uptake in an established human cell line (HT-29). The results show that human astrocytes were highly sensitive to the cytotoxic properties of T-2 toxin, and apoptosis, induced at low concentrations, was identified for the first time as the mechanism of toxic action in NHA. Furthermore, a strong accumulation of T-2 toxin in NHA and HT-29 cells was detected, and T-2 toxin was subjected to metabolism leading to HT-2 toxin, a commonly found metabolite after T-2 toxin incubation in both cell types. This formation seems to occur within the cells since incubations of T-2 toxin with cell depleted culture medium did not lead to any degradation of the parent toxin. The results of this study emphasize the neurotoxic potential of T-2 toxin in human astrocytes at low concentrations after short incubation times. PMID:23363530

  13. Cholesterol-lowering potential in human subjects of fat from pigs fed rapeseed oil.

    PubMed

    Sandström, B; Bügel, S; Lauridsen, C; Nielsen, F; Jensen, C; Skibsted, L H

    2000-08-01

    The possibility of achieving blood-lipid-lowering characteristics of pig fat by increasing the content of unsaturated fat in pig feed was evaluated. Three pig feeding regimens were applied: basal feed (no added fat or vitamin E), basal feed + rapeseed oil (60 g/kg feed), and basal feed + rapeseed oil (60 g/kg) + vitamin E (200 mg/kg). Meat and meat products from the three pig groups were incorporated into diets providing 86 g pig fat/10 MJ. The diets were served to twelve healthy human male subjects for 3 weeks each in a randomised crossover design. The diets prepared from pigs fed rapeseed oil had a lower content of saturated fatty acids (approximately 9 v. 11% of energy) and a higher content of polyunsaturated fatty acids (approximately 6 v. 4% of energy) than the diet prepared from pigs fed the basal feed. Diets based on fat from pigs fed the rapeseed oil resulted in significantly lower (approximately 4%, P = 0.019) total serum cholesterol concentration compared with the diet from pigs fed the basal feed. No differences were observed in LDL-, HDL- or VLDL-cholesterol, or in triacylglycerol or VLDL-triacylglycerol concentrations. Addition of vitamin E to the pig feed resulted in only a minor increase in vitamin E content in the human subjects' diet and the vitamin E content was low in all three pig diets. Plasma vitamin E concentration in the human subjects at the end of the period with diets from pigs fed rapeseed oil without vitamin E was significantly lower (P = 0.04) than in the other two diet periods. In conclusion, an increased content of rapeseed oil in pig feed changes the fatty acid composition of the pig fat in a way that has a potential to reduce blood cholesterol concentrations in human subjects. However, intake of pig fat with a higher content of unsaturated fatty acids needs to be matched by a higher dietary intake of vitamin E.

  14. Feature extraction of event-related potentials using wavelets: an application to human performance monitoring

    NASA Technical Reports Server (NTRS)

    Trejo, L. J.; Shensa, M. J.

    1999-01-01

    This report describes the development and evaluation of mathematical models for predicting human performance from discrete wavelet transforms (DWT) of event-related potentials (ERP) elicited by task-relevant stimuli. The DWT was compared to principal components analysis (PCA) for representation of ERPs in linear regression and neural network models developed to predict a composite measure of human signal detection performance. Linear regression models based on coefficients of the decimated DWT predicted signal detection performance with half as many free parameters as comparable models based on PCA scores. In addition, the DWT-based models were more resistant to model degradation due to over-fitting than PCA-based models. Feed-forward neural networks were trained using the backpropagation algorithm to predict signal detection performance based on raw ERPs, PCA scores, or high-power coefficients of the DWT. Neural networks based on high-power DWT coefficients trained with fewer iterations, generalized to new data better, and were more resistant to overfitting than networks based on raw ERPs. Networks based on PCA scores did not generalize to new data as well as either the DWT network or the raw ERP network. The results show that wavelet expansions represent the ERP efficiently and extract behaviorally important features for use in linear regression or neural network models of human performance. The efficiency of the DWT is discussed in terms of its decorrelation and energy compaction properties. In addition, the DWT models provided evidence that a pattern of low-frequency activity (1 to 3.5 Hz) occurring at specific times and scalp locations is a reliable correlate of human signal detection performance. Copyright 1999 Academic Press.

  15. The Asteroid Impact and Deflection Assessment Mission and its Potential Contributions to Human Exploration of Asteroids

    NASA Technical Reports Server (NTRS)

    Abell, Paul A.; Rivkin, Andy S.

    2014-01-01

    The joint ESA and NASA Asteroid Impact and Deflection Assessment (AIDA) mission will directly address aspects of NASA's Asteroid Initiative and will contribute to future human exploration. The NASA Asteroid Initiative is comprised of two major components: the Grand Challenge and the Asteroid Mission. The first component, the Grand Challenge, focuses on protecting Earth's population from asteroid impacts by detecting potentially hazardous objects with enough warning time to either prevent them from impacting the planet, or to implement civil defense procedures. The Asteroid Mission, involves sending astronauts to study and sample a near-Earth asteroid (NEA) prior to conducting exploration missions of the Martian system, which includes Phobos and Deimos. AIDA's primary objective is to demonstrate a kinetic impact deflection and characterize the binary NEA Didymos. The science and technical data obtained from AIDA will aid in the planning of future human exploration missions to NEAs and other small bodies. The dual robotic missions of AIDA, ESA's Asteroid Impact Monitor (AIM) and NASA's Double Asteroid Redirection Test (DART), will provide a great deal of technical and engineering data on spacecraft operations for future human space exploration while conducting in-depth scientific examinations of the binary target Didymos both prior to and after the kinetic impact demonstration. The knowledge gained from this mission will help identify asteroidal physical properties in order to maximize operational efficiency and reduce mission risk for future small body missions. The AIDA data will help fill crucial strategic knowledge gaps concerning asteroid physical characteristics that are relevant for human exploration considerations at similar small body destinations.

  16. Radioactivity contents in dicalcium phosphate and the potential radiological risk to human populations.

    PubMed

    Casacuberta, N; Masqué, P; Garcia-Orellana, J; Bruach, J M; Anguita, M; Gasa, J; Villa, M; Hurtado, S; Garcia-Tenorio, R

    2009-10-30

    Potentially harmful phosphate-based products derived from the wet acid digestion of phosphate rock represent one of the most serious problems facing the phosphate industry. This is particularly true for dicalcium phosphate (DCP), a food additive produced from either sulphuric acid or hydrochloric acid digestion of raw rock material. This study determined the natural occurring radionuclide concentrations of 12 DCP samples and 4 tricalcium phosphate (TCP) samples used for animal and human consumption, respectively. Metal concentrations (Al, Fe, Zn, Cd, Cr, As, Hg, Pb and Mg) were also determined. Samples were grouped into three different clusters (A, B, C) based on their radionuclide content. Whereas group A is characterized by high activities of 238U, 234U (approximately 10(3) Bq kg(-1)), 210Pb (2 x 10(3) Bq kg(-1)) and (210)Po ( approximately 800 Bq kg(-1)); group B presents high activities of (238)U, (234)U and (230)Th (approximately 10(3) Bq kg(-1)). Group C was characterized by very low activities of all radionuclides (< 50 Bq kg(-1)). Differences between the two groups of DCP samples for animal consumption (groups A and B) were related to the wet acid digestion method used, with group A samples produced from hydrochloric acid digestion, and group B samples produced using sulphuric acid. Group C includes more purified samples required for human consumption. High radionuclide concentrations in some DCP samples (reaching 2 x 10(3) and 10(3) Bq kg(-1) of 210Pb and 210Po, respectively) may be of concern due to direct or indirect radiological exposure via ingestion. Our experimental results based on 210Pb and 210Po within poultry consumed by humans, suggest that the maximum radiological doses are 11 +/- 2 microSv y(-1). While these results suggest that human health risks are small, additional testing should be conducted.

  17. Feature Extraction of Event-Related Potentials Using Wavelets: An Application to Human Performance Monitoring

    NASA Technical Reports Server (NTRS)

    Trejo, Leonard J.; Shensa, Mark J.; Remington, Roger W. (Technical Monitor)

    1998-01-01

    This report describes the development and evaluation of mathematical models for predicting human performance from discrete wavelet transforms (DWT) of event-related potentials (ERP) elicited by task-relevant stimuli. The DWT was compared to principal components analysis (PCA) for representation of ERPs in linear regression and neural network models developed to predict a composite measure of human signal detection performance. Linear regression models based on coefficients of the decimated DWT predicted signal detection performance with half as many f ree parameters as comparable models based on PCA scores. In addition, the DWT-based models were more resistant to model degradation due to over-fitting than PCA-based models. Feed-forward neural networks were trained using the backpropagation,-, algorithm to predict signal detection performance based on raw ERPs, PCA scores, or high-power coefficients of the DWT. Neural networks based on high-power DWT coefficients trained with fewer iterations, generalized to new data better, and were more resistant to overfitting than networks based on raw ERPs. Networks based on PCA scores did not generalize to new data as well as either the DWT network or the raw ERP network. The results show that wavelet expansions represent the ERP efficiently and extract behaviorally important features for use in linear regression or neural network models of human performance. The efficiency of the DWT is discussed in terms of its decorrelation and energy compaction properties. In addition, the DWT models provided evidence that a pattern of low-frequency activity (1 to 3.5 Hz) occurring at specific times and scalp locations is a reliable correlate of human signal detection performance.

  18. Human Milk Contains Novel Glycans That Are Potential Decoy Receptors for Neonatal Rotaviruses*

    PubMed Central

    Yu, Ying; Lasanajak, Yi; Song, Xuezheng; Hu, Liya; Ramani, Sasirekha; Mickum, Megan L.; Ashline, David J.; Prasad, B. V. Venkataram; Estes, Mary K.; Reinhold, Vernon N.; Cummings, Richard D.; Smith, David F.

    2014-01-01

    Human milk contains a rich set of soluble, reducing glycans whose functions and bioactivities are not well understood. Because human milk glycans (HMGs) have been implicated as receptors for various pathogens, we explored the functional glycome of human milk using shotgun glycomics. The free glycans from pooled milk samples of donors with mixed Lewis and Secretor phenotypes were labeled with a fluorescent tag and separated via multidimensional HPLC to generate a tagged glycan library containing 247 HMG targets that were printed to generate the HMG shotgun glycan microarray (SGM). To investigate the potential role of HMGs as decoy receptors for rotavirus (RV), a leading cause of severe gastroenteritis in children, we interrogated the HMG SGM with recombinant forms of VP8* domains of the RV outer capsid spike protein VP4 from human neonatal strains N155(G10P[11]) and RV3(G3P[6]) and a bovine strain, B223(G10P[11]). Glycans that were bound by RV attachment proteins were selected for detailed structural analyses using metadata-assisted glycan sequencing, which compiles data on each glycan based on its binding by antibodies and lectins before and after exo- and endo-glycosidase digestion of the SGM, coupled with independent MSn analyses. These complementary structural approaches resulted in the identification of 32 glycans based on RV VP8* binding, many of which are novel HMGs, whose detailed structural assignments by MSn are described in a companion report. Although sialic acid has been thought to be important as a surface receptor for RVs, our studies indicated that sialic acid is not required for binding of glycans to individual VP8* domains. Remarkably, each VP8* recognized specific glycan determinants within a unique subset of related glycan structures where specificity differences arise from subtle differences in glycan structures. PMID:25048705

  19. MicroRNA-138 is a potential regulator of memory performance in humans

    PubMed Central

    Schröder, Julia; Ansaloni, Sara; Schilling, Marcel; Liu, Tian; Radke, Josefine; Jaedicke, Marian; Schjeide, Brit-Maren M.; Mashychev, Andriy; Tegeler, Christina; Radbruch, Helena; Papenberg, Goran; Düzel, Sandra; Demuth, Ilja; Bucholtz, Nina; Lindenberger, Ulman; Li, Shu-Chen; Steinhagen-Thiessen, Elisabeth; Lill, Christina M.; Bertram, Lars

    2014-01-01

    Genetic factors underlie a substantial proportion of individual differences in cognitive functions in humans, including processes related to episodic and working memory. While genetic association studies have proposed several candidate “memory genes,” these currently explain only a minor fraction of the phenotypic variance. Here, we performed genome-wide screening on 13 episodic and working memory phenotypes in 1318 participants of the Berlin Aging Study II aged 60 years or older. The analyses highlight a number of novel single nucleotide polymorphisms (SNPs) associated with memory performance, including one located in a putative regulatory region of microRNA (miRNA) hsa-mir-138-5p (rs9882688, P-value = 7.8 × 10−9). Expression quantitative trait locus analyses on next-generation RNA-sequencing data revealed that rs9882688 genotypes show a significant correlation with the expression levels of this miRNA in 309 human lymphoblastoid cell lines (P-value = 5 × 10−4). In silico modeling of other top-ranking GWAS signals identified an additional memory-associated SNP in the 3′ untranslated region (3′ UTR) of DCP1B, a gene encoding a core component of the mRNA decapping complex in humans, predicted to interfere with hsa-mir-138-5p binding. This prediction was confirmed in vitro by luciferase assays showing differential binding of hsa-mir-138-5p to 3′ UTR reporter constructs in two human cell lines (HEK293: P-value = 0.0470; SH-SY5Y: P-value = 0.0866). Finally, expression profiling of hsa-mir-138-5p and DCP1B mRNA in human post-mortem brain tissue revealed that both molecules are expressed simultaneously in frontal cortex and hippocampus, suggesting that the proposed interaction between hsa-mir-138-5p and DCP1B may also take place in vivo. In summary, by combining unbiased genome-wide screening with extensive in silico modeling, in vitro functional assays, and gene expression profiling, our study identified miRNA-138 as a potential molecular regulator of

  20. Potentials-attract or likes-attract in human mate choice in China.

    PubMed

    He, Qiao-Qiao; Zhang, Zhen; Zhang, Jian-Xin; Wang, Zhi-Guo; Tu, Ying; Ji, Ting; Tao, Yi

    2013-01-01

    To explain how individuals' self-perceived long-term mate value influences their mate preference and mate choice, two hypotheses have been presented, which are "potentials-attract" and "likes-attract", respectively. The potentials-attract means that people choose mates matched with their sex-specific traits indicating reproductive potentials; and the likes-attract means that people choose mates matched with their own conditions. However, the debate about these two hypotheses still remains unsolved. In this paper, we tested these two hypotheses using a human's actual mate choice data from a Chinese online dating system (called the Baihe website), where 27,183 users of Baihe website are included, in which there are 590 paired couples (1180 individuals) who met each other via the website. Our main results show that not only the relationship between individuals' own attributes and their self-stated mate preference but also that between individuals' own attributes and their actual mate choice are more consistent with the likes-attract hypothesis, i.e., people tend to choose mates who are similar to themselves in a variety of attributes.

  1. Bioaccumulation of heavy metals in mollusca species and assessment of potential risks to human health.

    PubMed

    Abdallah, Maha Ahmed Mohamed

    2013-05-01

    Along the Alexandria coast of the Egyptian Mediterranean Sea, five edible species of bivalve molluscs and one gastropoda species (Mactra coralline, Ruditapes decussates, Paphia undulate, Venerupis rhomboids, Crista pectinata and Coralliophila meyendorffi) were analyzed for content of metals (Cadmium, Chromium, Lead, Cobalt and Nickel) in the muscle and in the sediments where they live. The potential health risks of metals to humans via consumption of seafood were assessed by estimated daily intake and target hazard quotient. Significant positive correlations (p < 0.05) were obtained between tissue concentrations for all pairs of metals, with the exception of Cadmium. Significant positive correlations were also obtained for the concentrations of Cd and Ni in tissues of all studied species relative to their concentrations in surface sediments. However, correlations between tissue and sediment concentrations for Chromium, Lead and Cobalt were negative. Ruditapes decussates and C. meyendorffi had the highest values for the summed target hazard quotient and may pose a potential risk to local inhabitants through their consumption in the diet. The potential risk would arise from exposure to high tissue concentrations of Cd and Pb, which exceeded published guidelines for safety of seafood products in some cases. Chromium contributed a considerable fraction of the total target hazard quotient for all metals combined, but did not exceed the published guidelines. Cobalt and Ni did not contribute greatly overall to the target hazard quotient, except in the case of Ni in V. rhomboids.

  2. The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer's disease.

    PubMed

    Lee, Hyun Ju; Lee, Jong Kil; Lee, Hyun; Shin, Ji-woong; Carter, Janet E; Sakamoto, Toshiro; Jin, Hee Kyung; Bae, Jae-sung

    2010-08-30

    The neuropathological hallmarks of Alzheimer's disease (AD) include the presence of extracellular amyloid-beta peptide (Abeta) in the form of amyloid plaques in the brain parenchyma and neuronal loss. The mechanism associated with neuronal death by amyloid plaques is unclear but oxidative stress and glial activation has been implicated. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) are being scrutinized as a potential therapeutic tool to prevent various neurodegenerative diseases including AD. However, the therapeutic impact of hUCB-MSCs in AD has not yet been reported. Here we undertook in vitro work to examine the potential impact of hUCB-MSCs treatment on neuronal loss using a paradigm of cultured hippocampal neurons treated with Abeta. We confirmed that hUCB-MSCs co-culture reduced the hippocampal apoptosis induced by Abeta treatment. Moreover, in an acute AD mouse model to directly test the efficacy of hUCB-MSCs treatment on AD-related cognitive and neuropathological outcomes, we demonstrated that markers of glial activation, oxidative stress and apoptosis levels were decreased in AD mouse brain. Interestingly, hUCB-MSCs treated AD mice demonstrated cognitive rescue with restoration of learning/memory function. These data suggest that hUCB-MSCs warrant further investigation as a potential therapeutic agent in AD.

  3. Potentials-attract or likes-attract in human mate choice in China.

    PubMed

    He, Qiao-Qiao; Zhang, Zhen; Zhang, Jian-Xin; Wang, Zhi-Guo; Tu, Ying; Ji, Ting; Tao, Yi

    2013-01-01

    To explain how individuals' self-perceived long-term mate value influences their mate preference and mate choice, two hypotheses have been presented, which are "potentials-attract" and "likes-attract", respectively. The potentials-attract means that people choose mates matched with their sex-specific traits indicating reproductive potentials; and the likes-attract means that people choose mates matched with their own conditions. However, the debate about these two hypotheses still remains unsolved. In this paper, we tested these two hypotheses using a human's actual mate choice data from a Chinese online dating system (called the Baihe website), where 27,183 users of Baihe website are included, in which there are 590 paired couples (1180 individuals) who met each other via the website. Our main results show that not only the relationship between individuals' own attributes and their self-stated mate preference but also that between individuals' own attributes and their actual mate choice are more consistent with the likes-attract hypothesis, i.e., people tend to choose mates who are similar to themselves in a variety of attributes. PMID:23565153

  4. Introducing the potential of antimicrobial materials for human and robotic spaceflight activities

    NASA Astrophysics Data System (ADS)

    Hahn, Claudia; Reitz, Guenther; Moeller, Ralf; Rettberg, Petra; Hans, Michael; Muecklich, Frank

    One major goal of space research is to discover past or present life on foreign planets such as Mars (Horneck et al., 2010). To detect extraterrestrial life on other planets it is important to prevent microbial contamination imported from the Earth, also known as forward contamination. Until now missions to Mars are solely progressed by robots like the Mars Science Laboratory mission with the Curiosity lander. The assembly of spacecraft components is performed in special bioburden controlled clean rooms. Nevertheless, the microbial diversity in these clean rooms is enormous (Vaishampayan et al., 2013). The propagation of microorganisms and in particular the spread of environmental and human-associated species can be facilitated through numerous exposure routes (e.g., air, personal contact, water, excretions, etc.). Besides robotic missions, on-board the International Space Station (ISS) and in (future) space vehicles for long-term journeys to special targets of astrobiological interests in the solar system, astronauts will have the unique opportunity for scientific exploration. The manned exploration of new environments (e.g. asteroids, Mars) require long-term residence in confined stations and habitats (e.g. space stations, spacecraft, vehicles). During these missions, the health of the crew members has to be protected, and the integrity of the materials and facilities should be carefully monitored (van Houdt et al., 2012). A major concern is the microbiological burden in enclosed environments, where human inhabitants are continuously exposed to potential harmful microorganisms over a long-duration, which may affect the health and performance of the human subjects (Horneck et al., 2010) in addition to potential risks by biofilm formation and biocorrosion of materials. In both scenarios, the application of antimicrobial surfaces is an encouraging approach to reduce microorganisms in a straightforward way. Antimicrobial agents and materials are characterized by

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

    PubMed Central

    Glassman, E. Katelyn; Hughes, Michelle L.

    2012-01-01

    Objectives Current cochlear implants (CIs) have telemetry capabilities for measuring the electrically evoked compound action potential (ECAP). Neural Response Telemetry (NRT™; Cochlear) and Neural Response Imaging (NRI; Advanced Bionics [AB]) can measure ECAP responses across a range of stimulus levels to obtain an amplitude growth function. Software-specific algorithms automatically mark the leading negative peak, N1, and the following positive peak/plateau, P2, and apply linear regression to estimate ECAP threshold. Alternatively, clinicians may apply expert judgments to modify the peak markers placed by the software algorithms, and/or use visual detection to identify the lowest level yielding a measurable ECAP response. The goals of this study were to: (1) assess the variability between human and computer decisions for (a) marking N1 and P2, and (b) determination of linear regression threshold (LRT) and visual detection threshold (VDT); and (2) compare LRT and VDT methods within and across human and computer decision methods. Design ECAP amplitude growth functions were measured for three electrodes in each of 20 ears (10 Cochlear Nucleus® 24RE/CI512, and 10 AB CII/90K). LRT, defined as the current level yielding an ECAP with zero amplitude, was calculated for both computer- (C-LRT) and human-picked peaks (H-LRT). VDT, defined as the lowest level resulting in a measurable ECAP response, was also calculated for both computer- (C-VDT) and human-picked peaks (H-VDT). Because NRI assigns peak markers to all waveforms but does not include waveforms with amplitudes less than 20 μV in its regression calculation, C-VDT for AB subjects was defined as the lowest current level yielding an amplitude ≥20 μV. Results Overall, there were significant correlations between human and computer decisions for peak-marker placement, LRT, and VDT for both manufacturers (r = 0.78 to 1.00, p < 0.001). For Cochlear devices, LRT and VDT correlated equally well for both computer- and

  6. Cryopreservation Effect on Proliferative and Chondrogenic Potential of Human Chondrocytes Isolated from Superficial and Deep Cartilage

    PubMed Central

    Muiños-López, Emma; Rendal-Vázquez, Mª Esther; Hermida-Gómez, Tamara; Fuentes-Boquete, Isaac; Díaz-Prado, Silvia; Blanco, Francisco J

    2012-01-01

    Objectives: To compare the proliferative and chondrogenic potential of fresh and frozen chondrocytes isolated from superficial and deep articular cartilage biopsies. Materials and Methodology: The study included 12 samples of fresh and frozen healthy human knee articular cartilage. Cell proliferation was tested at 3, 6 and 9 days. Studies of mRNA quantification, protein expression and immunofluorescence for proliferation and chondrogenic markers were performed. Results: Stimulation of fresh and frozen chondrocytes from both superficial and deep cartilage with fetal bovine serum produced an increase in the proliferative capacity compared to the non-stimulated control group. In the stimulated fresh cells group, the proliferative capacity of cells from the deep biopsy was greater than that from cells from the superficial biopsy (0.046 vs 0.028, respectively, p<0.05). There was also a significant difference between the proliferative capacity of superficial zone fresh (0.028) and frozen (0.051) chondrocytes (p<0.05). CCND1 mRNA and protein expression levels, and immunopositivity for Ki67 revealed a higher proliferative capacity for fresh articular chondrocytes from deep cartilage. Regarding the chondrogenic potential, stimulated fresh cells showed higher SOX9 and Col II expression in chondrocytes from deep than from superficial zone (p<0.05, T student test). Conclusions: The highest rate of cell proliferation and chondrogenic potential of fresh chondrocytes was found in cells obtained from deep cartilage biopsies, whereas there were no statistically significant differences in proliferative and chondrogenic capacity between biopsy origins with frozen chondrocytes. These results indicate that both origin and cryopreservation affect the proliferative and chondrogenic potential of chondrocytes. PMID:22523526

  7. Statistical Modeling and Analysis of Laser-Evoked Potentials of Electrocorticogram Recordings from Awake Humans

    PubMed Central

    Chen, Zhe; Ohara, Shinji; Cao, Jianting; Vialatte, François; Lenz, Fred A.; Cichocki, Andrzej

    2007-01-01

    This article is devoted to statistical modeling and analysis of electrocorticogram (ECoG) signals induced by painful cutaneous laser stimuli, which were recorded from implanted electrodes in awake humans. Specifically, with statistical tools of factor analysis and independent component analysis, the pain-induced laser-evoked potentials (LEPs) were extracted and investigated under different controlled conditions. With the help of wavelet analysis, quantitative and qualitative analyses were conducted regarding the LEPs' attributes of power, amplitude, and latency, in both averaging and single-trial experiments. Statistical hypothesis tests were also applied in various experimental setups. Experimental results reported herein also confirm previous findings in the neurophysiology literature. In addition, single-trial analysis has also revealed many new observations that might be interesting to the neuroscientists or clinical neurophysiologists. These promising results show convincing validation that advanced signal processing and statistical analysis may open new avenues for future studies of such ECoG or other relevant biomedical recordings. PMID:18369410

  8. Difference, adapted physical activity and human development: potential contribution of capabilities approach.

    PubMed

    Silva, Carla Filomena; Howe, P David

    2012-01-01

    This paper is a call to Adapted Physical Activity (APA) professionals to increase the reflexive nature of their practice. Drawing upon Foucault's concept of governmentality (1977) APA action may work against its own publicized goals of empowerment and self-determination. To highlight these inconsistencies, we will draw upon historical and social factors that explain the implicit dangers of practice not following policy. We propose that APA practitioners work according to ethical guidelines, based upon a capabilities approach (Nussbaum, 2006, 2011; Sen, 2009) to counteract possible adverse effects of APA practitioner action. A capabilities approach is conducive to the development of each individual's human potential, by holistically considering the consequences of physical activity (i.e., biological, cultural, social, and psychological dimensions). To conclude, this paper will offer suggestions that may lead to an ethical reflection aligned with the best interest of APA's users.

  9. [Decrease of latency of auditory evoked potentials in humans practicing transcendental meditation (author's transl].

    PubMed

    Wandhöfer, A; Kobal, G; Plattig, K H

    1976-06-01

    Slow cortical auditory responses were recorded from humans practicing transcendental meditation. The potentials were computated according to Fig. 1, and the latencies of the positive peaks P1 and P2 and of the negative peaks N1 and N2 were measured as well as the areas of the on-effect FON, of the off-effect FOFF and of the DC-shift FDC during the stimulus duration. Latencies for most of the initial peaks during TM as well as during normal consciousness were significantly shorter than in a control group in a dozing state or during normal consciousness (Table 1 and Fig. 2). Certain differences were also found in regard to other parameters such as amplitudes and areas of the auditory evoked response.

  10. Oncogenic potential of Human Papillomavirus (HPV) and its relation with cervical cancer

    PubMed Central

    2011-01-01

    Human Papillomavirus (HPV) is the most common cause of cervical cancer. Cervical cancer being the second most common cancer after lung cancer, affecting women of different age groups; has a prevalence of about 20% in young sexually active women. Among different types of HPV, HPV16 the major strain causing this cancer and is sexually transmitted had been unnoticed for decades. Keeping in mind the multiple risk factors related with cervical cancer such as early age sexual activities, teenage pregnancies, smoking, use of oral contraceptives, having multiple sex partners, hormone replacement therapies and various other unknown factors lead to the onset of the disease. Awareness for various diagnostic procedures such as Pap smears screening prove to be an effective way in eradicating the oncogenic potential of HPV. PMID:21635792

  11. PIAS3 may represent a potential biomarker for diagnosis and therapeutic of human colorectal cancer.

    PubMed

    Li, Heping; Gao, Hua; Bijukchhe, Sunil Man; Wang, Yunhai; Li, Tao

    2013-12-01

    Colorectal cancer (CRC) is a challenging problem both for the developed and underdeveloped countries. Despite numerous improvements in early diagnosis and treatment, the incidence and mortality is still keeping in a high level. Molecule targeted therapy has drawn much attention as next generation anticancer agents for diagnosis and therapeutic of CRC. Protein Inhibitor of Activated Signal Transducer and Activators of Transcription 3 (PIAS3) as a novel biomarker has been focused to have a role in the development of malignancy, which was expressed at a higher level in most common malignancies compared with corresponding normal tissues. Furthermore, evidences suggest that the expression of PIAS3 can affect the growth of cancer cells by inhibiting the JAK/STAT and PI3-K/Akt signaling pathways or regulating its SUMO (small-ubiquitin like modifiers) ligase activity in some malignancy. Therefore, we hypothesized that PIAS3 may be a potential biomarker target for early cancer detection and therapeutic of human CRC.

  12. Potential of mean force for human lysozyme camelid vhh hl6 antibody interaction studies

    NASA Astrophysics Data System (ADS)

    Wang, Yeng-Tseng; Liao, Jun-Min; Chen, Cheng-Lung; Su, Zhi-Yuan; Chen, Chang-Hung; Hu, Jeu-Jiun

    2008-04-01

    Calculating antigen-antibody interaction energies is crucial for understanding antigen-antibody associations in immunology. To shed further light into this equation, we study a separation of human lysozyme-camelid vhh hl6 antibody (cAb-HuL6) complex. The c-terminal end-to-end stretching of the lysozyme-antibody complex structures have been studied using potential of mean force (PMF) calculations based on molecular dynamics (MD) and explicit water model. For the lysozyme-antibody complex, there are six important intermediates in the c-terminal extensions process. Inclusion of our simulations may help to understand the binding mechanics of lysozyme-cAb-HuL6 antibody complex.

  13. Positive selection moments identify potential functional residues in human olfactory receptors

    NASA Technical Reports Server (NTRS)

    Singer, M. S.; Weisinger-Lewin, Y.; Lancet, D.; Shepherd, G. M.

    1996-01-01

    Correlated mutation analysis and molecular models of olfactory receptors have provided evidence that residues in the transmembrane domains form a binding pocket for odor ligands. As an independent test of these results, we have calculated positive selection moments for the alpha-helical sixth transmembrane domain (TM6) of human olfactory receptors. The moments can be used to identify residues that have been preferentially affected by positive selection and are thus likely to interact with odor ligands. The results suggest that residue 622, which is commonly a serine or threonine, could form critical H-bonds. In some receptors a dual-serine subsite, formed by residues 622 and 625, could bind hydroxyl determinants on odor ligands. The potential importance of these residues is further supported by site-directed mutagenesis in the beta-adrenergic receptor. The findings should be of practical value for future physiological studies, binding assays, and site-directed mutagenesis.

  14. PVA/STMP based hydrogels as potential substitutes of human vitreous.

    PubMed

    Leone, Gemma; Consumi, Marco; Aggravi, Marianna; Donati, Alessandro; Lamponi, Stefania; Magnani, Agnese

    2010-08-01

    PVA based hydrogels were synthesised using, as crosslinking agent, trisodium trimetaphosphate (STMP) to obtain potential substitutes for the vitreous body of the eye. The hydrogels, obtained using different amounts of STMP, were characterised by Infrared Spectroscopy which confirmed the successful occurrence of crosslinking reaction. The mechanical spectra of the fully hydrated samples confirmed covalently crosslinked systems (i.e. G' > G''). The rheological analysis pointed out that only one of the hydrogels (PVA STMP 8:1) showed a behaviour similar to that of human vitreous. The hydrogel was also subjected to injection through a small needle, a procedure that is essential in the use of vitreous substitutes. Further analysis in terms of light transmittance, water content measurements, diffusion coefficient and cytotoxicity confirmed the applicability of such a hydrogel as vitreous substitute. PMID:20499140

  15. Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization

    PubMed Central

    Yanez, Livia Z.; Han, Jinnuo; Behr, Barry B.; Pera, Renee A. Reijo; Camarillo, David B.

    2016-01-01

    The causes of embryonic arrest during pre-implantation development are poorly understood. Attempts to correlate patterns of oocyte gene expression with successful embryo development have been hampered by the lack of reliable and nondestructive predictors of viability at such an early stage. Here we report that zygote viscoelastic properties can predict blastocyst formation in humans and mice within hours after fertilization, with >90% precision, 95% specificity and 75% sensitivity. We demonstrate that there are significant differences between the transcriptomes of viable and non-viable zygotes, especially in expression of genes important for oocyte maturation. In addition, we show that low-quality oocytes may undergo insufficient cortical granule release and zona-hardening, causing altered mechanics after fertilization. Our results suggest that embryo potential is largely determined by the quality and maturation of the oocyte before fertilization, and can be predicted through a minimally invasive mechanical measurement at the zygote stage. PMID:26904963

  16. Structure of human dual-specificity phosphatase 7, a potential cancer drug target

    PubMed Central

    Lountos, George T.; Austin, Brian P.; Tropea, Joseph E.; Waugh, David S.

    2015-01-01

    Human dual-specificity phosphatase 7 (DUSP7/Pyst2) is a 320-residue protein that belongs to the mitogen-activated protein kinase phosphatase (MKP) subfamily of dual-specificity phosphatases. Although its precise biological function is still not fully understood, previous reports have demonstrated that DUSP7 is overexpressed in myeloid leukemia and other malignancies. Therefore, there is interest in developing DUSP7 inhibitors as potential therapeutic agents, especially for cancer. Here, the purification, crystallization and structure determination of the catalytic domain of DUSP7 (Ser141–Ser289/C232S) at 1.67 Å resolution are reported. The structure described here provides a starting point for structure-assisted inhibitor-design efforts and adds to the growing knowledge base of three-dimensional structures of the dual-specificity phosphatase family. PMID:26057789

  17. Potential, pH, and arachidonate gate hydrogen ion currents in human neutrophils.

    PubMed Central

    DeCoursey, T E; Cherny, V V

    1993-01-01

    Indirect evidence indicates that a proton-selective conductance is activated during the respiratory burst in neutrophils. A voltage- and time-dependent H(+)-selective conductance, gH, in human neutrophils is demonstrated here directly by the whole-cell patch-clamp technique. The gH is extremely low at large negative potentials, increases slowly upon membrane depolarization, and does not inactivate. It is enhanced at high external pH or low internal pH and is inhibited by Cd2+ and Zn2+. Arachidonic acid, which plays a pivotal role in inflammatory reactions, amplifies the gH. The properties of the gH described here are compatible with its activation during the respiratory burst in stimulated neutrophils, in which it may facilitate sustained superoxide anion release by dissipating metabolically generated acid. PMID:7506066

  18. Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization.

    PubMed

    Yanez, Livia Z; Han, Jinnuo; Behr, Barry B; Reijo Pera, Renee A; Camarillo, David B

    2016-01-01

    The causes of embryonic arrest during pre-implantation development are poorly understood. Attempts to correlate patterns of oocyte gene expression with successful embryo development have been hampered by the lack of reliable and nondestructive predictors of viability at such an early stage. Here we report that zygote viscoelastic properties can predict blastocyst formation in humans and mice within hours after fertilization, with >90% precision, 95% specificity and 75% sensitivity. We demonstrate that there are significant differences between the transcriptomes of viable and non-viable zygotes, especially in expression of genes important for oocyte maturation. In addition, we show that low-quality oocytes may undergo insufficient cortical granule release and zona-hardening, causing altered mechanics after fertilization. Our results suggest that embryo potential is largely determined by the quality and maturation of the oocyte before fertilization, and can be predicted through a minimally invasive mechanical measurement at the zygote stage. PMID:26904963

  19. Electroencephalography (EEG) and event-related potentials (ERPs) with human participants.

    PubMed

    Light, Gregory A; Williams, Lisa E; Minow, Falk; Sprock, Joyce; Rissling, Anthony; Sharp, Richard; Swerdlow, Neal R; Braff, David L

    2010-07-01

    Understanding the basic neural processes that underlie complex higher-order cognitive operations and functional domains is a fundamental goal of cognitive neuroscience. Electroencephalography (EEG) is a non-invasive and relatively inexpensive method for assessing neurophysiological function that can be used to achieve this goal. EEG measures the electrical activity of large, synchronously firing populations of neurons in the brain with electrodes placed on the scalp. This unit outlines the basics of setting up an EEG experiment with human participants, including equipment, and a step-by-step guide to applying and preparing an electrode cap. Also included are support protocols for two event-related potential (ERP) paradigms, P50 suppression, and mismatch negativity (MMN), which are measures of early sensory processing. These paradigms can be used to assess the integrity of early sensory processing in normal individuals and clinical populations, such as individuals with schizophrenia.

  20. Dynamic regulation of human endogenous retroviruses mediates factor-induced reprogramming and differentiation potential.

    PubMed

    Ohnuki, Mari; Tanabe, Koji; Sutou, Kenta; Teramoto, Ito; Sawamura, Yuka; Narita, Megumi; Nakamura, Michiko; Tokunaga, Yumie; Nakamura, Masahiro; Watanabe, Akira; Yamanaka, Shinya; Takahashi, Kazutoshi

    2014-08-26

    Pluripotency can be induced in somatic cells by overexpressing transcription factors, including POU class 5 homeobox 1 (OCT3/4), sex determining region Y-box 2 (SOX2), Krüppel-like factor 4 (KLF4), and myelocytomatosis oncogene (c-MYC). However, some induced pluripotent stem cells (iPSCs) exhibit defective differentiation and inappropriate maintenance of pluripotency features. Here we show that dynamic regulation of human endogenous retroviruses (HERVs) is important in the reprogramming process toward iPSCs, and in re-establishment of differentiation potential. During reprogramming, OCT3/4, SOX2, and KLF4 transiently hyperactivated LTR7s--the long-terminal repeats of HERV type-H (HERV-H)--to levels much higher than in embryonic stem cells by direct occupation of LTR7 sites genome-wide. Knocking down LTR7s or long intergenic non-protein coding RNA, regulator of reprogramming (lincRNA-RoR), a HERV-H-driven long noncoding RNA, early in reprogramming markedly reduced the efficiency of iPSC generation. KLF4 and LTR7 expression decreased to levels comparable with embryonic stem cells once reprogramming was complete, but failure to resuppress KLF4 and LTR7s resulted in defective differentiation. We also observed defective differentiation and LTR7 activation when iPSCs had forced expression of KLF4. However, when aberrantly expressed KLF4 or LTR7s were suppressed in defective iPSCs, normal differentiation was restored. Thus, a major mechanism by which OCT3/4, SOX2, and KLF4 promote human iPSC generation and reestablish potential for differentiation is by dynamically regulating HERV-H LTR7s.

  1. 'Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells.

    PubMed

    Okamoto, Kazuma; Miyoshi, Shunichiro; Toyoda, Masashi; Hida, Naoko; Ikegami, Yukinori; Makino, Hatsune; Nishiyama, Nobuhiro; Tsuji, Hiroko; Cui, Chang-Hao; Segawa, Kaoru; Uyama, Taro; Kami, Daisuke; Miyado, Kenji; Asada, Hironori; Matsumoto, Kenji; Saito, Hirohisa; Yoshimura, Yasunori; Ogawa, Satoshi; Aeba, Ryo; Yozu, Ryohei; Umezawa, Akihiro

    2007-07-15

    The clinical application of cell transplantation for severe heart failure is a promising strategy to improve impaired cardiac function. Recently, an array of cell types, including bone marrow cells, endothelial progenitors, mesenchymal stem cells, resident cardiac stem cells, and embryonic stem cells, have become important candidates for cell sources for cardiac repair. In the present study, we focused on the placenta as a cell source. Cells from the chorionic plate in the fetal portion of the human placenta were obtained after delivery by the primary culture method, and the cells generated in this study had the Y sex chromosome, indicating that the cells were derived from the fetus. The cells potentially expressed 'working' cardiomyocyte-specific genes such as cardiac myosin heavy chain 7beta, atrial myosin light chain, cardiac alpha-actin by gene chip analysis, and Csx/Nkx2.5, GATA4 by RT-PCR, cardiac troponin-I and connexin 43 by immunohistochemistry. These cells were able to differentiate into cardiomyocytes. Cardiac troponin-I and connexin 43 displayed a discontinuous pattern of localization at intercellular contact sites after cardiomyogenic differentiation, suggesting that the chorionic mesoderm contained a large number of cells with cardiomyogenic potential. The cells began spontaneously beating 3 days after co-cultivation with murine fetal cardiomyocytes and the frequency of beating cells reached a maximum on day 10. The contraction of the cardiomyocytes was rhythmical and synchronous, suggesting the presence of electrical communication between the cells. Placenta-derived human fetal cells may be useful for patients who cannot supply bone marrow cells but want to receive stem cell-based cardiac therapy.

  2. Multilineage potential and proteomic profiling of human dental stem cells derived from a single donor

    SciTech Connect

    Patil, Rajreddy; Kumar, B. Mohana; Lee, Won-Jae; Jeon, Ryoung-Hoon; Jang, Si-Jung; Lee, Yeon-Mi; Park, Bong-Wook; Byun, June-Ho; Ahn, Chun-Seob; Kim, Jae-Won; Rho, Gyu-Jin

    2014-01-01

    Dental tissues provide an alternative autologous source of mesenchymal stem cells (MSCs) for regenerative medicine. In this study, we isolated human dental MSCs of follicle, pulp and papilla tissue from a single donor tooth after impacted third molar extraction by excluding the individual differences. We then compared the morphology, proliferation rate, expression of MSC-specific and pluripotency markers, and in vitro differentiation ability into osteoblasts, adipocytes, chondrocytes and functional hepatocyte-like cells (HLCs). Finally, we analyzed the protein expression profiles of undifferentiated dental MSCs using 2DE coupled with MALDI-TOF-MS. Three types of dental MSCs largely shared similar morphology, proliferation potential, expression of surface markers and pluripotent transcription factors, and differentiation ability into osteoblasts, adipocytes, and chondrocytes. Upon hepatogenic induction, all MSCs were transdifferentiated into functional HLCs, and acquired hepatocyte functions by showing their ability for glycogen storage and urea production. Based on the proteome profiling results, we identified nineteen proteins either found commonly or differentially expressed among the three types of dental MSCs. In conclusion, three kinds of dental MSCs from a single donor tooth possessed largely similar cellular properties and multilineage potential. Further, these dental MSCs had similar proteomic profiles, suggesting their interchangeable applications for basic research and call therapy. - Highlights: • Isolated and characterized three types of human dental MSCs from a single donor. • MSCs of dental follicle, pulp and papilla had largely similar biological properties. • All MSCs were capable of transdifferentiating into functional hepatocyte-like cells. • 2DE proteomics with MALDI-TOF/MS identified 19 proteins in three types of MSCs. • Similar proteomic profiles suggest interchangeable applications of dental MSCs.

  3. Potential animal and environmental sources of Q fever infection for humans in Queensland.

    PubMed

    Tozer, S J; Lambert, S B; Strong, C L; Field, H E; Sloots, T P; Nissen, M D

    2014-03-01

    Q fever is a vaccine-preventable disease; despite this, high annual notification numbers are still recorded in Australia. We have previously shown seroprevalence in Queensland metropolitan regions is approaching that of rural areas. This study investigated the presence of nucleic acid from Coxiella burnetii, the agent responsible for Q fever, in a number of animal and environmental samples collected throughout Queensland, to identify potential sources of human infection. Samples were collected from 129 geographical locations and included urine, faeces and whole blood from 22 different animal species; 45 ticks were removed from two species, canines and possums; 151 soil samples; 72 atmospheric dust samples collected from two locations and 50 dust swabs collected from domestic vacuum cleaners. PCR testing was performed targeting the IS1111 and COM1 genes for the specific detection of C. burnetii DNA. There were 85 detections from 1318 animal samples, giving a detection rate for each sample type ranging from 2.1 to 6.8%. Equine samples produced a detection rate of 11.9%, whilst feline and canine samples showed detection rates of 7.8% and 5.2%, respectively. Native animals had varying detection rates: pooled urines from flying foxes had 7.8%, whilst koalas had 5.1%, and 6.7% of ticks screened were positive. The soil and dust samples showed the presence of C. burnetii DNA ranging from 2.0 to 6.9%, respectively. These data show that specimens from a variety of animal species and the general environment provide a number of potential sources for C. burnetii infections of humans living in Queensland. These previously unrecognized sources may account for the high seroprevalence rates seen in putative low-risk communities, including Q fever patients with no direct animal contact and those subjects living in a low-risk urban environment. PMID:23663407

  4. Maximum diastolic potential of human induced pluripotent stem cell-derived cardiomyocytes depends critically on I(Kr).

    PubMed

    Doss, Michael Xavier; Di Diego, José M; Goodrow, Robert J; Wu, Yuesheng; Cordeiro, Jonathan M; Nesterenko, Vladislav V; Barajas-Martínez, Héctor; Hu, Dan; Urrutia, Janire; Desai, Mayurika; Treat, Jacqueline A; Sachinidis, Agapios; Antzelevitch, Charles

    2012-01-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) hold promise for therapeutic applications. To serve these functions, the hiPSC-CM must recapitulate the electrophysiologic properties of native adult cardiomyocytes. This study examines the electrophysiologic characteristics of hiPSC-CM between 11 and 121 days of maturity. Embryoid bodies (EBs) were generated from hiPS cell line reprogrammed with Oct4, Nanog, Lin28 and Sox2. Sharp microelectrodes were used to record action potentials (AP) from spontaneously beating clusters (BC) micro-dissected from the EBs (n = 103; 37°C) and to examine the response to 5 µM E-4031 (n = 21) or BaCl(2) (n = 22). Patch-clamp techniques were used to record I(Kr) and I(K1) from cells enzymatically dissociated from BC (n = 49; 36°C). Spontaneous cycle length (CL) and AP characteristics varied widely among the 103 preparations. E-4031 (5 µM; n = 21) increased Bazett-corrected AP duration from 291.8±81.2 to 426.4±120.2 msec (p<0.001) and generated early afterdepolarizations in 8/21 preparations. In 13/21 BC, E-4031 rapidly depolarized the clusters leading to inexcitability. BaCl(2), at concentrations that selectively block I(K1) (50-100 µM), failed to depolarize the majority of clusters (13/22). Patch-clamp experiments revealed very low or negligible I(K1) in 53% (20/38) of the cells studied, but presence of I(Kr) in all (11/11). Consistent with the electrophysiological data, RT-PCR and immunohistochemistry studies showed relatively poor mRNA and protein expression of I(K1) in the majority of cells, but robust expression of I(Kr.) In contrast to recently reported studies, our data point to major deficiencies of hiPSC-CM, with remarkable diversity of electrophysiologic phenotypes as well as pharmacologic responsiveness among beating clusters and cells up to 121 days post-differentiation (dpd). The vast majority have a maximum diastolic potential that depends critically on I(Kr) due to the

  5. Analysis of Potential Alternatives to Reduce NASA's Cost of Human Access to Space

    NASA Technical Reports Server (NTRS)

    1998-01-01

    The purpose of this report is to analyze NASA's potential options for significantly reducing the cost of human access to space. The opinions expressed in this report are based on Hawthorne, Krauss & Associates' ("HKA") interaction with NASA and several of its key contractors over the past nine months. This report is not intended to be an exhaustive quantitative analysis of the various options available to NASA. Instead, its purpose is to outline key decision-related issues that the agency should consider prior to making a decision as to which option to pursue. This report attempts to bring a private-sector perspective to bear on the issue of reducing the cost of human access to space. HKA believes that the key to the NASA's success in reducing those costs over the long-term is the involvement of the private-sector incentives and disciplines--which is achieved only through the assumption of risk by the private sector, not through a traditional contractor relationship--is essential to achieve significant long-term cost reductions.

  6. Auditory information processing during human sleep as revealed by event-related brain potentials.

    PubMed

    Atienza, M; Cantero, J L; Escera, C

    2001-11-01

    The main goal of this review is to elucidate up to what extent pre-attentive auditory information processing is affected during human sleep. Evidence from event-related brain potential (ERP) studies indicates that auditory information processing is selectively affected, even at early phases, across the different stages of sleep-wakefulness continuum. According to these studies, 3 main conclusions are drawn: (1) the sleeping brain is able to automatically detect stimulus occurrence and trigger an orienting response towards that stimulus if its degree of novelty is large; (2) auditory stimuli are represented in the auditory system and maintained for a period of time in sensory memory, making the automatic-change detection during sleep possible; and (3) there are specific brain mechanisms (sleep-specific ERP components associated with the presence of vertex waves and K-complexes) by which information processing can be improved during non-rapid eye movement sleep. However, the remarkably affected amplitude and latency of the waking-ERPs during the different stages of sleep suggests deficits in the building and maintenance of a neural representation of the stimulus as well as in the process by which neural events lead to an orienting response toward such a stimulus. The deactivation of areas in the dorsolateral pre-frontal cortex during sleep contributing to the generation of these ERP components is hypothesized to be one of the main causes for the attenuated amplitude of these ERPs during human sleep. PMID:11682341

  7. The potential of autofluorescence spectroscopy to detect human urinary tract infection.

    PubMed

    Perinchery, Sandeep Menon; Kuzhiumparambil, Unnikrishnan; Vemulpad, Subramanyam; Goldys, Ewa M

    2010-08-15

    Urinary tract infections (UTIs) are known to alter the normal urine composition which, in principle, can lead to changes in urine autofluorescence. This paper describes the study of human urine (normal and UTI) by using UV fluorescence excitation/emission matrices and synchronous spectra and proposes a method of diagnosing UTI without any sample preparation. The method is based on excitation in the shorter UV region (250-350 nm) which shows good discrimination between the normal urine and UTI samples. The synchronous scans with an offset of Deltalambda=90 nm were also able to differentiate between normal urines and UTI samples. These differences were observed even though the two known major urine fluorophores, tryptophan and indoxyl sulfate were present in the normal urine and UTI samples in similar concentration as established by HPLC analysis. Although the identity of substances responsible for the altered autofluorescence in UTI is not established, our study shows that autofluorescence has the potential to differentiate between normal human urine samples and those with UTI. PMID:20678645

  8. Characterization of a Ligand Binding Site in the Human Transient Receptor Potential Ankyrin 1 Pore

    PubMed Central

    Klement, Göran; Eisele, Lina; Malinowsky, David; Nolting, Andreas; Svensson, Mats; Terp, Gitte; Weigelt, Dirk; Dabrowski, Michael

    2013-01-01

    The pharmacology and regulation of Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel activity is intricate due to the physiological function as an integrator of multiple chemical, mechanical, and temperature stimuli as well as differences in species pharmacology. In this study, we describe and compare the current inhibition efficacy of human TRPA1 on three different TRPA1 antagonists. We used a homology model of TRPA1 based on Kv1.2 to select pore vestibule residues available for interaction with ligands entering the vestibule. Site-directed mutation constructs were expressed in Xenopus oocytes and their functionality and pharmacology assessed to support and improve our homology model. Based on the functional pharmacology results we propose an antagonist-binding site in the vestibule of the TRPA1 ion channel. We use the results to describe the proposed intravestibular ligand-binding site in TRPA1 in detail. Based on the single site substitutions, we designed a human TRPA1 receptor by substituting several residues in the vestibule and adjacent regions from the rat receptor to address and explain observed species pharmacology differences. In parallel, the lack of effect on HC-030031 inhibition by the vestibule substitutions suggests that this molecule interacts with TRPA1 via a binding site not situated in the vestibule. PMID:23442958

  9. Characterization of a ligand binding site in the human transient receptor potential ankyrin 1 pore.

    PubMed

    Klement, Göran; Eisele, Lina; Malinowsky, David; Nolting, Andreas; Svensson, Mats; Terp, Gitte; Weigelt, Dirk; Dabrowski, Michael

    2013-02-19

    The pharmacology and regulation of Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel activity is intricate due to the physiological function as an integrator of multiple chemical, mechanical, and temperature stimuli as well as differences in species pharmacology. In this study, we describe and compare the current inhibition efficacy of human TRPA1 on three different TRPA1 antagonists. We used a homology model of TRPA1 based on Kv1.2 to select pore vestibule residues available for interaction with ligands entering the vestibule. Site-directed mutation constructs were expressed in Xenopus oocytes and their functionality and pharmacology assessed to support and improve our homology model. Based on the functional pharmacology results we propose an antagonist-binding site in the vestibule of the TRPA1 ion channel. We use the results to describe the proposed intravestibular ligand-binding site in TRPA1 in detail. Based on the single site substitutions, we designed a human TRPA1 receptor by substituting several residues in the vestibule and adjacent regions from the rat receptor to address and explain observed species pharmacology differences. In parallel, the lack of effect on HC-030031 inhibition by the vestibule substitutions suggests that this molecule interacts with TRPA1 via a binding site not situated in the vestibule.

  10. Potential toxicity of sulfanilamide antibiotic: binding of sulfamethazine to human serum albumin.

    PubMed

    Chen, Jiabin; Zhou, Xuefei; Zhang, Yalei; Gao, Haiping

    2012-08-15

    Antibiotics are widely used in daily life but their abuse has posed a potential threat to human health. The interaction between human serum albumin (HSA) and sulfamethazine (SMZ) was investigated by capillary electrophoresis, fluorescence spectrometry, and circular dichroism. The binding constant and site were determined to be 1.09×10(4) M(-1) and 1.14 at 309.5 K. The thermodynamic determination indicated that the interaction was driven by enthalpy change, where the electrostatic interaction and hydrogen bond were the dominant binding force. The binding distance between SMZ and tryptophan residue of HSA was obtained to be 3.07 nm according to Fǒrster non-radioactive energy transfer theory. The site marker competition revealed that SMZ bound into subdomain IIA of HSA. The binding of SMZ induced the unfolding of the polypeptides of HSA and transferred the secondary conformation of HSA. The equilibrium dialysis showed that only 0.13 mM SMZ decreased vitamin B(2) by 38% transported on the HSA. This work provides a new quantitative evaluation method for antibiotics to cause the protein damage. PMID:22750172

  11. The Human Cathelicidin Antimicrobial Peptide LL-37 and Mimics are Potential Anticancer Drugs

    PubMed Central

    Kuroda, Kengo; Okumura, Kazuhiko; Isogai, Hiroshi; Isogai, Emiko

    2015-01-01

    Antimicrobial peptides (AMPs) play a critical role in innate host defense against microbial pathogens in many organisms. The human cathelicidin, LL-37, has a net positive charge and is amphiphilic, and can eliminate pathogenic microbes directly via electrostatic attraction toward negatively charged bacterial membranes. A number of studies have shown that LL-37 participates in various host immune systems, such as inflammatory responses and tissue repair, in addition to its antibacterial properties. Moreover, recent evidence suggests that it is also involved in the regulation of cancer. Indeed, previous studies have suggested that human LL-37 is involved in carcinogenesis via multiple reporters, such as FPR2 (FPRL1), epidermal growth factor receptor, and ERBb2, although LL-37 and its fragments and analogs also show anticancer effects in various cancer cell lines. This discrepancy can be attributed to peptide-based factors, host membrane-based factors, and signal regulation. Here, we describe the association between AMPs and cancer with a focus on anticancer peptide functions and selectivity in an effort to understand potential therapeutic implications. PMID:26175965

  12. Using human extra-cortical local field potentials to control a switch

    NASA Astrophysics Data System (ADS)

    Kennedy, Philip; Andreasen, Dinal; Ehirim, Princewill; King, Brandon; Kirby, Todd; Mao, Hui; Moore, Melody

    2004-06-01

    Individuals with profound paralysis and mutism require a communication channel. Traditional assistive technology devices eventually fail, especially in the case of amyotrophic lateral sclerosis (ALS) subjects who gradually become totally locked-in. A direct brain-to-computer interface that provides switch functions can provide a direct communication channel to the external world. Electroencephalographic (EEG) signals recorded from scalp electrodes are significantly degraded due to skull and scalp attenuation and ambient noise. The present system using conductive skull screws allows more reliable access to cortical local field potentials (LFPs) without entering the brain itself. We describe an almost locked-in human subject with ALS who activated a switch using online time domain detection techniques. Frequency domain analysis of his LFP activity demonstrates this to be an alternative method of detecting switch activation intentions. With this brain communicator system it is reasonable to expect that locked-in, but cognitively intact, humans will always be able to communicate. Financial disclosure. Authors PK and DA may derive some financial gain from the sale of this device. A patent has been applied under US and international law: 10/675,703.

  13. Potentials and limitations for human control over historic fire regimes in the boreal forest.

    PubMed

    Granström, Anders; Niklasson, Mats

    2008-07-12

    Fire, being both a natural and cultural phenomenon, presents problems in disentangling the historical effect of humans from that of climate change. Here, we investigate the potential impact of humans on boreal fire regimes from a perspective of fuels, ignitions and culture. Two ways for a low technology culture to impact the fire regime are as follows: (i) by altering the number of ignitions and their spatial distribution and timing and (ii) by hindering fire spread. Different cultures should be expected to have quite different impacts on the fire regimes. In northern Fennoscandia, there is evidence for fire regime changes associated with the following: a reindeer herding culture associated with few ignitions above the natural; an era of cattle husbandry with dramatically increased ignitions and somewhat higher fire frequency; and a timber exploitation era with decreasing fire sizes and diminishing fire frequency. In other regions of the boreal zone, such schemes can look quite different, but we suggest that a close look at the resource extraction and land use of different cultures should be part of any analysis of past fire regimes.

  14. Human scalp potentials reflect a mixture of decision-related signals during perceptual choices.

    PubMed

    Philiastides, Marios G; Heekeren, Hauke R; Sajda, Paul

    2014-12-10

    Single-unit animal studies have consistently reported decision-related activity mirroring a process of temporal accumulation of sensory evidence to a fixed internal decision boundary. To date, our understanding of how response patterns seen in single-unit data manifest themselves at the macroscopic level of brain activity obtained from human neuroimaging data remains limited. Here, we use single-trial analysis of human electroencephalography data to show that population responses on the scalp can capture choice-predictive activity that builds up gradually over time with a rate proportional to the amount of sensory evidence, consistent with the properties of a drift-diffusion-like process as characterized by computational modeling. Interestingly, at time of choice, scalp potentials continue to appear parametrically modulated by the amount of sensory evidence rather than converging to a fixed decision boundary as predicted by our model. We show that trial-to-trial fluctuations in these response-locked signals exert independent leverage on behavior compared with the rate of evidence accumulation earlier in the trial. These results suggest that in addition to accumulator signals, population responses on the scalp reflect the influence of other decision-related signals that continue to covary with the amount of evidence at time of choice.

  15. Size-dependent effect of zinc oxide on toxicity and inflammatory potential of human monocytes.

    PubMed

    Sahu, Devashri; Kannan, G M; Vijayaraghavan, R

    2014-01-01

    With the rapid development of nanomedicines, it is important to understand their potential immunotoxicity. Zinc oxide (ZnO) nanoparticles have several applications in the pharmaceutical and biomedicine industries. This study investigates the effect of particles size (nano and micro) of ZnO on viability, phagocytosis, and cytokine induction in human monocytes, THP-1 cells, a model of the innate immune system. Cells were incubated with nano (approximately 100 nm) and micro (approximately 5 μm) sized ZnO particles in a concentration range of 10-100 μg/ml. The parameters measured included the MTT assay, phagocytosis assay, enzyme-linked immunosorbent assay (ELISA), gene expression, and DNA analysis. ZnO particles significantly decreased cell viability in a size- and concentration-dependent manner associated with significant alterations in phagocytic capacity of monocytes. Exposure of THP-1 cells to both sizes of ZnO stimulated and increased release of proinflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6, as well as chemokine IL-8, and upregulated the expression of monocyte chemoattractant protein-1 and cyclooxygenase-2 genes. However, ZnO particles did not markedly affect monocytes DNA. Collectively, these results suggest higher propensity of nano ZnO particles in inducing cytotoxicity and inflammation in human monocytes regardless of micro size, and caution needs to be taken concerning their biological application. PMID:24555677

  16. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder.

    PubMed

    Sabbagh, Ubadah; Mullegama, Saman; Wyckoff, Gerald J

    2016-01-01

    The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES). A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

  17. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder

    PubMed Central

    Mullegama, Saman; Wyckoff, Gerald J.

    2016-01-01

    The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES). A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study. PMID:27088090

  18. In vitro differentiation potential of human haematopoietic CD34(+) cells towards pancreatic β-cells.

    PubMed

    Sunitha, Manne Mudhu; Srikanth, Lokanathan; Santhosh Kumar, Pasupuleti; Chandrasekhar, Chodimella; Sarma, Potukuchi Venkata Gurunadha Krishna

    2016-10-01

    Haematopoietic stem cells (HSCs) possess multipotent ability to differentiate into various types of cells on providing appropriate niche. In the present study, the differentiating potential of human HSCs into β-cells of islets of langerhans was explored. Human HSCs were apheretically isolated from a donor and cultured. Phenotypic characterization of CD34 glycoprotein in the growing monolayer HSCs was confirmed by immunocytochemistry and flow cytometry techniques. HSCs were induced by selection with beta cell differentiating medium (BDM), which consists of epidermal growth factor (EGF), fibroblast growth factor (FGF), transferrin, Triiodo-l-Tyronine, nicotinamide and activin A. Distinct morphological changes of differentiated cells were observed on staining with dithizone (DTZ) and expression of PDX1, insulin and synaptophysin was confirmed by immunocytochemistry. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed distinct expression of specific β-cell markers, pancreatic and duodenal homeobox-1 (PDX1), glucose transporter-2 (GLUT-2), synaptophysin (SYP) and insulin (INS) in these differentiated cells compared to HSCs. Further, these cells exhibited elevated expression of INS gene at 10 mM glucose upon inducing with different glucose concentrations. The prominent feature of the obtained β-cells was the presence of glucose sensors, which was determined by glucokinase activity and high glucokinase activity compared with CD34(+) stem cells. These findings illustrate the differentiation of CD34(+) HSCs into β-cells of islets of langerhans. PMID:27514733

  19. CCK1 receptor antagonist, dexloxiglumide: effects on human isolated gallbladder. Potential clinical applications.

    PubMed

    Maselli, M A; Mennuni, L

    2003-09-01

    Cholecystokinin is the main hormonal regulator of gallbladder motility. Dexloxiglumide, the active enantiomer of loxiglumide, interacts competitively with CCK1 receptors as determined in preclinical studies, such as specific radioligand binding assays or functional studies on isolated guinea pig gallbladder, where it inhibited smooth muscle cell contractions induced by cholecystokinin-octapeptide (CCK-8), the most prominent active forms of cholecystokinin. Dexloxiglumide has a potent antagonistic effect, of a competitive nature, on human gallbladder cholecystokinin type 1 receptors. In isolated human gallbladder, dexloxiglumide produced a concentration-dependent rightward shift of the cholecystokinin-octapeptide curve, without affecting its maximal response. Gallbladder motility was evaluated in clinical studies. Dexloxiglumide, orally administered to healthy volunteers at putative therapeutic doses, did not interfere with post-prandial gallbladder kinetics, despite an increase of fasting gallbladder volume. At present, dexloxiglumide is in an advanced stage of clinical research in gastroenterology. Overall, clinical observations suggest that dexloxiglumide may become an effective treatment in several gastrointestinal disorders. Moreover, the beneficial effects can be obtained without increasing the risk of gallstones formation, a potential hazard subsequent to the inhibition of gallbladder contractions and the resulting bile stasis. The potent and selective antagonist dexloxiglumide may offer a possible therapeutic tool for use not only in functional gastrointestinal disorders, such as irritable bowel syndrome, constipation, gastroesophageal reflux disease and functional dyspepsia, but also in other pathologies, such as biliary colics, pancreatic diseases and gastrointestinal tumors. PMID:16484960

  20. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder.

    PubMed

    Sabbagh, Ubadah; Mullegama, Saman; Wyckoff, Gerald J

    2016-01-01

    The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES). A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study. PMID:27088090

  1. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder

    PubMed Central

    Mullegama, Saman; Wyckoff, Gerald J.

    2016-01-01

    The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES). A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study. PMID:27088090

  2. Autologous red blood cells potentiate antibody synthesis by unfractionated human mononuclear cell cultures.

    PubMed

    Rugeles, M T; La Via, M; Goust, J M; Kilpatrick, J M; Hyman, B; Virella, G

    1987-08-01

    We have tried to determine the most favourable conditions for the in vitro induction of specific antibody (Ab) responses to tetanus toxoid (TT) and keyhole limpet haemocyanin (KLH). Human peripheral blood mononuclear cells (PBMNC) were obtained from normal volunteers and stimulated with PWM, TT, KLH, and mixtures of PWM and antigens in the presence or absence of autologous red blood cells (RBC) (1:50 ratio of PBMNC/RBC). The cultures were harvested on day 11; immunoglobulins were determined immunonephelometrically and Ab levels by ELISA with human antibodies used for calibration. While anti-TT responses were easy to induce with PBMNC from recently boosted individuals, the production of anti-TT from PBMNC obtained from non-recently boosted individuals was only possible when PBMNC were stimulated with TT and PWM in the presence of autologous RBC. Similarly, anti-KLH responses were easier to induce with PBMNC from an immune donor; maximal response was observed after stimulation with PWM + KLH in the presence of autologous RBC. Stimulation of primary anti-KLH responses with PBMNC from non-immune donors was only successful when the cells were stimulated with KLH + PWM in the presence of autologous RBC. The potentiation of human B-cell responses with autologous RBC can be abrogated by pretreatment of PBMNC with anti-CD2 antibodies and is associated with increased expression of IL-2 receptors and increased production of gamma interferon (IFN-gamma). However, addition of IFN-gamma in different doses and at different times to PWM-stimulated PBMNC cultures was not as effective as addition of RBC in enhancing the production of immunoglobulin and antibody. PMID:3114872

  3. Human enteric viruses--potential indicators for enhanced monitoring of recreational water quality.

    PubMed

    Updyke, Erin Allmann; Wang, Zi; Sun, Si; Connell, Christina; Kirs, Marek; Wong, Mayee; Lu, Yuanan

    2015-10-01

    Recreational waters contaminated with human fecal pollution are a public health concern, and ensuring the safety of recreational waters for public use is a priority of both the Environmental Protection Agency (EPA) and the Centers for Disease Control and Prevention (CDC). Current recreational water standards rely on fecal indicator bacteria (FIB) levels as indicators of human disease risk. However present evidence indicates that levels of FIB do not always correspond to the presence of other potentially harmful organisms, such as viruses. Thus, enteric viruses are currently tested as water quality indicators, but have yet to be successfully implemented in routine monitoring of water quality. This study utilized enteric viruses as possible alternative indicators of water quality to examine 18 different fresh and offshore recreational waters on O'ahu, Hawai'i, by using newly established laboratory techniques including highly optimized PCR, real time PCR, and viral infectivity assays. All sample sites were detected positive for human enteric viruses by PCR including enterovirus, norovirus genogroups I and II, and male specific FRNA coliphage. A six time-point seasonal study of enteric virus presence indicated significant variation in virus detection between the rainy and dry seasons. Quantitative PCR detected the presence of norovirus genogroup II at levels at which disease risk may occur, and there was no correlation found between enteric virus presence and FIB counts. Under the present laboratory conditions, no infectious viruses were detected from the samples PCR-positive for enteric viruses. These data emphasize both the need for additional indicators for improved monitoring of water quality, and the feasibility of using enteric viruses as these indicators. PMID:26494480

  4. Induction of histone deacetylases (HDACs) in human abdominal aortic aneurysm: therapeutic potential of HDAC inhibitors.

    PubMed

    Galán, María; Varona, Saray; Orriols, Mar; Rodríguez, José Antonio; Aguiló, Silvia; Dilmé, Jaume; Camacho, Mercedes; Martínez-González, José; Rodriguez, Cristina

    2016-05-01

    Clinical management of abdominal aortic aneurysm (AAA) is currently limited to elective surgical repair because an effective pharmacotherapy is still awaited. Inhibition of histone deacetylase (HDAC) activity could be a promising therapeutic option in cardiovascular diseases. We aimed to characterise HDAC expression in human AAA and to evaluate the therapeutic potential of class I and IIa HDAC inhibitors in the AAA model of angiotensin II (Ang II)-infused apolipoprotein-E-deficient (ApoE(-/-)) mice. Real-time PCR, western blot and immunohistochemistry evidenced an increased expression of HDACs 1, 2 (both class I), 4 and 7 (both class IIa) in abdominal aorta samples from patients undergoing AAA open repair (n=22) compared with those from donors (n=14). Aortic aneurysms from Ang-II-infused ApoE(-/-) mice exhibited a similar HDAC expression profile. In these animals, treatment with a class I HDAC inhibitor (MS-275) or a class IIa inhibitor (MC-1568) improved survival, reduced the incidence and severity of AAA and limited aneurysmal expansion evaluated by Doppler ultrasonography. These beneficial effects were more potent in MC-1568-treated mice. The disorganisation of elastin and collagen fibres and lymphocyte and macrophage infiltration were effectively reduced by both inhibitors. Additionally, HDAC inhibition attenuated the exacerbated expression of pro-inflammatory markers and the increase in metalloproteinase-2 and -9 activity induced by Ang II in this model. Therefore, our data evidence that HDAC expression is deregulated in human AAA and that class-selective HDAC inhibitors limit aneurysm expansion in an AAA mouse model. New-generation HDAC inhibitors represent a promising therapeutic approach to overcome human aneurysm progression.

  5. Phytate degradation by human gut isolated Bifidobacterium pseudocatenulatum ATCC27919 and its probiotic potential.

    PubMed

    Haros, Monika; Carlsson, Nils-Gunnar; Almgren, Annette; Larsson-Alminger, Marie; Sandberg, Ann-Sofie; Andlid, Thomas

    2009-09-30

    The growing awareness of the relationship between diet and health has led to an increasing demand for food products that support health above and beyond providing basic nutrition. Probiotics are live organisms present in foods, which yield health benefits related to their interactions with the gastrointestinal tract. Phytases are a subgroup of phosphatases that catalyse the desphosphorylation of phytate, which reduces its negative impact on mineral bioavailability, and generates lower inositol phosphates. The aims of this investigation were to (i) study the ability of the probiotic candidate Bifidobacterium pseudocatenulatum to degrade phytate in synthetic medium, to (ii) identify the lower inositol phosphates generated, to (iii) study its survival under conditions mimicking gastrointestinal passage and finally to (iv) assess adhesion of the bacteria to Caco-2 cells. The first steps of InsP(6) degradation by B. pseudocatenulatum phytate-degrading enzyme/s were preferentially initiated at the DL-6-position and 5-position of the myo-inositol ring. It suggests that the main InsP(6) degradation pathway by B. pseudocatenulatum by sequential removal of phosphate groups was D/L-Ins(1,2,3,4,5)P(5) or D/L-Ins(1,2,3,4,6)P(5); D/L-Ins(1,2,3,4)P(4); to finally Ins(1,2,3)P(3) and D/L-Ins(1,2,4)P(3)/D/L-Ins(1,3,4)P(3). This human strain also showed a notable tolerance to bile as well as a selective adhesion capacity (adhesion to control surfaces was zero), to human intestinal Caco-2 cells comparable to the commercial probiotic B. lactis. The phytate-degrading activity constitutes a novel metabolic trait which could contribute to the improvement of mineral absorption in the intestine as a nutritional probiotic feature with potential trophic effect in human gut. PMID:19674804

  6. Induction of histone deacetylases (HDACs) in human abdominal aortic aneurysm: therapeutic potential of HDAC inhibitors

    PubMed Central

    Galán, María; Varona, Saray; Orriols, Mar; Rodríguez, José Antonio; Aguiló, Silvia; Dilmé, Jaume; Camacho, Mercedes; Martínez-González, José; Rodriguez, Cristina

    2016-01-01

    ABSTRACT Clinical management of abdominal aortic aneurysm (AAA) is currently limited to elective surgical repair because an effective pharmacotherapy is still awaited. Inhibition of histone deacetylase (HDAC) activity could be a promising therapeutic option in cardiovascular diseases. We aimed to characterise HDAC expression in human AAA and to evaluate the therapeutic potential of class I and IIa HDAC inhibitors in the AAA model of angiotensin II (Ang II)-infused apolipoprotein-E-deficient (ApoE−/−) mice. Real-time PCR, western blot and immunohistochemistry evidenced an increased expression of HDACs 1, 2 (both class I), 4 and 7 (both class IIa) in abdominal aorta samples from patients undergoing AAA open repair (n=22) compared with those from donors (n=14). Aortic aneurysms from Ang-II-infused ApoE−/− mice exhibited a similar HDAC expression profile. In these animals, treatment with a class I HDAC inhibitor (MS-275) or a class IIa inhibitor (MC-1568) improved survival, reduced the incidence and severity of AAA and limited aneurysmal expansion evaluated by Doppler ultrasonography. These beneficial effects were more potent in MC-1568-treated mice. The disorganisation of elastin and collagen fibres and lymphocyte and macrophage infiltration were effectively reduced by both inhibitors. Additionally, HDAC inhibition attenuated the exacerbated expression of pro-inflammatory markers and the increase in metalloproteinase-2 and -9 activity induced by Ang II in this model. Therefore, our data evidence that HDAC expression is deregulated in human AAA and that class-selective HDAC inhibitors limit aneurysm expansion in an AAA mouse model. New-generation HDAC inhibitors represent a promising therapeutic approach to overcome human aneurysm progression. PMID:26989193

  7. Mouse model predicts effects of smoking and varenicline on event-related potentials in humans

    PubMed Central

    Rudnick, Noam D.; Strasser, Andrew A.; Phillips, Jennifer M.; Jepson, Christopher; Patterson, Freda; Frey, Joseph M.; Turetsky, Bruce I.; Lerman, Caryn

    2010-01-01

    Background: Nicotine alters auditory event-related potentials (ERPs) in rodents and humans and is an effective treatment for smoking cessation. Less is known about the effects of the partial nicotine agonist varenicline on ERPs. Methods: We measured the effects of varenicline and nicotine on the mouse P20 and varenicline and smoking on the human P50 in a paired-click task. Eighteen mice were tested following nicotine, varenicline, and their combination. One hundred and fourteen current smokers enrolled in a placebo-controlled within-subject crossover study to test the effects of varenicline during smoking and abstinence. Thirty-two subjects participated in the ERP study, with half receiving placebo first and half varenicline first (VP). Results: Nicotine and varenicline enhanced mouse P20 amplitude, while nicotine improved P20 habituation by selectively increasing the first-click response. Similar to mice, abstinence reduced P50 habituation relative to smoking by reducing the first-click response. There was no effect of varenicline on P50 amplitude during abstinence across subjects. However, there was a significant effect of medication order on P50 amplitude during abstinence. Subjects in the PV group displayed reduced P50 during abstinence, which was blocked by varenicline. However, subjects in the VP group did not display abstinence-induced P50 reduction. Conclusions: Data suggest that smoking improves sensory processing. Varenicline mimics amplitude changes associated with nicotine and smoking but fails to alter habituation. The effect of medication order suggests a possible carryover effect from the previous arm. This study supports the predictive validity of ERPs in mice as a marker of drug effects in human studies. PMID:20395358

  8. A Novel Computational Model of the Human Ventricular Action Potential and Ca Transient

    PubMed Central

    Grandi, Eleonora; Pasqualini, Francesco S.; Bers, Donald M.

    2009-01-01

    We have developed a detailed mathematical model for Ca handling and ionic currents in the human ventricular myocyte. Our aims were to: 1) simulate basic excitation-contraction coupling phenomena; 2) use realistic repolarizing K current densities; 3) reach steady-state. The model relies on the framework of the rabbit myocyte model previously developed by our group, with subsarcolemmal and junctional compartments where ion channels sense higher [Ca] vs. bulk cytosol. Ion channels and transporters have been modeled on the basis of the most recent experimental data from human ventricular myocytes. Rapidly and slowly inactivating components of Ito have been formulated to differentiate between endocardial and epicardial myocytes. Transmural gradients of Ca handling proteins and Na pump were also simulated. The model has been validated against a wide set of experimental data including action potential duration (APD) adaptation and restitution, frequency-dependent increase in Ca transient peak and [Na]i. Interestingly, Na accumulation at fast heart rate is a major determinant of APD shortening, via outward shifts in Na pump and Na-Ca exchange currents. We investigated the effects of blocking K currents on APD and repolarization reserve: IKs block does not affect the former and slightly reduces the latter; IK1 blockade modestly increases APD and more strongly reduces repolarization reserve; IKr blockers significantly prolong APD, an effect exacerbated as pacing frequency is decreased, in good agreement with experimental results in human myocytes. We conclude that this model provides a useful framework to explore excitation-contraction coupling mechanisms and repolarization abnormalities at the single myocyte level. PMID:19835882

  9. In-vitro suppression of metabolic activity in malignant human glioblastomas due to pulsed - low frequency electric potential exposures

    NASA Astrophysics Data System (ADS)

    Schlichting, Abby; Waynant, Ronald W.; Tata, Darrell B.

    2010-02-01

    The role of pulsed - low repetition frequency electric potential was investigated in suppressing the metabolic activities of aggressive human brain cancer cells. Twenty four hours post exposure the glioblastomas were found to be significantly inhibited in their metabolic activity. The findings herein reveal a near complete inhibition of glioblastoma's metabolic activity through selective applications of low frequency pulsed electric potentials.

  10. Human thermal comfort antithesis in the context of the Mediterranean tourism potential

    NASA Astrophysics Data System (ADS)

    Nastos, Panagiotis T.; Zerefos, Christos S.; Kapsomenakis, Ioannis N.; Eleftheratos, Kostas; Polychroni, Iliana

    2016-04-01

    Weather and climate information are determinative factors in the decision of a touristic destination. The evaluation of the thermal, aesthetical and physical components of the climate is considered an issue of high importance in order to assess the climatic tourism potential. Mediterranean is an endowed region with respect to its temperate climate and impressive landscapes over the coastal environment and numerous islands. However, the harmony of the natural beauty is interrupted by extreme weather phenomena, such as heat and cold waves, heavy rains and stormy conditions. Thus, it is very important to know the seasonal behavior of the climate for touristic activities and recreation. Towards this objective we evaluated the antithesis in the human thermal perception as well as the sultriness, stormy, foggy, sunny and rainy days recorded in specific Greek touristic destinations against respective competitive Mediterranean resorts. Daily meteorological parameters, such as air temperature, relative humidity, wind speed, cloudiness and precipitation, were acquired from the most well-known touristic sites over the Mediterranean for the period 1970 to present. These variables were used on one hand to estimate the human thermal burden, by means of the thermal index of Physiologically Equivalent temperature (PET) and on the other hand to interpret the physical and aesthetic components of the tourism potential, by utilizing specific thresholds of the initial and derived variables in order to quantify in a simple and friendly way the environmental footprint on desired touristic destinations. The findings of this research shed light on the climate information for tourism in Greece against Mediterranean destinations. Greek resorts, especially in the Aegean Islands appear to be more ideal with respect to thermal comfort against resorts at the western and central Mediterranean, where the heat stress within the summer season seems to be an intolerable pressure on humans. This could

  11. Identification of potentially hazardous human gene products in GMO risk assessment.

    PubMed

    Bergmans, Hans; Logie, Colin; Van Maanen, Kees; Hermsen, Harm; Meredyth, Michelle; Van Der Vlugt, Cécile

    2008-01-01

    Genetically modified organisms (GMOs), e.g. viral vectors, could threaten the environment if by their release they spread hazardous gene products. Even in contained use, to prevent adverse consequences, viral vectors carrying genes from mammals or humans should be especially scrutinized as to whether gene products that they synthesize could be hazardous in their new context. Examples of such potentially hazardous gene products (PHGPs) are: protein toxins, products of dominant alleles that have a role in hereditary diseases, gene products and sequences involved in genome rearrangements, gene products involved in immunomodulation or with an endocrine function, gene products involved in apoptosis, activated proto-oncogenes. For contained use of a GMO that carries a construct encoding a PHGP, the precautionary principle dictates that safety measures should be applied on a "worst case" basis, until the risks of the specific case have been assessed. The potential hazard of cloned genes can be estimated before empirical data on the actual GMO become available. Preliminary data may be used to focus hazard identification and risk assessment. Both predictive and empirical data may also help to identify what further information is needed to assess the risk of the GMO. A two-step approach, whereby a PHGP is evaluated for its conceptual dangers, then checked by data bank searches, is delineated here.

  12. Beyond topoisomerase inhibition: antitumor 1,4-naphthoquinones as potential inhibitors of human monoamine oxidase.

    PubMed

    Coelho-Cerqueira, Eduardo; Netz, Paulo A; do Canto, Vanessa P; Pinto, Angelo C; Follmer, Cristian

    2014-04-01

    Monoamine oxidase (MAO) action has been involved in the regulation of neurotransmitters levels, cell signaling, cellular growth, and differentiation as well as in the balance of the intracellular polyamine levels. Although so far obscure, MAO inhibitors are believed to have some effect on tumors progression. 1,4-naphthoquinone (1,4-NQ) has been pointed out as a potential pharmacophore for inhibition of both MAO and DNA topoisomerase activities, this latter associated with antitumor activity. Herein, we demonstrated that certain antitumor 1,4-NQs, including spermidine-1,4-NQ, lapachol, and nor-lapachol display inhibitory activity on human MAO-A and MAO-B. Kinetic studies indicated that these compounds are reversible and competitive MAO inhibitors, being the enzyme selectivity greatly affected by substitutions on 1,4-NQ ring. Molecular docking studies suggested that the most potent MAO inhibitors are capable to bind to the MAO active site in close proximity of flavin moiety. Furthermore, ability to inhibit both MAO-A and MAO-B can be potentialized by the formation of hydrogen bonds between these compounds and FAD and/or the residues in the active site. Although spermidine-1,4-NQs exhibit antitumor action primarily by inhibiting topoisomerase via DNA intercalation, our findings suggest that their effect on MAO activity should be taken into account when their application in cancer therapy is considered.

  13. Broader prevalence of Wolbachia in insects including potential human disease vectors.

    PubMed

    de Oliveira, C D; Gonçalves, D S; Baton, L A; Shimabukuro, P H F; Carvalho, F D; Moreira, L A

    2015-06-01

    Wolbachia are intracellular, maternally transmitted bacteria considered the most abundant endosymbionts found in arthropods. They reproductively manipulate their host in order to increase their chances of being transmitted to the offspring, and currently are being used as a tool to control vector-borne diseases. Studies on distribution of Wolbachia among its arthropod hosts are important both for better understanding why this bacterium is so common, as well as for its potential use as a biological control agent. Here, we studied the incidence of Wolbachia in a broad range of insect species, collected from different regions of Brazil, using three genetic markers (16S rRNA, wsp and ftsZ), which varied in terms of their sensitivity to detect this bacterium. The overall incidence of Wolbachia among species belonging to 58 families and 14 orders was 61.9%. The most common positive insect orders were Coleoptera, Diptera, Hemiptera and Hymenoptera, with Diptera and Hemiptera having the highest numbers of Wolbachia-positive families. They included potential human disease vectors whose infection status has never been reported before. Our study further shows the importance of using quantitative polymerase chain reaction for high-throughput and sensitive Wolbachia screening.

  14. Dynamics of the Transcriptome during Human Spermatogenesis: Predicting the Potential Key Genes Regulating Male Gametes Generation.

    PubMed

    Zhu, Zijue; Li, Chong; Yang, Shi; Tian, Ruhui; Wang, Junlong; Yuan, Qingqing; Dong, Hui; He, Zuping; Wang, Shengyue; Li, Zheng

    2016-01-01

    Many infertile men are the victims of spermatogenesis disorder. However, conventional clinical test could not provide efficient information on the causes of spermatogenesis disorder and guide the doctor how to treat it. More effective diagnosis and treating methods could be developed if the key genes that regulate spermatogenesis were determined. Many works have been done on animal models, while there are few works on human beings due to the limited sample resources. In current work, testis tissues were obtained from 27 patients with obstructive azoospermia via surgery. The combination of Fluorescence Activated Cell Sorting and Magnetic Activated Cell Sorting was chosen as the efficient method to sort typical germ cells during spermatogenesis. RNA Sequencing was carried out to screen the change of transcriptomic profile of the germ cells during spermatogenesis. Differential expressed genes were clustered according to their expression patterns. Gene Ontology annotation, pathway analysis, and Gene Set Enrichment Analysis were carried out on genes with specific expression patterns and the potential key genes such as HOXs, JUN, SP1, and TCF3 which were involved in the regulation of spermatogenesis, with the potential value serve as molecular tools for clinical purpose, were predicted. PMID:26753906

  15. Therapeutic potentials of human adipose-derived stem cells on the mouse model of Parkinson's disease.

    PubMed

    Choi, Hee Soon; Kim, Hee Jin; Oh, Jin-Hwan; Park, Hyeong-Geun; Ra, Jeong Chan; Chang, Keun-A; Suh, Yoo-Hun

    2015-10-01

    The treatment of Parkinson's disease (PD) using stem cells has long been the focus of many researchers, but the ideal therapeutic strategy has not yet been developed. The consistency and high reliability of the experimental results confirmed by animal models are considered to be a critical factor in the stability of stem cell transplantation for PD. Therefore, the aim of this study was to investigate the preventive and therapeutic potential of human adipose-derived stem cells (hASC) for PD and was to identify the related factors to this therapeutic effect. The hASC were intravenously injected into the tail vein of a PD mouse model induced by 6-hydroxydopamine. Consequently, the behavioral performances were significantly improved at 3 weeks after the injection of hASC. Additionally, dopaminergic neurons were rescued, the number of structure-modified mitochondria was decreased, and mitochondrial complex I activity was restored in the brains of the hASC-injected PD mouse model. Overall, this study underscores that intravenously transplanted hASC may have therapeutic potential for PD by recovering mitochondrial functions.

  16. Identification of potentially hazardous human gene products in GMO risk assessment.

    PubMed

    Bergmans, Hans; Logie, Colin; Van Maanen, Kees; Hermsen, Harm; Meredyth, Michelle; Van Der Vlugt, Cécile

    2008-01-01

    Genetically modified organisms (GMOs), e.g. viral vectors, could threaten the environment if by their release they spread hazardous gene products. Even in contained use, to prevent adverse consequences, viral vectors carrying genes from mammals or humans should be especially scrutinized as to whether gene products that they synthesize could be hazardous in their new context. Examples of such potentially hazardous gene products (PHGPs) are: protein toxins, products of dominant alleles that have a role in hereditary diseases, gene products and sequences involved in genome rearrangements, gene products involved in immunomodulation or with an endocrine function, gene products involved in apoptosis, activated proto-oncogenes. For contained use of a GMO that carries a construct encoding a PHGP, the precautionary principle dictates that safety measures should be applied on a "worst case" basis, until the risks of the specific case have been assessed. The potential hazard of cloned genes can be estimated before empirical data on the actual GMO become available. Preliminary data may be used to focus hazard identification and risk assessment. Both predictive and empirical data may also help to identify what further information is needed to assess the risk of the GMO. A two-step approach, whereby a PHGP is evaluated for its conceptual dangers, then checked by data bank searches, is delineated here. PMID:18384725

  17. Corrective Action Investigation Plan for Corrective Action Unit 528: Polychlorinated Biphenyls Contamination, Nevada Test Site, Nevada, Rev. 0

    SciTech Connect

    U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office

    2003-05-08

    This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 528, Polychlorinated Biphenyls Contamination (PCBs), Nevada Test Site (NTS), Nevada, under the Federal Facility Agreement and Consent Order. Located in the southwestern portion of Area 25 on the NTS in Jackass Flats (adjacent to Test Cell C [TCC]), CAU 528 consists of Corrective Action Site 25-27-03, Polychlorinated Biphenyls Surface Contamination. Test Cell C was built to support the Nuclear Rocket Development Station (operational between 1959 and 1973) activities including conducting ground tests and static firings of nuclear engine reactors. Although CAU 528 was not considered as a direct potential source of PCBs and petroleum contamination, two potential sources of contamination have nevertheless been identified from an unknown source in concentrations that could potentially pose an unacceptable risk to human health and/or the environment. This CAU's close proximity to TCC prompted Shaw to collect surface soil samples, which have indicated the presence of PCBs extending throughout the area to the north, east, south, and even to the edge of the western boundary. Based on this information, more extensive field investigation activities are being planned, the results of which are to be used to support a defensible evaluation of corrective action alternatives in the corrective action decision document.

  18. Potentiation of luteolin cytotoxicity by flavonols fisetin and quercetin in human chronic lymphocytic leukemia cell lines.

    PubMed

    Sak, Katrin; Kasemaa, Kristi; Everaus, Hele

    2016-09-14

    Despite numerous studies chronic lymphocytic leukemia (CLL) still remains an incurable disease. Therefore, all new compounds and novel strategies which are able to eradicate CLL cells should be considered as valuable clues for a potential future remedy against this malignancy. In the present study, the cytotoxic profiles of natural flavonoids were described in two human CLL cell lines, HG-3 and EHEB, indicating the flavone luteolin as the most potent flavonoid with half-maximal inhibitory constants (IC50) of 37 μM and 26 μM, respectively. Luteolin significantly increased the apoptotic cell population in both cell lines by increasing the activities of caspases-3 and -9 and triggering the intrinsic apoptotic pathway. Two flavonols, fisetin and quercetin, were somewhat less efficient in suppressing cellular viability, whereas baicalein, chrysin, (+)-catechin and hesperetin exerted only a small or no response at doses as high as 100 μM. Both fisetin and quercetin were able to augment the cytotoxic activity of luteolin in both cell lines by reducing the IC50 values up to four fold. As a result of this, luteolin displayed cytotoxicity activity already at low micromolar concentrations that could potentially be physiologically achievable through oral ingestion. No other tested flavonoids were capable of sensitizing CLL cells to luteolin pointing to a specific binding of fisetin and quercetin to the cellular targets which interfere with the signaling pathways induced by luteolin. Although further molecular studies to unravel this potentiating mechanism are certainly needed, this phenomenon could contribute to future remedies for prevention and treatment of chronic lymphocytic leukemia.

  19. Potentiation of luteolin cytotoxicity by flavonols fisetin and quercetin in human chronic lymphocytic leukemia cell lines.

    PubMed

    Sak, Katrin; Kasemaa, Kristi; Everaus, Hele

    2016-09-14

    Despite numerous studies chronic lymphocytic leukemia (CLL) still remains an incurable disease. Therefore, all new compounds and novel strategies which are able to eradicate CLL cells should be considered as valuable clues for a potential future remedy against this malignancy. In the present study, the cytotoxic profiles of natural flavonoids were described in two human CLL cell lines, HG-3 and EHEB, indicating the flavone luteolin as the most potent flavonoid with half-maximal inhibitory constants (IC50) of 37 μM and 26 μM, respectively. Luteolin significantly increased the apoptotic cell population in both cell lines by increasing the activities of caspases-3 and -9 and triggering the intrinsic apoptotic pathway. Two flavonols, fisetin and quercetin, were somewhat less efficient in suppressing cellular viability, whereas baicalein, chrysin, (+)-catechin and hesperetin exerted only a small or no response at doses as high as 100 μM. Both fisetin and quercetin were able to augment the cytotoxic activity of luteolin in both cell lines by reducing the IC50 values up to four fold. As a result of this, luteolin displayed cytotoxicity activity already at low micromolar concentrations that could potentially be physiologically achievable through oral ingestion. No other tested flavonoids were capable of sensitizing CLL cells to luteolin pointing to a specific binding of fisetin and quercetin to the cellular targets which interfere with the signaling pathways induced by luteolin. Although further molecular studies to unravel this potentiating mechanism are certainly needed, this phenomenon could contribute to future remedies for prevention and treatment of chronic lymphocytic leukemia. PMID:27489195

  20. Aerobic bacterial oral flora of garter snakes: development of normal flora and pathogenic potential for snakes and humans.

    PubMed Central

    Goldstein, E J; Agyare, E O; Vagvolgyi, A E; Halpern, M

    1981-01-01

    Garter snakes that are used for scientific laboratory studies or kept as exotic pets often become ill and die early in captivity. They may also act as reservoirs of potential human pathogens or transmit infection to man. A total of 126 strains of aerobic and facultative bacteria, most potential human and snake pathogens, were isolated from 82 garter snake oropharyngeal cultures. Coagulase-negative Staphylococcus species were the most common species isolated. Acinetobacter calcoaceticus var. anitratus, Hafnia alvei, Arizona hinshawii, Salmonella species, Shigella species, Klebsiella oxytoca, and Pseudomonas aeruginosa were among the potential pathogens isolated. The spectrum of bacteria with potential for causing oral and pulmonary infections in garter snakes is greater than has been previously appreciated. Garter snakes should also be considered reservoirs of human pathogens, and appropriate precautions should be taken by laboratory personnel and pet owners. PMID:7240404

  1. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    PubMed Central

    Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

    2015-01-01

    Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new therapeutics. This requires further in-depth knowledge of the similarities and differences between mouse and human RPE. Methods We performed a microarray study to identify and functionally annotate RPE specific gene expression in mouse and human RPE. We used a meticulous method to determine C57BL/6J mouse RPE signature genes, correcting for possible RNA contamination from its adjacent layers: the choroid and the photoreceptors. We compared the signature genes, gene expression profiles and functional annotations of the mouse and human RPE. Results We defined sets of mouse (64), human (171) and mouse–human interspecies (22) RPE signature genes. Not unexpectedly, our gene expression analysis and comparative functional annotation suggested that, in general, the mouse and human RPE are very similar. For example, we found similarities for general features, like “organ development” and “disorders related to neurological tissue”. However, detailed analysis of the molecular pathways and networks associated with RPE functions, suggested also multiple species-specific differences, some of which may be relevant for the development of AMD. For example, CFHR1, most likely the main complement regulator in AMD pathogenesis was highly expressed in human RPE, but almost absent in mouse RPE. Furthermore, functions assigned to mouse and human RPE expression profiles indicate (patho-) biological differences related to AMD, such as oxidative stress, Bruch’s membrane, immune-regulation and outer blood retina barrier. Conclusion These differences may be important for the development of new therapeutic strategies and translational studies in age-related macular

  2. Scientific Investigations To Prepare For The Potential Human Exploration Of Mars

    NASA Astrophysics Data System (ADS)

    Hays, Lindsay; Beaty, David; Whitley, Ryan

    2016-07-01

    decreased the importance of this measurement) • Dust physical, chemical and electrical properties (rover data from multiple locations has provided sufficient information on these properties) New: • Measure solar energetic particles at the martian surface throughout the ~11 year solar cycle to characterize "extreme conditions" • Test ISRU atmospheric processing system to measure resilience with respect to dust and other environmental challenge performance parameters. • Identify and map a set of candidate water resource deposits that have the potential to be relevant for future human exploration. What would it take to respond to the remaining SKGs? Missions such as Mars 2020, a future orbiter (with potential instruments such as those detailed by the Next Orbiter Science Analysis Group), potential sample return and precursor missions (including an EDL pathfinder and resource prospectors) would reduce the priority of most of the remaining SKGs, or retire them entirely.

  3. Hypoxia Potentiates Palmitate-induced Pro-inflammatory Activation of Primary Human Macrophages.

    PubMed

    Snodgrass, Ryan G; Boß, Marcel; Zezina, Ekaterina; Weigert, Andreas; Dehne, Nathalie; Fleming, Ingrid; Brüne, Bernhard; Namgaladze, Dmitry

    2016-01-01

    Pro-inflammatory cytokines secreted by adipose tissue macrophages (ATMs) contribute to chronic low-grade inflammation and obesity-induced insulin resistance. Recent studies have shown that adipose tissue hypoxia promotes an inflammatory phenotype in ATMs. However, our understanding of how hypoxia modulates the response of ATMs to free fatty acids within obese adipose tissue is limited. We examined the effects of hypoxia (1% O2) on the pro-inflammatory responses of human monocyte-derived macrophages to the saturated fatty acid palmitate. Compared with normoxia, hypoxia significantly increased palmitate-induced mRNA expression and protein secretion of IL-6 and IL-1β. Although palmitate-induced endoplasmic reticulum stress and nuclear factor κB pathway activation were not enhanced by hypoxia, hypoxia increased the activation of JNK and p38 mitogen-activated protein kinase signaling in palmitate-treated cells. Inhibition of JNK blocked the hypoxic induction of pro-inflammatory cytokine expression, whereas knockdown of hypoxia-induced transcription factors HIF-1α and HIF-2α alone or in combination failed to reduce IL-6 and only modestly reduced IL-1β gene expression in palmitate-treated hypoxic macrophages. Enhanced pro-inflammatory cytokine production and JNK activity under hypoxia were prevented by inhibiting reactive oxygen species generation. In addition, silencing of dual-specificity phosphatase 16 increased normoxic levels of IL-6 and IL-1β and reduced the hypoxic potentiation in palmitate-treated macrophages. The secretome of hypoxic palmitate-treated macrophages promoted IL-6 and macrophage chemoattractant protein 1 expression in primary human adipocytes, which was sensitive to macrophage JNK inhibition. Our results reveal that the coexistence of hypoxia along with free fatty acids exacerbates macrophage-mediated inflammation. PMID:26578520

  4. Angiogenic Potential and Secretome of Human Apical Papilla Mesenchymal Stem Cells in Various Stress Microenvironments.

    PubMed

    Bakopoulou, Athina; Kritis, Aristeidis; Andreadis, Dimitrios; Papachristou, Eleni; Leyhausen, Gabriele; Koidis, Petros; Geurtsen, Werner; Tsiftsoglou, Asterios

    2015-11-01

    Stem cells from the apical papilla (SCAP) of human adult teeth are considered an accessible source of cells with angiogenic properties. The aims of this study were to investigate the endothelial transdifferentiation of SCAP, the secretion of pro- and antiangiogenic factors from SCAP, and the paracrine effects of SCAP when exposed to environmental stress to stimulate tissue damage. SCAP were exposed to serum deprivation (SD), glucose deprivation (GD), and oxygen deprivation/hypoxia (OD) conditions, individually or in combination. Endothelial transdifferentiation was evaluated by in vitro capillary-like formation assays, real-time polymerase chain reaction, western blot, and flow cytometric analyses of angiogenesis-related markers; secretome by antibody arrays and enzyme-linked immunosorbent assays (ELISA); and paracrine impact on human umbilical vein endothelial cells (HUVECs) by in vitro transwell migration and capillary-like formation assays. The short-term exposure of SCAP to glucose/oxygen deprivation (GOD) in the presence, but mainly in deprivation, of serum (SGOD) elicited a proangiogenesis effect indicated by expression of angiogenesis-related genes involved in vascular endothelial growth factor (VEGF)/VEGFR and angiopoietins/Tie pathways. This effect was unachievable under SD in normoxia, suggesting that the critical microenvironmental condition inducing rapid endothelial shift of SCAP is the combination of SGOD. Interestingly, SCAP showed high adaptability to these adverse conditions, retaining cell viability and acquiring a capillary-forming phenotype. SCAP secreted higher numbers and amounts of pro- (angiogenin, IGFBP-3, VEGF) and lower amounts of antiangiogenic factors (serpin-E1, TIMP-1, TSP-1) under SGOD compared with SOD or SD alone. Finally, secretome obtained under SGOD was most effective in inducing migration and capillary-like formation by HUVECs. These data provide new evidence on the microenvironmental factors favoring endothelial

  5. Calcium regulation by temperature-sensitive transient receptor potential channels in human uveal melanoma cells.

    PubMed

    Mergler, Stefan; Derckx, Raissa; Reinach, Peter S; Garreis, Fabian; Böhm, Arina; Schmelzer, Lisa; Skosyrski, Sergej; Ramesh, Niraja; Abdelmessih, Suzette; Polat, Onur Kerem; Khajavi, Noushafarin; Riechardt, Aline Isabel

    2014-01-01

    Uveal melanoma (UM) is both the most common and fatal intraocular cancer among adults worldwide. As with all types of neoplasia, changes in Ca(2+) channel regulation can contribute to the onset and progression of this pathological condition. Transient receptor potential channels (TRPs) and cannabinoid receptor type 1 (CB1) are two different types of Ca(2+) permeation pathways that can be dysregulated during neoplasia. We determined in malignant human UM and healthy uvea and four different UM cell lines whether there is gene and functional expression of TRP subtypes and CB1 since they could serve as drug targets to either prevent or inhibit initiation and progression of UM. RT-PCR, Ca(2+) transients, immunohistochemistry and planar patch-clamp analysis probed for their gene expression and functional activity, respectively. In UM cells, TRPV1 and TRPM8 gene expression was identified. Capsaicin (CAP), menthol or icilin induced Ca(2+) transients as well as changes in ion current behavior characteristic of TRPV1 and TRPM8 expression. Such effects were blocked with either La(3+), capsazepine (CPZ) or BCTC. TRPA1 and CB1 are highly expressed in human uvea, but TRPA1 is not expressed in all UM cell lines. In UM cells, the CB1 agonist, WIN 55,212-2, induced Ca(2+) transients, which were suppressed by La(3+) and CPZ whereas CAP-induced Ca(2+) transients could also be suppressed by CB1 activation. Identification of functional TRPV1, TRPM8, TRPA1 and CB1 expression in these tissues may provide novel drug targets for treatment of this aggressive neoplastic disease.

  6. Therapeutic potential of chlorotoxin-like neurotoxin from the Chinese scorpion for human gliomas.

    PubMed

    Fu, Yue-Jun; Yin, Li-Tian; Liang, Ai-Hua; Zhang, Chao-Feng; Wang, Wei; Chai, Bao-Feng; Yang, Jian-Yi; Fan, Xiao-Jun

    2007-01-22

    Chlorotoxin, one of the key toxins in scorpion Leiurus quinquestriatus venom, has been shown to bind specifically to glioma cell surface as a specific chloride channel blocker. In this study, a purified, recombinant chlorotoxin-like peptide from the scorpion Buthus martensii Karsch (named rBmK CTa) was characterized by in vivo and in vitro studies. The results from cell proliferation assay with human glioma (SHG-44) cells showed that rBmK CTa inhibits the growth of glioma cells in a dose-dependent manner, with an IC(50) value of approximately 0.28microM. Under the same conditions, the IC(50) value for normal astrocytes increased to 8microM. This clearly indicated that rBmK CTa had specific toxicity against glioma cells but not astrocytes. Results from whole-cell patch-clamp recording showed that chloride current in SHG-44 was inhibited by rBmK CTa in a voltage-dependent manner and percent inhibitions for the blocking action of rBmK CTa (0.07 and 0.14microM) on I(Cl) was 17.64+/-3.06% and 55.86+/-2.83%, respectively. Histological analysis of rBmK CTa treated mice showed that brain, leg muscle and cardiac muscle were the target organs of this toxin. These results suggest that rBmK CTa may have potential therapeutic application in clinical treatment of human glioma. It represents an approach for developing a novel therapeutic agent.